Life-threatening hyperkalaemia caused by tacrolimus induced type 4 renal tubular acidosis in a post liver transplant patient: A case report

Life-threatening hyperkalaemia caused by tacrolimus induced type 4 renal tubular acidosis in a post liver transplant patient: A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Life-threatening hyperkalaemia caused by tacrolimus induced type 4 renal tubular acidosis in a post liver transplant patient: A case report Chiranthi Welhenge, Ravi Maharaja Roshiban This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8751708/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Tacrolimus is a calcineurin inhibitor which remains an integral part of the post-transplantation immunosuppression regime. It is known to cause many adverse effects including Type 4 Renal Tubular Acidosis (T4-RTA), which is a well known, but rare side effect. Unrecognised and untreated T4-RTA can cause refractory hyperkalemia which may lead to life-threatening cardiac arrythmias. Although several cases of Tacrolimus induced T4-RTA has been reported in post kidney transplant patients, it has been rarely reported in the post liver transplant setting. Case presentation We report a rare case of refractory hyperkalaemia due to T4-RTA caused by Tacrolimus in a 47-year-old Sri Lankan male, who underwent orthotopic deceased-donor liver transplantation for autoimmune hepatitis induced liver cirrhosis, which was successfully treated with Fludrocortisone replacement. Conclusion We wish to highlight the significance of this life-threatening entity, which every transplant team should be aware of, for early recognition and timely treatment. Tacrolimus Calcineurin inhibitors Liver transplantation Hyperkalemia Renal tubular acidosis Type 4 RTA Background Calcineurin inhibitors, especially tacrolimus, are considered the backbone of immunosuppressive regimens for transplant recipients. Tacrolimus is considerd to be a better immunosuppressant than cylosporine when their efficacies arecompared ( 1 ), with better rates of graft survival, especially after liver transplantation ( 2 ). However, their renal adverse effects remain a major concern and a significant hindrance to their effective use ( 1 , 2 ). These include nephrotoxicity manifesting as a reduced glomerular filtration rate due to renal vasoconstriction ( 3 ) and tubular dysfunction manifesting as renal tubular acidosis (RTA), mainly the distal form (Type 1) ( 4 – 6 ). More concerning is the hyperkalemic form of RTA : Type 4 which is rarely reported. Tacrolimus-related acid-base disorders are well documented following renal transplantation ( 7 – 12 ), whereas it is rare following liver transplantation. Herein we describe our experience in the diagnosis and management of a patient with tacrolimus-induced Type 4 RTA in a patient after deceased donor liver transplantation. Case presentation A 47-year-old Sri Lankan male with type 2 diabetes mellitus and hyperthyroidism who was diagnosed with autoimmune hepatitis-related cirrhosis (CTP B, MELD 13) was referred to our specialized liver transplant clinic two years back for a liver transplant (LT) workup. He was found to have a well-differentiated hepatocellular carcinoma (HCC) in segment IV and he underwent percutaneous ethanol injection once as bridging therapy to LT. While awaiting further cycles of ethanol injection he developed episodes of decompensation (CTP C, MELD 17), which warranted early liver transplantation. He underwent orthotopic LT with no intraoperative complications apart from hypotension which required vasopressors, which were tailed off gradually. The summary of investigations during the post-operative period is shown below (Table 1 ). Table 1 Summary of investigations D1 D3 D6 D8 D13 D15 D18 D20 D21 D22 D24 WBC (x10 9 /L) 15.06 11.5 11 11.5 16.6 14.4 11.9 10.6 13.8 15.2 9.56 Neu (x10 9 /L) 11.6 9.43 7.04 7.13 12.1 11.23 7.85 7.2 10.2 10.3 5.83 Lym (x10 9 /L) 21.3 1.49 2.97 3.2 3.81 2.3 2.85 2.86 2.62 4.10 3.15 Hb (g/L) 10.4 7.6 9.3 8.4 8.6 8.8 9.3 10.3 11 11.5 10.1 PLT (x10 9 /L) 93 62 75 128 185 185 169 180 183 190 140 Scr (µmol/L) 143 193.6 115 128 156 156 180 161 172 184 154 Urea (mmol/L) 49.5 89 76 65 103 133 161 168 191 179 140 Na (mEq/L) 142 150 143 145 138 136 126 123 126 127 129 K (mEq/L) 4.1 3.3 4.5 4.3 4.6 5 5.7 7 6.15 4.9 4.9 Ca (mmol/L) 9.5 7.4 8.6 7.9 7.5 7.8 8.8 11 11.2 9.4 Phosphate(mmol/L) 2 2.1 3.3 2.2 2.2 4.1 4.9 Mg (mmol/L) 1.5 1.6 1.4 1.3 1.3 2.2 1.6 Cl (mmol/L) 111 112 103 107 100 98 88 85 98.8 89 ALT (U/L) 132 59 58 82 45 40 30 22 22 23 19 AST (U/L) 444 60 43 67 15 16 19 16 15 16 16 ALP (U/L) 80 62 75 111 109 114 109 109 97 106 GGT (U/L) 72 70 142 190 119 115 97 96 105 97 78 T bil (µmol/L) 12.6 0.6 0.7 0.7 0.6 0.7 0.6 0.7 0.7 0.9 0.7 D Bil (µmol/L) 8.3 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.3 0.1 T Protein (g/dL) 4.3 4.5 5.3 6.2 6.2 6.8 7 7.3 8.2 7.7 6.6 Albumin (g/dL) 2.8 2.3 2.6 3.6 3.8 4.2 4.3 4.5 5.6 4.8 4.2 Globulin (g/dL) 1.5 2.2 2.7 2.6 2.4 2.6 2.7 2.8 3.2 2.7 2.4 INR 1.18 1.12 CRP (mg/L) 23.4 35.5 10.6 3.1 4 7.5 3.9 2.4 1.7 2.7 4.5 Procalcitonin(ng/ml) 0.59 0.57 0.31 pH 7.25 pCO 2 (mmHg) 45.7 pO 2 (mmHg) 26.4 HCO 3 (mEq/L) 20.2 Lactate (mmol/L) 1.8 Tacrolimus level (ng/ml) 2.5 5.8 6.1 Urine Na (mEq/L) 66 45 Urine Cl (mEq/L) 73 Urine K (mEq/L) 25 Urine osmolality (mOsm/kg) 341 Serum osmolality (mOsm/kg) 291 He was noted to have a non-oliguric Acute Kidney Injury (AKI) during the immediate post-operative period while on intravenous furosemide infusion, which was managed with fluid resuscitation and titration of the furosemide dose. Initial hypokalemia was also noted which required correction with IV potassium chloride (KCl). He was started on IV steroids initially and later converted to oral steroids. Tacrolimus was started from a dose of 0.5mg twice a day on post-operative day 2 and gradually titrated while mycophenolate mofetil (MMF) was started on day 6 at a dose of 250mg twice a day. Spironolactone was started at a dose of 25mg daily from D7 due to oedema and up-titrated gradually. Furosemide infusion was converted to oral furosemide by day 11 and increased along with spironolactone to manage the persistent oedema. Liver biochemistry improved gradually with the recovery of synthetic functions. By D13 he was again noted to develop an AKI which required adjustment of diuretic doses. By day 18 investigations revealed a new onset hyperkalemia and hyponatremia, due to which all his diuretics were stopped, and medical correction of hyperkalemia was attempted. However, hyperkalemia was refractory, and ECG showed tall T waves without arrhythmias. Continuous medical correction of hyperkalemia was done, and tacrolimus, cotrimoxazole and fluconazole were stopped by Day 19 while increasing MMF. Blood gas analysis revealed a normal anion gap metabolic acidosis with a positive urinary anion gap. Serum aldosterone levels could not be performed due to unavailability. An endocrinology opinion was sought, and he was started on Fludrocortisone 50 micrograms per day with furosemide 20mg twice a day while continuing low-dose tacrolimus (0.5mg/twice a day). However, hyperkalemia was slow to respond, and the possibility of a Type 4 RTA was considered attributed to tacrolimus. The fludrocortisone dose was increased gradually while correcting acidosis with sodium bicarbonate after stopping tacrolimus along with medical management of hyperkalemia. With this, the hyperkalemia and hyponatremia started to improve. The patient was started on cyclosporine A on day 24 after his metabolic derangements settled and AKI improved, and the dose was adjusted monitoring cyclosporine A levels. There was no evidence of graft rejection during this period. The patient was discharged eventually and two months after LT he remainswithout evidence of graft rejection and normal metabolic parameters. Discussion and Conclusions Evaluation of the biochemical changes of our patient during the immediate post-LT period is a good demonstration of the renal effects of tacrolimus. The initial rise in serum creatinine was attributed to a grade 1 prerenal acute kidney injury (AKI) which improved with fluid resuscitation and adjustment of diuretic doses. His creatinine remained stable even after the initiation of tacrolimus. However, with the initiation of spironolactone on day 7, a second rise in serum creatinine was noted by postoperative day 13. It was also a grade 1 AKI attributed to prerenal causes. He had hypokalemia during the initial post-operative period which required correction with IV KCL. A sharp rise in potassium (K) was observed from day 15, which was not in keeping with the grade 1 AKI. By this time, he was on spironolactone, cotrimoxazole, fluconazole and tacrolimus, all of which could have contributed to hyperkalemia. Despite the discontinuation of the first three medications and dose reduction of tacrolimus, hyperkalemia remained resistant to medical management, which prompted us to evaluate for other causes of resistant hyperkalemia. There was no evidence of diabetic nephropathy, chronic kidney disease or reflux nephropathy and the patient remained asymptomatic during this period. Concomitant hyponatremia suggested the possibility of adrenal insufficiency; however, the patient was already on adequate steroids which made this possibility unlikely. Further evaluation revealed a normal anion gap metabolic acidosis with chloride in the upper normal range and a positive urinary anion gap. The trans tubular potassium gradient (TTKG) was 4.3. A type 4 RTA was suspected with concomitant aldosterone deficiency which was attributed to tacrolimus. Since aldosterone level was not available, empirical treatment was initiated with fludrocortisone after stopping tacrolimus. He made a dramatic improvement with fludrocortisone confirming our suspicion of type 4 RTA. Two types of hyperkalemic RTAs due to tacrolimus have been described in the literature, namely a voltage-dependent distal RTA (dRTA) ( 8 , 13 , 14 ) and a type 4 RTA ( 7 , 9 – 12 , 15 , 16 ). Distal hyperkalemic RTAs usually respond to tacrolimus dose reduction ( 14 ) while type 4 RTAs should be treated with fludrocortisone ( 8 ). Our patient failed to respond to initial tacrolimus dose reduction, which makes a dRTA unlikely in our patient. Type 4 RTA is characterized by severe hyperkalemia, hyperchloremic acidosis, normal anion gap metabolic acidosis and a positive urinary anion gap. Hypoaldosteronism is the pathophysiological basis of hyperkalemia in type 4 RTA, which could be the result of reduced production (hyporeninemic hypoaldosteronism), resistance at the epithelial sodium channels of the kidney or antagonism at these receptors ( 17 , 18 ). Calcineurin inhibitors can cause both these pathological effects ( 19 , 20 ). Direct inhibition of Na + /K + -ATPase activity in renal tubules by calcineurin inhibitors also contributes to the inhibition of kaliuresis and hyperkalemia ( 21 ). Hyperkalemia resulting from these mechanisms along with hypoaldosteronism inhibits NH4 + excretion by reducing ammonia genesis in proximal tubular cells and reduced medullary NH4 + reabsorption which results in metabolic acidosis ( 22 ). Both cyclosporine and tacrolimus have been implicated in RTA in post-transplant patients. Cyclosporine-induced type 4 RTA and voltage-dependent dRTA have been reported in renal transplant patients ( 7 , 8 ) but not in LT patients. Tacrolimus-induced dRTA is commoner than type 4 RTA, with three studies reported in LT patients ( 8 , 13 , 14 ) and one each in renal and cardiac transplant patients ( 8 ). Type 4 RTA has been reported in four studies of renal transplant patients ( 9 – 12 ) but only in two LT patients ( 15 , 16 ). A recurrence of the RTA was not evident in our patient despite starting on cyclosporine after stopping tacrolimus. Tacrolimus is known to cause hyperkalemia and hyponatremia more frequently than cyclosporine ( 23 ). Although both medications can cause RTA, it has been shown that tacrolimus can be replaced by cyclosporine without any adverse effects ( 24 ), with no reported cases of cyclosporine-induced RTA in post-LT patients. Although calcineurin inhibitors have been implicated in type 4 RTAs, there’s a paucity of published evidence supporting this in LT. We wish to draw the attention of the medical community involved in LT medicine, to this uncommon entity, to facilitate early recognition and proper management of post-transplant immunosuppressive-related complications. Abbreviations WBC White blood cell count Neu Neutrophil count Lym Lymphocyte count Hb Haemoglobin PLT Platelet count Scr Serum creatinine Na Sodium K Potassium Ca Calcium Mg Magnesium Cl Chloride ALT Alaninine transaminase AST Aspartate transaminase GGT Gamma glutamyl trasferase ALP Alkaline phosphatase T Bil Total biliribin D Bil Direct bilirubin T Protein Total protein INR International normalized ratio CRP C reactive protein pO 2 Partial pressure of oxygen pCO 2 Partial pressure of carbon dioxide HCO 3 Bicarbonate NH4 + - Ammonium Declarations Ethics approval and consent to participate Not applicable Consent for publication Informed written consent to publish the details of the patient was taken from the patient before drafting the manuscript and before submission. Availability of data and materials This case report did not involve collection of data. However, patient’s clinical data is available from the bed head ticket. Competing interests Authors report no competing interests to declare. Funding None Authors' contributions CW and RMR, are the co-authors of the article. They drafted the initial manuscript and did the literature searches. All authors participated in manuscript revision, agreed to submit the manuscript, and approved the final version of the manuscript. All authors had full access to clinical data. Acknowledgements We acknowledge the support given by Prof. Madnil Niriella, Professor in Gastroenterology and Dr. Uditha Dassanayake, Consultant Gastroenterologist, for their valuable guidance in preparation of this manuscript. We would like to extend our thanks to all individuals involved in the management of the patient. References Winkler M, Christians U. A risk-benefit assessment of tacrolimus in transplantation. Drug Saf. 1995;12(5):348–57. Peters DH, Fitton A, Plosker GL, Faulds D. Tacrolimus: a review of its pharmacology, and therapeutic potential in hepatic and renal transplantation. Drugs. 1993;46:746–94. Moutabarrik A, Ishibashi M, Kameoka H, Takano Y, Kokado Y, Sonoda T, Takahara S, Okuyama A, Fukunaga M. FK506 mechanism of nephrotoxicity: stimulatory effect on endothelin secretion by cultured kidney cells. InTransplant International Official Journal of the European Society for Organ Transplantation: Proceedings of the 5th Congress of the European Society for Organ Transplantation, Maastricht, October 7–10, 1991 1992 (pp. 93–97). Springer Berlin Heidelberg. Mohebbi N, Mihailova M, Wagner CA. The calcineurin inhibitor FK506 (tacrolimus) is associated with transient metabolic acidosis and altered expression of renal acid-base transport proteins. Am J Physiology-Renal Physiol. 2009;297(2):F499–509. Heering P, Ivens K, Aker S, Grabensee B. Distal tubular acidosis induced by FK506. Clin Transplant. 1998;12(5):465–71. Schwarz C, Benesch T, Kodras K, Oberbauer R, Haas M. Complete renal tubular acidosis late after kidney transplantation. Nephrol Dialysis Transplantation. 2006;21(9):2615–20. Rangel EB, Gomes SA, Machado PG, dos Santos BC, Pestana JM, Pacheco-Silva A, Heilberg IP. Severe hyperkalemic type 4 renal tubular acidosis after kidney transplantation: a case report. InTransplantation proceedings 2006 Nov 1 (Vol. 38, No. 9, pp. 3112–3115). Elsevier. Lin W, Mou L, Tu H, Zhu L, Wang J, Chen J, Hu Y. Clinical analysis of hyperkalemic renal tubular acidosis caused by calcineurin inhibitors in solid organ transplant recipients. J Clin Pharm Ther. 2017;42(1):122–4. Alabdulqader MA, Azzam A, Alshami AA. Incidence of hyperkalemic RTA in pediatric post-renal transplant patients and the role of fludrocortisone. Pediatr Transplant. 2021;25(6):e14029. Kulkarni M. Type 4 renal tubular acidosis in a kidney transplant recipient. Biomedical J. 2016;39(1):85. Sivakumar V, Sriramnaveen P, Krishna C, Manjusha Y, Reddy SY, Sridhar N, Subramanian S. Role of fludrocortisone in the management of tacrolimus-induced hyperkalemia in a renal transplant recipient. Saudi J Kidney Dis Transplantation. 2014;25(1):149–51. Gama RM, Makanjuola D, Wahba M, Quan V, Phanish M. Fludrocortisone is an effective treatment for hyperkalaemic metabolic acidosis in kidney transplant recipients on tacrolimus: a case series. Nephron. 2022;146(2):190–6. Riveiro-Barciela M, Campos-Varela I, Tovar JL, Vargas V, Simón-Talero M, Ventura-Cots M, Crespo M, Bilbao I, Castells L. Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report. InTransplantation proceedings 2011 Dec 1 (Vol. 43, No. 10, pp. 4016–4018). Elsevier. Oishi M, Yagi T, Urushihara N, Takakura N, Inagaki M, Sadamori H, Mastukawa H, Inoue T, Oda S, Tanaka N. A case of hyperkalemic distal renal tubular acidosis secondary to tacrolimus in living donor liver transplantation. InTransplantation proceedings 2000 (Vol. 32, No. 7, pp. 2225–2226). Elsevier USA. Ogita K, Takada N, Taguchi T, Suita S, Soejima Y, Suehiro T, Shimada M, Maehara Y. Renal tubular acidosis secondary to FK506 in living donor liver transplantation: a case report. Asian J Surg. 2003;26(4):218–20. Schmoyer C, Mishra S, Fulco F. Tacrolimus-Induced Type IV Renal Tubular Acidosis following Liver Transplantation. Case Rep Hepatol. 2017;2017(1):9312481. Smulders YM, Frissen PJ, Slaats EH, Silberbusch J. Renal tubular acidosis: pathophysiology and diagnosis. Arch Intern Med. 1996;156(15):1629–36. Lagunas-Muñoz J, Muñoz R. Hyperkalemic Renal Tubular Acidosis (RTA Type IV). InRenal Tubular Acidosis in Children: New Insights in Diagnosis and Treatment 2022 Feb 2 (pp. 125–42). Cham: Springer International Publishing. Heering PJ, Kurschat C, Vo DT, Klein-Vehne N, Fehsel K, Ivens K. Aldosterone resistance in kidney transplantation is in part induced by a down-regulation of mineralocorticoid receptor expression. Clin Transplant. 2004;18(2):186 – 92. 10.1046/j.1399-0012.2003.00154.x . PMID: 15016134. Bantle JP, Nath KA, Sutherland DE, Najarian JS, Ferris TF. Effects of cyclosporine on the renin-angiotensin-aldosterone system and potassium excretion in renal transplant recipients. Arch Intern Med. 1985;145(3):505–8. PMID: 3883934. Tumlin JA, Sands JM. Nephron segment-specific inhibition of Na+/K(+)-ATPase activity by cyclosporin A. Kidney Int. 1993;43(1):246 – 51. 10.1038/ki.1993.38 . PMID: 8381891. Soleimani M, Rastegar A. Pathophysiology of renal tubular acidosis: core curriculum 2016. Am J Kidney Dis. 2016;68(3):488–98. Higgins R, Ramaiyan K, Dasgupta T, Kanji H, Fletcher S, Lam F, Kashi H. Hyponatraemia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities. Nephrol Dialysis Transplantation. 2004;19(2):444–50. Emre S, Genyk Y, Schluger LK, Fishbein TM, Guy SR, Sheiner PA, Schwartz ME, Miller CM. Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients. Transpl Int. 2000;13(1):73–8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8751708","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":596045157,"identity":"18aba7b8-c266-4197-b97b-228391be7e66","order_by":0,"name":"Chiranthi Welhenge","email":"data:image/png;base64,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","orcid":"","institution":"National Hospital of Sri Lanka","correspondingAuthor":true,"prefix":"","firstName":"Chiranthi","middleName":"","lastName":"Welhenge","suffix":""},{"id":596045158,"identity":"2c1032fb-8697-41bb-8291-24cfd21ad7ec","order_by":1,"name":"Ravi Maharaja Roshiban","email":"","orcid":"","institution":"National Hospital of Sri Lanka","correspondingAuthor":false,"prefix":"","firstName":"Ravi","middleName":"Maharaja","lastName":"Roshiban","suffix":""}],"badges":[],"createdAt":"2026-01-31 17:39:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8751708/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8751708/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109263266,"identity":"7b1a2948-6f11-4096-bf10-468491059401","added_by":"auto","created_at":"2026-05-14 11:56:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":314369,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8751708/v1/b1199988-9203-4807-b9c3-bc43c6e40a66.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Life-threatening hyperkalaemia caused by tacrolimus induced type 4 renal tubular acidosis in a post liver transplant patient: A case report","fulltext":[{"header":"Background","content":"\u003cp\u003eCalcineurin inhibitors, especially tacrolimus, are considered the backbone of immunosuppressive regimens for transplant recipients. Tacrolimus is considerd to be a better immunosuppressant than cylosporine when their efficacies arecompared (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e), with better rates of graft survival, especially after liver transplantation (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). However, their renal adverse effects remain a major concern and a significant hindrance to their effective use (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). These include nephrotoxicity manifesting as a reduced glomerular filtration rate due to renal vasoconstriction (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) and tubular dysfunction manifesting as renal tubular acidosis (RTA), mainly the distal form (Type 1) (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). More concerning is the hyperkalemic form of RTA : Type 4 which is rarely reported. Tacrolimus-related acid-base disorders are well documented following renal transplantation (\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), whereas it is rare following liver transplantation. Herein we describe our experience in the diagnosis and management of a patient with tacrolimus-induced Type 4 RTA in a patient after deceased donor liver transplantation.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 47-year-old Sri Lankan male with type 2 diabetes mellitus and hyperthyroidism who was diagnosed with autoimmune hepatitis-related cirrhosis (CTP B, MELD 13) was referred to our specialized liver transplant clinic two years back for a liver transplant (LT) workup. He was found to have a well-differentiated hepatocellular carcinoma (HCC) in segment IV and he underwent percutaneous ethanol injection once as bridging therapy to LT. While awaiting further cycles of ethanol injection he developed episodes of decompensation (CTP C, MELD 17), which warranted early liver transplantation. He underwent orthotopic LT with no intraoperative complications apart from hypotension which required vasopressors, which were tailed off gradually. The summary of investigations during the post-operative period is shown below (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of investigations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eD3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eD6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eD8\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eD13\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eD15\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eD18\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eD20\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eD21\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eD22\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eD24\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWBC (x10\u003c/b\u003e\u003csup\u003e\u003cb\u003e9\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e15.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeu (x10\u003c/b\u003e\u003csup\u003e\u003cb\u003e9\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLym (x10\u003c/b\u003e\u003csup\u003e\u003cb\u003e9\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHb (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e10.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePLT (x10\u003c/b\u003e\u003csup\u003e\u003cb\u003e9\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eScr (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e193.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e154\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrea (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e191\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNa (mEq/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e129\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eK (mEq/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e6.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCa (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e11.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePhosphate(mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMg (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCl (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e98.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALT (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAST (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALP (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGGT (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eT bil (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eD Bil (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eT Protein (g/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlbumin (g/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlobulin (g/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eINR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP (mg/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProcalcitonin(ng/ml)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e7.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epCO\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e \u003cb\u003e(mmHg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e45.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epO\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e \u003cb\u003e(mmHg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e26.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHCO\u003c/b\u003e\u003csub\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sub\u003e \u003cb\u003e(mEq/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e20.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLactate (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTacrolimus level (ng/ml)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrine Na (mEq/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrine Cl (mEq/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrine K (mEq/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrine osmolality (mOsm/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSerum osmolality\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(mOsm/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHe was noted to have a non-oliguric Acute Kidney Injury (AKI) during the immediate post-operative period while on intravenous furosemide infusion, which was managed with fluid resuscitation and titration of the furosemide dose. Initial hypokalemia was also noted which required correction with IV potassium chloride (KCl). He was started on IV steroids initially and later converted to oral steroids. Tacrolimus was started from a dose of 0.5mg twice a day on post-operative day 2 and gradually titrated while mycophenolate mofetil (MMF) was started on day 6 at a dose of 250mg twice a day. Spironolactone was started at a dose of 25mg daily from D7 due to oedema and up-titrated gradually. Furosemide infusion was converted to oral furosemide by day 11 and increased along with spironolactone to manage the persistent oedema. Liver biochemistry improved gradually with the recovery of synthetic functions.\u003c/p\u003e \u003cp\u003eBy D13 he was again noted to develop an AKI which required adjustment of diuretic doses. By day 18 investigations revealed a new onset hyperkalemia and hyponatremia, due to which all his diuretics were stopped, and medical correction of hyperkalemia was attempted. However, hyperkalemia was refractory, and ECG showed tall T waves without arrhythmias. Continuous medical correction of hyperkalemia was done, and tacrolimus, cotrimoxazole and fluconazole were stopped by Day 19 while increasing MMF. Blood gas analysis revealed a normal anion gap metabolic acidosis with a positive urinary anion gap. Serum aldosterone levels could not be performed due to unavailability.\u003c/p\u003e \u003cp\u003eAn endocrinology opinion was sought, and he was started on Fludrocortisone 50 micrograms per day with furosemide 20mg twice a day while continuing low-dose tacrolimus (0.5mg/twice a day). However, hyperkalemia was slow to respond, and the possibility of a Type 4 RTA was considered attributed to tacrolimus.\u003c/p\u003e \u003cp\u003eThe fludrocortisone dose was increased gradually while correcting acidosis with sodium bicarbonate after stopping tacrolimus along with medical management of hyperkalemia. With this, the hyperkalemia and hyponatremia started to improve. The patient was started on cyclosporine A on day 24 after his metabolic derangements settled and AKI improved, and the dose was adjusted monitoring cyclosporine A levels. There was no evidence of graft rejection during this period. The patient was discharged eventually and two months after LT he remainswithout evidence of graft rejection and normal metabolic parameters.\u003c/p\u003e "},{"header":"Discussion and Conclusions","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cp\u003eEvaluation of the biochemical changes of our patient during the immediate post-LT period is a good demonstration of the renal effects of tacrolimus. The initial rise in serum creatinine was attributed to a grade 1 prerenal acute kidney injury (AKI) which improved with fluid resuscitation and adjustment of diuretic doses. His creatinine remained stable even after the initiation of tacrolimus. However, with the initiation of spironolactone on day 7, a second rise in serum creatinine was noted by postoperative day 13. It was also a grade 1 AKI attributed to prerenal causes. He had hypokalemia during the initial post-operative period which required correction with IV KCL. A sharp rise in potassium (K) was observed from day 15, which was not in keeping with the grade 1 AKI. By this time, he was on spironolactone, cotrimoxazole, fluconazole and tacrolimus, all of which could have contributed to hyperkalemia. Despite the discontinuation of the first three medications and dose reduction of tacrolimus, hyperkalemia remained resistant to medical management, which prompted us to evaluate for other causes of resistant hyperkalemia.\u003c/p\u003e \u003cp\u003eThere was no evidence of diabetic nephropathy, chronic kidney disease or reflux nephropathy and the patient remained asymptomatic during this period. Concomitant hyponatremia suggested the possibility of adrenal insufficiency; however, the patient was already on adequate steroids which made this possibility unlikely. Further evaluation revealed a normal anion gap metabolic acidosis with chloride in the upper normal range and a positive urinary anion gap. The trans tubular potassium gradient (TTKG) was 4.3. A type 4 RTA was suspected with concomitant aldosterone deficiency which was attributed to tacrolimus. Since aldosterone level was not available, empirical treatment was initiated with fludrocortisone after stopping tacrolimus. He made a dramatic improvement with fludrocortisone confirming our suspicion of type 4 RTA.\u003c/p\u003e \u003cp\u003eTwo types of hyperkalemic RTAs due to tacrolimus have been described in the literature, namely a voltage-dependent distal RTA (dRTA) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) and a type 4 RTA (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Distal hyperkalemic RTAs usually respond to tacrolimus dose reduction (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) while type 4 RTAs should be treated with fludrocortisone (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Our patient failed to respond to initial tacrolimus dose reduction, which makes a dRTA unlikely in our patient.\u003c/p\u003e \u003cp\u003eType 4 RTA is characterized by severe hyperkalemia, hyperchloremic acidosis, normal anion gap metabolic acidosis and a positive urinary anion gap. Hypoaldosteronism is the pathophysiological basis of hyperkalemia in type 4 RTA, which could be the result of reduced production (hyporeninemic hypoaldosteronism), resistance at the epithelial sodium channels of the kidney or antagonism at these receptors (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Calcineurin inhibitors can cause both these pathological effects (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Direct inhibition of Na\u003csup\u003e+\u003c/sup\u003e/K\u003csup\u003e+\u003c/sup\u003e-ATPase activity in renal tubules by calcineurin inhibitors also contributes to the inhibition of kaliuresis and hyperkalemia (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Hyperkalemia resulting from these mechanisms along with hypoaldosteronism inhibits NH4\u003csup\u003e+\u003c/sup\u003e excretion by reducing ammonia genesis in proximal tubular cells and reduced medullary NH4\u003csup\u003e+\u003c/sup\u003e reabsorption which results in metabolic acidosis (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBoth cyclosporine and tacrolimus have been implicated in RTA in post-transplant patients. Cyclosporine-induced type 4 RTA and voltage-dependent dRTA have been reported in renal transplant patients (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) but not in LT patients. Tacrolimus-induced dRTA is commoner than type 4 RTA, with three studies reported in LT patients (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) and one each in renal and cardiac transplant patients (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Type 4 RTA has been reported in four studies of renal transplant patients (\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) but only in two LT patients (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA recurrence of the RTA was not evident in our patient despite starting on cyclosporine after stopping tacrolimus. Tacrolimus is known to cause hyperkalemia and hyponatremia more frequently than cyclosporine (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Although both medications can cause RTA, it has been shown that tacrolimus can be replaced by cyclosporine without any adverse effects (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), with no reported cases of cyclosporine-induced RTA in post-LT patients.\u003c/p\u003e \u003cp\u003eAlthough calcineurin inhibitors have been implicated in type 4 RTAs, there\u0026rsquo;s a paucity of published evidence supporting this in LT. We wish to draw the attention of the medical community involved in LT medicine, to this uncommon entity, to facilitate early recognition and proper management of post-transplant immunosuppressive-related complications.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWhite blood cell count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNeu\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeutrophil count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLym\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLymphocyte count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHb\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHaemoglobin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePLT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePlatelet count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eScr\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSerum creatinine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNa\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSodium\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePotassium\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCa\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCalcium\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMg\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnesium\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCl\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChloride\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlaninine transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAspartate transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGGT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGamma glutamyl trasferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlkaline phosphatase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eT Bil\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTotal biliribin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eD Bil\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDirect bilirubin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eT Protein\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTotal protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eINR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational normalized ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003epO\u003csub\u003e2\u003c/sub\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePartial pressure of oxygen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003epCO\u003csub\u003e2\u003c/sub\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePartial pressure of carbon dioxide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHCO\u003csub\u003e3\u003c/sub\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBicarbonate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e\u003cp\u003eNH4\u003csup\u003e+ -\u0026nbsp;\u003c/sup\u003eAmmonium\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed written consent to publish the details of the patient was taken from the patient before drafting the manuscript and before submission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report did not involve collection of data. However, patient’s clinical data is available from the bed head ticket.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors report no competing interests to declare.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCW and RMR, are the co-authors of the article. They drafted the initial manuscript and did the literature searches. All authors participated in manuscript revision, agreed to submit the manuscript, and approved the final version of the manuscript. All authors had full access to clinical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge the support given by Prof. Madnil Niriella, Professor in Gastroenterology and Dr. Uditha Dassanayake, Consultant Gastroenterologist, for their valuable guidance in preparation of this manuscript. We would like to extend our thanks to all individuals involved in the management of the patient.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWinkler M, Christians U. A risk-benefit assessment of tacrolimus in transplantation. Drug Saf. 1995;12(5):348\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeters DH, Fitton A, Plosker GL, Faulds D. Tacrolimus: a review of its pharmacology, and therapeutic potential in hepatic and renal transplantation. Drugs. 1993;46:746\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoutabarrik A, Ishibashi M, Kameoka H, Takano Y, Kokado Y, Sonoda T, Takahara S, Okuyama A, Fukunaga M. FK506 mechanism of nephrotoxicity: stimulatory effect on endothelin secretion by cultured kidney cells. InTransplant International Official Journal of the European Society for Organ Transplantation: Proceedings of the 5th Congress of the European Society for Organ Transplantation, Maastricht, October 7\u0026ndash;10, 1991 1992 (pp. 93\u0026ndash;97). Springer Berlin Heidelberg.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohebbi N, Mihailova M, Wagner CA. The calcineurin inhibitor FK506 (tacrolimus) is associated with transient metabolic acidosis and altered expression of renal acid-base transport proteins. Am J Physiology-Renal Physiol. 2009;297(2):F499\u0026ndash;509.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeering P, Ivens K, Aker S, Grabensee B. Distal tubular acidosis induced by FK506. Clin Transplant. 1998;12(5):465\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwarz C, Benesch T, Kodras K, Oberbauer R, Haas M. Complete renal tubular acidosis late after kidney transplantation. Nephrol Dialysis Transplantation. 2006;21(9):2615\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRangel EB, Gomes SA, Machado PG, dos Santos BC, Pestana JM, Pacheco-Silva A, Heilberg IP. Severe hyperkalemic type 4 renal tubular acidosis after kidney transplantation: a case report. InTransplantation proceedings 2006 Nov 1 (Vol. 38, No. 9, pp. 3112\u0026ndash;3115). Elsevier.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin W, Mou L, Tu H, Zhu L, Wang J, Chen J, Hu Y. Clinical analysis of hyperkalemic renal tubular acidosis caused by calcineurin inhibitors in solid organ transplant recipients. J Clin Pharm Ther. 2017;42(1):122\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlabdulqader MA, Azzam A, Alshami AA. Incidence of hyperkalemic RTA in pediatric post-renal transplant patients and the role of fludrocortisone. Pediatr Transplant. 2021;25(6):e14029.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKulkarni M. Type 4 renal tubular acidosis in a kidney transplant recipient. Biomedical J. 2016;39(1):85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSivakumar V, Sriramnaveen P, Krishna C, Manjusha Y, Reddy SY, Sridhar N, Subramanian S. Role of fludrocortisone in the management of tacrolimus-induced hyperkalemia in a renal transplant recipient. Saudi J Kidney Dis Transplantation. 2014;25(1):149\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGama RM, Makanjuola D, Wahba M, Quan V, Phanish M. Fludrocortisone is an effective treatment for hyperkalaemic metabolic acidosis in kidney transplant recipients on tacrolimus: a case series. Nephron. 2022;146(2):190\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiveiro-Barciela M, Campos-Varela I, Tovar JL, Vargas V, Sim\u0026oacute;n-Talero M, Ventura-Cots M, Crespo M, Bilbao I, Castells L. Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report. InTransplantation proceedings 2011 Dec 1 (Vol. 43, No. 10, pp. 4016\u0026ndash;4018). Elsevier.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOishi M, Yagi T, Urushihara N, Takakura N, Inagaki M, Sadamori H, Mastukawa H, Inoue T, Oda S, Tanaka N. A case of hyperkalemic distal renal tubular acidosis secondary to tacrolimus in living donor liver transplantation. InTransplantation proceedings 2000 (Vol. 32, No. 7, pp. 2225\u0026ndash;2226). Elsevier USA.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgita K, Takada N, Taguchi T, Suita S, Soejima Y, Suehiro T, Shimada M, Maehara Y. Renal tubular acidosis secondary to FK506 in living donor liver transplantation: a case report. Asian J Surg. 2003;26(4):218\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmoyer C, Mishra S, Fulco F. Tacrolimus-Induced Type IV Renal Tubular Acidosis following Liver Transplantation. Case Rep Hepatol. 2017;2017(1):9312481.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmulders YM, Frissen PJ, Slaats EH, Silberbusch J. Renal tubular acidosis: pathophysiology and diagnosis. Arch Intern Med. 1996;156(15):1629\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLagunas-Mu\u0026ntilde;oz J, Mu\u0026ntilde;oz R. Hyperkalemic Renal Tubular Acidosis (RTA Type IV). InRenal Tubular Acidosis in Children: New Insights in Diagnosis and Treatment 2022 Feb 2 (pp. 125\u0026ndash;42). Cham: Springer International Publishing.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeering PJ, Kurschat C, Vo DT, Klein-Vehne N, Fehsel K, Ivens K. Aldosterone resistance in kidney transplantation is in part induced by a down-regulation of mineralocorticoid receptor expression. Clin Transplant. 2004;18(2):186\u0026thinsp;\u0026ndash;\u0026thinsp;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/j.1399-0012.2003.00154.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1399-0012.2003.00154.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 15016134.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBantle JP, Nath KA, Sutherland DE, Najarian JS, Ferris TF. Effects of cyclosporine on the renin-angiotensin-aldosterone system and potassium excretion in renal transplant recipients. Arch Intern Med. 1985;145(3):505\u0026ndash;8. PMID: 3883934.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTumlin JA, Sands JM. Nephron segment-specific inhibition of Na+/K(+)-ATPase activity by cyclosporin A. Kidney Int. 1993;43(1):246\u0026thinsp;\u0026ndash;\u0026thinsp;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/ki.1993.38\u003c/span\u003e\u003cspan address=\"10.1038/ki.1993.38\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 8381891.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoleimani M, Rastegar A. Pathophysiology of renal tubular acidosis: core curriculum 2016. Am J Kidney Dis. 2016;68(3):488\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHiggins R, Ramaiyan K, Dasgupta T, Kanji H, Fletcher S, Lam F, Kashi H. Hyponatraemia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities. Nephrol Dialysis Transplantation. 2004;19(2):444\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEmre S, Genyk Y, Schluger LK, Fishbein TM, Guy SR, Sheiner PA, Schwartz ME, Miller CM. Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients. Transpl Int. 2000;13(1):73\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tacrolimus, Calcineurin inhibitors, Liver transplantation, Hyperkalemia, Renal tubular acidosis, Type 4 RTA","lastPublishedDoi":"10.21203/rs.3.rs-8751708/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8751708/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTacrolimus is a calcineurin inhibitor which remains an integral part of the post-transplantation immunosuppression regime. It is known to cause many adverse effects including Type 4 Renal Tubular Acidosis (T4-RTA), which is a well known, but rare side effect. Unrecognised and untreated T4-RTA can cause refractory hyperkalemia which may lead to life-threatening cardiac arrythmias. Although several cases of Tacrolimus induced T4-RTA has been reported in post kidney transplant patients, it has been rarely reported in the post liver transplant setting.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003eWe report a rare case of refractory hyperkalaemia due to T4-RTA caused by Tacrolimus in a 47-year-old Sri Lankan male, who underwent orthotopic deceased-donor liver transplantation for autoimmune hepatitis induced liver cirrhosis, which was successfully treated with Fludrocortisone replacement.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWe wish to highlight the significance of this life-threatening entity, which every transplant team should be aware of, for early recognition and timely treatment.\u003c/p\u003e","manuscriptTitle":"Life-threatening hyperkalaemia caused by tacrolimus induced type 4 renal tubular acidosis in a post liver transplant patient: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-25 12:36:02","doi":"10.21203/rs.3.rs-8751708/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c07ec1a7-7d99-44cf-b7e9-071481eb5dd1","owner":[],"postedDate":"February 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T11:56:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-25 12:36:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8751708","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8751708","identity":"rs-8751708","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}