Infantile Lupus Nephritis: Diagnostic Challenges and Successful Triple Immunosuppression - A Case Report and Literature Review

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Akikusa, Joshua Kausman This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9345664/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background : Lupus nephritis (LN) presenting in infancy is an extremely rare form of systemic lupus erythematosus (SLE). Diagnosis and treatment are challenging in this age group, and it can be misdiagnosed as congenital or infantile nephrotic syndrome. Case Report : We report a 4-month-old preterm female (32 weeks’ gestation) who presented with nephrotic syndrome and multi-organ involvement including failure to thrive, hypotonia, raised intracranial pressure and abnormal liver function tests. Other laboratory evaluation demonstrated positive ANA, markedly elevated DSDNA antibodies, hypocomplementemia, and microscopic haematuria, with preserved kidney function. Rapid trio exome sequencing was negative, and kidney biopsy confirmed class IV and V LN. Induction therapy consisted of triple therapy with corticosteroids, mycophenolate mofetil, and tacrolimus. Proteinuria improved substantially by 6 months and complete renal response was achieved by 12 months (UPCR <50 mg/mmol) with stable kidney function and serological improvement. Conclusion: Infantile lupus nephritis is rare and often presents with multi-systemic complications and predominantly proliferative renal histology. Early recognition and aggressive induction therapy are frequently required to achieve complete renal response. To our knowledge, this is the first reported case of infantile lupus nephritis successfully treated with triple therapy, demonstrating the effectiveness of this approach in this age group. Infantile Lupus Nephritis Systemic lupus erythematosus Renal Biopsy Nephrology glomerulonephritis Figures Figure 1 Figure 2 Figure 3 Introduction Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune multisystem disease characterized by heterogeneous clinical manifestations and a more aggressive disease course compared with adult-onset SLE ( 1 ). cSLE accounts for approximately 15–20% of all SLE cases and is typically associated with higher disease activity, increased organ involvement, and greater long-term morbidity ( 1 ). Among the various organ manifestations, lupus nephritis (LN) remains one of the most serious complications, representing a major determinant of prognosis in affected children ( 2 ). Nearly two-thirds of paediatric patients with cSLE develop LN, which significantly contributes to both morbidity and mortality ( 3 ). Systemic lupus erythematosus presenting during infancy is exceedingly rare, and reports of lupus nephritis in this age group are particularly uncommon. Infantile SLE has been associated with a more severe clinical phenotype, frequent multi-organ involvement, and significant diagnostic and therapeutic challenges ( 1 ). Here we describe the clinical, laboratory, and histopathological features of infantile lupus nephritis in a 4-month-old infant, detailing the response to induction therapy with a triple immunosuppressive regimen over a 12-month follow-up period. We further compare this case with the 14 previously reported cases of infantile lupus nephritis, highlighting disease characteristics, treatment approaches, and outcomes, and discussing the specific challenges of managing lupus nephritis in this exceptionally young population. Case Report 4 months old female, born at 32 weeks and birth weight 1830g by emergency caesarean section due to maternal pre-eclampsia. The dichorionic diamniotic pregnancy was complicated with twin-to-twin transfusion syndrome, the case being the recipient twin. She required neonatal intensive care unit (NICU) admission for prematurity monitoring and polycythaemia required exchange transfusion with severe jaundice required multiple phototherapy sessions. She was discharged after 2 weeks from NICU in good condition. At 8 weeks post discharge, she had no weight gain where she required nasogastric tube feeding and also found to have central hypotonia and poor suck. Investigations revealed normal urine metabolic screen, creatinine kinase, ammonia and lactate. Hypercholesterolemia with cholesterol of 5.4 mmol/l, high triglycerides 4.7 mmol/l. Nerve conduction performed on both upper and lower limbs motor and sensory nerves showed evidence of a mild generalised demyelinating motor and sensory polyneuropathy, but no abnormality on brain MRI and normal microarray. At 4 months of age, she was admitted with gastroenteritis, associated with periorbital and generalized oedema and abdominal distension. On examination both her height and weight were below 3rd centile. She was hypertensive with blood pressure 118/62 mmHg. She did not have skin rashes, arthritis, oral or palatal ulcers, lymphadenopathy or hepatosplenomegaly. Investigations showed hypoalbuminemia, nephrotic range proteinuria and urine microscopy 400 red cells/mcl, but normal creatinine, Investigations summarized in (Table 1 ). Pancytopenia was evident with white cell count 4.6 x10e9/L, haemoglobin 7.2 g/dl, Platelets 104 x10e9/L. Deranged liver function test (LFT) with Alanine Aminotransferase (ALT) 203 U/L, Gamma glutamyl transferase (GGT) 224 U/L. Lactate Dehydrogenase (LDH) 352 U/L and normal Haptoglobin 0.88 g/L. Urine microscopy was negative for white cell counts. She was provisionally diagnosed with infantile nephrotic syndrome. Infective causes including TORCH screen (Toxoplasmosis, measles, Syphilis, Rubella, Cytomegalovirus and Epstein-Barr virus, Herpes simplex virus), Hepatitis B and C, varicella and HIV all were negative. Anti PLA2R antibodies were negative. Ophthalmological assessment was normal with no signs of CMV retinitis, microcoria or retinal abnormalities seen with Pierson syndrome. Her echocardiogram only showed a trivial ASD. Doppler renal ultrasound to exclude renal vein thrombosis was normal. Her thyroid function test showed elevated thyroid stimulating hormone (TSH) 13.08 mlU/L and she was started on levothyroxine. Her fluid overload was managed with fluid restriction and regular albumin and furosemide infusions which required central venous access and prophylactic enoxaparin. Hypertension was managed with amlodipine, lisinopril, propranolol, hydrochlorothiazide and spironolactone. During admission she was noticed to have a bulging anterior fontanelle and a cranial ultrasound showed dilated ventricles and communicating hydrocephalus, requiring ventriculo-peritoneal (VP) shunt insertion. Investigations for an autoimmune cause of her presentation revelated a strongly positive ANA (1:2560), high dsDNA antibodies (> 500 ml/IU, Farr assay) and hypocomplementemia (C3: 0.39 g/L and C4 0.02 g/L). Maternal autoimmune serology was checked and no auto-antibodies were identified. Genetic testing (Clinical Exome Rapid Comprehensive Trio Analysis for genes listed as: Metabolic Disorders Superpanel v8.408, Intellectual disability syndromic and non-syndromic v0.6465, Regression v0.565, Neuromuscular Superpanel v3.268, Kidneyome_SuperPanel v8.79, Long QT Syndrome v0.61, Immunological disorders_SuperPanel v9.323, Mendeliome v1.2063, All genes excl Incidentalome v1.202407) returned on the 3rd week of admission with no mutation detected. An urgent kidney biopsy was then performed and revealed diffuse and global extra-capillary and endocapillary proliferation, with 6 of 27 glomeruli showing segmental or global sclerosis; one cellular crescent (Fig. 1 ); full-house immunohistochemistry expression (IgA, IgG, IgM, C1q, C3c) (Fig. 2 ); minimal interstitial fibrosis, focal inflammation and no tubular atrophy, no vascular changes; electron microscopy showed subepithelial and intramembranous subendothelial electron dense deposits (Fig. 3 ), all in keeping with lupus nephritis ISN/RPS Class IV-G and V with an activity score of 7 and chronicity score of 2. Immunosuppression management incorporated IV methylprednisolone (15 mg/kg/day) for 3 doses, followed by triple therapy with oral prednisolone (2 mg/kg/day), mycophenolate mofetil (MMF) (800 mg/m2/day) and tacrolimus (0.1 mg/kg/day). Non- Immune treatment with lisinopril and calcium supplements. At 6 months clinic follow up, she was clinically improving with no oedema and partial renal response with urine protein/creatinine ratio of 594 mg/mmol, improved 10-fold from presentation. Her albumin was 29 g/L and kidney function remained stable with creatinine 16 mmol/L. Blood pressure was controlled on lisinopril. Her complement levels normalized (C3 0.94 g/L) and DSDNA antibodies improved to 60 ml/IU. Prednisolone weaned to 4mg and she remained on MMF and tacrolimus with tacrolimus target level of 5–8 ug/L. At 9 months, she was admitted to the hospital with irritability and fever and treated for a VP shunt infection with 3 weeks of IV antibiotics. Blood and CSF cultures were negative and she improved to her baseline without any lupus flare: creatinine 13 mcmol/L, albumin 33 g/L, urine protein creatinine ratio of 88 mg/mmol, C3 0.94 g/L and DSDNA antibodies 75 ml/IU. Normal full blood count with haemoglobin 11.5 g/dL, WBC 5.6 x10e9/L and platelets 492 x10e9/L. At 12 months clinic follow up, she achieved complete renal response with urine protein/creatinine ratio < 50 mg/mmol, serum creatinine 18 mcmol/L, C3: 1.23 g/L and DSDNA antibodies 11 ml/IU (EliA Assay). BP was normal. Prednisolone was weaned to 2 mg and she remained on MMF (800 mg/m2/day) and tacrolimus. Discussion This case presented with infantile NS and multiorgan involvement. At her age of presentation genetic or syndromic NS and rapid turnaround Clinical Exome Rapid Comprehensive Trio Analysis was negative. Laboratory evidence of infantile SLE subsequently emerged with positive ANA, positive DSDNA antibodies, anaemia, thrombocytopenia, low complements and presence of microscopic haematuria. In contrast to neonatal lupus erythematosus, which is a transient alloimmune disease resulting from the transplacental passage of autoimmune antibodies, our patient was found to have an immune serological profile and organ involvement consistent with SLE in the absence of any demonstrable maternal antibodies. The patient was initially managed for congenital nephrotic syndrome with angiotensin converting enzyme inhibitor (ACEI) to reduce her proteinuria, intravenous albumin and furosemide infusions and blood pressure control. Once the genetic testing came back negative, kidney biopsy was performed, which confirmed the diagnosis of infantile lupus nephritis Class IV and V. SLE and lupus nephritis are rare below 2 years of age. Multisystem involvement is reported more frequently at the time of diagnosis compared to older patients and has a more severe disease course. A genetic cause for such an early presentation was suspected and while genetic testing did not identify a cause, research-based testing is currently underway. There are 14 published case reports of infantile lupus nephritis, identified through a search of published literature. To allow comparison across reports, laboratory values reported in different units were converted to standard international units, where applicable (Table 2 ). Including the present case, 8 out of 15 were female (53.3%). Median age at diagnosis was 6 months (IQR 3–10; range 1.5–12). Nephrotic syndrome and/or nephrotic-range proteinuria were present in all cases (15/15, 100%). Fever and SLE like rash were each reported in 6/15 (40.0%). Gross haematuria at presentation was described in 5/15 (33.3%), while prematurity, hypertension, and neurological involvement (e.g., seizures, hypo/hypertonia, intracranial haemorrhage or calcifications) each occurred in 4/15 (26.7%). Regarding histopathological classification, Class IV was the most frequent histopathological pattern, reported in 8/15 (53.3%) cases, with an additional 1/15 (6.7%) demonstrating mixed Class IV/V disease (present case). Class V (membranous LN) alone was reported in 3/15 (20.0%), while Class III occurred in 2/15 (13.3%) and Class II in 1/15 (6.7%). Overall, proliferative LN (Class III/IV ± V) accounted for 11/15 (73.3%) cases, highlighting a predominance of proliferative pathology in this age group (Table 2 ). Regarding laboratory findings, anaemia was reported in 11/15 (73.3%) and thrombocytopenia in 10/15 (66.7%). Nephrotic-range proteinuria was present in 9/15 (60.0%), proteinuria status was not reported in 5/15 (33.3%) and sub-nephrotic range proteinuria was reported in 1/15 (6.7%). Renal impairment at presentation was described in 2/15 (13.3%) cases; notably, both required dialysis at presentation. Creatinine was not reported in 5/15 (33.3%) cases. In the remaining 8/15 (53.3%), kidney function was reported as preserved or with creatinine within the normal range. Microscopic haematuria was present in 9/15 (60.0%), absent in 4/15 (26.7%), and unknown in 2/15 (13.3%). Immunologically, low complements were reported in 14/15 (93.3%), ANA positivity in 13/15 (86.7%), and anti-dsDNA positivity in 12/15 (80.0%) (with unknown anti-dsDNA in 1/15) (Table 2 ). Regarding induction therapy in infantile lupus nephritis has generally been similar to therapies used contemporaneously in older children and adults. In one case, no immunosuppressive treatment was reported due to spontaneous recovery. IV methylprednisolone (IVMP) pulses were used in 6/15 (40.0%) and prednisolone alone was used in 6/15 (40.0%). Prednisolone and azathioprine (AZA) were reported in 3/15 (20.0%), prednisolone and intravenous cyclophosphamide (IV CYC) in 4/15 (26.7%), and triple therapy with prednisolone, MMF and tacrolimus reported in this present case 1/15 (6.7%) (Table 2 ). Regarding the outcomes, overall mortality rate was 29%; significantly higher than seen in childhood SLE in developed countries ( 4 ). Among cases treated with prednisolone alone, death occurred in 4/6 (66.7%); both survivors had good outcomes, in one the outcome was not clearly reported, and the other case had normal urinalysis and full remission at final follow up. For the 3 patients treated with prednisolone and azathioprine, end stage kidney disease (ESKD) occurred in 1/3, partial renal response with persistent non nephrotic range proteinuria in 1/3, and renal outcome data were insufficient and reported to have a relapse in 1/3 (33.3%). Patients treated with prednisolone and intravenous cyclophosphamide (IV CYC) (4/15), complete renal response was reported in 3/4 and partial renal response in ¼. The present case is the first to be treated with triple therapy (prednisolone, MMF and tacrolimus) and successfully achieved complete renal response ( 5 ) (Table 2 ). In conclusion we report a rare case of infantile onset lupus nephritis presenting with nephrotic syndrome. It is important that clinicians be aware that although rare, SLE can present under 1 year of age, may lack other clinical features typically associated with SLE in older children and adults and occurs in males with equal frequency as females. Although historically reported to follow a severe course with high mortality, in our experience the use of the modern treatment approach for proliferative LN in children and adults with triple therapy using steroids, mycophenolate mofetil and tacrolimus was effective. Table 1 Laboratory Investigations: Laboratory Investigation Normal Values Presentation 6 months follow up 12 months follow up Haemoglobin (g/dL) 12.0–16.0 g/dL 8.5 g/dL 13.4 g/dL 12.8 g/dL Platelet count (x 10^9g/L) 150–400 x10^9 g/L 316 x 10^9g/L 271 x 10^9g/L 492 x 10^9g/L Creatinine (umol/L) 10–50 umol/L 31 umol/L 16 umol/L 18 umol/L *CKiD U25 eGFR (mL/min/1.73m2 ) > 90 mL/min/1.73m2 57.5 mL/min/1.73m2 139.1 mL/min/1.73m2 115.3 mL/min/1.73m2 Albumin (g/L) 33–47 g/L 21 g/L 29 g/L 51 g/L Erythrocyte Sedimentation Rate (mm/hr) 2–10 mm/hr 2 mm/hr 5 mm/hr 8 mm/hr DSDNA antibodies (EliA) (IU/mL) 365 IU/mL 60 IU/mL 11 IU/mL Urine Protein creatinine ratio (mg/mmol) < 20 mg/mmol 6191 mg/mmol 594 mg/mmol < 50 mg/mmol Urine Red Blood Cells Count (x10e6/L) < 11 (x10^6/L x10^6/L) 400 (x10^6/L x10^6/L) 0 (x10^6/L x10^6/L) 0 (x10^6/L x10^6/L) Complements C3 (g/L) 0.70–2.06 g/L 0.39 g/L 0.94 g/L 1.23 g/L Complement C4 (g/L) 0.11–0.61 g/L 0.02 g/L 0.04 g/L 0.03 g/L Systemic Lupus Erythematosus Disease Activity Index 2000 More than 3–4 to indicate active disease 16 4 6 Table 2 Demographic characteristics, Clinical presentation, Laboratory findings, Histopathological class, Management, Outcome of 14 Infantile Lupus Nephritis case reports in the literature: Case (reference) Age/Gender Clinical presentation Laboratory findings Histopathological class Management Outcome Date 1 ( 6 ) 11 Months/female Skin Rash, oral ulcers, alopecia, Seizures, Nephrotic Syndrome. Leukopenia and thrombocytopenia, Normal Hb and Complements, positive ANA, normal urinalysis. N/A creatinine, N/A UPCR, N/A Albumin and DSDNA antibodies Class V Corticosteroids Died after 6 months (Infection) 1975 2 ( 7 ) 6 months/female Nephrotic Syndrome, Anasarca, Haematuria Thrombocytopenia and leukopenia, N/A creatinine, N/A Albumin, positive Proteinuria and Haematuria, positive ANA and DSDNA antibodies, low complements. Class V Corticosteroids Favourable response to steroids N/A renal response 1979 3 ( 8 ) 9 months/female Skin rash, hypertonia, hepatosplenomegaly, lymphadenopathy, cerebral calcification, Nephrotic Syndrome and Hypertension Anaemia, low complements, positive ANA and DSDNA antibodies. N/A creatinine, N/A Albumin, N/A UPCR, N/A urinalysis or microscopy Class IV Corticosteroids Died at age of 3 years due to multiorgan failure. N/A Renal response 1981 4 ( 9 ) 2.5 months/female Skin rash, fever, HSM, Nephrotic syndrome, progressive renal failure, Hypertension, serositis. Anaemia and thrombocytopenia. Creatinine 35 umol/L, Albumin 18 g/L, 24 hours urine protein > 3000 mg, positive microscopic haematuria. Low complements, negative ANA and DSDNA Class IV IV pulse steroids 10 mg/kg/day for 3 days then oral steroids 2 mg/kg/day Peritoneal dialysis at presentation Died after 2 months of diagnosis (Fungal sepsis) 1984 5 ( 10 ) 3 months/male Prematurity 28 weeks, Irritability, oedema, Nephrotic Syndrome Thrombocytopenia, Normal Creatinine, N/A Albumin, 24 hours urine protein 1.43 g/m2/day, microscopic haematuria,, positive ANA and DSDNA antibodies, low complements C3: 0.32 g/L and C4: 0.09 g/L Class III Prednisolone 2 mg/kg/day and discontinued at 7 months. Renal relapse at age of 12 months required another steroids course and maintained after on 0.5-1 mg/kg on alternative days At 24 months, Healthy, Normal urinalysis, N/A urine protein, N/A creatinine or renal response 1985 6 ( 11 ) 9 months/Female Fever, failure to thrive, heart failure, Nephrotic Syndrome. Anaemia, Thrombocytopenia. Low complements, positive ANA and Anti-DsDNA antibodies. N/A creatinine and Albumin, N/A urine protein, N/A urine microscopy or urinalysis Class V Corticosteroids Died after 3 months of diagnosis due to congestive heart failure 1989 7 ( 12 ) 1.5 Months/Female Irritability, Nephrotic syndrome and haematuria Anaemia, Creatinine 26.5 umol/L, Albumin 38 g/L, positive ANA and DSDNA antibodies, Low complements.C3: 0.63 g/L., N/A UPCR Class IV Peritoneal Dialysis after 5 months of diagnosis Prednisolone 2 mg/kg/day and Azathioprine 2 mg/kg/day ESKD after 5 months of diagnosis Renal Transplant in 2 years 1994 8 ( 12 ) 3 months/Female Prematurity 32 weeks, Fever, Nephrotic syndrome, diarrhea, lymphadenopathy Anaemia, Creatinine 35.4 umol/L, Albumin 10 g/L, urinalysis > 3g proteins and > 100 erythrocytes. Low complements C3 0.14 g/L and C4 0.04 g/L. Positive ANA and DSDNA antibodies Class IV Prednisolone 2 mg/kg/day and Azathioprine 2 mg/kg/day Renal relapse in 2.5 years, second biopsy showed class V with 30% sclerosis 1994 9 ( 13 ) 3 months/male Fever, Pneumonia, Nephrotic Syndrome, lymphadenopathy Anaemia Hb 9.3 g/dl, Thrombocytopenia 130 ×109/l, Albumin 20 g/L, creatinine 46 umol/L, UPCR 3651 mg/mmol, microscopic haematuria, low complements C3: 0.51 g/l, positive ANA and DSDNA antibodies Class II Spontaneous recovery with no intervention. At 14 months, flare with Rash, HTN, GI bleeding and LVH started prednisolone 2mg/kg/day At 12 months, urinalysis for protein + 1, Albumin 27, normal creatinine 37 umol/L 1996 10 ( 14 ) 8 months/male Prematurity 26 weeks, Irritability, Anasarca, purpuric Rash, oral ulcers Anaemia Hb 9.3 g/dl, creatinine 26 umol/L, N/A Albumin, UPCR 2486 mg/mmol, positive microscopic haematuria with RBC casts, Positive ANA and DSDNA antibodies, low complements C3: 0.54 g/L, C4: 0.08 g/L Class IV IV pulse steroids 20 mg/kg/day for 3 days then oral steroids 2 mg/kg/day and monthly 500 mg/m2 IV cyclophosphamide for 6 months then every 3 months After 12 months, achieved complete renal response with Creatinine 0.4 mg/dl, urine protein creatinine ratio was 0.2, normal complements 1998 11 ( 15 ) 3.5 months/Male Nephrotic Syndrome hypertension, haematuria and progressive renal failure. Pulmonary haemorrhage. Anaemia, Thrombocytopenia, Creatinine 159 umol/L, Albumin 26 g/L, UPCR 66.3, microscopic haematuria, positive ANA and DSDNA, low complements C3: 0.39 g/L and C4: <0.01 g/L Class IV Haemodialysis at presentation IV pulse steroids 30 mg/kg/day for 3 days then oral steroids 2 mg/kg/day and monthly 500 mg/m2 IV cyclophosphamide for 6 months then every 3 months At 15 months, MMF added due to relapse At 12 months, achieved partial renal response Creatinine 0.4 mg/dl, urine protein/creatinine ratio 0.8, normal complements 2005 12 ( 16 ) 10 months/Male Fever, skin rashes, melena, cerebral haemorrhage, nephrotic syndrome, arthritis Thrombocytopenia, N/A creatinine, N/A Albumin, positive ANA and DSDNA antibodies, low complements C4 with normal C3 Class III IV pulse steroids 20 mg/kg/day for 3 days then oral steroids 2 mg/kg/day and Azathioprine 2 mg/kg/day On follow up, present of proteinuria 0.2 g/day, N/A creatinine 2008 13 ( 17 ) 10 months/male Skin rash, photosensitivity, fever, haematuria Anaemia Hb 9,9 g/dl, Thrombocytopenia, creatinine 34 umol/L, Albumin 35 g/L, UPCR 1492 mg/mmol, Urinalysis: 100/hpf of RBC, positive ANA and DSDNA antibodies low complements C3: 0.23 g/L and C4: 0.04 g/L Class IV Weekly IV pulse steroids 30 mg/kg/day for 3 days then oral steroids 2 mg/kg/day After 3 weeks, monthly 500–750 mg/m2 IV cyclophosphamide for 6 months, bimonthly after the fourth dose At 9 months: After completing sixth IV CYC dose achieved complete renal remission Urine protein creatinine ratio > 0.1 mg/mg and normal kidney function At 2 years: on remission with normal kidney function and urinalysis 2013 14 ( 1 ) 12 months/male Nephrotic syndrome, haematuria, pulmonary thromboembolism Anaemia Hb 6.7 g/dl Thrombocytopenia PLT 52000/mm2, Creatinine 8 umol/L, Albumin 15 g/L, UPCR 2418 mg/mmol, urinalysis positive for microscopic haematuria, low complements C3: 0.73 g/L, C4: 0.3 g/L, negative ANA and DSDNA antibodies Class IV Steroids start at 8 mg/kg/day for 10 day for autoimmune haemolytic anaemia then 2 mg/kg/day and monthly 500 mg/m2 IV cyclophosphamide for 6 months At 3 months: achieved complete remission with normal kidney function and protein creatinine ratio 0.3 mg/mg Commenced on MMF as maintenance and at 20 months still on complete renal remission 2021 Our Case 4 months/Female Prematurity 32 weeks, Nephrotic syndrome, hypertension, central hypotonia, failure to thrive Anaemia 8.5 g/dl, creatinine 31 umol/L, Albumin 24 g/L, UPCR 6191 mg/mmol, microscopic haematuria, positive ANA and DSDNA antibodies, low complements C3: 0.39 g/L C4: 0.02 g/L Class IV/V IV pulse steroids (15 mg/kg/day) for 3 days then Triple therapy: oral prednisolone 2 mg/kg/day, MMF (800mg/m2/day) and Tacrolimus At 12 months: achieved complete renal response, urine protein/creatinine ratio was 49 mg/mmol. Normal kidney function with creatinine 18 mmol/L 2025 Declarations Acknowledgment: We would like to thank the patient and her family for providing consent for this report to be published. Author’s Contribution: Omar Alomar conceptualized and designed the report, wrote the manuscript, and contributed to all stages of this case report. Joshua Kausman and Jonathan Akikusa supervised the case report, edited all drafts and the final manuscript. All authors read and approved the final manuscript. Conflict of Interest: The authors declare no conflict of interest. References Akar EM, Özçakar ZB, Çakar N, Kiremitçi S, Kurt-Şükür ED, Fitöz S, et al. Infantile systemic lupus erythematous presenting as nephrotic syndrome in a 12-month-old boy: a case report. The Turkish journal of pediatrics [Internet]. 2021;63(2):339–43. Rovin BH, Ayoub I, Tak Mao Chan, Liu Z, Mejía-Vilet JM, Jürgen Floege. KDIGO 2024 Clinical Practice Guideline for the management of LUPUS NEPHRITIS. 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Infantile systemic lupus erythematosus with onset simulating congenital nephrotic syndrome. The Journal of Pediatrics. 1994 Jan 1;124(1):27–31. Dudley J, Fenton T, Unsworth J, Chambers T, MacIver A, Tizard J. Systemic lupus erythematosus presenting as congenital nephrotic syndrome. Pediatric Nephrology. 1996 Nov 18;10(6):752–5. Saberi MS, Jones BA. Remission of infantile systemic lupus erythematosus with intravenous cyclophosphamide. Pediatric nephrology (Berlin, Germany) [Internet]. 1998 Feb;12(2):136–8. Kreindler J, Ellis D, Vats A, Kurland G, Ranganathan S, Moritz ML. Infantile systemic lupus erythematosus presenting with pulmonary hemorrhage. Pediatric nephrology (Berlin, Germany) [Internet]. 2005 Apr;20(4):522–5. Zulian F, Pluchinotta F, Martini G, Da Dalt L, Zacchello G. Severe clinical course of systemic lupus erythematosus in the first year of life. Lupus. 2008 Sep;17(9):780–6. Kishi N, Suga K, Matsuura S, Kinoshita Y, Urushihara M, Kondo S, et al. A case of infantile systemic lupus erythematosus with severe lupus nephritis and EBV infection. CEN Case Reports [Internet]. 2013 Feb 14 [cited 2022 Sep 6];2(2):190–3. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 27 Apr, 2026 Reviewers invited by journal 22 Apr, 2026 Editor assigned by journal 15 Apr, 2026 First submitted to journal 11 Apr, 2026 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9345664","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":627852054,"identity":"bd9cc29f-f303-446f-a453-c0ed9631a5f8","order_by":0,"name":"Omar Alomar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACewhlI8cPoh4wMBgQ1GLYAKbSjCUbGBgbEojRYnAATB1O3HCAaC23Dx/d8HPPYcbNx3vMHyRU2BgzsANF8Go5l5Z2s+dZOrPZmTOGDQln0swYeNLSbuDVcobH7AbPAWs2sxs5hg2JbYdtGCSAIoS03PxzgJnHeAYpWm7zHHCWMJCAaDEjqMWwhy3ttsyBNAOJM8cKZwD9YsxGyC/2PMzHbr45YFPf39684cOHChvDfvbDx/BqwQRspCkfBaNgFIyCUYANAADdXU8ZzUwZ0gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-1080-7751","institution":"The Royal Children's Hospital Melbourne","correspondingAuthor":true,"prefix":"","firstName":"Omar","middleName":"","lastName":"Alomar","suffix":""},{"id":627852055,"identity":"4d72217d-d7eb-4d42-b907-b8d3f325c429","order_by":1,"name":"Jonathan D. Akikusa","email":"","orcid":"","institution":"The Royal Children's Hospital Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"D.","lastName":"Akikusa","suffix":""},{"id":627852056,"identity":"61f35c42-5542-4ce1-a2e2-2b5b9eb13ad2","order_by":2,"name":"Joshua Kausman","email":"","orcid":"","institution":"The Royal Children's Hospital Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Joshua","middleName":"","lastName":"Kausman","suffix":""}],"badges":[],"createdAt":"2026-04-07 13:14:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9345664/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9345664/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108808172,"identity":"ed56769c-e3d9-4d15-8988-4ec0f6232081","added_by":"auto","created_at":"2026-05-08 15:40:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":660536,"visible":true,"origin":"","legend":"\u003cp\u003eRenal Light Microscopy (LM) biopsy specimens: A) Hematoxylin and Eosin (H/E) stain showing globally sclerosed glomeruli and glomeruli with hypercellularity; B) PAS stain showing cellular crescent.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9345664/v1/70a867968ff5825ae5c63f9e.png"},{"id":108808176,"identity":"5bafd72e-81b1-40d0-bf37-2dfab682fb37","added_by":"auto","created_at":"2026-05-08 15:40:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":644095,"visible":true,"origin":"","legend":"\u003cp\u003eImmunoperoxidase staining of biopsy specimens: A) C3; B) IgM; C) IgG; D) IgA; E) C1q\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9345664/v1/68cb12360d27b6d3b35187c0.png"},{"id":108808186,"identity":"4ccdf8f7-0728-4dad-bda8-053a34925a3f","added_by":"auto","created_at":"2026-05-08 15:40:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":546099,"visible":true,"origin":"","legend":"\u003cp\u003eRenal electron microscopy (EM) biopsy specimens: A) Endothelial cell with tubuloreticular inclusions with irregular thickened glomerular basement membrane and partially resorbed deposits; B) subepithelial, intramembranous and focally subendothelial electron dense deposits with podocyte microvillus transformation.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9345664/v1/910d299360374649e50c2c78.png"},{"id":108817141,"identity":"6a8ee830-44e8-48ad-a366-99d96bef4f9f","added_by":"auto","created_at":"2026-05-08 16:27:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2140339,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9345664/v1/e73b81e7-25fe-4984-95dc-08bd04779566.pdf"}],"financialInterests":"","formattedTitle":"Infantile Lupus Nephritis: Diagnostic Challenges and Successful Triple Immunosuppression - A Case Report and Literature Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChildhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune multisystem disease characterized by heterogeneous clinical manifestations and a more aggressive disease course compared with adult-onset SLE (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). cSLE accounts for approximately 15\u0026ndash;20% of all SLE cases and is typically associated with higher disease activity, increased organ involvement, and greater long-term morbidity (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Among the various organ manifestations, lupus nephritis (LN) remains one of the most serious complications, representing a major determinant of prognosis in affected children (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Nearly two-thirds of paediatric patients with cSLE develop LN, which significantly contributes to both morbidity and mortality (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSystemic lupus erythematosus presenting during infancy is exceedingly rare, and reports of lupus nephritis in this age group are particularly uncommon. Infantile SLE has been associated with a more severe clinical phenotype, frequent multi-organ involvement, and significant diagnostic and therapeutic challenges (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHere we describe the clinical, laboratory, and histopathological features of infantile lupus nephritis in a 4-month-old infant, detailing the response to induction therapy with a triple immunosuppressive regimen over a 12-month follow-up period. We further compare this case with the 14 previously reported cases of infantile lupus nephritis, highlighting disease characteristics, treatment approaches, and outcomes, and discussing the specific challenges of managing lupus nephritis in this exceptionally young population.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003e4 months old female, born at 32 weeks and birth weight 1830g by emergency caesarean section due to maternal pre-eclampsia. The dichorionic diamniotic pregnancy was complicated with twin-to-twin transfusion syndrome, the case being the recipient twin. She required neonatal intensive care unit (NICU) admission for prematurity monitoring and polycythaemia required exchange transfusion with severe jaundice required multiple phototherapy sessions. She was discharged after 2 weeks from NICU in good condition. At 8 weeks post discharge, she had no weight gain where she required nasogastric tube feeding and also found to have central hypotonia and poor suck. Investigations revealed normal urine metabolic screen, creatinine kinase, ammonia and lactate. Hypercholesterolemia with cholesterol of 5.4 mmol/l, high triglycerides 4.7 mmol/l. Nerve conduction performed on both upper and lower limbs motor and sensory nerves showed evidence of a mild generalised demyelinating motor and sensory polyneuropathy, but no abnormality on brain MRI and normal microarray.\u003c/p\u003e \u003cp\u003eAt 4 months of age, she was admitted with gastroenteritis, associated with periorbital and generalized oedema and abdominal distension. On examination both her height and weight were below 3rd centile. She was hypertensive with blood pressure 118/62 mmHg. She did not have skin rashes, arthritis, oral or palatal ulcers, lymphadenopathy or hepatosplenomegaly. Investigations showed hypoalbuminemia, nephrotic range proteinuria and urine microscopy 400 red cells/mcl, but normal creatinine, Investigations summarized in (Table\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Pancytopenia was evident with white cell count 4.6 x10e9/L, haemoglobin 7.2 g/dl, Platelets 104 x10e9/L. Deranged liver function test (LFT) with Alanine Aminotransferase (ALT) 203 U/L, Gamma glutamyl transferase (GGT) 224 U/L. Lactate Dehydrogenase (LDH) 352 U/L and normal Haptoglobin 0.88 g/L. Urine microscopy was negative for white cell counts. She was provisionally diagnosed with infantile nephrotic syndrome. Infective causes including TORCH screen (Toxoplasmosis, measles, Syphilis, Rubella, Cytomegalovirus and Epstein-Barr virus, Herpes simplex virus), Hepatitis B and C, varicella and HIV all were negative. Anti PLA2R antibodies were negative. Ophthalmological assessment was normal with no signs of CMV retinitis, microcoria or retinal abnormalities seen with Pierson syndrome. Her echocardiogram only showed a trivial ASD. Doppler renal ultrasound to exclude renal vein thrombosis was normal. Her thyroid function test showed elevated thyroid stimulating hormone (TSH) 13.08 mlU/L and she was started on levothyroxine. Her fluid overload was managed with fluid restriction and regular albumin and furosemide infusions which required central venous access and prophylactic enoxaparin. Hypertension was managed with amlodipine, lisinopril, propranolol, hydrochlorothiazide and spironolactone. During admission she was noticed to have a bulging anterior fontanelle and a cranial ultrasound showed dilated ventricles and communicating hydrocephalus, requiring ventriculo-peritoneal (VP) shunt insertion.\u003c/p\u003e \u003cp\u003eInvestigations for an autoimmune cause of her presentation revelated a strongly positive ANA (1:2560), high dsDNA antibodies (\u0026gt;\u0026thinsp;500 ml/IU, Farr assay) and hypocomplementemia (C3: 0.39 g/L and C4 0.02 g/L). Maternal autoimmune serology was checked and no auto-antibodies were identified. Genetic testing (Clinical Exome Rapid Comprehensive Trio Analysis for genes listed as: Metabolic Disorders Superpanel v8.408, Intellectual disability syndromic and non-syndromic v0.6465, Regression v0.565, Neuromuscular Superpanel v3.268, Kidneyome_SuperPanel v8.79, Long QT Syndrome v0.61, Immunological disorders_SuperPanel v9.323, Mendeliome v1.2063, All genes excl Incidentalome v1.202407) returned on the 3rd week of admission with no mutation detected. An urgent kidney biopsy was then performed and revealed diffuse and global extra-capillary and endocapillary proliferation, with 6 of 27 glomeruli showing segmental or global sclerosis; one cellular crescent (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e); full-house immunohistochemistry expression (IgA, IgG, IgM, C1q, C3c) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e); minimal interstitial fibrosis, focal inflammation and no tubular atrophy, no vascular changes; electron microscopy showed subepithelial and intramembranous subendothelial electron dense deposits (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), all in keeping with lupus nephritis ISN/RPS Class IV-G and V with an activity score of 7 and chronicity score of 2.\u003c/p\u003e \u003cp\u003eImmunosuppression management incorporated IV methylprednisolone (15 mg/kg/day) for 3 doses, followed by triple therapy with oral prednisolone (2 mg/kg/day), mycophenolate mofetil (MMF) (800 mg/m2/day) and tacrolimus (0.1 mg/kg/day). Non- Immune treatment with lisinopril and calcium supplements.\u003c/p\u003e \u003cp\u003eAt 6 months clinic follow up, she was clinically improving with no oedema and partial renal response with urine protein/creatinine ratio of 594 mg/mmol, improved 10-fold from presentation. Her albumin was 29 g/L and kidney function remained stable with creatinine 16 mmol/L. Blood pressure was controlled on lisinopril. Her complement levels normalized (C3 0.94 g/L) and DSDNA antibodies improved to 60 ml/IU. Prednisolone weaned to 4mg and she remained on MMF and tacrolimus with tacrolimus target level of 5\u0026ndash;8 ug/L.\u003c/p\u003e \u003cp\u003eAt 9 months, she was admitted to the hospital with irritability and fever and treated for a VP shunt infection with 3 weeks of IV antibiotics. Blood and CSF cultures were negative and she improved to her baseline without any lupus flare: creatinine 13 mcmol/L, albumin 33 g/L, urine protein creatinine ratio of 88 mg/mmol, C3 0.94 g/L and DSDNA antibodies 75 ml/IU. Normal full blood count with haemoglobin 11.5 g/dL, WBC 5.6 x10e9/L and platelets 492 x10e9/L.\u003c/p\u003e \u003cp\u003eAt 12 months clinic follow up, she achieved complete renal response with urine protein/creatinine ratio\u0026thinsp;\u0026lt;\u0026thinsp;50 mg/mmol, serum creatinine 18 mcmol/L, C3: 1.23 g/L and DSDNA antibodies 11 ml/IU (EliA Assay). BP was normal. Prednisolone was weaned to 2 mg and she remained on MMF (800 mg/m2/day) and tacrolimus.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case presented with infantile NS and multiorgan involvement. At her age of presentation genetic or syndromic NS and rapid turnaround Clinical Exome Rapid Comprehensive Trio Analysis was negative. Laboratory evidence of infantile SLE subsequently emerged with positive ANA, positive DSDNA antibodies, anaemia, thrombocytopenia, low complements and presence of microscopic haematuria. In contrast to neonatal lupus erythematosus, which is a transient alloimmune disease resulting from the transplacental passage of autoimmune antibodies, our patient was found to have an immune serological profile and organ involvement consistent with SLE in the absence of any demonstrable maternal antibodies. The patient was initially managed for congenital nephrotic syndrome with angiotensin converting enzyme inhibitor (ACEI) to reduce her proteinuria, intravenous albumin and furosemide infusions and blood pressure control. Once the genetic testing came back negative, kidney biopsy was performed, which confirmed the diagnosis of infantile lupus nephritis Class IV and V. SLE and lupus nephritis are rare below 2 years of age. Multisystem involvement is reported more frequently at the time of diagnosis compared to older patients and has a more severe disease course. A genetic cause for such an early presentation was suspected and while genetic testing did not identify a cause, research-based testing is currently underway.\u003c/p\u003e \u003cp\u003eThere are 14 published case reports of infantile lupus nephritis, identified through a search of published literature. To allow comparison across reports, laboratory values reported in different units were converted to standard international units, where applicable (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIncluding the present case, 8 out of 15 were female (53.3%). Median age at diagnosis was 6 months (IQR 3\u0026ndash;10; range 1.5\u0026ndash;12). Nephrotic syndrome and/or nephrotic-range proteinuria were present in all cases (15/15, 100%). Fever and SLE like rash were each reported in 6/15 (40.0%). Gross haematuria at presentation was described in 5/15 (33.3%), while prematurity, hypertension, and neurological involvement (e.g., seizures, hypo/hypertonia, intracranial haemorrhage or calcifications) each occurred in 4/15 (26.7%). Regarding histopathological classification, Class IV was the most frequent histopathological pattern, reported in 8/15 (53.3%) cases, with an additional 1/15 (6.7%) demonstrating mixed Class IV/V disease (present case). Class V (membranous LN) alone was reported in 3/15 (20.0%), while Class III occurred in 2/15 (13.3%) and Class II in 1/15 (6.7%). Overall, proliferative LN (Class III/IV\u0026thinsp;\u0026plusmn;\u0026thinsp;V) accounted for 11/15 (73.3%) cases, highlighting a predominance of proliferative pathology in this age group (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegarding laboratory findings, anaemia was reported in 11/15 (73.3%) and thrombocytopenia in 10/15 (66.7%). Nephrotic-range proteinuria was present in 9/15 (60.0%), proteinuria status was not reported in 5/15 (33.3%) and sub-nephrotic range proteinuria was reported in 1/15 (6.7%). Renal impairment at presentation was described in 2/15 (13.3%) cases; notably, both required dialysis at presentation. Creatinine was not reported in 5/15 (33.3%) cases. In the remaining 8/15 (53.3%), kidney function was reported as preserved or with creatinine within the normal range. Microscopic haematuria was present in 9/15 (60.0%), absent in 4/15 (26.7%), and unknown in 2/15 (13.3%). Immunologically, low complements were reported in 14/15 (93.3%), ANA positivity in 13/15 (86.7%), and anti-dsDNA positivity in 12/15 (80.0%) (with unknown anti-dsDNA in 1/15) (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegarding induction therapy in infantile lupus nephritis has generally been similar to therapies used contemporaneously in older children and adults. In one case, no immunosuppressive treatment was reported due to spontaneous recovery. IV methylprednisolone (IVMP) pulses were used in 6/15 (40.0%) and prednisolone alone was used in 6/15 (40.0%). Prednisolone and azathioprine (AZA) were reported in 3/15 (20.0%), prednisolone and intravenous cyclophosphamide (IV CYC) in 4/15 (26.7%), and triple therapy with prednisolone, MMF and tacrolimus reported in this present case 1/15 (6.7%) (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegarding the outcomes, overall mortality rate was 29%; significantly higher than seen in childhood SLE in developed countries (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Among cases treated with prednisolone alone, death occurred in 4/6 (66.7%); both survivors had good outcomes, in one the outcome was not clearly reported, and the other case had normal urinalysis and full remission at final follow up. For the 3 patients treated with prednisolone and azathioprine, end stage kidney disease (ESKD) occurred in 1/3, partial renal response with persistent non nephrotic range proteinuria in 1/3, and renal outcome data were insufficient and reported to have a relapse in 1/3 (33.3%). Patients treated with prednisolone and intravenous cyclophosphamide (IV CYC) (4/15), complete renal response was reported in 3/4 and partial renal response in \u0026frac14;. The present case is the first to be treated with triple therapy (prednisolone, MMF and tacrolimus) and successfully achieved complete renal response (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn conclusion we report a rare case of infantile onset lupus nephritis presenting with nephrotic syndrome. It is important that clinicians be aware that although rare, SLE can present under 1 year of age, may lack other clinical features typically associated with SLE in older children and adults and occurs in males with equal frequency as females. Although historically reported to follow a severe course with high mortality, in our experience the use of the modern treatment approach for proliferative LN in children and adults with triple therapy using steroids, mycophenolate mofetil and tacrolimus was effective.\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\u003eLaboratory Investigations:\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory Investigation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal Values\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePresentation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 months follow up\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 months follow up\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\u003eHaemoglobin (g/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.0\u0026ndash;16.0 g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.5\u0026nbsp;g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.4\u0026nbsp;g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.8\u0026nbsp;g/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlatelet count (x\u0026nbsp;10^9g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150\u0026ndash;400 x10^9 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e316\u0026nbsp;x\u0026nbsp;10^9g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e271\u0026nbsp;x\u0026nbsp;10^9g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e492\u0026nbsp;x\u0026nbsp;10^9g/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCreatinine (umol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u0026ndash;50 umol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 umol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 umol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18 umol/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e*CKiD U25 eGFR (mL/min/1.73m2 )\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;90 mL/min/1.73m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.5 mL/min/1.73m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139.1 mL/min/1.73m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e115.3 mL/min/1.73m2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlbumin (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33\u0026ndash;47 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u0026nbsp;g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51 g/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eErythrocyte Sedimentation Rate (mm/hr)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;10 mm/hr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 mm/hr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mm/hr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 mm/hr\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDSDNA antibodies (EliA) (IU/mL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;= 10\u0026nbsp;IU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;365\u0026nbsp;IU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 IU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 IU/mL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrine Protein creatinine ratio (mg/mmol)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;20 mg/mmol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6191 mg/mmol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e594 mg/mmol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50 mg/mmol\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrine Red Blood Cells Count (x10e6/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;11 (x10^6/L x10^6/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e400 (x10^6/L x10^6/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (x10^6/L x10^6/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (x10^6/L x10^6/L)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplements C3 (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.70\u0026ndash;2.06 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.39 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.23 g/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplement C4 (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11\u0026ndash;0.61 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.02 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.04 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.03 g/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystemic Lupus Erythematosus Disease Activity Index 2000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMore than 3\u0026ndash;4 to indicate active disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics, Clinical presentation, Laboratory findings, Histopathological class, Management, Outcome of 14 Infantile Lupus Nephritis case reports in the literature:\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase (reference)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge/Gender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical presentation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLaboratory findings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHistopathological class\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eManagement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDate\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\u003e1\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 Months/female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSkin Rash, oral ulcers, alopecia, Seizures, Nephrotic Syndrome.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeukopenia and thrombocytopenia, Normal Hb and Complements, positive ANA, normal urinalysis. N/A creatinine, N/A UPCR, N/A Albumin and DSDNA antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCorticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDied after 6 months (Infection)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1975\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 months/female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNephrotic Syndrome, Anasarca, Haematuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThrombocytopenia and leukopenia, N/A creatinine, N/A Albumin, positive Proteinuria and Haematuria, positive ANA and DSDNA antibodies, low complements.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCorticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFavourable response to steroids\u003c/p\u003e \u003cp\u003eN/A renal response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1979\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 months/female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSkin rash, hypertonia, hepatosplenomegaly, lymphadenopathy, cerebral calcification, Nephrotic Syndrome and Hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia, low complements, positive ANA and DSDNA antibodies. N/A creatinine, N/A Albumin, N/A UPCR, N/A urinalysis or microscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCorticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDied at age of 3 years due to multiorgan failure. N/A Renal response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1981\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.5 months/female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSkin rash, fever, HSM, Nephrotic syndrome, progressive renal failure, Hypertension, serositis.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia and thrombocytopenia. Creatinine 35 umol/L, Albumin 18 g/L, 24 hours urine protein\u0026thinsp;\u0026gt;\u0026thinsp;3000 mg, positive microscopic haematuria. Low complements, negative ANA and DSDNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIV pulse steroids 10 mg/kg/day for 3 days then oral steroids 2 mg/kg/day\u003c/p\u003e \u003cp\u003ePeritoneal dialysis at presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDied after 2 months of diagnosis (Fungal sepsis)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1984\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 months/male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePrematurity 28 weeks, Irritability, oedema, Nephrotic Syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThrombocytopenia, Normal Creatinine, N/A Albumin, 24 hours urine protein 1.43 g/m2/day, microscopic haematuria,, positive ANA and DSDNA antibodies, low complements C3: 0.32 g/L and C4: 0.09 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePrednisolone 2 mg/kg/day and discontinued at 7 months.\u003c/p\u003e \u003cp\u003eRenal relapse at age of 12 months required another steroids course and maintained after on 0.5-1 mg/kg on alternative days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt 24 months, Healthy, Normal urinalysis, N/A urine protein, N/A creatinine or renal response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1985\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 months/Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFever, failure to thrive, heart failure, Nephrotic Syndrome.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia, Thrombocytopenia. Low complements, positive ANA and Anti-DsDNA antibodies. N/A creatinine and Albumin, N/A urine protein, N/A urine microscopy or urinalysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCorticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDied after 3 months of diagnosis due to congestive heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5 Months/Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIrritability, Nephrotic syndrome and haematuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia, Creatinine 26.5 umol/L, Albumin 38 g/L, positive ANA and DSDNA antibodies, Low complements.C3: 0.63 g/L., N/A UPCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePeritoneal Dialysis after 5 months of diagnosis\u003c/p\u003e \u003cp\u003ePrednisolone 2 mg/kg/day and Azathioprine 2 mg/kg/day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eESKD after 5 months of diagnosis\u003c/p\u003e \u003cp\u003eRenal Transplant in 2 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1994\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 months/Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePrematurity 32 weeks, Fever, Nephrotic syndrome, diarrhea, lymphadenopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia, Creatinine 35.4 umol/L, Albumin 10 g/L, urinalysis\u0026thinsp;\u0026gt;\u0026thinsp;3g proteins and \u0026gt;\u0026thinsp;100 erythrocytes. Low complements C3 0.14 g/L and C4 0.04 g/L. Positive ANA and DSDNA antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePrednisolone 2 mg/kg/day and Azathioprine 2 mg/kg/day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRenal relapse in 2.5 years, second biopsy showed class V with 30% sclerosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1994\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 months/male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFever, Pneumonia, Nephrotic Syndrome, lymphadenopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia Hb 9.3 g/dl, Thrombocytopenia 130 \u0026times;109/l, Albumin 20 g/L, creatinine 46 umol/L, UPCR 3651 mg/mmol, microscopic haematuria, low complements C3: 0.51 g/l, positive ANA and DSDNA antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSpontaneous recovery with no intervention.\u003c/p\u003e \u003cp\u003eAt 14 months, flare with Rash, HTN, GI bleeding and LVH started prednisolone 2mg/kg/day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt 12 months, urinalysis for protein\u0026thinsp;+\u0026thinsp;1, Albumin 27, normal creatinine 37 umol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1996\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 months/male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePrematurity 26 weeks, Irritability, Anasarca, purpuric\u003c/p\u003e \u003cp\u003eRash, oral ulcers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia Hb 9.3 g/dl, creatinine 26 umol/L, N/A Albumin, UPCR 2486 mg/mmol, positive microscopic haematuria with RBC casts, Positive ANA and DSDNA antibodies, low complements C3: 0.54 g/L, C4: 0.08 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIV pulse steroids 20 mg/kg/day for 3 days then oral steroids 2 mg/kg/day and monthly 500 mg/m2 IV cyclophosphamide for 6 months then every 3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAfter 12 months, achieved complete renal response with Creatinine 0.4 mg/dl, urine protein creatinine ratio was 0.2, normal complements\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5 months/Male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNephrotic Syndrome hypertension, haematuria and progressive renal failure. Pulmonary haemorrhage.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia, Thrombocytopenia, Creatinine 159 umol/L, Albumin 26 g/L, UPCR 66.3, microscopic haematuria, positive ANA and DSDNA, low complements C3: 0.39 g/L and C4: \u0026lt;0.01 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHaemodialysis at presentation\u003c/p\u003e \u003cp\u003eIV pulse steroids 30 mg/kg/day for 3 days then oral steroids 2 mg/kg/day and monthly 500 mg/m2 IV cyclophosphamide for 6 months then every 3 months\u003c/p\u003e \u003cp\u003eAt 15 months, MMF added due to relapse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt 12 months, achieved partial renal response Creatinine 0.4 mg/dl, urine protein/creatinine ratio 0.8, normal complements\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 months/Male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFever, skin rashes, melena, cerebral haemorrhage, nephrotic syndrome, arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThrombocytopenia, N/A creatinine, N/A Albumin, positive ANA and DSDNA antibodies, low complements C4 with normal C3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIV pulse steroids 20 mg/kg/day for 3 days then oral steroids 2 mg/kg/day and Azathioprine 2 mg/kg/day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOn follow up, present of proteinuria 0.2 g/day, N/A creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e13\u003c/b\u003e (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 months/male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSkin rash, photosensitivity, fever, haematuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia Hb 9,9 g/dl, Thrombocytopenia, creatinine 34 umol/L, Albumin 35 g/L, UPCR 1492 mg/mmol, Urinalysis: 100/hpf of RBC, positive ANA and DSDNA antibodies low complements C3: 0.23 g/L and C4: 0.04 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWeekly IV pulse steroids 30 mg/kg/day for 3 days then oral steroids 2 mg/kg/day\u003c/p\u003e \u003cp\u003eAfter 3 weeks, monthly 500\u0026ndash;750 mg/m2 IV cyclophosphamide for 6 months, bimonthly after the fourth dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt 9 months: After completing sixth IV CYC dose achieved complete renal remission Urine protein creatinine ratio\u0026thinsp;\u0026gt;\u0026thinsp;0.1 mg/mg and normal kidney function\u003c/p\u003e \u003cp\u003eAt 2 years: on remission with normal kidney function and urinalysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e14\u003c/b\u003e (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 months/male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNephrotic syndrome, haematuria, pulmonary thromboembolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia Hb 6.7 g/dl Thrombocytopenia PLT 52000/mm2, Creatinine 8 umol/L, Albumin 15 g/L, UPCR 2418 mg/mmol, urinalysis positive for microscopic haematuria, low complements C3: 0.73 g/L, C4: 0.3 g/L, negative ANA and DSDNA antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSteroids start at 8 mg/kg/day for 10 day for autoimmune haemolytic anaemia then 2 mg/kg/day and monthly 500 mg/m2 IV cyclophosphamide for 6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt 3 months: achieved complete remission with normal kidney function and protein creatinine ratio 0.3 mg/mg\u003c/p\u003e \u003cp\u003eCommenced on MMF as maintenance and at 20 months still on complete renal remission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOur Case\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 months/Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePrematurity 32 weeks, Nephrotic syndrome, hypertension, central hypotonia, failure to thrive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnaemia 8.5 g/dl, creatinine 31 umol/L, Albumin 24 g/L, UPCR 6191 mg/mmol, microscopic haematuria, positive ANA and DSDNA antibodies, low complements C3: 0.39 g/L C4: 0.02 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClass IV/V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIV pulse steroids (15 mg/kg/day) for 3 days then Triple therapy: oral prednisolone 2 mg/kg/day, MMF (800mg/m2/day) and Tacrolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt 12 months: achieved complete renal response, urine protein/creatinine ratio was 49 mg/mmol. Normal kidney function with creatinine 18 mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the patient and her family for providing consent for this report to be published.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthor\u0026rsquo;s Contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOmar Alomar conceptualized and designed the report, wrote the manuscript, and contributed to all stages of this case report. Joshua Kausman and Jonathan Akikusa supervised the case report, edited all drafts and the final manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAkar EM, \u0026Ouml;z\u0026ccedil;akar ZB, \u0026Ccedil;akar N, Kiremit\u0026ccedil;i S, Kurt-Ş\u0026uuml;k\u0026uuml;r ED, Fit\u0026ouml;z S, et al. Infantile systemic lupus erythematous presenting as nephrotic syndrome in a 12-month-old boy: a case report. The Turkish journal of pediatrics [Internet]. 2021;63(2):339\u0026ndash;43.\u003c/li\u003e\n\u003cli\u003eRovin BH, Ayoub I, Tak Mao Chan, Liu Z, Mej\u0026iacute;a-Vilet JM, J\u0026uuml;rgen Floege. KDIGO 2024 Clinical Practice Guideline for the management of LUPUS NEPHRITIS. Kidney International. 2024 Jan 1;105(1):S1\u0026ndash;69.\u003c/li\u003e\n\u003cli\u003eGroot N, Nienke de Graeff, Marks SD, Brogan PA, Tadej Avcin, Bader-Meunier B, et al. European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative. 2017 Dec 1;76(12):1965\u0026ndash;73.\u003c/li\u003e\n\u003cli\u003eTektonidou MG, Lewandowski LB, Hu J, Dasgupta A, Ward MM. Survival in adults and children with systemic lupus erythematosus: a systematic review and Bayesian meta-analysis of studies from 1950 to 2016. Annals of the Rheumatic Diseases. 2017 Aug 9;76(12):2009\u0026ndash;16.\u003c/li\u003e\n\u003cli\u003e\u003cdel cite=\"mailto:omar%20Alomar%20Royal%20Children%20Hospital\" datetime=\"2026-03-22T20:05\"\u003e\u0026zwnj;\u003c/del\u003e5- Sammaritano LR, Askanase A, Bermas BL, Dall\u0026rsquo;Era M, Duarte‐Garc\u0026iacute;a A, Hiraki LT, et al. 2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis. Arthritis \u0026amp; Rheumatology. 2025 May 7;\u003c/li\u003e\n\u003cli\u003eGrossman J, Schwartz RH, Callerame ML, Condemi JJ. Systemic lupus erythematosus in a 1-year-old child. American journal of diseases of children (1960) [Internet]. 1975 Jan;129(1):123\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eTy A, Fine B. Membranous nephritis in infantile systemic lupus erythematosus associated with chromosomal abnormalities. Clinical nephrology [Internet]. 1979 Sep;12(3):137\u0026ndash;41.\u003c/li\u003e\n\u003cli\u003eAnderson JR. INTRACEREBRAL CALCIFICATION IN A CASE OF SYSTEMIC LUPUS ERYTHEMATOSUS WITH NEUROLOGICAL MANIFESTATIONS. Neuropathology and Applied Neurobiology. 1981 Mar 1;7(2):161\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eJordan SC, Lemire JM, Border W, Sakai R, Ettenger RB, Fine RN. False-negative anti-DNA antibody activity in infantile systemic lupus erythematosus (SLE). Journal of clinical immunology [Internet]. 1984 Mar;4(2):156\u0026ndash;62. \u003c/li\u003e\n\u003cli\u003eCummings NP, Hansen J, Hollister JR. Systemic lupus erythematosus in a premature infant. Arthritis and rheumatism [Internet]. 1985 May;28(5):573\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eJordan, JM, Valenstein, P, Kredich, DW. Systemic lupus erythematosus with Libman-Sachs endocarditis in a 9-month-old infant with neonatal lupus erythematosus and congenital heart block. Pediatrics 1989; 84: 574\u0026ndash;578.\u003c/li\u003e\n\u003cli\u003eMassengill SF, Richard GA, Donnelly WH. Infantile systemic lupus erythematosus with onset simulating congenital nephrotic syndrome. The Journal of Pediatrics. 1994 Jan 1;124(1):27\u0026ndash;31.\u003c/li\u003e\n\u003cli\u003eDudley J, Fenton T, Unsworth J, Chambers T, MacIver A, Tizard J. Systemic lupus erythematosus presenting as congenital nephrotic syndrome. Pediatric Nephrology. 1996 Nov 18;10(6):752\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eSaberi MS, Jones BA. Remission of infantile systemic lupus erythematosus with intravenous cyclophosphamide. Pediatric nephrology (Berlin, Germany) [Internet]. 1998 Feb;12(2):136\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eKreindler J, Ellis D, Vats A, Kurland G, Ranganathan S, Moritz ML. Infantile systemic lupus erythematosus presenting with pulmonary hemorrhage. Pediatric nephrology (Berlin, Germany) [Internet]. 2005 Apr;20(4):522\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eZulian F, Pluchinotta F, Martini G, Da Dalt L, Zacchello G. Severe clinical course of systemic lupus erythematosus in the first year of life. Lupus. 2008 Sep;17(9):780\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eKishi N, Suga K, Matsuura S, Kinoshita Y, Urushihara M, Kondo S, et al. A case of infantile systemic lupus erythematosus with severe lupus nephritis and EBV infection. CEN Case Reports [Internet]. 2013 Feb 14 [cited 2022 Sep 6];2(2):190\u0026ndash;3. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Infantile Lupus Nephritis, Systemic lupus erythematosus, Renal Biopsy, Nephrology, glomerulonephritis","lastPublishedDoi":"10.21203/rs.3.rs-9345664/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9345664/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Lupus nephritis (LN) presenting in infancy is an extremely rare form of systemic lupus erythematosus (SLE). Diagnosis and treatment are challenging in this age group, and it can be misdiagnosed as congenital or infantile nephrotic syndrome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Report\u003c/strong\u003e: We report a 4-month-old preterm female (32 weeks’ gestation) who presented with nephrotic syndrome and multi-organ involvement including failure to thrive, hypotonia, raised intracranial pressure and abnormal liver function tests. Other laboratory evaluation demonstrated positive ANA, markedly elevated DSDNA antibodies, hypocomplementemia, and microscopic haematuria, with preserved kidney function. Rapid trio exome sequencing was negative, and kidney biopsy confirmed class IV and V LN. Induction therapy consisted of triple therapy with corticosteroids, mycophenolate mofetil, and tacrolimus. Proteinuria improved substantially by 6 months and complete renal response was achieved by 12 months (UPCR \u0026lt;50 mg/mmol) with stable kidney function and serological improvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003eInfantile lupus nephritis is rare and often presents with multi-systemic complications and predominantly proliferative renal histology. Early recognition and aggressive induction therapy are frequently required to achieve complete renal response. To our knowledge, this is the first reported case of infantile lupus nephritis successfully treated with triple therapy, demonstrating the effectiveness of this approach in this age group.\u003c/p\u003e","manuscriptTitle":"Infantile Lupus Nephritis: Diagnostic Challenges and Successful Triple Immunosuppression - A Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-07 16:54:06","doi":"10.21203/rs.3.rs-9345664/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-04-27T09:14:29+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-22T15:02:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-15T06:28:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2026-04-11T04:32:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"89807bf3-e973-4999-86a1-0494a3de4174","owner":[],"postedDate":"May 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T16:54:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-07 16:54:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9345664","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9345664","identity":"rs-9345664","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}