Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients.

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Victor Gueutin, Aurore Cardineau, Alexis Mathian, Antoine Lanot, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4667296/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Oct, 2024 Read the published version in BMC Nephrology → Version 1 posted 4 You are reading this latest preprint version Abstract Background Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If renal histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Methods Patients with active cancer who had a renal biopsy (RB) between 2015 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Results Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute renal failure, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of RBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a functional cause (15 patients) and renal disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. Conclusions During onconephrology practice, renal toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of renal biopsy and the complexity of its management. Chronic histological lesions were very common. immunotherapy nephrotoxicity onconephrology renal pathology thrombotic microangiopathy Figures Figure 1 Figure 2 Figure 3 Figure 4 BACKGROUND Cancer is the second leading cause of premature death in 127 countries worldwide and the leading cause in 57 countries ( 1 ). The increase in the prevalence of cancer is due to multiple factors, including great progress in terms of anticancer treatments ( 2 ). There are several reasons for the increase in the number of patients with both nephropathy and cancer ( 3 – 8 ). First, the increased life expectancy of cancer patients makes it a chronic disease in which other comorbidities, such as kidney failure, can occur ( 9 ). Second, the life expectancy of patients with chronic kidney disease has increased, and the management of elderly patients on dialysis has improved, explaining the higher incidence of cancer in this population ( 3 , 6 ). Renal complications from cancer are also numerous, whether secondary to the neoplasia itself, such as paraneoplastic nephropathies or mechanical complications of cancers, or to its diagnostic and therapeutic management ( 10 ). All these complex interactions between oncology and nephrology have made the development of a specific field of knowledge essential: onconephrology ( 11 – 15 ). This developing discipline aims to improve the management of these multimorbid patients ( 16 , 17 ). The occurrence of a nephrological complication has a major impact on the prognosis of cancer patients, and precise knowledge of the mechanisms underlying worsening renal function is essential to propose the best therapeutic approach ( 18 ). For the time being, this management is essentially based on experience owing to the absence of recommendations, particularly concerning the histological aspects of some of these complications. However, renal histology seems to be an indispensable key to understand, diagnose, follow up, and treat the extremely varied nephrological disorders of onconephrology patients ( 19 ). Histological data are scarce in these patients, for whom referral to a nephrologist is not always systematic. A recent study in February 2021 by Chang et al. identified 77 patients who were followed for solid or hematological cancer and biopsied between July 2015 and July 2019 ( 19 ). They revealed that the extent of chronic tubulointerstitial damage on biopsies was correlated with the risk of end-stage renal disease and death and concluded that histology has a significant role in the management of these patients. The aim of our retrospective study was to describe the histological characteristics of onconephrology patients followed for solid cancer. We were interested in the histological damage of these cancer patients, integrating it with the demographic, clinical and biological characteristics of this population with multiple comorbidities, for whom nephrologists and oncologists must cooperate. METHODS Description of study cohorts, explanatory variables and outcomes We conducted an observational and retrospective study in 2 centers (Pitié-Salpêtrière Hospital in Paris and Caen University Hospital). We identified 154 patients (> 18 years old) who had a history of solid organ cancer and its treatment and presented a renal complication during follow-up that required a renal biopsy between November 2014 and June 2020. Patients were excluded if their cancer was considered cured or if they had hematological malignancies. The statistical analyses were conducted in July and August 2021. The data were retrieved from the hospitalization, consultation, and renal biopsy reports. They were collected retrospectively between July 2019 and January 2021. Obtained data on demographic characteristics at the time of the biopsy were the age, sex, and body mass index (BMI) of the patients; their history of diabetes, hypertension, and chronic renal disease (CKD); and, if applicable, their glomerular filtration rate (GFR). Patients with renal impairment were classified by CKD stage according to the KDIGO classification ( 20 ). The obtained data on cancer were the date of diagnosis, the organ involved, the histological type, and the modalities of treatment (surgical treatment, radiotherapy on the renal area, and anticancer therapy, including chemotherapies, targeted therapies, and immunotherapies (specifying the number of treatment lines, the agents and classes used in the current line and in previous lines, and whether extrarenal side effects occurred)). The use of noncancerous nephrotoxic agents, such as iodinated contrast agents, biphosphonates, NSAIDs or antibiotics, was recorded. The nephrological event prompting the consultation, namely, hypertension, acute kidney injury (AKI) or proteinuria, was recorded. From the biological assessment carried out at the time of the renal biopsy, we noted the serum creatinine value and the GFR estimated according to the CKD-EPI formula expressed in ml/min/1.73 m 2 , the signs of hemolysis, the proteinuria rate, and the presence of hematuria and leukocyturia. The analysis of histological lesions was made on the basis of the descriptions in the renal biopsy reports (Supplementary Table S1 and S2). The diagnosis made after the renal biopsy was noted and classified as TMA (thrombotic microangiopathy), MN (membranous nephropathy), IGAN (IgA nephropathy), MPGN (membranoproliferative glomerulonephritis), MCD (minimal change disease), FSGS (focal and segmental glomerulosclerosis), IFTA (interstitial fibrosis with tubular atrophy), TD (tubular dystrophy), ATN (acute tubular necrosis), AIN (acute interstitial nephritis), or NAS (nephroangiosclerosis). Glomerular TMA was identified as a glomerular lesion. Finally, we noted the etiology determined by the nephrologist specializing in onconephrology during a dedicated consultation following RB (renal biopsy) (Supplementary Table S3). The study was approved by the Local Ethics Committee of Caen University Hospital (ref: 3155 bis/2022) in accordance with the declaration of Helsinki and health data processing in compliance with the European regulation of April 27, 2016 on the protection of individuals with regard to the processing of personal data. No consent was required for this retrospective study. Statistical analyses Statistical analyses were performed during July and August 2021. Quantitative variables are presented as the median and first and third quartiles. Qualitative variables are presented as their numbers and percentages. This was a descriptive analysis of the data, and therefore, no statistical tests were performed. Statistical analyses were performed using R software version 3.1.1 (R foundation for statistical computing). RESULTS General demographic characteristics of the population. We included 154 patients who underwent RB between April 2014 and September 2020. The main demographic characteristics are detailed in Table 1. The mean age was 58.1 years old, and 83 of the patients were female (53.9%). Twenty patients were diabetic (13.0%), 73 had hypertension (47.4%) and 30 had CKD (19.5%), with a mean GFR of 55 ml/min/1.73 m². Six patients were stage 2, 16 were stage 3A, 2 were stage 3B, and 1 was stage 4. The mean BMI was 25.2 kg/m². The main locations of cancer were gynecologic (n = 34, 22%), lungs (n = 25, 16%), kidneys (n = 19, 12%), and skin (n = 19, 12%). Table 1 : Demographic characteristics of the population Characteristics Age, mean (year) Female, n (%) Baseline SCr, median (IQR) (µmol/l) 58.1 83 (53.9%) 132 (88.5-168.2) Comorbidités Diabetes, n (%) 20 (13.0%) Hypertension, n (%) 73 (47.4%) Chronic kidney failure, n (%) Cancer Pelvic gynecologic cancer, n (%) Pulmonary cancer, n (%) 30 (19.5%) 34 (22%) 25 (16%) Urinary cancer, n (%) Skin cancer, n (%) Prior chemotherapies 1 2 3 or more Indication for consultation and RB HTA, n (%) Pu, n (%) AKI, n (%) Mixed, n (%) 19 (12.3%) 18 (11.7%) 58 (37.7%) 44 (28.6%) 52 (33.7%) 49 (31.8%) 112 (72.7%) 95 (61.8%) 90 (58.4%) Clinicobiological presentation at the time of PBR. The reason for the referral of the patients for an onconephrology consultation included acute kidney injury for 95 patients (61.8%), with a mean creatinine level for these patients at 179 µmol/L (vs. 77 µmol/L in patients without acute renal failure at the time of RB); proteinuria in 112 patients (72.7%); and uncontrolled or de novo hypertension for 49 patients (31.8%). Thirty-six patients had isolated AKI, 25 had isolated proteinuria, and 2 had isolated hypertension. Forty-three patients were referred for the combination of AKI and proteinuria; 30 for the combination of hypertension and proteinuria; 5 for the combination of AKI and hypertension; and 12 for the combination of AKI, hypertension, and proteinuria. Seven patients had biological hemolysis but had many missing data (50.6%). Among the patients tested, hematuria was found in 38/110 patients (35%), and leukocyturia was found in 40/106 patients (38%). Treatment All patients were receiving anticancer therapy at the time of RB. The number of previous treatment of anticancer therapy ranged from 1 to 7, with a median of 1.98, and a majority of patients had received a single line (37.6%) (Supplementary Figure S1). Fifty-six patients (36%) received cytotoxic chemotherapies at the time of RB, including alkylating agents in 22 and antimetabolites in 20 patients. Targeted therapies were used in 98 patients (64%), including tyrosine kinase inhibitors in 46 patients and monoclonal antibodies in 52 patients. Immunotherapy was ongoing in 42 patients (27%) and included anti-PD1 in 27 patients and anti-PDL1 in 10 patients (Supplementary Table S4). Twenty-two patients had previously received nephrotoxic treatments before RB, including iodinated contrast media for 8 patients, biphosphonates for 4 patients, NSAIDs for 4 patients, and unspecified for 4 patients. Histological lesions The basic histological lesions were essentially chronic and predominated in the interstitial, tubular and vascular areas (Figure 1). The main described lesions were interstitial fibrosis (n=114, 74%), followed by arteriolar hyalinosis (n=90, 58%), fibrous endarteritis (n=87, 56%), and tubular atrophy (n=85, 55%). Acute lesions were mainly found in the tubular area with acute tubular necrosis (ATN) (n=79, 51%), interstitial inflammation (n= 46, 30%), glomeruli with glomerular thrombi (n=46, double contours on 45 RB, mesangiolysis on 39, and glomerular thrombi on 22 RB) and immunofluorescence deposits (n=47). Cytotoxic chemotherapies were mainly associated with ATN (17 patients: 9 patients receiving alkylating agents and 8 patients receiving antimetabolites) (Figure 2). Patients undergoing targeted therapies mostly presented a thrombotic microangiopathy pattern (42 patients: 10 patients receiving tyrosine kinase inhibitors, 32 patients receiving monoclonal antibodies). Patients undergoing immunotherapy mainly presented ATN (17/42 patients, 40%), and only 6 had AIN (6/42, 14%). Onconephrology diagnosis After RB, an onconephrological diagnosis for the underlying etiology of kidney injury was provided as the diagnostic category, as summarized in Table 2. Cancer treatment toxicity was the diagnostic category chosen for 121 patients (78%). The majority were thrombotic microangiopathies (46 patients), acute tubular necrosis (34 patients) and acute interstitial nephritis (9 patients). The other most common diagnostic categories were the toxicity of noncancer drug treatments, including iodinated contrast products, in 12 patients (7.8%); complications of nondrug cancer management in 10 patients (2.6%); direct complications of the cancer in 12 patients (7.8%), namely, paraneoplastic glomerulopathies, including MN in 2 patients; functional causes in 13 patients (8.4%); obstructive causes in 6 patients (3.9%); and renal disease unrelated to cancer or treatment in 32 patients (20.7%). Table 2 : Diagnostic category retained after RB Diagnostic category n (%) AKI (%) Pu (%) HTA (%) Cancer treatment toxicity Functional cause Kidney disease unrelated to cancer Other treatment toxicity (non anticancer) Direct cancer complication Consequence of surgery or radiotherapy in the renal area Obstructive cause No conclusion 124 (80.5%) 13 (8.4%) 32 (20.8%) 12 (7.8%) 12 (7.8%) 3 (1.9%) 6 (3.9%) 3 (1.9%) 69 (55.6%) 9 (69.2%) 25 (78.1%) 12 (100%) 7(58.3%) 3 (100%) 6 (100%) 92 (74.2%) 10 (76.9%) 22 (68.8%) 9 (75%) 11 (91.7%) 2 (66.7%) 5 (83.3%) 44 (12.9%) 2 (15.4%) 8 (25%) 1 (8.3%) 3 (25%) 1 (33.3%) 1 (16.7%) Classification of histological lesions according to diagnostic category: The most common etiologies according to diagnostic category are summarized in Figure 3. Supplementary Table 3 reports the basic histological lesions according to the diagnostic category. As shown in Figure 3, 84 patients had only one underlying cause of kidney injury, while 47 had multiple causes. For 3 patients, no diagnosis could be made because of the RB findings were inconclusive. Cluster analysis Cluster analysis allowed the identification of 4 groups (dendogram, Supplementary Figure S4). Clusters 2 and 4 corresponded histologically to TMA, with or without arteriolar thrombi for Cluster 4 and Cluster 2, respectively. The treatments most frequently used in Cluster 2 were anti-VEGF, PDL1 inhibitors and alkylating agents. The treatments used in Cluster 4 were anti-VEGF, multikinase inhibitors and antimetabolites. These patients were not necessarily more often hypertensive. Cluster 3 identified patients with the most interstitial fibrosis and vascular lesions along with more severe interstitial inflammation. The most commonly used treatment was immunotherapy. It was also frequently used in Cluster 1 in combination with alkylates or antimetabolites, but interstitial inflammation was minimal. No clinical or biological data distinguished Clusters 1 and 3 (Figure 4). No difference between clusters was found (Supplementary Figure S5, 6, 7). DISCUSSION Renal histological analysis is a key examination in nephrology for diagnostic, prognostic and therapeutic purposes. The use of renal biopsy and histological analysis in onconephrology patients is still poorly developed. Our study gathers important renal histological data that have rarely been reported in the literature. The nephrotoxicity of anticancer treatment was the most common etiological diagnosis made following RB in our cohort, corresponding to 78%. Until recently, the nephrotoxicity of anticancer drugs seemed to concern mostly cytotoxic chemotherapies ( 15 , 21 ), particularly platinum salts ( 15 , 22 , 23 ), but the modification of treatment regimens in oncology has led to rapid growth in the field of onconephrology ( 24 ). The emergence of targeted therapy and then immunotherapy since 2014 has played a role in these changes, which continue with the widespread use of this class of therapy and the continuous expansion of indications ( 25 – 27 ). In our study, of the 98 patients who received targeted therapies, 42 had TMA and 23 had ATN, compared with 9 and 17, respectively, of the 56 patients who received cytotoxic chemotherapy. There is a selection bias since the renal toxicity of cytotoxic chemotherapies is well known ( 28 ), and the use of RB was probably less systematic. TMA is the most common complication of cancer treatment identified in RB and is mostly associated with treatment with monoclonal antibodies. These data are consistent with a study by Izzedine et al. ( 29 ), in which 100 patients on anti-VEGF were included over 8 years, 73 of whom had TMA. Half of the TMA cases were exclusively renal, with signs of biological hemolysis in 50% of the patients. The pathophysiology of thrombus formation in anti-VEGF therapy is not fully understood ( 30 – 32 ). One study compared thrombi in patients taking bevacizumab with thrombi in patients with proven acute TMA, including patients with atypical hemolytic and uremic syndrome ( 33 ). In patients receiving bevacizumab, there was always nephrotic proteinuria (17/17) without a deterioration of renal function or thrombocytopenia. Thrombi were exclusively glomerular, hyaline, nonfibrinous, and associated with significant dilatation of glomerular capillaries and moderate mesangial and endothelial hypercellularity. On immunohistochemistry, these thrombi did not contain platelets (negative CD61 labeling), but IgG labeling was present. This presentation differs from that of patients with authentic TMA. They did not all have nephrotic proteinuria (3/8) but always had elevated creatinine levels, and 5 patients had thrombocytopenia. On light microscopy, the thrombi were fibrinous. Immunohistochemistry showed a significant presence of platelets (CD61 positive), IgG labeling was negative. The preferred etiology hypothesis is an increase in the permeability of endothelial cells in glomerular capillaries, which is secondary to the inhibition of anti-VEGF by bevacizumab and favors the passage of serum proteins into the subendothelium. These deposits lead to the activation of coagulation ( 34 ). Histologically, in our study, of the 5 patients with arteriolar thrombosis, 3 were on bevacizumab, 1 on regorafenib and 1 on gemcitabine. This differs from the study of Izzedine et al ( 29 ), in which TMA with anti-VEGF was only glomerular, and may be related to the small proportion of patients with thromboses. Two clusters corresponded to patients treated with anti-VEGF whose known histological outcome was TMA. However, the drug associations were different in Clusters 2 and 4, with an association with anti-PDL1 in Cluster 2 with more varied histological lesions and the presence of arteriolar thrombi exclusively in Cluster 4. However, the number of patients in Cluster 4 does not allow definitive conclusions to be drawn. In our cohort, immunotherapy was not systematically associated with interstitial nephritis, as in other series ( 35 ). Indeed, out of 42 patients receiving immunotherapy, only 6 had an AIN considered to be due to immunotherapy. In Cluster 2, the primary lesion was ATN, although patients were primarily treated with immunotherapy, anti-VEGF and alkylating agents. Thus, patients on immunotherapy have AKI related to ATN or AIN, which can be distinguished only by renal biopsy and has consequences in therapy and prognosis( 36 ). Cluster analysis showed that patients receiving immunotherapy can have the same clinical and biological presentation, while renal histology shows either chronic lesions or inflammatory lesions requiring treatment. It is interesting to note the importance of chronic histological lesions. Seventy-four percent of patients had interstitial fibrosis, 59% had arteriolar hyalinosis, 56% had fibrous endarteritis, and 55% had tubular atrophy. However, none of the patients were biopsied for CKD, and only 19.5% had a GFR < 60 m/min/1.73 m 2 at baseline. This result illustrates the lack of a strong correlation of clinical assessment, histological damage and, in this case, nephron reserve. These data are consistent with a study ( 37 ) that found that 50% of a patient population with cancer had a GFR < 90 ml/min/1.73 m 2 and 12% had a GFR < 60 ml/min/1.73 m 2 . Another study reported 30% of CKD patients with a GFR < 45 ml/min/1.73 m 2 among 4077 cancer patients ( 38 ). The discrepancy between baseline creatinine levels and the extent of chronic damage on RB may be related to numerous biases in the use of conventional estimators of renal function in oncology patients. This is a population sample that experienced malnutrition, with lower muscle mass than in the general population, which results in lower blood creatinine levels, and the threshold of 60 ml/min/1.73 m 2 may not be appropriate. In a study by Launay et al., 1 in 5 patients followed for cancer with a normal creatinine level actually had asymptomatic renal failure, as evidenced by a measurement of renal clearance ( 39 ). The overestimation of renal function in patients treated for cancer by conventional measurement methods exposes them to more nephrotoxicity ( 40 , 41 ). Another striking result is the importance of mixed diagnostic categories in the same patient, attesting to the complexity of nephrological damage in oncology patients, which is often multifactorial and difficult to characterize without histological analysis. This illustrates the difficulty of establishing a diagnosis without the contribution of nephrological expertise and histological analysis. This expertise is all the more indicated since current recommendations call for the suspension or even the cessation of the treatment in progress at the time of the nephrological event ( 42 ). The suspension of treatment when the etiology of the nephrological event is not the nephrotoxicity of anticancer drugs (for example, in our study, paraneoplastic glomerulopathy or a previously unrecognized primary glomerulopathy) may have important consequences in the management of the cancer and should be avoided. CONCLUSIONS Onconephrology is a rapidly growing field in which anatomopathological analysis is essential. The nephrotoxicity of anticancer drugs is the most common etiology of renal injury identified in renal biopsies of patients followed for cancer. Similar to nephrology in its early days, a disambiguation of treatment-related complications by renal histology is useful in research to answer questions that are raised by the rapid advent of new oncology treatments. The benefit of histology in other areas of onconephrology is also important, especially in the differentiation of paraneoplastic and primary glomerulopathies, with the emergence of diagnostic probability scores based primarily on pathology. The appreciation of chronic histological lesions, too often underestimated in this population, is another of the fundamental assets of renal histology in onconephrology. Further studies are needed to continue to advance the field of onconephrology, and these future advances seem to be possible in large part thanks to renal histology. Abbreviations AKI: acute kidney injury AIN: acute interstitial nephritis ATN: acute tubular necrosis BMI: body mass index CKD: chronic renal disease CKD-EPI: CKD-EPIdemiology FSGS: focal and segmental glomerulosclerosis GFR: glomerular filtration rate IFTA: interstitial fibrosis with tubular atrophy IGAN: IgA nephropathy MCD: minimal change disease MN: membranous nephropathy MPGN: membranoproliferative glomerulonephritis NAS: nephroangiosclerosis NSAID: non-steroidal anti-inflammatory drugs RB: renal biopsy TD: tubular dystrophy TMA: thrombotic microangiopathy Declarations Ethics approval and consent to participate The study was approved by the Local Ethics Committee of Caen University Hospital (ref: 3155 bis/2022) in accordance with the declaration of Helsinki and health data processing in compliance with the European regulation of April 27, 2016 on the protection of individuals with regard to the processing of personal data. No consent was required for this retrospective study. Consent for publication Not applicable. Data Availability Statement The data underlying this article will be shared on reasonable request to the corresponding author. Conflict of Interest Statement None declared. Funding None Authors’ Contributions VG, AC, and HI contributed study conception, design, analysis and interpretation of data. VG and AC drafted the manuscript. Each author contributed important intellectual content during manuscript revision and approved the final manuscript Acknowledgements None References Bray F, Laversanne M, Weiderpass E, Soerjomataram I. The ever‐increasing importance of cancer as a leading cause of premature death worldwide. Cancer [Internet]. 4 juin 2021 [cité 12 juill 2021];cncr.33587. Disponible sur: https://onlinelibrary.wiley.com/doi/10.1002/cncr.33587 The International Agency for Research on Cancer. 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Disponible sur: http://www.nature.com/articles/s41581-018-0035-1 Manohar S, Leung N. Cisplatin nephrotoxicity: a review of the literature. J Nephrol [Internet]. févr 2018 [cité 29 août 2021];31(1):15‑25. Disponible sur: http://link.springer.com/10.1007/s40620-017-0392-z Izzedine H, Escudier B, Lhomme C, Pautier P, Rouvier P, Gueutin V, et al. Kidney Diseases Associated With Anti-Vascular Endothelial Growth Factor (VEGF): An 8-year Observational Study at a Single Center. Medicine [Internet]. nov 2014 [cité 7 août 2021];93(24):333‑9. Disponible sur: https://journals.lww.com/00005792-201411040-00002 Izzedine H, Massard C, Spano JP, Goldwasser F, Khayat D, Soria JC. VEGF signalling inhibition-induced proteinuria: Mechanisms, significance and management. European Journal of Cancer [Internet]. janv 2010 [cité 29 sept 2022];46(2):439‑48. Disponible sur: https://linkinghub.elsevier.com/retrieve/pii/S0959804909008387 Lafayette RA, McCall B, Li N, Chu L, Werner P, Das A, et al. Incidence and Relevance of Proteinuria in Bevacizumab-Treated Patients: Pooled Analysis from Randomized Controlled Trials. Am J Nephrol [Internet]. 2014 [cité 29 sept 2022];40(1):75‑83. Disponible sur: https://www.karger.com/Article/FullText/365156 Abbas A, Mirza MM, Ganti AK, Tendulkar K. Renal Toxicities of Targeted Therapies. Targ Oncol [Internet]. déc 2015 [cité 29 sept 2022];10(4):487‑99. Disponible sur: http://link.springer.com/10.1007/s11523-015-0368-7 Person F, Rinschen MM, Brix SR, Wulf S, Noriega M de las M, Fehrle W, et al. Bevacizumab-associated glomerular microangiopathy. Mod Pathol [Internet]. mai 2019 [cité 29 sept 2022];32(5):684‑700. Disponible sur: http://www.nature.com/articles/s41379-018-0186-4 Keir LS, Firth R, Aponik L, Feitelberg D, Sakimoto S, Aguilar E, et al. VEGF regulates local inhibitory complement proteins in the eye and kidney. Journal of Clinical Investigation [Internet]. 5 déc 2016 [cité 29 sept 2022];127(1):199‑214. Disponible sur: https://www.jci.org/articles/view/86418 Gupta S, Short SAP, Sise ME, Prosek JM, Madhavan SM, Soler MJ, et al. Acute kidney injury in patients treated with immune checkpoint inhibitors. J Immunother Cancer. oct 2021;9(10):e003467. Belliere J, Mazieres J, Meyer N, Chebane L, Despas F. Renal Complications Related to Checkpoint Inhibitors: Diagnostic and Therapeutic Strategies. Diagnostics. 30 juin 2021;11(7):1187. Launay-Vacher V, Oudard S, Janus N, Gligorov J, Pourrat X, Rixe O, et al. Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: The renal insufficiency and anticancer medications (IRMA) study. Cancer [Internet]. 15 sept 2007 [cité 24 sept 2021];110(6):1376‑84. Disponible sur: https://onlinelibrary.wiley.com/doi/10.1002/cncr.22904 Iff S, Craig JC, Turner R, Chapman JR, Wang JJ, Mitchell P, et al. Reduced estimated GFR and cancer mortality. Am J Kidney Dis. janv 2014;63(1):23‑30. Launay-Vacher V, Izzedine H, Rey JB, Rixe O, Chapalain S, Nourdine S, et al. Incidence of renal insufficiency in cancer patients and evaluation of information available on the use of anticancer drugs in renally impaired patients. Med Sci Monit. mai 2004;10(5):CR209-212. Casal MA, Nolin TD, Beumer JH. Estimation of Kidney Function in Oncology: Implications for Anticancer Drug Selection and Dosing. CJASN [Internet]. 5 avr 2019 [cité 29 sept 2022];14(4):587‑95. Disponible sur: https://cjasn.asnjournals.org/lookup/doi/10.2215/CJN.11721018 Launay-Vacher V, Chatelut E, Lichtman SM, Wildiers H, Steer C, Aapro M. Renal insufficiency in elderly cancer patients: International Society of Geriatric Oncology clinical practice recommendations. Annals of Oncology [Internet]. août 2007 [cité 29 sept 2022];18(8):1314‑21. Disponible sur: https://linkinghub.elsevier.com/retrieve/pii/S0923753419428937 Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. JCO [Internet]. 10 juin 2018 [cité 30 sept 2021];36(17):1714‑68. Disponible sur: https://ascopubs.org/doi/10.1200/JCO.2017.77.6385 Additional Declarations No competing interests reported. Supplementary Files SupplementaldataandtablesBMCNGueutinetal.docx Cite Share Download PDF Status: Published Journal Publication published 19 Oct, 2024 Read the published version in BMC Nephrology → Version 1 posted Editorial decision: Revision requested 12 Jul, 2024 Editor assigned by journal 12 Jul, 2024 Submission checks completed at journal 12 Jul, 2024 First submitted to journal 01 Jul, 2024 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. 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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-4667296","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":326054532,"identity":"d4bebdcd-06fa-44ea-8050-af44a6f5c16b","order_by":0,"name":"Victor Gueutin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYNACAyBmb2CD8z8Q1HEApIXnAFwL4wzCWkCERAKRWuQjko9Jfyi4w2Bw8/GzxzwMdvL80g2MzRV4tBjeSEuTOGDwjMHgdpq5MQ9DsuHMOQcYG8/g0zIjxwyo5XD9zNk5bNK8/w4wbriRwP6wAa+W/G8gLQySM8+wSfMwHLDffyOBsRGfFnmJHDawFn4JHrCWxA0SBLQY8DwztjgD0sKTZiY5hyE5ecaNxEb8trQnP7xR8ecwAxv74WcSbxjsbPtnJB/Eb8sBTDFGfBqAtuCXHgWjYBSMglEABADpA0nEfS7gHwAAAABJRU5ErkJggg==","orcid":"","institution":"Nephrology Department, University Hospital Caen","correspondingAuthor":true,"prefix":"","firstName":"Victor","middleName":"","lastName":"Gueutin","suffix":""},{"id":326054533,"identity":"0a2448f4-ff90-4f13-9c86-7858557ce988","order_by":1,"name":"Aurore Cardineau","email":"","orcid":"","institution":"Nephrology Department, Hopital Mémorial France Etats Unis","correspondingAuthor":false,"prefix":"","firstName":"Aurore","middleName":"","lastName":"Cardineau","suffix":""},{"id":326054535,"identity":"5d743dd8-6b0e-46e5-8047-7024aaa3ebe7","order_by":2,"name":"Alexis Mathian","email":"","orcid":"","institution":"Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Service de Médecine Interne 2, Institut E3M","correspondingAuthor":false,"prefix":"","firstName":"Alexis","middleName":"","lastName":"Mathian","suffix":""},{"id":326054537,"identity":"f1668efa-2a1d-4793-866d-9b1782069792","order_by":3,"name":"Antoine Lanot","email":"","orcid":"","institution":"Nephrology Department, University Hospital Caen","correspondingAuthor":false,"prefix":"","firstName":"Antoine","middleName":"","lastName":"Lanot","suffix":""},{"id":326054539,"identity":"8e8f6060-e6c8-4efa-9eb8-7f474e6a5be4","order_by":4,"name":"Francois Comoz","email":"","orcid":"","institution":"Pathology Department, University Hospital Caen","correspondingAuthor":false,"prefix":"","firstName":"Francois","middleName":"","lastName":"Comoz","suffix":""},{"id":326054541,"identity":"34d6f4d1-b500-4f60-81c2-c3940e9415a9","order_by":5,"name":"Isabelle Brocheriou","email":"","orcid":"","institution":"Pathology Department, Pitié-Sâlpétrière Hospital","correspondingAuthor":false,"prefix":"","firstName":"Isabelle","middleName":"","lastName":"Brocheriou","suffix":""},{"id":326054543,"identity":"194047c3-bbe9-4e98-8f39-7a54ffaf8a70","order_by":6,"name":"Hassan Izzedine","email":"","orcid":"","institution":"Nephrology Department, Private Hospital of the Peupliers","correspondingAuthor":false,"prefix":"","firstName":"Hassan","middleName":"","lastName":"Izzedine","suffix":""}],"badges":[],"createdAt":"2024-07-01 10:29:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4667296/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4667296/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12882-024-03812-7","type":"published","date":"2024-10-19T15:57:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":62221261,"identity":"362d410d-a049-49b4-b4a9-3d22aa3a6599","added_by":"auto","created_at":"2024-08-11 12:26:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":58263,"visible":true,"origin":"","legend":"\u003cp\u003eHistological lesions according to current anti-cancer treatment at the time of renal biopsy\u003c/p\u003e\n\u003cp\u003eExpressed in number. AIN: acute interstitial nephropathy, ATN: Acute tubular Necrosis, CC: cytotoxic chemotherapy, FSGS: focal and segmental glomerular sclerosis, IgAN: IgA nephropathy, IMT: immunotherapy, MPGN: membranoproliferative glomerulonephritis, MN: membranous nephropathy, TMA: thrombotic microangiopathy, TT: targeted therapy.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4667296/v1/566bac67833acf5faaec323b.png"},{"id":62221258,"identity":"b7735d75-36b2-4bf9-8a09-fc278ee31711","added_by":"auto","created_at":"2024-08-11 12:26:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":33974,"visible":true,"origin":"","legend":"\u003cp\u003eKidney damage according to diagnostic category\u003c/p\u003e\n\u003cp\u003eExpressed in number of the 154 patients. TMA: thrombotic microangiopathy, ATN: acute tubular necrosis, AIN: acute interstitial nephritis, FSGS: segmental and focal glomerular sclerosis, MCD: minimal change disease, NAS: nephroangiosclerosis, IFTA: interstitial fibrosis and tubular atrophy\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4667296/v1/acdc97783e500ffa0ba11ecd.png"},{"id":62221259,"identity":"fc5eb351-af50-4238-bbf3-40961d4f711f","added_by":"auto","created_at":"2024-08-11 12:26:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":51112,"visible":true,"origin":"","legend":"\u003cp\u003eUpSet diagram of patients with multiple associated diagnostic categories\u003c/p\u003e\n\u003cp\u003eDistribution of underlying cause of kidney injury by mechanism and number. Data for single occurrence are not shown. A = nephrotoxicity of cancer treatment, B = kidney disease unrelated to cancer, C = paraneoplastic complication, D = functional cause, E = nephrotoxicity of non-cancer treatment, F = obstructive cause, G = abnormality in tubular creatine secretion, H = single kidney, I = independent kidney disease, J = unknown, K = complication of non-drug treatment of cancer (radiotherapy or nephrectomy)\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4667296/v1/345c8970ffa0352ab68ec5de.png"},{"id":62221262,"identity":"f9ecc9dd-4245-40a5-a4e1-2e0e9fda7885","added_by":"auto","created_at":"2024-08-11 12:26:39","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":72158,"visible":true,"origin":"","legend":"\u003cp\u003eCluster distribution of oncologic treatment according\u003c/p\u003e\n\u003cp\u003eDistribution of cancer treatment by cluster, expressed in percentage of the whole cohort\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4667296/v1/a17b52a7b99b664383244613.png"},{"id":67149112,"identity":"3c6a5853-57ea-435a-ae68-8ba4c4315fba","added_by":"auto","created_at":"2024-10-21 16:12:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":736616,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4667296/v1/e0c210b9-4f5f-4dc1-acac-f760f09443a8.pdf"},{"id":62221260,"identity":"ffed2d4a-f864-4fa9-8f65-bdd9f6b2c67a","added_by":"auto","created_at":"2024-08-11 12:26:39","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":415376,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaldataandtablesBMCNGueutinetal.docx","url":"https://assets-eu.researchsquare.com/files/rs-4667296/v1/fd882956708723c6b88cffe0.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients.","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eCancer is the second leading cause of premature death in 127 countries worldwide and the leading cause in 57 countries (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The increase in the prevalence of cancer is due to multiple factors, including great progress in terms of anticancer treatments (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). There are several reasons for the increase in the number of patients with both nephropathy and cancer (\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). First, the increased life expectancy of cancer patients makes it a chronic disease in which other comorbidities, such as kidney failure, can occur (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Second, the life expectancy of patients with chronic kidney disease has increased, and the management of elderly patients on dialysis has improved, explaining the higher incidence of cancer in this population (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Renal complications from cancer are also numerous, whether secondary to the neoplasia itself, such as paraneoplastic nephropathies or mechanical complications of cancers, or to its diagnostic and therapeutic management (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). All these complex interactions between oncology and nephrology have made the development of a specific field of knowledge essential: onconephrology (\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). This developing discipline aims to improve the management of these multimorbid patients (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The occurrence of a nephrological complication has a major impact on the prognosis of cancer patients, and precise knowledge of the mechanisms underlying worsening renal function is essential to propose the best therapeutic approach (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). For the time being, this management is essentially based on experience owing to the absence of recommendations, particularly concerning the histological aspects of some of these complications. However, renal histology seems to be an indispensable key to understand, diagnose, follow up, and treat the extremely varied nephrological disorders of onconephrology patients (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Histological data are scarce in these patients, for whom referral to a nephrologist is not always systematic. A recent study in February 2021 by Chang et al. identified 77 patients who were followed for solid or hematological cancer and biopsied between July 2015 and July 2019 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). They revealed that the extent of chronic tubulointerstitial damage on biopsies was correlated with the risk of end-stage renal disease and death and concluded that histology has a significant role in the management of these patients.\u003c/p\u003e \u003cp\u003e The aim of our retrospective study was to describe the histological characteristics of onconephrology patients followed for solid cancer. We were interested in the histological damage of these cancer patients, integrating it with the demographic, clinical and biological characteristics of this population with multiple comorbidities, for whom nephrologists and oncologists must cooperate.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDescription of study cohorts, explanatory variables and outcomes\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eWe conducted an observational and retrospective study in 2 centers (Piti\u0026eacute;-Salp\u0026ecirc;tri\u0026egrave;re Hospital in Paris and Caen University Hospital). We identified 154 patients (\u0026gt;\u0026thinsp;18 years old) who had a history of solid organ cancer and its treatment and presented a renal complication during follow-up that required a renal biopsy between November 2014 and June 2020. Patients were excluded if their cancer was considered cured or if they had hematological malignancies. The statistical analyses were conducted in July and August 2021. The data were retrieved from the hospitalization, consultation, and renal biopsy reports. They were collected retrospectively between July 2019 and January 2021. Obtained data on demographic characteristics at the time of the biopsy were the age, sex, and body mass index (BMI) of the patients; their history of diabetes, hypertension, and chronic renal disease (CKD); and, if applicable, their glomerular filtration rate (GFR). Patients with renal impairment were classified by CKD stage according to the KDIGO classification (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The obtained data on cancer were the date of diagnosis, the organ involved, the histological type, and the modalities of treatment (surgical treatment, radiotherapy on the renal area, and anticancer therapy, including chemotherapies, targeted therapies, and immunotherapies (specifying the number of treatment lines, the agents and classes used in the current line and in previous lines, and whether extrarenal side effects occurred)). The use of noncancerous nephrotoxic agents, such as iodinated contrast agents, biphosphonates, NSAIDs or antibiotics, was recorded. The nephrological event prompting the consultation, namely, hypertension, acute kidney injury (AKI) or proteinuria, was recorded. From the biological assessment carried out at the time of the renal biopsy, we noted the serum creatinine value and the GFR estimated according to the CKD-EPI formula expressed in ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e, the signs of hemolysis, the proteinuria rate, and the presence of hematuria and leukocyturia. The analysis of histological lesions was made on the basis of the descriptions in the renal biopsy reports (Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and S2). The diagnosis made after the renal biopsy was noted and classified as TMA (thrombotic microangiopathy), MN (membranous nephropathy), IGAN (IgA nephropathy), MPGN (membranoproliferative glomerulonephritis), MCD (minimal change disease), FSGS (focal and segmental glomerulosclerosis), IFTA (interstitial fibrosis with tubular atrophy), TD (tubular dystrophy), ATN (acute tubular necrosis), AIN (acute interstitial nephritis), or NAS (nephroangiosclerosis). Glomerular TMA was identified as a glomerular lesion. Finally, we noted the etiology determined by the nephrologist specializing in onconephrology during a dedicated consultation following RB (renal biopsy) (Supplementary Table S3).\u003c/p\u003e\u003cp\u003e The study was approved by the Local Ethics Committee of Caen University Hospital (ref: 3155 bis/2022) in accordance with the declaration of Helsinki and health data processing in compliance with the European regulation of April 27, 2016 on the protection of individuals with regard to the processing of personal data. No consent was required for this retrospective study.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eStatistical analyses were performed during July and August 2021. Quantitative variables are presented as the median and first and third quartiles. Qualitative variables are presented as their numbers and percentages. This was a descriptive analysis of the data, and therefore, no statistical tests were performed. Statistical analyses were performed using R software version 3.1.1 (R foundation for statistical computing).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eGeneral demographic characteristics of the population.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included 154 patients who underwent RB between April 2014 and September 2020. The main demographic characteristics are detailed in Table 1. The mean age was 58.1 years old, and 83 of the patients were female (53.9%). Twenty patients were diabetic (13.0%), 73 had hypertension (47.4%) and 30 had CKD (19.5%), with a mean GFR of 55 ml/min/1.73 m\u0026sup2;. Six patients were stage 2, 16 were stage 3A, 2 were stage 3B, and 1 was stage 4. The mean BMI was 25.2 kg/m\u0026sup2;. The main locations of cancer were gynecologic (n = 34, 22%), lungs (n = 25, 16%), kidneys (n = 19, 12%), and skin (n = 19, 12%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eTable 1\u003c/u\u003e: Demographic characteristics of the population\u003cem\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.47933884297521%\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.52066115702479%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.47933884297521%\" valign=\"top\"\u003e\n \u003cp\u003eAge, mean (year)\u003c/p\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003cp\u003eBaseline SCr, median (IQR) (\u0026micro;mol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.52066115702479%\" valign=\"top\"\u003e\n \u003cp\u003e58.1\u003c/p\u003e\n \u003cp\u003e83 (53.9%)\u003c/p\u003e\n \u003cp\u003e132 (88.5-168.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.47933884297521%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidit\u0026eacute;s\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.52066115702479%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (13.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.47933884297521%\" valign=\"top\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.52066115702479%\" valign=\"top\"\u003e\n \u003cp\u003e73 (47.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.47933884297521%\" valign=\"top\"\u003e\n \u003cp\u003eChronic kidney failure, n (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCancer\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePelvic gynecologic cancer, n (%)\u003c/p\u003e\n \u003cp\u003ePulmonary cancer, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.52066115702479%\" valign=\"top\"\u003e\n \u003cp\u003e30 (19.5%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34 (22%)\u003c/p\u003e\n \u003cp\u003e25 (16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.47933884297521%\" valign=\"top\"\u003e\n \u003cp\u003eUrinary cancer, n (%)\u003c/p\u003e\n \u003cp\u003eSkin cancer, n (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePrior chemotherapies\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e3 or more\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIndication for consultation and RB\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHTA, n (%)\u003cbr\u003e\u0026nbsp;Pu, n (%)\u003c/p\u003e\n \u003cp\u003eAKI, n (%)\u003c/p\u003e\n \u003cp\u003eMixed, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.52066115702479%\" valign=\"top\"\u003e\n \u003cp\u003e19 (12.3%)\u003c/p\u003e\n \u003cp\u003e18 (11.7%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58 (37.7%)\u003c/p\u003e\n \u003cp\u003e44 (28.6%)\u003c/p\u003e\n \u003cp\u003e52 (33.7%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e49 (31.8%)\u003c/p\u003e\n \u003cp\u003e112 (72.7%)\u003c/p\u003e\n \u003cp\u003e95 (61.8%)\u003c/p\u003e\n \u003cp\u003e90 (58.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eClinicobiological presentation at the time of PBR.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe reason for the referral of the patients for an onconephrology consultation included acute kidney injury for 95 patients (61.8%), with a mean creatinine level for these patients at 179 \u0026micro;mol/L (vs. 77 \u0026micro;mol/L in patients without acute renal failure at the time of RB); proteinuria in 112 patients (72.7%); and uncontrolled or de novo hypertension for 49 patients (31.8%). Thirty-six patients had isolated AKI, 25 had isolated proteinuria, and 2 had isolated hypertension. Forty-three patients were referred for the combination of AKI and proteinuria; 30 for the combination of hypertension and proteinuria; 5 for the combination of AKI and hypertension; and 12 for the combination of AKI, hypertension, and proteinuria. Seven patients had biological hemolysis but had many missing data (50.6%). Among the patients tested, hematuria was found in 38/110 patients (35%), and leukocyturia was found in 40/106 patients (38%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients were receiving anticancer therapy at the time of RB. The number of previous treatment of anticancer therapy ranged from 1 to 7, with a median of 1.98, and a majority of patients had received a single line (37.6%) (Supplementary Figure S1). Fifty-six patients (36%) received cytotoxic chemotherapies at the time of RB, including alkylating agents in 22 and antimetabolites in 20 patients. Targeted therapies were used in 98 patients (64%), including tyrosine kinase inhibitors in 46 patients and monoclonal antibodies in 52 patients. Immunotherapy was ongoing in 42 patients (27%) and included anti-PD1 in 27 patients and anti-PDL1 in 10 patients (Supplementary Table S4). Twenty-two patients had previously received nephrotoxic treatments before RB, including iodinated contrast media for 8 patients, biphosphonates for 4 patients, NSAIDs for 4 patients, and unspecified for 4 patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistological lesions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe basic histological lesions were essentially chronic and predominated in the interstitial, tubular and vascular areas (Figure 1). The main described lesions were interstitial fibrosis (n=114, 74%), followed by arteriolar hyalinosis (n=90, 58%), fibrous endarteritis (n=87, 56%), and tubular atrophy (n=85, 55%). Acute lesions were mainly found in the tubular area with acute tubular necrosis (ATN) (n=79, 51%), interstitial inflammation (n= 46, 30%), glomeruli with glomerular thrombi (n=46, double contours on 45 RB, mesangiolysis on 39, and glomerular thrombi on 22 RB) and immunofluorescence deposits (n=47).\u003c/p\u003e\n\u003cp\u003eCytotoxic chemotherapies were mainly associated with ATN (17 patients: 9 patients receiving alkylating agents and 8 patients receiving antimetabolites) (Figure 2). Patients undergoing targeted therapies mostly presented a thrombotic microangiopathy pattern (42 patients: 10 patients receiving tyrosine kinase inhibitors, 32 patients receiving monoclonal antibodies). Patients undergoing immunotherapy mainly presented ATN (17/42 patients, 40%), and only 6 had AIN (6/42, 14%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOnconephrology diagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter RB, an onconephrological diagnosis for the underlying etiology of kidney injury was provided as the diagnostic category, as summarized in Table 2. Cancer treatment toxicity was the diagnostic category chosen for 121 patients (78%). The majority were thrombotic microangiopathies (46 patients), acute tubular necrosis (34 patients) and acute interstitial nephritis (9 patients). The other most common diagnostic categories were the toxicity of noncancer drug treatments, including iodinated contrast products, in 12 patients (7.8%); complications of nondrug cancer management in 10 patients (2.6%); direct complications of the cancer in 12 patients (7.8%), namely, paraneoplastic glomerulopathies, including MN in 2 patients; functional causes in 13 patients (8.4%); obstructive causes in 6 patients (3.9%); and renal disease unrelated to cancer or treatment in 32 patients (20.7%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eTable 2\u003c/u\u003e: Diagnostic category retained after RB\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"734\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.463215258855584%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnostic category\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.623978201634877%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.716621253405995%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAKI (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166212534059945%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePu (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.029972752043598%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHTA (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.463215258855584%\" valign=\"top\"\u003e\n \u003cp\u003eCancer treatment toxicity\u003c/p\u003e\n \u003cp\u003eFunctional cause\u003c/p\u003e\n \u003cp\u003eKidney disease unrelated to cancer\u003c/p\u003e\n \u003cp\u003eOther treatment toxicity (non anticancer)\u003c/p\u003e\n \u003cp\u003eDirect cancer complication\u003c/p\u003e\n \u003cp\u003eConsequence of surgery or radiotherapy in the renal area\u003c/p\u003e\n \u003cp\u003eObstructive cause\u003c/p\u003e\n \u003cp\u003eNo conclusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.623978201634877%\" valign=\"top\"\u003e\n \u003cp\u003e124 (80.5%)\u003c/p\u003e\n \u003cp\u003e13 (8.4%)\u003c/p\u003e\n \u003cp\u003e32 (20.8%)\u003c/p\u003e\n \u003cp\u003e12 (7.8%)\u003c/p\u003e\n \u003cp\u003e12 (7.8%)\u003c/p\u003e\n \u003cp\u003e3 (1.9%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (3.9%)\u003c/p\u003e\n \u003cp\u003e3 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.716621253405995%\" valign=\"top\"\u003e\n \u003cp\u003e69 (55.6%)\u003c/p\u003e\n \u003cp\u003e9 (69.2%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (78.1%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (100%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7(58.3%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (100%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166212534059945%\" valign=\"top\"\u003e\n \u003cp\u003e92 (74.2%)\u003c/p\u003e\n \u003cp\u003e10 (76.9%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (68.8%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (75%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (91.7%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.029972752043598%\" valign=\"top\"\u003e\n \u003cp\u003e44 (12.9%)\u003c/p\u003e\n \u003cp\u003e2 (15.4%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (25%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (8.3%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (25%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (16.7%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eClassification of histological lesions according to diagnostic category:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe most common etiologies according to diagnostic category are summarized in Figure 3. Supplementary Table 3 reports the basic histological lesions according to the diagnostic category. As shown in Figure 3, 84 patients had only one underlying cause of kidney injury, while 47 had multiple causes. For 3 patients, no diagnosis could be made because of the RB findings were inconclusive.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCluster analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCluster analysis allowed the identification of 4 groups (dendogram, Supplementary Figure S4). Clusters 2 and 4 corresponded histologically to TMA, with or without arteriolar thrombi for Cluster 4 and Cluster 2, respectively. The treatments most frequently used in Cluster 2 were anti-VEGF, PDL1 inhibitors and alkylating agents. The treatments used in Cluster 4 were anti-VEGF, multikinase inhibitors and antimetabolites. These patients were not necessarily more often hypertensive. Cluster 3 identified patients with the most interstitial fibrosis and vascular lesions along with more severe interstitial inflammation. The most commonly used treatment was immunotherapy. It was also frequently used in Cluster 1 in combination with alkylates or antimetabolites, but interstitial inflammation was minimal. No clinical or biological data distinguished Clusters 1 and 3 (Figure 4). No difference between clusters was found (Supplementary Figure S5, 6, 7).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eRenal histological analysis is a key examination in nephrology for diagnostic, prognostic and therapeutic purposes. The use of renal biopsy and histological analysis in onconephrology patients is still poorly developed. Our study gathers important renal histological data that have rarely been reported in the literature. The nephrotoxicity of anticancer treatment was the most common etiological diagnosis made following RB in our cohort, corresponding to 78%. Until recently, the nephrotoxicity of anticancer drugs seemed to concern mostly cytotoxic chemotherapies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), particularly platinum salts (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), but the modification of treatment regimens in oncology has led to rapid growth in the field of onconephrology (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The emergence of targeted therapy and then immunotherapy since 2014 has played a role in these changes, which continue with the widespread use of this class of therapy and the continuous expansion of indications (\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In our study, of the 98 patients who received targeted therapies, 42 had TMA and 23 had ATN, compared with 9 and 17, respectively, of the 56 patients who received cytotoxic chemotherapy. There is a selection bias since the renal toxicity of cytotoxic chemotherapies is well known (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), and the use of RB was probably less systematic. TMA is the most common complication of cancer treatment identified in RB and is mostly associated with treatment with monoclonal antibodies. These data are consistent with a study by Izzedine et al. (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), in which 100 patients on anti-VEGF were included over 8 years, 73 of whom had TMA. Half of the TMA cases were exclusively renal, with signs of biological hemolysis in 50% of the patients. The pathophysiology of thrombus formation in anti-VEGF therapy is not fully understood (\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). One study compared thrombi in patients taking bevacizumab with thrombi in patients with proven acute TMA, including patients with atypical hemolytic and uremic syndrome (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). In patients receiving bevacizumab, there was always nephrotic proteinuria (17/17) without a deterioration of renal function or thrombocytopenia. Thrombi were exclusively glomerular, hyaline, nonfibrinous, and associated with significant dilatation of glomerular capillaries and moderate mesangial and endothelial hypercellularity. On immunohistochemistry, these thrombi did not contain platelets (negative CD61 labeling), but IgG labeling was present. This presentation differs from that of patients with authentic TMA. They did not all have nephrotic proteinuria (3/8) but always had elevated creatinine levels, and 5 patients had thrombocytopenia. On light microscopy, the thrombi were fibrinous. Immunohistochemistry showed a significant presence of platelets (CD61 positive), IgG labeling was negative. The preferred etiology hypothesis is an increase in the permeability of endothelial cells in glomerular capillaries, which is secondary to the inhibition of anti-VEGF by bevacizumab and favors the passage of serum proteins into the subendothelium. These deposits lead to the activation of coagulation (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Histologically, in our study, of the 5 patients with arteriolar thrombosis, 3 were on bevacizumab, 1 on regorafenib and 1 on gemcitabine. This differs from the study of Izzedine \u003cem\u003eet al\u003c/em\u003e (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), in which TMA with anti-VEGF was only glomerular, and may be related to the small proportion of patients with thromboses. Two clusters corresponded to patients treated with anti-VEGF whose known histological outcome was TMA. However, the drug associations were different in Clusters 2 and 4, with an association with anti-PDL1 in Cluster 2 with more varied histological lesions and the presence of arteriolar thrombi exclusively in Cluster 4. However, the number of patients in Cluster 4 does not allow definitive conclusions to be drawn.\u003c/p\u003e \u003cp\u003eIn our cohort, immunotherapy was not systematically associated with interstitial nephritis, as in other series (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Indeed, out of 42 patients receiving immunotherapy, only 6 had an AIN considered to be due to immunotherapy. In Cluster 2, the primary lesion was ATN, although patients were primarily treated with immunotherapy, anti-VEGF and alkylating agents. Thus, patients on immunotherapy have AKI related to ATN or AIN, which can be distinguished only by renal biopsy and has consequences in therapy and prognosis(\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Cluster analysis showed that patients receiving immunotherapy can have the same clinical and biological presentation, while renal histology shows either chronic lesions or inflammatory lesions requiring treatment.\u003c/p\u003e \u003cp\u003eIt is interesting to note the importance of chronic histological lesions. Seventy-four percent of patients had interstitial fibrosis, 59% had arteriolar hyalinosis, 56% had fibrous endarteritis, and 55% had tubular atrophy. However, none of the patients were biopsied for CKD, and only 19.5% had a GFR\u0026thinsp;\u0026lt;\u0026thinsp;60 m/min/1.73 m\u003csup\u003e2\u003c/sup\u003e at baseline. This result illustrates the lack of a strong correlation of clinical assessment, histological damage and, in this case, nephron reserve. These data are consistent with a study (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) that found that 50% of a patient population with cancer had a GFR\u0026thinsp;\u0026lt;\u0026thinsp;90 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e and 12% had a GFR\u0026thinsp;\u0026lt;\u0026thinsp;60 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e. Another study reported 30% of CKD patients with a GFR\u0026thinsp;\u0026lt;\u0026thinsp;45 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e among 4077 cancer patients (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). The discrepancy between baseline creatinine levels and the extent of chronic damage on RB may be related to numerous biases in the use of conventional estimators of renal function in oncology patients. This is a population sample that experienced malnutrition, with lower muscle mass than in the general population, which results in lower blood creatinine levels, and the threshold of 60 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e may not be appropriate. In a study by Launay et al., 1 in 5 patients followed for cancer with a normal creatinine level actually had asymptomatic renal failure, as evidenced by a measurement of renal clearance (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). The overestimation of renal function in patients treated for cancer by conventional measurement methods exposes them to more nephrotoxicity (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnother striking result is the importance of mixed diagnostic categories in the same patient, attesting to the complexity of nephrological damage in oncology patients, which is often multifactorial and difficult to characterize without histological analysis. This illustrates the difficulty of establishing a diagnosis without the contribution of nephrological expertise and histological analysis. This expertise is all the more indicated since current recommendations call for the suspension or even the cessation of the treatment in progress at the time of the nephrological event (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). The suspension of treatment when the etiology of the nephrological event is not the nephrotoxicity of anticancer drugs (for example, in our study, paraneoplastic glomerulopathy or a previously unrecognized primary glomerulopathy) may have important consequences in the management of the cancer and should be avoided.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eOnconephrology is a rapidly growing field in which anatomopathological analysis is essential. The nephrotoxicity of anticancer drugs is the most common etiology of renal injury identified in renal biopsies of patients followed for cancer. Similar to nephrology in its early days, a disambiguation of treatment-related complications by renal histology is useful in research to answer questions that are raised by the rapid advent of new oncology treatments. The benefit of histology in other areas of onconephrology is also important, especially in the differentiation of paraneoplastic and primary glomerulopathies, with the emergence of diagnostic probability scores based primarily on pathology. The appreciation of chronic histological lesions, too often underestimated in this population, is another of the fundamental assets of renal histology in onconephrology. Further studies are needed to continue to advance the field of onconephrology, and these future advances seem to be possible in large part thanks to renal histology.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAKI: acute kidney injury\u003c/p\u003e\n\u003cp\u003eAIN: acute interstitial nephritis\u003c/p\u003e\n\u003cp\u003eATN: acute tubular necrosis\u003c/p\u003e\n\u003cp\u003eBMI: body mass index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCKD: chronic renal disease\u003c/p\u003e\n\u003cp\u003eCKD-EPI: CKD-EPIdemiology\u003c/p\u003e\n\u003cp\u003eFSGS: focal and segmental glomerulosclerosis\u003c/p\u003e\n\u003cp\u003eGFR: glomerular filtration rate\u003c/p\u003e\n\u003cp\u003eIFTA: interstitial fibrosis with tubular atrophy\u003c/p\u003e\n\u003cp\u003eIGAN: IgA nephropathy\u003c/p\u003e\n\u003cp\u003eMCD: minimal change disease\u003c/p\u003e\n\u003cp\u003eMN: membranous nephropathy\u003c/p\u003e\n\u003cp\u003eMPGN: membranoproliferative glomerulonephritis\u003c/p\u003e\n\u003cp\u003eNAS: nephroangiosclerosis\u003c/p\u003e\n\u003cp\u003eNSAID: non-steroidal anti-inflammatory drugs\u003c/p\u003e\n\u003cp\u003eRB: renal biopsy\u003c/p\u003e\n\u003cp\u003eTD: tubular dystrophy\u003c/p\u003e\n\u003cp\u003eTMA: thrombotic microangiopathy\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study\u0026nbsp;was approved by\u0026nbsp;the\u0026nbsp;Local Ethics\u0026nbsp;Committee\u0026nbsp;of Caen University Hospital (ref: 3155\u0026nbsp;bis/2022) in accordance with the declaration of Helsinki and health data processing in compliance with the European regulation of April 27, 2016 on the protection of individuals with regard to the processing of personal data. No consent was required for this retrospective study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this article will be shared on reasonable request to the corresponding author.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVG, AC, and HI contributed study conception, design, analysis and interpretation of data. VG and AC drafted the manuscript. Each author contributed important intellectual content during manuscript revision and approved the final manuscript\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Weiderpass E, Soerjomataram I. The ever‐increasing importance of cancer as a leading cause of premature death worldwide. Cancer [Internet]. 4 juin 2021 [cit\u0026eacute; 12 juill 2021];cncr.33587. Disponible sur: https://onlinelibrary.wiley.com/doi/10.1002/cncr.33587\u003c/li\u003e\n\u003cli\u003eThe International Agency for Research on Cancer. 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Disponible sur: https://ascopubs.org/doi/10.1200/JCO.2017.77.6385\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"immunotherapy, nephrotoxicity, onconephrology, renal pathology, thrombotic microangiopathy","lastPublishedDoi":"10.21203/rs.3.rs-4667296/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4667296/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOnconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If renal histology is an essential key, the anatomopathological data remain weak although essential to this complex management.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients with active cancer who had a renal biopsy (RB) between 2015 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOur cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute renal failure, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of RBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a functional cause (15 patients) and renal disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eDuring onconephrology practice, renal toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of renal biopsy and the complexity of its management. 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