Kidney biopsies among persons living in hotspots of CKDu: a position statement from the International Society of Nephrology’s Consortium of Collaborators on CKDu

Chronic kidney disease of unknown etiology (CKDu) is a progressive primary tubulointerstitial kidney disease affecting persons in rural, agricultural communities worldwide. Some of the other terms used to identify this disease include Mesoamerican nephropathy (MeN) in Central America, Uddanam nephropathy in India, and chronic interstitial nephritis in agricultural communities (CINAC). Well-described hotspots exist in Central America, Sri Lanka, and India, with investigations to assess epidemiology and cause(s) ongoing in many regions of the world.1John O. Gummudi B. Jha A. et al.Chronic kidney disease of unknown etiology in India: What do we know and where we need to go.Kidney Int Rep. 2021; 6: 2743-2751Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar,2Gifford F.J. Gifford R.M. Eddleston M. Dhaun N. Endemic nephropathy around the world.Kidney Int Rep. 2017; 2: 282-292Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar Although the disease is suggested in a person living in a CKDu endemic area and presenting with declining kidney function without alternative explanations (e.g., diabetes, heavy proteinuria or hematuria indicative of glomerulonephritis, or structural kidney disease), definitive diagnosis requires findings of chronic tubulointerstitial disease on kidney biopsy. However, clinicians may not be enthusiastic about performing kidney biopsies among patients suspected to have CKDu, for several reasons. These reasons include the following: (i) undefined thresholds of kidney function decline at which to pursue biopsy; (ii) the experiential evidence that a clinical diagnosis of CKDu is predictive of biopsy diagnosis; (iii) the lack of a specific treatment for CKDu at present; and (iv) concerns about safety and risk and cost to the patient. Kidney biopsies offer definitive diagnosis, provide prognostic information, and advance our knowledge about the spectrum of disease putatively to enable the institution of preventive and/or therapeutic strategies. The tension among limited resources, patient burden, and quest for accuracy in disease diagnostics leads to the following question: Are kidney biopsies clinically indicated among persons suspected of having CKDu in regions known to be CKDu hotspots? In 2022 and 2023, the International Society of Nephrology's (ISN) i3C (International Consortium CKDu Collaborators) Working Group and the ISN Renal Pathology Working Group held 3 consensus-building meetings to explore the pros and cons of pursuing kidney biopsies in CKDu hotspots. In addition, a survey was circulated to ISN members through 3 ISN regional boards (Latin America, South Asia, and Oceania and South East Asia) to assess biopsy practices in nonproteinuric kidney diseases. Acknowledging that a group of research-intensive, internationally engaged nephrologists and associated research scientists participated in this endeavor, we summarize the key considerations and describe the group's consensus. The contents of this article were reviewed by the chairpersons of the 3 ISN Regional Boards. We note that, ideally, a rigorous, research-based approach to biopsies will be pursued in many CKDu hotspots, but the reality on the ground, including the lack of resources to apply advanced tissue-processing techniques, means that such studies may not have a broad or immediate reach, and in the meantime, clinicians are faced with counseling patients with CKDu. Thus, our aim is to provide practicing clinicians with a framework around which to anchor personalized discussions with patients, and to maximize the clinical and scientific output of clinically indicated biopsies in CKDu hotspots. Traditional indications for kidney biopsy emphasize proteinuria (with or without hematuria), or unexplained acute kidney injury. Persons with CKDu may not fall under any of these categories, as they may experience variable and insidious loss of kidney function without an active urinary sediment. We implemented a simple survey posing several scenarios of nonproteinuric kidney disease presentation at young and middle age and in patients of male and female sex (Figure 1). A total of 68 nephrologists responded, a majority from affected regions (32% and 36% from South Asia and Latin America). A total of 40% of the responding nephrologists would opt to recommend a kidney biopsy on a 36-year-old male or female, with an estimated glomerular filtration rate (eGFR) of 80 ml/min per 1.73 m2, and evidence of kidney function decline by an eGFR change > 5 ml/min per 1.73 m2 over a short time frame; fewer (∼25%) would pursue a biopsy if the patient were a 60-year-old male. A similar pattern of responses held if eGFR were < 60 ml/min per 1.73 m2 and no clear evidence of eGFR decline over a short time frame. More than 70% would pursue biopsy in patients with an eGFR of 58 ml/min per 1.73 m2, and evidence of eGFR decline, independent of age or sex. A biopsy in any of these 3 scenarios, with CKDu being suspected, could address diagnostic uncertainty, and even in the case of pathologically confirmed tubulointerstitial nephritis, could potentially point to known etiologies other than CKDu (e.g., nephrocalciniosis, oxalate nephropathy, granulomatous inflammation indicating tuberculosis or sarcoid, or plasma-rich infiltrate indicating IgG4 disease). In addition, kidney biopsy can provide valuable information for prognostication by quantifying the extent of tubular atrophy, interstitial fibrosis, and secondary glomerulosclerosis, which is essential for developing a treatment plan. Conceivably, clinical trials targeting either tubular inflammation or fibrosis may be offered in the near future, and a kidney biopsy could facilitate patient enrollment. The uncertainty that exists in the utility of kidney biopsy was acknowledged by ISN i3C Working Group discussants, especially in the context of socioeconomic constraints on the patients, many of whom may need to travel or miss work to undergo the procedure. Some clinically important questions—such as, does biopsy alter outcomes—remain unanswered, and in fact, they can be answered only with systematic approaches to biopsy. Furthermore, the ISN i3C Working Group consists largely of academically focused nephrologists who aim to investigate CKDu in depth, and thus, they have an inherent bias toward gaining more information when doing so is feasible. Ultimately, the decision to pursue biopsy in clinical encounters is reliant on physician-facilitated personalized discussion of risks and benefits, with patient autonomy at the center of these discussions. The best-described CKDu hotspots exist in low- and middle-income countries.3Johnson R.J. Wesseling C. Newman L.S. Chronic kidney disease of unknown cause in agricultural communities.N Engl J Med. 2019; 380: 1843-1852Crossref PubMed Scopus (182) Google Scholar A recent review of 39 studies described safety data from 19,500 kidney biopsies performed in 18 low- and middle-income countries across 6 regions.4Kajawo S. Ekrikpo U. Moloi M.W. et al.A systematic review of complications associated with percutaneous native kidney biopsies in adults in low- and middle-income countries.Kidney Int Rep. 2021; 6: 78-90Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar In comparison to a meta-analysis drawing the majority of its data from high-income countries, the biopsy complication rates were similar (Table 1).5Poggio E.D. McClelland R.L. Blank K.N. et al.Systematic review and meta-analysis of native kidney biopsy complications.Clin J Am Soc Nephrol. 2020; 15: 1595-1602Crossref PubMed Scopus (93) Google Scholar Complication rates were lower with real-time ultrasound-guided biopsies, as compared to pre-marked and blind procedures (12.4% vs. 14.9% and 24.5%, respectively).Table 1Metanalyses data on the complication risk in kidney biopsies, by settingComplicationLMICHICBiopsy, n19,500118,064Hematuria1.48%3.5%Hematomas2.4%11%Transfusion0.24%1.6%Nephrectomy/intervention0.04%0.3%Death0.01%0.06%HIC, high-income countries; LMIC, low- and middle-income countries.Data are from Kajawo et al. 4Kajawo S. Ekrikpo U. Moloi M.W. et al.A systematic review of complications associated with percutaneous native kidney biopsies in adults in low- and middle-income countries.Kidney Int Rep. 2021; 6: 78-90Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar (LMIC) and Poggio et al.5Poggio E.D. McClelland R.L. Blank K.N. et al.Systematic review and meta-analysis of native kidney biopsy complications.Clin J Am Soc Nephrol. 2020; 15: 1595-1602Crossref PubMed Scopus (93) Google Scholar (HIC). Open table in a new tab HIC, high-income countries; LMIC, low- and middle-income countries. Data are from Kajawo et al. 4Kajawo S. Ekrikpo U. Moloi M.W. et al.A systematic review of complications associated with percutaneous native kidney biopsies in adults in low- and middle-income countries.Kidney Int Rep. 2021; 6: 78-90Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar (LMIC) and Poggio et al.5Poggio E.D. McClelland R.L. Blank K.N. et al.Systematic review and meta-analysis of native kidney biopsy complications.Clin J Am Soc Nephrol. 2020; 15: 1595-1602Crossref PubMed Scopus (93) Google Scholar (HIC). The ISN i3C Working Group discussants noted that typical patients with suspected CKDu are young, normotensive, and have normal or low body mass index: thus, they do not have the well documented risk factors for bleeding complications post-biopsy.6Hogan J.J. Mocanu M. Berns J.S. The native kidney biopsy: update and evidence for best practice.Clin J Am Soc Nephrol. 2016; 11: 354-362Crossref PubMed Scopus (187) Google Scholar Furthermore, they also are less likely to be on antiplatelet or anticoagulant therapy or to have severe acute kidney injury needing hospitalization. Thus, the ISN i3C Working Group concluded that a kidney biopsy is likely to be as safe, if not safer, as it is for the traditional indications of kidney biopsy, as long as a trained nephrologist or a radiologist is performing the procedure with ultrasound guidance and using an automated biopsy gun. For cases in which the patient and treating nephrologist mutually agree to proceed with a kidney biopsy, the group discussed approaches to maximizing both the clinical and research benefit of a biopsy. Through consensus, we developed a case report form (Supplementary Appendix S1) to collect relevant clinical information before and after the procedure. We prioritized this form not only to be concise and practical for clinicians practicing in regions with a high prevalence of kidney disease, but also to enable research outputs when collated across multiple suspected CKDu hotspots. Several benefits exist for such standardized data gathering, some of which will be directly and immediately relevant to patient care. For example, we could inform the pretest probability of kidney biopsy altering the diagnosis from primary tubulointerstitial kidney disease of unknown cause to a diagnosis attributable to specific cause or treatment. Also, the diagnostic certainty can conceivably affect prognosis; again, systematic clinical data matched to briefly collected outcome data could answer this question. Although available literature indicates that a higher degree of fibrosis will be associated with a worse prognosis, the precision with which we can make prognostic predictions will improve drastically with systematically available clinical data and standardized biopsy reporting. Finally, systematic approaches will elucidate the entire spectrum of pathology findings associated with the final clinical diagnosis of "CKDu," as both acute and severely chronic presentations with substantial secondary glomerusclerosis have been described. The value of standardized biopsy reporting has been demonstrated in several disease entities: specifically, the Banff classification for reporting of kidney transplant biopsies and the MEST-C (for mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and the presence of crescents) score for IgA nephropathy scores are examples of standardized biopsy reporting that facilitated comparisons across sites and/or regions and have led to improved understanding of disease processes. Biopsy diagnosis and prognostication in presumed tubulointerstitial disease currently faces high interobserver and pathologist variability. Having a preconsensus overview with training sessions, and using standardized descriptors to document the pathologic findings in the kidney biopsy, has proven to be the best approach to improve concordance.7Barisoni L. Troost J.P. Nast C. et al.Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images.Modern Pathol. 2016; 29: 671-684Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Thus, building on the pathology discussions at the National Institutes of Health (NIH)-sponsored Third International Workshop on Chronic Kidney Disease of Uncertain Etiology in 2019, templates introduced by Wijkstrom and colleagues,8Wijkstrom J. Annadata K.C. Elinder C.G. et al.Clinical findings and kidney morphology in chronic kidney disease of unknown cause in India.J Intern Med. 2023; 294: 492-505Crossref PubMed Scopus (3) Google Scholar and input of pathologists in the ISN Renal Pathology Working Group, we present a reporting form that facilitates the systematic description of each compartment in the biopsy (Supplementary Appendix S2). Electron microscopy capability may not exist in a majority of settings, but technology enables later review of formalin-fixed paraffin-embedded (FFPE) tissue for electron microscopy, and increasingly, the application of additional molecular techniques. Careful record keeping of procedures and conditions of tissue storage would enable the creation of a core tissue bank with the potential to test multiple hypotheses. The clinical scenarios of persons with suspected CKDu represent outliers to conventional indications for kidney biopsy. No disease-specific treatment exists at the present time, and many believe that a reasonable probability exists of clinical and pathologic diagnostic concordance in CKDu hotspots. However, without systematic clinical data and pathology review of kidney biopsies, we cannot be certain of such an assumption. Until recently, biopsies in people with presumed diagnoses (such as diabetes and hypertension) had not been thought to be of clinical value. With the Kidney Precision Medicine Program, and the advent of increasingly sophisticated technologies for assessment of kidney tissue, nephrologists need to reexamine previous attitudes toward performing biopsies in CKD. The ISN i3C Working Group thoroughly considered the various perspectives on the risks and benefits of performing kidney biopsy in people with suspected CKDu. The Working Group concluded that kidney biopsies for a clinical indication should be considered routinely in cases of suspected CKDu. Biopsies are justified given the need to both confirm a diagnosis and assess prognosis based on the acuity and severity of histologic features (Table 2). This justification was considered within the context of a low risk for complications in a "standard-of-care" setting of kidney biopsies performed by an ultrasound-guided nephrologist or a radiologist. The ISN i3C Working Group suggested that an informed patient-centered discussion be conducted so that patients are made aware of the current lack of disease-specific treatment, the potential patient-borne costs, and the individual risks for procedural complications.Table 2ISN i3C recommendations for kidney biopsy in CKDu endemic regionsRecommendationRationaleKidney biopsies for clinical indication should be considered routinely in cases of suspected CKDuDiagnostic uncertainty without biopsyPrognostic dataPhenotype of potentially affected patients has low risk for complicationsStandard of care for kidney biopsy safety must exist when offering kidney biopsies: ultrasound guidance, biopsy gun, trained nephrologist or radiologist, biochemical and bleeding risk profile reviewDecreases risk for complications when these conditions are met, regardless of resource settingStandard clinical data inclusive of occupational history and residence, biopsy processing protocol, and pathology review output should be gathered among all persons undergoing biopsy for any reason in CKDu-endemic regionStandard minimal dataset and pathology scoring approach will enable optimal use of available clinical data with a minimum of additional resourcesCKD, chronic kidney disease; CKDu, chronic kidney disease of unknown etiology; ISN i3C, International Society of Nephrology International Consortium of Collaborators on Chronic Kidney Disease of Unknown Etiology. Open table in a new tab CKD, chronic kidney disease; CKDu, chronic kidney disease of unknown etiology; ISN i3C, International Society of Nephrology International Consortium of Collaborators on Chronic Kidney Disease of Unknown Etiology. Another major recommendation by the ISN i3C Working Group is for nephrology clinics in CKDu hotspots to standardize case report forms and pathology report forms. This standardization will enable collaborative approaches to advancing knowledge about the disease (Figure 2). At minimum, such an approach would facilitate large-scale intra- and cross-country comparisons on disease presentation, delineate a spectrum of pathology findings, and correlate specific findings in the tubulointerstitial compartment to outcomes. CKDu remains an important problem in a number of regions around the world. This position statement prepared by the ISN i3C Working Group provides guidance to those working in endemic regions regarding clinical indications for kidney biopsies in individuals suspected of having CKDu. EW reports being a member of the data and safety monitoring board (DSMB) for a CKDu project in Sri Lanka conducted by Stanford University and the National Hospital Kandy; Deputy Chair of the i3C Working Group of the International Society of Nephrology (ISN i3C [CKDu] WG), and President-Elect of the Sri Lanka Society of Nephrology. BC reports receiving grants or contracts from UK Medical Research Council and Colt Foundation (both paid to his institution). VSP reports receiving payment or honoraria from Bayer, AstraZeneca, Novartis, and Sanofi; and being the General Secretary of the Latin American Society of Nephrology and Hypertension (unpaid role). DF reports receiving grants or contracts from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), the Department of Defense, royalties or licenses from Beth Israel Deaconess Medical Center, consulting fees from Vertex; payment or honoraria from Sanofi; having patents related to APOL1; and participating as a member for DSMB for the National Institutes of Health (NIH). MM reports receiving payment, grants, contracts, honoraria, and/or support for travelling and/or meetings from AztraZeneca and Boehringer; and having a leadership role at International Society of Peritoneal Dialysis (ISPD) Council, the Kidney Disease: Improving Global Outcomes (KDIGO) writing group for the CKD Guideline; being the KDIGO Chair Executive Committee and Kidney International editor. VJ reports receiving grants, contracts, payment and/or consulting fees from GlaxoSmith Klein, Baxter Healthcare, Biocon, Vera, Biocryst, GSK, Bayer, Astrazeneca, Boehringer, Ingelheim, NephroPlus, Zydus, and Cadilla (all paid directly to his institution); and participating as a member for DSMB for Zydus Cadilla. NK reports receiving all support for this article from 5R01DK12713803: NIH (Stanford University), grants or contracts from 5U01DK13006002: NIH (Stanford University), and payment from Elsevier for Amirsys series book on renal pathology. AL reports receiving support for attending meetings and/or travelling by International Society of Nephrology and NIH; participating as a member for DSMB for NIH Chronic kidney disease of UnceRtain Etiology in Agricultural Communities (CURE) Consortium; and having a leadership role on the ISN Research Committee and in the ISN Advocacy Working Group. SA reports that all support for this article comes from US NIH NIDDK R01DK127138, Doris Duke Charitable Fund, Stanford Center for Innovation in Global Health and King Center; serving as medical director for a Satellite Healthcare Dialysis unit; receiving consulting fees from Vera Therapeutics (Consultancy) and HealthPals; and participating as a member for a DSMB for NIA funded clinical trial on metabolic acidosis and CKD; serving as Chair of the ISN i3C Working Group and as a Board Member of the ISN US NIH NIAID U01, and as Executive Committee member for American Nephrologists of Indian Origin; and that Ascend Clinical and Abbott lab funds testing for US NIH NIAID funded U01. SB reports receiving payment or honoraria for educational purposes from Baxter, Astra Zeneca, and Boehringer Ingleheim; participating on the Astra Zeneca advisory board for hyperkalaemia management; being a Member of the Board of Directors (National Kidney Foundation of Malaysia), the Chair of ISN Oceania and South East Asia (OSEA) Regional Board, Executive Committee member of the Asian Pacific Society of Nephrology (APSN), and a KDIGO Executive Committee member. JB reports receiving grants or contracts from NIH (NIH R01 DK125351). PE reports receiving grants or contracts from the Federal Ministry of Education and Research (BMBF) and Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ). AFF reports being President (2019–2021) of the Latin American Society of Nephrology and Hypertension, with no payments made, and being Deputy Chair (2023–2025) of the ISN Latin America Regional Board. AZF reports receiving grants or contracts (R01DK127138 [to SA]), and participating on the Advisory group for NIH Program Project U01DK130060. RSBF reports receiving all support for the present article from the Texas A&M University School of Public Health, and receiving grants or contracts from NIH Fogarty International Center. RJJ reports receiving grants or contracts from NIH (NIH R01 DK125351), payment or honoraria from Horizon Pharma and Dinora LLC (paid to him), stocks from XORTX Therapeutics (to him); and having financial or nonfinancial interests in Colorado Research Partners (Equity). All the other authors declared no competing interests. This work was supported by in-kind administrative support from the International Society of Nephrology. Shuchi Anand, Division of Nephrology, Stanford University School of Medicine, Palo Alto, California, USA Carmen Avila-Casado, Department of Laboratory Medicine & Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada Sunita Bavanandan, Department of Nephrology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia Divya Bajpai, Department of Nephrology, Seth G.S.M.C. and K.E.M. Hospital, Mumbai, India Suman Behera, Division of Nephrology, McMaster University, Hamilton, Ontario, Canada; William Osler Health System, Brampton, Ontario, Canada Jared M. Brown, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA Ben Caplin, University College London Department of Renal Medicine, London, UK; Royal Free London NHS Foundation Trust, London, UK Christoph Daniel, Department of Nephropathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany Marc de Broe, Department Physiopathology, University Antwerpen, Antwerpen, Belgium Philipp Enghard, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany; Deutsches Rheumaforschungszentrum, and Institute of the Leibniz Foundation, Berlin, Germany Alejandro Ferreiro Fuentes, Centro de Nefrología, Universidad de la República, Montevideo, Uruguay Andrew Z. Fire, Departments of Pathology and Genetics, Stanford University School of Medicine, Palo Alto, California, USA Rebecca S.B. Fischer, Department of Epidemiology & Biostatistics, School of Public Health, Texas A&M University, College Station, Texas, USA David Friedman, Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA Pablo Garcia, Department of Medicine (Nephrology), University of New Mexico, Albuquerque, New Mexico, USA Marvin González-Quiroz, Department of Renal Medicine, University College London, London, UK; WUQU' KAWOQ, Maya Health Alliance, Tecpán, Guatemala; School of Medicine, Universidad Nacional de Chimborazo, Riobamba, Ecuador Chula Herath, Sri Lanka Society of Nephrology, Colombo, Sri Lanka Eva Honsova, Unilabs Pathology and Charles University, Prague, Czech Republic Vivekanand Jha, George Institute for Global Health, UNSW, New Delhi, India; School of Public Health, Imperial College, London, UK; Prasanna School of Public Health, Manipal Academy of Medical Education, Manipal, India Richard J. Johnson, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA Talerngsak Kanjanabuch, Division of Nephrology, Department of Medicine and Center of Excellence in Kidney Metabolic Disorders, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; PD Excellent Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand Neeraja Kambham, Department of Pathology, Stanford University School of Medicine, Palo Alto, California, USA Varun Kumar Bandi, Dr. Pinnamaneni Siddharatha Institute of Medical Sciences & RF, Andhra Pradesh, India Adeera Levin, Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada Magdalena Madero, Instituto Nacional de Cardiologia Ignacio Chávez, Mexico City, Mexico Sreedhar Mandayam, Dialysis Services, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA Alexei Mikhailov, Atrium Wake Forest Baptist Medical Center, Medical Center Drive, Winston-Salem, North Carolina, USA Nishantha Nanayakkara, National Hospital Kandy Sri Lanka, Kandy, Sri Lanka Nadeesha Nishanthi, ESE Nephrology, TH Anuradahpura dialysis and transplant Center, North Central Province, Sri Lanka Yannick M. Nlandu, Nephrology Unit, Kinshasa University Hospital, University of Kinshasa, Kinshasa, Democratic Republic of The Congo Maria Pippias, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; North Bristol NHS Trust, Renal Unit, Bristol, UK Narayan Prasad, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Muhammad Rafiqul Alam, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; ISN South Asia Regional Board, International Society of Nephrology, Brussels, Belgium; Bangladesh Renal Journal, Dhaka, Bangladesh Vicente Sanchez Polo, Nephrology and Kidney Transplant Division, Social Security Guatemalan Institute, Concepción, Guatemala Surya V. Seshan, Weill Cornell Medicine, New York, New York, USA David Sheikh-Hamad, Selzman Institute for Kidney Health, Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA Geetika Singh, Renal Pathology and Electron Microscopy Laboratory, All India Institute of Medical Sciences, New Delhi, India Anna Strasma, Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA Carmen Tzanno-Martins, Renalclass, São Paulo, Brazil Ifeoma Ulasi, Renal Unit, Department of Medicine, College of Medicine, University of Nigeria, Nsukka , Enugu , Nigeria Benjamin A. Vervaet, Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany; Laboratory of Pathophysiology, University Antwerp, Antwerp, Belgium Sushrut S. Waikar, Section of Nephrology, Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine, Boston, USA Eranga Wijewickrama, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka Julia Wijkström, Division of Renal Medicine, Department of CLINTEC, Karolinska Institutet, Solna, Stockholm, Sweden Chih-Wei Yang, Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan Download .docx (.03 MB) Help with docx files Supplementary File (Word) Supplementary Appendix S1. Case report form. Supplementary Appendix S2. Standardized biopsy report form.