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Introduction:Cure Glomerulonephropathy (CureGN) is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy. We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility, and correlation with clinical parameters at biopsy. Methods:Definitions were established for glomerular, tubular, interstitial, and vascular lesions evaluated semiquantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence. Cases with curated pathology materials as of April 2019 were scored by a randomly assigned pathologist, with at least 10% of cases scored by a second pathologist. Scoring reproducibility was assessed using Gwet’s agreement coefficient (AC)1 statistic and correlations with clinical variables were performed. Results:Of 800 scored biopsies (134 MCD, 194 FSGS, 206 MN, 266 IgA), 94 were scored twice (11.8%). Of 60 pathology features, 46 (76.7%) demonstrated excellent (AC1>0.8), and 12 (20.0%) had good (AC1 0.6–0.8) reproducibility. Mesangial hypercellularity scored as absent, focal, or diffuse had moderate reproducibility (AC1 = 0.58), but good reproducibility (AC1 = 0.71) when scored as absent or focal versus diffuse. The percent glomeruli scored as no lesions had fair reproducibility (AC1 = 0.34). Strongest correlations between pathologic features and clinical characteristics at biopsy included interstitial inflammation, interstitial fibrosis, and tubular atrophy with estimated glomerular filtration rate, foot process effacement with urine protein/creatinine ratio, and active crescents with hematuria. Conclusions:Most scored pathology features showed excellent reproducibility, demonstrating consistency for these features across multiple pathologists. Correlations between certain pathologic features and expected clinical characteristics show the value of this approach for future studies on clinicopathologic correlations and biomarker discovery.

Introduction:There is an increasing need to return genetic testing results to patients with kidney disease who were first genotyped on a research basis. Operationalizing this process in nephrology clinics is challenged by a limited number of genetic providers with whom to partner and a general lack of support services for all clinicians. Methods:We administered a survey in March 2022 to assess the current ability and ongoing needs of nephrology divisions to return clinically significant research genetic results to patients and to implement clinical genetic testing. This survey was distributed to institutions within the Nephrotic Syndrome Study Network (NEPTUNE) as part of the planning process for return of research genetic results to participants with pathogenic variants in Mendelian nephrotic syndrome genes. Results:Twenty-seven of 28 sites (96%) completed the survey. 59% (n= 16) of sites said they could handle return of research genetic results independently, with the rest expressing hesitation about the volume and complexity of patients and the limited resources and access to genetics services. 81% (n= 22) of these institutions did have a genetics clinic and 26% (n= 7) have a nephrology genetics clinic. However, 70% (n= 10) of these clinics have a waiting time over 1 month. 89% of divisions (n= 24) were conducting genetic testing and 96% of those (n= 23) used a kidney multi-gene panel. In 46% of divisions (n= 11), nephrologists were handling logistics of obtaining genetic testing samples themselves. Conclusion:We identified specific areas of support needed for return of clinically significant genetic results from research studies. While the surveyed nephrologists were conducting genetic testing, there were limitations in the support services available. This survey will help guide other research studies that wish to return genetic results to participants and also highlight the need for increasing support to effectively operationalize genetic testing in nephrology clinics.