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Background: The kidney biopsy is the gold standard for diagnosing glomerular diseases. Large-scale, epidemiologic studies describing the prevalence of kidney diseases are lacking, especially in the United States. We aimed to determine the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise., Methods: We identified all patients with a native kidney biopsy performed or reviewed at the Cleveland Clinic from January 2015 to September 2021. Retrospective chart review was performed to obtain clinical and demographic characteristics. Results were stratified by age, sex, race, and location to determine epidemiologic trends., Results: Of >9600 patients, we excluded transplant and donor biopsies and unavailable records, and included 4128 patients with native kidney biopsy data. The median age was 60 years, with 46% female patients. Self-reported racial demographics included 73% White, 22% Black, 3% multiracial, and 2% Asian background, with 5% Hispanic. Common diagnoses were: FSGS ( n =633, 15%), diabetic kidney disease (DKD) ( n =602, 15%), IgA nephropathy ( n =319, 8%), lupus nephritis (LN) ( n =289, 7%), pauci-immune glomerulonephritis ( n =275, 7%), membranous nephropathy ( n =211, 5%), and amyloidosis ( n =110, 3%). There were 3322 patients in Ohio, with 361 patients in Florida. Using multivariate analysis, those aged >70 years were more likely to have FSGS, whereas those <45 years were more likely to have IgA nephropathy or LN. Males were more likely to have FSGS or IgAN, and less likely to have LN. Black patients were more likely to have FSGS, DKD, or LN. Hispanic patients were more likely to have DKD. Finally, patients in Florida were more likely to have LN. There was no change in the disease spectrum before and during the COVID-19 pandemic., Conclusion: Our study catalogs the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise. This lays the foundation for glomerular disease clinical trials, and highlights the need for a standardized national kidney biopsy registry to bolster glomerular and kidney disease research in the United States., Competing Interests: S. Bobart reports having honorarium from Travere Therapeutics and other interests or relationships as Faculty for the GlomCon fellowship. L. Herlitz reports having consultancy agreements with ChemoCentryx; and reports having an advisory or leadership role on the ASN Kidney360 editorial board. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)