Genetic diagnosis and renal biopsy findings in the setting of a renal genetics clinic.

ABSTRACT

As genetic testing becomes more available, its utilization as an early diagnostic tool in nephrology is more common. The objective of the study is to examine diagnostic agreement between the renal biopsy findings and genetic diagnoses. A retrospective study was conducted in February 2022. A total of 28 patients had both genetic diagnosis and histologic results (n = 1 nephrectomy, n = 27 biopsy). We collected clinical, renal biopsy findings, and genetic information. The relationship between the histologic findings and the genetic diagnoses was classified as concordant, nonspecific, and discordant. A total of 15 males and 13 females were included (mean age = 9.6 years). Clinical suspicion of Alport syndrome was the most common reason for referral (n = 11, 39.3%), followed by nephrotic syndrome (n = 8, 28.5%), "other" (n = 6, 21.4%), cystic kidney disease (n = 1, 3.6%), isolated hematuria (n = 1, 3.6%), and non-nephrotic proteinuria (n = 1, 3.6%). The overall concordance rate between renal histologic and genetic diagnoses was 71.4% (20/28), nonspecific biopsy results were observed in 17.9% (5/28), and discordant results were observed in 10.7% (3/28). All patients referred for suspected Alport Syndrome had pathogenic/likely pathogenic variants in one of the COL4A genes. Two cases of Lowe syndrome and one of PAX2-associated nephropathy had discordant histology findings. Agreement between renal histologic findings and genetic results varies based on the reason for referral. There was a complete agreement for patients referred for Alport Syndrome; However, there were examples that renal biopsy showed secondary findings that were not specifically associated with the underlying genetic results.