Correlation of Genetic Testing with Kidney Biopsy Findings

Background: Commercialy available gene tests are widely used in clinical practice to identify genes causing kidney disease. While the biopsy is the gold standard for diagnosing kidney disease, the procedure comes with risk. It is unclear whether gene testing can yield a suitable diagnosis and prevent the need for biopsy. Methods: We analyzed data from all patients undergoing a kidney biopsy from 2021 to 2025 who also had genetic testing from a commercially available gene test (Natera). Biopsies were restricted to native kidney biopsy. Biopsies were excluded if tissue obtained was unable to yield an adequate diagnosis. A positive genetic diagnosis was reported for patients with autosomal dominant or recessive pathogenic variants and patients with APOL1 G1/G2 high risk alleles. Clinical data for creatinine, proteinuria, and biopsy diagnosis were correlated with genetic findings. Results: Out of 58 biopsies with genetic testing there were 8 positive results with a rate of 13.8%. Genes identified were APOL1 (3), Col4A4 (2), TTR (1), HNF1B (1), and INF2 (1). In patients with APOL1, pathology did not correlate with disease severity. Out of the 3 patients with APOL1 positivity, all three were CKD stage 3A, with one patient having no proteinuria, one patient having < 1 gm of proteinuria and 1 patient having > 1 gm but < 3 gm proteinuria. Biopsy findings were all consistent with mild interstitial fibrosis and tubular atrophy (IFTA). In 2 patients with Col4A4 mutations, neither patient had a known family history of CKD. One patient had CKD stage 3A and the other patient CKD stage 3B, with both patients having mild proteinuria (< 1 gm). Biopsy findings were consistent with mild IFTA and minimal glomerulosclerosis. In the one patient with INF2 positivity, there was moderate proteinuria and CKD stage 3. Biopsy was consistent with minimal glomeruloscloerosis. In one patient with HNF1B positivity, there was CKD stage 3a with minimal proteinuria. Biopsy findings were consistent with moderate to severe IFTA. In one patient positive for TTR, there was CKD stage 3A with no proteinuria and a biopsy consistent with mild IFTA. Conclusion: Gene testing has a positive yield of approximately 10% in patients undergoing kidney biopsy. APOL1 and collagen genes are most likely to correlate with biopsy findings. Pre-emptive gene testing may prevent the need for kidney biopsies in the future