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. 2022 Dec 13;5(2):100585.
doi: 10.1016/j.xkme.2022.100585. eCollection 2023 Feb.

Renal Genetics Clinic: 3-Year Experience in the Cleveland Clinic

Xin Yee Tan  1 , Chloe Borden  2 , Mary-Beth Roberts  3 , Sarah Mazzola  3 , Queenie K-G Tan  3 , Richard Fatica  1 , James Simon  1 , Juan Calle  1 , Jonathan Taliercio  1 , Katherine Dell  4 , Laura Ferreira Provenzano  1 , Diana Deitzer  1 , Hernan Rincon-Choles  1 , Ali Mehdi  1 , Michael Lioudis  5 , Emilio D Poggio  1 , Georges Nakhoul  1 , Saul Nurko  1 , Tarek Ashour  1 , Raed N Bou Matar  4 , Charles Kwon  4 , Brian Stephany  1 , George Thomas  1 , Yu-Wei Cheng  6 , Deanna Leingang  3 , Adnan Alsadah  3 , Rhyan Maditz  1 , Heyka Robert  1 , Tushar Vachhrajani  1 , John Sedor  1 , Crystal Gadegbeku  1 , Xiangling Wang  1   2   3   7   8
Affiliations

Renal Genetics Clinic: 3-Year Experience in the Cleveland Clinic

Xin Yee Tan et al. Kidney Med. .

Abstract

Rationale & objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience.

Study design: Retrospective cohort.

Setting & participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed.

Analytical approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs.

Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management.

Limitations: Retrospective and single-center study.

Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

Keywords: Genetic testing; kidney disease; renal genetics.

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Figures

Figure 1
Figure 1
Referrals from multiple specialties to the Renal Genetics Clinic. Abbreviations: OBGYN, obstetrician-gynecologist; ENT, ear, nose, and throat specialist.
Figure 2
Figure 2
Examples of dysmorphic features noted in the Renal Genetics Clinic. (A) Microcephaly with backward-sloping forehead. (B) Ear malformation. (C) Dental anomaly. (D) Syndactyly.
Figure 3
Figure 3
Genetics testing modalities in the Renal Genetics Clinic. (A) Venn graph showing utilization of more than one genetic testing modality (overlapping area) in patients. (B) Number of patients who were tested by each modality. Abbreviations: CMA, chromosomal microarray; ES, exome sequencing; WES, whole exome sequencing.
Figure 4
Figure 4
The diagnostic yield in the Renal Genetics Clinic. (A) Test results among all patients who were suggested for genetic testing (n=256). (B) Diagnostic yield among patients with different presentations. (C) Diagnostic yield of each testing modality. Abbreviations: CAKUT, congenital anomalies of the kidney and urinary tract; CMA, chromosomal microarray; ES, exome sequencing; VUS, variant of unknown significance.
Figure 5
Figure 5
Common genetic findings in the Renal Genetics Clinic.
See this image and copyright information in PMC

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