Kidney Week

Abstract: FR-PO596

Understanding the Clinical Genetics of Kidney Stone Disease Using a Kidney Disease-Specific Genetic Test Panel

Session Information

• Genetic Diseases: Tubulopathies
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Labagnara, Kevin, Albert Einstein College of Medicine, Bronx, New York, United States

Kevin Labagnara,

• Patel, Rutul D., Montefiore Medical Center, New York, New York, United States

Rutul D. Patel,

• Green, Benjamin, Albert Einstein College of Medicine, Bronx, New York, United States

Benjamin Green,

• Zhu, Michael, Albert Einstein College of Medicine, Bronx, New York, United States

Michael Zhu,

• Gupta, Kavita, Montefiore Medical Center, New York, New York, United States

Kavita Gupta,

• Asencio, Andrea A., Montefiore Medical Center, New York, New York, United States

Andrea A. Asencio,

• Sharma, Deep, Montefiore Medical Center, New York, New York, United States

Deep Sharma,

• Chen, Wei, Montefiore Medical Center, New York, New York, United States

Wei Chen,

• Raskolnikov, Dima, Montefiore Medical Center, New York, New York, United States

Dima Raskolnikov,

• Donnelly, Jillian, Montefiore Medical Center, New York, New York, United States

Jillian Donnelly,

• Watts, Kara, Montefiore Medical Center, New York, New York, United States

Kara Watts,

• Small, Alexander, Montefiore Medical Center, New York, New York, United States

Alexander Small,

Background

The etiology of kidney stone disease (KSD) is multifactorial. Emerging data suggest that genetics may play a larger role than previously thought. 11% to 56% of KSD has heritable stone-related genetic mutations. We aimed to better understand the genetics of KSD using a kidney disease focused genetic test at our diverse, urban academic center.

Methods

A single-center, prospective study was conducted on patients with recurrent stones or a single stone with family history. Those with known causes of urolithiasis, active UTI or acutely passing a stone were excluded. All underwent standard stone analysis, serum metabolic evaluation, 24-hour urine studies and buccal DNA screen for 385 kidney disease-linked genes using the Natera Renasight^TM kit. Variants were categorized as “positive” if pathologic, “carrier” if autosomal recessive, or of “uncertain significance” (VUS).

Results

89 patients were enrolled. 55% were female, 60% were Hispanic, and 30% reported a first-degree family history. Median (IQR) patient age was 49 years (IQR 41-60) with 2 (IQR 1-3) stone episodes in the prior 5 years. 61% formed calcium oxalate stones.

7 (8%) subjects were positive for amyloidosis (TTR), Alport syndrome (COL4A3), cystinuria (SLC7A9), polycystic kidney disease (PKD1), or FSGS (APOL1). 39 (44%) were carriers for 30 unique genes and all patients had multiple VUS spanning 247 unique genes. Positive/carrier patients were similar to negative patients in demographics, comorbidities, stone analysis and 24-hour urine studies. They had lower median vitamin D (22.3 vs 29.7 ng/ml; p=0.041) and higher potassium (4.4 vs 4.2 mEq/ml; p=0.090).

Conclusion

Our study sheds light on potential genetic variants in recurrent stone formers in our diverse patient population. The initial wide range of results support the complex and polygenetic expression of KSD.

Funding

• Commercial Support – Natera