Snoek R, et al. - Researchers evaluated homozygous NPHP1 full gene deletions in adult-onset ESRD in order to determine the prevalence of nephronophthisis (NPH) in adults. NPH was identified as a relatively frequent monogenic cause of adult-onset ESRD, taking into account that other mutation types in NPHP1 or mutations in other NPH-causing genes were not analyzed. Clinical diagnosis of NPH was lacking in 88% of patients, therefore, wider application of genetic testing in adult-onset ESRD may be warranted.

Methods

• Single-nucleotide polymorphism genotyping was performed in adult renal transplant recipients from 5 cohorts of the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN).
• Based on median log2 ratios and B-allele frequency patterns, autosomal copy number variants (such as deletions) were determined after quality control.
• Independent validation of the findings was carried out in one cohort.
• The analysis included only those patients who had adult-onset ESRD, defined as start of RRT at ≥18 years old.

Results

• A total of 5606 patients with adult-onset ESRD were included; of those, 26 (0.5%) showed homozygous NPHP1 deletions.
• Homozygosity for this deletion was not demonstrated by donor controls.
• For patients with NPH, the reported median age at ESRD onset was 30 (range, 18–61) years, with 54% of patients age ≥30 years old.
• As per data, only three (12%) patients were phenotypically classified as having NPH, whereas most patients were defined as having CKD with unknown etiology (n=11; 42%).