Association between nephrolithiasis and kidney disease progression in patients with autosomal dominant polycystic kidney disease: a prospective cohort study

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ABSTRACT Background Nephrolithiasis is a common complication in autosomal dominant polycystic kidney disease (ADPKD), yet its impact on long-term kidney outcomes remains uncertain. Although experimental and retrospective studies suggest a potential role of kidney stones in accelerating disease progression, prospective evidence based on imaging-confirmed nephrolithiasis is limited. Methods This prospective cohort study included 410 patients with ADPKD from the HOPE-PKD cohort who underwent baseline abdominal computed tomography (CT) within 1 year of enrollment. Nephrolithiasis was defined as radiopaque lesions located within the collecting system, whereas cyst wall calcifications were excluded based on established CT criteria. The primary outcome was initiation of renal replacement therapy (RRT) due to kidney failure. The secondary outcome was a composite of ≥50% decline in estimated glomerular filtration rate, doubling of serum creatinine, or initiation of RRT. Multivariable Cox proportional hazards models were constructed with adjustment for demographic, metabolic, genetic, and imaging-based risk factors, including imaging-based risk stratification. Results During a median follow-up of 5.18 years, 51 (12.4%) and 96 (23.4%) participants reached the primary and secondary endpoints, respectively. After adjustment for demographic, metabolic, and disease severity factors, the stone group showed a significantly higher risk of both the primary [Hazard ratio (HR) 2.84; 95% Confidence interval (CI) 1.26–6.38; P = .012] and secondary (HR 1.83; 95% CI 1.03–3.27; P = .041) endpoints compared with the no-stone group. Associations appear to be more pronounced in males, individuals with higher body mass index, worse baseline kidney function, larger kidney volume, and PKD1 genotype. Conclusions Imaging-confirmed nephrolithiasis is independently associated with adverse kidney outcomes in patients with ADPKD. Early detection and targeted management of kidney stones may improve risk stratification and kidney prognosis in this population.

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