Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria

Area of Science:

• Nephrology
• Genetics
• Urology

Background:

• Primary hyperoxaluria (PH) is a genetic disorder characterized by oxalate overproduction, leading to kidney stone formation and nephrocalcinosis.
• The relative contribution of nephrocalcinosis versus stone events to kidney damage in PH remains unclear.

Purpose of the Study:

• To investigate whether kidney damage from nephrocalcinosis and/or stone-related events contributes to end-stage kidney disease (ESKD) in patients with primary hyperoxaluria.

Main Methods:

• Analysis of clinical data from 348 PH patients in the Rare Kidney Stone Consortium registry.
• Inclusion of demographic, laboratory, and imaging features.
• Statistical analysis to assess the association between nephrocalcinosis, stone events, and ESKD risk, adjusting for PH type, diagnosis method, and age.

Main Results:

• Nephrocalcinosis was present in 34% of patients, more common in PH type 1.
• High urine oxalate correlated with increased risk of nephrocalcinosis and stone number.
• Low urine citrate was a risk factor for stone events and number.
• History of nephrocalcinosis increased ESKD risk (HR 1.7); new-onset nephrocalcinosis showed a higher risk (HR 4.0).
• Stone number and stone events were not significantly associated with ESKD risk.

Conclusions:

• Nephrolithiasis and nephrocalcinosis are distinct pathophysiological entities in primary hyperoxaluria.
• Nephrocalcinosis, particularly new-onset, is a significant predictor of end-stage kidney disease in PH patients.
• Management strategies should focus on preventing and treating nephrocalcinosis to mitigate ESKD progression.