Biomarker Linked to Slower Kidney Function Decline in ADPKD

Patients with higher endogenous beta-hydroxybutyrate ketone levels have a slower rate of kidney function decline during autosomal dominant polycystic kidney disease (ADPKD), investigators report.

Among 521 patients with ADPKD not treated with disease-modifying drugs and free from type 2 diabetes, the median concentration of beta-hydroxybutyrate ketone was 94 µmol/L. In adjusted models, every doubling in beta-hydroxybutyrate ketone level was significantly associated with a 0.33 mL/min/1.73 m² improvement in annual change in estimated glomerular filtration rate (eGFR) slope, Maatje D.A. van Gastel, PhD, of the University of Groningen in the Netherlands, and colleagues reported in Nephrology Dialysis Transplantation.

In longitudinal analyses, higher beta-hydroxybutyrate ketone levels were significantly associated with a positive annual eGFR slope of 0.35 mL/min/1.73 m², but not with kidney growth, the investigators pointed out. Beta-hydroxybutyrate ketone levels were not associated with eGFR or height-adjusted total kidney volume (htTKV) in cross-sectional analyses.

Cystic cells depend on glucose and aerobic glycolysis and are poorly able to use other energy sources such as ketone bodies, Dr van Gastel’s team explained. Beta-hydroxybutyrate ketone can alter cell signaling, suppress oxidative stress, diminish fibrosis, and reduce inflammation. In animal models of ADPKD, raising ketone body concentration reduced disease progression.

“Our observational data support the hypothesis that raising beta-hydroxybutyrate levels by diet or drugs could reduce the rate of disease progression in patients with ADPKD,” the investigators wrote.

Of the 521 patients in the Developing Intervention Strategies to Halt Progression of ADPKD (DIPAK) cohort, 61% were female and mean age was 47.3 years. At baseline, htTKV was 834 mL/m and eGFR was 63.3 mL/min/1.73 m². None of the patients had beta-hydroxybutyrate ketone levels in the ketogenic range.