Decline in Kidney Function Accelerated in Patients With ADPKD With Truncating Mutations

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the accumulation of fluid-filled cysts in the kidneys, resulting in renal volume enlargement and progressive impairment of kidney function. Allelic and genetic heterogeneity contribute to variation in disease severity among patients with ADPKD.

Hamid Ali, MD, and colleagues conducted a single center, retrospective cohort study designed to examine genotype-phenotype correlations between PKD1 truncating and nontruncating mutations and decline in kidney function in that patient population. Results were reported in the American Journal of Nephrology.

The study was conducted in Kuwait. The researchers followed all patients with a clinically and genetically confirmed diagnosis of PKD1-ADPKD. To analyze repeated measures of kidney function across mutation type, generalized additive mixed effects models with random intercepts were fitted for each individual. A Cox proportional hazards model was then used to calculate survival time to kidney failure. Models were adjusted for sex, age at visit, and birth year.

The study cohort included 42 patients (22 truncating and 20 nontrucating). Patients were followed for an average of 6.6 years.

The rate of decline in estimated glomerular filtration rate was more rapid among patients in the group with PKD1 truncating group compared with those with nontruncating mutations (–4.7 mL/min/1.73 m² per year [95% CI, –5.0 to –4.4] vs –3.5 mL/min/1.73 m² per year [95% CI, –4.0 to –3.1]; P for interaction. <.001). Results of Kaplan-Meier survival analysis of time to kidney failure demonstrated that patients with PKD1 truncating mutations had a shorter renal survival time compared with those in the group with nontruncating mutations (median 51 years vs median 56 years; P for log rank=.008).

In conclusion, the authors said, “In longitudinal and survival analyses, patients with PKD1 truncating mutations showed a faster decline in kidney function compared with patients with PKD1 nontruncating mutations. Early identification of patients with PKD1 truncating mutations can, at best, inform early clinical interventions, or, at least, help suggest aggressive monitoring.”

Source: American Journal of Nephrology