Parameters associated with progression, prognosis and tolvaptan indication in autosomal dominant polycystic kidney disease (adpkd)

Abstract BACKGROUND AND AIMS The identification of possible risk factors for the progression of autosomal dominant polycystic kidney disease (ADPKD) is an emerging field, especially after the introduction of tolvaptan as the first disease-specific treatment. The present study aims to explore the associations between epidemiological, clinical and imaging data in a large cohort of ADPKD patients. METHOD This study was from a single outpatient clinic, following patients with ADPKD. Patients were included in the study if they had recently undergone a magnetic resonance imaging for the measurement of total kidney volume (TKV). For all patients, the Mayo Clinic Imagining Category (MCIC) and the prediction of end-stage renal disease (ESRD) (future estimated-glomerular filtration rate [e-GFR] <10 mL/min) based on the Mayo Clinic formula were calculated. Patients eligible for tolvaptan treatment (MCIC 1C, 1D, 1E, age <55 years old and e-GFR ≥25 mL/min) were identified. Characteristics including individual medical history, clinical and laboratory data were examined for possible associations with renal and imaging parameters using multinomial logistic regression and linear regression models. RESULTS A total of 250 patients were included. Based on measurements of height-adjusted TKV (ht-TKV) and age, 8.4% of the patients were classified as 1A, 19.6% as 1B, 34% as 1C, 24.8% as 1D and 13.2% as 1E, MCIC. In multivariable analysis, patient's age (P < 0.001), male sex (P < 0.001), parent's age at ESRD (adjusted for patient age) (P < 0.001) and hypertension (P = 0.009) were associated with log (ht-TKV). Parent's age at ESRD differed significantly between the MCICs of the offspring (mean±SD), 65.63 (12.13) in 1A, 61.9 (11.3) in 1B, 55.6 (9.6) in 1C, 51.64 (9.2) in 1D and 49.7 (8.3) in 1E, (P < 0.001). Similarly, there were significant differences in the presence and age of hypertension onset (P =0.0005 and P = 0.0004, respectively). In 157 patients (74 females and 83 males) who were eligible for tolvaptan treatment, the age at ADPKD diagnosis, the age at hypertension onset and the parent's age at ESRD were significantly lower (P < 0.001 for all) when compared to noneligible patients. Finally, factors associated with the prediction score of ESRD were hypertension, uric acid and the age at ESRD of the affected parent (P = 0.038, 0.014 and 0.010, respectively). CONCLUSION As a heritability estimator, the age at which an affected parent had reached ESRD was significantly associated with a worse phenotype, prognosis and tolvaptan indication. Hypertension was associated with poor prognosis and an aggravated phenotype, whereas age at diagnosis of the disease and hypertension onset were associated with tolvaptan indication in ADPKD.