Kidney function reserve capacity in early and later stage autosomal dominant polycystic kidney disease

Abstract

Background and objectives It is assumed that in autosomal dominant polycystic kidney disease (ADPKD), kidney function remains in the normal range for several decades because of hyperfiltration of remnant nephrons. In this study, we investigate the extent to which patients with ADPKD hyperfilter. Design, setting, participants, & measurements In this cross-sectional study, we measured GFR as urinary clearance using continuous infusion of 125I-iothalamate. Kidney function reserve capacity was determined as increase in measured GFR after adding a dopamine infusion of 4.4–6 mg/h. Potential kidney donors were used as healthy controls and matched by age and sex to patients with ADPKD for comparisons across age groups and CKD stages. Hyperfiltration was defined by a loss of kidney function reserve capacity compared with healthy controls. Results A total of 300 participants were studied. In the youngest age group (18–29 years),measured GFRwas not different between patients with ADPKD and healthy controls (103621 versus 111±9ml/min per 1.73m2; P=0.14). In this age group kidney function reserve capacity was higher compared with healthy controls (11.1%±8.3% versus 5.3%66.5%;P=0.04). Moreover, kidney function reserve capacity was similar to healthy controls in patients with ADPKD with early-stage disease (eGFR≥60ml/min per 1.73m2), either overall orwhen divided into fast or slow progressors according to their Mayo height-adjusted total kidney volume class. However, in patients with ADPKD, lower measured GFR was associated with lower kidney function reserve capacity (α=1.0 [95% confidence interval, 0.5 to 1.5] %per 10 ml/min per 1.73m2; P<0.001). Kidney function reserve capacity was therefore lower compared with healthy controls at older age and later CKD stages. Conclusions Patients with early-stage ADPKD, either classified as having rapidly or slowly progressive disease, are able to increase theirGFRinresponse todopamine. Hyperfiltration, defined by a loss of kidney function reserve capacity, may therefore not be an early phenomenon in ADPKD.