Recent Advances in the Management of Autosomal Dominant Polycystic Kidney Disease

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic cause of ESKD, is characterized by relentless development of kidney cysts, hypertension, and destruction of the kidney parenchyma. Over the past few years, major advancements in diagnosing, prognosticating, and understanding the pathogenesis and natural course of the disease have been made. Currently, no kidney disease is more suitable for nephron-protective strategies. Early nephrology referral and implementation of these strategies may have a substantial effect. Total kidney volume is a good prognostication marker and allows stratification of patients into slow or rapid progressing disease, with implications for their management. Measurement of total kidney volume, disease stratification, and prognostication are possible using readily available tools. Although some patients require only monitoring and basic optimized kidney protective measures, such as rigorous BP control and various lifestyle and dietary changes, others will benefit from disease-modifying treatments. Vasopressin V2 receptor antagonists, a likely disease-modifying treatment, has been approved in several countries and recently by the US Food and Drug Administration; other therapies, such as somatostatin analogs and other novel agents, are currently in clinical trials. The purpose of this article is to present our views on the optimal management to delay kidney disease progression in ADPKD.

Keywords: ADPKD; Antidiuretic Hormone Receptor Antagonists; Cysts; Dietary Sodium; Disease Progression; Kidney Failure, Chronic; Nephrons; Polycystic Kidney, Autosomal Dominant; Receptors, Vasopressin; Referral and Consultation; Somatostatin; United States Food and Drug Administration; blood pressure; hypertension; vasopressin.

Figure 1.

Basic universal management should be recommended to all patients with ADPKD. The first step is to confirm ADPKD diagnosis, then classify the patient on the basis of imaging features and total kidney volume. Basic optimized management should be recommended to all patients with ADPKD. BMI, body mass index, CT, computed tomography, MRI, magnetic resonance imaging.

Figure 2.

Imaging of different patients with ADPKD who enrolled in the CRISP study (creatinine clearance ≥70 ml/min), showing the large spectrum of disease severity from very mild to very severe disease at the baseline visit. These examples depict the large phenotypic variability and emphasize the importance of prognostication using imaging. htTKV, height adjusted total kidney volume (ml/m).

Figure 3.

Mayo Clinic classification diagram (modified from Nephrology, Dialysis and Transplantation, in press). HtTKV, height adjusted total kidney volume (ml/m).

Figure 4.

Example depicting stepwise method to calculate TKV in the clinician’s office using the Mayo Clinic ADPKD classification online tool. The first three steps involve measuring the maximal sagittal, coronal, and axial width and depth of each kidney. These measurements can be done using the ruler tool available in most imaging viewing software. The following steps include plugging in the numbers to obtain TKV, classification, and estimation of future eGFR (see http://www.mayo.edu/research/documents/pkd-center-adpkd-classification/doc-20094754).

Figure 5.

Example of two patients with ADPKD with the same age and GFR, who have a substantial difference in their prognosis on the basis of their total kidney volume and predicted rate of decline of eGFR. Patient A is classified as Mayo Clinic class 1E and would benefit form a disease-modifying treatment. Patient B has better prognosis (class 1B) and would need monitoring.