Updated Canadian Expert Consensus on Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease

Abstract

Purpose:The purpose of this article is to update the previously published consensus recommendations from March 2017 discussing the optimal management of adult patients with autosomal dominant polycystic kidney disease (ADPKD). This document focuses on recent developments in genetic testing, renal imaging, assessment of risk regarding disease progression, and pharmacological treatment options for ADPKD.Sources of information:Published literature was searched in PubMed, the Cochrane Library, and Google Scholar to identify the latest evidence related to the treatment and management of ADPKD.Methods:All pertinent articles were reviewed by the authors to determine if a new recommendation was required, or if the previous recommendation needed updating. The consensus recommendations were developed by the authors based on discussion and review of the evidence.Key findings:The genetics of ADPKD are becoming more complex with the identification of new and rarer genetic variants such as GANAB. Magnetic resonance imaging (MRI) and computed tomography (CT) continue to be the main imaging modalities used to evaluate ADPKD. Total kidney volume (TKV) continues to be the most validated and most used measure to assess disease progression. Since the publication of the previous consensus recommendations, the use of the Mayo Clinic Classification for prognostication purposes has been validated in patients with class 1 ADPKD. Recent evidence supports the benefits of a low-osmolar diet and dietary sodium restriction in patients with ADPKD. Evidence from the Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trial supports the use of ADH (antidiuretic hormone) receptor antagonism in patients with ADPKD 18 to 55 years of age with eGFR (estimated glomerular filtration rate) of 25 to 65 mL/min/1.73 m2 or 56 to 65 years of age with eGFR of 25 to 44 mL/min/1.73 m2 with historical evidence of a decline in eGFR >2.0 mL/min/1.73 m2/year.Limitations:Available literature was limited to English language publications and to publications indexed in PubMed, the Cochrane Library, and Google Scholar.Implications:Advances in the assessment of the risk of disease progression include the validation of the Mayo Clinic Classification for patients with class 1 ADPKD. Advances in the pharmacological management of ADPKD include the expansion of the use of ADH receptor antagonism in patients 18 to 55 years of age with eGFR of 25 to 65 mL/min/1.73 m2 or 56 to 65 years of age with eGFR of 25 to 44 mL/min/1.73 m2 with historical evidence of a decline in eGFR >2.0 mL/min/1.73 m2/year, as per the results of the REPRISE study.

Tolvaptan or transplant: why wait?

“…A small, single-center study from Edwards and colleagues 4 addressed this concern and demonstrated the sustained efficacy of tolvaptan in slowing the loss of GFR by w1 ml/ min per 1.73 m 2 per year for up to 11.2 years (average follow-up, 4.6 years). In order to understand the impact of tolvaptan in delaying ESRD, we estimated the potential benefit of tolvaptan for patients who are considered eligible to receive tolvaptan by expert guidelines or consensus publications [5][6][7] ; that is, individuals aged 55 years or younger, with a Mayo imaging class of 1C, 1D, or 1E. We did not consider individuals older than age 55 years or those with Mayo imaging classes of 1A, 1B, or 2, who would be considered to have low risk of rapid progression.…”

“…12 This result has been incorporated into some clinical guidelines for the use of tolvaptan, which suggest that maintenance of urine osmolality below 280-300 mOsm/kg is adequate. 5,6 Aquaresis and vasopressin levels also can be decreased with reduction of dietary solute (protein and salt). 13 Therapy for chronic medical conditions commonly managed by nephrologists, such as hypertension, diabetes, and fluid overload due to chronic kidney disease or nephrotic syndrome, requires the patient and nephrologist to accept years of treatment and possible treatment-associated side effects in the expectation of a clinical benefit.…”

CT of Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: Accuracy, Reproducibility, and Radiation Dose

“…Although our sample size precluded statistical comparisons between the methods, the Mayo ellipsoid tended to have the best performance in terms of accuracy and variability, which further supports the use of this already commonly used method. A barrier to the adoption of TKV measurements is the time required for the manual planimetry method (7,10,11); similar to prior publications, the interpreting radiologists performed ellipsoid measurements in a fraction of the time required for planimetry.…”

Autosomal dominant polycystic kidney disease

“…Inhibition of the renin-angiotensin-aldosterone system and aggressive blood pressure control (< 110/75 mm Hg) should be considered in patients with autosomal dominant polycystic kidney disease who are younger than 50 years and have preserved kidney function. 3 Cyst infections should be treated with cyst-penetrating antibiotics (i.e., fluoroquinolone) for a minimum of two to four weeks, and possible cyst drainage. 4 Chronic abdominal discomfort is common and acute-on-chronic pain secondary to cyst hemorrhage or nephrolithiasis can occur.…”

“…cmaj.ca/lookup/suppl/doi:10.1503/cmaj.170443/-/DC1) with preserved kidney function, with benefit balanced by cost, aquaretic adverse effects and potential hepatotoxicity. 3 PRACTICE | FIVE THINGS TO KNOW ABOUT ...…”