Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) causes the development of renal cysts and leads to a decline in renal function. Limited guidance exists in clinical practice on the use of tolvaptan. A decision algorithm from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups of Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) has been proposed to identify candidates for tolvaptan treatment; however, this algorithm has not been assessed in clinical practice. Methods: Eighteen-month cross-sectional, unicenter, observational study assessing 305 consecutive ADPKD patients. The ERA-EDTA WGIKD/ERBP algorithm with a stepwise approach was used to assess rapid progression (RP). Subsequently, expanded criteria based on the REPRISE trial were applied to evaluate the ­impact of extended age (≤55 years) and estimated glomerular filtration rate (eGFR; ≥25 mL/min/1.73 m²). Results: Historical eGFR decline, indicative of RP, was fulfilled in 26% of 73 patients who were candidates for RP assessment, mostly aged 31–55 years. Further tests including ultrasound and MRI measurements of kidney volume plus genetic testing enabled the evaluation of the remaining patients. Overall, 15.7% of patients met the criteria for rapid or likely RP using the algorithm, and the percentage increased to 27% when extending age and eGFR. Conclusions: The ERA-EDTA WGIKD/ERBP algorithm provides a valuable means of identifying in routine clinical practice patients who may be eligible for treatment with tolvaptan. The impact of a new threshold for age and eGFR may increase the percentage of patients to be treated.

Prediction models used in the progression of chronic kidney disease: A scoping review

“…Three studies [ 49 , 64 , 65 ] performed an evaluation of the Kidney Failure Risk Equation (KFRE), and three other studies developed their own unique scoring algorithm that predicted ESKD [ 55 , 63 , 66 ].…”

Recent advances in the clinical management of autosomal dominant polycystic kidney disease

“…The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups on Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) developed a hierarchical decision-making algorithm that may offer guidance on the identification and prediction of rapid disease progression in patients with ADPKD and subsequently identify candidates for tolvaptan treatment 39 . When this algorithm was tested in a cohort of 305 patients, it was found that 15.7% fulfilled the ERA-EDTA criteria and that the overall proportion of patients with rapid progression rose to 27% upon incorporation of expanded criteria based on data from the REPRISE (Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD) trial 40 (that is, age of less than 56 years and estimated glomerular filtration rate [eGFR] of more than 30 mL/min/m 2 ) 41 . This study, together with a recent assessment of an unpublished large series of patients, calls into question the suitability of the algorithm, especially in its first steps when limiting for age/eGFR and using retrospective eGFR.…”

An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International

“…This entry criterion remains very important to exclude individuals who clearly do not have rapid disease progression at an early stage in the decision-making process. In retrospect, the thresholds defined in the original WGIKD algorithm were rather conservative, potentially excluding patients who could have been eligible for therapy [ 9 , 22 ]. Based on the additional evidence and increased experience in real-life settings, these limits are revised in the updated version to allow more patients to benefit from treatment.…”

“…An increase in TKV ≥5% per year was also included as a marker indicating rapid disease progression in the original ERA position statement. However, such an approach would require at least three serial MRI or CT scans that are usually not available in clinical practice [ 22 ]. Furthermore, variance of volume determination between different timepoints is a concern.…”