Can we further enrich autosomal dominant polycystic kidney disease clinical trials for rapidly progressive patients? Application of the PROPKD score in the TEMPO trial

Emilie Cornec-Le Gall, Jaime D. Blais, Maria V. Irazabal, Olivier Devuyst, Ron T. Gansevoort, Ron D. Perrone, Arlene B. Chapman, Frank S. Czerwiec, John Ouyang, Christina M. Heyer, Sarah R. Senum, Yannick Le Meur, Vicente E. Torres, Peter C. Harris

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background. The PROPKD score has been proposed to stratify the risk of progression to end-stage renal disease in autosomal dominant polycystic kidney disease (ADPKD) subjects. We aimed to assess its prognostic value in a genotyped subgroup of subjects from the Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (TEMPO3/4) trial. Methods. In the post hoc analysis, PKD1 and PKD2 were screened in 770 subjects and the PROPKD score was calculated in mutation-positive subjects (male: 1 point; hypertension <35 years: 2 points; first urologic event <35 years: 2 points; nontruncating PKD1 mutation: 2 points; truncating PKD1 mutation: 4 points). Subjects were classified into low-risk (LR; 0-3 points), intermediate-risk (IR; 4-6 points) and high-risk (HR; 7-9 points) groups. Results. The PROPKD score was calculated in 749 subjects (LR=132, IR=344 and HR=273); age was inversely related to risk (LR=43.6 years, IR=39.5 years, HR=36.2 years; P<0.001). Subjects fromthe HR group had significantly higher height-adjusted total kidney volume (TKV) and rates of TKV growth.While baseline renal function was similar across all risk groups, the rate of estimated glomerular filtration rate (eGFR) decline significantly increased from LR to HR in the placebo group. Tolvaptan treatment effectiveness to reduce TKV growth was similar in all three risk categories. While tolvaptan significantly slowed eGFR decline in the IR (tolvaptan=-2.34 versus placebo=-3.33mL/min/1.73m2/year; P=0.008) and HR groups (tolvaptan=-2.74 versus placebo=-3.94mL/min/ 1.73 m2/year; P=0.002), there was no difference in the LR group (tolvaptan=-2.35 versus placebo=-2.50mL/min/1.73 m 2 /year; P=0.72). Excluding the LR subjects from the analysis improved the apparent treatment effect of tolvaptan on eGFR decline. Conclusion. This study confirms the prognostic value of the PROPKD score and suggests that it could reduce costs and enhance endpoint sensitivity by enriching future study populations for rapidly progressing ADPKD subjects.

Original languageEnglish (US)
Pages (from-to)645-652
Number of pages8
JournalNephrology Dialysis Transplantation
Volume33
Issue number4
DOIs
StatePublished - Apr 1 2018

Keywords

  • PKD1
  • PKD2
  • TEMPO 3/4
  • autosomal dominant polycystic kidney disease
  • genetics

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Fingerprint Dive into the research topics of 'Can we further enrich autosomal dominant polycystic kidney disease clinical trials for rapidly progressive patients? Application of the PROPKD score in the TEMPO trial'. Together they form a unique fingerprint.

Cite this