Peritoneal and renal DKK3 clearance in peritoneal dialysis

Abstract

Background: Urinary Dickkopf 3 (DKK3) excretion is a recently established biomarker of renal functional development. Its excretion into the peritoneal cavity has not been reported. We here studied DKK3 in peritoneal dialysis.

Methods: DKK3 was assessed in serum, urine and dialysate in a prevalent adult peritoneal dialysis cohort and its concentration analyzed in relation to creatinine and clinical characteristics.

Results: Highest DKK3 concentrations were found in serum, followed by urine. Dialysate concentrations were significantly lower. Dialysate DKK3 correlated with both other compartments. Serum, dialysate and urine values were stable during three months of follow-up. Continuous ambulatory dialysis (CAPD) but not cycler-assisted peritoneal dialysis (CCPD) volume-dependently increased peritoneal DKK3 in relation to creatinine. RAAS blockade significantly decreased urinary, but not serum or peritoneal DKK3.

Conclusion: Our data provide a detailed characterization of DKK3 in peritoneal dialysis. They support the notion that the RAAS system is essential for renal DKK3 handling.

Keywords: DKK3; Peritoneal dialysis; RAAS blockade.

Fig. 1

Flow diagram of patient recruitment. RRT renal replacement therapy, PD peritoneal dialysis, HD hemodialysis

Fig. 2

Peritoneal dialysate DKK3 correlates with serum and urine. (A-D) DKK3 levels were assessed in serum, urine and peritoneal dialysate as absolute concentrations and relative to creatinine. (A, B) Absolute (A) and concentrations relative to creatinine (B) (n = 29 patients, Tukey’s after ANOVA). (C, D) Correlations of absolute (C) and relative to creatinine (D) dialysate concentrations to serum and urine (results of linear regression analyses are shown)

Fig. 3

DKK3 concentrations are stable in peritoneal dialysis outpatients. (A-F) DKK3 levels were assessed in serum, urine and peritoneal dialysate as absolute concentrations and relative to creatinine. Correlations of longitudinal DKK3 assessments at least three months apart in serum (A, B), urine (C, D) and peritoneal dialysate (E, F) are given as absolute concentrations (A, C, E) and relative to creatinine (B, D, F) (results of linear regression analyses are shown). TP time point

Fig. 4

Peritoneal DKK3 clearance depending on dialysis regimen. (A, B) Peritoneal dialysate DKK3 absolute (A) and relative to creatinine (B) levels according to CAPD, CCPD and IPD regimens (statistical analysis of CAPD versus CCPD: t-test with Welch’s correction). (C) DKK3 urine and peritoneal removal in mg/24 h according to dialysis regimen. (D) Dialysate DKK3 levels in for CAPD and CCPD in relation to dialysate volume (linear regression analyses)

Fig. 5

Decreased urinary DKK3 excretion during RAAS blockade. (A-E) DKK3 levels in serum (A, B), urine (C, D) and peritoneal dialysate (E, F) in relation to RAAS blockade are shown as absolute concentrations (A, C, E) and relative to creatinine (B, D, F)(n = 7 patients without and n = 22 with blockade (n = 18 ACEi or ARB, n = 4 MRA Mann-Whitney tests)