Effect of Oral Administration of Losartan, Prazosin, and Verapamil on Peritoneal Solute Transport in Continuous Ambulatory Peritoneal Dialysis Patients

Abstract

Background Several intraperitoneally administered drugs have been shown to modify transport of peritoneal solute and fluid. Fewer studies, however, have evaluated the effect of orally administered drugs. The present study was performed to evaluate the effects of oral losartan, prazosin, and verapamil on peritoneal membrane transport during a peritoneal equilibration test (PET), as well as the effects on creatinine clearance (CrCl), Kt/V urea, 24-hour protein in drained dialysate, and drained volume. Methods This was an open, controlled, crossover clinical trial performed in 20 patients on continuous ambulatory peritoneal dialysis. All subjects used four 2-L 1.5% glucose dialysis exchanges per day. After a 7-day washout period (without antihypertensives), they had a baseline standard PET and dialysis adequacy assessment performed. Subsequently, they were randomly allocated to receive the first of three study drugs (losartan, prazosin, and verapamil), which were administered orally for a 7-day period. Immediately after each drug period, patients had a new 3-day washout and subsequently started the next drug, until they had received each of the three drugs. On the last day of administration of each drug, patients were subjected to a new PET and adequacy of dialysis evaluation. Results None of the studied drugs significantly modified the peritoneal transport of creatinine, glucose, urea, sodium, potassium, or total protein as evaluated by PET. Verapamil significantly increased peritoneal CrCl [51.3 (44.3 – 53.3) vs baseline 45.8 (41.4 – 50.5) L/week/1.73 m2, p < 0.05], weekly Kt/V urea [1.75 (1.60 – 1.78) vs baseline 1.59 (1.54 – 1.73), p < 0.05], and drained dialysate volume [8.80 (8.30 – 8.96) vs baseline 8.44 (8.20 – 8.50) L/day, p < 0.05]. Conclusions Oral administration of losartan, prazosin, and verapamil did not modify the peritoneal transport of solutes during a 4-hour PET. Oral verapamil significantly increased CrCl, Kt/V urea, and 24-hour drained dialysate volume. It is most likely that verapamil increases peritoneal (hydraulic) conductivity, and then net ultrafiltration volume and convective transport of urea, creatinine, and protein. Verapamil could be considered as an alternative in patients requiring increased dialysis dose and/or ultrafiltration.

Effectiveness of Renin-Angiotensin-Aldosterone System Blockade on Residual Kidney Function and Peritoneal Membrane Function in Peritoneal Dialysis Patients: A Network Meta-Analysis

“…After screening of titles/abstracts, 101 full-text articles of potentially relevant studies were acquired. After appraising these articles against study inclusion/exclusion criteria (Supplementary, Table S1), we included 10 RCTs 12–14,25,31–36 and 10 non-randomised studies 11,20–24,26,37–39 that compared RAAS blockade classes with active control (Table 1). Four RAAS blockade classes were compared with active control—ACEIs, ARBs MRAs, and mixed ACEIs/ARBs, however, no data for DRIs in any outcome of interest.…”

“…However, the role of RAAS blockade in PD patients has not been fully elucidated. Some studies have revealed the protective properties 11–15,19 , whereas others have not 20–26 . Previous systematic reviews have shown that ACEIs/ARBs substantially benefit in preserving rGFR in PD patients, while a lack of evidence exist regarding the relative efficacy of MRAs and direct renin inhibitors (DRIs) 27–29 .…”

Peritoneal Total Protein Transport Assessed from Peritoneal Equilibration Tests Using Different Dialysate Glucose Concentrations

“…Alternatively, high concentrations of glucose could bias the estimations of dialysate total protein or albumin concentration-more so during the 3.86% PET than the 2.27% PET. The reported methods of estimation of dialysate protein concentration are heterogeneous (7)(8)(9)(10)13,31,33,(36)(37)(38), although the nephelometry and colorimetric methods are the most common. In general, glucose is not considered to interfere markedly in the estimation of plasma or dialysate protein level, but concentrations as high as those observed during a 3.86% PET may have not been routinely tested for most of the methods.…”

Lercanidipine-Induced Chyloperitoneum in Patients on Peritoneal Dialysis

“…In the current study, we observed that CCBs can have two separate effects on PD: increasing UF and causing chyloperitoneum. CCBs have been reported in the past to have various effects on PD, including increasing peritoneal clearance (4), reducing peritoneal glucose uptake (5,6), and increasing UF (1,6-10). The most commonly studied CCBs in these series were verapamil and diltiazem, or both.…”