Effectiveness of oral route isosorbide 5-mononitrate on peritoneal solute and fluid transports in CAPD patients.
BACKGROUND
Addition of sodium nitroprusside (NaNTP), a nitric oxide (NO) donor to peritoneal solution could enlarge the effective peritoneal surface area and the peritoneal pore size. This would be leading to increased clearance of all solutes. Generalized clinical usage of NaNTP in CAPD patients however is not practical because it has a very short half-life and needs a specific route of administration. Organic nitrate, another NO donor, has a longer half-life and could be more easily absorbed via many routes.


OBJECTIVE
The present study was conducted to determine the effect and mechanism of oral active nitrate (isosorbide 5-mononitrate: ISMN) on solute andfluid transports in stable CAPD patients.


METHODS
A prospective randomized placebo control with a crossover study was performed in nine stable CAPD patients. In group I (n = 4), the treatment included 1) oral ISMN at the dose of 20 mg bid for 5 days 2) wash out period for 7 days, and 3) placebo for 5 days. In group 2 (n = 5), the treatment regimens were placebo, wash out, and ISMN periods.


RESULTS
The MTACs of low molecular weight (LMW) solutes in the ISMN period were greater than the placebo period: median urea, 16.7 vs 13.8 ml/min; creatinine (Cr), 7.9 vs 6.9 ml/min; and urate, 6.1 vs 5.5 ml/min (p < 0.05 for all except MTAC of urea). Administration of ISMN could also enhance the clearances of high molecular weight (HMW) solute with a magnitude of increase as follows: 10% for beta2-microglobulin, 50% for albumin, and 15% for immunoglobulin G (p < 0.05 for all). However, the values of restrictive coefficient of LMW as well as HMW solutes of both groups were not different, indicating that the increased solute transports are not due to alteration in the peritoneal membrane permeability. Despite the increased peritoneal solute clearance, net ultrafiltration (UF) was unchanged after drug administration, 110 (ISMN group) vs 120 ml (placebo group), (NS).


CONCLUSIONS
ISMN has a similar effect as NaNTP in enhancing peritoneal clearances of both LMW and HMW solutes. The effect of ISMN, however, is mediated only via expansion of peritoneal surface area without significant change in pore size. As such, administration of oral ISMN to stable CAPD patients would be practically beneficial in enhancing the achievement of target solute clearances suggested by NKF- DOQI Guidelines.
Kanjanabuch
Talerngsak
T
Division of Nephrology, Department of Medicine, King Chulalongkorn Memorial Hospital.
Eiam-Ong
Somchai
S
D000284:Administration, Oral; D001692:Biological Transport / Q000187:drug effects*; D018592:Cross-Over Studies; D015314:Dialysis Solutions; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000379:methods*; D011446:Prospective Studies; D016896:Treatment Outcome
D015314:Dialysis Solutions; D020030:Nitric Oxide Donors; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate