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Nephrol Dial Transplant (2001) 16: 803-808
© 2001 European Renal Association-European Dialysis and Transplant Association

Prostaglandin inhibition by intraperitoneal indomethacin has no effect on peritoneal permeability during stable CAPD

Caroline E. Douma,1, Dirk R. de Waart2, Désirée Zemel1, Dirk G. Struijk3 and Raymond T. Krediet1

1 Renal Unit, Department of Medicine and 2 Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam and 3 the Foundation of Home Dialysis Midden-West Nederland, Utrecht, The Netherlands

Background. Prostaglandins can affect the vascular response and are locally produced in the peritoneal cavity. Prostaglandin inhibition in continuous ambulatory peritoneal dialysis (CAPD) patients during peritonitis using indomethacin intraperitoneally was found to decrease the intrinsic permeability to macromolecules.

Methods. In the present study the effects of prostaglandin inhibition were studied during stable, uninfected CAPD. Two standard peritoneal permeability analyses (1.36% glucose) were performed in 10 stable CAPD patients within 1 week with and without addition of 12.5 mg/l indomethacin. Furthermore, possible effects on the parameters of nitric oxide synthesis were determined. In five other patients a high dose of indomethacin was tested. The night before the indomethacin test, 12.5 mg/l indomethacin was added to the nightdwell and the test was performed with 25 mg/l indomethacin.

Results. In the normal dose indomethacin group, the dialysate concentrations of prostaglandin (PG) 6-keto-PGF1{alpha} and thromboxane (Tx) TxB2 were significantly lower with indomethacin (IND) compared with the control dwell (C): 6-keto-PGF1{alpha} median 93 (C) vs 7.5 (IND) ng/l, P=0.006 and TxB2 12.3 (C) vs 9.0 (IND) ng/l, P=0.04. The dialysate concentration of PGE2 was not different during the control dwell (68.5 ng/l) compared with the indomethacin experiment (50.3 ng/l, P=0.5). The mass transfer area coefficients (MTAC) of nitrate and cGMP, and parameters of nitric oxide synthesis, were similar during both experiments. The MTAC of creatinine and urate were not different with indomethacin: creatinine median 9.5 (C) vs 10.2 ml/min (IND), P=0.2 and urate 7.2 (C) vs 7.3 ml/min (IND), P=0.3. Only the MTAC of urea was marginally higher with indomethacin: 16.0 (C) vs 16.6 ml/min (IND), P=0.04. No differences were found in the clearances of the macromolecules ß2-microglobulin, albumin, IgG and {alpha}2-microglobulin. With the high indomethacin dose no inhibition of PGE2 was found: 69 (C) vs 63 ng/l(IND), not significant. Furthermore, no differences were found in the transport rates of small solutes or proteins. This indicates no effect of indomethacin on the peritoneal surface area and the size-selective permeability to macromolecules. In both groups no effect was found on the transcapillary ultrafiltration and the effective lymphatic absorption rate during the 4-h dwell. Consequently, the net ultrafiltration, the difference between these, did not change.

Conclusions. The indomethacin induced inhibition of the synthesis of 6-keto-PGF1{alpha} and TxB2 did not lead to alterations in functional parameters of the peritoneal surface area, the intrinsic permeability to macromolecules and fluid kinetics. Therefore, these prostaglandins are not likely to be involved in the regulation of peritoneal transport during stable CAPD.

Keywords: CAPD; indomethacin; permeability; prostaglandins; nitric oxide

Correspondence and offprint requests to: Caroline E. Douma MD, PhD, Academic Medical Center, University of Amsterdam, Department of Nephrology, F4-215, PO Box 22700, 1100 DE Amsterdam, The Netherlands.


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