| Abstract|| |
In this study, the effect of indomethacin a nonsteroidal anti-inflammatory drug (NSAID) was studied to evaluate the effect of its short-term use on peritoneal clearance of urea and creatinine as well as protein excretion in nine chronic renal failure patients on intermittent peritoneal dialysis therapy. Four of them were males and five were females with mean age of 54.4 years. Clearance values and protein excretion in the dialysate effluents were measured before and after administering the indomethacin. There was no significant effect on the urea and creatinine clearance after the use of this drug. However, the mean ± SE protein concentration in the dialysate effluents decreased significantly after the use of indomethacin from 43.1 + 4.5 to 37.0 + 3.5 mg/dl (p<0.01). This reduction of protein excretion in the dialysate after the use of indomethacin might enhance the nutritional status of patients on peritoneal dialysis.
Keywords: Clearance, End stage renal failure (ESRF), Indomethacin, Intermittent peritoneal dialysis, Non-steroidal anti-inflammatory drugs, Prostaglandin synthetase inhibitors, Protein excretion.
|How to cite this article:|
Abbas EE, Albawab IM, Safarini SK, Alhassan RA, Khatim MS. The Effect of Short Term Use of Indomethacin, a Non-Steroidal Anti-inflammatory Drug, on Peritoneal Dialysis Patients. Saudi J Kidney Dis Transpl 1996;7:10-4
|How to cite this URL:|
Abbas EE, Albawab IM, Safarini SK, Alhassan RA, Khatim MS. The Effect of Short Term Use of Indomethacin, a Non-Steroidal Anti-inflammatory Drug, on Peritoneal Dialysis Patients. Saudi J Kidney Dis Transpl [serial online] 1996 [cited 2020 May 27];7:10-4. Available from: http://www.sjkdt.org/text.asp?1996/7/1/10/39532
| Introduction|| |
Peritoneal dialysis is one of the main replacement therapeutic modalities in the management of patients with renal failure. It has gained popularity in the last two decades, especially after the advent of CAPD. There are many factors which may affect diffusion and clearance of solutes through he human peritoneal membrane, including: temperature of fluid infused into the peritoneal cavity, rate of exchange of fluid and its volume, solute concentration gradients, membrane and solute charges, other solute characteristics, capillary pore size, capillary dilatation and constriction, and bowel characteristics ,,, . Many drugs can alter peritoneal permiability by changing some of those factors affecting clearance ,,,,, .
Peritoneal clearance is important to clinicians since it indicates the efficiency of dialysis , . In some patients it would be desirable to use pharmacological or physical factors to augment solute clearance. However, pharmacological agents in this regard are not in use in clinical practice at present.
Peritoneal clearance measured under the same conditions of dialysis solution flow rates and technique remains usually constant in the same patient during short term follow up ,,,,, , while it decreases on long term peritoneal dialysis , .
Non-steroidal anti-inflammatory drugs (NSAIDS) are potent prostaglandin inhibitors and are used widely in clinical practice , . This study was undertaken to evaluate the short term effect of indomethacin a NSAID on peritoneal clearance of urea, creatinine, and protein excretion in the dialysate.
| Materials and Methods|| |
We studied prospectively nine in-patients with end stage renal disease. All of them consented for IPD, as well as to undergo the trial. The inclusion criteria were absence of: peritonitis, gastrointestinal symptoms, allergy to indomethacin, febrile or any intercurrent illness. There were no changes of medications on any of these patients during the study period. [Table - 1] shows the age, sex and etiology of the ESRD of the study patients. There were four males and five females included in the study. The mean age was 54.4 years with a range between 25 and 70 years.
After insertion of PD catheter, hourly manual exchanges were done. The fluid used was two liters peritoneal solution with dextrose 1.36%, Na 132 mmol/L, Cl 102 mmol/L, Ca 1.75 mmol/L, Mg 0.75 mmol/L and lactate 35 mmol/L  . The fluid was warmed in a water bath to 37° centigrade.
The patients were started on peritoneal dialysis on day 0. On the following day (day 1), a set of clearance studies were done using the formula CdxVd/PT ,,,,, where Cd was the concentration of the substance in the dialysate in milligrams percent, Vd was the dialysate drain volume in milliliters, P was the concentration of the substance in the plasma measured at the exchange midpoint in milligrams per deciliter and T was equal the time of exchange between the start of infusion of peritoneal fluid into the peritoneal cavity up to the time of complete drainage in minutes, which was always around sixty minutes. On day 2, indomethacin was given in three doses of 50 mg orally every 8 hours to the patients. On day 3, another set of studies of clearances was done after discontinuing the drug. The studies of clearances were done in the second exchange each morning for all the patients. Protein concentration in dialysate effluents was measured during each study of clearances.
The experiment was repeated in all nine patients after one week, making a total of eighteen observations. The means of the two clearance values as well as the protein concentration in dialysate effluents were recorded in each of the patients.
| Statistics|| |
The data collected were tabulated, graphed and analyzed using the Wilcoxon matched paired signed rank test. This method calculates the difference between two groups in paired samples ,, .
| Results|| |
[Table - 2] shows the mean urea and creatinine clearances, as well as the protein concentration in dialysate effluents in each of the nine study patients before and after the NSAID. There were no statistically significant changes in the means of clearances of urea or creatinine after the intake of indomethacin compared with the clearances before it. However, there was a statistically significant decrease in the mean + standard error (SE) of protein concentration in the dialysate effluents before and after administering indomethacin (43.1 ± 4.5 to 37.0 ± 3.5 mg/dl, P< 0.01).
| Discussion|| |
The vasodilator prostaglandins given intraperitoneally augment peritoneal clearance of creatinine by 10-20%, while the vasconstrictor prostaglandins decrease clearance by 18%, however there was no effect if prostaglandins were given intravenously ,,,, . Prostaglandin synthetase inhibitors and stimulators had no pronounced effects on peritoneal transport under baseline conditions in animals when given intravenously, intraperitoneally or orally  . The failure of indomethacin in our study to reduce peritoneal clearances of small solutes; ie, urea and creatinine, may be due to the inhibition of both the vasodilating and the vasoconstricting prostaglandins, thus maintaining a balanced net effect on the regional peritoneal blood flow. This is consistent with the results shown in animal studies using intravenous, intraperitoneal and oral prostaglandin inhibitors ,, .
The use of NSAIDS in patients undergoing peritoneal dialysis was reported to have deleterious effects on renal function , . This may be due to the unopposed effect of other vasoconstrictors in the kidneys which are not inhibited by NSAIDS such as angiotensin. This mechanism may not be operating in the peritoneal membrane.
Indomethacin was used to reduce protein excretion in nephrotic syndrome patients , . The significant decrease in protein excretion in the peritoneal dialysate effluent after the use of indomethacin is not clear. This may be due to stronger inhibition of the vasodilatory effect in comparison to the vasoconstrictor effect, leading to lesser loss of protein in the dialysate.
In patients on peritoneal dialysis, it is essential to maintain a positive nitrogen balance so as to prevent malnutrition and to compensate for the protein losses in dialysate during PD ,,,, .
In our study indomethacin decreased protein excretion in peritoneal dialysate effluents. It remains to be seen whether this is going to be beneficial in patients on PD with a negative nitrogen balance. Adminis, tering indomethacin may reduce their dialysate protein losses. The long term effect of prostaglandin inhibitors on protein excretion and the nutritional status of patients on PD need further evaluation.
| References|| |
|1.||Maher JF. Peritoneal transport rates: mechanisms, limitations and methods for augmentation. Kidney Int Suppl 1980;Suppl 10:S117-20. |
|2.||Felt J, Richard C, McCaffrey C, Levy M. Peritoneal clearance of creatinine and inulin during dialysis in dogs: effect of splanchnic vasodilators. Kidney Int 1979;16:459-69. |
|3.||Rubin J, Nolph K, Arfania D, Brown P, Moore H, Rust P. Influence of patient characteristics on peritoneal clearance. Nephron 1981;27:118-21. |
|4.||Brown ST, Ahearn DJ, Nolph KD. Reduced peritoneal clearance in scleroderma increased by intraperitoneal isoproterenol. Ann Intern Med 1973;78:891-4. |
|5.||Nolph KD, Ghods AJ, Van-Stone J, Brown PA. The effects of intraperitoneal vasodilators on peritoneal clearances. Trans Am Soc Artif Intern Organs 1976;22:586-94. |
|6.||Hare HG, Valtin H, Gosselin RE. Effect of drugs on peritoneal dialysis in the dog. J Pharmacol Exp Ther 1964;145:122-9. |
|7.||Maher JF, Hirszed P, Lascrich M. Model for study of pharmacologic and hormonal influence on peritoneal dialysis. Contr Nephrol Krager, Basel 1979;17:131-8. |
|8.||Hirszel P, Maher JF, Chamberlin M. Augmented peritoneal mass transport with intraperitoneal nitropruside. J Dial 1978;2:131-42. |
|9.||Maher JF, Shea C, Cassetta M, Hohnadel DC. Isoproterenol enhancement of peritoneal permeability. J Dial 1977;1:319-31. |
|10.||Nolph KD, Ghodes AJ, Brown VJ, Miller FN, Weirgman DL, Harris PD. Actors affecting peritoneal dialysis efficiency. Dial Transplant 1977;6:52-64. |
|11.||Rubin J, Nolph K, Arfania D, Brown P, Prowant B. Follow-up of peritoneal clearances in patients undergoing continuous ambulatory peritoneal dialysis. Kidney Int 1979;16:619-23. |
|12.||Nolph KD. Peritoneal clearances. J Lab Clin Med 1979;94:519-25. Faller B, Lameire N. Evolution of clinical parameters and peritoneal function in a cohort of CAPD patients followed over 7 years. Nephrol Dial Transplant 1994;9(3):280-6. |
|13.||Nolph KD, Stoltz ML, Maher JF. Altered peritoneal permeability in patients with systemic vasculitis. Ann Intern Med 1971;75:753-5. |
|14.||Slingeneyer A, Canaud B, Mion C. Permanent loss of ultrafiltration capacity of the peritoneum in long-term peritoneal dialysis: an epidemiological study. Nephron 1983;33:133-8. |
|15.||Messina EJ, Weiner R, Kaley G. Prostaglandins and local circulatory control. Fed Proc 1976;35:2367-75. |
|16.||Nakano J, McCurdy JR. Hemodynamic effects of prostaglandins El, Al and F2alpha in dogs. Proc Soc Exp Biol Med 1968;128:39-42. |
|17.||Rubin J, Nolph KD, Arafaania D, Wiegman DL, Miller FN, Harris PD. Comparison of the effects of lactate and acetate on clinical peritoneal clearance. Clin Nephrol 1979;12(4):145-7. |
|18.||Barbour GL, Joe C, Patterson RM. Measurement of peritoneal clearances in self dialysis patients. J Lab Clin Med 1979;94(4):526-31. |
|19.||Forrester JC, Ury HK. The signed rank (Wilcox-on) test in the rapid analysis of biological data. Lancet 1969;1:239-41. |
|20.||West ED. The signed rank (Wilcoxon) test. Lancet 1969;1:526. |
|21.||Colten T. Non parametric methods 7, in Statistics in Medicine Boston, Little Brown and Company 1974;219-27. |
|22.||Messina EJ, Kaley G. Microcirculatory responses to prostacyclin and PGE2 in the rat cremaster muscle. Adv Prostaglandin Thromboxane Res 1980;7:719-22. |
|23.||Maher JF, Hirszel P, Lasrich M. Modulation of peritoneal transport rates by prostaglandins. Adv Prostaglandin Thromboxane Res 1980;7:695-700. |
|24.||Maher JF, Hirszel P, Larsrich M. Prostaglandin effect on peritoneal transport. Proc 2nd Int Symposium on Peritoneal Dialysis 1981;2:65. |
|25.||Blackshear JL, Davidman M, Stillman MT. Identification of risk for renal insufficiency from nonsteroidal antiinflammatory drugs. Arch Intern Med 1983;143:1130-4. |
|26.||Walshe JJ, Venuto RC. Acute oliguric renal failure induced by indomethacin: Possible mechanisms. Ann Intern Med 1979;91:47-9. |
|27.||Kooijmans Coutinho MF, Tegzess AM, Bruijn JA, Florijn KW, van Es LA, van der Woude FJ. Indomethacin treatment of recurrent nephrotic syndrome and focal segmental glomerulosclerosis after renal transplantation. Nephrol Dial Transplant 1993;8(5):469-73. |
|28.||Tiggeler RG, Hulm B, Wijdeveld PG. Effect of indomethacin on glomerular permeability in nephrotic syndrome. Kidney Int 1979; 16:312-21. |
|29.||Enia G, Sicuso C, Alati G, Zoccali C. Subjective global assessment of nutrition in dialysis patients. Nephrol Dial Transplant 1993;8(10): 1094-8. |
|30.||Young GA, Kopple JD, Lindholm B, et al. Nutritional assessment of continuous ambulatory peritoneal dialysis patients: an international study. Am J Kidney Dis 1991;17(4):462-71. |
|31.||Conty CA, Long term dietary management of dialysis patients. J Am Diet Assoc 1985;54:439-44. |
|32.||Blumenkrantz MJ, Gahl GM, Kopple JD, et al. Protein losses during peritoneal dialysis. Kidney Int 1981;19:593-6.2. |
|33.||Lindholm B, Alverstrand A, Furst P, Tranaeus A, Bergstrom J. Efficiency and clinical experience of CAPD. Stokholm, Sweden; In: Atkinson, Thomson, Farrel: Peritoneal Dialysis. Churchill, Livingstone, Edinburg 1981;147-61. |
|34.||von-Baeyer H, Gahl GM, Riedinger H, Borowzak B, Kessel M. Nutritional behavior of patients on continuous ambulatory peritoneal dialysis. Proc F.nr Dial Transolant Assoc 1981:18:193-8. |
Elhadi E Abbas
Consultant Physician and Head of Department, P.O. Box 5797, Ras Al Khaimah
United Arab Emirates
[Table - 1], [Table - 2]