Effects of nonsteroidal antiinflammatory drugs on renal function in sickle cell anemia.
Renal hemodynamics and solute and water handling were evaluated in 19 sickle cell patients and 8 matched normal subjects during water diuresis, before and after acute oral administration of a nonsteroidal antiinflammatory drug (NSAID). Baseline GFR and RPF were higher in the patients compared to the normals. In contrast to normals, indomethacin and sulindac induced a 16% and 14% decrease in GFR, respectively. Indomethacin resulted in a slight increase in UOsm in normals, but a substantially greater rise in the patients. Following indomethacin a greater fall in FENa, fractional solute delivery to the diluting segment of the nephron [(CH2O + CNa + K)/GFR], fractional solute reabsorption in the diluting segment [CH2O/GFR] and the fraction of distally delivered solute reabsorbed [CH2O/(CH2O + CNa + K)] was observed in the sickle cell patients than in the normal subjects. A similar trend, but of significantly lesser magnitude than that induced by indomethacin, was observed following sulindac in the sickle cell patient. The data imply that the supranormal GFR observed in the sickle cell patients was prostaglandin-mediated. The effects of NSAID's on renal solute and water handling in the sickle cell patients are compatible with a prostaglandin-dependent decreased salt reabsorption in the medullary thick ascending limb of Henle, together with a hyperfunctioning proximal tubule. The data also imply an additional indomethacin-sensitive antinatriuretic effect in the diluting segment in these patients. Moreover, the results suggest that in sickle cell anemia sulindac may not have a "renal sparing" advantage over other NSAID's.
Allon
M
M
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Lawson
L
L
Eckman
J R
JR
Delaney
V
V
Bourke
E
E
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000503:physiopathology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000652:urine; D011453:Prostaglandins / Q000652:urine; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D012964:Sodium; D011188:Potassium