Summary
We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albumimiria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253pg/min) was significantly elevated in eight Type 1 (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95pg/min) and 11 non-diabetic women (132 pg/min), respectively (p<0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized doubleblind trial, with the patients receiving either indomethacin (150mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%, p<0.01), glomerular filtration rate diminished from 120±18 to 106±17ml/min/1.73m2 (p<0.05), albuminuria declined from 148 to 69 μg/min (median and range) (p<0.05) and fractional clearance of albumin diminished 42% (p<0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4±4 versus 14.2±3 mmol/l, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins.
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Borch-Johnson K, Andersen PK, Decken T (1985) The effect of proteinuria on relative mortality in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 28: 590–596
Parving H-H, Smidt UM, Friisberg B, Bonnevie-Nielsen V, Andersen AR (1981) A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Diabetologia 20: 457–461
Viberti GC, Bilous RW, Mackintosh D, Keen H (1983) Monitoring glomerular function in diabetic nephropathy. Am J Med 74/ 256–264
Mauer SM, Steffens MW, Ellis EM, Sutherland DER, Brown DM, Goetz FC (1984) Structural-functional relationships in diabetic nephropathy. J Clin Invest 74: 1143–1155
Østerby R, Andersen AR, Gregersen G, Gundersen HJG, Hommel E, Hørlyck A, Jørgensen HE, Løkkegaard H, Mogensen CE, Nyberg G, Parving H-H, Svalander C (1986) Quantitative structural data on the development of diabetic nephropathy. Diabetic Nephr 5: 10–11
Jensen PK, Steven K, Blashr H, Christiansen JS, Parving H-H (1986) Effects of indomethacin on glomerular hemodynamics in experimental diabetes. Kidney Int 29: 490–495
Donker AJM, Arisz L, Brentjens JRH, von der Hem GK, Hollemans HJG (1976) The effect of indomethacin on kidney function and plasma renin activity in man. Nephron 17: 288–296
Arisz L, Donker AJM, Brentjens JRH, von der Hem GK (1976) The effect of indomethacin on proteinuria and kidney function in the nephrotic syndrome. Acta Med Scand 199: 121–125
Bröchner-Mortensen J (1972) A simple method for determination of glomerular filtration rate. Scand J Clin Lab Invest 30: 271–274
Bröchner-Mortensen J (1985) Current status on assessment and measurement of glomerular filtration rate. Clin Physiol 5: 1–17
Miles DW, Mogensen CE, Gundersen HJG (1970) Radioimmunoassay for urinary albumin using a single antibody. Scand J Clin Lab Invest 26: 5–11
Frölich JC, Wilson TW, Sweetman BJ, Smigel M, Nies AS, Carr K, Watson T, Oates JA (1975) Urinary prostaglandins. Identification and origin. J Clin Invest 55: 763–770
Jensen KM (1978) Determination of indomethacin in serum by an extractive alkylation technique and gas-liquid chromatography. J Chromatography 153: 195–202
Laurell CB (1966) Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Analyt Biochem 15: 45–52
Mortensen HB (1980) Quantitative determination of hemoglobin A1c by thin-layer isoelectric focusing. J Chromatography 182: 325–333
Hilsted J, Jensen SB (1979) A simple test for autonomie neuropathy in juvenile diabetics. Acta Med Scand 205: 385–387
Dunn M, Hood VL (1977) Prostaglandins and the kidney. Am J Physiol 233: F169-F184
Schlondorff D, Ardaillou R (1986) Prostaglandins and other arachidonic acid metabolites in the kidney. Kidney Int 29: 108–119
Schambelan M, Blake S, Sraer J, Bens M, Nivez M-P, Wahbe F (1985) Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus. J Clin Invest 75: 404–412
Chaudhari A, Kirschenbaum MA (1984) Effect of experimental diabetes mellitus on eicosanoid biosynthesis in isolated rat glomeruli. Kidney Int 25: 326 (Abstract)
Kimberly RP, Gill JR, Bowden RE, Keiser HR, Plotz PH (1978) Elevated urinary prostaglandins and the effect of aspirin on renal function in lupus erythematosus. Ann Int Med 89: 336–341
Ciabattoni G, Cinotti GA, Pierucci A, Simonetti BM, Manzi M, Pugliese F, Barsotti P, Pecci G, Taggi F, Patrono C (1984) Effects of sulindac and ibuprofen in patients with chronic glomerular disease. N Engl J Med 310: 279–283
Tiggeler RGWL, Hulme B, Widfeveld PGAB (1979) Effect of indomethacin on glomerular permeability in the nephrotic syndrome. Kidney Int 16: 312–321
Niwa T, Maeda K, Naotsuka Y, Asada H, Kobayashi S, Yokoyama M, Kawaguchi S, Shibala M (1982) Improvement of renal function with prostaglandin E1 infusion in patients with chronic renal disease. Lancet 1: 687
Clive DM, Sloff JS (1984) Renal snydromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med 310: 563–572
Christiansen JS, Feldt-Rasmussen B, Parving H-H (1985) Shortterm inhibition of prostaglandin synthesis has no effect on the elevated glomerular filtration rate of early insulin-dependent diabetes. Diabet Med 2: 17–20
Esmatjes E, Fernandez MR, Halperin I, Camps J, Gaya J, Arroyo V, Rivera F, Figuerola D (1985) Renal hemodynamic abnormalities in patients with short term insulin-dependent diabetes mellitus: role of renal prostaglandins. J Clin Endocrinol Metab 60: 1231–1236
Frimodt-Møller C (1976) Diabetic cystopathy. II: Relationship to some late-diabetic manifestations. Dan Med Bull 23: 279–286
Brenner BM, Humes HO (1977) Mechanisms of glomerular ultrafiltration. N Engl J Med 297: 148–154
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Hommel, E., Mathiesen, E., Arnold-Larsen, S. et al. Effects of indomethacin on kidney function in Type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 30, 78–81 (1987). https://doi.org/10.1007/BF00274575
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DOI: https://doi.org/10.1007/BF00274575