Summary
The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. Twenty-six hypercholesterolaemic (total cholesterol ≽ 5.5 mmol/l) Type 1 diabetic patients with nephropathy were enrolled in a double-blind randomized placebo-controlled study for 12 weeks. The active treatment group (n -14) received simvastatin (10–20 mg/day) for 12 weeks while the remaining 12 patients received treatment with placebo. The results during simvastatin treatment (baseline vs 12 weeks): total cholesterol 6.6 vs 4.8 mmol/1 (p < 0.01), LDL-cholesterol 4.25 vs 2.57 mmol/l (p < 0.01) and apolipoprotein B 1.37 vs 1.06 mmol/l (p < 0.01). HDL-cholesterol, and apolipoprotein A-I remained unchanged. Total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein A–I, apolipoprotein B remained unchanged during placebo treatment. Albuminuria measured during the simvastatin and the placebo treatment (baseline vs 12 weeks) (the data are logarithmically transformed before analysis because of their positively skewed transformation; geometric mean (×/÷ antilog SE) is indicated) was 458 (×/÷ 1.58) vs 393 (×/÷ 1.61) and 481 (×/÷ 1.62) vs 368 (×/÷ 1.78 μg/min (NS). Glomerular filtration rate during simvastatin and placebo treatment (baseline vs 12 weeks) was 64 vs 63 and 72 vs 74 ml·min−1·1.73 m−2, respectively. Two patients receiving simvastatin treatment were withdrawn, one due to gastrointestinal side effects and one due to myalgia. In conclusion, our short-term study in Type 1 diabetic patients with diabetic nephropathy did not reveal any beneficial effect on albuminuria despite a striking lipid-lowering effect of simvastatin in diabetic nephropathy.
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Parving H-H, Smidt U, 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
Borch-Johnson K, Andersen PK, Deckert T (1985) The effect of proteinuria on relative mortality in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 28: 590–596
Kostner GM, Karadi I (1988) Lipoprotein alterations in diabetes mellitus. Diabetologia 31: 717–722
Moorhead JF, El-Nahas M, Chan MK, Varghese Z (1982) Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 11: 1310–1311
Mulec H, Johnson S-AA, Björck S (1990) Relation between serum cholesterol and diabetic nephropathy. Lancet 335: 1537–1538
Diamond JR, Karnovsky MJ (1987) Exacerbation of chronic aminonucleoside nephrosis by dietary cholesterol supplementation. Kidney Int 32: 671–677
Kasiske BI, O'Donnell M, Clearly MP, Keane WF (1989) Effects of reduced renal mass on tissue lipids and renal injury in hyperlipidemic rats. Kidney Int 35: 40–47
Rabelink AJ, Hene RJ, Erkelens DW, Joles JA, Koomans HA (1990) Partial remission of nephrotic syndrome in patients on long-term simvastatin. Lancet 335: 1045–1046
Parving H-H, Andersen AR, Smidt UM, Svendsen PA (1983) Early aggressive antihypertensive treatment reduces the rate of decline in diabetic nephropathy. Lancet 1: 1175–1179
Kattermann R, Joworek D, Möller G (1984) Multicenter study of a new enzymatic method of cholesterol determination. J Clin Chem Clin Biochem 22: 245–251
Friedewald WT, Levy RI, Frederikson DS (1972) Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 18: 499–502
Andersen I, Hannibal S (1983) Analytical and economical optimization of a glucose method with immobilized enzymes. J Automatic Chemistry 4: 188–192
Goldstein DE, Peth SB, England JD, Randall LH, DaCosta J (1980) Effects of acute changes in blood glucose on HbA1c. Diabetes 29: 623–628
Bröchner-Mogensen J (1972) A simple method for the determination of glomerular filtration rate. Scand J Clin Lab Invest 30: 271–274
Miles DW, Mogensen CE, Gundersen HJG (1970) Radioimmunoassay for urinary albumin using a single antibody. Scand J Clin Lab Invest 26: 5–11
Maroni BJ, Steinman TI, Mitch WE (1985) A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int 27: 58–65
Isaksson B (1980) Urinary nitrogen output as a validity test in dietary surveys. Am J Clin Nutr 33: 4–5
Carlsen J, Køber L, Hansen A-D, Sindling A, Andersen P (1988) Electronic measurement of blood pressure. Technical and clinical assessment of medical UA 751. Ugeskr Laeger 150: 1280–1282
Kasiske BI, O'Donnell MP, Keane WF (1987) The obese Zucker rat model of glomerular injury in Type 1 (insulin-dependent) diabetes. J Diab Compl 1: 26–29
Kasiske BL, O'Donnell MP, Garvis WJ, Keane WF (1988) Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectorny model of chronic renal failure. Circ Res 62: 367–374
Kasiske BL, O'Donnell MP, Schmitz PG et al. (1990) Renal injury of diet-induced hypercholesterolemia in rats. Kidney Int 37: 880–891
Kasiske BL, O'Donnell MP, Clearly MP, Keane WF (1988) Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats. Kidney Int 33: 667–672
Hostetter TT, Rennke HG, Brenner BM (1982) The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med 72: 375–380
Parving H-H, Viberti GC, Keen H, Christiansen JS, Lassen NA (1983) Hemodynamic factors in the genesis of diabetic microangiopathy. Metabolism 32: 943–949
Zatz R, Prado EBA, Prado MJBA (1989) Aging analbuminemic rats fail to develop focal glomerular sclerosis. Kidney Int 35: 442
Sasaki T, Kuratya H, Nomura K, Utsunomiya K, Ikeda Y (1990) Amelioration of proteinuria with Pravastatin in hypercholesterolemic patients with diabetes mellitus. Jpn J Med 29: 156–163
Deslypere JP, Delanghe J, Vermeulen A (1990) Proteinuria as complication of simvastatin treatment. Lancet 336: 1045–1046
Parving H-H, Kastrup J, Smidt UM, Andersen AR, Feldt-Rasmussen B, Sandahl Christiansen J (1984) Impaired autoregulation of glomerular filtration rate in Type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 27: 547–542
Hommel E, Mathiesen E, Edsberg B, Bahnsen M, Parving H-H (1986) Acute reduction of arterial blood pressure reduces urinary albumin excretion in Type 1 (insulin-dependent) diabetic patients with incipient nephropathy. Diabetologia 29: 211–215
Wiseman MJ, Bognetti ZE, Dodds R, Keen H, Viberti GC (1987) Changes in renal function in response to protein restricted diet in Type 1 (insulin-dependent) diabetic patients. Diabetologia 30: 154–159
Hommel E, Mathiesen E, Arnold-Larsen S, Edsberg B, Olsen UB, Parving H-H (1987) Effects of indomethacin on kidney function in Type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 30: 78–81
Mathiesen ER, Hommel E, Olsen UB, Parving H-H (1988) Elevated urinary prostaglandin excretion and the effect of indomethacin on renal function in incipient nephropathy. Diab Med 5: 145–149
Garg A, Grundy SM (1988) Lovastatin for lowering cholesterol levels in non-insulin-dependent diabetes mellitus. N Engl J Med 318: 81–86
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Hommel, E., Andersen, P., Gall, M.A. et al. Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy. Diabetologia 35, 447–451 (1992). https://doi.org/10.1007/BF02342442
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DOI: https://doi.org/10.1007/BF02342442