Background: Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It is also characterized by elevated plasma levels of total homocysteine (tHcy). Hyperhomocysteinemia has been shown to be a risk factor for atherosclerosis in both the general population and in patients with end-stage renal disease. Aim: To analyze whether elevated tHcy levels also may contribute to a higher rate of progression of renal insufficiency in patients with moderately advanced renal failure. Methods: To investigate whether tHcy concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of tHcy with the progressive decline of renal function in an observational study of human chronic renal disease. Results: Sixty-three nondiabetic patients (49 men, 14 women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.0 years, and the mean rate of decline in glomerular filtration rate (51Cr- EDTA clearance) was –3.2 ± (SD) 3.9 ml/min × 1.73 m2 body surface area. The mean plasma concentration of tHcy at the beginning of the study was 28.3 ± 12.0 µmol/l. Plasma tHcy concentrations correlated significantly with the glomerular filtration rate (r = –0.32, p < 0.01). However, there was no association between the initial plasma level of tHcy and the rate of progression as assessed by linear regression analysis (r = 0.02; NS). In contrast, increased levels of apolipoprotein B, low-density lipoprotein cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Conclusions: Patients with moderately advanced chronic renal insufficiency have elevated plasma levels of homocysteine. The tHcy plasma levels increase in parallel with the degree of reduction in renal function. However, the hyperhomocysteinemia is not prospectively associated with a higher rate of progression of the renal functional impairment. Hence, there is no indication that elevated homocysteine levels play a contributing role for an accelerated glomerulosclerotic process.

1.
Massy ZA: Hyperhomocyst(e)inaemia in renal failure: What are the implications? Nephrol Dial Transplant 1996;11:2392–2393.
2.
Bostom A, Lathrop L: Hyperhomocysteinemia in end-stage renal disease: Prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 1997;52:10–20.
3.
Chauveau P, Chadefaux B, Coudé M, Aupetit J, Hannedouche T, Kamoun P, Jungers P: Hyperhomocysteinemia, a risk factor for atherosclerosis in chronic uremic patients. Kidney Int 1993;41(suppl 43):72–77.
4.
Arnadottir M, Hultberg B, Nilsson-Ehle P, Thysell H: The effect of reduced glomerular filtration rate on plasma total homocysteine concentration. Scand J Clin Lab Invest 1996;56:41–46.
5.
Bachman J, Tepel M, Raidt H, et al: Hyperhomocysteinemia and the risk for vascular disease in hemodialysis patients. J Am Soc Nephrol 1995;6:121–125.
6.
Massy ZA, Chadefaux-Vekemans B, Chevalier A, Bader CA, Drüeke TB, Legendre C, Lacour B, Kamoun P, Kreis H: Hyperhomocysteinemia: A significant risk factor for cardiovascular disease in renal transplant recipients. Nephrol Dial Transplant 1994;9:1103–1108.
7.
Kim SS, Hirose S, Tamura H, Nagasawa R, Tokushima H, Mitarai T, Isoda K: Hyperhomocysteinemia as a possible role for atherosclerosis in CAPD patients. Adv Perit Dial 1994;10:282–285.
8.
Moustapha A, Naso A, Nahlawi M, Gupta A, Arheart KL, Jacobsen DW, Robinson K, Dennis VW: Prospective study of hyperhomocysteinemia as an adverse cardiovascular risk factor in end-stage renal disease. Circulation 1998;97:138–141.
9.
Boushey CJ, Beresford SAA, Omenn GS, Motulsky AG: A quantitative assessment of plasma homocysteine as a risk factor for cardiovascular disease: Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049–1057.
10.
Zidek W: Homocysteine – a new arteriosclerotic risk factor in end-stage renal failure. Nephron 1997;75:249–250.
11.
Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullman D, Tishler PV, Hennekens CH: A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in United States physicians. JAMA 1992;268:877–881.
12.
Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG: Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995;346:1395–1398.
13.
Moghadasian MH, McManus BM, Frohlich JJ: Homocyst(e)ine and coronary artery disease: Clinical evidence and genetic and metabolic background. Arch Intern Med 1997;157:2299–2308.
14.
McCully KS: Homocysteine, folate, vitamin B6 and cardiovascular disease. JAMA 1998;279:392–393.
15.
Stamler JS; Osborne JA, Jaraki O, et al: Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993;91:308–318.
16.
Keane WF, Kasiske BL, O’Donnel MP: Lipids and progressive glomerulosclerosis: A model analogous to atherosclerosis. Am J Nephrol 1988;8:261–271.
17.
Attman P-O, Samuelsson O, Alaupovic P: Lipid metabolism and renal failure. Am J Kidney Dis 1993;21:373–592.
18.
Samuelsson O, Mulec H, Knight-Gibson C, Attman P-O, Kron B, Larsson R, Weiss L, Alaupovic P: Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency. Nephrol Dial Transplant 1997;12:1908–1915.
19.
Jagenburg R, Attman P-O, Aurell M, Bucht H: Determination of glomerular filtration rate in advanced renal insufficiency. Scand J Urol Nephrol 1978;12:133–137.
20.
Wang C-S, Alaupovic P, Gregg RE, Brewer HB Jr: Studies on the mechanism of hypertriglyceridemia in Tangier disease: Determination of plasma lipolytic activities, k1 values and apolipoprotein composition of the major lipoprotein density classes. Biochim Biophys Acta 1987;920:9–19.
21.
Warnick GR, Albers JJ: A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 1978;19:65–76.
22.
Curry MD, Alaupovic P, Suenram CA: Determination of apolipoprotein A and its constitutive AI and AII polypeptides by separate electroimmunoassays. Clin Chem 1976;22:315–322.
23.
Curry MD, Gustafson A, Alaupovic P, McConathy WJ: Electroimmunoassay, radioimmunoassay, and radial immunodiffusion assay evaluated for quantification of human apolipoprotein B. Clin Chem 1978;24:280–286.
24.
Curry MD, McConathy WJ, Fesmire JD, Alaupovic P: Quantitative determination of human apolipoprotein C-III by electroimmunoassay. Biochim Biophys Acta 1980;617:505–513.
25.
Curry MD, McConathy WJ, Alaupovic P, Ledford JD, Popovic M: Determination of human apolipoprotein E by electroimmunoassay. Biochim Biophys Acta 1976;439:413–425.
26.
Malinow MR, Kang SS, Taylor LM, Wong PWK, Coull B, Inahara T, Mukerjee D, Sexton G, Upson B: Prevalence of hyperhomocyst(e)- inemia in patients with peripheral arterial occlusive disease. Circulation 1989;79:1180–1188.
27.
Walser M: Progression of chronic renal failure in man. Kidney Int 1990;37:1195–1210.
28.
Hultberg B, Andersson A, Sterner G: Plasma homocysteine in renal failure. Clin Nephrol 1993;40:230–234.
29.
Bostom AG, Shemin D, Verhoef P, Nadeau MR, Jacques PF, Selhub J, Dworkin L, Rosenberg IH: Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients: A prospective study. Arterioscler Thromb Vasc Biol 1997;17:2554–2558.
30.
Wilcken DEL, Gupta VJ: Sulphur containing amino acids in chronic renal failure with particular reference to homocystine and cysteine-homocysteine mixe disulphide. Eur J Clin Invest 1979;9:301–307.
31.
Wilcken DEL, Dudman NPB, Tyrell PA, Robertson MR: Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: Possible implications for prevention of vascular disease. Metabolism 1988;37:697–701.
32.
Dellana F, Kissinger GL, Pollok M, Switkowski R, Baldamus CA: Hyperhomocysteinemia in predialysis and posttransplant chronic renal insufficiency (abstract). J Am Soc Nephrol 1997;8:66.
33.
Guttormsen AB, Ueland PM, Svarstad E, Refsum H: Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997;52:495–502.
34.
Robinson K, Gupta A, Dennis V, Arheart K, Chaudhary D, Green R, Vigo P, Mayer EL, Selhub J, Kutner K, Jacobsen DW: Hyperhomocysteinemia confers an independent increased risk of atherosclerosis in end-stage renal disease and is closely linked to plasma folate and pyridoxine concentrations. Circulation 1996;94:2743–2748.
35.
Jacobson HR: Chronic renal failure: Pathophysiology. Lancet 1991;338:419–423.
36.
Samuelsson O, Attman P-O, Knight-Gibson C, Larsson R, Mulec H, Weiss L, Alaupovic P: Complex apolipoprotein B-containing lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency. J Am Soc Nephrol 1998;9:1482–1488.
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