Lipid abnormalities in nephrotic syndrome
- Jai Radhakrishnan, MD, MS
Jai Radhakrishnan, MD, MS
- Professor of Medicine
- Columbia University Medical Center
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Brad H Rovin, MD
Brad H Rovin, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine and Pathology
- The Ohio State University College of Medicine
Abnormal lipid metabolism is common in patients with renal disease [1-6]. This effect is most prominent in the nephrotic syndrome, where marked elevations in the plasma levels of cholesterol, LDL, triglycerides and lipoprotein(a) often occur [1-5,7,8]. Total HDL cholesterol levels are usually normal or reduced in the nephrotic syndrome and there is often a pronounced decline in the cardioprotective HDL2 fraction. The mechanism by which this occurs is unclear, but elevations in the plasma concentration of cholesteryl ester transfer protein in nephrotic patients may contribute by shuttling cholesteryl esters from HDL2 to very low-density lipoproteins (VLDL) [9,10].
The concentration of plasma apolipoproteins in the nephrotic syndrome generally reflects the alterations in lipoprotein metabolism. Thus, there are elevated levels of apo B, C-II, and E, which are associated with VLDL and LDL; on the other hand, the levels of the major apolipoproteins associated with HDL, apo A-I and A-II, are usually normal . A review of the functions of the different apolipoproteins is discussed separately. (See "Lipoprotein classification, metabolism, and role in atherosclerosis".)
This topic will review the pathogenesis and treatment of lipid abnormalities in patients with the nephrotic syndrome. The pathogenesis and significance of lipid abnormalities in patients with chronic kidney disease and following kidney transplantation are discussed separately. (See "Indications for statins in nondialysis chronic kidney disease" and "Lipid abnormalities after renal transplantation".)
Marked hypercholesterolemia is common in patients with the nephrotic syndrome:
●Among 207 adults with nephrotic syndrome due to nondiabetic renal disease (mean proteinuria 7.2 g/24 hours), the mean total cholesterol concentration was 302 mg/dL (7.8 mmol/L) 
- D'Amico G. Statins and renal diseases: from primary prevention to renal replacement therapy. J Am Soc Nephrol 2006; 17:S148.
- Kwan BC, Kronenberg F, Beddhu S, Cheung AK. Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol 2007; 18:1246.
- Wheeler DC, Bernard DB. Lipid abnormalities in the nephrotic syndrome: causes, consequences, and treatment. Am J Kidney Dis 1994; 23:331.
- Appel G. Lipid abnormalities in renal disease. Kidney Int 1991; 39:169.
- Radhakrishnan J, Appel AS, Valeri A, Appel GB. The nephrotic syndrome, lipids, and risk factors for cardiovascular disease. Am J Kidney Dis 1993; 22:135.
- Weiner DE, Sarnak MJ. Managing dyslipidemia in chronic kidney disease. J Gen Intern Med 2004; 19:1045.
- Stenvinkel P, Berglund L, Heimbürger O, et al. Lipoprotein(a) in nephrotic syndrome. Kidney Int 1993; 44:1116.
- Crew RJ, Radhakrishnan J, Appel G. Complications of the nephrotic syndrome and their treatment. Clin Nephrol 2004; 62:245.
- Moulin P, Appel GB, Ginsberg HN, Tall AR. Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome: role in dyslipidemia. J Lipid Res 1992; 33:1817.
- Vaziri ND. Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences. Kidney Int 2016; 90:41.
- Joven J, Villabona C, Vilella E, et al. Abnormalities of lipoprotein metabolism in patients with the nephrotic syndrome. N Engl J Med 1990; 323:579.
- Kronenberg F, Lingenhel A, Lhotta K, et al. Lipoprotein(a)- and low-density lipoprotein-derived cholesterol in nephrotic syndrome: Impact on lipid-lowering therapy? Kidney Int 2004; 66:348.
- Yamauchi A, Fukuhara Y, Yamamoto S, et al. Oncotic pressure regulates gene transcriptions of albumin and apolipoprotein B in cultured rat hepatoma cells. Am J Physiol 1992; 263:C397.
- BAXTER JH, GOODMAN HC, ALLEN JC. Effects of infusions of serum albumin on serum lipids and lipoproteins in nephrosis. J Clin Invest 1961; 40:490.
- Vaziri ND, Liang KH. Acyl-coenzyme A:cholesterol acyltransferase inhibition ameliorates proteinuria, hyperlipidemia, lecithin-cholesterol acyltransferase, SRB-1, and low-denisty lipoprotein receptor deficiencies in nephrotic syndrome. Circulation 2004; 110:419.
- Demant T, Mathes C, Gütlich K, et al. A simultaneous study of the metabolism of apolipoprotein B and albumin in nephrotic patients. Kidney Int 1998; 54:2064.
- Vega GL, Toto RD, Grundy SM. Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia. Kidney Int 1995; 47:579.
- Wang L, Shearer GC, Budamagunta MS, et al. Proteinuria decreases tissue lipoprotein receptor levels resulting in altered lipoprotein structure and increasing lipid levels. Kidney Int 2012; 82:990.
- Warwick GL, Packard CJ, Demant T, et al. Metabolism of apolipoprotein B-containing lipoproteins in subjects with nephrotic-range proteinuria. Kidney Int 1991; 40:129.
- Shearer GC, Stevenson FT, Atkinson DN, et al. Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome. Kidney Int 2001; 59:179.
- Davies RW, Staprans I, Hutchison FN, Kaysen GA. Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat. J Clin Invest 1990; 86:600.
- Joles JA, Bijleveld C, van Tol A, et al. Plasma triglyceride levels are higher in nephrotic than in analbuminemic rats despite a similar increase in hepatic triglyceride secretion. Kidney Int 1995; 47:566.
- Clement LC, Macé C, Avila-Casado C, et al. Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome. Nat Med 2014; 20:37.
- Ordoñez JD, Hiatt RA, Killebrew EJ, Fireman BH. The increased risk of coronary heart disease associated with nephrotic syndrome. Kidney Int 1993; 44:638.
- Gentile MG, Fellin G, Cofano F, et al. Treatment of proteinuric patients with a vegetarian soy diet and fish oil. Clin Nephrol 1993; 40:315.
- Keilani T, Schlueter WA, Levin ML, Batlle DC. Improvement of lipid abnormalities associated with proteinuria using fosinopril, an angiotensin-converting enzyme inhibitor. Ann Intern Med 1993; 118:246.
- Massy ZA, Ma JZ, Louis TA, Kasiske BL. Lipid-lowering therapy in patients with renal disease. Kidney Int 1995; 48:188.
- Rabelink AJ, Hené RJ, Erkelens DW, et al. Effects of simvastatin and cholestyramine on lipoprotein profile in hyperlipidaemia of nephrotic syndrome. Lancet 1988; 2:1335.
- Thomas ME, Harris KP, Ramaswamy C, et al. Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria. Kidney Int 1993; 44:1124.
- Kong X, Yuan H, Fan J, et al. Lipid-lowering agents for nephrotic syndrome. Cochrane Database Syst Rev 2013; :CD005425.
- Brown CD, Azrolan N, Thomas L, et al. Reduction of lipoprotein(a) following treatment with lovastatin in patients with unremitting nephrotic syndrome. Am J Kidney Dis 1995; 26:170.
- Bianchi S, Bigazzi R, Caiazza A, Campese VM. A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Am J Kidney Dis 2003; 41:565.
- Dogra GK, Watts GF, Herrmann S, et al. Statin therapy improves brachial artery endothelial function in nephrotic syndrome. Kidney Int 2002; 62:550.
- Valeri A, Gelfand J, Blum C, Appel GB. Treatment of the hyperlipidemia of the nephrotic syndrome: a controlled trial. Am J Kidney Dis 1986; 8:388.
- Hattori M, Chikamoto H, Akioka Y, et al. A combined low-density lipoprotein apheresis and prednisone therapy for steroid-resistant primary focal segmental glomerulosclerosis in children. Am J Kidney Dis 2003; 42:1121.
- Muso E, Mune M, Fujii Y, et al. Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group. Kidney Int Suppl 1999; 71:S122.
- Kobayashi S. Applications of LDL-apheresis in nephrology. Clin Exp Nephrol 2008; 12:9.