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Hyperlipidemia in childhood nephrotic syndrome

  • Practical Pediatric Nephrology
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Abstract

Hyperlipidemia is an important characteristic of nephrotic syndrome (NS). Elevation of plasma total cholesterol, or more specifically low-density lipoprotein cholesterol, is the major lipid abnormality in NS, although hypertriglyceridemia may develop as the disorder progresses. The pathophysiology of nephrotic hyperlipidemia is complex. The prevailing view is that both hepatic synthesis of lipids and of apolipoproteins is increased, and that the clearance of chylomicrons and very low-density lipoproteins is reduced. The precise contribution of increased lipogenesis and decreased lipid catabolism to hyperlipidemia, and their relationship to urinary protein loss, hypoalbuminemia and reduced serum oncotic pressure remain controversial. There are two potential risks of elevated plasma lipids: atherosclerosis and progression of glomerular injury. Although neither of these complications has been proved with certainty, there is growing evidence that both may be long-term consequences of NS. Therefore, the diagnosis and treatment of lipid abnormalities, important aspects of the management of nephrotic children, is summarized here to provide pediatric nephrologists with an informed choice.

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References

  1. Berlyne G, Mallick N (1969) Ischemic heart disease as a complication of nephrotic syndrome. Lancet II:399–400

    Google Scholar 

  2. Hopper J, Ryan P, Lee J, Rosenau W (1970) Lipoid nephrosis in 31 adult patients: renal biopsy study by light, electron and fluorescence microscopy with experience in treatment. Medicine (Baltimore) 49:321–341

    Google Scholar 

  3. Wass V, Jarrett R, Chilvers C, Cameron J (1979) Does the nephrotic syndrome increase the risk of cardiovascular disease? Lancet II:664–667

    Google Scholar 

  4. Pooling Project Research Group (1978) Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the pooling project. J Chron Dis 31:201–306

    Google Scholar 

  5. Martin M, Hulley S, Browner W, Kuller L, Wentworth D (1986) Serum cholesterol, blood pressure and mortality: implications from a cohort of 361,662 men. Lancet II:934–936

    Google Scholar 

  6. Grundy SM, Vega GL (1989) Rational and management of hyperlipidemia of the nephrotic syndrome. Am J Med 87:3N-11N

    Google Scholar 

  7. Wheeler DC, Varghese Z, Moorhead JF (1989) Hyperlipidemia in nephrotic syndrome. Am J Nephrol 9:78–84

    Google Scholar 

  8. Strauss J, Zilleruelo G, Freundlich M, Abitbol C (1987) Less commonly recognized features of childhood nephrotic syndrome. Pediatr Clin North Am 34:591–607

    Google Scholar 

  9. Kaysen GA (1991) Hyperlipidemia of nephrotic syndrome. Kidney Int 39:S8-S15

    Google Scholar 

  10. Appel GB, Valeri A, Apple AS, Blum C (1989) The hyperlipidemia of nephrotic syndrome. Am J Med 87:45N-50N

    Google Scholar 

  11. Vlahcevic ZR, Heuman DM, Hylemon PB (1991) Regulation of bile acid synthesis. Hepatology 13:590–600

    Google Scholar 

  12. Dietschy JM (1990) LDL cholesterol: its regulation and manipulation. Hosp Pract [Off] 25:67–78

    Google Scholar 

  13. Baxter JH, Goodman HC, Havel RJ (1960) Serum lipids and lipoprotein alterations in nephrosis. J Clin Invest 39:455–464

    Google Scholar 

  14. McKenzie IFC, Nestel PJ (1968) Studies on the turnover of triglyceride and esterified cholesterol in subjects with the nephrotic syndrome. J Clin Invest 47:1685–1695

    Google Scholar 

  15. Gherardi E, Rota E, Calandra S Genova R, Tamborino A (1977) Relationship among the concentrations of serum lipoproteins and changes in their chemical composition in patients with untreated nephrotic syndrome. Eur J Clin Invest 7:563–570

    Google Scholar 

  16. Ohta T, Matsuda I (1981) Lipid and apolipoprotein levels in patients with nephrotic syndrome. Clin Chim Acta 117: 133–143

    Google Scholar 

  17. DeMendoza S, Kashyap M, Chen C, Lutmer R (1976) High density lipoproteinuria in nephrotic syndrome. Metabolism 25:1143–1149

    Google Scholar 

  18. Oetliker O, Mordasini R, Lutschg J, Riesen W (1980) Lipoprotein metabolism in nephrotic syndrome in children. Pediatr Res 14:64–66

    Google Scholar 

  19. Chan M, Persaud J, Ramdial L, Varghese Z, Sweny P, Moorhead J (1981) Hyperlipidemia in untreated nephrotic syndrome, increased production or decreased removal? Clin Chim Acta 117:317–323

    Google Scholar 

  20. Cameron S, Wass V, Jarrett R, Chilvers C (1979) nephrotic syndrome and cardiovascular disease. Lancet II:1017–1019

    Google Scholar 

  21. Cohen L, Cramp D, Lewis A, Tikner T (1980) The mechanism of hyperlipidemia in the nephrotic syndrome: role of low albumin and the LCAT reaction. Clin Chim Acta 104:393–400

    Google Scholar 

  22. Sokolovskaya IV, Nikiforova NV (1984) High-density lipoprotein cholesterol in patients with untreated and treated nephrotic syndrome. Nephron 37:49–53

    Google Scholar 

  23. Zilleruelo G, Hsia S, Freundlich M, Gorman H, Strauss J (1984) Persistence of serum lipid abnormalities in children with idiopathic nephrotic syndrome. J Pediatr 104:61–64

    Google Scholar 

  24. Marsh J, Drabkin D (1960) Experimental reconstruction of metabolic pattern of lipid nephrosis: key role of hepatic protein synthesis in hyperlipidemia. Metabolism 9:946–955

    Google Scholar 

  25. Gherardi E, Calandra S (1980) Experimental nephrotic syndrome induced in the rat by puromycin aminonucleoside hepatic synthesis of neutral lipids and phospholipids from3H-water and3H-palmitate. Lipids 15:108–112

    Google Scholar 

  26. Golper TA, Feingold KR, Fulford MH, Siperstein MD (1986) The role of circulating mevalonate in nephrotic hypercholesterolemia in the rat. J Lipid Res 27:1044–1051

    Google Scholar 

  27. Marsh JB, Drabkin DL (1958) Metabolic channeling in experimental nephrosis. V. Lipid metabolism in the early stages of the disease. J Biol Chem 230:1083–1091

    Google Scholar 

  28. Goldberg CARK, Helena CF, Oliveira ED, Quintao CR, McNamara DJ (1982) Increased hepatic cholesterol production due to liver hypertrophy in rat experimental nephrosis. Biochim Biophys Acta 710:71–75

    Google Scholar 

  29. Marsh JB, Drabkin DL (1955) Metabolic channeling in experimental nephrosis. II. Lipid metabolism. J Biol Chem 212:633–639

    Google Scholar 

  30. Thabet MA, Challa A, Chan JCM, Vlahcevic ZR, Pandak WM (1992) Mechanism of hypercholesterolemia in nephrotic syndrome (abstract). Pediatr Res 31:344A

    Google Scholar 

  31. Bernard DB (1988) Extrarenal complications of the nephrotic syndrome. Kidney Int 33:1184–1202

    Google Scholar 

  32. Kaysen G, Gambertoglio J, Felts J, Hutchison F (1987) Albumin synthesis, albuminuria and hyperlipidemia in nephrotic patients. Kidney Int 31: 1368–1376

    Google Scholar 

  33. Marsh J, Sparks C (1979) Hepatic secretion of lipoproteins in the rat and the effect of experimental nephrosis. J Clin Invest 64: 1229–1237

    Google Scholar 

  34. Radding C, Steinberg D (1960) Studies on the synthesis and secretion of serum lipoproteins by rat liver slices. J Clin Invest 39: 1560–1569

    Google Scholar 

  35. Baxter J, Goodman H, Allen J (1961) Effects of infusions of serum albumin on serum lipids and lipoproteins in nephrosis. J Clin Invest 40: 490–498

    Google Scholar 

  36. Marsh JB (1984) Lipoprotein metabolism in experimental nephrosis. J Lipid Res 25: 1619–1623

    Google Scholar 

  37. Golper TA, Schartz SH (1982) Impaired renal mevalonate metabolism in nephrotic syndrome: a stimulus for increased hepatic cholesterologensis independent of GFR and hypoalbuminemia. Metabolism 31: 471–476

    Google Scholar 

  38. Goldstein JL, Brown MS (1977) The low density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 46: 897–930

    Google Scholar 

  39. Garber DW, Gottlieb BA, Marsh JB, Sparks CE (1984) Catabolism of very low density lipoproteins in experimental nephrosis. J Clin Invest 74: 1375–1383

    Google Scholar 

  40. Chan M, Persaud J, Varghese Z, Moorhead J (1984) Post-heparin hepatic and lipoprotein lipasc activities in nephrotic syndrome. Aust NZJ Med 14: 841–847

    Google Scholar 

  41. Gutman A, Shafrir E (1963) Adipose tissue in experimental nephrotic syndrome. Am J Physiol 205: 702–706

    Google Scholar 

  42. Yamada M, Matsuda J (1970) Lipoprotein lipase in clinical and experimental nephrosis. Clin Chim Acta 30: 787–794

    Google Scholar 

  43. Calandra S, Gottardi E, Tarugi P (1983) Plasma postheparin lipolytic activity in rats with nephrotic syndrome. Horm Metab Res 15: 361–362

    Google Scholar 

  44. Rosenman RH, Byers OS (1960) Lipoprotein lipase metabolism in experimentally nephrotic rats. Proc Soc Exp Biol Med 103: 31–36

    Google Scholar 

  45. Furukawa S, Hirano T, Mamo JCL, Nagano S, Takahashi T (1990) Catabolic defect of triglyceride is associated with abnormal verylow-density lipoprotein in experimental nephrosis. Metabolism 39: 101–107

    Google Scholar 

  46. Davies RW, Staprans I, Hutchinson FN, Kaysen GA (1990) Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat. J Clin Invest 86: 600–605

    Google Scholar 

  47. Staprans I, Anderson CD, Lurz FW, Felts JM (1980) Separation of a lipoprotein lipase cofactor from the alpha-acid glycoprotein fraction from urine of nephrotic patients. Biochim Biophys Acta 617: 514–523

    Google Scholar 

  48. Jungst D, Caselmann WH, Kutschera P, Weisweiler P (1987) Relation of hyperlipemia in serum and loss of high density lipoproteins in urine in the nephrotic syndrome. Clin Chim Acta 168: 159–167

    Google Scholar 

  49. Appel GB, Blum, CB, Chien S, Kunis CL, Appel AS (1985) The hyperlipidemia of the nephrotic syndrome. N Engl J Med 312: 1544–1548

    Google Scholar 

  50. Ordonez JD, Hiatt R, Killebrrew E, Fireman B (1990) The risk of coronary artery disease among patients with the nephrotic syndrome (abstract). Kidney Int 37: 243A

    Google Scholar 

  51. Gilboa N (1976) Incidence of coronary heart disease associated with nephrotic syndrome. Med J Aust 1: 207–208

    Google Scholar 

  52. Alexander JH, Schapel GJ, Edwards KDG (1974) Increased incidence of coronary heart disease associated with combined elevation of serum triglycerides and cholesterol in the nephrotic syndrome in man. Med J Aust 2: 119–122

    Google Scholar 

  53. Moorhead JF (1991) Lipids and progressive kidney disease. Kidney Int 39: S35-S40

    Google Scholar 

  54. Keane WF, Kasiske BL, O'Donnell MP, Schmitz PG (1989) Therapeutic implications of lipid-lowering agents in the progression of renal disease. Am J Med 87: 21N-24N

    Google Scholar 

  55. Diamond JR (1989) Hyperlipidemia of nephrosis: pathophysiologic role in progressive glomerular disease. Am J Med 87: 25N-29N

    Google Scholar 

  56. Schmitz PG, Kariske BI, O'Donnell MP, Keane WF (1989) Lipids and progressive renal injury. Semin Nephrol 9: 354–369

    Google Scholar 

  57. Keane WF, Kasiske BL, O'Donnell MP (1988) Lipids and progressive glomerulosclerosis: a model analogous to atherosclerosis. Am J Nephrol 8: 261–271

    Google Scholar 

  58. Moorhead JF, El-Nahas M, Chan MK, Varghese Z (1982) Lipid nephrotoxicity in chronic glomerular and tubulo-interstitial disease. Lancet II: 1309–1311

    Google Scholar 

  59. Keane WF, Kasiske BL, O'Donnell JP (1988) Hyperlipidemia and the progression of renal disease. Am J Clin Nutr 47: 157–160

    Google Scholar 

  60. Klahr S, Schreiner G, Ichikawa I (1988) The progression of renal disease. N Engl J Med 318: 1657–1666

    Google Scholar 

  61. Diamond JR, Karnovsky MJ (1988) Focal and segmental glomerulosclerosis: analogies to atherosclerosis. Kidney Int 33: 917–924

    Google Scholar 

  62. Newmark SR, Anderson CF, Donadio JV (1975) Lipoprotein profile in adult nephrotics. Mayo Clin Proc 50: 359–364

    Google Scholar 

  63. Short CD, Danington PN, Malhick NP, Hunt LP, Tetlow L, Ishola M (1986) Serum and urinary high density lipoprotein in glomerular disease with proteinuria. Kidney Int 29: 1224–1228

    Google Scholar 

  64. Moorhead JF, Wheeler DC, Fernando R (1989) Injury to rat mesangial cells in culture by low density lipoproteins (abstract). Kidney Int 35: 433A

    Google Scholar 

  65. Kasiske BL, O'Donnell MP, Cleary MP (1988) Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats. Kidney Int 33: 667–672

    Google Scholar 

  66. Harris KPG, Purkerson ML, Yates J (1989) Lowering cholesterol ameliorates renal disease in experimental nephrotic syndrome (abstract). Kidney Int 35: 429A

    Google Scholar 

  67. Kasiske BL, O'Donnell MP, Garvis WJ, Keane WF (1988) Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure. Circ Res 62: 367–374

    Google Scholar 

  68. O'Donnell MP, Kasiske BL, Kim Y, Atluru D, Keane WF (1993) Lovastatin inhibits proliferation of rat mesangial cells. J Clin Invest 91: 83–87

    Google Scholar 

  69. Keane WF, Mulchahy WS, Kasiske BL, Kim Y, O'Donnell MP (1991) Hyperlipidemia and progressive renal disease. Kidney Int 39: S40-S47

    Google Scholar 

  70. Diamond JR (1991) Analogous pathobiologic mechanisms in glomerulosclerosis and atherosclerosis: roles of hypercholesterolemia and the glomerular macrophage. Kidney Int 39: S28-S33

    Google Scholar 

  71. Barcelli O (1991) Effect of dietary prostaglandin precursors on the progression of renal disease in animals. Kidney Int 39: S56-S63

    Google Scholar 

  72. Havel RJ (1989) Rationale for cholesterol lowering. Am J Med 87: 2–4

    Google Scholar 

  73. Brett AS (1989) Treating hypercholesterolemia. How should practicing physicians interpret the published data for patients? N Engl J Med 321: 676–679

    Google Scholar 

  74. D'Amico G, Gentile MG (1991) Pharmacological and dietary treatment of lipid abnormalities in nephrotic patients. Kidney Int 39: S65-S69

    Google Scholar 

  75. Kasiske BL, Velosa JA, Halstenson CE, La Belle P, Langendorfer A, Keane WF (1990) The effects of lovastatin in hyperlipidemic patients with nephrotic syndrome. Am J Kidney Dis 15: 8–15

    Google Scholar 

  76. Coggins CH, Cornell BF (1988) Nutritional management of nephrotic syndrome. In: Mitch WE, Klahr S (eds) Nutrition and the kidney. Little Brown, Boston, pp 239–249

    Google Scholar 

  77. Grundy SM (1990) Management of hyperlipidemia of kidney disease. Kidney Int 37: 847–853

    Google Scholar 

  78. Shepherd J, Packard CJ, Bicker S, Lawrie TDV, Morgan HG (1980) Cholestyramine promotes receptor mediated low density lipoprotein catabolism. N Engl J Med 302: 1219–1222

    Google Scholar 

  79. Valeri A, Gelfand J, Blum C, Appel GB (1986) Treatment of the hyperlipidemia of the nephrotic syndrome: a controlled trial. Am J Kidney Dis 8: 388–396

    Google Scholar 

  80. Rabelink AJ, Erkelens DW, Hene RJ, Joles JA, Koomans HA (1988) Effects of simvastatin and cholestyramine on lipoprotein profile in hyperlipidaemia of nephrotic syndrome. Lancet II: 1335–1338

    Google Scholar 

  81. Kesaniemi YA, Grundy SM (1984) Influence of probucol on cholesterol and lipoprotein metabolism in man. J Lipid Res 25: 780–790

    Google Scholar 

  82. Parthasarathy S, Young SG, Witztum JL, Pittman RC, Steinberg D (1986) Probucol inhibits oxidative modification of low density lipoprotein. J Clin Invest 77: 641–644

    Google Scholar 

  83. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320: 915–923

    Google Scholar 

  84. Iida H, Izumino K, Azaka M, Fujita M, Nishino A, Sasayama S (1987) Effect of probucol on hyperlipidemia in patients with nephrotic syndrome. Nephron 47: 280–283

    Google Scholar 

  85. Bridgeman JF, Rosen SM, Thorp JM (1972) Complications during clofibrate treatment of nephrotic syndrome hyperlipoproteinemia. Lancet II: 506–509

    Google Scholar 

  86. Grundy SM (1988) HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med 319: 24–33

    Google Scholar 

  87. Kovanen PT, Bilheimer DW, Goldstein JL, Brown MS (1981) Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog. Proc Natl Acad Sci USA 78: 1194–1198

    Google Scholar 

  88. Vega GL, Grundy SM (1988) Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. Kidney Int 33: 1160–1168

    Google Scholar 

  89. Schaefer EJ, Levy RI (1985) Pathogenesis and management of lipoprotein disorders. N Engl J Med 312: 1300–1310

    Google Scholar 

  90. Olsson AG, Walldius G, Wahlberg G (1986) Pharmacological control of hyperlipidaemia: nicotinic acid and its analogues—mechanisms of action, effects, and clinical usage. In: Fears R, Prous JR (eds) Pharmacological control of hyperlipidaema. Science Publishers, Barcelona, pp 217–230

    Google Scholar 

  91. Grundy SM, Vega GL, Bilheimer DW (1985) Influence of combined therapy with mevinolin and interruption of bile-acid reasbsorption on low density lipoproteins in heterozygous familial hypercholesterolemia. Ann Intern Med 103: 339–343

    Google Scholar 

  92. Vega GL, Grundy SM (1987) Treatment of primary moderate hypercholesterolemia with lovastatin (Mevinolin) and colestipol. JAMA 257: 33–38

    Google Scholar 

  93. Keane WF, St Peter JV, Kasiske BL (1992) Is the aggressive management of hyperlipidemia in nephrotic syndrome mandatory? Kidney Int 38: S134-S141

    Google Scholar 

  94. Curry RC Jr, Roberts WC (1977) Status of the coronary arteries in the nephrotic syndrome. Analysis of 20 necropsy patients aged 15 to 35 years to determine if coronary atherosclerosis is accelerated. Am J Med 63: 183–192

    Google Scholar 

  95. Pandak WM, Vlahcevic ZR, Heuman DM, Hylemon PB (1990) Regulation of bile acid synthesis. V. Inhibition of conversion of 7-dehydrocholesterol to cholesterol is associated with down-regulation of cholesterol 7α-hydroxylase activity and inhibition of bile acid synthesis. J Lipid Res 31: 2149–2158

    Google Scholar 

  96. Bernard DB (1982) Metabolic abnormalities in nephrotic syndrome: pathophysiology and complications. In: Brenner BM, Stein JH (eds) Contemporary issues in nephrology. Churchill-Livingstone, New York, pp 85–120

    Google Scholar 

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Authors and Affiliations

  1. Nephrology Division, Children's Medical Center, Department of Pediatrics, Medical College of Virginia, Health Sciences Division of Virginia Commonwealth University, Richmond, Virginia, USA

    Mohamed Alaa Eldin Hassan Thabet & James C. M. Chan

  2. Department of Pediatrics, New Jersey Medical School, Newark, New York, USA

    Jose R. Salcedo

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  1. Mohamed Alaa Eldin Hassan Thabet
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  2. Jose R. Salcedo
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Hassan Thabet, M.A.E., Salcedo, J.R. & Chan, J.C.M. Hyperlipidemia in childhood nephrotic syndrome. Pediatr Nephrol 7, 559–566 (1993). https://doi.org/10.1007/BF00852550

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