Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease

A survey of 246 suggested coronary risk factors

Background and Methods. Patients with the nephrotic syndrome characteristically have multiple abnormalities of lipoprotein metabolism, but the cause and exact nature of these abnormalities are uncertain. In this study, we measured serum lipids and apoproteins in 57 patients with the nephrotic syndrome. We also determined the kinetic indexes of low-density lipoprotein (LDL) metabolism in six patients, and again in three of the six after recovery. Results. The patients with the nephrotic syndrome had elevated serum concentrations of cholesterol, triglycerides, and phospholipids, which were confined to the lipoproteins containing apoprotein B. The serum concentrations of high-density lipoproteins and the associated A-I and A-II apoproteins were similar in the patients with the nephrotic syndrome and normal subjects. The relative proportions of lipids and their positive association with the increased serum concentrations of apoproteins B, C-II, C-III, and E suggest quantitative rather than qualitativ...

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Abnormalities of lipoprotein metabolism in patients with the nephrotic syndrome.

https://www.kidney-international.org/article/S0085-2538(15)57104-4/pdf

Lipid abnormalities in renal disease

Lipid abnormalities in patients with the nephrotic syndrome have long been recognized. However, the significance of these lipid abnormalities, the mechanisms producing them, and their potential treatment have all been a cause of debate. Recent data have helped clarify each of these areas of controversy. Studies of the lipoprotein abnormalities of patients with the uncomplicated nephrotic syndrome have shown that many will have elevated levels of total and low-density lipoprotein cholesterol, whereas only a few will have elevated levels of high-density lipoprotein cholesterol. If these lipid abnormalities have the same significance in this population as in other populations studied, then some patients with unremitting nephrotic syndrome will be at high risk for cardiovascular disease. The elevated cholesterol levels noted in the nephrotic syndrome are caused primarily by enhanced hepatic synthesis, with lesser contributions by decreased clearance and altered enzyme activities. The signal for enhanced hepatic lipogenesis may relate to changes in plasma albumin concentration, plasma oncotic pressure, a local effect of viscosity at the hepatic sinusoidal level, or a loss of urinary proteins or other liporegulatory substances. Recently, a number of short-term studies in nephrotic patients have documented the safety and efficacy of lipid-lowering drugs such as the bile acid-binding resins, probucol, and the HMGCoA (hydroxymethylglutaryl coenzyme A) reductase inhibitors.

The Hyperlipidemia of the Nephrotic Syndrome

. The quantitative and qualitative changes of serum lipoproteins have been studied in twelve patients with untreated uncomplicated nephrotic syndrome. The lipoprotein disorders found in these patients were characterized by an elevation of VLDL (d < 1.006 g ml-1), LDL (d 1.006–1.019 g ml-1) and LDL2 (d 1.019–1.063 g ml-1) and a diminution of HDL2 (d 1.063–1.125 g ml-1). These changes were strictly correlated with the concentration of serum albumin and were more pronounced in the patients with serum albumin < 20 g l-1.



The study of the relationship among the concentrations of the various lipoprotein classes indicated that (i) the levels of VLDL and LDL1 were reciprocally related to that of the high density lipoproteins and (ii) the level of LDL2 rose with the moderately increased VLDL and LDL1 but at the high concentrations of VLDL and LDL1 observed in the severe nephrotic syndrome it did not show any further increase, suggesting a defect in the conversion of VLDL to LDL2.



The nephrotic syndrome was associated with marked changes in the composition of all lipoprotein fractions which were found to contain more phospholipid but less protein than normal. Major changes in composition were observed in VLDL and LDL1 which were rich in esterified cholesterol and phopholipids and had an esterified cholesterol: triglyceride molar ratio (CE/TG) higher than the corresponding fractions of the control subjects. Furthermore, CE/TG ratio in these fractions increased as their serum concentration increased.



These observations indicate that in severe, untreated uncomplicated nephrotic syndrome there is a progressive accumulation of d < 1.019 g ml-1 lipoproteins rich in esterified cholesterol. Chemically these resemble VLDL and chylomicron remnants and are possibly related to some defect in the conversion of VLDL to LDL2.

R. Genova

Papers

Relationship among the concentrations of serum lipoproteins and changes in their chemical composition in patients with untreated nephrotic syndrome