Hyperlipidemia, nephrotic syndrome

Hyperlipidemia, secondary causes Prior to initiating therapy, exclude secondary causes of hyperlipidemia (eg, poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) and measure total-C, HDL-C, and triglycerides. 

Hyperlipidemia (mainly hypercholesterolemia) is a regular part of nephrotic syndrome (K13, W6). Serum levels of cholesterol are often markedly elevated, usually above 10 mmol/L. However, in severely malnourished patients, normal or even decreased serum cholesterol level can be found. Serum levels of triacylglyc-erols fluctuate, from normal values to markedly elevated values (mainly in patients with proteinuria higher than 10 g/24 hr). There is a variable increase in plasma concentrations of very low density lipoproteins (VLDL, they correlate negatively with serum albumin level), intermediate-density lipoproteins (IDL), andLDL however, plasma concentrations of HDL are usually normal (J3). Levels of lipoprotein(a) [Lp(a)j are also increased (W4). Remission of nephrotic syndrome or decrease of proteinuria may result in the decrease of plasma concentrations of Lp(a) (G2). Concentration of free fatty acids in serum is commonly decreased because they are normally bound to albumin and albumin is lost into the urine. The activity of lecithin cholesterol acyltransferase (LCAT) is usually decreased. 

Diagnosis of nephrotic syndrome depends on the identification of both the clinical signs (edema) and laboratory disorders (proteinuria, hypoproteinemia, hypoal-buminemia, hyperlipidemia). Lipid and coagulation abnormalities that also must be monitored are described in detail in the appropriate sections. 

Persistent nephrotic syndrome is a life-threatening disease (mainly due to the risk of thromboembolic and infectious complications) and clearly confers a high risk of progression into end-stage renal failure, which is related to the degree of proteinuria (Jl). The therapeutic goal is therefore the remission of nephrotic syndrome, or at least reduction of proteinuria. In patients with persistent nephrotic syndrome, symptomatic treatment (or prevention) of hyperlipidemia, hypercoagulability, and sodium and water retention is also warranted. 

Nephrotic syndrome is a clinical and laboratory syndrome caused by the increased permeability of the glomerular capillary wall for macromolecules. Nephrotic syndrome is a potentially life-threatening state and persistent nephrotic syndrome has a poor prognosis with a high risk of progression to end-stage renal failure and a high risk of cardiovascular complications due to severe hyperlipidemia. 

Nephrotic hyperlipidemia is accompanied with increased risk of cardiovascular complications and should be treated in all patients with persistent nephrotic syndrome. The putative positive effect of hypolipidemic drugs (namely statins) on the cardiovascular risk and potentially also on the rate of progression of chronic renal failure remains to be demonstrated in prospective controlled studies. 

Nephrotic syndrome (proteinuria, edema, hypoalbumine-mia, hyperlipidemia) is a rare and idiosyncratic complication of lithium therapy it usually resolves on withdrawal, and can recur on rechallenge (397,398). Lithium-associated nephrotic syndrome occurred in a 59-year-old woman with lithium toxicity (serum concentration 1.9 mmol/1) whose renal biopsy showed focal segmental glomerulosclerosis. Lithium withdrawal led to resolution of edema and marked improvement in proteinuria and albuminemia (398). 

Toto RD, Grundy SM, Vega GL. Pravastatin treatment of very-low-density, intermediate-density and low-density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome. Am J Nephrol 2000 20 12-17. 

Although the data are not conclusive, hyperlipidemia has been associated as a susceptibility factor for CKD in both animal and human studies. The use of lipid-lowering agents in some animal models has been found to decrease the extent of glomerular injury when both underlying renal disease and hyperlipidemia are present. Therefore the correction of lipid abnormalities in patients with CKD was proposed to have a beneficial effect on the rate of progression of the disease. CKD with or without nephrotic syndrome is frequently accompanied by abnormalities in fipoprotem metabolism. The prevalence of hyperlipidemia appears to increase as kidney function declines and with the presence of the nephrotic syndrome. ... 

The prevalence of hyperlipidemia appears to increase as kidney function declines. In patients with CKD without nephrotic syndrome, hypertriglyceridemia (plasma concentrations >200 mg/ dL) is observed in approximately 40% to 50% of patients. In addition, 20% to 30% of these patients have total cholesterol levels greater than 240mg/dL, while 10% to 45% have LDL concentrations >130mg/dL. 

The best approach to the treatment of hyperlipidemia in patients with nephrotic syndrome is to induce remission of the disease (see Chap. 47), or at least to reduce urine protein excretion by aggressive treatment of concurrent hypertension and/or administration of ACEIs or ARBs. Several trials have assessed the effect of L-carnitine supplementation on abnormal lipid metabolism in dialysis patients, but results have been contradictory. ... 

Nephrotic syndrome is characterized by proteinuria greater than 3.5 g/day per 1.73 m, hypoproteinemia, edema, and hyperlipidemia. A hypercoagulable state may also be present in some patients. The syndrome may be the result of primary diseases of the glomerulus, or be associated with systemic diseases such as diabetes mellitus, lupus, amyloidosis, and preeclampsia. Hypoproteinemia, especially hypoal-buminemia, results from increased urinary loss of albumin and an increased rate of catabolism of filtered albumin by proximal tubular cells. The compensatory increase in hepatic synthesis of albumin is insufficient to replenish the protein loss, probably because of malnutrition. 

Most patients present initially with edema, frequently acute in onset, following a nonspecific upper respiratory tract infection, allergic reaction, or vaccinations, which might have activated the T lymphocytes. Nephrotic syndrome with massive proteinuria (substantially more than 40 mg/m per hour for children and 3 g/day for adults), edema, hypoalbuminemia, and hyperlipidemia is common. The patient s weight may be increased dramatically because of sodium and fluid retention. Nephrotic features such as gross hematuria are uncommon. However, microscopic hematuria may be seen in up to 20% to 25% of patients. Hypertension and decreased renal function are uncommon in children but are more common in older adults. In some patients, volume depletion may result in mild to moderate azotemia. 

In cases when gastrointestinal or pancreatic toxicity is present, plasma lipids will be affected. The nephrotic syndrome is characterized by hyperlipidemia, hypopro-teinemia, and hyperproteinuria in several species, and lipid changes may also be observed with chronic renal damage (Moestrup and Nielsen 2005). 

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