Statins in nephrotic syndrome: A new weapon against tissue injury

Abstract

The nephrotic syndrome is characterized by metabolic disorders leading to an increase in circulating lipoproteins levels. Hypertriglyceridemia and hypercholesterolemia in this case may depend on a reduction in triglyceride-rich lipoproteins catabolism and on an increase in hepatic synthesis of Apo B-containing lipoproteins. These alterations are the starting point of a self-maintaining mechanism, which can accelerate the progression of chronic renal failure. Indeed, hyperlipidemia can affect renal function, increase proteinuria and speed glomerulosclerosis, thus determining a higher risk of progression to dialysis. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is the rate-limiting enzyme in cholesterol synthesis from mevalonate and its inhibitors, or statins, can therefore interfere with the above-mentioned consequences of hyperlipidemia. Statins are already well known for their effectiveness on primary cardiovascular prevention, which cannot be explained only through their hypolipemic effect. As far as kidney diseases are concerned, statin therapy has been shown to prevent creatinine clearance decline and to slow renal function loss, particularly in case of proteinuria, and its favorable effect may depend only partially on the attenuation of hyperlipidemia. Statins may therefore confer tissue protection through lipid-independent mechanisms, which can be triggered by other mediators, such as angiotensin receptor blockers. Possible pathways for the protective action of statins, other than any hypocholesterolemic effect, are: cellular apoptosis/proliferation balance, inflammatory cytokines production, and signal transduction regulation. Statins also play a role in the regulation of the inflammatory and immune response, coagulation process, bone turnover, neovascularization, vascular tone, and arterial pressure. In this study, we would like to provide scientific evidences for the pleiotropic effects of statins, which could be the starting point for the development of new therapeutical strategies in different clinical areas.

Comparison of Signalment, Clinicopathologic Findings, Histologic Diagnosis, and Prognosis in Dogs with Glomerular Disease with or without Nephrotic Syndrome

“…The cause of hypercholesterolemia in human patients with NS is unclear, but it may reflect a nonspecific increase in hepatic protein synthesis in response to hypoalbuminemia, low plasma oncotic pressure, or altered plasma viscosity. 5 Unlike hypercholesterolemia, hypertriglyceridemia is not a defining feature of NS in people, and increases in serum cholesterol concentration are not always accompanied by increases in triglycerides. 5,26 Hyperlipidemia is associated with increased prevalence of atherosclerosis and progressive azotemia, and human patients with persistent hypercholesterolemia commonly are treated with the ''statin'' class of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors.…”

“…3,4 Serum albumin concentration in these patients is often o2.5 g/dL and total cholesterol concentration is usually 4240 mg/dL. 3,5 People with NS are at higher risk than those with nonnephrotic glomerular disease (NNGD) for development of complications, including hypernatremia, thromboembolic disease, hypertension, and progressive renal failure. 1,2,[6][7][8] Minimal change disease and membranous nephropathy are the primary glomerular diseases most commonly diagnosed in children and adults with NS, respectively, whereas diabetic nephropathy and amyloidosis are the most commonly diagnosed secondary glomerular diseases in adults with NS.…”

Amelioration of steroids and cyclosporine-resistant nephrotic syndrome by pravastatin

“…Lowering lipid levels may protect against systemic atherosclerosis and slow the rate of progression of Fig. 1 Clinical course of our patient the underlying renal disease [9,10]. We initially used pravastatin as a lipid-lowering agent in this patient who had been in a nephrotic condition for over 6 years, in spite of various treatments.…”

Diabetic Kidney Disease: A Renin-Angiotensin-Aldosterone System Focused Review

“…For patients with DKD not receiving dialysis, no renal dosage adjustments are warranted. 1,5,21 Treatment of dyslipidemia will decrease the risk of a CHD event for patients with DKD, but there are conflicting results from studies to determine whether correction of abnormal lipid levels will actually slow the progression of kidney damage. More studies need to be conducted to find a definitive answer.…”