Hyperlipidemias: Remuzzi G

Cravedi P, Ruggenenti P, Remuzzi G. · Department of Medicine and Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. · J Ren Care. · Pubmed #19160879 No free full text.

Abstract: The level of proteinuria is one of the most important predictors for progressive renal function loss in kidney disease. Reduction of urinary protein levels by renin-angiotensin-system (RAS) inhibitors limits renal function decline in patients with non-diabetic and diabetic nephropathies to the point that remission of the disease and regression of renal lesions have been reported. The increasing use of these drugs is possibly at the basis of the stabilization of rates of new cases of kidney failure reported to the US Renal Data System after a 2-decade period of progressive increases. RAS inhibition, however, may not be effective to the same degree in all patients. For those patients who do not reach a complete remission of proteinuria, treatment procedures to implement renoprotection should include strict blood pressure control (and metabolic control in diabetics), lowering of blood lipids, and lifestyle modifications. Early intervention may be important to maximize renoprotection, especially in diabetics.

Cravedi P, Remuzzi G. · Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Bergamo, Italy. · Kidney Int Suppl. · Pubmed #19034321 No free full text.

Abstract: The incidence of chronic renal and cardiovascular diseases is increasing worldwide. Since renal disease is the strongest risk factor for cardiovascular morbidity and mortality, strategies able to reduce renal disease progression are expected to translate into a decreased incidence of cardiovascular events. To this purpose, inhibition of the renin-angiotensin system, both by angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, represents the best available option. Several large, randomized studies have convincingly shown that these treatments are associated with a significant reduction in the risk for renal disease progression in diabetic and non diabetic patients with chronic kidney disease. Importantly, improvement of renal outcomes is paralleled by a reduction of the cardiovascular risk. However, a significant proportion of patients with chronic nephropathies still progresses to end-stage renal failure or dies for cardiovascular events. A more complex strategy, including strict control of BP and proteinuria, lowering of blood lipids, tight metabolic control of diabetes, and lifestyle changes may improve morbidity and mortality of patients with chronic renal disease as compared with single or dual intervention on the renin-angiotensin system. Moreover, prevention strategies are urgently needed to face the burden of chronic renal disease and cardiovascular morbidity and mortality. This is particularly true for developing countries, where the incidence of these chronic diseases is growing with the highest rate.

Cattaneo D, Remuzzi G. · Department of Medicine and Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. · J Ren Nutr. · Pubmed #15648011 No free full text.

Abstract: Observational studies in different populations indicate a positive relationship between dyslipidemia, cardiovascular events, and kidney disease progression. Patients with chronic renal diseases usually present with conditions (inflammation, oxidative stress) that can induce quantitative and qualitative changes in lipoprotein composition, making these particles more atherogenic. Several large randomized trials have shown that lowering cholesterol with statins reduces coronary mortality and morbidity across a wide range of cholesterol levels. Moreover, statins ameliorated renal function and structure in experimental models of progressive renal disease as well as in patients with proteinuric disease. It has been hypothesized that statins may directly modulate intracellular signaling systems involved in cellular proliferation, inflammatory, and fibrogenic responses. In addition, studies in animals have shown that the mevalonate pathway also may be involved in the regulation of the renin-angiotensin system, providing the rationale for the use of statins in combination with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor antagonists, 2 classes of drugs that have evidenced beneficial effects in different forms of renal diseases. Preliminary studies have shown that a multidrug approach may induce remission of proteinuria, lessen renal injury, and protect from loss of function in those patients whose condition does not fully respond to a single treatment.

Schieppati A, Remuzzi G. · Clinical Research Centre for Rare Diseases, Aldo e Cele Daccò, Ranica, Italy. · Acta Paediatr Suppl. · Pubmed #14989459 No free full text.

Abstract: Chronic renal diseases that involve proteinuria are typically characterized by an inexorable progression to end-stage renal failure. Many studies suggest that this progression may be the result of factors, such as intraglomerular hypertension and glomerular hypertrophy, that are unrelated to the initial disease. This paper reviews the mechanisms of progression of chronic renal diseases and discusses therapeutic strategies that should prevent or minimize further renal damage and the applicability of these strategies to patients with the rare X-linked lysosomal storage disorder Fabry disease. Renal involvement is a major feature of Fabry disease, which is characterized by vacuolated epithelial cells in the glomerulus and distal tubules, resulting from lipid inclusions within these cells. Although enzyme replacement therapy is the key strategy to halt the progression of Fabry disease, additional therapeutic options include blood pressure control, reduction of proteinuria, lipid control and inhibition of the renin-angiotensin system. CONCLUSION: A range of therapeutic options, used in conjunction with enzyme replacement therapy, may have beneficial effects on the renal manifestations of Fabry disease.

Ruggenenti P, Mise N, Pisoni R, Arnoldi F, Pezzotta A, Perna A, Cattaneo D, Remuzzi G. · Clinical Research Center for Rare Diseases Aldo and Cele Daccò, Mario Negri Institute, Bergamo, Italy. · Circulation. · Pubmed #12566371 links to  free full text

Abstract: BACKGROUND: Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria. METHODS AND RESULTS: In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients. CONCLUSIONS: In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.