pitavastatin and Albuminuria

In non-dialysis chronic kidney disease (CKD) patients with dyslipidemia, statin therapy is recommended to prevent cardiovascular complications. Dyslipidemia has been also shown to be an independent risk factor for the progression of CKD. However, it is still unclear whether statin therapy exerts an inhibitory effect on renal deterioration in CKD patients with dyslipidemia. The purpose of the present study was to examine possible therapeutic effects of statin add-on therapy on renal function as well as parameters of lipid and glucose metabolism, arterial stiffness and oxidative stress, in comparison to diet therapy, in CKD patients with dyslipidemia.. This study was a randomized, open-label, and parallel-group trial consisted of a 12-months treatment period in non-dialysis CKD patients with alubuminuria and dyslipidemia. Twenty eight patients were randomly assigned either to receive diet counseling alone (diet therapy group) or diet counseling plus pitavastatin (diet-plus-statin therapy group), to achieve the LDL-cholesterol (LDL-C) target of <100 mg/dl.. The statin treatment by pitavastatin was well tolerated in all of the patients without any significant adverse events and the average dose of pitavastatin was 1.0 ± 0.0 mg daily after treatment. After the 12-months treatment period, LDL-C was significantly lower in the diet-plus-statin therapy group compared with the diet therapy group (diet vs diet-plus-statin: LDL-C, 126 ± 5 vs 83 ± 4 mg/dL, P < 0.001). On the other hand, the diet-plus-statin therapy did not significantly reduce albuminuria or delay the decline in eGFR compared with the diet therapy, and there was no relationship between the change in LDL-C and the change in eGFR or albuminuria. However, diet therapy as well as diet-plus-statin therapy exerted similar lowering effects on the pentosidine levels (diet therapy group, baseline vs 12 months: 40 ± 4 vs 24 ± 3 ng/mL, P = 0.001; diet-plus-statin therapy, 46 ± 7 vs 34 ± 6 ng/mL, P = 0.008). Furthermore, the results of multivariate regression analysis indicated that the change in pentosidine was a significant contributor to the change in eGFR (β = -0.536, P = 0.011).. Although statin add-on therapy did not show additive renal protective effects, the diet therapy as well as the diet-plus-statin therapy could contribute to the reduction in plasma pentosidine in CKD patients with albuminuria and dyslipidemia.

Topics: Aged; Albuminuria; Anticholesteremic Agents; Arginine; Cholesterol, HDL; Cholesterol, LDL; Diet; Dyslipidemias; Female; Glomerular Filtration Rate; Glycation End Products, Advanced; Humans; Lysine; Male; Middle Aged; Oxidative Stress; Quinolines; Renal Insufficiency, Chronic; Triglycerides; Vascular Stiffness

The effect of pitavastatin and pravastatin treatment on renal function was compared in type 2 diabetic patients with nephropathy in a randomized, controlled, open-label, parallel and multi-centre study. Type 2 diabetic patients with modest renal impairment (serum creatinine level <1.4 mg/dl) accompanied by albuminuria (30-600 mg/g creatinine) were randomly assigned to receive 2 mg of pitavastatin (n = 44) or 10 mg of pravastatin (n = 43) for 12 months. At 12 months, pitavastatin significantly reduced urinary albumin-to-creatinine ratio than pravastatin in subjects with macroalbuminuria (-67.2% vs. +14.5%, p = 0.0040), but not in subjects with microalbuminuria. There was no significant difference in the change in estimated glomerular filtration rate between the two groups. Pitavastatin is more effective than pravastatin for the reduction of albuminuria in type 2 diabetic patients with early stage of diabetic nephropathy.

Topics: Aged; Albuminuria; Biomarkers; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Humans; Male; Pravastatin; Quinolines; Treatment Outcome

The aim of the present study was to evaluate the factors that modulate the protective action of statins on cardiorenal function, regardless of the lipid-lowering effect. To treat abnormal serum lipid profiles, low-dose pitavastatin (1.0 mg/day) was administered to 65 hyperlipidemic patients. The exclusion criteria included left ventricular ejection fraction <40% and apparent renal disease. Age- and gender-matched patients with hyperlipidemia (n = 40) served as the controls. After 12 to 16 weeks of pitavastatin treatment, pitavastatin had decreased low-density lipoprotein cholesterol (from 143.5 ± 31.4 to 98.2 ± 19.4 mg/dl, p <0.01), triglycerides (from 157.7 ± 57.2 to 140.5 ± 60.7 mg/dl, p <0.01), E/e' (from 10.8 ± 6.2 to 9.0 ± 4.5, p <0.05), a parameter of left ventricular diastolic function, and albuminuria (from 47.6 ± 55.9 to 28.5 ± 40.0 mg/g creatinine, p <0.01). Furthermore, pitavastatin decreased serum transforming growth factor-β1 (from 709 ± 242 to 550 ± 299 pg/ml, p <0.01), urinary 8-hydroxy-2'-deoxyguanosine (from 6.6 ± 4.1 to 5.0 ± 3.1 μg/g creatinine, p <0.01), an oxidative stress marker, and increased urinary nitrate and nitrite (from 22.5 ± 14.6 to 29.4 ± 27.6 nmol/g creatinine, p <0.05). No such changes were observed in the controls. Multiple regression analysis in the pitavastatin group revealed the effect of pitavastatin on cardiorenal function was associated with suppression of oxidative stress, but not on low-density lipoprotein cholesterol reduction. In conclusion, pitavastatin decreases E/e' and albuminuria, which is associated with suppression of oxidative stress.

Topics: Aged; Albuminuria; Case-Control Studies; Cholesterol, LDL; Diastole; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Male; Middle Aged; Quinolines; Treatment Outcome; Triglycerides; Ventricular Function, Left

The present study was undertaken to compare the efficacy of pitavastatin and colestimide in patients with diabetes mellitus complicated by hyperlipidemia and metabolic syndrome. 48 diabetic patients with metabolic syndrome were randomly assigned to a pitavastatin group or colestimide group. The clinical parameters, serum lipids, fasting (FPG) and postprandial plasma glucose(PPG), HOMA-IR, hemoglobin A1c(HbA1c), hs-CRP and urinary albumin were measured before/after 24-week administration. Treatment with pitavastatin reduced LDL-C and TG, while that with colestimide significantly reduced waist circumference, BMI, LDL-C, HbA1c, FPG, PPG, HOMA-R , hs-CRP and urinary albumin. Percent improvement in LDL-C was greater in the pitavastatin group than in the colestimide group. Colestimide appeared to be useful in the management of Japanese patients with diabetes mellitus complicated by metabolic syndrome, since it alleviates obesity and insulin resistance in addition to exhibiting lipid profile-improving effects, and can thus improve markers of atherosclerosis.

Topics: Adult; Aged; Albuminuria; Atherosclerosis; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Diabetes Complications; Epichlorohydrin; Female; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Hyperlipidemias; Hypolipidemic Agents; Imidazoles; Insulin Resistance; Japan; Male; Metabolic Syndrome; Middle Aged; Obesity; Quinolines; Resins, Synthetic; Triglycerides; Weight Loss

Liver-type fatty acid-binding protein (l-FABP) is expressed in renal proximal tubules and is reported to be a useful marker for progression of chronic glomerulonephritis. The aim of this study was to determine whether urinary l-FABP levels are altered at various stages of diabetic nephropathy and whether pitavastatin affects urinary l-FABP levels in early diabetic nephropathy.. Fifty-eight patients with type 2 diabetes (34 men and 24 women, median age 52 years) and 20 healthy, age-matched subjects (group E) were recruited for the study. The diabetic patients included 12 patients without nephropathy (group A), 20 patients with microalbuminuria (group B), 14 patients with macroalbuminuria and normal renal function (group C), and 12 patients with chronic renal failure but not undergoing hemodialysis (blood creatinine >1.2 mg/dl; mean 2.5 mg/dl, group D). Twenty group B patients were randomly assigned to receive 1 mg/day pitavastatin (10 patients, group B1) or placebo (10 patients, group B2). Treatment was continued for 12 months. Urinary l-FABP levels were measured by enzyme-linked immunosorbent assay. Urinary 8-hydroxydeoxyguanosine and serum free fatty acids (FFAs) were also measured in group B.. Urinary l-FABP levels in groups A-D were 6.2 +/- 4.6 microg/g creatinine, 19.6 +/- 13.5 microg/g creatinine, 26.8 +/- 20.4 microg/g creatinine, and 52.4 +/- 46.8 microg/g creatinine, respectively. Urinary l-FABP levels in groups B-D were significantly higher than those in healthy subjects (group E, 5.8 +/- 4.0 microg/g creatinine) (group B, P < 0.05; group C, P < 0.01; group D, P < 0.01). In group B1, urinary albumin excretion (UAE) and urinary l-FABP levels were decreased after pitavastatin treatment (UAE before, 110 +/- 74 microg/min; 6 months, 88 +/- 60 microg/min, P < 0.05; 12 months, 58 +/- 32 microg/min, P < 0.01; l-FABP before, 18.6 +/- 12.5 microg/g creatinine; 6 months, 12.2 +/- 8.8 microg/g creatinine, P < 0.05; 12 months, 8.8 +/- 6.4 microg/g creatinine, P < 0.01). In group B2, UAE and l-FABP levels showed little change during the experimental period. In group B1, urinary 8-hydroxydeoxyguanosine was decreased 12 months after pitavastatin treatment (before 32.5 +/- 19.5 ng/mg creatinine, after 18.8 +/- 14.5 ng/mg creatinine, P < 0.01), but in group B2, these showed little difference during the experimental period. In both groups B1 and B2, serum FFAs showed little difference during the experimental period.. Urinary l-FABP levels appear to be associated with the progression of diabetic nephropathy, and pitavastatin may be effective in ameliorating tubulointerstitial damage in early diabetic nephropathy.

Topics: Adult; Albuminuria; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Enzyme Inhibitors; Fatty Acid-Binding Proteins; Female; Humans; Male; Middle Aged; Quinolines; Regression Analysis; Time Factors

Clinical trials show potent renoprotective effects of pitavastatin (PTV), although the precise mechanism for these renoprotective effects is not fully clarified. The aim of this study was to examine the antihypertensive and renoprotective effects of PTV, focusing on the nitric oxide (NO) system.. Male, 6-week-old, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were randomized to receive vehicle or PTV (2 mg/kg bodyweight) for 8 weeks. Blood pressure and urinary albumin excretion were measured every 2 weeks. After 8 weeks, plasma biochemical parameters and renal histology were examined. NO synthase isoform (neuronal, nNOS; inducible, iNOS; and endothelial, eNOS) expression and eNOS phosphorylation were examined by western blotting.. PTV attenuated hypertension and albuminuria development in SHR. PTV decreased glomerular desmin expression and medullary interstitial fibrosis in SHR. PTV tended to increase plasma NO in both strains but significantly increased urinary NO excretion only in WKY. PTV significantly increased nNOS and eNOS expression, enhanced eNOS phosphorylation at serine1177, and inhibited eNOS phosphorylation at threonine495 in the kidney of both strains.. PTV treatment led to increased renal NOS expression and upregulated eNOS activity in both SHR and WKY. The antihypertensive and renoprotective effects of PTV may be related to upregulation of the NO system.

Topics: Albuminuria; Animals; Antihypertensive Agents; Blood Pressure; Disease Models, Animal; Hypertension; Kidney; Male; Nitric Oxide; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Phosphorylation; Quinolines; Rats, Inbred SHR; Rats, Inbred WKY; Up-Regulation

Chronic kidney disease (CKD) is a serious health problem worldwide. Therapies that can halt the progression of CKD are limited, and the identification of new strategies for CKD treatment is therefore important. Pitavastatin, one of the newest statins introduced to the market, has been shown to exhibit some beneficial effects on renal and endothelial function.. We enrolled 12 healthy volunteers for our study. With or without pitavastatin administration, creatinine clearance (Ccr), urinary albumin excretion, lipid status, and oxidative stress markers were evaluated in acute and early phases after administration of the drug.. A single pitavastatin administration increased Ccr and reduced oxidative stress parameters, such as 8-OHdG levels and isoprostane production, within 6 h, without altering lipid status in healthy participants. A two-week treatment with pitavastatin lowered total and LDL cholesterol and triglycerides but not HDL cholesterol at 7 and 14 days. This change in lipid profile is associated with enhanced Ccr and the suppression of oxidative stress parameters. Urinary albumin excretion was reduced after either acute or chronic administration of pitavastatin, although this effect was not yet significant.. We found that pitavastatin augmented Ccr and reduced oxidative stress parameters in healthy subjects. These data suggest that pitavastatin affects renal outcomes in both lipid status-dependent and -independent manners. These observations suggest that pitavastatin treatment could be beneficial for CKD patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Albuminuria; Algorithms; Cholesterol, LDL; Creatinine; Deoxyguanosine; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoprostanes; Lipids; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Quinolines

Recent studies suggest a potential benefit of the lipid-lowering medication in the treatment of chronic kidney disease (CKD) such as diabetic nephropathy. Although statins have been widely used to lower serum cholesterol levels, the effect of these drugs on diabetic nephropathy has not been fully elucidated. In the present study, therefore, we addressed the role of different kinds of statins on diabetic nephropathy in db/db mice. Mice were fed with a standard diet with 0.005% (w/w) of pitavastatin, rosuvastatin, and pravastatin for 8 weeks starting from 8 weeks of age. The treatment with statins did not affect the food intake, body weight gain, adiposity, or blood pressure in db/db mice. Treatment with statins also had no effect on plasma lipid levels. In terms of the effect on albuminuria, pitavastatin and rosuvastatin reduced the urinary excretion of albumin by 60 and 40%, respectively, but not pravastatin, suggesting the effect of these two drugs on diabetic nephropathy. Furthermore, pitavastatin and rosuvastatin improved glomerular hypertrophy. All statins treatment improved insulin resistance. In addition, rosuvastatin and pravastatin treatment reduced oxidative stress measured by urinary 8-OHdG level, whereas the statins had no effect on the inflammatory response in the kidney of db/db mice. These results are not consistent with the renoprotective effect of statins. In conclusion, our data suggest that pitavastatin and rosuvastatin can improve diabetic nephropathy through the suppression of glomerular hypertrophy, independent of lipid-lowering or anti-oxidative effects.

Topics: Adiposity; Albuminuria; Animals; Blood Pressure; Body Weight; Creatinine; Diabetic Nephropathies; Fluorobenzenes; Insulin Resistance; Male; Mice; Oxidative Stress; Pravastatin; Pyrimidines; Quinolines; Real-Time Polymerase Chain Reaction; Rosuvastatin Calcium; Sulfonamides

Recent studies have uncovered various pleiotrophic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase-inhibiting drugs (statins). Several studies have identified a beneficial effect of statins on diabetic nephropathy; however, the molecular mechanisms are unclear. In this study, we show that statin ameliorates nephropathy in db/db mice, a rodent model of type 2 diabetes, via downregulation of NAD(P)H oxidase NOX4, which is a major source of oxidative stress in the kidney. Pitavastatin treatment for 2 weeks starting at 12 weeks of age significantly reduced albuminuria in the db/db mice concomitant with a reduction of urinary 8-hydroxy-2'-deoxyguanosine and 8-epi-prostaglandin F(2alpha). Immunohistochemical analysis found increased amounts of 8-hydroxy-2'-deoxyguanosine and NOX4 protein in the kidney of db/db mice. Quantitative reverse transcription-polymerase chain reaction also showed increased levels of NOX4 mRNA. Pitavastatin normalized all of these changes in the kidneys of diabetic animals. Additionally, 12-week treatment with the statin completely normalized the levels of transforming growth factor-beta1 and fibronectin mRNA as well as the mesangial expansion characteristic of diabetic nephropathy. Our study demonstrates that pitavastatin ameliorates diabetic nephropathy in db/db mice by minimizing oxidative stress by downregulating NOX4 expression. These findings may provide insight into the mechanisms of statin therapy in early stages of diabetic nephropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Albuminuria; Animals; Blood Glucose; Body Weight; Cell Proliferation; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dinoprost; Disease Models, Animal; Down-Regulation; Fibronectins; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Mesangial Cells; Mice; NADPH Oxidase 4; NADPH Oxidases; Oxidative Stress; Quinolines; RNA, Messenger; Time Factors; Transforming Growth Factor beta1