An overview of statin-associated proteinuria

Tiwari, Atul

doi:10.1016/j.drudis.2006.03.017

Cited by 26 publications

(29 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several studies have shown beneficial effects of statin therapy on proteinuria;35 however, others have shown increase in tubular proteinuria 36. Since proteinuria data are not available in ALLHAT participants, we cannot study the effects of pravastatin therapy on proteinuria or assess the role of proteinuria level as a predictor of response to statin therapy.…”

Section: Discussionmentioning

confidence: 96%

Progression of Kidney Disease in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin Versus Usual Care: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Rahman

Baimbridge

Davis

et al. 2008

American Journal of Kidney Diseases

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 96%

Progression of Kidney Disease in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin Versus Usual Care: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Rahman

Baimbridge

Davis

et al. 2008

American Journal of Kidney Diseases

View full text Add to dashboard Cite

show abstract

“…Although data on the potential renal toxicity of high-potency statins are controversial (Tiwari 2006; Golomb and Evans 2008; Dodiya et al 2011), two meta-analyses showed that statin therapy is safe and effective in preventing mortality and major cardiovascular events in patients with non-dialysis-dependent chronic kidney disease (CKD) (Upadhyay et al 2012, 2013; Palmer et al 2012). However, these studies provide very limited evidence to support the use of statins in patients on dialysis, and statin therapy was not found to be effective in reducing the risk of kidney failure or decline in kidney function (Upadhyay 2013).…”

Section: Discussionmentioning

confidence: 99%

Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney

et al. 2014

View full text Add to dashboard Cite

The effects of high-potency statins on renal function are controversial. To address the impact of statins on renal morpho-functional aspects, normotensive young mice were treated with rosuvastatin (Rvs). Moreover, because statins may impair mitochondrial function, mice received either dietary supplementation with an amino acid mixture enriched in essential amino acids (EAAm), which we previously demonstrated to increase mitochondrial biogenesis in muscle or an unsupplemented control diet for 1 month. Mitochondrial biogenesis and function, apoptosis, and insulin signaling pathway events were studied, primarily in cortical proximal tubules. By electron microscopy analysis, mitochondria were more abundant and more heterogeneous in size, with dense granules in the inner matrix, in Rvs- and Rvs plus EAAm-treated animals. Rvs administration increased protein kinase B and endothelial nitric oxide synthase phosphorylation, but the mammalian target of rapamycin signaling pathway was not affected. Rvs increased the expression of sirtuin 1, peroxisome proliferator-activated receptor γ coactivator-1α, cytochrome oxidase type IV, cytochrome c, and mitochondrial biogenesis markers. Levels of glucose-regulated protein 75 (Grp75), B-cell lymphoma 2, and cyclin-dependent kinase inhibitor 1 were increased in cortical proximal tubules, and expression of the endoplasmic reticulum–mitochondrial chaperone Grp78 was decreased. EAAm supplementation maintained or enhanced these changes. Rvs promotes mitochondrial biogenesis, with a probable anti-apoptotic effect. EAAm boosts these processes and may contribute to the efficient control of cellular energetics and survival in the mouse kidney. This suggests that appropriate nutritional interventions may enhance the beneficial actions of Rvs, and could potentially prevent chronic renal side effects.

show abstract

“…Because dipstick analysis (as used during the rosuvastatin phase III trials in which proteinuria was detected) is a highly insensitive measure for proteinuria; however, it was hoped that the greater sensitivity of proteomics would enable characterization of more subtle (subclinical) effects induced by statins at lower doses. In this context, it is also worth mentioning that few patients treated with rosuvastatin at 40 mg/day (2%) and a greater proportion of patients treated with 80 mg/day (33%) achieved a steady-state plasma drug concentration (<50 ng/mL), suggesting a potential threshold in the drug level at which the risk for distinct proteinuria is increased [14]. Although we expected to observe possible statin-induced effects already after a short treatment period, it is also possible that longer treatment periods are necessary to induce distinct effects.…”

Section: Discussionmentioning

confidence: 99%

“…Both pravastatin and rosuvastatin have a higher degree of renal secretion than the other marketed statins [14]. In the first instance, the total urine protein concentration and the concentration of albumin and retinol-binding protein in urine were analysed as accepted indices of the effect of the statins on tubular reabsorption of urinary proteins.…”

Section: Introductionmentioning

confidence: 99%

No Evidence for Statin‐induced Proteinuria in Healthy Volunteers asAssessed by Proteomic Analysis

Verhulst

Geryl

D’Haese

2011

BioMed Research International

View full text Add to dashboard Cite

In clinical studies of statins (class of drugs lowering plasma cholesterol levels), transient low-molecular-weight proteinuria was observed. The causes of statin-induced proteinuria in the patient background of those studies (cardiovascular and kidney disease) are multifactorial and, therefore, a matter of debate. In light of this, it seemed interesting to investigate the effect of statins on the urinary protein concentration and proteome in healthy volunteers. Six healthy volunteers were randomly treated with rosuvastatin (40 mg/day) or pravastatin (80 mg/day) in a double-blinded cross-over study. Total urinary protein concentration and the concentration of albumin/retinol-binding protein were analysed, after which the urinary proteome was investigated. From the results described in this study, it was concluded that statins do not induce major changes in the urinary protein concentration/proteome. High variability in the baseline urinary proteome/proteins among volunteers, however, made it very difficult to find subtle (possibly isolated to individuals) effects of statins.

show abstract

An overview of statin-associated proteinuria

Cited by 26 publications

References 51 publications

Progression of Kidney Disease in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin Versus Usual Care: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Progression of Kidney Disease in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin Versus Usual Care: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney

No Evidence for Statin‐induced Proteinuria in Healthy Volunteers asAssessed by Proteomic Analysis

Contact Info

Product

Resources

About