Renal tubular toxicity of HMG-CoA reductase inhibitors

Zyl-Smit, R. Van; Firth, Jean C.; Duffield, Maureen; Marais, A. David

doi:10.1093/ndt/gfh474

Cited by 24 publications

(21 citation statements)

References 6 publications

(4 reference statements)

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“…AKI from statin use is usually in the setting of rhabdomyolysis; however, a direct tubular toxicity independent of rhabdomyolysis has also been reported. 101 …”

Section: Acetaminophenmentioning

confidence: 99%

Drug-induced impairment of renal function

Pazhayattil¹,

Shirali²

2014

IJNRD

112

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Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies.

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“…AKI from statin use is usually in the setting of rhabdomyolysis; however, a direct tubular toxicity independent of rhabdomyolysis has also been reported. 101 …”

Section: Acetaminophenmentioning

confidence: 99%

Drug-induced impairment of renal function

Pazhayattil¹,

Shirali²

2014

IJNRD

112

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“…The renoprotective properties of statins have been, however, challenged by recent observations that, given at high doses to hypercholesterolemic subjects with normal renal function, these drugs may enhance urinary protein excretion rate [15,16,17,18,19]. Episodes of proteinuria – usually early after starting treatment – were transient, most frequently related to high doses of rosuvastatin (80 mg), and apparently not associated with worsening of renal function [20].…”

Section: Introductionmentioning

confidence: 99%

Effects of Rosuvastatin on Glomerular Capillary Size-Selectivity Function in Rats with Renal Mass Ablation

Corna

Sangalli

Cattaneo³

et al. 2007

Am J Nephrol

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Background: Evidence is accumulating that statins can reduce proteinuria and disease progression in chronic kidney disease. However, some safety concerns have been recently raised on the use of these agents, mainly due to transient episodes of proteinuria observed in patients receiving high doses of rosuvastatin. Methods: We investigated in rats with renal mass ablation (RMR) whether rosuvastatin (5 or 20 mg/day) worsens proteinuria as compared to untreated RMR animals. Moreover, we also examined whether rosuvastatin-induced changes in proteinuria would be due to the effect of the drug on permselective properties of glomerular capillary barrier, measured by the fractional clearance of graded-size Ficoll molecules and/or by proximal tubular mechanisms, by assessing urinary excretion of β₂-microglobulin. Results: RMR rats given rosuvastatin for 28 days showed a progressive increase in proteinuria, with values numerically but not significantly higher than those in RMR animals given the vehicle. In RMR rats, rosuvastatin did not significantly affect the fractional clearance of Ficoll as compared to vehicle-treated RMR animals. A significant correlation was found between urinary protein and β₂-microglobulin excretion in rats treated with rosuvastatin (r = 0.936, p < 0.001), but not in those given vehicle. Renal function, glomerular and tubulointerstitial injury were comparable in rosuvastatin-treated and untreated RMR rats at the end of the 28-day follow-up. Conclusion: In rats with RMR, rosuvastatin mildly enhances urinary protein excretion rate. This, however, was not the result of further changes in the size-permselective function of glomerular capillary barrier.

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“…Nevertheless, findings suggestive of direct renal tubular toxicity on high-dosage statin therapy without rhabdomyolysis was reported in a patient with familial hypercholesterolemia. 18 Current therapeutic modalities include withdrawal of myotoxic agents, intravenous volume expansion, urinary alkalinization, and forced diuresis. Prognosis of rhabdomyolysis depends on severity and comorbid conditions, with mortality of 52% in patients with ARF, compared with 14% in those without ARF, in a series of critically ill intensive PATHOPHYSIOLOGY of the RENAL BIOPSY www.jasn.org care unit patients with rhabdomyolysis.…”

Section: Discussionmentioning

confidence: 99%