Effects of statins on renal sodium and water handling: Acute and short-term effects of atorvastatin on renal haemodynamics, tubular function, vasoactive hormones, blood pressure and pulse rate in healthy, normocholesterolemic humans

Paulsen, L.; Holm, Charlotte; Bech, Jesper Nørgaard; Starklint, Jørn; Pedersen, E. B.

doi:10.1093/ndt/gfm807

Cited by 17 publications

(22 citation statements)

References 20 publications

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“…The pleiotropic effects of statins might thus include changes in renal function or vasoactive hormones. In a recent study, we found that atorvastatin had no acute or shortterm effects on renal hemodynamics in healthy men, but our results suggested that atorvastatin may influence renal handling of sodium [9]. No information is available about the effect of changes in dietary sodium intake on GFR and BP in healthy subjects during statin treatment.…”

Section: Introductioncontrasting

confidence: 64%

“…However, sodium balance was not controlled in these studies [9,[16][17][18]. Previously, we studied the acute and short-term effects of atorvastatin on GFR and RPF in healthy men and did not demonstrate any effect on renal haemodynamics, but measured a slight decrease in FE Na after treatment with atorvastatin [9]. These results prompted us to examine the effect of changes in dietary sodium intake on GFR and BP in a randomized, placebo-controlled, crossover study in atorvastatin-treated healthy men.…”

Section: Discussionmentioning

confidence: 96%

“…40 mg/day [8,17] or 80 mg/day [9]. However, sodium balance was not controlled in these studies [9,[16][17][18]. Previously, we studied the acute and short-term effects of atorvastatin on GFR and RPF in healthy men and did not demonstrate any effect on renal haemodynamics, but measured a slight decrease in FE Na after treatment with atorvastatin [9].…”

Section: Discussionmentioning

confidence: 98%

“…In one study, the dose was gradually increased to 80 mg/day [16], while a fixed dose was used in others, i.e. 40 mg/day [8,17] or 80 mg/day [9]. However, sodium balance was not controlled in these studies [9,[16][17][18].…”

Section: Discussionmentioning

confidence: 99%

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Glomerular filtration rate and blood pressure are unchanged by increased sodium intake in atorvastatin‐treated healthy men

Paulsen

Holst

Bech

et al. 2009

Scandinavian Journal of Clinical and Laboratory Investigation

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Section: Introductioncontrasting

confidence: 64%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Glomerular filtration rate and blood pressure are unchanged by increased sodium intake in atorvastatin‐treated healthy men

Paulsen

Holst

Bech

et al. 2009

Scandinavian Journal of Clinical and Laboratory Investigation

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“…The doses used in this work are not therefore predictive of those needed in humans to achieve the same result. A recent study examined the possible effect of atorvastatin administration on renal sodium and water handling in healthy volunteers [47]. Besides causing a modest and transitory decrease in fractional excretion of sodium, atorvastatin treatment had no significant effect on renal function.…”

Section: Discussionmentioning

confidence: 99%

Fluvastatin modulates renal water reabsorption in vivo through increased AQP2 availability at the apical plasma membrane of collecting duct cells

Procino

Barbieri

Carmosino

et al. 2011

Pflugers Arch - Eur J Physiol

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X-linked nephrogenic diabetes insipidus (XNDI), a severe pathological condition characterized by greatly impaired urine-concentrating ability of the kidney, is caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene. The lack of functional V2Rs prevents vasopressin-induced shuttling of aquaporin-2 (AQP2) water channels to the apical plasma membrane of kidney collecting duct principal cells, thus promoting water reabsorption from urine to the interstitium. At present, no specific pharmacological therapy exists for the treatment of XNDI. We have previously reported that the cholesterol-lowering drug lovastatin increases AQP2 membrane expression in renal cells in vitro. Here we report the novel finding that fluvastatin, another member of the statins family, greatly increases kidney water reabsorption in vivo in mice in a vasopressin-independent fashion. Consistent with this observation, fluvastatin is able to increase AQP2 membrane expression in the collecting duct of treated mice. Additional in vivo and in vitro experiments indicate that these effects of fluvastatin are most likely caused by fluvastatin-dependent changes in the prenylation status of key proteins regulating AQP2 trafficking in collecting duct cells. We identified members of the Rho and Rab families of proteins as possible candidates whose reduced prenylation might result in the accumulation of AQP2 at the plasma membrane. In conclusion, these results strongly suggest that fluvastatin, or other drugs of the statin family, may prove useful in the therapy of XNDI.

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Association between lipid-lowering agents and severe hyponatremia: a population-based case–control study

Skov

Falhammar

Calissendorff

et al. 2020

Eur J Clin Pharmacol

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Purpose Drug-induced hyponatremia is common, with medications from many drug-classes implicated. Lipid-lowering agents are among the most prescribed drugs. Limited evidence suggests an inverse association between statins and hyponatremia, while data on other lipid-lowering agents is absent. The objective of this investigation was to study the association between lipid-lowering drugs and hospitalization due to hyponatremia. Methods This was a register-based case–control study of the general Swedish population. Those hospitalized with a main diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between severe hyponatremia and the use of lipid-lowering drugs. Results Unadjusted ORs (95% CI) for hospitalization due to hyponatremia were 1.28 (1.22–1.35) for statins, 1.09 (0.79–1.47) for ezetimibe, 1.38 (0.88–2.12) for fibrates, and 2.12 (1.31–3.35) for resins. After adjustment for confounding factors the adjusted odds ratios (95% CI) compared with controls were 0.69 (0.64–0.74) for statins, 0.60 (0.41–0.86) for ezetimibe, 0.87 (0.51–1.42) for fibrates, and 1.21 (0.69–2.06) for resins. Conclusions Use of statins and ezetimibe was inversely correlated with severe hyponatremia. Consequently, these drugs are unlikely culprits in patients with hyponatremia, and they appear safe to initiate in hyponatremic patients. A potential protective effect warrants further studies on how statins and other lipid-lowering drugs are linked to dysnatremias.

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Effects of statins on renal sodium and water handling: Acute and short-term effects of atorvastatin on renal haemodynamics, tubular function, vasoactive hormones, blood pressure and pulse rate in healthy, normocholesterolemic humans

Cited by 17 publications

References 20 publications

Glomerular filtration rate and blood pressure are unchanged by increased sodium intake in atorvastatin‐treated healthy men

Glomerular filtration rate and blood pressure are unchanged by increased sodium intake in atorvastatin‐treated healthy men

Fluvastatin modulates renal water reabsorption in vivo through increased AQP2 availability at the apical plasma membrane of collecting duct cells

Association between lipid-lowering agents and severe hyponatremia: a population-based case–control study

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