Effects of atorvastatin on renal function in patients with chronic renal failure

Bruno Cianciaruso, Serena Torraca, Giovanni Somma, Antonio Pisani and Massimo Sabbatini

University Frederico II, Department of Nephrology, Naples, Italy Email: cianciar{at}unina.it

Sir,

We read with great interest the paper recently published by Van Dijk et al. [1]. In that study the authors showed that a 4-week treatment with simvastatin (40 mg/day) was able to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) in normotensive patients with polycystic renal disease and normal renal function. They also found that simvastatin improved the vascular reactivity, a marker of endothelial function, as shown by the nitric oxide (NO)-dependent increase of the forearm blood flow. However, in that study, despite the presence of this non-immunological renal disease, the authors studied subjects with normal renal function (GFR 124±4 ml/min) and normal blood pressure (mean 135/80 mmHg); moreover, the dosage of simvastatin was higher than that currently used in clinical practice to lower cholesterol plasma levels (4.24 mmol/l).

In contrast with the aforementioned study, we tested the renal haemodynamic effects of atorvastatin, a long-acting HMG-CoA-reductase inhibitor, in patients with chronic renal failure (GFR=38±15). Moderate-advanced renal failure is a well-known condition of low nitric oxide production [2], and responsible mechanisms are potentially responsive to statin treatment, like enhanced atherosclerosis, dyslipidaemia, generation of reactive oxygen species, and hypertension [3,4]. Since the beneficial action of statins on vascular reactivity and hypertension have been related to increased NO production, it is very important to understand whether these substances also work in the setting of chronic renal failure, and at which dosage; the gain of even a few millilitres of GFR may provide the patient with years free of dialysis treatment. To date, the only attempt made to increase NO production in chronic renal failure through L-arginine supplements failed to improve GFR and proteinuria [5]. Nine patients with chronic renal failure from different causes (six with glomerulonephritis, two with inherited nephropathies and one with nephrosclerosis), and with GFR ranging between 10 and 55 ml/min were studied. Seven patients were hypertensive and five were being treated with angiotensin-converting enzyme inhibitors. The basal procedure was the collection of laboratory data such as serum lipids, 24-h urinary excretion of proteins, electrolytes, and nitrates; GFR and RPF were determined with inulin and para-amino-hippurate renal clearances, with timed urine collections (three periods of 45 min). After the basal evaluation, the patients were given atorvastatin (10 mg/day) for 4 weeks, and at the end of the treatment period they underwent a new assessment of the renal dynamics and 24-h urinary collection. To establish whether there is a dose-dependent response in the effects of statins in chronic renal failure, and to avoid undesirable side-effects, we started with the lowest recommended dosage of this statin.

Administration of atorvastatin produced a significant decrease in total cholesterol plasma levels, but influenced neither HDL cholesterol nor triglycerides. GFR was not modified after the statin nor were changes detected in RPF or systolic and diastolic blood pressures. Urinary excretion of nitrates was slightly increased after atorvastatin, but no change in proteinuria was observed (Table 1Go).


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Table 1.  Study results

 
Our data show that low-dose atorvastatin does not significantly influence renal and endothelial function in patients with chronic renal failure, despite a significant reduction of cholesterolaemia. Further studies are in progress in our laboratory to test whether higher doses of atorvastatin (20, 40 mg/day) may elicit more positive effects.

References

  1. Van Dijk MA, Kamper AM, van Veen S et al. Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant2001; 16: 2152–2157[Abstract/Free Full Text]
  2. Schmidt RJ, Baylis C. Total nitric oxide production is low in patients with chronic renal disease. Kidney Int2000; 58: 1261–1266[ISI][Medline]
  3. Oda H, Keane WF. Recent advances in statins and the kidney. Kidney Int1999; 56 [Suppl 71]: S2–S5
  4. Wassmann S, Laufs U, Baumer AT et al. HMG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species. Hypertension2001; 37: 1450–1457[Abstract/Free Full Text]
  5. De Nicola L, Bellizzi V, Minutolo R et al. Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure. Kidney Int1999; 56: 674–684[ISI][Medline]




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