Anti-Inflammatory Interventions in End-stage Kidney Disease: A Randomized, Double-Blinded, Controlled and Crossover Clinical Trial on the Use of Pravastatin in Continuous Ambulatory Peritoneal Dialysis

doi:10.1016/j.arcmed.2013.10.016

Archives of Medical Research

Volume 44, Issue 8, November 2013, Pages 633-637

https://doi.org/10.1016/j.arcmed.2013.10.016 Get rights and content

Background and Aims

Inflammation is highly prevalent in patients on dialysis. Statins have anti-inflammatory actions but their use has been scarcely studied in continuous ambulatory peritoneal dialysis (CAPD). We undertook this study to compare the effect of pravastatin vs. placebo on the serum concentrations of C-reactive protein (CRP) in patients on CAPD.

Methods

In a double-blind, controlled and crossover clinical trial, 76 CAPD patients were randomized to either pravastatin or placebo for 2 months. After this first period of treatment, patients had a 1-month wash-out period and, finally, they were crossed-over to receive the other drug (or placebo) for 2 more months. Measurement of clinical and biochemical variables and CRP was performed at the beginning and at the end of each treatment period.

Results

Median CRP was only significantly decreased in the pravastatin group in both periods of treatment: first period (baseline vs. final, mg/L): pravastatin 7.4 (2–21) vs. 2.6 (1–6), p <0.05; placebo 3.9 (2–10) vs. 6.8 (3–12), pNS; second period: pravastatin 4.3 (2–15) vs. 1.9 (1–7), p <0.05; placebo 4.9 (2–17) vs. 6.8 (2–19), p <0.05. Results were significantly different (p <0.05) between groups only at the end of each treatment period. Additionally, total and LDL-cholesterol significantly decreased in the pravastatin group.

Conclusions

Pravastatin significantly reduced serum levels of CRP and total and LDL-cholesterol compared to placebo. This treatment may be of great help to decrease the inflammatory status and probably the cardiovascular disease of CAPD patients.

Introduction

Chronic inflammation is highly prevalent in patients with end-stage renal disease (ESRD) (1) and strongly linked to atherosclerosis, cardiovascular disease and malnutrition 2, 3, 4. Moreover, morbidity and mortality in these patients are remarkably higher than for the general population, largely due to atherosclerotic cardiovascular disease 3, 4, 5.

Benefits of statins have been reported on all-cause and cardiovascular mortality in chronic kidney disease (CKD) patients; however, some topics remain to be clarified (6). Such beneficial effect of statins were particularly observed in patients with non-dialysis CKD (7), but not in ESRD patients on dialysis 8, 9. A more recent study, however, suggests that statins may be beneficial even in dialysis patients (10).

In addition to their well-known hypolipidemic actions, statins have anti-inflammatory effects, which have been extensively demonstrated in patients without kidney disease (11). In patients with ESRD on hemodialysis, statins have been shown to decrease C-reactive protein (CRP) 9, 12, 13; however, data in patients on peritoneal dialysis are sparse and limited.

Therefore, the aim of this study was to compare the effect of pravastatin vs. placebo on the serum concentrations of CRP in patients on continuous ambulatory peritoneal dialysis (CAPD).

Section snippets

Study Design

The present study was a randomized, double-blind, controlled and crossover clinical trial. Patients from the Regional General Hospital No. 110, Mexican Institute of Social Security (IMSS), Guadalajara, Mexico were invited to participate if they were 18–70 years old and had at least 1 month on CAPD. Subjects were excluded if they had any of the following: inflammatory cause of ESRD, hepatic or malignant disease, any infectious disease within the last 3 months, drug intake with anti-inflammatory

Results

Seventy-six patients were included, 43 (57%) males and 33 (43%) females. In the whole sample, mean age was 54.4 ± 12.4 years, median dialysis vintage 15.0 (10–24) months, and previous peritonitis rate 1.0 (0–1) episode/patient/year. Main cause of ESRD was diabetes mellitus in 49 (65%) patients. No significant demographic differences were found between the two treatment sequences at the beginning of the study (Table 1).

Regarding clinical and biochemical variables (Table 2), the only significant

Discussion

Patients included in this study are representative of the CAPD population of our setting, with similar sociodemographic and clinical characteristics to those reported in other series 15, 16.

Due to the poor outcomes observed in ERSD patients with inflammation (particularly those on dialysis), in the absence of an obvious cause (for example, infectious disease), the use of drugs with anti-inflammatory effect might be indicated (17). A number of studies in non-renal patients have shown

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgments

We appreciate the kind help of Adolfo Cota in processing laboratory samples. This work was funded by a Grant (2005/1/I/108) from the Fondo de Investigación en Salud, IMSS.

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If malnutrition is identified in association with a decreased intake of nutrients, the use of nutritional supplements, besides diet counseling, could be useful. However, if systemic inflammation is also present, a drug [19,31] or nutrient with anti-inflammatory effect [32] may have a potential role, otherwise, the improvement on nutritional status could be expected to be limited. In conclusion, the presence of systemic inflammation in malnourished CAPD patients seemed to limit the trend for improvement on nutritional status observed with counseling and an oral egg albumin-based protein supplement in patients without inflammation.
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The presence of systemic inflammation in malnourished CAPD patients seemed to limit the trend for improvement on nutritional status observed with counseling and oral egg albumin-based protein supplement in patients without inflammation.
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However, one should be cautious to apply this meta-analysis to PD patients because most of the trials included HD patients. A recent randomized, placebo-controlled, cross-over study reported that treatment with pravastatin significantly reduced serum CRP and total cholesterol level in patients on continuous ambulatory peritoneal dialysis.96 Interestingly, in vitro study showed that epithelial-mesenchymal transition, one of the hallmarks of peritoneal fibrosis, and submesothelial thickening was attenuated by simvastatin, possibly via inhibition of isoprenylation of small rho–guanosine triphosphatases.97
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Original ArticleClinicalAnti-Inflammatory Interventions in End-stage Kidney Disease: A Randomized, Double-Blinded, Controlled and Crossover Clinical Trial on the Use of Pravastatin in Continuous Ambulatory Peritoneal Dialysis

Background and Aims

Methods

Results

Conclusions

Introduction

Section snippets

Study Design

Results

Discussion

Conflict of Interest

Acknowledgments

Kidney Int

Kidney Int

Lancet

Kidney Int

Am J Kidney Dis

Atherosclerosis

Atherosclerosis

Atherosclerosis

The malnutrition, inflammation, and atherosclerosis (MIA) syndrome—the heart of the matter

Nephrol Dial Transplant

Inflammation in renal disease

Am J Cardiol

The role of statins in chronic kidney disease

Am J Nephrol

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis

Cochrane Database Syst Rev

Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis

N Engl J Med

Rosuvastatin and cardiovascular events in patients undergoing hemodialysis

N Engl J Med

Original Article
Clinical
Anti-Inflammatory Interventions in End-stage Kidney Disease: A Randomized, Double-Blinded, Controlled and Crossover Clinical Trial on the Use of Pravastatin in Continuous Ambulatory Peritoneal Dialysis