Anti-Inflammatory Effect of Atorvastatin on the Kidney Graft of Living Donor Transplants

Abstract

BackgroundRecent studies have demonstrated that statins have anti-inflammatory and immunomodulatory properties, which could be considered beneficial in kidney transplantations. This study assesses the anti-inflammatory effect of atorvastatin on the kidney grafts of living donor transplants.Material/MethodsIn a randomized clinical trial, kidney donors were divided into 2 groups. The study group constituted 24 donors who received 40 mg atorvastatin, and 24 donors who received a placebo control, 4 weeks prior to transplantation. Serum C-reactive protein (CRP) levels were measured before and after atorvastatin administration. CRP and renal function of kidney recipients were measured at baseline and 1, 6, and 24 hours after transplantation.ResultsAfter 4 weeks of treatment, the CRP level was 5.62±3.82 mg/dL in the control group and 3.27±0.62 mg/dL in the study group (P=0.007). Upon reperfusion, CRP levels in recipients at 1 hour were, 5.8±3.9 and 3.8±1.0 mg/dL, respectively (P=0.04). Twenty-four hours after the kidney transplantations, serum creatinine levels were 2.5±1.5 mg/dL in the study group and 3.7±2.4 mg/dL in the control group (P=0.04).ConclusionsOur study suggests that the use of atorvastatin prior to allograft procurement of kidney transplant, reduces the acute kidney inflammatory burden profile, and promotes an improved kidney function recovery following transplantation.

Atorvastatin inhibits renal inflammatory response induced by calcium oxalate crystals via inhibiting the activation of TLR4/NF‐κB and NLRP3 inflammasome

“…Satoh et al 37 showed that ATV inhibited the development of chronic inflammation and atherosclerosis progression by downregulating the expression of NLRP3 inflammasome in coronary heart disease. Previous evidence also demonstrated that ATV inhibited the expression of transforming growth factor-β and NADPH oxidase in kidney tissue, increased the levels of SOD and catalase, and finally inhibited the deposition of intrarenal crystals [34]. Our data were consistent with all these findings.…”

“…It has been reported that the pretreatment of high‐dose ATV significantly decreased the prevalence of acute kidney injury caused by contrast agents in patients with coronary angiography . Fuentes et al found that ATV reduced the acute inflammatory load of the transplanted kidney and promoted the recovery of renal function. In the present study, we found that ATV was effective in inhibiting CaOx crystals‐induced oxidative stress, suppressing the activation of TRL4/NF‐κB and NLRP3 inflammasome pathways, decreasing the expressions of TRL4, NF‐κB, NLRP3, and cleaved caspase‐1, reducing the production of inflammatory mediators, and ameliorating the damage and crystal deposition in HK‐2 cells and rat kidney.…”

The Effect of Statin Therapy on Inflammatory Biomarkers: A Systematic Review

“…Statins, while exhibiting an anti-inflammatory effect, also aid clinically in an immunomodulatory effect. An RCT conducted by Orozco et al showed a significant (P=0.007) reduction in pre-transplant and posttransplant Hs-CRP in renal transplant donors and recipients [13]. Compared to the larger study by Kitas et al, a similar dose of atorvastatin 40mg vs. placebo therapy was used, although for a much shorter duration of four weeks [11,13].…”

Promoting cardiovascular health post‐transplant through early diagnosis and adequate management of hypertension and dyslipidemia

“…Atorvastatin treatment of human peripheral blood mononuclear cells (PBMCs) increased the number of CD4 + CD25+Foxp3 + Treg cells 137 . By increasing the proportion of Treg cells and decreasing Teff cells, statins may reduce rejection and have direct anti‐atherogenic activity 138‐140 …”

“…128 However, in a 2-year extension study, a statistically significant difference in MACE was seen in the fluvastatin group without an observed difference in overall mortality or graft loss. 129 [138][139][140] Ezetimibe inhibits the absorption of cholesterol at the jejunal enterocyte brush border and is effective at lowering LDL in both adults and children. 141,142 A small study in pediatric kidney transplant recipients using ezetimibe in combination therapy with statins showed a notable decrease in LDL, total cholesterol, and triglycerides with no change in calcineurin inhibitor trough levels or allograft function.…”