Mayo Clinic Staff. P -value adjusted for all those variables and individual propensity score. dizziness. The total difference in eGFR was 3.35 ml/min/1.73 m2 in the high-intensity statin group compared with control. In a subgroup analysis of the CARE study a post hoc analysis similarly found no effect of statins on GFR overall, but in the subjects with the most severe impairment in GFR, pravastatin was associated with a less severe fall in GFR during follow up [ 19 ]. Another study showed that high-dose statins were 34 percent more likely to cause kidney damage in the first 120 days of treatment, but its also possible that statins at lower doses may not cause such side effects. Discrepant opinions between authors were resolved by consensus. 8600 Rockville Pike Some people report sleep problems while taking statins . Statins, a common medication taken to lower cholesterol, may worsen chronic kidney disease. * Significant side effects (p<0.05) in the statin group compared with the control group. GUID:A602D90C-F5C2-44D7-AA97-86B106DA36E0, GUID:BAE70E35-70C3-453A-8358-C32C9511EE10, GUID:56498CDF-8A94-4C98-A128-880C34EB69FD, GUID:0E428F45-9F70-4EBA-8C7D-54916889864A, GUID:3A10BE1A-6F51-4EA6-BEFF-5D1447D952D0, GUID:AB3C8272-20CA-4E47-86A9-432251F0BD51, Early recognition and prevention of chronic kidney disease. Statins work by blocking an enzyme in your liver that controls cholesterol production. In the present analysis, 788 subjects were included, of whom follow-up on treatment was complete ( n = 644) or follow-up of at least 3 months on treatment (the time that UAE and GFR were first measured on treatment) was available ( n = 144). Heart disease is a major cause of death for people with kidney disease, which is why medications to control cholesterol and blood pressure are usually prescribed. Zoja C, Corna D, Rottoli D, Cattaneo D, Zanchi C, Tomasoni S, et al. Background: Statins improve cardiovascular outcome, but less is known on the renal outcome. Proteinuria at baseline was also associated with a much greater protective effect of pravastatin use.14. HHS Vulnerability Disclosure, Help The local medical ethics committee approved the PREVEND and the PREVEND-IT studies. 10.1016/j.ijcard.2012.05.010 Abstract Background: However, conflicting results have been reported regarding their renal effects. We excluded studies from our meta-analysis if they had poor quality. Strengths of our study include only enrolling CKD participants with a baseline eGFR less than 60 ml/min/1.73 m2 and a comprehensive MEDLINE, EMBASE and Cochrane Databases database search. Your body needs some phosphate, but in larger-than-normal amounts, phosphate can. In both of our studies, we found no lowering of UAE in subjects using statins, as was suggested from some previous reports [ 9 , 10 ]. The heterogeneity of effect size estimates across these studies was quantified using the I2 statistic and Q statistic. In Taiwan, in adults with eGFR <60 mL/min/1.73 m 2 and without chronic dialysis, statins therapy is recommended only if low-density lipoprotein cholesterol levels are 100 mg/dL 9. Low-density lipoprotein (LDL) cholesterol. In the second analysis, we compared the association between statins and the progression of UAE and categorical changes (>10%) in GFR, and calculated univariate and multivariate relative risks (RRs) with adjustment for potential confounders and for individual propensity scores [ 27 ]. Analyzed the data: AS SU. Body mass index (BMI) was calculated as weight (kg) divided by the square of height (m 2 ). Since there is only one prospective cohort study [23], only RCTs were included in the meta-analyses. Adults and teens can take statins. For example, a lipid profile every year or two in a CKD patient under the age of 50 years who is not currently on statin therapy would help to risk stratify this patient and determine when statin therapy should be initiated. Two authors (AS and SU) independently reviewed titles and abstracts of all citations that were identified. In our clinical trial, we compared the change in log-transformed UAE and the percentage change in GFR between pravastatin and placebo using Student's t -test. GFR fell in 4 years in both statin users and non-users (4.6 13.5 and 2.4 11.2, respectively). Treat to goal Non-HDL <130 mg/dL and LDL <100 mg/dL, Consider starting drug therapy for Non-HDL 130 mg/dL or LDL 100 mg/dL. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. Post-marketing surveillance studies frequently bring new effects of a drug under attention, be it positive or negative. As a library, NLM provides access to scientific literature. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America, 5 Conceived and designed the experiments: AS. Sample size of the included studies ranged from thirty-eight to 6,245. This is because we separately analyzed studies with the outcome of total change in eGFR and rate of eGFR change per year as they used different units and we did not have enough information to change them into the same unit. Results. Medications are also prescribed to treat other conditions associated with kidney failure. In the event that they started using statins after the first screening, they were defined as starters. After all abstracts were reviewed, data comparisons between investigators were conducted to ensure completeness and reliability. (2016). In our cohort study, the propensity score was used to correct for bias caused by non-randomized assignment between statin users and non-users. The fall in GFR, when analysed as 10% change was also not significantly different between the statin users (30.2%) and non-statin users (23.6%)(RR 1.17; 95% CI 0.911.51). Erectile dysfunction (ED) is often a symptom . Palmer SC, et al. Statins (HMG-CoA reductase inhibitor) are widely used for lowering low density lipoprotein (LDL) and total cholesterol levels in blood. In healthy humans, a normal decline in renal function begins soon after maturity and constitutes a fairly constant decrease in glomerular filtration, which averages 8 ml/min lost glomerular filtration rate (GFR) (6%) for each . HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis, The Cochrane database of systematic reviews. Effects of lipid-lowering therapy with rosuvastatin on atherosclerotic burden in patients with chronic kidney disease. Abbreviation: CHD = coronary heart disease, DM = diabetes mellitus, eGFR = estimated glomerular filtration rate, HTN = hypertension, LDL = Low-density lipoprotein, RCT = Randomized controlled trial. Participants who received dialysis, renal replacement therapy or renal transplantation were excluded from the analysis. Kendrick J, Shlipak MG, Targher G, Cook T, Lindenfeld J, Chonchol M. Effect of lovastatin on primary prevention of cardiovascular events in mild CKD and kidney function loss: a post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study. While there is a clear benefit of statin treatment in stage 1-4 CKD and kidney transplant, there does not appear to be a benefit to treating people on chronic dialysis, likely due to excessive competing risk. Bethesda, MD 20894, Web Policies (See related article by Marcello Tonelli. GFR-1, (GFR at first screening), GFR-2, (GFR at second screening); # All subjects who used statins (defined as subjects who had used any statins a year prior to second screening, see Methods section); PDD, prescribed daily dose; * P -value indicates whether GFR differs between first and second screening (using paired sample t -test); P -value (crude) indicates whether delta GFR differs between groups (using one way ANOVA); P -value associated with dummy variable for group, adjusted for baseline age, sex, blood pressure, cholesterol, glucose, GFR, BMI, history of myocardial infarction, start use RAAS, change on blood pressure, type of statins (for PDD) and PDD (for type of statins) (using multivariate linear regression analysis). painful or difficult urination. heartburn, indigestion, nausea or stomach discomfort. Other side effects reported by people taking statins include: weakness. The baseline characteristics of the 788 subjects from the randomized clinical trial , who fulfilled the inclusion criteria for the present analysis, are also given in Table 1 , according to the use of placebo or pravastatin. One of the proposed mechanisms for progressive CKD in patients with renovascular disease is endothelial dysfunction, oxidative stress, and systemic inflammation of the glomerular capillary wall [2]. Hou W, Lv J, Perkovic V, Yang L, Zhao N, Jardine MJ, et al. Rationale. We performed this meta-analysis to investigate the effects of statins versus placebo or control on eGFR and proteinuria using a random effects model. government site. The PDD was divided into PDD <1.00, between 1.00 and 2.00, and >2.00. Third, a propensity scores technique cannot adjust for residual unmeasured covariates which probably influenced both prescription of statins and clinical outcomes, and thus residual bias is still possible. In the observational study, a rise in UAE was observed in the subjects who used statins, especially when used continuously, for a longer time and in a higher dose. In both studies, we assessed the change in UAE and GFR from first vs second screening as continuous variable. The initial search yielded 4,291 articles (Fig 1); 4,141 articles were excluded because they were not RCTs or observational studies (1,866 articles), did not involve CKD participants (1,426 articles), included dialysis patients or did not have primary outcome (849 articles). Indeed, most of the subjects in the observational cohort study who used statins were subjects with the disease. The estimated propensity score for statin treatment was obtained from the fit of a logistic regression model for which we considered the following variables: age, gender, history of myocardial infarction, smoking status, BMI, systolic blood pressure, diastolic blood pressure, serum cholesterol level, blood glucose level, UAE (in class category), e-GFR, use of anti-hypertensives, RAS agents and anti-diabetic medications. Human data mostly report a statin-induced lowering of UAE in patients with advanced renal disease [ 8 ] and in type 2 diabetic patients with microalbuminuria [ 911 ], but no change [ 12 ] or even an increase in albuminuria has also been described [ 1316 ]. We included participants aged 18 years or older who had CKD stages 3 to 4 (defined as eGFR 1559 ml/min/1.73 m2) and had a baseline eGFR, creatinine clearance or protein concentration in urine. Randomized controlled trials (RCTs) demonstrate that statins reduce cardiovascular (CV) risk in diverse clinical populations - including reductions in all-cause mortality, myocardial infarction, stroke, and the need for coronary revascularization [ 1 ]. Our clinical trial data show no effect of 4 years of treatment with pravastatin on UAE or on GFR. This side effect is typically temporary, does not cause symptoms, and often . Among the ten included studies, nine were RCTs, and one was a prospective cohort study. References of selected retrieved articles were also examined. Careers, Unable to load your collection due to an error. Different foods can affect the function of your kidneys. The association between raised blood pressure and adverse renal outcome in hypertension2 and in diabetes3 has become universally accepted, with control of blood pressure now being the cornerstone of nephroprotection.4 Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have achieved pre-eminent status among antihypertensive drugs, with suggestions that their actions go further than can be explained by a reduction of blood pressure alone.5 However, several other important risk factors for the development of renal failure have been identified that, independently or in concert with blood pressure, can cause renal deterioration.6 These include sex, smoking, proteinuria, and dyslipidaemia.4. To assess the stability of the results of the meta-analysis of comparison in total change of eGFR and rate of eGFR change, sensitivity analyses were conducted by excluding one study at a time. being unable to get an erection at any time. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR. For Permissions, please email: journals.permissions@oxfordjournals.org. Our clinical trial patients, though older, were in general in better health as expressed by a lower blood pressure, less frequent a previous myocardial infarction, and less frequent use of anti-hypertensive, lipid- and glucose-lowering drugs than in the observational cohort. The authors found a lower rate of GFR decline for lipid lowering drugs compared with placebo [difference being 1.9 (0.33.4)ml/min/year] [ 18 ]. It received a total of 8 stars (4 stars for selection, 2 stars for comparability, and 2 stars for ascertainment of outcome). First, we included a relatively small number of studies. We performed meta-analysis of RCT and cohort studies separately. None of the results was significantly altered, indicating that our results were robust. KDOQI US commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD. the contents by NLM or the National Institutes of Health. In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. Memory loss. However, there is no recommendation to stop therapy in dialysis patients who are already receiving statins or statin/ezetimibe combinations.3 These recommendations are based on several trials including 4D (Die Deutsche Diabetes Dialyse), AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis), and sub-group analysis of SHARP.6,10,11, In all three trials looking at treating hemodialysis patients with statins or statin plus ezetimibe versus placebo, the primary outcome of CVD death, MI, or stroke was not different between the treatment and placebo arms. In a meta-analysis of over 1.4 million people, there was a linear increase in cardiovascular mortality seen with decreasing estimated glomerular filtration rate (eGFR) below a threshold eGFR of 75 mL/min/1.73 m2, with mortality rates twice as high in stage 3 CKD (eGFR 30-59 mL/min/1.73 m2) and three times as high in stage 4 CKD (eGFR 15-29 mL/min/1.73 m2).2 Patients with CKD have also been shown to have similar rates of myocardial infarction (MI) or coronary heart disease (CHD) compared to those with diabetes, which is why it is considered a CHD equivalent by many thought leaders.3. Wrote the paper: AS EK. Chronic kidney failure develops slowly over time but certain measures can slow its progression. Unadjusted serum creatinine concentrations increased for all patients, with or without diabetes, over a period of 4.6 years; however, allocation to simvastatin significantly reduced the rise in serum creatinine in both cohorts.16. Subjects with missing data were not different from the included subjects with respect to baseline characteristics. When high levels of low-density lipoprotein (LDL) or bad cholesterol are present, they can begin to build up in your blood vessels, causing a blockage. GFR fell 4.6% (13.5) in those who used statins ( P < 0.001) as compared with 2.4% (11.2) ( P < 0.001) in those who never used a statin. lower cholesterol treat anemia relieve swelling from retaining fluids People also often take supplements to protect their bones, like calcium and vitamin D. How do statins work? If you've been having trouble controlling your cholesterol levels, your doctor may have recommended that you take a statin drug. Colantonio LD, Baber U, Banach M, et al. The kidneys filter waste materials from the, Healthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. Per the NLA approach, all patients with stage 3B (eGFR 30-44 mL/min/1.73 m2) or stage 4 CKD are considered high risk and would be treated to a goal non-HDL-C <130 mg/dL and LDL-C <100 mg/dL.8. Primary outcome was change of eGFR or creatinine clearance from baseline. Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, United States of America, 6 Specialist involvement is suggested for patients with fasting triglyceride levels >1000 mg/dL or LDL-C levels >190 mg/dL. The changes in UAE and GFR from baseline compared with the second screening were studied in relation to the use of statins. Efficacy of Vitamin K on bone fragility: puzzling findings from which we should learn how to draw a rigorous study, Reserved gait capacity and mortality among patients undergoing hemodialysis, Urinary lithogenic profile of patients with non-alcoholic fatty liver disease, Chronic kidney disease is a key risk factor for aortic stenosis progression, Measure and risk: Cystatin C, creatinine and controversy in CKD, http://www.fda.gov/cder/foi/nda/2003/21-366_Crestor_Medr_P1.pdf, www.fda.gov/ohrms/dockets/ac/03/briefing/3968B1_02_A-FDA-Clinical%20Review.pdf, Receive exclusive offers and updates from Oxford Academic, e-Glomerular filtration rate (ml/min/1.73m, Copyright 2023 European Renal Association. We studied whether atorvastatin influences kidney function decline and assessed the association between individual kidney function slopes and cardiovascular outcome. A comparison of baseline characteristics did not reveal any statistically significant difference between the placebo and active drug treatment groups. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Abstract. A total score of 3 or less was considered poor, 46 was considered moderate, and 79 was deemed high quality. Statins lower cardiovascular risk, which may relate to beneficial effects on kidney function. The authors thank the Dutch Kidney Foundation for supporting the PREVEND study (Grant E033). 2023 American College of Cardiology Foundation. KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease. Adiponectin regulates albuminuria and podocyte function in mice. The primary outcome was the differences in the change of eGFR. Statins were not found to decrease proteinuria in patients with CKD. An advantage of using observational drug utilization data is that they reflect routine practice for large and representative populations, in contrast to the much smaller and selected populations in clinical trials [ 22 ]. Our website services, content, and products are for informational purposes only. We limited searches to human only. In the observational study, we even found a rise in UAE among statin users, in particular in association with longer duration of use. The MD of total change in eGFR was 1.78 ml/min/1.73 m2 (95% CI: -0.26 to 3.81). In addition, since the American College of Cardiology/American Heart Association (ACC/AHA) Guidelines [9] have emphasized different statin intensities in patients with different risk of atherosclerotic cardiovascular disease, we hypothesized that there is a dose-response relationship between statin intensities and renal outcome. We also assessed a rise in UAE and a fall in GFR as a categorical variable. The results of our subgroup analysis of statin intensity is shown (Fig 3). During physical examination, weight, height and blood pressure were measured. Fellstrm BC, Jardine AG, Schmieder RE, et al. See J Clin Pathol. The study duration ranged from twelve to sixty-three months. Review authors' judgments about each risk of bias. Patients on atorvastatin showed a 12% rise in CrCl, patients on other statins a 4.9% rise in CrCl, and statin free patients a 5.2% fall in CrCl over 36 months of follow up. In conclusion, our data show that, in contrast to the literature, statins do not lower UAE in subjects with only modest renal damage (stages 13 CKD), either in the RCT, or in the observational cohort study. Rarely, statins may cause bad side effects, including: Confusion. All calculations were performed with the SPSS version 12.0.1 software (SPSS, Chicago, IL, USA). Differences in population characteristics at baseline in the various groups under investigation were tested for continuous variables by Student's t -test and for categorical variables by a chi-square test. Your serum creatinine level, age, and sex are used to calculate your GFR number. People who suffer from kidney failure who do not receive a kidney transplant receive dialysis treatment, which is a medical process where waste is artificially removed from the blood. Before initiating a statin, perform baseline blood tests to ensure that lipid-modification treatment is appropriate. We similarly registered the use of anti-hypertensive medication with a split up in agents interfering in the reninangiotensin system (RAS), such as ACE inhibitors or angiotensin II receptor blockers, and other anti-hypertensives. We did not use filter for study design or limit for adults. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. The names of cooperators in the PREVEND study can be found at www.PREVEND.org (for scientifically interested/cooperators). Chronic kidney disease (CKD) is a global health concern 1.According to systemic review data and a meta-analysis of observational studies until September 2014, the global prevalence of CKD was approximately 13.4%, and the prevalence of stage 3-5 CKD was 10.6% 1.An estimated 5.4 million people will be receiving dialysis due to end-stage renal disease (ESRD) in 2030, and globally . In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. sharing sensitive information, make sure youre on a federal To investigate potential publication bias, we examined the contour-enhanced funnel plot of the included studies in assessing total change in eGFR. In our observational study, in the primary analyses we compared the percentage change in log-transformed UAE between the first and second screening for each category of statin-user with the Student's t -test. Use of statins in relation to GFR in the observational cohort study. All relevant data are within the paper and its Supporting Information files. We feel that these data are, however, of interest for the general nephrologists, as early renal damage is also associated with an impaired renal and vascular prognosis. Most people don't have side effects from statins, but you shouldn't take them if you're pregnant, nursing or . Although there are many effective interventions, organisational (health service resource allocation) and motivational (because alterations to patients lifestyles are often required) challenges often need to be overcome first. The fall in GFR between groups was not different after adjustment ( P = 0.11). 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