title: Lipid-lowering agents for nephrotic syndrome.
abstract: BACKGROUND
  Nephrotic syndrome is the collective name given to a group of symptoms that include proteinuria, lipiduria, hypoalbuminaemia, oedema, hypercholesterolaemia, elevated triglycerides, and hyperlipidaemia. Hyperlipidaemia is thought to aggravate glomerulosclerosis (hardening of blood vessels in the kidneys) and enhance progression of glomerular disease. Studies have established that reduction in total cholesterol and low density lipoprotein (LDL) cholesterol is associated with reduction in risk of cardiovascular diseases. In 2011, the European Society of Cardiology and European Atherosclerosis Society guidelines for the management of dyslipidaemia recommended use of statins as first-line agents in the management of nephrotic dyslipidaemia. However, the effectiveness and safety of statins for people with nephrotic syndrome remains uncertain. Furthermore, the efficacy of second-line lipid-lowering drugs, such as ezetimibe and nicotinic acid, has not been proven in patients with nephrotic syndrome who are unable to tolerate statin therapy.
  
  
  OBJECTIVE
  This review aimed to evaluate the benefits and harms of lipid-lowering agents in adults and children with nephrotic syndrome.
  
  
  METHODS
  We searched the Cochrane Renal Group's Specialised Register (to 18 March 2013) through contact with the Trials Search Co-ordinator using search terms relevant to this review.
  
  
  METHODS
  All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at participants with nephrotic syndrome that compared any lipid-lowering agent to placebo, no treatment or other lipid-lowering agents, given for not less than four weeks, were included.
  
  
  METHODS
  Two authors independently assessed study eligibility and risk of bias, and extracted data. Statistical analyses were performed using a random effects model. Dichotomous results were expressed as risk ratios (RR) with 95% confidence intervals (CI). For continuous measures mean difference (MD) was used, or the standardised mean difference (SMD) where different scales had been used.
  
  
  RESULTS
  We included five RCTs enrolling a total of 203 participants. Of these, four studies compared statins with no treatment or placebo, and one compared fibrates with placebo. We found no published studies comparing second-line agents such as ezetimibe, bile acid sequestrants, and nicotinic acid with placebo or no treatment. Our assessment of the risk of bias found that one study was judged overall to be at low risk of bias and the remaining four were judged to be at high risk of bias.Most outcomes were supported by single study data. One study reported significantly increased high density lipoprotein (HDL) cholesterol among participants in the statin arm compared with the no treatment group (MD 5.40 mg/dL, 95% CI 2.31 to 8.49). Another study reported higher serum albumin in the statin group compared to those who received no treatment (MD 0.60 g/dL, 95% CI 0.14 to 1.06). No serious adverse events, such as rhabdomyolysis, were reported, however some minor events occurred. One study reported no significant difference in the number of participants with elevated liver enzymes (RR 3.00, 95% CI 0.13 to 69.52); three studies reported liver enzymes remained within the normal range (no data provided). Four studies reported creatinine phosphokinase (CPK). One study indicated that CPK values fluctuated in both the simvastatin and placebo groups (no data provided); the remaining three studies reported CPK either stayed within the normal range (one study) or there was no significant difference between the lipid lowering agents and placebo.
  
  
  CONCLUSIONS
  None of the included studies reported patient-centred outcomes including all-cause mortality, cardiovascular mortality, or non-fatal myocardial infarction; only single studies reported cholesterol (HDL, LDL and total cholesterol), triglycerides, serum creatinine, blood urea nitrogen, liver enzymes, and protein (serum, urine). High quality RCTs need to be conducted to assess the safety and efficacy of lipid-lowering drugs for people with nephrotic syndrome.
authors: Department of Epidemiology and Biostatistics, School of Public Health, Chengdu Medical College, Chengdu, China.
authors: Xiangyu
authors: X
authors: Kong
authors: Hao
authors: H
authors: Yuan
authors: Junming
authors: J
authors: Fan
authors: Zi
authors: Z
authors: Li
authors: Taixiang
authors: T
authors: Wu
authors: Lanhui
authors: L
authors: Jiang
mesh_terms: D000328:Adult; D002648:Child; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D000077340:Fluvastatin; D015248:Gemfibrozil / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008148:Lovastatin / Q000627:therapeutic use; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000627:therapeutic use
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007211:Indoles; D000077340:Fluvastatin; D008148:Lovastatin; D019821:Simvastatin; D015248:Gemfibrozil