| Objective: Autosomal dominant polycystic kidney disease (ADPKD) is the mostcommon monogenic hereditary kidney disease. Multiple cysts continue growing in thekidneys of ADPKD, and will slowly reach end stage renal disease (ESRD) about50years’old. This study aimed to analyze:1, endothelial nitric oxide synthase (eNOS) genepolymorphisms on the risk of ESRD, ESRD onset age and the risk of hypertension in patientswith ADPKD;2, analyse the efficacy and safety of the drugs which inhibited cAMP pathway,anti-hypertension drugs and mTOR inhibitors in the treatment of ADPKD, respectively;3,compare the efficacy and safety of laparoscopic and open nephrectomy in ADPKD.Methods: We searched the Medline database (1990, November2013), Embasedatabases (1990-2013November), Google scholar, Web of Science database, ChineseBiomedical Literature Database (1990-2013in December) and the Cochrane organizationRCT registration database (2013section6). Meta-analysis was used to combine the relevantstudies.Results:Six study assessed Glu298Asp eNOS gene polymorphism on the risk of ESRD inADPKD patients. GG phenotype reduced about30%risk of ESRD compared with (GT+TT)phenotypes in patients with ADPKD (OR=0.70;95%CI,0.53,0.93; P=0.02). GG delayedESRD1.93years in ADPKD patients (WMD=1.93;95%CI,0.71,3.15; P=0.002)compared to T allele. However, Glu298Asp did not statistically affect the risk of hypertensionin ADPKD patients (OR=1.04;95%CI,0.66,1.66, P=0.86).Four RCTs studied somatostatin analogue in ADPKD. Somatostatin analogs inhibited9%annual growth rate of total kidney volume (TKV)(95%CI,-10.33,-7.58); P <0.001)compared to placebo. Somatostatin analogs decreased TKV growth about85.73ml (95%CI,-134.9,-36.57, P <0.0006), but GFR decline was not statistically significant (WMD=0.89ml/min,95%CI,-7.76,-9.54, P=0.84) compared to placebo. Tolvaptan effectivelyprotected the GFR (WMD2.58ml/min,95%CI0.28,4.87, P=0.03) and reduced TKVgrowth (WMD-138.51ml,95%CI,-162.00,-115.02, P <0.00001) in patients with ADPKD.The renin-angiotensin system can reduce antagonist (RAAS-I) reduced GFR loss about5.45ml/min (95%CI,-10.78,-0.11); P=0.05) compared to placebo and other classes ofantihypertensive drugs. RAAS-I lowered urinary microalbuminuria level-18.66mg/d (-36.19,-1.14, P=0.04). ARB is most likely (33%) to be the best antihypertensive drugs in ADPKD. The efficacies from high to low were: angiotensin receptor blockers, angiotensin convertingenzyme inhibitors, β-blockers, placebo, diuretics and calcium antagonists.MTOR inhibitors reducef the growth of TKV compared to placebo (5studies,619patients, WMD-90.01ml,95%CI,-235.49,55.47, P=0.23). There is no significant effect onGFR (WMD4.94ml/min,95%CI,-0.81,10.68, P=0.09).The average length of stay in hospital was significantly shorter in laparoscopicnephrectomy group than in open nephrectomy (WMD,-4.38d,95%CI,-5.93,-2.83, P=0.00001). Blood transfusion risk was significantly lower in laparoscopic nephrectomy group(OR,0.25,95%CI,0.10,0.62; P=0.003), but the ratio of total complications was notstatistically significant (OR,0.51,95%CI,0.24,1.06).Conclusion:The GG phenotype in Glu298Asp polymorphism of ENOS gene slowed ADPKDpatients from entering into ESRD, and reduced the risk of ESRD, but had no significanteffect on the incidence of hypertension in patients with ADPKD.Somatostatin analogs inhibited the growth of TKV in ADPKD patients, but theprotective effect of GFR are needed to prove in the follow-up studies. Tolvaptan protectedGFR decline better and slowed the growth of TKV in patients with ADPKD.The efficacy of delaying the kidney progress of ADPKD by antihypertensive drugs isuncertain, which still needs more RCTs to prove. RAAS-I is the most suitableantihypertensive drugs for the treatment of hypertension in patients with ADPKD.Long term treatment with mTOR inhibitors neither reduces TKV nor attenuates the GFRdecline in patients with ADPKD. Clinical use of mTOR inhibitors needs to be taken intocaution.The application of laparoscopic nephrectomy reduced the hospitalization time and bloodtransfusion risk compared to open surgery in ADPKD. But the operation time was extended,and the surgical complications between the two groups had no significant differences. |
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