常染色體顯性多囊腎病遺傳因素對(duì)疾病進(jìn)展的影響及治療策略的薈萃分析
發(fā)布時(shí)間：2018-07-14 22:29
【摘要】：研究目的：常染色體顯性多囊腎�。ˋDPKD）是最常見(jiàn)的單基因遺傳性腎病。主要表現(xiàn)為腎臟多發(fā)囊腫的不斷生長(zhǎng)，常在患者50歲左右緩慢進(jìn)展至終末期腎病(ESRD)。本研究旨在分析：1、內(nèi)皮型一氧化氮合酶(eNOS)基因多態(tài)性對(duì)ADPKD患者ESRD發(fā)病風(fēng)險(xiǎn)、ESRD發(fā)病年齡及高血壓發(fā)病風(fēng)險(xiǎn)的影響；2、分別評(píng)估抑制cAMP通路藥物、抗高血壓藥物和mTOR抑制劑治療ADPKD的的有效性和安全性；3、比較腹腔鏡手術(shù)與開(kāi)腹手術(shù)切除ADPKD腎臟的的有效性和安全性。 研究方法：計(jì)算機(jī)檢索Medline數(shù)據(jù)庫(kù)（1990年-2013年11月）、Embase數(shù)據(jù)庫(kù)（1990年-2013年11月）、Google scholar、Web of Science database、中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)（1990年-2013年12月）和Cochrane組織RCT注冊(cè)數(shù)據(jù)庫(kù)（2013年第6期）。納入相關(guān)文獻(xiàn)進(jìn)行薈萃分析。 結(jié)果： 1、共6項(xiàng)研究評(píng)估了eNOS基因Glu298Asp多態(tài)性與ADPKD患者發(fā)生ESRD的風(fēng)險(xiǎn)，GG表型患者相比（GT+TT）表型患者降低了30%的患ESRD的風(fēng)險(xiǎn)(OR=0.70；95%CI，0.53，0.93；P=0.02)，GG相比T等位基因型可以延緩ADPKD患者進(jìn)入ESRD1.93年（WMD=1.93；95%CI，0.71，3.15；P=0.002），但對(duì)ADPKD患者發(fā)生高血壓風(fēng)險(xiǎn)的影響無(wú)統(tǒng)計(jì)學(xué)意義(OR=1.04；95%CI，0.66，1.66，P=0.86)。 2、關(guān)于生長(zhǎng)抑素類(lèi)似物延緩ADPKD共4項(xiàng)RCT研究，生長(zhǎng)抑素類(lèi)似物相比安慰劑能夠抑制總腎臟體積（TKV）9%的年增長(zhǎng)率（95%CI，-10.33，-7.58）；P 0.001）,降低TKV生長(zhǎng)約85.73ml（95%CI，-134.9，-36.57，P 0.0006)，但對(duì)延緩GFR減退不具有統(tǒng)計(jì)學(xué)意義(WMD=0.89ml/min，95%CI，-7.76，-9.54，P=0.84)。托伐普坦可以有效保護(hù)ADPKD患者GFR (WMD2.58ml/min，95%CI0.28，4.87，P=0.03)并減少TKV的增長(zhǎng)（WMD-138.51ml，95%CI，-162.00，-115.02，P 0.00001）。 3、腎素血管緊張素系統(tǒng)拮抗劑（RAAS-I）相比安慰劑和其他類(lèi)降壓藥能夠減少GFR下降值5.45ml/min（95%CI，-10.78，-0.11）；P=0.05），降低尿微量蛋白尿水平-18.66mg/d（-36.19，-1.14，P=0.04）。ARB最有可能（33%）成為療效最好的降壓藥，療效順序從高到低分別為：血管緊張素受體阻斷劑、血管緊張素轉(zhuǎn)化酶抑制劑、β受體阻滯劑、安慰劑、利尿劑和鈣離子拮抗劑。 4、mTOR抑制劑相比安慰劑不能減少TKV的增長(zhǎng)(5項(xiàng)研究，619例患者，WMD-90.01ml，95%CI，-235.49，55.47，P=0.23)，對(duì)GFR同樣沒(méi)有顯著影響（WMD4.94ml/min，95%CI，-0.81，10.68，P=0.09)。 5、腹腔鏡腎切除ADPKD腎臟組患者的平均住院日顯著短于開(kāi)放手術(shù)組患者（WMD，-4.38d，95%CI，-5.93，-2.83，P=0.00001），輸血風(fēng)險(xiǎn)比值比顯著低于開(kāi)放手術(shù)組患者（OR，0.25，，95%CI，0.10，0.62；P=0.003），但總并發(fā)癥發(fā)生比值比沒(méi)有統(tǒng)計(jì)學(xué)差異（OR，0.51，95%CI，0.24，1.06）。 結(jié)論： 1、eNOS基因Glu298Asp多態(tài)性中GG表型減緩了ADPKD患者進(jìn)入ESRD的時(shí)間，降低了ESRD的發(fā)病風(fēng)險(xiǎn)，但對(duì)ADPKD患者高血壓的發(fā)病無(wú)顯著影響。 2、生長(zhǎng)抑素類(lèi)似物可以有效抑制ADPKD患者TKV的增長(zhǎng)，但對(duì)GFR的保護(hù)作用有待更長(zhǎng)時(shí)間隨訪的研究來(lái)證明；托伐普坦是較好的延緩ADPKD患者GFR下降和TKV增長(zhǎng)的藥物。 3、降壓藥物延緩ADPKD腎病進(jìn)展的療效尚不確定，仍需要更多的RCT來(lái)證明。RAAS-I相比其他降壓藥是最適合ADPKD患者治療高血壓的藥物。 4、mTOR抑制劑不能給ADPKD患者帶來(lái)減少TKV和保護(hù)GFR的療效，臨床使用需謹(jǐn)慎。 5、應(yīng)用腹腔鏡腎切除術(shù)相比開(kāi)放手術(shù)治療ADPKD可以減少住院時(shí)間，輸血風(fēng)險(xiǎn)。但手術(shù)時(shí)間會(huì)延長(zhǎng)，兩種手術(shù)方式的總并發(fā)癥率無(wú)明顯差異。
[Abstract]:Objective : autosomal dominant polycystic kidney disease ( ADPKD ) is the most common type of single - gene hereditary nephropathy . It is mainly characterized by the continuous growth of renal multiple cysts , which is slowly progressing slowly to end - stage renal disease ( end - stage renal disease ) at the age of 50 years . The aim of this study is to analyze the effects of 1 , endothelial nitric oxide synthase ( eNOS ) gene polymorphism on the risk of onset , age and risk of hypertension in patients with ADPKD .
2 , respectively evaluating the effectiveness and safety of inhibiting the treatment of ADPKD by the cAMP pathway drugs , the antihypertensive drugs and the mtor inhibitor ;
3 . To compare the efficacy and safety of laparoscopic surgery with open abdominal surgery for ADPKD kidney .
Study Methods : Computer - searched Medline database ( 1990 - November 2013 ) , Embase database ( 1990 - November 2013 ) , Google Analytics , Web of Science database , Chinese Biomedical Literature Database ( 1990 - December 2013 ) , and the RCTs registry database ( Phase 6 , 2013 ) . Meta - analysis was conducted in the relevant literature .
Results :
1 . A total of 6 studies assessed that the Glu298Asp polymorphism of eNOS gene was associated with the risk of patients with ADPKD and the risk of patients with GG phenotype ( GT + TT ) was reduced by 30 % ( OR = 0.70 ;
95 % CI , 0.53 , 0.93 ;
P = 0.02 ) , GG compared with T allele could delay ADPKD patients into ESRD1 . 93 years ( WMD = 1.93 ;
95 % CI , 0.71 , 3.15 ;
P = 0.002 ) , but there was no statistically significant effect on the risk of hypertension in ADPKD patients ( OR = 1.04 ;
95 % CI , 0.66 , 1.66 , P = 0.86 ) .
2 . With respect to somatostatin analogues delayed ADPKD total 4 RCTs , somatostatin analogues inhibited the annual growth rate of 9 % of total renal volume ( TKV ) compared to placebo ( 95 % CI , - 10.33 , - 7.58 ) ;
P 0.001 ) , reduced TKV growth by about 85.73 ml ( 95 % CI , - 134.9 , - 36.57 , P 0.0006 ) , but did not have statistical significance for slowing down GFR ( WMD = 0.89 ml / min , 95 % CI , - 7.76 , - 9.54 , P = 0.84 ) . torvastatin can effectively protect ADPKD patients from GFR ( WMD2.58ml / min , 95 % CI 0.28 , 4.87 , P = 0.03 ) and reduce TKV growth ( WMD - 138.51 ml , 95 % CI , - 162.00 , - 15.02 , P 0.00001 ) .
3 . RAAS - I reduced GFR by 5.45ml / min ( 95 % CI , - 10.78 , - 0.11 ) compared with placebo and other antihypertensive agents ;
P = 0.05 ) , urinary microalbuminuria level - 18.66mg / d ( - 36.19 , - 1.14 , P = 0.04 ) . ARBs are most likely ( 33 % ) to be the best antihypertensive agents for efficacy , ranging from high to low : angiotensin receptor blockers , angiotensin - converting enzyme inhibitors , beta - blocker , placebo , diuretic and calcium ion antagonists .
4 . There was no significant effect on GFR compared to placebo ( 5 studies , 619 patients , WMD - 90.01 ml , 95 % CI , - 235.49 , 55.47 , P = 0.23 ) , which did not significantly affect GFR ( WMD4.94 ml / min , 95 % CI , - 0.81 , 10.68 , P = 0.09 ) .
5 . The average hospitalization days of patients with ADPKD renal resection were significantly shorter than those in open surgery group ( WMD , - 4.38 , 95 % CI , - 5.93 , - 2.83 , P = 0.00001 ) , and the odds ratio of blood transfusion risk was significantly lower than that in open surgery group ( OR , 0.25 , 95 % CI , 0.10 , 0.62 ;
There was no statistical difference ( OR , 0.51 , 95 % CI , 0.24 , 1.06 ) .
Conclusion :
1 . The GG phenotype in the Glu298Asp polymorphism of eNOS gene slowed the time of entry of ADPKD patients into end - stage and reduced the risk of development , but had no significant effect on the onset of hypertension in ADPKD patients .
2 . The growth of TKV in ADPKD patients can be effectively inhibited by somatostatin analogues , but the protective effect on GFR needs to be proved by longer - term follow - up .
torvastatin is a good drug for delaying the decrease in GFR and TKV growth in ADPKD patients .
3 . The efficacy of antihypertensive drugs in delaying the progression of ADPKD nephropathy is uncertain , and more RCTs are needed to demonstrate that RAAS - I is the most suitable drug for the treatment of hypertension in patients with ADPKD .
4 . The effect of reducing TKV and protecting GFR in ADPKD patients is not brought to ADPKD patients , and careful clinical use is needed .
5 . Compared with open surgery , ADPKD can reduce the hospitalization time and blood transfusion risk compared with open surgery , but the operation time can be prolonged . There is no significant difference in the total complication rate of the two procedures .
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R692
本文編號(hào)：2123161
[Abstract]:Objective : autosomal dominant polycystic kidney disease ( ADPKD ) is the most common type of single - gene hereditary nephropathy . It is mainly characterized by the continuous growth of renal multiple cysts , which is slowly progressing slowly to end - stage renal disease ( end - stage renal disease ) at the age of 50 years . The aim of this study is to analyze the effects of 1 , endothelial nitric oxide synthase ( eNOS ) gene polymorphism on the risk of onset , age and risk of hypertension in patients with ADPKD .
2 , respectively evaluating the effectiveness and safety of inhibiting the treatment of ADPKD by the cAMP pathway drugs , the antihypertensive drugs and the mtor inhibitor ;
3 . To compare the efficacy and safety of laparoscopic surgery with open abdominal surgery for ADPKD kidney .
Study Methods : Computer - searched Medline database ( 1990 - November 2013 ) , Embase database ( 1990 - November 2013 ) , Google Analytics , Web of Science database , Chinese Biomedical Literature Database ( 1990 - December 2013 ) , and the RCTs registry database ( Phase 6 , 2013 ) . Meta - analysis was conducted in the relevant literature .
Results :
1 . A total of 6 studies assessed that the Glu298Asp polymorphism of eNOS gene was associated with the risk of patients with ADPKD and the risk of patients with GG phenotype ( GT + TT ) was reduced by 30 % ( OR = 0.70 ;
95 % CI , 0.53 , 0.93 ;
P = 0.02 ) , GG compared with T allele could delay ADPKD patients into ESRD1 . 93 years ( WMD = 1.93 ;
95 % CI , 0.71 , 3.15 ;
P = 0.002 ) , but there was no statistically significant effect on the risk of hypertension in ADPKD patients ( OR = 1.04 ;
95 % CI , 0.66 , 1.66 , P = 0.86 ) .
2 . With respect to somatostatin analogues delayed ADPKD total 4 RCTs , somatostatin analogues inhibited the annual growth rate of 9 % of total renal volume ( TKV ) compared to placebo ( 95 % CI , - 10.33 , - 7.58 ) ;
P 0.001 ) , reduced TKV growth by about 85.73 ml ( 95 % CI , - 134.9 , - 36.57 , P 0.0006 ) , but did not have statistical significance for slowing down GFR ( WMD = 0.89 ml / min , 95 % CI , - 7.76 , - 9.54 , P = 0.84 ) . torvastatin can effectively protect ADPKD patients from GFR ( WMD2.58ml / min , 95 % CI 0.28 , 4.87 , P = 0.03 ) and reduce TKV growth ( WMD - 138.51 ml , 95 % CI , - 162.00 , - 15.02 , P 0.00001 ) .
3 . RAAS - I reduced GFR by 5.45ml / min ( 95 % CI , - 10.78 , - 0.11 ) compared with placebo and other antihypertensive agents ;
P = 0.05 ) , urinary microalbuminuria level - 18.66mg / d ( - 36.19 , - 1.14 , P = 0.04 ) . ARBs are most likely ( 33 % ) to be the best antihypertensive agents for efficacy , ranging from high to low : angiotensin receptor blockers , angiotensin - converting enzyme inhibitors , beta - blocker , placebo , diuretic and calcium ion antagonists .
4 . There was no significant effect on GFR compared to placebo ( 5 studies , 619 patients , WMD - 90.01 ml , 95 % CI , - 235.49 , 55.47 , P = 0.23 ) , which did not significantly affect GFR ( WMD4.94 ml / min , 95 % CI , - 0.81 , 10.68 , P = 0.09 ) .
5 . The average hospitalization days of patients with ADPKD renal resection were significantly shorter than those in open surgery group ( WMD , - 4.38 , 95 % CI , - 5.93 , - 2.83 , P = 0.00001 ) , and the odds ratio of blood transfusion risk was significantly lower than that in open surgery group ( OR , 0.25 , 95 % CI , 0.10 , 0.62 ;
There was no statistical difference ( OR , 0.51 , 95 % CI , 0.24 , 1.06 ) .
Conclusion :
1 . The GG phenotype in the Glu298Asp polymorphism of eNOS gene slowed the time of entry of ADPKD patients into end - stage and reduced the risk of development , but had no significant effect on the onset of hypertension in ADPKD patients .
2 . The growth of TKV in ADPKD patients can be effectively inhibited by somatostatin analogues , but the protective effect on GFR needs to be proved by longer - term follow - up .
torvastatin is a good drug for delaying the decrease in GFR and TKV growth in ADPKD patients .
3 . The efficacy of antihypertensive drugs in delaying the progression of ADPKD nephropathy is uncertain , and more RCTs are needed to demonstrate that RAAS - I is the most suitable drug for the treatment of hypertension in patients with ADPKD .
4 . The effect of reducing TKV and protecting GFR in ADPKD patients is not brought to ADPKD patients , and careful clinical use is needed .
5 . Compared with open surgery , ADPKD can reduce the hospitalization time and blood transfusion risk compared with open surgery , but the operation time can be prolonged . There is no significant difference in the total complication rate of the two procedures .
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R692
【參考文獻(xiàn)】
相關(guān)期刊論文 前4條
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2 張彤;付莉莉;梅長(zhǎng)林;;霉酚酸酯與雷帕霉素對(duì)多囊腎囊腫襯里上皮細(xì)胞增殖和凋亡影響的比較[J];第二軍醫(yī)大學(xué)學(xué)報(bào);2008年08期
3 劉春艷;梅長(zhǎng)林;袁莉;張懿;付莉莉;蔡厚安;王雪琦;;雷帕霉素抑制人多囊腎囊腫襯里上皮細(xì)胞增殖及VEGF表達(dá)[J];基礎(chǔ)醫(yī)學(xué)與臨床;2010年07期
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