The Adverse Effects Of Chronic Kidney Disease On Pregnancy And The Effects Of Pregnancy On The Onset And Progression Of Chronic Kidney Disease

Introduction Chronic kidney disease(CKD)is a group of diseases with different etiology,pathological types and degrees of renal impairment.The clinical symptoms of CKD also vary by etiology and pathology.However,regardless of the cause,the common clinical manifestations are hypertension,proteinuria and progressive renal disfunction.CKD was clearly defined by K/DIGO in 2012: 1)renal pathological changes or abnormalities in any types in blood,urine and imaging testing,or the glomerular filtration rate(e GFR)decreased ? 60ml/min/1.75m2;2)the above situation lasts for more than 3 months.According to previous epidemiological studies,the prevelance of CKD varies from10.8% to 16%.The incidence of CKD in women of childbearing age was 0.1% to 4%.CKD is a continuous process.Therefore,patients with CKD at childbearing age are faced with a series of problems such as whether they can get pregnant and risk assessment of pregnancy.It is important to evaluate the pregnancy risk of women with chronic kidney disease and the prognostic effect of pregnancy on chronic kidney disease.At the same time,it is important to pay attention to whether the physiological process peculiar to women,pregnancy and the common complication of pregnancy,preeclampsia(PE),have an effect on the development of chronic kidney disease.About 10% of women develop pregnancy-related hypertension during pregnancy.PE is a special manifestation of abnormal blood pressure during pregnancy,clinical diagnostic criteria for: new onset hypertention after 20 weeks of gestation(systolic blood pressure140 mm Hg or diastolic blood pressure,90 mm Hg or higher)with proteinuria(24-hour proteinuria or 300 mg/d)or original proteinuria is aggravating,or have other organ damage(elevated liver enzymes,thrombocytopenia,and acute kidney injury).Although it occurs during pregnancy,most of these symptoms disappear after delivery.However,previous studies have confirmed that HDP is closely related to subsequent cardiovascular disease in women.The incidence of myocardial ischemia and myocardial infarction was increased in women with PE after delivery.Further studies have shown that HDP causes postpartum cardiovascular events mainly for two reasons: elevated blood pressure and vascular endothelial injury.Whether HDP is a risk factor for postpartum CKD is unclear.We undertook a systematic review and meta-analysis of published cohort studies and case-control studies to estimate the risk of pregnancy complications among patients with CKD versus those without CKD,and to estimate the risk of CKD progression among pregnant patients versus non-pregnant controls with CKD.We also conducted a meta-analysis and systematic review of cohort and case-control studies on whether HDP increased the incidence of CKD.Materials and methods:Relevant studies were conducted according to the meta-analysis guidelines,using a prespecified protocol: the following two sections of literature were searched in medline and Embase databases:(1)We included cohort studies and case-control studies that reported maternal or fetal outcomes in pregnant women with CKD and without CKD as a comparator group who may or may not have had other comorbidities(such as diabetes mellitus);or reported renal outcomes in pregnant women with CKD and non-pregnant women with CKD as a comparator group.(2)whether PE was a high risk factor for CKD: cohort and case-control studies were selected to search the literature from 1946 to July 2018.The follow-up time after the end of pregnancy was ? 0.5 years,and the number of cases was no less than 5 patients.The above two parts are not limited to published languages and are analyzed by random effect model.The total effect categorical variables were described using the odds ratio(Odds Ratio)and the 95% confidence interval(CI),and the continuous variables were described using the mean(`X)±standard deviation(SD).Heterogeneity was tested by I2 statistics.The quality of the included studies was evaluated by two authors,independently.The evidential level of each outcome was determined in accordance with the Grading of Recommendations Assessment,Development and Evaluation(GRADE)system and conducted with GRADE profiler 3.6.Publication bias was assessed by creating and examining funnel plots.A sensitivity analysis was performed by omitting studies with the smallest number of participants and investigating the influence on the overall meta-analysis estimate.Result:1.To evaluate the effect of CKD on pregnancy and renal prognosis of patients with CKD(1)The effect of CKD on PE16 studies evaluated the risk of PE in women with CKD,and the results showed that the risk of PE in pregnant women with CKD was significantly higher than control group(OR: 9.74,95%CI: 4.54—20.91,P<0.001).Subgroup analysis showed that the risk of PE was higher if earlier publication years,smaller sample size,lower age,diabetic nephropathy,macroalbuminuria before pregnancy,and serious renal impairment.At the same time,there are significant differences in different regions.(2)the effect of CKD on preterm19 studies evaluated the risk of preterm in women with CKD,and the results showed that the risk of preterm in pregnant women with CKD was significantly higher than control group(OR:6.72,95%CI:3.76—12.00,P<0.001).Subgroup analysis showed that published in the early age,older age,diabetic nephropathy,macroalbuminuria and higher level of renal damage before pregnancy are higher risk of preterm.(3)the effect of CKD on Small Gestational Age(SGA)12 studies evaluated the risk of SGA in women with CKD,and the results showed that the risk of SGA in pregnant women with CKD was significantly higher than control group(OR: 5.46,95% CI: 2.49—11.99,P<0.001).Subgroup analysis showed that the younger age,diabetic nephropathy,macroalbuminuria and more serious renal damage before pregnancy group are higher risk of SGA.(4)the effect of CKD on Low Birth Weight(LBW)6 articles were compared,the results showed that chronic kidney disease(CKD)with pregnancy is significantly increased the risk of LBW(OR: 4.59,95% CI: 2.27—9.27,P<0.001).(5)The effect of CKD on type in delivery11 articles were compared the results showed that chronic kidney disease(CKD)merging pregnancy is significantly increased the risk of cesarean delivery(OR: 2.85,95% CI: 1.52—5.34,P<0.001).Subgroup analysis showed that earlier published year,macroalbuminuria and less renal damage were more risk of cesarean section.(6)Effects of CKD on failure of pregnancy14 articles were compared,there was no statistics difference between two groups(OR:3.00,95%CI: 0.97—9.27,P=0.057).Subgroup analysis showed that the pregnancy failure rate was higher in the group with later publication year and macroalbuminuria.(7)Effect of pregnancy on end-stage renal disease(ESRD)/creatinine doubling in CKD patients8 studies and 9 groups compared the risk of ESRD/ doubling increasing creatinine level in pregnant women with CKD compared the non-pregnant women.The mean follow-up time of 9.04 years showed no statistical difference in the risk of ESRD/ creatinine doubling between the two groups(OR: 0.98,95%CI: 0.70—1.37,P=0.894).Subgroup analysis showed that publication age,sample size,follow-up year,primary disease,age,baselinel blood pressure level,baseline serum creatinine level,baseline e GFR level,baseline urinary protein level had no effect on the results.(8)Effects of pregnancy on e GFR/CCr level,the end point of follow-up in CKD patients4 studies and 5 groups compared the level of e GFR/CCr at the follow-up end point.The mean follow-up time of 5.5 years.Results showed no statistical difference in the level of e GFR/CCr at the follow-up end point in CKD women with or without pregnancy(WMD: 3.37 ml/min,95%CI:-0.93—7.66,P=0.124).(9)Effect of pregnancy on s Cr level at follow-up end point in CKD women5 studies compared the level of s Cr at the follow-up end point.The mean follow-up time was 7.2 years.There was no statistical difference in the s Cr level between two groups(WMD:-5.45 umol/l,95%CI:-23.77—12.86,P=0.559).2.Evaluation of the effect of HDP on the occurrence of postpartum CKD:(1)Microalbuminuria12 studies evaluated the postpartum urinary microalbumin in women with or without HDP history,and the results showed that the risk of microalbuminuria in HDP women was higher than those with normal pregnancy(OR=2.16,95%CI:1.45—3.22,P<0.001).(2)ESRD Only 4 studies evaluated the risk of ESRD after delivery when women with HDP.The risk of ESRD at the end of follow-up is higher than control(RR:4.26,95%CI:1.48—12.30,P<0.001).Two studies evaluated the adjusted RR or HR for ESRD.The risk of ESRD still higher than women without HDP after adjusted some confounding factors.(2)Glomerular filtration rate(e GFR)level of follow-up end point e GFR at the end of follow-up was assessed in 15 studies,with an average follow-up time of 10.96 years.Results showed no significant difference in e GFR/CCr levels between the HDP group and control group(WMD-2.03 ml/min/1.75m2,95%CI:-4.37—0.31,P=0.101).Subgroup analysis showed that HDP patients with higher systolic blood pressure(SBP)levels at the end point of follow-up,longer follow-up period showed lower e GFR/CCr levels than control group. (3)Serum creatinine(s Cr)level of follow-up end point The s Cr level of follow-up end point was assessed in 8 studies,with an average follow-up time of 9.16 years.Results showed no significant difference in s Cr level between HDP group and control group(WMD 0.74umol/l,95%CI:-0.60 —2.09,P=0.280).Conclusion:The risk of adverse pregnancy complications such as PE,preterm delivery,cesarean section,SGA,LBW and pregnancy failure in patients with CKD is higher than those women without CKD,and the risk is associated with a variety of influencing factors,including the age of women at pregnancy,primary causes of CKD,basic proteinuria level before pregnancy and basic renal function.Pregnancy,however,was not risk factor for CKD progression,and there was no statistically significant difference between the incidence of ESRD and creatinine multiplication,or between the e GFR/CCr and s Cr levels at the end of follow-up compared women without CKD.Compared with normal pregnant women,HDP women have an increased risk of postpartum microalbuminuria and ESRD,and the risk of renal function delining were partly casused by higher SBp after delivery.But further studies are needed to confirm whether the risk of renal loss is increased.