Prepregnancy Serum Creatinine Research Articles

Transplantation and Pregnancy

Transplantation is becoming increasingly widespread worldwide as a life-saving treatment for patients with end-stage organ failure. While the woman's quality of life improves rapidly after transplantation, the improvement of the endocrine system helps to regain fertility. The success of conception and successful pregnancy rates are quite low compared to the general population. Particular attention should be paid to obstetric complications such as hypertension, preeclampsia, fetal growth restriction, and preterm delivery during pregnancy. Ideally, preconception counseling should begin in the period before transplantation. Initiating contraception immediately after transplantation is ideal and long-acting reversible methods such as intrauterine devices and subcutaneous implants may be preferable. Factors that influence pregnancy outcomes in women undergoing organ transplantation include good general health within two years of transplantation, no evidence of organ rejection in the last year, stable graft conditions, absence of acute infections affecting the fetus, and adequate doses of immunosuppression drugs. However, factors that may adversely affect pregnancy include the etiology of the disease requiring transplantation, chronic allograft dysfunction, renal failure, cardiopulmonary diseases, hypertension, diabetes, obesity, and infections such as hepatitis B, hepatitis C, and Cytomegalovirus (CMV). Postponing pregnancy for at least 1 year after transplantation is very important to optimize pregnancy outcomes. Pregnancy in the early post-transplant period increases the risk of acute rejection, infection risk, and graft-related problems. In general, transplanted women can have successful pregnancies and live birth rates are above 70% on average. Although perinatal morbidity and mortality rates are high, most newborns are healthy and develop normally. Specific criteria such as pre-pregnancy serum creatinine levels and blood pressure control, as well as adherence to immunosuppressive therapy, significantly influence pregnancy success in transplant patients. In this review, optimizing pregnancy outcomes often involves addressing maternal and fetal risks, regular graft monitoring to detect potential complications such as organ rejection, and regulation of transplant medications to ensure safety and efficacy during pregnancy. Successful management relies on a multidisciplinary approach with contributions from obstetricians, neonatologists, nephrologists, hepatologists, and transplant surgeons.

Association Between Blunted Glomerular Hyperfiltration in Pregnancy and Severe Maternal Morbidity-A Research Letter.

Background:Glomerular hyperfiltration is one physiological adaptation to pregnancy, marked by a decline in serum creatinine (SCr) concentration by 16 weeks’ gestation. It is not known whether blunted glomerular hyperfiltration leads to adverse maternal outcomes, including severe maternal morbidity (SMM).Objective:To evaluate the association between blunted glomerular hyperfiltration and subsequent SMM or death.Design:Population-based cohort studySetting:Ontario, Canada, from 2008 to 2019.Participants:Included were births among women who had ≥ 1 SCr measured as an outpatient within 10 weeks before conception (“preconception”), and again, at 110/7 to 206/7 weeks’ gestation (“in-pregnancy”). Excluded were women who died before birth, who had end-stage renal disease or kidney transplantation before conception, or whose pre-pregnancy SCr was 125 μmol/L.Exposure:Net glomerular hyperfiltration defined as the preconception minus the in-pregnancy SCr.Measures:The primary study outcome was SMM or death arising from 23 weeks’ gestation up to 42 days after the index birth.Methods:Adjusted relative risks (aRRs) were calculated using Modified Poisson regression per 1-SD net blunting of glomerular hyperfiltration adjusting for important covariates.Results:A total of 10,323 births met all inclusion criteria. The mean (SD) SCr was 61.7 (11.0) μmol/L preconception, 48.0 (9.2) μmol/L in-pregnancy, and the mean net difference 13.6 (8.2) μmol/L. Among these births, the adjusted RR of SMM or death from 23 weeks’ gestation up to 42 days post-partum was 1.16 (95% confidence interval 1.14-1.30) per 1-SD (8.2 μmol/L) net blunting of glomerular hyperfiltration.Limitations:As SCr assessment is not a routine part of pregnancy care, its measurement could have been for a specific health condition thereby imparting selection bias.Conclusions:Blunted glomerular hyperfiltration in pregnancy may identify some women at higher risk of SMM. Further prospective research is needed about the implications of glomerular hyperfiltration in early pregnancy.

Prepregnancy renal function and risk of preterm birth and related outcomes.

Prepregnancy kidney dysfunction has been associated with preterm birth, which is the leading cause of neonatal morbidity and mortality; however, the relation is not well understood. We determined the risk of preterm birth in women with prepregnancy kidney dysfunction, defined using pregnancy-specific serum creatinine cut points. This population-based cohort study in the province of Ontario, Canada, involved women aged 16 to 50 years who had a singleton birth between 2006 and 2016 and measurement of serum creatinine within 10 weeks preceding their estimated conception date. The exposure was abnormally elevated prepregnancy serum creatinine, defined as greater than the 95th percentile (> 77 μmol/L), a value derived from a population-based sample of women without known kidney disease who became pregnant soon after the measurement was obtained. The main outcome was any preterm birth from 23 to 36 weeks' gestation. Secondary outcomes included provider-initiated preterm birth before 37 weeks' gestation and spontaneous preterm birth before 37 weeks. Among 55 946 pregnancies, preterm birth before 37 weeks' gestation occurred in 3956 women (7.1%). The risk of preterm birth before 37 weeks was higher among women with prepregnancy creatinine above the 95th percentile, relative to those with prepregnancy creatinine at or below the 95th percentile (9.1% v. 7.0%; adjusted relative risk [RR] 1.23, 95% confidence interval [CI] 1.09 to 1.38). The effect was significant for provider-initiated preterm birth (adjusted RR 1.30, 95% CI 1.11 to 1.52) but not for spontaneous preterm birth (adjusted RR 1.12, 95% CI 0.91 to 1.37). Given that prepregnancy kidney dysfunction conferred an increased risk of preterm birth, measurement of serum creatinine (a relatively inexpensive blood test) may form part of the assessment of risk for preterm birth among those planning pregnancy.

Risk of severe maternal morbidity or death in relation to elevated hemoglobin A1c preconception, and in early pregnancy: Apopulation-based cohort study.

BackgroundThe relation between prepregnancy average glucose concentration and a woman’s risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM).Methods and findingsA population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16–50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks’ gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14–1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13–1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07–1.14; p < 0.001) and without (1.15, 95% CI 1.02–1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11–1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04–1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06–1.62; p = 0.01) in those with a preconception A1c of 5.8%–6.4%, and 2.84 (95% CI 2.31–3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76–6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women.ConclusionsOur findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.

269. Impact of hypertension in pregnancy outcomes and graft function in kidney transplanted women

Introduction Hypertension, elevated serum creatinine and proteinuria are prepregnancy factors described in association with adverse pregnancy outcomes and graft dysfunction. Obstetric and neonatal complications include preeclampsia, gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), preterm delivery, cesarean section, low and very low birth weight (LBW/VLBW). Objective/hypothesis To evaluate obstetric, neonatal and graft outcomes in kidney transplanted women with prepregnancy hypertension. Methods Retrospective and comparative analyses of 41 pregnancies in 33 renal recipients followed in our department from 1989 to 2017. We considered two groups: women with prepregnancy hypertension (group 1) and women without prepregnancy hypertension (group 2 – control group). Statistical analysis was performed using IBM SPSS® Statistics v22 (p-value Results There were 13 (31.7%) pregnancies in group 1 and 28 (68.3%) in group 2. The mean maternal age, mean time between transplant and pregnancy and mean prepregnancy serum creatinine were similar in both groups. The incidence of GDM (25.0% vs 4.2%, p = 0.07), preeclampsia (16.7% vs 8.3%, p = 0.47), anemia (50.0% vs 20.8%, p = 0.08), IUGR (41.7% vs 12.5%, p = 0.05) and preterm delivery (66.7% vs 54.2%, p = 0.47) was higher in group 1. All cases of preeclampsia were diagnosed before 34 weeks in this group. Newborns with LBW (75.0% vs 45.8%, p = 0.09) and VLBW (33.3% vs 0.0%, p Discussion According to our results, prepregnancy hypertension is associated with worse obstetric and neonatal outcomes in pregnancies after kidney transplantation, although it seems to have no impact on graft function.

Pregnancy outcomes and impact of pregnancy on graft function in women after kidney transplantation.

Kidney transplantation facilitates pregnancy in women with end-stage kidney disease; however, the impact of pregnancy on short and longer-term graft function is uncertain. Obstetric, fetal, and graft outcomes for pregnancies from a large Australian transplant unit (1976-2015) were reviewed. There were 56 pregnancies in 35 women with mean age at conception 30.4±0.6years and mean transplant-pregnancy interval 5.5±0.5years. The live birth rate was 78.9%. Preterm birth (<37weeks) occurred in 56.5%. Hypertensive disorders affected 76% of women (pre-eclampsia in 30%). Median prepregnancy serum creatinine (SCr) was 100μmol/L (interquartile range (IQR), 80, 114μmol/L). One-third had deterioration in graft dysfunction during pregnancy; of these, 63.2% did not return to baseline. At 2years post-partum, median SCr was 96.4μmol/L (IQR, 81.5-124.3). Women with prepregnancy SCr>110μmol/L had increased risk of pre-eclampsia (OR 4.4; 95% CI 1.2-16.8; P=.03), but not preterm birth (OR 5.4; 95% CI 0.5-53; P=.04) or low birth-weight babies (OR 1.2; 95% CI 0.5-2.9; P=.04). Women with SCr>140μmol/L preconception had worst SCr trajectory, including higher rates of graft loss. Kidney transplantation pregnancies remain at high risk of obstetric complications, particularly pre-eclampsia. Prepregnancy graft function can be used to predict risk of adverse pregnancy outcomes and deterioration in graft function during and after delivery.

Pregnancy Outcomes after Clinical Recovery from AKI.

The effect of clinically recovered AKI (r-AKI) on future pregnancy outcomes is unknown. We retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General Hospital to assess whether a previous episode of r-AKI associated with subsequent adverse maternal and fetal outcomes, including preeclampsia. AKI was defined as rise in serum creatinine concentration to 1.5-fold above baseline. We compared pregnancy outcomes in women with r-AKI without history of CKD (eGFR>90 ml/min per 1.73 m2 before conception; n=105) with outcomes in women without kidney disease (controls; n=24,640). The r-AKI and control groups had similar prepregnancy serum creatinine measurements (0.70±0.20 versus 0.69±0.10 mg/dl; P=0.36). However, women with r-AKI had increased rates of preeclampsia compared with controls (23% versus 4%; P<0.001). Infants of women with r-AKI were born earlier than infants of controls (37.6±3.6 versus 39.2±2.2 weeks; P<0.001), with increased rates of small for gestational age births (15% versus 8%; P=0.03). After multivariate adjustment, r-AKI associated with increased risk for preeclampsia (adjusted odds ratio [aOR], 5.9; 95% confidence interval [95% CI], 3.6 to 9.7) and adverse fetal outcomes (aOR, 2.4; 95% CI, 1.6 to 3.7). When women with r-AKI and controls were matched 1:2 by age, race, body mass index, diastolic BP, parity, and diabetes status, r-AKI remained associated with preeclampsia (OR, 4.7; 95% CI, 2.1 to 10.1) and adverse fetal outcomes (OR, 2.1; 95% CI, 1.2 to 3.7). Thus, a past episode of AKI, despite return to normal renal function before pregnancy, associated with adverse outcomes in pregnancy.

Preeclampsia and ESRD: The Role of Shared Risk Factors

Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors. Population-based nested case-control study. The US Renal Data System was used to identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was matched to 2 controls based on year of birth (±1 year), age at first pregnancy (±2 years), and parity (±1 or≥4). Preeclamptic pregnancy, confirmed by medical record review. ESRD. Prepregnancy serum creatinine and urine protein measurements were recorded. Comorbid conditions existing prior to pregnancy were abstracted from medical records and included kidney disease, obesity, diabetes, and hypertension. There was evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases and 1 of 88 (<1%) controls. Per chart review, 8 of 44 (18%) cases versus 4 of 88 (5%) controls had preeclamptic pregnancies (unadjusted OR, 4.0; 95% CI, 1.21-13.28). Results were similar after independent adjustment for race, education, diabetes, and hypertension prior to pregnancy. However, the association was attenuated and no longer significant after adjustment for obesity (OR, 3.25; 95% CI, 0.93-11.37). The limited number of ESRD cases and missing data for prepregnancy kidney function. Our findings confirm that there is a sizable association between preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed.

Predictive factors for adverse pregnancy outcomes after renal transplantation

Several predictive factors associated with adverse pregnancy outcomes in female renal recipients have been suggested. Our study aimed to determine the most important factor for prediction of adverse pregnancy outcomes in female renal recipients. We studied 41 pregnancies in 29 female renal recipients retrospectively. We reviewed pregnancy outcomes and possible predictive factors including pre-pregnancy serum creatinine (SCr), pre-pregnancy glomerular filtration rate (GFR), pre-pregnancy hypertension, pre-pregnancy proteinuria, transplantation-pregnancy interval and type of immunosuppressants. We defined an adverse pregnancy-related outcomes index (APOI) that included the following conditions: (i) preeclampsia; (ii) fetal growth restriction (FGR); (iii) prematurity before 34 wk of gestation; (iv) fetal loss (v) graft dysfunction during pregnancy or within three months from delivery. The cutoff of pre-pregnancy serum creatinine and GFR was determined by receiver operating characteristics curves for the prediction of each adverse outcome and APOI. Only pre-pregnancy serum creatinine was associated with adverse pregnancy outcome, and 1 mg/dL was determined to be a useful cutoff for the prediction of each adverse outcomes. Pre-pregnancy SCr ≥ 1 mg/dL was associated with 7.7 times increased risk of preeclampsia and 6.9 times increased risk of APOI. Pre-pregnancy serum creatinine is the most powerful predictive factor for adverse pregnancy outcomes, and <1 mg/dL may be used as a screen for successful pregnancy outcome.

Parenthood Posttransplantation: 50 Years Later

Parenthood Posttransplantation: 50 Years Later

Pregnancy After Organ Transplantation: A Report From the U.K. Transplant Pregnancy Registry

Maternal and fetal complications in pregnancies after renal transplantation have been highlighted in several reports, but information on their main predisposing factors is limited. The U.K. Transplant Pregnancy Registry was established in 1997 to obtain detailed information on pregnancies in female organ transplant recipients across the U.K. For each female kidney, liver, or cardiothoracic organ transplant recipient who had had a recent pregnancy, data on maternal and fetal factors and pregnancy outcomes were collected using forms completed by their transplant follow-up and obstetric units. For kidney transplant recipients, the factors that influence pregnancy outcome were studied using logistic regression, and the effect of pregnancy on graft function was analyzed. There were live births in 83%, 69%, and 79% of pregnancies in cardiothoracic organ, liver, and kidney recipients, respectively. In 50% of live births from renal patients, delivery was preterm (<37 weeks), with 83% of the preterm infants delivered via caesarean. Preterm delivery was associated with maternal drug-treated hypertension and impaired renal function. A matched case-control study showed no evidence of increased renal allograft loss after pregnancy. A univariate survival analysis, however, suggested an association between drug-treated hypertension during pregnancy and poorer postpregnancy graft survival. In patients with prepregnancy serum creatinine (SCr) >150 micromol/L, a trend toward increased postpregnancy SCr was identified. Pregnancy is likely to end in a live birth in a majority of organ transplant recipients. In patients with greater prepregnancy SCr and/or drug-treated hypertension during pregnancy, however, subsequent renal function may be adversely affected.

Pregnancy in renal transplant recipients: the Royal Free Hospital experience.

For women with end-stage renal failure of child-bearing age, renal transplantation offers a chance to start a family. Pregnancies in renal transplant recipients involve risks for graft and fetus, and need to be carefully managed. To identify graft, fetal and maternal outcomes in our patients, and compare our results with those of the large national transplant registries. Retrospective case-note review. We assessed the outcomes of 48 pregnancies in 24 renal transplant recipients. Obstetric data and renal parameters were examined in 27-30 pregnancies that progressed to delivery. Mean time from transplantation to pregnancy was 6.5 years, with an unfavourable outcome in patients who conceived within 1 year. There was a 41% incidence of fetal growth restriction (FGR), and 33% of infants were small for gestational age. FGR was associated with maternal hypertension, a pre-pregnancy serum creatinine (SCr) >/= 133 micro mol/l (1.5 mg/dl), calcineurin inhibitors and the use of cardioselective beta blockers. Two patients with pre-pregnancy SCr > 200 micro mol/l lost their grafts within 3 years of delivery. A permanent significant decline in graft function occurred in 20%, by 6 months post delivery. FGR with SGA infants occurs frequently. Atenolol should be avoided in pregnancy and Metoprolol should not be combined with calcineurin inhibitors. Pregnancy appeared to have a deleterious effect on graft function in patients with SCr > 155 micro mol (1.75 mg/dl). Patients with pre-pregnancy SCr 200 micro mol/l are at greatest risk.

Outcome of pregnancy in patients with insulin-dependent diabetes mellitus and nephropathy with moderate renal impairment.

This study examines the effect of pregnancy on fetal outcome and maternal renal function in 17 women with Type 1 diabetes mellitus and nephropathy attending a joint diabetic-antenatal clinic between 1985 and 1993. There were 7 successful pregnancies in 6 women with moderate renal impairment, mean pre-pregnancy serum creatinine 165 mumol l-1 (Group 1), and 12 in 11 women with proteinuria and preserved renal function (Group 2). Median gestation of pregnancy was 31 + 3 weeks in Group 1 and 36 + 4 weeks in Group 2 (p < 0.05). All babies in Group 1 required neonatal intensive care for a median of 19 days (range 8-271) as compared to only 5 of 13 in Group 2 whose median stay was 13 (7-17) days (p < 0.05). There was one late death in Group 1. Longitudinal creatinine data in those with moderate renal impairment suggest no systematic adverse long-term effect of pregnancy on maternal renal function, although differing changes in renal function were observed during pregnancy. The generally favourable outcome achieved relied heavily upon neonatal care expertise.