Marilisa Biolcati

Pregnancy in CKD: whom should we follow and why?

BACKGROUND Chronic kidney disease (CKD) has a high prevalence in pregnancy. In a period of cost constraints, there is the need for identification of the risk pattern and for follow-up. METHODS Patients were staged according to K-DOQI guidelines. The analysis was prospective, January 2000-June 2011. Two hundred and forty-nine pregnancies were observed in 225 CKD patients; 176 singleton deliveries were recorded. The largest group encompasses stage 1 CKD patients, with normal renal function, in which 127 singleton deliveries were recorded. No hard outcomes occurred (death; dialysis); therefore, surrogate outcomes were analysed [caesarean section, prematurity, need for neonatal intensive care unit (NICU)]. Stage 1 patients were compared with normal controls (267 low-risk pregnancies followed in the same setting) and with patients with CKD stages 2-4 (49 singleton deliveries); two referral patterns were also analysed (known diagnoses; new diagnoses). RESULTS The risk for adverse pregnancy rises significantly in stage 1 CKD, when compared with controls: odds ratios were caesarean section 2.73 (1.72-4.33); preterm delivery 8.50 (4.11-17.57); NICU 16.10 (4.42-58.66). The risks rise in later stages. There is a high prevalence of new CKD diagnosis (overall: 38.6%; stage 1: 43.3%); no significant outcome difference was found across the referral patterns. Hypertension and proteinuria are confirmed as independent risk factors. CONCLUSIONS CKD is a risk factor in pregnancy; all patients should be followed within dedicated programmes from stage 1. There is need for dedicated interventions and educational programmes for maximizing the diagnostic and therapeutic potentials in early CKD stages.

IVF twins have similar obstetric and neonatal outcome as spontaneously conceived twins: a prospective follow-up study

Studies comparing the outcome of spontaneous versus IVF twin pregnancies report heterogeneous results. This may depend on differences in the studied populations and/or in the management approach to twin pregnancy. The aim of the present study was to compare both maternal and perinatal outcomes in dichorionic diamniotic twin pregnancies who where spontaneously conceived or originated by successful homologous IVF. In order to get homogeneous observations, monochorionic twin pregnancies and triplet pregnancies were excluded. Moreover, to avoid any possible bias deriving from differences in the obstetric management, all pregnancies were managed by the same team applying fixed obstetric protocols. The study included 223 twin pregnancies, 84 conceived by IVF and 139 spontaneously conceived. Overall, maternal and perinatal outcomes were similar in the two groups: no significant differences were observed as far as gestational age at delivery, birthweight, perinatal morbidity and mortality, and rate of malformations were concerned. The rate of Caesarean section was slightly, but not significantly, higher in IVF pregnancies. In conclusion, the outcome of IVF twin pregnancies is comparable to that of spontaneously conceived twin pregnancies, provided that the same management criteria are applied.

Accuracy of the umbilical arteries Doppler flow velocity waveforms in detecting adverse perinatal outcomes in a high-risk population

Objective. To define the accuracy of the umbilical artery Doppler flow velocity waveforms, according to different cut‐off values, in predicting adverse perinatal outcomes among fetuses at high risk of hypoxic complications.

Pregnancy in chronic kidney disease: need for a common language.

INTRODUCTION Chronic kidney disease (CKD) is a growing health care problem, affecting 3% of women of childbearing age. AIM This study attempted to systematically review the literature for 2000-2009 on pregnancy in CKD, as a guide for counseling. METHODS Data sources included a Medline search for 2000-2009, employing MESH and free terms on pregnancy and CKD, limited to humans and English-language publications. Only studies observing at least 25 pregnancies were considered. The bibliographic search, abstract screening and data extraction were performed in duplicate. Out of over 3,000 references and 276 full texts, 23 studies fulfilled the selection criteria; 3 were added from references. RESULTS The 26 studies reported on over 2,000 pregnancies. Five main categories were identified: CKD (399 pregnancies, excluding 2 population studies), lupus nephropathy (431 pregnancies), diabetic nephropathy (386 pregnancies), hematuria (310 pregnancies), kidney donors (586 pregnancies) and other. Definitions of diseases, outcomes and stratifications were nonhomogeneous, thus impairing meta-analytic pooling and quantification of the risks. Within these limits, 3 major qualitative determinants of outcome were confirmed as relevant in all subsets: CKD stage, hypertension and proteinuria. Their combination may multiply the interrelated major risks (for the mother: preeclampsia, renal function impairment and proteinuria; for the offspring: small babies, prematurity, death). Specifically, mothers with lupus nephritis have a relevant risk of death (1.15%), and share with diabetic nephropathy, the risk for perinatal death (up to 23% in lupus, 10% in diabetes). Malformations were not increased, except for urinary tract malformation in reflux nephropathy. CONCLUSIONS There is a strong need to unify definitions and stratifications to allow quantitative evidence-based counseling for pregnant patients with CKD.

Fetal heart rate tracings : observers versus computer assessment

UNLABELLED Cardiotocography (CTG) is widely used despite the fact that its diagnostic accuracy is far from satisfying. This is due, among other reasons, to the great intra- and interobserver variation in reading the fetal heart rate tracings. Computerized analysis might be a means to overcome the latter problem. OBJECTIVE the present study was designed to assess the reproducibility of CTG readings among observers and between observers and a computer system. STUDY DESIGN 63 fetal heart rate tracings were read by 4 clinicians (2 experienced and 2 inexperienced) and by the 2CTG computerized system. The variables considered were: baseline fetal heart rate (FHR), long-term variability (amplitude bandwidth around the baseline), number of large accelerations and number and type of decelerations. RESULTS the agreement among observers, assessed by means of kappa coefficient, ranges from fair to good. The agreement between each of the observers and the computer readings, ranges from 0.18 to 0.48 for FHR baseline, from 0.16 to 0.74 for variability, from 0.37 to 0.64 for the number of accelerations and from 0.41 to 0.54 for the number of decelerations. The agreement on the type of decelerations is very low (0.01-0.25). CONCLUSION it is concluded that interobserver variability between experienced observers, inexperienced observers and 2CTG is considerable and that the use of a computer system should overcome this problem.

Association of Low-Protein Supplemented Diets with Fetal Growth in Pregnant Women with CKD

BACKGROUND AND OBJECTIVES Women affected by CKD increasingly choose to get pregnant. Experience with low-protein diets is limited. The aim of this study was to review results obtained from pregnant women with CKD on supplemented vegan-vegetarian low-protein diets. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a single-arm, open intervention study between 2000-2012 of a low-protein diet in pregnant patients with stages 3-5 CKD or severe proteinuria (>1 g/d in the first trimester or nephrotic at any time). Stages 3-5 CKD patients who were not on low-protein diets for clinical, psychologic, or logistic reasons served as controls. The setting was the Obstetrics-Nephrology Unit dedicated to kidney diseases in pregnancy. The treated group included 24 pregnancies--21 singleton deliveries, 1 twin pregnancy, 1 abortion, and 1 miscarriage. Additionally, there were 21 controls (16 singleton deliveries, 5 miscarriages). The diet was a vegan-vegetarian low-protein diet (0.6-0.8 g/kg per day) with keto-acid supplementation and 1-3 protein-unrestricted meals allowed per week. RESULTS Treated patients and controls were comparable at baseline for median age (35 versus 34 years), referral week (7 versus 8), eGFR (59 versus 54 ml/min), and hypertension (43.5% versus 33.3%); median proteinuria was higher in patients on the low-protein diet (1.96 [0.1-6.3] versus 0.3 [0.1-2.0] g/d; P<0.001). No significant differences were observed in singletons with regard to gestational week (34 versus 36) or Caesarean sections (76.2% versus 50%). Kidney function at delivery was not different, but proteinuria was higher in the diet group. Incidence of small for gestational age babies was significantly lower in the diet group (3/21) versus controls (7/16; chi-squared test; P=0.05). Throughout follow-up (6 months to 10 years), hospitalization rates and prevalence of children below the third percentile were similar in both groups. CONCLUSION Vegan-vegetarian supplemented low-protein diets in pregnant women with stages 3-5 CKD may reduce the likelihood of small for gestational age babies without detrimental effects on kidney function or proteinuria in the mother.

Outcomes of Pregnancies after Kidney Transplantation: Lessons Learned from CKD. A Comparison of Transplanted, Nontransplanted Chronic Kidney Disease Patients and Low-Risk Pregnancies: A Multicenter Nationwide Analysis

Background Kidney transplantation (KT) may restore fertility in chronic kidney disease (CKD). The reasons why maternofetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling. Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of nontransplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. Methods We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD, and 1418 low-risk controls recruited in 2 large Italian Units in the same period (2000-2014). The following outcomes were considered: maternal and fetal death; malformations; preterm delivery; small for gestational age (SGA) baby; need for the neonatal intensive care unit; doubling of serum creatinine or increase in CKD stage. Data were analyzed according to kidney diseases, renal function (staging according to CKD-epidemiology collaboration), hypertension, maternal age, parity, ethnicity. Results Maternofetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. Kidney transplantation patients with estimated glomerular filtration rate greater than 90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases (“progressive CKD”) are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 vs 1: relative risk 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. Conclusions The maternofetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney disease.

Nucleated Red Blood Cells in Term Fetuses: Reference Values Using an Automated Analyzer

Background: Nucleated red blood cells (NRBCs) are present in small numbers in the cord blood of healthy fetuses at birth. Acute and chronic stimuli, such as fetal hypoxia, cause increased circulating levels of NRBCs. Manual counting is presently the only way to quantify NRBCs, but it is time-consuming and inaccurate. Recently, automated approaches have been developed in order to quantify NRBCs. Objectives: Our aim was to compare manual vs. automated NRBC counting and derive reference values in umbilical cord blood samples from healthy term fetuses. Methods: We analyzed blood samples from 131 healthy term fetuses by the automated approach and calculated reference values of NRBC counts as percentiles. To compare automated NRBC count with manual count we obtained umbilical cord blood samples from 50 further fetuses. Results: Significant positive correlation was obtained between the two methods (r2 = 0.988, Bland-Altman plot mean difference NRBCs/100 WBC: –0.590). The median for NRBCs/100 WBC was 3.05 (range 0–11.6) and the median for absolute NRBC counts ×109/l was 0.39 (range 0–1.8). Conclusions: We demonstrate that values obtained with the automated NRBC counting method are comparable to those obtained with the microscopic manual evaluation and give reference values for umbilical cord NRBCs at term that can be used in clinical practice.

Is It Possible to Differentiate Chronic Kidney Disease and Preeclampsia by means of New and Old Biomarkers? A Prospective Study

Objective. Chronic kidney disease (CKD) and preeclampsia (PE) may both present with hypertension and proteinuria in pregnancy. Our objective is to test the possibility of distinguishing CKD from PE by means of uteroplacental flows and maternal circulating sFlt-1/PlGF ratio. Design. Prospective analysis. Population. Seventy-six patients (35 CKD, 24 PE, and 17 other hypertensive disorders), with at least one sFlt-1/PlGF and Doppler evaluation after the 20th gestational week. Methods. Maternal sFlt-1-PlGF were determined by immunoassays. Abnormal uterine artery Doppler was defined as resistance index ≥ 0.58. Umbilical Doppler was defined with gestational-age-adjusted Pulsatility Index. Clinical diagnosis was considered as reference. Performance of Doppler study was assessed by sensitivity analysis; sFlt-1/PlGF cut-off values were determined by ROC curves. Results. The lowest sFlt-1/PlGF ratio (8.29) was detected in CKD, the highest in PE (317.32) (P < 0.001). Uteroplacental flows were mostly preserved in CKD patients in contrast to PE (P < 0.001). ROC analysis suggested two cut-points: sFlt-1/PlGF ≥ 32.81 (sensitivity 82.93%; specificity 91.43%) and sFlt-1/PlGF ≥ 78.75 (sensitivity 62.89%, specificity 97.14%). Specificity reached 100% at sFlt-1/PlGF ≥ 142.21 (sensitivity: 48.8%). Early-preterm delivery was associated with higher sFlt-1/PlGF ratio and abnormal uteroplacental flows relative to late-preterm and term deliveries. Conclusions. sFlt-1/PlGF ratio and uteroplacental flows significantly correlated with PE or CKD and preterm delivery.

Is renal hyperfiltration protective in chronic kidney disease-stage 1 pregnancies? A step forward unravelling the mystery of the effect of stage 1 chronic kidney disease on pregnancy outcomes

The correlation between advanced or proteinuric chronic kidney disease (CKD) and adverse pregnancy outcomes is intuitive, although how early CKD affects pregnancy remains unknown. Glomerular hyperfiltration is a physiological response to pregnancy, correlated with outcomes in hypertension or collagen diseases. The aim of the study was to correlate first trimester hyperfiltration with pregnancy outcomes in stage 1 CKD patients.