Rossella Attini

Pregnancy in dialysis patients: is the evidence strong enough to lead us to change our counseling policy?

BACKGROUND AND OBJECTIVES Although successful pregnancy is rare, results attained with higher dialysis efficiency and the spread of dialysis to different cultural and religious settings are changing the panorama. In this study, we systematically review the recent literature (2000 through 2008) on pregnancy in dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Medline on OVID was searched in November 2008, with MESH and free terms on pregnancy and chronic kidney disease or dialysis; limits were human subjects and English-language articles. Case reports were excluded to minimize publication bias. The final selection and extraction of data were performed in duplicate. RESULTS From 2840 references, 241 full-text articles were retrieved; eight fulfilled the selection criteria, and two were added from reference lists. In the 10 studies (nine of 10 monocentric), 90 pregnancies were observed in 78 patients (range of cases five to 15). The studies were heterogeneous for definition of outcomes, duration (2 to 16 yr), period (1988 through 1998 to 2000 through 2006), age (25 to 35 yr), and support and dialysis therapy. Daily dialysis was frequently used; type of treatment, membranes, and flows varied widely. Hypertension and anemia were frequent concerns for the mothers. Intrauterine deaths, hydramnios, and small-for-gestational-age or preterm infants were frequent. The possibility of a healthy offspring ranged from 50 to 100% (overall 76.25%). CONCLUSIONS Evidence on pregnancy in dialysis is heterogeneous; however, the growing number of reports worldwide and the improving results suggest that we should reconsider our counseling policy, which only rarely includes pregnancy in dialysis patients.

Chronic kidney disease may be differentially diagnosed from preeclampsia by serum biomarkers

Preeclampsia, affecting 5-8% of pregnancies, is the main cause of fetal-maternal mortality and morbidity. The differential diagnosis with chronic kidney disease (CKD) is a challenge owing to the overlapping clinical features. No biomarker has been found to discriminate between the two conditions. Here, we tested whether maternal serum levels of placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1), markers of preeclampsia, could be used to discriminate between 34 patients with preeclampsia, 23 patients with CKD during pregnancy, and 38 healthy pregnant women. Serum levels of PlGF and sFlt-1 were determined during the third trimester by commercially available immunoassays. In preeclampsia, sFlt-1 levels were significantly increased in comparison with that in CKD and in the control women. Serum levels of PlGF in preeclampsia were significantly decreased relative to both controls and patients with CKD. The sFlt-1 to PlGF ratio was significantly increased in preeclampsia (median 436) compared with controls (median 9.4) and CKD (median 4.0). No differences were found between controls and patients with CKD. Thus, our study suggests that it is possible to discriminate between preeclampsia and CKD during pregnancy by determining maternal serum levels of sFlt-1 and PlGF and their ratio.

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.

Kidney biopsy in pregnancy: evidence for counselling? A systematic narrative review

Kidney diseases, which have a prevalence of 3% in women of childbearing age, are increasingly encountered in pregnancy. Glomerulonephritis may develop or flare up in pregnancy, and a differential diagnosis with pre‐eclampsia may be impossible on clinical grounds. Use of kidney biopsy is controversial, but a systematic review has not been carried out to date.

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.

Vegan–vegetarian diets in pregnancy: danger or panacea? A systematic narrative review

Although vegan–vegetarian diets are increasingly popular, no recent systematic reviews on vegan–vegetarian diets in pregnancy exist.

A best practice position statement on the role of the nephrologist in the prevention and follow-up of preeclampsia: the Italian study group on kidney and pregnancy

Preeclampsia (PE) is a protean syndrome causing a transitory kidney disease, characterised by hypertension and proteinuria, ultimately reversible after delivery. Its prevalence is variously estimated, from 3 to 5% to 10% if all the related disorders, including also pregnancy-induced hypertension (PIH) and HELLP syndrome (haemolysis, increase in liver enzyme, low platelets) are included. Both nephrologists and obstetricians are involved in the management of the disease, according to different protocols, and the clinical management, as well as the role for each specialty, differs worldwide. The increased awareness of the role of chronic kidney disease in pregnancy, complicating up to 3% of pregnancies, and the knowledge that PE is associated with an increased risk for development of CKD later in life have recently increased the interest and redesigned the role of the nephrologists in this context. However, while the heterogeneous definitions of PE, its recent reclassification, an emerging role for biochemical biomarkers, the growing body of epidemiological data and the new potential therapeutic interventions lead to counsel long-term follow-up, the lack of resources for chronic patients and the increasing costs of care limit the potential for preventive actions, and suggest tailoring specific interventional strategies. The aim of the present position statement of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology is to review the literature and to try to identify theoretical and pragmatic bases for an agreed management of PE in the nephrological setting, with particular attention to the prevention of the syndrome (recurrent PE, presence of baseline CKD) and to the organization of the postpartum follow-up.

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.

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.