Gianfranca Cabiddu

Pregnancy in women with pre-existing lupus nephritis: Predictors of fetal and maternal outcome

BACKGROUND Only few data are available on pregnancy in patients with lupus nephritis (LN) diagnosed before conception. The aim of this study was to identify the risk factors for complicated pregnancy in women with pre-existing LN. METHODS In a multicentre study, we collected data on 113 pregnancies occurring in 81 women with pre-existing biopsy-proven LN. Primary outcomes were fetal loss including perinatal death and renal flares during and 12 months after pregnancy. Univariate and logistic regression analyses were used to identify predictors of outcomes. RESULTS Renal biopsy performed 7.2 +/- 4.9 years before pregnancy showed the following WHO classes: 6 patients in II, 8 in III, 48 in IV and 19 in V. At conception, most patients were in complete (49%) or partial (27%) remission. There were nine spontaneous abortions, one stillbirth and five neonatal deaths. Thirty-one deliveries were preterm. Birth weight was <2500 g in 34 newborns. During pregnancy or after delivery, there were 34 renal flares, most of which (20) were reversible. Three patients had a progressive decline of glomerular filtration rate (one on dialysis). At logistic regression analysis, the pregnancy outcome was predicted by hypocomplementaemia at conception (RR 19.02; 90% CI 4.58-78.96) and aspirin during pregnancy (RR 0.11; 90% CI 0.03-0.38). Renal flare was predicted by renal status (partial remission RR 3.0; 90% CI 1.23-7.34, nonremission RR 9.0; 90% CI 3.59-22.57). CONCLUSIONS Pregnancy can be successful in most women with pre-existing LN, even for those with a severe renal involvement at onset. Renal flares during and after pregnancy are not uncommon and can be predicted by renal status assessed before pregnancy. Normocomplementaemia and low-dose aspirin therapy during pregnancy are independent predictors of a favourable fetal outcome.

Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study

Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal complications.

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.

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.

Type 1 Diabetes, Diabetic Nephropathy, and Pregnancy: A Systematic Review and Meta-Study

BACKGROUND In the last decade, significant improvements have been achieved in maternal-fetal and diabetic care which make pregnancy possible in an increasing number of type 1 diabetic women with end-organ damage. Optimal counseling is important to make the advancements available to the relevant patients and to ensure the safety of mother and child. A systematic review will help to provide a survey of the available methods and to promote optimal counseling. OBJECTIVES To review the literature on diabetic nephropathy and pregnancy in type 1 diabetes. METHODS Medline, Embase, and the Cochrane Library were scanned in November 2012 (MESH, Emtree, and free terms on pregnancy and diabetic nephropathy). Studies were selected that report on pregnancy outcomes in type 1 diabetic patients with diabetic nephropathy in 1980-2012 (i.e. since the detection of microalbuminuria). Case reports with less than 5 cases and reports on kidney grafts were excluded. Paper selection and data extraction were performed in duplicate and matched for consistency. As the relevant reports were highly heterogeneous, we decided to perform a narrative review, with discussions oriented towards the period of publication. RESULTS Of the 1058 references considered, 34 fulfilled the selection criteria, and one was added from reference lists. The number of cases considered in the reports, which generally involved single-center studies, ranged from 5 to 311. The following issues were significant: (i) the evidence is scattered over many reports of differing format and involving small series (only 2 included over 100 patients), (ii) definitions are non-homogeneous, (iii) risks for pregnancy-related adverse events are increased (preterm delivery, caesarean section, perinatal death, and stillbirth) and do not substantially change over time, except for stillbirth (from over 10% to about 5%), (iv) the increase in risks with nephropathy progression needs confirmation in large homogeneous series, (v) the newly reported increase in malformations in diabetic nephropathy underlines the need for further studies. CONCLUSIONS The heterogeneous evidence from studies on diabetic nephropathy in pregnancy emphasizes the need for further perspective studies on this issue.

Old and new perspectives on peritoneal dialysis in Italy emerging from the Peritoneal Dialysis Study Group Census.

♦ Background: To understand how peritoneal dialysis (PD) was being used in Italy in 2005 and 2008, a census of all centers was carried out. ♦ Methods: In 2005 and 2008, data were collected from, respectively, 222 and 223 centers, with respect to 4432 and 4094 prevalent patients. ♦ Results: In the two periods, the PD incidence remained stable (24.3% vs 22.9%), varying from center to center. Continuous ambulatory PD (CAPD) was the main initial method (55%), but APD was more widespread among prevalent patients (53%). Among patients returning to dialysis from transplantation (Tx), PD was used in 10%. The use of incremental CAPD increased significantly from 2005 to 2008, in terms both of the number of centers (27.0% vs 40.9%) and of patients (13.6% vs 25.7%). Late referrals remained stable at 28%, with less use of PD. The overall drop-out rate (episodes/100 patient-years) remained unchanged (31.0 vs 32.8), with 13.1 and 12.9 being the result of death, and 11.8 and 12.4 being the result of a switch to hemodialysis, mainly after peritonitis. A dialysis partner was required by 21.8% of the PD patients. The incidence of peritonitis was 1 episode in 36.5 and 41.1 patient-months, with negative cultures occurring in 17.1% of cases in both periods. The incidence of encapsulating peritoneal sclerosis (episodes/100 patient-years) was 0.70, representing 1.26% of patients treated. The catheter types used and the sites and methods of insertion varied widely from center to center. ♦ Conclusions: These censuses confirm the good results of PD in Italy, and provide insight into little-known aspects such as the use of incremental PD, the presence of a dialysis partner, and the incidence of encapsulating peritoneal sclerosis.

Controversial issues in CKD clinical practice: position statement of the CKD-treatment working group of the Italian Society of Nephrology

This position paper of the study group “Conservative treatment of Chronic Kidney Disease—CKD” of the Italian Society of Nephrology addresses major practical, unresolved, issues related to the conservative treatment of chronic renal disease. Specifically, controversial topics from everyday clinical nephrology practice which cannot find a clear, definitive answer in the current literature or in nephrology guidelines are discussed. The paper reports the point of view of the study group. Concise and practical advice is given on several common issues: renal biopsy in diabetes; dual blockade of the renin–angiotensin–aldosterone system (RAAS); management of iron deficiency; low protein diet; dietary salt intake; bicarbonate supplementation; treatment of obesity; the choice of conservative therapy vs. dialysis. For each topic synthetic statements, guideline-style, are reported.

Compliance, illiteracy and low-protein diet: multiple challenges in CKD and a case of self-empowerment

BackgroundLow-protein diets (LPD) are an important means of delaying the need for dialysis and attaining a stable metabolic balance in chronic kidney disease (CKD). Many authors consider a low educational level and illiteracy to be adverse features for a good dietary compliance.Case presentationWe report the case of a 77-year old woman, illiterate, affected by advanced CKD (stage 4 according to KDIGO guidelines). She was initially ashamed of her problem and did not declare it, leading to an overzealous reduction in protein intake. However, with her daughter’s help, who translated the dietary prescription into images, she overcame the barrier represented by illiteracy and was able to correctly follow the prescriptions, attaining good kidney function stability and preserving an adequate nutritional status.ConclusionsThe case underlines the importance of a personalized approach to dietary prescriptions and suggests that it is possible to achieve a good compliance to the dietary treatment of CKD also in patients with relevant cultural barriers.

Pregnancy and kidney disease: from medicine based on exceptions to exceptional medicine

The Webster dictionary defines exception as an anomaly, a person or thing that does not follow a rule, while the adjective exceptional has a different nuance, and means “above average”. These two words may describe how obstetric nephrology has shifted from the description of very rare cases, to the development of a complex new and fascinating branch of medicine, that counterbalances obstetricians’ usually optimistic outlook by focusing on subtle challenges posed by chronic diseases, and mitigate the frequently grim approach of nephrologists, with a message of hope: women with kidney disease can have the same basic life goals as healthy women their age. Although studies relating to kidney disease in pregnancy are being published more frequently, not all questions have been considered or answered, and clinicians are often challenged by a lack of detailed information and practical guidelines. Thus in this complex, difficult, but also fascinating and evolving panorama, the Journal of Nephrology is publishing a issue dedicated to obstetric nephrology, in an attempt to contribute to the development of this field, with the specific aim of offering practical insights and critical contributions capable of helping clinicians in the management of these “exceptional exceptions”.

Incremental start to PD as experienced in Italy: results of censuses carried out from 2005 to 2014

BackgroundIt is not known how widely used in Italy an incremental start to in peritoneal dialysis (Incr-PD) is.MethodsBy analyzing the peritoneal dialysis (PD) censuses conducted by the PD Study Group (GSDP-SIN) for the years 2005, 2008, 2010, 2012 and 2014 in all the Centers performing PD in Italy, the use of Incr-PD, i.e. continuous ambulatory peritoneal dialysis (CAPD) with 1 or 2 exchanges/day or automated peritoneal dialysis (APD) with 3–4 sessions/week, was examined among incident PD patients.ResultsIn 2014 PD was started in Italy by 1,652 patients, 455 (27.5%) of whom incrementally (Incr-CAPD 82.2% vs. Incr-APD 17.8%). Incr-PD was used in 53.5% of the 225 Centers. The number of patients and of Centers using Incr-DP increased constantly over the years up to 2012 (in 2005 Incr-PD was used in 33.4% of Centers, and in 11.9% of patients). The use of Incr-PD was greater in Centers with a more extensive PD program and greater use of PD in general. The most widely-used modality in Incr-PD was CAPD.ConclusionsIncr-PD is used in Italy in a large number of incident PD patients. The reasons for this increase need to be clarified, as current adequacy targets are based on full-dose studies with a very low glomerular filtration rate (GFR).