Marilisa Biolcati

Background Preeclampsia (PE) and chronic kidney disease (CKD) are linked by an only partially known cause-effect relationship. Knowledge on prevalence of CKD in PE patients is needed for evaluating the diagnostic yield of nephrology work-up after PE. Methods The study was undertaken in the Centre Hospitalier Le Mans (CHM), setting of tertiary level obstetric service (about 3500 deliveries/year). PE was identified on hospital’s discharge codes; after review, the study included 99 patients, 36 of which were also evaluated in Nephrology. A descriptive analysis was performed as appropriate. Logistic multiple regression tested the outcome “CKD diagnosis”; covariates that emerged as significant were selected; only singletons were included. Analysis was performed in SPSS. The ethics committee of the CHM approved the study. Results Prevalence of CKD was 14%; CKD was in stage 1 in 8/14 (57%); 5 patients were in stage 2 (36%), 1 in stage 3 (7%). CKD was known or acknowledged in 1 case only. Diagnoses included reflux nephropathy-other malformations (5 cases), kidney stones-chronic pyelonephritis (3), PKD (1), interstitial nephropathy (2), diabetic nephropathy (1), albuminuria in metabolic syndrome (2). At the logistic regression analysis, preterm delivery [OR 7.849 (1.667–36.968)] and a baby normal for gestational age [> 10th centile; OR 6.193 (1.400–27.394)] were significantly correlated with the diagnosis of CKD. Conclusions Within the limits of a single-center study, our data quantify CKD as common in PE women and suggest the presence of a “CKD phenotype” characterised by preterm delivery and adequate growth, implying that CKD is compatible with good placental function up to the last phase of pregnancy.

Background: Protein restriction may retard the need for renal replacement therapy; compliance is considered a barrier, especially in elderly patients. Methods: A feasibility study was conducted in a newly organized unit for advanced kidney disease; three diet options were offered: normalization of protein intake (0.8 g/kg/day of protein); moderate protein restriction (0.6 g/kg/day of protein) with a “traditional” mixed protein diet or with a “plant-based” diet supplemented with ketoacids. Patients with protein energy wasting (PEW), short life expectancy or who refused were excluded. Compliance was estimated by Maroni-Mitch formula and food diary. Results: In November 2017–July 2018, 131 patients started the program: median age 74 years (min–max 24-101), Charlson Index (CCI): 8 (min-max: 2–14); eGFR 24 mL/min (4–68); 50.4% were diabetic, BMI was ≥ 30 kg/m² in 40.4%. Normalization was the first step in 75 patients (57%, age 78 (24–101), CCI 8 (2–12), eGFR 24 mL/min (8–68)); moderately protein-restricted traditional diets were chosen by 24 (18%, age 74 (44–91), CCI 8 (4–14), eGFR 22 mL/min (5–40)), plant-based diets by 22 (17%, age 70 (34–89), CCI 6.5 (2–12), eGFR 15 mL/min (5–46)) (p < 0.001). Protein restriction was not undertaken in 10 patients with short life expectancy. In patients with ≥ 3 months of follow-up, median reduction of protein intake was from 1.2 to 0.8 g/kg/day (p < 0.001); nutritional parameters remained stable; albumin increased from 3.5 to 3.6 g/dL (p = 0.037); good compliance was found in 74%, regardless of diets. Over 1067 patient-months of follow-up, 9 patients died (CCI 10 (6–12)), 7 started dialysis (5 incremental). Conclusion: Protein restriction is feasible by an individualized, stepwise approach in an overall elderly, high-comorbidity population with a baseline high-protein diet and is compatible with stable nutritional status.

Background: IgA nephropathy is the most common primary glomerulonephritis in pregnancy and shares with other immunologic diseases and kidney diseases a relationship with adverse maternal outcomes, whose entity and pattern is only partially quantified. Recent studies provide new information and a systematic review regarded progression of kidney disease. The discussion of the outcomes with respect to low-risk pregnancies may help to perfect the estimation of the risks, and to identify specific research needs. Methods: A search strategy was built on Medline, EMBASE and the Cochrane review for the period January 2000–April 2017, aimed at retrieving both case series (defined as with at least 6 pregnancies in women with IgA nephropathy) and case reports, to look into rare occurrences. All papers, with or without control groups, were selected if they reported on at least one pregnancy outcome, or on long-term kidney function. Search strategy, paper selection and data extraction were done in duplicate (PROSPERO N 42016042623). Meta-analysis of case series was performed with Metanalyst Beta 3.13. Case reports were analysed narratively. Results: The search retrieved 556 papers, of which 27 were included (13 series and 14 case-reports). The case series report on 581 women with 729 pregnancies. The analysis was performed in comparison to the available control groups: 562 non-pregnant controls were available for the analysis of progression of kidney disease. As for pregnancy related outcomes (preeclampsia (PE), pregnancy induced hypertension (PIH), preterm birth, small babies), we meta-analyzed the data with respect to the only series of low-risk pregnancies (1418 pregnancies). When compared with women who never got pregnant after diagnosis of IgA nephropathy, in the present meta-analysis pregnancy in women with IgA nephropathy was not associated with a higher risk of progression of kidney disease, possibly due to the overall preserved kidney function at baseline: end-stage kidney disease (OR 0.68; CI 0.28–1.65). Conversely, the incidence of adverse pregnancy-related outcomes was increased compared to low-risk controls: PE and PIH were more than ten-fold increased (OR 11.80; CI 7.53–18.48 and OR 10.39; CI 5.45–19.80), while the increase in risk of preterm birth and “low birth weight babies” was less marked (OR 3.37; CI 1.91–5.95 and OR 2.36; CI 1.52–3.66), a discrepancy suggesting the occurrence of “late” or “maternal” PE, that may affect less severely foetal growth or shorten gestation. In conclusion, in the present meta-analysis IgA nephropathy was not associated with an increased progression of kidney disease. The more than ten-fold increased risk of PIH and PE, in combination with a doubled risk of small babies, suggests the occurrence of “late” or “maternal” PE, usually less affecting early foetal growth. This finding may be of help in defining control policies, while further research is needed to guide clinical management.

Choice of dialysis is context sensitive, explored for PD and extracorporeal dialysis, but less studied for haemodialysis (HD) and hemodiafiltration (HDF), both widely employed in Italy and France; reasons of choice and differences in prescriptions may impact on dialysis-related variables, particularly relevant in elderly, high-comorbidity patients. The study involved two high-comorbidity in-hospital cohorts, treated in Centers with similar characteristics, in Italy (Cagliari) and France (Le Mans). All patients (204) agreed to participate. Stable cases on thrice-weekly dialysis, with at least 2 months follow-up were selected (180 patients, Males 59.4%, median age 71 years, vintage 4.3 years, Charlson index 9). Univariate and multivariate correlations between baseline data, HD-HDF, dialysis efficiency and nutritional markers were assessed. In Le Mans HDF was mainly chosen to increase efficiency (large surface dialysers, high convective volume; 76.3% of the patients), in Cagliari to improve tolerance (smaller surfaces, lower convective volume; 59% of patients). Kt/V was similar in HD and HDF, and in both settings(median Kt/V Daugirdas 2: 1.6); in the setting of high efficiency no correlation was found between Kt/V, BMI, urea, creatinine, n-PCR and phosphate. The relationship between Kt/V and albumin was divergent: a weak consensual increase was present in Cagliari, a decrease in Le Mans, suggesting a role of albumin losses with high convective volumes. In the multivariate analysis, after adjustment for other covariates (including comorbidity and type of treatment) low albumin level < 3.5 g/dl was highly correlated with setting of study: Le Mans (OR: 7.155 (2.955–17.324)). The multivariate analysis confirmed a role of type of treatment, with higher risk of low albumin levels in HDF (OR: 3.592 (1.466–8.801)), and of comorbidity (Charlson index> = 7 (OR: 3.153 (1.311–7.582)), MIS index> = 7 (OR: 5.916 (2.457–14.241)). The different prescriptions of HD and HDF may have similar effects on dialysis efficiency, but diverging effects on crucial nutritional markers, such as albumin levels, probably more evident in high-comorbidity populations.

INTRODUCTION AND AIMS: Pregnancy is increasingly common in patients with advanced or intensely proteinuric CKD, posing ethical and pragmatic problems. Previous experiences with plant based diets showed better stabilisation of kidney function and proteinuria and equal or better foetal growth at delivery as compared with patients on unrestricted diet. No data were so far available on fetal growth during pregnancy. Aim of the study was to analyse foetal growth and Doppler indexes (uterine and umbilical arteries) in pregnant CKD patients followed-up in the same settings, who did or did not follow the study diet in pregnancy.

INTRODUCTION AND AIMS: Women with autosomal dominant polycystic kidney disease (ADPKD) display a vast array of disease severity in childbearing age, from fully asymptomatic (pregnancy may be the occasion for diagnosis) to different degrees of renal function impairment, hypertension and, more rarely proteinuria. While ADPKD has been considered as a risk factor for cyst complications in pregnancy, less is known on hypertensive disorders and preterm delivery. Our objective was to analyse the main pregnancy-related outcomes in ADPKD patients followed in the Gynaecology and Obstetrics Unit of the Sant’Anna Hospital, Città della Salute e della Scienza, University of Turin (Turin, Italy).

We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR. HMGB1, RAGE protein levels were assessed by western blot assay. Physiological term placental explants were treated by 0.5 U LMWH for 24 or 48 h. HMGB1 and RAGE expression and association were evaluated in LMWH explants by RAGE immunoprecipitation followed by HMGB1 immunoblot. HMGB1 spatial localization was evaluated by immuofluorescent staining (IF). HMGB1 expression was increased in PE relative to physiological placentae while RAGE was unvaried. 24 h LMWH treatment significantly up-regulated HMGB1 expression but inhibited HMGB1/RAGE complex formation in physiological explants. RAGE expression decreased in treated relative to untreated explants at 48 h. IF showed HMGB1 localization in both cytoplasm and nucleus of mesenchymal and endothelial cells but not in the trophoblast. IL-6 and TNFα gene expression were significantly increased at 24 h relative to controls, while they were significantly down-regulated in 48 h vs. 24 h LMWH explants. Our data depicted a new molecular mechanism through which LMWH exerts its anti-inflammatory effect on PE placentae, underlying the importance of HMGB1/RAGE axis in PE inflammatory response.

The aim of the present study is to test the hypothesis that Growth Restricted foetuses (FGR) have the tendency to develop more pathological cardiotocograpic tracings during labour than do appropriate for gestational age foetuses and that there is a shorter time lapse from the beginning of labour and the advent of a pathological cardiotocograpic tracing. The study was carried out at the Maternal-Foetal Medicine Unit of the Sant’Anna University Hospital, Turin, Italy. A total of 930 foetuses born at term between January and December 2012 were analysed: 355 small for gestational age (SGA) comprising both constitutional small for gestational age and growth restricted foetuses (cases group) and 575 Appropriate for Gestational Age (AGA) foetuses (control group). Tracings were evaluated independently by two obstetric consultants, according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. The main outcomes considered were the incidence of pathological cardiotocograpic tracings and the time interval between the beginning of labour and the advent of pathological cardiotocograpic tracing. The Student’s t-test, chi-square test and ANOVA were used for comparisons between cases and controls and amongst groups. Significance was set at <0.05. Univariate and multivariate odds-ratios were calculated. Foetuses with birthweight <3rd centile (growth restricted foetuses) more frequently presented pathological cardiotocograpic tracings in labour than did controls (43.8% vs. 21.6%; p < 0.001). Pathological cardiotocograpic tracing developed faster in the foetuses with birthweight <3rd centile group (53′, 0′-277′) than it did in the control group (170.5′, 0′-550′; p < 0.05). A higher induction rate was observed in the cases (29.6%) than in the control group (17%), with statistical significance p < 0.001. To correct for this possible confounding factor a multivariate logistic regression analysis was performed. It confirmed a statistically significant increased risk of pathological cardiotocographic tracings in the FGR group (OR 1.63; CI 1.30–2.05). The results confirm the hypothesis that Growth Restricted foetuses (FGR) have fewer oxygen reserves to deal with labour. Our results underscore the importance of the prenatal detection of these foetuses and of their continuous cardiotocographic monitoring during labour.

INTRODUCTION AND AIMS: Background: Reflux nephropathy is the one of the most common urinary tract malformation, and a substantial cause of morbidity in young patients, including women in childbearing age. The follow-up of patients without kidney insufficiency often occurs in a Urology setting. While some recent studies provide information on pregnancy-related outcomes, a systematic, meta-analytic review is not yet available and may help interpreting their heterogeneous results and improve information for counseling.