Efficiency and nutritional parameters in an elderly high risk population on hemodialysis and hemodiafiltration in Italy and France: different treatments with similar names?

BACKGROUND: 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. METHODS: 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. RESULTS: 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)). CONCLUSIONS: 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.

Maternal outcomes in first and second trimester termination of pregnancy: which are the risk factors?

AIMS: To evaluate maternal complications of first trimester and second trimester termination of pregnancy (TOP) performed after first or second trimester positive prenatal diagnosis (PD). RESULTS: We performed a retrospective study from January 2007 to December 2011, on 844 patients, who underwent a TOP after positive amniocentesis or chorionic villus sampling (CVS) for foetal aneuploidies, performed for maternal age ≥35 years of age, positive prenatal screening (PS) or for genetic reasons. Exclusions criteria were gestational age >22+0 weeks, twin pregnancy and co-existing maternal pathologies. We compared maternal complications of first trimester and second trimester TOP and we established which risk factors were correlated to higher maternal complications (haemorrhages, transfusion, repeated uterine curettage and infections). Maternal complications were significantly higher in second trimester TOP. Previous uterine surgery is a significant risk factor for maternal complications in second trimester TOP, but not in first trimester TOP. Six uterine ruptures and three hysterectomies occurred, all in multiparous women with second trimester TOP. All uterine ruptures occurred in women with previous caesarean sections. CONCLUSIONS: First trimester TOP in women with risks factors for maternal complications guarantees better maternal outcomes and less health costs. Thus, in these women we should prefer a first trimester PS and PD.

Maternal-foetal outcomes in pregnant women with glomerulonephritides. Are all glomerulonephritides alike in pregnancy?

In spite of the interest for chronic renal diseases (CKD) in pregnancy data on specific diseases is fragmentary; while recent studies analysed the most common glomerulonephritides (GN), none was addressed at GN as a group. The aim of our study was to analyse the main pregnancy-related outcomes in GN patients in a large multicentre cohort. Patients with a diagnosis of GN were selected from the TOCOS cohort (TOCOS: TOrino Cagliari Observational Study): out of 714 singleton deliveries GN was the diagnosis in 126; lupus GN and IgA nephropathy accounted for 37 and 33 cases; 1418 low-risk singleton deliveries followed-up in the same Centers served as controls (non diabetic, non nephropathic, non obese women, without any other known chronic illness; pregnancies after ovodonation or in vitro fertilisation were excluded, if declared). Multiple regression analysis considered: pre-term (<37 weeks), early preterm delivery (<34 weeks), small for gestational age baby (SGA) and the development of hypertension, proteinuria and preeclampsia (PE) limiting this outcome to the cases without hypertension and proteinuria at baseline. The population consisted mainly of early CKD stages (stage 1: 61.9%; hypertension 27.8%; proteinuria <0.5 g/day: 55.7%). Age and parity were not different in cases and low-risk controls (age: 31.20 ± 5.5 vs 31.24 ± 5.5 years, primiparous 56.3% vs 57.5%). The incidence of preterm and early preterm delivery was higher in GN versus controls and increased commensurately with CKD stage. In the multivariate analysis, CKD stage was significantly associated with early preterm delivery and development-doubling of proteinuria (odds ratio (OR) around 3 in both), while the OR for baseline hypertension did not reach statistical significance. While the risk pattern did not differ in lupus and non-lupus GN, a significantly higher OR of PE was observed in IgA nephropathy (OR 28.09 versus other GN); risk for pre-term delivery was not increased (OR 0.27 (0.06-1.11)), thereby suggesting "late-maternal" PE. In conclusion, within the limits of heterogeneity and small numbers, our analysis identifies proteinuria as the most reliable risk marker for adverse pregnancy outcomes and suggests a specific association between IgA nephropathy and late-maternal PE.

Evidence of lower oxygen reserves during labour in the growth restricted human foetus: a retrospective study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

The HMGB1/RAGE Pro-Inflammatory Axis in the Human Placenta: Modulating Effect of Low Molecular Weight Heparin.

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.

Pregnancy outcomes after kidney graft in Italy: are the changes over time the result of different therapies or of different policies? A nationwide survey (1978-2013).

BACKGROUND: Kidney transplantation is the treatment of choice to restore fertility to women on renal replacement therapy. Over time, immunosuppressive, support therapies and approaches towards high-risk pregnancies have changed. The aim of this study was to analyse maternal-foetal outcomes in two cohorts of transplanted women who delivered a live-born baby in Italy in 1978-2013, dichotomized into delivery before and after January 2000. METHODS: A survey involving all the Italian transplant centres was carried out, gathering data on all pregnancies recorded since the start of activity at each centre; the estimated nationwide coverage was 75%. Data on cause of ESRD, dialysis, living/cadaveric transplantation, drug therapy, comorbidity, and the main maternal-foetal outcomes were recorded and reviewed. Data were compared with a low-risk cohort of pregnancies from two large Italian centres (2000-14; Torino and Cagliari Observational Study cohort). RESULTS: The database consists of 222 pregnancies with live-born babies after transplantation (83 before 2000 and 139 in 2000-13; 68 and 121 with baseline and birth data, respectively), and 1418 low-risk controls. The age of the patients significantly increased over time (1978-99: age 30.7 ± 3.7 versus 34.1 ± 3.7 in 2000-13; P < 0.001). Azathioprine, steroids and cyclosporine A were the main drugs employed in the first time period, while tacrolimus emerged in the second. The prevalence of early preterm babies increased from 13.4% in the first to 27.1% in the second period (P = 0.049), while late-preterm babies non-significantly decreased (38.8 versus 33.1%), thus leaving the prevalence of all preterm babies almost unchanged (52.2 and 60.2%; P = 0.372). Babies below the 5th percentile decreased over time (22.2 versus 9.6%; P = 0.036). In spite of high prematurity rates, no neonatal deaths occurred after 2000. The results in kidney transplant patients are significantly different from controls both considering all cases [preterm delivery: 57.3 versus 6.3%; early preterm: 22.2 versus 0.9%; small for gestational age (SGA): 14 versus 4.5%; P < 0.001] and considering only transplant patients with normal kidney function [preterm delivery: 35 versus 6.3%; early preterm: 10 versus 0.9%; SGA: 23.7 versus 4.5% (P < 0.001); risks increase across CKD stages]. Kidney function remained stable in most of the patients up to 6 months after delivery. Multiple regression analysis performed on the transplant cohort highlights a higher risk of preterm delivery in later CKD stages, an increase in preterm delivery and a decrease in SGA across periods. CONCLUSIONS: Pregnancy after transplantation has a higher risk of adverse outcomes compared with the general population. Over time, the incidence of SGA babies decreased while the incidence of 'early preterm' babies increased. Although acknowledging the differences in therapy (cyclosporine versus tacrolimus) and in maternal age (significantly increased), the decrease in SGA and the increase in prematurity may be explained by an obstetric policy favouring earlier delivery against the risk of foetal growth restriction.

Hypertension in CKD Pregnancy: a Question of Cause and Effect (Cause or Effect? This Is the Question).

Chronic kidney disease (CKD) is increasingly encountered in pregnancy, and hypertension is frequently concomitant. In pregnancy, the prevalence of CKD is estimated to be about 3%, while the prevalence of chronic hypertension is about 5-8%. The prevalence of hypertension and CKD in pregnancy is unknown. Both are independently related to adverse pregnancy outcomes, and the clinical picture merges with pregnancy-induced hypertension and preeclampsia. Precise risk quantification is not available, but risks linked to CKD stage, hypertension, and proteinuria are probably multiplicative, each at least doubling the rates of preterm and early preterm delivery, small for gestational age babies, and related outcomes. Differential diagnosis (based upon utero-placental flows, fetal growth, and supported by serum biomarkers) is important for clinical management. In the absence of guidelines for hypertension in CKD pregnancies, the ideal blood pressure goal has not been established; we support a tailored approach, depending on compliance, baseline control, and CKD stages, with strict blood pressure monitoring. The choice of antihypertensive drugs and the use of diuretics and of erythropoiesis-stimulating agents (ESAs) are still open questions which only future studies may clarify.

Vegan-vegetarian low-protein supplemented diets in pregnant CKD patients: fifteen years of experience.

BACKGROUND: Pregnancy in women with advanced CKD becoming increasingly common. However, experience with low-protein diets in CKD patients in pregnancy is still limited. Aim of this study is to review the results obtained over the last 15 years with moderately restricted low-protein diets in pregnant CKD women (combining: CKD stages 3-5, proteinuria: nephrotic at any time, or > =1 g/24 at start or referral; nephrotic in previous pregnancy). CKD patients on unrestricted diets were employed for comparison. STUDY PERIOD: January, 2000 to September, 2015: 36 on-diet pregnancies (31 singleton deliveries, 3 twin deliveries, 1 pregnancy termination, 1 miscarriage); 47 controls (42 singleton deliveries, 5 miscarriages). The diet is basically vegan; since occasional milk and yoghurt are allowed, we defined it vegan-vegetarian; protein intake (0.6-0.8 g/Kg/day), keto-acid supplementation, protein-unrestricted meals (1-3/week) are prescribed according to CKD stage and nutritional status. Statistical analysis was performed as implemented on SPSS. RESULTS: Patients and controls were similar (p: ns) at baseline with regard to age (33 vs 33.5), referral week (7 vs 9), kidney function (CKD 3-5: 48.4 % vs 64.3 %); prevalence of hypertension (51.6 % vs 40.5 %) and proteinuria >3 g/24 h (16.1 % vs 12.2 %). There were more diabetic nephropathies in on-diet patients (on diet: 31.0 % vs controls 5.3 %; p 0.007 (Fisher)) while lupus nephropathies were non-significantly higher in controls (on diet: 10.3 % vs controls 23.7 %; p 0.28 (Fisher)). The incidence of preterm delivery was similar (<37 weeks: on-diet singletons 77.4 %; controls: 71.4 %). The incidence of other adverse pregnancy related outcomes was non-significantly lower in on-diet patients (early preterm delivery: on diet: 32.3 % vs controls 35.7 %; birth-weight = <1.500 g: on diet: 9.7 % vs controls 23.8 %). None of the singletons in the on-diet series died, while two perinatal deaths occurred among the controls (p = 0.505). The incidence of small for gestational age (SGA <10th centile) and/or extremely preterm babies (<28th week) was significantly lower in singletons from on-diet mothers than in controls (on diet: 12.9 % vs controls: 33.3 %; p: 0.04 (Fisher)). CONCLUSION: Moderate protein restriction in the context of a vegan-vegetarian supplemented diet is confirmed as a safe option in the management of pregnant CKD patients.

Risk of Adverse Pregnancy Outcomes in Women with CKD.

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; "general" combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1% versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a "baseline risk" for adverse pregnancy-related outcomes linked to CKD.

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.

BACKGROUND: 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. METHODS: A historical prospective study was conducted on the database of our Unit, gathering all pregnant CKD patients referred since 1 January 2000. From 383 pregnancies referred in 2000-2013, 75 patients were selected (stage 1 CKD, referred within the 14th gestational week, singleton deliveries, absence of diabetes, hypertension or nephrotic proteinuria at referral, body mass index [BMI] < 30); 267 'low-risk' pregnancies, followed in the same setting, served as controls. Glomerular filtration rate (GFR) was assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and dichotomized at 120 mL/min. The odds for Caesarean section, prematurity, need for Neonatal Intensive Care Unit (NICU) were assessed by univariate analysis and logistic regression. RESULTS: Risk for adverse pregnancy outcomes was not affected by hyperfiltration (univariate OR GFR ≥ 120 mL/min: Caesarean section 1.30 (0.46-3.65); preterm delivery: 0.84 (0.25-2.80)). In contrast, even in these cases with normal kidney function, stage 1 CKD was associated with prematurity (17.3% vs 4.9% P = 0.001), lower birth weight (3027 ± 586 versus 3268 ± 500 P < 0.001) need for NICU (12% vs 1.1% P < 0.001). In the multivariate analysis, the risks were significantly increased by proteinuria and maternal age but not by GFR. CONCLUSIONS: In pregnant Stage 1 CKD patients, hyperfiltration was not associated with maternal-foetal outcomes, thus suggesting a need to focus attention on qualitative factors, eventually enhanced by age, as vascular stiffness, endothelial damage or oxidative stress.

Pre-eclampsia or chronic kidney disease? The flow hypothesis.

BACKGROUND: Chronic kidney disease (CKD) and pre-eclampsia (PE) occur in 3-5% of pregnancies. They often share hypertension and proteinuria and a differential diagnosis may be impossible. However, in PE, the pathogenesis is related to abnormal placentation, which can be detected by abnormal uterine and umbilical Doppler flow velocities, while in CKD, an intrinsic kidney disease is present. We hypothesize that Doppler studies can help to differentiate PE from CKD, as the flow velocities are altered in PE and normal in CKD. METHODS: We retrospectively selected patients who were followed in our Materno-Foetal Unit (2005-10) and had at least one flow measurement in our setting. CKD patients were included in the presence of proteinuria (≥ 300 mg/day) and hypertension, mimicking PE. The clinical charts were reviewed by the same operators; the clinical diagnoses were taken as reference. Three flow patterns were considered: alteration of both flow velocity waveforms (FVWs) (uterine and umbilical arteries), hypothesized as predictive of PE; normal FVWs at both levels, hypothesized as predictive of CKD; altered FVW in either artery, considered 'mixed'. Uterine FVWs were considered pathological according to the classical cut-point (RI > 0.58). Umbilical flows were evaluated according to standards adjusted for gestational age. Statistical analysis was performed in SPSS. RESULTS: The analysis included 61 cases. The presence of normal FVWs was significantly associated with the diagnosis of CKD (P = 0.0018). Conversely, the presence of both altered flows was significantly associated with PE (P = 0.0233). CONCLUSIONS: In the presence of proteinuria and hypertension, normal flows suggest CKD altered flows PE. Prospective studies are needed to refine this hypothesis based on the first Doppler criteria supporting the differential diagnosis between CKD and PE.

Vegetarian low-protein diets supplemented with keto analogues: a niche for the few or an option for many?

BACKGROUND: Low-protein diets are often mentioned but seldom used to slow chronic kidney disease (CKD) progression. The aim of the study was to investigate the potential for implementation of a simplified low-protein diet supplemented with alpha-keto analogues (LPD-KA) as part of the routine work-up in CKD patients. METHODS: In an implementation study (December 2007-November 2011), all patients with CKD Stages IV-V not on dialysis, rapidly progressive Stage III and/or refractory proteinuria, were offered either a simplified LPD-KA, or commercially available low-protein food. LPD-KA consisted of proteins 0.6 g/kg/day, supplementation with Ketosteril 1 pill/10 Kg, 1-3 free-choice meals/week and a simplified schema based on 'allowed' and 'forbidden' foods. 'Success' was defined as at least 6 months on LPD-KA. Progression was defined as reduction in glomerular filtration rate (GFR)[(Chronic Kidney Disease Epidemiology Collaboration) formula CKD-EPI] in patients with at least 6 months of follow-up. RESULTS: Of about 2500 patients referred (8% CKD Stages IV-V), 139 started LPD-KA; median age (70 years) and prevalence of comorbidity (79%) were in line with the dialysis population. Start of dialysis was the main reason for discontinuation (40 cases, unplanned in 7); clinical reasons were recorded in 7, personal preference in 14 and improvement and death in 8 each. The low gross mortality (4% per year) and the progression rate (from -8 to 0 mL/min/year at 6 months) are reassuring concerning safety. None of the baseline conditions, including age, educational level, comorbidity or kidney function, discriminated the patients who followed the diet for at least 6 months. CONCLUSIONS: Our data suggest a wider offer of LPD-KA to patients with severe and progressive CKD. The promising results in terms of mortality and progression need confirmation with different study designs.

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.

The clinical and imaging presentation of acute "non complicated" pyelonephritis: a new profile for an ancient disease.

BACKGROUND: Acute pyelonephritis (APN) is differently defined according to imaging or clinical criteria. In adults information on the relationship between imaging and clinical data is lacking.Our study was aimed at analysing the relationship between the clinical and imaging presentation of APN, defined according to imaging criteria (parenchymal involvement at MR or CT scan). METHODS: All consecutive patients hospitalized for "non-complicated" APN were considered (June 2005-December 2009). Clinical, biochemical and imaging data at hospitalization were analyzed by univariate and logistic regression analysis. RESULTS: There were 119 patients, all females, median age 32 years (15-72). At hospitalization, inflammatory markers were elevated (CRP median: 12.1 mg/dL, normal < 0.8). Incomplete presentations were frequent: fever was absent in 6.7%, pain in 17.8%, lower urinary tract symptoms in 52.9%. At CT or MR scan the lesions were bilateral in 12.6%, multiple in 79.8%; abscesses were present in 39.5%. Renal scars were found in 15.1%. Positive cultures were correlated with multiple foci (multivariate OR 4.2; CI 1.139-15.515). No other sign/symptom discriminated between small lesions, abscesses or multifocal involvement. CONCLUSIONS: APN is a protean disease. In the absence of strict correlation with clinical or biochemical markers, imaging studies are required to assess the severity of kidney involvement.

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.

Chronic kidney disease in preeclamptic patients: not found unless searched for-Is a nephrology evaluation useful after an episode of preeclampsia?

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.

Reflux nephropathy and the risk of preeclampsia and of other adverse pregnancy-related outcomes: a systematic review and meta-analysis of case series and reports in the new millennium.

BACKGROUND: Reflux nephropathy is a common urinary tract malformation, and a substantial cause of morbidity in women of childbearing age. While recent studies provide further new information on pregnancy-related outcomes, their results are heterogeneous and a systematic meta-analysis may help the interpretation. The aim of this review was to analyze pregnancy-related outcomes in the recent literature on reflux nephropathy (2000-2016), to perfect the estimation of risks, and to identify specific research needs. METHODS: We searched Medline, EMBASE and the Cochrane review databases for the period 2000-2016 (PROSPERO registration no. 42016042713). SELECTION CRITERIA: all case series and case reports dealing with reflux nephropathy and reporting on at least one pregnancy outcome. Data were extracted from eligible case series (≥ 6 cases). For the outcomes preeclampsia (PE), pregnancy-induced hypertension (PIH), preterm birth, and newborns small for gestational age, we employed as a control group the low-risk pregnancies from a multicenter database including 1418 live-born singletons. Case reports were analyzed narratively. RESULTS: The search retrieved 2507 papers, of which 7 case series and 4 case reports were retained. The series report on 434 women with 879 pregnancies; no study reported controls. Compared to the low-risk controls, the meta-analysis showed an increased risk of PIH (odds ratio, OR 5.55; confidence interval, CI 3.56-8.66), PE (OR 6.04; CI 2.41-15.13), and all hypertensive disorders combined (OR 10.43; CI 6.90-15.75). No difference was observed in preterm delivery and caesarean sections. A higher incidence of stillbirth was reported in one paper. Conversely, the 4 case reports (on 10 pregnancies) alert us to a potentially severe complication, hydro(uretero)nephrosis with or without infection. CONCLUSION: Reflux nephropathy is associated with an increased risk of PIH and PE, but not of preterm delivery, suggesting the occurrence of late 'maternal' PE. The finding of a higher incidence of stillbirths in one series requires further analysis. Strict follow-up of these women is needed, in particular in late pregnancy stages, to avoid and manage in particular hypertensive pregnancy complications.

Moderate Protein Restriction in Advanced CKD: A Feasible Option in An Elderly, High-Comorbidity Population. A Stepwise Multiple-Choice System Approach.

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.

A Systematic Review on Materno-Foetal Outcomes in Pregnant Women with IgA Nephropathy: A Case of "Late-Maternal" Preeclampsia?

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.

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.