The estimated prevalence of antiphospholipid antibodies and criteria-antiphospholipid syndrome in subjects with renal thrombotic microangiopathy.

BACKGROUND: While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL in subjects with Thrombotic Microangiopathy (TMA) is still not fully elucidated. Thus, we conducted a systematic review to estimate the frequency of aPL in subjects with biopsy-proven renal TMA. METHODS: We conducted in the PubMed database a search for English-language studies investigating the presence of aPL in subjects with biopsy-proven renal TMA from January 1985 to December 2022. Keywords used in the search included: 'antiphospholipid syndrome', 'antiphospholipid antibodies' and 'thrombotic microangiopathy'. Cohorts of HUS patients were excluded due to the risk of over-estimating the prevalence of aPL in these populations. The median frequency for positive aPL including anticardiolipin antibodies (aCL), antibodies against ß2-glycoprotein-I (anti-ß2GPI) and lupus anticoagulant (LA) was then calculated. RESULTS: 522 articles were identified through the literature search. Six studies, assessing the prevalence of aPL in 211 subjects with renal TMA, were retrieved. The overall aPL prevalence was estimated as 24.4% (range 22-56). The estimated prevalence of aCL (IgG/IgM), anti-ß2GPI, (IgG/IgM) and LA was 4.0% (range 3-27), 4.0% (range 3-16) and 18.9% (range 13-25), respectively. APS was diagnosed in 16.3% (range 11-29) of the patients. Of note, a high level of heterogeneity was observed when comparing the reported aPL profiles for each study. CONCLUSIONS: This comprehensive systematic analysis of studies investigating the prevalence of aPL in renal TMA showed that, despite the high heterogeneity of the included studies, aPL are present in about one case out of four renal-TMA cases.

Adding creatinine to routine pregnancy tests: a decision tree for calculating the cost of identifying patients with CKD in pregnancy.

BACKGROUND: Even in its early stages, chronic kidney disease (CKD) is associated with adverse pregnancy outcomes. The current guidelines for pregnancy management suggest identifying risk factors for adverse outcomes but do not mention kidney diseases. Since CKD is often asymptomatic, pregnancy offers a valuable opportunity for diagnosis. The present analysis attempts to quantify the cost of adding serum creatinine to prenatal screening and monitoring tests. METHODS: The decision tree we built takes several screening scenarios (before, during and after pregnancy) into consideration, following the hypothesis that while 1:750 pregnant women are affected by stage 4-5 CKD and 1:375 by stage 3B, only 50% of CKD cases are known. Prevalence of abortions/miscarriages was calculated at 30%; compliance with tests was hypothesized at 50% pre- and post-pregnancy and 90% during pregnancy (30% for miscarriages); the cost of serum creatinine (production cost) was set at 0.20 euros. A downloadable calculator, which makes it possible to adapt these figures to other settings, is available. RESULTS: The cost per detected CKD case ranged from 111 euros (one test during pregnancy, diagnostic yield 64.8%) to 281.90 euros (one test per trimester, plus one post-pregnancy or miscarriage, diagnostic yield 87.7%). The best policy is identified as one test pre-, one during and one post-pregnancy (191.80 euros, diagnostic yield 89.4%). CONCLUSIONS: This study suggests the feasibility of early CKD diagnosis in pregnancy by adding serum creatinine to routinely performed prenatal tests and offers cost estimates for further discussion.

What a paediatric nephrologist should know about preeclampsia and why it matters.

Preeclampsia is a protean syndrome causing a kidney disease characterised by hypertension and proteinuria, usually considered transitory and reversible after delivery. Its prevalence ranges from 3-5 to 10% if all the related disorders are considered. This narrative review, on behalf of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology, focuses on three reasons why preeclampsia should concern paediatric nephrologists and how they can play an important role in its prevention, as well as in the prevention of future kidney and cardiovascular diseases. Firstly, all diseases of the kidney and urinary tract diagnosed in paediatric age are associated with a higher risk of adverse pregnancy-related outcomes, including preeclampsia. Secondly, babies with low birth weights (small for gestational age, born preterm, or both) have an increased risk of developing the full panoply of metabolic diseases (obesity, hypertension, early-onset cardiopathy and chronic kidney disease) and girls are at higher risk of developing preeclampsia when pregnant. The risk may be particularly high in cases of maternal preeclampsia, highlighting a familial aggregation of this condition. Thirdly, pregnant teenagers have a higher risk of developing preeclampsia and the hypertensive disorders of pregnancy, and should be followed up as high risk pregnancies. In summary, preeclampsia has come to be seen as a window on the future health of both mother and baby. Identification of subjects at risk, early counselling and careful follow-up can contribute to reducing the high morbidity linked with this disorder.

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia.

Preeclampsia is a pregnancy-related syndrome of variable severity, classically characterized by acute kidney involvement, with hypertension and/or proteinuria and reduced kidney function. Once considered a self-limited disease healed by delivery, it is now acknowledged that preeclampsia can affect cardiovascular and kidney health in the long term. The entity of risk has not been established and consequently follow-up policies have not been defined. Here we undertook a systematic review to gain better insights into the need for post-preeclampsia follow-up. Articles published between January 2000 and March 2018 were selected, dealing with at least 20 preeclampsia patients, with follow-up of 4 years or more (MEDLINE, Embase, and Cochrane Library). No quality selection or language restriction was performed. Of the 10,510 titles and abstracts originally considered, 21 papers were selected, providing information on 110,803 cases with and 2,680,929 controls without preeclampsia, with partial overlap between studies on the same databases. Heterogeneity was high, and a random meta-analytic model selected. The increase in risk of end stage renal disease after preeclampsia was significant (meta-analytic risk ratios (95% confidence interval) 6.35 (2.73-14.79)); the risk of albuminuria and chronic kidney disease increased but statistical significance was not reached (4.31 (0.95-19.58) and 2.03 (0.58-7.32), respectively). Translating meta-analytic risk into the number of patients who need follow-up to detect one adverse event, 310 patients with preeclampsia are needed to identify one woman with end stage renal disease or four to identify one woman with albuminuria. Heterogeneity in definitions, insufficient follow-up and incomplete recruitment may account for discrepancies. Thus, preeclampsia significantly increases the risk of end stage renal disease. However, there is lack of sufficient data to show a relationship between preeclampsia, albuminuria and chronic kidney disease, underlining the need for further prospective studies.

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.

Pregnancy in dialysis patients in the new millennium: a systematic review and meta-regression analysis correlating dialysis schedules and pregnancy outcomes.

BACKGROUND: Advances have been made in the management of pregnancies in women receiving dialysis; however, single-centre studies and small numbers of cases have so far precluded a clear definition of the relationship between dialysis schedules and pregnancy outcomes. The aim of the present systematic review was to analyse the relationship between dialysis schedule and pregnancy outcomes in pregnancies in chronic dialysis in the new millennium. METHODS: Medline-PubMed, Embase and the Cochrane library were searched (1 January 2000-31 December 2014: MESH, Emtree, free terms on pregnancy and dialysis). A separate analysis was performed for case series (more than five cases) and case reports. Meta-regression was performed in case series dealing with the larger subset of haemodialysis (HD) patients; case reports were analysed separately [according to peritoneal dialysis (PD) versus HD; conception before or during dialysis]. RESULTS: We obtained 190 full texts and 25 congress abstracts from 2048 references. We selected 101 full papers and 25 abstracts (36 series; 90 case reports), for a total of 681 pregnancies in 647 patients. In the case series (574 pregnancies in 543 patients), preterm delivery was extremely frequent (83%). Meta-regression analysis showed a relationship between hours of dialysis per week in HD and preterm delivery, and was significant for preterm deliveries (<37 gestational weeks: P = 0.044; r2 = 0.22) and for small for gestational age (SGA) (P = 0.017; r2 = 0.54). SGA was closely associated with the number of dialysis sessions per week (P = 0.003; r2 = 0.84). Case report analysis suggests a lower incidence of SGA on HD versus PD (31 versus 66.7%; P = 0.015). No evidence of an increased risk of congenital abnormality was found in the retrieved papers. CONCLUSIONS: Data on pregnancy on dialysis are heterogeneous but rapidly accumulating; the main determinant of outcomes on HD is the dialysis schedule. The differences between PD and HD should be further analysed.

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.

Type D Personality and Essential Hypertension in Primary Care: A Cross-Sectional Observational Study Within a Cohort of Patients Visiting General Practitioners.

To estimate the relationship between type D personality and essential hypertension among patients visiting their GPs for any health problem, 101 hypertensive and 138 nonhypertensive patients were consecutively recruited and assessed using the Type D Personality Scale (DS14). The predictive value of type D personality was determined using a logistic regression model, taking into account the differences in recognized confounders between groups. Type D personality in the hypertension group was twice as frequent as in the no hypertension group and hypertension was more frequent among type D than non-type D patients. Logistic regression showed a significant predictive value of type D personality for hypertension, adjusting for sex, age, body mass index, family history of hypertension, living condition, education, and employment. Therefore, type D personality was strongly related to hypertension and it was a noteworthy predictor of hypertension in a real-world cohort of primary care patients.

Diet as a system: an observational study investigating a multi-choice system of moderately restricted low-protein diets.

BACKGROUND: There is no single, gold-standard, low-protein diet (LPD) for CKD patients; the best compliance is probably obtained by personalization. This study tests the hypothesis that a multiple choice diet network allows patients to attain a good compliance level, and that, in an open-choice system, overall results are not dependent upon the specific diet, but upon the clinical characteristics of the patients. METHODS: Observational study: Three LPD options were offered to all patients with severe or rapidly progressive CKD: vegan diets supplemented with alpha-ketoacids and essential aminoacids; protein-free food in substitution of normal bread and pasta; other (traditional, vegan non supplemented and tailored). Dialysis-free follow-up and survival were analyzed by Kaplan Meier curves according to diet, comorbidity and age. Compliance and metabolic control were estimated in 147 subjects on diet at March 2015, with recent complete data, prescribed protein intake 0.6 g/Kg/day. Protein intake was assessed by Maroni Mitch formula. RESULTS: Four hundreds and forty nine patients followed a LPD in December, 2007- March, 2015 (90% moderately restricted LPDs, 0.6 g/Kg/day of protein, 10% at lower targets); age (median 70 (19-97)) and comorbidity (Charlson index: 7) characterized our population as being in line with the usual CKD European population. Median e-GFR at start of the diet was 20 mL/min, 33.2% of the patients were diabetics. Baseline data differ significantly across diets: protein-free schemas are preferred by older, high-comorbidity patients (median age 76 years, Charlson index 8, GFR 20.5 mL/min, Proteinuria: 0.3 g/day), supplemented vegan diets by younger patients with lower GFR and higher proteinuria (median age 65 years, Charlson index 6, GFR 18.9 mL/min; Proteinuria: 1.2 g/day); other diets are chosen by an intermediate population (median age 71 years, Charlson index 6; GFR 22.5 mL/min; Proteinuria: 0.9 g/day); (p <0.001 for age, Charlson index, proteinuria, GFR). Adherence was good, only 1.1% of the patients were lost to follow-up and protein intake was at target in most of the cases with no differences among LPDs (protein intake: 0.47 (0.26-0.86) g/Kg/day). After adjustment for confounders, and/or selection of similar populations, no difference in mortality or dialysis start was observed on the different LPDs. Below the threshold of e-GFR 15 mL/min, 50% of the patients remain dialysis free for at least two years. CONCLUSION: A multiple choice LPD system may allow reaching good adherence, without competition among diets, and with promising results in terms of dialysis-free follow-up. The advantages with respect to a non-customized approach deserve confirmation in further comparative studies or RCTs.

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.

Gender Differences in Heroin Addiction and Treatment: Results from the VEdeTTE Cohort.

BACKGROUND: Gender differences strongly affect heroin addiction, from risk factors to patterns of consumption, access to treatments, and outcomes. OBJECTIVES: To investigate gender differences in the VEdeTTE cohort of heroin addicts. METHODS: VEdeTTE is a cohort of 10,454 heroin users enrolled between 1998 and 2001 in 115 public drug treatment centres in Italy. Clinical and personal information were collected at intake through a structured interview. Treatments were recorded using a standardized form. Gender differences were explored with regard to characteristics at intake, treatments, and retention in methadone maintenance and therapeutic community. Cox Proportional models were carried out to identify risk factors for treatment abandon. RESULTS: Compared with men, at their first access to treatment women with drug addiction were younger, more frequently married, legally separated, divorced or widow, unemployed though better educated, HIV+; more frequently they lived with their partner and sons. They reported a higher use of sedatives, but a lower use of alcohol; more frequently they had psychiatric comorbidity, including depression, self-injuries, and suicide attempts. Psychotherapy was more frequently prescribed to women, pharmacological treatments to men. Methadone maintenance was less frequently abandoned by women. Drug abuse severity factors predicted abandon of methadone among women. High methadone doses and the combination with psychotherapy improved treatment retention in both genders. Low education level and severity factors among women and young age among men predicted abandon of therapeutic community. CONCLUSIONS: Gender differences in the VEdeTTE cohort suggest the need of a gender sensitive approach to improve treatment outcomes among heroin addicts.

Influence of posterior vitreous detachment and type of intraocular lens on lipid peroxidation in the human vitreous.

PURPOSE: The aim of this study was to evaluate the relationship between oxidative stress and human vitreous degeneration, using the presence of an evident posterior vitreous detachment (PVD) as a clinical sign and thiobarbituric acid-reactive substances (TBARS) and nitrite as oxidative biomarkers. METHODS: We collected 42 vitreous samples from patients undergoing pars plana vitrectomy for two groups of vitreoretinal diseases (macular holes and epimacular membranes). TBARS and nitrite were assessed spectrophotometrically and compared to the presence of an evident PVD, considering other clinical features potentially related to the oxidative stress in the vitreous: diabetes, plasma fibrinogen, type of intraocular lens (IOL), and the vitreoretinal disease requiring the surgery. RESULTS: Vitreous TBARS levels were significantly higher in patients with artificial IOLs compared to those with natural lenses and cataracts (1.39±0.64 versus 0.75±0.45; p=0.003). Furthermore, patients with PVD had a significant increase in vitreous TBARS compared to those without PVD (1.45±0.54 versus 0.53±0.38; p=0.001). The plasma fibrinogen levels explained 17% of the TBARS variance, with a significant correlation between these two markers (p=0.011). No significant differences were observed when nitrites were used as biomarkers. CONCLUSIONS: Current IOLs, even with ultraviolet (UV) absorber, do not ensure the same photoprotection offered by natural lenses affected by corticonuclear cataracts. Furthermore, we observed a relevant correlation between the increased presence of peroxidation products in the vitreous and an evident PVD, but the nature of this relationship requires further study.

Universal school-based prevention for illicit drug use.

BACKGROUND: Drug addiction is a chronic, relapsing disease. Primary interventions should aim to reduce first use or to prevent the transition from experimental use to addiction. School is the appropriate setting for preventive interventions. OBJECTIVES: To evaluate the effectiveness of universal school-based interventions in reducing drug use compared to usual curricular activities or no intervention. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group's Trials Register (September 2013), the Cochrane Central Register of Controlled Trials (2013, Issue 9), PubMed (1966 to September 2013), EMBASE (1988 to September 2013) and other databases. We also contacted researchers in the field and checked reference lists of articles. SELECTION CRITERIA: Randomised controlled trials (RCT) evaluating school-based interventions designed to prevent illicit drugs use. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 51 studies, with 127,146 participants. Programmes were mainly delivered in sixth and seventh grade pupils. Most of the trials were conducted in the USA. Social competence approach versus usual curricula or no intervention Marijuana use at < 12 months follow-up: the results favoured the social competence intervention (risk ratio (RR) 0.90; 95% confidence interval (CI) 0.81 to 1.01, four studies, 9456 participants, moderate quality evidence). Seven studies assessed this outcome (no data for meta-analysis): two showed a positive significant effect of intervention, three showed a non-significant effect, one found a significant effect in favour of the control group and one found a trend in favour of the control group.Marijuana use at 12+ months: the results favoured the social competence intervention (RR 0.86; 95% CI 0.74 to 1.00, one study, 2678 participants, high quality evidence). Seven studies assessed this outcome (no data for meta-analysis): two showed a significant positive effect of intervention, three showed a non-significant effect, one found a significant effect in favour of the control group and one a trend in favour of the control group.Hard drug use at < 12 months: we found no difference (RR 0.69; 95% CI 0.40 to 1.18, one study, 2090 participants, moderate quality evidence). Two studies assessed this outcome (no data for meta-analysis): one showed comparable results for the intervention and control group; one found a statistically non-significant trend in favour of the social competence approach.Hard drug use at 12+ months: we found no difference (mean difference (MD) -0.01; 95% CI -0.06 to 0.04), one study, 1075 participants, high quality evidence). One study with no data for meta-analysis showed comparable results for the intervention and control group.Any drug use at < 12 months: the results favoured social competence interventions (RR 0.27; 95% CI 0.14 to 0.51, two studies, 2512 participants, moderate quality evidence). One study with 1566 participants provided continuous data showing no difference (MD 0.02; 95% CI -0.05 to 0.09, moderate quality evidence). Social influence approach versus usual curricula or no intervention Marijuana use at < 12 months: we found a nearly statistically significant effect in favour of the social influence approach (RR 0.88; 95% CI 0.72 to 1.07, three studies, 10,716 participants, moderate quality evidence). One study with 764 participants provided continuous data showing results that favoured the social influence intervention (MD -0.26; 95% CI -0.48 to -0.04).Marijuana use at 12+ months: we found no difference (RR 0.95; 95% CI 0.81 to 1.13, one study, 5862 participants, moderate quality evidence). One study with 764 participants provided continuous data and showed nearly statistically significant results in favour of the social influence intervention (MD -0.22; 95% CI -0.46 to 0.02). Of the four studies not providing data for meta-analysis a statistically significant protective effect was only found by one study.Hard drug use at 12+ months: one study not providing data for meta-analysis found a significant protective effect of the social influence approach.Any drug use: no studies assessed this outcome. Combined approach versus usual curricula or no intervention Marijuana use at < 12 months: there was a trend in favour of intervention (RR 0.79; 95% CI 0.59 to 1.05, three studies, 8701 participants, moderate quality evidence). One study with 693 participants provided continuous data and showed no difference (MD -1.90; 95% CI -5.83 to 2.03).Marijuana use at 12+ months: the results favoured combined intervention (RR 0.83; 95% CI 0.69 to 0.99, six studies, 26,910 participants, moderate quality evidence). One study with 690 participants provided continuous data and showed no difference (MD -0.80; 95% CI -4.39 to 2.79). Two studies not providing data for meta-analysis did not find a significant effect.Hard drug use at < 12 months: one study with 693 participants provided both dichotomous and continuous data and showed conflicting results: no difference for dichotomous outcomes (RR 0.85; 95% CI 0.63 to 1.14), but results in favour of the combined intervention for the continuous outcome (MD -3.10; 95% CI -5.90 to -0.30). The quality of evidence was high.Hard drug use at 12+ months: we found no difference (RR 0.86; 95% CI 0.39 to 1.90, two studies, 1066 participants, high quality evidence). One study with 690 participants provided continuous data and showed no difference (MD 0.30; 95% CI -1.36 to 1.96). Two studies not providing data for meta-analysis showed a significant effect of treatment.Any drug use at < 12 months: the results favoured combined intervention (RR 0.76; 95% CI 0.64 to 0.89, one study, 6362 participants).Only one study assessed the effect of a knowledge-focused intervention on drug use and found no effect. The types of comparisons and the programmes assessed in the other two groups of studies were very heterogeneous and difficult to synthesise. AUTHORS' CONCLUSIONS: School programmes based on a combination of social competence and social influence approaches showed, on average, small but consistent protective effects in preventing drug use, even if some outcomes did not show statistical significance. Some programmes based on the social competence approach also showed protective effects for some outcomes.Since the effects of school-based programmes are small, they should form part of more comprehensive strategies for drug use prevention in order to achieve a population-level impact.

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.

COVID-19 in Pregnancy: Influence of Body Weight and Nutritional Status on Maternal and Pregnancy Outcomes-A Review of Literature and Meta-Analysis.

In the last two and a half years, COVID-19 has been one of the most challenging public health issues worldwide. Based on the available evidence, pregnant women do not appear to be more susceptible to infection than the general population but having COVID-19 during pregnancy may increase the risk of major complications for both the mother and the fetus. The aim of this study is to identify the correlation between BMI and nutritional status and the likelihood of contracting COVID-19 infection in pregnancy, its severity, and maternal pregnancy outcomes. We carry out a systematic literature search and a meta-analysis using three databases following the guidelines of the Cochrane Collaboration. We include 45 studies about COVID-19-positive pregnant women. Compared with normal-weight pregnant women with COVID-19, obesity is associated with a more severe infection (OR = 2.32 [1.65-3.25]), increased maternal death (OR = 2.84 [2.01-4.02]), and a higher rate of hospital admission (OR = 2.11 [1.37-3.26]). Obesity may be associated with adverse maternal and pregnancy outcomes by increasing symptom severity and, consequently, hospital and Intensive Care Unit (ICU) admission, and, finally, death rates. For micronutrients, the results are less definite, even if there seems to be a lower level of micronutrients, in particular Vitamin D, in COVID-19-positive pregnant women.

Plant-based diets for CKD patients: fascinating, trendy, but feasible? A green nephrology perspective.

Climate change is inducing us to rethink our way of life. There is widespread awareness that we need to adopt environmentally friendly approaches and reduce the amount of waste we generate. In medicine, nephrology was one of the first specialties to adopt a green approach. Plant-based or vegan-vegetarian diets, which are planet-friendly and associated with a reduced carbon footprint, were rapidly acknowledged as a valid method for reducing protein intake in the conservative management of chronic kidney disease (CKD). However, how the transition from an omnivorous to a plant-based diet should be managed is not universally agreed; there is little data in the literature and indications based on randomized trials fail to consider feasibility and patients' preferences. Nonetheless, in some conditions the use of plant-based diets has proved safe and effective. For example, in CKD pregnancies, it has reduced unfavorable maternal and fetal outcomes. This review will present the available evidence on the benefits of plant-based diets in CKD, as well as old and new criticisms of their use, including emerging issues, such as contaminants, additives and pesticides, from a green nephrology perspective.

The Hypertensive Disorders of Pregnancy: A Focus on Definitions for Clinical Nephrologists.

About 5-10% of pregnancies are complicated by one of the hypertensive disorders of pregnancy. The women who experience these disorders have a greater risk of having or developing kidney diseases than women with normotensive pregnancies. While international guidelines do not provide clear indications for a nephrology work-up after pregnancy, this is increasingly being advised by nephrology societies. The definitions of the hypertensive disorders of pregnancy have changed greatly in recent years. The objective of this short review is to gather and comment upon the main definitions of the hypertensive disorders of pregnancy as a support for nephrologists, who are increasingly involved in the short- and long-term management of women with these disorders.

History of Preeclampsia in Patients Undergoing a Kidney Biopsy: A Biphasic, Multiple-Hit Pathogenic Hypothesis.

Introduction: It is not fully elucidated whether preeclampsia (PE) is a marker or a cause of chronic kidney disease (CKD). To test the hypothesis of a biphasic relationship between PE and CKD, we assessed PE prevalence in women who underwent a kidney biopsy. Methods: This retrospective, observational study recruited patients who underwent a kidney biopsy after delivery in 2014 to 2019 in 3 Italian Centers (Cagliari, Bari, Messina); low-risk pregnancies observed in Cagliari served as controls. A history of PE was assessed on the clinical charts and by phone interview. Results: In the biopsy cohort (379 pregnancies, 205 patients; 38 PE in 32 patients), kidney biopsy shows clustering in the first 5 years after PE (11 of 32). Pre-existing CKD was detected in 8 of 11 of these cases. Focal-segmental glomerulosclerosis (FSGS) and complex lesions were found in 12 of 32 biopsies. The odds ratio (OR) of having had a PE episode, compared with 561 low-risk pregnancies, was 10.071 (95% CI: 4.859-20.875; P < 0.001); multiparity maintained a protective effect (OR: 0.208). The delivery-to-biopsy time was significantly shorter in women with PE, both considering the first or the last PE versus the first or last delivery in patients with or without PE episodes. The characteristics of PE did not differ as compared with low-risk controls. Conclusion: Within the limitation of the retrospective design, our study, quantifying the association between needing a kidney biopsy and history of PE, suggests a biphasic pattern, with a peak in the first 5 years after delivery (probably due to pre-existing diseases) and a later increase, suggesting that PE may have later played as one hit in a multiple-hit pathogenesis.

COVID-19 Vaccine Hesitancy in Patients on Dialysis in Italy and France.

INTRODUCTION: Patients on dialysis (HDPs) are a category at high risk from COVID-19 and thus a high-priority group for vaccination. COVID-19 vaccine hesitancy has been a concern since the availability of the first vaccine. The objective of this study was to determine hesitancy rates and factors associated with hesitancy toward COVID-19 vaccination in HDP. METHODS: HDP were surveyed with an ad hoc questionnaire in 4 large dialysis facilities in Europe: Le Mans and Paris, in France, and Cagliari and Pavia, in Italy. The questionnaire explored different domains associated with vaccine hesitancy, such as perception of disease severity, sources of information about the vaccine and the disease, and confidence in the health care system. RESULTS: A total of 417 patients (average age 69 years, 60% men) agreed to answer the questionnaire. Hesitancy was associated with younger age (P = 0.003), lower perception of disease severity (P < 0.001) and vaccine efficacy (P < 0.001), and lower trust in vaccination (P < 0.001) and in the health care system and scientists (P < 0.001) in the univariate analysis. In the multivariate models, concerns about side effects (P = 0.004) and vaccine efficacy (P < 0.001) and living in France (P = 0.04) remained associated with higher vaccine hesitancy, whereas having received an influenza vaccine (P = 0.032) and trusting scientists (P = 0.032) were associated with a more positive attitude toward vaccination. CONCLUSIONS: HDPs have a good understanding of the risks associated with COVID-19. Vaccine hesitancy was not associated with educational level, age, or gender but rather with lack of confidence in vaccine efficacy and concerns about safety. HDPs were quite skeptical about the health care system but generally trusted scientists.