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.

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.

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.

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.

A follow-up study of heroin addicts (VEdeTTE2): study design and protocol.

BACKGROUND: In Italy, a large cohort study (VEdeTTE1) was conducted between 1998-2001 to evaluate the effectiveness of treatments in reducing mortality and increasing treatment retention among heroin addicts. The follow-up of this cohort (VEdeTTE2) was designed to evaluate the effectiveness of treatments on long-term outcomes, such as rehabilitation and social re-integration. The purpose of this paper is to describe the protocol of the VEdeTTE2 study, and to present the results of the pilot study carried out to assess the feasibility of the study and to improve study procedures. METHODS: The source population for the VEdeTTE2 study was the VEdeTTE1 cohort, from which a sample of 2,200 patients, traced two or more years after enrollment in the cohort, were asked to participate. An interview investigates drug use; overdose; family and social re-integration. Illegal activity are investigated separately in a questionnaire completed by the patient. Patients are also asked to provide a hair sample to test for heroin and cocaine use. Information on treatments and HIV, HBV and HCV morbidity are obtained from clinical records. A pilot phase was planned and carried out on 60 patients. RESULTS: The results of the pilot phase pointed out the validity of the procedures designed to limit attrition: the number of traced subjects was satisfactory (88%). Moreover, the pilot phase was very useful in identifying possible causes of delays and attrition, and flaws in the instruments. Improvements to the procedures and the instruments were subsequently implemented. Sensitivity of the biological test was quite good for heroin (78%) but lower for cocaine (42.3%), highlighting the need to obtain a hair sample from all patients. CONCLUSION: In drug addiction research, studies investigating health status and social re-integration of subjects at long-term follow-up are lacking. The VEdeTTE2 study aims to investigate these outcomes at long-term follow-up. Results of the pilot phase underline the importance of the pilot phase when planning a follow-up study.

Methadone treatment in clinical practice in Italy: need for improvement.

BACKGROUND: Methadone at appropriate doses has been demonstrated to be the most effective means for retaining patients in treatment and suppressing heroin use. AIM: To describe the modalities of day-to-day provision of methadone maintenance treatments (MMT) in Italian public health centres and to analyze the duration of MMTs by dose and by association with psychosocial treatments. PATIENTS AND METHODS: We analyzed 8,378 subjects, 18 years of age or over, enrolled between September 1998 and March 2001 in one of 115 public treatment centres for heroin dependence in Italy. Treatment data were collected for each subject from enrolment to the end of the study period (maximum of 18 months). RESULTS: Of the total of 29,495 treatments delivered, 21.0% were methadone maintenance, and 34.4% were methadone detoxification. Fifty percent of MMTs offered had a mean dose less than or equal to 40 mg/day, and only 19% had doses higher than or equal to 60 mg/day; treatments with doses higher than 60 mg/day lasted longer than treatments with lower doses. Differences in treatment length were observed between MMTs associated with a psychosocial treatment and those offered alone, only for doses <60 mg/day. CONCLUSIONS: In Italy, MMTs are delivered at inappropriate doses in more than 80% of the cases. The increase of methadone doses to adequate levels as indicated by the literature is necessary to ensure proper and effective use of MMTs in public treatment centres for heroin users.