Spectrum of Kidney Involvement in Patients with Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are characterized by a high prevalence of associated autoimmune manifestations. Kidney involvement has been rarely reported in MDS patients. We report on the spectrum of kidney pathological findings in MDS patients. We retrospectively identified MDS patients who had undergone a kidney biopsy between 2001 and 2019 in nine Swiss and French nephrology centres. Nineteen patients (median age 74 years [63-83]) were included. At the time of kidney biopsy, eleven (58%) patients had extra-renal auto-immune manifestations and sixteen (84%) presented with acute kidney injury. Median serum creatinine at diagnosis was 2.8 mg/dL [0.6-8.3] and median urinary protein to creatinine ratio was 1.2 g/g [0.2-11]. Acute tubulo-interstitial nephritis (TIN) was present in seven (37%) patients. Immunofluorescence study in one patient with acute TIN disclosed intense IgG deposits along the tubular basement membrane and Bowman's capsule. Other kidney pathological features included ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis (n = 3), membranous nephropathy (n = 2), IgA nephropathy (n = 1), IgA vasculitis (n = 1), immunoglobulin-associated membrano-proliferative glomerulonephritis type I (n=1), crescentic C3 glomerulopathy (n = 1), fibrillary glomerulonephritis (n = 1) and minimal change disease (n = 1). Eleven (58%) patients received immunosuppressive treatments, among whom one developed a severe infectious complication. After a median follow-up of 7 month [1-96], nine (47%) patients had chronic kidney disease stage 3 (n = 6) or 4 (n = 3) and five (26%) progressed to end-stage kidney disease. Three patients died. MDS are associated to several autoimmune kidney manifestations, predominantly acute TIN. MDS are to be listed among the potential causes of autoimmune TIN

Underrepresentation of Elderly People in Randomised Controlled Trials. The Example of Trials of 4 Widely Prescribed Drugs

BACKGROUND: We aimed to determine the representation of elderly people in published reports of randomized controlled trials (RCTs). We focused on trials of 4 medications--pioglitazone, rosuvastatin, risedronate, and valsartan-frequently used by elderly patients with chronic medical conditions. METHODS AND FINDINGS: We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest. Estimates of the community-based "on-treatment" population were from a national health insurance database (SNIIR-AM) covering approximately 86% of the population in France. From this database, we evaluated data claims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months. Of the 155 RCT reports selected, only 3 studies were exclusively of elderly patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%) for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged 65 or older was within or above that treated in clinical practice. In 62.2% of the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and 70.2% for valsartan, the proportion of patients aged 65 or older was lower than half that in the treated population. The representation of elderly people did not differ by publication date or sample size. CONCLUSIONS: Elderly patients are poorly represented in RCTs of drugs they are likely to receive

A systematic review of interventions to improve knowledge and self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis

This systematic review aimed to determine the effectiveness of interventions for improving knowledge and/or self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis (RA). We searched four databases (MEDLINE, CINAHL, Cochrane Trials, PsycINFO) using a comprehensive search strategy. Studies were eligible if they were prospective, published in English from 2004 to 2015, included participants with RA and tested an intervention designed to improve knowledge and/or self-management skills relating to family planning, pregnancy or breastfeeding. As no studies met the latter criterion, the search strategy was expanded to include all prospective studies evaluating RA educational and/or self-management interventions. Data on study characteristics, participant characteristics and programme content were extracted to summarise the evidence base for interventions to support people with RA during their reproductive years. Expanded literature searches identified 2290 papers, of which 68 were eligible. Of these, nine papers (13 %) specifically excluded pregnant women/breastfeeding mothers or recruited only older people.Only one study (1 %) explicitly evaluated pregnancy-focused education via a motherhood decision aid, while eight studies (12 %) incorporated relevant (albeit minor) components within broader RA educational or self-management interventions. Of these, three studies provided methotrexate education in relation to conception/pregnancy/breastfeeding; three incorporated discussions on RA and relationships, impact of RA on the family or sexual advice; one provided information regarding contraception and fertility; and one issued a warning regarding use of biologic therapy in pregnancy/breastfeeding. In conclusion, information regarding family planning, pregnancy or breastfeeding represents a negligible part of published RA educational interventions, with scope to develop targeted resources

Race-free estimated glomerular filtration rate equation in kidney transplant recipients:development and validation study

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P 30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m 2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m 2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P 30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P 30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys.TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.</p

Pain in elderly people with severe dementia: A systematic review of behavioural pain assessment tools

BACKGROUND: Pain is a common and major problem among nursing home residents. The prevalence of pain in elderly nursing home people is 40–80%, showing that they are at great risk of experiencing pain. Since assessment of pain is an important step towards the treatment of pain, there is a need for manageable, valid and reliable tools to assess pain in elderly people with dementia. METHODS: This systematic review identifies pain assessment scales for elderly people with severe dementia and evaluates the psychometric properties and clinical utility of these instruments. Relevant publications in English, German, French or Dutch, from 1988 to 2005, were identified by means of an extensive search strategy in Medline, Psychinfo and CINAHL, supplemented by screening citations and references. Quality judgement criteria were formulated and used to evaluate the psychometric aspects of the scales. RESULTS: Twenty-nine publications reporting on behavioural pain assessment instruments were selected for this review. Twelve observational pain assessment scales (DOLOPLUS2; ECPA; ECS; Observational Pain Behavior Tool; CNPI; PACSLAC; PAINAD; PADE; RaPID; Abbey Pain Scale; NOPPAIN; Pain assessment scale for use with cognitively impaired adults) were identified. Findings indicate that most observational scales are under development and show moderate psychometric qualities. CONCLUSION: Based on the psychometric qualities and criteria regarding sensitivity and clinical utility, we conclude that PACSLAC and DOLOPLUS2 are the most appropriate scales currently available. Further research should focus on improving these scales by further testing their validity, reliability and clinical utility

aHUS caused by complement dysregulation: new therapies on the horizon

Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement regulators [complement factor H (CFH), complement factor I (CFI), complement factor H-related proteins (CFHR), and membrane cofactor protein (MCP)], as well as complement activators [complement factor B (CFB) and C3]. More recently, mutations have also been identified in thrombomodulin (THBD), an anticoagulant glycoprotein that plays a role in the inactivation of C3a and C5a. Inhibitory autoantibodies to CFH account for an additional 5–10% of cases and can occur in isolation or in association with mutations in CFH, CFI, CFHR 1, 3, 4, and MCP. Plasma therapies are considered the mainstay of therapy in aHUS secondary to defective complement regulation and may be administered as plasma infusions or plasma exchange. However, in certain cases, despite initiation of plasma therapy, renal function continues to deteriorate with progression to end-stage renal disease and renal transplantation. Recently, eculizumab, a humanized monoclonal antibody against C5, has been described as an effective therapeutic strategy in the management of refractory aHUS that has failed to respond to plasma therapy. Clinical trials are now underway to further evaluate the efficacy of eculizumab in the management of both plasma-sensitive and plasma-resistant aHUS

Adaptive hyperphagia in patients with postsurgical malabsorption.

International audienceThe specific nutritional consequences of malabsorption after small-bowel surgery were studied in a consecutive series of 48 ambulatory patients who had had small-bowel resection (n = 43) or bypass (n = 5) and in 10 patients who had an ileal pouch (n = 10). The patients received a 3-day standardized oral regimen providing daily 30 kcal/kg of ideal body weight (IBW). Throughout the study, 41 patients had malabsorption (fecal fat greater than 5%); 17 had fecal fat less than 5% and served as controls. The malabsorption patients absorbed 70% of protein and 71% of fat. Twenty-one were normonourished and 20 had features of mild energy malnutrition, vs. 15 and 2 controls, respectively. Compared with controls, malabsorption patients had decreased body weight and triceps skin-fold but no features of protein malnutrition. their mean daily food intake at home was significantly enhanced (39.6 +/- 13.1 kcal/IBW kg) vs. controls (28.8 +/- 5.8 kcal/IBW kg, P less than 0.001). In the malabsorption group, caloric intake was higher in the normonourished patients than in those with mild malnutrition. This study shows that a chronic malabsorption has limited nutritional consequences. The patients compensate for their absorptive handicap by increasing their oral intake

Fanconi syndrome due to deferasirox

Deferasirox is an innovative iron-chelating treatment. However, preliminary data have suggested that kidney toxicity may be a major issue in the management of patients receiving this drug. We report a case of Fanconi syndrome associated with acute renal insufficiency in a patient receiving deferasirox. The latter has to be added to the expanding list of drugs that may induce Fanconi syndrome. Careful monitoring of kidney function and markers of proximal tubular injury are mandatory in patients undergoing treatment with deferasirox