Is there sex disparity in vascular access at dialysis initiation in France? A mediation analysis using data from the Renal Epidemiology and Information Network registry.

Background: This study was conducted to estimate the direct effect of sex on the proportion of hemodialysis (HD) catheters used at dialysis initiation and to investigate whether predialysis care or socioeconomic status acted as a mediator of the sex effect. Methods: Patients who started dialysis between January 1, 2017, and June 30, 2018, in France were included using the data of the Renal Epidemiology and Information Network (REIN) registry. We performed logistic regression to study the association between sex and the proportion of HD catheters used. A mediation analysis with a counterfactual approach was carried out to evaluate whether there was an indirect effect of sex through the proxies of predialysis care {hemoglobin, albumin levels, glomerular filtration rate [GFR] at dialysis initiation} and socioeconomic status. Because an interaction between sex and social deprivation has been identified, we performed a subgroup analysis on deprived and nondeprived patients. Results: The study included 16 032 patients, and the sex ratio (male to female) was 10 405:5627. In the multivariable analysis, women were associated with a greater risk of starting dialysis with a catheter {odds ratio [OR], 1.32 [95% confidence interval (CI): 1.23-1.42]}. There was an indirect effect of sex on the proportion of HD catheters through proxies for predialysis care {albuminemia <30 g/L [OR, 1.08 (95% CI: 1.05-1.10)], hemoglobin <11 g/dL [OR, 1.03 (95% CI: 1.02-1.04)], glomerular filtration rate <7 mL/min [OR, 1.05 (95% CI: 1.04-1.07)]}. Among deprived patients, there was no direct effect of sex on catheter proportion. Conclusions: Women were associated with a higher risk of starting dialysis through an HD catheter. The effect of sex was mediated by predialysis care, particularly for deprived patients.

Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma Exchanges.

BACKGROUND: Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. METHODS: We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). RESULTS: No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (-15.9%; 95% CI, -29.4 to -2.5) compared with the PLEX not recommended group (-4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. CONCLUSIONS: PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making.

New clinical forms of hereditary apoA-I amyloidosis entail both glomerular and retinal amyloidosis.

Apolipoprotein A1 amyloidosis (ApoAI) results from specific mutations in the APOA1 gene causing abnormal accumulation of amyloid fibrils in diverse tissues. The kidney is a prominent target tissue in ApoAI amyloidosis with a remarkable selectivity for the renal medulla. Here, we investigated six French families with ApoAI Glu34Lys, p.His179Profs∗47, and a novel p.Thr185Alafs∗41 variant revealing unprecedented clinical association of a glomerular with a retinal disease. Comprehensive clinicopathological, molecular and proteomics studies of numerous affected tissues ensured the correlation between clinical manifestations, including novel unrecognized phenotypes, and apoA-I amyloid deposition. These ophthalmic manifestations stemmed from apoA-I amyloid deposition, highlighting that the retina is a previously unrecognized tissue affected by ApoAI amyloidosis. Our study provides the first molecular evidence that a significant fraction of ApoAI amyloidosis cases with no family history result from spontaneous neomutations rather than variable disease penetrance. Finally, successful hepatorenal transplantation resulted in a life- and vision-saving measure for a 32-year-old man with a hitherto unreported severe ApoAI amyloidosis caused by the very rare Glu34Lys variant. Our findings reveal new modes of occurrence and expand the clinical spectrum of ApoAI amyloidosis. The awareness of glomerular and ocular manifestations in ApoAI amyloidosis should enable earlier diagnosis and avoid misdiagnosis with other forms of renal amyloidosis. Thus, documented apoA-I amyloid deposition in the retina offers new biological information about this disease and may change organ transplantation practice to reduce retinal damage in patients with ApoAI amyloidosis.

Extracorporeal photopheresis for the treatment of graft rejection in 33 adult kidney transplant recipients.

Background - Extracorporeal photopheresis (ECP) has shown encouraging results in the prevention of allograft rejection in heart transplantation. However, the role of ECP in kidney transplant (KT) rejection needs to be determined. Methods - This multicentre retrospective study included 33 KT recipients who were treated with ECP for allograft rejection (23 acute antibody-mediated rejections (AMRs), 2 chronic AMRs and 8 acute cellular rejections (ACRs)). The ECP indications were KT rejection in patients who were resistant to standard therapies (n = 18) or in patients for whom standard therapies were contraindicated because of concomitant infections or cancers (n = 15). Results - At 12 months (M12) post-ECP, 11 patients (33%) had a stabilization of kidney function with a graft survival rate of 61%. The Banff AMR score (g + ptc + v) was a risk factor for graft loss at M12 (HR 1.44 [1.01-2.05], p < 0.05). The factorial mixed data analysis identified 2 clusters. Patients with a functional graft at M12 tended to have cellular and/or chronic rejections. Patients with graft loss at M12 tended to have acute rejections and/or AMR; higher serum creatinine levels; DSA levels and histologic scores of AMR; and a longer delay between the rejection and ECP start than those of patients with functional grafts. Conclusions - ECP may be helpful to control ACR or moderate AMR in KT recipients presenting concomitant opportunistic infections or malignancies when it is initiated early.

Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers or both in incident end-stage renal disease patients without cardiovascular disease: a propensity-matched longitudinal cohort study.

BACKGROUND: End-stage renal disease (ESRD) patients even without known cardiovascular (CV) disease have high mortality rates. Whether neurohormonal blockade treatments improve outcomes in this population remains unknown. The aim of this study was to assess the effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs), ß-blockers or both in all-cause mortality rates in incident ESRD patients without known CV disease starting renal replacement therapy (RRT) between 2009 and 2015 in the nationwide Réseau Epidémiologie et Information en Néphrologie registry. METHODS: Patients with known CV disease and those who started emergency RRT, stopped RRT or died within 6 months were excluded. Propensity score matching models were used. The main outcome was all-cause mortality. RESULTS: A total of 13 741 patients were included in this analysis. The median follow-up time was 24 months. When compared with matched controls without antihypertensive treatment, treatment with ACEi/ARBs, ß-blockers and ACEi/ARBs + ß-blockers was associated with an event-rate reduction per 100 person-years: ACEi/ARBs 7.6 [95% confidence interval (CI) 7.1-8.2] versus matched controls 9.5 (8.8-10.1) [HR 0.76 (95% CI 0.69-0.84)], ß-blocker 7.1 (6.6-7.7) versus matched controls 9.5 (8.5-10.2) [HR 0.72 (0.65-0.80)] and ACEi/ARBs + ß-blockers 5.8 (5.4-6.4) versus matched controls 7.8 (7.2-8.4) [HR 0.68 (0.61-0.77)]. CONCLUSIONS: Neurohormonal blocking therapies were associated with death rate reduction in incident ESRD without CV disease. Whether these relationships are causal will require randomized controlled trials.

The Prevalence of Renal Impairment in Patients with Spondyloarthritis: Results from the International ASAS-COMOSPA Study.

OBJECTIVE: To assess the prevalence and association of renal dysfunction in patients with spondyloarthritis (SpA). METHODS: The ASAS-COMOSPA (Assessment of Spondyloarthritis international Society-COMOrbidities in SPondyloArthritis) was an international study (22 participating countries from 4 continents) investigating comorbidities in SpA. Renal function was assessed based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease equation. SpA characteristics and risk factors for renal impairment were collected. Nonsteroidal antiinflammatory drug (NSAID) use was assessed based on current intake (last 3 mos). RESULTS: Of the 3984 patients recruited, 2098 (52.6%) were analyzed after excluding outliers and patients with no available eGFR measurement [male sex: 63.5%; age: 45.3 yrs; disease duration: 8.6 years; HLA-B27+: 73.1%; Bath Ankylosing Spondylitis Activity Index (BASDAI): 3.6/10]. Overall, 153 patients (5.2%, mean age: 53.6 yrs) exhibited an eGFR < 60 ml/min/1.73 m2. In univariate analysis, renal impairment was associated with age (p < 0.001), HLA-B27 positivity (p = 0.003), several cardiovascular (CV) risk factors (history of hypertension, p < 0.001; systolic blood pressure, p = 0.009; diabetes, p = 0.005; and Framingham risk score, p < 0.001), disease activity scores [BASDAI, p = 0.001; Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), p < 0.001], functional variables (Bath Ankylosing Spondylitis Functional Index, p < 0.001), inflammatory biomarkers (erythrocyte and CRP, both p < 0.001), and NSAID intake since onset of disease (percentage of days, p = 0.008). However, there was no association with disease duration, disease severity, or ASAS-NSAID score. In multivariate analysis, age (45-59 yrs: OR 1.9, > 60 yrs: OR 6.2), HLA-B27 positivity (OR 0.51), and CRP (OR 1.3) remained significantly associated with eGFR < 60 ml/min/1.73 m2. CONCLUSION: Renal impairment was associated with age, HLA-B27 positivity, and inflammation, though not with CV risk factors, disease severity, or NSAID intake in patients with SpA.

Survival advantage of planned haemodialysis over peritoneal dialysis: a cohort study.

Background: Previous studies comparing the outcomes in haemodialysis (HD) with those in peritoneal dialysis (PD) have yielded conflicting results. Methods: The aim of the study was to compare the survival of planned HD versus PD patients in a cohort of adult incident patients who started renal replacement therapy (RRT) between 2006 and 2008 in the nationwide REIN registry (Réseau Epidémiologie et Information en Néphrologie). Patients who started RRT in emergency or stopped RRT within 2 months were excluded. Adjusted Cox models, propensity score matching and marginal structural models (MSMs) were used to compensate for the lack of randomization and provide causal inference from longitudinal data with time-dependent treatments and confounders including transplant censorship, modality change over time and time-varying covariates. Results: Among a total of 13 767 dialysis patients, 13% were on PD at initiation of RRT and 87% were on HD. The median survival times were 53.5 months or 4.45 years and 38.6 months or 3.21 years for patients starting on HD and PD, respectively. Regardless of the model used, there was a consistent advantage in terms of survival for HD patients: hazard ratio (HR) 0.76 [95% confidence interval (95% CI) 0.69-0.84] with the Cox model using propensity score; HR 0.67 (95% CI 0.62-0.73) in the Cox model with censorship for each treatment change; and HR 0.82 (95% CI 0.69-0.97) with MSMs. However, MSMs tended to reduce the survival gap between PD and HD patients. Conclusion: This large cohort study using various statistical methods to minimize the bias appears to demonstrate a better survival in planned HD than in PD.

Prevalence of Renal Impairment in Patients With Rheumatoid Arthritis: Results From a Cross-Sectional Multicenter Study.

OBJECTIVE: To assess the prevalence and associations of renal dysfunction in patients with rheumatoid arthritis (RA). METHODS: COMEDRA is a French nationwide cross-sectional multicenter study on comorbidities in RA. Renal function was assessed from the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation. RA characteristics and risk factors for renal impairment were collected. Two logistic regression models, 1 with and 1 without the Framingham Risk Score, were constructed from variables that were significantly associated with an eGFR of <60 ml/minute/1.73 m(2) or were clinically relevant. RESULTS: Of the 970 recruited patients, 931 were analyzed (women 79.6%, mean age 57.8 years, disease duration 11.1 years, Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] 3.1). A total of 82 patients (8.8%) had an eGFR <60 ml/minute/1.73 m(2) and 9% had proteinuria. In univariate analysis, renal impairment was associated with age (P < 0.001), history of hypertension (P < 0.001), high systolic blood pressure (P = 0.03), and the Systematic Coronary Risk Evaluation (SCORE) equation (P = 0.002), but not with sex, disease duration, disease activity (as assessed by DAS28-ESR), nonsteroidal antiinflammatory drug use, disease severity (erosions, joint replacement), or RA medications. Multivariate analysis models showed that age (odds ratio [OR] 1.05 [95% confidence interval (95% CI) 1.03-1.09]) and hypertension (OR 2.5 [95% CI 1.5-4.3]) were associated with renal impairment. A second model showed that the SCORE equation (OR 1.33 [95% CI 1.06-1.67]) was associated with renal impairment. CONCLUSION: Renal impairment is relatively common in RA and is associated with cardiovascular risk factors such as age, hypertension, and the SCORE equation but not with disease activity or severity.

Plasma exchanges for the treatment of severe systemic necrotizing vasculitides in clinical daily practice: Data from the French Vasculitis Study Group.

The use of plasma exchanges (PLEX) in systemic necrotizing vasculitides (SNV) still need to be codified. To describe indications, efficacy and safety of PLEX for the treatment of SNV, we conducted a multicenter retrospective study on patients with ANCA-associated vasculitis (AAV) or non-viral polyarteritis nodosa (PAN) treated with PLEX. One hundred and fifty-two patients were included: GPA (n = 87), MPA (n = 56), EGPA (n = 4) and PAN (n = 5). PLEX were used for rapidly progressive glomerulonephritis (RPGN) in 126 cases (86%), alveolar hemorrhage in 64 cases (42%), and severe mononeuritis multiplex in 23 cases (15%). In patients with RPGN, there was a significant improvement in renal function compared to baseline value (P < 0.0001), the plateau being reached at month 3 after PLEX initiation, and estimated glomerular filtration rate improved especially as the number of PLEX increased. In patients with alveolar hemorrhage, mechanical ventilation was discontinued in all patients after a median time of 15 days. Patients treated for mononeuritis multiplex showed improvement of severe motor weakness. After a median follow of 22 months, 18 deaths (12%) were recorded, mainly in patients with RPGN and within the first 6 months. Incidence of end-stage renal disease and/or death was similar between groups of different baseline renal function, but was increased in MPO-ANCA compared to PR3-ANCA. Adverse events attributable to PLEX were recorded in 63%. No death occurred during PLEX. This large series describes indications, efficacy and safety of PLEX in daily practice. Randomized controlled studies are ongoing to define optimal indications, PLEX regimen and concomitant medications.

Unusual presentation of cytomegalovirus infection in patients after organ transplant.

OBJECTIVES: Cytomegalovirus (CMV) infection has an enormous impact in solid-organ transplant patients. In immunocompromised patients, CMV is associated with well-known direct effects. We herein describe 3 unusual patterns occurring in the setting of tissue-invasive CMV associated with high viral load. MATERIALS AND METHODS: Of our 3 cases, the first patient after kidney transplant presented with cholestasis related to radiological cholangitis; the second patient after heart transplant presented with erythema nodosum with CMV infection as the sole cause; and the third patient after kidney transplant presented with acute renal failure related to mild interstitial nephritis with acute tubular necrosis and tubulitis. RESULTS: The first patient's cholestasis resolved with antiviral therapy, as did the erythema nodosum and CMV infection of the heart transplant patient. The third patient's acute renal failure resolved by increased steroid dosage, plasma exchanges, and ganciclovir therapy. CONCLUSIONS: These 3 unusual presentations of tissue invasive CMV had favorable outcomes with antiviral therapy.