Impact of First Wave COVID-19 Crisis on Dialysis Parameters of COVID-Free Hemodialysis Patients: A NephoCare France Longitudinal Retrospective Cohort Study.

BACKGROUND: Chronic hemodialysis (HD) patients are at high risk of severe COVID-19 with a high risk of death. The organization of dialysis units to treat chronic HD patients with COVID-19 is demanding to prevent virus transmission both in COVID-free patients and the staff. These constraints may have an impact on the dialysis delivery to COVID-free HD patients. We report our experience in French NephroCare (NC) centers. METHODS: We report retrospectively dialysis and nutritional indicators among COVID-free prevalent chronic HD patients' cohort treated in French NC units from February 2020 to April 2020. The COVID-free HD patients were split into 2 subgroups for the analysis, Paris region and other regions because the incidence of COVID-19 was different according to the French regions. RESULTS: The Paris region was the most impacted by COVID-19 with 73% of all the contaminations that occurred in French NC units (n = 118). The dialysis frequency was not reduced all over the NC regions. 2,110 COVID-free HD patients were split into 2 subgroups including Paris region (748 patients) and other regions (1,362 patients). The weekly treatment time decreased significantly in Paris region from February to April (723-696 min [p < 0.00001]) but remained stable in the other regions. The processed blood volume, KT/V, and convective volume declined significantly in the Paris region subgroup but not in other regions. The 3-month weight loss significantly increased in the whole group of patients whatever the region from 0.0 to 0.2% between February 2020 and April 2020 (p < 0.00001). Ultrafiltration rate (UFR) and the normalized proteic catabolic rate remained stable all along the period. The stepwise regression analysis identified February serum albumin level and April UFR as negatively associated with 3-month weight loss. CONCLUSION: HD delivery to COVID-free HD patients was negatively impacted in the Paris region because of the strong constraints on units' organization related to the treatment of COVID-19+ HD patients and with a higher proportion of limited care/self-care units with less staff resources. The 3-month weight loss increase may be related to the suppression of intradialytic snack that impacted mostly the more malnourished patients or patients with lower interdialytic weight gain. These consequences of the COVID-19 crisis on COVID-free HD patients must be recognized and corrected to prevent further deleterious effects on patients' outcomes.

Is high-volume post-dilution haemodiafiltration associated with risk of fluid volume imbalance? A national multicentre cross-sectional cohort study.

BACKGROUND: Fluid overload is frequent among hemodialysis (HD) patients. Dialysis therapy itself may favor sodium imbalance from sodium dialysate prescription. As on-line hemodiafiltration (OL-HDF) requires large amounts of dialysate infusion, this technique can expose to fluid accumulation in case of a positive sodium gradient between dialysate and plasma. To evaluate this risk, we have analyzed and compared the fluid status of patients treated with HD or OL-HDF in French NephroCare centers. METHOD: This is a cross-sectional and retrospective analysis of prevalent dialysis patients. Data were extracted from the EUCLID5 data base. Patients were split in 2 groups (HD and OL-HDF) and compared as whole group or matched patients for fluid status criteria including predialysis relative fluid overload (RelFO%) status from the BCM®. RESULTS: 2242 patients (age 71 years; female: 39%; vintage: 38 months; Charlson index: 6) were studied. 58% of the cohort were prescribed post-dilution OL-HDF. Comparing the HD and OL-HDF groups, there was no difference between HD and OL-HDF patients regarding the predialysis systolic BP, the interdialytic weight gain, the dialysate-plasma sodium gradient, and the predialysis RelFO%. The stepwise logistic regression did not find dialysis modality (HD or OL-HDF) associated with fluid overload or high predialysis systolic blood pressure. In OL-HDF patients, monthly average convective or weekly infusion volumes per session were not related with the presence of fluid overload. CONCLUSIONS: In this cross-sectional study we did not find association between the use of post-dilution OL-HDF and markers of fluid volume excess. Aligned dialysis fluid sodium concentrations to patient predialysis plasma sodium and regular monitoring of fluid volume status by bioimpedance spectroscopy may have been helpful to manage adequately the fluid status in both OL-HDF and HD patients.

Early changes in body weight and blood pressure are associated with mortality in incident dialysis patients.

BACKGROUND: While much research is devoted to identifying novel biomarkers, addressing the prognostic value of routinely measured clinical parameters is of great interest. We studied early blood pressure (BP) and body weight (BW) trajectories in incident haemodialysis patients and their association with all-cause mortality. METHODS: In a cohort of 357 incident patients, we obtained all records of BP and BW during the first 90 days on dialysis (over 12 800 observations) and analysed trajectories using penalized B-splines and mixed linear regression models. Baseline comorbidities and all-cause mortality (median follow-up: 2.2 years) were obtained from the French Renal Epidemiology and Information Network (REIN) registry, and the association with mortality was assessed by Cox models adjusting for baseline comorbidities. RESULTS: During the initial 90 days on dialysis, there were non-linear decreases in BP and BW, with milder slopes after 15 days [systolic BP (SBP)] or 30 days [diastolic BP (DBP) and BW]. SBP or DBP levels at dialysis initiation and changes in BW occurring in the first month or during the following 2 months were significantly associated with survival. In multivariate models adjusting for baseline comorbidities and prescriptions, higher SBP value and BW slopes were independently associated with a lower risk of mortality. Hazard ratios of mortality and 95% confidence intervals were 0.92 (0.85-0.99) for a 10 mmHg higher SBP and 0.76 (0.66-0.88) for a 1 kg/month higher BW change on Days 30-90. CONCLUSIONS: BW loss in the first weeks on dialysis is a strong and independent predictor of mortality. Low BP is also associated with mortality and is probably the consequence of underlying cardiovascular diseases. These early markers appear to be valuable prognostic factors.

Cardiovascular risk stratification in hemodialysis patients in the era of highly sensitive troponins: should we choose between hs-troponin I and hs-troponin T?

BACKGROUND: New highly sensitive (hs) assays have challenged the interpretation of cardiac troponins (cTn). The present study was designed to evaluate simultaneously conventional cTnT and cTnI together with their corresponding highly sensitive determinations in stable hemodialysis (HD) patients. Ability of cTn to stratify HD patient risk was assessed. METHODS: A total of 224 stable HD patients was included in this observational study. cTnT and hs-cTnT were measured using Roche cTnT/hs-cTnT assays based on a Cobas e601® analyzer. cTnI and hs-cTnI were measured using Beckman AccuTnI/hs-TnI IUO assays on Access II system. Patients were followed up prospectively during 9 years. Relationship between cTn level and mortality was assessed through Cox survival analysis. RESULTS: The median cTnT and cTnI concentrations were 38.5 ng/L (IQR, 18.8-76) and 10 ng/L (IQR, 10-20), respectively. The median hs-cTnT and hs-cTnI concentrations were 62.5 ng/L (IQR, 38.8-96.3) and 13.9 ng/L (IQR, 8.4-23.6), respectively. The prevalence of values above the 99th percentile was significantly more marked with cTnT (85.3 and 97.8% for conventional and hs cTnT, respectively) than with cTnI (7.6 and 67.4% for conventional and hs cTnI, respectively). During the follow-up, 167 patients died, mainly from cardiac cause (n=77). The optimized cut-off values, determined by bootstrap method, predicting mortality were 38, 69, 20 and 11 ng/L for cTnT, hs-cTnT, cTnI and hs-cTnI, respectively. After full adjustment, elevated plasma concentrations of all troponin were significant predictors of mortality. CONCLUSIONS: A large proportion of patients free of acute coronary syndrome (ACS) has hs-cTn I or T higher than the 99th percentile which could be seen as a limiting factor for ACS screening. However, all generation and type of troponin assays could be reliable indicators of prognosis risk in HD patients.

The PPARgamma agonist pioglitazone ameliorates aging-related progressive renal injury.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against nondiabetic chronic kidney disease in experimental models. Here, we found that the PPAR-gamma agonist pioglitazone protected against renal injury in aging; it reduced proteinuria, improved GFR, decreased sclerosis, and alleviated cell senescence. Increased local expression of PPAR-gamma paralleled these changes. Underlying mechanisms included increased expression of klotho, decreased systemic and renal oxidative stress, and decreased mitochondrial injury. Pioglitazone also regulated p66(Shc) phosphorylation, which integrates many signaling pathways that affect mitochondrial function and longevity, by reducing protein kinase C-beta. These results suggest that PPAR-gamma agonists may benefit aging-related renal injury by improving mitochondrial function.

[Glomerular lesions in adult patients]. / Lésions élémentaires des glomérules chez l'adulte.

Classification of glomerular nephropathies is based on the histopathological analysis of a bioptic sample of renal parenchyma. The present article reviews successively the morphological features of normal glomerulus, the various glomerular lesions and main clinicopathological entities.

Complications, effects on dialysis dose, and survival of tunneled femoral dialysis catheters in acute renal failure.

BACKGROUND: Availability of a functional vascular access is a mandatory prerequisite for extracorporeal renal replacement therapy in patients with acute renal failure. The femoral site of insertion commonly is chosen because it is an easy and convenient access. However, an array of complications may substantially alter the quality of treatment, and it appears that catheter-related morbidity and dysfunction are more frequent with the femoral than internal jugular site. This study is designed to evaluate the potential benefits of using soft silicone tunneled catheters ((ST)Caths) at the femoral site. METHODS: Thirty patients with acute renal failure treated by intermittent hemodialysis (IHD) and/or continuous venovenous hemodiafiltration (CVVHDF) were assigned to either twin (ST)Caths or twin polyurethane nontunneled femoral catheters. Time necessary for catheter insertion, catheter-related complications, and catheter lifespan were monitored. Catheter performance during IHD and the effect of catheter type on dialysis dose were evaluated. RESULTS: The time necessary for (ST)Cath insertion was significantly longer. The incidence of vein thrombosis and catheter-related infection was lower, and the ratio of venous return pressure to catheter blood flow was better with an (ST)Cath. Recirculation rates were similar for both types of catheters. Whether treated by using IHD or CVVHDF, patients with an (ST)Cath benefited from a greater delivered dialysis dose. Multivariate analysis confirmed that (ST)Cath use was a determinant factor to optimize dialysis dose delivery. (ST)Cath patency was significantly longer. CONCLUSION: In patients with acute renal failure, use of an (ST)Cath minimizes catheter-related morbidity and improves dialysis efficiency compared with conventional femoral catheters.

Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism.

BACKGROUND: Persistent hyperparathyroidism (HPT) is observed in approximately 50% of kidney transplant recipients one year after transplantation. It may result in hypercalcemia, hypophosphatemia, bone demineralization, vascular calcification, lithiasis, and participate in chronic allograft nephropathy. We evaluated the use of the calcimimetic cinacalcet chloride to correct chronic hypercalcemia in posttransplant HPT, in a prospective single-center study. METHODS: Nine patients with persistent hypercalcemia (>2.6 mmol/L) and stable graft function were treated with cinacalcet (30 mg/day, thereafter adapted to obtain normal serum Ca levels) for six months. Their immunosuppressive schedule included mycophenolate mofetil (MMF), steroids, and cyclosporine A (4), tacrolimus (4), or sirolimus (2). RESULTS: Serum Ca levels significantly decreased from 2.75+/-0.15 to 2.59+/-0.10, 2.42+/-0.29 and 2.44+/-0.25 mmol/L by one, two, and six months, respectively (P<0.02, Wilcoxon test for paired data, for all the data points). Parathyroid hormone (PTH) serum levels decreased from 171+/-102 to 134+/-63 pg/ml by two months (P<0.05) and stabilized thereafter (148+/-99 pg/ml at six months; NS). No changes in glomerular filtration rate (49.8+/-18.6 and 51.3+/-19 ml/min at initiation and six months, respectively) and no variation in serum concentration of the immunosuppressive drugs were observed. Three patients withdrew the treatment because gastrointestinal intolerance. CONCLUSION: Cinacalcet allows the correction of hypercalcemia with no interference in immunosuppressive treatment or renal function. However, whether the increased intolerance observed was due to the association of cinacalcet chloride with other drugs required in renal transplantation (e.g., MMF) needs to be assessed.

[Delayed graft function: a frequent but still unsolved problem in renal transplantation]. / La reprise retardée de fonction: une complication fréquente, non résolue, en transplantation rénale.

Delayed graft function (DGF) is a frequent and well-known complication of renal transplantation, which occurs in 30% of cadaver kidney allografts. It has an economic cost that is the result of prolonged patient hospitalization and the need for hemodialysis sessions; it also increases the risk of acute allograft rejection and may affect long-term graft survival. Lots of risk factors were identified, like donor hemodynamic compromise or prolonged cold ischemia time; however, incidence of DGF remains high due to the frequent use of marginal donors due to organ shortage. Recent advances in the pathophysiology of DGF point the importance of the ischemia-reperfusion injury mechanisms and some therapeutics that may reduce them are under investigation, like the use of new solutions to improve organ preservation and the use of some antioxidant and anti-inflammatory drugs.