Fine-tuned continuous renal replacement therapy with calcium-free dialysate to manage severe hypercalcemia refractory to medical and intermittent hemodialysis.

Malignancy-related hypercalcemia is a leading cause of hypercalcemia among hospitalized patients that carries poor prognosis. Parathyroid carcinoma is a rare form of primary hyperparathyroidism that may be associated with PTH dependent hypercalcemia. Severe hypercalcemia is life-threatening and may require management in an intensive care unit by means of medical therapy consisting of volume expansion, loop diuretics, cinacalcet, calcitonin and bisphosphonates. Renal replacement therapy such as intermittent hemodialysis has been successfully used among patients with severe hypercalcemia who become refractory to medical treatment. However, little data are available for cases of severe refractory hypercalcemia that fail to respond to both optimal medical therapy and hemodialysis. Our present case illustrates the successful use of continuous veno-venous hemodiafiltration (CVVHDF) with calcium-free dialysate calcium and markedly increased dialysate flow rate, to restore normal calcemia in a patient with metastatic parathyroid carcinoma with severe refractory hypercalcemia.

Glycine increases fat-free mass in malnourished haemodialysis patients: a randomized double-blind crossover trial.

BACKGROUND: Protein energy wasting is associated with negative outcome in patients under chronic haemodialysis (HD). Branched-chain amino acids (BCAAs) may increase the muscle mass. This post hoc analysis of a controlled double-blind randomized crossover study assessed the impact of BCAAs on nutritional status, physical function, and quality of life. METHODS: We included 36 chronic HD patient features of protein energy wasting as plasma albumin <38 g/L, and dietary intakes <30 kcal/kg/day and <1 g protein/kg/day. Patients received either oral BCAA (2 × 7 g/day) or glycine (2 × 7 g/day) for 4 months (Period 1), followed by a washout period of 1 month, and then received the opposite supplement (Period 2). The outcomes were lean body mass measured by dual-energy X-ray absorptiometry, fat-free mass index measured by bioelectrical impedance, resting energy expenditure, dietary intake and appetite rating, physical activity and function, quality of life, and blood parameters. Analyses were performed by multiple mixed linear regressions including type of supplementation, months, period, sex, and age as fixed effects and subjects as random intercepts. RESULTS: Twenty-seven patients (61.2 ± 13.7 years, 41% women) were compliant to the supplementations (consumption >80% of packs) and completed the study. BCAA did not affect lean body mass index and body weight, but significantly decreased fat-free mass index, as compared with glycine (coeff -0.27, 95% confidence interval -0.43 to -0.10, P = 0.002, respectively). BCAA and glycine intake had no effect on the other clinical parameters, blood chemistry tests, or plasma amino acids. CONCLUSIONS: Branched-chain amino acid did not improve lean body mass as compared with glycine. Unexpectedly, glycine improved fat-free mass index in HD patients, as compared with BCAA. Whether long-term supplementation with glycine improves the clinical outcome remains to be demonstrated.

Gut barrier and microbiota changes with glycine and branched-chain amino acid supplementation in chronic haemodialysis patients.

BACKGROUND: We have previously shown that glycine increases fat-free mass in chronic haemodialysis patients with features of malnutrition as compared with branched-chain amino acids (BCAAs). This multicentre randomized double-blind crossover study evaluates the impact of these amino acids on the gut barrier and microbiota. METHODS: Haemodialysis patients were included if they had plasma albumin <38 g/L or weight loss >5% of dry body weight, and daily dietary intakes <30 kcal/kg and <1 g protein/kg. They consumed glycine or BCAA (7 g twice daily) for 4 months and underwent a 1 month washout period, before crossover of supplementations. Faecal microbiota (16S rRNA gene sequencing) and immunoglobulin A (IgA), serum levels of cytokines, surrogate markers of intestinal permeability, appetite mediators, and endocannabinoids were obtained at the start and end of each supplementation. Supplementations were compared by multiple mixed linear regression models, adjusted for age, sex, month of supplementation (0 and 4 in each period), and period (Period 1: first 4 months; Period 2: last 4 months). Microbiota comparisons were performed using principal coordinate analysis and permutational multivariate analysis of variance, Shannon diversity index estimate and analysis of composition of microbiomes analysis, and Wilcoxon tests. RESULTS: We analysed 27 patients compliant to the supplementations. Multiple mixed linear regression models were significant only for interleukin-6 (P = 0.002), glucagon-like peptide 1 (P = 0.028), cholecystokinin (P = 0.021), and peptide YY (P = 0.002), but not for the other outcomes. The significant models did not show any impact of the type of supplementation (P < 0.05 in all models). Principal coordinate analysis and permutational multivariate analysis of variance (P = 0.0001) showed strong microbiota clustering by subject, but no effect of the amino acids. Bacterial alpha diversity and zero-radius operational taxonomic unit richness remained stable, whatever the supplementation. Lacticaseibacillus paracasei (0.030; Q1-Q3 0.008-0.078 vs. 0.004; Q1-Q3 0.001-0.070) and Bifidobacterium dentium (0.0247; Q1-Q3 0.002-0.191 vs. 0.003; Q1-Q3 0.001-0.086) significantly decreased with the BCAA supplementation. CONCLUSIONS: The BCAA and glycine supplementations had no impact on the serum levels of cytokines, appetite mediators, intestinal permeability, endocannabinoids, or faecal IgA. Overall faecal microbiota composition and microbial diversity did not change with the glycine or BCAA supplementation but decreased the abundance of L. paracasei and B. dentium.

Eculizumab as a New Treatment for Severe Acute Post-infectious Glomerulonephritis: Two Case Reports.

Acute post-infections glomerulonephritis (APIGN) is a frequent cause of glomerulonephritis and represents the most common cause of acute glomerulonephritis in children. It can evolve to severe acute renal failure and chronic kidney disease or even end-stage kidney disease. The precise pathophysiological mechanisms of APIGN are still incompletely understood. The implication of the alternative complement pathway and the potential benefits of C5 blockade have been recently highlighted, in particular in the presence of a C3 Nephritic Factor (C3Nef), anti-Factor B or H autoantibodies. We report two children with severe APIGN, successfully treated with eculizumab. The first patient presented a severe form of APIGN with advanced renal failure and anuria, associated with a decreased level of C3 and an increased level of soluble C5b-9, in the presence of a C3NeF autoantibody. The second case had a severe oliguric APIGN associated with low C3 level. Kidney biopsy confirmed the diagnosis of APIGN in both cases. Eculizumab allowed full renal function recovery and the avoidance of dialysis in both cases. In conclusion, the alternative and terminal complement pathways activation might be common in PIGN, and in severe cases, eculizumab might help.

Case Report: A Rare Truncating Variant of the CFHR5 Gene in IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Despite appropriate therapy, 20-40% of affected-patients evolve toward end-stage kidney disease (ESKD). Mesangial IgA deposits are the hallmark of IgAN, and complement deposition (C3) seems to differentiate latent IgA mesangial deposits from active IgAN. Atypical hemolytic uremic syndrome (aHUS), another disease in which complement plays an important role, is caused by inherited or acquired deregulation of the alternative pathway (AP) of complement. A subgroup of IgAN shows thrombotic microangiopathy (TMA) lesions in kidney biopsies, the histological characteristic of aHUS. Genetic variants of complement Factor H (CFH), known to be present in aHUS, have been associated with rapidly progressive forms of IgAN and a clinical pattern of aHUS. Genome-wide association studies (GWAS) have confirmed that the 1q32 region, encoding for CFH and its related proteins, is an IgAN susceptibility locus. A 30 year-old man was admitted for seizures and malignant hypertension. The kidney biopsy showed IgAN associated with features of TMA. Despite five plasma exchanges, the patient remained dialysis-dependent, and ESKD was diagnosed. Functional and genetic complement analysis were performed. A monoallelic protein-truncating, likely loss-of-function variant was identified in the CFHR5 gene. Eculizumab is the treatment of aHUS. As it has been successfully used in a few cases of rapidly progressive IgAN, it was decided to administer eculizumab over a period of 12 months in addition to the usual immunosuppression for renal transplantation. After a follow-up of 3 years, there was no clinical disease recurrence. Systematic biologic and genetic screening of complement in individuals with IgAN might be useful to better delineate the role of the AP of complement in renal disease progression, and this may have therapeutic implications.

Phenotypes influencing low physical activity in maintenance dialysis.

OBJECTIVE: The "Pas à Pas" initiative aimed at evaluating the weekly physical activity (PA) and its determinants in a large cohort of dialysis patients. SETTING: Physical inactivity is a risk factor for mortality in maintenance dialysis patients and is still poorly documented in this population. DESIGN: A prospective national epidemiological study was performed. SUBJECTS: A total of 1,163 patients on maintenance dialysis (hemodialysis and peritoneal dialysis) were included. INTERVENTION AND MAIN OUTCOME MEASURE: PA was recorded during seven consecutive days using a pedometer to measure daily step numbers. RESULTS: Median age was 63 years (Q1 51-Q3 75). Sixty-three percent were sedentary (<5000 steps/day) with a median of 3,688 steps/day (1,866-6,271)]. PA level was similar between hemodialysis patients and those on peritoneal dialysis (3,693 steps [1,896-6,307] vs. 3,320 [1,478-5,926], P = .33). In hemodialysis patients, PA was lower on dialysis days compared with nondialysis days (2,912 [1,439-5,232] vs. 4,054 [2,136-7,108], respectively, P < .01). PA gradually decreased with age, 57% being sedentary between 50 and 65 years and 83% of patients after 80 years. Beyond this age effect, we identified, for the first time, specific phenotypes of patients with lower PA, such as inflammation, cardiovascular disease, protein energy wasting, obesity, and diabetes. By contrast, previous kidney transplantation and a higher muscle mass were associated with higher PA. CONCLUSIONS: Dialysis patients present a very low level of PA with high sedentary. Acting on patient's modifiable phenotypes may help to increase PA to improve morbidity, mortality, and quality of life.

Fish oil for prevention of sudden death in hemodialysis patients?

Friedman et al. report that hemodialysis patients with the highest levels of n-3 fatty acids had impressively low odds of sudden cardiac death. The study is limited by a small sample size, and the analysis relies on only a single baseline measurement of blood levels. Recent randomized evidence indeed fails to support that n-3 fatty acids may prevent sudden death in nonrenal patients. More evidence is needed to advocate fish oil in this setting.

High prevalence of anti-apolipoprotein/A-1 autoantibodies in maintenance hemodialysis and association with dialysis vintage.

Autoantibodies to apolipoprotein/A-1 (anti-ApoA-1 IgG) have pro-atherogenic properties in patients at high cardiovascular risk, but its prevalence in patients with end-stage kidney disease is unknown. The aims of this single-center, cross-sectional study were to assess the prevalence of anti-ApoA-1 antibodies in patients on maintenance hemodialysis (MHD), and to examine its correlation with inflammatory biomarkers related to atherosclerotic plaque vulnerability and dialysis vintage. To this purpose, anti-ApoA-1 IgG levels and the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), metalloproteinase-9 (MMP-9), tumor necrosis factor-α, and C-reactive protein (CRP) were assessed in the sera of 66 MHD patients (mean age: 68 ± 14 years, 36% women, 32% diabetics). Anti-ApoA-1 IgG positivity (defined as a blood value ≥ 97.5(th) percentile of the normal distribution as assessed in healthy blood donors) was 20%. Circulating levels of anti-ApoA-1 IgG correlated positively with dialysis vintage, but not with cardiovascular risk factors or previous cardiovascular events; no significant correlations were found between the anti-ApoA1 IgG levels and circulating levels of IL-6, IL-8, MCP-1, MMP-9, CRP, or low-density lipoprotein-cholesterol. In multivariable linear regression, adjusted for age and sex, only dialysis vintage remained positively and independently associated with anti-ApoA-1 titers (ß = 0.05, 95% CI: 0.006; 0.28, P = 0.049). In conclusion, the prevalence of anti-ApoA-1 IgG is raised in the MHD-population, and positively associated with dialysis vintage, a major determinant of cardiovascular outcome. Whether antiApoA-1 antibodies play a role in the pathophysiology of accelerated atherosclerosis in the MHD-population merits further study.

Adipokines as uremic toxins.

The adipose tissue has pleiotropic functions far beyond the mere storage of energy, and it secretes a number of hormones and cytokines, called adipokines, which have biological effects that impact heath and disease. Adipokines are markedly elevated in the plasma of uremic patients, mainly due to decreased renal excretion. They have pluripotent signaling effects on inflammation/oxidative stress (leptin, adiponectin, resistin), protein-energy wasting (leptin, adiponectin), insulin signaling (adiponectin, leptin, visfatin), endothelial dysfunction (visfatin), and vascular damage (adiponectin, leptin, resistin), which are prevalent in uremic patients. Obesity superimposed to uremia may further aggravate hyperadipokinemia, with the exception of adiponectinemia, which is mitigated by adiposity. Among adipokines and until more data become available, only leptin may be considered as a full uremic toxin owing to adverse effects on protein-energy wasting, cardiovascular damage, inflammation, and the immune system, which have been documented both clinically and experimentally. Resistin and visfatin display some features of uremic toxins, but more data are needed to consider these adipokines as true uremic toxins. In contrast, high levels of adiponectin and chemerin seen in uremia appear to be beneficial. Further research is needed to investigate whether selective removal of leptin, resistin, and visfatin and increments of adiponectin and chemerin levels may have clinical relevance in uremic patients.

Influence of inflammation on total energy expenditure in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Studies show that inflammation can contribute to an increase in resting energy expenditure in patients with chronic kidney disease; however, findings about total energy expenditure (TEE) have not been reported. The aim of this study was to evaluate the effects of inflammation on TEE and physical activity energy expenditure in hemodialysis (HD) patients. DESIGN: This was a cross-sectional study. SETTING: This study was conducted from Hôpital Edouard Herriot, Lyon, France. PATIENTS: This study included 24 HD patients and 18 healthy subjects. MAIN OUTCOME MEASURE: TEE and step counts were measured over a 7-day period by the SenseWear Pro2 Armband in 24 HD patients (15 patients with C-reactive protein <5 mg/L, aged 67.0 ± 14.7 years, and 9 with C-reactive protein >5 mg/L, aged 69.0 ± 18.0 years) and compared with 18 healthy subjects (62.3 ± 15.3 years). RESULTS: Mean estimated TEE measured with SenseWear Pro2 Armband was significantly lower (25.5 ± 4.1 kcal/kg/day) in patients with inflammation when compared with those without inflammation (32.0 ± 6.7 kcal/kg/day) and with healthy subjects (31.8 ± 7.0 kcal/kg/day) (P = .012). There was a difference in the physical activity (step counts) between patient groups (P < .05). Healthy subjects and patients without inflammation walked more (8,107 ± 5,419 and 6,016 ± 3,752 steps/day, respectively) as compared with patients with inflammation (2,801 ± 2,754 steps/day, P = .001). CONCLUSION: Our findings suggest that patients with inflammation have a lower TEE when compared with healthy subjects and patients without inflammation. TEE is influenced by physical activity because patients with inflammation appear to be less active.

Weight loss in obese patients with chronic kidney disease: who and how?

Obesity has adverse consequences in the general population. In patients with chronic kidney disease (CKD), it is associated with increased inflammation, insulin resistance, hypertension and dyslipidaemia, which are important risk factors for CKD progression and death. In adults with CKD stages 1-4, weight loss should be encouraged, it reduces proteinuria and glomerular hyperfiltration, which are frequent in obese patients. Proposals for modifications of lifestyle, physical activity and calorie restriction are the first measures. Pharmacological treatments are generally unsafe in these patients, except orlistat, but that has modest efficacy. Bariatric surgery may be the only option in severe obesity, if all other measures fail. For obese patients on dialysis treatment, who are eligible for kidney transplantation, weight loss is mandatory to prevent obesity-related surgical complications and improve patient and graft survival after transplantation. Interventions should place an emphasis on exercise to increase muscle mass, and calorie but not protein restriction. Bariatric surgery should be carried out by experienced surgeons due to the high risk of complications. For obese patients who are not considered transplant candidates the benefits of weight loss remain uncertain.

[Severe renal insufficiency secondary to renal cholesterol emboli: therapeutical options revisited]. / Insuffisance rénale severe sur maladie des emboles de cholestérol: controverses thérapeutiques revisitées.

Disseminated cholesterol crystal embolism is observed in elderly men with severe atherosclerosis. This syndrome may be triggered by arterial catheterizations, major vascular surgery, thrombolytic and/or anticoagulation treatment. Cutaneous signs, subacute renal insufficiency, a marked inflammatory syndrome and eosinophilia are common. Immunologic testing is normal except for hypocomplementaemia. The diagnosis may be confirmed by biopsy (skin, gastrointestinal or renal), and/or by a fundoscopic examination. The treatment consists in withdrawing all form of anticoagulation, proscribing vascular surgery and arterial catheterization, prescribing aspirin and statins, and controlling arterial blood pressure. Corticosteroids may be given in refractory cases. The prognosis of cholesterol crystal embolism is poor but may be improved by statins.

New measurements of energy expenditure and physical activity in chronic kidney disease.

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.