Use of rituximab as an induction therapy in anti-glomerular basement-membrane disease.

BACKGROUND: Anti-glomerular basement-membrane (anti-GBM) disease (or Goodpasture disease) is characterized by severe kidney and lung involvement. Prognoses have improved with treatments that combine plasma exchange and immunosuppressive drugs. However, patients with severe renal involvement can have poor renal outcomes and cyclophosphamide can cause significant complications. Anti-GBM antibodies have a direct pathogenic effect on the disease: thus, therapeutics that can decrease their production, such as rituximab, could be a good alternative. METHODS: The medical files of five patients that had received rituximab as a first-line therapy (instead of cyclophosphamide), plus plasma exchange and steroids, were reviewed. All patients had severe disease manifestations. RESULTS: Four patients required dialysis at diagnosis and remained dialysis-dependent over the mean follow-up of 15 months. Three patients had pulmonary involvement, but recovered even though mechanical ventilation was required. Anti-GBM antibodies became rapidly undetectable in all patients. One infectious and two hematological complications were observed. CONCLUSIONS: We report the outcomes of five patients with Goodpasture disease and treated with rituximab as a first-line treatment. This strategy was effective at treating pulmonary manifestations and was associated with a good biological response with no major serious adverse events. However, renal outcomes were not significantly improved.

Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.

BACKGROUND: There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis. CASE PRESENTATION: A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids. CONCLUSION: We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.

Serum sclerostin: the missing link in the bone-vessel cross-talk in hemodialysis patients?

UNLABELLED: We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients. INTRODUCTION: Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients. METHODS: Fifty-three MHD patients, aged 53 years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above). RESULTS: In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1 ng/mL increase [95 % confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results. CONCLUSIONS: Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients.

Prolonged hemodialysis for acute kidney injury in myeloma patients.

OBJECTIVE: Cast nephropathy, due to free light chain (FLC) toxicity, is the main cause of acute kidney injury in multiple myeloma, with about 10% of patients requiring dialysis. In these patients, in addition to chemotherapy that prevents FLC production, daily hemodialysis using high cutoff or adsorptive membranes, showed promising results by decreasing quickly toxic serum FLC concentrations. CASE HISTORY: We report here the case of 2 patients presenting with acute kidney injury and high FLC serum concentration and M-components one with IgG Kappa and the other with IgD lambda. Both were treated with bortezomib and dexamethasone and received a 24-h continuous hemodialysis using a high and sharp cutoff (around 35,000 Daltons) polysulfone membrane (ultraflux® HD 1000, Fresenius Medical Care GmbH, Bad Homburg, Germany) with citrate regional anticoagulation using a safe and dedicated device (multi filtrate Ci-Ca®). CONCLUSION: Despite similar range of depuration, serum plasma FLC decreased importantly in the patient with the kappa type who recovered but was unchanged in the lambda type patient who remained under maintenance dialysis. Further studies are needed to confirm this new approach therapy.

Body mass index, muscle and fat in chronic kidney disease: questions about survival.

The human body can be roughly divided into two major compartments, fat mass and lean body mass. Adipose tissue is now considered to be a highly active tissue and, in addition to storing calories as triglycerides, it also secretes a large variety of compounds, including cytokines, chemokines and hormone-like factors such as leptin, adiponectin and resistin. On the other hand, muscle plays a central role in whole-body protein metabolism by serving as the principal provider for amino acids to maintain protein synthesis in vital tissues and organs and by providing hepatic gluconeogenic precursors. Although not a good indicator of body composition, the Quetelet index, also called body mass index (BMI), is often used for practical reasons. It is well known that high BMI predicts mortality and cardiovascular disease (CVD) in the general population. However, observational reports in the dialysis population have suggested that obesity is associated with improved survival, a phenomenon that is not well understood and subject to controversies. This review describes the characteristics of BMI in the general population and in chronic kidney disease (CKD) patients, as well as the respective role of muscle, whole body fat and fat distribution towards mortality, with particular emphasis on patients with CKD.

Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects.

BACKGROUND/OBJECTIVES: Consumption of n-3 polyunsaturated fatty acids (PUFA) has a favourable impact on inflammation and cardiovascular disease. However, the Western diet is characterized by a low n-3 PUFA intake and an imbalance in the n-6/n-3 PUFA ratio. Study the effect 10-week of diet modification to decrease the n-6/n-3 PUFA ratio on cardiovascular risk factors and resting energy expenditure. SUBJECTS AND METHODS: Ten-week dietary intervention in 17 healthy subjects. Dietary intake, euglycemic hyperinsulinemic clamp, indirect calorimetry, lipid profile, hormones, inflammatory markers and erythrocyte membrane fatty acid composition were recorded before and at the end of the intervention. Comparisons are between baseline and post-treatment levels. RESULTS: Dietary records of the linoleic acid/alpha-linolenic acid ratio (baseline: 32.2 (s.d. 3.7) vs post-intervention: 2.2 (s.d. 0.1), P<0.0001) and erythrocyte membrane fatty acid composition reflected good compliance. Dietary intervention was associated with significant reductions in TNF-alpha (baseline: 2.2 (s.d. 0.3), post-intervention: 1.5 (s.d. 0.3) pg/ml, P=0.01) and low-density lipoprotein-cholesterol (baseline: 2.5 (s.d. 0.2), post-intervention: 2.3 (s.d. 0.1) mmol/l, P=0.03) and increased adiponectin (baseline: 6.5 (s.d. 0.7), post-intervention: 7.6 (s.d. 0.6) microg/ml, P=0.02). Fasting lipid oxidation was increased (baseline: 0.7 (s.d. 0.1), post-intervention: 0.9 (s.d. 0.1) mg/kg x min, P=0.01), whereas glucose oxidation decreased in both fasting (baseline: 1.6 (s.d. 0.1), post-intervention: 1.3 (s.d. 0.1) mg/kg x min, P=0.02) and hyperinsulinaemic conditions (baseline: 3.6 (s.d. 0.1), post-intervention: 3.3 (s.d. 0.1) mg/kg x min, P=0.04). Insulin sensitivity was not affected by the intervention. CONCLUSION: A decreased n-6/n-3 PUFA ratio can be achieved with simple dietary counselling, resulting in multiple, potentially favourable effects on the metabolic and inflammatory profiles.

ICU survival and need of renal replacement therapy with respect to AKI duration in critically ill patients.

BACKGROUND: Transient and persistent acute kidney injury (AKI) could share similar physiopathological mechanisms. The objective of our study was to assess prognostic impact of AKI duration on ICU mortality. DESIGN: Retrospective analysis of a prospective database via cause-specific model, with 28-day ICU mortality as primary end point, considering discharge alive as a competing event and taking into account time-dependent nature of renal recovery. Renal recovery was defined as a decrease of at least one KDIGO class compared to the previous day. SETTING: 23 French ICUs. PATIENTS: Patients of a French multicentric observational cohort were included if they suffered from AKI at ICU admission between 1996 and 2015. INTERVENTION: None. RESULTS: A total of 5242 patients were included. Initial severity according to KDIGO creatinine definition was AKI stage 1 for 2458 patients (46.89%), AKI stage 2 for 1181 (22.53%) and AKI stage 3 for 1603 (30.58%). Crude 28-day ICU mortality according to AKI severity was 22.74% (n = 559), 27.69% (n = 327) and 26.26% (n = 421), respectively. Renal recovery was experienced by 3085 patients (58.85%), and its rate was significantly different between AKI severity stages (P < 0.01). Twenty-eight-day ICU mortality was independently lower in patients experiencing renal recovery [CSHR 0.54 (95% CI 0.46-0.63), P < 0.01]. Lastly, RRT requirement was strongly associated with persistent AKI whichever threshold was chosen between day 2 and 7 to delineate transient from persistent AKI. CONCLUSIONS: Short-term renal recovery, according to several definitions, was independently associated with higher mortality and RRT requirement. Moreover, distinction between transient and persistent AKI is consequently a clinically relevant surrogate outcome variable for diagnostic testing in critically ill patients.

[Metabolic consequences of inflammation in kidney failure]. / Conséquences métaboliques de l'inflammation au cours des néphropathies.

Chronic inflammation is very common in patients on maintenance dialysis. It is associated with an increase of many cytokines (especially: IL-1, IL-6 and TNF alpha). This inflammation leads to hormonal dysregulation (leptin, adiponectin, insulin). Increase in cytokines is associated with a high cardio-vascular morbi-mortality for general population as well as for uremic patients. Many metabolic abnormalities are due to chronic inflammation: protein catabolism, anorexia and many others. Among them, the "metabolic" syndrome includes adiposis, dyslipemia, insulinoresistance and high blood pressure very often present in chronic uremic patients. It is still unknown whether anti-inflammatory treatments would improve inflammation consequences in dialysis.