Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients.

There is no established treatment for progressive IgA nephropathy refractory to steroids and immunosuppressant drugs (r-IgAN). Interleukin 17 (IL-17) blockade has garnered interest in immune-mediated diseases involving the gut-kidney axis. However, single IL-17A inhibition induced paradoxical effects in patients with Crohn's disease and some cases of de novo glomerulonephritis, possibly due to the complete Th1 cell response, along with the concomitant downregulation of regulatory T cells (Tregs). Seven r-IgAN patients were treated with at least six months of oral paricalcitol, followed by the addition of subcutaneous anti-IL-17A (secukinumab). After a mean follow-up of 28 months, proteinuria decreased by 71% (95% CI: 56-87), P < 0.001. One patient started dialysis, while the annual eGFR decline in the remaining patients [mean (95% CI)] was reduced by 4.9 mL/min/1.73 m2 (95% CI: 0.1-9.7), P = 0.046. Circulating Th1, Th17, and Treg cells remained stable, but Th2 cells decreased, modifying the Th1/Th2 ratio. Intriguingly, accumulation of circulating Th17.1 cells was observed. This novel sequential therapy appears to optimize renal advantages in patients with r-IgAN and elicit alterations in potentially pathogenic T helper cells.

Monthly Continuous Erythropoietin Receptor Activator Versus Weekly Epoetin-Beta, Similar Hemoglobinization but Different Anisocytosis Degree in Hemodialysis Patients: A Randomized Controlled Trial.

BACKGROUND: The monthly continuous erythropoietin receptor activator (CERA) utilization maintains stable hemoglobin (Hb) after conversion from weekly epoetin-ß (EB); however, how the different pharmacologic properties affect the red blood cell (RBC) size determined by RBC distribution width (RDW) has not been evaluated yet. We assess the potential differences in iron metabolism, plasma erythropoietin (EPO), hepcidin, and soluble α-Klotho (α-Klotho) levels as an emergent hematopoiesis factor. METHODS: Thirty-seven chronic hemodialysis patients were included from January 2010 to November 2011 and randomized (1:1) to continue with EB or to convert to monthly CERA. Primary outcome was the mean change in Hb between groups at months 0, 3 and 6, and the percentage of patients who maintained stable Hb (Hb ± 1 g/dL from baseline level to month 6). Secondary outcomes were the influence on the erythropoietic process and iron metabolism markers. Thirty-one patients completed the study (CERA: n = 15, EB: n = 16). RESULTS: The mean (95% confidence interval (CI)) Hb difference between groups was 0.28 g/dL (-0.36 to 0.93). There was no difference between the percentages of patients with stable Hb levels. In the CERA group RDW values increased progressively (interaction erythropoietin-stimulating agent (ESA) type and time on RDW values, F (1.57, 45.60) = 17.17, P < 0.01, partial η2 = 0.37) and the mean corpuscular volume changed at the different time points, (F (2, 28) = 29.12, P = 0.03, partial η2 = 0.23). During the evaluation period, in the CERA group, EPO was higher, and hepcidin and ferritin decreased significantly. α-Klotho decreased in both groups and correlated negatively with the changes on the RDW and positively with transferrin and serum iron. The number of serious adverse events was higher at the CERA group. CONCLUSIONS: Monthly CERA maintained Hb concentrations; however, it showed a significant effect on RDW, probably due to its impact on the EPO and hepcidin levels. α-Klotho decreased significantly in both groups, and its changes correlated with the changes in iron metabolism. Whether the RDW evolution was associated with the serious adverse events (SAEs) is a feasible hypothesis that needs to be confirmed in large studies.

Impact of a multidisciplinary team for the management of thrombotic microangiopathy.

BACKGROUND: Thrombotic microangiopathy (TMA) is an important complication associated with several diseases that are rare and life-threatening. TMA is common to thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP is defined by a severe deficiency of ADAMTS13, and early treatment is associated with good prognosis. The diagnosis of HUS can be difficult due to the potential multiple etiologies, and the best treatment option in most cases is not well-established yet. The implementation of a multidisciplinary team (MDT) could decrease the time to diagnosis and treatment for HUS and may improve the outcomes of these patients. OBJECTIVE: To determine the impact of MDT on morbidity and mortality [death or chronic renal replacement therapy (CRRT) requirements], incidence and response time [(RT) defined as the period between hospital admission and the first day of direct therapy administration], length of stay at an intensive care unit (ICU-LOS) and total hospitalization (T-LOS) were also assessed. METHODS: We compared a pre-MDT implementation period (from January/2008 to May/2016) versus post-MDT period (from May/2016 to December/2016). The screening TMA diagnosis was made according the following criteria: hemolytic anemia, thrombocytopenia and acute renal damage and without ADAMTS13 deficiency. An online chat was implemented to provide instant medical information. RESULTS: Twenty-eight patients were included. The incidence changed from 2.3 cases/pre-MDT: (all cases: n = 18) to 10 cases/year post-MDT (all cases: n = 10). Two patients died in pre-MDT and post- MDT (11% versus 20%, P = 0.60). From pre-MDT, the number of patients who required CRRT by post-MDT decreased from 7 (39%) to 0, P = 0.03. Similarly, RT, ICU-LOS and T-LOS [median(p25-p75)] decreased from 10 (2-12) days to 0.5 (0-1.5) days, P = 0.04, from 16 (9-30) days to 10 (4-13) days, P = 0.01 and from 33 (22-53) days to 16 (12-32) days, P < 0.01, respectively. CONCLUSION: MDT implementation was associated with a greater number of patients who meet TMA criteria. A decrease in the RT and T-LOS periods were observed and associated with better outcomes in these patients.

Early-onset anemia after kidney transplantation is an independent factor for graft loss: a multicenter, observational cohort study.

BACKGROUND: The association of anemia with outcomes after renal transplantation (RT) is unclear. METHODS: We performed a retrospective study that included patients who received a RT in Spain in 2007. We collected data on anemia (hemoglobin [Hb] <11 g/dL and/or erythropoietic agents and/or transfusion in the previous month) as well as transplantation and clinical data during follow-up. We used multivariate Cox models to predict graft and patient survival. RESULTS: We included 639 patients; 7.2% lost their graft and 6.3% died. The prevalence of anemia was 84% at 7 days, 77% at 1 month, 41% at 2 months, 16% at 12 months, 14% at 24 months, and 18% at 36 months. After adjusting by glomerular filtration rate (hazard ratio [95% confidence interval], 0.96 [0.93-0.98]), low Hb levels at 1 month remained as an independent predictor of graft loss (hazard ratio for each 1 g/dL increase, 0.72 [0.54-0.96]) along with a maximum panel-reactive antibody of more than 10% (3.80 [1.73-8.36]), a donor with stroke (3.30 [1.31-8.28]), and one or more acute rejection episode (13.89 [4.78-40.37]). Tacrolimus use was a protective factor (0.24 [0.11-0.50]). CONCLUSIONS: Low Hb levels in the early posttransplantation period (1 month) seem to be an independent prognostic factor for graft loss, but not for mortality, in Spanish RT patients regardless of graft function, recipient and donor characteristics, unfavorable events within the first month, and immunosuppression.