Sumida K.,Nephrology Center
Arthritis care & research | Year: 2013
To elucidate the safety of adalimumab for rheumatoid arthritis (RA) patients with renal insufficiency, including those with end-stage renal disease undergoing hemodialysis. Sixty-five RA patients, including 2 patients undergoing hemodialysis, treated with adalimumab in our hospital from December 1, 2008 to June 30, 2011 were retrospectively analyzed. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) calculated from the Cockcroft-Gault formula at the start and end of followup after adalimumab treatment. The proportion of the patients who discontinued or switched adalimumab treatment and the change of the eGFR were compared between patients with (n = 39) and without (n = 26) renal insufficiency, defined as an eGFR <60 ml/minute/1.73 m(2) . There was no significant difference between the 2 groups in the proportion of the patients who discontinued or switched adalimumab treatment (51.3% versus 50.0%; P = 0.53). The mean ± SD changes of eGFR were from 41.6 ± 13.3 to 43.4 ± 17.9 ml/minute/1.73 m(2) in patients with renal insufficiency and from 83.6 ± 17.5 to 83.0 ± 16.8 ml/minute/1.73 m(2) in patients without renal insufficiency, and the differences in each group were not statistically significant (P = 0.92 and P = 0.78, respectively). No severe infections or other severe adverse events were observed in either group during adalimumab treatment. Our data indicate that adalimumab does not worsen renal function and has no serious adverse events even for RA patients with renal insufficiency, including those undergoing hemodialysis, and suggest that it could be a potential therapeutic option for them. Copyright © 2013 by the American College of Rheumatology.
Koch M.,Nephrology Center |
Treiber W.,Renal and Hypertension Center |
Fliser D.,Saarland University
Clinical Drug Investigation | Year: 2013
Background: Correction of low hemoglobin (Hb) levels is associated with improved survival and greater quality of life in dialysis patients, but frequent administration of erythropoiesis stimulating agent (ESA) therapy is unsatisfactory for peritoneal dialysis patients. Objective: The objective of this study was to assess Hb stability in an unselected population of maintenance peritoneal dialysis patients receiving once-monthly treatment with C.E.R.A., a continuous erythropoietin receptor activator. Methods: In a prospective, non-interventional, single-arm study at 33 Germany dialysis centers, peritoneal dialysis patients with or without ESA treatment prior to study entry received once-monthly treatment with C.E.R.A. Hb stability was assessed by the proportion of patients for whom all measured Hb values during months 6-8 (the evaluation phase) were within the range 11-12, 11-13, 10-12 or 11-12.5 g/dL. Results: 220 patients received at least one dose of C.E.R.A. During the evaluation phase, 185 patients provided ≥1 Hb measurement (efficacy population) and 162 patients provided ≥2 Hb measurements (the modified efficacy population). The mean (SD) time between C.E.R.A. doses was 28.2 (7.2) days and mean (SD) C.E.R.A. dose was 109 (57) μg per application. Mean (SD) Hb level was 11.1 (1.4) g/dL at baseline and 11.5 (1.3) g/dL at the end of the study (modified efficacy population). The primary efficacy variable, all measured Hb values in the range 11-12 g/dL, was 18.4 % (34/185) and 14.8 % (24/162) in the efficacy and modified efficacy populations, respectively. The mean (SD) maximum intra-individual fluctuation in Hb level was 0.56 (0.50) g/dL in the efficacy population and 0.58 (0.49) g/dL in the modified efficacy population, with maximum intra-individual fluctuation ≤1 g/dL in 85.4 % (158/185) and 83.3 % (135/162) of patients, respectively. No adverse drug reactions were reported during the study. Conclusion: In this large population of maintenance peritoneal dialysis patients, once-monthly administration of C.E.R.A. achieved a high degree of Hb stability and was well-tolerated. © 2013 The Author(s).
Tang S.C.W.,University of Hong Kong |
Lai K.N.,University of Hong Kong |
Lai K.N.,Nephrology Center
Contributions to Nephrology | Year: 2013
Hepatitis C virus (HCV) infection remains a major global health burden. In addition to liver-related morbidity and mortality due to hepatic decompensation and development of hepatocellular carcinoma, extrahepatic manifestations of hepatitis C are frequent. Type I membranoproliferative glomerulonephritis associated with type II cryoglobulinemia is the most frequent association. The pathogenesis of the renal lesions is related to glomerular deposition of immune complexes. International guidelines recommend that patients with HCV-related glomerulopathies should be treated with antiviral therapy in the form of standard or pegylated interferon-α and ribavirin. The recent development of direct-acting antiviral agents that inhibit the various steps of the viral life cycle represents a major milestone for the treatment of chronic HCV infection. Initial reports suggest that they are safe in ESRD subjects. However, data is lacking on their efficacy and safety in HCV-related glomerulonephritis. Copyright © 2013 S. Karger AG, Basel.
Lai K.N.,Nephrology Center
Nature Reviews Nephrology | Year: 2012
Since its first description in 1968, IgA nephropathy has remained the most common form of idiopathic glomerulonephritis leading to chronic kidney disease in developed countries. The exact pathogenesis of IgA nephropathy is still not well defined. Current data implicate an important genetic factor, especially in promoting the overproduction of an aberrant form of IgA1. The immunochemical aberrancy of IgA nephropathy is characterized by the undergalactosylation of O-glycans in the hinge region of IgA1. However, such aberrant glycosylation alone does not cause renal injury. The next stage of disease development requires the formation of glycan-specific IgG and IgA antibodies that recognize the undergalactosylated IgA1 molecule. These antibodies often have reactivity against antigens from extrinsic microorganisms and might arise from recurrent mucosal infection. B cells that respond to mucosal infections, particularly tonsillitis, might produce the nephritogenic IgA1 molecule. With increased immune-complex formation and decreased clearance owing to reduced uptake by the liver, IgA1 binds to the glomerular mesangium via an as yet unidentified receptor. Glomerular IgA1 deposits trigger the local production of cytokines and growth factors, leading to the activation of mesangial cells and the complement system. Emerging data suggest that mesangial-derived mediators following glomerular deposition of IgA1 lead to podocyte and tubulointerstitial injury via mesangio-podocytic-tubular crosstalk. This Review summarizes the latest findings in the pathogenesis of IgA nephropathy. © 2012 Macmillan Publishers Limited. All rights reserved.
Hoshino J.,Nephrology Center |
Yamagata K.,University of Tsukuba |
Nishi S.,Kobe University |
Nakai S.,University of Tsukuba |
And 3 more authors.
American Journal of Nephrology | Year: 2014
Background/Aims: This study aims to identify current risk factors for developing dialysis-related amyloidosis using carpal tunnel syndrome (CTS) as proxy for general amyloidosis. Methods: The cohort consisted of 166,237 patients on dialysis (mean age 66.1 ± 12.4 years; mean dialysis vintage 7.2 ± 6.4 years) who could be followed for a year between 2010 and 2011. Of these, 2,157 (1.30%) needed first-time CTS surgery during the study period. Odds ratios (ORs) for CTS were calculated at a 95% confidence interval (95% CI) after adjusting for age, gender, primary kidney disease, history of smoking, history of hypertension vintage, dialysis modality, use of high-flux membrane, body mass index, serum albumin, Kt/V, normalized protein catabolic rate, C-reactive protein, pretreatment β2-microglobulin (β2MG), and β2MG clearance. Results: Adjusted ORs of first-time CTS for vintages 10-15, 15-20, 20-25 (referent), 25-30, and >30 years were, respectively, 0.18 (0.12-0.26), 0.43 (0.31-0.62), 1.00, 2.37 (1.64-3.40), and 3.87 (2.52-5.93). Adjusted ORs for ages 40-50, 50-60 (referent), 60-70, 70-80, and >80 were 0.53 (0.30-0.94), 1.00, 1.89 (1.41-2.52), 1.52 (1.08-2.14), and 1.04 (0.60-1.80). Female gender, low serum albumin, and diabetic nephropathy were also associated with CTS. Pretreatment serum β2MG and β2MG clearance <80% were not significant, although β2MG clearance >80% was negatively associated with CTS [OR 0.34 (0.13-0.90)]. Conclusion: ORs of first-time CTS almost doubled with every 5-year increase in dialysis vintage. ORs of CTS were highest for patients aged 60-70. Other factors associated with CTS were gender, serum albumin, and diabetic nephropathy. β2MG clearance >80% may decrease the incidence of CTS. © 2014 S. Karger AG, Basel.