A trial of complement inhibition in a patient with cryoglobulin-induced glomerulonephritis

Cryoglobulinemia induces an immune complex-mediated glomerulonephritis that is characterized by the presence of large immune deposits, including complement C3 and C5b-9, marked macrophage influx and mesangial cell proliferation. The precise role of complement in cryoglobulin-induced glomerulonephritis in humans remains unclear, whereas in mice there has been evidence that complement activation might be a central factor favoring glomerular inflammation, particularly by the recruitment of neutrophils. We report on an exceptional case of cryoglobulin-induced glomerulonephritis in a patient with mixed essential cryoglobulinemia type II. The clinical features included relapsing proteinuria and renal function impairment that were controlled by plasmapheresis. Complement was low in plasma and two renal biopsies at 1-year interval showed prominent immunoglobulin and complement deposits, with unusual high numbers of neutrophils. In a 1-patient clinical trial, we tested whether the monoclonal anti-C5 antibody eculizumab would be sufficient to control renal function at the time of a relapse. Although during the initial weeks renal function was stabilized, slow increase in creatinine could not be controlled by this treatment, so that plasmapheresis was reinstituted. This result suggests that despite evidence for a role of complement in enhancing renal damage in this patient, other inflammatory processes dominated

Darbepoetin alpha in lower-than-equimolar doses maintains haemoglobin levels in stable haemodialysis patients converting from epoetin alpha/beta

BACKGROUND: The conversion of patients on stable epoetin therapy to darbepoetin alpha is usually carried out according to the '1 microg darbepoetin =200 U epoetin' rule, which is based on the protein content of the two compounds. Since several observations have suggested that this conversion factor leads to an overestimate of the required darbepoetin dose, the present multicentre study was designed to assess the true conversion ratio by prospectively evaluating the change in darbepoetin alpha dose after conversion from epoetin, which was required to keep haemoglobin (Hb) stable. METHODS: Haemodialysis patients with stable Hb and maintained on either s.c. or i.v. epoetin (alpha or beta) were switched to intravenously administered darbepoetin alpha according to the 1:200 rule. Subjects treated with epoetin two or three times per week received one weekly dose of darbepoetin alpha, subjects on weekly epoetin received darbepoetin alpha every 2 weeks. For 20 weeks, darbepoetin alpha was changed every 2 weeks according to a pre-specified algorithm, if this was needed to keep Hb within +/-1.0 g/dl of each subject's individual baseline. Thereafter, patients entered a 4-week evaluation period. RESULTS: One hundred ad thirty-two patients in 17 Swiss centres were enrolled and 100 completed the study throughout the evaluation period. While mean Hb was maintained stable between baseline and evaluation period (11.8+/-0.6 g/dl in both), the mean required darbepoetin alpha dose decreased from 34.7+/-2.1 to 26.0+/-1.8 microg (-25%, Por=5000 IU of epoetin per week is more likely to follow a 1:250 to 1:350 conversion rule. If pricing is based on the 1:200 rule such as in Switzerland, this may translate into cost savings

Darbepoetin alpha in lower-than-equimolar doses maintains haemoglobin levels in stable haemodialysis patients converting from epoetin alpha/beta

BACKGROUND: The conversion of patients on stable epoetin therapy to darbepoetin alpha is usually carried out according to the '1 microg darbepoetin =200 U epoetin' rule, which is based on the protein content of the two compounds. Since several observations have suggested that this conversion factor leads to an overestimate of the required darbepoetin dose, the present multicentre study was designed to assess the true conversion ratio by prospectively evaluating the change in darbepoetin alpha dose after conversion from epoetin, which was required to keep haemoglobin (Hb) stable. METHODS: Haemodialysis patients with stable Hb and maintained on either s.c. or i.v. epoetin (alpha or beta) were switched to intravenously administered darbepoetin alpha according to the 1:200 rule. Subjects treated with epoetin two or three times per week received one weekly dose of darbepoetin alpha, subjects on weekly epoetin received darbepoetin alpha every 2 weeks. For 20 weeks, darbepoetin alpha was changed every 2 weeks according to a pre-specified algorithm, if this was needed to keep Hb within +/-1.0 g/dl of each subject's individual baseline. Thereafter, patients entered a 4-week evaluation period. RESULTS: One hundred ad thirty-two patients in 17 Swiss centres were enrolled and 100 completed the study throughout the evaluation period. While mean Hb was maintained stable between baseline and evaluation period (11.8+/-0.6 g/dl in both), the mean required darbepoetin alpha dose decreased from 34.7+/-2.1 to 26.0+/-1.8 microg (-25%, Por=5000 IU of epoetin per week is more likely to follow a 1:250 to 1:350 conversion rule. If pricing is based on the 1:200 rule such as in Switzerland, this may translate into cost savings

Adherence to, and patient convenience of, prolonged-release tacrolimus in stable kidney and liver transplant recipients after conversion from immediate-release tacrolimus in routine clinical practice in Switzerland

Non-adherence to immunosuppressive therapy in patients following solid organ transplantation is associated with an increased risk of transplant rejection and graft loss. A high pill burden can adversely affect patients’ implementation of their treatment regimens and may lead to omitting doses of medication. The aim of this study was to investigate medication implementation adherence in liver and kidney transplant recipients converted from twice-daily, immediate-release tacrolimus to once-daily, prolonged-release tacrolimus