Laura Rodriguez-Osorio

Timing of eculizumab therapy for C3 glomerulonephritis

Eculizumab is an anti-C5 antibody that inhibits C5 cleavage and prevents the generation of the terminal complement complex C5b-9. Eculizumab is licensed to treat paroxysmal nocturnal haemoglobinuria or atypical haemolytic uraemic syndrome (aHUS). Clinical trials are ongoing for C3 glomerulopathy. Given the unfamiliarity of physicians with these rare diseases and the variability of clinical presentation, a delayed initiation of eculizumab therapy is common. Thus, the question arises as to what extent improvement of kidney function may be expected when patients have been dialysis dependent for weeks or months already when eculizumab is initiated. Furthermore, given the high cost and potential adverse effects of eculizumab, the question arises of when to stop therapy because of futility when patients with kidney-only manifestations remain dialysis dependent. In literature reports, eculizumab was stopped as early as after 3 weeks because the patient remained dialysis dependent. In this issue of CKJ, Inman et al. report on eculizumab-induced reversal of dialysis-dependent kidney failure from C3 glomerulonephritis, illustrating both the potential benefit of eculizumab for this complement-mediated disease and the need for lengthy therapy—dialysis independency was reached after 5 months of eculizumab. Indeed, there are reports of renal function recovery when eculizumab was initiated after 4 months on dialysis and of recovery of renal function 2.0–3.5 months after initiation of eculizumab in dialysis-dependent patients with C3 glomerulopathy or aHUS.

Combination use of medicines from two classes of renin–angiotensin system blocking agents: risk of hyperkalemia, hypotension, and impaired renal function

European and United States regulatory agencies recently issued warnings against the use of dual renin–angiotensin system (RAS) blockade therapy through the combined use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) or aliskiren in any patient, based on absence of benefit for most patients and increased risk of hyperkalemia, hypotension, and renal failure. Special emphasis was made not to use these combinations in patients with diabetic nephropathy. The door was left open to therapy individualization, especially for patients with heart failure, when the combined use of an ARB and ACEI is considered absolutely essential, although renal function, electrolytes and blood pressure should be closely monitored. Mineralocorticoid receptor antagonists were not affected by this warning despite increased risk of hyperkalemia. We now critically review the risks associated with dual RAS blockade and answer the following questions: What safety issues are associated with dual RAS blockade? Can the safety record of dual RAS blockade be improved? Is it worth trying to improve the safety record of dual RAS blockade based on the potential benefits of the combination? Is dual RAS blockade dead? What is the role of mineralocorticoid antagonists in combination with other RAS blocking agents: RAAS blockade?

Use of sevelamer in chronic kidney disease: beyond phosphorus control

espanolEl sevelamer es un captor no calcico de fosforo que se utiliza en la ERC avanzada y en dialisis para el control de la hiperfosforemia. Varios estudios experimentales, observacionales y ensayos clinicos han mostrado que el sevelamer tiene efectos pleiotropicos, mas alla del control de la hiperfosforemia, incluyendo acciones sobre la inflamacion, el estres oxidativo, el perfil lipidico y la aterogenesis, la calcificacion vascular, la disfuncion endotelial y la disminucion de diversas toxinas uremicas, todo lo cual seria la base biologica de su efecto global sobre la morbilidad y la mortalidad cardiovascular en pacientes con enfermedad renal cronica. En esta revision, se hace enfasis en estas acciones pleiotropicas del sevelamer y su impacto en la salud cardiovascular, con la experiencia publicada despues de mas de 10 anos de experiencia clinica EnglishSevelamer is a calcium-free phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis to control hyperphosphatemia. Several experimental and observational studies and clinical trials have shown that sevelamer has pleiotropic effects that go beyond controlling hyperphosphatemia; these pleiotropic effects include acting on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and decreasing various uremic toxins. All of these represent the biological basis for the global effect of sevelamer on cardiovascular morbidity and mortality in patients with CKD. In this review, we emphasis these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than 10 years of clinical experience.Sevelamer is a non-calcium phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis for hyperphosphataemia control. Several experimental, observational studies and clinical trials have shown that sevelamer has pleiotropic effects, beyond hyperphosphataemia control, including actions on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and the reduction of several uremic toxins. This is the biological basis for its global effect on cardiovascular morbidity and mortality in patients with chronic kidney disease. This review focuses on these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than ten years of clinical expertise.

A decrease in intact parathyroid hormone (iPTH) levels is associated with higher mortality in prevalent hemodialysis patients

Background The mortality of dialysis patients is 10- to 100-fold higher than in the general population. Baseline serum PTH levels, and more recently, changes in serum PTH levels (ΔPTH) over time, have been associated to mortality in dialysis patients. Methods We explored the relationship between ΔPTH over 1 year with mortality over the next year in a prospective cohort of 115 prevalent hemodialysis patients from a single center that had median baseline iPTH levels within guideline recommendations. Results Median baseline iPTH levels were 205 (116.5, 400) pg/ml. ΔiPTH between baseline and 1 year was 85.2 ± 57.1 pg/ml. During the second year of follow-up, 27 patients died. ΔiPTH was significantly higher in patients who survived (+157.30 ± 25.82 pg/ml) than in those who died (+39.03 ± 60.95 pg/ml), while baseline iPTH values were not significantly different. The highest mortality (48%) was observed in patients with a decrease in ΔiPTH (ΔiPTH quartile 1, negative ΔiPTH) and the lowest (12%) mortality in quartile 3 ΔiPTH (ΔiPTH increase 101–300 pg/ml). In a logistic regression model, ΔiPTH was associated with mortality with an odds ratio (OR) of 0.998 (95% CI 0.996–0999, p = 0.038). In multivariable analysis, mortality risk was 73% and 88% lower for patients with ΔiPTH 0–100 pg/ml and 101–300 pg/ml, respectively, than for those with a decrease in ΔiPTH. In patients with a decrease in ΔiPTH, the OR for death was 4.131 (1.515–11.27)(p = 0.006). Conclusions In prevalent hemodialysis patients with median baseline iPTH values within the guideline recommended range, a decrease in ΔiPTH was associated with higher mortality. Further studies are required to understand the mechanisms and therapeutic implications of this observation that challenges current clinical practice.

Decreasing incidence of renal replacement therapy over time at the critical 50-59-year age range suggests a role for nephroprotective therapy in ADPKD.

Department of Medicine, Fredericia Hospital, Fredericia, Denmark; Department of Biostatistics, Aarhus University, Aarhus, Denmark; Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Herlev, Denmark and Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark Correspondence: Christian D. Peters, Department of Renal Medicine, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. E-mail: cdp@ana.au.dk

MP721A DECREASE IN INTACT PARATHYROID HORMONE (iPTH) LEVELS IS ASSOCIATED WITH HIGHER MORTALITY

Seroconversion rates were compared between the two vaccines using chi squared test. RESULTS: ENG patients (N = 24,677) were older (63. 9 vs. 63.1 years), had a higher eKt/V (1.6 vs. 1.5), a higher proportion of diabetics (61.5% vs. 54.9%), fewer patients with congestion heart failure (12.3% vs. 16.1%), lower dialysis vintage (0.8 vs. 1.1 years) and lower hemoglobin (11.2 vs. 11.5 g/dL) compared to REC patients (N = 1,320) (Table 1). Seroconversion rates were significantly higher with ENG compared to REC (1st series: 73.7% vs. 64.3%, D=9.4% 95% CI: 6.7 % to 12.1%); 1st and 2nd series combined: 78.5% vs. 64.6%, D=13.9%, 95% CI: 11.2% to 16.5%) (Figure 1). CONCLUSIONS: When administering full vaccination courses as outlined above, Engerix-B yields substantially higher primary seroconversion rates than RecombivaxHB. The same is true when looking at cumulative response rates for the 1 and 2 series combined. These results hold true even after adjusting for differences in population characteristics. Reference 1)Rustgi VK., Comparative study of the immunogenicity and safety of Engerix-B administered at 0, 1, 2 and 12 months and Recombivax HB administered at 0, 1, and 6 months in healthy adults. Vaccine. 1995 Dec; 13(17):1665-8. 2) Rault R., Efficacy of different hepatitis B vaccination strategies in patients receiving hemodialysis. ASAIO J. 1995 Jul-Sep;41(3):M717-9. 3)Lacson E., Antibody response to Engerix-B and Recombivax-HB hepatitis B vaccination in end-stage renal disease. Hemodial Int. 2005 Oct;9(4):367-75.

Increasing serum calcium levels and recent return from transplantation as clues to the tuberculous nature of refractory peritoneal dialysis peritonitis

Peritoneal tuberculosis is an uncommon complication of peritoneal dialysis in Europe. It is more common in Asian immigrants. A delayed diagnosis is frequent and impairs patient outcomes. We present two cases of peritoneal tuberculosis with common features that may help suspect the disease early countries with a low incidence. Both patients were females (of Spanish origin) who had recently restarted peritoneal dialysis following kidney transplantation. Both developed bacterial peritonitis clinically that was refractory to conventional antibiotics, despite clearance of bacteria. Both stopped calcium-containing phosphate binders because of increasing serum calcium that in one case led to frank hypercalcemia that persisted despite low calcium dialysate. Peritoneal biopsy was the first positive test in both cases. This report emphasizes the recent return from transplantation and rising serum calcium levels as features that should alert the physician of a potential underlying tuberculous peritonitis.