Steven E. Bradshaw

Polycystic kidney disease: Renal transplantation in patients with ADPKD—the good, the bad and ugly

Polycystic kidney disease: Renal transplantation in patients with ADPKD—the good, the bad and ugly

Transplantation: 5-year benefits of rituximab for ABO-mismatched renal grafts

Clinical uses of the anti-CD20 monoclonal antibody rituximab extend to a wide variety of hematological and autoimmune disorders. According to results from a new study conducted in Japan, rituximab also improves the outcomes of patients with ABOincompatible kidney grafts. “...we found that the rituximab-containing preconditioning regimen achieved ... effects that far exceeded our initial expectation,” write the authors. Fuchinoue and co-workers assessed the clinical outcomes of 408 patients with end-stage renal disease who had received kidney allografts from spouses or living related donors between January 2002 and December 2008. The patients were grouped according to their ABO graft compatibility status and whether rituximab had been used in addition to the standard preoperative immunosuppression induction regimen. The groups were as follows: 280 patients who underwent ABO-compatible kidney transplantation (control group), 63 patients who underwent ABOincompatible kidney transplantation without rituximab induction but with splenectomy during transplantatation, TRANSPLANTATION

Dialysis: Dialysis options|[mdash]|elderly patients should be given an informed choice

concludes Brown, who highlights attitudes among clinicians as a possible factor underlying the shift towards hemodialysis. older patients tend to have comorbidities, which increase the risk of dialysis complications. Furthermore, they are often presumed to have impaired independence and decreased ability to perform peritoneal self-dialysis. in reality, few data actually support these negative perceptions. Brown is hopeful that the BolDe findings will change health-care professionals’ views about the suitability of peritoneal dialysis for elderly patients—who are unlikely to ever receive a kidney transplant, and thus will be on dialysis until the end of their life. From this perspective, peritoneal dialysis offers important benefits; for example, this home-based therapy causes less disruption to the lifestyles of the patient and their family than does hemodialysis. the researchers also recommend approaches to enable patients to make an dialysis

Pathology: Electron microscopy illuminates the pathology of Fabry nephropathy

enzyme-replacement therapy (ert) can slow the decline of renal function in patients with Fabry disease, but once proteinuria develops, responsiveness to ert is limited. Fresh research has discovered early changes in podocytes that correlate with the markers of progression of Fabry nephropathy. “Fabry nephropathy is a very heterogeneous disease,” notes Behzad najafian, the paper’s lead author. thus, standardized dosing of ert is unlikely to suit all patients. “these biomarkers can potentially be used to guide clinical decisions for when to start ert and how to adjust the dosage,” he points out. najafian et al. used quantitative stereological electron microscopy to assess the relationship between glomerular structure and renal function in young patients with Fabry disease who had little or no proteinuria. Kidney biopsy specimens were obtained from 14 such patients, who had not yet received primary ert, and compared with biopsy samples from nine healthy, living kidney donors. Fabry disease was associated with significantly increased podocyte foot process width and significantly decreased endothelial cell fenestrations in glomeruli. inclusion bodies containing globotriaosylceramide (Gl-3, which accumulates in patients with Fabry disease owing to the absence of α-galactosidase) occurred in podocyte, endothelial and mesangial cells from the patients, but were most abundant in the cytoplasm of podocytes. the fractional volume of podocytes occupied by Gl-3 inclusion bodies increased with patient age, and correlated closely with the amount of proteinuria (r = 0.68) and with the width of foot processes (r = 0.81). the accumulation of Gl-3 in podocytes is thought to induce cellular injury that manifests as proteinuria. najafian’s team is now researching the effect of ert on structural glomerular changes in adults and children with Fabry disease. “structural parameters that can closely predict renal function ... could be used as diagnostic or prognostic biomarkers, or can be used as primary end points in clinical trials,” he suggests. these biomarkers might also help to identify patients at high risk of progression.

Dialysis options—elderly patients should be given an informed choice: Dialysis

concludes Brown, who highlights attitudes among clinicians as a possible factor underlying the shift towards hemodialysis. older patients tend to have comorbidities, which increase the risk of dialysis complications. Furthermore, they are often presumed to have impaired independence and decreased ability to perform peritoneal self-dialysis. in reality, few data actually support these negative perceptions. Brown is hopeful that the BolDe findings will change health-care professionals’ views about the suitability of peritoneal dialysis for elderly patients—who are unlikely to ever receive a kidney transplant, and thus will be on dialysis until the end of their life. From this perspective, peritoneal dialysis offers important benefits; for example, this home-based therapy causes less disruption to the lifestyles of the patient and their family than does hemodialysis. the researchers also recommend approaches to enable patients to make an dialysis

Dialysis: High hemoglobin levels|[mdash]|a hemodialysis risk factor?

as esa doses required to correct anemia in hemodialysis show wide variation. Goodkin et al. analyzed data from the Dialysis outcomes and Practice Patterns study, a prospective, observational study of patients with CKD. among the 29,796 participants, the researchers identified 545 who maintained higher hemoglobin levels without esas. the researchers attribute the ability to sustain robust erythropoiesis to the retention of the capability to produce sufficient endogenous erythropoietin. the most important finding was that hemoglobin levels >120 g/l in the esafree subgroup were not linked with any increase in mortality compared with the rest of the cohort. in fact, unadjusted mortality risk was lower in this subgroup than in the rest of the cohort, but this difference disappeared after careful adjustment for confounding variables. “our results suggest that there are [hemodialysis] patient subgroups for whom hemoglobin concentration [>120 g/l] is acceptable and that there is no dialysis