Randomized trial comparing pulse calcitriol and alfacalcidol for the treatment of secondary hyperparathyroidism in haemodialysis patients

Aim: Calcitriol and alfacalcidol are used extensively for the treatment of secondary hyperparathyroidism. Unfortunately, there is limited published data comparing the efficacy and tolerability of both active vitamin D sterols. This study was undertaken to determine whether calcitriol provides a therapeutic advantage to alfacalcidol. Methods: This was a randomized, active controlled study. Patients with intact parathyroid hormone (iPTH) >32 pmol/L were randomized to receive orally calcitriol or alfacalcidol after each haemodialysis for up to 24 weeks. Reduction of PTH, changes of plasma albumin‐corrected calcium and phosphorus were analysed. The initial dose of alfacalcidol was twice that of calcitriol. Results: Sixteen patients were randomized into each group. At baseline, plasma albumin‐corrected calcium, phosphorus and PTH were no different between groups. At 24 weeks, PTH changes were ?50.8 ± 31.8% and ?49.4 ± 32.5% from the baseline in the calcitriol and alfacalcidol groups, respectively (P = 0.91). The patients who achieved target PTH of 16–32 pmol/L were 82% in the calcitriol and 67% in the alfacalcidol group (P = 0.44). Plasma albumin‐corrected calcium and phosphorus were not significantly different but showed trends toward gradually increasing from baseline in both groups (calcium, 6.0 ± 7.2% vs 10.9 ± 6.5% (P = 0.10); phosphorus, 13.0 ± 29.4% vs 16.7 ± 57.2% (P = 0.83) in calcitriol and alfacalcidol, respectively). The mean dose of calcitriol and alfacalcidol were 4.1 and 6.9 µg/week, respectively (P < 0.0001). Conclusion: Alfacalcidol can be used to control secondary hyperparathyroidism at doses of 1.5–2.0 times that of calcitriol. The two drugs are equally efficacious and lead to similar changes in calcium and phosphorus.     

Evaluating the clinical course and prognostic factors of posttransplantation immunoglobulin A nephropathy

INTRODUCTION: Previous reports have suggested that posttransplantation immunoglobulin (Ig) A nephropathy displays a relatively benign course, hardly ever affecting graft function. However, more recent studies with longer follow-up have shown that posttransplantation IgA nephropathy may be a significant contributor to graft loss. Additionally, there may be other clinical or pathological factors that affect long-term graft outcome. We retrospectively analyzed 30 kidney transplant recipients with biopsy-proven IgA nephropathy in their allografts to determine the clinical course and prognostic factors in posttransplantation IgA nephropathy. The median duration of follow-up was 36 months (range, 1 month-17 years). The median onset of IgA nephropathy was 33.6 months posttransplantation (range, 5 days-103 months). The most common presentation was an abnormal urine examination (96.6%). Fifteen (50%) displayed microscopic hematuria with proteinuria more than 1 g/d. Fifteen patients (50%) lost their grafts at a median time of 24 months after the onset of disease (range, 1-93 months). Allograft loss was associated with a high serum creatinine level at the time of diagnosis (3.68 +/- 2.23 vs 1.79 +/- 0.34 mg/dL; P = .006), a greater level of proteinuria at the time of diagnosis (2.43 +/- 0.76 vs 1.29 +/- 1.07 g/d; P = .003), and more than 50% extracapillary proliferation (P = .05). Fibrinoid necrosis on allograft pathology impacted 1-year allograft survival (P = .025). CONCLUSION: Posttransplantation IgA nephropathy worsens allograft outcomes among patients with increased serum creatinine level or significant proteinuria at presentation or significant glomerular inflammation and/or tubulointerstitial damage.     

Chronic Kidney Disease-Mineral Bone Disorder: Definitions and Rationale for a Systemic Disorder

Over the past decade there has been an increasing awareness of the complexity of bone and mineral complications observed in chronic kidney disease (CKD) and recognition that the consequences of these abnormalities affect not only the skeleton, but also the cardiovascular system. These scientific advances led to the naming of a systemic disorder, ??Chronic Kidney Disease-Mineral Bone Disorder?? (CKD-MBD) defined as abnormalities in mineral-related biochemistries, bone modeling/remodeling and strength, and extraskeletal calcification. CKD-MBD begins early in the course of progressive CKD, at estimated glomerular filtration rates of 60?ml/min or earlier, with progression such that all dialysis patients have one or more components. The older term, renal osteodystrophy is one component of CKD-MBD and should be used exclusively to define the histopathologic abnormalities of CKD-related bone remodeling. This diagnostic criteria has been further refined using a new classification system ??turnover, mineralization, and volume??, that defines bone turnover, mineralization, and volume to allow for a more complete evaluation of renal osteodystrophy. The recognition of this inter-relationship between biochemical changes, bone, and extraskeletal calcification as the systemic disorder CKD-MBD allows for enhanced communication, increased awareness/diagnosis, and improved treatment approaches with the ultimate goal of improving morbidity and mortality in patients with CKD.