Lack of long-term benefits of steroid withdrawal in renal transplant recipients.

Glucocorticoids used in renal transplantation have been associated with numerous adverse effects. Most studies that showed short-term benefits of steroid withdrawal made comparisons for patients administered prednisone, 10 to 17.5 mg/d, versus no prednisone. Few have studied long-term benefits of steroid withdrawal. We performed a retrospective review and identified 58 patients administered cyclosporine, azathioprine, and prednisone who underwent complete steroid withdrawal. Post-steroid withdrawal follow-up was 7.6 +/- 1.9 years. Nine patients restarted prednisone therapy, 3 patients lost their grafts (2 of those restarted on prednisone therapy), and 2 patients died with functioning grafts. When prednisone dosage was tapered from 10 mg/d to 10 mg every other day, clinically significant improvements were seen in weight, systolic and diastolic blood pressure, blood pressure medications, glycosylated hemoglobin level, and diabetic medications. No further benefits were seen in these parameters and total cholesterol level on complete steroid withdrawal from prednisone, 10 mg every other day. Most of the earlier benefits were not sustained on long-term follow-up, and the increase in these parameters was similar to that of a similar matched control group (that underwent transplantation during the same period) maintained on prednisone, 5 mg/d. Major differences were decreases in creatinine clearances and hemoglobin levels, which were greater in the steroid-withdrawal group (7.4 +/- 1.9 mL/min and 1.2 +/- 0.2 g/dL, respectively) compared with the control group (2.6 +/- 1.5 mL/min and 0.5 +/- 0.2 g/dL, respectively). In conclusion, most of the metabolic benefits were seen with steroid dosage taper from prednisone, 10 mg/d to 10 mg every other day, with no further benefits with steroid withdrawal. Most of these benefits were not sustained on long-term follow-up, questioning the utility of steroid withdrawal.

Cystinosis with sclerotic bone lesions.

A 26-year-old male with nephropathic cystinosis treated with cysteamine and renal transplantation presented for evaluation of multiple sclerotic bone lesions, which were an incidental finding on chest computerized tomography. These lesions were in a pattern consistent with osteoblastic metastases. He did not have a history of clinically significant hyperparathyroidism or cytopenias either preceding or following his transplant. Bone and tumor markers (including alkaline phosphatase and calcium) were all normal. A percutaneous bone biopsy of the lesions showed changes compatible with cystine deposition. Our case demonstrates that sclerotic bone lesions can be a feature of cystinosis in patients with normal parathyroid function and that significant bone marrow infiltration with cystine can be present even in the absence of cytopenias.

Homocyst(e)ine and vascular access complications in haemodialysis patients: insights into a complex metabolic relationship.

BACKGROUND: As elevated total homocyst(e)ine (tHcy) is associated with increased risk of vascular thrombosis, we hypothesized that the elevated levels of tHcy seen in patients on haemodialysis may be associated with an increased risk of thrombosis of native arteriovenous fistulae (vascular access failure). Our study was designed to investigate the relationship between tHcy and vascular access failure. The relationship between tHcy and mortality was explored as a secondary analysis. METHODS: The study comprised a cross-sectional analysis of 96 haemodialysis patients at a single university-affiliated hospital and a subsequent 9-month prospective follow-up of 88 of the 96 patients. RESULTS: Levels of tHcy (median 30 micromol/l) were elevated. In the initial cross-sectional sample, there was an inverse relationship between tHcy and history of vascular access failure which was not observed in the prospective study. Variables influencing the risk of vascular access failure in the prospective study included history of previous vascular access failure (RR=2.93, P=0.03), use of antiplatelet agents (RR=0.13, P=0.01), increased urea reduction ratio (RR=0.55 for a 5% increase, P=0.01) and increased weight (RR=0.61 for a 10 kg increase, P=0.02). Secondary analysis showed an unexpected inverse relationship between tHcy and mortality (RR=0.033 for 1 log increase in tHcy, P=0.006), such that the lower levels of tHcy were associated with an increased risk of death in short-term follow-up. CONCLUSION: We did not demonstrate a relationship between tHcy and risk of vascular access failure. Patients with the lowest levels of tHcy appeared to be at increased risk of death in this short-term follow-up. The relationship of tHcy to vascular access complications and death in haemodialysis patients appears complex and requires further study.