Histomorphometric diagnostics of renal osteopathy in chronic dialysis patients at high risk of cardiovascular disease.

UNLABELLED: Chronic kidney disease-mineral and bone disorder (CKD-MBD) ranks among clinically and pathogenetically significant complications in patients with CKD. Numerous factors are involved in its development, and histomorphometric analysis of the bone tissue is still necessary for accurate diagnosis. METHODS: The open, pilot, prospective study aimed at performing a comprehensive histomorphometric bone analysis in 26 dialysis patients and assessing the relationships of different types of CKD-MBD to selected parameters of calcium and phosphate metabolism, densitometry, activity of parathyroid glands, presence of diabetes mellitus, and duration of dialysis treatment. RESULTS: Comparison of the histomorphometric characteristics demonstrated statistically significant correlations between the volume of bone trabeculae and s-procollagen 1 (.754) as well as s-calcitonin (.856). Similarly, there was a positive correlation between the size of tetracycline lines and volume of bone trabeculae (.705) and a strong negative correlation with the thickness of trabeculae (-.442). When assessing the serum levels of s-osteoprotegerin and serum RANKL, there was a correlation with osteoid thickness and bone trabeculae thickness. In case of s-osteoprotegerin, a statistical power was demonstrated in relation to osteoid thickness (.880); in case of s-RANKL, a statistical power was demonstrated in relation to the thickness of trabeculae (.830). When assessing the influence of dialysis duration, relationships to the volume of trabecular bone (.665) and volume of bone trabeculae (.949) were demonstrated. Finally, a relationship between s-1,25-hydroxyvitamin D and s-osteoprotegerin was observed (.739); also the relationships demonstrated were significantly lower volume of bone trabeculae in men (p = 0.067) and lower values of s-osteocalcin and s-procollagen 1 in diabetic patients (p = 0.014). CONCLUSION: The results provide new noninvasive possibilities of CKD-MBD detection that are based on selected serum parameters of bone metabolism. Presented are possibilities of noninvasive assessment of different types of CKD-MBD using serum osteomarkers in relation to comprehensive CKD-MBD histomorphometry.

Protocol biopsy of a transplanted kidney as a tool for monitoring adequacy of immunosuppressive therapy: 10 years of experience from a single transplant center.

BACKGROUND: The aims of this prospective study were to determine the prevalence of clinically silent rejection changes and of nephrotoxicity of calcineurin inhibitors among repeated protocol biopsies of transplanted kidneys and to assess their impacts on chronic graft function and damage at the end of 1 year. METHODS: We performed 424 protocol biopsies among 158 patients over the first year after transplantation. We monitored parameters of graft function and progression of chronic changes among subjects with clinically silent rejection or toxicity for comparison with a control cohort showing normal histological findings. The results of statistical tests were considered to be significant at a level of P < .05. RESULTS: At 3 weeks, 3 months, and 12 months, there were normal histological findings among 30 (19%), 21 (14.8%), and 14 (11.3%) patients, respectively; subclinical rejection changes occurred in 49 (31%), 36 (25.4%), and 20 (16.2%) grafts, respectively. At the third week, histological signs of toxicity occurred in 33 (20.9%) patients with significant persistence despite reductions in calcineurin inhibitor doses. At the end of 1 year of follow-up, both subclinical and toxic changes produced similar increases in chronic changes as quantified by the Banff score and were significantly different from the control group (P < .05). Serum creatinine concentrations and glomerular filtration rates did not accurately reflect the degree of graft damage in the early posttransplantation period. CONCLUSIONS: Subclinical rejection and toxic changes among a significant proportion of grafts are associated with progression of chronic changes already over the first year following transplantation. Hence they represent independent risk factors for the development of irreversible graft damage. Protocol biopsy seems to be an important method to monitor immunosuppressive therapy.