Calcium, phosphate and parathyroid metabolism in kidney transplanted patients (original) (raw)
Related papers
Transplantation Proceedings, 2009
Introduction. While kidney transplantation successfully reverses many complications of uremia that are not corrected with dialysis therapy, elevated parathyroid hormone (PTH) levels and other alterations of mineral metabolism persist in transplant recipients. Patients and Methods. A single-center cohort retrospective database analysis was performed of 497 consecutive adult patients who underwent first kidney transplantation between 1994 and 2004. At 1-and 5-year follow-up, a descriptive analysis was performed of mineral metabolism parameters of chronic kidney disease stage according to NKF KDOQI (National Kidney Foundation Kidney Disease Outcomes Quality Initiative) in patients with a functional graft at 1 year. Glomerular filtration rate was estimated using the abbreviated MDRD (Modification of Diet in Renal Disease) equation. Results. Most of the transplants (99.2%) were from cadaveric donors. Mean (SD) patient age was 47.7 (13.3) years, and 69% of patients were men. The causes of chronic kidney disease were glomerular (35.4%), congenital (15.4%), systemic (14.1%), vascular (11.3%), interstitial (10.1%), and other (Ͻ1%). The percentage of patients in each stage of chronic kidney disease with calcium levels less than 8.5 mg/dL, phosphorus greater than 4.5 mg/dL, and PTHi greater than 150 pg/mL increased as graft function declined. Six posttransplantation parathyroidectomies were performed. Only 130 patients received secondary hyperparathyroidism treatment within 5 years after transplantation: calcium carbonate, 36.9%; calcium acetate, 1.5%; calcium carbonate plus cholecalciferol, 21%; calcitriol, 71%; and calcifediol, 0.8%. Conclusions. The prevalence of hypocalcemia, hyperphosphatemia, and elevated PTH level increased with chronic kidney disease stage. Classification of renal transplant recipients by KDOQI stage may enable clinicians to identify patients at increased risk and to target appropriate therapy to improve outcome. There is an opportunity for enhanced management of secondary hyperparathyroidism in these patients.
In Practice CKD – Mineral and Bone Disorder Management in Kidney Transplant Recipients
2012
Kidney transplantation, the most effective treatment for the metabolic abnormalities of chronic kidney disease (CKD), only partially corrects CKD–mineral and bone disorders. Posttransplantation bone disease, one of the major complications of kidney transplantation, is characterized by accelerated loss of bone mineral density and increased risk of fractures and osteonecrosis. The pathogenesis of posttransplantation bone disease is multifactorial and includes the persistent manifestations of pretransplantation CKD–mineral and bone disorder, peritransplantation changes in the fibroblast growth factor 23– parathyroid hormone–vitamin D axis, metabolic perturbations such as persistent hypophosphatemia and hypercalcemia, and the effects of immunosuppressive therapies. Posttransplantation fractures occur more commonly at peripheral than central sites. Although there is significant loss of bone density after transplantation, the evidence linking posttransplantation bone loss and subsequent f...
CKD–Mineral and Bone Disorder Management in Kidney Transplant Recipients
American Journal of Kidney Diseases, 2013
Kidney transplantation, the most effective treatment for the metabolic abnormalities of chronic kidney disease (CKD), only partially corrects CKD-mineral and bone disorders. Posttransplantation bone disease, one of the major complications of kidney transplantation, is characterized by accelerated loss of bone mineral density and increased risk of fractures and osteonecrosis. The pathogenesis of posttransplantation bone disease is multifactorial and includes the persistent manifestations of pretransplantation CKD-mineral and bone disorder, peritransplantation changes in the fibroblast growth factor 23parathyroid hormone-vitamin D axis, metabolic perturbations such as persistent hypophosphatemia and hypercalcemia, and the effects of immunosuppressive therapies. Posttransplantation fractures occur more commonly at peripheral than central sites. Although there is significant loss of bone density after transplantation, the evidence linking posttransplantation bone loss and subsequent fracture risk is circumstantial. Presently, there are no prospective clinical trials that define the optimal therapy for posttransplantation bone disease. Combined pharmacologic therapy that targets multiple components of the disordered pathways has been used. Although bisphosphonate or calcitriol therapy can preserve bone mineral density after transplantation, there is no evidence that these agents decrease fracture risk. Moreover, bisphosphonates pose potential risks for adynamic bone disease. Am J Kidney Dis. xx(x):xxx.
Calcium and Bone Metabolism Pre- and Post-Kidney Transplantation
Endocrinology and Metabolism Clinics of North America, 2007
Chronic kidney disease (CKD) is associated with significant disturbances in bone and mineral metabolism representing a major cause of skeletal and cardiovascular morbidity, particularly in end-stage CKD. Successful kidney transplantation corrects many of these disturbances, but the degree of improvement is often incomplete, and disorders of bone remodeling may persist or worsen after transplantation. Because the function of a renal graft deteriorates with time, disturbances are likely to reappear within the 10to 12-year life span of a kidney transplant.
Management of mineral and bone disorders in renal transplant recipients
Nephrology
The management of post-transplantation bone disease is a complex problem that remains under-appreciated in clinical practice. In these patients, preexisting metabolic bone disorder is further impacted by the use of immunosuppressive medications (glucocorticoids and calcineurin-inhibitors), variable post-transplantation renal allograft function and post-transplantation diabetes mellitus. The treatment of post-transplantation bone loss should begin pre-transplantation. All patients active on transplant waiting lists should be screened for bone disease. Patients should also be encouraged to take preventative measures against osteoporosis such as regular weight-bearing exercise, smoking cessation and reducing alcohol consumption. Biochemical abnormalities of disordered mineral metabolism should be corrected prior to transplantation wherever possible, and because these abnormalities commonly persist, post transplant hypophosphatemia, persistent hyperparathyroidism and low vitamin D levels should be regularly monitored and treated. Bone loss is greatest in the first 6-12 months post-transplantation, during which period any intervention is likely to be of greatest benefit. There is strong evidence that bisphosphonates prevent post-transplantation bone loss; however, data are lacking that this clearly extends to a reduction in fracture incidence. Denosumab is a potential alternative to vitamin D receptor agonists and bisphosphonates in reducing post-transplantation bone loss; however, further studies are needed to demonstrate its safety in patients with a significantly reduced estimated glomerular filtration rate. Clinical judgement remains the cornerstone of this complex clinical problem, providing a strong rationale for the formation of combined endocrinology and nephrology clinics to treat patients with Chronic Kidney Disease-Mineral and Bone Disorder, before and after transplantation.
BMC Nephrology
Background: Vitamin D, apart from being an important part of the "calcium-vitamin D-parathyroid hormone" endocrine axis, has diverse range of "non-calcemic" biological actions. A high prevalence of vitamin D deficiency has been observed in renal transplant recipients (RTRs) worldwide. This study aimed to determine the prevalence of hypovitaminosis D in Nepalese RTRs and interrelations between serum 25-hydroxyvitamin D [25(OH) D] and other biochemical parameters. Methods: A total of 80 adult RTRs visiting a university hospital were enrolled in this cross sectional study. Serum 25(OH) D and intact parathyroid hormone (iPTH) were measured using Enhanced Chemiluminiscent Immunoassay. The RTR population was categorized into recent transplant recipients (≤1 year) and long term recipients (> 1 year). The vitamin D status was defined as per NKF/KDOQI guidelines. SPSS version 20.0 was used to analyze the data. Appropriate statistical tests were applied to compare variables between groups and establish correlation. P < 0.05 was considered to be statistically significant. Results: The mean age of the recipients was 38.11 ± 11.47 years (68 males, 85.0%). Chronic glomerulonephritis was the leading cause of CKD. The two RTR groups (recent and long term) didn't differ in demographic and biochemical characteristics. 83.75% of the recipients had PTH levels above the upper limit of the recommended range for their stage of CKD. 57.5% had hypocalcemia and none of the recipients had hypercalcemia. The median serum 25(OH) D was 24.15 ng/ml (8.00-51.50 ng/ml). Only 27.5% had sufficient vitamin D status whereas 53.8% were vitamin D insufficient and 18.8% were vitamin D deficient, the distribution almost comparable in the 2 transplant group. The serum 25(OH) D was not significantly affected by the time post-transplant, gender and sunlight avoidance. There was a significant negative correlation between serum 25(OH) D and iPTH (Pearson's r = − 0.35, P = 0.001), but not so with the graft function. Conclusion: There is a high prevalence of vitamin D insufficiency in RTRs. The deficiency status is not corrected despite of nutritional improvement and normalization of GFR post-transplantation and likely exacerbates secondary hyperparathyroidism. Vitamin D supplementation coupled with sensible sun exposure could be important strategies in optimization of the vitamin D status in this population.
Vitamin D Status, Bone Mineral Density, and Inflammation in Kidney Transplantation Patients
Transplantation Proceedings, 2009
Vitamin D has immunomodulatory and anti-inflammatory activities in the healthy population and in various disease states. There are few data on the quantification of vitamin D status and inflammation with respect to changes in bone mineral density among renal transplantation patients. We analyzed the influence of vitamin D levels on allograft function and inflammatory status at the time of enrollment and at 1-year follow-up. Sixty-four renal transplant patients, including 38 males, showed an overall age of 38.61 Ϯ 1.05 years, had a mean graft age of 6.15 Ϯ 3.17 years. We excluded patients who had diabetes mellitus, chronic inflammatory disease, or chronic allograft nephropathy. We obtained pre-and posttransplantation serum samples and daily proteinuria on each patient. Measurements of bone mineral density were performed by dual-energy X-ray absortiometry. After enrollment, we followed the patients for 1 year. Thereafter we assessed serum creatinine, C-reactive protein, albumin, and spot urinary protein levels. The patients were divided into two groups based upon vitamin D levels: group I (n ϭ 29), Ͻ20 g/L versus group II (n ϭ 35), Ն20 g/L. There was no significant difference in intact parathyroid hormone levels between the two groups. Vitamin D level positively correlated with serum creatinine (r ϭ .32, P ϭ .01) and serum albumin levels (r ϭ .28, P ϭ .023) at the time of enrollment. At 1 year, patients in group I showed significantly higher creatinine (P Ͻ .001) and proteinuria levels (P Ͻ .05) than those in group II. Low vitamin D levels are not uncommon among renal transplant recipients. There was a significant association of vitamin D levels with renal allograft function. Low vitamin D levels may be a predictor of worsening of graft function and increasing proteinuria.
Bone mineral content after renal transplantation
Journal of Molecular …, 1984
Forearm bone mineral content (BMC), as evaluated by photonabsorption densitometry, was measured in 28 cadaver kidney donor recipients who entered the study 8 weeks postoperatively and were followed up for 18 months. BMC decreased significantly (p<0.05) but marginally in placebo-treated patients (n=t4) (initial BMC 1.09±0.25g/cm; final BMC 1.05±0.24). Fourteen patients were prophylactically given 1,25(OH)2vitamin D 3 in a dose which avoided hypercalcemia and hypercalciuria (~0.25 gg/day); under 1,25(OH)z vitamin D 3 prophylaxis a significant decrease of forearm BMC was observed no longer (initial BMC 0.94_+.0.21 g/cm; final BMC 0.95 +_ 0.21), but the difference between placebo and 1,25(Ott)z vitamin D 3 narrowly missed statistical significance (p = 0.066). It is concluded that the decrease of forearm BMC is negligible in transplant recipients with low steroid regimens. The data suggest a trend for prophylaxis with 1,25(OH)z vitamin D 3 to slightly ameliorate forearm (cortical) BMC loss.
Scientific Reports
Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19-2.14, 1.60 per mg/dL; 1.14-2.23 and 0.82 per 10 pg/mL; 0.68-0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of ptH and phosphate levels may provide additional information regarding renal allograft prognosis. Kidney transplantation (KTx) is the preferred renal replacement therapy in terms of cost, quality of life, and mortality when compared with maintenance dialysis 1-3. Over the past decades, short-term graft survival has been improved by the introduction of new immunosuppressants (e.g., calcineurin inhibitors and antimetabolic agents), which help to prevent acute rejection; nonetheless, long-term graft failure remains a major concern 4. The kidney transplant community needs to identify modifiable factors to further improve longer-term graft survival. Chronic kidney disease (CKD)-mineral bone disorder (MBD) is a common complication in patients with CKD, and it affects cardiovascular morbidity and mortality 5. Calcium, phosphate, parathyroid hormone (PTH),