Prognostic associations of serum calcium, phosphate and calcium phosphate concentration product with outcomes in kidney transplant recipients (original) (raw)
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Elevated calcium phosphate product after renal transplantation is a risk factor for graft failure
Clinical Transplantation, 2007
Persistent abnormalities of mineral metabolism are common after renal transplantation. In dialysis patients, elevations in serum phosphorous (P), calcium (Ca), CaP product, and parathyroid hormone (PTH) are strongly associated with cardiovascular disease and increased overall morbidity and mortality (1-3). In renal transplant recipients, vascular disease is a major contributor to recipient death and chronic allograft nephropathy (4). After successful renal transplantation, many recipients have lingering abnormalities of Ca and P metabolism related to persistent hyperparathyroidism, medications, and residual cardiovascular disease. For these reasons, we hypothesized that renal transplant recipients with persistent abnormalities of mineral metabolism may have an associated Egbuna OI, Taylor JG, Bushinsky DA, Zand MS. Elevated calcium phosphate product after renal transplantation is a risk factor for graft failure.
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),
Calcium, phosphate and parathyroid metabolism in kidney transplanted patients
International Urology and Nephrology, 2009
Introduction Impaired kidney function is common in kidney-transplanted patients and complications of chronic kidney disease (CKD), such as mineral and bone disorders (MBD) are also prevalent in this population. Similarly to other stages of CKD, increasing evidence supports the association between MBD and cardiovascular risk after kidney transplantation as well. Still, little is known about the prevalence, clinical correlates of MBD and its management in transplanted patients. In this study, we aimed to examine the characteristics of MBD and its associations with clinical parameters in a large prevalent cohort of patients after kidney transplantation. Methods Nine hundred and ninety stable patients followed at a single kidney transplant outpatient clinic were included in the study. Detailed medical history, demographic data and routine laboratory results, including Ca, P and intact PTH were collected. Estimated GFR was calculated using the abbreviated MDRD formula, patients were stratified into three groups based on eGFR. Target levels for Ca, P and iPTH were based on CKD stages according to the NKF-K/DOQI guidelines. Standard statistical procedures, binomial and multinomial regressions were used in the analysis.
Renal Phosphate Loss in Long-Term Kidney Transplantation
Clinical Journal of the American Society of Nephrology, 2011
Background and objectives Renal phosphate wasting occurs early postkidney transplantation as a result of an accumulation of parathyroid hormone and fibroblast growth factor 23 from the CKD period. Serum phosphate, parathyroid hormone, and fibroblast growth factor 23 return to baseline 1 year postkidney transplantation. What happens beyond this period is unknown. Design, setting, participants, & measurements Mineral parameters were obtained from 229 kidney transplant recipients at least 1 year posttransplantation; 46 normal subjects and 202 CKD patients with similar GFR served as controls. Factors associated with phosphate metabolism were analyzed. Results Despite the reduced graft function, most kidney transplant recipients had lower serum phosphate than normal subjects accompanied by renal phosphate loss. Fibroblast growth factor 23 was mostly lower or comparable with normal subjects, whereas parathyroid hormone was elevated in most patients. Hyperparathyroidism is also more common among kidney transplant recipients compared with CKD patients. Both parathyroid hormone and fibroblast growth factor 23 showed relationships with renal phosphate excretion, but only parathyroid hormone displayed an independent association. Parathyroid hormone showed the highest area under the curve in predicting renal phosphate leak. When patients were categorized according to parathyroid hormone and fibroblast growth factor 23 levels, only subset of patients with high parathyroid hormone had an increased renal phosphate excretion. Conclusions Relatively low serum phosphate from renal phosphate leak continued to present in long-term kidney transplantation. Both parathyroid hormone and fibroblast growth factor 23 participated in renal tubular phosphate handling, but persistent hyperparathyroidism seemed to have a greater influence in this setting.
American Journal of Kidney Diseases, 1998
Elevated serum phosphorus is a predictable accompaniment of end-stage renal disease (ESRD) in the absence of dietary phosphate restriction or supplemental phosphate binders. The consequences of hyperphosphatemia include the development and progression of secondary hyperparathyroidism and a predisposition to metastatic calcification when the product of serum calcium and phosphorus (Ca ؋ PO 4 ) is elevated. Both of these conditions may contribute to the substantial morbidity and mortality seen in patients with ESRD. We have analyzed the distribution of serum phosphorus in two large national, random, cross-sectional samples of hemodialysis patients who have been receiving dialysis for at least 1 year. Data were obtained from two special studies of the United States Renal Data System, the Case Mix Adequacy Study (1990) and the Dialysis Morbidity and Mortality Study Wave 1 (1993). The relative risk of death by serum phosphorus quintiles is described after adjusting for age at onset of ESRD, race, sex, smoking status, and the presence of diabetes, the acquired immunodeficiency syndrome, and/or neoplasm. Logistic regression analysis is then used to describe the demographic, comorbid, and laboratory parameters associated with high serum phosphorus. Serum phosphorus was similar in these two study populations and averaged 6.2 mg/dL. Ten percent of patients had levels greater than 9 mg/dL and at least 30% of each group had serum phosphorus levels greater than 7 mg/dL. The adjusted relative risk of death by serum phosphorus level was not uniform across all quintiles, being constant below a level of 6.5 mg/dL and increasing significantly above this level. The relative risk of death for those with a serum phosphorus greater than 6.5 mg/dL was 1.27 relative to those with a serum phosphorus of 2.4 to 6.5 mg/dL. This increased risk was not diminished by statistical adjustment for coexisting medical conditions, delivered dose of dialysis, nutritional parameters, or markers of noncompliance. Evaluation of predictors of serum phosphorus greater than 6.5 mg/dL revealed in multivariate analysis that younger age at onset of ESRD, female sex, white race, diabetes, active smoking, and higher serum creatinine levels were all significant predictors. Analysis of serum calcium revealed no correlation with relative risk of death. The Ca ؋ PO 4 product, however, showed a mortality risk trend similar to that seen with serum phosphorus alone. Those in the highest quintile of the Ca ؋ PO 4 product (G72 mg 2 /dL 2 ) had a relative mortality risk of 1.34 relative to those with products of 42 to 52 mg 2 /dL 2 . The relative mortality risk by log parathyroid hormone (PTH) level was elevated for patients with higher levels, but the mortality risk associated with hyperphosphatemia was independent of PTH. For hemodialysis patients who have been receiving dialysis for at least 1 year, we conclude that a large percentage have a serum phosphorus level above 6.5 mg/dL and that this places them at increased risk of death. This increased risk is independent of PTH. The mechanism(s) responsible for death is unknown, but may be related to an abnormally high Ca ؋ PO 4 product. Although mechanisms are not clearly established, this study supports the need for vigorous control of hyperphosphatemia to improve patient survival.
Lack of increased urinary calcium-oxalate supersaturation in long-term kidney transplant recipients
Kidney International, 1997
Lack of increased urine calcium-oxalate supersaturation in long-term kidney transplant recipients. Nephrolithiasis is uncommon after kidney transplantation. However, calcium (Ca) supplementation, which has been proposed as a treatment of post-transplant osteopenia, might increase calciuria and bolster Ca stone formation. Therefore, in 24-hour urine of 82 normocalcemic long-term renal transplant recipients (RT) and in 82 healthy subjects (HS), we assessed some Ca ncphrolithiasis risk factors and the Ca-salt saturation estimated by the ion-activity product index (AP) and relative supersaturation (RS). In RT, calciuria was lower (mean SD, 3.20 2.25 vs. 4.61 1.71 mmol/day; P < 0.001), urinary volume higher (2.41 0.83 vs. 1.39 0.53 liter/day; P < 0.001), oxaluria higher (419 191 vs. 311 79 smol/day; P < 0.001) and citraturia lower (1.40 1.36 vs. 3.77 1.36 mmol/day; P < 0.001) than in HS. As a result, Ca-oxalate supersaturation was lower in RT than HS (AP, 1.07 0.69 vs. 2.07 1.13, P < 0.001; and RS, 0.62 0.26 vs. 0.94 0.21, P < 0.001), and was similar in subgroups of RT (N = 37) and HS (N = 37) matched for urinary volume, demonstrating that even without any larger urinary volume, Ca-oxalate saturation was not higher in RT than HS, and suggesting that opposite changes in Ca and oxalate in RT likely canceled their effects on lithogenic risk. In RT which had similar urinary pH and phosphate (P) than HS, CaP supersaturation was lower than in HS for brushite (AP, 3.25 6.67 vs. 6.01 4.85, P < 0.001; RS,-0.33 0.76 vs. 0.48 0.53, P < 0.001) and octacalcium phosphate (RS,-0.95 0.72 vs. 0.21 0.85, P < 0.001), and similar for apatite. Finally, fasting calciuria and calciuric response to a single oral Ca load were similar in RT (N = 19) and HS (N = 8). Together, these results argue strongly against a higher risk of Ca stone formation in RT than HS, even in case of Ca supplementation. Bone loss commonly occurs after kidney transplantation and aggravates the pre-existing renal osteodystrophy, leading to osteopenia, which is considered a major complication in graft recipients [11. Among the drugs commonly used to oppose rejection of the graft, steroids are known to induce osteoporosis and cyclosporine has been hypothetized to contribute to hone loss [21. In addition, persistent hyperparathyroidism and renal phosphate wasting are frequently observed in renal transplant recipients (RT), in whom they likely contribute to post-tranpiant bone disease [3-I• A single calcium (Ca) load acutely relieved the two
Kidney International, 1981
Decreased phosphate reabsorption after renal transplantation: Evidence for a mechanism independent of calcium and parathyroid hormone. We studied a group of 73 transplant recipients who had had stable renal function for more than 6 months after their transplant surgery. Of these 73 patients, 23 had fasting plasma phosphate concentrations less than 2.5 mg/dl (normal, 3 to 5 mgI dl). The concentration of plasma phosphates was 2.1 0.1 mg/dl in the hypophosphatemic transplant-recipient group compared with 3.0 0.1 mg/dl in the total transplant-recipient population. The hypophosphatemic patients had similar fractional phosphate reabsorption when compared with the total transplant-recipient population, and their renal phosphate threshold (Tm04IGFR) was reduced from 3.0 0.1 mg/dl in the total population to 1.4 0.2 mg/dl. Although PTH levels correlated inversely with the Tmp04IGFR in the total transplant-recipient group, the hypophosphatemic patients appeared to exhibit lower renal phosphate thresholds than did normophosphatemic transplant-recipients with similar PTH levels. To further evaluate the relationship between PTH and renal phosphate handling, we performed calcium infusion and phosphate titration studies on 11 hypophosphatemic transplant-recipients. The data revealed that 5 of the II patients with only mildly abnormal PTH levels failed to decrease their rate of phosphate excretion, their phosphate clearances, and their fractional excretion of phosphate during calcium infusion. The 5 nonresponders to calcium infusion also exhibited smaller increments in their plasma phosphate concentration and TmQ4/GFR than did the 6 patients who responded to calcium infusion with reductions in phosphate excretion rates. Before calcium infusion, cyclic 3'5'-adenosine monophosphate excretion rates were similar in both responders and nonresponders and were decreased to the same degree by the calcium infusions. These data indicate the presence of either a defect in phosphate reabsorption that is independent of the action of PTH and calcium or a heightened sensitivity to PTH with a decreased suppressibility of response to PTH. Diminution de Ia reabsorption de phosphate après transplantation rénale: Preuve de l'existence d'un mécanisme indépendant du calcium et de l'hormone parathyroidienne. Dans un groupe de 73 receveurs de reins ayant une fonction rénale stable, 23 avaient
Transplantation Proceedings, 2006
Background. Disorders of calcium homeostasis are one of the most common problems in patients with end-stage renal disease (ESRD). Elevated calcium levels increase the incidence of cardiovascular mortality in ESRD patients, and appear to be a risk factor for the occurrence of delayed graft function (DGF) after kidney transplantation. Therefore, we investigated the impact of pretransplant serum calcium levels on outcomes after kidney transplantation: DGF, acute rejection, graft function, and survival, as well as the incidence of cardiovascular events. Methods. We studied 285 patients (96.9% of all transplanted patients) who underwent their first transplantation between 1995 and 2004. Demographic data were extracted from hospital records or were documented during follow-up; serum samples were collected at the time of transplantation. Results. In our cohort the incidence of DGF was 16.5% and 35.4% of acute rejection episodes (ARE). However, pretransplant calcium levels were not related to DGF or ARE in our patient cohort. Furthermore, there was no correlation between pretransplant serum calcium level with the incidence of cardiovascular events or mortality, as well as graft function or survival. Conclusion. In our study population pretransplant calcium levels showed no effect on DGF, ARE rate, the occurrence of cardiovascular events or death, renal graft function, or survival. Therefore, pretransplant calcium level is not a helpful marker for risk stratification at the time of transplantation.
Calcium and Phosphorus Metabolism Disturbances After Renal Transplantation
Transplantation Proceedings, 2007
Introduction. Several studies have noted that, despite beneficial correction of abnormalities of mineral metabolism after successful renal transplantation, renal functional recovery is incomplete. Also, persistence of hyperparathyroidism and metabolic acidosis among patients with chronic impairment of graft function together with the use of loop diuretics and immunosuppressive drugs with adverse effects may alter mineral metabolism. We determined calcium and phosphorus levels in recipients. Methods. This cross-sectional study enrolled 398 recipients in 2 medical centers in Iran from 1988 to 2004 to evaluate serum calcium and phosphorus levels after 1 month in relation to graft and patient survivals. Cyclosporine was the constant part of the immunosuppressive treatment in all study subjects. Results. The median follow-up time was 8 months (range, 1-180 months). One and 10-year survival rates of patients were 97.9% and 91.1%. Mean (SD) serum calcium levels before and after transplantation were 8.79 (1.26) and 8.50 (1.39) mg/dL, respectively (P ϭ .020). The mean (SD) phosphate levels before and after transplantation were 6.43 (2.42) and 3.64 (1.71) mg/dL, respectively (P ϭ .000). There was no significant difference in survival considering changes in serum calcium and phosphorus levels. There was no correlation between serum calcium and phosphorus level changes among study patients. Conclusions. Despite reports suggesting hypercalcemia as a posttransplantation finding, we did not observe this condition, but, consistent with other reports in this field, we observed a significant decrease in serum phosphorus levels showing correction of this mineral level.