Incidence of De Novo Post-Transplant Malignancies in Thai Adult Kidney Transplant Recipients: A Single-Center, Population-Controlled, Retrospective Cohort Study at the Highest Volume Kidney Transplant Center in Thailand.

Kidney transplant recipients (KTRs) are at increased risk of developing de novo post-transplant malignancies (PTMs), with regional differences in types with excess risk compared to the general population. A single-center, population-controlled, retrospective cohort study was conducted at a tertiary care center in Thailand among all adults who underwent their first kidney transplant from 1986 to 2018. Standardized incidence ratios (SIRs) of malignancy by age, sex, and place of residence were obtained using data from the National Cancer Registry of Thailand as population control. There were 2,024 KTRs [mean age, 42.4 years (SD 11.4); female patients, 38.6%] during 16,495 person-years at risk. Of these, 125 patients (6.2%) developed 133 de novo PTMs. The SIR for all PTMs was 3.85 (95% CI 3.22, 4.56), and for pooled solid and hematologic PTMs, it was 3.32 (95% CI 2.73, 3.99). Urothelial malignancies had the largest excess risk, especially in women [female SIR 114.7 (95% CI 66.8, 183.6); male SIR 17.5 (95% CI 8.72, 31.2)]. The next two most common cancers were non-Hodgkin's lymphoma and skin cancer [SIR 20.3 (95% CI 13.6, 29.1) and 24.7 (95% CI 15.3-37.8), respectively]. Future studies are needed to identify the risk factors and assess the need for systematic screening among PTMs with excess risk in KTRs.

Years of life lost and long-term outcomes due to glomerular disease in a Southeast Asian Cohort.

Death and end-stage kidney disease (ESKD) are major outcomes of glomerular disease. (GD) The years of potential life lost (YLL) may provide additional insight into the disease burden beyond death rates. There is limited data on premature mortality in GD. In this retrospective observational cohort study, we evaluated the mortality, ESKD rates, and YLL in Thais with biopsy-proven GD. The mortality and combined outcome rates were determined by log-rank test and ESKD by using a competing risk model. YLL and premature life lost before age 60 were calculated for different GD based on the life expectancy of the Thai population. Patients with GD (n = 949) were followed for 5237 patient years. The death rate and ESKD rates (95%CI) were 4.2 (3.7-4.9) and 3.3 (2.9-3.9) per 100 patient-years, respectively. Paraprotein-related kidney disease had the highest death rate, and diabetic nephropathy had the highest ESKD rate. Despite not having the highest death rate, lupus nephritis (LN) had the highest YLL (41% of all GD) and premature loss of life before age 60. In conclusion, YLL provided a different disease burden assessment compared to mortality rates and identified LN as the major cause of premature death due to GD in a Southeast Asian cohort.

Role of Parathyroid Hormone and Parathyroid Hormone-Related Protein in Protein-Energy Malnutrition.

Parathyroid hormone (PTH) is an endocrine peptide found exclusively in the parathyroid glands, whereas parathyroid hormone-related protein (PTHrP) is expressed in a wide range of tissues and organs and exerts endocrine, paracrine, and autocrine actions. PTH and PTHrP have a similar homology, sharing the initial 13 amino acid residues at the N-terminus and binding to the same type 1 PTH receptor (PTH1R), which regulates calcium homeostasis. An abnormal increase in PTH production can occur in primary and secondary hyperparathyroidism, whereas PTHrP can be produced in large quantities by malignant cancer cells from solid organs. In addition to increased bone resorption and hypercalcemia, recent evidence suggests that excess PTH and PTHrP can result in protein-energy wasting, malnutrition, and cachexia. Through binding to PTH1R and activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A in white adipose tissue, PTH and PTHrP can stimulate the expression of thermogenic genes causing adipose tissue browning. This change results in an increase in resting energy expenditure, loss of muscle and fat mass, and weight loss. These findings provide a mechanistic link for the long-established relationship between hyperparathyroidism and myopathy, as well as cancer and cachexia. The purpose of this review is to provide a summary of the emerging evidence from both experimental and clinical studies on the role of PTH and PTHrP in protein-energy malnutrition.

Improvement of nutritional status after parathyroidectomy in patients receiving maintenance hemodialysis.

Aims/Introduction: Parathyroidectomy is associated with improved survival in patients with end-stage kidney disease. Protein-energy wasting (PEW) is common in patients with kidney failure and predicts poor outcomes. Recent clinical trials have linked hyperparathyroidism to PEW. The present retrospective cohort study examined whether parathyroidectomy was associated with improvement in nutritional status in maintenance hemodialysis patients. Materials and methods: One hundred twenty-nine maintenance hemodialysis patients who had successful parathyroidectomy during 2012-2018 were identified (PTX group) and matched 1:1 to 479 patients with parathyroid hormone (PTH) levels ≤1,000 pg./mL (non-PTX control group) and 187 patients with PTH levels >1,000 pg./mL (pre-PTX control group) by propensity score. The matchings yielded 120 matched pairs from PTX and non-PTX groups (cohort 1) and 76 matched pairs from PTX and pre-PTX groups (cohort 2). Baseline and follow-up nutritional parameters associated with PEW were compared over the 12-month study period. Results: In cohort 1, substantially lower serum albumin and serum creatinine/body surface area (Cr/BSA) and higher proportions of patients with serum albumin ≤38 g/L (low albumin) and serum Cr/BSA ≤380 µmol/L/m2 (low Cr/BSA) were observed in the PTX group. These parameters improved significantly after parathyroidectomy. Total lymphocyte count (TLC) was comparable at baseline but the percentage of patients with TLC <800 cells/mm3 (low TLC) decreased substantially after parathyroidectomy. At follow-up, serum albumin, serum Cr/BSA and proportions of patients with low albumin and Cr/BSA became comparable with the non-PTX control group. The percentage of patients with low TLC became lower in the PTX group. Mixed-models analysis confirmed significant differences in the changes in serum albumin, serum Cr/BSA, and proportions of patients with low albumin and TLC between the two groups. In cohort 2, nutritional parameters were comparable at baseline. At follow-up, serum Cr/BSA was higher and proportions of patients with body mass index ≤18.5 kg/m2, low TLC and low Cr/BSA were lower in the PTX group. Weight gain was more frequent and of greater magnitude in the PTX group in both cohorts. A substantial reduction in blood pressure was also observed in the PTX group. Conclusion: Severe hyperparathyroidism was associated with nutritional impairment which improved considerably after parathyroidectomy.

Persistent hyperparathyroidism in long-term kidney transplantation: time to consider a less aggressive approach.

PURPOSE OF REVIEW: Persistent hyperparathyroidism affects 50% of long-term kidney transplants with preserved allograft function. Timing, options and the optimal target for treatment remain unclear. Clinical practice guidelines recommend the same therapeutic approach as patients with chronic kidney disease. RECENT FINDINGS: Mild to moderate elevation of parathyroid hormone (PTH) levels in long-term kidney transplants may not be associated with bone loss and fracture. Recent findings on bone biopsy revealed the lack of association between hypercalcaemic hyperparathyroidism with pathology of high bone turnover. Elevated PTH levels may be required to maintain normal bone volume. Nevertheless, several large observational studies have revealed the association between hypercalcemia and the elevation of PTH levels with unfavourable allograft and patient outcomes. Both calcimimetics and parathyroidectomy are effective in lowering serum calcium and PTH. A recent meta-analysis suggested parathyroidectomy may be performed safely after kidney transplantation without deterioration of allograft function. SUMMARY: Treatment of persistent hyperparathyroidism is warranted in kidney transplants with hypercalcemia and markedly elevated PTH levels. A less aggressive approach should be applied to those with mild to moderate elevation. Whether treatments improve outcomes remain to be elucidated.

Risk Factors of Renal Tubular Dysfunction in Thai People Living with HIV Receiving Tenofovir Disoproxil Fumarate.

Tenofovir disoproxil fumarate (TDF) associates with renal tubular dysfunction (RTD) in some people living with HIV (PLWH). We studied clinical and genetic factors associated with RTD in Thai PLWH receiving TDF. RTD was diagnosed in 13 of 65 (20%) patients. The median (interquartile range) age and CD4 cell counts were 43.8 (40.4-50.9) years and 554 (437-716) cells/mm3, respectively. The median duration of TDF use was 46.9 (31.5-54.1) months. Univariate logistic regression demonstrated body mass index (BMI), concomitant use of protease inhibitor (PI), hyperlipidemia, and homozygous C/C SNP rs1059751 of ABCC4 gene as predisposing factors of RTD. In multivariate model, concomitant use of PI [adjusted odds ratio (aOR) 11.39; 95% confidence interval (CI), 1.59- 81.56; P = 0.015], hyperlipidemia (aOR 8.59; 95% CI, 1.46-50.40; P = 0.017), and BMI (aOR 0.76; 95% CI, 0.59-0.98; P = 0.037) remained associated with RTD in patients receiving TDF. PLWH receiving TDF with the presence of these factors should be closely monitored for RTD.

Severe hyperparathyroidism is associated with nutritional impairment in maintenance hemodialysis patients.

Severe hyperparathyroidism predicts poor outcomes in patients with kidney failure. Mechanisms underlying the relationship between high parathyroid hormone (PTH) and decreased survival other than bone loss are largely unexplored. Recent evidence suggests the role of excess PTH in adipose tissue browning resulting in protein-energy wasting. The present retrospective observational study examined nutritional status among patients receiving maintenance hemodialysis with different degree of hyperparathyroidism. Seven hundred forty-five patients were categorized into four groups according to PTH levels: group 0, < 200; group 1, 200-599; group 2, 600-1,499; and group 3, ≥1,500 pg/ml. Group 0 was excluded because of the relationship between low PTH with aging and malnutrition. Patients in groups 1 and 2 were matched to group 3 by propensity score yielding 410 patients in the final analysis. Nutritional parameters at baseline and the preceding 1 and 2 years were examined. At baseline, lower serum albumin, creatinine/body surface area (Cr/BSA), height in female and higher percentage of patients with serum albumin < 38 g/L were observed in group 3 compared to groups 1 and 2. Higher PTH level was independently associated with serum albumin < 38 g/L and Cr/BSA < 380 µmol/L/m2. The longitudinal decline in serum albumin and Cr/BSA and the increase in the frequency of patients with serum albumin < 38 g/L were observed among patients in group 3. Between group comparisons confirmed a significant decline in serum albumin and Cr/BSA in association with an increase in the proportion of patients with serum albumin < 38 g/L and Cr/BSA < 380 µmol/L/m2 in group 3 compared to groups 1 and 2. Weight loss was more significant and was of greater magnitude among patients in group 3 compared to groups 1 and 2. Normalized protein catabolic rate in 3 groups were comparable. There was no significant difference in any of the nutritional parameters between groups 1 and 2. In conclusion, patients receiving maintenance hemodialysis with severe hyperparathyroidism showed deterioration of nutritional status compared to patients with moderate hyperparathyroidism and patients with PTH level in the recommended range. These findings support the role of extreme PTH level in protein-energy wasting emphasizing the importance of early management of hyperparathyroidism.

Prevalence and predictors of asymptomatic vertebral fracture in patients with end-stage renal disease.

Objective: This study aimed to investigate the prevalence and predictors of asymptomatic vertebral fracture in patients with end-stage renal disease undergoing hemodialysis. Methods: This cross-sectional study included 80 patients with end-stage renal disease undergoing hemodialysis. Medical history, Fracture Risk Assessment Tool and anteroposterior and lateral radiographs of the thoracolumbar and lumbosacral spine were obtained. Vertebral fractures were identified using the Genant semiquantitative assessment. Results: Radiography demonstrated asymptomatic vertebral fracture in 22 patients (27.5%). FRAX® results for major osteoporotic fracture (area under the curve, 0.64) and hip fracture (area under the curve, 0.62) were able to discriminate patients with prevalent asymptomatic vertebral fracture. A multivariate analysis demonstrated that a 1-year average corrected calcium (odds ratio, 0.38), steroid use (odds ratio, 8.99), and a serum albumin concentration <25 g/dL (odds ratio, 28.82) significantly predicted prevalent asymptomatic vertebral fracture (clinical model; area under the curve, 0.82). Combining the 1-year average corrected calcium and serum albumin concentration <25 g/dL with FRAX® results for major osteoporotic fracture (area under the curve, 0.78) and FRAX® results for hip (area under the curve, 0.75) produced a significantly greater area under the curve value to predict fracture when compared with FRAX® result for major osteoporotic fracture and FRAX® result for hip (P = 0.022). Conclusion: Asymptomatic vertebral fracture is prevalent. FRAX® results for major osteoporotic fracture and hip provided lower ability in predicting asymptomatic vertebral facture when compared to the clinical model. Combining a 1-year average corrected calcium and serum albumin concentration <25 g/dL with FRAX® result for major osteoporotic fracture or hip improved the model's performance and provided comparable area under the curve to the clinical model.

Dialysate Magnesium and Coronary Artery Calcification, Bone Mineral Density, and Cramping in Maintenance Hemodialysis: A Quasi-experimental Study.

RATIONALE & OBJECTIVE: Recent evidence suggests a role for magnesium as a calcification inhibitor. Increased magnesium abundance may attenuate vascular calcification and promote bone formation. STUDY DESIGN: Parallel-group, 1:1-allocation-ratio, quasi-experimental study. SETTING & PARTICIPANTS: The study was conducted at hemodialysis centers in Bangkok, Thailand. Patients receiving maintenance hemodialysis were screened for coronary artery calcification (CAC) and bone mineral density (BMD), and those with a CAC score of ≥300 were included and matched according to the initial CAC score. The intervention and control groups consisted of 20 patients in each arm. INTERVENTIONS: A high (1.75 mEq/L) or standard (0.7 mEq/L) dialysate magnesium concentration was delivered for 26 weeks. OUTCOMES: Changes in the CAC score and BMD and the progression of CAC. The safety outcomes included occurrence of cramps recorded as per usual care. RESULTS: The median CAC score of all patients was 1,792. Serum and ionized magnesium concentrations increased substantially in the high dialysate magnesium group. At the end of the study, the CAC score increased significantly in both the groups, with no significant difference between the groups. The number of participants with CAC progression was comparable between the 2 groups. In exploratory subgroup analyses stratified by the median CAC score, a significant decline in CAC and fewer participants with CAC progression were observed in the subgroup with lower CAC scores that received the high dialysis magnesium concentration. Bone mineral density was largely unchanged in both groups. The number of participants experiencing cramps and the number of episodes of muscle cramps were markedly lower among patients who received the high dialysis magnesium concentration. LIMITATIONS: The participants had severe vascular calcification at baseline; therefore, the findings might not apply to those with less-established calcification. Moreover, cramps were not systematically ascertained. CONCLUSIONS: The high dialysis magnesium concentration did not alleviate the progression of CAC or improve BMD in patients with severe calcification receiving hemodialysis; however, muscle cramps were less frequent among those treated with high dialysate magnesium. Further study is required to determine a possible favorable effect of high dialysis magnesium concentration in individuals with mild-to-moderate calcification.

Parathyroidectomy is associated with slow progression of vascular calcification in maintenance haemodialysis patients: A propensity score-matched case-control study.

Parathyroidectomy has been the mainstay of treatment of severe hyperparathyroidism in patients with kidney failure until the introduction of calcimimetic. Several large observational studies demonstrated the improvement in patient outcomes after parathyroidectomy. The benefit of parathyroidectomy on vascular calcification remains largely unexplored. AIM: To examine the association between parathyroidectomy and the progression of vascular calcification as well as overall survival in maintenance haemodialysis patients. METHOD: This is a matched case-control study undertaken between 2012 and 2020. Patients who underwent parathyroidectomy were identified and matched 1:1 to non-parathyroidectomized (non-PTX) haemodialysis patients using propensity score matching method resulting in 120 patients in each arm. Aortic arch calcification (AoAC) score was determined annually in the posteroanterior chest x-ray. The average follow-up period was 38 months. RESULTS: Baseline demographic, laboratory data and AoAC score were comparable among the two groups of patients. The prevalence of AoAC was 59% in the PTX group and 54% in the non-PTX group (p = .43). Progression of AoAC occurred in 33% in the PTX group and 47% in the non-PTX group (p = .04). Multivariate generalized linear model revealed parathyroidectomy as an independent protective factor [ß (95% CI) -1.04 (-1.68, -0.41)] and increased serum calcium as a potentiating factor [ß (95% CI) 0.62 (0.25, 0.1)] for progression of AoAC. Linear mixed models revealed an increase in AoAC score in both groups but between group comparisons indicated substantially slower progression in the PTX group. Rapid progression of AoAC was also observed more frequently among non-PTX patients. Death occurred in 7 and 16% in the PTX and non-PTX groups, respectively. Kaplan-Meier survival curve revealed better survival associated with parathyroidectomy (p = .01). More rapid progression of AoAC also correlated with worse survival. CONCLUSION: Parathyroidectomy was associated with slow progression of vascular calcification in maintenance haemodialysis patients.

Mechanisms of Vascular Calcification in Kidney Disease.

The increase in prevalence and severity of vascular calcification in chronic kidney disease is a result of complex interactions between changes in the vascular bed, mineral metabolites, and other uremic factors. Vascular calcification can occur in the intima and the media of arterial wall. Under permissive conditions, vascular smooth muscle cells (VSMCs) can transform to osteoblast-like phenotype. The membrane-bound vesicles released from transformed VSMCs and the apoptotic bodies derived from dying VSMCs serve as nucleating structures for calcium crystal formation. Alterations in the quality and the quantity of endogenous calcification inhibitors also give rise to an environment that potentiates calcification.

Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification.

Phosphate is essential for life but its accumulation can be detrimental. In end-stage renal disease, widespread vascular calcification occurs as a result of chronic phosphate load. The accumulation of phosphate is likely to occur long before the rise in serum phosphate above the normal range since several observational studies in both general population and early-stage CKD patients have identified the relationship between high-normal serum phosphate and adverse cardiovascular outcomes. Consumption of food high in phosphate increases both fasting and postprandial serum phosphate and habitual intake of high phosphate diet is associated with aging, cardiac hypertrophy, endothelial dysfunction, and subclinical atherosclerosis. The decline in renal function and dietary phosphate load can increase circulating fibroblast growth factor-23 (FGF-23) which may have a direct impact on cardiomyocytes. Increased FGF-23 levels in both CKD and general populations are associated with left ventricular hypertrophy, congestive heart failure, atrial fibrillation, and mortality. Increased extracellular phosphate directly affects endothelial cells causing cell apoptosis and vascular smooth muscle cells (VSMCs) causing transformation to osteogenic phenotype. Excess of calcium and phosphate in the circulation can promote the formation of protein-mineral complex called calciprotein particles (CPPs). In CKD, these CPPs contain less calcification inhibitors, induce inflammation, and promote VSMC calcification.

Abdominal aorta and pelvic artery calcifications on plain radiographs may predict mortality in chronic kidney disease, hemodialysis and renal transplantation.

PURPOSE: Vascular calcification is common in chronic kidney disease (CKD) and predicts poor patient outcomes. While computed tomography is the gold standard for evaluation of vascular calcification, plain radiograph offers a simpler and less costly alternative. The calcification of abdominal aorta, iliac and femoral arteries has been evaluated by plain radiograph, but the data on their outcome predictabilities are still limited. The present study investigated the role of abdominal aortic calcification (AAC) and pelvic arterial calcification (PAC) in predicting overall morality in non-dialysis CKD stages 2-5 (CKD 2-5), maintenance hemodialysis (HD) and long-term kidney transplant (KT) patients. METHODS: Four hundred and nineteen patients were included. Lateral abdominal and pelvic radiographs were obtained. The degree of AAC and PAC was evaluated according to the methods described previously by Kaupplia et al. and Adragao et al. Patients were followed prospectively for 5 years. RESULTS: AAC and PAC scores correlated well with the correlation coefficients of 0.442 for CKD 2-5, 0.438 for HD and 0.586 for KT (p < 0.001). Patients with AAC score > 6 or PAC score > 1 were older, showed higher prevalence of DM and had higher serum phosphate and PTH but lower serum albumin and eGFR. A more severe degree of AAC was associated with an increase in KT duration, whereas a more severe degree of PAC was associated with worsening kidney function and prolonged dialysis vintage. Kaplan-Meier survival curves revealed AAC score > 6 as a significant predictor of all-cause mortality in CKD 2-5 but not in HD or KT, whereas PAC score > 1 was a significant predictor of all-cause mortality in all three populations. After adjusting for age, the predictability of AAC was lost, whereas PAC remained an independent predictor of mortality in all three populations. Adjustments for cardiovascular and CKD risk factors including age, gender, BMI, DM, serum albumin, calcium and phosphate attenuated the predictability of PAC in HD but not in CKD 2-5 or KT patients. CONCLUSION: PAC was better than AAC in predicting mortality in CKD, HD and KT patients.

Absence of JC polyomavirus (JCPyV) viremia in early post-transplant JCPyV nephropathy: A case report.

JC polyomavirus (JCPyV)-associated nephropathy (JCPyVAN) occurs in <3% of PVAN cases after renal transplantation. We report the first confirmed case to our knowledge of JCPyVAN diagnosed by kidney biopsy in the early 6 months post transplant in Thailand. In this case report, recovery of renal allograft function was not observed after reduction of immunosuppressive agents and administration of intravenous immunoglobulin and cidofovir. Despite persistent JCPyV viruria, no significant further decline in allograft function was documented at 15 months post transplant.

Role of different imaging modalities of vascular calcification in predicting outcomes in chronic kidney disease.

Vascular calcification (VC) is common among patients with chronic kidney disease (CKD). The severity of VC is associated with increased risk of cardiovascular events and mortality. Risk factors for VC include traditional cardiovascular risk factors as well as CKD-related risk factors such as increased calcium and phosphate load. VC is observed in arteries of all sizes from small arterioles to aorta, both in the intima and the media of arterial wall. Several imaging techniques have been utilized in the evaluation of the extent and the severity of VC. Plain radiographs are simple and readily available but with the limitation of decreased sensitivity and subjective and semi-quantitative quantification methods. Mammography, especially useful among women, offers a unique way to study breast arterial calcification, which is largely a medial-type calcification. Ultrasonography is suitable for calcification in superficial arteries. Analyses of wall thickness and lumen size are also possible. Computed tomography (CT) scan, the gold standard, is the most sensitive technique for evaluation of VC. CT scan of coronary artery calcification is not only useful for cardiovascular risk stratification but also offers an accurate and an objective analysis of the severity and progression.

Hyperparathyroidism and increased fractional excretion of phosphate predict allograft loss in long-term kidney transplant recipients.

BACKGROUND: After kidney transplantation, fibroblast growth factor-23 (FGF-23) normally returns to baseline within 1 year whereas hyperparathyroidism persists in most kidney transplant (KT) recipients. As a result, serum phosphate remains relatively low in association with increased serum calcium and urinary phosphate excretion when compared to chronic kidney disease patients. The relationship between mineral metabolism and outcomes in long-term KT recipients has not been extensively studied. This study investigated whether the alteration in mineral metabolism influenced graft survival in long-term KT recipients. METHODS: This study included 273 KT recipients after 1 year of transplantation. Mineral parameters were obtained at the time of enrolment and patients were followed prospectively for an average of 71 months. RESULTS: Graft loss (death-censored) occurred in 41 (15%) patients. In univariate analysis, deceased donor transplantation, decreased serum albumin and estimated glomerular filtration rate, increased serum phosphate, parathyroid hormone (PTH), FGF-23 and fractional excretion of phosphate (FePi) predicted future allograft loss. After adjustments for cardiovascular disease risk factors, donor type, dialysis vintage, serum albumin and allograft function, only increased PTH and FePi remained associated with the outcome. Relationships between increased serum phosphate and FGF-23 with graft survival were lost after adjustments. Adjusted survival curves revealed the association between PTH > 90 pg/mL and FePi > 20% with worse graft survival. CONCLUSIONS: Hyperparathyroidism and increased FePi predicted allograft loss in long-term KT recipients.

Serum Phosphorus and Progression of CKD and Mortality: A Meta-analysis of Cohort Studies.

BACKGROUND: Recent studies have indicated that phosphorus may play an independent pathogenic role in chronic kidney disease (CKD) progression, but some of those studies were underpowered and yielded inconsistent results. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Non-dialysis-dependent patients with CKD (transplant recipients were excluded). SELECTION CRITERIA FOR STUDIES: Studies assessing the risk ratio of serum phosphorus level on kidney failure and mortality for non-dialysis-dependent patients with CKD published from January 1950 to June 2014 were included following systematic searching of MEDLINE, EMBASE, and the Cochrane Library. PREDICTOR: Serum phosphorus level. OUTCOME: Kidney failure, defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease. RESULTS: In 12 cohort studies with 25,546 patients, 1,442 (8.8%) developed kidney failure and 3,089 (13.6%) died. Overall, every 1-mg/dL increase in serum phosphorus level was associated independently with increased risk of kidney failure (hazard ratio, 1.36; 95% CI, 1.20-1.55) and mortality (hazard ratio, 1.20; 95% CI, 1.05-1.37). LIMITATIONS: Existence of potential residual confounding could not be excluded. CONCLUSIONS: This meta-analysis suggests an independent association between serum phosphorus level and kidney failure and mortality among non-dialysis-dependent patients with CKD and suggests that large-scale randomized controlled trials should target disordered phosphorus homeostasis in CKD.

Mineral and bone disorder after kidney transplantation.

After successful kidney transplantation, accumulated waste products and electrolytes are excreted and regulatory hormones return to normal levels. Despite the improvement in mineral metabolites and mineral regulating hormones after kidney transplantation, abnormal bone and mineral metabolism continues to present in most patients. During the first 3 mo, fibroblast growth factor-23 (FGF-23) and parathyroid hormone levels decrease rapidly in association with an increase in 1,25-dihydroxyvitamin D production. Renal phosphate excretion resumes and serum calcium, if elevated before, returns toward normal levels. FGF-23 excess during the first 3-12 mo results in exaggerated renal phosphate loss and hypophosphatemia occurs in some patients. After 1 year, FGF-23 and serum phosphate return to normal levels but persistent hyperparathyroidism remains in some patients. The progression of vascular calcification also attenuates. High dose corticosteroid and persistent hyperparathyroidism are the most important factors influencing abnormal bone and mineral metabolism in long-term kidney transplant (KT) recipients. Bone loss occurs at a highest rate during the first 6-12 mo after transplantation. Measurement of bone mineral density is recommended in patients with estimated glomerular filtration rate > 30 mL/min. The use of active vitamin D with or without bisphosphonate is effective in preventing early post-transplant bone loss. Steroid withdrawal regimen is also beneficial in preservation of bone mass in long-term. Calcimimetic is an alternative therapy to parathyroidectomy in KT recipients with persistent hyperparathyroidism. If parathyroidectomy is required, subtotal to near total parathyroidectomy is recommended. Performing parathyroidectomy during the waiting period prior to transplantation is also preferred in patients with severe hyperparathyroidism associated with hypercalcemia.

Are there ways to attenuate arterial calcification and improve cardiovascular outcomes in chronic kidney disease?

The risk of cardiovascular mortality among patients with end-stage renal disease is several times higher than general population. Arterial calcification, a marker of atherosclerosis and a predictor of cardiovascular mortality, is common in chronic kidney disease (CKD). The presence of traditional cardiovascular risk factors such as diabetes, hypertension, hyperlipidemia, and advanced age cannot fully explain the high prevalence of atherosclerosis and arterial calcification. Other factors specific to CKD such as hyperphosphatemia, excess of calcium, high dose active vitamin D and prolonged dialysis vintage play important roles in the development of arterial calcification. Due to the significant health risk, it is prudent to attempt to lower arterial calcification burden in CKD. Treatment of hyperlipidemia with statin has failed to lower atherosclerotic and arterial calcification burden. Data on diabetes and blood pressure controls as well as smoking cessation on cardiovascular outcomes in CKD population are limited. Currently available treatment options include non-calcium containing phosphate binders, low dose active vitamin D, calcimimetic agent and perhaps bisphosphonates, vitamin K and sodium thiosulfate. Preliminary data on bisphosphonates, vitamin K and sodium thiosulfate are encouraging but larger studies on efficacy and outcomes are needed.

Low hip bone mineral density predicts mortality in maintenance hemodialysis patients: a five-year follow-up study.

BACKGROUND: Bone loss is common among hemodialysis patients and contributes to mortality. The association between bone loss and vascular calcification may explain the increased mortality risk. Studies on the association between decreased bone mass and mortality in maintenance hemodialysis patients are limited. METHODS: Eighty-three hemodialysis patients underwent bone mineral density (BMD) and coronary artery calcification (CAC) measurements. The relationship between BMD and mortality was analyzed after a 5-year follow-up period. RESULTS: Eighty percent of the patients had reduced hip BMD. In univariate Cox regression analyses, age, cardiovascular disease, dyslipidemia, increased CAC score, increased comorbidity score and decreased hip BMD were associated with mortality. Low hip BMD remained independently associated with mortality after adjustments for cardiovascular risk factors, comorbidity score and CAC score. Patients with BMD in the lowest tertile had the worst survival. CONCLUSION: Low hip BMD predicted mortality in maintenance hemodialysis patients independent of CAC.