Effect of paricalcitol on the urinary peptidome of kidney transplant patients

Background and Objective

Disorders in bone mineral metabolism are common after kidney transplantation, covering, among other pathologic conditions, secondary hyperparathyroidism. Paricalcitol, a selective vitamin D receptor activator, is indicated in the prevention and treatment of secondary hyperparathyroidism. Recent evidence suggests that paricalcitol is also associated, by mechanisms not yet clarified, with improved patient survival. To clarify these unknown mechanisms, the aim of this study was to determine whether 3 months of treatment with paricalcitol modified the urinary peptidome of kidney transplant patients.

Methods

This prospective study included 42 stable kidney transplant patients, randomized in 2 groups: a group treated with 1 μg/d paricalcitol (n = 25) and a control group that did not receive paricalcitol (n = 17). Urine samples of all patients were collected at baseline and after 3 months. The proteomic approach was based on magnetic bead technology coupled to MALDI-TOF mass spectrometry.

Results

Paricalcitol treatment produced significant changes in urinary peptidome of kidney transplant patients. Variations in urinary peptides were independent of the degree of proteinuria and of the decrease in parathyroid hormone levels.

Conclusions

With this preliminary study, we obtained a profile of urinary peptides in which changes occurred due to treatment with paricalcitol. The identification of proteins to which these peptides belong may improve our knowledge about the possible pleiotropic effects of paricalcitol.     

Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure: An Observational Cohort Study

Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3–1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0–3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P<0.001) than at 1, 2, and 5 years after transplant (AUC 0.73, 0.71, and 0.77, respectively, all P<0.001). Independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The discriminatory power of proteinuria for these intragraft injury processes was better in biopsy samples obtained >3 months after transplant (AUC 0.73, P<0.001) than in those obtained earlier (AUC 0.56, P<0.01), with 85% specificity but lower sensitivity (47.8%) for proteinuria >1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis.     

Oral Paricalcitol Reduces the Prevalence of Posttransplant Hyperparathyroidism: Results of an Open Label Randomized Trial

Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 μg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24‐h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1‐year posttransplant. Eighty‐seven patients completed the trial. One‐year posttransplant, 29% of paricalcitol‐treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 μg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.     

Efficacy and tolerability of intravenous paricalcitol in calcitriol-resistant hemodialysis patients with secondary hyperparathyroidism: 12-month prospective study

RATIONALE/OBJECTIVES: Data are limited regarding the use of paricalcitol in calcitriol-resistant patients with secondary hyperparathyroidism (SHPT). We aimed to evaluate the effects of paricalcitol in calcitriol-resistant hemodialysis patients with SHPT. METHODS: This is a 12-month, open-label, prospective study. Forty patients with calcitriol-resistant and/or calcitriol-intolerant SHPT were included. After a washout period, all patients converted to paricalcitol with a 1:3 conversion ratio. Serum calcium and phosphorus were monitored monthly, while serum intact parathyroid hormone (iPTH) once in every 3 months. Paricalcitol dose was reduced or discontinued in case of hypercalcemia and/or hyperphosphatemia. Pre- and posttreatment electrolyte and iPTH values were compared with Student's t-test and Wilcoxon signed-rank test, respectively. MAIN FINDINGS: Forty patients completed the study. Mean initiation dose of paricalcitol was 23 ± 7 μg/week. Mean serum calcium was 8.9 ± 0.8 mg/dL at baseline and 9.4 ± 0.7 mg/dL at study end (p = 0.07). Mean monthly serum phosphorus levels stayed stable. Paricalcitol was effective in reducing iPTH levels when compared with pretreatment values (747.9 ± 497.2 pg/mL, 307.3 ± 417.1 pg/mL, respectively; p < 0.001). Thirty-two patients had to discontinue intravenous (IV) paricalcitol at some time during their treatment. Main reasons for discontinuation were as follows: hyperphosphatemia (58%), hypercalcemia (25%), and iPTH < 150 pg/mL (17%). PRINCIPLE CONCLUSIONS: Paricalcitol was found to be effective in reducing iPTH levels in calcitriol-resistant patients with SHPT despite relatively frequent drug discontinuation rates.     

Ankle-Brachial Index and Bone Turnover in Patients on Dialysis

An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH.     

Antiproteinuric effect of oral paricalcitol in chronic kidney disease

BACKGROUND: Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients. METHODS: In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N= 107, mean dose 9.5 microg/week) or placebo (N= 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of paricalcitol on proteinuria. RESULTS: At baseline, proteinuria was present in 57 patients randomized to oral paricalcitol and 61 patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P= 0.004 (odds for reduction in proteinuria 3.2 times greater for paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive > or =30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS). CONCLUSION: Our results demonstrate that the reduction in proteinuria was associated with paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.     

Intact parathyroid hormone levels in renal insufficiency

To define the onset of the rise in intact parathyroid hormone (PTH) levels in renal insufficiency, we conducted a cross-sectional study of parameters of mineral metabolism in patients with varying degrees of renal impairment. Using an immunoradiometric assay to measure intact PTH levels, we found elevations in intact PTH levels as creatinine clearance approaches 60 ml/minute (serum creatinine near 1.8) and a significant inverse relationship between indices of renal function and intact PTH levels (r=-0.60, P<0.001 for intact PTH and creatinine clearance). Calcium and phosphate levels correlate less strongly with the degree of hyperparathyroidism (r=-0.39, P<0.001 for total calcium; r=0.31, P<0.05 for phosphate). As a group, only patients with severe renal failure (creatinine clearance <20 ml/minute) had 1,25-dihydroxyvitamin D levels below normal (11±4 [SEM] pg/dl, normal range 15–60). Intact and n-terminal PTH measurements correlate well in this patient population with varying degrees of renal insufficiency (r=0.9, P<0.001). Intact PTH can be elevated in patients with mild to moderate renal insufficiency, thus efforts to prevent the development of secondary hyperparathyroidism in renal failure should be undertaken early in the course of renal insufficiency.     

Evolution of Bone Disease at 2 Years After Transplantation: A Single-Center Study

Posttransplant bone disease is caused by renal osteodystrophy. We sought to examine bone mineral density (BMD) among 90 renal allograft recipients of mean age 42.7 ± 11.4 years to identify factors preventing bone loss at 2 years posttransplant. Subjects treated with cyclosporine or tacrolimus plus azathioprine/MMF and prednisone underwent BMD estimates of the lumbar spine (LS) and of the proximal femur using dual energy x-ray absorptiometry (DEXA) at 3 months and every 6 months for 2 years. We assayed markers of bone remodeling: intact parathyroid hormone (iPTH), calcitriol, osteocalcin, and carboxyterminal telopeptide of type I collagen on day 3, as well as month 1 and every 6 months after transplantation. At the initial measurement, we observed osteopenia (OSP) among 35% in the LS and 52% in the femur: there was osteoporosis in 8.3%. The prevalence of OSP increased during the first year, thereafter decreasing to the initial value, but the rate of osteoporosis did not change significantly (8.3% vs 6.0%). BMD and Z-score decreased during the first and increased in the second year; 27% of patients regained initial values and 38% higher ones. BMD gains in the LS and femur were observed among subjects with higher calcitriol levels during the first 6 months (P < .01), higher osteocalcin (P < .05), higher estimated glomerular filtration rate during 1–24 months and in the tacrolimus group. Improvement of LS BMD occurred in younger patients (38 vs 46 years; P < .027); BMD gain in the femur correlated with higher levels of iPTH from 1–12 months (P < .01). The tacrolimus group showed higher Z-scores in the LS and femur at 24 months (P < .05). Two years after transplantation >60% of recipients showed stabilization or gain in bone mass. A sufficient calcitriol level in the early transplant period, an adequate iPTH, good renal function, and tacrolimus therapy prevented BMD disease progression.     

Early biochemical response to parathyroidectomy for primary hyperparathyroidism and its predictive value for recurrent hypercalcemia and recurrent primary hyperparathyroidism

BackgroundThe traditional definition of cure after parathyroidectomy (PTX) for primary hyperparathyroidism is normocalcemia. Our hypothesis was that early postoperative levels of serum calcium and parathyroid hormone after PTX would have predictive value for later recurrence.MethodsWe performed a retrospective study of 1,146 patients with primary hyperparathyroidism who underwent PTX and had long-term biochemical follow-up. The first postoperative serum level of calcium and parathyroid hormone values were used to categorize patients into the following four early biochemical response groups: (1) complete response (normal calcium and normal parathyroid hormone), (2) partial response with hyperparathormonemia (normal calcium and increased parathyroid hormone), (3) partial response with hypercalcemia (increased calcium and normal parathyroid hormone), and (4) non-response (increases in both calcium and parathyroid hormone). Incidences of recurrent hypercalcemia and recurrent primary hyperparathyroidism >6 months after operation were then analyzed.ResultsThe overall rate of any elevated serum levels of calcium and any increase in serum levels of parathyroid hormone during >6-month follow-up was 9.8% (112 of 1146), with 6.6% (57 of 861) for group 1, 27% (35 of 129) for group 2, and 16% (20 of 127) for group 3 (P < .02). Partial biochemical responses with either increased serum calcium or increased parathyroid hormone levels were the strongest predictors of any episode of increased serum levels of calcium after 6 months and was associated with 2.7× to 4.3× the risk of recurrent primary hyperparathyroidism, respectively.ConclusionThis study demonstrates the importance of measuring parathyroid hormone in the early postoperative period to better predict later recurrent primary hyperparathyroidism.     

How low is too low? Intraoperative parathyroid hormone decline in normohormonal primary hyperparathyroidism

BackgroundIn normohormonal primary hyperparathyroidism, parathyroid hormone levels are normal but inappropriately elevated for the degree of hypercalcemia. The study goals were to determine intraoperative parathyroid hormone parameters predictive of (1) cure and (2) hypocalcemia in this subgroup.MethodsWe performed a retrospective cohort study comparing patients who underwent parathyroidectomy (2002–2019) for normohormonal and classic primary hyperparathyroidism. The primary outcomes were cure (calcium <10.3 mg/dL) and hypocalcemia (≤8.4 mg/dL) ≥6 months postoperatively.ResultsIn the study, 127 of 1,087 patients (11.7%) had normohormonal primary hyperparathyroidism. The groups experienced similar rates of cure (91.3% vs 94.1%, P = .23) and hypocalcemia (3.9% vs 2.9%, P = .53). However, intraoperative parathyroid hormone decline in cured patients was lower in those with normohormonal primary hyperparathyroidism (66.4% vs 84.5%, P < .0001). Receiver operating characteristic curves provided Youden’s indices of 52% and 75% (cure) and 75% and 88% (hypocalcemia) for patients with normohormonal and classic primary hyperparathyroidism, respectively. Cure rates with ≥50% intraoperative parathyroid hormone decline were similar (94.1% vs 95.0%, P = .72), but hypocalcemia was more prevalent in patients with normohormonal primary hyperparathyroidism and ≥70% intraoperative parathyroid hormone decline (10.4% vs 3.3%, P = .01).ConclusionIn patients with normohormonal primary hyperparathyroidism, intraoperative parathyroid hormone declines of ≥50% and ≥70% were predictive of postoperative cure and hypocalcemia, respectively. These parameters may inform intraoperative decision making and postoperative management.     

Has Dialysis Payment Reform Led to Initial Racial Disparities in Anemia and Mineral Metabolism Management?

Implementation of the Medicare ESRD prospective payment system (PPS) and changes to dosing guidelines for erythropoiesis-stimulating agents (ESAs) in 2011 appear to have influenced use of injectable medications among dialysis patients. Given historically higher ESA and vitamin D use among black patients, we assessed the effect of these policy changes on racial disparities in the management of anemia and mineral metabolism. Analyses used cross-sectional monthly cohorts for a period-prevalent sample of 7384 maintenance hemodialysis patients at 132 facilities from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor. Linear splines with knots at each policy change were used in survey-weighted regressions to estimate time trends in hemoglobin (Hgb), erythropoietin (EPO) dose, intravenous (IV) iron dose, ferritin, transferrin saturation (TSAT) concentration, parathyroid hormone (PTH), IV vitamin D dose, cinacalcet use, and phosphate binder use. From August 2010 to December 2011, mean Hgb declined from 11.5 to 11.0 g/dl (P<0.001), mean EPO dose declined from 20,506 to 14,777 U/wk (P<0.001), and mean serum PTH increased from 340 to 435 pg/ml (P<0.001). No meaningful differences by race were observed regarding the rates of change of management practices or laboratory measures (all P>0.21). Mean EPO and vitamin D dose and serum PTH levels remained higher in blacks. Despite evidence that anemia and mineral metabolism management practices have changed significantly over time, there was no immediate indication of racial disparities resulting from implementation of the PPS or ESA label change. Further studies are needed to examine effects among patient and facility subgroups.     

The effect of chronic kidney disease on intraoperative parathyroid hormone: A linear mixed model analysis

BackgroundReduced creatinine clearance is an indication for surgery in asymptomatic primary hyperparathyroidism, and a significant proportion of patients undergoing parathyroidectomy have chronic kidney disease. The purpose of this study was to evaluate the kinetics of intraoperative parathyroid hormone decline during parathyroidectomy in patients who have chronic kidney disease compared with those with who have normal renal function.MethodsThis is a single-center, retrospective study of patients with primary hyperparathyroidism undergoing parathyroidectomy (n = 646). Patients were grouped based on estimated glomerular filtration rate greater than (normal renal function) or less than (chronic kidney disease) 60 mL/min/1.73m². All patients had intraoperative parathyroid hormone monitoring and ≥6-month postoperative serum studies to confirm surgical cure. Intraoperative parathyroid hormone kinetic curves were analyzed using a linear mixed model.ResultsDespite similar pre-excision values, patients with chronic kidney disease had significantly higher intraoperative parathyroid hormone values at 5 minutes (76 vs 58 pg/mL, P = .02) and 10 minutes (54 vs 37 pg/mL, P = .004) postexcision. No significant difference was observed in whether patients met Miami criterion by 5 minutes (chronic kidney disease 71%, normal renal function 78%, P = .255) or by 10 minutes (chronic kidney disease 95%, normal renal function 96%, P = .751) postexcision. Using a linear mixed model, glomerular filtration rate did not have a significant effect on the change in intraoperative parathyroid hormone over time.ConclusionPatients with chronic kidney disease had significantly higher postexcision intraoperative parathyroid hormone levels. However, renal function did not affect the change in intraoperative parathyroid hormone over time, nor did renal function ultimately affect the likelihood of meeting the Miami criterion. Intraoperative parathyroid hormone monitoring remains useful in this population, although additional time points may be needed to observe normalization of values.     

A single-center experience of parathyroidectomy in 1500 cases for secondary hyperparathyroidism: a retrospective study

BackgroundChronic kidney disease (CKD) is a global public health problem. With the deterioration of renal function, a certain proportion of CKD patients enter the uremic stage, and secondary hyperparathyroidism (SHPT) becomes a challenge. For refractory hyperparathyroidism, parathyroidectomy (PTX) plays a key role in reducing mortality and improving prognosis. Nevertheless, no consensus has been reached on the optimal surgical method. We aimed to provide evidence for the effectiveness of surgical treatment by summarizing the experience from our center.MethodsClinical data from 1500 patients undergoing parathyroidectomy were recorded, which included 1419 patients in a total parathyroidectomy without autotransplantation (tPTX) group, 54 patients in a total parathyroidectomy plus autotransplantation (tPTX + AT) group, and 27 patients in the other group. Perioperative basic data, intact parathyroid hormone (i-PTH) levels, serum calcium levels, serum phosphorus levels, pathological reports, coexisting thyroid diseases, short-term outcomes and complications were analyzed. Moreover, postoperative complications were compared between the tPTX and tPTX + AT groups.ResultsParathyroid hormone, serum calcium and phosphorus levels decreased significantly post-surgery. Two patients died during the perioperative period. As the two most common complications, the incidences of severe hypocalcemia and hyperkalemia were 36.20% (543 cases) and 24.60% (369 cases), respectively. Pre-iPTH levels (OR = 1.001, 95% CI: 1.001–1.001, p < 0.01), serum alkaline phosphatase (ALP) levels (OR = 1.002, 95% CI: 1.001–1.002, p < 0.01) and the mass of excised parathyroid gland (OR = 3.06, 95% CI: 1.24–7.55, p = 0.02) were positively associated with postoperative severe hypocalcemia, while age and serum calcium were negatively associated with it. Pathological reports of resected parathyroid and thyroid glands indicated that 96.49% had parathyroid nodular hyperplasia, 13.45% had thyroid nodular hyperplasia, and 4.08% had thyroid papillary carcinoma.ConclusionsParathyroidectomy is a safe and effective treatment for refractory secondary hyperparathyroidism. Severe hypocalcemia is the main complication, and coexistent thyroid diseases should never be neglected.     

Efficacy of calcium carbonate and low-dose vitamin D/1,25(OH)2D3 in reducing the risk of developing renal osteodystrophy in children on continuous ambulatory peritoneal dialysis

Eight children with terminal renal insufficiency on continuous ambulatory peritoneal dialysis were followed for 12 months to evaluate laboratory parameters of mineral ion and bone metabolism. Calcium carbonate (range 47–295 mg/kg body weight per day) was given in combination with low doses of either vitamin D or 1,25(OH₂D₃. Blood urea nitrogen and serum phosphate concentrations remained well controlled throughout the observation period. A significant increase in serum calcium levels from 2.35±0.18 to 2.61±0.22 mmol/l (mean ± SD) was observed during the first 6 months. Alkaline phosphatase activity and mid-C-regional parathyroid hormone, both indirect parameters of bone metabolism, revealed no evidence of severe secondary hyperparathyroidism. Our data indicate that calcium carbonate may be sufficient to induce relative hypercalcaemia in uraemic children, and thus reduce the risk of developing renal osteodystrophy. Unwanted side-effects of vitamin D preparations, i. e. increased intestinal phosphate absorption and hypercalcaemia after successful renal transplantation, may thus be avoided.     

No difference between alfacalcidol and paricalcitol in the treatment of secondary hyperparathyroidism in hemodialysis patients: a randomized crossover trial

Alfacalcidol and paricalcitol are vitamin D analogs used for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease, but have known dose-dependent side effects that cause hypercalcemia and hyperphosphatemia. In this investigator-initiated multicenter randomized clinical trial, we originally intended two crossover study periods with a washout interval in 86 chronic hemodialysis patients. These patients received increasing intravenous doses of either alfacalcidol or paricalcitol for 16 weeks, until parathyroid hormone was adequately suppressed or calcium or phosphate levels reached an upper threshold. Unfortunately, due to a period effect, only the initial 16-week intervention period for 80 patients was statistically analyzed. The proportion of patients achieving a 30% decrease in parathyroid hormone levels over the last four weeks of study was statistically indistinguishable between the two groups. Paricalcitol was more efficient at correcting low than high baseline parathyroid hormone levels, whereas alfacalcidol was equally effective at all levels. There were no differences in the incidence of hypercalcemia and hyperphosphatemia. Thus, alfacalcidol and paricalcitol were equally effective in the suppression of secondary hyperparathyroidism in hemodialysis patients while calcium and phosphorus were kept in the desired range.     

Vitamin D Status, Bone Mineral Density, and Inflammation in Kidney Transplantation Patients

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 ± 1.05 years, had a mean graft age of 6.15 ± 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 = 29), <20 μg/L versus group II (n = 35), ≥20 μg/L. There was no significant difference in intact parathyroid hormone levels between the two groups. Vitamin D level positively correlated with serum creatinine (r = .32, P = .01) and serum albumin levels (r = .28, P = .023) at the time of enrollment. At 1 year, patients in group I showed significantly higher creatinine (P < .001) and proteinuria levels (P < .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.     

Incremento de la densidad mineral ósea en pacientes con hiperparatiroidismo terciario tras paratiroidectomía total y autotrasplante de glándula paratiroides

IntroductionChanges in bone metabolism and bone mineral density are observed in renal transplant patients with tertiary hyperparathyroidism. The objective of this work was to analyse the increase in bone mineral density, as well the laboratory results, after total parathyroidectomy and autotransplantation in renal transplant patients with tertiary hyperparathyroidism.Material and methodsA retrospective study was conducted in which the bone mineral density values at femoral and lumbar level were analysed, together with the serum levels of calcium, phosphorous, parathyroid hormone (PTH), and alkaline phosphatase in 13 renal transplant patients with tertiary hyperparathyroidism before and after total parathyroidectomy and autotransplantation of the parathyroid glands.ResultsParathyroidectomy is associated with an increase in bone mineral density at femoral and lumbar level, with an increase of 8.6 ± 6.7% at lumbar level, and 4 ± 16.1% at femoral level. The decrease in calcium after the parathyroidectomy was 2.8 mg/dL (95% CI; 1.9-4). The decrease in PTH was 172 pg/mL (95% CI; 98-354) and the decrease in alkaline phosphatase was 229 U/L (95% CI; 70-371).ConclusionsTotal parathyroidectomy and autotransplantation of the parathyroid glands in renal transplant patients with tertiary hyperparathyroidism increases the bone mineral density. Furthermore, the calcium, PTH and alkaline phosphatase returned to normal in the long-term.     

Intraoperative parathyroid hormone (IOPTH) assay might be better than the second-generation assay in parathyroidectomy for primary hyperparathyroidism

BackgroundIt is unclear whether the third-generation intraoperative parathyroid hormone assay can improve surgical outcomes over second-generation assay in primary hyperparathyroidism. We aimed to compare the rate of decrease and diagnostic accuracy between the two assays after parathyroid adenoma excision.MethodsConsecutive patients undergoing parathyroidectomy with intraoperative parathyroid hormone were analyzed. Blood was drawn before and 10 minutes and 20 minutes after excision of the adenoma. The same blood sample was run simultaneously in the second-generation assays (Elecsys PTH STAT) and third-generation assays (Elecsys 1–84 PTH). Biochemical cure meant >50% intraoperative parathyroid hormone decrease at 10 minutes. Cure meant normocalcemia 6 months after operation.ResultsRelative to the second-generation assay, the value of the intraoperative parathyroid hormone level was less in the third-generation assay before excision (P < .001), at 10 minutes (P < .001), and at 20 minutes (P < .001). The intraoperative parathyroid hormone rate of decrease and the proportion of normalized post-excision intraoperative parathyroid hormone were greater in the third-generation assay (P < .001), but the prediction accuracy appeared similar between the 2 (91.5% vs 91.0%). Patients with worse renal function (estimated glomerular filtration rate <80mL/min/1.73m²) had a slower intraoperative parathyroid hormone decrease in the second-generation but not in the third-generation assay.ConclusionDespite comparable accuracy between the two generations of assay, the third-generation assay might be better than the second-generation assay because of the more rapid decrease in the intraoperative parathyroid hormone and a greater percentage of normalized intraoperative parathyroid hormone, regardless of baseline renal function.     

Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody–Mediated Kidney Allograft Rejection

Urinary levels of C-X-C motif chemokine 9 (CXCL9) and CXCL10 can noninvasively diagnose T cell–mediated rejection (TCMR) of renal allografts. However, performance of these molecules as diagnostic/prognostic markers of antibody-mediated rejection (ABMR) is unknown. We investigated urinary CXCL9 and CXCL10 levels in a highly sensitized cohort of 244 renal allograft recipients (67 with preformed donor–specific antibodies [DSAs]) with 281 indication biopsy samples. We assessed the benefit of adding these biomarkers to conventional models for diagnosing/prognosing ABMR. Urinary CXCL9 and CXCL10 levels, normalized to urine creatinine (Cr) levels (CXCL9:Cr and CXCL10:Cr) or not, correlated with the extent of tubulointerstitial (i+t score; all P<0.001) and microvascular (g+ptc score; all P<0.001) inflammation. CXCL10:Cr diagnosed TCMR (area under the curve [AUC]=0.80; 95% confidence interval [95% CI], 0.68 to 0.92; P<0.001) and ABMR (AUC=0.76; 95% CI, 0.69 to 0.82; P<0.001) with high accuracy, even in the absence of tubulointerstitial inflammation (AUC=0.70; 95% CI, 0.61 to 0.79; P<0.001). Although mean fluorescence intensity of the immunodominant DSA diagnosed ABMR (AUC=0.75; 95% CI, 0.68 to 0.82; P<0.001), combining urinary CXCL10:Cr with immunodominant DSA levels improved the diagnosis of ABMR (AUC=0.83; 95% CI, 0.77 to 0.89; P<0.001). At the time of ABMR, urinary CXCL10:Cr ratio was independently associated with an increased risk of graft loss. In conclusion, urinary CXCL10:Cr ratio associates with tubulointerstitial and microvascular inflammation of the renal allograft. Combining the urinary CXCL10:Cr ratio with DSA monitoring significantly improves the noninvasive diagnosis of ABMR and the stratification of patients at high risk for graft loss.