Hyperleptinemia positively correlated with metabolic syndrome in renal transplant recipients

Lee M‐C, Lee C‐J, Ho G‐J, Lee C‐C, Shih M‐H, Chou K‐C, Hsu B‐G. Hyperleptinemia positively correlated with metabolic syndrome in renal transplant recipients.
Clin Transplant 2010: 24: E124–E129.
© 2010 John Wiley & Sons A/S. Abstract: Objective: Our aim was to evaluate the relationship between metabolic syndrome and fasting serum leptin concentration in renal transplant recipients. Patients and methods: Fasting blood samples were obtained from 55 renal transplant recipients. Metabolic syndrome and its components were defined using the diagnostic criteria of the International Diabetes Federation. Results: Thirteen patients (23.6%) had metabolic syndrome. Fasting leptin concentrations were positively correlated with metabolic syndrome (p = 0.003). Univariate linear regression analysis indicated fasting serum leptin values were positively correlated with waist circumference (r = 0.284; p = 0.036), body mass index (r = 0.358; p = 0.007), body fat mass (r = 0.610; p < 0.001), triglycerides (r = 0.268; p = 0.048), high‐sensitivity C‐reactive protein (hs‐CRP) (r = 0.377; p = 0.005), triceps skinfold (r = 0.335; p = 0.012), and mid‐arm fat area (r = 0.351; p = 0.009). Multivariate forward stepwise linear regression analysis of the significant variables revealed that body fat mass (R² change = 0.373; p < 0.001) and hs‐CRP (R² change = 0.045; p = 0.049) were the independent predictors of fasting serum leptin concentration. Conclusion: Serum leptin concentration correlates positively with metabolic syndrome in renal transplant recipients.     

N-Terminal Pro–B-type Natriuretic Peptide Is Inversely Related to Bone Mineral Density in Renal Transplant Recipients

IntroductionBone mineral density (BMD) was significantly lower in heart failure patients. Our aim was to evaluate the relationship between BMD and fasting serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in renal transplant recipients.MethodsFasting blood samples were obtained from 69 renal transplant recipients. BMD was measured by dual energy x-ray absorptiometry in lumbar vertebrae (L2–L4). Serum NT-proBNP levels were measured by electrochemiluminescence immunoassay.ResultsAmong the renal transplant recipients, 8 patients (11.6%) had osteoporosis and 28 (40.6%) had osteopenia; 33 had a normal BMD. Increased serum NT-proBNP (P < .001) and decreased body mass index (P = .033) and body weight (P = .010) were significantly correlated with low lumbar T-score cutoff points between groups (normal, osteopenia, and osteoporosis). Women had lower lumbar BMD than did men (P = .013). Menopause in women (P = .005), use of tacrolimus (P = .020), and use of cyclosporine (P = .046) among renal transplant recipients were associated with lower lumbar BMD. Multivariate forward stepwise linear regression analysis of the significant variables revealed that log-transformed NT-proBNP (β, ?0.545; R² = 0.331; P < .001), and body weight (β, 0.273, R² = 0.104; P = .005) were independent predictors of lumbar BMD values among the renal transplant recipients.ConclusionsSerum NT-proBNP concentrations correlate negatively with lumbar BMD values among renal transplant recipients and may be an alternative to energy x-ray absorptiometry for identifying at risk of osteoporosis in renal transplant recipients.     

Association of high IFN‐γ plasma levels with low B‐cell counts in renal transplant recipients with stable long‐term graft function

Daniel V, Naujokat C, Sadeghi M, Renner FC, Weimer R, Opelz G. Association of high IFN‐γ plasma levels with low B‐cell counts in renal transplant recipients with stable long‐term graft function.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01067.x
© 2009 John Wiley & Sons A/S. Abstract: Recently, we reported that patients with long‐term stable good graft function had higher interferon‐gamma (IFN‐γ) and lower IL‐4 plasma levels late as compared with early post‐transplant. These patients had more often detectable CD3⁺CD4⁺CD25⁺IFN‐γ⁺Foxp3⁺ peripheral blood lymphocytes (PBL) late post‐transplant than patients with impaired graft function. We therefore speculated that high plasma IFN‐γ late post‐transplant might contribute to the maintenance of graft acceptance. Using ELISA and four‐color flow cytometry, plasma cytokines and PBL subpopulations were measured in 65 renal transplant recipients with stable graft function late post‐transplant. High IFN‐γ plasma levels were associated with low CD19⁺ B PBL (r = ?0.329; p = 0.009) and low activated CD3⁺CD8⁺DR⁺ T PBL (r = ?0.266; p = 0.035). Plasma IFN‐γ increased with time post‐transplant (r = 0.288; p = 0.022) and was not associated with the dose of immunosuppressive drugs (p = n.s.). High plasma IFN‐γ was not associated with serum creatinine (r = 0.038; p = 0.765). Five patients showed evidence of chronic allograft nephropathy in previous biopsies and none of them exhibited increased plasma IFN‐γ. In patients with good long‐term graft function, high IFN‐γ plasma levels were associated with low numbers of B PBL and activated CD8⁺ T PBL. High IFN‐γ plasma levels might prevent the development of an immunological alloresponse and thereby contribute to the maintenance of graft acceptance.     

Age at Transplant—One of the Factors Affecting Bone Mineral Density in Kidney Recipients—A Single-Center Retrospective Study

Abstract

Background: Osteoporosis/osteopenia after kidney transplantation is multifactorial, and the mechanism responsible for this condition is unclear. A cumulative steroid dose and female gender are two likely major risk factors for osteoporosis/osteopenia after transplantation, but there is no consensus as to which risk factors are most strongly associated with reduced bone mineral density (BMD). Methods: We assessed 84 kidney recipients who had received transplants at least 5 months prior to enrollment in the study. BMD at the lumbar spine, hip, and femoral neck was evaluated by dual-energy X-ray absorptiometry. We used the average BMD (BMDa), defined as the average of the sum of the lumbar spine, hip, and femoral neck mineral density values, as representative of body BMD. Results: This retrospective study revealed inverse correlations between the BMDa and creatinine level and age at transplant as well as a positive correlation with male gender. Osteoporosis occurred in transplantations where the duration since transplantation was longer. Conclusion: This retrospective study demonstrated that a decrease in BMD, reflecting a bone condition tending toward osteoporosis/osteopenia, is inversely correlated with male gender, creatinine level, and age at transplant in kidney recipients. Nonetheless, the time since transplant is higher in the osteoporosis group than in the osteopenia group.     

磁共振扩散加权成像表观扩散系数、信号强度比对腰椎骨质疏松的定量评价

目的:探讨磁共振扩散加权成像(diffusion weighted imaging,DWI)表观扩散系数(apparent diffusion coefficient,ADC),信号强度比(signal intensity ratio,SIR)在腰椎骨质疏松定量评价中的应用价值。方法:选取2017年5月至2019年10月接受双能X线吸收(dualenergy X ray absorption,DXA)骨密度(bone mineral density,BMD),腰椎常规MRI扫描和DWI扫描检查的腰椎疾病患者175例。根据DXA骨密度T值分为骨质疏松组(64例)、骨量减少组(53例)、骨量正常组(58例)。测量比较3组腰椎L_2-L_4的ADC、SIR值;分析ADC、SIR值与BMD的相关性;采用受试者工作特征(receiver operator characteristic,ROC)曲线分析ADC,SIR值对腰椎骨质疏松与骨量减少,腰椎骨质疏松与骨量正常及腰椎骨质疏松的鉴别诊断价值。结果:3组ADC、SIR值比较差异均有统计学意义(F=41.386、37.114,均P=0.000);骨质疏松组ADC值低于骨量减少组、骨量正常组(t=3.540、9.069,P=0.001、0.000);骨质疏松组SIR值高于骨量减少组、骨量正常组(t=5.083、8.523,均P=0.000)。Spearman相关性分析显示:ADC值与BMD呈正相关(r=0.313,P=0.004);SIR值与BMD呈负相关(r=-0.589,P=0.000)。ROC曲线分析显示:ADC、SIR诊断腰椎骨质疏松骨量减少的曲线下面积(area under curve,AUC),敏感度,特异度分别为0.742,89.1%,52.8%和0.729,89.1%,50.9%(均P=0.000);ADC、SIR诊断腰椎骨质疏松骨量正常的AUC,敏感度,特异度分别为0.815,100.0%,50.0%和0.856,65.6%,93.1%(均P=0.000);ADC、SIR诊断腰椎骨质疏松的AUC,敏感度,特异度分别为0.78,89.1%,51.4%和0.795,50.0%,94.6%(均P=0.000);均有一定诊断价值。结论:ADC、SIR能够较好地反映腰椎疾病患者BMD情况,可对骨质疏松的椎体进行定量评价,二者水平对腰椎骨质疏松具有重要的辅助诊断作用。     

Prevalence of osteoporosis, osteopenia, and vertebral fractures in long-term renal transplant recipients

BACKGROUND: Osteopenia and osteoporosis are frequent complications early after transplantation. Their long-term prevalences and associations with the risk of fractures are not well known. The objective of the present work was to determine the incidence of osteopenia and osteoporosis versus vertebral fractures in renal transplant recipients with stable graft function and with a follow-up of at least 10 years. PATIENTS AND METHODS: Forty renal transplant recipients, 24 men and 16 women, were included in the study. The mean age was 41.8 years and the follow-up was 130 +/- 14 months. Initial immunosuppression consisted of cyclosporine with or without an antiproliferative agent. Measurements of bone mass density (BMD) were performed by dual-energy X-ray absorptiometry (DEXA). The assessment of vertebral fracture using conventional radiography was evaluated by semiquantitative criteria. RESULTS: Eleven patients (27.5%) displayed lumbar spine osteoporosis (T-score < -2.5); 21 (52.5%), osteopenia (T-score > -2.5 and < -1) and 8 (20.0%), normal BMD. However, BMD was better preserved at the femoral neck: 14 patients (35.0%) had normal BMD; 20 (50.0%) osteopenia, and 6 (15.0%), osteoporosis. When analyzed together, patients with osteoporosis or osteopenia showed worse graft function at 1 and 8 years compared with normal BMD patients (1.75 +/- 0.634 vs 1.32 +/- 0.33 mg/dL at 1 year; P < .014) and (1.7 +/- 0.4 vs 1.2 +/- 0.2 mg/dL at 5 years; P < .01) and a greater number were prescribed vitamin D (50% vs 23%). Mild vertebral fractures were observed in 60.0% patients with osteoporosis; 70% with osteopenia; and 43% with normal lumbar BMD. Peripheral fractures were more common in patients with osteoporosis (P = .053). CONCLUSIONS: Osteoporosis and osteopenia are common among long-term renal transplant recipients are associated with poorer graft function. Lumbar spine BMD osteoporosis is associated with peripheral fractures. However, mild vertebral deformities are not associated with the presence of osteopenia or osteoporosis.     

Serum uric acid level is associated with cardiac hypertrophy in renal transplant recipients

Caliskan Y, Gorgulu N, Yelken B, Akturk F, Yazici H, Turkmen A, Sever MS. Serum uric acid level is associated with cardiac hypertrophy in renal transplant recipients.
Clin Transplant 2011: 25: 368–374. © 2010 John Wiley & Sons A/S. Abstract: Background: Serum uric acid (UA) level as a significant and independent risk factor for cardiovascular disease, and the link between this marker and left ventricular hypertrophy (LVH) in renal transplant recipients remains to be clarified. Methods: A total of 141 renal transplant recipients (83 men), between ages of 18 and 69 (mean age 37 ± 11), were included in this single center study. In addition to demographic, clinical, and laboratory parameters, serum UA concentrations were evaluated. LVH was determined by two‐dimensional and M‐mode echocardiography. Results: Serum UA levels were significantly higher (6.14 ± 1.15 mg/dL) in patients with LVH (n = 54) when compared to patients (n = 87) who did not have this abnormality (5.29 ± 1.43 mg/dL) (p = 0.006). Serum UA levels were significantly correlated with septal wall thickness, LV posterior wall thickness, LV mass index (LVMI), and pulmonary arterial pressure. Multiple linear regression analysis revealed that UA predicted LVMI (r² = 0.150, β = 0.369, p = 0.001). However, serum creatinine (β = 0.060, p = 0.593) and age (β = 0.146, p = 0.175) were not predictors of LVMI. Conclusion: High serum UA levels are associated with LVH in renal transplant recipients, which underlines the importance of treating hyperuricemia.     

Fasting long-acting natriuretic peptide correlates inversely with metabolic syndrome in kidney transplant patients

The metabolic syndrome (MetS) is a risk factor for posttransplant diabetes mellitus, chronic graft dysfunction, graft loss, occurrence of atherosclerotic events, and patient death among kidney transplantation patients. Long-acting natriuretic peptide (LANP) is among the peptide hormones in atrial natriuretic peptide prohormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. This study was undertaken to evaluate the relationship between MetS and fasting serum LANP concentration among kidney transplanted patients. Fasting blood samples were obtained from 69 kidney recipients. The MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation. Fasting LANP levels were measured using a commercial enzyme immunoassay kit. The prevalence rate of MetS was 20.3% (14/69). Fasting LANP level negatively correlated with MetS among these patients (P = .010). Using univariate linear regression analysis, serum LANP values were negatively correlated with hemoglobin (r = −0.252; P = .037), and positively correlated with blood urea nitrogen (r = 0.254; P = .035) and creatinine (r = 0.311; P = .009). Multivariate forward stepwise linear regression analysis of the significant variables revealed that creatinine (R² change = 0.097; P = .009) was an independent predictor of fasting serum LANP concentration among kidney transplanted patients. Serum LANP concentration correlates inversely with MetS; for these patients, creatinine is an independent predictor of the serum LANP value.     

Bone mineral density in live related kidney transplant children and adolescents

Successful kidney transplantation corrects many of the metabolic abnormalities associated with development of renal osteodystrophy, but despite a well-functioning graft, osteopenia, remains prevalent in adult and pediatric kidney recipients. The factors that affect the bone mineral density (BMD) and the long term course of BMD after transplantation in children is still unknown. We performed a cross sectional study to determine BMD in 83 recipients who received living renal allotransplants in Mansoura Urology & Nephrology Center between 1981 and 2002 (mean age at transplantation 13.2 ± 3.1 years) by dual energy x-ray absorptiometry at various time intervals up to 16 years after transplantation (mean duration after transplantation was 48 ± 34 months, range 12–192 months). The mean ± SD for BMD was −2.28 ± 2.06 for lumbar 2-4 spine and −1.44 ± 1.44 for the total body BMD as corrected for body surface area. Osteopenia/osteoporosis were present in about two thirds of our kidney transplant recipients. The significant risk factors for osteopenia/osteoprosis using univariate analysis were the cyclosporine based immunosuppressive regimen, cumulative dose of steroids/m² surface area, graft dysfunction and the urinary deoxypyridinoline. Using logistic regression analysis the cumulative steroid dose/m² surface area and the urinary deoxypyridinoline were the major significant predictors for bone loss. In conclusion, osteopenia and osteoprosis are common in pediatric and adolescent renal transplant patients. The cumulative steroid dose and the urinary deoxypyridinoline were the major predictors for bone loss. This revised version was published online in August 2006 with corrections to the Cover Date.     

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.     

Lumbar bone mineral density in very long-term renal transplant recipients: Impact of circulating sex hormones

The influence of circulating sex hormones and gender on the bone mineral density (BMD) in long-term renal transplant recipients needs further investigation. We performed a retrospective analysis of lumbar BMD between 6 years and 20 years after renal transplantation. In 67 patients (47±12 years, 38 male) with a minimum interval of 72 months after transplantation, lumbar BMD measurements (dual energy X-ray absorptiometry) were performed (=complete cohort). Thirty-one patients (=longitudinal cohort) underwent at least three serial BMD measurements (mean follow-up 39±18 months, start at 86±22 months). All patients received prednisolone. In the complete cohort, BMD was significantly reduced in comparison to young healthy (mean T -score –1.33±1.40) and age-matched controls (mean Z -score –0.91±1.45) at 88±31 months ( p <0.05). Osteopenia or osteoporosis were present in two-thirds of patients. In the longitudinal cohort, a mean annual lumbar BMD loss of –0.6±1.9% was detectable equivalent to a –0.03±0.15 reduction of Z -scores per year (regression analysis). Impact of hormonal status: In the complete cohort, postmenopausal status was associated with significantly lower BMD levels compared to men ( p =0.0441). Women and men within the lowest tertile of sex hormone levels (LH, FSH, DHEAS, testosterone, progesterone, estradiol) did not exhibit significant differences in terms of lumbar BMD compared to those in the highest tertile. The mean annual bone loss was statistically indistinguishable between men and women. There was no significant correlation of sex hormone levels and BMD in men and premenopausal women. In postmenopausal women, however, low estradiol and high LH levels correlated with the extent of annual BMD loss ( p <0.05). Our data confirm significantly reduced lumbar T -scores in the very late period after renal transplantation. The lumbar BMD decreased by –0.6±1.9% per year. In postmenopausal long-term renal transplant recipients, low estradiol levels were associated with accelerated bone loss.The data were presented in part at the 37th annual meeting of the American Society of Nephrology, ASN 2004 (Renal Week 2004)     

Reduced bone mineral density in male renal transplant recipients: evidence for persisting hyperparathyroidism

Background: Osteoporosis is increasingly recognized as a major source of morbidity following renal transplantation. The aim of this cross-sectional study was to determine the prevalence of osteoporosis in a cohort of male transplant recipients and examine factors that may influence their bone loss. Methods: Bone mineral density (BMD) and biochemical markers of bone metabolism were measured in 134 out of 154 male renal allograft recipients in our center. Results: The mean age of the patients was 49.7 years (range 26–76) with a median of 6 years post-transplant. Only 17% had normal BMD, 30% were osteoporotic at either hip or spine, and this proportion rose to 41% if the ultradistal radius was included. Parathyroid hormone (PTH) was negatively correlated with BMD at all skeletal sites. In a multiple regression model, independent predictors of femoral neck BMD included body mass index (p=0.004), diabetes (p=0.025), and PTH (p=0.049). The only independent predictor of BMD at the ultradistal radius was PTH (p<0.001). Nineteen men sustained a total of 25 appendicular fractures after transplantation (median time to fracture was 3 years). Prevalent vertebral fractures were only identified in five men. PTH was elevated in 72.4% of patients (mean PTH 142 ± 118 pg/ml). Bone resorption markers were increased in 48% of patients. PTH was positively correlated with serum carboxyterminal telopeptide of type 1 collagen (r=0.473, p<0.001) and procollagen type 1 amino terminal propeptide (r=0.419, p<0.001). Conclusions: Osteopenia and osteoporosis are common in male transplant recipients, and the hip and radius are the most severely affected sites. Elevated rates of bone resorption driven by hyperparathyroidism appear to be the most important contributing factor.     

Clinical predictors of incipient vertebral fractures and bone mineral density in kidney transplant patients

Purpose

Kidney transplant recipients are prone to metabolic bone diseases and consequent fractures. This study aimed to evaluate the incidence of incipient vertebral fractures, osteopenia, osteoporosis, and the clinical factors associated with incipient vertebral fractures in a group of kidney transplant patients.

Methods

Two hundred sixty-four patients (F/M 124/140, 45.3 ± 13 years) who had undergone kidney transplantation in tertiary care centers were included. Vertebral fractures were assessed semiquantitatively using conventional thoracolumbar lateral radiography in 202 of the patients.

Results

Vertebral fractures were observed in 56.4% (n = 114) of the study group. The frequency of osteoporosis was 20.0% (53 of 264 patients), and osteopenia was 35.6% (94 of 264 patients). Bone mineral density (BMD) levels were in the normal range in 40.3% (n = 46) of the subjects with vertebral fractures. It was in the osteoporotic range in 20.1% (n = 23) and the osteopenic range in 40.3% (n = 46). Vertebral fractures were associated with age, duration of hemodialysis, BMI, and femoral neck Z score (R² 37.8%, p = 0.027).

Conclusion

As incipient vertebral fractures can be observed in patients with normal BMD levels in kidney transplant recipients, conventional X-ray screening for vertebral fractures may be beneficial for a proper therapy decision of metabolic bone disease in kidney transplant recipients.

     

Taking immunosuppressive medications effectively (TIMELink): a pilot randomized controlled trial in adult kidney transplant recipients

Russell C, Conn V, Ashbaugh C, Madsen R, Wakefield M, Webb A, Coffey D, Peace L. Taking immunosuppressive medications effectively (TIMELink): a pilot randomized controlled trial in adult kidney transplant recipients.
Clin Transplant 2011: 25: 864–870. © 2010 John Wiley & Sons A/S. Abstract: Background: Immunosuppressive medication non‐adherence is one of the most prevalent but preventable causes of poor outcomes in adult renal transplant recipients, yet there is a paucity of studies testing interventions in this area. Methods: Using a randomized controlled trial design, 30 adult renal transplant recipients were screened for medication non‐adherence using electronic monitoring. Fifteen non‐adherent participants were randomized to receive either a continuous self‐improvement intervention or attention control management. The six‐month continuous self‐improvement intervention involved the participant and clinical nurse specialist collaboratively identifying the person’s life routines, important people, and possible solutions to enhance medication taking. The participant then received individual monthly medication taking feedback delivered via a graphic printout of daily medication taking generated from electronic monitoring. Results: The mean medication adherence score for the continuous self‐improvement intervention group (n = 8) was statistically significantly higher than the attention control group’s (n = 5) mean medication adherence score (p = 0.03). The continuous self‐improvement intervention effect size (Cohen’s d) was large at 1.4. Participants’ perceptions of the intervention were highly favorable. Conclusions: The continuous self‐improvement intervention shows promise as an effective and feasible approach to improve medication adherence in adult renal transplant recipients. A fully‐powered study with a diverse sample is needed to confirm these preliminary findings.     

Evaluation of tacrolimus abbreviated area‐under‐the‐curve monitoring in renal transplant patients who are potientially at risk for adverse events

Hon YY, Chamberlain CE, Kleiner DE, Ring MS, Hale DA, Kirk AD, Mannon RB. Evaluation of tacrolimus abbreviated area‐under‐the‐curve monitoring in renal transplant patients who are potientially at risk for adverse events.
Clin Transplant 2010: 24: 557–563.
© 2009 John Wiley & Sons A/S. Abstract: In a cohort of 32 renal transplant patients who are potentially at risk for adverse events, we compared tacrolimus (TAC) abbreviated AUC values calculated by a method developed in Asians (AUCw) with those derived for Caucasians (AUCa). The relationships between TAC trough (C0), abbreviated AUC, and biopsy results were also assessed. Forty‐eight AUCs and 15 associated biopsies were evaluated. For AUCs obtained only from Caucasian patients, median AUCw value was lower than that of AUCa (104 vs. 115 ng × h/mL, n = 29, p < 0.0001). AUCs obtained from the two methods for all patients correlated with C0 (r_s > 0.72, n = 48, p < 0.0001). Median AUCw (72.9 vs. 174 ng × h/mL, p = 0.043) and AUCa (81.0 vs. 203 ng × h/mL, p = 0.043) were lower in patients experiencing biopsy‐proven acute rejection (AR) than those with normal histology. C0 tended to be lower in biopsies showing AR >6 months post‐transplant (5.80 vs. 11.0 ng/mL, p = 0.110). Thus, lower abbreviated AUCs were obtained for Caucasians using a method developed in Asians. C0 correlated well with abbreviated AUCs. Lower C0 and AUC appeared to be associated with biopsy‐proven AR > 6 months post‐transplant. Further prospective evaluation of TAC AUC and C0 monitoring in a larger cohort of patients is warranted.     

Outcomes of bisphosphonate therapy in kidney transplant recipients: a systematic review and meta‐analysis

Mineral and bone disorders that precede kidney transplantation are exacerbated in the post‐transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens. Bone mineral density (BMD) decreases following transplantation, leading to increased fracture risk. The effect of bisphosphonates on fracture is unknown. The aim of this study was to update estimates of change in BMD and fracture rates in bisphosphonate‐treated kidney transplant recipients through meta‐analysis. Studies comparing bisphosphonate therapy to standard of care were included if follow‐up duration was more than 6 months. We performed random‐effects meta‐analysis to determine the effect of bisphosphonates on lumbar spine and femoral neck BMD and fracture rates. Bisphosphonates improved femoral neck and lumbar spine BMD compared with controls (0.055 g/cm², 95% CI 0.012–0.099 and 0.053 g/cm², 95% CI 0.032–0.074, respectively) without adversely affecting serum creatinine or calcium. This corresponded to an unweighted improvement in BMD of 6.0% and 7.4%, respectively. There was no difference in fracture incidence in the two groups. Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck. There was no difference in fracture incidence. Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels.     

Prospective study of polyomavirus BK replication and nephropathy in renal transplant recipients in China: a single‐center analysis of incidence,reduction in immunosuppression and clinical course

Huang G, Chen L‐Z, Qiu J, Wang C‐X, Fei J‐G, Deng S‐X, Li J, Chen G‐D, Zhang L, Fu Q, Zeng W‐T, Zhao D‐Q. Prospective study of polyomavirus BK replication and nephropathy in renal transplant recipients in China: a single‐center analysis of incidence, reduction in immunosuppression and clinical course.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01141.x
© 2009 John Wiley & Sons A/S. Abstract: Background: BK virus (BKV)‐associated nephropathy (BKVAN) in renal transplant recipients is an important cause of renal transplant dysfunction. Our aim was to determine the kinetics of BKV load within one yr after kidney transplantation under the impact of intensive monitoring and reduction in maintenance immunosuppression, the incidence of BKVAN, and the outcome of BKVAN treatment. Methods: Urine and peripheral blood (PB) were taken from 90 renal transplant recipients for BKV cytological testing and real‐time PCR for BKV DNA at one, three, six, nine, and 12 months after transplantation and treatment. Graft biopsies and urinary sediments of recipients with BKVAN were taken to monitor viral particles by conventional transmission electron microscopy (TEM). Results: By one post‐transplant year, urinary decoy cells (median, 8/10 HPF), BKV viruria (median, 2.60 × 10⁵ copies/mL), viremia (median, 9.65 × 10³ copies/mL ) , and BKVAN occurred in 42.2%, 45.6%, 22.2%, and 5.6% of patients, respectively. The incidence of BK infection was lower in patients who received cyclosporine A (CsA) (28.9%) compared to tacrolimus (FK506) (57.7%) (p = 0.007). An increased hazard of BK infection was associated with the use of FK506 (HR 2.6, p = 0.009) relative to CsA. After reduction in immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction, or graft loss. BKVAN was diagnosed in five patients (5.6%). The treatment of immunosuppression reduction was effective (i.e., decreased the viral load and number of decoy cells, and improved graft function) in our five patients with BKVAN. Quantitative count of decoy cells (e.g., >10 per 10 HPF) as a marker of viremia and BKVAN had increased positive predictive values of 85.7% and 57.1%, respectively. Conclusions: Choice of FK506 as immunosuppressive agent is an independent risk factor affecting BKV infection. Monitoring and pre‐emptive of immunosuppression reduction were associated with resolution of viremia and showed effective in BKVAN recipients at the early stage without acute rejection or graft loss. Quantitative count of urine cytology is a very convenient, useful, and sensitive method for evaluating BKV infection in renal transplant recipients.     

Osteoporosis is a prevalent finding in patients with solid organ failure awaiting transplantation – a population based study

Dolgos S, Hartmann A, Isaksen GA, Simonsen S, Bjørtuft Ø, Boberg KM, Bollerslev J. Osteoporosis is a prevalent finding in patients with solid organ failure awaiting transplantation – a population based study
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2010.01231.x.
© 2010 John Wiley & Sons A/S. Abstract: Post‐transplant bone disease is common in solid organ recipients; however, there is limited information on their pre‐transplant bone status. We aimed to compare bone mineral density (BMD) in different categories of patients with end‐stage organ failure awaiting transplantation (Tx) in Norway. Overall 291 adult patients were enrolled, including 60, 84, 81 and 66 patients with end‐stage lung, liver, kidney and heart failure, respectively. Mean age was 51 ± 12 yr with no significant differences between the groups. We measured BMD in lumbar spine, femur, proximal one third and ultra‐distal radius by dual energy X‐ray absorptiometry. Differences in T‐ and Z‐scores between the groups were compared by ANOVA. Low bone mass was found in all four groups of patients. Both T‐ and Z‐scores differed (p < 0.05) at all measured sites between the groups. Patients with lung failure had the highest prevalence of osteoporosis (67%) and lowest Z‐scores, followed by patients with liver (31%), kidney (24%), and heart (23%) failure. Osteoporosis is prevalent in all groups of organ transplant candidates, and poor bone health is remarkably pronounced in patients with chronic lung disease. General practitioners and specialists who care for these patients before they are referred for transplantation should consider measures to prevent osteoporosis at an earlier stage.     

Timing and quantification of bone loss in cardiac transplant recipients

To evaluate osteopenic bone disease in heart transplant patients, we prospectively measured bone mineral density (BMD) in 33 consecutive male recipients before hospital discharge and 1 year later, using dual photon absorptiometry. At hospital discharge BMD measurement at the lumbar spine was only 90% of that expected in healthy age- and sex-matched controls (P=0.005). One year later BMD had further decreased by 8.5% at the lumbar spine and by 10.4% at the femoral neck (P=0.0001). Five patients suffered vertebral compression fractures during the 1st post-operative year. Our results indicate that osteopenia of the lumbar spine is already present at the time of hospital discharge after transplantation and that further bone loss occurs at a considerable rate during the 1st postoperative year at the lumbar spine and at the femoral neck.     

Can DXA Predict Fractures in Renal Transplant Patients?

Renal transplant patients have a high prevalence of osteopenia, osteoporosis and fractures. The aim of the study was to investigate whether dual‐energy x‐ray absorptiometry (DXA) is of value to predict fractures. In 1995–2007, 238 renal transplant patients underwent 670 DXA investigations. Osteopenia (46.0%), osteoporosis (13.9%) and absolute bone mineral density (BMD) (median 0.9, range 0.4–2.0 g/cm²) in the hip region were used to evaluate fracture risk. Data on fractures were collected at the occasion of each DXA, and a questionnaire was filled in by 191 patients at regular outpatient visits. Reported fractures were verified by consultation of medical records. In all, 46 patients had 53 fractures. Cumulative hazard of fracture was significantly different among normal BMD, osteopenia and osteoporosis in the hip (p < 0.0001). A Cox proportional hazard analysis also including age, gender and diabetic nephropathy showed significantly increased fracture risk for osteoporosis (3.5 times, CI 1.8–6.4, p = 0.0001) as well as for osteopenia (2.7 times, 1.6–4.6, p = 0.0003). A significantly increased risk was also found with absolute BMD estimates below the median. Osteopenia and an absolute bone density below 0.9 g/cm² in the hip region confer an increased risk of fracture.