Function of the ovaries in female kidney transplant recipients

OBJECTIVES: One of the effects of an improved general health state after successful kidney transplantation in women of reproductive age is recurrence of regular menstrual function. MATERIALS AND METHODS: Sixty-three ovarian cycles in female kidney transplant recipient, aged from 18 to 44 years, at 1.5 to 15 years after transplantation, were compared with 50 cycles of healthy women. We monitored the menstrual cycle duration as well as follicle stimulation hormone (FSH), leutinizing hormone (LH), estradiol, progesterone, prolactin, creatinine, and testosterone serum concentrations as well as hematocrit and obtained sonographic observations of ovarian follicle growth and ovulation. RESULTS: Of the recipients, 68.1% had regular menstrual cycles. Ovulatory cycles were observed in 45% of patients. Estradiol concentration established in the first phase of the cycle was significantly higher among the transplanted group (mean value 226.86 +/- 97.45 pg/mL vs 140.00 +/- 61.00 in the controls). A significantly lower level of progesterone (15.05 +/- 17.34 ng/mL vs 30.79 +/- 18.48 ng/mL in the controls) and of testosterone were observed in kidney recipients. Other hormonal parameters did not differ significantly between the groups. CONCLUSIONS: Similar serum FSH, LH, and prolactin concentrations as well as increased levels of estrogens were observed in kidney transplant recipients compared with healthy nonrecipients. The rate of ovulatory cycles in regularly menstruated kidney graft recipients was similar to that of healthy women. Stabilization of graft function resulted in restoration of normal ovarian hormone metabolism and ovulatory cycles in female kidney transplanted recipients.     

Renal pathology and clinical presentations of polyomavirus nephropathy in simultaneous kidney pancreas transplant recipients compared with kidney transplant recipients

INTRODUCTION: The purpose of this study was to describe and compare the renal histopathology and clinical course of simultaneous kidney-pancreas transplant (SKP) recipients with kidney transplant (KT) recipients with polyomavirus nephropathy (PVN). METHODS: Between 1997 and 2002, 20 patients (7 SKP, 13 KT) were diagnosed with PVN. Clinical characteristics and outcomes of PV-N were correlated with histopathologic examinations of renal allograft biopsy and compared between SKP and KT recipients. RESULTS: There were no differences in demographics between SKP and KT recipients with PV-N. The mean time to PVN was 611 (172 to 1174) days posttransplant in SKP and 343 (83 to 720) days posttransplant in KT (P =.05). The serum creatinine at the time of diagnosis was similar between SKP and KT recipients. All patients were treated with reduction in immunosuppression. After a median follow-up of 2 years, the patient survival was 71% in SKP and 100% in KT. Four grafts (57%) were lost owing to PVN in SKP group and three grafts (23%) were lost owing to PVN in the KT group. More patients (43%) in SKP had a history of acute rejection prior to diagnosis of PVN compared to KT (8%) and biopsy-proven tacrolimus nephrotoxicity prior to PVN was more common in SKPT (86%) than in KT (8%) patients (P <.05). SKP patients with evidence of diffuse fibrosis and high total sum scores at time of presentation all subsequently lost their grafts. CONCLUSIONS: SKP recipients with PVN had a worse clinical course than KT recipients.     

Associations between calcineurin inhibitors and arterial compliance in kidney transplant recipients

INTRODUCTION: Several studies have suggested an effect of calcineurin inhibitors on arterial compliance in kidney transplant recipients. We aimed to investigate whether the type of calcineurin inhibitor influences large and small artery compliance in these patients independently of other determinants. METHODS: Patients (104 men, 56 women; 124 treated with cyclosporine, 32 with tacrolimus), aged 44.5 +/- 11.0 years (20-69), with kidney graft functioning for 3.7 +/- 2.5 years (0.25-14.2), were studied. Arterial compliance was assessed with the HDI/Pulse Wave CR-2000 System, which estimates large (C1) and small artery (C2) elasticity indices. Blood cell count, serum lipid profile, calcium x phosphate product, concentrations of CRP, total protein and albumin, plasma fibrinogen and glomerular filtration rate were estimated. Multiple linear regression analysis was employed to check for associations between C1, C2 and patients' demographic, clinical and laboratory profiles, including type of calcineurin inhibitor used. RESULTS: Both C1 and C2 correlated positively with body surface area and negatively with age and mean blood pressure. Furthermore, C1 was associated negatively with pulse rate (beta=-0.37; p<0.00001), while C2 was related positively to the interaction term of the current use of tacrolimus x its duration (beta=0.19; p<0.005) and negatively to the simultaneous use of cyclosporine and beta-blocker (beta=-0.18; p<0.003), as well as tacrolimus and low-dose aspirin (beta=-0.24; p<0.0002). CONCLUSIONS: Calcineurin inhibitors differentially influence small artery compliance in kidney transplant recipients. Use of tacrolimus appears to improve small artery compliance proportionally to the duration of treatment, but combinations of tacrolimus and low-dose aspirin, as well as cyclosporine and beta-blocker seem to exert a negative influence.     

Association between serum resistin level and outcomes in kidney transplant recipients

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio‐demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition‐Inflammation in Transplant—Hungary Study (MINIT‐HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6‐year follow‐up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow‐up period (median [IQR]: 22[15–26] vs. 19[14–22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16–1.54) and 1.21(1.01–1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.     

Association between cytomegalovirus disease and chronic rejection in kidney transplant recipients

BACKGROUND: It has long been suggested that cytomegalovirus (CMV) disease plays a role in the pathogenesis of chronic rejection (CR). However, its role has been difficult to prove, given the strong association between acute rejection and CMV, and the even stronger association between acute rejection and CR. To try to isolate the relative contribution of CMV infection in the pathogenesis of CR, we used multivariate techniques to examine risk factors for CR, including CMV disease. METHODS: Our study population consisted of adult recipients of a first kidney graft who underwent transplantation at a single center between 1/1/85 and 6/30/97 (n = 1339). RESULTS: Multivariate analysis using time to CR as the dependent variable demonstrated acute rejection to be the strongest risk factor (relative risk [RR] = 17.8, P = 0.0001), followed by older donor age (RR = 1.46, P = 0.01). The presence of CMV disease showed a trend toward increased risk for CR (RR = 1.30, P = 0.10), although the association was not as strong as with the other two variables. Comparing only those recipients with acute rejection and CMV disease versus those with acute rejection but no CMV disease, the relative risk of developing CR was 1.37 times higher in the former group. Recipients with acute rejection and CMV developed CR sooner and with a higher incidence versus those with acute rejection but no CMV (P = 0.002). It is interesting, however, that CMV disease was only a risk factor for CR in the presence of acute rejection. Recipients with no acute rejection and CMV disease did not have a higher incidence of CR versus those with no acute rejection and no CMV (P = NS). CONCLUSION: CMV disease seems to play some role in the pathogenesis of CR but only in the presence of acute rejection. Reasons may include (i) the inability to adequately treat acute rejection due to the presence of CMV disease or (ii) the increased virulence of latent CMV virus in recipients being treated for acute rejection. Our data may suggest a role for more aggressive prophylaxis against CMV disease, especially at the time of treatment for acute rejection.     

Inhibitory interactions between BK and JC virus among kidney transplant recipients

BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (P=0.001). The co-detection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (P=0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other.     

肾移植术后病人昼夜血压变化规律与心血管并发症的相关性研究

目的：预防肾移植术后心血管并发症，提高肾移植病人长期存活率。方法：采用非侵入性方法对86例肾移植术后病人昼夜血压变化和24h动态心电图进行连续监测，并对数据进行比较分析。结果：86例病人发生高血压者55例，病人昼夜平均血压差别、昼夜心电图ST段或T波的异常改变平均次数差别有显著性意义。昼夜CsA浓度差别、昼夜血肌酐、血清胆固醇、血糖、甘油三脂及K^ 、Na^ 、Cl^-、TCO2、Ca^2 等指标差别无显著性意义。结论：肾移植术后心血管并发症可能与夜间高血压发生率高有关，昼夜血压节律消失与抗排斥反应药物及常规抗高血压药物无关。     

女性肾移植受者妊娠结果及子代健康状况随访

目的 评价女性肾移植受者妊娠结果及子代健康状况的长期随访结果. 方法 回顾性分析1978年4月至2011年4月妊娠＞5个月的15例肾移植受者资料,并对其子代进行随访.妊娠时年龄(28.5±5.7)岁,妊娠距移植时间(53.4±19.7)个月.产后随访(11.5±6.9)年. 结果 15例受者采用以环孢素或他克莫司为主的免疫抑制剂方案.12例母、子女身体状况及移植肾功能正常;1例产下一男婴2周后因并发肺部感染、心力衰竭,带正常功能移植肾死亡;2例分别于妊娠第21、23周发生移植肾慢性排斥反应,终止妊娠,经治疗无效后摘除移植肾.13例胎儿均经剖宫产娩出后存活,胎龄(35.2±4.0)周,出生体质量(2510 ±68)g,Apgar评分均为10分.13例婴儿出生时无生理缺陷,体格发育无异,出生后以人工喂养.13例儿童智力、体格以及心理发育与同龄者无异常,7例0～2岁时发生反复呼吸道感染,1例诊断为注意力缺陷多动障碍.目前子代年龄3 ～21岁. 结论 严格妊娠指征,肾移植女性受者在术后3年后能够成功妊娠、分娩,长期随访显示患者子代健康状况良好.     

肾移植患者他克莫司血药浓度与肝肾毒性分析

目的分析我院肾移植患者他克莫司血药浓度的控制情况,探讨他克莫司血药浓度与肝肾功能之间的关系,以期为临床的合理用药提供依据。方法收集我院2011年11月至2013年4月96例肾移植患者他克莫司血药浓度的数据,及血药浓度测定当天的生化检测结果。根据他克莫司血药浓度（A）测定结果,将其分为4组（I组,A≤6 ng/mL;II组,6〈A≤10 ng/mL;III组,10〈A≤15 ng/mL;IV组,A〉15 ng/mL）,对4组中的各项生化指标及不良反应比例进行统计分析。结果红细胞（P=0.57）,血红蛋白（P=0.60）,血小板（P=0.12）,总胆红素（P=0.58）,谷氨酰基转移酶（P=0.46）,天门冬氨酸氨基转移酶（P=0.98）和丙氨酸氨基转移酶（P=0.40）在4组之间没有统计学意义;而白细胞（P=0.007）,碱性磷酸酶（P=0.004）和血尿素氮（P=0.007）在4组之间差异有统计学意义。当患者的他克莫司血药浓度维持在6-15 ng/mL 时,其肾小球滤过率估计值（estimated glo-merular filtration rate,eGFR）（70.2 mL/min）要明显高于≤6 ng/mL（58.2 mL/min）和〉15 ng/mL （66.2 mL/min）。同时,感染及中重度贫血的风险也较低,但他克莫司血药浓度与肝功能异常比例之间未发现显著的相关性。结论他克莫司血药浓度维持在6-15 ng/mL有利于患者肾功能的维持,同时能够降低感染和中重度贫血的风险,这一结果将有利于他克莫司的临床使用。     

Associations between use of cyclosporine-sparing agents and outcome in kidney transplant recipients

BACKGROUND: Diltiazem, widely used as a cyclosporine-sparing agent, has been suggested to confer a benefit on graft and patient outcome in kidney transplantation related to immunomodulatory properties. Use of cyclosporine-sparing agents (CsSpA) is routinely recorded by the Australia & New Zealand Dialysis and Transplant (ANZDATA) Registry, and we used these data to examine the associations between CsSpA use and outcomes. METHODS: Graft and patient survival were analyzed for a cohort of 3913 people who received kidney transplants in Australia or New Zealand between 1 April 1993 and 30 March 2001. Patients were followed to death or loss of graft function. Graft and patient survival analyses were performed using Cox proportional hazards models, including a time varying covariate for CsSpA use in analyses of graft failure. Occurrence of delayed graft function (DGF) and acute rejection also were examined as secondary outcomes. RESULTS: There was no difference in patient survival in the first 12 months post transplantation, but from 12 months onwards there is a survival advantage associated with CsSpA use among cadaveric donor (CD) recipients in both univariate hazard ratio (HR) 0.56, 95% CI 0.41 to 0.76, P < 0.001 and multivariate (HR 0.56, 95% CI 0.40 to 0.79, P < 0.001) analyses. This was consistent across subgroups examined. Lower rates of early graft loss (censored for death) were associated with CsSpA use [odds ratio (OR) 0.61, 95% CI 0.50 to 0.75, P < 0.0001]. Lower rates of use of antibody therapy for rejection also were observed, but not lower rates of biopsy-proven rejection. CONCLUSIONS: CsSpA use was associated with improved patient mortality after kidney transplantation. Whether this was a direct drug effect or due to other factors associated with diltiazem use cannot be inferred directly from these data, although several plausible mechanisms exist which might mediate a diltiazem effect.     

Treatment of hyperparathyroidism with cinacalcet in kidney transplant recipients

Background

After successful kidney transplantation, hyperparathyroidism can persist in 10%–50% of patients and can harmfully affect bone metabolism. Calcimimetic cinacalcet is a new treatment option in the management of persistent hyperparathyroidism in these patients.

Methods

This prospective, clinical study of 11 patients included those who had a serum intact parathyroid hormone (iPTH) concentration >65 ng/L, a serum creatinine concentration was <200 μmol/L, stable kidney graft function, and were >1 year since transplantation. Patients were not treated with drugs other than calcitriol that could influence bone metabolism. During the 6-month observation period, in which the stability of measured parameters was determined, and in the 12-month treatment period (cinacalcet 30 mg/d), we followed serum concentrations of calcium, phosphate, iPTH, creatinine, vitamin 25OH D₃, bone-specific alkaline phosphatase (ALP), osteocalcin, collagen degradation fragments (CTX), urinary calcium excretion, and bone mineral density (BMD).

Results

During the treatment period, the serum calcium concentration decreased significantly (from 2.50 ± 0.12 to 2.32 ± 0.12 mmol/L; P < .01). Serum iPTH concentration decreased significantly (from 247 [range, 199–362] at time 0 to 198 [range, 165–233] ng/L after 1 month of treatment; P < .05), but increased slightly thereafter. After 6 months of treatment, the serum concentration of ALP and CTX increased significantly, but decreased thereafter. There were no significant changes in the other parameters assessed. Renal function remained stable during the treatment period. The BMD of the lumbar spine, hip, and forearm did not change during the 12 months of treatment.

Conclusion

Cinacalcet was effective in treating posttransplant hyperparathyroidism, resulting in decreased calcemia and transient decreased iPTH. ALP and CTX transiently increased during therapy, but other markers of bone metabolism remained unchanged. Twelve months of cinacalcet treatment did not result in a change in BMD. Cinacalcet seems to be a safe drug with no negative effect on renal function.     

Hyperuricemia in kidney transplant recipients with intact graft function

Objectives

The aim of this study was to investigate the prevalence of hyperuricemia and factors predicting its occurrence, and to establish the relationship over time between serial changes in estimated glomerular filtration rate (eGFR) and uric acid (UR) concentration in kidney transplant (KT) recipients with eGFR >60 mL/min/1.73 m².

Methods

Adult patients who underwent KT at the Asan Medical Center between 1990 and 2008 and maintained eGFR >60 mL/min/1.73 m² were retrospectively assessed. Clinical and laboratory data were obtained from inpatient and outpatient charts and from the hospital electronic database.

Results

Of 356 patients, 301 (84.55%) had normal UR levels and 55 (15.45%) had hyperuricemia. After multivariate adjustment, transplant duration, male gender, eGFR, diabetes mellitus (DM), and calcium level were associated with higher mean UR levels. Mean UR level increased significantly and mean eGFR decreased significantly during the first year after transplantation, but there were no significant differences over the next 4 years. Serial UR and eGFR levels changed almost simultaneously.

Conclusions

Transplantation duration, male gender, eGFR level, DM, and serum calcium level were risk factors for hyperuricemia in kidney recipients with intact graft function. Increased uric acid after KT did not significantly affect graft function.     

Hyperlipidemia in pediatric kidney transplant recipients treated with cyclosporine

Hyperlipidemia is a risk factor for cardiovascular disease in adult kidney transplant (Tx) recipients. We sought to determine the prevalence of, and the risk factors associated with, hyperlipidemia in pediatric kidney Tx recipients on cyclosporine (CsA). We identified 59 patients (mean age 8.2+/-5.7 years) transplanted between 1 January 1991 and 31 December 1993. Pre Tx, 34% had elevated total cholesterol [TC >200 mg/dl (5.17 mmol/l)]; 54% had elevated triglycerides [TG >200 mg/dl (2.26 mmol/L)]. Mean TG was higher pre Tx in dialysis (versus nondialysis) patients: 306 mg/dl (3.46 mmol/l) versus 228 mg/dl (2.58 mmol/l) ( P=0.04). Mean TC was higher in peritoneal dialysis than hemodialysis patients: 222 mg/dl (5.74 mmol/l) versus 169 mg/dl (4.37 mmol/l) ( P=0.03). Pre Tx and 3-year values correlated (TC, r=0.49, P=0.0008; TG, r=0.41, P=0.001); 3- and 5-year TC values correlated ( r=0.57, P=0.003). At 5 years post Tx, 41% of the recipients had elevated TC; 14% had elevated TG. Recipients with elevated TC had higher mean CsA concentrations at 1 year post Tx ( P=0.03). Recipients with elevated TG tended to receive more prednisone ( P=0.06). At 5 years post Tx, recipients had a high prevalence of hyperlipidemia. The identification and treatment of hyperlipidemia should be included in pediatric kidney Tx protocols.     

Experience with belatacept rescue therapy in kidney transplant recipients

In kidney transplant recipients with chronic graft dysfunction, long‐term immunosuppression with calcineurin inhibitors (CNIs) or mTOR inhibitors (mTORi) can be challenging due to adverse effects, such as nephrotoxicity and proteinuria. Seventy‐nine kidney transplant recipients treated with CNI‐based or mTORi‐based maintenance immunosuppression who had CNI‐induced nephrotoxicity or severe adverse events were switched to belatacept. Mean time from transplantation to belatacept conversion was 69.0 months. Mean estimated glomerular filtration rate (eGFR) ± standard deviation at baseline was 26.1 ± 15.0 ml/min/1.73 m², increasing to 34.0 ± 15.2 ml/min/1.73 m² at 12 months postconversion (P < 0.0005). Renal function improvements were also seen in patients with low eGFR (<25 ml/min/1.73 m²) or high proteinuria (>500 mg/l) at conversion. The Kaplan–Meier estimates for patient and graft survival at 12 months were 95.0% and 85.6%, respectively. The discontinuation rate due to adverse events was 7.9%. One case of post‐transplant lymphoproliferative disorder occurred at 17 months postconversion. For comparison, a historical control group of 41 patients converted to mTORi‐based immunosuppression because of biopsy‐confirmed CNI‐induced toxicity was examined; eGFR increased from 27.6 ± 7.2 ml/min/1.73 m² at baseline to 31.1 ± 11.9 ml/min/1.73 m² at 12 months (P = 0.018). Belatacept‐based immunosuppression may be an alternative regimen for kidney transplant recipients with CNI‐ or mTORi‐induced toxicity.