Primary Cytomegalovirus Infection Significantly Impacts Circulating T Cells in Kidney Transplant Recipients

Cytomegalovirus (CMV) infection profoundly affects the T cell compartment and is associated with alterations in T cell aging parameters and generation of cytotoxic CD4⁺CD28null T cells. Hence, the effect of a primary CMV infection post–kidney transplantation (KT) on the peripheral T cell compartment was examined. As aging parameters, we determined the T cell differentiation status, T cell receptor excision circle (TREC) content, CD31⁺ naïve T cell numbers and relative telomere length (RTL) pre‐KT and 12 months post‐KT. CMV‐seronegative KT recipients, receiving a kidney from a CMV‐seropositive donor (D+/R?) were compared to D+/R+ KT recipients. Eleven out of the 22 D+/R? KT recipients had CMV viremia post‐KT. They developed CMV‐specific CD4⁺ and CD8⁺ T cells and their T cell compartment shifted towards a more differentiated memory phenotype with expansion of CD4⁺CD28null and CD8⁺CD28null cells. One year post‐KT, the CD8⁺ T cell count was almost doubled compared to nonviremic D+/R? and D+/R+ KT recipients. In addition, the RTL of the CD8⁺ T cell was significantly lower and both the TREC content and CD31⁺ naïve T cell numbers significantly decreased. Moreover, primary CMV infection was associated with a negative impact on glomerular filtration rate. In conclusion, primary CMV infection has a substantial impact on the number and phenotype of peripheral T cells and may negatively affect renal allograft function.

     

Gene Expression Profiling of Peripheral Blood From Kidney Transplant Recipients for the Early Detection of Digestive System Cancer

Background

Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplantation malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained from kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas, and biliary tract).

Hepatocellular Carcinoma in Kidney Transplant Recipients

Objective

A kidney transplant is a suitable surgical management for end-stage renal disease patients; however, posttransplantation malignancy is an unwanted outcome. In Taiwan, hepatocellular carcinoma (HCC) is a major malignancy not only among the general population but also in the post-kidney transplant group. Therefore, regular imaging studies for posttransplantation follow-up are necessary. We examined the imaging characteristics and the efficacy of radiologic diagnostic criteria and the American Joint Committee on Cancer (AJCC) staging system in post-kidney transplantation HCC.

Patients and Methods

We retrospectively reviewed 15 patients with post-transplantation HCC among 554 hospital-based kidney transplant recipients. From 1988 to 2008 we analyzed the patient profiles, imaging studies, histopathologic diagnosis, treatment methods, and outcomes. The 6th-edition AJCC radiologic staging system was applied for validation in this study.

Results

Using the AJCC staging system, all 15 patients with histopathologically confirmed HCC were enrolled as stage I (n = 7), stage II (n = 2), stage IIIA (n = 5), or stage IV (n = 1) cases. The 5-year survival rates were 71.4% in stage I, 50% in stage II, 20% in stage IIIA, and 0% in stage IV. Over one-half of post-kidney transplantation HCC were sized 2.5-6.0 cm in diameter with mixed echogenicity. The positive diagnostic rate for radiologic criteria was 83.3%.

Conclusions

The AJCC staging system and the radiologic diagnostic criteria were validated in post-kidney transplantation HCC. Surgical resection and transcatheter arterial embolization for early-stage HCC in kidney transplant recipients showed satisfactory outcomes. A noncirrhotic liver in a kidney transplant recipient makes surgical resection the treatment of choice because of the better prognosis.     

Bone Resorption in Kidney Transplant Recipients

Early diagnosis of persistent hyperparathyroidism (HP) following kidney transplantation may prevent worsening of osteodystrophy and potential damage to the graft. We evaluated the utility of collagen pyridinoline (PYD) and deoxypyridinoline (DPD) urinary cross-links beyond the common HP markers to evaluate 70 selected stable recipients between 1997 and 2006 who were divided into 2 group depending on the immunosuppressive protocol. All patients showed elevated levels of urinary cross-links even though calcemia and phosphoremia values were normal. Their mean creatinine level was slightly increased. Data were assessed as mean values ± SD. All variables underwent a correlation matrix analysis and a stepwise regression, with posttransplant intact parathyroid hormone (iPTH) as the dependent variable and other variables as regressors. A statistically significant correlation was observed between PYD and alkaline phosphatase (ALP; P = .0026, r = .41); PYD and DPD (P = .015, r = .34); pre- and posttransplant iPTH (P = .024, r = .31); and creatinine and ALP (P = .024, r = .31). Taking the groups separately, there were significant correlations between PYD and ALP (P = .0076, r = .42); PYD and DPD (P = .017, r = .38); ALP and posttransplant iPTH (P = .038, r = .33); osteocalcin (OC) and posttransplant iPTH (P = .048, r = .32); and pre- and posttransplant iPTH (P = .019, r = .37) among subjects in the first group, whereas subjects in the second group showed a correlation between posttransplant iPTH and age at transplantation (P = .032, r = .61). In conclusion, we showed that urinary cross-links may be helpful to reveal bone resorption in kidney recipients when usual bone metabolism parameters do not demonstrate hyperparathyroidism.     

Outcomes in Obese Kidney Transplant Recipients

BackgroundKidney transplantation (KT) in obese patients is controversial. The present study aimed to evaluate patient and graft survival and post-transplantation complications between obese and nonobese recipients.MethodsPatients (n = 3,054) receiving a KT from 1998 to 2008 were divided according to body mass index (BMI) into 3 groups for analysis: group I: BMI <30 kg/m² (nonobese); group II: ≥30–34.9 kg/m² (class I obese); and group III: ≥35 kg/m² (class II and III obese).ResultsMean BMIs were: group I (n = 2,822): 22.6 ± 3.3 kg/m²; group II (n = 185): 31.9 ± 1.3 kg/m²; and group III (n = 47): 36.8 ± 1.7 kg/m². There were no differences among the 3 groups in patient demographic variables regarding race, sex, or organ source. One-year (I, 98%; II, 98%; III, 95%) and 5-year (I, 90%; II, 92%; III, 89%) patient survival rates were similar among groups. Graft survival rates at 1 year were 96% for groups I and II and 91.5% for group III. Five-year graft survivals were: I, 81%; II, 96%; and III, 79%. The most common cause of graft loss was death, and the main cause of death was infection in all groups. Obese patients were more likely to experience wound dehiscence (I, 1.9%; II, 7.6%; III, 19.1%; P < .001), develop new-onset diabetes after transplantation (NODAT; I, 16.2%; II, 27%; III, 36%; P < .001), and have a prolonged length of hospital stay (I, 11.3 ± 11.4 d; II, 14.5 ± 14.3 d; III, 15.9 ± 16.7 d; P < .001).ConclusionsObese recipients demonstrated outcomes similar to nonobese patients regarding patient and graft survival. However, they had higher rates of prolonged length of hospital stay, wound dehiscence, and NODAT.     

Endocan Concentration in Kidney Transplant Recipients

Introduction

Endocan is a novel soluble dermatan sulfate proteoglycan derived from endothelium. It has the capacity of binding to different biologically active molecules associated with cellular signaling, adhesion and regulating proliferation, differentiation, migration, and adhesion of different cell types in health and pathology. Elevated endocan levels are connected with endothelial activation/damage, neo-angiogenesis, and inflammation or carcinogenesis.

Pregnancy Outcomes for Kidney Transplant Recipients

Pregnancy outcomes in a transplant population have not been well documented. Data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the National Perinatal Epidemiology and Statistics Unit (NPESU) were analyzed. We described pregnancy outcomes within the transplant population and compared these to outcomes for the general population. Six hundred ninety‐two pregnancies in 447 transplant recipients were reported between 1971 and 2010 (ANZDATA); a corresponding 5 269 645 pregnancies were reported nationally in Australia between 1991 and 2010 (NPESU). At pregnancy transplant mothers had a median age of 31 years (interquartile range [IQR]: 27, 34), a median creatinine of 106 µmol/L (IQR: 88, 1103 µmol/L) and a functioning transplant for a median of 5 years (IQR: 3, 9). The mean gestational age at birth was 35 ± 5 weeks in transplant recipients, significantly shorter than the national average of 39 weeks (p < 0.0001). Mean live birth weight for transplant recipients was 873 g lower than the national average (2485 ± 783 g vs. 3358 ± 2 g); a significant difference remained after controlling for gestational age. There was lower perinatal survival rate in babies born to transplant recipients, 94% compared with 99% nationally (p < 0.001). Although transplant pregnancies are generally successful, outcomes differ from the general population, indicating these remain high‐risk pregnancies despite good allograft function.     

Polyomavirus Nephropathy in Pediatric Kidney Transplant Recipients

Given the limited information regarding BK virus-associated nephropathy (BKVN) in pediatric kidney transplant recipients, we assessed the incidence, risk factors, clinical and virologic features of BKVN in pediatric renal transplant recipients at a single transplant center by means of a retrospective cohort study. Histologically confirmed BKVN developed in 6 of 173 (3.5%) kidney transplant recipients at a median of 15 months post-transplant (range: 4-47 months). At a median follow-up of 28 months (range: 5-32), all patients had functioning grafts with mean creatinine and GFR of 1.9 mg/dL and 58 mL/min/1.73 m2, respectively. At the time of diagnosis, all cases had viruria (median 6.1 x 10(6) copies/mL, range: 10(5) to 3.9 x 10(8) copies/mL) and viremia (median 21,000 copies/mL, range: 10,000-40,000 copies/mL). Recipient seronegativity for BKV was significantly associated with the development of BKVN (p = 0.01). BKVN is an important cause of late allograft dysfunction and is strongly associated with recipient seronegativity in pediatric kidney transplant recipients. Further studies to confirm this finding and to define the clinical utility of routine pre-transplant BKV serologic testing are warranted.     

Gout Severity in Recipients of Kidney Transplant

PurposeThis retrospective analysis of medical chart data was performed to compare severity and treatment of gout in patients with or without a history of kidney transplantation (KT).MethodsVia an online survey, a panel of board-certified US nephrologists (N = 104) provided the following deidentified chart data for their 3 most recent patients with gout: age, sex, serum uric acid, numbers of swollen or tender joints, visible tophi, gout flare events (prior 12 months), gout drug treatment history, and KT history. The presence of “severe, uncontrolled gout” was defined as: serum uric acid ≥ 7.0 mg/dL, ≥1 tophi and ≥2 flares in the last 12 months, and history of xanthine oxidase inhibitor treatment.ResultsTwenty-five out of 312 (8.0%) gout patients had a history of KT. Univariate analysis found that patients with gout and history of kidney transplants had: greater prevalence of severe uncontrolled gout (27% vs 8%, P = .007) and tophi (36% vs 17%, P = .030), and higher rates of failure or physician perceived contraindication to allopurinol (44% vs 23%, P = .028).ConclusionThis study provides preliminary evidence that gout in patients with history of KT is more severe and poses greater challenges to pharmacologic management. Although gout has been linked to worse outcomes among kidney recipients in the literature, there are presently no publications on gout severity among patients with KT in comparison to other patients with gout. Further investigation of disease severity and appropriate, effective treatment options in recipients of kidney transplant with a diagnosis of gout, especially prior to the transplant, is warranted.     

Hyperpolypharmacy and Frailty in Kidney Transplant Recipients

BackgroundKidney transplant recipients (KTRs) take multiple medications including immunosuppressants every day. Although polypharmacy is associated with frailty, the situation remains unknown in KTRs. The aim of the present study is to investigate the association between hyperpolypharmacy and frailty in KTRs.MethodsThis study was a single-center, cross-sectional investigation carried out on KTRs between August 2018 and February 2019 at Osaka City University Hospital. Frailty was evaluated using the Kihon Checklist (KCL). The number of medications was determined from the regular medicines the participants took by mouth every day. Hyperpolypharmacy was defined as 10 or more medications. Statistical analyses were performed using multivariable logistic regression analyses and multivariable linear regression analyses.ResultsOf 211 KTRs enrolled in this study, the mean (SD) number of medicines taken orally regularly was 9.4 (3.4), and hyperpolypharmacy participants accounted for 41%. Hyperpolypharmacy was associated with both the total KCL score (odds ratio, 1.13; P = .016) and being frail compared with being robust (odds ratio, 5.70; P = .007) after adjustments for age, sex, and body mass index. The number of medications was associated with both the total KCL score (β = 0.20; P < .001) and being frail compared with being robust (β = 2.51; P < .001) after adjustments for age, sex, body mass index, dialysis vintage, time after transplant, serum albumin, and estimated glomerular filtration rate. The optimal cutoff value for the number of medications to detect frailty was 12 (area under the curve, 0.81).ConclusionsIn KTRs, hyperpolypharmacy was prevalent and was associated with frailty.