Association between Serum 25-Hydroxyvitamin D Levels and Sarcopenia in Patients Undergoing Chronic Haemodialysis.

INTRODUCTION: Sarcopenia and vitamin D deficiency are highly prevalent among patients undergoing haemodialysis. Although vitamin D deficiency, assessed using serum 25-hydroxyvitamin D (25(OH)D) levels, is known to be associated with sarcopenia in the general population, whether serum 25(OH)D levels are associated with sarcopenia in patients undergoing haemodialysis with suppressed renal activation of 25(OH)D remains unclear. This study aimed to examine the association between serum 25(OH)D levels and sarcopenia in patients undergoing haemodialysis. METHODS: Serum 25(OH)D level measurements and assessment of sarcopenia using the Asian Working Group for Sarcopenia criteria were conducted in 95 stable outpatients undergoing maintenance haemodialysis therapy. RESULTS: Sarcopenia was observed in 22 (23.1%) patients. In multiple logistic regression analysis, serum 25(OH)D levels were associated with sarcopenia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.039) independent of traditional risk factors for sarcopenia. In multiple linear regression analyses, serum 25(OH)D levels were associated with parameters of skeletal muscle mass and strength (ß = 0.145, p = 0.046, and ß = 0.194, p = 0.020, respectively). The adjusted OR for sarcopenia was 5.60 (95% CI 1.52-20.57, p = 0.009) in the vitamin D deficiency group categorized based on the cut-off serum 25(OH)D level of 10 ng/mL. Regarding model discrimination, adding vitamin D deficiency to the traditional risk factors significantly improved the integrated discrimination improvement score (0.093, p = 0.007). CONCLUSION: Lower serum 25(OH)D levels were associated with sarcopenia independent of traditional risk factors in patients undergoing haemodialysis with suppressed vitamin D activation in the kidney. This finding implies that circulating 25(OH)D may have an important relationship with the skeletal muscle function of patients undergoing haemodialysis, and its measurement may be recommended to identify patients at high risk for sarcopenia among those undergoing haemodialysis.

Coexistence of Low Muscle Mass and Osteoporosis as a Predictor of Fragility Fractures in Long-Term Kidney Transplant Recipients.

INTRODUCTION: Sarcopenia and osteoporosis are highly prevalent among kidney transplant recipients (KTRs). Although osteoporosis is known to increase fracture risk in KTRs, it is unclear whether sarcopenia or osteosarcopenia is associated with this increased risk. Thus, we aimed to investigate the association of the coexistence of low muscle mass (LMM) and osteoporosis with the risk of fracture in long-term KTRs. METHODS: Exactly 342 stable KTRs underwent dual-energy X-ray absorptiometry and skeletal muscle mass index (SMI) measurement using bioelectrical impedance analysis. RESULTS: LMM and osteoporosis were observed in 109 (31.9%) and 93 patients (27.2%), respectively. During a follow-up period of 5.1 years, 48 (14.0%) fractures occurred. KTRs with LMM had a higher fracture risk, but this was not significant (adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 0.94-3.50, p = 0.073). Similar results were obtained in KTRs with osteoporosis (aHR 1.84, 95% CI 0.96-3.47, p = 0.063). We divided the KTRs into four groups according to the presence of LMM and/or osteoporosis. The cumulative incidence rates of fractures were 13.0%, 11.1%, 10.5%, and 31.3% in the KTRs without both LMM and osteoporosis, those with LMM alone, those with osteoporosis alone, and those with both, respectively. The KTRs with both LMM and osteoporosis had a 2.92fold higher risk of fractures (95% CI 1.29-6.49; p = 0.010) than those without both LMM and osteoporosis. CONCLUSION: Long-term KTRs with the coexistence of LMM and osteoporosis had an independently higher risk of fragility fractures than those without both LMM and osteoporosis. The combination of SMI and osteoporosis definitions can be used to identify KTRs with a high fracture risk.

Efficacy of pre-emptive kidney transplantation for adults with end-stage kidney disease: a systematic review and meta-analysis.

BACKGROUND: Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively. METHODS: This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I. RESULTS: Seventy-six studies were included in the systematic review (sample size, 23-121,853; enrollment year, 1968-2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66-0.92]), and lower death-censored graft failure (0.81 [0.67-0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58-1.40); biopsy-proven acute rejection, 0.75 (0.55-1.03); cytomegalovirus infection, 1.04 (0.85-1.29); and urinary tract infection, 0.89 (0.61-1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification. CONCLUSIONS: The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.

Two-year outcomes of low-exposure extended-release tacrolimus and mycophenolate mofetil regimen in de novo kidney transplantation: A multi-center randomized controlled trial.

BACKGROUND: Once-daily extended-release tacrolimus (TACER) is commonly administered following kidney transplantation (KTx); however, its optimal dosage remains unknown. METHODS: In this multi-center, randomized controlled trial, 62 living donor KTx recipients were assigned to either standard-exposure (SE; n = 32) or low-exposure (LE; n = 30) TACER (Graceptor®, Astellas Pharm Inc.) groups. All patients received basiliximab and mycophenolate mofetil (MMF). The primary outcomes were acute rejection, graft/patient survival, and the secondary outcomes were incidence of cytomegalovirus infection, and de novo donor-specific antibodies (dnDSA) production. RESULTS: The tacrolimus trough level and estimated area under the blood concentration-time curve (eAUC) were significantly higher in SE than in LE (SE vs. LE; 1 year: 5.0 ± 0.9 ng/ml and 206.9 ± 26.8 ng h/ml vs. 3.4 ± 1.0 ng/ml and 153.9 ± 26.4 ng h/ml; 2 years: 4.8 ± 1.0 ng/ml and 204.9 ± 30.1 ng h/ml vs. 3.8 ± 0.9 ng/ml and 164.4 ± 27.0 ng h/ml). In contrast, the dosage and eAUC of MMF did not differ between groups. Two-year graft and patient survival rates were 100% in both groups, and acute rejection rates were 0% and 10% in the SE and LE, respectively (p = 0.11). The mean estimated glomerular filtration rates did not differ between the groups. Cytomegalovirus infection was slightly lower in the LE (SE: 12.5% and LE: 6.7%, p = 0.37). In the LE, four cases of dnDSA were noted within 2 years of transplantation; no case was observed in the SE (p = 0.034). CONCLUSIONS: Although the LE TACER regimen showed similar rates of acute rejection, as well as graft and patient survival compared with SE after KTx, LE was significantly more associated with dnDSA. Further investigation of its long-term effect on graft survival is warranted. (University Hospital Medical Information Network Clinical Trials Registry ID: UMIN000033089).

Lateral spine dual-energy X-ray absorptiometry and the risk of fragility fractures in long-term kidney graft recipients.

BACKGROUND: Although the prevalence of osteoporosis and fractures in the first 6-12 months post-renal transplantation is high, little is known about the utility of bone mineral density (BMD) to predict fractures in long-term kidney graft recipients. Lateral spine dual-energy X-ray absorptiometry (DXA) scanning is a reliable tool for measuring glucocorticoid-induced and age-related bone loss in the elderly population. However, little is known about the utility of lateral spine DXA for patients with chronic kidney diseases. This study aimed to analyze the utility of lateral spine BMD for fragility fractures in long-term kidney graft recipients. METHODS: A total of 357 stable kidney transplant recipients for a minimum of 1 year after kidney transplantation underwent DXA measurements at several sites, including the lateral spine between January 2017 and December 2018. We collected data on new incident fractures from the patients' medical records. RESULTS: The median post-transplantation time at baseline DXA measurement was 12.6 years. During the median follow-up period of 3.5 years, 41 (11.4%) fractures occurred. The lateral spine BMDs were independently associated with fractures (adjusted hazard ratio 0.076; 95% confidence interval 0.012-0.42, p = 0.003). The cumulative incidence rate of fractures was significantly higher in the lower lateral spine BMD group (< 0.471 g/cm2, optimal cut-off value by receiver operating characteristic curve) than in the higher lateral spine BMD group (23.4 vs. 7.4%, adjusted hazard ratio 4.92; 95% confidence interval 2.33-10.74, p < 0.001). CONCLUSION: Lateral lumbar spine BMD can be used to predict the risk of fragility fractures in long-term kidney graft recipients.

CMV specific T cell immune response in hepatitis C negative kidney transplant recipients receiving transplant from hepatitis C viremic donors and hepatitis C aviremic donors.

Kidney transplants (KT) from hepatitis C (HCV) viremic donors to HCV negative recipients has shown promising renal outcomes, however, high incidence of cytomegalovirus (CMV) viremia were reported. We performed a prospective cohort study of 52 HCV negative KT recipients from Methodist University Hospital including 41 receiving transplants from HCV aviremic donors and 11 from HCV viremic donors. CMV specific CD4+ and CD8 + T cell immunity was measured by intracellular flow cytometry assay. Primary outcome was the development of positive CMV specific CD4+ and CD8 + T cell immune response in the entire cohort and each subgroup. The association between donor HCV status and CMV specific CD4+ and CD8 + T cell immune response was analyzed by Cox proportional hazard models. Mean recipient age was 48 ± 13 years, with 73% male and 82% African American. Positive CMV specific CD4+ and CD8 + T cell immune response was found in 53% and 47% of the cohort at 1 month, 65% and 70% at 2 months, 80% and 75% at 4 months, 89% and 87% at 6 months, and 94% and 94% at 9 months post-transplant, respectively. There was no significant difference in the incidence of positive CMV specific T cell immune response between recipients of transplants from HCV aviremic donors compared to HCV viremic donors in unadjusted (for CD8+: HR = 1.169, 95%CI: 0.521-2.623; for CD4+: HR = 1.208, 95%CI: 0.543-2.689) and adjusted (for CD8+: HR = 1.072, 95%CI: 0.458-2.507; for CD4+: HR = 1.210, 95%CI: 0.526-2.784) Cox regression analyses. HCV viremia in donors was not associated with impaired development of CMV specific T cell immunity in this cohort.

The effect of cholecalciferol supplementation on allograft function in incident kidney transplant recipients: A randomized controlled study.

It is unknown whether cholecalciferol supplementation improves allograft outcomes in kidney transplant recipients (KTRs). We conducted a single-center randomized, double-blind, placebo-controlled trial of daily 4000 IU cholecalciferol supplementation in KTRs at 1-month posttransplant. The primary endpoint was the change in eGFR from baseline to 12-month posttransplant. Secondary endpoints included severity of interstitial fibrosis and tubular atrophy (IFTA) at 12-month posttransplant and changes in urinary biomarkers. Of 193 randomized patients, 180 participants completed the study. Changes in eGFR were 1.2 mL/min/1.73 m2 (95% CI; -0.7 to 3.1) in the cholecalciferol group and 1.8 mL/min/1.73 m2 (95% CI, -0.02 to 3.7) in the placebo group, with no significant between-group difference (-0.7 mL/min/1.73 m2 [95% CI; -3.3 to 2.0], p = 0.63). Subgroup analyses showed detrimental effects of cholecalciferol in patients with eGFR <45 mL/min/1.73 m2 (Pinteraction <0.05, between-group difference; -4.3 mL/min/1.73 m2 [95% CI; -7.3 to -1.3]). The degree of IFTA, changes in urine albumin-to-creatinine ratio, or adverse events including hypercalcemia and infections requiring hospitalization did not differ between groups. In conclusion, cholecalciferol supplementation did not affect eGFR change compared to placebo among incident KTRs. These findings do not support cholecalciferol supplementation for improving allograft function in incident KTRs. Clinical trial registry: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000020597 (please refer to the links below). UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023776.

Transplantation of Kidneys From Hepatitis C Virus-Infected Donors to Hepatitis C Virus-Negative Recipients: One-Year Kidney Allograft Outcomes.

RATIONALE & OBJECTIVE: Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. EXPOSURE: Predictor(s) of donor infection with HCV. OUTCOMES: Kidney allograft function and allograft biopsy findings during the first year following transplantation. ANALYTICAL APPROACH: We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. RESULTS: The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. LIMITATIONS: Generalizability from a single-center study and small sample size was limited. CONCLUSIONS: Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.

Association between ezetimibe usage and hepatitis C RNA levels in uninfected kidney transplant recipients who received hepatitis C infected kidneys.

Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients.

The importance of kidney volume as a marker in the assessment of living-donor kidney transplantation in Japan.

BACKGROUND: In living kidney transplantation, predicting the risk of end-stage kidney disease in the organ donors though crucial remains to be resolved. Thus, any useful biomarker to predict kidney outcome would be highly desirable to safeguard donors. METHODS: This retrospective study was conducted at Nagoya Daini Red Cross Hospital to confirm whether an increase in preserved kidney volume (PKV) was a predict marker of proteinuria. A change of PKV before and 1 year after kidney donation was measured, and its association with proteinuria 3 years after the donation was analyzed. RESULTS: A total of 119 kidney donors who met the Japanese donor guideline were enrolled. The mean age was 57.4 years, 46.2% were male. The mean values of the variables before kidney donation (baseline) were: BMI levels: 23.4 kg/m2, BSA-adjusted PKV: 132.9 cm3/1.73 m2, and estimated glomerular filtration rate (eGFRave): 82.9 mL/min/1.73 m2. A positive correlation was noted between BSA-adjusted PKV and eGFRave (r = 0.61, p < 0.001). BSA-adjusted PKV increased by 19.5% 1 year after donation, and the median urine protein was 0.04 g/gCre. Linear regression analyses showed that change of PKV and BSA-adjusted PKV before the donation were significantly associated with proteinuria 3 years after donation. CONCLUSION: Change of PKV and BSA-adjusted PKV before donation is important factors for proteinuria after donation under the Japanese donor guidelines. Further studies are needed to confirm whether these factors are associated with renal survival after donation.

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.

Donor hepatitis C antibody positivity misclassifies kidney donor profile index in non-hepatitis C-infected donors: time to revise the kidney donor profile index - a retrospective cohort study.

The kidney donor profile index (KDPI) defines an hepatitis C (HCV) positive donor based on HCV antibody (Ab) and/or nucleic acid amplification test (NAT) positivity, with donors who are not actively infected (Ab+/NAT-) also classified as HCV positive. From Scientific Registry of Transplant Recipients dataset, we identified HCV-negative recipients, who received a kidney transplant from HCV Ab+/NAT- (n = 116) and HCV Ab-/NAT- (n = 25 574) donor kidneys. We then compared recipients' estimated glomerular filtration rate (eGFR) at 6 months in matched cohorts, using combined exact matching (based on KDPI) and propensity score matching. We created two separate matched cohorts: for the first cohort, we used the allocation KDPI, while for the second cohort we used an optimal KDPI, where the HCV component of KDPI was considered negative in Ab+/NAT- patients. The mean ± SD age of the allocation KDPI-matched cohort at baseline was 59 ± 10 years, 69% were male, 61% were white. Recipients' eGFR at 6 months after transplantation was significantly higher in the HCV Ab+/NAT- group compared to the HCV Ab-/NAT- group (61.1 ± 17.9 vs. 55.6 ± 18.8 ml/min/1.73 m2 , P = 0.011) in the allocation KDPI-matched cohort, while it was similar (61.8 ± 19.5 vs. 62.1 ± 20.1 ml/min/1.73 m2 , P = 0.9) in the optimal KDPI-matched cohort. Recipients who received HCV Ab positive, but NAT-negative donor kidneys did not experience worse 6-month eGFR than correctly matched HCV Ab-/NAT- recipients.

Two-year retrospective study of the effect of preemptive kidney transplantation and pretransplant mineral bone factors on calcium in post-kidney transplant recipients.

BACKGROUND: Preemptive kidney transplantation (PEKT) incidence has recently increased in Japan. The effect of PEKT and mineral bone factors before kidney transplantation (KTx) on long-term calcium (Ca) levels remains unknown. METHODS: Eighty-one consecutive patients at Nagoya Daini Red Cross Hospital were included in this study (PEKT group with 41 patients and non PEKT group with 40 patients). Ca metabolism, including intact fibroblast growth factor 23 (iFGF23), were measured before KTx and intact parathyroid hormone (iPTH), and corrected Ca (cCa) were measured before KTx and 6 months (M), 12 M, and 24 M after KTx. RESULTS: In PEKT group, cCa levels at 24 M were higher from the baseline level. At baseline, cCa levels had a positive correlation with iFGF23 levels (r = 0.51; p < 0.001) and a negative correlation with iPTH levels (r = 0.51; p < 0.001). The cCa difference between baseline and 24 M was 0.8 ± 0.6 mg/dL in PEKT group and 0.3 ± 0.7 mg/dL in non-PEKT group (p = 0.001). A multivariate linear regression analysis showed iFGF23 and iPTH at baseline in entire groups were useful markers on calcium levels at 24 M. However, in PEKT group, both markers were found to be not associated with Ca at 24 M, whereas in non PEKT group, iPTH was the only effective marker. CONCLUSIONS: This study suggested that iFGF23 and iPTH may be useful markers of the calcium status after KTx. However, no correlation was noted in PEKT group.

The effect of maintaining high hemoglobin levels on long-term kidney function in kidney transplant recipients: a randomized controlled trial.

BACKGROUND: Posttransplant anemia may be a major determinant of chronic allograft nephropathy. However, the impact of correcting anemia on graft function remains controversial. METHODS: A 3-year follow-up of an open-label, multicenter, randomized controlled trial involving kidney transplantation recipients examined whether sustained maintenance of target hemoglobin (Hb) concentrations at a high level (12.5-13.5 g/dL, n = 64) with either darbepoetin alfa or epoetin beta pegol would slow the graft function decline rate as the primary efficacy endpoint, compared with maintenance of a low Hb concentration (10.5-11.5 g/dL, n = 63). RESULTS: The mean blood pressures in the two groups were well controlled throughout the study. In the high Hb group, mean Hb concentrations increased to >12 g/dL at 3 months, reaching the target range at 18 months. At the end of this study (36 months), the mean Hb concentration was 12.8 ± 0.7 g/dL in the high Hb group and 11.5 ± 1.2 g/dL in the low Hb group. The decline rate of the estimated glomerular filtration (eGFR) rate was considerably greater in the low Hb group (ΔeGFR, -5.1 ± 9.5 mL/min/1.73 m2) than in the high Hb group (-1.0 ± 8.4 mL/min/1.73 m2) (P = 0.02). Of note, only a few high Hb patients developed cardiovascular events and returned to hemodialysis, but the low Hb patients did not. CONCLUSION: This prospective study suggests that correcting anemia to the target Hb level range (12.5-13.5 g/dL) slows renal function deterioration by >3 years in the chronic phase of allograft nephropathy.

The efficacy of exercise training in kidney transplant recipients: a meta-analysis and systematic review.

BACKGROUND: The effectiveness of exercise in kidney transplant recipients is not well established. We, therefore, performed a systematic review of the effects of exercise training in kidney transplantation recipients. METHODS: We searched two electronic databases for articles up to April 2017. Inclusion criteria were as follows: randomized controlled trial and kidney transplant recipients aged 18 years or older. The main outcomes were allograft function (estimated glomerular filtration rate, eGFR), exercise tolerance (VO2 peak), and quality of life (QOL). RESULTS: After screening of 1303 references in PubMed and Ichushi, six randomized control trials were analyzed. For kidney transplant recipients, supervised exercise training was shown to significantly improve VO2 peak [mean difference 2.42; 95% confidence interval (95%CI) 0.22-4.63] and QOL (mean difference 7.23; 95%CI 0.94-13.52). However, exercise training did not improve allograft kidney function (mean difference 6.22; 95%CI - 13.00 to 25.44). No reporting bias was observed in any of the outcomes. There were no reports including patient survival rates and the harm associated with exercise training. CONCLUSIONS: Exercise training for kidney transplant recipients significantly improved exercise tolerability and QOL, but a significant improvement was not obtained with respect to allograft kidney function. Evaluation of patient survival rates and the harm associated with exercise training has not been reported, therefore, future studies are needed to resolve these issues.

Triglyceride metabolism in Japanese kidney transplant recipients.

BACKGROUND: Residual cardiovascular risk factors, such as triglyceride (TG), can cause cardiovascular disease. The role of TG metabolism in kidney transplantation remains unclear. METHODS: Sixty-three consecutive stable recipients at 1 year after their kidney transplants were included in the study from January to September 2014 at Nagoya Daini Red Cross Hospital. We performed the cookie test to evaluate TG metabolism. TG, blood sugar, and remnant-like particle cholesterol (RLP-C) were measured at fasting (f) and 2 and 4 h after ingestion. Low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) and apoB levels were measured at fasting. RESULTS: Mean TGf and RLP-Cf were 139.4 ± 62.6 and 5.6 ± 3.4 mg/dl, respectively, and were within normal ranges; however, both mean TG 2 and 4 h were >200 mg/dl, and both mean RLP-C 2 and 4 h were >9 mg/dl. A negative correlation was seen between TGf and eGFR (r = -0.48, p < 0.001). TGf positively correlated with RLP-C, non-HDL-C, LDL-C/apoB ratio, and body mass index (r = 0.80, p < 0.001; r = 0.47, p < 0.001; r = 0.48, p < 0.001; and r = 0.38, p = 0.002, respectively). LDL-C levels were controlled because of the use of statin, but LDL-C/apoB ratio levels in 50% of the recipients were <1.2, indicating that the rate of small dense LDL-C in LDL-C had increased. CONCLUSION: The prevalence of postprandial hypertriglyceridemia among kidney transplant recipients was high; however, the question of whether or not it should be treated remains unknown.

Two novel APOA1 gene mutations in a Japanese renal transplant recipient with recurrent apolipoprotein A-I related amyloidosis.

Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder of APOA-1 gene characterized by the deposition of apolipoprotein A-I in various organs and can be classified into either hereditary or nonhereditary form in the absence of a family history. Renal disease caused by Apolipoprotein A-I amyloidosis commonly manifested as slowly progressive renal function impairment without heavy proteinuria. Apolipoprotein A-I-related amyloidosis of kidney is of pathogenetic interest because the renal failure is due to peritubular and interstitial amyloid deposits without glomerular deposits. Tubulointerstitial lesion of amyloid deposits was diagnosed in half of carriers of APOA1 gene mutation, only 13% of patients progressed to renal failure requiring hemodialysis or kidney transplantation. Recurrence of apolipoprotein A-I-related amyloidosis after kidney transplantation is very rare. We report a case of a 63-year-old Japanese female without a family history of kidney and/or liver disease who showed slowly progressive renal graft dysfunction without overt proteinuria. Graft biopsy revealed characteristic Congo red stain positive amyloid deposits localized in the renal interstitial area. No glomerular, vascular and tubular amyloid deposits were noted. Laser microdissection-liquid chromatography tandem mass spectrometry-based proteomic analysis elucidated the type of amyloidosis as apolipoprotein A-I amyloidosis. Genetic analysis of DNA sequence study revealed two novel APOA1 gene mutations of Leu202Arg and Lys262Asn. This is a first and very rare case report of the recurrence of non-familial hereditary apolipoprotein A-I amyloidosis in Japanese transplant recipient.

Favorable results in ABO-incompatible renal transplantation without B cell-targeted therapy: Advantages and disadvantages of rituximab pretreatment.

The effectiveness of desensitization with rituximab in ABO-incompatible renal transplantation (ABO-I) has been widely reported. However, ABO-I outcomes are still worse than those of ABO-identical or ABO-compatible renal transplantation (ABO-Id/C). We retrospectively examined the outcomes in consecutive living donor ABO-Id/C (n = 412) and ABO-I (n = 205) cases to elucidate the causes of inferiority in ABO-I. ABO-I cases included recipients treated with rituximab (RIT, n = 131), splenectomy (SPX, n = 21), or neither because of low anti-A/B antibody titers (NoR/S, n = 53). Graft survival, infection, and de novo HLA antibody production were compared for ABO-I and ABO-Id/C, followed by stratification into RIT and NoR/S groups. Propensity score-based methods were employed to limit selection bias and potential confounders. Overall graft survival for ABO-I was significantly lower than that for ABO-Id/C (92.8% vs 97.2% after 5 years, P = .0037). Graft loss due to infection with ABO-I was significantly more frequent than that with ABO-Id/C, whereas acute antibody-mediated rejection (AMR) caused no graft failure in ABO-I recipients. Stratified analysis demonstrated significantly higher infection risk with RIT than with NoR/S. Safe reduction or avoidance of rituximab in desensitization protocols might contribute to further improvement of ABO-I outcome.

Characteristics of Persistent Hyperparathyroidism After Renal Transplantation.

BACKGROUND: Persistent hyperparathyroidism (HPT) after renal transplantation (RTx), termed tertiary HPT (THPT), is not uncommon. However, risk factors and appropriate operative procedures for THPT are poorly understood. METHODS: A retrospective study of patients who underwent RTx without pre-transplant parathyroidectomy (PTx) was performed at our hospital between January 2001 and March 2011. Risk factors for the development of THPT were investigated by comparing THPT and non-THPT groups. We retrospectively analyzed patients with THPT who underwent total PTx with forearm autograft. Pre- and postoperative (1 year after PTx) laboratory results were analyzed for PTx efficacy. RESULTS: Data for 520 patients were analyzed. On multivariate analysis, long dialysis duration (p = 0.009, hazard ratio (HR) 1.01), large maximum parathyroid gland size before RTx (p = 0.003, HR 1.23), pre-RTx high intact parathyroid hormone (iPTH) (p = 0.041, HR 1.01), post-RTx (<2 weeks) high calcium (Ca) (p < 0.001, HR 25.04), and post-RTx high alkaline phosphatase (ALP) (p = 0.027, HR 0.99) were identified as risk factors for THPT. Patients who underwent PTx showed significant improvement compared with baseline for serum Ca, phosphorus, iPTH, and ALP. Serum creatinine showed no significant difference. CONCLUSIONS: Several risk factors for THPT development were identified. PTx for patients with THPT significantly improved serum Ca, iPTH, ALP, and phosphorous levels. There was no significant difference in renal function after PTx. Therefore, total PTx with forearm autograft may be an appropriate surgical approach for patients with THPT.