Pre-Transplant Calcimimetic Use and Dose Information Improves the Accuracy of Prediction of Tertiary Hyperparathyroidism after Kidney Transplantation: A Retrospective Cohort Study.

Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether pre-transplant calcimimetic use and dose information would improve THPT prediction accuracy, this retrospective cohort study evaluated patients who underwent KTx between 2010 and 2022. The primary outcome was the development of clinically relevant THPT. Logistic regression analysis was used to evaluate pre-transplant calcimimetic use as a determinant of THPT development. Participants were categorized into four groups according to calcimimetic dose, developing two THPT prediction models (with or without calcimimetic information). Continuous net reclassification improvement (CNRI) and integrated discrimination improvement (IDI) were calculated to assess ability to reclassify the degree of THPT risk by adding pre-transplant calcimimetic information. Of the 554 patients, 87 (15.7%) developed THPT, whereas 139 (25.1%) received pre-transplant calcimimetic treatment. Multivariate logistic regression analysis revealed that pre-transplant calcimimetic use was significantly associated with THPT development. Pre-transplant calcimimetic information significantly improved the predicted probability accuracy of THPT (CNRI and IDI were 0.91 [p < 0.001], and 0.09 [p < 0.001], respectively). The THPT prediction model including pre-transplant calcimimetic information as a predictive factor can contribute to the prevention and early treatment of THPT in the era of calcimimetics.

Letermovir safety and efficacy for cytomegalovirus prophylaxis in adult Japanese kidney transplant recipients: a multicenter, open-label, noncomparative Phase 3 study.

BACKGROUND: Letermovir is approved for cytomegalovirus (CMV) prophylaxis in adult allogeneic hematopoietic cell transplantation recipients worldwide and is also approved in the United States for CMV prophylaxis in adult high-risk (D+/R-) kidney transplant recipients (KTRs). The safety and efficacy of letermovir for CMV prophylaxis in adult Japanese KTRs are reported here. METHODS: In this Phase 3, single-arm, open-label study, adult Japanese KTRs with CMV serostatuses D+/R-, D+/R+, and D-/R+ received letermovir 480 mg daily orally within 7 days post-transplant through Week 28. Participants were followed through Week 52. The primary objective was to evaluate letermovir safety and tolerability. Efficacy was a secondary objective, measured by CMV disease, CMV disease or infection requiring intervention, and quantifiable CMV DNAemia. All CMV disease cases were confirmed by an independent adjudication committee. RESULTS: Among 22 participants (12 were D+/R-) who received letermovir prophylaxis, 20 (90.9%) experienced ≥ 1 AE through Week 28. Most AEs were mild to moderate in severity; no deaths were reported. During the prophylaxis period through Week 28, one transient case of quantifiable CMV DNAemia was detected, but no CMV disease or infection requiring intervention was reported. Through Week 52, four D+/R- participants met the endpoint of CMV disease or infection requiring intervention, of whom two had committee-confirmed CMV syndrome; all recovered with CMV therapy. A total of 5 participants had quantifiable CMV DNAemia through Week 52. CONCLUSION: Letermovir was generally well tolerated, and the data support its use for the prevention of CMV disease/infection in adult Japanese KTRs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04129398.

Lung cancer after kidney transplantation: a 50-year experience at a single institution.

PURPOSE: To investigate the clinical characteristics of lung cancer that develops after kidney transplantation. METHODS: The clinical data of patients with lung cancer diagnosed after kidney transplantation were collected retrospectively. The medical records were extracted from our database. All patients underwent routine chest examination after kidney transplantation. RESULTS: In total, 17 lung tumors were detected in 15 (0.6%) of 2593 patients who underwent kidney transplantation at our institution. Eleven lung tumors were completely resected from a collective 10 patients (surgical group). The remaining five patients did not receive surgical treatment (nonsurgical group). The surgical group underwent wedge resection (n = 5), segmentectomy (n = 1), lobectomy (n = 3), and bilobectomy (n = 1). The pathological stages were 0 (n = 1), IA1 (n = 2), IA2 (n = 4), IA3 (n = 2), and IB (n = 1). The surgical group had a significantly better prognosis than the nonsurgical group. There were no perioperative complications related to kidney transplantation in either group. CONCLUSIONS: Routine chest examination would be useful for the early diagnosis and treatment of lung cancer after kidney transplantation. Moreover, surgical resection for early-stage lung cancer was associated with a better prognosis for kidney transplantation patients.

Optimal dose of rituximab in ABO-incompatible kidney transplantation in patients with low anti-A/B antibody titers: A single-center retrospective cohort study.

BACKGROUND: The clinical outcomes of ABO-incompatible (ABOi) kidney transplantation have improved with the introduction of desensitization therapy with rituximab. However, rituximab prevents not only antibody-mediated rejection (AMR) but also increases the risk of adverse events, such as infection. For ABOi kidney transplantation in patients with low anti-A/B antibody titers, we previously used a rituximab-free desensitization protocol and then initiated a single dose of 100 mg rituximab in 2016. We retrospectively compared the outcomes of ABOi kidney transplantation in patients with low anti-A/B antibody titers before and after the introduction of rituximab. METHODS: ABOi kidney transplantations (n = 142) in patients with low anti-A/B antibody titers between 2007 and 2021 were included. Patients were divided into two groups (with and without rituximab) for desensitization. The primary outcomes were the incidence of acute AMR and infection. RESULTS: Sixty-six patients were desensitized without rituximab (rituximab-free group), and 76 were pretreated with 100 mg rituximab (rituximab group) before transplantation. The incidence of acute AMR was significantly lower in the rituximab group than in the rituximab-free group (.0% [0/76] vs. 7.6% [5/66], respectively; p = .047). Post-transplantation anti-A/B antibody titers were also lower in the rituximab group than in the rituximab-free group. There was no significant difference in the incidence of adverse events, including infections, between the two groups. CONCLUSION: In ABOi kidney transplantation patients with low anti-A/B antibody titers, the desensitization protocol with a single dose of 100 mg rituximab was effective in preventing acute AMR without increasing the risk of other adverse events.

Short-term outcomes of second kidney transplantation compared with those of first transplantation in Japanese patients: a single-center, retrospective, observational study.

BACKGROUND: Among patients who undergo kidney transplantation, a subsequent second kidney transplantation (TX2) is often necessary. The TX2 outcomes remain controversial, however, and only limited data are available on clinical outcomes of TX2 in Japanese patients. This study aimed to assess graft and patient survival rates of TX2 and compared these rates with those of first kidney transplantation (TX1) in Japanese patients. METHODS: Of the 898 kidney transplantations performed between 2010 and 2019 at our institution, 33 were TX2. We performed survival analysis using weighted Kaplan-Meier analysis and Cox proportional hazards analysis with propensity score matching, specifically inverse probability of treatment weighting (IPTW). RESULTS: Death-censored graft survival (DCGS) rates at 1, 3, and 5 years for the TX1 versus TX2 groups were 99.3, 97.9, and 95.0% versus 100, 96.0, and 91.2%, respectively. Overall survival (OS) rates at 1, 3, and 5 years for the TX1 versus TX2 groups were 99.4, 98.9, and 97.8% versus 100, 100, and 94.4%, respectively. Using the log-rank test, IPTW-weighted Kaplan-Meier curves showed no significant differences for TX1 versus TX2 in DCGS (p = 0.535) and OS (p = 0.302). On Cox proportional hazards analysis for TX2 versus TX1, the IPTW-adjusted hazard ratio (HR) for DCGS was 1.75 (95% CI, 0.28-10.9; p = 0.550) and for OS was 2.71 (95% CI, 0.40-18.55; p = 0.311). CONCLUSIONS: For patients who require TX2, this treatment is an acceptable option based on the short-term outcomes data for DCGS and OS.

Persistent hyperparathyroidism after preemptive kidney transplantation.

BACKGROUND: Long-term dialysis vintage is a predictor of persistent hyperparathyroidism (HPT) after kidney transplantation (KTx). Recently, preemptive kidney transplantation (PKT) has increased. However, the incidence, predictors, and clinical implications of HPT after PKT are unclear. Here, we aimed to elucidate these considerations. METHODS: In this retrospective cohort study, we enrolled patients who underwent PKT between 2000 and 2016. Those who lost their graft within 1 year posttransplant were excluded. HPT was defined as an intact parathyroid hormone (PTH) level exceeding 80 pg/mL or hypercalcemia unexplained by causes other than HPT. Patients were divided into two groups based on the presence of HPT 1 year after PKT. The primary outcome was the predictors of HPT after PKT, and the secondary outcome was graft survival. RESULTS: Among the 340 consecutive patients who underwent PKT, 188 did not have HPT (HPT-free group) and 152 had HPT (HPT group). Multivariate logistic regression analysis revealed that pretransplant PTH level (P < 0.001; odds ratio [OR], 5.480; 95% confidence interval [CI], 2.070-14.50) and preoperative donor-estimated glomerular filtration rate (P = 0.033; OR, 0.978; 95% CI, 0.957-0.998) were independent predictors of HPT after PKT. Death-censored graft survival was significantly lower in the HPT group than that in the HPT-free group (90.4% vs. 96.4% at 10 years, P = 0.009). CONCLUSIONS: Pretransplant PTH levels and donor kidney function were independent predictors of HPT after PKT. In addition, HPT was associated with worse graft outcomes even after PKT.

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).

Risk factors for subchondral insufficiency fracture of the femoral head in renal transplant patients.

INTRODUCTION: Risk factors associated with subchondral insufficiency fracture (SIF) of the femoral head have not been established. The aim of the present study was to determine the incidence and risk factors for SIF of the femoral head following renal transplantation (RT). MATERIALS AND METHODS: We analyzed the cases of 681 RT patients (mean age at surgery: 49.5 ± 13.6 years, 249 women, 432 men) to determine the incidence of SIF. Hip magnetic resonance imaging (MRI) was performed 6 months post-RT. The following potential predictors of SIF were evaluated: (1) patient's condition at RT: bone mineral density (BMD), pre-RT laboratory values including calcium (Ca), phosphorus (P), calcium-phosphorus product (Ca × P), and intact parathyroid hormone; the patient and donor's blood relationship; and mismatching number of human leukocyte antigens (HLAs), and (2) post-RT dosage(s) of steroid(s), the immunosuppressive regimen, and the incidence of acute rejection. RESULTS: SIF was observed in 15 hips (13 patients, 1.9%). We successfully matched 39 patients without SIF. A multivariate logistic regression analysis adjusted for cumulative dosages of steroids, revealed the following were risk factors for SIF: osteoporosis (OR: 11.4, p = 0.046), lumbar BMD (OR: 0.003, p = 0.038), pre-RT serum P (OR 2.68, p = 0.004), and pre-RT serum Ca × P (OR: 1.11, p = 0.005). CONCLUSION: Since osteoporosis, the lumbar BMD, serum P, and serum Ca × P were identified as risk factors for a post-RT SIF, these factors should be evaluated before RT for the prediction of the SIF risk.

Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation.

AIM: Bacterial and fungal infections are serious, life-threatening conditions after kidney transplantation. The development of oral/oesophageal candidiasis after kidney transplantation is not a reported risk factor for subsequent severe infection. This study was performed to investigate the relationship between oral/oesophageal candidiasis after kidney transplantation and the development of subsequent infection requiring hospitalization. METHODS: This retrospective study included 522 consecutive patients who underwent kidney transplantation at Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital from 1 January 2010 to 1 February 2019. Ninety-five percentage of patients were living donor transplant recipients. Visual examination was performed to detect oral candidiasis, beginning immediately after kidney transplantation; upper gastrointestinal endoscopy was performed 8-10 months after kidney transplantation. Twenty-five patients developed candidiasis (Candida-onset group) and 497 did not (non-Candida-onset group). The follow-up periods were 67 (37-86) months in the Candida-onset group and 55 (34-89) months in the non-Candida-onset group. Severe infection was defined as bacterial or fungal infection requiring hospitalization; viral infections were excluded. RESULTS: Severe infection developed in 9/25 (36%) patients in the Candida-onset group and in 77/497 (15%) patients in the non-Candida-onset group (p = .006). Binomial logistic analysis revealed that Candida infection (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.06-6.06; p = .037) and use of rituximab (OR 1.81, 95% CI 1.12-2.93; p = .016) were significant predictors of subsequent severe infection. CONCLUSION: Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation and suggests an over-immunosuppressive state, which should prompt evaluation of immunosuppression.

Elevated parathyroid hormone one year after kidney transplantation is an independent risk factor for graft loss even without hypercalcemia.

BACKGROUND: Hypercalcemic hyperparathyroidism has been associated with poor outcomes after kidney transplantation (KTx). However, the clinical implications of normocalcemic hyperparathyroidism after KTx are unclear. This retrospective cohort study attempted to identify these implications. METHODS: Normocalcemic recipients who underwent KTx between 2000 and 2016 without a history of parathyroidectomy were included in the study. Those who lost their graft within 1 year posttransplant were excluded. Normocalcemia was defined as total serum calcium levels of 8.5-10.5 mg/dL, while hyperparathyroidism was defined as when intact parathyroid hormone levels exceeded 80 pg/mL. The patients were divided into two groups based on the presence of hyperparathyroidism 1 year after KTx. The primary outcome was the risk of graft loss. RESULTS: Among the 892 consecutive patients, 493 did not have hyperparathyroidism (HPT-free group), and 399 had normocalcemic hyperparathyroidism (NC-HPT group). Ninety-five patients lost their grafts. Death-censored graft survival after KTx was significantly lower in the NC-HPT group than in the HPT-free group (96.7% vs. 99.6% after 5 years, respectively, P < 0.001). Cox hazard analysis revealed that normocalcemic hyperparathyroidism was an independent risk factor for graft loss (P = 0.002; hazard ratio, 1.94; 95% confidence interval, 1.27-2.98). CONCLUSIONS: Normocalcemic hyperparathyroidism 1 year after KTx was an independent risk factor for death-censored graft loss. Early intervention of elevated parathyroid hormone levels may lead to better graft outcomes, even without overt hypercalcemia.

Prognostic value of geriatric nutritional risk index for aspiration pneumonia: a retrospective observational cohort study.

BACKGROUND: The clinical characteristics and prognostic factors of aspiration pneumonia remain poorly defined. Geriatric nutrition risk index (GNRI) has recently been reported to exhibit a prognostic value for several diseases in older adults. AIMS: We investigated the clinical characteristics and prognostic significance of GNRI for aspiration pneumonia in older adult patients. METHODS: In this retrospective observational cohort study, conducted in a single-institute acute-phase community hospital, patients with aspiration pneumonia diagnosed at our institute between April 2014 and March 2016 were enrolled. Data on patient characteristics, microbiological findings, and clinical course were collected. The outcome was in-hospital mortality. Receiver operating characteristic curve (ROC) analysis was conducted to compare the predictive value of each parameter. Logistic regression analysis was performed to identify independent prognostic factors. RESULTS: Overall, 587 aspiration pneumonia patients aged ≥ 65 years were enrolled. Their mean age was 86 years. Among them, 97 (16.5%) died. In ROC analysis for in-hospital mortality, as compared to albumin, body mass index, and A-DROP score, GNRI had a greater area under the curve value, with a significant difference between GNRI and albumin (p = 0.0058). Male sex (p = 0.028), chronic heart failure (p = 0.023), history of malignancy (p = 0.0025), lower GNRI (p < 0.001), and initial antibiotic change (p < 0.001) were identified as independent adverse prognostic factors in multivariate analysis. DISCUSSION AND CONCLUSIONS: Our findings indicate that GNRI is a potential prognostic marker for older adults with aspiration pneumonia and may act as a proxy for disease severity. Our results support the use of GNRI in the clinical management of aspiration pneumonia.

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.

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.

The usefulness of a combination of age, body mass index, and blood urea nitrogen as prognostic factors in predicting oxygen requirements in patients with coronavirus disease 2019.

INTRODUCTION: Risk factors for seriously ill coronavirus disease 19 (COVID-19) patients have been reported in several studies. However, to date, few studies have reported simple risk assessment tools for distinguishing patients becoming severely ill after initial diagnosis. Hence, this study aimed to develop a simple clinical risk nomogram predicting oxygenation risk in patients with COVID-19 at the first triage. METHODS: This retrospective study involved a chart review of the medical records of 84 patients diagnosed with COVID-19 between February 2020 and March 2021 at ten medical facilities. The patients were divided into requiring no oxygen therapy (non-severe group) and requiring oxygen therapy (severe group). Patient characteristics were compared between the two groups. We utilized univariate logistic regression analysis to confirm determinants of high risks of requiring oxygen therapy in patients with moderate COVID-19. RESULTS: Thirty-five patients ware in severe group and forty-nine patients were in non-severe group. In comparison with patients in the non-severe group, patients in the severe group were significantly older with higher body mass index (BMI), and had a history of hypertension and diabetes. Serum blood urea nitrogen (BUN), lactic acid dehydrogenase (LDH), and C-reactive protein (CRP) levels were significantly higher in the severe group. Multivariate analysis showed that older age, higher BMI, and higher BUN levels were significantly associated with oxygen requirements. CONCLUSIONS: This study demonstrated that age, BMI, and BUN were independent risk factors in the moderate-to-severe COVID-19 group. Elderly patients with higher BMI and BUN require close monitoring and early treatment initiation.

Comparison of Pre- and Post-transplant Parathyroidectomy in Renal Transplant Recipients and the Impact of Parathyroidectomy Timing on Calcium Metabolism and Renal Allograft Function: A Retrospective Single-Center Analysis.

BACKGROUND: The effect of parathyroidectomy (PTx) timing on serum calcium (Ca) levels and renal functions in renal transplant recipients with severe hyperparathyroidism (HPT) remains unclear. We retrospectively aimed to investigate and compare the clinical data of patients who underwent pre- and post-transplant PTx and elucidated the impact of PTx timing on serum Ca levels and renal graft outcomes after renal transplantation (RTx). METHODS: During January 2000-December 2016, 53 and 55 patients underwent post-transplant PTx (Post-RTx group) and pretransplant PTx (Pre-RTx group), respectively. The serum Ca levels and estimated glomerular filtration rate (eGFR) were assessed in both groups. RESULTS: At the end of the follow-up, the serum Ca levels were significantly higher and the incidence of hypocalcemia was significantly lower in the Pre-RTx group than in the Post-RTx group [9.5 vs. 8.9 mg/dL, P < 0.001; 14.5% vs. 34.0%, P = 0.024]. The decrease in the eGFR 12-36 months after RTx was more significant in the Post-RTx group than in the Pre-RTx group (-13.8% vs. -0.9%; P = 0.001). A logistic regression involving age, sex, dialysis period, and serum parathormone level revealed that post-transplant PTx is an independent risk factor for persistent hypocalcemia at the end of the follow-up (P = 0.034) and for a >20% decrease in the eGFR 12-36 months after RTx (P = 0.029). CONCLUSIONS: In renal transplant candidates with severe HPT, pretransplant PTx should be considered to prevent persistent hypocalcemia and deterioration of the renal graft function.

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.

Incidence and risk factors for osteonecrosis of the hip in renal transplant patients: a prospective single-centre study.

BACKGROUND: There is a lack of evidence about the risk factors associated with osteonecrosis of the femoral head (ONFH). PURPOSES: To determine the incidence and risk factors for ONFH following renal transplantation (RT). METHODS: In total, data of 681 RT patients (mean age at surgery, 49.5 ± 13.6 years; 249 women and 432 men) were evaluated to determine the incidence of ONFH. Hip magnetic resonance imaging (MRI) was performed six months after RT. The following potential predictors of ONFH were evaluated: (1) patient's condition at RT; laboratory test results including calcium (Ca), phosphorus (P), calcium-phosphorus product (Ca × P), and intact parathyroid hormone before RT; blood relationship between the patient and donor; and mismatching number of human leukocyte antigens (HLAs), especially HLA class I and class II and (2) dosages of steroids after RT, immunosuppressive regimen, and incidence of acute rejection. RESULTS: ONFH was observed in 30 hips (21 cases, 3.1%). We successfully matched 63 patients without ONFH. Multivariate logistic regression analysis, adjusted for cumulative dosages of steroids, revealed that mismatching number of HLA (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.10-2.36; p = 0.014), HLA class II (HR, 3.73; 95% CI, 1.46-9.56; p = 0.001), P before RT (HR, 1.62; 95% CI, 1.02-2.58; p = 0.041), and Ca × P  before RT (HR, 1.06; 95% CI, 1.01-1.11; p = 0.024) were risk factors for ONFH. CONCLUSION: A greater number of HLA mismatches, HLA class II, serum P, and serum Ca × P were risk factors for ONFH after RT. Therefore, these factors should be evaluated in order to predict ONFH after RT.

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.

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.