Clinical effectiveness of zoster vaccine live in kidney transplant recipients immunized prior to transplantation: a retrospective single-centre cohort study.

OBJECTIVES: Kidney transplant (KT) recipients have an increased risk of herpes zoster (HZ) and its complications. Although recombinant zoster vaccine is favoured over zoster vaccine live (ZVL), ZVL is also recommended to prevent HZ for KT candidates. We aimed to evaluate the clinical effectiveness of ZVL in KT recipients immunized before transplantation. METHODS: Adult patients who received kidney transplantation from January 2014 to December 2018 were enrolled. Patients were observed until HZ occurrence, death, loss of allograft, loss to follow-up, or 5 years after transplantation. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare the incidence of HZ after transplantation between vaccinated and unvaccinated patients. RESULTS: A total of 84 vaccinated and 340 unvaccinated patients were included. The median age was higher in the vaccinated group (57 vs. 54 years, p 0.003). Grafts from deceased donors were more frequently transplanted in the unvaccinated group (16.7% vs. 51.8%, p < 0.001). Five-year cumulative HZ incidence was 11.9%, which translated to 26.27 (95% CI, 19.33-34.95) per 1000 person-years. The incidence in the vaccinated and unvaccinated groups was 3.9% and 13.7%, respectively. After adjustment, vaccination showed significant protective effectiveness against HZ (adjusted hazard ratio, 0.18, 95% CI, 0.05-0.60). In addition, all four cases of disseminated zoster occurred in the unvaccinated group. DISCUSSION: Our study, the first on the clinical effectiveness of zoster vaccines for KT recipients, suggests that ZVL before transplantation effectively prevents HZ.

Invasive Fungal Diseases in Kidney Transplant Recipients: Risk Factors for Mortality.

BACKGROUND: Invasive fungal disease (IFD) is common in solid organ transplant (SOT) recipients and contributes to high morbidity and mortality. Although kidney transplantation (KT) is a commonly performed SOT, data on the risk factors for IFD-related mortality are limited. METHODS: A 1:2 retrospective case-control study was performed in an experienced single center in the Republic of Korea. We reviewed the electronic medical records of patients with IFD after KT between February 1995 and March 2015. RESULTS: Of 1963 kidney transplant recipients, 48 (2.5%) were diagnosed with IFD. The median interval from KT to IFD diagnosis was 172 days. Invasive aspergillosis (IA) was the most common, followed by invasive candidiasis (IC). Diabetes mellitus (DM) (odds ratio (OR) 3.72, 95% confidence interval (CI) 1.34-10.31, p = 0.011) and acute rejection (OR 3.41, 95% CI 1.41-8.21, p = 0.006) were associated with IFD development. In the subgroup analyses, concomitant bacterial infection was associated with IC development (OR 20.10, 95% CI 3.60-112.08, p = 0.001), and delayed graft function was associated with IA occurrence (OR 10.60, 95% CI 1.05-106.84, p = 0.045). The 12-week mortality rate in all patients was 50.0%. Mortality rates were significantly higher in older patients (adjusted hazard ratio (aHR) 1.06, 95% CI 1.02-1.11, p = 0.004), or those with DM (aHR 2.61, 95% CI 1.02-6.68, p = 0.044), deceased donor transplantation (aHR 2.68, 95% CI 1.03-6.95, p = 0.043), lymphocyte-depleting antibody usage (aHR 0.26, 95% CI 0.08-0.80, p = 0.019), acute rejection (aHR 0.38, 95% CI 0.15-0.97, p = 0.044), and concomitant bacterial infection (aHR 8.76, 95% CI 1.62-47.51, p = 0.012). CONCLUSIONS: A total of 50% of IFD cases occurred six months or later after transplantation. The IFD-related mortality rate was high in kidney transplant recipients despite the low incidence. DM and acute rejection were associated with high mortality, as well as IFD development. As old age, deceased donor transplantation, lymphocyte-depleting antibody usage, and concomitant bacterial infection are risk factors for IFD-related mortality, efforts for its early diagnosis and appropriate treatment are required.

Risk factors for development and mortality of invasive pulmonary Aspergillosis in kidney transplantation recipients.

Invasive pulmonary aspergillosis (IPA) is a high mortality opportunistic infection among kidney transplant recipients. This study assessed the risk factors and outcomes of IPA after KT. A retrospective study was conducted at a tertiary-care referral hospital in Korea. Electronic medical records of patients diagnosed with IPA after KT between February 1995 and March 2015 were reviewed. The control patients comprised two patients who received KT before and after each IPA case. Twenty-six cases were diagnosed with IPA among 1963 recipients at a median of 58 years old. The most common cause of end-stage renal disease was diabetic nephropathy. The median time to diagnosis was 161 days. Delayed graft function was associated with the development of IPA. The overall 12-week mortality rate of IPA was 57.5%. Serum GM level ≥ 2 and BAL GM level ≥ 5 were associated with 12-week mortality in the Kaplan-Meier survival analyses. Approximately half of IPA in KT recipients developed during the late posttransplant period (> 6 months), especially after treatment for acute rejection. Careful monitoring for IPA is required in patients with delayed graft function, DM, and who received rejection therapy. Higher serum and BAL GM were associated with 12-week mortality.

The clinical outcomes of second kidney transplantation in IgA nephropathy: a multicenter retrospective study.

BACKGROUND: Recurrent IgA nephropathy (IgAN) after kidney transplantation (KT) has been reported to range between 12 and 65%. However, few data are available on second transplantation in recurrent IgAN. Therefore, this study aimed to build bottom-line data for the possibility of second transplantation in patients who lost first transplanted kidney due to recurrent IgAN. METHODS: Patients who received KT twice due to recurrent IgAN at four large academic hospitals in Korea between March 1985 and December 2013 were reviewed. They were followed up until October 2014. All patients were identified as having recurrent IgAN in the first graft biopsies. The clinical outcomes of the second KT in these patients were compared with the first KT and with all cases of second KT (n = 169) performed at one center in the same period. RESULTS: 28 patients were enrolled in this study. First grafts failed after 106.64 ± 48.72 months (mean ± SD). Following the second transplantation, recurrent IgAN was identified in only 2 patients during the follow-up of 61.61 ± 47.23 months. In 1 patient, the second graft was lost due to chronic rejection without mesangial IgA deposit. The second KT showed comparable graft survival compared with the first KT and the overall second KT (p = 0.308 by log-rank test). At the final follow-up, the serum creatinine level was 1.16 ± 0.33 mg/dL in the second graft except in 1 patient. CONCLUSIONS: Second KT in recurrent IgAN showed reasonably good long-term results. Therefore, clinicians might be able to suggest second transplantation as an option for patients who lost the first graft due to recurrent IgAN.

Efficacy of mitiglinide and sitagliptin, alone or in combination, on postprandial excursion and glycemic variability assessed by continuous glucose monitoring: a post hoc analysis with single-day treatment.

OBJECTIVE: To compare the efficacy of mitiglinide and sitagliptin, alone or in combination, on postprandial excursion and glycemic variability assessed by continuous glucose monitoring (CGM) in a single-day treatment setting. METHODS: This was a post hoc analysis of a randomized crossover study comparing the efficacy of sitagliptin, mitiglinide and the combination of these two drugs. Twenty-four hour CGM was performed before and after a single-day treatment with each drug alone or in combination. RESULTS: Mean glucose levels were decreased in all groups. The average of three postprandial glucose excursions AUC (average of all three 4-h postprandial periods throughout the day) (AUCpp-average) decreased in the mitiglinide and combination treatment groups, but not in the sitagliptin group. The lowering effect on AUCpp-average was greater in patients given mitiglinide (-47 mg/dl, p < 0.001) or combination treatment (-66 mg/dl, p < 0.001) compared with sitagliptin alone (-18 mg/dl). The reduction in mean amplitude of glycemic excursion was greater with mitiglinide (-29.3 mg/dl, p < 0.001) and combination treatment (-28.3 mg/dl, p < 0.01) than with sitagliptin alone (-8.9 mg/dl). CONCLUSIONS: Mitiglinide or combination treatment resulted in lower glycemic variability and postprandial glucose excursion than sitagliptin alone; however, the results of this single-day pharmacodynamics study cannot be generalized to a clinical setting.

Impact of donor kidney function and donor age on poor outcome of living-unrelated kidney transplantation (KT) in comparison with living-related KT.

Living-unrelated donors (LURD) have been widely used for kidney transplantation (KT). We retrospectively reviewed 779 patients who underwent living-donor KT from 2000 to 2012, to compare outcomes of 264 KT from LURD and 515 from living-related donors (LRD), and to identify risk factors for living KT. Median follow-up was 67 months. Mean donor age, total human leukocyte antigen (HLA) mismatches, and HLA-DR mismatches were higher, and mean estimated glomerular filtration rate (eGFR) was lower in LURD. Acute rejection (AR)-free survival (p = 0.018) and graft survival (p = 0.025) were lower for LURD than LRD, whereas patient survival rate was comparable. Cox regression analysis showed HLA-DR mismatches (OR 1.75 for one mismatch; OR 2.19 for two mismatches), recipient age ≤ 42 yr, and donor age > 50 yr were significant risk factors for acute rejection. For graft survival, AR and donor eGFR (OR 1.90, p = 0.035) were significant. We also identified significant impact of recipient age > 50 yr and diabetes for patient survival. However, KT from LURD was not a significant risk factor for AR (p = 0.368), graft survival (p = 0.205), and patient survival (p = 0.836). Our data suggest that donor eGFR and donor age are independent risk factors for clinical outcomes of living KT, which can be related with poor outcome of KT from LURD.

A novel UMOD mutation (c.187T>C) in a Korean family with juvenile hyperuricemic nephropathy.

Familial juvenile hyperuricemic nephropathy (FJHN; OMIM 162000) is an autosomal dominant disorder characterized by hyperuricemia and gouty arthritis due to reduced kidney excretion of uric acid and progressive renal failure. Gradual progressive interstitial renal disease, with basement membrane thickening and glomerulosclerosis resulting from fibrosis, starts in early life. In most cases of FJHN, uromodulin gene (UMOD) is responsible for the disease; however, there has been only one report of a genetically confirmed FJHN family in Korea. Here we report another Korean family with FJHN, in which three male members. a father and 2 sons.developed gout and progressive renal insufficiency. The clinical, laboratory, and radiological findings were consistent with FJHN, and renal biopsy showed chronic parenchymal damage, which can be found in FJHN but is not specific to this disease. In order to confirm the diagnosis, sequence analysis of the UMOD was performed, and a novel heterozygous missense variant (c.187T>C; p.Cys63Arg) in exon 3 was identified. We assume that this variant is likely to be the causative mutation in this family, as the variant segregated with the disease. In addition, approximately two-thirds of the known mutations lead to a cysteine amino acid change in uromodulin, and all such variants have been shown to cause UMOD-associated kidney disease. In summary, we report a Korean FJHN family with three affected members by genetic analysis of the UMOD, and provide the first report of a novel heterozygous missense mutation.

Impact of parathyroidectomy on allograft outcomes in kidney transplantation.

We performed retrospective, multi-center study of the impacts of parathyroidectomy (PTX) after or before kidney transplantation on allograft outcomes. A total of 63 patients who underwent PTX after kidney transplantation were identified. Deterioration in eGFR by more than 25% at 1 month after PTX occurred in 20% of the patients. The baseline eGFR was significantly lower in impairment group than nonimpairment group [adjusted odds ratio (OR) 0.87, 95% confidence interval (CI) 0.77-0.99, P = 0.033]. Low iPTH concentration after PTX was also a significant risk factor for the renal impairment (OR 0.96, CI 0.94-0.99, P = 0.009). A total of 37 patients who underwent PTX before transplantation were identified. Thirty-six percent of the patients had persistent hyperparathyroidism by 1 year after transplantation. A high iPTH level before PTX was a significant risk factor for persistent post-transplant hyperparathyroidism (adjusted OR 1.002, CI 1.000-1.005, P = 0.039). Finally, eGFR values during the first 5 years after transplantation were significantly lower in the patients who underwent PTX at less than 1 year after transplantation, than the pretransplant PTX patients (P = 0.032). As PTX after kidney transplantation has a risk of deterioration of allograft function, pretransplant PTX should be considered for patients with severe hyperparathyroidism, who could undergo post-transplant PTX.

Effect of genetic polymorphisms on the pharmacokinetics and efficacy of glimepiride in a Korean population.

BACKGROUNDS: Glimepiride is a commonly used sulfonylurea hypoglycemic agent. There is considerable interindividual variation in the response to sulfonylurea for patients with type 2 diabetes. The purpose of this study was to investigate whether genetic variations influence the efficacy of glimepiride in healthy Korean subjects. METHODS: A single 2-mg oral dose of glimepiride was administered to 46 healthy volunteers. Serial blood sampling for 12h after oral dosing was performed for determination of plasma glimepiride, glucose and insulin levels. We tested the association of seven single nucleotide polymorphisms (SNPs) in four candidate genes with the efficacy of glimepiride. RESULTS: Pharmacodynamic profiles for plasma glucose and insulin showed no statistically significant differences among genotype groups, and parameters were not different from one another. There were no association of the KCNJ11, NOS1AP, TCF7L2 and ABCC8 gene polymorphisms and the efficacy of glimepiride. CONCLUSIONS: Knowledge of these polymorphisms provides no clinical useful information for the pharmacogenetic therapeutic approach for Korean patients with type 2 diabetes.

Association between changes in N-terminal pro-brain natriuretic peptide levels and changes in left ventricular mass index in stable hemodialysis patients.

BACKGROUND/AIMS: Left ventricular (LV) hypertrophy is a powerful predictor of mortality in dialysis patients. Serial measurements of LV mass provide prognostic information. We evaluated the association between changes in biomarkers and changes in LV mass index (LVMI) in hemodialysis (HD) patients. METHODS: This was a prospective study of 21 stable HD patients with preserved LV ejection fraction (> or =50%). Echocardiography and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) and cardiac troponin T were performed on the same day and repeated 6 and 12 months later. RESULTS: At baseline, the NT-proBNP and BNP levels correlated with LVMI. Percent changes in LVMI were positively associated with those in log-transformed NT-proBNP levels during both the first (baseline vs. month 6, r = 0.78, p < 0.001) and the second 6 months (months 6 vs. 12, r = 0.73, p < 0.001). Among the 3 biomarkers, NT-proBNP was the only one that was related to changes in LVMI by multivariate correlation analysis, including age, sex, blood pressure, predialysis weight and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. CONCLUSION: Our results show that changes in LVMI are closely correlated with variation in NT-proBNP levels in HD patients. These data have significant implications for the application of NT-proBNP as a biomarker for assessing changes in LVMI in HD patients.

Incidence and radio-uptake patterns of femoral head avascular osteonecrosis at 1 year after renal transplantation: a prospective study with planar bone scintigraphy.

OBJECTIVES: We prospectively investigated the incidence of femoral head avascular osteonecrosis (AVN) and radio-uptake patterns of femoral heads on bone scintigraphy at 1 year after renal transplantation. METHODS: A total of 237 subjects (473 femoral heads) were included. A bone scintigraphy was performed at 12 +/- 1.1 months after renal transplantation, and 17 hips were painful at the time of bone scintigraphy. We graded the radioactivity in each femoral head as normal (grade 0), mildly increased (grade I), and definitely increased (grade II). Typical photon defects in the upper lateral femoral heads were evaluated separately. AVN was confirmed with clinical follow-up of more than 1 year and MRI and/or plain radiography findings. RESULTS: Femoral head AVN was detected in 15 of the 237 patients and 23 of the 473 femoral heads. When grade I and II activities were used as positive criteria, bone scintigraphy had a sensitivity of 91.3% (100% with pain) and specificity of 74.0% (100% with pain) for AVN diagnosis. When only grade II activity was considered positive, the rates were 56.5% (80.0% with pain) and 99.5% (100% with pain), respectively. The presence of a typical photon defect had a low sensitivity of 47.8%, although the specificity was high (99.1%). CONCLUSIONS: The incidence of femoral head AVN was low among a prospective cohort of renal transplantation recipients at the time of 1 year after engraftment. Planar bone scintigraphy is sufficient to diagnose AVN in symptomatic patients at risk for femoral head AVN using grade I and II activities as positive criteria.

Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients.

Human parvovirus B19 (B19) infection has been known to cause chronic anemia, pure red cell aplasia (PRCA), glomerulopathy, and allograft dysfunction in kidney transplant (KT) recipients. The aim of this study was to evaluate the incidence and clinical significance of B19 infection in KT recipients. A total of 537 serum samples from 167 KT recipients were included in the present study. The incidence of B19 infection was based on either qualitative polymerase chain reaction (PCR) or quantitative PCR with LightCycler Parvovirus B19 Quantitation kit. Clinical significance of B19 infection was investigated by a retrospective review of hemoglobin (Hb) levels and the results of kidney and bone marrow biopsies. The overall PCR positive rate was 18.3% (98/537), and 52 of 167 (31.1%) KT recipients showed at least one positive PCR. In addition, 20 of 167 subjects (12.0%) showed PCR-positivity more than two consecutive times, and they had significantly lower Hb levels than those with negative or one positive PCR (p < 0.0001). Furthermore, two patients suffered from PRCA, which was confirmed by bone marrow biopsy. However, B19 infection did not seem to affect the graft outcome. In conclusion, the B19 infection in KT recipients was not uncommon and was associated with low Hb levels and PRCA after KT.

Analysis of depression in continuous ambulatory peritoneal dialysis patients.

It is well known that depression and sense of hopelessness worsen the quality of life in end-stage renal disease (ESRD) patients receiving dialysis. However, the characteristics of depression in continuous ambulatory peritoneal dialysis (CAPD) patients have not been analyzed in detail. We performed this study to investigate the severity of depression and the factors affecting depression in CAPD patients. With 96 CAPD patients, we evaluated each patient's depressive mood and hopelessness with CES-D (Center for Epidemiologic Studies Depression) scale and Beck Hopelessness Scale. We also evaluated the degree of stress of each patient with internal individual stress scale. Most CAPD patients experienced severe depression compared with the general population. Their depression was better explained by psychological factors, such as stress and sense of hopelessness, than by demographic or physical factors. On the basis of these findings, we suggest that the treatment of depression in CAPD patients might be possible by modulation of psychological factors.