Risk factors for Pneumocystis pneumonia with acute respiratory failure among kidney transplant recipients.

PURPOSE: One of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation. MATERIALS AND METHODS: This is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression. RESULTS: Among the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01-1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86-0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05-40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29-53.20; p = 0.026). CONCLUSION: Patients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.

Phthalate Plasticizers in Children's Products and Estimation of Exposure: Importance of Migration Rate.

Plasticizers are added to diverse consumer products including children's products. Owing to their potential for endocrine disruption, the use of phthalate plasticizers is restricted in many children's products. In this study, exposure to five phthalate esters (dibutylphthalate, di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate, di-isobutyl phthalate, and diisononyl phthalate (DINP)) and an alternative (di-ethylhexyl adipate) was assessed by the use of children's products based on chemical analysis of 3345 products purchased during 2017 and 2019 in Korea. Plasticizers were found above the detection limits in 387 products, and DEHP and DINP were the two most predominantly detected plasticizers. Deterministic and probabilistic estimation of the margin of exposure at a screening level revealed that the use of children's products might be an important risk factor. However, it is also highly likely that the exposure could be overestimated, because the migration rate was estimated based solely on the content of plasticizers in children's products. Chemical migration is a key process determining the absorption of plasticizers from products; thus, further refinements in experimental determination or model estimation of the migration rate are required.

Urinary transglutaminase 2 as a potent biomarker to predict interstitial fibrosis and tubular atrophy of kidney allograft during early posttransplant period in deceased donor kidney transplantation.

PURPOSE: Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis. METHODS: We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis. RESULTS: Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures. CONCLUSION: Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis.

Comparison of Clinical Outcomes Between Preemptive Transplant and Transplant After a Short Period of Dialysis in Living-Donor Kidney Transplantation: A Propensity-Score-Based Analysis.

BACKGROUND The permissible extent of pretransplant dialysis for patient and allograft survival is unclear. We assumed that a short period of dialysis before living donor kidney transplantation (LDKT) will show the similar results as preemptive kidney transplantation (PKT). MATERIAL AND METHODS We retrospectively evaluated the outcomes of LDKT according to pretransplant dialysis duration in both unmatched cohorts (n=1984) and propensity-score-matched cohorts (n=986) cohorts. The primary study endpoint was post-transplantation patient survival and death-censored graft survival (DCGS) according to the duration of pretransplant dialysis by 19 months which was the best cutoff value to differentiate clinical outcomes with the use of the time-dependent area under the curve. RESULTS Of 1984 patients with LDKT at our center between January 2005 and September 2016, PKT was performed in 429 patients. The durations of pretransplant dialysis were <19 months in 962 recipients and ≥19 months in 593 recipients. There was no significant difference in mortality and DCGS between PKT and non-PKT recipients with pretransplant dialysis of <19 months. Patient survival (P=0.024) and DCGS (P=0.001) were worse in non-PKT recipients with pretransplant dialysis of ≥19 months. In the matched cohort, DCGS was significantly lower in non-PKT recipients with pretransplant dialysis of ≥19 months (P=0.037). It is likely that the incidence of biopsy-proven acute rejection was higher in this group (P=0.083). CONCLUSIONS Patient survival and DCGS were worse when the pretransplant dialysis duration was ³19 months in a propensity-score-matched LDKT cohort.

A composite of urinary biomarkers for differentiating between tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in kidney allografts.

BACKGROUNDS/AIMS: Compared with a single urinary biomarker, a composite of multiple urinary biomarkers may be more helpful for differentiating tubulointerstitial inflammation from interstitial fibrosis/tubular atrophy (IFTA) in kidney allografts. METHODS: In this cross-sectional cohort study, we collected urine samples from 115 patients with for-cause biopsy, 53 patients with stable allografts, and 50 living kidney donors. We measured the urinary levels of transglutaminase 2 (TG2), syndecan-4 (SDC4), alpha 1 microglobulin (A1M), interferon-inducible protein 10 (IP-10), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). RESULTS: The for-cause biopsy group showed significantly higher levels of logeTG2/Cr, logeA1M/Cr, logeIL-6/Cr, and logeMCP-1/Cr compared with other groups. In the for-cause biopsy group, logeTG2/Cr level was positively correlated with the severity of IFTA. After adjusting for age, sex, body mass index, diabetes, hypertension, cardiovascular disease, and the interval between kidney transplant and biopsy, TG2 and the interval between transplant and biopsy were significantly correlated variables for the severity of IFTA. Regarding tubulointerstitial inflammation, Body mass index, TG2, SDC4, and IP-10 were positively-correlated variables, and MCP-1 and the interval between transplant and biopsy were negatively-correlated variables. CONCLUSIONS: Our results show that post-transplant urinary levels of TG2, SDC4, MCP-1 and IP-10 may be a useful biomarker for tubulointerstitial inflammation and IFTA.

Does Enteric Conversion Affect Graft Survival After Pancreas Transplantation with Bladder Drainage?

BACKGROUND Although bladder drainage is effective for monitoring urine amylase levels to detect graft rejection, enteric drainage is performed more frequently. The optimal method for monitoring pancreatic enzyme secretions remains unclear. We investigated graft survival in recipients of bladder drainage and assessed the risk of graft rejection and failure after enteric conversion. MATERIAL AND METHODS From January 1999 to October 2015, we performed 318 pancreas transplantations at our institution. We enrolled 180 recipients who underwent pancreas transplantation with bladder drainage (82 underwent enteric conversion and the rest did not). RESULTS The mean interval between pancreas transplantation and enteric conversion was 20±24 months. The graft survival rate was significantly higher in the enteric conversion group for 10 years after pancreas transplantation than in the maintain bladder drainage group. After enteric conversion, 14 recipients lost graft function. The interval between enteric conversion and graft failure was 43±26 months. In the enteric conversion group, immediate postoperative thromboembolectomy (HR=12.729, p=0.000), renal failure (HR=5.710, p=0.005), pancreas graft rejection after EC (HR=19.006, p=0.000), and delayed graft function (HR=7.021, p=0.001) had a significant relationship with graft failure. CONCLUSIONS Enteric conversion can be safe and effective for improving short- and long-term graft survival if performed after approximately 9 months. Caution should be exercised with enteric conversion if recipients have a history of thromboembolectomy, delayed graft function, or renal failure.

Long-term effects of pancreas transplant alone on nephropathy in type 1 diabetic patients with optimal renal function.

BACKGROUND: Limited data are available regarding optimal selection criteria for pancreas transplant alone (PTA) to minimize aggravation of diabetic nephropathy. METHODS: A total of 87 type 1 diabetic patients were evaluated before and after PTA at a single center from January, 1999 to December, 2015, together with 87 matched non-transplanted type 1 diabetic subjects who were candidates for PTA to compare deterioration of native kidney function. A total of 163 patients (79 in the transplanted group and 84 in the nontransplanted group) were finally enrolled after excluding nine patients with estimated glomerular filtration rate less than 60 mL/min/1.73 m2 and two patients with moderate proteinuria (≥ 1.5 g/day). RESULTS: A total of seven recipients (8.9%) had end-stage renal disease post-transplant whereas only one patient (1.2%) developed end-stage renal disease in the nontransplanted group during their follow-up period (median 12.0, range 6-96 months) (p = 0.03). Furthermore, a composite of severe renal dysfunction and end-stage renal disease (31.6% vs 2.4%) was significantly higher in the transplanted group (p < 0.001). Multivariate Cox regression analysis revealed that a higher level of tacrolimus at six months post-transplant (HR = 1.648, CI = 1.140-2.385, p = 0.008) was the only significant factor associated with end-stage renal disease. CONCLUSIONS: There is a considerable risk for deterioration of renal function in PTA recipients post-transplant compared with non-transplant diabetic patients. With rather strict selection criteria such as preoperative proteinuria and estimated glomerular filtration rate, PTA should be considered in diabetic patients to minimize post-transplant aggravation of diabetic nephropathy.

Long-term Metabolic Outcomes of Functioning Pancreas Transplants in Type 2 Diabetic Recipients.

BACKGROUND: Limited data are available regarding the long-term metabolic outcomes of functioning pancreas transplants in patients with type 2 diabetes mellitus (T2DM). METHODS: To compare the long-term effects of pancreas transplantation in terms of insulin resistance and ß cell function, comparison of metabolic variables was performed between type 1 diabetes mellitus (T1DM) and T2DM patients from 1-month posttransplant to 5 years using generalized, linear-mixed models for repeated measures. RESULTS: Among 217 consecutive patients who underwent pancreas transplantation at our center between August 2004 and January 2015, 193 patients (151 T1DM and 42 T2DM) were included in this study. Throughout the follow-up period, postoperative hemoglobin A1c did not differ significantly between T1DM and T2DM patients, and the levels were constantly below 6% (42 mmol/mol) until 5 years posttransplant, whereas C-peptide was significantly higher in T2DM (P = 0.014). There was no difference in fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, HOMA ß cell, or the insulinogenic index between the groups. Furthermore, fasting insulin and HOMA-insulin resistance steadily decreased in both groups during the follow-up period. CONCLUSIONS: There was no significant difference in the insulin resistance or ß-cell function after pancreas transplantation between T1DM and T2DM patients. We demonstrated that pancreas transplantation is capable of sustaining favorable endocrine functions for more than 5 years in T2DM recipients.