A prospective, randomized, non-blinded, non-inferiority pilot study to assess the effect of low-dose anti-thymocyte globulin with low-dose tacrolimus and early steroid withdrawal on clinical outcomes in non-sensitized living-donor kidney recipients.

BACKGROUND: The optimal dose of anti-thymocyte globulin (ATG) as an induction regimen in Asian living-donor kidney recipients is unclear. METHODS: This is a pilot study in which 36 consecutive patients undergoing living-donor kidney transplantation were randomly assigned to receive either 4.5 mg/kg (n = 19) or 6.0 mg/kg (n = 17) of ATG; all patients had corticosteroid withdrawal within 7 days. The primary end point was a composite of biopsy-proven acute rejection, de novo donor-specific antibody formation, and graft failure. RESULTS: At 12 months post-transplant, biopsy-proven acute rejection was more common in the ATG4.5 group (21.1%) than in the ATG6.0 group (0%)(P = .048). Importantly, the rate of the composite end point was significantly higher in the ATG4.5 group (36.8% vs 0%)(P = .006). There were significant differences in neither the renal function nor adverse events between the two groups. One case of death-censored graft failure occurred in the ATG4.5 group and no mortality was observed overall. Compared with pre-transplantation, T cells, natural killer (NK) cells, and natural killer T (NKT) cells were significantly decreased in the first week post-transplantation except for B cells. Although T and NKT cells in both groups and NK cells in the ATG4.5 group had recovered to the pre-transplant levels, NK cells in the ATG6.0 group remained suppressed until six months post-transplant. CONCLUSIONS: Compared with ATG 6.0 mg/kg, ATG 4.5 mg/kg with early corticosteroid withdrawal and low dose maintenance regimen was associated with higher rates of acute rejection in non-sensitized Asian living-donor kidney recipients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02447822.

Outcome of ABO-Incompatible Kidney Transplantation According to ABO Type of Transfused Plasma: Comparative Analysis Between "Universal" AB and Donor-Type Plasma.

OBJECTIVE: We compared the clinical outcomes of recipients of ABO-incompatible (ABOi) kidney transplantation (KT) according to the blood group of the plasma transfused. MATERIALS AND METHODS: We retrospectively analyzed the data of 60 recipients of ABOi-KT with blood type O and A or B donors. Demographic and clinical characteristics were compared between 2 groups of recipients: 1 group received AB plasma regardless of the donor's blood type (n = 30), and the other group received donor-type plasma (n = 30). RESULTS: There were no significant differences between the groups in terms of demographic characteristics. Transfusion of donor-type plasma was noninferior to transfusion of type AB plasma in terms of both rejection-free survival and rejection rate (P = .455, P = .335). CONCLUSION: There was no significant prognostic difference between the 2 groups. In terms of blood supply and inventory management, we suggest that the blood group of the plasma should match the donor's type.

Characteristics and Prognosis of Colorectal Cancer after Liver or Kidney Transplantation.

BACKGROUND: The purpose of this study was to evaluate the characteristics and prognosis of de novo CRC patients who underwent liver or kidney transplantation. METHODS: We retrospectively reviewed the medical records of 66 de novo CRC patients selected from 8,734 liver transplant (LT) or kidney transplant (KT) recipients. We analyzed characteristics and survival outcomes of de novo CRC patients and sporadic CRC patients who underwent radical surgery with stage I-III in Asan Medical Center between 2005 and 2016. Survival outcomes were analyzed via the 1:4 matching method. RESULTS: The standard incidence ratio (SIR) of de novo CRC in KT recipients is 1.67 in men and 2.54 in women. That in LT recipients is 3.10 in men and 2.25 in women. Compared with sporadic CRC patients, de novo CRC patients had more colon cancer than rectal cancer (p=0.041). In 9 patients (13.6%), CRC was diagnosed within one year after transplantation, 21 patients (31.8%) were diagnosed between 1-5 years, and the remaining 36 patients (54.6%) were diagnosed thereafter. There were no significant differences in recurrence-free survival and overall survival between the two groups (p=0.211 and p=0.324, respectively). CONCLUSIONS: The risk of developing de novo CRC in transplant recipients was higher than in the general population. The survival outcome of de novo CRC was no different compared with the sporadic CRC. Therefore, regular surveillance is essential for timely diagnosis and treatment for transplantation patients. A large prospective study for an intense CRC surveillance program in transplantation patients is needed.

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study.

OBJECTIVE: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study. METHODS: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids. RESULTS: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm. CONCLUSION: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).

Lack of Improvement in Insulin Sensitivity After Pancreas Transplantation in Recipients With a High Level of Calcineurin Inhibitors.

OBJECTIVES: This study aimed to assess posttransplant changes in insulin sensitivity and ß-cell function of pancreas transplant recipients according to the type of diabetes mellitus (DM) and the pretransplant insulin sensitivity measured by the Matsuda Index (MI). METHODS: We analyzed 60 patients who underwent pancreas transplantation and oral glucose tolerance test pretransplant and at 1 month posttransplant. RESULTS: At 1 month posttransplant, insulin sensitivity did not show significant improvement; particularly, the MI was significantly lower after transplant in recipients with type 1 DM (T1DM) and those with pretransplant MI of 5 or greater. ß-cell function was significantly improved after transplant in all recipients regardless of the type of DM and pretransplant MI values. Glucose control was significantly improved in recipients with T1DM and in all recipients regardless of the pretransplant MI values. Additional oral glucose tolerance test at 1 year posttransplant revealed that insulin sensitivity remained unimproved and ß-cell function was higher compared with pretransplant. Glucose control had partially reverted to pretransplant levels in recipients with T1DM and those with pretransplant MI of 5 or greater. CONCLUSIONS: Unlike ß-cell function and glucose control, insulin sensitivity did not significantly improve until posttransplant 1 year after pancreas transplantation regardless of the type of DM or the degree of pretransplant insulin sensitivity.

Islet isograft transplantation improves insulin sensitivity in a murine model of type 2 diabetes.

PURPOSE: Type 2 diabetes develops in the presence of chronic overnutrition and genetic susceptibility, and causes insulin resistance and relative insulin deficiency. We hypothesized that islet transplantation can improve insulin sensitivity by modifying the mediators of insulin sensitivity in the pancreas, liver, muscle, and adipose tissues. METHODS: Eight-week-old male mice were used as both recipients and donors in this study. To induce type 2 diabetes with partial ß-cell failure, the mice were fed a high-fat diet for 4 weeks and then injected with low-dose streptozotocin. Approximately 400 islet cells from a donor mouse were injected into the renal capsule of a recipient mouse for islet transplantation. After 6 weeks following transplantation, the mediators of insulin sensitivity in the pancreas, liver, muscle, and adipose tissues were quantitatively compared between islet-transplanted and non-transplanted groups. RESULTS: Intravenous glucose tolerance test showed that whereas the non-transplanted mice failed to show notable reductions in the glucose level, the islet-transplanted mice showed significant reductions in the serum glucose level to ~200 mg/dL at 6 weeks after islet transplantation. The islet-transplanted mice showed significantly higher Matsuda index and significantly lower HOMA-IR than did the non-transplanted mice, thus signifying improved insulin sensitivity. CONCLUSIONS: Islet transplantation resulted in improvements in multiple indices of insulin sensitivity in a murine model of type 2 diabetes. Islet transplantation may be utilized to improve insulin sensitivity in patients with type 2 diabetes.

Serum procalcitonin as a biomarker for differentiating between infectious and non-infectious fever after pancreas transplantation.

Laboratory biomarkers that can differentiate non-infectious fever from infectious fever after pancreas transplantation have yet to be discovered. Non-infectious fever was defined as the presence of fever (>38.3°C) in the absence of a documented clinical diagnosis of infection or a positive culture. Among 184 consecutive recipients, a total of 91 recipients developed fever within 1-month post-transplant, of whom 46 had infectious fever and 45 had non-infectious fever at our center between August 2014 and July 2019. The onset of fever was earlier in the non-infectious fever group (14.4 ± 3.7 post-transplant days) compared with the infectious fever group (16.5 ± 5.8 post-transplant days; p = .033). Multivariate analysis showed that serum procalcitonin at the peak of fever could significantly differentiate infectious fever from non-infectious fever (OR 53.378, 95% CI: 6.819-417.802, p < .001). The area under the curve for differentiating between the two groups was 0.853 (95% CI, 0.780-0.926) for procalcitonin and 0.667 (95% CI, 0.549-0.785) for CRP. The best cutoff values of serum procalcitonin and CRP were 0.405 ng/ml (sensitivity, 77.1%; specificity, 80.8%) and 7.355 mg/dl (sensitivity, 66.7%; specificity, 67.3%), respectively. Serum procalcitonin may be useful for differentiating non-infectious fever from infectious fever after pancreas transplantation.

Simultaneous liver-kidney transplantation: A single-center experience in Korea.

BACKGROUNDS/AIMS: Simultaneous liver and kidney transplantation (SLKT) has been established as the treatment of choice for patients with concurrent end-stage liver and end-stage kidney diseases. The objective of this study was to analyze the nationwide incidence of SLKT in Korea and the outcomes of SLKT in a high-volume transplant center. METHODS: Databases of the Korean Network for Organ Sharing (KONOS) and Asan Medical Center from 2000 to 2019 were retrospectively reviewed to determine the incidence of SLKT. RESULTS: During 20 years from 2000 to 2019, deceased donor SLKT was performed for 38 cases in the KONOS database. The proportion of deceased donor SLKT was 0.6% (20 of 3333) before adoption of MELD score, which was significantly increased to 1.2% (18 of 1524) after the adoption of MELD score (p=0.034). In our institution, there were 11 cases of SLKT (2 cases with deceased donors and 9 cases with living donors). SLKT accounted for 0.2% (11 of 6468) of total liver transplantation volume. During follow-up, five patients died due to hepatocellular carcinoma recurrence (n=2), infection (n=2), or unknown cause (n=1). The 1-year and 10-year overall patient survival rates were 90.9% and 81.8%, respectively. CONCLUSIONS: Results of this study revealed that the incidence of deceased donor SLKT was very low. An increase of such incidence is not anticipated unless the number of deceased donors is markedly increased. Currently, sequential living donor liver transplantation and kidney transplantation with deceased or living donors are mainstays of transplantation rather than SLKT in our institution.

Outcomes of Living-Donor Kidney Transplantation in Female Recipients with Possible Pregnancy-Related Pre-Sensitization According to Donor Relationship.

BACKGROUND Given that pregnancy is an immune-sensitizing event, female kidney transplant recipients who receive allografts from their offspring or husbands may have a higher risk of rejection and graft failure due to pre-sensitization acquired during pregnancy or childbirth. We investigated the association between donor relatedness (i.e., offspring, husband, unrelated) and graft survival among female living-donor kidney transplant (LDKT) recipients with pregnancy histories. MATERIAL AND METHODS From January 2009 to January 2018, a total of 2060 LDKTs were performed at Asan Medical Center, Seoul, Korea. After excluding HLA-incompatible transplantation, re-transplantation, and those without a clear history of childbirth, 390 female recipients were included and categorized into group I (offspring-to-mother, n=175), group II (husband-to-wife, n=159), and group III (unrelated, n=56). The primary endpoint was biopsy-proven acute rejection (BPAR) and graft survival. We also evaluated delayed graft function (DGF), death-censored graft failure, and mortality. RESULTS Group I had the lowest number of HLA mismatches (p<0.001), and group II had the highest number of ABO-incompatible transplantations (p=0.005). At 5 years after transplant, graft survival and death-censored graft survival did not significantly differ among the 3 groups (graft survival: 96.0% vs. 95.5% vs. 93.3%, p=0.685; death-censored graft survival: 98.3% vs. 97.5% vs. 100%, p=0.732). Five-year BPAR-free survival showed no significant differences among the 3 groups (88.6 vs. 88.7 vs. 88.6%, p=0.842). Group II had the highest rate of clinical rejection (p=0.103) and DGF (p=0.174), but the difference was not statistically significant. CONCLUSIONS Female LDKT recipients with possible pregnancy-related pre-sensitization who received grafts from offspring or husbands did not show significantly worse clinical outcomes than those who received grafts from unrelated donors.

Acute Rejection and Infectious Complications in ABO- and HLA-Incompatible Kidney Transplantations.

BACKGROUND Patients receiving ABO-incompatible (ABOi) or human leukocyte antigen (HLA)-incompatible (HLAi) kidney transplantation (KT) require potent immunosuppression and are thus at a higher risk of infectious complications. We evaluated the clinical outcomes of KT stratified by ABO and HLA incompatibilities and identified the factors associated with the clinical outcomes. MATERIAL AND METHODS Recipients who underwent living-related KT between 2012 and 2017 were included and classified into 4 groups: ABO-compatible and HLA-compatible (ABOc/HLAc), HLA-incompatible (ABOc/HLAi), ABO-incompatible (ABOi/HLAc), and ABO-incompatible and HLA-incompatible (ABOi/HLAi). Cox proportional hazards regression analyses were carried out to evaluate the risk factors of acute rejection. Out of the 1732 patients who underwent KT, 1190, 131, 358, and 53 were in the ABOc/HLAc, ABOi/HLAc, ABOc/HLAi, and ABOi/HLAi groups, respectively. RESULTS The ABO/HLAi group showed the lowest 5-year graft survival rate (91.7%). Death-censored graft survival was not significantly different among the groups. The mortality rate from infections was significantly higher in the ABOi/HLAi group (7.5%) than the other groups. Antibody-mediated rejection-free graft survival was the lowest in the ABOi/HLAi group, with significant differences compared with the ABOi/HLAc group (P=0.02) and the ABOc/HLAi group (P=0.03). ABOi/HLAi (hazard ratio [HR], 2.63; 95% confidence interval [CI], 1.04-6.65; P<0.01) and combined infection (HR, 1.91; 95% CI, 1.45-2.51; P<0.01) were significant risk factors for acute rejection. CONCLUSIONS Patients with both ABO and HLA incompatibilities showed inferior rates of overall patient and graft survival due to infectious complications. Infection was a prominent risk factor of acute rejection following KT after adjusting for possible confounders including ABO and HLA incompatibility.

Long-Term Outcome of Live Kidney Donation in South Korea.

BACKGROUND Kidney donors may be at increased risk for end-stage renal disease (ESRD) as well as cardiovascular and all-cause mortality. In particular, data on long-term safety after kidney donation in Asian populations are lacking. We aimed to assess the safety of live kidney donation in Korean donors by using a matched control group. MATERIAL AND METHODS We conducted a retrospective cohort study using a hospital-based database (Asan Medical Center, Seoul, Korea) and a control group from the national health insurance claims database in South Korea. We analyzed the health status of 1608 kidney donors who underwent donation between September 1990 and December 2015, and we compared their characteristics with those of matched 6426 non-donors (1: 4 ratio). We also measured the glomerular filtration rate (GFR) with 5¹Cr EDTA and urinary albumin excretion and assessed the prevalence of hypertension, diabetes, and general health status in 200 volunteer donors. RESULTS Mortality was significantly lower in kidney donors compared with the matched controls (130.2 vs. 185.4 per 100,000 person-years, P=0.02). There was no significant difference in mortality if a donor had hypertension or was a current smoker at the time of donation. There was also no significant difference in ESRD (43.1 vs. 35.2 per 100,000 person-years, P=0.07) between the 2 groups regardless of hypertension and smoking status. Among the 200 donors with measured GFR, 11.5% had GFR values <60 ml/min/1.73 m² at 9.4±5.3 years after donation. Older age (P=0.001) and female sex (P=0.021) were significantly associated with GFR values <60 mL/min/1.73 m². CONCLUSIONS Mortality and ESRD were uncommon in carefully selected kidney donors. However, donors with pre-existing risk factors should be followed up more closely to ensure long-term safety.

The usefulness of quantitative interferon-gamma releasing assay response for predicting active tuberculosis in kidney transplant recipients: A quasi-experimental study.

OBJECTIVES: We evaluated the effectiveness of IGRA-based isoniazid (INH) treatment with the diagnostic value of quantitative IGRA titer for post-transplant tuberculosis (TB) in kidney transplant (KT) recipients. METHODS: All adult KT recipients were enrolled from January 2014 to December 2017. The development of TB after KT was observed, stratified by quantitative IGRA results as well as by IGRA results with/without INH treatment. RESULTS: Of 1150 KT recipients, 322 (28%) revealed positive IGRA results (≥0.35 IU/mL) and 12 (1.0%) developed TB. Seven (3.2%) of 217 patients with positive IGRA without INH developed TB, whereas none of 105 patients with positive IGRA with INH developed TB (rate difference -1616 per 100,000 person-years, P = 0.016) and 5 (0.6%) of 828 patients with negative or indeterminate IGRA developed TB (rate difference -1388 per 100,000 person-years, P<0.001). Among the 217 positive IGRA patients without INH, 6 (6.4%) of 94 patients who had positive IGRA titer>2.96 IU/mL developed TB, whereas one (0.8%) of 123 patients who had positive IGRA titer≤2.96 IU/mL developed TB (rate difference 2964 per 100,000 person-years, P = 0.017). CONCLUSIONS: IGRA-based INH treatment with risk stratification by quantitative IGRA results appears to be effective to prevent the development of TB in KT recipients.

Wound healing adverse events in kidney transplant recipients receiving everolimus with reduced calcineurin inhibitor exposure or current standard-of-care: insights from the 24-month TRANSFORM study.

OBJECTIVES: In TRANSFORM, de novo kidney transplant recipients received either everolimus in combination with reduced-exposure calcineurin inhibitor (EVR+rCNI) at standard EVR pre-dose concentrations of 3-8 ng/mL or mycophenolic acid plus standard-exposure CNI (MPA+sCNI). The authors analyzed the incidence of wound healing adverse events (WHAEs) over the 2-year study period 15. METHODS: Patients were randomized to either EVR+rCNI or MPA+sCNI, both combined with induction therapy and steroids 19. RESULTS: The safety population consisted of 2,026 patients (EVR+rCNI: 1,014, MPA+sCNI: 1,012). The proportion of patients with at least 1 WHAE was comparable between EVR+rCNI and MPA+sCNI treatment groups [20.6% vs. 17.3%; risk ratio (RR): 1.19; 95% confidence interval (CI): 0.99, 1.43] at month 24. The numerical difference between EVR+rCNI and MPA+sCNI was mainly caused by an increased proportion of EVR patients with lymphocele and wound dehiscence [7.5% vs. 5.1% (RR: 1.46; 95% CI: 1.04, 2.05) and 3.9% vs. 1.8% (RR: 2.22; 95%CI: 1.28, 3.84), respectively] 20. CONCLUSION: The immediate introduction of EVR+rCNI after kidney transplantation was associated with an overall comparable incidence of WHAEs versus current standard-of-care over the 24-month study period. There was an increased relative risk of experiencing lymphocele and wound dehiscence but the absolute risks were rather low in both groups 21. CT.GOV IDENTIFIER: NCT01950819.

Pneumocystis pneumonia occurrence and prophylaxis duration in kidney transplant recipients according to perioperative treatment with rituximab.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening fungal infection that can occur in kidney transplantation (KT) recipients. A growing number of KT recipients are receiving perioperative treatment with rituximab, which is associated with prolonged B-cell depletion and possible risk of PCP occurrence; however, the optimal prophylaxis duration according to rituximab treatment is yet unknown. We compared the occurrence of PCP and the duration of prophylaxis in KT recipients according to rituximab treatment. METHODS: We retrospectively analyzed 2110 patients who underwent KT between January 2009 and December 2016, who were divided into non-Rituximab group (n = 1588, 75.3%) and rituximab group (n = 522, 24.7%). RESULTS: In the rituximab group, the estimated number needed to treat (NNT) for prophylaxis prolongation from 6 to 12 months was 29.0 with a relative risk reduction of 90.0%. In the non-rituximab group, the estimated NNT value was 133.3 and the relative risk reduction was 66.4%. Rituximab treatment (hazard ratio (HR) = 3.09; P <  0.01) and acute rejection (HR = 2.19; P = 0.03) were significant risk factors for PCP in multivariate analysis. CONCLUSIONS: Our results suggest that maintaining PCP prophylaxis for 12 months may be beneficial in KT recipients treated with rituximab for desensitization or acute rejection treatment.

ABO-incompatible kidney transplantation can be successfully conducted by monitoring IgM isoagglutinin titers during desensitization.

BACKGROUND: Recent advances in desensitization techniques and immunosuppressive therapy have led to improved outcomes after ABO-incompatible (ABO-i) kidney transplantation (KT). However, questions remain unanswered, particularly regarding which type of ABO isoagglutinin-immunoglobulin M (IgM) or immunoglobulin M (IgG)-is significantly involved in antibody-mediated rejection (AMR). STUDY DESIGN AND METHODS: We retrospectively analyzed data from 120 patients who underwent ABO-i KT between 2012 and 2014. Preoperative plasma exchange was performed until the IgM isoagglutinin titer was 4 or less, regardless of the IgG titer. Clinical data were compared between patient groups with pre-KT IgG isoagglutinin titer 16 or greater (high IgG; titer range, 16-256; n = 39) and 8 or less (low IgG; titer range, -8; n = 81). RESULTS: The median follow-up periods were 59 (high IgG) and 55 (low IgG) months. Patient survival at 5 years (p = 0.314) was 100% (high IgG) and 97.4% (low IgG). Graft survival at 5 years (p = 0.480) was 100% (high IgG) and 98.7% (low IgG). AMR by anti-ABO antibody occurred in only one patient in the low-IgG group. CONCLUSION: Patients with high pre-KT IgG isoagglutinin titers had equally successful outcomes as those with low IgG titers. ABO-i KT can be successfully performed by reducing the pre-KT IgM isoagglutinin titer to 4 or less, as determined by the immediate spin tube method.

Epidemiology and risk factors associated with Pneumocystis jirovecii pneumonia in kidney transplant recipients after 6-month trimethoprim-sulfamethoxazole prophylaxis: A case-control study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in kidney transplant recipients (KTRs), and prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is recommended. The aim of this study was to investigate incidence and risk factors for PCP in KTRs after 6-month TMP-SMX prophylaxis. METHODS: We conducted a case-control study of patients with PCP who received 6-month PCP prophylaxis with TMP-SMX after kidney transplantation (KT). In cases of rejection, PCP prophylaxis was provided for six additional months after anti-rejection therapy. Cytomegalovirus (CMV) infection was not considered an indication for PCP prophylaxis due to concerns of nephrotoxicity associated with TMP-SMX. RESULTS: Among 3941 kidney or pancreas-kidney transplant recipients, 67 (1.7%) developed PCP after discontinuing TMP-SMX. A total of 47 patients with KT PCP and 94 controls were included. Duration of PCP prophylaxis was similar between cases and controls (median 6 months, P = .53). In multivariate analysis, rejection (OR 3.9; 95% CI 1.4-11.1) and CMV infection (OR 2.4; 95% CI 1.0-5.8) were independently associated with PCP development after TMP-SMX. Rejection or CMV infection was observed in 70% of patients with PCP. Time to PCP development after rejection (median [IQR] 6 [5-19] months) was slightly shorter than after CMV infection (median [IQR] 9 [5-12] months; P = .18). CONCLUSION: Post-prophylaxis PCP occurred in <2% of KTRs, and about two-thirds of these experienced rejection or CMV infection. These data suggest that at least 6 to 9-month additional chemoprophylaxis may be needed to prevent PCP in KTRs with transplant rejection or CMV infection.

Diagnostic usefulness of the cytomegalovirus (CMV)-specific T cell-based assay for predicting CMV infection after kidney transplant.

BACKGROUND/AIMS: We evaluated the usefulness in kidney transplant (KT) candidates of cytomegalovirus (CMV)-specific enzyme-linked immunospot (ELISPOT) assays for predicting the development of post-transplant CMV infections. METHODS: All adult recipients admitted for living-donor KT between March 2014 and March 2015 were prospectively enrolled except donor CMV-seropositive and recipient seronegative (D+/R-) recipients. All the enrolled patients underwent CMV-specific ELISPOT assays before transplant, and a researcher blinded to the results of these assays examined the patients for CMV infection at least 6 months post-transplant. RESULTS: Of 133 KT recipients, 44 (33%) developed CMV infections. When we used the cut-off determined by receiver operator characteristic curve, 16 of the 34 patients (47%) with negative pp65-specific ELISPOT results (< 11 spots/200,000 cells) developed CMV infections, whereas 28 of the 99 patients (39%) with positive pp65-specific ELISPOT results at baseline (≥ 11 spots/200,000 cells) developed CMV infections after KT (p = 0.02). Based on the multivariable Cox regression model, negative pp65-specific ELISPOT assay results was an independent risk factor for CMV infection (adjusted hazard ratio [AHR], 1.87; 95% confidence interval [CI], 1.01 to 3.46; p = 0.047) as well as age (AHR, 1.05; 95% CI, 1.01 to 1.08; p = 0.007). CONCLUSION: Pre-transplant CMV-specific ELISPOT assay appears to predict the development of CMV infections after KT in recipients at moderate risk such as CMV-seropositive recipients (Clinical Trial Registration Number NCT02025335).

Effect of arteriovenous access closure and timing on kidney function in kidney transplant recipients.

This study aimed to determine whether the closure of a functioning arteriovenous (AV) access affects the estimated glomerular filtration rate (eGFR) and to compare outcomes according to the timing of AV access closure after kidney transplantation (KT). From 2009 to 2015, medical records were retrospectively reviewed for 142 kidney transplant recipients (KTRs) who underwent AV access closure. The 142 KTRs were categorized into three groups: AV access closure was performed within 6 months after KT in Group 1 (n = 45), at 6-12 months after KT in Group 2 (n = 49), and at 12-24 months after KT in Group 3 (n = 48). The baseline (at the time of AV access closure) and follow-up eGFR values during the 3-year follow-up period were compared. Linear mixed model analysis revealed no significant association between longitudinally observed eGFR values and the amount of time elapsed after AV access closure in the study population (P = 0.36). There was no significant association between 3-year eGFR values and the timing of AV access closure (P = 0.58). In conclusion, after successful KT, AV access closure did not affect the eGFR significantly, and the timing of AV access closure was not significantly associated with outcomes.

Effect of simultaneous presence of anti-blood group A/B and -HLA antibodies on clinical outcomes in kidney transplantation across positive crossmatch: a nationwide cohort study.

ABO-incompatible (ABOi) and positive crossmatch (XM) kidney transplantation (KT) have been considered immunologically challenging. The present study analyzed the clinical outcomes in XM positive KT based on ABO incompatibility. We used data from the Korea Organ Transplantation Registry, a nationwide database, and a single-center registry. A total of 263 patients with positive XM were divided into an ABO compatible (ABOc) & XM positive (ABOc/XM+, n = 176) group and an ABOi & XM positive (ABOi/XM+, n = 87) group. The overall rejection rate one year after KT was significantly higher in the ABOi/XM+ group than in the ABOc/XM+ group (P < 0.01). A total of four mortalities occurred, all in the ABOi/XM+ patients (P < 0.01). There were no differences in surgical complications or the occurrence of infection-related complications, including BK virus nephropathy. Multivariate analysis indicated that female vs. male (odds ratio (OR), 2.27; P = 0.03), DSA class I (MFI/1000) (OR, 1.10; P = 0.03), DSA class II (MFI/1000) (OR, 1.10; P < 0.01), and ABOi & XM+ status (OR, 2.38; P < 0.01) were significant risk factors for acute rejection during the year after transplantation. Overall graft survival was inferior in ABOi/XM+ patients than in ABOc/XM+ patients (P = 0.02). ABO incompatibility in XM-positive KT patients was found to be a significant risk factor for the development of rejection within one year after transplantation as well as for long-term graft survival. The anti-blood group A, B and anti-HLA antibodies may show synergistic activity.