Posttransplant-Alloantibodies Against MICA Antigens Associated With Decreased Long-Term Allograft Survival of Kidney Transplant Recipients

BackgroundPrevious evidence showed that antibodies against major histocompatibility complex class I-related chain A (MICA) could lead to antibody-mediated rejection in kidney transplantation in case where the patients had no alloantibodies against HLA. However, the effects of posttransplant anti-MICA antibodies on long-term renal allograft survival and function remained unsettled. We tested the posttransplant anti-MICA antibodies in 150 kidney transplant patients. The aim of this study was to compare the long-term graft survival and function between patients who were MICA positive and those who were negative.MethodsThe posttransplant serum samples from 150 patients receiving kidney transplantation in our center from 2012 to 2013 were tested for MICA antibodies and HLA antibodies by Luminex single antigen array technology. Graft survival and function were followed up for a mean time of 74.2 months. The research was conducted in accordance with the Helsinki Congress and the Declaration of Istanbul.ResultsOf the 150 patients, 38 (25.3%) were sensitized against MICA after transplantation. The anti-MICA antibodies-positive (anti-MICA+) group had a worse long-term renal allograft survival than that of anti-MICA-negative (anti-MICA–) group (P = .029), even when stratified by posttransplant HLA sensitization status or donor source. Anti-MICA antibodies also had a detrimental impact on renal allograft function, but only at 1 year posttransplantation (estimated glomerular filtration rates at 1 year: anti-MICA+ 66.6 mL/min/1.73 m² vs anti-MICA– 78.7 mL/min/1.73 m²; P = .023).ConclusionPosttransplant anti-MICA antibodies were associated with decreased long-term renal allograft survival and short-term renal allograft function.     

Urinary Type III Procollagen Is Associated With Chronic Allograft Dysfunction and Predicts Graft Survival

Background

Chronic allograft dysfunction (CAD) is the most important clinical problem in solid organ transplantation. Interstitial fibrosis and tubular atrophy contribute to long-term renal allograft failure. Urinary type III procollagen N-terminal propeptide (PIIINP), has been shown to associate fibrotic processes.

Association of Serum Uric Acid With Graft Survival After Kidney Transplantation: A Time‐Varying Analysis

The association of serum uric acid (UA) with kidney transplant outcomes is uncertain. We examined the predictive value of UA during the first year posttransplant as a time‐varying factor for graft survival after adjustment for time‐dependent and independent confounding factors. Four hundred and eighty‐eight renal allograft recipients transplanted from January 2004 to June 2006 and followed for 41.1 ± 17.7 months were included. Data on UA, estimated glomerular filtration rate (eGFR), tacrolimus level, mycophenolate mofetil (MMF) and prednisone doses, use of allopurinol, angiotensin‐converting enzyme‐inhibitor/angiotensin‐receptor‐blocker (ACEi/ARB) and diuretics at 1, 3, 6, 9 and 12 months were collected. Primary endpoint of the study was graft loss, defined as graft failure and death. Cox proportional hazard models and generalized estimating equations were used for analysis. UA level was associated with eGFR, gender, retransplantation, decease‐donor organ, delayed graft function, diuretics, ACEi/ARB and MMF dose. After adjustment for these confounders, UA was independently associated with increased risk of graft loss (HR: 1.15, p = 0.003; 95% CI: 1.05–1.27). Interestingly, UA interacted with eGFR (HR: 0.996, p < 0.05; 95% CI: 0.993–0.999 for interaction term). Here, we report a significant association between serum UA during first year posttransplant and graft loss, after adjustment for corresponding values of time‐varying variables including eGFR, immunosuppressive drug regimen and other confounding factors. Its negative impact seems to be worse with lower eGFR.     

VAV1 Gene Polymorphism is Associated With Kidney Allograft Rejection

BackgroundVAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells. Several studies suggest that VAV1 signaling plays significant roles in allograft rejection. The aim of this study was to examine the association between VAV1 gene polymorphisms and renal allograft function.MethodsThe study included 270 patients after allograft renal transplantation. We examined the associations between VAV1 gene polymorphisms and complications after transplantation, such as delayed graft function, acute rejection, and chronic allograft dysfunction.ResultsThere were no statistically significant associations between VAV1 genotypes and delayed graft function and chronic allograft dysfunction. Among patients with acute allograft rejection, we observed decreased frequencies of VAV1 rs2546133 TT and CT genotypes (P = .03) and T allele (P = .02), as well as VAV1 rs2617822 GG and AG genotypes (P = .05) and G allele (P = 0.04). In the multivariate regression analysis, the higher number of VAV1 rs2546133 T alleles showed a protective effect against the acute rejection in kidney allograft recipients.ConclusionsThe results of our study suggest that polymorphisms in the VAV1 gene are associated with kidney allograft rejection.     

Long-term Allograft Survival After Kidney Transplantation

BackgroundTechnical and medical advances over the past few years have produced an important increase in the functionality of renal allografts. The aim of this study was to identify the factors associated with allograft survival 15 years after transplantation in our series.MethodsA retrospective study of kidney transplantations was carried out at Reina Sofia Hospital in Cordoba from February 1979 to December 1997, with follow-up through June 2012. A subanalysis of the series was undertaken, and Kaplan-Meier analysis and Cox proportional hazards model regression used to achieve the main objective of the study.ResultsA total of 487 renal allografts with a mean follow-up of 114 months were studied, of which 37% (n = 180) survived for >15 years. Of the 180 patients, the main causes of graft failure were chronic allograft nephropathy in 29 (66%) and patient death in 13 (29.5%). Multivariate analysis identified the number of HLA mismatches (hazard ratio [HR] 1.25, 95% CI 1.01–1.56), panel reactive antibodies (HR 2.61, 95% CI 1.28–5.26), and delayed graft function (HR 11.25, 95% CI 1.33–95.28) as being significantly associated with graft loss after 15 years.ConclusionsThe high immunologic risk of the patients was independently associated with graft loss. Delayed graft function was the most important factor in the speed of graft failure beyond 15 years.     

Catecholamine Vasopressor Exposure Is Associated With Early Poor Allograft Function and Adverse Events in Living Donor Kidney Transplant Recipients

BackgroundHypoperfusion leads to allograft injury during kidney transplantation. Catecholamine vasopressors are used to maintain blood pressure in the perioperative period but have demonstrated negative outcomes in the deceased-donor kidney transplant population. Little is known regarding living donor kidney transplants (LDKTs) and vasopressor use. The aim of this study is to describe the incidence of vasopressor use in LDKT and characterize its effects on allograft function and patient outcomes.MethodsThis retrospective, observational cohort study included adult patients who underwent an isolated LDKT between August 1, 2017, and September 1, 2018. Patients were divided into those who received perioperative vasopressors and those who did not. The primary objective was to compare allograft function between LDKT recipients that received vasopressors and those who did not. Secondary outcomes included safety endpoints and the identification of clinical variables associated with vasopressor use.ResultsA total of 67 patients received an LDKT during the study period. Of those, 25 (37%) received perioperative vasopressors, and 42 (62%) did not. Poor graft function, as defined by the development of slow or delayed graft function, occurred more frequently in patients receiving perioperative vasopressors compared with those who did not (6 [24%] vs 1 [2.4%], P = .016). In multivariable regression modeling, only perioperative vasopressors were statistically significantly associated with poor graft function. In addition, patients exposed to vasopressors experienced more postoperative arrhythmias (8 [32%] vs 1 [4.8%], P = .0025).ConclusionUsing perioperative vasopressors was independently associated with worsened early renal allograft function, including delayed graft function and adverse events in the LDKT population.     

Cytomegalovirus Replication Within the Lung Allograft Is Associated With Bronchiolitis Obliterans Syndrome

Early studies reported cytomegalovirus (CMV) pneumonitis as a risk factor for development of bronchiolitis obliterans syndrome (BOS) following lung transplantation. While improvements in antiviral prophylaxis have resulted in a decreased incidence of CMV pneumonitis, molecular diagnostic techniques allow diagnosis of subclinical CMV replication in the allograft. We hypothesized that this subclinical CMV replication was associated with development of BOS. We retrospectively evaluated 192 lung transplant recipients (LTR) from a single center between 2001 and 2009. Quantitative (PCR) analysis of CMV viral load and histological evidence of CMV pneumonitis and acute cellular rejection was determined on 1749 bronchoalveolar lavage (BAL) specimens and 1536 transbronchial biopsies. CMV was detected in the BAL of 41% of LTR and was significantly associated with the development of BOS (HR 1.8 [1.1–2.8], p = 0.02). This association persisted when CMV was considered more accurately as a time‐dependent variable (HR 2.1 [1.3–3.3], p = 0.003) and after adjustment for significant covariates in a multivariate model. CMV replication in the lung allograft is common following lung transplantation and is associated with increased risk of BOS. As antiviral prophylaxis adequately suppresses CMV longer prophylactic strategies may improve long‐term outcome in lung transplantation.     

Donor Characteristics Associated With Reduced Survival of Transplanted Kidney Grafts in Korea

Background

Certain donor characteristics are known to be associated with increased graft failure in kidney transplantation.

Methods

We analyzed donor and recipient characteristics among deceased donor kidney transplantations performed from 1995 to 2008, excluding multiorgan, pediatric, and retransplantation cases.

Results

The 299 cases underwent analysis of donor characteristics including age, sex, cause of brain death, history of hypertension, cardiac arrest, length of intensive care unit (ICU) stay, last serum creatinine before organ donation, and change in creatinine during ICU stay. Cox regression analysis identified two factors that independently predicted a greater risk of graft failure. The factors were cerebrovascular accident (CVA) as the cause of brain death and a history of hypertension. Compared with donors with causes of brain death other than CVA, the adjusted hazard ratios for graft failure (GF) of kidneys from donors with CVA were 2.37 (1.34-4.19, P = .003). The hazard ratio for GF was 2.42 (1.34-4.37, P = .003) for kidneys from those with a history of hypertension. Donors meeting the criteria of CVA as the cause of brain death or history of hypertension comprised 43% of transplantation cases (128/299). Donor age and last serum creatinine level, which were identified in previous studies to show higher risks of graft failure, did not apply in our patients.

Conclusion

Donor history of hypertension and CVA as the cause of brain death were significant determinants of reduced graft survival after DDKT in Korea.     

Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival

Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival.     

Characteristics of Recipients With 10 or More Years of Allograft Survival in Deceased Donor Kidney Transplantation

Background

The development of immunosuppressants improved the short-term outcomes of deceased donor kidney transplantation (DDKT), but the long-term survival rate was not improved.

Symptomatic BK Virus Infection Is Associated With Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause‐specific hazard of kidney function decline, and the Fine–Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft‐versus‐host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.     

Risk Factors Associated With Graft Loss and Patient Survival After Kidney Transplantation

Objective

To evaluate the influence of traditional risk factors on major kidney transplantation outcome.

Patients and Methods

Data from kidney transplantation procedures performed between 2003 and 2006 were retrospectively analyzed for the influence of traditional risk factors on transplantation outcome. Of 2364 transplants, 67% were from living donors, 27% were from donors who met standard criteria, and 6% were from donor who met expanded criteria. Two hundred thirty-nine procedures (10%) were performed in pediatric patients. Immunosuppression was selected on the basis of subgroup population.

Results

At 1 year posttransplantation, cumulative freedom from a treated acute rejection episode (ARE) was 76.7%, with no difference between black vs nonblack recipients (75.0% vs 73.4%; P = .79). At 2 years, survival for patients (95.3% vs 88.3% vs 82.1%; P < .001) and grafts 92.3% vs 80.3% vs 70.9%; P < .001) was better in recipients of living donor grafts compared with donors who met standard or expanded criteria, respectively. Moreover, graft survival was poorer in black vs nonblack patients (83.6% vs 88.7%; P < .05) because of high mortality (13% vs 7%; P<.001). Risk factors associated with death included cadaveric donor organ (odds ratio [OR], 2.4) and black race (OR, 1.8), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.1), extended-criteria criteria donor organ (OR, 2.0), delayed graft function (OR, 1.8), and any ARE (OR, 3.5). At 6 months posttransplantation, risk factors associated with death included cadaveric donor organ (OR, 2.5) or ARE (OR, 2.4), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.0), extended-criteria donor organ (OR, 2.6), ARE (OR, 9.5), and impaired graft function (creatinine concentration >1.5 mg/dL; OR, 2.1).

Conclusion

Traditional risk factors are still associated with transplantation outcome. Poorer graft survival in black vs nonblack recipients was due to higher mortality rather than graft loss.