Sandesh Parajuli

Renal Function and Transplantation in Liver Disease.

Abstract Kidney injury is associated with increased morbidity and mortality in liver transplant recipients. Since the introduction of the model for end-stage liver disease for the allocation of organs for liver transplantation in 2002, the heavy weighting of serum creatinine in the model for end-stage liver disease score has significantly increased the incidence of renal dysfunction seen among patients undergoing liver transplantation. As a result, the frequency of simultaneous liver-kidney (SLK) transplantation compared to liver transplantation alone (LTA) has also increased. The decision to perform SLK rather than LTA is an important one because the benefits to the liver transplant recipient receiving a kidney transplant must be balanced with the benefits of using that organ for a patient with end-stage renal disease. However, predicting whether or not a patient with liver failure has reversible kidney disease, and therefore does not also need a kidney transplant, is difficult. The severity and duration of pretransplant renal dysfunction, hepatitis c, diabetes, and other risk factors for kidney disease are associated with an increased risk of posttransplant end-stage renal disease. However, there are currently no clinical findings that accurately predict renal recovery post liver transplant. As a result, the rate of SLK versus LTA differs significantly between transplant centers. To increase consistency across centers, multiple guidelines have been proposed to guide the decision between SLK and LTA, but their poor predictive value has limited their uniform adoption. Nevertheless, adoption of uniform rules for the allocation of kidneys would reduce the variability between centers in rates of SLK transplant.

In kidney transplant recipients with BK polyomavirus infection, early BK nephropathy, microvascular inflammation, and serum creatinine are risk factors for graft loss.

Little information is available on the risk factors for graft loss in kidney transplant recipients with BK polyomavirus (BKPyV) nephropathy (BKVN) in the presence or absence of antibody‐mediated rejection (AMR).

Concurrent biopsies of both grafts in recipients of simultaneous pancreas and kidney demonstrate high rates of discordance for rejection as well as discordance in type of rejection – a retrospective study

It is commonly assumed that in simultaneous pancreas and kidney (SPK) recipients, rejection of the two organs is concordant. As a result, concurrent biopsies of both organs are rarely performed and there are limited histological data on how often rejection is in fact discordant. We reviewed all SPK recipients transplanted at the University of Wisconsin between January 01, 2001, and December 31, 2016, that underwent biopsy of both organs. We included all patients whose biopsies were within 30 days. If patients were treated for rejection between biopsies, they were excluded if the biopsies were more than 4 days apart. Ninety‐one simultaneous biopsies were performed within 30 days of each other, and 40 met our inclusion criteria. A total of 25 (62.5%) patients had concordance of biopsy findings: 11 had rejection of both organs, and 14 had no rejection of either organ. The other 15 (37.5%) were discordant for rejection, with 10 having pancreas‐only rejection and five kidney‐only rejection. It was striking to find that four of the 11 patients with concordance for rejection (36%) had different types (AMR, ACR, or mixed) of rejection in the two organs. This large series of simultaneous pancreas and kidney biopsies demonstrates the continued utility of performing biopsies of both organs.

Is Kidney Transplantation a Better State of CKD? Impact on Diagnosis and Management

Patients with CKD are at increased risk for cardiovascular events, hospitalizations, and mortality. Kidney transplantation (KTx) is the preferred treatment for end-stage kidney disease. Although comorbidities including anemia and bone and mineral disease improve or are even halted after KTx, kidney transplant recipients carry higher cardiovascular mortality risk than the general population, as well as an increased risk of infections, malignancies, fractures, and obesity. When comparing CKD with CKD after transplantation (CKD-T), the rate of decline of estimated glomerular filtration rate (eGFR) is significantly lower in CKD-T. Higher rate of decline of eGFR has been associated with increased risk of mortality. However, due to the significant increased risk of mortality due to cardiovascular events, infections, and malignancies, many kidney transplant recipients may not benefit of decline in the rate of eGFR. Patients with CKD-T are a unique subset of patients with multiple traditional and transplant-specific risk factors. Proper management and appropriate preventive health measures may improve long-term patient and allograft survival in patients with CKD-T.

Outcomes in the highest panel reactive antibody recipients of deceased donor kidneys under the new kidney allocation system.

Since the institution of the new kidney allocation system in December 2014, kidney transplant candidates with the highest calculated panel reactive antibodies (cPRA) of 99‐100 have been transplanted at much higher rates. However, concerns have been raised that outcomes in these patients might be impaired due to higher immunological risk and longer cold ischemia times resulting from long‐distance sharing of kidneys. Here, we compare outcomes at the University of Wisconsin between study patients with cPRA 99‐100 and all other recipients of deceased donor kidneys transplanted between 12/04/2014 and 12/31/2015. All patients had at least 6 months post‐transplant follow‐up. The mean follow‐up was 13.9±3 months in cPRA ≥99% and 12.3±3.5 months in cPRA ≤98%. There was a total of 152 transplants, 25 study patients, and 127 controls. No statistically significant differences were found between the two groups in delayed graft function, rejection, kidney function, graft and patient survival, or infections. We conclude that transplanting the most highly sensitized patients with kidneys shared outside their local donation service areas is associated with excellent short‐term outcomes that are comparable to controls.

Utility of Protocol Kidney Biopsies for De Novo Donor Specific Antibodies

There is limited information about the role of protocol kidney biopsies for de novo donor‐specific antibodies (dnDSA) in kidney transplant recipients, especially in those with stable graft function. We initiated a routine posttransplant DSA monitoring and surveillance biopsy program for dnDSA since 2014. We identified 45 kidney transplant recipients with dnDSA detected between January 2014 and February 2017 who underwent kidney biopsy within 60 days of detection of dnDSA. Twenty‐nine (64%) had stable graft function and 16 (36%) had impaired graft function at the time of dnDSA detection. Even in the group with stable graft function, we found a high rate of rejection (53%) on biopsy. Eighty‐eight percent of patients with impaired graft function had rejection. Those patients with impaired graft function had significantly lower estimated glomerular filtration rate at 12 months postbiopsy and at last follow‐up. Those with impaired graft function had more graft failures; however, this result was not statistically significant. The high rate of asymptomatic rejection, and the fact that outcomes in asymptomatic patients are poor, is in support of the utility of surveillance biopsies in patients with dnDSA.

Self-Reported Employment Status and Social Participation After Successful Kidney Transplantation

Introduction: Kidney transplantation (KTX) is considered the treatment of choice for most individuals with end-stage kidney disease. The purpose of this study was to assess the employment status and social participation after successful KTX. Methods: This was a retrospective cross-sectional study. Eligible participants were patients who received a transplant ≥1 year ago and who were previously on hemodialysis (HD) for ≥1 year. Two hundred individuals participated in this study. Results: A significant number (93.5%) of patients reported they were working prior to HD versus 35% while on HD. Only 14% reported receiving disability benefits prior to HD versus 75% receiving disability while on HD. Comparing transplant recipients with pre-HD patients, 35.5% versus 93.5% reported working, and 74.5% versus 14% reported receiving disability benefits, respectively. After transplant, patients were more likely to join recreational clubs, travel frequently, and participate in recreational/religious activities and social events than when they were on HD. Conclusion: Posttransplant, these individuals are more likely to participate in social and leisure activities, but the majority did not resume employment and continued to receive disability payments. Future studies could explore barriers to employment in patients who underwent successful transplantation and the causes and factors as to why these individuals continue to receive disability benefits.

Outpatient Management of Delayed Graft Function is Associated with Reduced Length of Stay without an Increase in Adverse Events

Delayed graft function (DGF) is a common and costly complication of kidney transplantation. In July 2011, we established a multidisciplinary DGF clinic managed by nurse practitioners to facilitate early discharge and intensive management of DGF in the outpatient setting. We compared length of stay, 30‐day readmission, acute rejection, and patient/graft survival in 697 consecutive deceased donor kidney transplantations performed between July 2009 and July 2014. Patients were divided into three groups: no DGF (n = 487), DGF before implementation of the DGF clinic (n = 118), and DGF clinic (n = 92). Baseline characteristics including age, gender, panel reactive antibody, retransplantation rates, HLA mismatches, induction, and maintenance immunosuppression were not significantly different between pre‐ and post‐DGF clinic groups. Length of stay was significantly longer in pre‐DGF clinic (10.9 ± 6.2 vs. 6.1 ± 2.1 days, p < 0.001). Thirty‐day readmission (21% vs. 16%), graft loss (7% vs. 20%), and patient death (2% vs. 11%) did not differ significantly between pre‐ and post‐DGF clinic. Patients in the DGF clinic were less likely to develop acute rejection (21% vs. 40%, p = 0.006). Outpatient management of DGF in a specialized clinic is associated with substantially shorter hospitalization and lower incidence of acute rejection without significant difference in 30‐day readmission or patient and graft survival.

In Kidney Transplant Recipients With a Positive Virtual Crossmatch, High PRA was Associated With Lower Incidence of Viral Infections.

Background There is little information on the incidence, risk factors, and outcomes associated with CMV and BK infections in sensitized patients. Methods We examined 254 consecutive kidney transplant recipients with positive virtual crossmatch and negative flow crossmatch. Results A total of 111 patients (43%) developed CMV disease or BK infection or nephropathy (BKVN). Specifically, 78 patients (30.7%) developed BK infection, 19 (7.5%) had BKVN, and 33 (12.9%) presented with CMV disease. Four patients (1.5%) developed both infections. Mean time from transplant to diagnosis for BK and CMV was 4.07 ± 3.10 and 8.35 ± 5.20 months, respectively. African American (HR, 2.64; 95% CI, 1.37-5.07; P = 0.003), thymoglobulin induction (HR, 2.18; 95% CI, 1.38-3.43; P = 0.0008), DSA greater than 500 MFI at transplant (HR, 1.64; 95% CI, 1.05-2.57; P = 0.03), history of diabetes (HR, 1.62; 95% CI, 1.01-2.60; P = 0.04), CMV D+/R- (HR, 2.30; 95% CI, 1.06-5.01; P = 0.03), and acute rejection (HR, 1.49; 95% CI, 0.99-2.24; P = 0.05) were associated with increase incident of BK/CMV, whereas rituximab (HR, 0.47; 95% CI, 0.24-0.91; P = 0.02), peak PRA greater than 80% (HR, 0.48; 95% CI, 0.27-0.84; P = 0.01), and living donor transplant (HR, 0.57; 95% CI, 0.36-0.87; P = 0.01) were associated with a lower likelihood of infection. Thymoglobulin induction (HR, 2.50; 95% CI, 1.02-6.13; P = 0.04), and peak PRA greater than 80% (HR, 0.45; 95% CI, 0.23-0.86; P = 0.02) remained significant predictors of infection after multivariate adjustment. Conclusions Although more than 40% of patients with a positive virtual crossmatch presented with BK infection/CMV disease, high PRA greater than 80% seemed to be protective.

Which is more nephrotoxic for kidney transplants: BK nephropathy or rejection?

Little data exist comparing outcomes following BK nephropathy (BKN) vs acute rejection. We reviewed outcomes among recipients who had a primary diagnosis of biopsy‐proven BKN or rejection between 1 and 18 months post‐transplant. There were 96 cases of BKN and 256 cases of rejections. We compared outcomes of BKN with all rejection combined and also with cellular rejection. Seven of 256 (2.7%) patients developed BKN after treatment of rejection. Conversely, 8 of 96 (8.3%) developed rejection after BKN. The eGFR at time of diagnosis in the BKN group (33.7 ± 12.6) was lower than the rejection group (44.8 ± 23.3, P < .001). The eGFR at 6 months after diagnosis of BKN was 32.7 ± 14.9 and for rejection was 48.8 ± 20.7 (P ≤ .001). The mean eGFR at 3 years postdiagnosis was 41.6 ± 18.5 in BKN and 53 ± 21.3 for rejection (P = .001). The graft failure incidence rates were similar between 2 groups. A similar pattern was observed comparing BKN with cellular rejection. While the difference in rate of graft loss between BKN and rejection did not reach statistical significance, kidney function up to 3 years after diagnosis was worse for BKN than for rejection, suggesting that BKN is at least as damaging to kidneys as rejection.