Risk factors and outcomes of persistent post-transplant hypotension among simultaneous pancreas and kidney transplant recipients.

BACKGROUND: The risk factors and outcomes associated with post- transplant hypotension after simultaneous pancreas and kidney (SPK) Transplantation are poorly defined. METHODS: SPK recipients at our center between 2010 and 2021 with functioning pancreas and kidney grafts for >6 months were included. Recipients were then divided into three groups based on active medications for the treatment of hypo-or hypertension at 6-months post-transplant: those with normal blood pressure (NBP) not requiring medication (NBP group), those on antihypertensive medications (HTN group), and those on medications for hypotension (fludrocortisone and/or midodrine) (Hypotensive group). RESULTS: A total of 306 recipients were included in the study: 54 (18%) in the NBP group, 215 (70%) in the HTN group, and 37 (12%) in the Hypotensive group. On multivariate analysis, the use of T-depleting induction (aHR = 9.64, p = .0001, 95% Cl = 3.12-29.75), pre-transplant use of hypotensive medications (aHR = 4.53, p = .0003, 95% Cl = 1.98-10.38), and longer duration of dialysis (aHR = 1.02, p = .01, 95% Cl = 1.00-1.04) were associated with an increased risk of post-transplant hypotension. Post-transplant hypotension was not associated with an increased risk of death-censored kidney or pancreatic allograft failure, or patient death. CONCLUSION: Hypotension was common even 6 months post-SPK transplantation. With appropriate management, hypotension was not associated with detrimental graft or patient outcomes.

Delayed Graft Function Among Kidney Transplant Recipients Is Associated With an Increased Risk of Urinary Tract Infection and BK Viremia.

Background: Delayed graft function (DGF) among deceased donor kidney transplant recipients (DDKTRs) is a well-known risk factor for allograft rejection, decreased graft survival, and increased cost. Although DGF is associated with an increased risk of rejection, it is unclear whether it also increases the risk of infection. Methods: We reviewed all adult DDKTRs at our center between 2010 and 2018. The primary outcomes of interest were BK viremia, cytomegalovirus viremia, pneumonia, and urinary tract infection (UTI) within the first year of transplant. Additional analysis was made with censoring follow-up at the time of allograft rejection. Results: A total of 1512 DDKTRs were included, of whom 468 (31%) had DGF. As expected, several recipient, donor, and baseline immunological characteristics differed by DGF status. After adjustment, DGF was significantly associated with an increased risk of BK viremia (hazard ratio: 1.34; 95% confidence interval, 1.0-1.81; P = 0.049) and UTI (hazard ratio: 1.70; 95% confidence interval, 1.31-2.19; P < 0.001) but not cytomegalovirus viremia or pneumonia. Associations were similar in models censored at the time of rejection. Conclusions: DGF is associated with an increased risk of early infectious complications, mainly UTI and BK viremia. Close monitoring and appropriate management are warranted for better outcomes in this unique population.

A Randomized Controlled Trial of Envarsus Versus Immediate Release Tacrolimus in Kidney Transplant Recipients With Delayed Graft Function.

BACKGROUND: The incidence of delayed graft function (DGF) among kidney transplant recipients (KTRs) in the United States continues to increase. The effect of immediate-release tacrolimus (tacrolimus) compared with extended-release tacrolimus (Envarsus) among recipients with DGF is unknown. METHODS: This was a single-center open-label randomized control trial among KTRs with DGF (ClinicalTrials. gov, NCT03864926). KTRs were randomized either to continue on tacrolimus or switch to Envarsus at a 1:1 ratio. Duration of DGF (study period), number of dialysis treatments, and need for adjustment of calcineurin inhibitor (CNI) doses during the study period were outcomes of interest. RESULTS: A total of 100 KTRs were enrolled, 50 in the Envarsus arm and 50 in the tacrolimus arm; of those, 49 in the Envarsus arm and 48 in the tacrolimus arm were included for analysis. There were no differences in the baseline characteristics, all P > .5, except donors in the Envarsus arm had higher body mass index (mean body mass index 32.9 ± 11.3 vs 29.4 ± 7.6 kg/m2 [P = .007]) compared with the tacrolimus arm. The median duration of DGF (5 days vs 4 days, P = .71) and the number of dialysis treatments (2 vs 2, P = .83) were similar between the groups. However, the median number of CNI dose adjustments during the study period in the Envarsus group was significantly lower (3 vs 4, P = .002). CONCLUSIONS: Envarsus patients had less fluctuation in the CNI level, requiring fewer CNI dose adjustments. However, there were no differences in the DGF recovery duration or number of dialysis treatments.

The current state of transplant advanced practice providers: results of the advanced practice provider practice survey.

Advanced practice providers (APPs) are trained, licensed health care providers. The American Society of Transplant APP community of practice developed an electronic survey to investigate transplant APP demographics, scope of practice, and academic activities. We defined the top of scope of practice as delivering health care to the fullest extent of APP education and training as allowed by state laws and regulations. From July 11, 2020, to August 31, 2020, 307 invitations were e-mailed and survey links were distributed electronically on the community of practice hub and social media. Two hundred fifty-three APPs responded. APPs practice in inpatient and outpatient settings. Among the respondent APPs, 11.5% assist in the operating room (OR), 46.3% of inpatient and 46.6% of outpatient APPs perform procedures, and 17.8% run specialized APP clinics. 26.2% feel they do not function at the top of their scope of practice and 29.7% were expected to function as a coordinator some or all of the time. Forty-three percent gave invited lectures, 41.5% have published, and 69.2% teach physician trainees. 74.7% and 35.1%, respectively, would like to participate in research and teach but are limited by time, opportunity, and experience. APPs should practice at the top of their scope of practice. Clinical workloads and lack of time limit the ability of APP to teach and contribute to evidence-based practice.

In kidney recipients from the same deceased donor, discordance in delayed graft function is associated with the worst outcomes.

INTRODUCTION: Delayed graft function (DGF) is a common complication among deceased donor kidney transplant recipients (DDKTs) and is associated with worse outcomes. The effect on outcomes of concordance versus discordance in DGF between two different recipients of kidneys from the same donor is largely unknown. METHODS: We reviewed all adult DDKTs for which both kidneys were transplanted to two different recipients at our center between 2014-2019. DDKTs were divided into four groups based on the DGF status: concordance no DGF (cc-no-DGF); discordance no DGF(dd-no-DGF); discordance DGF (dd-DGF) and concordance in DGF (cc-DGF). Acute rejection (AR) and death censored graft failure (DCGF) were outcomes of interest. RESULTS: A total of 578 DDKTs fulfilled our selection criteria, 280were in cc-no-DGF, 83 in dd-no-DGF, 83 in dd-DGF, and 132 in cc-DGF. Compared to cc-no-DGF, in univariate analysis, dd-DGF was associated with an increased risk of AR (HR: 1.60; 95% CI: 1.0-2.56) but cc-DGF was not (HR: 1.01; 95% CI: 0.63-1.62). dd-DGF was not associated with an increased risk of AR in multivariate analysis. In multivariate analysis, dd-DGF was associated with an increased risk of DCGF (HR: 2.70; 95% CI: 1.05-6.93) but cc-DGFwas not (HR: 2.36; 95% CI: 0.97-5.70). CONCLUSION: Discordance in DGF is associated with worse outcomes and may need closefollow-up and monitoring to improve the outcomes.

Kidney delayed graft function after combined kidney-solid organ transplantation: A review.

Kidney delayed graft function (K-DGF) is a common post-kidney transplant complication associated with adverse outcomes. With continued advances in solid organ transplantation (SOT), combined kidney-solid organ transplantation (CKSOT) is an ever-growing transplant option for patients with advanced kidney disease in the setting of concurrent solid organ failure. K-DGF in this setting is understudied. In this review, we aimed to abridge the representative literature on K-DGF in CKSOT. K-DGF occurs at different rates across combined and sequential kidney-solid organ transplantation (SKSOT), in simultaneous-pancreas kidney (SPK) transplant (8-23%), simultaneous heart-kidney (SHK) transplant (27-37%), simultaneous-liver kidney (SLiK) transplant (16-49%), and kidney after thoracic (13.6-19.2%) and abdominal (13.6-25%) transplantation. Though many K-DGF risk factors span across various subtypes of combined KSOT, some effect particular transplant types more specifically and may be modifiable to reduce K-DGF incidence. While more studies are needed to prevent and manage K-DGF in combined kidney-solid organ transplantation, we hope our review will provide context of this disease and spur further inquiry.

Continuation of Peritoneal Dialysis in Adult Kidney Transplant Recipients With Delayed Graft Function.

INTRODUCTION: Peritoneal dialysis (PD) has been used increasingly in past decade. Many of these patients undergo transplantation and may require dialysis for delayed graft function (DGF). The outcomes of DGF based on the post-transplantation dialysis modality are not well known. METHODS: We retrospectively reviewed all adult kidney transplant recipients (KTRs) from the University of Wisconsin School of Medicine and Public Health who developed DGF between November 2015 and April 2019. Patients were divided into those who received hemodialysis (HD) or PD during the DGF period. Immediate graft explant, DGF among living donor KTRs, or those requiring just a single dialysis treatment were excluded. RESULTS: Of 224 KTRs with DGF during the study period, 167 fulfilled our selection criteria. There were 16 patients in the PD and 151 in the HD group. Baseline characteristics were similar between the two groups, except diabetes was more prevalent in the HD group. Five of 16 PD patients had to be transitioned to HD. There was no difference in DGF duration, hospital length of stay, infectious or surgical complications, rejection at various time periods, graft function at last follow-up, or graft failure. In multivariate analysis, only rejection within the first year of transplantation (hazard ratio [HR]: 4.26; 95% confidence interval [CI]: 1.20-15.08; P = 0.02) and post-surgical complications (HR: 3.79; 95% CI: 1.03- 13.91; P = 0.04) were associated with death-censored graft failure (DCGF). The use of PD for treatment of DGF was not associated with DCGF. CONCLUSIONS: In carefully selected patients, PD can be continued safely for DGF without any effect on short-term or long-term transplant outcomes.

Outcomes of Delayed Graft Function in Kidney Transplant Recipients Stratified by Histologic Biopsy Findings.

Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.

Risk factors and outcomes for delayed kidney graft function in simultaneous heart and kidney transplant recipients: A UNOS/OPTN database analysis.

There are no prior studies assessing the risk factors and outcomes for kidney delayed graft function (K-DGF) in simultaneous heart and kidney (SHK) transplant recipients. Using the OPTN/UNOS database, we sought to identify risk factors associated with the development of K-DGF in this unique population, as well as outcomes associated with K-DGF. A total of 1161 SHK transplanted between 1998 and 2018 were included in the analysis, of which 311 (27%) were in the K-DGF (+) group and 850 in the K-DGF (-) group. In the multivariable analysis, history of pretransplant dialysis (OR: 3.95; 95% CI: 2.94 to 5.29; p < .001) was significantly associated with the development of K-DGF, as was donor death from cerebrovascular accident and longer cold ischemia time of either organ. SHK recipients with K-DGF had increased mortality (HR: 1.99; 95% CI: 1.52 to 2.60; p < .001) and death censored kidney graft failure (HR: 3.51; 95% CI: 2.29 to 5.36; p < .001) in the multivariable analysis. Similar outcomes were obtained when limiting our study to 2008-2018. Similar to kidney-only recipients, K-DGF in SHK recipients is associated with worse outcomes. Careful matching of recipients and donors, as well as peri-operative management, may help reduce the risk of K-DGF and the associated detrimental effects.

The Utility of Donor-specific Antibody Monitoring and the Role of Kidney Biopsy in Simultaneous Liver and Kidney Recipients With De Novo Donor-specific Antibodies.

BACKGROUND: There is limited information about the utility of donor-specific antibody (DSA) against HLA monitoring and the role of protocol kidney biopsy for de novo DSA (dnDSA) in simultaneous liver and kidney (SLK) transplant recipients. METHODS: We analyzed SLK transplant recipients transplanted between January 2005 and December 2017, who had DSA checked posttransplant. Patients were divided into 2 groups based on whether they developed dnDSA posttransplant (dnDSA+) or not (dnDSA-). Kidney graft rejection ±45 d of dnDSA and a kidney death-censored graft survival were the primary endpoints. RESULTS: A total of 83 SLK transplant recipients fulfilled our selection criteria. Of those, 23 were dnDSA+ and 60 were dnDSA-. Twenty-two of 23 dnDSA+ patients had DSA against class II HLA, predominantly against DQ. Fifteen recipients underwent kidney biopsy ±45 d of dnDSA. Six of these were clinically indicated due to kidney graft dysfunction. The other 9 had a protocol kidney biopsy only due to dnDSA, and 6 of these 9 had a rejection. Also, 3 recipients had sequential biopsies of both the kidney and liver grafts. Among those with sequential biopsies of both grafts, there was a difference between the organs in the rate and types of rejections. At last follow up, dnDSA was not associated with graft failure of either the kidney or liver. CONCLUSIONS: Although our study was limited by a small sample size, it suggests the potential utility of DSA monitoring and protocol kidney biopsy for dnDSA.

A Single-Center Assessment of Delayed Graft Function in Recipients of Simultaneous Liver and Kidney Transplant.

BACKGROUND: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients. METHODS: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest. RESULTS: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality. CONCLUSION: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.

Delayed kidney graft function in simultaneous pancreas-kidney transplant recipients is associated with early pancreas allograft failure.

Delayed graft function (DGF) is a common complication associated with significant untoward effects in kidney-alone transplantation. The incidence and outcomes following kidney delayed graft function (K-DGF) among patients undergoing simultaneous pancreas-kidney (SPK) transplantation are less certain. We analyzed SPK recipients transplanted at our center between January 1994 and December 2017. A total of 632 recipients fulfilled the selection criteria, including 69 (11%) with K-DGF and 563 without. The incidence of K-DGF was significantly higher in recipients of organs from older donors and donation after circulatory death (DCD). The presence of K-DGF was significantly associated with an increased risk of pancreas graft failure during the first 90 days (n = 9, incidence rate [IR] 2.45/100 person-months), but not with late pancreas failure (n = 32, IR 0.84/100 person-months), kidney graft failure, or patient death. Although DCD was associated with K-DGF, it was not associated with either pancreas (hazard ratio [HR] 0.91, 95% CI 0.58-1.44, P = .69) or kidney (HR 1.09, 95% CI 0.66-1.82, P = .74) graft failure after adjustment for potential confounders. We found K-DGF to be a significant risk factor for pancreas graft failure but not kidney graft failure, with the major risk period being early (<90 days) posttransplant, and the major donor risk factor being older donor age.

More Than 25 Years of Pancreas Graft Survival After Simultaneous Pancreas and Kidney Transplantation: Experience From the World's Largest Series of Long-term Survivors.

BACKGROUND: The first simultaneous pancreas and kidney (SPK) transplant was performed in 1966. Early procedures were associated with significant morbidity and mortality and were performed in very low numbers in select patients. METHODS: This study includes all recipients of an SPK at the University of Wisconsin-Madison between 1986 and 1993, who were actively followed and had a functional pancreas allograft for >25 years as of October 31, 2018. RESULTS: A total of 291 SPK were performed during the study period; of these, 39 patients still had a functional graft at last follow up and 9 (18.8%) pancreas grafts were lost due to patient death or graft failure after >25 years. At last follow up, all 39 patients with functional pancreas graft had at least one comorbidity, such as hypertension, hyperlipidemia, or coronary artery disease. Twenty-seven required enteric conversion; 11 patients experienced renal allograft failure (10 underwent a repeat kidney transplant); and 6 required amputation of part of the lower extremity. In the Cox regression analysis, bladder drained pancreas was associated with lower probability of prolonged pancreas graft survival (hazard ratio: 0.52; confidence interval: 0.32-0.85; P = 0.01). CONCLUSIONS: With careful and detailed follow-up and attention to complications, some recipients of pancreas grafts have outstanding outcomes. As the number of pancreas recipients with prolonged graft survival may be rising, healthcare providers should be aware of the management of complications associated with this unique group of patients.

Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression.

BACKGROUND: The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy. AIM: To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications. METHODS: In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy. RESULTS: We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy (IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy (TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR (40%), TG (17%), and IFTA (13%). Most grafts failed within two years of post-transplant (36%). Subsequently, approximately 10%-15% of grafts failed every two years: > 2-4 years (16%), > 4-6 years (13%), > 6-8 years (11%), > 8-10 years (9%) and > 10 years (16%). AR was the most common cause of graft failure in the first six years (48%), whereas TG was the most prevalent cause of graft failure after 6 years (32%) of transplant. CONCLUSION: In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

Blessing and a curse of outpatient management of delayed graft function.

Delayed graft function (DGF) is a common complication occurring most often after deceased donor kidney transplant with several donor characteristics as well as immunologic factors that lead to its development post-transplant. These patients require dialysis and close kidney function monitoring until sufficient allograft function is achieved. This has resulted in limited options for DGF management, either prolonged hospitalization until graft function improves to the point where dialysis is no longer needed or discharge back to their home dialysis unit with periodic follow up in the transplant clinic. DGF is associated with a higher risk for acute rejection, premature graft failure, and 30-d readmission; therefore, these patients need close monitoring, immunosuppression management, and prompt allograft biopsy if prolonged DGF is observed. This may not occur if these patients are discharged back to their home dialysis unit. To address this issue, the University of Wisconsin-Madison created a clinic in 2011 specialized in outpatient DGF management. This clinic was able to successfully reduce hospital length of stay without an increase in 30-d readmission, graft loss, and patient death.

Donor-Specific Antibodies in the Absence of Rejection Are Not a Risk Factor for Allograft Failure.

INTRODUCTION: Donor-specific antibodies (DSAs) are considered an important risk factor for graft injury and failure. However, there is limited information on long-term outcomes for kidney transplant recipients with positive DSAs in the absence of rejection on biopsy. METHODS: We evaluated all patients at the University of Wisconsin who underwent a kidney allograft biopsy between January 1, 2013, and December 31, 2016. All patients with clinical indication or protocol biopsies that were negative for acute rejection and lacked significant acute pathological features were included in the study and divided into 2 groups based on DSAs at the time of biopsy. There were a total of 1102 kidney biopsies during the study period of which 587 fulfilled our selection criteria (DSA+, n = 192, and DSA-, n = 395). The incidence of subsequent rejection and death-censored graft failure (DCGF) were outcomes of interest. RESULTS: There was no difference in acute (i + t + v + c4d + ptc + g = 0 in both groups) or chronic (ci + ct + cv + cg = 2.4 ± 2.2 vs. 2.7 ± 2.4; cg = 0.12 ± 0.48 vs. 0.13 ± 0.48) Banff scores in the index biopsy. Patients were followed for a mean of 33.1 ± 16.8 months. Kaplan-Meier analyses demonstrated a higher incidence of DCGF in DSA- group (n = 83) but this was not observed for subsequent rejection (n = 76). In multivariate Cox regression analyses, the interval from transplant to biopsy, de novo DSA, and younger age remained independently associated with increased risk of subsequent rejection. Notably, there was no association between subsequent rejection or DSA (pretransplant, de novo, persistant, Class I/II, MFIsum, or MFImax) and graft failure. CONCLUSION: This study suggests that in the absence of biopsy-proven rejection and acute inflammation, human leukocyte antigen (HLA) DSAs are not associated with increased risk of graft failure.

Subclinical Antibody-mediated Rejection After Kidney Transplantation: Treatment Outcomes.

BACKGROUND: Antibody-mediated rejection (AMR) is a leading cause of morbidity and mortality after kidney transplantation. Early diagnosis and treatment of subclinical AMR based on the donor-specific antibody (DSA) testing may result in better outcomes. METHODS: We tested this hypothesis in 220 kidney transplant recipients who underwent an indication or DSA-based surveillance protocol biopsies between March 1, 2013 and December 31, 2016. Patients were divided into 3 groups: clinical AMR (n = 118), subclinical AMR (n = 25), or no rejection on protocol biopsy (controls; n = 77). RESULTS: Both clinical and subclinical AMR groups underwent similar treatment including plasmapheresis, pulse steroids, IVIG, and rituximab (P = ns). Mean follow-up after AMR was 29.5 ± 16.8 months. There were 2 (3%), 2 (8%), and 54 (46%) death-censored graft failures in the control, subclinical, and clinical AMR groups, respectively (P < 0.001). Graft outcomes were similar in the subclinical rejection and control groups. In adjusted Cox regression analysis, only clinical rejection (hazards ratio [HR], 4.31; 95% confidence interval [CI], 1.01-18.94; P = 0.05) and sum chronicity scores (HR, 1.16; 95% CI, 1.01-1.35; P = 0.03) were associated with increased risk of graft failure, while estimated glomerular filtration rate at time of biopsy (HR, 0.98; 95% CI, 0.96-0.99; P = 0.01) was associated with decreased risk of graft failure. CONCLUSIONS: Our study suggests that early diagnosis and treatment of subclinical AMR using DSA monitoring may improve outcomes after kidney transplantation.

Risk factors for graft loss in kidney transplant recipients with g3 glomerulitis: A single-center experience
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BACKGROUND: Risk factors for graft loss in kidney transplant recipients with g3 lesions are poorly defined. MATERIALS AND METHODS: We evaluated outcomes in 37 consecutive kidney transplant biopsies diagnosed with g3 glomerulitis based on Banff 2013 criteria in a single-center observational study. RESULTS: The diagnosis of g3 glomerulonephritis was made 6.1 ± 6.6 years after transplant. The majority of patients were Caucasian (86%), male (65%), and received basiliximab induction (54%). At the time of biopsy, all were on triple therapy with tacrolimus, mycophenolate, and prednisone. Mean serum creatinine (Scr) was 2.85 ± 2.1 mg/dL. Notably, 20 (54%) were positive for donor-specific antibodies (DSA+) and 8 (22%) were C4d+, while 24 (65%) had transplant glomerulopathy (TG). Treatment included pulse steroids/intravenous immunoglobulin (IVIG) (73%) and rituximab (51%). Patients were followed for up to 4 years after the biopsy. Eleven grafts (30%) were lost during the follow-up. Cox regression analyses determined Scr (HR = 1.63, 95% CI 1.19 - 2.24, p = 0.002), live donor status (HR = 0.18, 95% CI 0.04 - 0.90, p = 0.03), t-score (HR = 2.75, 95% CI 1.30 - 5.81, p = 0.008), and ct-score (HR = 2.19, 95% CI 1 - 4.75, p = 0.04) as significant predictors of graft loss. CONCLUSION: Severe glomerulitis was associated with a high prevalence of TG and graft loss at 4 years. Live donor status, kidney function (Scr), and tubular injury (t- and ct-scores) were independently associated with graft loss. Interventional mechanistic clinical trials are needed to better understand the pathogenesis and outcomes of g3 glomerulitis.
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Management of Tumor Necrosis Factor α Inhibitor Therapy After Renal Transplantation: A Comparative Analysis and Associated Outcomes.

BACKGROUND: Biologic agents inhibiting the tumor necrosis factor α pathway (TNFα-Is) are used to treat systemic inflammatory diseases. The best management of these agents after renal transplantation is unknown. OBJECTIVE: Evaluate peritransplant use of TNFα-Is and associated outcomes. METHODS: Retrospective, single-center study of adult renal-transplant-recipients (RTRs) transplanted between 1/1/1998-12/31/2017, who received TNFα-Is for inflammatory disease prior to transplant. Qualifying patients were divided into 2 cohorts: patients who resumed TNFα-Is after transplant and those who did not. Outcomes were evaluated. RESULTS: A total of 5256 renal transplants occurred in the study window; 14 patients met inclusion criteria. Primary indication for TNFα-I was Crohn's-disease (CD; 57.1%). Infliximab was utilized most frequently (50%). Seven RTRs resumed TNFα-I posttransplant; mean time to resumption of 10.6±4.35 months (median=6 months), 85.7% for CD. Immunosuppression was modified in 2 patients (28.6%) in response to restarting TNFα-I therapy. Seven RTRs did not resume TNFα-Is following transplant; the majority of these had rheumatic diseases. There was no significant difference in time to first bacterial or fungal infection, rejection, or patient survival between the 2 groups. Last measured estimated glomerular-filtration-rate was similar between groups (TNFα-I: 41 ± 14.2 vs 48.6 ± 8.6, P = 0.25). No patient had cytomegalovirus infection; however, 42.8% of each cohort had documented BK virus infection. Malignancy occurred more frequently in the cohort that resumed TNFα-Is (42.8% vs 14.3%, P = 0.24); however, this was not statistically significant. Conclusion and Relevance: TNFα-I therapy prior to renal-transplant is relatively uncommon. The decision to continue therapy after transplant must balance risks of infection and malignancy against inflammatory disease recurrence. A multidisciplinary treatment approach is necessary as use of TNFα-I affects immunosuppressive management and appears to affect transplant outcomes. Future studies are needed to further clarify the role of TNFα-I therapy use in RTRs with inflammatory disorders focusing on its correlation with both BK and malignancy.