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.

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.

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.

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.

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.

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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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.

Predictors and outcomes of delayed graft function after living-donor kidney transplantation.

Delayed graft function (DGF) following deceased donor kidney transplantation is associated with inferior outcomes. Delayed graft function following living-donor kidney transplantation is less common, but its impact on graft survival unknown. We therefore sought to determine risk factors for DGF following living-donor kidney transplantation and DGF's effect on living-donor kidney graft survival. We analyzed living-donor kidney transplants performed between 2000 and 2014 in the UNOS dataset. A total of 64 024 living-donor kidney transplant recipients were identified, 3.6% developed DGF. Cold ischemic time, human leukocyte antigen mismatch, donor age, panel reactive antibody, recipient diabetes, donor and recipient body mass index, recipient race and gender, right nephrectomy, open nephrectomy, dialysis status, ABO incompatibility, and previous transplants were independent predictors of DGF in living-donor kidney transplants. Five-year graft survival among living-donor kidney transplant recipients with DGF was significantly lower compared with graft survival in those without DGF (65% and 85%, respectively, P < 0.001). DGF more than doubled the risk of subsequent graft failure (hazard ratio = 2.3, 95% confidence interval: 2.1-2.6; P < 0.001). DGF after living-donor kidney transplantation is associated with inferior allograft outcomes. Minimizing modifiable risk factors may improve outcomes in living-donor kidney transplantation.

Older kidney transplant patients experience less antibody-mediated rejection: a retrospective study of patients with mild to moderate sensitization.

BACKGROUND: There is a paucity of data stratifying by age the incidence of antibody-mediated rejection (AMR) in kidney transplant patients. METHODS: We performed a retrospective study of all adult, renal transplant recipients at a single institution between December 12, 2009, and March 16, 2011. Mildly and moderately sensitized patients were defined as patients with positive donor-specific antibody (DSA) and negative flow cross-match. RESULTS: One hundred and forty-six patients were determined to have mild to moderate pre-transplantation sensitization. Thirty percent of patients younger than 40 yr of age experienced AMR vs. 15% in the older group (p = 0.04). There was a disproportionate increase in DSA for younger patients at 12 months, particularly for antibodies to class II. Histologic presence of C4d deposition was independently associated with AMR on multivariate analysis. CONCLUSIONS: Following renal transplantation, moderately sensitized patients aged 40 yr old and older were less likely to develop AMR when compared with younger patients.

Serum ß2-microglobulin at discharge predicts mortality and graft loss following kidney transplantation.

Serum ß(2)-microglobulin (ß(2)M), a novel marker of kidney function, predicts mortality and kidney failure in the general population, and its elevation following transplantation is a marker of acute rejection. The association between post-transplant serum ß(2)M and outcomes following kidney transplantation, however, is unknown. To help determine this, we conducted a retrospective cohort study of 2190 individuals receiving a primary kidney transplant with serum ß(2)M measured at discharge. A total of 452 deaths and 347 graft failures before death (669 total graft losses) occurred over a median of 4.1 years of follow-up. After adjustment, the highest quintile of ß(2)M (5.0 mg/l and above), compared with the lowest quintile (<2.3 mg/l), was associated with a hazard ratio of 4.6 (95% confidence interval 2.8, 7.5) for death, 4.1 (2.4, 7.0) for death-censored graft loss, and 3.8 (2.5, 5.6) for total graft loss. Serum ß(2)M was more strongly associated with each outcome than was serum creatinine. Higher serum ß(2)M at discharge was independently associated with each outcome in models stratified by the presence of delayed graft function, donor type, or estimated glomerular filtration rate at discharge. Thus, serum ß(2)M at discharge is a potent predictor of long-term mortality and graft loss in kidney transplant recipients, providing information on allograft function beyond that of serum creatinine.

Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients.

In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.

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.

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.

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.

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.

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.

Increase in proteinuria >200 mg/g after late rejection is associated with poor graft survival.

BACKGROUND: There is no information on the effects of proteinuria on outcomes following rejection. METHODS: We addressed this question in a retrospective study of 925 kidney transplant recipients between January 2003 and December 2007. Selection criteria were based on (i) biopsy proven diagnosis of a first episode of acute rejection, and (ii) available data on urine protein to creatinine (UPC) ratios at baseline (lowest serum creatinine before biopsy), time of biopsy and 1 month after biopsy. We examined the effects of a change in UPC (DeltaUPC = UPC 1 month after biopsy-baseline UPC) on outcomes. RESULTS: We identified 82 patients with both acute rejection and available data on proteinuria. Mean time (+/-SE) to acute rejection was 19 +/- 2.3 months, and patients were followed up for 38.7 +/- 2.6 months after transplant. Median DeltaUPC was 200 mg/g (95% confidence interval 0.00 to 0.300). Forty-two patients had a DeltaUPC > or =200 (high proteinuria group). Baseline characteristics were similar between high and low proteinuria groups except for more induction therapy with interleukin-2 receptor blockade in the former (71 vs. 47%, P = 0.04). Patient with DeltaUPC > or =200 had higher rates of graft loss (26 vs. 15%, P = 0.01) or combined graft loss or death (38 vs. 20%, P = 0.002 by log-rank). In univariate and multivariate Cox regression analyses, DeltaUPC > or =200 mg/g, sirolimus therapy 1 month after rejection and re-transplant status were significant factors associated with death-censored graft loss (hazard ratio (HR) 4.4, 14.9 and 6.2, P < or = 0.008) or combined graft loss or patient death (HR 3.8, 6.5 and 3.9, P < or = 0.03). Conclusions. An increase in proteinuria > or =200 mg/g after late acute rejection is associated with poor graft and patient outcomes. Clinical trials are needed to determine whether post-rejection anti-proteinuric strategies improve outcomes.