Impact of delayed listing after initiating kidney transplant evaluation on transplant outcomes.

OBJECTIVE: Longer end-stage renal disease time has been associated with inferior kidney transplant outcomes. However, the contribution of transplant evaluation is uncertain. We explored the relationship between time from evaluation to listing (ELT) and transplant outcomes. METHODS: This retrospective study included 2535 adult kidney transplants from 2000 to 2015. Kaplan-Meier survival curves, log-rank tests, and Cox regression models were used to compare transplant outcomes. RESULTS: Patient survival for both deceased donor (DD) recipients (p < .001) and living donor (LD) recipients (p < .0001) was significantly higher when ELT was less than 3 months. The risks of ELT appeared to be mediated by other risks in DD recipients, as adjusted models showed no associated risk of graft loss or death in DD recipients. For LD recipients, ELT remained a risk factor for patient death after covariate adjustment. Each month of ELT was associated with an increased risk of death (HR = 1.021, p = .04) but not graft loss in LD recipients in adjusted models. CONCLUSIONS: Kidney transplant recipients with longer ELT times had higher rates of death after transplant, and ELT was independently associated with an increased risk of death for LD recipients. Investigations on the impact of pretransplant evaluation on post-transplant outcomes can inform transplant policy and practice.

A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design.

Background: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. Methods: We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. Discussion: Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.

Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial.

BACKGROUND: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates TNF α production that amplifies allograft inflammation and may negatively affect transplant outcomes. METHODS: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase 2 clinical trial. A total of 225 primary transplant recipients of deceased-donor kidneys (KTx; 38.2% Black/African American, 44% White) were randomized to receive intravenous infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated before kidney reperfusion. All patients received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary end point was the difference between groups in mean 24-month eGFR. RESULTS: There was no difference in the primary end point of 24-month eGFR between IFX (52.45 ml/min per 1.73 m 2 ; 95% CI, 48.38 to 56.52) versus PLBO (57.35 ml/min per 1.73 m 2 ; 95% CI, 53.18 to 61.52; P =0.1). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ, and day 7 post-KTx plasma analyses showed approximately ten-fold lower TNF ( P <0.001) in IFX versus PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) versus PLBO (13.4%; P =0.004), with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) versus PLBO (4.9%; P =0.06). CONCLUSIONS: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peritransplant inflammation as a strategy to improve KTx outcomes.Clinical Trial registry name and registration number:clinicaltrials.gov (NCT02495077).

Clinical Utility in Adopting Race-free Kidney Donor Risk Index.

Recent events of racial injustice prompted us to study potential impact of removing race from kidney donor risk index (KDRI) calculator. Methods: We used Scientific Registry for Transplant Recipients data to analyze outcomes of 66 987 deceased-donor kidney transplants performed in the United States between 2010 and 2016. Graft failure (GF) was defined as death or return to dialysis or requiring repeat transplant. We compared original KDRI and a race-free KDRI (Black donor coefficient zeroed out in the KDRI formula) with respect to recategorization of perceived GF risk (based on KDPI categories: ≤20, 21-34, 35-85, ≥86)' risk discrimination (using the C statistic) and predictive accuracy (using Brier score), and GF risk prediction (using Cox regression on time-to-GF). We used logistic regression to study the impact of donor race on discard probability. Results: There were 10 949 (16.3% of recipients) GF, and 1893 (17% of GFs) were among recipients of kidneys from Black donors. The use of race-free KDRI resulted in reclassification of 49% of kidneys from Black donors into lower GF risk categories. The impact on GF risk discrimination was minimal, with a relative decrease in C statistic of 0.16% and a change in GF predictive accuracy of 0.07%. For a given recipient/donor combination, transplants from Black (compared with non-Black) donors are estimated to decrease predicted graft survival at 1-y by 0.3%-3%, and 5-y by 1%-6%. Kidneys from Black donors are significantly more likely to be discarded (odds ratio adjusted for KDRI except race = 1.24). We estimate that an equal discard probability for Black and non-Black donors would yield 70 additional kidney transplants annually from Black donors. Conclusions: Use of race-free KDRI did not impact GF risk discrimination or predictive accuracy and may lower discard of kidneys from Black donors. We recommend use of race-free KDRI calculator acknowledging the possibility of miscalculation of GF risk in small proportion of kidneys from Black donors.

CT-measured Cortical Volume Ratio Is an Accurate Alternative to Nuclear Medicine Split Scan Ratio Among Living Kidney Donors.

BACKGROUND: The 125I-iothalamate clearance and 99mTc diethylenetriamine-pentaacetic acid (99mTc-DTPA) split scan nuclear medicine studies are used among living kidney donor candidates to determine measured glomerular filtration rate (mGFR) and split scan ratio (SSR). The computerized tomography-derived cortical volume ratio (CVR) is a novel measurement of split kidney function and can be combined with predonation estimated GFR (eGFR) or mGFR to predict postdonation kidney function. Whether predonation SSR predicts postdonation kidney function better than predonation CVR and whether predonation mGFR provides additional information beyond predonation eGFR are unknown. METHODS: We performed a single-center retrospective analysis of 204 patients who underwent kidney donation between June 2015 and March 2019. The primary outcome was 1-y postdonation eGFR. Model bases were created from a measure of predonation kidney function (mGFR or eGFR) multiplied by the proportion that each nondonated kidney contributed to predonation kidney function (SSR or CVR). Multivariable elastic net regression with 1000 repetitions was used to determine the mean and 95% confidence interval of R2, root mean square error (RMSE), and proportion overprediction ≥15 mL/min/1.73 m2 between models. RESULTS: In validation cohorts, eGFR-CVR models performed best (R2, 0.547; RMSE, 9.2 mL/min/1.73 m2, proportion overprediction 3.1%), whereas mGFR-SSR models performed worst (R2, 0.360; RMSE, 10.9 mL/min/1.73 m2, proportion overprediction 7.2%) (P < 0.001 for all comparisons). CONCLUSIONS: These findings suggest that predonation CVR may serve as an acceptable alternative to SSR during donor evaluation and furthermore, that a model based on CVR and predonation eGFR may be superior to other methods.

Evaluation of the Effectiveness of Screening for Iliac Arterial Calcification in Kidney Transplant Candidates.

BACKGROUND Peripheral vascular disease and iliac arterial calcification are prevalent in kidney transplant candidates and jeopardize graft outcomes. We report our experience with computed tomography (CT) screening for iliac arterial calcification. MATERIAL AND METHODS We retrospectively reviewed electronic medical records of 493 renal transplant candidates from protocol initiation in 2014. Non-contrast CT was performed or retrospectively reviewed if any of the following criteria were present: diabetes, ESRD >6 years, 25 pack-years of smoking or current smoker, diagnosis of peripheral vascular disease, parathyroidectomy, and coronary artery disease intervention. Differences in evaluation and transplant outcomes between groups were compared with chi-squared analysis. Multivariate logistic regression identified predictive criteria for presence of iliac arterial calcification. RESULTS Of 493 candidates evaluated, CTs were reviewed in 346 (70.2%). Iliac arterial calcification was identified in 119 screened candidates (34.4%). Of candidates with iliac arterial calcification identified on CT, 16 (13.4%) were excluded for CT findings, and 9 (7.6%) had their surgical management plan changed. Overall, 91 (76.5%) candidates with iliac arterial calcification on CT were approved, compared to 203 (89.4%) without calcification (P<0.001). The percentage of screened patients with iliac arterial calcification on CT increased with increasing age (P<0.0005). Age and diabetes mellitus were predictive of calcification. CONCLUSIONS Many kidney transplant candidates are at risk for iliac arterial calcification, although such calcification does not prevent transplantation for most candidates who have it. Algorithmic pre-operative screening has clinical value in determining transplant candidacy and potentially improving postoperative outcomes in patients requiring kidney transplantation.

Variable Benefits of Antibody Induction by Kidney Allograft Type.

BACKGROUND: Kidneys from acute renal failure (ARF), expanded criteria donors (ECD), and donation after cardiac death (DCD) donors are often discarded due to concerns for delayed graft function (DGF) and graft failure. Induction immunosuppression may be used to minimize these risks, but practices vary widely. Furthermore, little is known regarding national outcomes of transplant recipients receiving induction immunosuppression for receipt of high-risk kidneys. MATERIALS AND METHODS: Using a center-level retrospective study, deceased donor transplants (115,485) from the Scientific Registry of Transplant Recipients from January 2003 to June 2016 were evaluated. Patients who received induction immunosuppression, including lymphocyte immune globulin, muromonab CD-3, IL-1 receptor antagonist, anti-thymocyte globulin, daclizumab, basiliximab, alemtuzumab, and rituximab, were included. Associations of center-level induction use with acute rejection in the first post-transplant year, graft failure, and patient mortality were evaluated using multivariable Cox and logistic regression. RESULTS: Among all kidneys, increasing percentage of center-level induction was associated with lower risk of graft failure, acute rejection, and patient mortality. In recipients of ARF kidneys, the beneficial association of induction on graft failure and acute rejection was greater than in those that received non-ARF kidneys. Marginally greater benefit of induction was seen for acute rejection in ECD compared to standard criteria donor (SCD) recipients and for graft failure in DCD compared to donors after brain death (DBD). No benefit of induction was detected for patient and graft survival in ECD recipients, acute rejection in DCD recipients, and patient survival in DGF recipients. No difference in the benefit of induction was detected in any other comparisons. CONCLUSIONS: While seemingly beneficial for recipients of all kidneys, induction has more robust associations with lower graft failure and acute rejection probability for recipients of ARF kidneys. Given the lack of observed benefit for ECD recipients, induction policies should be carefully considered in these patients.

Prognostic score matching methods for estimating the average effect of a non-reversible binary time-dependent treatment on the survival function.

In evaluating the benefit of a treatment on survival, it is often of interest to compare post-treatment survival with the survival function that would have been observed in the absence of treatment. In many practical settings, treatment is time-dependent in the sense that subjects typically begin follow-up untreated, with some going on to receive treatment at some later time point. In observational studies, treatment is not assigned at random and, therefore, may depend on various patient characteristics. We have developed semi-parametric matching methods to estimate the average treatment effect on the treated (ATT) with respect to survival probability and restricted mean survival time. Matching is based on a prognostic score which reflects each patient's death hazard in the absence of treatment. Specifically, each treated patient is matched with multiple as-yet-untreated patients with similar prognostic scores. The matched sets do not need to be of equal size, since each matched control is weighted in order to preserve risk score balancing across treated and untreated groups. After matching, we estimate the ATT non-parametrically by contrasting pre- and post-treatment weighted Nelson-Aalen survival curves. A closed-form variance is proposed and shown to work well in simulation studies. The proposed methods are applied to national organ transplant registry data.

The impact of intraoperative fluid management during laparoscopic donor nephrectomy on donor and recipient outcomes.

BACKGROUND: Intraoperative fluid management during laparoscopic donor nephrectomy (LDN) may have a significant effect on donor and recipient outcomes. We sought to quantify variability in fluid management and investigate its impact on donor and recipient outcomes. METHODS: A retrospective review of patients who underwent LDN from July 2011 to January 2016 with paired kidney recipients at a single center was performed. Patients were divided into tertiles of intraoperative fluid management (standard, high, and aggressive). Donor and recipient demographics, intraoperative data, and postoperative outcomes were analyzed. RESULTS: Overall, 413 paired kidney donors and recipients were identified. Intraoperative fluid management (mL/h) was highly variable with no correlation to donor weight (kg) (R = 0.017). The aggressive fluid management group had significantly lower recipient creatinine levels on postoperative day 1. However, no significant differences were noted in creatinine levels out to 6 months between groups. No significant differences were noted in recipient postoperative complications, graft loss, and death. There was a significant increase (P < 0.01) in the number of total donor complications in the aggressive fluid management group. CONCLUSIONS: Aggressive fluid management during LDN does not improve recipient outcomes and may worsen donor outcomes compared to standard fluid management.

Resident perceptions and evaluations of fellow-led and resident-led surgical services.

BACKGROUND: The impact of fellowship training on general surgery residency has remained challenging to assess. Surgical resident perceptions of fellow-led and resident-led surgical services have not been well described. METHODS: Retrospective cross-sectional data were collected from residents' service evaluations from 7/2014 through 7/2017. Surgical services were categorized as resident-led or fellow-led. 31 variables were evaluated and collapsed into 7 factors including clinical experience, educational experiences, clinical staff, workload, feedback, treatment of residents, and overall rotation. RESULTS: Among all PGY levels, fellow-led surgical services were rated significantly higher (p < 0.05) regarding clinical experience, clinical staff, treatment of residents, and overall rotation. PGY1-2 residents rated resident-led services significantly higher in the area of educational experiences, while PGY 3 residents rated resident-led services higher in the area of workload. However, PGY4-5 residents rated fellow-led services significantly higher in all 7 categories. Individual fellow-led services were rated significantly higher for various categories at different PGY levels. CONCLUSIONS: Surgical residents appear to value the educational experiences of fellow-led services. Each fellow-led service may ultimately provide unique educational opportunities and resources for different PGY levels.

Outcomes of Kidney Transplant Recipients With Posttransplant Genitourinary Infectious Complications: A Single Center Study.

OBJECTIVES: Long-term outcomes of kidney transplant recipients with postoperative genitourinary tract infections are not well characterized. In this single center retrospective study, we aimed to investigate the long-term effects of early posttransplant genitourinary infections under a protocol that included 1 month of antibiotic prophylaxis on graft failure and patient outcomes. MATERIALS AND METHODS: Electronic medical records of 1752 recipients of kidney-alone transplant between January 2000 and December 2008 were reviewed. Of these, 344 patients had postoperative genitourinary tract infections within 6 months of transplant. Infections included urinary tract infections, recurrent urinary tract infections, and pyelonephritis. All patients received 1-month of treatment with antibiotic prophylaxis for genitourinary infections after graft placement. Kaplan-Meier survival curves and multivariable regression modeling were performed to determine survival outcomes. RESULTS: In the 344 patients with postoperative infections, the most common cause was Escherichia coli (34.9%). Kaplan-Meier graft survival results showed no significant differences (P = .08) among those with and those without postoperative urinary tract infections; however, patient survival (P = .01) was significantly different. Multivariate analysis demonstrated no significant trend regarding graft failure (hazard ratio: 1.28; 95% confidence interval, 0.95-1.71; P = .09) or patient death (hazard ratio: 1.33; 95% confidence interval, 0.98-1.79; P = .06) in patients with and without genitourinary infections. The major cause of graft failure was infection in the infection cohort (17.4%). CONCLUSIONS: Kidney transplant recipients who develop urinary tract infections within 6 months of transplant may be at increased risk of graft failure or patient death; however, further studies are needed to elucidate the relationship between posttransplant infections and long-term outcomes.

Reevaluation of the Kidney Donor Risk Index.

BACKGROUND: The Kidney Donor Risk Index (KDRI) is a score applicable to deceased kidney donors which reflects relative graft failure risk associated with deceased donor characteristics. The KDRI is widely used in kidney transplant outcomes research. Moreover, an abbreviated version of KDRI is the basis, for allocation purposes, of the "top 20%" designation for deceased donor kidneys. Data upon which the KDRI model was based used kidney transplants performed between 1995 and 2005. Our purpose in this report was to evaluate the need to update the coefficients in the KDRI formula, with the objective of either (a) proposing new coefficients or (b) endorsing continued used of the existing formula. METHODS: Using data obtained from the Scientific Registry of Transplant Recipients, we analyzed n = 156069 deceased donor adult kidney transplants occurring from 2000 to 2016. Cox regression was used to model the risk of graft failure. We then tested for differences between the original and updated regression coefficients and compared the performance of the original and updated KDRI formulas with respect to discrimination and predictive accuracy. RESULTS: In testing for equality between the original and updated KDRIs, few coefficients were significantly different. Moreover, the original and updated KDRI yielded very similar risk discrimination and predictive accuracy. CONCLUSIONS: Overall, our results indicate that the original KDRI is robust and is not meaningfully improved by an update derived through modeling analogous to that originally employed.

Acute Kidney Injury After Liver Transplantation.

Since the implementation of the Model of End-stage Liver Disease score-based allocation system, the number of transplant candidates with impaired renal function has increased. The aims of this review are to present new insights in the definitions and predisposing factors that result in acute kidney injury (AKI), and to propose guidelines for the prevention and treatment of postliver transplantation (LT) AKI. This review is based on both systematic review of relevant literature and expert opinion. Pretransplant AKI is associated with posttransplant morbidity, including prolonged post-LT AKI which then predisposes to posttransplant chronic kidney disease. Prevention of posttransplant AKI is essential in the improvement of long-term outcomes. Accurate assessment of baseline kidney function at evaluation is necessary, taking into account that serum creatinine overestimates glomerular filtration rate. New diagnostic criteria for AKI have been integrated with traditional approaches in patients with cirrhosis to potentially identify AKI earlier and improve outcomes. Delayed introduction or complete elimination of calcineurin inhibitors during the first weeks post-LT in patients with early posttransplant AKI may improve glomerular filtration rate in high risk patients but with higher rates of rejection and more adverse events. Biomarkers may in the future provide diagnostic information such as etiology of AKI, and prognostic information on renal recovery post-LT, and potentially impact the decision for simultaneous liver-kidney transplantation. Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late chronic kidney disease.

Risk of peritoneal dialysis catheter-associated peritonitis following kidney transplant.

OBJECTIVE: Peritoneal dialysis (PD) patients have equivalent or slightly better kidney transplant outcomes when compared to hemodialysis (HD) patients. However, given the risk for postoperative infection, we sought to determine the risk factors for PD catheter-associated infections for patients who do not have the PD catheter removed at the time of engraftment. METHODS: Demographic and outcomes data were collected from 313 sequential PD patients who underwent kidney transplant from 2000 to 2015. Risk factors for postoperative peritonitis were analyzed using logistical regression. RESULTS: Of 329 patients with PD catheters at transplant, 16 PD catheters were removed at engraftment. Of the remaining 313 patients, 8.9% suffered post-transplant peritonitis. On univariate analysis, patients with peritonitis were significantly more likely to have used the PD catheter or HD within 6 weeks after transplant. Multivariate analysis had similar findings, with increased risk for those using the PD catheter after transplant, with a trend for those who underwent HD only within 6 weeks of transplant. CONCLUSION: These results suggest that delayed graft function requiring any type of dialysis is associated with increased post-transplant peritonitis risk.

Impact of screening for metabolic syndrome on the evaluation of obese living kidney donors.

BACKGROUND: We report our experience with metabolic syndrome screening for obese living kidney donor candidates to mitigate the long-term risk of CKD. METHODS: We retrospectively reviewed 814 obese (BMI≥30) and 993 nonobese living kidney donor evaluations over 12 years. Using logistic regression, we explored interactions between social/clinical variables and candidate acceptance before and after policy implementation. RESULTS: Obese donor candidate acceptance decreased after metabolic syndrome screening began (56.3%, 46.3%, p < 0.01), while nonobese candidate acceptance remained similar (59.6%, 59.2%, p = 0.59). Adjusting for age, gender, race, BMI, and number of prior evaluations, acceptance of obese candidates decreased significantly more than nonobese (p = 0.025). In candidates without metabolic syndrome, there was no significant change in how age, sex, race, or BMI affected a donor candidate's probability of acceptance. CONCLUSION: Metabolic syndrome screening is a simple stratification tool for centers with liberal absolute BMI cut-offs to exclude potentially higher-risk obese candidates.

Inequity in organ allocation for patients awaiting liver transplantation: Rationale for uncapping the model for end-stage liver disease.

BACKGROUND & AIM: The goal of organ allocation is to distribute a scarce resource equitably to the sickest patients. In the United States, the Model for End-stage Liver Disease (MELD) is used to allocate livers for transplantation. Patients with greater MELD scores are at greater risk of death on the waitlist and are prioritized for liver transplant (LT). The MELD is capped at 40 however, and patients with calculated MELD scores >40 are not prioritized despite increased mortality. We aimed to evaluate waitlist and post-transplant survival stratified by MELD to determine outcomes in patients with MELD >40. METHODS: Using United Network for Organ Sharing data, we identified patients listed for LT from February 2002 through to December 2012. Waitlist candidates with MELD ⩾40 were followed for 30days or until the earliest occurrence of death or transplant. RESULTS: Of 65,776 waitlisted patients, 3.3% had MELD ⩾40 at registration, and an additional 7.3% had MELD scores increase to ⩾40 after waitlist registration. A total of 30,369 (46.2%) underwent LT, of which 2,615 (8.6%) had MELD ⩾40 at transplant. Compared to MELD 40, the hazard ratio of death within 30days of registration was 1.4 (95% CI 1.2-1.6) for patients with MELD 41-44, 2.6 (95% CI 2.1-3.1) for MELD 45-49, and 5.0 (95% CI 4.1-6.1) for MELD ⩾50. There was no difference in 1- and 3-year survival for patients transplanted with MELD >40 compared to MELD=40. A survival benefit associated with LT was seen as MELD increased above 40. CONCLUSIONS: Patients with MELD >40 have significantly greater waitlist mortality but comparable post-transplant outcomes to patients with MELD=40 and, therefore, should be given priority for LT. Uncapping the MELD will allow more equitable organ distribution aligned with the principle of prioritizing patients most in need. Lay summary: In the United States (US), organs for liver transplantation are allocated by an objective scoring system called the Model for End-stage Liver Disease (MELD), which aims to prioritize the sickest patients for transplant. The greater the MELD score, the greater the mortality without liver transplant. The MELD score, however, is artificially capped at 40 and thus actually disadvantages the sickest patients with end-stage liver disease. Analysis of the data advocates uncapping the MELD score to appropriately prioritize the patients most in need of a liver transplant.

Outcomes of Kidney Transplant Recipients With Percutaneous Ureteral Interventions: A Single-Center Study.

BACKGROUND: Long-term outcomes of kidney transplantation recipients with percutaneous ureteral management of transplant ureteral complications are not well characterized. METHODS: Electronic records of 1753 recipients of kidney-alone transplant between January 2000 and December 2008 were reviewed. One hundred thirty-one patients were identified to have undergone percutaneous ureteral management, with placement of percutaneous nephrostomy tube or additional intervention (nephroureteral stenting and/or balloon dilation). Indications for intervention included transplant ureteral stricture or ureteral leak. Kaplan-Meier survival curves and multivariable regression modeling were performed to determine survival outcomes. RESULTS: Kaplan- Meier graft survival (P = 0.04) was lower in patients with percutaneous ureteral intervention for transplant ureteral complication. Graft survival at 1, 5, and 10 years was 94.3% 78.3%, and 59.1% for no intervention and 97.2%, 72.1%, and 36.2% for intervention cohort. Patient survival (P = 0.69) was similar between cohorts. Multivariate analysis demonstrated no association with graft failure (hazard ratio, 1.21; 95% confidence interval, 0.67-2.19; P = 0.53) or patient death (hazard ratio, 0.56; 95% confidence interval, 0.22-1.41; P = 0.22) in intervention group. The major cause of graft failure was infection for percutaneous ureteral intervention group (20.4%) and chronic rejection for those without intervention (17.3%). CONCLUSIONS: Kidney transplant recipients with percutaneous ureteral interventions for ureteral complications do not have a significant difference in graft and patient survival outcomes. Therefore, aggressive nonoperative management can be confidently pursued in the appropriate clinical setting.

Use of complement binding assays to assess the efficacy of antibody mediated rejection therapy and prediction of graft survival in kidney transplantation.

BACKGROUND: The Luminex® single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ⩾50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR. METHODS: We tested pre- and post-treatment sera of 30 kidney transplant patients receiving plasmapheresis and low-dose IVIG for biopsy-proven AMR. IgG-DSA and C1q-DSA MFI were measured and correlated with graft loss or survival. Patients were classified as nonresponders (NR) when treatment resulted in <50% reduction in MFI of IgG-DSA and/or C1q-DSA was detectable following therapy. RESULTS: Differences in the percentage of patients deemed NR depended upon the end-point criterion (73% by reduction in IgG-DSA MFI vs. 50% by persistent C1q-DSA activity). None of the seven patients with <50% reduction of IgG-DSA but non-detectable C1q-DSA-fixing activity after therapy experienced graft loss, suggesting that C1q-DSA activity may better correlate with response. Reduction of C1q-DSA activity predicted graft survival better than IgG-DSA in the univariate Cox analysis (20.1% vs. 5.9% in NR; log-rank P-value=0.0147). CONCLUSIONS: A rapid reduction of DSA concentration below the threshold required for complement activation is associated with better graft survival, and C1q-DSA is a better predictor of outcomes than IgG-DSA MFI reduction.