Outcomes of de novo belatacept-based immunosuppression regimen and avoidance of calcineurin inhibitors in recipients of kidney allografts at higher risk for underutilization.

To describe an experience using a protocol using de novo belatacept (DNB) based maintenance immunosuppression in the setting of lymphocyte depletion. A retrospective, observational study was performed on 37 kidney transplant recipients treated with the DNB protocol, which was defined as belatacept initiated within 7 days after a kidney transplant with steroids and mycophenolate with anti-thymocyte globulin (ATG) induction without concomitant calcineurin inhibitors (CNIs). Patients who received a deceased donor kidney meeting one or more of the following criteria: anticipated cold ischemia time (CIT) greater than 24 h, donation after cardiac death, donor acute kidney injury, and a Kidney Donor Profile Index (KDPI) >85% during the study period were included. Patient survival at 1 year was 97.3% and graft survival was 94.6%. Delayed graft function (DGF) occurred in 40.54% of the patients. Two patients experienced a Banff 1B acute cellular rejection. BK viremia was detected in 32.4% of patients. The mean estimated glomerular filtration rate (eGFR) calculated with the use of modification of diet in renal disease (MDRD) equation at 1 year in the study group was 54.7 ml/min/1.73 m2 . We believe that utilization of the DNB protocol, which allows early CNI avoidance, may decrease organ discard rates.

Bortezomib for Reduction of Proteinuria in IgA Nephropathy.

INTRODUCTION: IgA nephropathy is the most common glomerulonephritis in the world. We conducted a pilot trial (NCT01103778) to test the effect of bortezomib in patients with IgA nephropathy and significant proteinuria. METHODS: We treated 8 consecutive subjects from July 2011 until March 2016 with 4 doses of bortezomib. All subjects had biopsy-proven IgA nephropathy and proteinuria of greater than 1 g per day. They were given 4 doses of bortezomib i.v. at 1.3 mg/m2 of body surface area per dose. Changes in proteinuria and renal function were followed for 1 year after enrollment. The primary endpoint was full remission defined as proteinuria of less than 300 mg per day. RESULTS: All 8 subjects received and tolerated 4 doses of bortezomib over a 2-week period during enrollment. The median baseline daily proteinuria was 2.46 g (interquartile range: 2.29-3.16 g). At 1-year follow-up, 3 subjects (38%) had achieved the primary endpoint. The 3 subjects who had complete remission had Oxford classification T scores of 0 before enrollment. Of the remaining 5 subjects, 1 was lost to follow-up within 1 month of enrollment and 4 (50%) did not have any response or had progression of disease. CONCLUSION: Proteasome inhibition by bortezomib may reduce significant proteinuria in select cases of IgA nephropathy. Subjects who responded to bortezomib had Oxford classification T score of 0 and normal renal function.

Differences in Attitudes Toward Immunosuppressant Therapy in a Multi-ethnic Sample of Kidney Transplant Recipients.

Barriers for renal transplant patients to immunosuppressant medication adherence are poorly understood, despite the high rate and toll of non-adherence. We sought to assess factors that contribute to barriers to immunosuppressive medication adherence in an ethnically diverse sample of 312 renal transplant patients recruited from three transplant centers across New York City. Transplant patients who were at least 6 months post-transplant completed questionnaires while waiting for their medical appointment. Ethnic differences were observed on barriers to immunosuppressant adherence. Black and Hispanic participants reported significantly more barriers to adherence compared to Caucasian participants. Differences in perception about the potential harm and necessity of immunosuppressant medications also were present. Using hierarchical multiple regression, age and income were significant predictors of reported barriers to adherence, even while controlling for ethnicity. The most robust predictor of reported barriers was the perception of the medication cost-benefit differential, i.e., the balance between concerns about immunosuppressant medications and their perceived helpfulness (B = - 0.5, p < .001), indicating that varying beliefs about the medication's necessity and utility rather than ethnicity explain the differences in barriers to medication adherence. Future interventions targeting non-adherence should aim to reduce the barriers to adherence by addressing perceived risks and benefits of taking immunosuppressant medication.

Kidney allograft failure in the steroid-free immunosuppression era: A matched case-control study.

We studied the causes and predictors of death-censored kidney allograft failure among 1670 kidney recipients transplanted at our center in the corticosteroid-free maintenance immunosuppression era. As of January 1, 2012, we identified 137 recipients with allograft failure; 130 of them (cases) were matched 1-1 for recipient age, calendar year of transplant, and donor type with 130 recipients with functioning grafts (controls). Median time to allograft failure was 29 months (interquartile range: 18-51). Physician-validated and biopsy-confirmed categories of allograft failure were as follows: acute rejection (21%), glomerular disease (19%), transplant glomerulopathy (13%), interstitial fibrosis tubular atrophy (10%), and polyomavirus-associated nephropathy (7%). Graft failures were attributed to medical conditions in 21% and remained unresolved in 9%. Donor race, donor age, human leukocyte antigen mismatches, serum creatinine, urinary protein, acute cellular rejection, acute antibody-mediated rejection, BK viremia, and CMV viremia were associated with allograft failure. Independent predictors of allograft failure were acute cellular rejection (odds ratio: 18.31, 95% confidence interval: 5.28-63.45) and urine protein ≥1 g/d within the first year post-transplantation (5.85, 2.37-14.45). Serum creatinine ≤1.5 mg/dL within the first year post-transplantation reduced the odds (0.29, 0.13-0.64) of allograft failure. Our study has identified modifiable risk factors to reduce the burden of allograft failure.

In-Hospital Cardiovascular Complications After Pancreas Transplantation in the United States from 2003 to 2012.

Large database studies detailing the risk of perioperative cardiovascular complications after pancreas transplant has been limited, perhaps because these outcomes are not captured by transplant registries. Greater data on the incidence and risks of such outcomes could provide additional insight for referring physicians and inform potential recipients of their risk. We performed a serial, cross-sectional analysis of the National Inpatient Sample, the largest publicly available inpatient database in the United States, to assess for the risk of cardiovascular complications after pancreas transplants in the United States from 2003 to 2012 (n = 13,399). Using multivariable logistic regression models, the risk of cardiovascular outcomes after simultaneous pancreas-kidney transplants (SPK) was compared with solitary pancreas transplants (pancreas after kidney and pancreas transplant alone [PAK + PTA]). The unadjusted prevalence of in-hospital cardiovascular complications was higher in SPK than PAK + PTA (5.5% vs 3.7%, p <0.001). After multivariable adjustment, SPK remained associated with significantly higher odds of any cardiovascular complication (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.21 to 1.80, p = 0.01), and particularly stroke (OR 13.41, 95% CI 4.78 to 37.63, p <0.001), compared with PAK + PTA. However, there was no difference in perioperative mortality (OR 0.78, 95% CI 0.54 to 1.12, p = 0.18). In conclusion, these findings highlight the association between uremia and stroke in pancreas transplant patients, as well as the need for improved preoperative cardiac risk assessment and perioperative management, especially in those who underwent SPK.

Long term follow up of kidney donors with asymptomatic renal stones.

Patients with asymptomatic kidney stones have a high rate of progression to becoming symptomatic kidney stones when followed for several years. Small kidney stones are often found incidentally on imaging when evaluating patients for kidney donation, and there is a concern that after nephrectomy, the donor may become symptomatic and incur damage to the remaining kidney. We reviewed kidney donors at our institution with asymptomatic stones and surveyed them several years after donation to see if the stones became clinically active.

Development and validation of a prognostic index for allograft outcome in kidney recipients with transplant glomerulopathy.

We studied 92 patients with transplant glomerulopathy to develop a prognostic index based on the risk factors for allograft failure within five years of diagnosis (Development cohort). During 60 months (median) follow-up, 64 patients developed allograft failure. A chronic-inflammation score generated by combining Banff ci, ct and ti scores, serum creatinine and proteinuria at biopsy, were independent risk factors for allograft failure. Based on the Cox model, we developed a prognostic index and classified patients into risk groups. Compared to the low-risk group (median allograft survival over 60 months from diagnosis), patients in the medium risk group had a hazard ratio of 2.83 (median survival 25 months), while those in the high-risk group had a hazard ratio of 5.96 (median survival 3.7 months). We next evaluated the performance of the prognostic index in an independent external cohort of 47 patients with transplant glomerulopathy (Validation cohort). The hazard ratios were 2.18 (median survival 19 months) and 16.27 (median survival 1.6 months), respectively, for patients in the medium and high-risk groups, compared to the low-risk group (median survival 47 months). Our prognostic index model did well in measures of discrimination and calibration. Thus, risk stratification of transplant glomerulopathy based on our prognostic index may provide informative insight for both the patient and physician regarding prognosis and treatment.

High prevalence of colon adenomas in end-stage kidney disease patients on hemodialysis undergoing renal transplant evaluation.

The aim of this study was to determine whether patients with end-stage kidney disease (ESKD) on hemodialysis (HD) undergoing kidney transplant evaluation are at higher risk for colonic neoplasia than the general population. This is a retrospective cohort study of patients with ESKD who underwent a first screening colonoscopy while undergoing kidney transplant evaluation. Data were collected on the prevalence of adenomatous polyps and advanced adenomas in 70 patients with ESKD and 70 controls, undergoing their first screening colonoscopy, matched for age, gender, and endoscopist. At the time of the colonoscopy, an average time on HD was 3.2 ± 2.9 yr. The prevalence of adenomatous polyps was significantly higher in ESKD on HD (54.3% vs. 32.9%, p = 0.008) than in controls. In a multivariate analysis controlling for other factors, ESKD on HD remained a risk factor for the presence of adenomas (OR 3.06, 95% CI 1.21, 7.73). No colonoscopy-related complications were reported in the patients with ESKD on HD. We demonstrate a significantly higher prevalence of adenomatous polyps in patients with ESKD undergoing a first screening colonoscopy as part of kidney transplant evaluation. In addition, colonoscopy can be safely performed in this population.

Solicited kidney donors: Are they coerced?

Most non-directed donors (NDDs) decide to donate on their own and contact the transplant centre directly. Some NDDs decide to donate in response to community solicitation such as newspaper ads or donor drives. We wished to explore whether subtle coercion might be occurring in such NDDs who are part of a larger community. One successful organization in a community in Brooklyn, NY, provides about 50 NDDs per year for recipients within that community. The donors answer ads in local papers and attend donor drives. Herein, we evaluated the physical and emotional outcomes of community-solicited NDDs in comparison to traditional NDDs who come from varied communities and are not responding to a specific call for donation. An assessment of coercion was used as well.

Living Donor Kidney Transplantation: Improving Efficiencies in Live Kidney Donor Evaluation--Recommendations from a Consensus Conference.

The education, evaluation, and support of living donors before, during, and after donation have historically been considered the roles and responsibilities of transplant programs. Although intended to protect donors, ensure true informed consent, and prevent coercion, this structure often leaves referring nephrologists unclear about the donor process and uncertain regarding the ultimate outcome of potential donors for their patients. The aim of this article is to help the referring nephrologist understand the donor referral and evaluation process, help the referring nephrologist understand the responsibilities of the transplant program, and offer suggestions about how the referring nephrologist can help to improve efficiencies in the process of donor education and evaluation. A partnership between referring nephrologists and transplant programs is an important step in advancing living kidney donation. The referring nephrologists are the frontline providers and are in a unique position to offer education about living donation and improve efficiencies in the process. Understanding the donor referral and evaluation process, the responsibilities of the transplant program, and the potential role referring nephrologists can play in the process is critical to establishing such a partnership.

Is donating a kidney to a friend bad for your marriage?

Studies have shown that kidney donation to a spouse has a positive impact on marriage. This study was done to evaluate the impact on marriage when donation occurs to someone other than the spouse. Two groups of donors from our centre who donated around the same period were studied: donation to a spouse (spouse donor (SD)) or to someone other than the spouse (non-spouse donor (ND)). A survey, the Revised Dyadic Adjustment Scale, was used to evaluate the effect of donation on the marriage. This tool consists of 14 questions that measure how satisfying and stable the relationship is. The results showed equal or better marriage scores in the ND group compared with the SD group. The NDs scored higher on two questions, one regarding agreement or disagreement on career choices (P = 0.05) and the other regarding the frequency of having stimulating exchanges of ideas with one's spouse (P = 0.02). With the highest possible total score of 69, NDs scored 53.4 and SDs scored 47.7 (P = 0.16). Scores of 47 and below indicate marital distress. In one final additional question, 97% of NDs reported 'no change or good effect' on the marriage, similar to 91% for SDs (P = 0.46). This is the first study to evaluate the effect of kidney donation on the state of marriage when the spouse is not the recipient. It appears that marriage is not impacted negatively when kidney donation occurs to someone other than the spouse.

Semiautomated CT-Based Quantification of Donor Kidney Volume Applied to a Predictive Model of Outcomes in Renal Transplantation.

OBJECTIVE: The purpose of this study was to assess the use of semiautomated CT-based quantification of renal graft volume as a preoperative predictor of graft function. MATERIALS AND METHODS: All transplants over a 3-year period in which donors underwent CT and for which recipient outcomes were available were included. Two blinded readers used a commercially available reconstruction tool to independently measure donated kidney cortical volume and total parenchymal kidney volume. Transplant characteristics obtained by chart review included subject demographics, recipient pretransplant weight, immunologic matching, and recipient creatinine values at multiple time points. Intraclass correlation of measurements by the two readers was calculated. The ratios between donated kidney cortical volume and recipient pretransplant weight were correlated with graft function over 24 months and used in logistic regression models to calculate the odds of development of diminished renal function. RESULTS: After application of the inclusion and exclusion criteria, 153 transplants were included in the study. Donated kidney cortical and total parenchymal volume measurements had high correlation (R > 0.9) and high reproducibility (intraclass correlation coefficient, 0.93-0.94). Unadjusted correlations existed between estimated glomerular filtration rate (eGFR) and the ratio between donated kidney cortical volume and recipient pretransplant weight 12 months (R = 0.8489) and 24 months (R = 0.6839) after transplant. After adjustment for transplant parameters, recipients in the highest tertile for ratio between donated kidney cortical volume and recipient pretransplant weight (2.7 mL/kg) had higher mean eGFR values at all time points in the 24 months than did recipients in the lower tertiles (1.2 and 1.6 mL/kg). Recipients in the highest tertile had a significantly lower risk of development of diminished renal function 12 and 24 months after transplant (adjusted odds ratios, 0.25 at 12 months [95% CI, 0.09-0.66]; 0.27 at 24 months [95% CI, 0.10-0.71]). CONCLUSION: The CT-derived ratio between donated kidney cortical volume and recipient pretransplant weight is a noninvasively and readily obtained reproducible biomarker that is predictive of 12- and 24-month renal transplant outcomes.

Donors in chains: psychosocial outcomes of kidney donors in paired exchange.

BACKGROUND: Kidney paired donation chains are initiated by nondirected donors and propagated by donors within the chain of transplants, or chain donors. OBJECTIVE: To compare psychosocial and functional outcomes, and to test coercion, of chain donors in paired exchange versus traditional directed donors who have an established relationship with the recipient. METHODS: Thirty chain donors from a transplant center who were part of the National Kidney Registry paired exchange program were compared with 34 traditional donors who donated around the same time. Participants completed online surveys: the postdonation section of the Living Donor Expectancies Questionnaire was used to assess psychosocial and functional outcomes 1 to 6 years after donation. A survey to assess coercion was used as well. RESULTS: Chain donors and traditional donors were similar in terms of sex, race, age, and time after donation. The 2 groups had similar altruistic motives in donating their kidney, and both types of donors mentioned psychological benefits. No differences were found on questions regarding psychosocial outcomes save for the "quid pro quo scale" (P= .01), which suggested that the traditional donors felt more that the recipients are indebted to them. The 2 groups did not differ significantly in the coercion measure. Pressure to donate and stress of donation were not greater in chain donors than traditional donors (P= .60). CONCLUSION: Kidney donors in kidney paired donation chains do as well as traditional donors psychosocially without any increased tendency toward experiencing coercion.

HIV-infected kidney graft recipients managed with an early corticosteroid withdrawal protocol: clinical outcomes and messenger RNA profiles.

BACKGROUND: The outcome of HIV-infected kidney transplant recipients managed with an early corticosteroid withdrawal protocol is not known. METHODS: Eleven consecutive HIV-infected patients with undetectable plasma HIV RNA and more than 200/mm CD4 T cells underwent deceased-donor (n=8) or living-donor (n=3) kidney transplantation at our center. All were managed with an early corticosteroid withdrawal protocol; 9 of 11 received antithymocyte globulin and 2 received basiliximab induction. We analyzed patient and graft outcomes, acute rejection rate, HIV progression, BKV replication, infections, and urinary cell mRNA profiles. RESULTS: The median (range) follow-up was 44.5 (26-73) months. The incidence of acute rejection was 9% at 1 year and the patient and allograft survival rates were 100% and 91%, respectively. Estimated glomerular filtration rate at 1 year (mean ± SD) was 78 ± 39 mL/min/1.73 m. Plasma HIV RNA was undetectable at 24 months and none had BKV replication. Six of the 11 kidney recipients developed eight infections requiring hospitalization. Urinary cell levels of mRNA for complement components and complement regulatory proteins, cell lineage-specific proteins CD3, CD4, CD8, CTLA4, Foxp3, chemokine IP-10, cytotoxic perforin and granzyme B, and BKV VP1 mRNA were not different (P>0.05) between HIV-infected patients and HIV-negative recipients (n=22) with stable graft function and normal biopsy results. CONCLUSION: An early steroid withdrawal regimen with antithymocyte globulin induction was associated with excellent graft and patient outcomes in HIV-infected recipients of kidney allografts. Their urinary cell mRNA profiles are indistinguishable from those of HIV-negative patients with stable graft function and normal biopsy results.

Excellent outcomes with expanded criteria donor kidneys: the role of the recipient's age.

At the present time, the number of deceased donor kidney transplants performed annually has remained unchanged for 4 years. Desire for standard criteria donor (SCD) kidneys by recipients, coupled with high discard rates of donor kidneys, contributes to a lack of procedures being performed. A subgroup of recipients, those under age 50, may fare as well with an expanded criteria donor (ECD) allograft as those who receive an SCD kidney. The use of ECD allografts in recipients over 50 years of age, while projected to have poorer allograft survival than that produced with an SCD graft, still results in better recipient survival than patients who have elected to remain on dialysis.