Expanding the access to kidney transplantation: Strategies for kidney transplant programs.

Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such partnerships. Providing early culturally congruent and patient-centered education as well as maximizing the use of local resources to facilitate the transplant work up should be prioritized. Every opportunity to facilitate pre-emptive kidney transplantation and living donation must be taken. Promoting the use of telemedicine and kidney paired donation as standards of care can positively impact the work up completion and maximize the chances of a living donor kidney transplant.

Vasopressin for Post-kidney Transplant Hypotension.

Introduction: Hypotension after deceased donor kidney transplant (DDKT) is a risk factor for delayed graft function (DGF) and poor graft survival (GS). We hypothesize that vasopressin use in hypotensive DDKT recipients (DDKTRs) to increase blood pressure (BP) reduces DGF rates and is safe without increasing mortality. Methods: Group with vasopressin "study group" (n = 45) was defined as DDKTRs between 2012 and 2017 who required vasopressin for hypotension systolic BP (SBP) <120 mm Hg or diastolic BP (DBP) <60 mm Hg. DDKTRs with no-vasopressin "comparison group" (n = 90) were propensity score-matched DDKTRs between 2012 and 2017 without vasopressin use. Primary outcomes were GS, creatinine and allograft biopsy rate at 1 year, DGF rate, and death during transplant hospitalization. Results: Vasopressin group had lower mean maximum and minimum SBP and DBP in the operating room (OR). Median vasopressin start time post-DDKT was 2 hours (interquartile range [IQR] 1-6), and duration of use was 42 hours (IQR 24-63). DGF, creatinine at 1 year, and allograft biopsy rates were comparable. No deaths occurred during transplant hospitalization. Multivariable analysis did not find an effect of vasopressin use on GS. Conclusion: Treatment of hypotensive DDKTRs with vasopressin is safe and facilitated similar graft function and survival with that of nonhypotensive patients. In the absence of a randomized control trial, our study supports the safety of vasopressin therapy to prevent the adverse effects of hypotension.

Nondirected Living Kidney Donation and Recipient Outcomes in the United States: A 20-Year Review.

Introduction: Nondirected donation (NDD) of the kidneys is a growing practice where donors who do not have any genetic or emotional relationship are selected to donate to a wide variety of recipients with a range of selection criteria and decisions which are left up to individual transplant centers. Methods: We review all adult living kidney donor-recipient (DR) pairs and outcomes from NDDs who were recorded in United Network for Organ Sharing (UNOS) database as code 10 (anonymous) from October 1997 to September 2017 for demographics and outcomes. Results: A total of 2174 DR pairs were identified. The number of NDDs increased from 18 in 2000 to 256 in 2016. Survival analysis showed higher death-censored-graft survival (DC-GS) when recipient was 20 years or more older than donor followed by recipient-donor within 20 years of age and lowest when donor was 20 years or more older than recipient (P = 0.0114). Conclusion: Overall, the number of NDDs has increased significantly in the 20-year review period. Transplants from NDDs have excellent long-term outcomes. Better matching of controllable DR factors, such as age and body mass index (BMI), could further improve GS. Further research is needed to incorporate these DR factors into paired kidney donation programs potentially enhancing the utility and beneficence of this invaluable donation.

Patient and Graft Survival Outcomes During 2 Eras of Immunosuppression Protocols in Kidney Transplantation: Indiana University Retrospective Cohort Experience.

BACKGROUND: Since 1964 when Indiana University performed its first kidney transplant, immunosuppression protocol was steroid-based until 2004 when steroid-free immunosuppression protocol was adopted. We describe clinical outcomes on our patients administered early steroid withdrawal (ESW) protocol (5 days) compared with our historical cohort (HC), who were on chronic steroid-based immunosuppression. METHODS: We performed a retrospective study evaluating kidney transplant recipients between 1993 and 2003 (HC, n = 1689) and between 2005 and 2016 (ESW cohort, n = 2097) at the Indiana University program, with a median follow-up of 10.5 years and 6.1 years, respectively. Primary outcomes were patient and death-censored graft survival at 1, 3, and 5 years in both study cohorts. Secondary outcomes were 1-year rates of biopsy-proven acute rejection; graft function at 1, 3, and 5 years; and risk of post-transplant infection (BK virus and cytomegalovirus) in the ESW cohort. Cox proportional model and Kaplan-Meier estimates were used to estimate survival probabilities. Fisher exact tests were used to compare episodes of acute rejection in the ESW cohort. RESULTS: No difference was observed in patient survival between the ESW and HC cohorts (P = .13). Compared with the ESW cohort, death-censored graft survival was significantly worse in the HC (5 year: 86.4% vs 90.6%, log-rank P < .001). One-year acute rejection reported in the ESW cohort alone was 15.7% and significantly worse in Black patients and younger patients (P < .05). CONCLUSIONS: In this sizeable single-center cohort study with significant ethnic diversity, ESW is a viable alternative to steroid-based immunosuppression protocol in kidney transplant recipients.

A National Survey of Practice Patterns for Accepting Living Kidney Donors With Prior COVID-19.

INTRODUCTION: A critical question facing transplant programs is whether, when, and how to safely accept living kidney donors (LKDs) who have recovered from COVID-19 infection. The purpose of the study is to understand current practices related to accepting these LKDs. METHODS: We surveyed US transplant programs from 3 September through 3 November 2020. Center level and participant level responses were analyzed. RESULTS: A total of 174 respondents from 115 unique centers responded, representing 59% of US LKD programs and 72.4% of 2019 and 72.5% of 2020 LKD volume (Organ Procurement and Transplantation Network-OPTN 2021). In all, 48.6% of responding centers had received inquiries from such LKDs, whereas 44.3% were currently evaluating. A total of 98 donors were in the evaluation phase, whereas 27.8% centers had approved 42 such donors to proceed with donation. A total of 50.8% of participants preferred to wait >3 months, and 91% would wait at least 1 month from onset of infection to LD surgery. The most common reason to exclude LDs was evidence of COVID-19-related AKI (59.8%) even if resolved, followed by COVID-19-related pneumonia (28.7%) and hospitalization (21.3%). The most common concern in accepting such donors was kidney health postdonation (59.2%), followed by risk of transmission to the recipient (55.7%), donor perioperative pulmonary risk (41.4%), and donor pulmonary risk in the future (29.9%). CONCLUSION: Practice patterns for acceptance of COVID-19-recovered LKDs showed considerable variability. Ongoing research and consensus building are needed to guide optimal practices to ensure safety of accepting such donors. Long-term close follow-up of such donors is warranted.

Living Donor Gifted Lithiasis: Long-Term Outcomes in Recipients.

OBJECTIVES: Presence of nephrolithiasis in a living donor has been at least a relative contraindication to living donor nephrectomy. The concern for stone recurrence and outcomes has been one of the reasons for reluctance to consider these medically complex donors. We evaluate long-term outcomes in recipients of kidney grafts from donors with nephrolithiasis, or history of nephrolithiasis, and provide results from our experience at Indiana University. MATERIALS AND METHODS: We retrospectively reviewed 57 donor-recipient pairs, where the allograft was received from a living donor with symptomatic calculi, or with imaging evidence of kidney stones, between 2003 and 2018. This research study was done in compliance with the ethical standards set forth in the Helsinki Congress. RESULTS: The mean age of recipients was 46±19 years and 58% were male. Kidney recipients were followed for a median of 3.5 years and 59.6% of patients had follow-up imaging studies. None of the recipients had obstructing renal calculi or related infections. None of the recipients required any interventions for recurrent calculi and no stone episode lead to adverse event to the graft. Hyperoxaluria and hypercalciuria were the most common risk factors in 24-hour urine collections obtained from donors. CONCLUSIONS: Our findings from a single large center looking at kidney recipient outcomes over a long follow-up period found that gifted lithiasis is a safe procedure. Careful selection of "medically complex donors" with kidney stones based on appropriate guidelines is a key step. Further studies are needed to help develop consensus guidelines.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

Health insurance status affects hypertension control in a hospital based internal medicine clinic.

Hypertension is a worldwide disorder that contributes significantly to morbidity, mortality, and healthcare costs in both developed and developing communities. A retrospective cohort study of hypertensive patients attending the Internal Medicine continuity clinic at Nashville General Hospital (NGH) between January and December 2007 was conducted. Given the easy access to health care at NGH and affordable Blood pressure (BP) medications, we explored the ability to achieve optimal BP control <140/90 â€‹mmHg and evaluated which factors are associated. Of the 199 subjects, 59% achieved BP goal <140/90 â€‹mmHg. The mean BP was 139/80 â€‹mmHg. Health insurance status was associated with SBP and DBP (All P â€‹< â€‹0.046). Patients with health insurance had a 2.2 fold increased odds of achieving BP control compared to patients without health insurance (P â€‹= â€‹0.025). Furthermore, the number of BP medications used was significantly associated with SBP and DBP (All P â€‹< â€‹0.003). Patients taking more than three BP medications had a 58% reduced odds of achieving optimal BP control compared to patients taking one medication (P â€‹= â€‹0.039). Ethnicity was not associated with achieving BP control. Our study revealed the number of BP medications used and health insurance status, are factors associated with achieving BP control.

De Novo Donor-Specific Antibody Formation in Tacrolimus-Based, Mycophenolate Versus Mammalian Target of Rapamycin Immunosuppressive Regimens.

OBJECTIVES: De novo donor-specific antibody formation posttransplant is associated with decreased graft survival. It is not known whether mammalian target of rapamycin inhibitors may be advantageous or detrimental compared with mycophenolate in the prevention of de novo donor-specific antibody formation. MATERIALS AND METHODS: We compared 66 kidney and kidney-pancreas transplant recipients who received tacrolimus, mammalian target of rapamycin inhibitor, and prednisone (group 1; 36 of whom received everolimus and 30 of whom received sirolimus) versus 132 patients who received tacrolimus, mycophenolate, and prednisone (group 2) matched for age, sex, race, and type/timing of transplant from 2007 to 2012. RESULTS: Rates of de novo donor-specific antibody formation were comparable between groups at 1, 6, and 12 months (16.7%, 25.8%, and 28.8% for group 1 vs 9.8%, 15.2%, and 22.0% for group 2). There were no significant differences in class (I, II, or mixed), strength (mean fluorescence intensity) of de novo donor-specific antibody, glomerular filtration rate, proteinuria levels, or acute rejection between the groups. In those with de novo donor-specific antibody by 6 months, acute rejection was more common versus those without de novo donor-specific antibody formation (24.3% vs 5.6% at 6 mo; P = .002), with rates of 27.0% versus 6.8% at 1 year (P = .001) and 40.7% versus 11.3% at 2 years (P < .001). An associated reduction in glomerular filtration rate also occurred. CONCLUSIONS: Mammalian target of rapamycin inhibitors were neither protective nor permissive for de novo donor-specific antibody formation versus mycophenolate when used with clinically relevant tacrolimus dosing regimens.

Donor specific antibodies before and after kidney transplant: the University of Colorado Experience.

We summarize in this manuscript our donor specific antibody (DSA) screening experience in the past six years as it applies to pre-existing DSA, de novo DSA, and post-transplant DSA treatment. Of 547 patients receiving a kidney or kidney/pancreas with negative pre-transplant flow cytometry crossmatch (FCXM), 196 had DSA (mean fluorescence intensity, MFI >or= 500) detected prior to transplant by single antigen bead analysis. Acute rejection rates at one year were similar in DSA+ versus DSA- (15% versus 12%, respectively, p=0.22), although acute rejection occurred earlier in the DSA+ group. De novo DSA was detected in 65 of 261 patients (27%). All DSA was detected within the first posttransplant year. While acute rejection was more likely in patients with de novo DSA (29% versus 9.5% in those with no DSA), prospective DSA screening failed to predict this outcome as DSA was detected at the time of or after a rejection episode in 16 of 19 patients with both DSA and acute rejection. Two-year estimated graft survival was significantly worse in patients with versus without DSA, but was identical when removing patients with a prior acute rejection episode from the analysis. We have used a protocol of high dose (5 gm/kg) intravenous immunoglobulin infused over the course of 6 months in patients with DSA and either chronic graft dysfunction or following a recent acute antibody mediated rejection (AMR) episode. DSA MFI was reduced by 18% from the time of initiation to last follow up. This effect was largely due to reductions in class I DSA (-37%) and DSA in patients with a recent acute AMR (-51.5%), with a minimal effect on class II DSA and DSA in patients with chronic graft dysfunction. Despite treatment directed at antibody-producing plasma cells, antibody levels either persisted or worsened with no improvement in graft function. Overall, DSA is more amendable to treatment when associated with a recent acute rejection event.

Pulmonary hemorrhage with hematuria: do not forget IgA nephropathy.

IgA nephropathy is the commonest cause of glomerulonephritis worldwide, and is usually a renal-limited disease. In rare cases, IgA nephropathy may also present with a pulmonary-renal syndrome in which pulmonary hemorrhage is a critical feature. Patients presenting with IgA nephropathy and pulmonary hemorrhage have high morbidity and are at high risk for mortality unless rapid immunosuppressive therapy is instituted. We present a case of IgA nephropathy complicated by pulmonary hemorrhage in which immunosuppressive therapy led to a good outcome, and review the literature on similar cases and the outcome of therapy.

Retroperitoneal fibrosis: a rare cause of acute renal failure.

Introduction. Retroperitoneal fibrosis is a rare cause of acute renal failure (ARF) with only a handful of cases reported in literature. We report a case of a 40-year-old male with an incidental finding of retroperitoneal fibrosis. Case Presentation. Patient is a 40-year-old African American male with no significant past medical history who presented with a four-month history of low back pain and associated nausea with vomiting. Physical examination was significant for elevated blood pressure at 169/107 mmhg and bilateral pedal edema. Significant admission laboratory include blood urea nitrogen (BUN) of 108 mg/dL, serum creatinine (Cr) of 23 mg/dL, bicarbonate of 19 mg/dL, and potassium of 6.2 mmL/L. Renal ultrasound showed bilateral hydronephrosis. Post-void residual urine volume was normal. Abdominopelvic CT scan showed retroperitoneal fibrosis confirmed with fine-needle biopsy. He was treated with a combination of bilateral ureteral stent placement, hemodialysis, and steroid therapy. Four months after hospital discharge, his BUN and Cr levels Improved to 18 mg/dL and 1.25 mg/dL, respectively. Conclusion. Retroperitoneal fibrosis should be considered as a differential diagnosis in patients with acute renal failure and obstructive uropathy. Abdominal CT scan is the examination of choice for diagnosis. Full resolution with treatment depends on the duration of obstruction.