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Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.

OBJECTIVE To examine the largest single-center experience of simultaneous kidney/pancreas transplantation (SPK) transplantation among African-Americans (AAs). BACKGROUND Current dogma suggests that AAs have worse survival following SPK than white recipients. We hypothesize that this national trend may not be ubiquitous. METHODS From August 30, 1999, through October 1, 2014, 188 SPK transplants were performed at the University of Alabama at Birmingham (UAB) and 5523 were performed at other US centers. Using Kaplan-Meier survival estimates and Cox proportional hazards regression, we examined the influence of recipient ethnicity on survival. RESULTS AAs comprised 36.2% of the UAB cohort compared with only 19.1% nationally (P < 0.01); yet, overall, 3-year graft survival was statistically higher among UAB than US cohort (kidney: 91.5% vs 87.9%, P = 0.11; pancreas: 87.4% vs 81.3%; P = 0.04, respectively) and persisted on adjusted analyses [kidney adjusted hazard ratio (aHR): 0.58, 95% confidence interval (95% CI) 0.35-0.97, P = 0.04; pancreas aHR: 0.54, 95% CI 0.34-0.85, P = 0.01]. Among the UAB cohort, graft survival did not differ between AA and white recipients; in contrast, the US cohort experienced significantly lower graft survival rates among AA than white recipients (kidney 5 years: 76.5% vs 82.3%, P < 0.01; pancreas 5 years: 72.2% vs 76.3%, P = 0.01; respectively). CONCLUSION Among a single-center cohort of SPK transplants overrepresented by AAs, we demonstrated similar outcomes among AA and white recipients and better outcomes than the US experience. These data suggest that current dogma may be incorrect. Identifying best practices for SPK transplantation is imperative to mitigate racial disparities in outcomes observed at the national level.

Supplemental Digital Content is available in the text., Background. Surveillance biopsies permit early detection of subclinical inflammation before clinical dysfunction, but the impact of detecting early subclinical phenotypes remains unclear. Methods. We conducted a single-center retrospective cohort study of 441 consecutive kidney transplant recipients between 2015 and 2018 with surveillance biopsies at 6 months post-transplant. We tested the hypothesis that early subclinical inflammation (subclinical borderline changes, T cell-mediated rejection, or microvascular injury) is associated with increased incidence of a composite endpoint including acute rejection and allograft failure. Results. Using contemporaneous Banff criteria, we detected subclinical inflammation in 31%, with the majority (75%) having a subclinical borderline phenotype (at least minimal inflammation with mild tubulitis [>i0t1]). Overall, subclinical inflammation was independently associated with the composite endpoint (adjusted hazard ratio, 2.88; 1.11-7.51; P = 0.03). The subgroup with subclinical borderline inflammation, predominantly those meeting the Banff 2019 i1t1 threshold, was independently associated with 5-fold increased hazard for the composite endpoint (P = 0.02). Those with concurrent subclinical inflammation and subclinical chronic allograft injury had worse outcomes. The effect of treating subclinical inflammation was difficult to ascertain in small heterogeneous subgroups. Conclusions. Subclinical acute and chronic inflammation are common at 6 months post-transplant in kidney recipients with stable allograft function. The subclinical borderline phenotype with both tubulitis and interstitial inflammation was independently associated with poor long-term outcomes. Further studies are needed to elucidate the role of surveillance biopsies for management of allograft inflammation in kidney transplantation.

Purpose TruGraf™ blood test measures a specific gene expression signature in peripheral blood mononuclear cells for noninvasive assessment of kidney transplant recipients (KTRs) with stable renal function, excluding subclinical acute rejection (subAR) with high degree of confidence. Study objective was to correlate TruGraf™ test with 6-month surveillance biopsy (SBx). Methods Prospective, single-center study of 116 consecutive KTRs with SBx performed at 6 months post-transplant..TruGraf™ done at time of SBx; results compared with histology (Banff 2017) for concordance. Results Of 116 enrollees, 26 excluded, absent biopsy (n = 17), test quality control issues (n = 9), leaving 90 KTRs-66% deceased donor kidneys, 58% African American, and 59% male. TruGraf™ result negative in 67 subjects; 54 had normal biopsy, indicating SBx could have been avoided. Eight subjects had true positive result where biopsy justified. Unnecessary biopsy would have been performed in 15 subjects with false-positive TruGraf™, and subAR missed in 13 subjects with false-negative test. In overall population of 90 patients, SBx would have been avoided in 54 (60%). Conclusions Implementation of TruGraf™ testing in a "real-world" cohort at the time of SBx identified a significant proportion of KTRs that could have avoided SBx.

Following kidney donation, short-term quality of life outcomes compare favorably to US normative data but long-term effects on mood are not known. In the Renal and Lung Living Donors Evaluation Study (RELIVE), records from donations performed 1963–2005 were reviewed for depression and antidepressant use predonation. Postdonation, in a cross-sectional cohort design 2010–2012, donors completed the Patient Health Questionnaire (PHQ-9) depression screening instrument, the Life Orientation Test-Revised, 36-Item Short Form Health Survey and donation experience questions. Of 6909 eligible donors, 3470 were contacted and 2455 participated (71%). The percent with depressive symptoms (8%; PHQ-9 > 10) was similar to National Health and Nutrition Examination Survey participants (7%, p = 0.30). Predonation psychiatric disorders were more common in unrelated than related donors (p = 0.05). Postdonation predictors of depressive symptoms included nonwhite race OR = 2.00, p = 0.020), younger age at donation (OR = 1.33 per 10 years, p = 0.002), longer recovery time from donation (OR = 1.74, p = 0.0009), greater financial burden (OR = 1.32, p = 0.013) and feeling morally obligated to donate (OR = 1.23, p = 0.003). While cross-sectional prevalence of depression is comparable to population normative data, some factors identifiable around time of donation, including longer recovery, financial stressors, younger age and moral obligation to donate may identify donors more likely to develop future depression, providing an opportunity for intervention.

Posttransplant lymphoproliferative disorder (PTLD) is an uncommon neoplastic complication of kidney transplantation, affecting about 1% of recipients. It is generally associated with Epstein-Barr virus (EBV) infection of B-lineage lymphocytes. Central nervous system (CNS) involvement is rare. There is little clinical experience with treatment of CNS PTLD due to the relative rarity of the disease other than reduction or withdrawal of immunosuppression, but it is usually fatal. We describe six patients with renal allografts and histologically proven isolated CNS PTLD. Tissue analysis from the biopsy specimens was positive for EBV material in five of the six patients. All six patients were treated with high-dose intravenous methotrexate (HD IV MTX). Methotrexate was initiated at 8 g/m2, with later adjustments for creatinine clearance. With MTX therapy, four patients have had a sustained complete response, and two had progressive disease and were referred for radiation therapy. This finding suggests a subgroup of patients may benefit from MTX but our case series is inadequate to describe overall efficacy. No unexpected toxicities were encountered in 37 courses of treatment. HD IV MTX chemotherapy should be considered as an alternative for treatment of CNS PTLD.

Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C(2)) has been shown to be the most reliable, single-point surrogate marker for AUC. The objective of this study was to measure renal function beyond month 2 post-transplant using two different C(2) maintenance targets in combination with enteric-coated mycophenolate sodium (EC-MPS), corticosteroids, and basiliximab induction.In this open-label, multicenter trial, renal transplant recipients entered one of two randomized groups at day 61 post-transplant: group A (higher-C(2) range) or group B (lower-C(2) range).Patients (164) were recruited, and 141 patients were entered the randomized groups (group A, n = 66; group B, n = 75). At 12 months, the mean calculated creatinine clearance was significantly greater in group B than in group A (79.2 vs. 71.0 mL/min, p0.05). Biopsy-proven acute rejection occurred in 14.7% patients in group B and in 24.2% patients in group A (n.s.). During the 12-month trial, 17.7% patients discontinued EC-MPS because of adverse events. Group B (44.0%) had fewer serious adverse events when compared with group A (62.1%; p = 0.04). Overall patient and graft survival were 99.4% and 95.7% respectively. Among 99 high-risk patients (i.e., African-American race, previous transplant, PRA35% or4 HLA mismatches), mean creatinine clearance at 12 months was 65.6 mL/min and biopsy-proven rejection occurred in 20.2% patients.Low cyclosporine C(2) levels are associated with improved renal function compared with higher C(2) levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C(2) levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.

Background The introduction of increasingly effective immunosuppressants has raised the question of whether posttransplant lymphoproliferative disorder (PTLD), a complication of immunosuppression, would become more frequent. This study assessed the risk of PTLD in relation to immunosuppression during a period that saw the introduction and eventual market dominance of mycophenolate mofetil (MMF). Methods A case-control study was conducted at 23 U.S. transplant centers. All participants received a renal-only transplant on or after July 1, 1995. PTLD cases were reported by centers and confirmed by central review. The United Network for Organ Sharing (UNOS) supplemented case ascertainment and identified controls matched on center, transplant date, and age. Center personnel abstracted risk factor and therapy data for cases and up to four controls per case. Cases and controls were compared, using a matched multivariate analysis, to assess the impact of MMF as one component of triple-therapy adjusted for other drug therapies and known risk factors. Results Data were collected for 108 PTLD cases and 404 controls. PTLD risk for individuals on triple therapy with MMF was similar to the risk experienced by individuals on triple therapy with no MMF (adjusted odds ratio=1.19; 95% CI 0.55-2.55). There was no dose response relationship between MMF and PTLD risk. Conclusions Use of MMF was not associated with an increase in PTLD among patients who received triple immunosuppressive therapy, but an excess in risk as large as 155% or a reduction in risk by as much as 45% cannot be ruled out.

We undertook a study to ascertain the relationship between the presence of CD20-positive B-lymphocytes in renal allografts undergoing acute cellular rejection and graft survival. We identified 27 patients transplanted between January 1, 1998 and December 31, 2001, with biopsy-proven Banff 1-A or Banff 1-B rejection in the first year after transplantation, and stained the specimens for CD20 and C4d. At least 4 years of follow-up data were available for each patient studied. Six patients had CD20-positive B-cell clusters in the interstitium, and 21 patients were negative for CD20 infiltrates. The CD20-positive group was significantly more likely to have steroid-resistant rejection and reduced graft survival compared to CD20-negative controls. This study supports prospective identification of CD20-positive B-cell clusters in biopsy-proven rejection and offers a therapeutic rationale for a trial of monoclonal anti-CD20 antibody in such patients.

Background Posttransplant lymphoproliferative disorder (PTLD), a complication of immunosuppression, develops in approximately 1% of renal allograft recipients. Typically, PTLD is a proliferation of B-cells associated with Epstein-Barr virus (EBV) infection; it is said to be most often a systemic disease. Involvement occasionally is localized near the allograft. Methods This is a retrospective analysis of all cases of PTLD in recipients of 1474 renal transplants performed at University of Alabama at Birmingham between 1993 and 1997. Results Of 14 patients developing PTLD, 10 had disease localized near the allograft. The mean interval from transplantation to diagnosis was 221 +/- 70 days. All patients presented with renal dysfunction; an ultrasound examination revealed a hilar mass, with hydronephrosis in five and stenosis of renal vessels in eight. No patient had lymphadenopathy, according to computerized tomographic or magnetic resonance imaging findings. After reduction of immunosuppressive therapy, seven required a nephrectomy because of rejection, progressive dysfunction, or mass enlargement. Tissue recovered in four patients was consistent with PTLD; the tumors in the remaining three patients were unresectable and regressed. One patient died 1 month after a nephrectomy, and another died 4 years after surgery; neither had evidence of PTLD when they died. Three patients retain functional grafts without clinical or radiographical evidence of progression. All patients with disseminated disease died. Conclusions In a large cohort of renal allograft recipients, PTLD affected 1%. Disease localized near the allograft was the most common variant. For most patients with localized disease, the outcome was graft loss, and the mortality was low. Localized PTLD should be considered in the differential diagnosis of allograft dysfunction in the 1st posttransplant year.

Hypertension in renal allograft recipients is a common problem arising from multiple factors, including peripheral vascular damage caused by pretransplant hypertension, side effects of immunosuppressive medications, allograft dysfunction, renal artery stenosis, recurrent glomerulonephritis, synthesis of vasoconstrictive hormones by the native kidneys, and excessive dietary salt intake. Identification of modifiable factors causing hypertension and concurrent medical conditions, and measurement of glomerular filtration rate, cyclosporine/tacrolimus blood levels, and magnitude of proteinuria are essential to tailor treatment for an individual patient. Lifestyles that exacerbate hypertension should be modified. For pharmacological therapy, diuretics and calcium channel blockers are first-line agents in patients on cyclosporine shortly after transplant. Angiotensin-converting enzyme inhibitors are good choices for patients with significant proteinuria. Reduction of immunosuppression will improve hypertension in some patients, but entails a potential risk of rejection or graft loss. Angioplasty is necessary in patients with a functionally significant stenosis of the allograft renal artery. Other patients on maximal medical therapy may benefit from native nephrectomy.

While cautious criteria for selection of living kidney donors are credited for favorable outcomes, recent practice changes may include acceptance of less than ideal donors. To characterize trends in donor acceptance, the Renal and Lung Living Donors Evaluation (RELIVE) Study evaluated 8,951 kidney donors who donated between 1963 and 2007 at three major U.S. transplant centers. Over the study interval, there was an increase in the percentage of donors >40 years old from 38% to 51%; donors >60 years varied between 1% and 4%. The proportion of donors with obesity increased from 8% to 26% and with glucose intolerance from 9% to 25%. The percentage of hypertensive donors was consistent (5%–8%). Accepted donors ≥60 years old were more likely to have obesity, glucose intolerance, and/or hypertension compared to younger donors (p

Objective To determine the risk factors for recurrent lupus nephritis, allograft loss, and survival among patients with systemic lupus erythematosus (SLE) undergoing kidney transplantation. Methods The archival records of all kidney transplant recipients with a prior diagnosis of SLE (according to the American College of Rheumatology criteria) from June 1977 to June 2007 were reviewed. Patients who had died or lost the allograft within 90 days of engraftment were excluded. Time-to-event data were examined by univariable and multivariable Cox proportional hazards regression analyses. Results Two hundred twenty of nearly 7,000 renal transplantations were performed in 202 SLE patients during the 30-year interval. Of the 177 patients who met the criteria for study entry, the majority were women (80%) and African American (65%), the mean age was 35.6 years, and the mean disease duration was 11.2 years. Recurrent lupus nephritis was noted in 20 patients (11%), allograft loss in 69 patients (39%), and death in 36 patients (20%). African American ethnicity was found to be associated with a shorter time-to-event for recurrent lupus nephritis (hazard ratio [HR] 4.63, 95% confidence interval [95% CI] 1.29–16.65) and death (HR 2.47, 95% CI 0.91–6.71), although, with the latter, the association was not statistically significant. Recurrent lupus nephritis and chronic rejection of the kidney transplant were found to be risk factors for allograft loss (HR 2.48, 95% CI 1.09–5.60 and HR 2.72, 95% CI 1.55–4.78, respectively). In patients with recurrent lupus nephritis, the lesion in the engrafted kidney was predominantly mesangial, compared with a predominance of proliferative or membranous lesions in the native kidneys. Conclusion African American ethnicity was independently associated with recurrent lupus nephritis. Allograft loss was associated with chronic transplant rejection and recurrence of lupus nephritis. Recurrent lupus nephritis is infrequent and relatively benign, without influence on a patient's survival.

Individuals waiting for a renal transplant experience excessive cardiovascular mortality, which is not fully explained by the prevalence of ischemic heart disease in this population. Overt heart failure is known to increase the mortality of patients with ESRD, but the impact of lesser degrees of ventricular systolic dysfunction is unknown. For examination of the association between left ventricular ejection fraction(LVEF) and mortality of renal transplant candidates, the records of 2718 patients evaluated for transplantation at one institution were reviewed. During 6355 patient-years (median 27 mo) of follow-up, 681 deaths occurred. Patients with systolic dysfunction (LVEFor= 0.40) had significantly lower survival than those with higher systolic function (median 49 +/- 3.1 versus 72 +/- 4.0 mo; P 0.001) but had similar survival to patients with ischemia (48 +/- 2.5 mo). Multivariate modeling showed that those with systolic dysfunction were nearly twice as likely to die as those with normal systolic function, adjusted for risk factors including diabetes, left ventricular hypertrophy, and ischemia (adjusted hazard ratio 1.7; 95%confidence interval 1.43 to 2.07). In addition, a graded, reverse association between LVEF and mortality was identified. In conclusion, systolic dysfunction is strongly associated with mortality, in a graded manner, in renal transplant candidates.

The field of renal transplantation has grown exponentially as a result of a greater understanding of the immune system and the advent of numerous immunosuppressive agents. Although African Americans and whites have benefited from these advances, equivalent long-term success eludes African Americans who are disadvantaged in gaining access to renal transplantation. This review summarizes the obstacles for African Americans to end-stage renal disease(ESRD) care, focusing on transplantation. Factors that predispose African Americans for ESRD, impede this ethnic group from timely transplantation, and negatively influence graft survival are examined. Possible solutions to these persistent problems are offered.

OBJECTIVE. This report describes the imaging characteristics of focal posttransplantation lymphoproliferative disorder.CONCLUSION. Posttransplantation lymphoproliferative disorder may be limited to the allograft. A focal complex mass in the renal allograft hilum surrounding the main renal blood vessels is a common finding and can be visualized with sonography. MR imaging can help increase diagnostic confidence.

The results of increasing blood flow capability in a modified system for plasma exchange with a rotating filter are reported. There were 742 treatments performed with the authors' original system (OS), limited to blood flows of 100 ml/ min, and 327 treatments performed with the updated system (US), allowing for blood flows of 150 ml/min. Blood flows for OS were 98 +/- 5 ml/min (mean +/- SD) vs 145 +/- 12 ml/min for US (p < 0.001). Plasma flows were 65 +/- 7 ml/min for OS vs 98 +/- 12 ml/min for US (p < 0.001). Plasma removal rate was 42 +/- 8 ml/min for OS vs 61 +/- 14 ml/min for US (p < 0.001). Mean treatment time was reduced from 76 +/- 23 min for OS to 52 +/- 17 min for US (p < 0.001) in spite of providing a similar amount of plasma removed per treatment (3,113 +/- 577 ml/Rx for OS vs 3078 +/- 797 ml/Rx for US; p = 0.48). Despite statistical significance, there were only small differences in filtration fractions (65 +/- 12% for OS vs 62 +/- 11% for US; p < 0.001) and patient hematocrits (34 +/- 6% for OS vs 33 +/- 6% for US; p < 0.001). In conclusion, modification of the OS to allow for increased blood flow has resulted in a substantial improvement in procedure efficiency and a clinically useful decrease in treatment time.

Purpose: Historically, black patients have had 1-year renal allograft survival rates which is 8% to 10% worse than those for whites. With the use of quadruple immunosuppression, we have sought to find a reversal in this trend. Methods: The outcomes of 572 renal allografts—cadaveric (CAD, 477), living related [68; 0-HM (haplomatch), and 1-HM], and living unrelated (UNR, 37) between August 1995 and August 1998 were analyzed. There were 276 black recipients and 295 white recipients. Immunosuppression consisted of induction with either OKT3 10 mg/day for 7 to 10 days (485), Zenapax 1 mg/kg in two doses (86), or ATGAM 15 mg/kg for 10 days (1). Maintenance immunosuppression consisted of cellcept 2 to 3 g/day, prednisone 10 mg/day, and cyclosporine 2 to 4 mg/kg b.i.d. Cyclosporine levels were calculated by using standard fluorescence polarization immunoassay. Patients were followed for occurrence of rejection, infection, death, loss of graft, and other complications. Actuarial analysis of survival was performed by the Kaplan-Meier method, with p values generated by the Wilcoxon test. Confidence limits for survival analysis were expressed as 70%. A p value ≤ .05 was considered significant. All patients with a functioning graft have a minimum of 3 months of follow-up; graft loss was considered to be at the time of nephrectomy, return to dialysis, or death if the graft was functioning. The mean values of descriptive variables between groups were compared with the t -test, and the chi-square test or Fisher’s exact test was used to evaluate independence of groups. Results: Graft Survival BLACK WHITE COMBINED 1-yr (n) 2-yr (n) 1-yr (n) 2-yr (n) 1-yr (n) 2-yr (n) CAD 89% (179) 81% (81) 91% (147) 89% (80) 90% (326) 84% (161) 0-HM 84% (8) 84% (4) 83% (7) 83% (5) 84% (15) 84% (9) 1-HM 90% (5) 45% (1) 95% (5) n/a 94% (10) 78% (5) UNR n/a n/a 97% (30) 92% (17) 97% (30) 92% (17) Conclusions: With use of quadruple immunosuppression, there was no difference in 1-year CAD patient and graft survival between blacks and whites (p = n.s.); however, 2-year graft survival was worse in blacks (p ≤ .05). Despite the aggressive use of anti-T cell antibodies, there was no increase in infectious complications, graft loss due to death, or other complications among the groups (p = n.s.). Living related graft survival showed the same trend, with no difference at 1-year (p = n.s.). Increased graft loss between 1 and 2 years for black versus white CAD patients is attributed to a higher rate of acute/chronic rejection (p = .03). Therefore, improved renal allograft survival is possible in black patients with the use of quadruple immunosuppression; however, black patients remain at increased risk of graft loss due to rejection beyond 1 year.

A method of spontaneous note-writing has been presented. When the material is handled like any verbal associations in a therapeutic session, this technique has been especially helpful with the majority of patients in facilitating free association, overcoming resistance, gaining access to deep material more quickly, working through the positive and negative phases of the transference and promoting insight. It helps patients to expose themselves earlier in treatment, to express their conscious thoughts, and to furnish material for discussion. It is a form of mental catharsis.

As long ago as the 1930's various persons approached me to propose some kind of national association of specialists in pastoral counseling. Many other similar proposals, and even attempts, have come to my notice in the intervening years. They have carried many titles, such as pastoral counseling, pastoral psychology, religious counseling, religious therapy, and others. Without exception, they have included in their purposes not only conference and fellowship, study and advancement of knowledge, but also credentials or endorsement or accreditation or a certificate suitable for framing. I am and have always been flatly against any such proposal or organization on grounds of principle. In what follows, I shall t ry to indicate in summary form the bases of my opposition. Perhaps you can invite some others to comment on my analysis. The first point of principle is that we do not in fact have some ministers who are counselors and others who are not. All ministers do counseling whether they call it that or not. Some do it well and others, poorly. Some do much and others, little. If special credentials are offered to an elite group SEWARD HILTNER Professor of Pastoral Theology Federated Theological Faculty University of Chicago