Experience with a six-month regimen of Pneumocystis pneumonia prophylaxis in 122 HIV-positive kidney transplant recipients.

Anti-Pneumocystis pneumonia (PCP) prophylaxis is recommended for 3 to 6 months post-transplant in HIV-negative kidney transplant recipients. For HIV-positive kidney transplant recipients, there is no definite duration of primary prophylaxis and is often prescribed life-long. The objective of this study was to determine the incidence of PCP in HIV-positive recipients who received 6 months of prophylaxis with trimethoprim-sulfamethoxazole or an alternative agent. One hundred and twenty-two HIV-positive recipients received a kidney transplant from 2001 to 2017 at Hahnemann University Hospital. Most patients received induction immunosuppression with an IL-2 receptor antagonist, with or without intravenous immunoglobulin. Only one patient received anti-thymocyte globulin. Maintenance immunosuppression included a calcineurin-inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate or sirolimus), and prednisone. Mean CD4 cell count was 461 ± 127 cells/uL prior to transplant and 463 ± 229 cells/µL at 6 to 12 months after transplant. None of the recipients developed PCP after a median follow-up of 2.88 years (IQR 1.16-4.87). Based on our observation, a 6-month regimen of PCP prophylaxis may be sufficient among HIV-positive recipients, similar to those without HIV infection.

Barriers to kidney transplant evaluation in HIV-positive patients with advanced kidney disease: A single-center study.

BACKGROUND: HIV-positive kidney transplant (KT) recipients have similar outcomes to HIV-negative recipients. However, HIV-positive patients with advanced kidney disease might face additional barriers to initiating the KT evaluation process. We sought to characterize comorbidities, viral control and management, viral resistance, and KT evaluation appointment rates in a cohort of KT evaluation-eligible HIV-positive patients. METHODS: We included patients seen between January 1, 2008, and December 31, 2015, at a primary care HIV clinic who met KT evaluation eligibility by an estimated glomerular filtration rate ≤20 mL/min/1.73 meters2 or dialysis dependence. The primary outcome was a documented appointment for KT evaluation. RESULTS: Of 3735 patients evaluated at the HIV primary clinic during the study period, 42 (1.6%) were KT evaluation-eligible patients. The median age was 47 years, 77% were male, and 95%, black. Median CD4 count was 328 cells/mm3 (IQR 175-461). Among the 63% percent with antiretroviral therapy (ART) prescription, 40% had viral loads >200 copies. Among patients with HIV resistance profiles (50%, n = 21), 52% had resistance to at least one class of ART. A majority (60%, n = 25) were scheduled for KT evaluation appointment, but of those, only 8% (n = 2) had evidence of appointments before dialysis dependence. Those without appointments had more schizophrenia (29% vs 4%, P = .02), resistance (78% vs 33%, P = .04), ART prescription (76% vs 48%, P = .04), and more kidney disease of unknown etiology (53% vs 8%, P = .02). CONCLUSION: Kidney transplant evaluation-eligible HIV-positive patients had a high rate of evaluation appointments, but a low rate of preemptive evaluation appointments. Schizophrenia and viral resistance disproportionally affected patients without evaluation appointments. These data precede the recommendation for universal ART for all HIV+ patients, regardless of CD4 count and viral load, and must be interpreted in the context of this limitation.

Kidney Transplantation in HIV-Positive Patients: A Single-Center, 16-Year Experience.

Hahnemann University Hospital has performed 120 kidney transplantations in human immunodeficiency virus (HIV)-positive individuals during the last 16 years. Our patient population represents ∼10% of the entire US population of HIV-positive kidney recipients. In our earlier years of HIV transplantation, we noted increased rejection rates, often leading to graft failure. We have established a multidisciplinary team and over the years have made substantial protocol modifications based on lessons learned. These modifications affected our approach to candidate evaluation, donor selection, perioperative immunosuppression, and posttransplantation monitoring and resulted in excellent posttransplantation outcomes, including 100% patient and graft survival at 1 year and patient and graft survival at 3 years of 100% and 96%, respectively. We present key clinical data, including a granular patient-level analysis of the associations of antiretroviral therapy regimens with long-term survival, cellular and antibody-mediated rejection rates, and the causes of allograft failures. In summary, we provide details on the evolution of our approach to HIV transplantation during the last 16 years, including strategies that may improve outcomes among HIV-positive kidney transplantation candidates throughout the United States.

Association Between Weight Loss Before Deceased Donor Kidney Transplantation and Posttransplantation Outcomes.

RATIONALE & OBJECTIVE: There is debate on whether weight loss, a hallmark of frailty, signals higher risk for adverse outcomes among recipients of deceased donor kidney transplantation (DDKT). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Using national Organ Procurement and Transplantation Network data, we included all DDKT recipients in the United States between December 4, 2004, and December 3, 2014, who were adults (aged ≥ 18 years) when listed for DDKT. EXPOSURES: Relative pre-DDKT weight change as a continuous predictor and categorized as <5% weight change from listing to DDKT, ≥5% to <10% weight loss, ≥10% weight loss, ≥5% to <10% weight gain, and ≥10% weight gain. OUTCOMES: We examined 3 post-DDKT outcomes: (1) transplant hospitalization length of stay (LOS) in days, (2) all-cause graft failure, and (3) mortality. ANALYTIC APPROACH: Unadjusted fractional polynomial methods, multivariable log-gamma models, and multivariable Cox proportional hazards models. RESULTS: Among 94,465 recipients of DDKT, median pre-DDKT weight change was 0 (interquartile range, -3.5 to +3.9) kg. There were nonlinear unadjusted associations between relative pre-DDKT weight loss and longer transplant hospitalization LOS, higher all-cause graft loss, and higher mortality. Compared with recipients with <5% pre-DDKT weight change (n = 49,366; 52%), recipients who lost ≥10% of their listing weight (n = 10,614; 11%) had 0.66 (95% CI, 0.23-1.09) days longer average transplant hospitalization LOS (P = 0.003), 1.11-fold higher graft loss (adjusted HR [aHR], 1.11; 95% CI, 1.06-1.17; P < 0.001), and 1.18-fold higher mortality (aHR, 1.18; 95% CI, 1.11-1.25; P < 0.001) independent of recipient, donor, and transplant factors. Pre-DDKT dialysis exposure, listing body mass index category, and waiting time modified the association of pre-DDKT weight change with hospital LOS (interaction P < 0.10), but not with all-cause graft loss and mortality. LIMITATIONS: Unmeasured confounders and inability to identify volitional weight change. Also, the higher significance level set to increase the power of detecting interactions with the fixed sample size may have resulted in increased risk for type 1 error. CONCLUSIONS: DDKT recipients with ≥10% pre-DDKT weight loss are at increased risk for adverse outcomes and may benefit from augmented support post-DDKT.

Association of the kidney allocation system with dialysis exposure before deceased donor kidney transplantation by preemptive wait-listing status.

BACKGROUND: It is unknown whether the new kidney transplant allocation system (KAS) has attenuated the advantages of preemptive wait-listing as a strategy to minimize pretransplant dialysis exposure. METHODS: We performed a retrospective study of adult US deceased donor kidney transplant (DDKT) recipients between December 4, 2011-December 3, 2014 (pre-KAS) and December 4, 2014-December 3, 2017 (post-KAS). We estimated pretransplant dialysis durations by preemptive listing status in the pre- and post-KAS periods using multivariable gamma regression models. RESULTS: Among 65 385 DDKT recipients, preemptively listed recipients (21%, n = 13 696) were more likely to be white (59% vs 34%, P < 0.001) and have private insurance (64% vs 30%, P < 0.001). In the pre- and post-KAS periods, average adjusted pretransplant dialysis durations for preemptively listed recipients were <2 years in all racial groups. Compared to recipients who were listed after starting dialysis, preemptively listed recipients experienced 3.85 (95% Confidence Interval [CI] 3.71-3.99) and 4.53 (95% CI 4.32-4.74) fewer average years of pretransplant dialysis in the pre- and post-KAS periods, respectively (P < 0.001 for all comparisons). CONCLUSIONS: Preemptively wait-listed DDKT recipients continue to experience substantially fewer years of pretransplant dialysis than recipients listed after dialysis onset. Efforts are needed to improve both socioeconomic and racial disparities in preemptive wait-listing.

Barriers to listing for HIV-infected patients being evaluated for kidney transplantation.

Human immunodeficiency virus (HIV)-infected patients have excellent outcomes following kidney transplantation (KT) but still might face barriers in the evaluation and listing process. The aim of this study was to characterize the patient population, referral patterns, and outcomes of HIV-infected patients who present for KT evaluation. We performed a single-center retrospective cohort study of HIV-infected patients who were evaluated for KT. The primary outcome was time to determination of eligibility for KT. Between 2011 and 2015, 105 HIV-infected patients were evaluated for KT. Of the 105 patients, 73 were listed for transplantation by the end of the study period. For those who were deemed ineligible, the most common reasons cited were active substance abuse (n = 7, 22%) and failure to complete the full transplant evaluation (n = 7, 22%). Our cohort demonstrated a higher proportion of HIV-infected patients eligible for KT than in previous studies, likely secondary to advances in HIV management. Among those who were denied access to transplantation, we identified that many were unable to complete the evaluation process, and that active substance abuse was common. Future prospective studies should examine reasons and potential interventions for the lack of follow-through and drug use we observed in this population.

Association of tenofovir disoproxil fumarate with primary allograft survival in HIV-positive kidney transplant recipients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is an antiretroviral agent frequently used to treat human immunodeficiency virus (HIV). There are concerns regarding its potential to cause acute kidney injury, chronic kidney disease, and proximal tubulopathy. Although TDF can effectively suppress HIV after kidney transplantation, it is unknown whether use of TDF-based antiretroviral therapy (ART) after kidney transplantation adversely affects allograft survival. METHODS: We examined 104 HIV+ kidney transplant (KT) recipients at our center between 2001 and 2014. We generated a propensity score for TDF treatment using recipient and donor characteristics. We then fit Cox proportional hazards models to investigate the association between TDF treatment and 3-year, death-censored primary allograft failure, adjusting for the propensity score and delayed graft function (DGF). RESULTS: Of the 104 HIV+ KT candidates who underwent transplantation during the study period, 23 (22%) were maintained on TDF-based ART at the time of transplantation, and 81 (78%) were on non-TDF-based ART. Median age of the cohort was 48 years; 87% were male; 88% were black; and median CD4 count at transplantation was 450 cells/mm3 . Median kidney donor risk index was 1.2. At 3 years post transplantation, primary allograft failure occurred in 26% of patients on TDF-based ART and in 28% of patients on non-TDF-based ART (P=.5). TDF treatment was not associated with primary allograft failure at 3 years post transplant after adjusting for DGF and a propensity score for TDF use (hazard ratio 2.12, 95% confidence interval 0.41-10.9). CONCLUSIONS: In a large single-center experience of HIV+ kidney transplantation, TDF use following kidney transplantation was not significantly associated with primary allograft failure. These results may help inform management for HIV+ KT recipients in need of TDF therapy for adequate viral suppression.

Validation of the Maryland Aggregate Pathology Index (MAPI), a pre-implantation scoring system that predicts graft outcome.

Predicting graft outcome after renal transplantation based on donor histological features has remained elusive and is subject to institutional variability. We have shown in a retrospective study that the Maryland Aggregate Pathology Index score reliably predicts graft outcome. We sought to validate the scoring system in our center and a second transplant center. We analyzed 140 deceased donor kidneys pre-implantation biopsies from center 1 and 65 from center 2. The patients had a mean follow-up of 695 ± 424 and 656 ± 305 d respectively. Although MAPI scores were similar, there were significant differences in donor and recipient parameters between both centers. Despite this, MAPI was predictive of graft outcome for both centers by Cox univariate, multivariate and time dependent ROC analysis. For center 1 and 2, three yr graft survival within each MAPI group was statistically equivalent. The three-yr graft survival at center 1 for low, intermediate, and high MAPI groups were 84.3%, 56.5%, and 50.0%, respectively, p ≤ 0.0001, and at center 2 were 83.3%, 33.3%, and 33.3%, p = 0.006. MAPI, which is based on a pre-implantation biopsy, demonstrated similar predictive and outcome results from both centers. As expanded criteria donors (ECD) criteria have redefined marginal kidneys, MAPI has the potential to further define ECD kidneys, increase utilization, and ultimately improve outcomes.

The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir.

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRß repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRß clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.

Safety and Efficacy of Universal Postoperative Decolonization for Kidney Transplant Recipients.

OBJECTIVES: Infection is a common cause of morbidity and mortality after kidney transplant. Based on the well-documented successes of reducing infections with decolonization of patients in intensive care units, we began a universal immediate posttransplant decolonization program for all kidney transplant recipients. Herein, we report safety and efficacy of this decolonization program. MATERIALS AND METHODS: We compared a consecutive cohort of kidney transplant recipients who underwent universal decolonization (intervention group) with a cohort of transplant patients from an era immediately prior to this practice (control group). Universal decolonization included daily chlorhexidine body wash and nasal mupirocin ointment. RESULTS: Seventy-eight patients who underwent universal decolonization were compared with 43 patients in the control group. Ten microbiologically proven infections (8.3%) occurred in the 30 days after discharge: 7 (9%) in the intervention group and 3 (7%) in the control group. Forty-five transplant recipients (37.2%) were readmitted in the 30 days after discharge: 31 (39.7%) in the intervention group and 14 (32.6%) in the control group. No patients in the intervention group had adverse drug events from mupirocin and chlorhexidine use. CONCLUSIONS: A universal decolonization protocol was successfully implemented and was well tolerated by all patients. Despite successful implementation, we did not observe any significant differences in infection rates between treated patients and historical controls.

Comparison of four different immunosuppression protocols without long-term steroid therapy in kidney recipients monitored by surveillance biopsy: five-year outcomes.

Induction and maintenance immunosuppression protocols with or without long-term steroid therapy in kidney transplant recipients are variable and are transplant center-specific. The aim of this prospective randomized pilot study was to compare 5-year outcomes in kidney recipients maintained on 4 different calcineurin inhibitor (CNI)-based immunosuppression protocols without long-term steroid therapy. Two hundred consenting patients who received kidney transplants between June 2000 and October 2004 were enrolled in 4 immunosuppression protocol groups, with 50 patients in each group: cyclosporine (CSA)/mycophenolate mofetil (MMF), CSA/sirolimus (SRL), tacrolimus (TAC)/MMF, and TAC/SRL. Induction therapy was done with basiliximab and methylprednisolone. Steroids were withdrawn on post-transplant day 2, and long-term steroid therapy was not used. Demographic characteristics among the four groups were comparable; approximately 50% of the recipients were African American and > or =80% of the kidneys transplanted were from deceased donors. Clinical acute rejection (CAR) was confirmed by biopsy and treated with intravenous pulse steroid therapy. Steroid-unresponsive CAR was treated with Thymoglobulin. Surveillance biopsies were performed at 1, 6, 12, 24, 36, 48, and 60 months to evaluate subclinical acute rejection (SCAR), chronic allograft injury (CAI), and other pathological changes per the Banff 2005 schema. The primary end point was CAR, and secondary end points were 5-year patient and graft survival rates, renal function, SCAR, CAI, and adverse events. In the first year post-transplant, the incidence of CAR was 18% in the CSA/MMF group, 8% in the CSA/SRL group, 14% in the TAC/MMF group, and 4% in the TAC/SRL group (CSA/MMF vs. TAC/SRL; p=0.05). The incidence of SCAR was 22% in the CSA/MMF group, 8% in the CSA/SRL group, 16% in the TAC/MMF group, and 6% in the TAC/SRL group (CSA/MMF vs. CSA/SRL and TAC/SRL; p=0.05). After the first year, the incidences of CAR and SCAR decreased and were comparable in all 4 groups. At 5 years post-transplant, cumulative CAI due to interstitial fibrosis/tubular atrophy (IF/TA), hypertension (HTN), and chronic calcineurin inhibitor (CNI) toxicity was observed in 54%, 48%, and 8% of the CSA/MMF group vs. 16%, 36%, and 12% of the CSA/SRL group vs. 38%, 24% and 6% of the TAC/MMF group vs. 14%, 25% and 12% of the TAC/SLR group (IF/TA: CSA/MMF vs. CSA/SRL and TAC/SRL; p=0.04, HTN: CSA/MMF vs. TAC/MMF and TAC/SRL; p=0.05, CNI toxicity: TAC/SRL and CSA/SRL vs. TAC/MMF; p=0.05). Five-year patient and graft survival rates were 82% and 60% in the CSA/MMF group, 82% and 60% in the CSA/SRL group, 84% and 62% in the TAC/MMF group, and 82% and 64% in the TAC/SRL group (p=0.9). Serum creatinine levels and creatinine clearances at 5 years were comparable among the groups. Our data show that the rates of CAR and SCAR in the first year post-transplant were significantly lower in the CSA/SRL and TAC/SRL groups and that cumulative CAI rates due to IF/TA and HTN at 5 years were significantly lower in the TAC/MMF, TAC/SRL, and CSA/SRL groups than in the CSA/MMF group. Despite significant differences in the incidences of CAR and SCAR and prevalence of different types of CAI at 5 years, renal function and patient and graft survival rates at 5 years were comparable among kidney recipients maintained on 4 different immunosuppression protocols without long-term steroid therapy.

Meta-Analysis Comparing Outcomes and Need for Renal Replacement Therapy of Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement.

Acute kidney injury (AKI) is commonly associated with aortic valve replacement. Surgical aortic valve replacement (SAVR) is a known risk factor for AKI but little is known about the short- and long-term effects of transcatheter aortic valve implantation (TAVI). The purpose of our analysis is to identify the short- and long-term effect of TAVI on renal outcomes. We searched Medline and PUBMED from January 1, 2000 to November 6, 2017 for randomized control trials (RCTs) comparing TAVI to SAVR in patients with severe aortic stenosis. Three hundred sixty-nine trials were identified, 6 RCTs were included in our analysis. RevMan version 5.3 was used for statistical analysis. Heterogeneity is calculated using I2 statistics. Primary outcomes were AKI within 30 days and 1 year of TAVI, and requirement for renal replacement therapy. We included 5,536 patients (2,796 in TAVI and 2,740 in SAVR arm) from 6 RCTs. Baseline characteristics were similar. There was reduced incidence of AKI at 30 days of TAVI compared with SAVR, 57 versus 133 (odds ratio [OR] 0.40, confidence interval [CI] 0.28 to 0.56, p <0.00001, I2 = 7%) with no difference at 1 year (OR 0.65, CI 0.32 to 1.32, p = 0.23, I2 = 76%) and need for renal replacement therapy OR 0.95, CI 0.50 to 1.80, p = 0.87, I2 = 0%). Permanent pacemaker was more frequent in the TAVI arm compared with SAVR arm, 379 versus 110, (OR 3.75, CI 1.67 to 8.42, p = 0.001, I2 = 89%). In conclusion, TAVI is associated with a reduction in AKIs at 30 days despite the exposure to contrast and higher incidence of new permanent pacemaker placement.

Association between Medicaid Expansion under the Affordable Care Act and Preemptive Listings for Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Before 2014, low-income individuals in the United States with non-dialysis-dependent CKD had fewer options to attain health insurance, limiting their opportunities to be preemptively wait-listed for kidney transplantation. We examined whether expanding Medicaid under the Affordable Care Act was associated with differences in the number of individuals who were pre-emptively wait-listed with Medicaid coverage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using the United Network of Organ Sharing database, we performed a retrospective observational study of adults (age≥18 years) listed for kidney transplantation before dialysis dependence between January 1, 2011-December 31, 2013 (pre-Medicaid expansion) and January 1, 2014-December 31, 2016 (post-Medicaid expansion). In multinomial logistic regression models, we compared trends in insurance types used for pre-emptive wait-listing in states that did and did not expand Medicaid with a difference-in-differences approach. RESULTS: States that fully implemented Medicaid expansion on January 1, 2014 ("expansion states," n=24 and the District of Columbia) had a 59% relative increase in Medicaid-covered pre-emptive listings from the pre-expansion to postexpansion period (from 1094 to 1737 listings), compared with an 8.8% relative increase (from 330 to 359 listings) among 19 Medicaid nonexpansion states (P<0.001). From the pre- to postexpansion period, the adjusted proportion of listings with Medicaid coverage decreased by 0.3 percentage points among nonexpansion states (from 4.0% to 3.7%, P=0.09), and increased by 3.0 percentage points among expansion states (from 7.0% to 10.0%, P<0.001). Medicaid expansion was associated with absolute increases in Medicaid coverage by 1.4 percentage points among white listings, 4.0 percentage points among black listings, 5.9 percentage points among Hispanic listings, and 5.3 percentage points among other listings (P<0.001 for all comparisons). CONCLUSIONS: Medicaid expansion was associated with an increase in the proportion of new pre-emptive listings for kidney transplantation with Medicaid coverage, with larger increases in Medicaid coverage among racial and ethnic minority listings than among white listings.

Effect of rosuvastatin on C-reactive protein and renal function in patients with chronic kidney disease.

The purpose of this 20-week, open-label, randomized clinical trial was to evaluate the effect of rosuvastatin on fasting serum lipids and lipoproteins, high-sensitivity C-reactive protein (hs-CRP), and the glomerular filtration rate (GFR) in 91 patients with chronic kidney disease. Patients were randomized to rosuvastatin 10 mg/day (n = 48) or to no lipid-lowering treatment (n = 43) for 20 weeks. In contrast to patients not receiving rosuvastatin, patients receiving rosuvastatin tended to derive more favorable improvements from baseline values in low-density lipoprotein cholesterol (-43%, p <0.001, vs 7%, p = NS; p <0.001 for change with rosuvastatin treatment vs change with no antilipemic treatment), hs-CRP (-47%, p <0.001, vs 7%, p = NS; p <0.001 for change with rosuvastatin treatment vs change with no antilipemic treatment), and GFR (11%, p <0.05, vs 4%, p = NS; p = NS for change with rosuvastatin treatment vs change with no antilipemic treatment).

Kidney donor risk index (KDRI) fails to predict kidney allograft survival in HIV (+) recipients.

INTRODUCTION: We used the United Network of Organ Sharing Standard Transplant Analysis and Research Files (STAR files) to investigate the utility of the Kidney Donor Risk Index (KDRI) versus delayed graft function (DGF) to predict graft survival in the HIV (+) kidney transplant recipients. METHODS: Individual matching (one case to five controls) was used to investigate predictive ability of the KDRI for graft survival in HIV (+) recipients (cases) as compared to HIV (-) recipients (controls) leaving 400 HIV (+) recipients matched with 1,904 HIV (-) recipients. Cox proportional hazard regression model was used to test association of the KDRI and DGF with graft survival. The relationship of the KDRI with graft survival was also explored by using Kaplan-Meier analysis. RESULTS: HIV (+) and HIV (-) cohorts were well matched in terms of race, HCV co-infection, panel reactive antibody, and wait time except HIV + were more frequently diabetic. Donor qualities were similar between the cohorts, including method of allograft preservation pretransplant, HLA matching, and calculated KDRI. There was no significant difference in survival based on the KDRI quintiles among the HIV (+) cohort (logrank sum P=0.4986). Graft survival within the HIV (+) cohort was significantly worse in the DGF (+) group than the DGF (-) group (logrank P<0.01). DISCUSSION: We found that the KDRI did not predict graft survival for HIV (+) kidney transplant recipients; however, the presence of DGF continues to have a negative impact on the graft survival. Future predictive models should include DGF as a variable.

Bone disease in organ transplant patients: pathogenesis and management.

Bone disease is common in recipients of kidney, heart, lung, liver, and bone marrow transplants, and causes debilitating complications, such as osteoporosis, osteonecrosis, bone pain, and fractures. The frequency of fractures ranges from 6% to 45% for kidney transplant recipients to 22% to 42% for heart, lung, and liver transplant recipients. Bone disease in transplant patients is the sum of complex mechanisms that involve both preexisting bone disease before transplant and post-transplant bone loss due to the effects of immunosuppressive medications. Evaluation of bone disease should preferably start before the transplant or in the early post-transplant period and include assessment of bone mineral density and other metabolic factors that influence bone health. This requires close coordination between the primary care physician and transplant team. Patients should be stratified based on their fracture risk. Prevention and treatment include risk factor reduction, antiresorptive medications, such as bisphosphonates and calcitonin, calcitriol, and/or gonadal hormone replacement. A steroid-avoidance protocol may be considered.

High frequency of rejections in HIV-positive recipients of kidney transplantation: a single center prospective trial.

BACKGROUND: This is a single institution report of the incidence of combined acute antibody-mediated rejection (ABMR) + acute cellular rejection (ACR) [mixed rejection] in HIV (+) kidney transplant recipients. METHODS: We prospectively enrolled 92 HIV (+) patients who received a kidney transplant between 2001 and 2009. There were three cohorts: no rejection [n=26], ACR [n=53], and mixed rejections (ABMR and ACR) [n=13]. Immunosuppression comprised of basiliximab, cyclosporine, sirolimus, and steroid minimization. Fisher exact tests for categorical variables, t test for continuous variables, and Kaplan-Meier estimates were used to describe events. RESULTS: Mixed rejections were seen in all 13 HIV (+) kidney transplant recipients (14%) with a median time to ABMR of 48 days. Acute cellular rejection occurred in 28% at 1 month and 55% at 12 months. eGFR was lower for recipients who experienced ABMR versus those experiencing ACR and those never experiencing rejection up to 3 years (14 ± 9.4 vs 19 ± 3.3 vs 29 ± 7.3 mL/min, respectively). Kaplan-Meier showed that graft survival up to 9 years was worse in recipients experiencing mixed rejection. Suboptimal donors with terminal creatinine greater than 2.5 mg/dL was associated with increased incidence of mixed rejections versus cellular rejections and no rejection (42% vs 17% vs. 8%, respectively). CONCLUSIONS: Our single center study showed a relatively higher incidence of mixed rejection compared with that reported for non-HIV transplant recipients. A donor terminal serum creatinine greater than 2.5 mg/dL predicted mixed rejection, which was associated with poor outcomes. Donor selection and optimization of immunosuppression may be critical in these patients.

Renal failure in patients with cirrhosis.

Renal failure in cirrhosis poses unique diagnostic and therapeutic challenges. Laboratory values and predictive equations grossly overestimate renal function in patients with cirrhosis. Development of renal failure connotes a worse prognosis; mortality is especially high with hepatorenal syndrome. Classification of the causes of renal failure in patients with cirrhosis is provided with more extensive discussion of selected causes. Finally, a suggested diagnostic approach to renal failure in cirrhosis is given.

African American kidney transplantation survival: the ability of immunosuppression to balance the inherent pre- and post-transplant risk factors.

Among organ transplant recipients, the African American population historically has received special attention. This is because secondary to their disposition to certain disease states, for example hypertension, an African American patient has a propensity to reach end-stage renal disease and require renal replacement earlier than a Caucasian patient. Regardless of the initiative to replace dialysis therapy with organ transplantation, the African American patient has many barriers to kidney transplantation, thus extending their time on dialysis and waiting time on the organ transplant list. These factors are among the many negative causes of decreased kidney graft survival, realized before kidney transplantation. Unfortunately, once the African American recipient receives a kidney graft, the literature documents that many post-transplant barriers exist which limit successful outcomes. The primary post-transplant barrier relates to designing proper immunosuppression protocols. The difficulty in designing protocols revolves around (i) altered genetic metabolism/lower absorption, (ii) increased immuno-active cytokines and (iii) detrimental effects of noncompliance. Based on the literature, dosing of immunosuppression must be aggressive and requires a diligent practitioner. Research has indicated that, despite some success with proven levels of immunosuppression, the African American recipient usually requires a higher 'dose per weight' regimen. However, even with aggressive immunosuppressant dosing, African Americans still have worse outcomes than Caucasian recipients. Additionally, many of the targeted sites of action that immunosuppression exerts its effects on have been found to be amplified in the African American population. Finally, noncompliance is the most discouraging inhibitor of long-term success in organ transplantation. The consequences of noncompliance are biased by ethnicity and affect the African American population more severely. All of these factors are discussed further in this review in the hope of identifying an ideal healthcare model for caring for the African American transplant recipient, from diagnosing chronic kidney disease through to successful kidney graft outcomes. An indepth review of the literature is described and organized in a fashion that highlights all of the issues affecting success in African Americans. The compilation of the literature in this review will enable the reader to get closer to understanding the caveats of kidney transplantation in the African American patient, but falls short of delivering an actual 'equation' for post-transplant care in an African American kidney recipient.