Genetic evaluation of living kidney donor candidates: A review and recommendations for best practices.

The growing accessibility and falling costs of genetic sequencing techniques has expanded the utilization of genetic testing in clinical practice. For living kidney donation, genetic evaluation has been increasingly used to identify genetic kidney disease in potential candidates, especially in those of younger ages. However, genetic testing on asymptomatic living kidney donors remains fraught with many challenges and uncertainties. Not all transplant practitioners are aware of the limitations of genetic testing, are comfortable with selecting testing methods, comprehending test results, or providing counsel, and many do not have access to a renal genetic counselor or a clinical geneticist. Although genetic testing can be a valuable tool in living kidney donor evaluation, its overall benefit in donor evaluation has not been demonstrated and it can also lead to confusion, inappropriate donor exclusion, or misleading reassurance. Until more published data become available, this practice resource should provide guidance for centers and transplant practitioners on the responsible use of genetic testing in the evaluation of living kidney donor candidates.

Elevated Tacrolimus Levels at Time of Diagnosis of COVID-19 Compared to Baseline Among Hospitalized Organ Transplant Recipients.

BACKGROUND: The effect of COVID-19 on immunosuppressant drug levels in organ transplant recipients (OTRs) has not been adequately studied. OBJECTIVE: To study the effect of COVID-19 on tacrolimus trough levels (primary outcome) in OTRs and the association of the later with acute kidney injury, bacterial infection, and oxygen requirements. METHODS: We studied adult (>18-year-old) hospitalized OTRs with COVID-19, who were receiving tacrolimus between 3/1 and 12/16/2020. RESULTS: Among 30 OTRs, 67% were men, 90% had a kidney transplant. Median age was 60.5 (interquartile range [IQR]: 45-68) years, median time from transplant 36 (IQR: 20-84) months. Tacrolimus troughs were higher on admission for COVID-19 than baseline (average over 6 months prior) (P = .001). Eighteen patients (60%) had admission tacrolimus trough >10, 5 (17%) >20 ng/mL. Patients with diarrhea had borderline higher tacrolimus troughs, compared to those without diarrhea (P = .09). Organ transplant recipients with a tacrolimus trough >10 ng/mL were more likely to have elevated aspartate aminotransferase on admission (P = .01) and require supplemental oxygen. (P = .026). CONCLUSION AND RELEVANCE: Tacrolimus trough levels were elevated in most OTRs with COVID-19 at the time of hospital admission, compared to baseline. Potential mechanisms are diarrhea and hepatic involvement in COVID-19. In OTRs with COVID-19, including outpatients, immunosuppressant drug levels should be closely followed; management of immunosuppression should be individualized.

Treprostinil, a prostacyclin analog, ameliorates renal ischemia-reperfusion injury: preclinical studies in a rat model of acute kidney injury.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a major factor causing acute kidney injury (AKI). No pharmacological treatments for prevention or amelioration of I/R-induced renal injury are available. Here we investigate the protective effects of treprostinil, a prostacyclin analog, against renal IRI in vivo. METHODS: Male Sprague Dawley rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion for 1-168 h. Treprostinil (100 ng/kg/min) or placebo was administered subcutaneously for 18-24 h before ischemia. RESULTS: Treatment with treprostinil both significantly reduced peak elevation and accelerated the return to baseline levels for serum creatinine and blood urea nitrogen versus I/R-placebo animals following IRI. I/R-treprostinil animals exhibited reduced histopathological features of tubular epithelial injury versus I/R-placebo animals. IRI resulted in a marked induction of messenger RNA coding for kidney injury biomarkers, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin and for pro-inflammatory cytokines chemokine (C-C motif) ligand 2, interleukin 1ß, interleukin 6 and intracellular adhesion molecular 1 in animals treated with placebo only relative to sham controls. Upregulation of expression of all these genes was significantly suppressed by treprostinil. Treprostinil significantly suppressed the elevation in renal lipid peroxidation found in the I/R-placebo group at 1-h post-reperfusion. In addition, renal protein expression of cleaved poly(ADP-ribose) polymerase 1 and caspase-3, -8 and -9 in I/R-placebo animals was significantly inhibited by treprostinil. CONCLUSIONS: This study demonstrates the efficacy of treprostinil in ameliorating I/R-induced AKI in rats by significantly improving renal function early post-reperfusion and by inhibiting renal inflammation and tubular epithelial apoptosis. Importantly, these data suggest that treprostinil has the potential to serve as a therapeutic agent to protect the kidney against IRI in vivo.

Implementing a regional standardized BK polyomavirus screening protocol across eleven transplant centres.

BK polyomavirus (BKPyV) reactivation is regularly monitored after kidney transplant to prevent progression to BK associated nephropathy (BKAN). The New England BK Consortium, made up of 12 transplant centres in the northeastern United States, conducted a quality improvement project to examine adherence to an agreed upon protocol for BKPyV screening for kidney transplants performed in calendar years 2016-2017. In a total of 1047 kidney transplant recipients (KTR) from 11 transplant centres, 204 (19%) had BKPyV infection, defined as detection of BKPyV in plasma, with 41 (4%) KTR progressing to BKAN, defined by either evidence on biopsy tissues or as determined by treating nephrologists. BKPyV infection was treated with reduction of immune suppressants (RIS) in >70% of the patients in all but two centres. There was no graft loss because of BKAN during the two-year follow-up. There were nine cases of post-RIS acute rejection detected during this same period. Adherence to the protocol was low with 54% at 12 months and 38% at 24 months, reflecting challenges of managing transplant patients at all centres. The adherence rate was positively correlated to increased detection of BKPyV infection and was unexpectedly positively correlated to an increase in diagnosis of BKAN.

Successful recovery from COVID-19 in three kidney transplant recipients who received convalescent plasma therapy.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease that typically presents with greater severity in patients with underlying medical conditions or those who are immunosuppressed. We present a novel case series of three kidney transplant recipients with COVID-19 who recovered after receiving COVID-19 convalescent plasma (CCP) therapy. Physicians should be aware of this potentially useful treatment option. Larger clinical registries and randomized clinical trials should be conducted to further explore the clinical and allograft outcomes associated with CCP use in this population.

Physical activity and risk of cardiovascular events and all-cause mortality among kidney transplant recipients.

BACKGROUND: Insufficient physical activity (PA) may increase the risk of all-cause mortality and cardiovascular disease (CVD) morbidity and mortality among kidney transplant recipients (KTRs), but limited research is available. We examine the relationship between PA and the development of CVD events, CVD death and all-cause mortality among KTRs. METHODS: A total of 3050 KTRs enrolled in an international homocysteine-lowering randomized controlled trial were examined (38% female; mean age 51.8 ± 9.4 years; 75% white; 20% with prevalent CVD). PA was measured at baseline using a modified Yale Physical Activity Survey, divided into tertiles (T1, T2 and T3) from lowest to highest PA. Kaplan-Meier survival curves were used to graph the risk of events; Cox proportional hazards regression models examined the association of baseline PA levels with CVD events (e.g. stroke, myocardial infarction), CVD mortality and all-cause mortality over time. RESULTS: Participants were followed up to 2500 days (mean 3.7 ± 1.6 years). The cohort experienced 426 CVD events and 357 deaths. Fully adjusted models revealed that, compared to the lowest tertile of PA, the highest tertile experienced a significantly lower risk of CVD events {hazard ratio [HR] 0.76 [95% confidence interval (CI) 0.59-0.98]}, CVD mortality [HR 0.58 (95% CI 0.35-0.96)] and all-cause mortality [HR 0.76 (95% CI 0.59-0.98)]. Results were similar in unadjusted models. CONCLUSIONS: PA was associated with a reduced risk of CVD events and all-cause mortality among KTRs. These observed associations in a large, international sample, even when controlling for traditional CVD risk factors, indicate the potential importance of PA in reducing CVD and death among KTRs.

Hyperammonemia syndrome due to Ureaplasma urealyticum in a kidney transplant recipient: A case of disseminated disease from a fluoroquinolone-resistant isolate.

Ureaplasma species (spp.) are common colonizers of the urogenital tract but may cause systemic infection in immunocompromised patients. They release significant amounts of ammonia via urea hydrolysis and have been recently implicated in the pathogenesis of hyperammonemia syndrome after organ transplantation. We describe a unique case of hyperammonemia syndrome after kidney transplant caused by U urealyticum infection, and the first, to our knowledge, case of a fluoroquinolone-resistant Ureaplasma strain causing hyperammonemia syndrome. A 17-year-old female developed intermittent fevers, rising creatinine, sterile pyuria and debilitating polyarthritis approximately 1 year after kidney transplant. Serum ammonia level was elevated, and urine PCR was positive for U urealyticum. Near the end of treatment with levofloxacin, she had rebound hyperammonemia, which preceded clinical relapse of polyarthritis and encephalopathy. Blood and urine PCR and synovial fluid culture were positive for U urealyticum. Susceptibility testing showed fluoroquinolone resistance, but she responded well to azithromycin and doxycycline. The frequency of Ureaplasma spp. infection in immunocompromised patients is probably underestimated due to diagnostic challenges. Ammonia levels were helpful biomarkers of response to antimicrobial therapy in our case. Susceptibility testing of clinical isolates should be pursued. In serious Ureaplasma spp. infections, particularly in immunocompromised patients, two empiric antibiotics may be indicated given the potential for antimicrobial resistance.

A single-center analysis of early readmission after renal transplantation.

BACKGROUND: Thirty-day readmission rates (early hospital readmission, EHR) are an important benchmark for quality improvement. Nationally, patients undergoing renal transplantation incur a 31% EHR rate. While national databases provide useful data, the impact of EHR on individual centers has received little attention. We proposed that an institutional review of EHR after renal transplantation may provide a benchmark for individual transplant programs and identify modifiable program-specific issues to reduce EHR. METHODS: We reviewed 269 consecutive kidney transplant recipients over a five-year period (2012-2016). Early hospital readmission was modeled using generalized linear modeling assuming a binary distribution. RESULTS: About 21% of patients were readmitted within 30 days. Deceased kidney donation (DD), delayed graft functioning (DGF), anti-thymocyte globulin (ATG) induction, diabetes, public insurance, weekend discharge, and low glomerular filtration rate (eGFR) at discharge were all identified as risk factors for readmission. Early hospital readmission was not correlated with risk of death (5.4% at 44 months: HR 2.2 (95% CI [0.7, 6.6]; P = 0.1473) or graft loss. CONCLUSIONS: EHR after renal transplantation is common. Certain factors may predict an increased risk for EHR. A multi-disciplinary approach to discharge planning may limit some EHR, but most complications and adverse events are unpredictable and require hospital-level of care.

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients.

BACKGROUND: "T50," shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. METHODS: The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs). We conducted a longitudinal case-cohort analysis using a randomly selected subcohort of patients, and all individual cases who developed CVD. Serum T50 and fetuin-A were determined in this total of n = 685 FAVORIT trial participants at randomization. RESULTS: During a median surveillance of 2.18-years, 311 incident or recurrent CVD events occurred. Shorter T50 (minutes) or reduced fetuin-A concentrations (g/L) were associated with CVD after adjustment for treatment assignment, systolic blood pressure, age, sex, race, preexisting CVD and diabetes, smoking, body mass index, total cholesterol/HDL cholesterol, kidney allograft vintage and type, calcineurin inhibitor, or lipid-lowering drug use, estimated glomerular filtration rate, and urinary albumin/creatinine: tertile 1 (lowest) to tertile 3 (highest) comparisons, T50, (hazard ratio [HR] 1.86; 95% CI 1.20-2.89); fetuin-A, (HR 2.25; 95% CI 1.38-3.69). Elevated high sensitivity c-reactive protein (hsCRP) was an effect modifier of both these associations. CONCLUSIONS: Shortened T50, as well as reduced fetuin-A levels, ostensible promoters of vascular calcification, remained associated with greater risk for CVD outcomes, after adjustment for major CVD risk factors, measures of kidney function and damage, and KTR clinical characteristics and demographics, in a large, multiethnic cohort of long-term KTRs. Increased hsCRP was an effect modifier of these CVD risk associations.

Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure.

BACKGROUND: Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs). METHODS: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. RESULTS: The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77). CONCLUSIONS: Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.

New England BK consortium: Regional survey of BK screening and management protocols in comparison to published consensus guidelines.

INTRODUCTION: BK polyomavirus (BKPyV) continues to impact renal transplant recipients (RTR). The New England BK Consortium aims to jointly optimize screening and management of BKPyV. METHODS: Our first project was to survey centers' BKPyV screening protocols and compare them to consensus guidelines. RESULTS: Thirteen of 15 centers (86.7%) returned the survey. Only two center reported using monitoring parameters that were in line with consensus guidelines for BKPyV screening, while the majority of centers reported less intensive methods and shorter duration. One center reported performing renal biopsies in all patients with plasma viral loads >10 000 copies/mL, while all other centers only perform for-cause biopsies. For presumptive nephropathy, 11 centers recommend a biopsy for confirmation. For management of documented BKPyV-associated nephropathy, 12 centers propose further immunosuppression reduction. Nine centers report CNI dose reduction as their primary treatment. More than half of centers surveyed reported use of leflunomide, cidofovir or intravenous immunoglobulin. CONCLUSIONS: There was a large variance in BKPyV screening and management strategies among centers. Due to these results, all participating centers agreed to implement uniform screening and aim to optimize management protocols.

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort.

BACKGROUND: Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B-based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs. PREDICTOR: Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization. RESULTS: During a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92-1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15-1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04-1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00-1.31), transplant failure (HR, 1.72; 95% CI, 1.46-2.01), and mortality (HR, 1.34; 95% CI, 1.15-1.54). LIMITATIONS: We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites. CONCLUSIONS: Serum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted.

Urothelial cell carcinoma after BK polyomavirus infection in kidney transplant recipients: A cohort study of veterans.

BACKGROUND: BK polyomavirus (BKPyV) reactivation is a common clinical occurrence in kidney transplant recipients (KTR). Several other polyomaviruses have been implicated as pathogens with a direct role in the development of malignancies, raising the question of whether BKPyV might also be oncogenic. METHODS: This study is the first retrospective, multicenter cohort study evaluating the relative risk for urothelial cell carcinoma (UCC) associated with BKPyV infection among KTR, and was conducted among veterans who underwent transplantation between 2000 and 2009. BKPyV cases were defined as those veterans with any clinical evidence of BKPyV infection, including positive polymerase chain reaction testing of urine and/or serum for BKPyV or kidney biopsy showing BKPyV-associated nephropathy. RESULTS: Among the 646 veterans who met inclusion criteria for the study, 103 had clinical evidence of BKPyV infection (16%). The overall relative risk for developing any malignancy after BKPyV infection was 1.13 (95% confidence interval [CI] 0.89-1.44). The adjusted relative risk for malignancy after BKPyV infection was greatest with UCC (8.21, 95% CI 0.75-89.7) and with metastatic disease of unknown etiology (8.21, 95% CI 0.75-89.7). The screening prevalence for BKPyV infection increased from 18% for those veterans who underwent transplantation in 2000 to 86% for those veterans who underwent transplantation in 2009, during which time the measured prevalence of BKPyV infection increased from 7% to 24%. CONCLUSION: In this cohort of KTR veterans, no overall increased or decreased relative risk for malignancy was associated with evidence of prior BKPyV infection. A >8-fold increased risk of developing UCC after BKPyV infection was seen, although this risk was not found to be statistically significant.

Acute hypocalcemia following kidney transplantation may depend on the type of remote parathyroidectomy: a retrospective cohort study
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BACKGROUND: Secondary hyperparathyroidism is a common complication of chronic kidney disease. When medical management fails, parathyroidectomy (PTX) is a treatment option. The two most common types are subtotal PTX and total PTX with autotransplantation (AT). To date, there is no consensus as to which procedure is preferable, especially in patients who are candidates for future kidney transplantation. The aim of this study was to identify if the type of PTX is a risk factor for acute postrenal transplant (postRTX) hypocalcemia and a concern for problems with long-term calcium homeostasis. METHODS: Renal transplant recipients at Rhode Island Hospital from 2005 to 2014 were screened for prior PTX. Out of 297 participants, 11 patients met the criteria. They were further divided into subtotal PTX (n = 5) vs. total PTX+AT (n = 6). Immediate postoperative (14 days) and long-term (1 year) calcium levels were followed and analyzed. Linear growth models were used to determine the effects of type of parathyroidectomy (subtotal PTX, total PTX+AT) alone on hypocalcemia over time. In these models, pretransplant levels of calcium and PTH were included as covariates. RESULTS: Baseline characteristics showed that prerenal transplant (preRTX) parathyroid hormone (PTH) levels were lower in total PTX+AT vs. subtotal PTX (3.5 vs. 247.2 mg/dL, p < 0.005). PreRTX calcium levels were slightly lower in subtotal PTX (9.5 vs. 8.25 mg/dL, p < 0.01), but were within normal limits for both groups. No significant differences were noted between total vitamin D levels and time between PTX and RTX. Within 14 days postRTX, the total PTX+AT group had lower average calcium levels (5.8 vs 8.8 mg/dL, p < 0.001); however, both groups had normal and stable calcium levels from 1 month to 1 year after transplant. This was further supported after adjusting for preRTX levels of calcium and PTH, showing a significant interaction between treatment and time such that patients had lower calcium levels if they underwent total PTX+AT vs. subtotal PTX within 14 days postRTX (ß = -0.204, SE = 0.039, p < 0.001) (Figure 1) but not at 1 year postRTX (ß = 0.035, SE = 0.075, p = 0.640). CONCLUSION: This study suggests that total PTX+AT increases the risk for acute postRTX hypocalcemia but has no effect on long-term calcium homeostasis. We speculate that the acuity of the hypocalcemia may be compounded by high-dose glucocorticoids required for induction, in addition to the preoperative undetectable PTH. Thus, prior to RTX, physicians should take into account the type of remote PTX. If a patient had a total PTX+AT, then postRTX hypocalcemia is likely to occur.
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Immunosuppression in the failing and failed transplant kidney: optimizing outcomes.

There is little data to guide clinicians on the optimal management of immunosuppression in patients whose kidney transplant has failed and who have returned to dialysis. Nor is there robust data on whether to perform a transplant nephrectomy. Finally, management of late stage chronic kidney disease, including deciding on dialysis initiation, modality and access planning, must occur simultaneously with efforts aimed at preserving the failing kidney and residual renal function for as long as possible. In this article, we will review the evidence on these topics and suggest areas for improvement.

Pharmacokinetics of total and unbound prednisone and prednisolone in stable kidney transplant recipients with diabetes mellitus.

BACKGROUND: The corticosteroid prednisone is an important component of posttransplantation immunosuppressive therapy. Pharmacokinetic parameters of prednisone or its pharmacologically active metabolite, prednisolone, are not well characterized in transplant recipients. The objective of this study was to compare the pharmacokinetics of total and unbound prednisone and prednisolone in diabetic and nondiabetic stable kidney transplant recipients and to evaluate the factors influencing plasma protein binding of prednisolone. METHODS: Prednisone and prednisolone concentration-time profiles were obtained in 20 diabetic and 18 nondiabetic stable kidney transplant recipients receiving an oral dose of 5-10 mg prednisone per day. In addition to drug and metabolite exposures, factors influencing prednisolone protein binding were evaluated using a nonlinear mixed-effects modeling approach. This model takes into account the binding of prednisolone and cortisol to corticosteroid-binding globulin (CBG) in a saturable fashion and binding of prednisolone to albumin in a nonsaturable fashion. Finally, we have investigated the influence of several covariates including diabetes, glucose concentration, hemoglobin A1c, creatinine clearance, body mass index, gender, age, and time after transplantation on the affinity constant (K) between corticosteroids and their binding proteins. RESULTS: In patients with diabetes, the values of dose-normalized area under the concentration-time curves were 27% and 23% higher for total and unbound prednisolone, respectively. Moreover, the ratio of total prednisolone to prednisone concentrations (active/inactive forms) was higher in diabetic subjects (P < 0.001). Modeling protein binding results revealed that the affinity constant of corticosteroid-binding globulin-prednisolone (KCBG,PL) was related to the patient's gender and diabetes status. CONCLUSIONS: Higher prednisolone exposure could potentially lead to the increased risk of corticosteroid-related complications in diabetic kidney transplant recipients.

Unexpected Medical Conditions Discovered During Live Donor Kidney Evaluation: Single Center Study.

OBJECTIVES: Living donor kidney transplantation (LDKT) is the preferred method of treatment for patients with end-stage kidney disease. Potential living kidney donors (PLKD) are evaluated through a thorough medical, psychological and surgical work-up to ensure successful transplantation with minimal risks to all parties involved. The transplant center at Rhode Island Hospital has noticed an increasing number of PLKDs excluded from donation due to conditions newly diagnosed during the screening process. Our objective is to understand the local trends underlying the high PLKD exclusion rates in the context of newly diagnosed conditions, age, race, and sex of the excluded donors. STUDY DESIGN AND METHODS: Our study is a retrospective electronic medical record review of the 429 PLKDs screened at Rhode Island Hospital Kidney Transplant Center between December 2012 and April 2023. Age, race, gender, relationship to recipient, and reasons for exclusion were collected from the medical record for each PLKD. CONCLUSION: 115 of the 429 total PLKDs screened were excluded for newly diagnosed conditions, the most common of which were renal issues (49%), diabetes mellitus (33%), and hypertension (13%), with many comorbid diagnoses. While these donors were able to receive proper treatment after their diagnosis, the earliest intervention possible yields the best prognosis. The high prevalence of treatable yet undiagnosed conditions raise many public health concerns, such as primary care gaps or discontinuous healthcare, and increases awareness about the importance of follow-up care for the excluded PLKDs.

Quantification of treprostinil concentration in rat and human using a novel validated and rapid liquid chromatography-tandem mass spectrometry method: Experimental and clinical applications in ischemia-reperfusion injury.

Treprostinil (Remodulin®) is a Food and Drug Administration (FDA) approved prostacyclin analog to treat pulmonary arterial hypertension. Recently, treprostinil has been investigated to reduce ischemia-reperfusion injury (IRI) during transplantation, which currently has no approved treatment. A validated analytical method is necessary to measure treprostinil concentrations in biological specimens. Here, a novel, sensitive, and specific method to measure treprostinil concentrations in rat serum, human serum, and human plasma has been developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Biological samples were processed by protein precipitation before chromatography and 6-keto Prostaglandin F1α-d4 was used as an internal standard. A gradient method was established with a total run time of 4 min. The assay was linear over the range of 0.25-75.0 ng/ml with accuracy (92.97-107.87 %), intra-assay precision (1.16-3.34 %), and inter-assay precision (1.11-4.58 %) in all biological matrices, which are within FDA acceptance criteria. No significant variation in treprostinil or 6-keto Prostaglandin F1α-d4 concentrations were observed under the investigated storage conditions. This novel, sensitive, and specific LC/MS-MS method is cost-effective and suitable for measuring treprostinil concentrations in animal studies and human biological samples for clinical applications.

Immunosuppression after renal allograft failure: a survey of US practices.

BACKGROUND: Little data exist to guide the management of immunosuppression after renal graft failure. More aggressive tapering of immunosuppressive medications may reduce the risk of infection, but may increase the risk of rejection and sensitization. METHODS: To document current practices in the US, we emailed a questionnaire to medical and surgical transplant directors as identified by the United Network for Organ Sharing (UNOS). RESULTS: Emails were sent to 221 programs, of which 93 (42.1%) responded. About 24.7% of respondents reported adjusting immunosuppression according to a standard protocol; 75.3% said practices are physician dependent. The majority said that 80 or 100% of patients are off all immunosuppression one yr after returning to dialysis. The most important factors cited in deciding whether to stop immunosuppression were plans to retransplant (40.2%) and signs and symptoms of rejection (37.0%). When asked which immunosuppressive medications are continued indefinitely, 21.5% responded prednisone and 71.0% said none. Respondents most commonly said they performed graft nephrectomy only if there are signs and symptoms of rejection (47.3%) or if signs and symptoms of rejection fail to respond to steroids (34.4%). CONCLUSIONS: In the absence of good data to guide decisions on immunosuppression in patients with failed allografts, practices in the US vary greatly. More data are needed to determine which policies lead to the best outcomes.