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

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

Psychosocial characteristics of patients evaluated for kidney transplant and associations with functional and frailty metrics at a veterans affairs hospital.

BACKGROUND: The effect of psychosocial problems on listing outcomes and potential interactions with functional metrics is not well-characterized among Veteran transplant candidates. METHODS: The results from psychosocial evaluations, frailty metrics, and biochemical markers were collected on 375 consecutive Veteran kidney transplant candidates. Psychosocial diagnoses were compared between patients listed or denied for transplant. Functional abilities were compared among patients with or without psychosocial diagnoses and then evaluated based on reason for denial. RESULTS: Eighty-four percent of patients had a psychosocial diagnosis. Common issues included substance or alcohol abuse (62%), psychiatric diagnoses (50%), and poor adherence (25%). Patients with psychiatric diagnoses, cognitive impairments, and poor adherence were more likely to be denied for transplant (P < .05). Patients with depression, PTSD, and anxiety did not have worse functional ability, but experienced more exhaustion than patients without these problems. Patients denied for medical but not purely psychosocial reasons had worse troponin and functional metrics compared with listed patients. CONCLUSION: Over 80% of patients with a psychosocial diagnosis were listed; however, poor adherence was a particularly important reason for denial for purely psychosocial reasons. Patients with psychosocial diagnoses generally were not more functionally limited than their counterparts without psychosocial diagnoses or those listed for transplant.

Infiltrating Kaposi sarcoma presenting as acute kidney injury: An unexpected consequence of deliberate hepatitis C-positive organ transplantation.

Kaposi sarcoma (KS) following kidney transplantation can result from recipient reactivation of latent human herpesvirus 8 (HHV-8) infection or activation of donor-acquired HHV-8 infection. Post-transplant KS typically manifests with cutaneous pathology, but rare cases of renal allograft involvement have been reported. We describe two cases of donor-derived HHV-8 infection in two hepatitis C (HCV) viremia-negative transplant recipients who each received a kidney from a donor with HCV viremia. One recipient did not develop KS while the other presented with acute kidney injury caused by extensive KS infiltration of the renal parenchyma and metastatic disease. This report reviews the literature for cases of KS involving the renal allograft and highlights an unexpected consequence of deliberate HCV-positive organ transplantation.

Development and implementation of a Telenephrology dashboard for active surveillance of kidney disease: a quality improvement project.

BACKGROUND: Kidney disease accounts for more than 49 billion dollars in healthcare expenditures annually. Early detection and intervention may reduce the burden of disease. We describe a quality improvement project to develop a telenephrology dashboard that proactively monitors kidney disease. METHODS: One hundred eighty-four thousands Veterans within the Iowa City Veterans Affairs Health Care System were eligible for telenephrology consultation. The dashboard accessed the charts of 53,085 Veterans at risk for kidney disease. We utilized Lean-Six Sigma tools and principles and the Define-Measure-Analyze-Improve-Control Framework to develop and deploy a telenephrology dashboard in 4 community-based outpatient clinics (CBOCs). The primary measure was the number of days to complete consultation. Secondary measures included number of electronic consultations per month, distance and cost of Veteran travel saved, and number of steps for completion of consult. RESULTS: The data of 1384 Veterans at the 4 CBOCs were analyzed by the telenephrology dashboard, of which 459 generated telenephrology consults. The number of days to complete any type of consultation was unchanged (48.9 days in 2019, compared to 41.6 days in 2017). The average Veteran saved between $21.60 to $63.90 per trip to Iowa City. Between March 2019 and August 2019, there were 27.3 telenephrology consults per month. The number of steps needed to complete the consult request was decreased from 13 to 9. CONCLUSIONS: Utilization of the telenephrology dashboard system contributed to an increase in consultations completed through electronic means without decreasing face-to-face consults. Electronic consults now outnumber traditional face-to-face consultations at our institution. Telenephrology consultation improved early detection and identification of kidney disease and saved time and costs for Veterans in travel, but did not decrease the average number of days to complete consultation requests.

Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort.

Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10-5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P = .0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10-5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10-7 ; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.

BK virus histopathologic disease severity does not predict allograft outcome in renal transplant recipients.

AIMS: BK polyomavirus nephropathy (BKPyVN) is an important cause of allograft failure after renal transplantation. Despite early screening for the virus, allograft loss from BKPyVN is still experienced in up to 14% of all renal transplant recipients. The aim of this study was to investigate the association between BKPyVN histopathologic disease severity and allograft outcome at our center. METHODS: Kidney transplant recipients who had undergone transplantation between 2002 and 2014 with biopsy proven BKPyVN were eligible for this retrospective study. Each biopsy was re-evaluated by a single pathologist blinded to the clinical data and scored according to the Banff criteria for rejection and BKPyVN. Serum creatinine and BK viral load at the time of biopsy diagnosis as well as allograft outcomes to include allograft survival and serum BK viremia resolution were collected for each recipient to determine if BK virus histopathologic disease severity could predict allograft outcome. RESULTS: Twenty cases of BKPyVN were identified from 1031 total renal transplants performed. There was no statistical association between allograft loss and BKPyVN histopathology (p = 0.49). There was also no statistical association between BKPyVN histopathology and BK viral load at the time of biopsy diagnosis (p = 0.38) or serum BK viremia resolution (p = 0.16). CONCLUSIONS: BKPyVN histopathology does not appear to be useful in predicting renal allograft outcome in those recipients diagnosed with BKPyVN which is in contrast to some previously published data.

Sarcopenia is associated with survival in patients awaiting kidney transplant.

BACKGROUND: The relationship of sarcopenia to frailty and other survival determinants in patients waitlisted for kidney transplant is not well characterized. Our goal was to evaluate the relationship of muscle area to functional and frailty metrics and its impact on survival in patients waitlisted for kidney transplant. METHODS: Among 303 consecutively listed transplant candidates, 172 had a computed scan within 3 months of frailty and biochemical testing that permitted muscle area evaluation. Third lumbar level psoas muscle indices (total bilateral psoas area/height2) were calculated. Testing included frailty metrics, treadmill and pedometer ability, troponin, and brain natriuretic peptide levels. Associations between muscle area, demographic, biochemical, and frailty measures were analyzed. Log-rank test was used to evaluate waitlist survival on the basis of muscle area, and multivariate Cox proportional hazards modeling was used to evaluate factors independently associated with survival. RESULTS: Demographic factors associated with third lumbar level psoas muscle indices include male sex (P < .001), race (P = .02), age (P = .004), and body mass index (P < .0001). Grip strength, treadmill ability, and Sit-Stands positively correlated with third lumbar level psoas muscle indices (P < .01). Brain natriuretic peptide and Up and Go negatively correlated with third lumbar level psoas muscle indices (P < .01). Survival was significantly associated with third lumbar level psoas muscle indices (P = 0.02). Treadmill ability, Sit-Stands, Up and Go, race and muscle area were most closely associated with waitlist survival on multivariate modeling. CONCLUSION: Sarcopenia as assessed with muscle area measurements is independently associated with kidney waitlist survival. Functional ability and muscle area may be overlapping, but noncongruent, determinants of waitlist outcomes and may need to be individually assessed to create the most predictive survival model.

Walking Ability and Brain Natriuretic Peptide Are Highly Predictive of Kidney Transplant Waiting List Removal.

Kidney transplant waitlist management is complex because waiting time is long, and the patients have significant comorbidities. Identification of patients at highest risk for waiting list removal for death and medical complications could allow better outcomes and allocation of resources. Methods: Demographics, functional and frailty assessment' and biochemical data were retrospectively analyzed on 313 consecutive patients listed for kidney transplant. Troponin, brain natriuretic peptide, components of the Fried frailty metrics, pedometer activity, and treadmill ability were measured at the time of transplant evaluation and at subsequent re-evaluations. Cox proportional hazards models were used to identify factors associated with death or waiting list removal for medical reasons. Multivariate models were created to identify significant predictor sets. Results: Among 249 patients removed while waitlisted, 19 (6.1%) died and 51 (16.3%) were removed for medical reasons. Mean follow-up duration was 2.3 y (±1.5 y). 417 sets of measurements were collected. Significant (P < 0.05) non-time-dependent variables associated with the composite outcome identified on univariate analysis included N-terminal probrain natriuretic peptide (BNP), treadmill ability, pedometer activity, diagnosis of diabetes and the Center of Epidemiological Studies Depression Scale question asking how many days per week could you not get going. Significant time-dependent factors included BNP, treadmill ability, Up and Go, pedometer activity, handgrip, 30 s chair sit-stand test, and age. The optimal time-dependent predictor set included BNP, treadmill ability, and patient age. Conclusions: Changes in functional and biochemical markers are predictive of kidney waitlist removal for death and medical reasons. BNP and measures of walking ability were of particular importance.

Frailty measures can be used to predict the outcome of kidney transplant evaluation.

BACKGROUND: Experience incorporating frailty and functional metrics in the transplant evaluation process is limited. We hypothesized that simple tests correlate with kidney transplant listing outcomes. METHODS: Frailty metrics, treadmill ability, pedometer data, troponin T, and brain natriuretic peptide were collected on 375 consecutive kidney transplant evaluations between July 2015 and December 2018. Patients initially denied were compared with those listed or deferred. Frailty metrics included handgrip, chair sit-stand, up-and-go, chair sit-reach, and questions related to exhaustion. RESULTS: A total of 95 (25%) patients were initially denied. Those denied were older, diabetic, or had higher body mass indexes. Frailty metrics including chair sit-stand, up-and-go, chair sit-reach, grip strength, and exhaustion; biochemical markers troponin and brain natriuretic peptide; and pedometer and treadmill ability were all significantly associated with denial (P < .001). The best order three model combining parsimony and predictiveness included treadmill ability, exhaustion, and troponin. The most predictive pedometer model also included exhaustion and up-and-go. The best order three model excluding biochemical markers, pedometer, and treadmill results included up-and-go, exhaustion, and chair sit-reach. CONCLUSION: Outcomes after on-site kidney transplant evaluation strongly correlated with the results of common clinical and functional frailty metrics.

Hypertensive Emergency.

A rapid and severe increase in blood pressure resulting in new or progressive end-organ damage is defined as hypertensive emergency. Clinicians should effectively use the patient interview, physical examination, and additional testing to differentiate hypertensive emergency from nonemergent hypertension. Patients with evidence or high suspicion for end-organ damage should be expediently referred from the outpatient setting to a higher level of care. Knowledge of appropriate hypertensive emergency management and the ability to initiate this care in the clinic could help reduce patient morbidity in certain situations. Patients presenting with nonemergent hypertension can continue to be safely managed in the clinic.

Clinical and Genetic Factors Associated with Cutaneous Squamous Cell Carcinoma in Kidney and Heart Transplant Recipients.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) occurs with higher frequency and recurrence rates, increased morbidity and mortality, and more aggressive metastasis in kidney and heart transplant recipients compared to the general population but all transplant recipients do not develop cSCC. In addition, the phenotypic expression of cSCC among transplant recipients can vary between mild disease to extensive recurrent metastatic disease. These clinically observed differences in occurrence and severity of cSCC among transplant recipients suggest the possibility that an underlying genetic component might modify risk. METHODS: We identified 88 white post-transplant cSCC cases (71 kidney and 17 heart) and 300 white post-transplant controls (265 kidney and 35 heart) using a DNA biobank linked with de-identified electronic medical records. Logistic regression was used to determine adjusted odds ratios (OR) for clinical characteristics and single nucleotide polymorphisms (SNP) associated with cSCC in both a candidate SNP and genome wide analysis. RESULTS: Age (OR 1.08 [1.05-1.11], p<0.001) and azathioprine exposure (OR 8.64 [3.92-19.03], p<0.001) were significantly associated while gender, smoking tobacco use, dialysis duration and immunosuppression duration were not. Ten candidate SNPs previously associated with non-melanoma skin cancer in the general population were significantly associated with cSCC in transplant recipients. Genome wide association analysis implicated SNPs in genes previously associated with malignancy, CSMD1 (OR 3.14 [1.90-5.20]) and CACNA1D (OR 2.67 [1.73-4.10]). CONCLUSIONS: This study shows an association of increasing age and azathioprine exposure with cSCC and confirms a genetic contribution for cSCC development in kidney and heart transplant recipients.

A novel series of urea-based peptidomimetic calpain inhibitors.

A series of peptide aldehyde derivatives in which the P(2) chiral carbon has been replaced with nitrogen were synthesized as urea-based peptidomimetic inhibitors of mu-calpain. The compounds mirrored the general SAR of peptidyl aldehyde calpain inhibitors but displayed greater selectivity for mu-calpain over cathepsin B.