Faculty Bibliography

Liver allocation is based on current Model for End-Stage Liver Disease (MELD) scores, with priority in the case of a tie being given to those waiting the longest with a given MELD score. We hypothesized that this priority might not reflect risk: registrants whose MELD score has recently increased receive lower priority but might have higher wait-list mortality. We studied wait-list and posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By likelihood maximization, we empirically defined a MELD spike as a MELD increase ≥ 30% over the previous 7 days. At any given time, only 0.6% of wait-list patients experienced a spike; however, these patients accounted for 25% of all wait-list deaths. Registrants who reached a given MELD score after a spike had higher wait-list mortality in the ensuing 7 days than those with the same resulting MELD score who did not spike, but they had no difference in posttransplant mortality. The spike-associated wait-list mortality increase was highest for registrants with medium MELD scores: specifically, 2.3-fold higher (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD score and spikes predicted wait-list mortality risk much better than a model incorporating only the MELD score. Registrants with a sudden MELD increase have a higher risk of short-term wait-list mortality than is indicated by their current MELD score but have no increased risk of posttransplant mortality; allocation policy should be adjusted accordingly.

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002-2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P<0.001) that persisted when censoring for death (HR, 1.43; 95% CI, 1.12 to 1.84; P=0.005). However, compared with HIV-negative/hepatitis C virus (HCV)-negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P=0.02; 10-year: 36.2% versus 27.0%, P=0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P=0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P<0.01). However, PS was similar for HIV monoinfected recipients and HIV-negative/HCV-negative controls at both times. HIV/HCV coinfected recipients had worse PS compared with HIV-negative/HCV-infected controls (5-year: 67.0% versus 78.6%, P=0.007; 10-year: 29.3% versus 56.23%, P=0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P=0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.

There is significant variability amongst transplant centers, Organ Procurement Organizations (OPO), members of public, and patients about organs from Public Health Service increased risk donors. This has therefore required regulatory bodies like Centers for Disease Control and Prevention to formulate policies for transplant centers and OPOs to minimize risk of infectious transmission to recipients of solid-organ transplants from such donors.

BACKGROUND:The demographic and clinical correlates of gout after living kidney donation are not well described. METHODS:Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared the rates of renal diagnoses among donors with and without gout, matched in the ratio 1:3 by age, sex, and race. RESULTS:The study sample of 4,650 donors included 13.1% African Americans. By seven years, African Americans were almost twice as likely to develop gout as Caucasian donors (4.4 vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval (CI) 1.0-3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86; 95% CI 0.66-1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5-107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1-11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2-4.2). CONCLUSION/CONCLUSIONS:Donor subgroups at increased risk of gout include African Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment.

BACKGROUND:Frailty, a validated measure of physiologic reserve, predicts adverse health outcomes among adults with end-stage renal disease. Frailty typically is not measured clinically; instead, a surrogate-perceived frailty-is used to inform clinical decision-making. Because correlations between perceived and measured frailty remain unknown, the aim of this study was to assess their relationship. METHODS:146 adults undergoing hemodialysis were recruited from a single dialysis center in Baltimore, Maryland. Patient characteristics associated with perceived (reported by nephrologists, nurse practitioners (NPs), or patients) or measured frailty (using the Fried criteria) were identified using ordered logistic regression. The relationship between perceived and measured frailty was assessed using percent agreement, kappa statistic, Pearson's correlation coefficient, and prevalence of misclassification of frailty. Patient characteristics associated with misclassification were determined using Fisher's exact tests, t-tests, or median tests. RESULTS:Older age (adjusted OR [aOR] = 1.36, 95%CI:1.11-1.68, P = 0.003 per 5-years older) and comorbidity (aOR = 1.49, 95%CI:1.27-1.75, P < 0.001 per additional comorbidity) were associated with greater likelihood of nephrologist-perceived frailty. Being non-African American was associated with greater likelihood of NP- (aOR = 5.51, 95%CI:3.21-9.48, P = 0.003) and patient- (aOR = 4.20, 95%CI:1.61-10.9, P = 0.003) perceived frailty. Percent agreement between perceived and measured frailty was poor (nephrologist, NP, and patient: 64.1%, 67.0%, and 55.5%). Among non-frail participants, 34.4%, 30.0%, and 31.6% were perceived as frail by a nephrologist, NP, or themselves. Older adults (P < 0.001) were more likely to be misclassified as frail by a nephrologist; women (P = 0.04) and non-African Americans (P = 0.02) were more likely to be misclassified by an NP. Neither age, sex, nor race was associated with patient misclassification. CONCLUSIONS:Perceived frailty is an inadequate proxy for measured frailty among patients undergoing hemodialysis.

BACKGROUND:In response to recent studies, a better understanding of the risks of renal complications among African American and biologically related living kidney donors is needed. METHODS:We examined a database linking U.S. registry identifiers for living kidney donors (1987-2007) to billing claims from a private health insurer (2000-2007 claims) to identify renal condition diagnoses categorized by International Classification of Diseases 9th Revision coding. Cox regression with left and right censoring was used to estimate cumulative incidence of diagnoses after donation and associations (adjusted hazards ratios, aHR) with donor traits. RESULTS:Among 4650 living donors, 13.1% were African American and 76.3% were white; 76.1% were first-degree relatives of their recipient. By 7 years post-donation, after adjustment for age and sex, greater proportions of African American compared with white donors had renal condition diagnoses: chronic kidney disease (12.6% vs 5.6%; aHR, 2.32; 95% confidence interval [95% CI], 1.48-3.62), proteinuria (5.7% vs 2.6%; aHR, 2.27; 95% CI, 1.32-3.89), nephrotic syndrome (1.3% vs 0.1%; aHR, 15.7; 95% CI, 2.97-83.0), and any renal condition (14.9% vs 9.0%; aHR, 1.72; 95% CI, 1.23-2.41). Although first-degree biological relationship to the recipient was not associated with renal risk, associations of African American race persisted for these conditions and included unspecified renal failure and reported disorders of kidney dysfunction after adjustment for biological donor-recipient relationship. CONCLUSIONS:African Americans more commonly develop renal conditions after living kidney donation, independent of donor-recipient relationship. Continued research is needed to improve risk stratification for renal outcomes among African American living donors.

The Best Practice in Live Kidney Donation Consensus Conference held in June of 2014 included the Best Practices in Living Donor Education Workgroup, whose charge was to identify best practice strategies in education of living donors, community outreach initiatives, commercial media, solicitation, and state registries. The workgroup's goal was to identify critical content to include in living kidney donor education and best methods to deliver educational content. A detailed summary of considerations regarding educational content issues for potential living kidney donors is presented, including the consensus that was reached. Educational topics that may require updating on the basis of emerging studies on living kidney donor health outcomes are also presented. Enhancing the educational process is important for increasing living donor comprehension to optimize informed decision-making.

BACKGROUND:In the context of orthotopic liver transplantation (OLT), renal dysfunction is used as a criterion for simultaneous liver-kidney transplantation. Changes in glomerular filtration rate (GFR) the year before and after OLT have not been well defined. METHODS:In a cohort of 416 OLT patients from 1996 to 2009, estimated GFR (eGFR) was assessed during the 12 months before OLT (period A), at time of OLT (period B), and the 12 months after OLT (period C). Outcomes included progression to end stage renal disease (ESRD), length of stay, and mortality. RESULTS:The overall rate of progression to ESRD over 15 years of follow-up was 0.155/person-year and was strongly associated with eGFR <60 (hazard ratio [HR] = 2.7; P < 0.001), diabetes (HR = 2.6; P < 0.001), and with a combination of the 2 (HR = 5.5; P < 0.0001). Mean eGFR decreased from period A (86 mL/min per 1.73 m) to period B (77; P < 0.001) to period C (71; P < 0.001), with similar decreases in eGFR across subgroups of clinical variables. Patients with eGFR less than 60 mL/min per 1.73 m at OLT had acute and large decreases in eGFR from periods A to B, then increases to period C. Length of stay was associated with eGFR at OLT, hepatorenal syndrome, dialysis requirement, model for end-stage liver disease score, and alcoholic liver disease. Twelve-month mortality was strongly associated with time-dependent change in eGFR, hepatorenal syndrome, dialysis requirement, hepatitis C, and model for end-stage liver disease era transplantation but was not associated with eGFR at OLT. CONCLUSIONS:Among OLT patients, renal function worsened in all subgroups from before to after OLT, but the association of progression to ESRD was particularly high among patients with both diabetes and eGFR less than 60 at the time of OLT. This suggests that diabetes could be considered as a criterion when making decisions regarding simultaneous liver-kidney transplantation.

Concerns have been raised that optimized redistricting of liver allocation areas might have the unintended result of shifting livers from better-performing to poorer-performing organ procurement organizations (OPOs). We used liver simulated allocation modeling to simulate a 5-year period of liver sharing within either 4 or 8 optimized districts. We investigated whether each OPO's net liver import under redistricting would be correlated with 2 OPO performance metrics (observed to expected liver yield and liver donor conversion ratio), along with 2 other potential correlates (eligible deaths and incident listings above a Model for End-Stage Liver Disease score of 15). We found no evidence that livers would flow from better-performing OPOs to poorer-performing OPOs in either redistricting scenario. Instead, under these optimized redistricting plans, our simulations suggest that livers would flow from OPOs with more-than-expected eligible deaths toward those with fewer-than-expected eligible deaths and that livers would flow from OPOs with fewer-than-expected incident listings to those with more-than-expected incident listings; the latter is a pattern that is already established in the current allocation system. Redistricting liver distribution to reduce geographic inequity is expected to align liver allocation across the country with the distribution of supply and demand rather than transferring livers from better-performing OPOs to poorer-performing OPOs.