Natasha Gupta

Frailty and Mortality in Kidney Transplant Recipients

We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post‐KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single‐center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single‐center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17‐fold (95% CI: 1.01–4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post‐KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.

Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation.

Background Incompatible live donor kidney transplantation is associated with an increased rate of antibody-mediated rejection (AMR) and subsequent transplant glomerulopathy. For patients with severe, oliguric AMR, graft loss is inevitable without timely intervention. Methods We reviewed our experience rescuing kidney allografts with this severe AMR phenotype by using splenectomy alone (n=14), eculizumab alone (n=5), or splenectomy plus eculizumab (n=5), in addition to plasmapheresis. Results The study population was 267 consecutive patients with donor-specific antibody undergoing desensitization. In the first 3 weeks after transplantation (median=6 days), 24 patients developed sudden onset oliguria and rapidly rising serum creatinine with marked rebound of donor-specific antibody, and a biopsy that showed features of AMR. At a median follow-up of 533 days, 4 of 14 splenectomy-alone patients experienced graft loss (median=320 days), compared to four of five eculizumab-alone patients with graft failure (median=95 days). No patients treated with splenectomy plus eculizumab experienced graft loss. There was more chronic glomerulopathy in the splenectomy-alone and eculizumab-alone groups at 1 year, whereas splenectomy plus eculizumab patients had almost no transplant glomerulopathy. Conclusion These data suggest that for patients manifesting early severe AMR, splenectomy plus eculizumab may provide an effective intervention for rescuing and preserving allograft function.

Quantifying Renal Allograft Loss Following Early Antibody‐Mediated Rejection

Unlike antibody‐mediated rejection (AMR) with clinical features, it remains unclear whether subclinical AMR should be treated, as its effect on allograft loss is unknown. It is also uncertain if AMRs effect is homogeneous across donor (deceased/live) and (HLA/ABO) antibody types. We compared 219 patients with AMR (77 subclinical, 142 clinical) to controls matched on HLA/ABO‐compatibility, donor type, prior transplant, panel reactive antibody (PRA), age and year. One and 5‐year graft survival in subclinical AMR was 95.9% and 75.7%, compared to 96.8% and 88.4% in matched controls (p = 0.0097). Subclinical AMR was independently associated with a 2.15‐fold increased risk of graft loss (95% CI: 1.19–3.91; p = 0.012) compared to matched controls, but not different from clinical AMR (p = 0.13). Fifty three point two percent of subclinical AMR patients were treated with plasmapheresis within 3 days of their AMR‐defining biopsy. Treated subclinical AMR patients had no difference in graft loss compared to matched controls (HR 1.73; 95% CI: 0.73–4.05; p = 0.21), but untreated subclinical AMR patients did (HR 3.34; 95% CI: 1.37–8.11; p = 0.008). AMRs effect on graft loss was heterogeneous when stratified by compatible deceased donor (HR = 4.73; 95% CI: 1.57–14.26; p = 0.006), HLA‐incompatible deceased donor (HR = 2.39; 95% CI: 1.10–5.19; p = 0.028), compatible live donor (no AMR patients experienced graft loss), ABO‐incompatible live donor (HR = 6.13; 95% CI: 0.55–67.70; p = 0.14) and HLA‐incompatible live donor (HR = 6.29; 95% CI: 3.81–10.39; p < 0.001) transplant. Subclinical AMR substantially increases graft loss, and treatment seems warranted.

Changes in Frailty After Kidney Transplantation.

To understand the natural history of frailty after an aggressive surgical intervention, kidney transplantation (KT).

Perceived frailty and measured frailty among adults undergoing hemodialysis: a cross-sectional analysis.

BackgroundFrailty, 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.Methods146 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.ResultsOlder 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.ConclusionsPerceived frailty is an inadequate proxy for measured frailty among patients undergoing hemodialysis.

The Aggressive Phenotype Revisited: Utilization of Higher‐Risk Liver Allografts

Organ shortage has led to increased utilization of higher risk liver allografts. In kidneys, aggressive center‐level use of one type of higher risk graft clustered with aggressive use of other types. In this study, we explored center‐level behavior in liver utilization. We aggregated national liver transplant recipient data between 2005 and 2009 to the center‐level, assigning each center an aggressiveness score based on relative utilization of higher risk livers. Aggressive centers had significantly more patients reaching high MELDs (RR 2.19, 2.33 and 2.28 for number of patients reaching MELD > 20, MELD > 25 and MELD > 30, p < 0.001), a higher organ shortage ratio (RR 1.51, 1.60 and 1.51 for number of patients reaching MELD > 20, MELD > 25 and MELD > 30 divided by number of organs recovered at the OPO, p < 0.04), and were clustered within various geographic regions, particularly regions 2, 3 and 9. Median MELD at transplant was similar between aggressive and nonaggressive centers, but average annual transplant volume was significantly higher at aggressive centers (RR 2.27, 95% CI 1.47–3.51, p < 0.001). In cluster analysis, there were no obvious phenotypic patterns among centers with intermediate levels of aggressiveness. In conclusion, highwaitlist disease severity, geographic differences in organ availability, and transplant volume are the main factors associated with the aggressive utilization of higher risk livers.

Health-Related and Psychosocial Concerns about Transplantation among Patients Initiating Dialysis

BACKGROUND AND OBJECTIVES Disparities in kidney transplantation remain; one mechanism for disparities in access to transplantation (ATT) may be patient-perceived concerns about pursuing transplantation. This study sought to characterize prevalence of patient-perceived concerns, explore interrelationships between concerns, determine patient characteristics associated with concerns, and assess the effect of concerns on ATT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Prevalences of 12 patient-perceived concerns about pursuing transplantation were determined among 348 adults who recently initiated dialysis, recruited from 26 free-standing dialysis centers around Baltimore, Maryland (January 2009-March 2012). Using variable reduction techniques, concerns were clustered into two categories (health-related and psychosocial) and quantified with scale scores. Associations between patient characteristics and concerns were estimated using modified Poisson regression. Associations between concerns and ATT were estimated using Cox models. RESULTS The most frequently cited patient-perceived concerns were that participants felt they were doing fine on dialysis (68.4%) and felt uncomfortable asking someone to donate a kidney (29.9%). Older age was independently associated with having high health-related (adjusted relative risk, 1.35 [95% confidence interval, 1.20 to 1.51], for every 5 years older for those ≥ 60 years) or psychosocial (1.15 [1.00 to 1.31], for every 5 years older for those aged ≥ 60 years) concerns, as was being a woman (1.72 [1.21 to 2.43] and 1.55 [1.09 to 2.20]), having less education (1.59 [1.08 to 2.35] and 1.77 [1.17 to 2.68], comparing postsecondary education to grade school or less), and having more comorbidities (1.18 [1.08 to 1.30] and 1.18 [1.07 to 1.29], per one comorbidity increase). Having never seen a nephrologist before dialysis initiation was associated with high psychosocial concerns (1.48 [1.01 to 2.18]). Those with high health-related (0.37 [0.16 to 0.87]) or psychosocial (0.47 [0.23 to 0.95]) concerns were less likely to achieve ATT (median follow-up time 2.2 years; interquartile range, 1.6-3.2). CONCLUSIONS Patient-perceived concerns about pursuing kidney transplantation are highly prevalent, particularly among older adults and women. Reducing these concerns may help decrease disparities in ATT.

Center-level variation in the development of delayed graft function after deceased donor kidney transplantation

Background Patient-level risk factors for delayed graft function (DGF) have been well described. However, the Organ Procurement and Transplantation Network definition of DGF is based on dialysis in the first week, which is subject to center-level practice patterns. It remains unclear if there are center-level differences in DGF and if measurable center characteristics can explain these differences. Methods Using the 2003 to 2012 Scientific Registry of Transplant Recipients data, we developed a hierarchical (multilevel) model to determine the association between center characteristics and DGF incidence after adjusting for known patient risk factors and to quantify residual variability across centers after adjustment for these factors. Results Of 82,143 deceased donor kidney transplant recipients, 27.0% developed DGF, with a range across centers of 3.2% to 63.3%. A center’s proportion of preemptive transplants (odds ratio [OR], 0.83; per 5% increment; 95% confidence interval [95% CI], 0.74–;0.93; P = 0.001) and kidneys with longer than 30 hr of cold ischemia time (CIT) (OR, 0.95; per 5% increment; 95% CI, 0.92–;0.98; P = 0.001) were associated with less DGF. A center’s proportion of donation after cardiac death donors (OR, 1.12; per 5% increment; 95% CI, 1.03–;1.17; P < 0.001) and imported kidneys (OR, 1.06; per 5% increment; 95% CI, 1.03–;1.10; P < 0.001) were associated with more DGF. After patient-level and center-level adjustments, only 41.8% of centers had DGF incidences consistent with the national median and 28.2% had incidences above the national median. Conclusion Significant heterogeneity in DGF incidences across centers, even after adjusting for patient-level and center-level characteristics, calls into question the generalizability and validity of the current DGF definition. Enhanced understanding of center-level variability and improving the definition of DGF accordingly may improve DGF’s utility in clinical care and as a surrogate endpoint in clinical trials.

Ureteroscopy for Treatment of Upper Urinary Tract Stones in Children: Technical Considerations

The incidence of pediatric urolithiasis is increasing. While many smaller stones may pass spontaneously, surgical therapy is sometimes warranted. Surgical options include shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, and open surgery. Ureteroscopy represents a minimally invasive approach, and it is increasingly being used to treat pediatric upper tract calculi. Ureteroscopy is performed under anesthesia and fluoroscopic guidance, with basket extraction or lithotripsy of the calculi. Technical considerations include active or passive ureteral dilatation, the use of ureteral access sheaths for larger stone burdens, and post-operative stent placement. The current pediatric literature suggests high success rates (equal to or surpassing shock wave lithotripsy) and low complication rates. However, concerns remain regarding feasibility in patients with variant anatomies and risk due to intra-operative radiation exposure.

Assessment of resident and fellow knowledge of the organ donor referral process

Maximizing deceased donation rates can decrease the organ shortage. Non‐transplant physicians play a critical role in facilitating conversion of potential deceased donors to actual donors, but studies suggest that physicians lack knowledge about the organ donation process. As residency and fellowship are often the last opportunities for formal medical training, we hypothesized that deficiencies in knowledge might originate in residency and fellowship. We conducted a cross‐sectional survey to assess knowledge about organ donation, experience in donor conversion, and opinions of the process among residents and fellows after their intensive care unit rotations at the Johns Hopkins Hospital. Of 40 participants, 50% had previously facilitated donor conversion, 25% were familiar with the guidelines of the organ procurement organization (OPO), and 10% had received formal instruction from the OPO. The median score on the knowledge assessment was five of 10; higher knowledge score was not associated with level of medical training, prior training in or experience with donor conversion, or with favorable opinions about the OPO. We identified a pervasive deficit in knowledge among residents and fellows at an academic medical center with an active transplant program that may help explain attending‐level deficits in knowledge about the organ donation process.