Transplant Clinician Opinions on Use of Race in the Estimation of Glomerular Filtration Rate.

BACKGROUND AND OBJECTIVES: Current race-based eGFR calculators assign a higher eGFR value to Black patients, which could affect the care of kidney transplant candidates and potential living donors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a survey of staff at adult kidney transplant centers in the United States (December 17, 2020 to February 28, 2021) to assess opinions on use of race-based eGFR equations for waitlisting and living donor candidate evaluation, availability of serum cystatin C testing and measured GFR, and related practices. RESULTS: Respondents represented 57% (124 of 218) of adult kidney transplant programs, and the responding centers conducted 70% of recent kidney transplant volume. Most (93%) programs use serum creatinine-based eGFR for listing candidates. However, only 6% of respondents felt that current race-based eGFR calculators are appropriate, with desire for change grounded in concerns for promotion of health care disparities by current equations and inaccuracies in reporting of race. Most respondents (70%) believed that elimination of race would allow more preemptive waitlisting for Black patients, but a majority (79%) also raised concerns that such an approach could incur harms. More than one third of the responding programs lacked or were unsure of availability of testing for cystatin C or measured GFR. At this time, 40% of represented centers did not plan to remove race from eGFR calculators, 46% were planning to remove, and 15% had already done so. There was substantial variability in eGFR reporting and listing of multiracial patients with some Black ancestry. There was no difference in GFR acceptance thresholds for Black versus non-Black living donors. CONCLUSIONS: This national survey highlights a broad consensus that extant approaches to GFR estimation are unsatisfactory, but it also identified a range of current opinions.

Insulin Sensitivity After Living Donor Nephrectomy.

BACKGROUND: The kidney is essential for glucose and insulin metabolism. Living kidney donors (LKDs) experience a reduction in glomerular filtration rate of 25 to 30 mL/min after donor nephrectomy. Little is known about the effect of glomerular filtration rate decline on insulin sensitivity in LKDs. METHODS: We conducted a prospective pilot study on 9 LKDs (N = 9) who underwent dynamic metabolic testing (mixed meal tolerance test) to measure proxies of insulin sensitivity (homeostatic model assessment of insulin resistance, the area under curve [AUC] for insulin/glucose ratio, and Matsuda insulin sensitivity index) before and 3 months after donor nephrectomy. The primary outcome was the change in insulin sensitivity indices (delta [post-nephrectomy - pre-nephrectomy]). RESULTS: Four of the donors had a body mass index (BMI) between 32.0 and 36.7 predonation. Post-donor nephrectomy, compared with prenephrectomy values, median insulin AUC increased from 60.7 to 101.7 hr*mU/mL (delta median 33.3, P = .04) without significant change in median glucose AUC levels from 228.9 to 209.3 hr*mg/dL (delta median 3.2, P = .77). There was an increase in the median homeostatic model assessment of insulin resistance from 2 to 2.9 (delta median 0.8, P = .03) and the AUC insulin/glucose ratio from 30.9 to 62.1 pmol/mmol (delta median 17.5, P = .001), whereas the median Matsuda insulin sensitivity index decreased from 5.9 to 2.9 (delta median -2, P = .05). The changes were more pronounced in obese (BMI >32) donors. CONCLUSION: LKDs appear to have a trend toward a decline in insulin sensitivity post-donor nephrectomy in the short term, especially in obese donors (BMI >32). Further investigation with a larger sample size and longer follow-up is needed.

Induction regimen and survival in simultaneous heart-kidney transplant recipients.

BACKGROUND: Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED). METHODS: We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists. Survival rates were estimated using the Kaplan-Meier estimator. Multivariable inverse probability weighted Cox proportional hazard regression models were used to assess hazard ratios associated with post-transplant mortality as the primary outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year of follow-up. RESULTS: During the study period, the number of SHKTs increased nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r-ATG compared with no induction or interleukin-2 receptor-α induction. Compared with the no-induction group, an inverse probability weighted Cox proportional hazard model showed no independent association of induction therapy with the primary outcome. In sub-group analysis, r-ATG appeared to lower mortality in sensitized patients with panel reactive antibody of 10% or higher (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71). CONCLUSION: r-ATG may provide a survival benefit in SHKT, especially in sensitized patients maintained on TAC/MPA/PRED at hospital discharge.

Development of a Predictive Model for Drug-Related Problems in Kidney Transplant Recipients.

STUDY OBJECTIVE: Drug-related problems (DRPs) are associated with increased rates of infection, rejection, and graft loss in kidney transplant recipients. This study aimed to develop a model to predict which patients are at highest risk of DRPs to streamline pharmacists' workflow in a chronic kidney transplant clinic. DESIGN: Prospective observational study. SETTING: Chronic kidney transplant clinic at a large, tertiary care, academic hospital. PATIENTS: Two hundred thirty-seven adults seen in the kidney transplant clinic between September 16, 2015, and November 30, 2015, who were at least 90 days posttransplantation at the time of their clinic visit. MEASUREMENTS AND MAIN RESULTS: Prospective data detailing DRPs and a survey assessing baseline characteristics and patient-related outcomes were used to generate a predictive model to identify patients at risk of having six or more DRPs; the cutoff of six DRPs provided a threshold for identifying a subset of high-risk patients on whom the transplant pharmacists could focus their efforts. DRPs were categorized as nonadherence, overdosing or underdosing, duplication of therapy, preventable adverse drug reaction, missing medication, erroneous medication, conflicting provider information, undermonitoring or lack of monitoring, and wrong medication received. In total, 865 unique DRPs were identified, and the most common were erroneous medication, missing medication, and nonadherence, accounting for 38%, 21%, and 16% of the DRPs, respectively. A nine-variable model with a sensitivity of 62.5% and specificity of 66.7% (area under the receiver operating characteristic curve of 0.720) was developed to identify patients at risk of having six or more DRPs. The model included the following variables: age, Medicaid for prescription insurance, current employment status, medication affordability, difficulty or lack of difficulty obtaining medications from the pharmacy, negative impact of medications on quality of life, medication nonadherence, poor rating of current health status, and moderate or poor medication understanding. CONCLUSION: These results demonstrated that a straightforward, 5-minute survey completed by renal transplant recipients prior to their clinic visit may be capable of effectively determining those at risk of having six or more DRPs, potentially allowing use as a screening tool for transplant pharmacists' workflow prioritization. External validation is needed before this tool can be used in the outpatient setting.

A Case of BK Nephropathy without Detectable Viremia or Viruria.

BACKGROUND: BK nephropathy is an evolving challenge among kidney transplant recipients. Diagnosis of BK nephropathy depends on the presence of BK viral inclusions on renal biopsy. Most cases of BK nephropathy are preceded by BK viremia or viruria. CASE REPORT: We report a case of BK nephropathy found on protocol renal transplant biopsy without associated BK viremia or viruria. CONCLUSIONS: BK nephropathy may occur even in the absence of BK viremia or viruria. Protocol biopsy is a useful tool to detect these cases.

Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance.

BACKGROUND AND OBJECTIVES: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. RESULTS: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. CONCLUSIONS: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

Live Donor Renal Anatomic Asymmetry and Posttransplant Renal Function.

BACKGROUND: Relationship between live donor renal anatomic asymmetry and posttransplant recipient function has not been studied extensively. METHODS: We analyzed 96 live kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from computerized tomography angiograms) and their matching recipients. Split function differences (SFD) were quantified with technetium-dimercaptosuccinic acid renography. Implantation biopsies at time 0 were semiquantitatively scored. A comprehensive model using donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at 1 year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60 mL/min/1.73 m(2) at 1 year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the chronic kidney disease-epidemiology collaboration formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). RESULTS: In the study cohort, the mean Vol/Wgt and eGFR at 1 year were 2.04 mL/kg and 60.4 mL/min/1.73 m(2), respectively. Volume and split ratios between 2 donor kidneys were strongly correlated (r = 0.79, P < 0.001). The biopsy scores among SFD categories (<5%, 5%-10%, >10%) were not different (P = 0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR > 60 mL/min/1.73 m (odds ratio, 8.94, 95% CI 2.47-32.25, P = 0.001) and had a strong discriminatory power in predicting the risk of eGFR less than 60 mL/min/1.73 m(2) at 1 year [receiver operating curve (ROC curve), 0.78, 95% CI, 0.68-0.89]. CONCLUSIONS: In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at 1 year after transplantation. Renography can be replaced with CT volume calculation in estimating split renal function.

Hemoglobinuric acute kidney injury from aortic root graft malfunction.

Hemolysis and consequent hemoglobinuria is a well-known cause of acute kidney injury (AKI). Hemolysis has been associated with malpositioned prosthetic valves, but other prosthetic devices may rarely be associated with red cell shear stress. We report a case of a 56-year-old man who presented with hemolysis, AKI, and anemia. During workup, he was found to have anti-phospholipid antibodies, leading to a presumptive diagnosis of catastrophic anti-phospholipid antibody syndrome. However, further investigation revealed the cause of hemolysis to be from aortic root graft dysfunction. Following replacement of the prosthesis, there was complete resolution of his hemolysis and recovery of renal function. This case underscores the need to consider cardiac prosthetic devices in patients presenting with hemoglobinuric AKI.

Diagnostic tests and treatment options in glomerular disease: 2014 update.

Glomerular diseases historically have been challenging disorders to comprehend and treat for patients and physicians alike. Kidney biopsy is the gold standard of diagnosis, but the link between pathophysiology and the histologic representation of kidney injury has remained elusive in many of these diseases. As a result, treatment of glomerular disease usually involves therapies that are not specific to disease pathogenesis, such as blockade of the renin-angiotensin-aldosterone system and various immunosuppression regimens. Recent research has resulted in greater insight into some glomerular diseases, leading to the hope that new diagnostic tests and treatments targeting disease-specific mechanisms are on the horizon. We review recent progress on the understanding, diagnosis, and treatment of 4 glomerular diseases: immunoglobulin A nephropathy, focal segmental glomerulosclerosis, the C3 glomerulopathies, and idiopathic membranous nephropathy.

Lupus nephritis: treatment of resistant disease.

Lupus nephritis (LN) remains a major cause of ESRD and is associated with a >4-fold increase in mortality and significant morbidity in patients with lupus. The treatment of LN has evolved significantly over the past decade due to data from well conducted randomized controlled trials. We are currently in an era in which effective regimens exist in the form of induction and maintenance agents. Histopathologic classification of LN remains one of the main factors guiding therapy.

Acute kidney injury from pyelonephritis in an elderly man: case report.

Pyelonephritis is rarely considered in the differential diagnosis of acute kidney injury. Acute non-obstructed bacterial pyelonephritis is an infrequent and rarely considered cause of rapidly progressive acute kidney injury. A diagnostic challenge thus develops as it is difficult to clinically differentiate acute kidney injury secondary to ischemic or toxic acute tubular necrosis or papillary necrosis versus acute interstitial nephritis secondary to drugs or infectious pyelonephritis. We describe a case of acute kidney injury due to suppurative pyelonephritis in an elderly immunocompetent man who presented with dysuria, vomiting, and fever and later found to have histologic and radiologic proven pyelonephritis as the cause of acute kidney injury in the absence of hypotension, nephrotoxic agents, non-steroidal analgesics, immunosuppression, urinary tract obstruction, or other structural anomalies. The patient was managed with antimicrobial therapy, hemodialysis, and a short course of corticosteroids.