Racial Health Disparity and COVID-19.

The infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and resultant coronavirus diseases-19 (COVID-19) disproportionally affects minorities, especially African Americans (AA) compared to the Caucasian population. The AA population is disproportionally affected by COVID-19, in part, because they have high prevalence of underlying conditions such as obesity, diabetes, and hypertension, which are known to exacerbate not only kidney diseases, but also COVID-19. Further, a decreased adherence to COVID-19 guidelines among tobacco smokers could result in increased infection, inflammation, reduced immune response, and lungs damage, leading to more severe form of COVID-19. As a result of high prevalence of underlying conditions that cause kidney diseases in the AA population coupled with tobacco smoking make the AA population vulnerable to severe form of both COVID-19 and kidney diseases. In this review, we describe how tobacco smoking interact with SARS-CoV-2 and exacerbates SARS-CoV-2-induced kidney diseases including renal failure, especially in the AA population. We also explore the role of extracellular vesicles (EVs) in COVID-19 patients who smoke tobacco. EVs, which play important role in tobacco-mediated pathogenesis in infectious diseases, have also shown to be important in COVID-19 pathogenesis and organ injuries including kidney. Further, we explore the potential role of EVs in biomarker discovery and therapeutics, which may help to develop early diagnosis and treatment of tobacco-induced renal injury in COVID-19 patients, respectively.

Disagreement in Estimates of Kidney Function for Drug Dosing in Obese Inpatients.

BACKGROUND:: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are used to estimate kidney function. However, utility has been questioned in the obese population. OBJECTIVE:: To evaluate differences in estimates of kidney function in obese patients and implications for drug dosing. METHODS:: This was a retrospective study of adult inpatients with a body mass index ≥30 kg/m2 and stable kidney function. Patients were categorized based on creatinine clearance (CrCl): group 1-CrCl ≥ 60 mL/min and group 2-CrCl 15 to 59 mL/min. Mean estimates of kidney function and recommended doses of 8 renally eliminated medications were compared. RESULTS:: For the 166 patients included, mean estimates using CG, MDRD, and CKD-EPI for group 1 were 87 (23) mL/min, 91 (21) mL/min, and 96 (23) mL/min, respectively. Group 2 estimates were 42 (13) mL/min, 51 (15) mL/min, and 51 (16) mL/min, respectively. MDRD and CKD-EPI estimates were significantly higher than CG in 125 (75%) and 140 (84%) patients, respectively. Dose discrepancies were most often due to higher dose recommendations using MDRD or CKD-EPI compared to CG. CONCLUSION:: Careful consideration of the method used to estimate kidney function, the method used for developing dosing recommendations, and the risk-benefit profile is warranted when designing drug regimens in obese individuals.

Assessing Guideline-Directed Medication Therapy for Heart Failure in End-Stage Renal Disease.

BACKGROUND: Treatment of heart failure with reduced ejection fraction (HFrEF) requires guideline-directed medication therapy (GDMT) consisting of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker in combination with an indicated beta-blocker. There is concern that end-stage renal disease (ESRD) patients are not being prescribed GDMT. The study aim was to determine whether outcomes differ for patients with HFrEF and ESRD receiving GDMT compared to those not receiving GDMT. MATERIALS AND METHODS: Adult patients with ESRD and HFrEF admitted to a tertiary teaching hospital over a 2-year period were included. Patients were categorized into GDMT or non-GDMT groups based on their home medications. The length of stay (LOS), mortality, and 30-day hospital readmissions were compared between groups. The incidence of hyperkalemia, hypotension and bradycardia were also evaluated. RESULTS: A total of 109 patients were included: 88% African-American, 61% males, median age 63 (28-93) years with 25 in the GDMT group and 84 in the non-GDMT group. The LOS did not differ between the GDMT (5 days; 3-14) compared to the non-GDMT group (7 days; 3-28), P = 0.14. Thirty-day hospital readmission and in-hospital mortality were also similar. Hypotension occurred less frequently in the GDMT group compared to the non-GDMT group, 4% versus 27% (P = 0.01). CONCLUSIONS: Although there were no differences in the primary outcomes, the shorter LOS in the GDMT group may be clinically significant. The fact that most patients with ESRD and HFrEF were not receiving GDMT is a finding that requires further evaluation.

Breast cancer patient with everolimus-induced angioedema: A rare occurrence with potential for serious consequences.

Background The development of angioedema is a rare yet serious clinical event that may develop due to an adverse drug reaction. Rapid recognition and treatment of this adverse reaction is critical for optimal patient outcomes; however, prevention of this occurrence is preferred. Case report A 59-year-old woman presented to the emergency department with lingual angioedema caused by the addition of everolimus to her medication regimen. The patient improved after withdrawal of the offending agent and standard treatment. Early recognition by healthcare providers and management of everolimus-induced angioedema is vital for successful patient outcomes. This report increases awareness of everolimus as a potentially causative agent for the development of angioedema.

Belatacept conversion in African American kidney transplant recipients with severe renal dysfunction.

OBJECTIVES: Conversion from calcineurin inhibitor-based maintenance immunosuppression to belatacept in kidney transplant recipients has been demonstrated to improve renal function while maintaining efficacy against rejection. However, conversion studies to date have excluded patients with an estimated glomerular filtration rate < 35 mL/min/1.73 m2. METHODS: We describe two patients with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 who underwent conversion from maintenance calcineurin inhibitor to belatacept. RESULTS: Both patients experienced improvement in renal function following conversion. CONCLUSIONS: These results suggest that patients with more severe degrees of allograft impairment may benefit from conversion of maintenance calcineurin inhibitor to belatacept-based immunosuppression. Larger, randomized studies are warranted to evaluate the impact of such an approach.

The benefit of sirolimus maintenance immunosuppression and rabbit antithymocyte globulin induction in liver transplant recipients that develop acute kidney injury in the early postoperative period.

Published data are limited describing renal outcomes in orthotopic liver transplant (OLT) recipients prescribed sirolimus (SRL) maintenance immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We investigated whether SRL MIS and rATG induction facilitated recovery of acute kidney injury in the early postoperative period. This retrospective descriptive study screened 308 consecutive OLTs performed between 2006 and 2009. All patients received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with mycophenolate mofetil. A total of 197 patients were included: 168 (85%) received TAC and 29 (15%) received SRL for a median of 365 days. Demographics were similar between groups except for a higher incidence of pretransplant renal dysfunction in the SRL recipients (SRL 59% versus TAC 21%; P < 0.05). The eGFR was significantly (P < 0.05) higher for all time points in the TAC group with the exception of month 2. However, improvement in eGFR was significantly (P < 0.05) greater in the SRL group postoperatively. Our study suggests that rATG induction and SRL maintenance immunosuppression facilitate renal recovery for liver transplant recipients that develop acute kidney injury in the early postoperative period.

Rabbit antithymocyte induction and dosing in deceased donor renal transplant recipients over 60 yr of age.

BACKGROUND: Antithymocyte globulin (rATG) is a commonly used induction agent in renal transplantation; however, data in older kidney recipients are limited. METHODS: We reviewed charts of 301 deceased donor renal transplants who received a protocol consisting of 3-7 doses of rATG and triple maintenance therapy. Outcomes of patients >60 yr of age (n = 45) were compared to those aged 18-59 yr (n = 256). RESULTS: Older recipients had more diabetics, were more likely to receive expanded criteria donor kidneys (p < 0.01), and over 30% were sensitized. Recipients >60 received less cumulative rATG (4.6 vs. 5.1 mg/kg; p < 0.01). Three-yr acute rejection was lower in the >60 group (2% vs. 16%, p < 0.01) although glomerular filtration rates were similar between groups. Actuarial graft survival was similar; however, patient survival in the >60 group at three yr was lower (80% vs. 95%; p = 0.02). Specifically, patients >60 with delayed graft function and rATG cumulative dosing >6 mg/kg had a survival of <50% by two yr. CONCLUSION: Recipients over 60 yr receiving rATG induction have acceptable renal function and a low risk of rejection; however, reduced survival was noted among those receiving >6 mg/kg. These data suggest that when used, lower cumulative dosages of rATG are preferable in the older recipient.

Risk factors and consequences of delayed graft function in deceased donor renal transplant patients receiving antithymocyte globulin induction.

BACKGROUND: Induction rabbit antithymocyte globulin (rATG) is largely used in renal allograft recipients at risk for delayed graft function (DGF) and immunologic rejection. The purpose of our study was to characterize risk factors and outcomes associated with DGF when it occurs in recipients undergoing routine rATG induction. METHODS: We retrospectively reviewed our experience in a predominantly high-risk population receiving modern immunosuppressive regimens. RESULTS: Of 231 deceased-donor transplants, high-risk characteristics included African American race (68%), retransplants (12%), peak panel reactive antibody of atleast 20% (19%), expanded criteria donor kidney (15%), and cold ischemia time exceeding 24 hr (27%). DGF occurred in 29% of patients. rATG was continued to a dose of 7.3 mg/kg in DGF patients and 5 mg/kg in non-DGF patients (P<0.0001). Risk factors for DGF were recipient body mass index greater than 30 kg/m(2) (odds ratio [OR]=1.5, P=0.02), female donor/male recipient pairings (OR=1.5, P=0.033), sirolimus use (OR=1.7, P=0.003), and donor creatinine more than 1.5 mg/dL (OR=1.6, P=0.016). One-year patient survival (99% non-DGF, 91% DGF; P=0.001) and acute rejection incidence through 36 months (11% non-DGF, 22.4% DGF; P=0.025) differed between groups. DGF patients experienced a higher rejection rate during the second and third years posttransplant. Death-censored graft survival was similar throughout 36 months. CONCLUSION: In kidney transplantation with routine rATG induction, DGF was related to size and gender, donor creatinine, and immunosuppressive protocol. Despite low first-year rejection rates, DGF was associated with inferior patient survival. Importantly, patients with DGF continued to be at risk for rejection beyond the first year. Donor and recipient selection impacts short-term outcomes, and induction alone may not confer a long-term advantage without further modification of baseline therapy.

Short-term outcomes of Thymoglobulin induction in pediatric renal transplant recipients.

No data are currently available that describe the clinical outcomes associated with Thymoglobulin (rabbit polyclonal anti-thymocyte globulin) induction in pediatric renal transplant recipients. We report the outcomes of 17 pediatric renal transplant recipients (mean age 10.1+/-5.2 years) transplanted between 1 August 1999 and 31 July 2001. Eleven patients (65%) were Caucasian and 6 (35%) were African-American. Eleven (65%) recipients received cadaveric allografts. Two patients (12%) were second allograft recipients. One patient had primary allograft non-function secondary to vascular thrombosis. Two patients (12%) had delayed allograft function. Immunosuppression consisted of Thymoglobulin induction (mean number of doses 6+/-1.7) with tacrolimus (62%) or cyclosporine A (38%), mycophenolate mofetil, and prednisone. One year post transplant, patient and graft survival was 100% and 93%, respectively. No acute rejection episodes occurred during the first 6 months after transplantation in any of the recipients. Additionally, no rejection episode occurred among the 14 patients followed for 1 year after transplant. The incidences of asymptomatic cytomegalovirus (CMV) and Epstein-Barr virus (EBV) seroconversion at 1 year in seronegative recipients with a seropositive donor were 100% of 4 patients and 0% of 4 patients, respectively. No symptomatic CMV or EBV infections and no post-transplant lymphoproliferative disease have occurred in any patient. These short-term data suggest that Thymogobulin induction is safe and effective in combination with triple immunosuppressive therapy for preventing early rejection in pediatric renal transplant recipients.