Association of Inflammatory Biomarkers with Immunosuppression Management and Outcomes in Kidney Transplant Recipients with COVID-19.

BACKGROUND: Kidney transplant recipients with coronavirus disease 2019 (COVID-19) are at increased risk for adverse outcomes, such as acute kidney injury (AKI), intensive care unit (ICU) admission, and death. The association of inflammatory biomarkers with outcomes and the impact of changes in immunosuppression on biomarker levels are unknown. METHODS: We investigated factors associated with a composite of AKI, ICU admission, or death, and whether immunosuppression changes correlated with changes in inflammatory biomarkers and outcomes in kidney transplant recipients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction. RESULTS: Of 59 patients, 50% had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Patients who discontinued calcineurin inhibitors (CNIs) had higher peak high-sensitivity C-reactive protein (hs-CRP) than those who maintained the same dose (median, 344; interquartile range [IQR], 145-374 vs median, 41; IQR, 22-116 mg/L, P = .03). Of the patients, 73% were hospitalized, 22% had admissions to the ICU, and 20% died. Of the 56% with AKI, 35% required dialysis. All patients with AKI but without pulmonary manifestations recovered to 10% of baseline creatinine levels. Factors associated with the composite outcome were eGFR <60 mL/min/1.73 m2 (odds ratio [OR], 5.833; 95% confidence interval [CI], 1.880-18.099; P = .002), hs-CRP (OR, 1.011/unit increase; 95% CI, 1.002-1.021; P = .019), white blood cell count (OR, 1.173/unit increase; 95% CI, 1.006-1.368; P = .041), and decreased or discontinued CNI (OR, 4.286; 95% CI, 1.353-13.572; P = .013). eGFR<60 mL/min/1.73 m2 (OR, 11.176; 95% CI, 1.581-79.001; P = .016), and peak hs-CRP (OR, 1.010/unit increase; 95% CI, 1.000-1.020; P = .049) remained associated with the composite in the multivariable model. CONCLUSIONS: Kidney transplant recipients with COVID-19 have high rates of ICU admissions, AKI, and death. Those with eGFR<60 mL/min/1.73 m2 are at highest risk. CNI reduction is associated with higher inflammatory biomarkers, correlating with worse outcomes. More studies are needed to determine if this association should drive clinical management.

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.

Trends in utilization of deceased donor kidneys based on hepatitis C virus status and impact of public health service labeling on discard.

BACKGROUND: Kidneys from deceased donors infected with hepatitis C virus (HCV) are underutilized. Most HCV virus-infected donors are designated as Public Health Service increased donors (PHS-IR). Impact of PHS and HCV designations on discard is not well studied. METHODS: We queried the UNOS data set for all deceased donor kidneys between January 2015 and December 2018. The final study cohort donors (n = 38 702) were stratified into three groups based on HCV antibody (Ab) and NAT status: (a) Ab-/NAT- (n = 35 861); (b) Ab+/NAT- (n = 973); and (c) Ab±/NAT+ (n = 1868). We analyzed utilization/discard rates of these organs, the impact of PHS-IR and HCV designations on discard using multivariable two-level hierarchical logistic regression models, forecasted number of HCV viremic donors/kidneys by 2023. RESULTS: During the study period, (a) the number of viremic donor kidneys increased 2 folds; (b) the multilevel mixed-effects logistic regression models showed that, overall, the PHS labeling (OR 1.20, CI 95% CI 1.15-1.29) and HCV designation (OR 2.29; 95% CI 2.15-2.43) were independently associated with increased risk of discard; (c) contrary to the general perception, PHS-IR kidneys across all HCV groups, compared to PHS-IR kidneys were more likely to be discarded; (d) we forecasted that the number of kidneys from HCV viremic donor kidneys might increase from 1376 in 2019 to 2092 in 2023. CONCLUSION: Hepatitis C virus viremic kidneys might represent 10%-15% of deceased donor organ pool soon with the current rate of the opioid epidemic. PHS labeling effect on discard requires further discussion of the utility of this classification.

Lack of Benefit and Potential Harm of Induction Therapy in Simultaneous Liver-Kidney Transplants.

The number of simultaneous liver-kidney transplantations (SLKTs) and use of induction therapy for SLKT have increased recently, without much published evidence, especially in the context of maintenance immunosuppression containing tacrolimus (TAC) and mycophenolic acid (MPA). We queried the Organ Procurement and Transplant Network registry for SLKT recipients maintained on TAC/MPA at discharge in the United States for 2002-2016. The cohort was divided into 3 groups on the basis of induction type: rabbit antithymocyte globulin (r-ATG; n = 831), interleukin 2 receptor antagonist (IL2RA; n = 1558), and no induction (n = 2333). Primary outcomes were posttransplant all-cause mortality and acute rejection rates in kidney and liver allografts at 12 months. Survival rates were analyzed by the Kaplan-Meier method. A propensity score analysis was used to control potential selection bias. Multivariate inverse probability weighted Cox proportional hazard and logistic regression models were used to estimate the hazard ratios (HRs) and odds ratios. Among SLKT recipients, survival estimates at 3 years were lower for recipients receiving r-ATG (P = 0.05). Compared with no induction, the multivariate analyses showed an increased mortality risk with r-ATG (HR, 1.29; 95% confidence interval [CI], 1.10-1.52; P = 0.002) and no difference in acute liver or kidney rejection rates at 12 months across all induction categories. No difference in outcomes was noted with IL2RA induction over the no induction category. In conclusion, there appears to be no survival benefit nor reduction in rejection rates for SLKT recipients who receive induction therapy, and r-ATG appears to increase mortality risk compared with no induction.

Meta-analysis: comparison of F-18 Fluorodeoxyglucose-positron emission tomography and bone scintigraphy in the detection of bone metastases in patients with breast cancer.

PURPOSE: To evaluate the diagnostic properties of FDG-PET and bone scintigraphy in the detection of osseous metastases in patients with breast cancer. MATERIALS AND METHODS: Studies evaluating the diagnostic accuracy of FDG-PET and bone scintigraphy in the diagnosis of osseous metastasis were systematically searched for in the MEDLINE, CINAHL, and EBM Review databases from January 1995 to November 2006. Two reviewers independently abstracted data including research design, sample size, imaging technique and technical characteristics, reference standard, method of image interpretation, and totals of true positives, false positives, true negatives, and false negatives. Per-patient and per-lesion pooled sensitivity and specificity, and area under summary receiver operating characteristic curves were calculated using Meta-Test software. RESULTS: The pooled patient-based sensitivity for FDG-PET was 81% (95% CI: 70%-89%), specificity was 93% (95% CI: 84%-97%), and the area under the curve (AUC) was 0.08. The pooled sensitivity of bone scan was 78% (95% CI: 67%-86%), specificity was 79% (95% CI: 40%-95%), and the AUC was 0.43. The pooled lesion-based sensitivity for FDG-PET was 69% (95% CI: 28%-93%), specificity was 98% (95% CI: 87%-100%), and the AUC was 0.09. The pooled sensitivity for bone scan was 88% (95% CI: 82%-92%), specificity was 87% (95% CI: 29%-99%), and the AUC was 0.81. CONCLUSIONS: It remains inconclusive whether FDG-PET or bone scintigraphy is superior in detecting osseous metastasis from breast cancer. However, FDG-PET does have a higher specificity and may better serve as a confirmatory test than bone scintigraphy and used to monitor response to therapy.

Evidence-based medicine, part 6. An introduction to critical appraisal of clinical practice guidelines.

This article provides an introductory step-by-step process to appraise clinical practice guidelines. The authors introduce these principles using a systematic approach and case-based format. The process of assessing the validity of clinical practice guidelines, determining their importance, and applying them to an individual patient is reviewed. The concepts of study population homogeneity, equal treatment, and study completeness are discussed to help physicians determine the validity of clinical practice guidelines. Finally, information that is learned from the previously mentioned steps is applied to patient care. Study generalizability and the role of patient values, expectations, and concerns are also addressed. The skills learned from appraising clinical practice guidelines in the manner outlined provides a solid basis for life-long learning and improved patient care.