Integral Use of Thromboelastography With Platelet Mapping to Guide Appropriate Treatment, Avoid Complications, and Improve Survival of Patients With Coronavirus Disease 2019-Related Coagulopathy.

OBJECTIVES: Coagulopathy of coronavirus disease 2019 is largely described as hypercoagulability, yet both thrombotic and hemorrhagic complications occur. Although therapeutic and prophylactic anticoagulant interventions have been recommended, empiric use of antifactor medications (heparin/enoxaparin) may result in hemorrhagic complications, including death. Furthermore, traditional (antifactor) anticoagulation does not address the impact of overactive platelets in coronavirus disease 2019. The primary aim was to evaluate if algorithm-guided thromboelastography with platelet mapping could better characterize an individual's coronavirus disease 2019-relatedcoagulopathic state and, secondarily, improve outcomes. DESIGN SETTING AND PATIENTS: Coronavirus disease 2019 patients (n = 100), receiving thromboelastography with platelet mapping assay upon admission to an 800-bed tertiary-care hospital, were followed prospectively by a hospital-based thromboelastography team. Treating clinicians were provided with the option of using a pre-established algorithm for anticoagulation, including follow-up thromboelastography with platelet mapping assays. Two groups evolved: 1) patients managed by thromboelastography with platelet mapping algorithm (algorithm-guided-thromboelastography); 2) those treated without thromboelastography with platelet mapping protocols (non-algorithm-guided). Outcomes included thrombotic/hemorrhagic complications, pulmonary failure, need for mechanical ventilation, acute kidney injury, dialysis requirement, and nonsurvival. INTERVENTIONS: Standard-of-care therapy with or without algorithm-guided-thromboelastography support. MEASUREMENTS AND MAIN RESULTS: Although d-dimer, C-reactive protein, and ferritin were elevated significantly in critically ill (nonsurvivors, acute kidney injury, pulmonary failure), they did not distinguish between coagulopathic and noncoagulopathic patients. Platelet hyperactivity (maximum amplitude-arachidonic acid/adenosine diphosphate > 50 min), with or without thrombocytosis, was associated with thrombotic/ischemic complications, whereas severe thrombocytopenia (platelet count < 100,000/µL) was uniformly fatal. Hemorrhagic complications were observed with decreased factor activity (reaction time > 8 min). Non-algorithm-guided patients had increased risk for subsequent mechanical ventilation (relative risk = 10.9; p < 0.0001), acute kidney injury (relative risk = 2.3; p = 0.0017), dialysis (relative risk = 7.8; p < 0.0001), and death (relative risk = 7.7; p < 0.0001), with 17 of 28 non-algorithm-guided patients (60.7%) dying versus four algorithm-guided-thromboelastography patients (5.6%) (p < 0.0001). Thromboelastography with platelet mapping-guided antiplatelet treatment decreased mortality 82% (p = 0.0002), whereas non-algorithm-guided (compared with algorithm-guided-thromboelastography) use of antifactor therapy (heparin/enoxaparin) resulted in 10.3-fold increased mortality risk (p = 0.0001). CONCLUSIONS: Thromboelastography with platelet mapping better characterizes the spectrum of coronavirus disease 2019 coagulation-related abnormalities and may guide more tailored, patient-specific therapies in those infected with coronavirus disease 2019.

Long-term outcome of ketoconazole and tacrolimus co-administration in kidney transplant patients.

AIM: To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipients. METHODS: From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure (Group 1), while 149 patients did not receive any ketoconazole (Group 2). A combination of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction. RESULTS: Basic demographic data was similar between the 2 groups. The 5-year cumulative incidence of biopsy-confirmed and clinically-treated acute rejection was significantly higher in Group 1 than in Group 2 (34% vs 18%, P = 0.01). The 5-year Kaplan-Meier estimated graft survival (74.3% vs 76.4%, P = 0.58) and patient survival (87.8% vs 87.5%, P = 0.93) were not different between the 2 groups. Multivariable analyses identified ketoconazole usage as an independent risk of acute rejection (HR = 2.33, 95%CI: 1.33-4.07; P = 0.003) while tacrolimus dose in the 2(nd) month was protective (HR = 0.89, 95%CI: 0.75-0.96; P = 0.041). CONCLUSION: Co-administration of ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.

Obesity and metabolic syndrome in kidney transplantation.

The epidemic of obesity and metabolic syndrome (MS) contributes to the rapid growth of chronic kidney disease (CKD) and end-stage renal disease (ESRD). There is a reverse epidemiology, known as the "obesity paradox," in ESRD patients receiving maintenance dialysis. Obese patients are routinely referred for kidney transplant, and they have more surgical and medical complications than non-obese patients. However, compared to dialysis, kidney transplant provides a survival benefit for obese patients. After kidney transplant, obese patients tend to gain more body weight, and non-obese patients can develop new-onset obesity/MS. Obesity/MS is not only associated with serious morbidities, but also compromises the long-term graft and patient survival. The immunosuppressive drugs commonly used as maintenance therapy, including corticosteroids, calcineurin inhibitors and mammalian target-of-rapamycin inhibitors, contribute to obesity/MS. Development of novel immunosuppressive drugs free of metabolic adverse effects is needed, so that the full potential and benefits of kidney transplantation can be realized.

Early inhibition of the renin-angiotensin system improves the long-term graft survival of single pediatric donor kidneys transplanted in adult recipients.

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin-angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996-2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan-Meier estimated death-censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33-5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18-0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long-term graft survival among adults transplanted with single pediatric donor kidneys.

The metabolic syndrome and risk of chronic kidney disease: pathophysiology and intervention strategies.

Metabolic syndrome is characterized by a clustering of cardiovascular risk factors, including abdominal obesity, elevated blood pressure and glucose concentrations, and dyslipidemia. The presence of this clinical entity is becoming more pervasive throughout the globe as the prevalence of obesity increases worldwide. Moreover, there is increased recognition of the complications and mortality related to this syndrome. This paper looks to examine the link between metabolic syndrome and the development of chronic kidney disease.