Cheungpasitporn, Wisit

Tacrolimus is a first-line calcineurin inhibitor (CNI) and an integral part of the immunosuppressive strategy in solid organ transplantation. Being a dose-critical drug, tacrolimus has a narrow therapeutic index that necessitates periodic monitoring to maintain the drug’s efficacy and reduce the consequences of overexposure. Tacrolimus is characterized by substantial intra- and inter-individual pharmacokinetic variability. At steady state, the tacrolimus blood concentration to daily dose ratio (C/D ratio) has been described as a surrogate for the estimation of the individual metabolism rate, where a low C/D ratio reflects a higher rate of metabolism. Fast tacrolimus metabolism (low C/D ratio) is associated with the risk of poor outcomes after transplantation, including reduced allograft function and survival, higher allograft rejection, CNI nephrotoxicity, a faster decline in kidney function, reduced death-censored graft survival (DCGS), post-transplant lymphoproliferative disorders, dyslipidemia, hypertension, and cardiovascular events. In this article, we discuss the potential role of the C/D ratio in a noninvasive monitoring strategy for identifying patients at risk for potential adverse events post-transplant.

Acute kidney injury (AKI) is a complication of COVID-19. However, the incidence of AKI in COVID-19 varies among studies. Thus, we aimed to evaluate the pooled incidence of AKI and its association with mortality in patients with COVID-19 using a meta-analysis. We search Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible publications reporting the clinical characteristics of patients with COVID-19 without language restriction. Incidence of AKI and mortality were reported. Meta-regression was used to describe the association between outcomes. From 26 studies (n=5497), the pooled incidence of AKI in patients with COVID-19 was 8.4% (95% CI 6.0% to 11.7%) with a pooled incidence of renal replacement therapy of 3.6% (95% CI 1.8% to 7.1%). The incidence of AKI was higher in critically ill patients (19.9%) compared with hospitalized patients (7.3%). The pooled estimated odds ratio for mortality from AKI was 13.33 (95% CI 4.05 to 43.91). No potential publication bias was detected. By using meta-regression analyses, the incidence of AKI was positively associated with mortality after adjusted for age and sex (Q=26.18; p=0.02). Moreover, age (p<0.01), diabetes (p=0.02), hypertension (p<0.01) and baseline serum creatinine levels (p=0.04) were positively associated with AKI incidence in adjusted models. In conclusion, AKI is present in 8.3% of overall patients with COVID-19 and in 19.9% of critically ill patients with COVID-19. Presence of AKI is associated with 13-fold increased risk of mortality. Age, diabetes, hypertension, and baseline serum creatinine levels are associated with increased AKI incidence.

Background: There are limited data on the epidemiology and timing of in-hospital death (IHD) in patients with acute myocardial infarction-cardiogenic shock (AMI-CS). Methods: Adult admissions with AMI-CS with IHDs were identified using the National Inpatient Sample (2000–2016) and were classified as early (≤2 days), mid-term (3–7 days), and late (>7 days). Inter-hospital transfers and those with do-not-resuscitate statuses were excluded. The outcomes of interest included the epidemiology, temporal trends and predictors for IHD timing. Results: IHD was noted in 113,349 AMI-CS admissions (median time to IHD 3 (interquartile range 1–7) days), with early, mid-term and late IHD in 44%, 32% and 24%, respectively. Compared to the mid-term and late groups, the early IHD group had higher rates of ST-segment-elevation AMI-CS (74%, 63%, 60%) and cardiac arrest (37%, 33%, 29%), but lower rates of acute organ failure (68%, 79%, 89%), use of coronary angiography (45%, 56%, 67%), percutaneous coronary intervention (33%, 36%, 42%), and mechanical circulatory support (31%, 39%, 50%) (all p < 0.001). There was a temporal increase in the early (adjusted odds ratio (aOR) for 2016 vs. 2000 2.50 (95% confidence interval (CI) 2.22–2.78)) and a decrease in mid-term (aOR 0.75 (95% CI 0.71–0.79)) and late (aOR 0.34 (95% CI 0.31–0.37)) IHD. ST-segment-elevation AMI-CS and cardiac arrest were associated with the increased risk of early IHD, whereas advanced comorbidity and acute organ failure were associated with late IHD. Conclusions: Early IHD after AMI-CS has increased between 2000 and 2016. The populations with early vs. late IHD were systematically different.

Background: We aimed to describe the incidence of hospital-acquired dyschloremia and its association with in-hospital mortality in general hospitalized patients. Methods: All hospitalized patients from 2009 to 2013 who had normal admission serum chloride and at least two serum chloride measurements in the hospital were studied. The normal range of serum chloride was defined as 100–108 mmol/L. Hospital serum chloride levels were grouped based on the occurrence of hospital-acquired hypochloremia and hyperchloremia. The association of hospital-acquired hypochloremia and hyperchloremia with in-hospital mortality was analyzed using logistic regression. Results: Among the total of 39,298 hospitalized patients, 59% had persistently normal hospital serum chloride levels, 21% had hospital-acquired hypochloremia only, 15% had hospital-acquired hyperchloremia only, and 5% had both hypochloremia and hyperchloremia. Compared with patients with persistently normal hospital serum chloride levels, hospital-acquired hyperchloremia only (odds ratio or OR 2.84; p < 0.001) and both hospital-acquired hypochloremia and hyperchloremia (OR 1.72; p = 0.004) were associated with increased in-hospital mortality, whereas hospital-acquired hypochloremia only was not (OR 0.91; p = 0.54). Conclusions: Approximately 40% of hospitalized patients developed serum chloride derangements. Hospital-acquired hyperchloremia, but not hypochloremia, was associated with increased in-hospital mortality.

AbstractObjectiveCannabis is the most commonly used recreational drug in the United States, and transplant acceptability for cannabis using candidates varies among transplant centers. However, the prevalence and impact of cannabis use on outcomes of kidney transplant recipients remain unclear. This study aimed to summarize the prevalence and impact of cannabis use on outcomes after kidney transplantation.MethodsA literature search was performed using Ovid MEDLINE, EMBASE, and The Cochrane Library Databases from inception until September 2019 to identify studies assessing the prevalence of cannabis use among kidney transplant recipients, and reported adverse outcomes after kidney transplantation. Effect estimates from the individual studies were obtained and combined utilizing random‐effects, generic inverse variance method of DerSimonian‐Laird.ResultsA total of four cohort studies with a total of 55 897 kidney transplant recipients were enrolled. Overall, the pooled estimated prevalence of cannabis use was 3.2% (95% CI 0.4%‐20.5%). While the use of cannabis was not significantly associated with all‐cause allograft failure (OR = 1.31, 95% CI 0.70‐2.46) or mortality (OR = 1.52, 95% CI 0.59‐3.92), the use of cannabis among kidney transplant recipients was significantly associated with increased death‐censored graft failure with pooled OR of 1.72 (95% CI 1.13‐2.60).ConclusionsThe overall estimated prevalence of cannabis use among kidney transplant recipients is 3.2%. The use of cannabis is associated with increased death‐censored graft failure, but not mortality after kidney transplantation.

α-Klotho is a known anti-aging protein that exerts diverse physiological effects, including phosphate homeostasis. Klotho expression occurs predominantly in the kidney and is significantly decreased in patients with chronic kidney disease. However, changes in serum klotho levels and impacts of klotho on outcomes among kidney transplant (KTx) recipients and kidney donors remain unclear. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through October 2019 to identify studies evaluating serum klotho levels and impacts of klotho on outcomes among KTx recipients and kidney donors. Study results were pooled and analyzed utilizing a random-effects model. Ten cohort studies with a total of 431 KTx recipients and 5 cohort studies with a total of 108 living kidney donors and were identified. After KTx, recipients had a significant increase in serum klotho levels (at 4 to 13 months post-KTx) with a mean difference (MD) of 243.11 pg/mL (three studies; 95% CI 67.41 to 418.81 pg/mL). Although KTx recipients had a lower serum klotho level with a MD of = −234.50 pg/mL (five studies; 95% CI −444.84 to −24.16 pg/mL) compared to healthy unmatched volunteers, one study demonstrated comparable klotho levels between KTx recipients and eGFR-matched controls. Among kidney donors, there was a significant decrease in serum klotho levels post-nephrectomy (day 3 to day 5) with a mean difference (MD) of −232.24 pg/mL (three studies; 95% CI –299.41 to −165.07 pg/mL). At one year following kidney donation, serum klotho levels remained lower than baseline before nephrectomy with a MD of = −110.80 pg/mL (two studies; 95% CI 166.35 to 55.24 pg/mL). Compared to healthy volunteers, living kidney donors had lower serum klotho levels with a MD of = −92.41 pg/mL (two studies; 95% CI −180.53 to −4.29 pg/mL). There is a significant reduction in serum klotho levels after living kidney donation and an increase in serum klotho levels after KTx. Future prospective studies are needed to assess the impact of changes in klotho on clinical outcomes in KTx recipients and living kidney donors.

Background: This study aimed to assess the risk factors and the association of circulatory failure with treatments, complications, outcomes, and resource utilization in hospitalized patients for heatstroke in the United States. Methods: Hospitalized patients with a principal diagnosis of heatstroke were identified in the National Inpatient Sample dataset from the years 2003 to 2014. Circulatory failure, defined as any type of shock or hypotension, was identified using hospital diagnosis codes. Clinical characteristics, in-hospital treatment, complications, outcomes, and resource utilization between patients with and without circulatory failure were compared. Results: A total of 3372 hospital admissions primarily for heatstroke were included in the study. Of these, circulatory failure occurred in 393 (12%) admissions. Circulatory failure was more commonly found in obese patients, but less common in older patients aged ≥60 years. The need for mechanical ventilation, blood transfusion, and renal replacement therapy were higher in patients with circulatory failure. Hyperkalemia, hypocalcemia, metabolic acidosis, metabolic alkalosis, sepsis, ventricular arrhythmia or cardiac arrest, renal failure, respiratory failure, liver failure, neurological failure, and hematologic failure were associated with circulatory failure. The in-hospital mortality was 7.1-times higher in patients with circulatory failure. The length of hospital stay and hospitalization costs were higher when circulatory failure occurred while in the hospital. Conclusions: Approximately one out of nine heatstroke patients developed circulatory failure during hospitalization. Circulatory failure was associated with various complications, higher mortality, and increased resource utilizations.

Background/objectives Liver transplant recipients have an increased risk of Clostridioides difficile infection (CDI) which associated with higher morbidity and mortality. CDI in liver transplant has been argued to increase hospital costs, charges, and length of stay (LOS) in small studies. However, no recent nationwide analysis determines these outcomes. Methods This is a retrospective cohort study using the National Inpatient Sample 2016. All patients with ICD10CM diagnostic codes for CDI were included. The cohort was stratified for the history of liver transplant and liver transplant index admission. The primary outcome was the odds of CDI in both patient cohorts to patients without liver transplant. Secondary outcomes were inpatient morbidity, mortality, resource utilization, colectomy rates, LOS, and total hospital costs and charges. Results A total of 360 364 patients with CDI were identified, 1665 had a history of liver transplant and 155 had liver transplant during that admission. Patients with a history of liver transplant had increased odds of CDI compared to patients with no history of liver transplant (adjusted odds ratio 2.78; 95% confidence interval, 2.44–3.16). Patients with CDI had greater odds of shock, acute kidney injury, ICU stay, organ failure and significantly higher costs, charges and LOS. Conclusions Patients with a history of liver transplant increased odds of CDI. CDI with history of liver transplant and the index admission for liver transplant had higher odds of morbidity and resource utilization. Clinicians must maintain a high index of suspicion for CDI for early diagnosis and appropriate initiation of treatment.