Abstract
Kidney transplantation recipients (KTR) with coronavirus disease 2019 (COVID-19) are at higher risk of death than general population. However, mortality risk factors in KTR are still not ...clearly identified. Our objective was to systematically analyze published evidence for risk factors associated with mortality in COVID-19 KTR. Electronic databases were searched for eligible studies on 1 August 2021. All prospective and retrospective studies of COVID-19 in KTR were considered eligible without language restriction. Since data in case reports and series could potentially be subsets of larger studies, only studies with ≥ 50 patients were included. Random-effects model meta-analysis was used to calculate weighted mean difference (WMD) and pooled odds ratio (OR) of factors associated with mortality. From a total 1,137 articles retrieved, 13 were included in the systematic review and meta-analysis comprising 4,440 KTR. Compared with survivors, non-survivors were significantly older (WMD 10.5 years, 95% CI 9.3–11.8). KTR of deceased donor were at higher risk of death (OR 1.73, 95% CI 1.10–2.74). Comorbidities including diabetes mellitus, cardiovascular disease, and active cancer significantly increased mortality risk. KTR with dyspnea (OR 5.68, 95% CI 2.11–15.33) and pneumonia (OR 10.64, 95% CI 3.37–33.55) at presentation were at higher mortality risk, while diarrhea decreased the risk (OR 0.61, 95% CI 0.47–0.78). Acute kidney injury was associated with mortality (OR 3.24, 95% CI 1.36–7.70). Inflammatory markers were significantly higher in the non-survivors, including C-reactive protein, procalcitonin, and interleukine-6. A number of COVID-19 mortality risk factors were identified from KTR patient characteristics, presenting symptoms, and laboratory investigations. KTR with these risk factors should receive more intensive monitoring and early therapeutic interventions to optimize health outcomes.
In hemodialysis (HD) patients, protein-energy wasting (PEW) is highly prevalent and firstly treated with oral nutritional supplements (ONS). The extent to which intradialytic parenteral nutrition ...(IDPN) contributes to improve PEW status in HD patients intolerable to ONS remains unclear. Maintenance PEW HD patients being unable to tolerate ONS adverse effects, and having spontaneous energy and protein intake of ≥ 20 kcal/kg/day and ≥ 0.8 g/kg/day, respectively were randomly assigned 1:1 into IDPN and control groups. In IDPN group, most concentrated 3-in-1, fish-oil based parenteral nutrition was infused during HD for 3 months. The control group received intensive dietary counselling once weekly for 3 months. Both groups were then followed for additional 3 months after intervention. A total of 38 patients were randomized (mean age 67.6 years). After 3 months, serum albumin was significantly higher in the IDPN (n = 18) compared with control group (from 3.5 ± 0.3 to 3.8 ± 0.2 vs from 3.6 ± 0.3 to 3.5 ± 0.3 g/dL, respectively, p = 0.01). Spontaneous dietary intake (p = 0.04), body weight (p = 0.01), and malnutrition inflammation score (MIS, p = 0.01) were improved in the IDPN, but not in the control group. Muscle mass, strength, serum prealbumin, interleukin-6, high sensitivity-c reactive protein, and acylated ghrelin were not significantly different but leptin levels increased in the control group after 3 months (p = 0.03). At 6 months, serum albumin in the IDPN group was persistently higher than baseline (p = 0.04). Neither volume overload nor uncontrolled hyperglycemia was found throughout the study. In conclusion, a 3-month IDPN supplementation demonstrated a significant increase in serum albumin, body weight, spontaneous oral intake, and MIS; and appeared to be superior to continuing intensive dietary counselling among HD patients intolerable to ONS. The impacts of IDPN therapy on clinical outcomes may require larger scale with longer period of study.
The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while ...expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT.
FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT.
FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P < 0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002).
The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation.
clinicaltrials.gov, NCT02730117 . Registered 6 April 2016.
Obesity is a major public health with increasing numbers of obese individuals are at risk for kidney disease. However, the validity of serum creatinine-based glomerular filtration rate (GFR) ...estimating equations in obese population is yet to be determined.
We evaluated the performance of the reexpressed Modification of Diet in Renal Disease (MDRD), reexpressed MDRD with Thai racial factor, Thai estimated GFR (eGFR) as well as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations among obese patients, defined as body mass index (BMI) ≥25 kg/m2 with the reference measured GFR (mGFR) determined by 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA) plasma clearance method. Serum creatinine levels were measured using standardized enzymatic method simultaneously with GFR measurement. The statistical methods in assessing agreement for continuous data including total deviation index (TDI), concordance correlation coefficient (CCC), and coverage probability (CP) for each estimating equation were compared with the reference mGFR. Accuracy within 10% representing the percentage of estimations falling within the range of ±10% of mGFR values for all equations were also tested.
A total of 240 Thai obese patients were finally recruited with mean BMI of 31.5 ± 5.8 kg/m2. In the total population, all eGFR equations underestimated the reference mGFR. The average TDI values were 55% indicating that 90% of the estimates falling within the range of -55 to +55% of the reference mGFR. The CP values averaged 0.23 and CCC scores ranged from 0.75 to 0.81, reflecting the low to moderate levels of agreement between each eGFR equation and the reference mGFR. The proportions of patients achieving accuracy 10% ranged from 23% for the reexpressed MDRD equation to 33% for the Thai eGFR formula. Among participants with BMI more than 35 kg/m2 (n = 48), the mean error of all equations was extremely wide and significantly higher for all equations compared with the lower BMI category. Also, the strength of agreement evaluated by TDI, CCC, and CP were low in the subset of patients with BMI ≥35 kg/m2.
Estimating equations generally underestimated the reference mGFR in subjects with obesity. The overall performance of GFR estimating equations demonstrated poor concordance with the reference mGFR among individuals with high BMI levels. In certain clinical settings such as decision for dialysis initiation, the direct measurements of GFR are required to establish real renal function among obese population.
Introduction
Accumulation of protein-bound uremic toxins, including indoxyl sulfate and p-cresyl sulfate, are associated with increased cardiovascular disease and mortality in chronic kidney disease ...(CKD). We performed a systematic review and meta-analysis to synthesize the available strategies for lowering protein-bound uremic toxin levels in CKD patients.
Methods
We conducted a meta-analysis by searching the databases of MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials for observational studies and randomized controlled trials (RCTs) that examined the effect of dietary protein restrictions, biotic supplements (including prebiotics, probiotics, and synbiotics), AST-120, dialysis techniques, and the outcome of preservation of residual renal function (RRF) on indoxyl sulfate and p-cresyl sulfate levels. Random-effect model meta-analyses were used to compute changes in the outcomes of interest.
Results
A total of 38 articles (2,492 patients), comprising 28 RCTs, 8 single-arm or prospective cohort studies, and 2 cross-sectional studies were included in this meta-analysis. When compared with placebo, prebiotics, synbiotics, and AST-120 provided significantly lower levels of both serum indoxyl sulfate and p-cresyl sulfate. There were no significant reductions in serum indoxyl sulfate and p-cresyl sulfate levels in patients receiving probiotics. Preservation of RRF in dialysis patients resulted in lower levels of both of the protein-bound uremic toxins. When compared with conventional hemodialysis, hemodiafiltration significantly decreased serum p-cresyl sulfate alone, whereas a significant change in serum indoxyl sulfate levels was observed only in studies with long-term observation periods. Very low protein diet (VLPD) and other oral medications yielded insignificant differences in protein-bound uremic toxins.
Conclusions
The present meta-analysis demonstrated that prebiotics, synbiotics, and AST-120 can effectively reduce both serum indoxyl sulfate and p-cresyl sulfate in CKD patients when compared with placebo. Preservation of RRF was associated with lower serum indoxyl sulfate and p-cresyl sulfate levels. The effect of biotic supplements was detected only in dialysis patients. For non-dialysis CKD patients, the results were limited due to the small number of studies. Further studies are needed to determine the efficacy in these populations.
The objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when ...controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT.
Sarcopenia in end-stage kidney disease patients requiring dialysis is a frequent complication but remains an under-recognized problem. This meta-analysis was conducted to determine the prevalence of ...sarcopenia and explored its impacts on clinical outcomes, especially cardiovascular events, and mortality in dialysis patients. The eligible studies were searched from PubMed, Scopus, and Cochrane Central Register of Controlled trials up to 31 March 2022. We included studies that reported the interested outcomes, and the random-effects model was used for analysis. Forty-one studies with 7576 patients were included. The pooled prevalence of sarcopenia in dialysis patients was 25.6% (95% CI 22.1 to 29.4%). Sarcopenia was significantly associated with higher mortality risk (adjusted OR 1.83 (95% CI 1.40 to 2.39)) and cardiovascular events (adjusted OR 3.80 (95% CI 1.79 to 8.09)). Additionally, both low muscle mass and low muscle strength were independently related to increased mortality risk in dialysis patients (OR 1.71; 95% CI (1.20 to 2.44), OR 2.15 (95% CI 1.51 to 3.07)), respectively. This meta-analysis revealed that sarcopenia was highly prevalent among dialysis patients and shown to be an important predictor of cardiovascular events and mortality. Future intervention research to alleviate this disease burden in dialysis patients is needed.
Abstract
Leptospirosis can cause a high mortality rate, especially in severe cases. This multicenter cross-sectional study aimed to examine both host and pathogen factors that might contribute to the ...disease severity. A total of 217 leptospirosis patients were recruited and divided into two groups of non-severe and severe. Severe leptospirosis was defined by a modified sequential organ failure assessment (mSOFA) score of more than two or needed for mechanical ventilation support or had pulmonary hemorrhage or death. We found that leptospiremia, plasma neutrophil gelatinase-associated lipocalin (pNGAL), and interleukin 6 (IL-6) at the first day of enrollment (day 1) and microscopic agglutination test (MAT) titer at 7 days after enrollment (days 7) were significantly higher in the severe group than in the non-severe group. After adjustment for age, gender, and the days of fever, there were statistically significant associations of baseline leptospiremia level (OR 1.70, 95% CI 1.23–2.34, p = 0.001), pNGAL (OR 9.46, 95% CI 4.20–21.33, p < 0.001), and IL-6 (OR 2.82, 95% CI 1.96–4.07, p < 0.001) with the severity. In conclusion, a high leptospiremia, pNGAL, and IL-6 level at baseline were associated with severe leptospirosis.
Background
When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, ...bacterial products entering the circulation might contribute to the pathophysiology of COVID-19.
Methods
We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-β-
d
-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome.
Results
Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime.
Conclusions
Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.
Colorectal cancer (CRC) is the third most common cancer worldwide. Dysbiosis of human gut microbiota has been linked to sporadic CRC. This study aimed to compare the gut microbiota profiles of 80 ...Thai volunteers over 50 years of age among 25 CRC patients, 33 patients with adenomatous polyp, and 22 healthy controls. The 16S rRNA sequencing was utilized to characterize the gut microbiome in both mucosal tissue and stool samples. The results revealed that the luminal microbiota incompletely represented the intestinal bacteria at the mucus layer. The mucosal microbiota in beta diversity differed significantly among the three groups. The stepwise increase of Bacteroides and Parabacteroides according to the adenomas-carcinomas sequence was found. Moreover, linear discriminant analysis effect size showed a higher level of Erysipelatoclostridium ramosum (ER), an opportunistic pathogen in the immunocompromised host, in both sample types of CRC patients. These findings indicated that the imbalance of intestinal microorganisms might involve in CRC tumorigenesis. Additionally, absolute quantitation of bacterial burden by quantitative real-time PCR (qPCR) confirmed the increasing ER levels in both sample types of cancer cases. Using ER as a stool-based biomarker for CRC detection by qPCR could predict CRC in stool samples with a specificity of 72.7% and a sensitivity of 64.7%. These results suggested ER might be a potential noninvasive marker for CRC screening development. However, a larger sample size is required to validate this candidate biomarker in diagnosing CRC.
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