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.
Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for ...highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells.
We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28.
Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups.
PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression.
ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.
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.
A chronic kidney disease (CKD) causes uremic toxin accumulation and gut dysbiosis, which further induces gut leakage and worsening CKD. Lipopolysaccharide (LPS) of Gram-negative bacteria and ...(1➔3)-β-D-glucan (BG) of fungi are the two most abundant gut microbial molecules. Due to limited data on the impact of intestinal fungi in CKD mouse models, the influences of gut fungi and
L34 (L34) on CKD were investigated using oral
-administered 5/6 nephrectomy (5/6Nx) mice. At 16 weeks post-5/6Nx,
-5/6Nx mice demonstrated an increase in proteinuria, serum BG, serum cytokines (tumor necrotic factor-α; TNF-α and interleukin-6), alanine transaminase (ALT), and level of fecal dysbiosis (Proteobacteria on fecal microbiome) when compared to non-
-5/6Nx. However, serum creatinine, renal fibrosis, or gut barrier defect (FITC-dextran assay and endotoxemia) remained comparable between
- versus non-
-5/6Nx. The probiotics L34 attenuated several parameters in
-5/6Nx mice, including fecal dysbiosis (
and
), gut leakage (fluorescein isothiocyanate (FITC)-dextran), gut-derived uremic toxin (trimethylamine-
-oxide; TMAO) and indoxyl sulfate; IS), cytokines, and ALT. In vitro, IS combined with LPS with or without BG enhanced the injury on Caco-2 enterocytes (transepithelial electrical resistance and FITC-dextran permeability) and bone marrow-derived macrophages (supernatant cytokines (TNF-α and interleukin-1 β; IL-1β) and inflammatory genes (
,
,
, and
)), compared with non-IS activation. These injuries were attenuated by the probiotics condition media. In conclusion,
administration worsens kidney damage in 5/6Nx mice through systemic inflammation, partly from gut dysbiosis-induced uremic toxins, which were attenuated by the probiotics. The additive effects on cell injury from uremic toxin (IS) and microbial molecules (LPS and BG) on enterocytes and macrophages might be an important underlying mechanism.
Hypokalemia is a common electrolyte abnormality in patients on peritoneal dialysis (PD) and has been associated with increased risks of peritonitis and death. Whether correction of hypokalemia ...improves these outcomes is unknown.
Multicenter, open-label, prospective, randomized controlled trial.
Adult (aged ≥18 years) PD patients with hypokalemia (defined as at least 3 values or an average value <3.5 mEq/L in the past 6 months). Randomization was stratified according to center and residual urine output (≤100 or >100 mL/day).
Random assignment to either protocol-based potassium supplementation (titratable dose of oral potassium chloride to maintain serum potassium of 4-5 mEq/L) or conventional potassium supplementation (reactive supplementation when serum potassium is <3.5 mEq/L) over 52 weeks. Treatment groups were compared using intention-to-treat analyses implemented using Cox proportional hazards regression.
The primary outcome was time from randomization to first peritonitis episode (any organism). Secondary outcomes were all-cause mortality, cardiovascular mortality, hospitalization, and conversion to hemodialysis.
A total of 167 patients with time-averaged serum potassium concentrations of 3.33 ± 0.28 mEq/L were enrolled from 6 PD centers: 85 were assigned to receive protocol-based treatment, and 82 were assigned to conventional treatment. The median follow-up time was 401 (IQR, 315-417) days. During the study period, serum potassium levels in the protocol-based treatment group increased to 4.36 ± 0.70 mEq/L compared with 3.57 ± 0.65 mEq/L in the group treated conventionally (mean difference, 0.66 95% CI, 0.53-0.79 mEq/L; P < 0.001). The median time to first peritonitis episode was significantly longer in the protocol-based group (223 IQR, 147-247 vs 133 IQR, 41-197 days, P = 0.03). Compared with conventional treatment, the protocol-based group had a significantly lower hazard of peritonitis (HR, 0.47 95% CI, 0.24-0.93) but did not differ significantly with respect to any of the secondary outcomes. Asymptomatic hyperkalemia (>6 mEq/L) without characteristic electrocardiographic changes occurred in 3 patients (4%) in the protocol-based treatment group.
Not double-masked.
Compared with reactive potassium supplementation when the serum potassium level falls below 3.5 mEq/L, protocol-based oral potassium treatment to maintain a serum potassium concentration in the range of 4-5 mEq/L may reduce the risk of peritonitis in patients receiving PD who have hypokalemia.
Registered at the Thai Clinical Trials Registry with study number TCTR20190725004.
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Hepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in ...non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients.
Introduction. High protein intake may accelerate progression of chronic kidney disease (CKD). Estimation of dietary protein intake (DPI) is indispensable for management of CKD, but to achieve optimum ...DPI is quite challenging in routine clinical practice. We recently studied a beneficial effect of utilizing integrated care on the management of CKD at the rural community level. In that study, we created a short protein food-recall questionnaire (S-PFRQ) as a working tool to estimate DPI of the CKD patients during home visit by community health personnel. Herein, we reported the initial evaluation of the reliability of S-PFRQ from our previous study. Objective. We compared the amount of DPI obtained from S-PFRQ with that obtained from protein-equivalent of total nitrogen appearance (PNA). Methods. In the previous ESCORT-2 study, 914 patients with CKD stage 3 or 4, who were living in the rural area of Thailand, were prospectively followed while receiving integrated care for 36 consecutive months. During home visits by community nurses from subdistrict health centers, dietary food recall was made, recorded in S-PFRQ, and DPI was obtained. Among these, sixty patients were randomly selected, and 24-h urine was collected for urinary urea-N and estimation of PNA. A correlation was made between DPI obtained from S-PFRQ and PNA. Results. The DPIs derived from S-PFRQ and PNA were 28.8 ± 14.8 and 39.26 ± 17.79 g/day, respectively. The mean difference and 95% CI between the 2 methods was −10.43 (−7.1 to −13.8) g/day, respectively (P < 0.001). Interclass correlation between these 2 methods was 0.24, P = 0.007. The difference between the 2 methods remained constant across different amounts of DPI. Conclusion. The DPI estimated from S-PFRQ significantly correlated to that from PNA. However, the S-PFRQ method yielded a DPI value which was about 10 g of protein or 25% less than the PNA method. Despite this amount of difference, this S-PFRQ is user-friendly and could be used during field work as an easy and simple tool for DPI estimation in resource-limiting condition.
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