Effect of canagliflozin in non-diabetic obese patients with albuminuria: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) has been shown to improve renal outcomes in both diabetic and non-diabetic kidney disease. However, the effect of SGLT2i on renal outcomes in patients with non-diabetic obesity is still not established. MATERIALS AND METHODS: In this double-blind, randomized controlled trial, we assigned non-diabetic patients with body mass index (BMI) ≥ 25 kg/m2, persistent 24-hour urine albumin-creatinine ratio (UACR) ≥ 10 mg/gCr, and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2, who had been treated with renin-angiotensin system blockade, to canagliflozin 100 mg daily or placebo for 24 weeks. The reduction in UACR and eGFR at 12 and 24 weeks were explored. (Thai Clinical Trials Registry 20190203003). RESULTS: Of 247 non-diabetic obese patients screened, 32 patients met inclusion criteria and underwent randomization. The median baseline of UACR was 69.1 mg/gCr. There were no statistically significant differences in albuminuria reduction between the groups at 12 weeks and 24 weeks. The estimated GFR in the canagliflozin group decreased significantly from baseline at 12 weeks (-5.39 mL/min/1.73m2; 95% CI -9.81 to -0.97; p = 0.017) but not at 24 weeks (-1.16 mL/min/1.73m2; 95% CI -5.58 to 3.26; p = 0.66), and there was no significant change from baseline in the placebo group at both 12 and 24 weeks. CONCLUSION: Canagliflozin 100 mg daily was well tolerated but did not significantly reduce UACR in non-diabetic obese patients with microalbuminuria. However, a significant temporary decline in eGFR might reflect a subtle reduction in glomerular hyperfiltration.

The impacts of hypoxia-inducible factor stabilizers on laboratory parameters and clinical outcomes in chronic kidney disease patients with renal anemia: a systematic review and meta-analysis.

Renal anemia in chronic kidney disease (CKD) is associated with poor outcomes. Hypoxia-inducible factor (HIF) stabilizer, which induces endogenous erythropoietin synthesis and enhances iron mobilization, is a novel treatment for anemia in CKD. We conducted a systematic review and meta-analysis to analyze the effect of HIF stabilizers in anemic CKD patients. This meta-analysis included 43 officially published articles and 3 unpublished studies (27 338 patients). HIF stabilizer treatment significantly increased hemoglobin (Hb) level when compared with placebo (mean difference 1.19 g/dL; 95% confidence interval 0.94 to 1.44 g/dL; P < .001). There was no significant difference in Hb level when compared with erythropoiesis-stimulating agents (ESAs). Significant reductions of ferritin and transferrin saturation (TSAT) were observed, while total iron-binding capacity was increased in the HIF stabilizer group compared with placebo or ESAs. HIF stabilizers significantly reduced hepcidin, high-density lipoprotein, low-density lipoprotein and triglyceride levels. Acute kidney injury and thrombotic events were significantly observed in patients receiving HIF stabilizers. There were no significant differences in myocardial infarction, stroke, dialysis initiation, pulmonary hypertension and mortality between HIF stabilizer and control groups. The present meta-analysis provided evidence that HIF stabilizers increased Hb and TIBC levels and reduced hepcidin, ferritin and TSAT in CKD patients with renal anemia. Long-term follow-up studies on clinical outcomes of HIF stabilizers are still needed.

Metabolic effects of kidney donation: A Bayesian analysis of matched cohorts.

The kidney is a notable site of glycolysis, gluconeogenesis, and fatty acid oxidation. Loss of a kidney after kidney donation might, therefore, affect the glucose and lipid metabolism of the donors. This matched cohort study investigated the effect of nephrectomy on glucose and lipid metabolisms using Bayesian hypothesis testing. There were 77 pairs of matched donor-control pairs in the present study. Clinical and laboratory data of the participants, at baseline and 1-year, were extracted from electronic medical records. Comparisons between donor and control groups were performed using the Bayesian independent samples t-test or Bayesian Mann-Whitney test. The Bayes Factor for alternative hypothesis over null hypothesis (BF10 ) was used to compare the two competing hypotheses. The BF10 of 3 or more was considered evidence for the alternative hypothesis. Comparing changes from baseline to 1-year between donors and controls, the BF10 of triglycerides, high-density lipoprotein cholesterol (HDL-C), triglyceride-glucose (TyG) index of insulin resistance, and estimated glomerular filtration rate (eGFR) were 7.95, 3.96, 30.13, and 1.32 x 1041 , respectively signifying that the change of these variables in the donors differed from those in the controls (alternative hypothesis). Triglyceride, HDL-C, and TyG index of the donors increased more than those of the controls while eGFR of the donor decreased more than that of the controls. Our data suggest that triglycerides and insulin resistance increase after donor nephrectomy. Kidney donors should be informed about these metabolic changes and should adhere to lifestyle recommendations that may mitigate insulin resistance.

The dose of the normal saline pre-infusion and other risk factors for amphotericin B deoxycholate-associated acute kidney injury.

Background: Conventional amphotericin B deoxycholate (AmBd) is the preferred amphotericin B formulation in countries with limited resources despite its nephrotoxicity. Normal saline pre-infusion is a recommended measure to reduce the risk of nephrotoxicity in patients receiving AmBd. Objectives: To examine the effect of different normal saline solution (NSS) pre-infusion doses, and other potential risk factors, on the development of acute kidney injury (AKI) in patients with invasive fungal infection receiving AmBd. Methods: Adult patients with invasive fungal infections who received intravenous AmBd were included in this retrospective study. Doses of the normal saline pre-infusion were adjusted to the body weight (NSS/BW) and the daily dose of amphotericin B (NSS/AmBd). Kaplan-Meier survival analysis was used to estimate 14 d AKI-free survival rates, and the log-rank test was used to compare AKI-free survivals between groups. Results: The present study included 60 patients; 31 patients developed AKI during the AmBd therapy. The overall 14 d AKI-free survival was 48.3%. NSS/AmBd, but not NSS/BW, was associated with AKI-free survival in patients receiving AmBd: the higher the NSS/AmBd, the higher the AKI-free survival. Gender, baseline blood urea nitrogen (BUN), and baseline plasma bicarbonate (Bicarb) also affected AKI-free survival. Female gender, higher BUN, and lower Bicarb were associated with higher AKI-free survival. Conclusions: The present study suggests that low NSS/AmBd, male gender, low BUN, and high Bicarb are risk factors for AmBd-associated AKI. Excluding gender, these risk factors are potentially modifiable and would guide tailoring appropriate preventive measures for AmBd-associated AKI.

Candida Administration in 5/6 Nephrectomized Mice Enhanced Fibrosis in Internal Organs: An Impact of Lipopolysaccharide and (1→3)-ß-D-Glucan from Leaky Gut.

Uremic toxins and gut dysbiosis in advanced chronic kidney disease (CKD) can induce gut leakage, causing the translocation of gut microbial molecules into the systemic circulation. Lipopolysaccharide (LPS) and (1→3)-ß-D-glucan (BG) are the major gut microbial molecules of Gram-negative bacteria and fungi, respectively, and can induce inflammation in several organs. Here, the fibrosis in the kidney, liver, and heart was investigated in oral C. albicans-administered 5/6 nephrectomized (Candida-5/6 Nx) mice. At 20 weeks post 5/6 Nx, Candida-5/6 Nx mice demonstrated increased 24 h proteinuria, liver enzymes, and serum cytokines (TNF-α, IL-6, and IL-10), but not weight loss, systolic blood pressure, hematocrit, serum creatinine, or gut-derived uremic toxins (TMAO and indoxyl sulfate), compared to in 5/6 Nx alone. The gut leakage in Candida-5/6 Nx was more severe, as indicated by FITC-dextran assay, endotoxemia, and serum BG. The areas of fibrosis from histopathology, along with the upregulated gene expression of Toll-like receptor 4 (TLR-4) and Dectin-1, the receptors for LPS and BG, respectively, were higher in the kidney, liver, and heart. In vitro, LPS combined with BG increased the supernatant IL-6 and TNF-α, upregulated the genes of pro-inflammation and pro-fibrotic processes, Dectin-1, and TLR-4 in renal tubular (HK-2) cells and hepatocytes (HepG2), when compared with LPS or BG alone. This supported the pro-inflammation-induced fibrosis and the possible LPS-BG additive effects on kidney and liver fibrosis. In conclusion, uremia-induced leaky gut causes the translocation of gut LPS and BG into circulation, which activates the pro-inflammatory and pro-fibrotic pathways, causing internal organ fibrosis. Our results support the crosstalk among several organs in CKD through a leaky gut.

Langerhans Cell Histiocytosis Manifests with Acute Severe Hypernatremia during Hospitalization.

Central diabetes insipidus (DI) is characterized by a deficiency in arginine vasopressin (AVP), an antidiuretic hormone leading to excessive free water loss in the urine and hypernatremia. Central DI can be the first presentation of several occult diseases. However, patients with central DI who have functioning thirst mechanisms and access to water may initially exhibit normal sodium levels. We report a 57-year-old woman who was admitted to the hospital due to cholangitis. Her initial serum sodium was normal and she rapidly developed severe hypernatremia after fluid restriction. The results of the laboratory workup indicated DI, which dramatically responded to desmopressin. MRI showed an ill-defined faint hyper signal intensity in T1, T2/FLAIR lesions involving the bilateral hypothalamus. The histopathological findings confirmed the diagnosis of Langerhans cell histiocytosis (LCH) with multiorgan involvement. Serum sodium returned to normal after receiving desmopressin and water replacement therapy.

Early switching of tenofovir disoproxil fumarate (TDF) in HIV-infected patients with TDF-induced nephrotoxicity: a prospective study.

Background: Tenofovir disoproxil fumarate (TDF) can induce proximal renal tubulopathy (PRT) and necessitate changes in treatment regimen. This prospective study aimed to compare tubular function recovery following early switching versus late switching of TDF in human immunodeficiency virus (HIV)-infected patients with TDF-induced PRT.Methods: For this prospective study, conducted during 2017-2019, we enrolled HIV-1-infected, virologically suppressed adults undergoing TDF-containing combination antiretroviral therapy. Patients were separated into a late-switching group (LSG) and an early-switching group (ESG). The LSG included patients having an estimated glomerular filtration rate (eGFR) decrease ≥25% from the pretreatment level or Fanconi syndrome. The ESG included patients having ≥2 of the following indicators of PRT: fractional excretion of phosphate (FEUP) ≥10%, low tubular maximum reabsorption of phosphate (TmP)/GFR, or uricosuria; fractional uric acid excretion ≥10%; urine protein-creatinine index (UPCI) ≥500 mg/g creatinine, normoglycemic glycosuria, or decrease in eGFR of 15%-24%. Recovery of proximal tubular function at 6 and 12 months after TDF discontinuation was assessed. Complete recovery was defined as normalization of all abnormal tubular markers.Results: Thirty-three HIV-infected patients were enrolled (70% male). Except for tubular function markers, baseline characteristics were not significantly different between the two groups. The proportion of patients having complete recovery was significantly higher in the ESG (p = 0.007, log-rank test). FEUP improved significantly in the ESG after TDF discontinuation; improvements of eGFR and UPCI were greater in the LSG. An eGFR change of 10% from baseline was the only independent predictor of failure to achieve complete recovery after switching. After median follow-up of 2.25 years post-trial, sustained recovery of eGFR within 5% of pre-TDF eGFR was achieved only in the ESG.Conclusions: Early-switching of TDF in HIV patients with PRT may allow complete recovery of proximal renal tubular function.

Hydrodynamic model for renal microvascular filtration: Effects of physiological and hemodynamic changes on glomerular size-selectivity.

OBJECTIVE: The first step in renal urine formation is ultrafiltration across the glomerular barrier. The change in its nanostructure has been associated with nephrotic syndromes. Effects of physiological and hemodynamic factor alterations associated with diabetic nephropathy (DN) on glomerular permselectivity are examined through a mathematical model employing low-Reynolds-number hydrodynamics and hindered transport theory. METHODS: Glomerular capillaries are represented as networks of cylindrical tubes with multilayered walls. Glomerular basement membrane (GBM) is a fibrous medium with bimodal fiber sizes. Epithelial slit fiber spacing follows a lognormal distribution based on reported electron micrographs with the highest resolution. Endothelial fenestrae are filled with fibers the size of glycosaminoglycans (GAGs). Effects of fiber-macromolecule steric and hydrodynamic interactions are included. Focusing on diabetic nephropathy, the physiological and hemodynamic factors employed in the computation are those reported for healthy humans and patients with early-but-overt diabetic nephropathy. The macromolecule concentration is obtained as a finite element solution of the convection-diffusion equation. RESULTS: Computed sieving coefficients averaged along the capillary length agree well with ficoll sieving coefficients from studies in humans for most solute radii. GBM thickening and the loss of the slit diaphragm hardly affect glomerular permselectivity. GAG volume fraction reduction in the endothelial fenestrae, however, significantly increases macromolecule filtration. Increased renal plasma flow rate (RPF), glomerular hypertension, and reduction of lumen osmotic pressure cause a slight sieving coefficient decrease. These effects are amplified by an increased macromolecule size. CONCLUSION: Our results indicate that glomerular hypertension and the reduction in the oncotic pressure decreases glomerular macromolecule filtration. Reduction of RPF and changes in the glomerular barrier structure associated with DN, however, increase the solute sieving. Damage to GAGs caused by hyperglycemia is likely to be the most prominent factor affecting glomerular size-selectivity.

Efficacy of Potassium Supplementation in Hypokalemic Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Multicenter, open-label, prospective, randomized controlled trial. SETTING & PARTICIPANTS: 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). INTERVENTIONS: 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. OUTCOME: 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. RESULTS: 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. LIMITATIONS: Not double-masked. CONCLUSIONS: 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. TRIAL REGISTRATION: Registered at the Thai Clinical Trials Registry with study number TCTR20190725004.

Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-ß-D-Glucan, but Is Attenuated by Lacticaseibacillus rhamnosus L34.

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)-ß-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 Lacticaseibacillus rhamnosus L34 (L34) on CKD were investigated using oral C. albicans-administered 5/6 nephrectomy (5/6Nx) mice. At 16 weeks post-5/6Nx, Candida-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-Candida-5/6Nx. However, serum creatinine, renal fibrosis, or gut barrier defect (FITC-dextran assay and endotoxemia) remained comparable between Candida- versus non-Candida-5/6Nx. The probiotics L34 attenuated several parameters in Candida-5/6Nx mice, including fecal dysbiosis (Proteobacteria and Bacteroides), gut leakage (fluorescein isothiocyanate (FITC)-dextran), gut-derived uremic toxin (trimethylamine-N-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 ß; IL-1ß) and inflammatory genes (TNF-α, IL-1ß, aryl hydrocarbon receptor, and nuclear factor-κB)), compared with non-IS activation. These injuries were attenuated by the probiotics condition media. In conclusion, Candida 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.

Severe hyponatremia as the presenting manifestation of primary empty sella syndrome.

Severe hyponatremia is associated with neurological impairment and mortality. Furthermore, severe hyponatremia can be the first presentation of several diseases. Therefore, an appropriate investigation for the underlying causes of hyponatremia apart from the proper correction of sodium levels, might lead to a diagnosis of occult diseases.

Lactobacillus rhamnosus L34 attenuates chronic kidney disease progression in a 5/6 nephrectomy mouse model through the excretion of anti-inflammatory molecules.

BACKGROUND: Although pathogenic gut microbiota causes gut leakage, increases translocation of uremic toxins into circulation and accelerates CKD progression, the local strain of Lactobacillus rhamnosus L34 might attenuate gut leakage. We explored the effects of L34 on kidney fibrosis and levels of gut-derived uremic toxins (GDUTs) in 5/6 nephrectomy (5/6Nx) mice. METHODS: At 6 weeks post-5/6Nx in mice, either L34 (1 × 106 CFU) or phosphate buffer solution (as 5/6Nx control) was fed daily for 14 weeks. In vitro, the effects of L34-conditioned media with or without indoxyl sulfate (a representative GDUT) on inflammation and cell integrity (transepithelial electrical resistance; TEER) were assessed in Caco-2 (enterocytes). In parallel, the effects on proinflammatory cytokines and collagen expression were assessed in HK2 proximal tubular cells. RESULTS: At 20 weeks post-5/6Nx, L34-treated mice showed significantly fewer renal injuries, as evaluated by (i) kidney fibrosis area (P < 0.01) with lower serum creatinine and proteinuria, (ii) GDUT including trimethylamine-N-oxide (TMAO) (P = 0.02) and indoxyl sulfate (P < 0.01) and (iii) endotoxin (P = 0.03) and serum TNF-α (P = 0.01) than 5/6Nx controls. Fecal microbiome analysis revealed an increased proportion of Bacteroidetes in 5/6Nx controls. After incubation with indoxyl sulfate, Caco-2 enterocytes had higher interleukin-8 and nuclear factor κB expression and lower TEER values, and HK2 cells demonstrated higher gene expression of TNF-α, IL-6 and collagen (types III and IV). These indoxyl sulfate-activated parameters were attenuated with L34-conditioned media, indicating the protective role of L34 in enterocyte integrity and renal fibrogenesis. CONCLUSION: L34 attenuated uremia-induced systemic inflammation by reducing GDUTs and gut leakage that provided renoprotective effects in CKD.

The role of once-weekly online hemodiafiltration with low protein diet for initiation of renal replacement therapy: A case series.

Incremental hemodialysis (HD) has become an exciting approach according to the recognition of the importance of preserving residual kidney function (RKF). However, not all incident HD patients are suitable for this approach, particularly once-weekly HD. This is the first study which reported the effectiveness of once-weekly online-hemodiafiltration (OL-HDF) plus low protein diet (LPD) in incident HD patients. All stage 5 CKD patients who had chosen HD as their treatment modality at the HD center of King Chulalongkorn Memorial Hospital, Bangkok, Thailand, with RKF ⩾ 3 mL/min calculated by renal clearance of urea and urine output ⩾ 800 mL/day, started the treatment with once-weekly OL-HDF. Dietitians advised patients to consume LPD (0.6-0.8 g/kg/day) on non-dialysis days and a regular protein diet on the dialysis day (1.2 g/kg/day). Eleven incident HD patients were enrolled in the study. The mean RKF and urine volume at baseline were 4.56 ± 2.21 mL/min and 2,019.54 ± 743.73 mL/day, respectively. After 6 and 12 months of follow-up, the mean RKF of the patients who remained in the once-weekly OL-HDF protocol were 3.82 ± 1.68 mL/min and 3.28 ± 0.95 mL/min, respectively. The median duration of once-weekly OL-HDF before transitioning to twice- or thrice-weekly OL-HDF was 7 months (3-24 months). The most common indication for stepping prescription was too low RKF. We reported that dialysis initiation in the university-based center with once-weekly OL-HDF in carefully selected incident HD patients combined with LPD under serial monitoring is practical. Further studies on the clinical benefits of once-weekly OL-HDF are still required.

A Randomized Controlled Trial of Comparative Efficacy between Sodium Bicarbonate and Heparin as A Locking Solution for Tunneled Central Venous Catheters Among Patients Requiring Maintenance Hemodialysis.

BACKGROUND: Sodium bicarbonate (NaHCO3) is one of the promising solutions that has good safety profile and theoretical advantages regarding antimicrobial and antithrombotic properties but there are still limited reports. OBJECTIVE: To compare the efficacy in lowering rate of catheter loss due to catheter-related thrombosis (CRT) or catheter-related blood stream infection (CRBSI) between sodium bicarbonate and heparin lock in prevalent chronic hemodialysis (HD) patients. DESIGN: A multicenter, randomized, open-label study. SETTING: In a developing country, Thailand. PATIENTS: Chronic HD patients with tunneled central venous catheter. MEASUREMENTS: Catheter loss rate, rate of catheter-related blood stream infection, catheter-related thrombosis, and exit site or tunnel infection. METHODS: The prospective multicenter randomized controlled trial was conducted, we randomly assigned 118 patients undergoing HD with tunneled central venous catheter to receive a catheter locking solution of sodium bicarbonate or heparin. The primary outcome was a catheter loss rate due to CRT or CRBSI, while the secondary outcome was a composite outcome of CRT, CRBSI, or exit site/tunnel infection (ESI/TI). RESULTS: The present study was stopped early due to an excess of catheter-related thrombosis in the sodium bicarbonate group. From the first 6 weeks of follow-up, there were no catheter losses due to CRT or CRBSI in both groups. The sodium bicarbonate group had a significantly higher rate of the secondary composite outcomes and this was entirely caused by CRT with the median time to thrombosis of 23.6 days. Every CRT event could be successfully rescued by using a single dose of recombinant tissue plasminogen activator (rt-PA). LIMITATIONS: Short follow-up period. CONCLUSIONS: In prevalent HD patients with tunneled CVCs, use of a sodium bicarbonate locking solution for prevention of CRT is inferior to heparin and is associated with a high rate of catheter-related thrombosis. TRIAL REGISTRATION: The study was registered with the Thai Clinical Trials Registry TCTR 20200610003.

CONTEXTE: Le bicarbonate de sodium (NaHCO3) figure parmi les solutions prometteuses présentant un bon profil de tolérance et des bienfaits théoriques en matière de propriétés antimicrobiennes et antithrombotiques. Les rapports en faisant état demeurent toutefois limités. OBJECTIFS: Comparer l'efficacité du NaHCO3 par rapport à l'héparine en tant que solutions de verrouillage du cathéter dans la réduction du taux d'échec du cathéter en raison d'une thrombose due au cathéter (TDC) ou d'une septicémie due au cathéter (SDC) chez les patients suivant des traitements d'hémodialyse (HD) de façon chronique. TYPE D'ÉTUDE: Essai randomisé ouvert mené dans plusieurs centers. CADRE: Étude réalisée en Thaïlande, un pays en développement. SUJETS: Patients sous HD chronique par cathéter veineux central tunnelisé. MESURES: Le taux d'échec du cathéter, le taux de SDC, le taux de TDC et le taux d'infections au point d'émergence cutané ou de tunnelites. MÉTHODOLOGIE: Cet essai prospectif randomisé et contrôlé est multicentrique et porte sur 118 patients HD avec cathéter veineux central tunnelisé. Les sujets ont été répartis aléatoirement pour recevoir une solution de NaHCO3 ou d'héparine comme solution de verrouillage du cathéter. Le principal critère d'évaluation était l'échec du cathéter en raison d'une TDC ou d'une SDC. Le critère d'évaluation secondaire était un résultat combiné de TDC, de SDC ou d'une infection au point d'émergence/ tunnelite. RÉSULTATS: L'étude a été interrompue prématurément en raison d'un trop grand nombre de thromboses liées au cathéter dans le groupe recevant le NaHCO3. Dans les six premières semaines de suivi, aucun échec dû à une thrombose ou à une septicémie n'avait été observé dans les deux groupes. Le groupe NaHCO3 a montré un taux significativement plus élevé d'événements liés au critère d'évaluation secondaire, et cela était entièrement causé par TDC; le délai médian avant la thrombose était de 23,6 jours. Chaque TDC a pu être restaurée avec succès grâce à une seule dose d'activateur tissulaire du plasminogène (rt-PA). LIMITES: Courte période de suivi. CONCLUSION: Chez les patients prévalents suivant des traitements d'hémodialyse via un cathéter veineux central tunnelisé, l'utilization du NaHCO3 comme solution de verrouillage du cathéter a été associée à un taux élevé de thromboses dues au cathéter et s'est avérée moins efficace que l'héparine pour les prévenir. ENREGISTREMENT DE L'ESSAI: L'essai est enregistré au registre des essais cliniques thaïlandais TCTR 20200610003.

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial.

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups -5.61 mg/L; 95% CI -11.01 to -0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.

The impact of CASR A990G polymorphism in response to cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism.

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.

Factors Associated with the Incidence and Mortality of Coronavirus Disease 2019 (COVID-19) after 126-million Cases: A Meta-analysis.

OBJECTIVES: This meta-analysis was conducted to investigate the current global incidence and mortality of COVID-19 and also explored the associated factors including geographic variations, transmission scenarios, country economic status, and healthcare performance. METHODS: The search was conducted in online databases based on reports from national authorities by March 28, 2021. Random-effects model meta-analyses and meta-regression analyses were used to generate summary estimates and explored sources of heterogeneity. RESULTS: The cumulative number of confirmed COVID-19 cases was 125,704,789 reported by 216 countries. The pooled Daily Cumulative Index (DCI) was 1423.87 cases/day which was highest in South America (2759.15 cases/day) followed by North America (2252.49 cases/day), Europe (1858.44 cases/day), Asia (1484.84 cases/day), Africa (193.09 cases/day), and Australia/Oceania (18.55 cases/day). The overall pooled mortality rate of COVID-19 was 1.53%. Higher income countries and countries with community transmission had higher DCI. By meta-regression, country total health expenditure per capita, percentage of universal health coverage, and total number of tests were associated with higher DCI. On the contrary, country Gross Domestic Product (GDP) per capita were negatively correlated with mortality rate. CONCLUSION: To date, 216 countries around the world are affected by COVID-19. Higher income, GDP, and countries' investments on heath are associated with higher DCI while higher GDP correlates with lower mortality. Community transmission route have more impact on the incidence and mortality of COVID-19.

Hypokalemia in peritoneal dialysis patients in Thailand: the pivotal role of low potassium intake.

OBJECTIVE: Hypokalemia is highly prevalent in chronic peritoneal dialysis (PD) patients worldwide, particularly in Thailand. This study aims to investigate the major determinants of hypokalemia in Thai PD patients. METHODS: A cross-sectional study was performed in chronic PD patients at 4 PD centers in Bangkok, Thailand. Hypokalemia was defined if the average serum potassium level during the last 3 consecutive visits was < 3.5 mEq/L. Patients and/or their caregivers were asked to perform a 3-day dietary food record and take pre- and post-meal pictures following the instructed protocol. Daily dietary nutrients, including potassium, were estimated by a single dietician using INMUCAL-N software. Total potassium excretion was determined by 24-h PD effluents and urine collection. Intracellular and extracellular water values (ICW and ECW, respectively) were measured by electrical bioimpedance assay (BIA) to indirectly explore the role of intracellular potassium shift in hypokalemia. RESULTS: Among 60 eligible PD patients, 19 (31%) had hypokalemia. Hypokalemic patients had significantly lower dietary potassium intake (24.4 ± 11.1 vs. 30.5 ± 9.4 mEq/day, p = 0.031) and lower total potassium excretion (28.5 ± 8.4 vs. 36.7 ± 11.2 mEq/day, p = 0.006) compared to normokalemic patients. Both groups had comparable values of ICW and ECW. On logistic regression, there was no significant correlation between hypokalemia and daily PD exchange volume, total Kt/Vurea, residual renal function, concurrent medications (insulin, diuretics, renin-angiotensin-aldosterone inhibitor, and beta-blockers) or ICW. Low dietary potassium was an independent risk factor for hypokalemia. CONCLUSION: Low dietary potassium intake, rather than increased potassium excretion or intracellular shift, is the major contributing factor of hypokalemia in Thai chronic PD patients. Dietary intervention or potassium supplement protocol should be implemented.