KLOTHO methylation is linked to uremic toxins and chronic kidney disease

Epigenetic regulation plays a major role in uremic toxin-induced chronic kidney disease (CKD) progression. The KLOTHO protein is a key modulator of homeostasis in renal function. Uremic toxin accumulation can induce DNA methyltransferase (DNMT) protein expression, which is involved in the silencing of KLOTHO through hypermethylation. Treatment with DNMT inhibitors can induce a hypermethylated status of KLOTHO and suppress mRNA and protein expression. Epigenetic targeting of specific genes may become an effective strategy to prevent progression of uremia-related CKD

Investigation of varying louver angles and positions on cross ventilation in a generic isolated building using CFD simulation

Louvers are an integral component of natural ventilation. This study presents a numerical analysis using computational fluid dynamics (CFD) on cross ventilation in an isolated building equipped with louvers. Opening configurations of (i) center-center, (ii) top-top, (iii) bottom-bottom, (iv) top-bottom and (v) bottom-top (whereby the configurations are defined as ‘windward’-‘leeward’) with varying louver configurations of No-Louver (NL), 0◦, 15◦, 30◦ and 45◦ are studied. Atmospheric Boundary Layer (ABL) condition is applied at the inlet of the flow domain and Renormalization Group (RNG) k-ε turbulence model with enhanced wall function (EWT) is employed for the numerical simulations. Grid sensitivity analysis is performed using Grid Convergence Index (GCI) whilst model validation is performed using Factor of two of observation (FAC2) analysis. The highest dimensionless flow rate (DFR) is achieved by configuration top-top without louvers at 0.719. The highest air exchange efficiency (AEE) is obtained by louver angle of 15◦ for center-center configuration at 53.4%. The lowest AEE obtained is obtained at louver angle of 0◦ for top-top configuration at 20%, indicating short-circuiting of air. For configuration bottom-bottom with louver angle of 30◦, high AEE is obtained but at the cost of reduced DFR. The optimal balance between AEE and DFR can be obtained by factor-optimization (α) as presented in this paper. The study concludes that opening position alongside louver angle plays an integral role on the internal airflow, pressure coefficient, DFR and AEE in natural cross ventilation

Aldosterone-producing adenoma is associated with urolithiasis in primary aldosteronism

Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan–Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA

Reversible heart rhythm complexity impairment in patients with primary aldosteronism

Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1–5, area 6–15, and area 6–20 on MSE analysis (all p < 0.05). Area 1–5, area 6–15, area 6–20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy

Urinary angiotensin-converting enzyme 2 and its activity in cats with chronic kidney disease

IntroductionAngiotensin-converting enzyme 2 (ACE2) played an important role in the renin-angiotensin-aldosterone system (RAAS) and it was proved to be renoprotective in renal disease. Urinary angiotensin-converting enzyme 2 (uACE2) has been shown to reflect renal injury in human and experimental studies, but its role in feline kidney disease remains unknown.AimsOur objectives involve comparing uACE2 concentrations and activities in cats across CKD stages with healthy controls, investigating the relationship between uACE2 concentrations, activities, and clinicopathological data in feline CKD patients, and assessing the predictive abilities of both for CKD progression.MethodsA retrospective, case–control study. The concentration and activity of uACE2 were measured by commercial ELISA and fluorometric assay kits, respectively. The concentration was adjusted to give uACE2 concentration-to-creatinine ratios (UACCRs).ResultsIn total, 67 cats consisting of 24 control and 43 chronic kidney disease (CKD), including 24 early-stage CKD and 19 late-stage CKD, were enrolled in this study. UACCR values were significantly higher in both early-stage (2.100 [1.142–4.242] x 10−6) and late-stage feline CKD (4.343 [2.992–5.0.71] x 10−6) compared to healthy controls (0.894 [0.610–1.076] x 10−6; p &lt; 0.001), and there was also significant difference between-early stage group and late-stage group (p = 0.026). Urinary ACE2 activity (UAA) was significantly lower in CKD cats (1.338 [0.644–2.755] x pmol/min/ml) compared to the healthy cats (7.989 [3.711–15.903] x pmol/min/ml; p &lt; 0.001). UACCR demonstrated an independent, positive correlation with BUN (p &lt; 0.001), and UAA exhibited an independent, negative correlation with plasma creatinine (p &lt; 0.001). Both UACCR and UAA did not yield significant results in predicting CKD progression based on the ROC curve analysis.Conclusion and clinical importanceuACE2 concentration and activity exhibit varying changes as renal function declines, particularly in advanced CKD cats

Psoas Abscess Caused by Non-Typhoid Salmonella in a Patient with Severe Aplastic Anemia

The clinical spectrum of infections caused by non-typhoid Salmonella spp. includes gastroenteritis, enteric fever, bacteremia, and extraintestinal localized complications, especially in immunocompromised hosts. Here we report a patient with severe aplastic anemia developing left iliopsoas abscess caused by non-typhoid Salmonella (NTS), which was successfully treated by prolonged antibiotic treatment and repeated debridement. Our data indicate that aplastic anemia is a risk factor for infection caused by NTS

Advanced age affects the outcome-predictive power of RIFLE classification in geriatric patients with acute kidney injury

The RIFLE (risk, injury, failure, loss, and end-stage) classification is widely used to gauge the severity of acute kidney injury, but its efficacy has not been formally tested in geriatric patients. To correct this we conducted a prospective observational study in a multicenter cohort of 3931 elderly patients (65 years of age or older) who developed acute kidney injury in accordance with the RIFLE creatinine criteria after major surgery. We studied the predictive power of the RIFLE classification for in-hospital mortality and investigated the potential interaction between age and RIFLE classification. In general, the survivors were significantly younger than the nonsurvivors and more likely to have hypertension. In patients 76 years of age and younger, RIFLE-R, -I, or -F classifications were significantly associated with increased hospital mortality in a stepwise manner. There was no significant difference, however, in hospital mortality in those over 76 years of age between patients with RIFLE-R and RIFLE-I, although RIFLE-F patients had significantly higher mortality than both groups. Thus, the less severe categorizations of acute kidney injury per RIFLE classification may not truly reflect the adverse impact on elderly patients

Hospital Mortality of Septic Acute Kidney Injury Requiring Renal Replacement Therapy in the Postoperative Elderly

SummaryBackgroundSeptic acute kidney injury (AKI) is a common complication in intensive care units (ICU), it and portends a higher risk of morbidity and death than nonseptic AKI. However, its outcome and prognostic factors among elderly postoperative patients remain unknown. We aimed to determine the risk factors and predictors of mortality among postoperative elderly patients (≥ 65 years) with septic AKI requiring acute dialysis.MethodsThe study protocol was based on that of a clinical cohort study of renal failure patients in the database of the National Taiwan University Surgical ICU Acute Renal Failure (NSARF) Study Group. From January 2002 to July 2009, patients (aged > 18 years) with postoperative AKI requiring renal replacement therapy (RRT) were recruited for this study. Each case of septic AKI before operation was identified and patients with end-stage renal disease were excluded.ResultsA total of 292 postoperative patients with septic AKI requiring dialysis were identified during the study period. The mean (SD) age was 65.9 (11.9) years and 68.2% were men. Abdominal surgery was the most common type of surgery (42.8%), followed by cardiovascular (28.8%) and chest surgery (15.4%). The most common indications for RRT in this study cohort were azotemia in 223 patients (76.4%) and fluid overload in 62 patients (21.2%); 92 (31.5%) patients had one indication, 170 (58.2%) had two indications, and 30 (10.3%) had more than three indications. The elderly patients (those ≥ 65 years) had anemia, underwent abdominal surgery, and received dialysis for fluid overload more frequently than the young adults. By contrast, the young adults were more likely to present with shock requiring vasopressor use and have abnormal liver functions. In the elderly subgroup, the outcome was found to be associated with mechanical ventilator use, but not with disease severity, comorbidities, types of surgery and the indication for dialysis.ConclusionsThe hospital mortality of postoperative elderly patients with septic AKI was more than 60% and was not affected by age. Mechanical ventilator use was the major risk factor and prognostic factor for elderly patients in this clinical setting

Preoperative Proteinuria Is Associated with Long-Term Progression to Chronic Dialysis and Mortality after Coronary Artery Bypass Grafting Surgery

AIMS: Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but whether it is also associated with increased long-term mortality and end-stage renal disease (ESRD) is unknown. METHODS AND RESULTS: We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+) or heavy (2+ to 4+) according to the results of the dipstick test. A total of 276 (29.8%) patients had mild proteinuria before surgery and 119 (12.9%) patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17) was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88) and heavy proteinuria ([HR], 2.28) to predict all-cause mortality compared to no proteinuria. Mild ([HR], 2.57) and heavy proteinuria ([HR], 2.70) exhibited a stepwise increased ratio compared to patients without proteinuria for long-term composite catastrophic outcomes (mortality and ESRD), which were independent of the baseline GFR and postoperative acute kidney injury (AKI). CONCLUSION: Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients