Hepatorenal syndrome: Current concepts and future perspectives.

Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.

Cell-cell contacts via N-cadherin induce a regulatory renin secretory phenotype in As4.1 cells.

The lack of a clonal renin-secreting cell line has greatly hindered the investigation of the regulatory mechanisms of renin secretion at the cellular, biochemical, and molecular levels. In the present study, we investigated whether it was possible to induce phenotypic switching of the renin-expressing clonal cell line As4.1 from constitutive inactive renin secretion to regulated active renin secretion. When grown to postconfluence for at least two days in media containing fetal bovine serum or insulin-like growth factor-1, the formation of cell-cell contacts via N-cadherin triggered downstream cellular signaling cascades and activated smooth muscle-specific genes, culminating in phenotypic switching to a regulated active renin secretion phenotype, including responding to the key stimuli of active renin secretion. With the use of phenotype-switched As4.1 cells, we provide the first evidence that active renin secretion via exocytosis is regulated by phosphorylation/dephosphorylation of the 20 kDa myosin light chain. The molecular mechanism of phenotypic switching in As4.1 cells described here could serve as a working model for full phenotypic modulation of other secretory cell lines with incomplete phenotypes.

Renal Recovery After Liver Transplantation Alone in Patients With Liver Cirrhosis and Severe Chronic Kidney Disease With Normal Kidney Size.

BACKGROUND: Most guidelines recommend simultaneous liver-kidney transplantation (SLKT) in patients with liver cirrhosis (LC) and severe chronic kidney disease (CKD) over liver transplantation alone (LTA). CKD, however, is not irreversible. This study evaluates the reversibility of kidney disease after LTA based on kidney size. MATERIALS AND METHODS: In this single-center retrospective study, we classified 90 patients with LC and severe CKD into 3 groups: the normal kidney (NK)-LTA group (n=39), small kidney (SK)-LTA group (both kidneys <9 cm at the time of LTA, n=40), and SK-SLKT group (n=11). RESULTS: The NK-LTA group had a lower percentage of hepatocellular carcinoma and a higher pre-liver transplantation (LT) estimated glomerular filtration rate. This group, however, was older, received livers from a higher percentage of deceased donors, and had a higher Child-Pugh score. Renal recovery, defined as the return of creatinine to their baseline, or a persistent change from baseline but not persistent (≥3 months) need for renal replacement therapy after LT, was found in 79% in the NK-LTA group, which was higher than 7.5% in the SK-LTA group. Renal and patient survival was found in 56% of the NK-LTA group, which was higher than 2.5% of the SK-LTA group. CONCLUSIONS: There is a high percentage of renal recovery in the NK-LTA group, and accordingly, this does not justify SLKT, since this would result in a "waste" of kidneys. Therefore, KT after LT is recommended over SLKT for the LC patients with NK size.

Uncertain Clinical Effect of Polymyxin B Hemoperfusion in Patients with Septic Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

ABSTRACT: Polymyxin B hemoperfusion (PMX-HP) may improve the clinical outcomes of patients with sepsis and gram-negative bacteremia by reducing endotoxin levels. However, the recent studies with the variable degree of renal support have shown that the improvement of survival rate by PMX-HP remains unclear in such patients. Therefore, we investigated whether the addition of PMX-HP to continuous renal replacement therapy (CRRT) could improve the survival rate than CRRT alone. This study included 231 patients with sepsis undergoing CRRT alone or PMX-HP with CRRT. Primary outcomes were 28-day and 90-day all-cause mortality. Urine output, ventilator support, and Sequential Organ Failure Assessment (SOFA) score were not significantly different between the two groups. Crude 28-day and 90-day mortality rates were higher in the PMX-HP with CRRT group than in the CRRT-alone group. To correct for disease severity, propensity score (PS) matching was performed with acute respiratory distress syndrome, mechanical ventilation support, extracorporeal membrane oxygenation, infection source (abdomen), age, inotropic score, SOFA score, C-reactive protein, and procalcitonin levels. Sixty-six PS-matched pairs revealed significantly higher 28-day and 90-day mortality rates in the PMX-HP with CRRT group than in the CRRT-alone group. Considering the mortality rates after PS matching, the additional use of PMX-HP does not improve the clinical outcomes of patients with sepsis and acute kidney injury requiring CRRT.

Outcomes of arteriovenous access among cancer patients requiring chronic haemodialysis.

BACKGROUND: There are limited data focusing specifically on the types of arteriovenous (AV) access used and outcomes of AV access among cancer patients as a consequence of cancer. We aimed to describe outcomes of AV access among cancer patients requiring chronic haemodialysis, and also to compare outcomes between patients with and without cancer. METHODS: In this single-centre, retrospective, observational cohort study, 84 patients diagnosed with cancer before AV access placement were included; we analysed outcomes of AV access among these patients and compared these outcomes with our previous results. The study endpoints were AV access patency and early failure, defined as AV access abandonment within 12 months after AV access placement. RESULTS: Various cancer types, stages, and treatments were identified in our analysis. Autologous arteriovenous fistulas (AVFs) were used for 92.9% of this study population. Using our previous results for comparison, we found no significant difference in death-censored primary (P = 0.546) and secondary (P = 0.266) patency of AV access between patients with and without cancer; however, the rate of early AVF failure was statistically significantly higher among cancer patients (25.6% vs 13.9%; P = 0.008), and the most common cause of AVF failure was patient death. The rate of early failure was significantly higher among patients with advanced-stage cancer (59.1%) than among those with early-stage cancer (12.9%) (P <  0.001). CONCLUSIONS: Although AV access patency rates were similar among patients with and without cancer in the death-censored analysis, cancer patients were more prone to early AVF failure, mainly due to cancer-associated deaths, and this consideration needs to be carefully balanced against individual patients' life expectancies, according to cancer type and stage.

Febuxostat, a novel inhibitor of xanthine oxidase, reduces ER stress through upregulation of SIRT1-AMPK-HO-1/thioredoxin expression.

BACKGROUND: Endoplasmic reticulum (ER) stress has been implicated in the development of various renal diseases. Thus, inhibition of ER stress using pharmacological agents may serve as a promising therapeutic approach. We postulated that febuxostat, a novel xanthine oxidase inhibitor, could suppress the ER stress through upregulation of SIRT1 (silent mating type information regulation 2 homolog 1)-AMPK (AMP activated protein kinase)-HO-1 (heme oxygenase-1)/thioredoxin expression. METHODS: We examined the effect of febuxostat on the ER stress induced by a chemical inducer, tunicamycin and non-chemical agents such as angiotensin II, aldosterone, high glucose, and albumin in renal tubular cells. We further examined the in vivo effects of febuxostat using mouse model of kidney disease induced by unilateral ureteral obstruction (UUO). Expression of ER stress was measured by western blot analysis and immunohistochemical stain. RESULTS: Febuxostat suppressed the ER stress induced by tunicamycin and non-chemical agents, as shown by inhibition of increased GRP78 (glucose-related protein78) and p-eIF2α (phosphospecific-eukaryotic translation initiation factor 2α) expression. Inhibitory effect of febuxostat was mediated through upregulation of SIRT1-AMPK followed by induction of HO-1 and thioredoxin. In animal model of UUO, febuxostat reduced the UUO-induced ER stress, which was abolished by pretreatment with SIRT1 inhibitor (sirtinol) and AMPK inhibitor (compound C). CONCLUSION: Febuxostat could suppress the ER stress caused by various ER stress inducers through upregulation of SIRT1-AMPK-HO-1/thioredoxin expression. Targeting these pathways might serve as one of the possible therapeutic approaches in kidney diseases under excessive ER stress.

Comparison of outcomes between type 2 diabetic and non-diabetic incident hemodialysis patients with functioning arteriovenous fistulas.

This study compared clinical outcomes of patient survival and arteriovenous fistula (AVF) patency between incident hemodialysis patients with and without type 2 diabetes mellitus (T2DM).Between January 2011 and December 2013, 384 consecutive incident hemodialysis patients with confirmed first upper-extremity AVF placement were divided into a T2DM group (n = 180, 46.9%) and a non-DM group (n = 204, 53.1%) and analyzed retrospectively. The primary outcome was all-cause mortality, and secondary outcome was AVF patency.Patients in the T2DM group had a higher prevalence of hypertension (P = .02), smoking (P < .01), cardiovascular disease (P < .01), history of cerebrovascular accident (CVA) (P < .01), and peripheral arterial occlusive disease (P < .01) than those in the non-DM group. On Kaplan-Meier survival analysis, the overall survival and AVF patency rates were significantly higher in the non-DM group relative to the T2DM group (both P < .01). In the adjusted model, older age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02-1.06; P < .01), T2DM (HR, 1.76; 95% CI, 1.12-2.77; P = .014), and history of CVA (HR, 1.76; 95% CI, 1.04-2.98; P = .04) were significantly associated with an increased risk of mortality. Older age and T2DM were independently associated with decreased primary (HR, 1.03; 95% CI, 1.02-1.04; P < .01, HR, 1.69; 95% CI, 1.22-2.33; P < .01, respectively) and secondary (HR, 1.03; 95% CI, 1.01-1.04; P < .01, HR, 2.07; 95% CI, 1.42-3.00; P < .01, respectively) AVF patency during follow-up.Compared with patients in the non-DM group, patients in the T2DM group had a higher mortality rate and worse AVF patency rates.

Effects of patient age on patency of chronic hemodialysis vascular access.

BACKGROUND: In this single-center, retrospective observational study, we assessed the long-term patency of vascular access (VA) after first VA placement to uncover independent risk factors associated with VA patency in Asian hemodialysis (HD) patients stratified by age. We also investigated factors associated with VA patency among older HD patients according to the type of VA in the overall study population. METHODS: The study period was from January 2011 to December 2013. A total of 651 chronic HD patients with confirmed first upper-extremity VA placement were enrolled, and their records were analyzed retrospectively. A total of 445 patients (68.4%) made up the nonelderly group (< 65 years), and 206 patients (31.6%) were in the elderly group (≥ 65 years). Study outcomes were defined as primary or secondary VA patency. RESULTS: Autologous arteriovenous fistula (AVF) was more common in the nonelderly group (P <  0.01). Kaplan-Meier curve survival analysis indicated that primary patency was longer in the nonelderly group (P <  0.01); secondary patency, however, was similar between groups (P = 0.37). The multivariate analysis of factors associated with primary VA patency revealed that increased age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03; P <  0.01) was associated with shorter primary patency, and AVF (HR, 0.38; 95% CI, 0.28-0.51; P <  0.01) was associated with longer primary patency. AVF (HR, 0.57; 95% CI, 0.37-0.87; P = 0.010) and diabetes mellitus (HR, 1.56; 95% CI, 1.07-2.29; P = 0.02) were independently associated with longer and shorter secondary patency periods, respectively; however, increased age was not a risk factor for decreased secondary patency. CONCLUSIONS: Increased age was associated with shorter primary patency but not secondary patency, whereas AVF placement was associated with longer primary and secondary patency. Considering the similar rates of secondary patency between groups and the superior patency of AVF compared to arteriovenous graft, a fistula-first strategy should be applied to appropriate older patients.

A risk scoring model to predict renal progression associated with postcontrast acute kidney injury in chronic kidney disease patients.

Postcontrast acute kidney injury (AKI) occurs more frequently in patients with lower estimated glomerular filtration rate. We hypothesized that postcontrast AKI in chronic kidney disease (CKD) patients with distinct risk factors might be associated with accelerated renal progression.We undertook this retrospective cohort study to develop and validate a risk scoring model for predicting renal progression. In a development dataset, 18,278 contrast-enhanced CT scans were performed in 9097 patients with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m) who were not undergoing dialysis. Postcontrast AKI was observed in 5.8% (1051/18,278) of all contrast-enhanced CTs with 7.6% (689/9097) of the total CKD patients. We investigated the 1-year renal outcome in 224 eligible patients. A risk scoring model was developed with multivariate regression analysis and was assessed in external validation (independent 154 patients).Among 224 patients, 70 (31.3%) patients had progression of renal dysfunction at 1 year (defined as reduction in estimated GFR ≥25% at 1 year). A risk score of 4, 4, 6, 6, 7, or 6 was assigned to diabetes, baseline estimated GFR < 45 mL/min/1.73 m, hypertension, repeated contrast exposure, congestive heart failure, and persistent renal injury (defined as an elevation of serum creatinine ≥25% at 3 months), respectively. An increasing risk score was associated with renal progression. Of note, persistent renal injury was more prevalent in the progression group than in the non-progression group. The AUROC of the model in the development population was 0.765. In the validation dataset, however, the discriminative power decreased (AUROC = 0.653).Our suggested model provided the risk of renal progression, aiding in predicting prognosis, counseling, and improving outcomes in CKD patients complicated by postcontrast AKI.

Predictive Factors of Duration of Continuous Renal Replacement Therapy in Acute Kidney Injury Survivors.

The factors influencing continuous renal replacement therapy (CRRT) duration for critically ill patients with acute kidney injury (AKI) are unclear. Therefore, we investigated the clinical factors that could influence the duration of CRRT for AKI survivors. In this retrospective observational study, the medical records of all hospital survivors who required CRRT for AKI in intensive care units were analyzed. The CRRT duration (median, 6 days) was categorized as short-duration CRRT (≤ 6 days, n = 65) and long-duration CRRT (> 6 days, n = 59), according to the median CRRT duration. A urine output of less than 0.5 mL/kg/h (adjusted odds ratio [OR], 3.4; P = 0.010), mechanical ventilation use (adjusted OR, 7.9; P = 0.001), and extracorporeal membrane oxygenation (ECMO) use (adjusted OR, 6.5; P = 0.010) were independent predictors of long-duration CRRT, whereas serum creatinine and neutrophil gelatinase-associated lipocalin were not significant predictors. A clinical model demonstrated a good discriminatory ability to predict long-duration CRRT (area under the curve, 0.84; 95% confidence interval, 0.76-0.90). The urine output immediately before CRRT initiation and factors associated with disease severity significantly affected the duration of CRRT. Simultaneously considering the urine output, mechanical ventilation use, and ECMO use predicted CRRT duration in AKI survivors.

Patency rates of arteriovenous fistulas created before versus after hemodialysis initiation.

In an incident hemodialysis (HD) population, we aimed to investigate whether arteriovenous fistula (AVF) creation before HD initiation was associated with improved AVF patency compared with AVF creation from a central venous catheter (CVC), and also to compare patient survival between these patients. Between January 2011 and December 2013, 524 incident HD patients with identified first predialysis vascular access with an AVF (pre-HD group, n = 191) or an AVF from a CVC (on-HD group, n = 333) were included and analyzed retrospectively. The study outcome was defined as AVF patency and all-cause mortality (time to death). On Kaplan-Meier survival analysis, primary and secondary AVF patency rates did not differ significantly between the two groups (P = 0.812 and P = 0.586, respectively), although the overall survival rate was significantly higher in the pre-HD group compared with the on-HD group (P = 0.013). On multivariate analysis, well-known patient factors were associated with decreased primary (older age and diabetes mellitus [DM]) and secondary (DM and peripheral arterial occlusive disease) AVF patency, whereas use of a CVC as the initial predialysis access (hazard ratios, 1.84; 95% confidence intervals, 1.20-2.75; P = 0.005) was significantly associated with worse survival in addition to well-known patient factors (older age, diabetes mellitus, and peripheral arterial occlusive disease). Worse survival in the on-HD group was likely confounded by selection bias because of the retrospective nature of our study. Therefore, the observed lower mortality associated with AVF creation before HD initiation is not fully attributable to CVC use, but rather, affected by other patient-level prognostic factors. There were no CVC-related complications in the pre-HD group, whereas 10.2% of CVC-related complications were noted in the on-HD group. In conclusion, among incident HD patients, compared with patients who underwent creation of an AVF from a CVC, initial AVF creation showed similar primary and secondary AVF patency rates, but lower mortality risk. We also observed that an initial CVC use was an independent risk factor associated with worse survival. A fistula-first strategy might be the best option for incident HD patients who are good candidates for AVF creation.

Impact of transvenous cardiac implantable electronic devices in chronic hemodialysis patients: a single-center, observational comparative study.

BACKGROUND: We investigated the impact of a transvenous cardiac implantable electronic device (CIED) placement on outcomes and arteriovenous vascular access (VA) patency among chronic hemodialysis patients. METHODS: This is a single-center, observational comparative study between chronic hemodialysis patients with ipsilateral and contralateral CIED and VA. Forty-two consecutive patients who underwent both CIED placement and upper-extremity VA for hemodialysis, regardless of the sequence and time interval between these 2 procedures, were identified between January 2001 and December 2017. Patients with ipsilateral (n = 22, 52%, the ipsilateral group) and contralateral (n = 20, 48%, the contralateral group) CIED and VA were compared retrospectively; the primary outcome was any-cause mortality and cardiac mortality or the composite of any systemic complications, defined as central venous stenosis or occlusion, any device infections or tricuspid regurgitation; the secondary outcome was CIED or VA malfunction. RESULTS: During the median follow-up period of 101 months, primary outcome incidence was significantly higher in the ipsilateral group than the contralateral group (73% vs 40%, P = 0.03), although the incidences of any-cause mortality (P = 0.28) and cardiac mortality (P > 0.99) were similar between the groups. Secondary outcome incidence did not differ significantly between the 2 groups (55% vs 30%, P = 0.36). Kaplan-Meier survival analysis revealed similar primary and secondary VA patency rates in both groups. On subgroup analysis, patients with upper arm VA had similar primary and secondary patency to those with forearm VA. CONCLUSIONS: Despite some notable limitations of the study, the retrospective study design and small sample size, we found that the any-cause mortality incidence and VA patency did not differ between the 2 groups, but primary outcome incidence was significantly higher among patients with ipsilateral CIED and VA.

Change in alkaline phosphatase activity associated with intensive care unit and hospital length of stay in patients with septic acute kidney injury on continuous renal replacement therapy.

BACKGROUND: Evidence suggests that alkaline phosphatase attenuates inflammatory response in sepsis by lipopolysaccharide detoxification and adenosine triphosphate dephosphorylation. We sought to determine changes in alkaline phosphatase (AP) activity during septic acute kidney injury (AKI) and clinical parameters associated with AP activity. METHODS: In this retrospective study, we investigated baseline (when initiating CRRT) and follow-up AP activity on day 3, and associated outcomes in patients who underwent continuous renal replacement therapy (CRRT) due to septic AKI. RESULTS: We analyzed the baseline AP activity of 155 patients and day 3 AP activity in 123 patients. Baseline AP activity was not associated with renal or inflammatory biomarkers, or outcomes. It did not significantly differ between the 75 survivors and 80 non-survivors (p = 0.155). AP activity was higher on day 3 than at baseline (105 U/L [interquartile range, 79-156] vs 90 U/L [interquartile range, 59-133]). In particular, liver and bone isoforms increased significantly (p < 0.05), but intestine isoforms did not reach statistical significance (p = 0.367). In addition, day 3 AP activity showed a weak correlation with length of ICU stay (r = 0.213, p = 0.018) and length of hospital stay (r = 0.216, p = 0.017), but not with survival (r = - 0.035, p = 0.698). CONCLUSION: Endogenous AP activity significantly increased in patients with septic AKI. However, neither baseline nor follow-up AP activity was associated with survival.

Effects of Renal Impairment on the Pharmacokinetics and Safety of Udenafil.

Udenafil is a phosphodiesterase-5 inhibitor used to treat erectile dysfunction. Although udenafil is not predominantly eliminated by the kidney, renal impairment can alter its secretion/transport pathways. Drug pharmacokinetics and safety must therefore be assessed in subjects with a renal impairment. We investigated the effects of impaired renal function on the pharmacokinetics and safety of a single 100-mg oral dose of udenafil in a single-dose, open-label, parallel-group study of 31 subjects. Cockcroft-Gault creatinine clearance was used to stratify these subjects into healthy controls (>80 mL·min-1 ) and individuals with mild (50 to ≤80 mL·min-1 ), moderate (30 to ≤50 mL·min-1 ), and severe (<30 mL·min-1 ) renal impairment. Pharmacokinetic measurements and safety assessments indicated that the geometric mean of the area under the concentration-time curve to the last measurement in mildly, moderately, and severely renally impaired subjects was 1.30- (90% CI 1.05-1.60), 1.62- (90% CI 1.28-2.06), and 1.60- (90% CI 1.28-2.01) fold higher, respectively, than the healthy controls. The geometric mean of the maximum observed concentration was 1.41- (90% CI 1.05-1.88), 2.02- (90% CI 1.47-2.79), and 1.65- (90% CI: 1.21-2.24) fold higher, respectively. Significant correlations were observed among the creatinine clearance, oral clearance, and maximum concentration of udenafil (P < .01). All adverse events were mild, and no subject discontinued the study. Udenafil administration was well tolerated in all groups. In view of the clinical relevance of drug exposure, our findings indicate that a dose adjustment of udenafil is warranted in subjects with moderate or severe renal impairment.

Analysis of the development and progression of carbon monoxide poisoning-related acute kidney injury according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

CONTEXT: Acute kidney injury (AKI) can occur after carbon monoxide (CO) intoxication; however, limited data are available. This study aimed to evaluate the prognostic value of the development and progression of AKI in patients with acute CO poisoning. MATERIALS AND METHODS: We conducted a retrospective cohort study using a prospective registry of CO poisoning between January 2010 and December 2015. AKI was defined and classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariate logistic regression analysis was conducted to determine the association between AKI and adverse outcomes, defined as neurological deficits at discharge or 28-day mortality. RESULTS: A total of 661 patients were evaluated. According to KDIGO criteria, 114 patients (17.2%) had AKI (initial: stage 1, 70.2%; stage 2, 26.3%; stage 3, 3.5%) on admission and 119 (18.0%) finally developed AKI during their hospital stay (maximum: stage 1, 68.9%; stage 2, 23.5%; stage 3, 7.6%). Almost all patients (99.2%) were diagnosed as having their highest KDIGO stage within three days (median, one day). AKI development was associated with adverse outcomes (odds ratio (OR) 17.53, 95% confidence interval 45.00-77.14). Both initial and maximum AKI stages demonstrated a stepwise increase of adjusted OR for adverse outcomes. AKI stage progression occurred in 8.4% of patients with AKI and was an independent factor for adverse outcomes. CONCLUSION: CO poisoning- related AKI occurred in 18% and was mostly detected within one day after CO intoxication. The development and progression of AKI had a strong association with adverse outcomes and deserve further prospective investigation.

Numerical expression of volume status using the bioimpedance ratio in continuous ambulatory peritoneal dialysis patients: A pilot study.

BACKGROUND: Volume overload results in higher mortality rates in patients on continuous ambulatory peritoneal dialysis (CAPD). The ratio of bioimpedance (RBI) might be a helpful parameter in adjusting dry body weight in CAPD patients. This study examined whether it is possible to distinguish between non-hypervolemic status and hypervolemic status in CAPD patients by using only RBI. METHODS: RBI was calculated as follows: RBI = impedance at 50 kHz/impedance at 500 kHz. Based on the experts' judgements, a total of 64 CAPD patients were divided into two groups, a non-hypervolemic group and a hypervolemic group. The RBI was measured from right wrist to right ankle (rw-raRBI) by bioimpedance spectroscopy (BCM®, Fresenius Medical Care) before and after the peritosol was emptied. Other RBIs were measured from the right side of the anterior superior iliac spine to the ipsilateral ankle (rasis-raRBI) to control for the electro-physiological effects of peritoneal dialysate. RESULTS: The mean rw-raRBI of non-hypervolemic patients was higher than that of hypervolemic patients in the presence (1.141 ± 0.022 vs. 1.121 ± 0.021, P < 0.001) of a peritosol. Likewise, the mean rasis-raRBI of non-hypervolemic patients was higher than that of hypervolemic patients (presence of peritosol: 1.136 ± 0.026 vs. 1.109 ± 0.022, P < 0.001; absence of peritosol: 1.131 ± 0.022 vs. 1.107 ± 0.022, P < 0.001). CONCLUSION: The volume status of CAPD patients was able to be simply expressed by RBI. Therefore, this study suggests that when patients cannot be analyzed using BCM, RBI could be an alternative.

Nutritional Status Predicts 10-Year Mortality in Patients with End-Stage Renal Disease on Hemodialysis.

Protein-energy wasting (PEW) is associated with mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. The correct diagnosis of PEW is extremely important in order to predict clinical outcomes. However, it is unclear which parameters should be used to diagnose PEW. Therefore, this retrospective observational study investigated the relationship between mortality and nutritional parameters in ESRD patients on maintenance hemodialysis. A total of 144 patients were enrolled. Nutritional parameters, including body mass index, serum albumin, dietary intake, normalized protein catabolic rate (nPCR), and malnutrition inflammation score (MIS), were measured at baseline. Fifty-three patients died during the study. Survivors had significantly higher nPCR (1.10 ± 0.24 g/kg/day vs. 1.01 ± 0.21 g/kg/day; p = 0.048), energy intake (26.7 ± 5.8 kcal/kg vs. 24.3 ± 4.2 kcal/kg; p = 0.009) and protein intake (0.91 ± 0.21 g/kg vs. 0.82 ± 0.24 g/kg; p = 0.020), and lower MIS (5.2 ± 2.3 vs. 6.1 ± 2.1, p = 0.039). In multivariable analysis, energy intake <25 kcal/kg (HR 1.860, 95% CI 1.018-3.399; p = 0.044) and MIS > 5 (HR 2.146, 95% CI 1.173-3.928; p = 0.013) were independent variables associated with all-cause mortality. These results suggest that higher MIS and lower energy intake are harmful to ESRD patients on maintenance hemodialysis. Optimal energy intake could reduce mortality in these patients.

Early continuous renal replacement therapy in septic acute kidney injury could be defined by its initiation within 24 hours of vasopressor infusion.

PURPOSE: The optimal timing for the initiation of early continuous renal replacement therapy (CRRT) is uncertain and requires a practically feasible definition with acceptable evidence. MATERIALS AND METHODS: We investigated the clinical impacts of 3-time interval parameters on the morbidity and mortality of 177 patients with septic shock-induced acute kidney injury: (1) time from vasopressor initiation to CRRT initiation (Tvaso-CRRT), (2) time from intensive care unit (ICU) admission to CRRT initation (TICU-CRRT), and (3) time from endotracheal intubation to CRRT initiation (Tendo-CRRT). RESULTS: The proportion of the patients with Tvaso-CRRT less than 24 h (median, 14 h, interquartile range [IQR], 5-30 h) was significantly higher in the survival group than in the non-survival group (84.3% vs. 58.5%, p < 0.001). Tvaso-CRRT less than 24 h and Sequential Organ Failure Assessment score were independent factors associated with 28-day mortality and 90-day mortality. TICU-CRRT (median, 17 h, IQR, 5-72 h) and Tendo-CRRT (median, 13 h, IQR, 4-48 h) were significantly correlated with both the length of ICU stay (p < 0.001) and mechanical ventilation duration (p < 0.001), but not mortality. CONCLUSIONS: Considering the possible therapeutic measurement by physician on the basis of the results in this study, early CRRT could be defined by a Tvaso-CRRT less than 24 h.

Anti-Fibrotic Effect of Losartan, an Angiotensin II Receptor Blocker, Is Mediated through Inhibition of ER Stress via Up-Regulation of SIRT1, Followed by Induction of HO-1 and Thioredoxin.

Endoplasmic reticulum (ER) stress is increasingly identified as modulator of fibrosis. Losartan, an angiotensin II receptor blocker, has been widely used as the first choice of treatment in chronic renal diseases. We postulated that anti-fibrotic effect of losartan is mediated through inhibition of ER stress via SIRT1 (silent mating type information regulation 2 homolog 1) hemeoxygenase-1 (HO-1)/thioredoxin pathway. Renal tubular cells, tunicamycin (TM)-induced ER stress, and unilateral ureteral obstruction (UUO) mouse model were used. Expression of ER stress was assessed by Western blot analysis and immunohistochemical stain. ER stress was induced by chemical ER stress inducer, tunicamycin, and non-chemical inducers such as TGF-ß, angiotensin II, high glucose, and albumin. Losartan suppressed the TM-induced ER stress, as shown by inhibition of TM-induced expression of GRP78 (glucose related protein 78) and p-eIF2α (phosphospecific-eukaryotic translation initiation factor-2α), through up-regulation of SIRT1 via HO-1 and thioredoxin. Losartan also suppressed the ER stress by non-chemical inducers. In both animal models, losartan reduced the tubular expression of GRP78, which were abolished by pretreatment with sirtinol (SIRT1 inhibitor). Sirtinol also blocked the inhibitory effect of losartan on the UUO-induced renal fibrosis. These findings provide new insights into renoprotective effects of losartan and suggest that SIRT1, HO-1, and thioredoxin may be potential pharmacological targets in kidney diseases under excessive ER stress condition.

Clinical Outcomes of Cryopreserved Arterial Allograft Used as a Vascular Conduit for Hemodialysis.

This single center cohort study aimed to test the hypothesis that use of a cryopreserved arterial allograft could avoid the maturation or healing process of a new vascular access and to evaluate the patency of this technique compared with that of vascular access using a prosthetic graft. Between April 2012 and March 2013, 20 patients underwent an upper arm vascular access using a cryopreserved arterial allograft for failed or failing vascular accesses and 53 using a prosthetic graft were included in this study. The mean duration of catheter dependence, calculated as the time interval from upper arm access placement to removal of the tunneled central catheter after successful cannulation of the access, was significantly longer for accesses using a prosthetic graft than a cryopreserved arterial allograft (34.4 ± 11.39 days vs. 4.9 ± 8.5 days, P < 0.001). In the allograft group, use of vascular access started within 7 days in 16 patients (80%), as soon as from the day of surgery in 10 patients. Primary (unassisted; P = 0.314) and cumulative (assisted; P = 0.673) access survivals were similar in the two groups. There were no postoperative complications related to the use of a cryopreserved iliac arterial allograft except for one patient who experienced wound hematoma. In conclusion, upper arm vascular access using a cryopreserved arterial allograft may permit immediate hemodialysis without the maturation or healing process, resulting in access survival comparable to that of an access using a prosthetic graft.