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Renal infarction is a condition caused by sudden disturbance of renal arterial blood flow, which occurs frequently in cardioembolic disease, renal artery injury (trauma, Marfan syndrome, rarely Ehlers-Danlos syndrome), and in association with a hypercoagulable state. Ehlers-Danlos syndrome is a rare hereditary connective tissue disease characterized by skin fragility, hyperelasticity, hypermobility of small joints, and easy bruising. Among the subtypes, vascular Ehlers-Danlos syndrome is a very rare genetic disease caused by a mutation in the COL3A1 gene. As blood vessels are fragile due dysfunctional collagen synthesis, complications of bleeding due to arterial dissection or rupture are common in patients with this disease. Here, we report a case of vascular Ehlers-Danlos syndrome diagnosed based on a renal infarction caused by thrombus and renal artery injury; we also present a review of the relevant literature.

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 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.

Patients undergoing long-term hemodialysis may suffer upper extremity central venous access failure and require an alternative route. This study aimed to evaluate the safety and efficacy of transrenal hemodialysis catheter insertion/replacement in patients with upper extremity central venous access failure. A multicenter retrospective cohort study was made of transrenal hemodialysis catheter insertion/replacement performed between 2014 and 2020. The history of renal replacement therapy and central venous catheters and the technical details of transrenal hemodialysis catheter insertion/replacement, patency, removal and complications were obtained for all patients. Six insertion and four replacement procedures involving transrenal hemodialysis catheters were evaluated in six patients (M:F = 3:3; median age, 49.5 years). Percutaneous transrenal (right:left = 1:5) hemodialysis catheter insertion was technically successful without complication in all six patients. In two patients, the tract was not lost because the safety guidewire was still in place, so no second puncture was required. The mean procedure time was 33.0 ± 9.2 min. The mean primary patency duration was 107.3 ± 70.9 days. During the mean follow-up duration of 141.2 ± 137.1 days, four hemodialysis catheter replacement procedures were successfully performed for catheter malfunction (n = 2) and dislodgement (n = 2). Catheter removal was successfully performed in four patients after confirming normal coagulation, followed by subsequent renal replacement therapy. Percutaneous insertion/replacement of transrenal hemodialysis catheters is feasible, safe, and effective when upper extremity central venous access is exhausted, and the catheters can be maintained for a reasonable period of time. Level 4, Case Series.

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

Mixed connective tissue disease (MCTD) is a rheumatologic disorder that has combined features of systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis with the anti-U1 ribonucleoprotein (RNP) antibody. Although renal involvement is not included in any of the diagnostic criteria, it has been observed in 20% of MCTD patients. The most common renal disease is immune complex nephropathy, histologically classified as membranous glomerulonephritis, but minimal change disease (MCD) is very rare and has only been reported once previously. A previously healthy 33-year-old woman presented with generalized edema, puffy hands, arthralgia, and Raynaud’s phenomenon. We diagnosed MCD with proteinuria (> 9 g/day) and hypoalbuminemia (< 1.0 g/dL) by renal biopsy, and MCTD with a simultaneously high titer of the anti-U1 RNP antibody. The patient was treated with 200 mg/day cyclosporine and 30 mg/day prednisolone. The proteinuria and hypoalbuminemia normalized 2 months later. We report a patient with severe MCD associated with MCTD.

Sweet’s syndrome (SS) is an autoimmune-mediated acute febrile neutrophilic dermatosis with a number of possible etiologies, including infection, malignancy, and drug reactions. In contrast to its original description, it can rarely involve extracutaneous organs, including the central nervous system, cardiovascular system, lung, liver, gastrointestinal tract, spleen, and bone. To our knowledge, there have been only three cases of SS accompanied by acute kidney injury worldwide, and this is the first report in which the patient recovered completely from acute kidney injury as well as cutaneous lesions with early steroid administration. Here, we report a case of SS with acute kidney injury in a patient with myelodysplastic syndrome (MDS) whose skin lesions and renal function recovered fully with early diagnosis and steroid therapy along with a review of the relevant literature.

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.

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 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.

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 ( Results Autologous arteriovenous fistula (AVF) was more common in the nonelderly group (P P 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 P 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.

Supplemental Digital Content is available in the text, 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

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 (

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.

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. 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. 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). 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.

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.

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]

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.

Introduction High sodium intake is the main cause of fluid overload in hemodialysis (HD) patients, leading to increased cardiovascular mortality. High sodium intake is known to be associated with low salt taste acuity and/or high preference. As the zinc status could influence taste acuity, we analyzed the effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in HD patients. Methods A total of 77 HD patients was enrolled in this cross-sectional study. Zinc deficiency was defined as serum zinc level with below 70 µg/mL. The patients were divided into two groups based on serum zinc level. Salt taste acuity and preference were determined by a sensory test using varying concentrations of NaCl solution, and dietary sodium intake was estimated using 3-day dietary recall surveys. Findings The mean salt recognition threshold and salt taste preference were significantly higher in the zinc deficient group than in the non-zinc deficient group. And there was significant positive correlation between salt taste preference and dietary sodium intake in zinc deficient group (r = 0.43, P = 0.002). Although, the dietary sodium intake showed a high tendency with no significance (P = 0.052), interdialytic weight gain was significantly higher in the zinc deficient group than in the non-zinc deficient group (2.68 ± 1.02 kg vs. 3.18 ± 1.02 kg; P = 0.047). Discussion Zinc deficiency may be related to low salt taste acuity and high salt preference, leading to high dietary sodium intake in HD patients.

Background: Endoplasmic reticulum (ER) stress is emerging as an important factor in the development of organ fibrosis. Therefore, modulation of ER stress may serve as one of the possible therapeutic approaches to renal fibrosis. SIRT1, a class III histone deacetylase, has been found to exert beneficial effects in kidney diseases. However, it is largely unknown whether and how SIRT1 suppresses the ER stress. We postulated that upregulation of SIRT1 would suppress the ER stress through induction of heme oxygenase-1 (HO-1) and thioredoxin. Methods: HK-2 tubular cells, experimental mouse models of tunicamycin (TM)-induced ER stress and unilateral ureteral obstruction (UUO) were used. Expression of ER stress-induced protein was measured by Western blot analysis and immunohistochemical staining. ER stress was induced by chemical ER stress inducers [TM [,]thapsigargin (TG)] and non-chemical inducers such as angiotensin II, aldosterone, high glucose and albumin. Results: SIRT1 activator (SRT1720) induced SIRT1 expression in a time- and dose-dependent manner in HK-2 cells. SRT1720 suppressed the TM- or TG-induced ER stress, as shown by inhibition of TM- or TG-induced upregulation of glucose-related protein 78 (GRP78), phosphor-specific eukaryotic translation initiation factor-2α and C/EBP homologous protein through HO-1 and thioredoxin, which were abolished by pretreatment with SIRT1 inhibitor (sirtinol). SRT1720 also suppressed the ER stress induced by angiotensin II, aldosterone, high glucose and albumin. In animal studies, treatment with SRT1720 reduced the tubular expression of GRP78 and increased the expression of HO-1 and thioredoxin. SRT1720 also reduced the UUO-induced renal fibrosis. Conclusion: SIRT1 may serve as a promising therapeutic target by reducing ER stress and fibrosis.

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

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.

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.

Background: Endoplasmic reticulum (ER) stress induced by urinary albumin plays an important role in tubulointerstitial injury. We have shown that albumin-induced ER stress is regulated through reactive oxygen species (ROS)-c-Src kinase-mTOR signaling pathways. We postulated that peroxisome proliferator-activated receptor-γ (PPAR-γ) might also act as an upstream signaling molecule between c-Src kinase and mTOR. It has been suggested that AMP-activated protein kinase (AMPK) is involved in attenuation of ER stress. We examined whether and how activation of AMPK suppressed the albumin-induced ER stress and apoptosis in tubular epithelial cells. Method: HK-2 cells, a proximal tubular cell line, were used. Protein expressions were measured by Western blot analysis. Intracellular ROS and apoptosis were analyzed by flow cytometry. Results: Albumin-induced PPAR-γ expression and PPAR-γ inhibitor (GW9662) suppressed the albumin-induced ER stress. c-Src kinase inhibitor and GW9662 reduced the albumin-induced PPAR-γ and mTOR, respectively. Metformin (the best known clinical activator of AMPK) and another AMPK activator (AICAR) suppressed the albumin-induced ER stress via inhibition of ROS through induction of endogenous antioxidant thioredoxin. AMPK inhibitor blocked the effect of metformin and AICAR. Our in vivo animal study showed that metformin reduced the renal cortical expression of ER stress protein (GRP78) in protein-overload proteinuria rats. Metformin also reduced the caspase 3-dependent apoptosis induced by albumin. Conclusion: PPAR-γ was involved in albumin-induced ER stress as an upstream signaling molecule between c-Src kinase and mTOR. AMPK activation might be beneficial in attenuating the tubulointerstitial injury induced by albumin.

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 (T vaso-CRRT ), (2) time from intensive care unit (ICU) admission to CRRT initation (T ICU-CRRT ), and (3) time from endotracheal intubation to CRRT initiation (T endo-CRRT ). Results The proportion of the patients with T vaso-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 vaso-CRRT less than 24 h and Sequential Organ Failure Assessment score were independent factors associated with 28-day mortality and 90-day mortality. T ICU-CRRT (median, 17 h, IQR, 5–72 h) and T endo-CRRT (median, 13 h, IQR, 4–48 h) were significantly correlated with both the length of ICU stay ( p p Conclusions Considering the possible therapeutic measurement by physician on the basis of the results in this study, early CRRT could be defined by a T vaso-CRRT less than 24 h.

Introduction High sodium intake is the main cause of fluid overload in hemodialysis (HD) patients, leading to increased cardiovascular mortality. High sodium intake is known to be associated with low salt taste acuity and/or high preference. As the zinc status could influence taste acuity, we analyzed the effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in HD patients. Methods A total of 77 HD patients was enrolled in this cross-sectional study. Zinc deficiency was defined as serum zinc level with below 70 µg/mL. The patients were divided into two groups based on serum zinc level. Salt taste acuity and preference were determined by a sensory test using varying concentrations of NaCl solution, and dietary sodium intake was estimated using 3-day dietary recall surveys. Findings The mean salt recognition threshold and salt taste preference were significantly higher in the zinc deficient group than in the non-zinc deficient group. And there was significant positive correlation between salt taste preference and dietary sodium intake in zinc deficient group (r = 0.43, P = 0.002). Although, the dietary sodium intake showed a high tendency with no significance (P = 0.052), interdialytic weight gain was significantly higher in the zinc deficient group than in the non-zinc deficient group (2.68 ± 1.02 kg vs. 3.18 ± 1.02 kg; P = 0.047). Discussion Zinc deficiency may be related to low salt taste acuity and high salt preference, leading to high dietary sodium intake in HD patients.

We hypothesized that the time from sepsis to inception of continuous renal replacement therapy (CRRT) can be used to predict survival rates in patients with septic acute kidney injury (AKI). The survival predictability of CRRT inception time was compared with that of RIFLE criteria, which were previously used in clinical practice. We retrospectively analyzed outcomes in 55 patients with septic AKI admitted to the medical intensive care unit at Asan Medical Center (Seoul, Korea) between April 2009 and October 2010. These patients were stratified by the time of inception of CRRT from sepsis (early: ≤ 24 h and late: >24 h) and also by the RIFLE criteria (RIFLE-I and RIFLE-F). The primary outcome was 28-day mortality. Of the 55 patients, 38 (69.1%) were male. Patients' mean age was 62.6 years, the most common infection site was the lung (32, 58.2%), and 47 patients (85.5%) were on mechanical ventilation. Thirty patients (54.5%) were in the RIFLE-I, and the others were in the RIFLE-F. Twenty-eight-day mortality rates were lower in the early group than in the late group (19.4% vs. 47.4%; P = 0.03), but did not differ between RIFLE-I and RIFLE-F. Ventilator-free day at day 28 was longer in the early group than that in the late group (7.5 vs. 0 d; P = 0.033). After adjustment for covariates, we found that the late group (hazard ratio, 3.106; 95% confidence interval, 1.066-9.047) and Sequential Organ Failure Assessment at sepsis (hazard ratio, 1.410; 95% confidence interval, 1.108-1.796) were independent factors associated with 28-day mortality. This study suggests that the time interval from sepsis to CRRT inception may be a more useful predictor of 28-day mortality than RIFLE criteria in patients with septic AKI.

Recombinant human erythropoietin (r-HuEPO) is widely used to correct anemia in end-stage renal disease patients, who commonly suffer from atherosclerosis. Endothelin-1 (ET-1) has been implicated in the pathogenesis of atherosclerosis. Here, we tested whether darbepoetin alfa, a hypersialylated analogue of r-HuEPO, regulates tumor necrosis factor-α (TNF-α)-induced ET-1 production in human aortic endothelial cells, and sought to identify the signal pathways involved. Darbepoetin alfa attenuated TNF-α-induced ET-1 production. It also diminished TNF-α-induced reactive oxygen species (ROS) accumulation and subsequent activation of c-Jun NH2-terminal kinase (JNK), which regulates the DNA-binding activities of both AP-1 and NF-κB required for ET-1 gene transcription. Like a JNK inhibitor, darbepoetin alfa did not affect IκBα degradation or p65 nuclear translocation, but did inhibit mitogen- and stress-activated protein kinase 1 (MSK1) activation and attenuated p65 phosphorylation (serine 276), effects that may account for the reduction in NF-κB DNA-binding activity. Desialylation completely abolished darbepoetin alfa's inhibitory effects on TNF-α-induced ROS accumulation, MSK1 activation, and ET-1 gene expression, without affecting its stimulation of STAT5 activity. These data demonstrate that darbepoetin alfa suppresses TNF-α-induced ET-1 production through its antioxidant action and suggest that the sialic acid residues of darbepoetin alfa are essential for its antioxidant effect, possibly by scavenging ROS.

Background Graft dysfunction after liver transplantation (OLT) is a life- threatening condition. Molecular adsorbent recirculating system (MARS) or plasmapheresis (PLP) may be effective supportive therapy of graft dysfunction for patients who cannot undergo retransplantation. The aim of this study was to compare the effects of MARS and PLP in patients with graft dysfunction after OLT. Methods Between January 2002 and July 2007, 31 OLT recipients who experienced graft dysfunction, defined as hyperbilirubinemia (>10 mg/dL) without bile duct obstruction and/or presence of hepatic encephalopathy, were treated with MARS or PLP. Biochemical and hemodynamic data and survival were compared in MARS and PLP groups. Results Fifteen patients were treated with 41 MARS sessions and 16 with 105 PLP sessions. After a single MARS session, patients showed significant reductions in creatinine, urea nitrogen, bilirubin, and ammonia. After a single PLP session, patients showed significant improvements in prothrombin time, bilirubin, alanine aminotransferase, alkaline phosphatase, and albumin. After the completion of treatment, Both MARS and PLP significantly improved bilirubin values. at 90 days there were no differences in overall survival rates; 53% in MARS versus 56% in PLP. Conclusion Both MARS and PLP are alternative supportive treatments for graft dysfunction after OLT.

Background: Fatty acid-bearing albumin [FA(+) albumin] exerts more deleterious effects in tubular cells than albumin alone. We investigated the effect of FA(+) albumin on the vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of L-carnitine, since it was known to modulate intracellular fatty acid concentration. Methods: Activation of AP-1 and NF-ĸB was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinase was examined by Western blot analysis. VCAM-1 mRNA and protein expression were measured by Northern blot analysis and cell ELISA. Results: FA(+) albumin induced VCAM-1 expression via activation of AP-1 and NF-ĸB, which was mediated through activation of c-Src kinase, followed by MAP kinases (p38, ERK 1/2, JNK-1) and IĸB kinase and IĸB-α, respectively. Inhibitors of protein kinase C and tyrosine kinase, anti-oxidants and intracellular calcium chelator suppressed the FA(+) albumin-induced activation of c-Src kinase. L-Carnitine suppressed the FA(+) albumin-induced VCAM-1 expression via inhibition of c-Src kinase. Conclusions: VCAM-1 expression with activation of c-Src kinase-AP-1/NFĸB pathways might be one of the possible mechanisms that linked FA(+) albumin to tubulointerstitial injury. L-Carnitine might be beneficial in attenuating FA(+) albumin-induced tubular injury.

Background/Aims: The ratio of extracellular water to total body water (ECW/TBW) estimated by bioimpedance spectroscopy (BIS) may be a useful volume index in haemodialysis (HD) patients, but its direct relation to cardiovascular (CV) outcomes has been rarely evaluated. Methods: We investigated the relationship between ECW/TBW by BIS and cardiac troponin T (cTnT) level, a biochemical surrogate of CV mortality. Results: Seventy-four HD patients without ischemic heart disease (age 51.6 ± 13.2 years; male:female ratio 36:38; diabetes 37.8%) were recruited. Post-HD ECW/TBW was positively correlated to log cTnT levels (r = 0.60, p < 0.01). In multivariate regression models, male sex (β = 0.23, p = 0.03), diabetes mellitus (β = 0.21, p = 0.04), log high-sensitivity C-reactive protein (β = 0.21, p = 0.04) and post-HD ECW/TBW (β = 0.37, p < 0.01) were independent risk factors for elevated log cTnT levels. Conclusion: Post-HD ECW/TBW by BIS is worthy of further evaluation as a pathophysiological index for reducing CV mortality in HD patients.

Background/Aims: The development of renal injury in glomerulonephritis (GN) has been related to systemic inflammatory mediators. We investigated whether serum high-sensitivity C-reactive protein (hs-CRP) is a marker reflecting the inflammatory pathogenesis of primary GN. Methods: We compared serum hs-CRP levels in 192 patients with IgA nephropathy (IgAN), 43 patients with membranous nephropathy (MN), and 25 patients with minimal change disease (MCD) undergoing kidney biopsy and 638 matched controls. Results: There were no differences in hs-CRP levels between controls (median 0.08 mg/dl; range 0.03–1.87 mg/dl) and patients with IgAN (0.08 mg/dl; 0.03–3.13 mg/dl), MN (0.07 mg/dl; 0.03–0.99 mg/dl) or MCD (0.08 mg/dl; 0.03–1.75 mg/dl). In patients with IgAN, hs-CRP levels did not differ according to Haas’ pathological subclasses or subsequent renal outcomes. In the IgAN group, hs-CRP showed positive correlations with IgA, uric acid, systolic blood pressure, BMI and age. Hs-CRP level was significantly higher in male than in female IgAN patients. Serum IgA concentration was the strongest independent correlate with hs-CRP levels, and gender and BMI were also independently associated with hs-CRP. There were no correlations between hs-CRP and markers of disease activity. Conclusion: It is likely that hs-CRP does not closely reflect inflammatory pathogenesis in patients with IgAN, MN and MCD.

SUMMARY: Background: Although several previous studies have reported that kidney donors are not at increased risk for adverse effects, some donors have been found to progress to chronic kidney disease (CKD). We retrospectively evaluated the risk factors for estimated glomerular filtration rate (GFR) from abbreviated Modification of Diet in Renal Disease (MDRD) equation (MDRD-GFR) of less than 60 mL/min per 1.73 m2 in kidney donors. Methods: Of the 756 individuals who underwent open donor nephrectomy between 27 June 1990 and 30 April 2001, 104 had follow-up records for 50 months or more. MDRD-GFR of 60 mL/min per 1.73 m2 at final follow up divided these individuals into a normal group (n = 78) and a CKD-GFR group (n = 26). We compared several clinical parameters between the two groups at baseline and follow up to evaluate the risk factors for MDRD-GFR of less than 60 mL/min per 1.73 m2 in kidney donors. Results: The CKD-GFR group was significantly older than the normal group at baseline (47 ± 12 vs 41 ± 11 years old, P = 0.02). Hypertension was more prevalent in the CKD-GFR group at baseline (15% vs 2%, P = 0.005). Binary logistic regression analysis showed that age (Odds ratio (OR) 1.06, 95% confidence interval (CI) 1.01–1.10) and hypertension (OR 7.91, 95% CI 1.13–55.2) at baseline were independent risk factors for MDRD-GFR of less than 60 mL/min per 1.73 m2. At final follow up, the prevalence rates of hypertension (31% vs 8%, P = 0.006) and proteinuria (15% vs 0%, P = 0.003) were significantly higher in the CKD-GFR group. Conclusion: Older kidney donors and those with hypertension were significantly more likely to have a MDRD-GFR of less than 60 mL/min per 1.73 m2.

Backgrounds: Immunological staining of the transplanted kidney for C4d in peritubular capillaries (C4dPTC) has emerged as a useful method to detect antibody-mediated rejection in situ. In this retrospective study, we evaluated the prevalence of C4dPTC deposition in allograft renal biopsies diagnosed of IgA nephropathy (IgAN) and analysed its clinical significance. Method: Sixty-six biopsy specimens of post-transplant IgAN, which were obtained to evaluate azotemia and/or heavy proteinuria, were examined by immunohistochemical staining of the paraffin sections with polyclonal antibody for C4d. Results: C4d was stained positively in peritubular capillaries in 16 (24%) of the 66 cases. The C4dPTC-negative (n=50) and C4dPTC-positive groups (n=16) were not different in recipient gender, age, donor age, type of donor (living vs. cadaveric), interval from transplantation to graft biopsy (41.6± 21.8 vs. 48.3±26.1 months) and post-biopsy follow-up period (60.3±23.3 vs. 56.9±25.4 months). During the follow-up period, 12 of 50 (24%) although the incidence of graft failure was not different by the C4d deposition in peritubular capillaries, intervals from renal biopsy to graft failure tended to be shorter in C4dPTC-positive cases than C4dPTC-negative cases. In Kaplan–Meier analysis, the renal allograft function of the C4dPTC-positive group deteriorated more rapidly than that of the C4dPTC-negative group (p

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., Graphical Abstract

A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor is recommended in hemodialysis (HD) patients with hypercholesterolemia to improve their lipid profiles. We evaluated effects of simvastatin on markers for inflammation, oxidative stress, and coagulation in HD patients. Sixty-two maintenance HD patients with serum cholesterol levels of 200 mg/dL or greater were randomly assigned to the treatment group (n = 31; 8 men, 23 women; age, 63 +/- 11 years) and administered simvastatin, 20 mg/d, for 8 weeks or to the control group (n = 31; 10 men, 21 women; age, 60 +/- 12 years). We measured cholesterol, albumin, high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA; an index of lipid peroxidation), and D-dimer (a marker of intravascular coagulation) in blood at baseline and again at 8 weeks. Fifty-eight of 62 patients completed the study. In the control group, total cholesterol, serum albumin, hs-CRP, MDA, and D-dimer levels did not change. In the treatment group, simvastatin administration for 8 weeks significantly reduced total cholesterol levels from 232 +/- 25 to 165 +/- 39 mg/dL (P < 0.001) and hs-CRP levels from a median of 0.23 mg/dL (range, 0.05 to 1.63 mg/dL) to 0.12 mg/dL (range