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Background: Older patients with advanced chronic kidney disease (CKD) face the decision of whether to undergo dialysis. Currently available data on this issue are limited because they were generated by small, short-term studies with statistical drawbacks. Further research is urgently needed to provide objective information for dialysis decision making in older patients with advanced CKD. Methods: This nationwide population-based cohort study was conducted using Taiwanfs National Health Insurance Research Database. Data from 2000 to 2010 were extracted. A total of 8,341 patients ≥70 years old with advanced CKD and serum creatinine levels >6 mg/dl, who had been treated with erythropoiesis-stimulating agents were included. Cox proportional hazard models in which initiation of chronic dialysis was defined as the time-dependent covariate were used to calculate adjusted hazard ratios for mortality. The endpoint was all-cause mortality. Results: During a median follow-up period of 2.7 years, 6,292 (75.4%) older patients chose dialysis therapy and 2,049 (24.6%) received conservative care. Dialysis was initiated to treat kidney failure a median of 6.4 months after enrollment. Dialysis was associated with a 1.4-fold increased risk of mortality compared with conservative care (adjusted hazard ratio 1.39, 95% confidence interval 1.30 to 1.49). In subgroup analyses, the risk of mortality remained consistently increased, independent of age, sex and comorbidities. Conclusions: In older patients, dialysis may be associated with increased mortality risk and healthcare cost compared with conservative care. For patients who are ≥70 years old with advanced CKD, decision making about whether to undergo dialysis should be weighted by consideration of risks and benefits. [ABSTRACT FROM AUTHOR]

Background: The association between intravenous (IV) iron administration and outcomes in hemodialysis (HD) patients is still debated. Therefore, this study was aimed to assess the relationship between the IV administration of ferric chloride hexahydrate (Atofen®) and cardiovascular (CV) outcome and the interaction between iron-induced oxidative stress and endothelial dysfunction in chronic HD patients. Methodology/Principal Findings: A cohort of 1239 chronic HD patients was recruited. In a follow-up of 12 months, Kaplan- Meier survival curves showed that higher doses of IV Atofen associated with higher risks for CV events and deaths in HD patients. In multivariate Cox models, compared to no iron supplementation, IV Atofen administration was an independent predictor for CV events and overall mortality. However, the nature of the observational cohort study possibly bears selection bias. We further found that IV Atofen enhanced the superoxide production of mononuclear cells (MNCs), the levels of circulating soluble adhesion molecules, and the adhesion of MNCs to human aortic endothelial cells (HAECs). In vitro experiments showed that Atofen increased the expression of intracellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 in HAECs and aggravated the endothelial adhesiveness in a dose-dependent manner. These ironinduced changes were significantly attenuated by the co-treatment of HAECs with N-acetylcysteine and inhibitors of NADPH oxidase, nuclear factor κB, and activator protein-1. Conclusion: A cumulative dose of IV Atofen >800 mg within 6 months was associated with an adverse CV outcome and a higher mortality among chronic HD patients. The detrimental effects of IV iron supplementation were partly due to the increased oxidative stress and induction of MNC adhesion to endothelial cells, a pivotal index of early atherogenesis. [ABSTRACT FROM AUTHOR]

Background: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients. Methods: We retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months. Results: The baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group (-2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis. Conclusion: Add-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) have been employed as immunosuppressive agents for many years. However, it is still unclear how GCs instantly uncouple T cells from acute stressful inflammatory. In terms of time scale, the genomic activity of the classic GC receptor cannot fulfill this role under crisis; but a rapid non-genomic response can. In a previous study, intracellular acidification was found to be due to a rapid non-genomic inhibition of Na+/H+-exchange 1 (NHE1) and this event led to the immunosuppression of T cell proliferation by progesterone. The aim of this study was to examine whether there is a rapid acidification response caused by an inhibition of NHE1 activity and to explore the differential non-genomic effect on immunosuppression of hydrocortisone and dexamethasone. The IC50 values for NHE1-dependent pHi recovery by hydrocortisone and dexamethasone are 250 and 1 nM, respectively. Co-stimulation of GCs with phytohemagglutinin (PHA) is able to inhibit PHA-induced IL-2 secretion, IL-4 secretion, and T-cell proliferation. Furthermore, apoptosis in PHA-activated T cells is not induced by hydrocortisone but by dexamethasone. The mechanism of immunosuppression on proliferation by dexamethasone was found to be different of hydrocortisone and seems to involve cytotoxicity against T cells. Moreover, apoptosis induced by dexamethasone and impermeable dexamethasone–bovine serum albumin suggests that the apoptotic immunosuppression occurs through both the plasma membrane and cytoplasmic sites. The rapid inhibitory responses triggered by GCs would seem to release T cells instantly when an acute stress-related response is needed. Nonetheless, the apoptotic immunosuppression by dexamethasone is attributable to its severe cytotoxicity. J. Cell. Physiol. 223:679–686, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Protective effect of vitamin C on 8-hydroxy-2′-deoxyguanosine level in peripheral blood lymphocytes of chronic hemodialysis patients. Background. This study focused on the effect of vitamin C on the 8-hydroxy-2′-deoxyguanosine (8-OHdG) level of cellular DNA, as well as 8-oxoguanine-DNA glycosylase 1 ( hOGG1) and human MutT homologue ( hMTH1) gene expression in peripheral blood lymphocytes of chronic hemodialysis patients. Methods. Sixty chronic hemodialysis patients (35 men and 25 women) were recruited to participate in a randomized, placebo-controlled study. Treatment order is block-randomized with intravenous sodium ascorbate (vitamin C, 300 mg) or placebo (0.9% saline), administered postdialysis three times a week. We evaluated 8-OHdG level, intracellular reactive oxygen species (ROS) production, and gene expression of hOGG1 and hMTH1 in peripheral blood lymphocytes byusing high-performance liquid chromatography (HPLC) electrochemical detection method, flow cytometric analysis, andreverse transcription-polymerase chain reaction (RT-PCR),respectively. Results. A total of 51 patients completed the study (26 in placebo group and 25 in vitamin C group). Mean 8-OHdG levels significantly decreased in total subjects following 8 weeks of vitamin C supplementation (22.9 vs. 18.8/106 dG, P < 0.01). The decrease in 8-OHdG levels after vitamin C supplementation was also noted in the patients with ferritin <500 or ≥500 μg/Land transferrin saturation (TSAT) <50 or ≥50% ( P < 0.05). But 8-OHdG levels had no significant changes in total patients or in the four subgroups of patients treated with placebo as compared to their baselines. Intracellular ROS production by lymphocytes from the four subgroups of patients, either spontaneous ( P < 0.05) or phorbol-12-myristate-13-acetate (PMA)-stimulated ( P < 0.001), was significantly reduced after 8 weeks vitamin C supplementation. Steady-state hOGG1 mRNA levels were significantly up-regulated at 24 hours after vitamin C administration ( P < 0.05), but hMTH1 mRNA levels were not. The changes in the spontaneous and PMA-stimulated ROS production, and an up-regulation of hOGG1 mRNA expression were not observed in patients treated with placebo as compared to their baselines. Conclusion. Vitamin C supplementation in chronic hemodialysis patients can reduce the lymphocyte 8-OHdG levels and intracellular ROS production, as well as up-regulate hOGG1 gene expression for repair. There is no compelling evidence for an in vivo pro-oxidant effect of vitamin C on lymphocyte DNA base oxidation, even in the status of increased iron stores. [ABSTRACT FROM AUTHOR]

Two cases of lipoprotein glomerulopathy with a new apolipoprotein E (Apo E) genotype, ε3/ε4, were diagnosed recently. These 2 cases, together with other cases documented in English literature made a total of 6 common isoforms of Apo E encountered in lipoprotein glomerulopathy. Although the calculated allele frequency of ε2 is relative high in cases with lipoprotein glomerulopathy as compared with that in the general population (39.3 vs. 6.4–11.4%), the gradual emergence of Apo E isoforms other than E2/E3 in lipoprotein glomerulopathy implicates that the genetic susceptibility of certain Apo E isoforms may not be a crucial factor. An alteration in the local environment of glomerular capillaries may be more important in the pathogenesis of lipoprotein glomerulopathy. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 87-year-old female patient with gallstones, type 2 diabetes mellitus, and end-stage kidney disease. She had severe hemorrhage in the gallbladder after a percutaneous transhepatic gallbladder drainage (PTGBD) tube placed for her relapsing cholecystitis had a traumatic pulling-out episode. The uremic bleeding was managed via tranexamic acid (TXA) which was retained through the PTGBD tube, after which the bile became completely clear.

The article discusses the case of a 73-year-old man who developed giant pyohydronephrosis. It notes that the patient had been receiving regular haemodialysis via arteriovenous fistula. No evidence of vegetation was seen in echocardiography. Meanwhile, a giant left hydronephoris and hydroureter were revealed in the computed tomography of the abdomen. It cites the major causes of giant hydronephrosis including congenital ureteral narrowing and ureteropelvic tumours.

Serum ferritin level, the most commonly used marker for determining iron status in patients with chronic kidney disease, is influenced by factors such as inflammation and malnutrition. Moreover, there seems to be considerable biological variability and analytical variation between different serum ferritin assays. This Practice Point commentary discusses a recent paper by Ford et al. that examined the interassay differences and short-term intraindividual variability of serum ferritin measurements in patients on chronic hemodialysis. A comparison of six commonly used serum ferritin immunoassays revealed intermethod variation of up to 337 pmol/l among hemodialysis and nonhemodialysis patients. The intraindividual coefficients of variation for serum ferritin level in 60 stable hemodialysis patients ranged from 2% to 62% over an initial 2-week period and from 3% to 52% over a 6-week period. This commentary discusses Ford et al.'s paper and supports the conclusion that nephrologists should not use a single serum ferritin value to guide intravenous iron treatment in patients on chronic hemodialysis. [ABSTRACT FROM AUTHOR]

Presents a reply to a letter, previously published, that focused on analgesic use in hemodialysis patients.

* Context.--Galectin-9 reduces tissue damage in certain immune-mediated glomerular diseases. However, its role in structural and functional renal changes in patients with varying types of chronic kidney disease (CKD) is less clear. Objective.--To investigate the association between plasma galectin-9 levels, proteinuria, tubulointerstitial lesions, and renal function in different CKD stages. Design.--We measured plasma galectin-9 levels in 243 patients undergoing renal biopsy for determining the CKD etiology. mRNA and protein expression levels of intrarenal galectin-9 were assessed by quantitative real-time polymerase chain reaction and immunostaining. Relationships between plasma galectin-9, clinical characteristics, and tubulointerstitial damage were analyzed with logistic regression. We investigated galectin-9 expression patterns in vitro in murine J774 macrophages treated with differing stimuli. Results.--To analyze the relationship between galectin-9 and clinical features, we divided the patients into 2 groups according to median plasma galectin-9 levels. The high galectin-9 group tended to be older and to have decreased renal function, higher proteinuria, and greater interstitial fibrosis. After multivariable adjustment, elevated plasma galectin-9 levels were independently associated with stage 3b or higher CKD. An analysis of gene expression in the tubulointerstitial compartment in the biopsy samples showed a significant positive correlation between intrarenal galectin-9 mRNA expression and plasma galectin-9 levels. Immunohistochemistry confirmed increased galectin-9 expression in the renal interstitium of patients with advanced CKD, and most galectin-9--positive cells were macrophages, as determined by double-immunofluorescence staining. In vitro experiments showed that galectin-9 expression in macrophages was significantly increased after interferon-c stimulation. Conclusions.--Our findings suggest that plasma galectin- 9 is a good biomarker for diagnosing advanced CKD. [ABSTRACT FROM AUTHOR]

Presents a medical case of a woman complaining a progressive worsening abdominal pain. Development of nausea in association with menses; Rate of blood pressure and pulse beats during admission; Treatment given by hospital staff; Conduction of laboratory tests; Includes answer to the October case of the month.

Acute kidney injury (AKI)-related fibrosis is emerging as a major driver of chronic kidney disease (CKD) development. Aberrant kidney recovery after AKI is multifactorial and still poorly understood. The accumulation of indoxyl sulfate (IS), a protein-bound uremic toxin, has been identified as a detrimental factor of renal fibrosis. However, the mechanisms underlying IS-related aberrant kidney recovery after AKI is still unknown. The present study aims to elucidate the effects of IS on tubular damage and its involvement in the pathogenesis of AKI-to-CKD transition. Our results showed that serum IS started to accumulate associated with the downregulation of tubular organic anion transporter but not observed in the small-molecule uremic toxins of the unilateral ischemia-reperfusion injury (UIRI) without a contralateral nephrectomy model. Serum IS is positively correlated with renal fibrosis and binding immunoglobulin protein (BiP) and CAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression induction in the UIRI with a contralateral nephrectomy model (UIRI+Nx). To evaluate the effects of IS in the AKI-to-CKD transition, we administered indole, a precursor of IS, at the early stage of UIRI. Our results demonstrated IS potentiates renal fibrosis, senescence-associated secretory phenotype (SASP), and activation of endoplasmic reticulum (ER) stress, which is attenuated by synergistic AST-120 administration. Furthermore, we clearly demonstrated that IS exposure potentiated hypoxia-reperfusion (H/R) induced G2/M cell cycle arrest, epithelial-mesenchymal transition (EMT) and aggravated ER stress induction in vitro. Finally, the ER chemical chaperon, 4-phenylbutyric acid (4-PBA), successfully reversed the above-mentioned AKI-to-CKD transition. Taken together, early IS elimination in the early stage of AKI is likely to be a useful strategy in the prevention and/or treatment of the AKI-to-CKD transition. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented commenting on the relation between u-shaped mortality curve and platelet count among older people.

Long-term exposure to bioincompatible peritoneal dialysis (PD) solutions frequently results in peritoneal fibrosis and ultrafiltration failure, which limits the life-long use of and leads to the cessation of PD therapy. Therefore, it is important to elucidate the pathogenesis of peritoneal fibrosis in order to design therapeutic strategies to prevent its occurrence. Peritoneal fibrosis is associated with a chronic inflammatory status as well as an elevated oxidative stress (OS) status. Beyond uremia per se , OS also results from chronic exposure to high glucose load, glucose degradation products, advanced glycation end products, and hypertonic stress. Therapy targeting the cannabinoid (CB) signaling pathway has been reported in several chronic inflammatory diseases with elevated OS. We recently reported that the intra-peritoneal administration of CB receptor ligands, including CB 1 receptor antagonists and CB 2 receptor agonists, ameliorated dialysis-related peritoneal fibrosis. As targeting the CB signaling pathway has been reported to be beneficial in attenuating the processes of several chronic inflammatory diseases, we reviewed the interaction among the cannabinoid system, inflammation, and OS, through which clinicians ultimately aim to prolong the peritoneal survival of PD patients., Competing Interests: Conflict-of-interest statement: None.