Slc26a11, a chloride transporter, localizes with the vacuolar H(+)-ATPase of A-intercalated cells of the kidney

Chloride has an important role in regulating vacuolar H(+)-ATPase activity across specialized cellular and intracellular membranes. In the kidney, vacuolar H(+)-ATPase is expressed on the apical membrane of acid-secreting A-type intercalated cells in the collecting duct where it has an essential role in acid secretion and systemic acid base homeostasis. Here, we report the identification of a chloride transporter, which co-localizes with and regulates the activity of plasma membrane H(+)-ATPase in the kidney collecting duct. Immunoblotting and immunofluorescent labeling identified Slc26a11 (～72?kDa), expressed in a subset of cells in the collecting duct. On the basis of double-immunofluorescent labeling with AQP2 and identical co-localization with H(+)-ATPase, cells expressing Slc26a11 were deemed to be distinct from principal cells and were found to be intercalated cells. Functional studies in transiently transfected COS7 cells indicated that Slc26a11 (designated as kidney brain anion transporter (KBAT)) can transport chloride and increase the rate of acid extrusion by means of H(+)-ATPase. Thus, Slc26a11 is a partner of vacuolar H(+)-ATPase facilitating acid secretion in the collecting duct.     

Higher recipient body mass index is associated with post-transplant delayed kidney graft function

To examine whether a higher body mass index (BMI) in kidney recipients is associated with delayed graft function (DGF), we analyzed data from 11,836 hemodialysis patients in the Scientific Registry of Transplant Recipients who underwent kidney transplantation. The patient cohort included women, blacks, and diabetics; the average age was 49 years; and the mean BMI was 26.8 kg/m(2). After adjusting for relevant covariates, multivariate logistic regression analyses found that one standard deviation increase in pretransplant BMI was associated with a higher risk of DGF (odds ratio (OR) 1.35). Compared with patients with a pretransplant BMI of 22-24.99 kg/m(2), overweight patients (BMI 25-29.99 kg/m(2)), mild obesity patients (BMI 30-34.99 kg/m(2)), and moderate-to-severe obesity patients (BMI 35 kg/m(2) and over) had a significantly higher risk of DGF, with ORs of 1.30, 1.42, and 2.18, respectively. Similar associations were found in all subgroups of patients. Hence, pretransplant overweight or obesity is associated with an incrementally higher risk of DGF.     

Should we limit the ferritin upper threshold to 500 ng/ml in CKD patients?

The new National Kidney Foundation's Kidney Disease Outcome Quality Initiative clinical practice guidelines for anemia management in chronic kidney disease include several important modifications to the previous recommendations. These changes may have major implications in clinical practice and outcome of the chronic kidney disease patient population. Among the important guideline modifications are the elimination of the upper thresholds for hemoglobin (12 g/dL), transferrin saturation ratio (TSAT, v 50%) and ferritin (800 ng/ml). There are, however, additional recommendations pertaining to anemia management when hemoglobin is above 13 g/dL or serum ferritin above 500 ng/ml. The KDOQI anemia working group explains that the upper ferritin level of 500 ng/ml is not a stopping point for IV iron administration, but adds that decisions regarding IV iron administration should weigh erythropoietin responsiveness, hemoglobin and transferrin saturation level, and the patient's clinical status.The selected upper ferritin level of 500 ng/ml lacks adequate scientific evidence in the CKD population. Approximately half of all maintenance hemodialysis patients in the United States may have a serum ferritin above 500 ng/ml. Serum ferritin in 500-1,200 ng/ml range is not associated with increased death risk in hemodialysis patients if controlled for the confounding effect of malnutrition and inflammation. Given the lack of support from the literature, any attempt to contemplate an upper limit for serum ferritin would be arbitrary, and would not serve to improve the quality of treatment in the CKD population.     

Hepatitis C inflection in dialysis patients: a link to poor clinical outcome?

Among the 350,000 maintenance dialysis patients in the USA, the mortality rate is high (20–23% per year) as is the prevalence of hepatitis C virus (HCV) infection (5–15%). An additional same number of dialysis patients in the USA may be infected with HCV but have undetectable HCV antibodies. Almost half of all deaths in dialysis patients, including HCV-infected patients, are due to cardiovascular disease. Since over two-thirds of dialysis patients die within 5 years of initiating dialysis and because markers of malnutrition–inflammation complex syndrome (MICS), rather than traditional cardiovascular risk factors, are among the strongest predictors of early death in these patients, the impact of HCV infection on nutritional status and inflammation may be a main cause of poor survival in this population. Based on data from our cross-sectional and limited longitudinal studies, we hypothesize that HCV infection confounds the association between MICS and clinical outcomes in dialysis patients and, by doing so, leads to higher short-term cardiovascular events and death. Understanding the natural history of HCV and its association with inflammation, nutrition and outcomes in dialysis patients may lead to testing more effective anti-HCV management strategies in this and other similar patient populations, providing benefits not only for HCV infection but the detrimental consequences associated with this infection. In this article, we review the link between the HCV infection and mortality in dialysis patients and compare HCV antibody to molecular methods to detect HCV infection in these individuals. Funding source: Supported by a Young Investigator Award from the National Kidney Foundation; the National Institute of Diabetes, Digestive and Kidney Disease grant # DK61162; and a research grant from DaVita (for KKZ); and the National Institute of Allergy and Infectious Diseases grant # AI01831 (for LGM and HD41224 (for ESD)).     

Outcomes Associated with Race in Males with Nondialysis-Dependent Chronic Kidney Disease

Background and objectives: Blacks are over-represented among dialysis patients, but they have better survival rates than whites. It is unclear if the over-representation of blacks on dialysis is due to faster loss of kidney function or greater survival (or both) in predialysis stages of chronic kidney disease (CKD).Design, setting, participants & measurements: We compared predialysis mortality, incidence of end stage renal disease (ESRD), and slopes of estimated GFR (eGFR) in 298 black versus 945 white male patients with moderate and advanced nondialysis-dependent CKD (NDD-CKD) from a single medical center. Mortality and ESRD incidence were compared in parametric survival models, and slopes of eGFR were assessed in mixed-effects models.Results: Blacks had lower crude mortality and higher crude ESRD incidence. The lower mortality in blacks was explained by differences in case mix, especially a lower prevalence of cardiovascular disease, and the higher incidence of ESRD was explained by differences in case mix and baseline kidney function. The slopes of eGFR were similar in blacks and whites.Conclusions: Lower mortality in black versus white patients is also observed in NDD-CKD and can be accounted for by differences in clinical characteristics. Higher mortality of black patients in earlier stages of CKD may result in the selection of a subgroup with fewer comorbidities and better survival in later stages of CKD. The higher crude ESRD rate in blacks appears to result from lower mortality in late stages of CKD, not faster progression of CKD.Among individuals with chronic kidney disease (CKD) receiving maintenance dialysis therapy, the proportion of black patients is significantly higher compared with their white counterparts (1,2). This can be explained by various factors (1): higher incidence of CKD in blacks (2), lower mortality rates in blacks with nondialysis-dependent CKD (NDD-CKD) (3), lower transplantation rates in blacks (4), and faster rates of CKD progression leading to higher end-stage renal disease (ESRD) incidence.Previous studies have suggested that there was a higher population prevalence of CKD (3) or a faster rate of CKD progression in blacks (4). It is unclear, however, if differences in survival between black and white persons with moderate and advanced NDD-CKD can also have an impact on the higher ESRD incidence recorded in blacks. Because mortality and ESRD are competing end-points in NDD-CKD, lower mortality rates in blacks could inflate their ESRD rates independent of any differences in the prevalence or the progression of their kidney disease. Studies examining race-related survival have found paradoxically lower mortality in blacks compared with whites among dialysis patients (5–12), as opposed to the higher mortality seen in blacks with normal kidney function or mild to moderate CKD (13–17).There have been no studies to examine race-related survival and progression of CKD concomitantly in patients with moderate and advanced NDD-CKD. Such studies could provide important information to guide future allocation of resources into areas that promise to best address the reasons behind the discrepant outcomes of racial minorities in the United States. To discern the relative contributions of differences in mortality and CKD progression to race-related outcomes, we examined all-cause mortality, ESRD incidence, and progression of CKD (defined as slopes of estimated GFR [eGFR]) concomitantly in an unselected group of 1243 male veterans with moderate and advanced NDD-CKD from a single medical center.     

Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury

OBJECTIVE: Traumatic brain injury is one of the major causes of death and disability among young people. Methylphenidate, a neural stimulant and protective drug, which has been mainly used for childhood attention deficit/hyperactivity disorder, has shown some benefits in late psychosocial problems in patients with traumatic brain injury. Its effect on arousal and consciousness has been also revealed in the sub-acute phase of traumatic brain injury. We studied its effect on the acute phase of moderate and severe traumatic brain injury (TBI) in relation to the length of ICU and hospital admission. PATIENTS AND METHODS: Severely and moderately TBI patients (according to inclusion and exclusion criteria) were randomized to treatment and control groups. The treatment group received methylphenidate 0.3mg/kg per dose PO BID by the second day of admission until the time of discharge, and the control group received a placebo. Admission information and daily Glasgow Coma Scale (GCS) were recorded. Medical, surgical, and discharge plans for patients were determined by the attending physician, blinded to the study. RESULTS: Forty patients with severe TBI (GCS = 5-8) and 40 moderately TBI patients (GCS = 9-12) were randomly divided into treatment and control groups on the day of admission. In the severely TBI patients, both hospital and ICU length of stay, on average, were shorter in the treatment group compared with the control group. In the moderately TBI patients while ICU stay was shorter in the treatment group, there was no significant reduction of the period of hospitalization. CONCLUSION: There were no significant differences between the treatment and control groups in terms of age, sex, post resuscitation GCS, or brain CT scan findings, in either severely or moderately TBI patients. Methylphenidate was associated with reductions in ICU and hospital length of stay by 23% in severely TBI patients (P = 0.06 for ICU and P = 0.029 for hospital stay time). However, in the moderately TBI patients who received methylphenidate, there was 26% fall (P = 0.05) only in ICU length of stay.