Efficient oxygen utilization in the kidney may be supported by paracellular epithelial transport, a form of passive diffusion that is driven by preexisting transepithelial electrochemical gradients. Claudins are tight-junction transmembrane proteins that act as paracellular ion channels in epithelial cells. In the proximal tubule (PT) of the kidney, claudin-2 mediates paracellular sodium reabsorption. Here, we used murine models to investigate the role of claudin-2 in maintaining energy efficiency in the kidney. We found that claudin-2-null mice conserve sodium to the same extent as WT mice, even during profound dietary sodium depletion, as a result of the upregulation of transcellular Na-K-2Cl transport activity in the thick ascending limb of Henle. We hypothesized that shifting sodium transport to transcellular pathways would lead to increased whole-kidney oxygen consumption. Indeed, compared with control animals, oxygen consumption in the kidneys of claudin-2-null mice was markedly increased, resulting in medullary hypoxia. Furthermore, tubular injury in kidneys subjected to bilateral renal ischemia-reperfusion injury was more severe in the absence of claudin-2. Our results indicate that paracellular transport in the PT is required for efficient utilization of oxygen in the service of sodium transport. We speculate that paracellular permeability may have evolved as a general strategy in epithelial tissues to maximize energy efficiency.
♦ Objective: About half the patients on peritoneal dialysis (PD) in China need to be assisted by family members or home assistants. We explored whether these patients have a higher risk for peritonitis and death compared with self-care PD patients. ♦ Methods: We prospectively followed 313 incident PD patients until death or censoring. This cohort was divided into assisted and self-care PD groups according to the independence of bag exchange. Data on baseline demographics, Charlson comorbidity index, biochemistry, and residual renal function were recorded during the first 3 -6 months. The outcome variables were first episode of peritonitis and all-cause mortality. ♦ Results: Of the 313 patients in this cohort study, 122 needed assistance in performing bag exchanges (86 from a family member, 36 from a home assistant); the remaining 191 patients did not need assistance. During a follow-up period averaging 44.5 months, 122 patients developed a first episode of peritonitis, and 135 patients died. Compared with patients having a family assistant, those with a home assistant had similar peritonitis-free and survival times, but a higher risk of mortality after adjustments for variables such as age, sex, Charlson comorbidity score, hemoglobin, serum albumin, and residual renal function. Furthermore, compared with self-care patients, assisted patients overall had a similar peritonitis-free time, but a higher risk of mortality, even after adjusting for covariates. ♦ Conclusions: Based on our single-center experience in China, we conclude that assisted PD is a good option for patients with poor self-care ability. This result provides evidence for recruiting patients who need assistance to PD programs in China. Although peritoneal dialysis (PD) has many advantages, such as ease of training and accommodation, simple facilities, and good mobility, the procedure is difficult for patients who are physically disabled or noncompliant. Many studies have demonstrated that self-care difficulties contribute to the underutilization of PD as a kidney replacement therapy (1-3). Accordingly, assisted PD provides a good alternative in Europe. Lobbedez et al. (4) found that, compared with self-care patients, patients with nurse assistance had a higher peritonitis rate and a lower technique survival rate. Povlsen et al. (5) reported a higher risk of peritonitis and mortality in assisted patients than in autonomous patients, all of whom were elderly (>65 years) and receiving automated PD.The reasons that may potentially lead to unfavorable outcomes in assisted PD include inconsistent home care and inadequate training and education for assistants (6). However, in the past few years in our PD patient pool, patients and their home care providers have both been trained at dialysis initiation to be familiar with the procedures of bag exchange, volume control, and blood pressure and glucose monitoring. The major sources of home care providers are stable and provide good training.We conducted the present study to examine the risk factors for perito...
Background The Veterans Affairs Frailty Index (VA-FI) is an electronic frailty index developed to measure frailty using administrative claims and electronic health records data in Veterans. An update to ICD-10 coding is needed to enable contemporary measurement of frailty. Methods ICD-9 codes from the original VA-FI were mapped to ICD-10 first using the Centers for Medicaid and Medicare Services (CMS) General Equivalence Mappings. The resulting ICD-10 codes were reviewed by two geriatricians. Using nationals cohort of Veterans ≥65 years old, the prevalence of deficits contributing to the VA-FI and associations between the VA-FI and mortality over years 2012-2018 were examined. Results The updated VA-FI-10 includes 6422 codes representing 31 health deficits. Annual cohorts defined on October 1 of each year included 2 266 191 to 2 428 115 Veterans, for which the mean age was 76 years, 97-98% were male, 78-79% were white, and the mean VA-FI was 0.20-0.22. The VA-FI-10 deficits showed stability before and after the transition to ICD-10 in 2015, and maintained strong associations with mortality. Patients classified as frail (VA-FI ≥0.2) consistently had a hazard of death more than two-times higher than non-frail patients (VA-FI <0.1). Distributions of frailty and associations with mortality varied with and without linkage to CMS data and with different assessment periods for capturing deficits. Conclusions The updated VA-FI-10 maintains content validity, stability, and predictive validity for mortality in a contemporary cohort of Veterans ≥65 years old, and may be applied to ICD-9 and ICD-10 claims data to measure frailty.
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