Background and objectives: Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time.Design and setting: A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument.Results: Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role-physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 ؎ 10.2; female: 37.7 ؎ 10.8; P < 0.0001; diabetic: 37.3 ؎ 10.6; nondiabetic: 41.6 ؎ 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 ؎ 9.7; no: 40.3 ؎ 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 ؎ 10.0; no: 40.2 ؎ 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities.Conclusions: These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention.

The hemodialysis (HD) procedure has been implicated as a potential catabolic factor predisposing the chronic HD (CHD) patients to protein calorie malnutrition. To assess the potential effects of HD on protein and energy metabolism, we studied 11 CHD patients 2 h before, during, and 2 h after HD by use of primed constant infusion of L-[1-13C]leucine and L-[ring-2H5]phenylalanine. Our results showed that HD led to increased whole body (10%) and muscle protein (133%) proteolysis. Simultaneously, whole body protein synthesis did not change, and forearm synthesis increased (120%). The net result was increased net whole body protein loss (96%) and net forearm protein loss (164%). During the 2-h post-HD period, the muscle protein breakdown trended toward baseline, whereas whole body protein breakdown increased further. Substrate oxidation during the post-HD was significantly altered, with diminished carbohydrate and accelerated lipid and amino acid oxidation. These data demonstrate that hemodialysis is an overall catabolic event, decreasing the circulating amino acids, accelerating rates of whole body and muscle proteolysis, stimulating muscle release of amino acids, and elevating net whole body and muscle protein loss.

Distal renal tubular acidosis (dRTA) is characterized by defective urinary acidification by the distal nephron. Cl ؊ /HCO 3؊ exchange mediated by the AE1 anion exchanger in the basolateral membrane of type A intercalated cells is thought to be an essential component of lumenal H ؉ secretion by collecting duct intercalated cells. We evaluated the AE1 gene as a possible candidate gene for familial dRTA. We found in three unrelated families with autosomal dominant dRTA that all clinically affected individuals were heterozygous for a single missense mutation encoding the mutant AE1 polypeptide R589H. Patient red cells showed ϳ20% reduction in sulfate influx of normal 4,4-diisothiocyanostilbene-2,2-disulfonic acid sensitivity and pH dependence. Recombinant kidney AE1 R589H expressed in Xenopus oocytes showed 20 -50% reduction in Cl ؊ /Cl ؊ and Cl ؊ /HCO 3 ؊ exchange, but did not display a dominant negative phenotype for anion transport when coexpressed with wildtype AE1. One apparently unaffected individual for whom acid-loading data were unavailable also was heterozygous for the mutation. Thus, in contrast to previously described heterozygous loss-of-function mutations in AE1 associated with red cell abnormalities and apparently normal renal acidification, the heterozygous hypomorphic AE1 mutation R589H is associated with dominant dRTA and normal red cells.

IntroductionThe mortality and morbidity rate in end-stage renal disease (ESRD) patients in the United States is unacceptably high (1). Among several factors that have been identified as predictors of this poor outcome, lean-body wasting and protein calorie malnutrition (PCM) are important ones because they are potentially reversible (2).Factors that predispose ESRD patients on chronic hemodialysis (CHD) therapy to PCM are multiple and include several nondialysis and dialysis-related factors (3-5). Among these factors, decreased dietary protein and calorie intake and the hemodialysis-associated catabolism are important contributors. Several studies have highlighted the inadequate level of dietary intake in CHD patients (6-8). Furthermore, the hemodialysis (HD) procedure is associated with loss of substantial amounts of amino acids (AA) in the dialysate and decreased plasma AA concentrations, accelerated rates of whole-body and skeletal muscle proteolysis, and increased energy expenditure, resulting in net negative intradialytic protein and energy balance (9, 10). These metabolic derangements also impact protein and energy balance after the HD procedure is finished (9). The combination of these factors may be an important cause of muscle wasting and PCM observed in CHD patients.Several approaches have been proposed as potential therapeutic interventions for the treatment of malnourished CHD patients. A number of reports have emphasized the effectiveness of intradialytic parenteral nutrition (IDPN) (11-13). In particular, IDPN is a convenient and safe therapeutic intervention that provides nutrition during the HD procedure. However, not all studies have shown clear-cut benefits for IDPN, and Decreased dietary protein intake and hemodialysis-associated protein catabolism are among several factors that predispose chronic hemodialysis (CHD) patients to protein calorie malnutrition. Since attempts to increase protein intake by dietary counseling are usually ineffective, intradialytic parenteral nutrition (IDPN) has been proposed as a potential therapeutic approach in malnourished CHD patients. In this study, we examined protein and energy homeostasis during hemodialysis in seven CHD patients at two separate hemodialysis sessions, with and without IDPN administration. Patients were studied 2 hours before, during, and 2 hours following a hemodialysis session, using a primed constant infusion of L-(1-13 C) leucine and L-(ring-2 H 5 ) phenylalanine. Our results showed that IPDN promoted a large increase in whole-body protein synthesis and a significant decrease in whole-body proteolysis, along with a significant increase in forearm muscle protein synthesis. The net result was a change from an essentially catabolic state to a highly positive protein balance, both in whole-body and forearm muscle compartments. We conclude that the provision of calories and amino acids during hemodialysis with IDPN acutely reverses the net negative whole-body and forearm muscle protein balances, demonstrating a need for long-term clinical tri...

Most CKD patients are considered by their medical care providers to be suitable for PD. Enhanced patient education, promotion of home dialysis for suitable patients and empowerment of patient choice are expected to augment growth of home dialysis modalities.