Malnutrition in patients with chronic renal failure

Sammanfattning: Protein-energy malnutrition is common in patients with chronic renal failure (CRF) and may contribute to a poor clinical outcome. However, the role of nutrition in this regard has not been clearly defined. Malnutrition in patients with CRF may have many causes, including disturbances in protein and energy metabolism, hormonal derangements, as well as low food intake because of anorexia, caused by uremic toxicity, various superimposed illnesses and psychosocial problems. Although some of the catabolic effects of chronic uremia may diminish or disappear after start of maintenance dialysis therapy, others may still persist. In this thesis, subjective global nutritional assessment (SGNA), anthropometric measurements, plasma proteins including acute-phase proteins and the plasma amino acid (AA) profile were used as tools to identify the malnutrition among CRF patients. In study I, 115 predialysis CRF patients were investigated with SGNA, anthropometric measurements and hand- grip strength (HGS). Body composition including lean body mass was evaluated by dual energy X-ray absorptiometry and lean body mass was also estimated using anthropometrics and creatinine kinetics. The predialysis patients had a high prevalence of malnutrition (51%). HGS was found to be a reliable, cheap and easy performed nutritional parameter in patients with CRF. In contrast, serum albumin (s-Alb) seems to be a poor nutritional marker in these patients. In study II, the relationships between the dialysis dose, nutritional status and plasma free AA pattern were investigated in 128 hemodialysis (HD) patients. Clinical factors associated with malnutrition (prevalence, 65%) were high age, cardiovascular disease (CVD) and diabetes mellitus. Malnutrition was associated with low s-Alb and creatinine and low insulin-like growth factor-1 and branched-chain amino acids. The s-Alb level was independently influenced by age, sex and s-CRP. Elevated s-CRP, which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished and elderly patients. Plasma AA were poor predictors of nutritional status in the HD patients. In study III, 36 continuous peritoneal dialysis (CPD) patients were investigated by SGNA, anthropometrics, HGS, s-Alb, s-CRP and plasma AA. Malnutrition (prevalence, 69%) as assessed by SGNA was associated with high age, low protein intake, low dialysis dose, low HGS, acidosis, low s-Alb, and high s-CRP and haptoglobin levels; but not fasting plasma AA. The association between s-CRP and protein intake suggests that inflammation may contribute to a low protein intake. Malnutrition was associated with markedly increased mortality in the CPD patients. In study IV, 12 CPD and 10 renal transplant (Rtx) patients were investigated as regards tryptophan (Trp) metabolism. Tip is an essential AA for protein synthesis and deficiency of this AA may contribute to protein malnutrition. The CPD patients had low plasma free and total Tip but high muscle Trp; this may reflect a shift from the extra- to the intracellular space rather than a depletion of Tip. The Rtx patients had normal Tip metabolism with normal s-Alb and HGS. The CPD patients also had decreased ratio of muscle alkali-soluble protein relative to DNA, and low s-Alb, suggesting presence of malnutrition. In study V, in 30 renal transplant (Rtx) patients, the evaluation of muscle water, electrolyte and protein (ASP/DNA) composition and the free AA patterns in plasma and muscle, showed essentially normal values in the stable patients, indicating that metabolic and nutritional abnormalities typical for the uremic condition, persisting for sometime after Rtx, later vanish despite the continuous immunosuppressive therapy. In study VI, the 128 HD patients in study II were followed, and the effects of various nutritional factors on mortality was analysed. After 36 months, more female patients (60%) than male (34%) died. The main cause of death was cardiovascular disease (58%), followed by infection (18%) while malnutrition/cachexia (5%) was a less common cause. Sixteen (70%) of the 23 diabetic patients died. Cox analysis showed that age, gender, SGNA and CVD were independent predictors of 36 months mortality. s-CRP was a highly significant independent predictor but not s-Alb. In addition to malnutrition and co-morbidities (CVD, diabetes mellitus), inflammation (elevated s-CRP) was a significant independent risk factor for mortality. Inflammation, malnutrition and CVD were interrelated, each contributing to the high mortality in these patients. These studies show that malnutrition is: 1) common in CRF patients, 2) associated with inflammation and CVD, and 3) a major risk factor contributing substantially to the high mortality in CRF patients.