Inflammation Nutritional State and Outcome in End Stage Renal Disease

Abstract

Hypoalbuminemia and reduction in lean body mass are potentially a reflection of malnutrition and portend a poor prognosis in patients with end stage renal disease (ESRD). The classic understanding of this relationship has been that ESRD patients receive insufficient dialysis, reduce dietary intake and become malnourished. Inflammation also causes many of the same changes in serum protein composition and in body morphometry as malnutrition does even with adequate calorie and protein intake. It has recently been recognized that this, the acute phase response, occurs with frequency in ESRD patients and that both the physical attributes of malnutrition and reduction in the serum concentration of albumin, transferrin, prealbumin and apolipoprotein A-I all may lack a nutritional base. The serum concentration of the acute phase proteins, C reactive protein (CRP) and serum amyloid A (SAA), as well as the cytokines orchestrating the acute phase response, predict albumin concentration as well as a number of clinically important outcomes: specifically, erythropoietin resistance rejection of renal transplant and survival. ESRD per se does not cause the acute phase response, and indeed may blunt the response to infection. Activation of the acute phase response may be a consequence of the interaction of mononuclear cells with dialysis membranes, especially cuprophane, with endotoxin in dialysate, or represents either clinically evident or obscure infection. Evaluation of the acute phase response by measurement of CRP is advisable in the evaluation of hypoalbuminemia or other stigmata of malnutrition in dialysis patients.

Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia

“…This is another example where sensitivity to some cytokines is maintained, despite resistance to GH. These reports may be relevant to the situation in patients with end-stage renal disease, for chronic subclinical inflammation is common in dialysis patients and appears to be a major cause of malnutrition and increased cardiovascular morbidity (47). It is tempting to speculate that persistent subclinical inflammation with proinflammatory cytokine release may contribute to the malnutrition of uremia by worsening the GH resistance in these patients by increasing SOCS protein production.…”

Toxicity of Free p-Cresol: A Prospective and Cross-Sectional Analysis

“…However, to our knowledge, this hypothesis has never been tested in clinical and/or experimental conditions. This hypothesis becomes more interesting in view of the recent suggestion of a link between malnutrition and hypoalbuminemia on one hand and survival of hemodialysis patients on the other (8 ).…”

Erythropoietin Therapy in Pre-Dialysis Patients with Chronic Renal Failure: Lack of Need for Parenteral Iron

“…Further, recent literature suggests that this inflammatory state is a progressive spectrum, progressing with the progression of renal failure [10, 14, 17]. This state is highest in HD subjects, in part due to exposure to the dialysis membrane or antigen exposure via the dialysate, leading to activation of the acute phase response [11, 14, 18, 21, 22, 23, 24, 25]. Inflammatory markers are known to play a major role in the anemia of chronic disease.…”

“…Cytokines such as interleukin-1, tumor necrosis factor, interferon-beta and interferon-gamma suppress proliferation of erythroid precursors and erythropoietin production [2, 27]. Existing data supports this possibility, specifically the relation of the inherent inflammatory state of chronic renal failure to the anemia of renal failure, need for iron, and relative resistance to erythropoietin [11, 20, 22, 23, 28, 29, 30, 31]. CKD sera, from patients without overt inflammation, suppress erythropoiesis due to stimulation of inflammatory cytokines such as interferon-gamma and tumor necrosis factor-alpha, the same cytokines invoked in inflammatory anemia [27, 32].…”