Prevalence, patient burden and physicians' perception of pruritus in haemodialysis patients.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is an underrated symptom in patients with impaired kidney function. The present study assessed the prevalence, impact on quality of life (QoL) and risk factors for CKD-aP in a contemporary national cohort of patients on haemodialysis. In addition, we evaluated attending physicians' awareness and approach to therapy. METHODS: Validated patient's and physician's questionnaires on pruritus severity and QoL were used in combination with information obtained by the Austrian Dialysis and Transplant Registry. RESULTS: The prevalence of mild, moderate and severe pruritus in 962 observed patients was 34.4%, 11.4% and 4.3%. Physicians' estimated prevalence values were 25.0 (95% CI 16.8-33.2), 14.4 (11.3-17.6) and 6.3% (4.9-8.3), respectively. The estimated national prevalence estimate extrapolated from the observed patients was 45.0% (95% CI 39.5-51.2) for any, 13.9% (95% CI 10.6-17.2) for moderate and 4.2% (95% CI 2.1-6.2) for severe CKD-aP. CKD-aP severity was significantly associated with impaired QoL. Risk factors for moderate-severe pruritus were higher C-reactive protein [odds ratio (OR) 1.61 (95% CI 1.07-2.43)] and parathyroid hormone (PTH) values [OR 1.50 (95% CI 1.00-2.27)]. Therapy for CKD-aP included changes in the dialysis regimen, topical treatments, antihistamines, gabapentin and pregabalin and phototherapy in a majority of centres. CONCLUSIONS: While the overall prevalence of CKD-aP in our study is similar to that in previously published literature, the prevalence of moderate-severe pruritus is lower. CKD-aP was associated with reduced QoL and elevated markers of inflammation and PTH. The high awareness of CKD-aP in Austrian nephrologists may explain the lower prevalence of more severe pruritus.

The selective mineralocorticoid receptor antagonist eplerenone is protective in mild anti-GBM glomeru-lonephritis.

BACKGROUND: Growing evidence suggests that blockade of the aldosterone-receptor may preserve kidney function by anti-inflammatory effects independent of the blood pressure. We hypothesized that the selective aldosterone-receptor antagonist eplerenone has a profound anti-inflammatory effect in the autologous phase of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). METHODS: Mice received ≈200mg/kg body wt/day eplerenone via supplemented chow diet or standard chow starting at the day of immunization with rabbit IgG. Three days later the anti-GBM antibody was injected and the experiments were stopped at day 7 and 14. RESULTS: Mice receiving eplerenone showed significantly decreased albuminuria and glomerular sclerosis at day 7 and 14 after induction of anti-GBM GN. Eplerenone treatment significantly inhibited the infiltration of CD4+, CD8+ T cells and macrophages into the kidneys. Circulating levels and glomerular deposition of autologous IgG were comparable in both groups. At day 7 the pro-inflammatory cytokines MCP-1 and IL-6 were found to be significantly decreased in regional draining lymph nodes of eplerenone-treated mice, whereas the anti-inflammatory cytokine IL-10 was significantly upregulated. In line, splenocytes from eplerenone-treated nephritic mice produced significantly increased IL-10. CONCLUSION: Aldosterone-receptor blockade by eplerenone effectively attenuated proteinuria, kidney damage and the inflammatory response in anti-GBM GN by significantly decreasing pro-inflammatory cytokines in the regional draining lymph nodes of the kidney. Our results suggest that this selective aldosterone receptor antagonist is a possible additional tool in the treatment of GN.

Effect of iron treatment on circulating cytokine levels in ESRD patients receiving recombinant human erythropoietin.

BACKGROUND: Anemia in patients with end-stage renal disease (ESRD) is treated with recombinant human erythropoietin (rhEPO) often in combination with iron. However, iron catalyzes the formation of toxic radicals, which might promote vascular damage, is a nutrient for microorganisms, and negatively affects immune pathways, thus increasing the risk for severe infections. METHODS: We investigated 28 patients on chronic hemodialysis who were randomized to receive either rhEPO alone (N = 15) or rhEPO in combination with intravenous iron (N = 13) for a period of 12 weeks. We analyzed iron therapy associated changes in cytokine patterns and endogenous radical formation. RESULTS: Tumor necrosis factor-alpha (TNF-alpha) levels were increased in ESRD patients at study entry and then decreased significantly over time in subjects receiving additional iron, while they increased with rhEPO alone. In contrast, we found serum concentrations of the anti-inflammatory cytokine interleukin (IL)-4 to increase with iron therapy. A significant negative correlation between iron availability, as determined by transferrin saturation, and TNF-alpha levels (P = 0.008) and a positive one between transferring saturation and IL-4 (P = 0.02) pointed to the potential role of iron to induce immunologic changes. Interestingly, iron therapy resulted in a slight decrease in the amounts of endogenous peroxides, which may be referred to reduced TNF-alpha concentrations since peroxide concentrations were positively correlated to TNF-alpha levels (P = 0.046) and negatively to transferrin saturation (P = 0.02). CONCLUSION: Iron supplementation in ESRD patients down-regulates proinflammatory immune effector pathways and stimulates the expression of the anti-inflammatory cytokine IL-4. Such a condition is detrimental for host response toward invading pathogens. However, tissue damage by radicals such as endogenous peroxides may be reduced in this condition due to impaired TNF-alpha formation.

One-year growth hormone therapy improves granulocyte function without major effects on nutritional and anthropometric parameters in malnourished hemodialysis patients.

BACKGROUND/AIMS: Growth hormone (GH) resistance leads to enhanced protein catabolism and contributes to the malnutrition of patients with chronic renal failure (CRF). In short-term trials anabolic effects of rhGH therapy have been demonstrated in patients on chronic hemodialysis. METHODS: This study was initiated to determine the effects of 12 months of rhGH therapy on polymorphonuclear leukocyte (PMNL) function as well as on nutritional and anthropometric parameters. 0.125 IU/kg rhGH was given 3 times a week during the first 4 weeks and 0.25 IU/kg thereafter to 19 malnourished hemodialysis patients with a mean age of 59.3 +/- 13.4 years. RESULTS: Insulin-like growth factor I (IGF-I) concentrations rose significantly from 169.2 +/- 95.6 to 262.9 +/- 144.4 ng/ml (p < 0.01) in the first 3 months, but declined thereafter. Phagocytic activity of PMNLs also increased significantly in response to rhGH therapy and this activation remained stable over the whole 12-month period. Other parameters of PMNL function were not influenced by rhGH therapy. In addition, nutritional parameters such as albumin, prealbumin, transferrin, cholesterol, HDL-cholesterol, cholinesterase, predialytic creatinine and blood urea nitrogen were not affected by rhGH therapy. A decline of total body fat (TBF) was observed after 3 and 9 months of rhGH therapy (17.5 +/- 10 vs. 16.7 +/- 10% after 3 months, p < 0.017 and 16.8 +/- 8.7% after 9 months, p < 0.049), whereas lean body mass remained stable. CONCLUSIONS: Twelve months of rhGH therapy caused a significant increase in IGF-I levels, stimulated phagocytic activity of PMNLs and induced a decline of TBF. Other anthropometric and nutritional parameters were not affected, which might be related to the persistence of GH resistance.