[Pruritus and dryness of the skin in chronic kidney insufficiency and dialysis patients - a review]. / Pruritus und Hauttrockenheit bei chronischer Niereninsuffizienz und Dialysepatienten - eine Ubersicht.

The uremic pruritus is a very painful symptom suffered by chronic haemodialysis patients and is observed in 22 to 74% of the subjects. The causes of uremic pruritus have not yet been clarified. During the last 20 to 30 years it has been focused on altogether 5 different pathophysiological hypotheses: stimulating influences (e.g. calcium phosphate deposits in the epidermis), stimuli (e.g. secondary hyperparathyroidism), neuropathic injuries (e.g. disturbance of the cutaneous innervation in patients with uremic peripheral neuropathy), and central nervous changes (e.g. accumulation of endorphins in uremic patients which is associated with increasing pruritus), and immunologic conditions. The last mentioned immunological hypothesis has increasing importance, not at least based on the fact that the application of a topical calcineurin inhibitor (tacrolimus) improves the uremic pruritus. However, this fact could not be confirmed in a recent prospective placebo-controlled study from the USA. Only after kidney transplantation with a functioning transplant the uremic pruritus is stopped. That is why no causal therapy exists so far. Actually, the uremic pruritus has to be treated by topical and systemic means in a symptomatic and polypragmatic way only. Urea represents one of the most important "natural moisturizing factors" which are responsible for the hydration of the skin. It has been demonstrated that older patients have decreased urea levels within the stratum corneum of the epidermis, whereas in patients with terminal kidney insufficiency - despite dryness of the skin - as a paradox finding elevated levels of urea have been assessed in the stratum corneum. Because of this reason, the meaning of urea as part of the "natural moisturizing factors" system is not understood, until now. However, there are very promising results of clinical phase II studies showing a significant effect of topical application of 2.5% L-arginine hydrochlorid ointment - a semi-essential amino acid - on improvement of dryness and, in particular, on improvement of pruritus in haemodialysis patients.

Clinical nutrition scores are superior for the prognosis of haemodialysis patients compared to lab markers and bioelectrical impedance.

BACKGROUND: Malnutrition is closely related to inflammation and atherosclerosis in uraemic patients. There is still debate on how to quantify nutritional status in order to achieve the best prediction of mortality and hospitalization. METHODS: Different methods to detect malnutrition were prospectively investigated for their prognostic impact on mortality and hospitalization of haemodialysis (HD) patients. We compared clinical nutrition scores (body mass index, BMI; subjective global assessment, SGA; malnutrition inflammation score, MIS; and nutritional risk screening, NRS) to lab parameters of protein and lipid metabolism, or bioelectrical impedance analysis (BIA) in 90 HD patients. Over a 3-year follow-up, all-cause mortality and hospitalization were evaluated using a Cox regression model. RESULTS: The scores SGA, NRS, MIS, serum albumin, prealbumin, transferrin and BIA were predictive of both mortality and hospitalization. Elevated CRP predicted only a significantly higher mortality. After adjustment for age, gender, dialysis vintage and diabetes status, the best prognostic parameters for mortality were the clinical nutrition scores, MIS-Index > or = 10 [HR 6.25 (2.82-13.87), P < 0.001], NRS [HR 4.24 (1.92-9.38), P < 0.001] and SGA B/C [HR 2.70 (1.14-6.41), P < 0.05]. CONCLUSIONS: In HD patients, serum markers of protein metabolism and BIA can be used for evaluation of the nutritional status. However, with regard to mortality and hospitalization risk, the individual clinical nutrition scores are superior compared to lab markers and BIA. To confirm malnutrition, we propose using clinical nutrition score generally or at least in the case of two malnutrition-positive parameters (lab, BIA, BMI).

Impact of preoperative renal dysfunction on in-hospital mortality after solitary valve and combined valve and coronary procedures.

BACKGROUND: Limited information exists on the influence of preoperative renal dysfunction on in-hospital mortality after valve and combined valve and coronary procedures. The impact of preoperative renal dysfunction on patient outcome was investigated. METHODS: This was a retrospective observational study of 916 patients who underwent solitary valve or combined procedures. Primary outcome was in-hospital mortality. Preoperative estimated glomerular filtration rate (eGFR) was calculated with the abbreviated Modification of Diet in Renal Disease formula. RESULTS: Independent predictors of death were prolonged stay in the intensive care unit (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 to 1.05), preoperative atrial fibrillation (OR, 1.61; 95% CI, 1.02 to 2.54), chronic obstructive pulmonary disease (OR, 2.2; 95% CI, 1.06 to 4.55), and prolonged operation time (OR, 1.01; 95% CI, 1.00 to 1.01). Each unit of the eGFR (mL/min/1.73 m(2)) above average exerted a renoprotective effect (OR, 0.97; 95% CI, 0.96 to 0.98). The final regression model showed no lack of fit (Hosmer-Lemeshow test, p = 0.38) and a good discrimination performance in a receiver operating characteristic analysis (area under the curve, 0.84; 95% CI, 0.80 to 0.88). The lower the preoperative eGFR rate, the longer the postoperative stay at the intensive care unit. CONCLUSIONS: Renal dysfunction is an important independent predictor of in-hospital mortality in adult patients after valve and combined valve and coronary procedures.

Effect of immunoadsorption on refractory idiopathic focal and segmental glomerulosclerosis.

A case of a young adult with refractory nephrotic syndrome due to focal segmental glomerulosclerosis is reported. Several treatments had been used without success including steroids, cyclophosphamide, cyclosporine A, tacrolimus, and mycophenolate mofetil. Immunoadsorption was performed as a last resort to manage the nephrotic syndrome, which led to a drastic urinary protein reduction. We review the literature supporting immunoadsorption in primary focal segmental glomerulosclerosis.

Extravascular lung water index: a new method to determine dry weight in chronic hemodialysis patients.

To assess the dry weight of chronic hemodialysis (HD) patients, the extravascular lung water index (ELWI) as a volume parameter was investigated to identify fluid overload. Forty-two patients (30 males, 12 females) with a mean age of 55.7+/-13.0 years who were clinically not overhydrated were connected to the PiCCO system before starting HD treatment. We determined ELWI (normal range 3-7 mL/kg) and the following parameters: global end-diastolic volume index (GEDI, normal range 680-800 mL/m(2)) and intrathoracic blood volume index (ITBI, normal range 850-1000 mL/m(2)) before and after HD to assess the volume status. Brain natriuretic peptide (BNP), aldosterone, and renin as vasoactive hormones were measured at the beginning and at the end of HD treatment as well. In 28 of the 42 patients (67%), elevated values of ELWI were found, indicating interstitial volume overload. There were significant correlations between ELWI and cardiac function index (p=0.003; Pearson's coefficient -0.451), global ejection fraction (p=0.012; Pearson's coefficient -0.389), ITBI (p=0.004; Pearson's coefficient 0.437), and GEDI (p=0.004; Pearson's coefficient 0.437). No significant relations among ELWI and mean arterial pressure (MAP), BNP, aldosterone, and renin were found. In conclusion, the use of ELWI is safe in chronic HD patients and identifies fluid-overloaded patients, who show no obvious signs of hypervolemia. The determination of ELWI is an excellent method to quantify the exact volume in chronic HD patients.

Short-term administration of omega-3 fatty acids in hemodialysis patients with balanced lipid metabolism.

BACKGROUND: At present, it is discussed whether omega-3 fatty acids show anti-inflammatory, antithrombogenic, and antiatherosclerotic effects, also in patients with chronic renal failure. METHODS: In this prospective study, 11 hemodialysis (HD) patients, ages 59 +/- 17 years, who had balanced lipid metabolism and had been on HD for 53 +/- 47 months, were treated with a moderate dose of omega-3 fatty acids (1.2 g/day combined with 11.2 g/day pectin) for 12 weeks. Serum concentrations of c-reactive protein, homocysteine (Hcy), lipids, complement factors, blood gas analyses, 24-hour blood pressure, heart rate variability, electrocardiography, shunt blood flow, and recirculation, as well as peripheral oxygen saturation at the hand and foot, were measured at the start (t0w), and after 12 weeks (t12w) of therapy. Results Several assessed cardiovascular risk factors were significantly influenced. Levels of very-low-density lipoproteins (t0w, 77 +/- 26; t12w, 63 +/- 32 mg/dL; P <.05) and triglycerides (t0w, 261 +/- 157; t12w, 228 +/- 131 mg/dL; P =.068) were decreased. However, Hcy concentrations increased from 35.5 +/- 32.5 to 43.5 +/- 36.7 micromol/L ( P <.01) after 12 weeks. Anti-inflammatory and investigated clinical parameters did not significantly change during the study period. CONCLUSION: Limited positive effects on metabolic parameters were evaluated by short-term administration of omega-3 fatty acids in HD patients. Based on previous studies and on suspicion of atherosclerotic disorder in examined HD patients, we suppose that only high doses of omega-3 fatty acids given for a longer time influence inflammation and atherosclerosis.

Effects of reduced dialysate calcium on calcium-phosphorus product and bone metabolism in hemodialysis patients.

BACKGROUND: The safety of using reduced calcium dialysate (RDC) in hemodialysis (HD) patients is controversial due to related changes in bone metabolism. In the present study we investigated whether an 18-month treatment period with RDC may induce significant changes in calcium-phosphorus product (CaxP), bone metabolism, and components of the insulin-like growth factor (IGF) system in HD patients. STUDY DESIGN: In this prospective study, 13 HD patients with biochemical signs of diminished or low-normal bone turnover and high CaxP due to high serum calcium level were treated by lowering dialysate calcium from 3.5 to 2.5 mEq/l for 18 months. By specific immunometric assays, serum levels of intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), pyridinoline (PYR), desoxypyridinoline (D-PYR), 25-OH-vitamin D(3) (25-vit D(3)), 1,25-(OH)(2)-vitamin D(3) (1,25-vit D(3)), free IGF-I, IGF-II, and IGF-binding protein (IGFBP)-1 to -6 were measured. RESULTS: CaxP decreased significantly from 5.62 (baseline) to 3.95 mmol(2)/l(2) (at 18 months), whereas PTH increased from 81 +/- 57 pg/ml at baseline to 236 +/- 188 at 12 months (p < 0.01), remaining in this range thereafter. Parameters of bone resorption (PYR) as well as formation (B-ALP) significantly increased during RDC, with peak levels after 12 months. Despite increasing doses of oral alfacalcidol, levels of 25-vit D(3) and 1,25-vit D(3) subsequently declined during RDC. In parallel with the changes in bone markers, free IGF-I levels decreased (baseline: 1.9 +/- 0.9 ng/ml, after 18 months: 1.1 +/- 0.7; p < 0.01). The decline of free IGF-I correlated with decreasing levels of IGFBP-3 and increasing levels of IGFBP-1/-4. CONCLUSION: The treatment with RDC effectively lowered CaxP and stimulated bone formation and resorption. The different changes in bone markers and IGF system components mirror the complex effects on bone metabolism.

Cardiac beta-adrenoceptor desensitization due to increased beta-adrenoceptor kinase activity in chronic uremia.

Patients with chronic renal failure develop an autonomic dysfunction with impaired baroreflex control and attenuated cardiovascular beta-adrenoceptor response to noradrenaline. In rats that underwent 5/6-nephrectomy (SNX), cardiac beta-adrenoceptor responsiveness was reduced as well. Therefore, the aim of this study was to further investigate the mechanism underlying cardiac beta-adrenoceptor desensitization in SNX rats. For this purpose, right and left ventricular beta-adrenoceptor density, activity of the G-protein-coupled receptor kinase, and activity and density of the neuronal noradrenaline transporter (uptake1) were assessed in SNX rats. Seven weeks after SNX, rats had developed left heart hypertrophy. Plasma creatinine, urea, and noradrenaline levels were significantly increased; left and right ventricular noradrenaline content was significantly decreased when compared with sham-operated control rats. In these SNX rats, left, but not right, ventricular beta-adrenoceptor density was significantly reduced, and membrane-associated G-protein-coupled receptor kinase activity was significantly increased compared with sham-operated rats. Although right and left ventricular activity of uptake1 was unchanged, the neuronal noradrenaline transporter density was significantly reduced in both ventricles of SNX versus sham-operated rats. An increase in left ventricular G-protein-coupled receptor kinase activity, possibly triggered by enhanced cardiac noradrenaline release, might be responsible for the decrease in left ventricular beta-adrenoceptor responsiveness in SNX rats.