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This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m[SUP2] at day 1-3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m[SUP2/]d over 18 h), ifosfamide (4 g/m[SUP2]/d over 4 h) and etoposide (500 mg/m[SUP2]/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 μg kg[SUP1] subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min[SUP-1]) and 37% in the control patient group (107 to 67 ml min[SUP-1]) (P < 0.01). Amifostine-treated patients revealed a less pronounced increase in albumine and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT[SUB3]-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 μl[SUP-1]) and thrombocytes (> 25 000 μl[SUP-1]) were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a... [ABSTRACT FROM AUTHOR]

Background: Children have been considered a risk group for lead (Pb) toxicity, mainly because of neurophysiological or neuro-cognitive deficits following Pb exposure. Blood Pb levels (b-Pb) of 100 μg/l currently have been defined as the lowest adverse effect level. The aim of this study was to compare, with the help of urinary markers, the kidney function of children with b-Pb just above this threshold with that of unexposed children, to assess from a nephrological point of view whether the current threshold is justified and whether children really are a particularly vulnerable risk group in terms of Pb-induced kidney damage. [ABSTRACT FROM PUBLISHER]

Background: Vascular endothelial growth factor (VEGF) or vascular permeability factor (VPF) is a selective mitogen for endothelial cells; it increases microvascular permeability and has been shown to relax isolated canine coronary arteries by an endothelium-dependent mechanism. In many tissues VEGF/VPF is expressed after an appropriate stimulus, mostly hypoxia. In the kidney VEGF/VPF is constitutively expressed in glomerular podocytes and epithelia of collecting duct. Glomerular and peritubular capillary endothelia also constitutively express specific VEGF receptors. The in vivo function of renal VEGF/VPF is unknown. [ABSTRACT FROM PUBLISHER]

Background The anticancer drug cisplatin is known to have toxic side-effects on different segments of the nephron. The flavonoid silibinin has previously been shown to be protective in models of hepatotoxicity. The aim of the present study was to evaluate, whether silibinin can also ameliorate alterations in renal glomerular and tubular function and tubular morphology induced by cisplatin. Methods In a rat model renal damage was induced by a single injection of cisplatin (5 mg/kg body weight). The protective effects of silibinin were studied in rats that received the flavonoid (200 mg/kg body weight, i.v.) 1 h prior to the administration of cisplatin. Kidney function was monitored by analysing urinary markers of glomerular and tubular function over a period of 11 days. Animals of a second group, with identical treatment, were sacrificed 4 days after drug application for an evaluation of tubular morphology at the light-microscopical level. Results Administration of cisplatin caused a decline in kidney function within a day following treatment. Symptoms observed were for example decreases in creatinine clearance and increases in proteinuria, in the urinary activity of the proximal tubular enzymes alanine aminopeptidase and N-acetyl-β-D-glucosaminidase and in renal magnesium wasting. The effects of cisplatin on creatinine clearance and proteinuria were totally prevented by a pretreatment of the animals with silibinin. Impairment of proximal tubular function was ameliorated, that is enzymuria and magnesium wasting was less pronounced. Silibinin alone had no effect on kidney function. Treatment with silibinin distinctly diminished morphological alterations observed in the S3-segment of the proximal tubule 4 days after cisplatin administration. Conclusions The effects of cisplatin on glomerular and proximal tubular function as well as proximal tubular morphology could totally or partly be ameliorated by silibinin. It is concluded that silibinin can act as a nephroprotectant and it is suggested that it could have beneficial effects on the kidney in clinical settings. [ABSTRACT FROM PUBLISHER]

With established urinary markers of kidney integrity the early renal effects of lead have previously been considered to be mainly tubular or tubulointerstitial. In a cross-sectional study on 81 male lead-exposed workers and 45 age-matched controls (median blood lead concentrations 2.03 and 0.34 μmol/l respectively) not only well-established but also new urinary markers of renal integrity preferentially or exclusively located along the different nephron segments were analysed. Markers related to the glomerulus were 6-ketoprostaglandin, thromboxane B mainly produced in the glomerulus, and the extracellular matrix protein fibronectin. Markers of the proximal tubule were the brush-border antigens BBA, BB50, and HF5 and the intestinal alkaline phosphatase. Prostaglandin E and F, preferentially synthesized in the collecting duct and medullary interstitial cells, served as markers of these more distal nephron segments. In contrast to previous studies on the early phase of lead nephrotoxicity, not only tubular but also glomerular involvement could be shown in the study presented here by increases in the median values of 6-keto-prostaglandin, and decreases in fibronectin. The proximal tubular markers intestinal alkaline phosphatase and BBA confirmed that this particular segment of the nephron is affected by lead. Effects on the collecting tubule or medullary interstitial cells could also be observed. It is concluded that lead affects both the glomerulus and the tubular apparatus and that combinations of new and established markers could be valuable for a better definition and early detection of lead nephropathy. [ABSTRACT FROM PUBLISHER]

Fifteen various serum and urine parameters were evaluated as indicators of renal alterations induced by lead in 82 male workers of a battery plant chronically exposed to lead (median of blood lead concentration: 2.03 μmol/1). The control group comprised 44 non-exposed healthy volunteers (0.34 μmol/1). High-molecular-mass proteins (transferrin, immunoglobulin G (IgG), (albumin)) were determined in urine as markers of glomerular integrity; lowmolecular-weight proteins and parenchymal enzymes (α-microglobulin, β-microglobulin, retinol-binding protein, lysozyme, ribonuclease, N-acetyl-β-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), alkaline phosphatase (AP), γ-glutamyltransferase (GGT)) as indicators of changes in the proximal tubule; Tamm-Horsfall glycoprotein and kallikrein as markers of the distal tubule. There was a positive correlation between tubular indicators and blood lead concentration as well as the erythrocyte protoporphy-rin (EPP). About 30% of the lead-exposed workers showed an increased excretion of α-microglobulin, NAG, ribonuclease, and/or Tamm-Horsfall protein, whereas the glomerular indicators remained unchanged. The combined determination of NAG and α-microglobulin in urine could be helpful in the early detection of lead-induced changes in the nephron. [ABSTRACT FROM PUBLISHER]