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Pharmacokinetics of ciprofloxacin in healthy volunteers and patients with impaired kidney function.

The pharmacokinetics of ciprofloxacin were studied, in six healthy controls and in 18 patients with varying degrees of renal impairment, after administration of a single 100 mg intravenous dose. Pharmacokinetic parameters were calculated on a two compartment open model. The mean distribution volume was 2.1 (+/- 0.6) l/kg of ideal body weight; it did not correlate significantly with renal function. In the healthy volunteers 57 (+/- 9)% of the drug was eliminated by the kidney and 43% by other pathways. The renal clearance of ciprofloxacin correlated with creatinine clearance (rs = 0.93, P less than 0.001), and urinary excretion of the drug was markedly reduced in patients with the most severe degrees of renal impairment. Plasma clearance correlated with creatinine clearance (rs = 0.50, P less than 0.02). This together with the lack of correlation between non-renal clearance and renal function enables us to suggest an intravenous dosage schedule for patients with renal impairment.

Adult↗

[Tamm-Horsfall protein, alpha-1- and beta-2-microglobulin as kidney function markers in heart surgery].

After cardiac surgery, transient renal dysfunction often occurs. Regional differentiation of these processes is possible only using invasive techniques, including renal biopsy. Approximately 30 different plasma protein components have been identified in the urine of healthy individuals by means of qualitative and quantitative immunochemical methods. The detection of microalbuminuria has high diagnostic relevance for the early diagnosis of renal damage at a reversible stage. One typical urinary protein is Tamm-Horsfall protein (THp). After histochemical staining of human kidney sections, activity is seen in the loop of Henle and initial distal tubule. The assay of alpha-1 microglobulin (MG) in urine is considered one of the most efficient laboratory parameters for the diagnosis of tubular lesions. Serum concentrations of alpha-1 MG are less dependent on extrarenal changes than are those of other low-molecular-weight proteins. beta-2 MG is also one of the standards used in recent years for diagnostic relevance. Urinary albumin excretion, normally less than 30 mg per day, sometimes increases after glomerular damage. Some renal function tests are used daily in many intensive care units, e.g. creatinine clearance (CCr) or urea and sodium excretion. Renal dysfunction should, however, be further examined to localise regional damage and to seek new clinical standards in addition to the conventional tests. METHODS. After obtaining the agreement of the local ethics committee, 30 patients were divided into two groups of 15 each: group I without renal dysfunction and CCr more than 60 ml/min; and group II with CCr below 60 ml/min. THp and alpha-1 MG were measured pre- and postoperatively after open heart surgery with the ELISA and beta-2 MG with the nephelometric technique. These parameters were compared with clinical standards such as albumin excretion, blood urea nitrogen (BUN), urea clearance, and fractional sodium excretion. RESULTS. The CCr did not change in group I from the pre- to postoperative period (81.5 to 85.1 and 91.4 ml/min), nor did excretion of THp (20.1 to 25.0 and 24.8 mg/day), correlation r = 0.7; P < 0.001). The elimination of alpha-1 and beta-2 MG was significantly higher in the postoperative period in this group (alpha-1: 7.2 to 44.1 and 100.6 mg/day; beta-2: 0.3 to 2.1 and 3.2 mg/day). In group II CCr showed pathological values (36.8 to 31.1 and 36.3 ml/min), as did simultaneous THp (13.5 to 9.7 and 12.7 mg/day). alpha-1 and beta-2 MG values became more pathological in the postoperative period than in group I (alpha-1: 32.8 to 113.9 and 198.5 mg/day; beta-2: 0.7 to 5.8 and 16.9 mg/day). DISCUSSION. Measurement of the excretion of THp and alpha-1 and beta-2 MG is a useful addition to present clinical standards for recognising early changes in renal function. The increases in the postoperative period after cardiac surgery showed tubular damage even in patients without predictive risk factors or clinical signs. In patients with renal dysfunction open heart surgery and extracorporeal circulation led to significant tubular damage.

Aged↗

[Kidney function during total blood substitution in the rat (author's transl)].

Urine production, glomerular filtration rate (GFR) and Na+ transport of the kidney were studied in rats after complete substitution of the blood with a fluorocarbon emulsion. The urine production is found to be increased, the GFR lowered. The Na+ load as a function of the GFR is reduced while the relative Na+ reabsorption with values in the range of 98-99% of the load is normal.

Animals↗

Aprotinin improves kidney function and decreases tubular cell apoptosis and proapoptotic signaling after renal ischemia-reperfusion.

OBJECTIVE: The purpose of the study was to determine the effects of aprotinin on (1) renal function, (2) apoptosis and apoptotic signaling, and (3) the inflammatory response of the kidney after ischemia-reperfusion injury. METHODS: Male rats underwent a sham procedure or left renal ischemia for 1 hour. Rats were divided into three groups and received no reperfusion, reperfusion for 1 hour, or reperfusion for 24 hours. The animals undergoing ischemia received saline solution alone or aprotinin (60,000 kIU/kg). At the end of the experiment, a sample for serum creatinine was taken and the left kidney was harvested. The kidney was analyzed for expression of tumor necrosis factor alpha, interleukin 1beta, and interleukin 6 (enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction) and activation of p38 mitogen-activated protein kinase, caspase 3, and caspase 8 (Western blot). The kidney was assessed for apoptosis with enzyme-linked immunosorbent assay and by terminal deoxynucleotidyl transferase biotin-deoxyuridine triphosphate nick-end labeling staining of tissue slides. RESULTS: Aprotinin significantly decreased the rise in serum creatinine and apoptosis caused by ischemia-reperfusion. Aprotinin significantly reduced interleukin 1 and 6 messenger RNA production and showed a trend toward reducing tumor necrosis factor messenger RNA production after ischemia. Aprotinin also significantly reduced caspase 8 activation and showed a trend toward decreasing p38 mitogen-activated protein kinase activation after 1 hour of reperfusion. CONCLUSION: These results suggest that aprotinin provides protection from renal ischemia-reperfusion injury. They also suggest that aprotinin may do so by affecting apoptotic signaling and inflammatory cytokine production. Aprotinin is a potential therapeutic measure in clinical situations where renal ischemia-reperfusion injury can be anticipated, provided adequate heparinization is possible.

Animals↗

[Kidney function study by radioisotope renography in lymphogranulomatosis patients subjected to radiation treatment].

An analysis of the results of renography in 68 patients with lymphogranulomatosis is presented. In 57 patients, a radionuclide investigation of renal function was carried out after irradiation of the spleen, paraaortic and iliac lymph nodes. Renograms were evaluated both qualitatively and quantitatively. The investigation established an impaired renal function in 18% of patients examined prior to radiation therapy. According to radionuclide renography, the excretory function of the tubular renal apparatus remains quite satisfactory after partial irradiation of kidneys in a dose of 38-40 Gy.

Adolescent↗