Renal insufficiency is associated to an activation of the tissue factor coagulation pathway, to a platelet, monocyte and endothelial activation/injury and to a deficient tissue-factor induced response to activated protein C which culminate in end-stage disease and are increased by hemodialysis runs. This contributes to linked coagulation and cellular conditions for an enhanced atherosclerosis progression. Due to the TF pathway activation, the therapeutic use of recombinant TFPI should be evaluated.

The aim of this study was to characterise the pharmacokinetics of the anticancer agent topotecan, and explore the influence of patient covariates and interoccasion variability on drug disposition. Data were obtained from 190 patients who received the drug as a 30-min infusion (N ¼ 72) or orally (N ¼ 118). The population model was built with the use of NONMEM to identify candidate covariates, and obtain models for clearance (CL) and volume of distribution. The final models were based on first-order absorption with lag-time (oral data), and a two-compartment model with linear elimination from the central compartment. The Cockcroft -Gault creatinine clearance (CrCl) and WHO performance status (PS) were the only significant covariates: CL ¼ (12.8 þ 2.1 Â CrCl) Â (1À0.12 Â PS). For the volume of distribution, a correlation was found between body weight and the central volume (V1) ¼ 0.58 Â body weight. Based on the structural models, a limited-sampling strategy was developed with minor bias and good precision that can be applied a posteriori using timed samples obtained at 1.5, and 6 h after the administration of topotecan. In conclusion, a population pharmacokinetic model for topotecan has been developed that incorporates measures of renal function and PS to predict CL. In combination with drug monitoring, the limited sampling strategy allows individualised treatment for patients receiving oral topotecan.

The proposed cut-off value of 32 ng/ng for ARR (minimum renin value set at 5 ng/L) in one of two determinations had 100% sensitivity and 72% specificity with 20% positive and 100% negative predictive values for diagnosing APA.

Evidence from previous theoretical and experimental studies has indicated that angiotensin formed as a result of unilateral kidney disease will not produce chronic hypertension unless there is also a sodium and fluid retaining effect on the otherwise normal contralateral kidney. Therefore, the present experiments were conducted in dogs to determine whether or not blood angiotensin concentrations similar to those found in patients with unilateral kidney disease can cause significant water and salt retention by a normal dog kidney. Angiotensin was perfused directly into the renal artery of a semi-isolated perfused kidney preparation, and the effects on renal blood flow, glomerular filtration rate, degree of autoregulation of both renal blood flow and glomerular filtration rate, and rates of excretion of electrolytes and water were all determined at perfusion pressures between 75 and 200 mm Hg. The results showed that angiotensin in reasonably low dosages can cause the normal dog kidney to retain water and salt, but from a quantitative point of view it remains doubtful whether or not enough angiotensin is formed in patients with unilateral kidney disease to produce a similar effect. Studies on the various parameters of kidney function gave an insight into the mechanism of water and salt retention during angiotensin infusion and also explained why angiotensin infusion sometimes causes diuresis rather than antidiuresis.

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