Antiproteinuric efficacy of fosinopril after renal transplantation is determined by the extent of vascular and tubulointerstitial damage.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors have been successfully used for treatment of proteinuria after renal transplantation (RTx). Factors possibly responsible for the great inter-patient variance of the antiproteinuric effect (APE) have not yet been investigated in renal-transplanted patients. METHODS: 28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospectively with does of fosinopril (10-15 mg/d) which were not effective on systemic arterial blood pressure. Prior to initiation of fosinopril, renal graft biopsy was performed in all patients and renal graft artery stenosis was excluded by duplex ultrasound. Serum creatinine and proteinuria were measured prior to, as well as 3 and 8 months after initiation of ACE inhibition, mean arterial pressure was controlled via 24-h measurement and repeated spot measurements. Reduction of proteinuria was correlated with renal histology, serum creatinine, creatinine clearance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respectively. RESULTS: Therapy had to be stopped in 8/28 patients due to side effects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) proteinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.48 +/- 3.05 g/d after 3 and 8 months respectively, in the mean +/- SD. There was a significant inverse correlation between the APE and the extent of benign nephrosclerosis, interstitial fibrosis and tubular atrophy. No correlation of the APE to any of the other parameters could be demonstrated. CONCLUSIONS: Fosinopril can be administered effectively in a subgroup of proteinuric renal transplant recipients. However, because of a high proportion of patients developing side effects, careful monitoring is obligatory. Our results show that the lesser the degree of chronic morphological injury, the greater is the antiproteinuric effect. Thus, the degree of pre-existing histologically proven damage of the graft may serve as an indicator for the antiproteinuric efficacy of ACE inhibitor therapy after RTx.

[Endocrine reaction pattern: midazolam-fentanyl anesthesia versus inhalation anesthesia]. / Endokrine Reaktionsmuster: Midazolam-Fentanyl-Anästhesie versus Inhalationsanästhesie.

In a randomised controlled study in 16 orthopaedic patients, the influence of midazolam-fentanyl-N2O/O2 anesthesia (group A) resp. halothane-N2O/O2 anesthesia (group B) on the plasma concentrations of the endocrine parameters ACTH, aldosterone, cortisol, 17-DHEA, insulin, prolactin, T3, T4, TBG (thyroxine bounded globuline) as well as adrenaline, noradrenaline, and dopamine was investigated. Additionally the metabolites glucose, lactate, free glycerin, and acetacetate were measured. Beside prolactin values, only the values for ACTH, aldosterone, cortisol, and 17-DHEA differed with respect to both anesthesia methods. Under halothane-N2O/O2 anesthesia free T4 rose initially also, here represented by T4/TBG-ratio (= FTI). However, the fall of T3 concentration showed no phase - resp. anesthesia-specific changes. Catecholamine levels reached highest values towards the end of operation resp. one hour after extubation in both groups. The insulin secretion, however, was not significantly raised in either group during acute stress phases. As an expression of modified metabolic regulation comparable rises of plasma levels of glucose, lactate, free glycerin, and acetacetate were observed under midazolam-fentanyl-N2O/O2 anesthesia as well as under halothane-N2O/O2. According to presented data, both methods of anesthesia modulated the endocrine metabolic response of the organism to surgical stress, without showing any clinically relevant advantages or disadvantages attributable to either method.

[Combined midazolam-ketamine anesthesia in traumatologic interventions. Patterns of endocrine reactions]. / Midazolam-Ketamin-Kombinationsanaesthesie bei traumatologischen Eingriffen. Endokrine Reaktionsmuster.

For anesthesia, ataranalgesic combinations of benzodiazepines and ketamine have been reported to be advantageous alternatives to inhalation agents or high-dose opioids. In this study, the influence of midazolam-ketamine-N2O/O2 anesthesia on the endocrine metabolic response of patients during the course of reconstructive orthopedic surgery (n = 8) was investigated. METHODS. The dosage of anesthetic agents was calculated according to body weight. Thus, the amount of ketamine given in young adults (mean age = 24.1 years) was 30 micrograms/kg per minute. Pre-, intra-, and postoperatively, each of following hormones was measured by either radioimmunoassay or radioenzyme-linked assay: ACTH, aldosterone, cortisol, 17-dehydroepiandrosterone (17-DHEA), prolactin, insulin, T3, T4, thyroxine-binding globulin (TGB), epinephrine, norepinephrine, and dopamine. Additionally, the metabolites glucose, lactate, and free glycerin were measured perioperatively. RESULTS and CONCLUSION. The circulation remained relatively stable under midazolam-ketamine-N2O/O2 anesthesia (MAP +23%; HR +17%). ACTH secretion and prolactin secretion showed a significant rise (p less than 0.01) even before skin incision (Figs. 1, 3). A significant rise in cortisol levels occurred intraoperatively (+80%; p less than 0.01). Secretion of aldosterone (+246%; p less than 0.05) and 17-DHEA (+49%; p less than 0.05) essentially followed the secretory profile of cortisol, while insulin secretion did not rise significantly under acute surgical stress (Fig. 4).(ABSTRACT TRUNCATED AT 250 WORDS)