Ciclosporin Levels Research Articles

Disturbance in renal haemodynamics and physiology in bone marrow transplant recipients treated with ciclosporin A.

The vascular disturbance associated with ciclosporin (CS) nephrotoxicity is poorly defined in both the normal and transplanted human kidney. Six bone marrow transplant recipients were studied before, during and after administration of CS. By analysis of time activity curves and clearance of Tc-99m DTPA, renal blood flow (RBF), filtration fraction (FF) and GFR were shown to fall on CS (GFR: p less than 0.001; RBF, FF: p less than 0.01). These haemodynamic variables did not fully recover with dose reduction or after discontinuation of therapy. Plasma renin activity (PRA) aldosterone and atrial natriuretic peptide did not change although there appeared a tendency for PRA to fall on CS. There was a reversible normokalemic metabolic acidosis. CS levels stayed within the therapeutic range. The partial reversibility of GFR, RBF and FF is consistent with CS-induced functional disturbance and reflects sensitivity to microvascular and tubular injury of the normal human kidney.

Modification of the Pulmonary Connective Tissue Developmental Response in the Neonatal Rat by Ciclosporin

Neonatal rat pups were treated either with ciclosporin at 10 mg/kg/day dissolved in olive oil (experimental) or with pure olive oil (control). Lung protein biosynthesis was evaluated in a protocol which involved the measurement of total accumulated protein, collagen and elastin. Four time points were studied in the first 21 days of life, 12 animals contributing to each point (6 control and 6 ciclosporin). Ciclosporin levels in the treated group ranged widely (2,000-4,000 ng/ml). There were significant differences in total body weight and lung weight in treated vs. controls during and after the first week. DNA contents per unit wet weight varied significantly during the second week of life, indicating increased cellularity of the ciclosporin-treated animals. Associated with this was an increase in the lung protein/DNA ratio as well as the elastin/DNA ratio in the control animals, but not in the treated ones. The lung collagen/DNA ratio was not as dramatically affected by the ciclosporin treatment. However, the collagen content per unit wet weight of lung tissue was increased in the ciclosporin-treated animals at 15 days of life. We conclude that ciclosporin has a marked effect on lung connective tissue metabolism in early life, the long-term effects of which are unappreciated and undocumented but may well be of vital importance in the lungs of long-surviving organ transplant patients.

Acute Effects of Ciclosporin on Renal Hemodynamics and Urinary Protein Excretion in Patients with the Nephrotic Syndrome

The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)