Antihypertensive effect of amlodipine and lack of interference with cyclosporine metabolism in renal transplant recipients.

The catabolism of various calcium channel blockers through cytochrome P-450 is heterogeneous and may be modified by concomitant use of cyclosporin A. In an open study we investigated the antihypertensive effect and clinical tolerance of the dihydropyridine amlodipine and its effects on cyclosporine kinetics in stable hypertensive renal transplant recipients not taking corticosteroids. Ten adult hypertensive patients grafted for 21.4 +/- 8.9 months and well stabilized with normal renal function were included in the study. Renal artery stenosis was ruled out by normal Doppler echography. After 2 weeks of placebo, amlodipine was started at a daily dose of 5 mg. The dose was then adjusted to 10 mg if necessary. Blood and urine chemistries and whole-blood cyclosporine trough levels were measured weekly. Cyclosporine kinetics were determined on a hourly basis before amlodipine administration and after 4 weeks of treatment. Normal blood pressure was obtained with the use of 5 mg/d amlodipine in 7 patients and 10 mg/d in 3, diastolic blood pressure decreasing from 98.7 +/- 3.8 to 81.3 +/- 9.1 mm Hg (P = .0007). Heart rate slightly increased by 10% (P < .02). The drug was well tolerated, and only minor ankle edema was found in 3 patients. Cyclosporine doses were not modified and cyclosporine levels remained unchanged throughout the study. Cyclosporine kinetic parameters were not significantly different at the beginning and end of the study. Bioequivalence was demonstrated indicating that cyclosporine biotransformation was not altered by the concomitant administration of amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS)

False-negative results in anti-HLA antibody detection by Sangstat ELISA: complement dependent cytotoxicity is not yet obsolete.

Although ELISA on purified HLA molecules for detecting anti-HLA antibody (P-S ELISA) does detect some antibodies previously missed by the conventional complement dependent cytotoxicity method (C Cytotox), HLA ELISA should not fail to detect antibodies already detected by the conventional reference method to be able to make C Cytotox obsolete and to replace it in routine testing. Among 40 selected sera, 8 false-negative reactions were observed in P-S ELISA. These sera were reanalyzed blind in two laboratories and found to contain non-IgM, warm anti- HLA antibodies. These antibodies were directed in 4 cases against an HLA molecule expressed on a kidney transplant previously rejected by the subject. These antibodies, if missed, would have been potentially harmful in kidney transplantation. Thus P-S ELISA can't yet replace C Cytotox in routine anti-HLA class I detection. The cost/benefit ratio of P-S ELISA as a second-line test remains to be investigated.

Noninvasive experimental determination of the individual kidney filtration fraction by means of a dual-tracer technique.

A noninvasive method for measurement of the individual kidney filtration fraction (FF) is presented, based on an analysis of the early rise of the kidneys' time-activity curves obtained after simultaneous injection of tubular [131I] ortho-iodohippurate and glomerular (Tc-99m DTPA) tracers. The analysis is based on the assumption that an insignificant amount of tracer leaves the kidney during the first few moments following injection. Therefore the kidney activity during this period is directly proportional to the integral of the blood (heart) activity. The dual-tracer technique allows the direct calculation of the ratio of glomerular to tubular clearances, i.e., the FF. In vivo studies were performed on 12 dogs, including normals as well as others with acute ureteral ligation or Benemid-induced tubular blockade. The calculated FF correlated well with the FF obtained from single-shot clearances performed simultaneously. We conclude that the FF can be calculated directly for each kidney, noninvasively, from the early part of the tubular and glomerular time-activity curves by noninvasive external detection.

Long-term follow-up of acute renal failure caused by angiotensin converting enzyme inhibitors.

Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension and heart failure. However, acute renal failure (ARF) may occur in patients who are taking these drugs in situations associated with decreased glomerular filtration pressure, such as dehydration caused by acute diarrhea or diuretic therapy. Sixty-four patients who were admitted to the intensive care unit for ARF associated with ACE inhibitor therapy were followed for more than 5 years. In this historical retrospective study, we documented that 45 patients were treated for hypertension (group I) and 19 were treated for heart failure (group II). Their mean age was 71.2+/-11.6 years. Patients with ARF presented with overt dehydration in 91% and 84% of the cases in groups I and II, respectively. Hypovolemia was caused by diuretics or gastrointestinal fluid loss. Bilateral artery-renal stenosis or stenosis in a solitary kidney was documented in 22% and 10% of patients in groups I and II, respectively. The probability of survival was 91% and 49% at 1 year and 64% and 18% at 5 years, for groups I and II, respectively. Acute renal failure required hemodialysis in seven patients, but none of them became dialysis dependent. In the subgroup of patients with preexisting chronic renal failure, all the patients except for one who belonged to group II died within 2 years. In both groups, after resolution of ARF, plasma creatinine concentration returned to baseline level and the course of renal function was not significantly worsened. In conclusion, ARF associated with ACE inhibitors is likely to occur in many patients without renal artery stenosis after unexpected dehydration, especially in older patients with congestive heart failure. In both groups of patients, in the absence of preexisting chronic uremia, recovery of renal function occurred without sequelae, even after an episode of acute tubular necrosis requiring dialysis.

Successful parathyroid gland autotransplantation in the rat using a simplified cryopreservation technique.

In the present work a simplified technique for cryopreservation of parathyroid glands was compared to the generally used technique needing a programmed freezer. Four groups of rats had total parathyroidectomy. In two of them the glands were cryopreserved and reimplanted 10 days after ablation. The other two groups had, respectively, immediate parathyroid autotransplantation and no autotransplantation. During a follow-up of 60 days, plasma calcium remained low and plasma phosphorus elevated in all aparathyroid rats of the last group. In the group of rats with immediate parathyroid reimplantation, both mean plasma calcium and phosphorus values rapidly returned to the normal values observed before operation. In the rats that had the simplified parathyroid cryopreservation technique, mean plasma phosphorus also returned to the normal range and mean plasma calcium to nearly normal. However, in the group of rats with the classical cryopreservation method, the mean plasma calcium and phosphorus levels remained far from normal in the majority of animals. It was concluded that parathyroid glands of the rat could be successfully autografted after previous freezing using a simplified cryopreservation technique. The results obtained were comparable with, even though not as perfect as, that observed after immediate autotransplantation. If suitable for human parathyroid gland fragments, this technique would allow a more general application of parathyroid tissue cryopreservation.

Beta 2-microglobulin metabolism in uremic patients who are undergoing dialysis.

Plasma beta 2-microglobulin (beta 2m) is increased in chronically hemodialyzed patients and remains in a steady range once residual diuresis has stopped. Factors controlling such a steady state are unknown. We undertook metabolic studies to define whether plasma beta 2m is regulated by extrarenal proteolysis of the protein or by storage in a captation pool, a condition which may precede beta 2m-derived amyloidogenesis. Seventeen uremic patients on supportive therapy and five healthy controls were enrolled into the 6 to 10 day study. Using trace amounts of 131I-beta 2m and total body counting, half-life was between 2.4 and 8 days. 125I-beta 2m plasma kinetics was more suitable to calculate fractional catabolic rate and synthetic rate. A three compartment model was chosen to calculate turnover parameters in dialysis patients, whereas the regular two compartment model fitted best for healthy controls. beta 2m synthesis rate was increased in uremic patients when compared with controls (4.49 +/- 2.60 vs. 3.68 +/- 1.43 mg/kg/day, NS). The three compartment model did not integrate all the experimental data, since it was possible to calculate a captation compartment which accumulated beta 2m without fast proteolysis. The captation pool was positively correlated with plasma beta 2m concentration and comprised between 23% and 59% of the amount of the beta 2m disappearing from plasma per day. In conclusion, metabolic studies with radioiodinated beta 2m indicate a slight increase in beta 2m synthesis rate in uremic patients on supportive therapy, irrespective of the technique in use. Kinetic analysis requires a model taking into account a storage compartment which is more complex than the three compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)

Variations of protein C in uremic hemodialysed patients.

Protein C has been measured by three different assays (antigenic, amidolytic and chronometric) in 27 end-stage renal insufficient patients before and after hemodialysis. Protein C levels have been compared with other coagulation inhibitors (antithrombin III, protein S) and fibrinolytic parameters. Baseline anticoagulant activity of protein C has been found impaired in eight cases whereas other inhibitors were normal. In four cases, both anticoagulant and antigenic levels were low. In one case, amidolytic method could also found a low activity. Hemodialysis leads to an increase of protein C activity and antigen level. Heparinemia after hemodialysis does not interfere with the chronometric measurement of protein C anticoagulant activity. Total protein level, hematocrit, protein S and antithrombin III are also elevated after hemodialysis. Baseline fibrinolytic parameters are normal and remain unchanged after hemodialysis. The clinical relevance of such modifications is discussed.

Increased renal excretion of 3 hydroxyproline in patients with active glomerular nephropathies and with polycystic renal disease.

The renal excretion of 3 hydroxyproline (3 HYP) and 4 hydroxyproline (4 HYP) was investigated in control subjects and in patients with various renal diseases. In normal adult subjects urinary 3 HYP was 12.5 +/- 3.5 (SD) mumoles/24 hr, 4 HYP was 226 +/- 62 mumoles/24 hr and the percentage ratio 3 HYP/4 HYP 5.4 +/- 0.5. This ratio was reduced during growth because of a relative excess of 4 HYP. In patients with acute glomerular disease (n = 12) 3 HYP was increased to 17.1 +/- 5.8 mumoles/24 hr (P less than 0.01), and the ratio 3 HYP/4 HYP was 7.3 +/- 0.7% (P less than 0.01). Such an increase in 3 HYP was not observed in patients with chronic glomerulonephritis (n = 24) where 3 HYP was 9.6 +/- 5.0 mumoles/24 hr and 3 HYP/4 HYP 5.7 +/- 1.6% or with diabetic glomerulopathy (n = 6). In patients with chronic interstitial nephritis (n = 8) the 3 HYP/4 HYP ratio was decreased except in patients with polycystic renal disease (PKD) where it was increased (P less than 0.001). The daily urinary content of 3 HYP and 4 HYP was slightly altered by renal insufficiency. Urinary 3 HYP did not change significantly in patients with GN with the nephrotic syndrome whatever the histological lesion. These results indicate that urinary 3 HYP: 1) is increased when glomerulonephritis is clinically acute or subacute; 2) is increased in PKD whatever the level of renal insufficiency.

Assessment of divided renal function by renography. Validation in patients with separate urine collections from each kidney.

Divided renal function was measured by 99mTc-DTPA renography using a gamma camera and a computer-assisted program. In 14 patients with permanent bilateral ureterostomies (7) or temporary ureteric catheterization (7), split renal function was calculated by analysis of the initial phase of the kidney activity-time curve and measured simultaneously by conventional clearance techniques. A high correlation was found between individual clearances measured by computation and by the conventional procedure. The correlation coefficient between the results obtained by the two techniques was 0.94 (P less than 0.001). A high correlation was also shown to exist between the computed clearance and the renal uptake of mercury after administration of 197HgCl. It is concluded that 99mTc-DTPA is particularly useful for the measurement of divided renal function without the need for urine collection.

Evaluation of the safety and efficacy of telmisartan and enalapril, with the potential addition of frusemide, in moderate-renal failure patients with mild-to-moderate hypertension.

The effect on renal function and efficacy of the angiotensin II AT1-receptor blocker (ARB), telmisartan, were compared with those of the angiotensin-converting enzyme inhibitor, enalapril, for the treatment of mild-to-moderate hypertension (diastolic blood pressure [DBP] 95-114 mmHg) in the presence of moderate renal failure (creatinine clearance [Ccr] 30-80 ml/minute). The study was multicentre, double-blind, double-dummy and active-controlled in design, with patients randomised in a 2:1 ratio to receive telmisartanor enalapril. After a two-week placebo run-in period, the 71 eligible patients received either telmisartan, 40 mg, orenalapril, 10 mg, once-daily for four weeks. Thereafter, doses were titrated to telmisartan 80 mg or enalapril 20 mg once-daily if supine trough DBP was still > or =90 mmHg. After a further four weeks, dose titration was again performed, as required, to telmisartan, 80 mg,or enalapril, 20 mg, or frusemide was given in addition if the double dose was already being administered. Mean Ccr decreases of 4.6% for telmisartan and 2.8% forenalapril were not clinically significant. Adverse events occurred in 12 (26.7%) telmisartan-treated patients and in 12 (46.2%) patients receiving enalapril. The mean reduction in supine trough DBP from baseline to the last available value was 12.5 mmHg for telmisartan,compared with 11.9 mmHg for enalapril. A full (reduction of >or=10 mmHg) or partial (reduction of 7-9 mmHg) response occurred in 78% of telmisartanpatients and 65% of enalapril patients. In the enalapril group, 43% of patients required frusemide, compared with 29% of those in the telmisartan group. In conclusion, telmisartan lacks detrimental effect on renal function, is effective in the treatment of mild-to-moderate hypertension in patients with moderate renal failure,and is comparable to enalapril.

Effect of acute ethanol loading on parathyroid gland secretion in the rat.

Acute ethanol loading in the rat induces hypocalcemia and hypermagnesemia. In addition, hypocalcemia is not corrected by exogenous PTH. In the rat the mechanism of these changes was investigated by measuring plasma immunoreactive parathyroid hormone (PTH). PTH was also measured in culture medium in which parathyroid glands were incubated. The addition of ethanol to test tubes did not interfere with PTH measurement. Absolute ethyl alcohol diluted to 50% with distilled water was administered via an intragastric tube. It failed to induce an increase in plasma immunoreactive PTH level. Similarly, it prevented an increase in plasma PTH after disodium EDTA injection. Thus in the presence of ethyl alcohol plasma PTH failed to increase in spite of a significant decrease of plasma calcium. In vitro studies showed that the decrease of calcium concentration of the medium from 1.50 to 0.75 mmol/l was associated with a 3 to 5 times increase in PTH secretion rate. This increase was suppressed when ethanol was added to the culture medium. In conclusion, ethanol loading via gastric tubing induced: 1) decrease in plasma calcium; 2) suppression of immunoreactive PTH secretion in the presence of hypocalcemia. It is postulated that the acute hypocalcemic effect of ethanol loading is mediated by a dual effect at the level of the bone and the parathyroid gland.

Effect of parathyroid hormone on rat enterocyte Na transport in vitro.

In the presence of b.PTH (1.2 I.U./ml) in the incubation medium, the Na efflux rate constant (degree KNa) of isolated rat enterocytes was significantly reduced when compared to control experiments. The mean depression of degree KNa induced by b.PTH was 26% as compared to control (100%). No depressant effect of b.PTH on degree KNa was observed when the isolated enterocytes were incubated with ouabain (4.0mM). Thus, b.PTH appeared to inhibit the ouabain-sensitive Na pump. When incubating the isolated epithelial cells in an EGTA-containing Ca free medium, b.PTH lost its capacity to inhibit degree KNa. Thus, the presence of extracellular Ca appeared necessary for the inhibitory effect of b.PTH. In contrast to its effect on degree KNa, b.PTH induced no change of net Na uptake by isolated enterocytes. Moreover, b.PTH did not induce significant changes in enterocyte cAMP or cGMP concentrations. It was concluded that b.PTH exerted a direct inhibitory effect on the ouabain-sensitive Na efflux rate constant of isolated rat enterocytes. The effect of b.PTH occurred without a measureable activation of the cyclic nucleotide system but needed the presence of Ca in the incubation medium to be operative.

Effect of parathyroid hormone and volume expansion on jejunal calcium, sodium, and water transport in the rat.

The effects of PTH on jejunal calcium, sodium, and water transport were studied in the rat in situ. In TPTx rats, as well as in normal rats, bovine PTH induced a decrease in net calcium, sodium, and water absorption. Additionally, lumen-to-plasma calcium flux was found decreased in both groups. Stimulation of endogenous PTH secretion by calcium-poor hyperoncotic albumin resulted in a similar decrease in net calcium, sodium, and water absorption. It is suggested that PTH has a direct inhibitory effect on jejunal calcium, sodium, and water absorption.

Assessment of acetate free continuous veno-venous hemofiltration in acute renal failure.

Among the limitations of continuous renal replacement therapy (CRRT) in patients with severe acute renal failure (ARF) and cardiovascular instability is the use of acetate in the substitution fluid. Acetate is required to maintain acidity of the polyelectrolytic solution to avoid calcium carbonate precipitation in the presence of bicarbonate. In addition, in patients with cardiovascular instability, acetate metabolism is impaired and further compromises hemodynamics. A new CRRT technique is proposed in which bicarbonate is used as a buffer, but the acetate requirements are cancelled: acetate free veno-venous hemofiltration (AF-CVVH). This technique allows control of acid-base disturbances independent of urea removal. This preliminary report describes the feasibility of the technique based on separate infusion of water and electrolytes administered prefiltration, and isotonic sodium bicarbonate administered post filtration. The setting of the technique, adapted to the PRISMA device (Hospal, Lyon, France), was based on a model predicting the bicarbonate infusion rate for a target plasma bicarbonate level. The AF-CVVH was compared with conventional, continuous veno-venous hemofiltration (CVVH) in a crossover study that showed AF-CVVH allowed fastest control of acidosis, avoiding 70 to 80 mmol/d of acetate transfer to the patient. Urea removal was similar with both techniques. It was concluded that AF-CVVH, when compared with CVVH, has the main advantage of separately controlling urea retention and metabolic acidosis in patients with severe ARF and cardiovascular instability.

Detection of subclinical abdominal hernia by peritoneal scintigraphy.

This study investigated the incidence of subclinical abdominal hernia in patients starting peritoneal dialysis (PD). From April 1995 to August 1999, every new patient without clinical evidence of abdominal leakage underwent peritoneal scintigraphy. A total of 59 patients were enrolled in the study. Imaging of the peritoneal cavity was performed by mixing 74 MBq (2 mCi) of 99 m technetium sulfur colloid with 2 L of 1.36% dextrose peritoneal dialysis solution. Sequential gamma camera static images were obtained at 0 minutes, 60 minutes, and after drainage. Ten abdominal hernias (2 diaphragmatic leaks, 8 inguinal hernias) were observed in ten patients (6 males, 4 females; mean age: 65.1 years). One patient with diaphragmatic leak recovered partial renal function and stopped continuous ambulatory peritoneal dialysis (CAPD); the other was switched to automated peritoneal dialysis (APD). Among the eight patients with inguinal hernia, six had no clinical manifestations within eight months of follow-up. Two patients became symptomatic at 15 months and 25 months respectively. They underwent surgical repair. In CAPD patients without obvious abdominal hernias, peritoneal scintigraphy at onset of dialysis discovered 17% positive cases. The technique of scintigraphy is safe, with a low radiation exposure. Surgical repair for maintenance on CAPD is not always necessary, and a change in the PD strategy may be useful.

Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure.

OBJECTIVE: To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. DESIGN: Open randomised multicentre trial with three year follow up. SETTING: Outpatient departments of six French hospitals. PATIENTS: 100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). INTERVENTIONS: Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. RESULTS: 17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. CONCLUSION: In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.

[Value of renal scintigraphy in the diagnosis of vascular complications of renal transplantation]. / Intérêt de la scintigraphie rénale dans le diagnostic des complications vasculaires de la transplantation rénale.

Nuclear medicine can make an efficient contribution to the diagnosis and monitoring of renal disease and to the assessment of therapeutic interventions in the field of renal transplantation. The new radio pharmaceutical MAG 3 labelled with 99mTc provides renal imaging of quality in patients with impaired renal function and enables quantitative evaluation of renal function. We report on radionuclide evaluation, with special emphasis on the analysis of the vascular component of the scintigram, in the different clinical situations (i.e. renal failure) that may compromise the outcome of a successful renal transplant.

[Chronic renal failure and hypertension in community cardiology practice]. / Insuffisance rénale chronique et hypertension en pratique cardiologique de ville.

OBJECTIVE: A sustained increase in the incidence of vascular nephropa-thies has been recently documented in western countries and correlated with aging. Renal failure is often ignored in patients with hypertension and its diagnosis made too late, at the stage of replacement therapy, with an increased mortality rate and prolonged hospitalization time. In clinical practice, the diagnosis of renal insufficiency is based on the measurement of serum creatinine, which depends on muscular mass, gender and age of the subject and is regulated by glomerular filtration. Therefore, serum creatinine level does not give a correct estimate of renal function. According to Good Clinical Practice recommendations, serum creatinine must be used to calculate creatinine clearance, a surrogate of glomerular filtration. To avoid methodological constraints of clearance measurement with precise urine recollection, the index proposed by Cockcroft and Gault is highly reliable and widely used. PATIENTS AND METHOD: An epidemiological survey has been carried out to measure the prevalence of renal insufficiency in hypertensive patients regularly followed by cardiologists. This open, transverse study compared estimates of renal function based upon serum creatinine level and creatinine clearance using the Cockcroft and Gault's formula. Among 1,000 private cardiologists randomly selected in metropolitan France, 707 entered the study. During the last week of May 2000, they included 2,100 hypertensive patients using a questionnaire describing individual patient's demographic and clinical characteristics. RESULTS: The mean age of hypertensive patients was 65.9 +/- 12.2 years. They used antihypertensive drugs for a mean 10.3 +/- 7.7 years. The prevalence of renal failure, as defined by a creatinine clearance lower than 60 ml/min, was 32%, whereas 61% of the patients had a creatinine clearance below 80 ml/min. In contrast, 71% of the patients were subjectively considered to have a normal renal function. This discrepancy reflects underdiagnosis of mild to moderate renal failure. Hypertensive patients with renal failure did not present with excess cardiovascular risk factors and comorbidities when compared with those having a normal renal function. Prevalence of type 2 diabetes and hypercholesterolemia was similar in both groups. CONCLUSION: The present study outlines the discrepancy between theoretical knowledge and practical assessment of renal insufficiency in handling hypertensive patients, in the particular setting of cardiologist practice. In order to suppress this gap, the Cockcroft and Gault formula must be widely used. It is suggested that body weight, in addition to gender and age, may be printed together with serum creatinine concentration on the biology form given to patient.

[Early failure in kidney transplantation]. / Echecs précoces en transplantation rénale.

Parameters of early failure in kidney transplantation have been analyzed from 507 transplantations with transplant loss in the first month, selected among the 7541 cadaveric kidney transplantations performed in France between 1985 and 1989. These failures represent 6.7 percent of the population transplanted over this period of time, 68.6 percent of the failures that occurred in the first 3 months post-grafting, and 47 percent of the total number of the first year failures. Comparing patients with and without transplant failure in the first month, sex of the donor and the recipient, ABO group of the donor and the recipient, origin of the kidney, cold ischemia time, HLA compatibility, dialysis duration, number of previous transplantations, showed no influence on the occurrence of early failure. Three parameters appeared to be significant risk factors: donor's age less than 5 years, P = 0.00001; recipient's age less than 5 years, P = 0.05; pregraft immunization, P = 0.002. Furthermore, multifactorial analysis showed that the absence of HLA compatibilities between donor and recipient in hyperimmunized patients also has a significant influence on early graft loss. However, comparison of these same parameters in patients with transplant failure within the first month and between 2 and 12 months post-grafting revealed that the influence of these 4 significant parameters is longstanding and that none of them is specific of the precocity of graft loss.

[Synthesis of collagen in culture of endothelial cells of the human umbilical vein. Effects of cyclosporine A]. / Synthèse de collagène par les cellules endothéliales de veine ombilicale humaine en culture. Effets de la ciclosporine A.

Interstitial renal fibrosis and gingival hypertrophy are frequent side-effects of cyclosporin A which have been attributed to a dysfunction of extracellular matrix synthesis. Endothelial cells might participate in the matrix accumulation observed. We studied the effects of increasing concentrations of cyclosporin A on protein synthesis by human umbilical vein endothelial cells. Collagen synthesis decreased significantly to 800 ng/ml in both medium and cell layer. The percentage of hydroxylation of its proline residues decreased significantly as from 400 ng/ml. The main proteins, analysed by SDS-PAGE, were thrombospondin, fibronectin and the alpha 1 and alpha 2 chains of type IV collagen. These fractions did not show any change after 24 hours exposure to 200 ng/ml of cyclosporin A. These results demonstrate an inhibitory effect of cyclosporin A on collagen synthesis by human umbilical vein endothelial cells. Consequently, matrix accumulation by increased collagen synthesis in cyclosporin A treated patient may not be directly related to the drug effect on endothelial cells.