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1.
Anticancer Drugs ; 4(1): 85-90, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8457719

ABSTRACT

The aim of this study was to compare the renal tolerance of cisplatin and carboplatin in euvolemic and dehydrated rats. A total of 79 euvolemic or dehydrated male rats were randomly assigned to receive cisplatin (5 mg/kg body weight, i.p.), carboplatin (40 mg/kg body weight, i.p.) or vehicle. Body weight, serum creatinine, creatinine clearance, fractional excretion of sodium and urinary NAG excretion were recorded on days 1 and 5. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and renal histology were determined on day 5. In the euvolemic and dehydrated control and carboplatin groups we observed no change in serum electrolytes, serum creatinine, creatinine clearance, GFR and ERPF. In the euvolemic and dehydrated control groups we observed no change in urinary NAG excretion. Carboplatin induced a slight but significant increase in urinary NAG excretion. In dehydrated rats carboplatin induced a significantly higher increase in urinary NAG excretion than in euvolemic rats. Cisplatin induced a marked and significant decrease in GFR and ERPF, and a significant increase in NAG. Dehydration markedly potentiated cisplatin nephrotoxicity. Euvolemic rats treated with cisplatin exhibited slight renal lesions with a mean score which was similar to the control group. The most extensive lesions were observed in euvolemic and dehydrated cisplatin treated rats with tubular necrosis in the outer stripe of the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Carboplatin/toxicity , Cisplatin/toxicity , Dehydration/physiopathology , Kidney Diseases/chemically induced , Animals , Body Weight/drug effects , Creatinine/blood , Dehydration/blood , Dehydration/complications , Drug Tolerance , Glomerular Filtration Rate/drug effects , Kidney Diseases/blood , Kidney Diseases/physiopathology , Male , Plasma Volume/drug effects , Rats , Rats, Sprague-Dawley , Water-Electrolyte Balance/drug effects
2.
Ann Intern Med ; 117(7): 578-83, 1992 Oct 01.
Article in English | MEDLINE | ID: mdl-1524331

ABSTRACT

OBJECTIVE: To determine the renal side effects of long-term, low-dose cyclosporine therapy (initial dose, 5 mg/kg body weight per day) in patients with autoimmune idiopathic uvetis. DESIGN: Cohort study with at least 2 years of follow-up. SETTING: A teaching hospital in Paris, France (Hôpital Pitié-Salpétrière). PATIENTS: Sixteen patients with idiopathic autoimmune uveitis who were normotensive and had normal renal function before treatment. Cyclosporine was administered orally for at least 2 years at an initial dosage of 5 mg/kg body weight per day. RESULTS: After 2 years of treatment, the serum creatinine level increased by 35 +/- 5 mumol/L (0.40 +/- 0.06 mg/dL) (95% CI, 25 to 46 mumol/L, [73 +/- 4 to 108 +/- 4 mumol/L]). Creatinine clearance decreased significantly from 120 +/- 5 mL/min to 75 +/- 4 mL/min. Glomerular filtration rate decreased from 116 +/- 8 mL/min to 75 +/- 3 mL/min, and effective renal plasma flow decreased from 455 +/- 24 mL/min to 338 +/- 30 mL/min (P less than 0.05). Cyclosporine induced a significant increase in serum uric acid, total cholesterol, and serum potassium levels. Blood pressure was normal in all patients before treatment; 81% (95% CI, 64% to 98%) of these patients developed hypertension after 24 months of treatment. Blood pressure was controlled with a single drug in all but two patients. CONCLUSIONS: In patients with healthy native kidneys, long-term cyclosporine therapy, even at a low dose (5 mg/kg per day), is nephrotoxic and is associated with a high incidence of hypertension.


Subject(s)
Autoimmune Diseases/drug therapy , Cyclosporine/adverse effects , Hypertension/chemically induced , Kidney Diseases/chemically induced , Uveitis/drug therapy , Adult , Cholesterol/blood , Creatinine/blood , Cyclosporine/administration & dosage , Drug Administration Schedule , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Humans , Kidney Diseases/blood , Kidney Diseases/physiopathology , Male , Middle Aged , Potassium/blood , Triglycerides/blood , Uric Acid/blood , Uveitis/immunology
3.
Nephrol Dial Transplant ; 7(4): 300-5, 1992.
Article in English | MEDLINE | ID: mdl-1317519

ABSTRACT

The aims of the present study were to determine plasma endothelin (ET) in chronically uraemic patients, the renal clearance of endogenous ET in normal dog and man, and the effect of acute volaemic expansion on ET. The mean plasma ET concentration in haemodialysis patients was 57.5 +/- 5 pg/ml before haemodialysis and remained unchanged at 52.5 +/- 5 pg/ml after haemodialysis. They were thus significantly elevated both before and after haemodialysis (P less than 0.01) compared with plasma ET in normal subjects of 20.8 +/- 0.8 pg/ml. There was no evidence of ET clearance across the cuprophane membrane of the dialyser. Resting plasma ET values in the 15 non-dialysed uraemic patients ranged between 20 and 52.5 pg/ml (mean 38.2 +/- 2.3 pg/ml), significantly greater than those observed in controls (P less than 0.01). In CAPD patients, plasma ET was also significantly (P less than 0.01), elevated (63 +/- 10 pg/ml) when compared to controls, and similar to those observed in patients before haemodialysis. In dogs, mean ET did not diminish between the aorta and the renal vein (28.1 +/- 1 versus 28.4 +/- 2 pg/ml). In man mean ET did not significantly decline between the renal artery and the renal vein (17 +/- 3 to 13 +/- 0.8 pg/ml). In the seven healthy subjects who received 2000 ml of isotonic saline intravenously ET remained unchanged (24 +/- 2; 23 +/- 1 and 23 +/- 2 pg/ml before and 1 and 2 h after starting hydration respectively). We have thus shown that plasma ET is elevated in patients with chronic renal failure especially those on dialysis and CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Endothelins/blood , Kidney Failure, Chronic/blood , Animals , Blood Volume , Dogs , Female , Humans , Isotonic Solutions , Kidney Failure, Chronic/therapy , Male , Middle Aged , Peritoneal Dialysis, Continuous Ambulatory , Renal Dialysis , Sodium Chloride/administration & dosage , Uremia/blood , Uremia/therapy
4.
Am J Nephrol ; 12(6): 425-30, 1992.
Article in English | MEDLINE | ID: mdl-1337961

ABSTRACT

Renal tubular acidification function was studied in 12 patients treated with cyclosporine (Cy) for idiopathic uveitis (IU) and in 5 patients with IU not treated with Cy. After intravenous bicarbonate loading fractional bicarbonate excretion was similar in both groups indicating normal proximal tubular acidification function. Plasma renin activity, plasma aldosterone and transtubular potassium gradient were similar in both groups. Distal hydrogen ion secretion evaluated by the ability to increase urine-blood (U-B) pCO2 in a highly alkaline urine was impaired in Cy-treated patients (31.8 +/- 3.2 mm Hg) as compared to controls (47.9 +/- 0.5 mm Hg) (p < 0.005). We conclude that Cy therapy is associated with a distal acidification defect with a low U-B pCO2 gradient during sodium bicarbonate loading. Because none of our Cy-treated patients spontaneously developed over metabolic acidosis one could classify them as having an incomplete form of distal tubular acidosis.


Subject(s)
Cyclosporine/adverse effects , Kidney Tubules/drug effects , Uveitis/drug therapy , Acidosis, Renal Tubular/chemically induced , Adult , Aged , Aldosterone/blood , Bicarbonates/administration & dosage , Bicarbonates/blood , Bicarbonates/urine , Carbon Dioxide/blood , Carbon Dioxide/urine , Cyclosporine/therapeutic use , Electrolytes/blood , Female , Humans , Hydrogen-Ion Concentration , Kidney Tubules/metabolism , Male , Middle Aged , Osmolar Concentration , Potassium/metabolism , Sodium/administration & dosage , Sodium Bicarbonate , Urine
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