ABSTRACT
Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 çg/mL); CsA (100 µg/mL); sirolimus (50 and 250 çg/mL) + CsA (100 µg/mL); control; vehicle (20 percent ethanol). For in vivo studies, 3-week-old Wistar rats (150-250 g) were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I) in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po), I + CsA (3 mg·kg-1·day-1, sc), I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR) at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min) but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min) despite the reduction in renal blood flow (3.9 ± 0.5 mL/min). Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.
Subject(s)
Animals , Male , Rats , Cyclosporine/administration & dosage , Immunosuppressive Agents/administration & dosage , Kidney Tubules, Proximal/drug effects , Kidney/blood supply , Reperfusion Injury/drug therapy , Sirolimus/administration & dosage , Cyclosporine/adverse effects , Drug Therapy, Combination , Glomerular Filtration Rate/drug effects , Immunosuppressive Agents/adverse effects , Kidney/pathology , Nephrectomy , Rats, Wistar , Reperfusion Injury/pathologyABSTRACT
One hundred and fifty consecutive percutaneous renal biopsies were performed using ultrasonography to localise the site and depth of the lower pole of the left kidney. Renal tissue was obtained in 95% of cases and an accurate histopathological diagnosis was reached in 89% of patients. Gross haematuria following the procedure occurred in 6%, but was usually transient. No other complications were encountered. Ultrasonographic marking of the biopsy site and depth is a quick, simple, accurate and safe method of localizing the kidney for the purpose of a biopsy.