Chronic injury of human renal microvessels with low-dose cyclosporine therapy
| Autor: | Richard K. Sibley, Christopher Boshkos, William H. Frist, Lynne Newton, John A. Macoviak, Bryan D. Myers, Geraldine C. Derby, Mark G. Perlroth |
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| Rok vydání: | 1988 |
| Předmět: |
Graft Rejection
medicine.medical_specialty Cardiac Catheterization Afferent arterioles Renal glomerulus Urology Renal function Hemodynamics Cyclosporins Kidney Kidney Function Tests Renal Circulation Internal medicine Medicine Humans Transplantation business.industry Microcirculation Arcuate vein medicine.disease Endocrinology medicine.anatomical_structure Vascular resistance Heart Transplantation Kidney Diseases Azotemia business |
| Zdroj: | Transplantation. 46(5) |
| ISSN: | 0041-1337 |
| Popis: | Physiologic and morphologic techniques were used to study kidneys of cardiac transplant recipients treated with either low-dose (low-CsA) or high-dose (high-CsA) cyclosporine. After 12 months both low-CsA (4.6 +/- 0.4) and high-CsA (6.3 +/- 0.3 mg/Kg/24 hr, p less than 0.01) were associated with azotemia and hypertension; GFR with each regimen was depressed below values in a third group treated without CsA (no-CsA) by 40-47%, while corresponding renal vascular resistance was elevated greater than 2-fold (P less than 0.01). Morphologic changes in both CsA groups included an obliterative arteriolopathy with downstream collapse or sclerosis of glomeruli. Determination of renal arcuate vein occlusion pressure revealed an increasing renal artery-to-peritubular capillary pressure gradient between 1 and 12 months of CsA therapy. Fractional clearances of dextrans of graded size were elevated at each time compared with the no-CsA group. Analysis of dextran transport with an isoporous membrane model indicates that transglomerular hydraulic pressure difference (delta P) approximated 39 with no-CsA, but was reduced with low-CsA therapy to about 30 at 1 month, and about 34 mmHg after 12 months. We conclude that chronic CsA therapy induces constriction and eventual occlusion of afferent arterioles, causing downstream glomerular damage that is irreversible. Low versus high dosage of CsA confers only marginal protection against this serious microvascular injury. |
| Databáze: | OpenAIRE |
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