Vascular Biology – Hemodynamics – Hypertension
Kidney International (2003) 63, 994–1002; doi:10.1046/j.1523-1755.2003.00811.x
Mycophenolate mofetil prevents arteriolopathy and renal injury in subtotal ablation despite persistent hypertension
Edilia Tapia, Martha Franco, Laura G Sánchez-Lozada, Virgilia Soto, Carmen Avila-Casado, José Santamaría, Yasmir Quiroz, Bernardo Rodríguez-Iturbe and Jaime Herrera-Acosta
Departments of Nephrology and Pathology, Instituto Nacional de Cardiología "Ignacio Chávez," México City, México; and Renal Service and Laboratory, Hospital Universitario and Instituto de Investigaciones Biomédicas, Maracaibo, Venezuela
Correspondence: Edilia Tapia, M.D., Department of Nephrology, Instituto Nacional de Cardiología, Juan Badiano No. 1, México City, Tlalpan 14080, México. E-mail: ediliatapia@hotmail.com
Received 14 June 2002; Revised 6 September 2002; Accepted 16 November 2002.
Abstract
Mycophenolate mofetil prevents arteriolopathy and renal injury in subtotal ablation despite persistent hypertension.
Background
Although renal protective effect of interrupting the inflammatory process is well established, it is still controversial if it also prevents the glomerular hemodynamic disturbances that initiate renal injury. We investigated the effects of suppressing inflammation with mycophenolate mofetil (MMF) on glomerular hemodynamics, arteriolar structural changes, and renal histologic injury in rats with subtotal renal ablation
Methods
Micropuncture studies were performed 30 days after 5/6 nephrectomy in rats untreated and treated with MMF (30 mg/kg/day). Renal histology, immunohistochemistry for lymphocytes, macrophages and inducible nitric oxide synthase (iNOS) expression, as well as afferent arteriolar (AA) morphometry was evaluated.
Results
Renal ablation significantly increased proteinuria (6.8 to 82.7 mg/day), mean arterial pressure (MAP) (120 to 166 mm Hg), single-nephron glomerular filtration rate (SNGFR) (34.8 to 56.3 nL/min), glomerular plasma flow (QA) (117.7 to 246.9 nL/min), and glomerular capillary pressure (PGC) (48.9 to 61.0 mm Hg). Afferent resistance (AR), efferent resistance, and ultrafiltration coefficient remained unchanged. Despite persisting arterial hypertension (152 mm Hg), MMF prevented proteinuria (13.3 mg/day), and significantly reduced SNGFR (44.4 nL/min), PGC (49.1 mm Hg), and QA (163.2 nL/min) due to a rise in AR (3.13 vs. 2.18 1010 dyn/sec/cm-5). Glomerular sclerosis, tubulointerstitial damage, lymphocyte and macrophage infiltration, and iNOS expression were significantly reduced by MMF, in addition hypertrophy of AA resistance evaluated by the media/lumen ratio was prevented (P < 0.001).
Conclusions
Reduction in proteinuria, SNGFR, QA, and PGC, despite elevated MAP, indicate preservation of AA function. These results suggest that inflammation associated arteriolopathy of AA contributes to glomerular hemodynamic disturbances that participate in the progression of renal disease.
Keywords:
glomerular hemodynamics, arteriolopathy, mycophenolate mofetil, 5/6 nephrectomy, inflammation
