Sébastien Sammut1, Luc Behr2, Mehrak Hekmati2, Marie Claire Gubler3, Kathleen Laborde4, Martine Lelièvre Pégorier5. 1. 1] IMM Recherche, Institut Mutualiste Montsouris Recherche, Paris, France [2] INSERM U 872, Centre de Recherche des Cordeliers UMRS 872, Université Pierre et Marie Curie - Paris 6, Paris, France [3] Université Paris Descartes - Paris 5, Paris, France. 2. IMM Recherche, Institut Mutualiste Montsouris Recherche, Paris, France. 3. INSERM U983, Hôpital Necker - Enfants Malades, Université Paris Descartes - Paris 5, Paris, France. 4. Department of Physiology, Hôpital Necker - Enfants Malades, Université Paris Descartes - Paris 5, Paris, France. 5. 1] INSERM U 872, Centre de Recherche des Cordeliers UMRS 872, Université Pierre et Marie Curie - Paris 6, Paris, France [2] Université Paris Descartes - Paris 5, Paris, France.
Abstract
BACKGROUND: Clinical and experimental studies show that unilateral (1/2Nx) and subtotal nephrectomy (5/6Nx) in adults result in compensatory renal growth without formation of new nephrons. During nephrogenesis, the response to renal mass reduction has not been fully investigated. METHODS: Ovine fetuses underwent 1/2Nx, 5/6Nx, or sham surgery (sham) at 70 d of gestation (term: 150 d), when nephrogenesis is active. At 134 d, renal function was determined, fetuses were killed, and kidneys were further analyzed at the cellular and molecular levels. Additional fetuses subjected to 5/6Nx were killed at 80 and 90 d of gestation to investigate the kinetics of the renal compensatory process. RESULTS: At 134 d, in 1/2Nx, a significant increase in kidney weight and estimated glomerular number was observed. In 5/6Nx, the early and marked catch-up in kidney weight and estimated glomerular number was associated with a striking butterfly-like remodeling of the kidney that developed within the first 10 d following nephrectomy. In all groups, in utero glomerular filtration rates were similar. CONCLUSION: Compensatory renal growth was observed after parenchymal reduction in both models; however, the resulting compensatory growth was strikingly different. After 5/6Nx, the remnant kidney displayed a butterfly-like remodeling, and glomerular number was restored.
BACKGROUND: Clinical and experimental studies show that unilateral (1/2Nx) and subtotal nephrectomy (5/6Nx) in adults result in compensatory renal growth without formation of new nephrons. During nephrogenesis, the response to renal mass reduction has not been fully investigated. METHODS: Ovine fetuses underwent 1/2Nx, 5/6Nx, or sham surgery (sham) at 70 d of gestation (term: 150 d), when nephrogenesis is active. At 134 d, renal function was determined, fetuses were killed, and kidneys were further analyzed at the cellular and molecular levels. Additional fetuses subjected to 5/6Nx were killed at 80 and 90 d of gestation to investigate the kinetics of the renal compensatory process. RESULTS: At 134 d, in 1/2Nx, a significant increase in kidney weight and estimated glomerular number was observed. In 5/6Nx, the early and marked catch-up in kidney weight and estimated glomerular number was associated with a striking butterfly-like remodeling of the kidney that developed within the first 10 d following nephrectomy. In all groups, in utero glomerular filtration rates were similar. CONCLUSION: Compensatory renal growth was observed after parenchymal reduction in both models; however, the resulting compensatory growth was strikingly different. After 5/6Nx, the remnant kidney displayed a butterfly-like remodeling, and glomerular number was restored.