[Study on the role of the tubule in renal vasoconstriction induced by cyclosporine].
BACKGROUND
Cyclosporine (CyA) has proved to induce cell apoptosis on cultured proximal tubule cells. However, there is no much data about the in vivo functional consequences of this injury or the long time observed CyA-induced renal vasoconstriction.


METHODS
In a swine model of subacute CyA nephrotoxicity (10 mg/ Kg. dx 15 days), we performed a right nephrectomy, followed by left renal artery, vein and ureter catheterisati8n. After inducing water diuresis, three clearance periods of 15 minutes were performed before and after a furosemide 1 mg/kg infusion. Plasma and urine electrolytes, blood gas, acid excretion, plasma renin activity and aldosterone concentration, GFR, RPF, RBF, intra-renal vascular resistances, glomerular filtration pressure, distal Cl- delivery, water clearance and TTKG were measured or estimated on 7 control and 7 treated animals. Right kidney was processed for NaKATPase activity and immunostaining.


RESULTS
Treated animals presented detaching proximal cells, luminal blebbing and loss of tight junctions. Cortical but not medullar sodium pump was internalised and partially inactive. Treated animals showed much lower fractional excretions of Na+, with significantly higher distal fractional reabsorption of Cl. Distal shift in fluid load resulted in a significant rise in renal O2 consumption, and modifications in the global renal estequiometry of Na+ transport/O2 uptake. Several consequences followed this situation: preglomerular resistances increased 3 times with only minor changes in postglomerular resistances and renal blood and plasma flow were significantly reduced. Furosemide partially reversed these effects. A slight increase in fractional filtration prevented GFR differences to become statistically significant.


CONCLUSIONS
subacute CyA treatment even al doses not modifying GFR, may cause proximal tubule Na+ transport impairment, resulting in increased rates of distal delivery and absorption of fluid load. Renal uptake of O2 may be increased and tubule glomerular feedback should be expected to be activated. Absence of changes of GFR with furosemide is an early sign of CyA renal damage.
Camaño Páez
S
S
Servicio de Nefrologia, Laboratorio de Fisiopatología Renal, Hospital General Univ. Gregorio Mararñón, Madrid.
Lázaro Fernández
A
A
Callejas Martínez
R
R
Lázaro Manero
J A
JA
Castilla Barba
M
M
Martín-Vasallo
P
P
Martínez Escandell
A
A
Tejedor Jorge
A
A
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D014661:Vasoconstriction / Q000187:drug effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine