Studies on the Mechanism of Oliguria in a Model of Unilateral Acute Renal Failure

216

A B S T R A C T Administration of 25 mg/kg uranyl nitrate (UN) to rats leads to a brief period of polyuria followed by progressive oliguria with death at 5 days. Factors that determine glomerular filtration rate (GFR) were examined in control Munich-Wistar rats (n = 16) and 2 h after either 15 mg/kg (n = 8) or 25 mg/kg (n = 7) of UN (i.v.) utilizing direct measurements of hydrostatic and oncotic pressures and plasma flow. Total kidney GFR was reduced to 47% of control in the low dose group and to 21% in the high dose group. The simultaneous nephron filtration rate (sngfr) was 28.6± 0.8 nl/min/g kidney wt in control, 29.1-'-1.0 in the low dose group, and 18.1±+1.2 (P < 0.001) in the higher dose group. This disparity in UN effect upon GFR and sngfr was due to tubular back-diffusion of solute through damaged epithelia beyond the early proximal tubule as demonstrated by microinjection of inulin and mannitol in the proximal tubule. Inulin "leak" persisted at 6 h after UN when tubular pressure had returned to normal. Comparison of sngfr measured in early vs. late proximal tubule revealed no difference after high dose UN, suggesting no significant leak of inulin from the early proximal tubule, and that the decreased sngfr was due to primary reductions in ultrafiltration. Nephron plasma flow was equal to control at both doses of UN. Also directly measured hydrostatic pressure gradient across the glomerular capillary was not changed. The effective filtration pressure achieved equilibrium in control animals but became significantly positive at the efferent end of the capillary at both doses of UN and increased. Total glomerular permeability (LPA) was progressively reduced from control (0.089±0.005 nl/s/g kidney wt/mm Hg) at low Portions of this work were presented at the Annual Meeting of The

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

The mechanism of acute renal failure after uranyl nitrate.

Blantz¹

1975

216

“…The sequence of injection was alternated. Total RBF was measured using a modified indicator dilution technique with the microspheres as previously described and validated from this and other laboratories (11,14,15). Glomerular filtration rate (GFR) was estimated from the clearance of inulin.…”

Section: Methodsmentioning

confidence: 99%

The effect of inhibition of prostaglandin synthesis on urinary sodium excretion in the conscious dog.

Kirschenbaum¹,

Stein²

1976

115

A B S T R A C T Studies were performed to determine the effect of decreased endogenous release of renal prostaglandins on urinary sodium excretion. Two structurally dissimilar inhibitors of prostaglandin synthesis were employed, and studies were performed in conscious dogs allowed to recover from prior surgical instrumentation. Either meclofenamate (2 mg/kg) or the competitive prostaglandin inhibitor RO 20-5720 (1 mg/kg) was given to seven unanesthetized dogs undergoing a water diuresis. The administration of either prostaglandin inhibitor did not alter glomerular filtration rate, renal plasma flow, urinary volume, or potassium excretion. Sodium excretion, however, increased from 32 to 130 ueq/min (P <0.02). Essentially, the entire increase in sodium excretion was due to an increase in urinary sodium concentration from 7.7 to 28.3 meq/liter (P < 0.02). On a different day, the same animals were studied before and after administration of the diluent of the prostaglandin inhibitor. No change was noted in sodium excretion or any other parameter.Thus, these findings suggest that prostaglandin inhibition in the conscious dog is associated with a natriuresis without a change in urinary volume or potassium excretion during water diuresis. This may indicate that the natriuresis was due to diminished sodium reabsorption beyond the distal tubule.

“…In sodiumloaded rats, administration of UN did not significantly reduce GFR (Table IV) In glomerular capillaries, the total area of epithelial slit pores has been considered to be the major determinant of water permeability (8). In some models of acute renal failure epithelial alterations have been found and it has been suggested that these alterations may be responsible for the decline in glomerular Kf (4,5). However, several observations are against this possibility.…”

Section: Resultsmentioning

confidence: 99%

“…Reduction in ultrafiltration coefficient (Kf) of glomerular capillaries is one of the several abnormalities that has been identified in uranyl nitrate (UN)'-induced acute renal failure in rats (1)(2)(3)(4)(5)(6). However, the reason for the decline in glomerular capillary Kf is not understood.…”

Section: Introductionmentioning

confidence: 99%

Glomerular Endothelial Cells in Uranyl Nitrate-induced Acute Renal Failure in Rats

Avasthi¹,

Evan²,

Hay³

1980

A B S T R A C T In uranyl nitrate (UN)-induced acute renal failure (ARF) glomerular ultrafiltration coefficient (Kf) decreases because of unknown reasons. Since transport of water across the glomerular capillary wall occurs predominantly extracellularly through the endothelial fenestrae (EF), a reduction in the diameter and/or the density of EF can reduce the extracellular filtration area and the glomerular Kf. To examine this possibility, ARF was induced in rats by intravenous administration of UN in low (15 mg/kg) and high doses (25 mg/kg). Fenestral density (i±SEM) per 5 cm2 from the scanning electron micrographs (x30,000) was 107+10, 103+9, and 101+11 at 2, 7, and 17h after the intravenous administration of bicarbonate saline to the control rats. In the low-dose UN group the EF density was 91±2, 52+8, and 45± 11 at 2, 7, and 17 h after the injection, whereas for the high-dose group at corresponding time intervals the EF density was 95±3, 54±9, and 44± 10. Fenestral diameters, in Angstrom units (i± SEM), were 751±53, 765+43, and 764±37 at 2, 7, and 17 h after the injection of bicarbonate saline to control rats. At corresponding intervals after the administration of UN, the fenestral diameters were 501±61,472+28, and 438±98 for the lowu-dose group and 525+43, 470+39, and 440± 56 for the high-dose group. 2,7, and 17 h after the injection of UN, fenestral area of the low-dose group decreased to 52.1,30.1, and 24.6% ofthe controls, whereas in the high-dose group, the fenestral area declined to 54.3, 30.2, and 23.6% of the controls. Administration of UN (15 mg/kg) to sodium-loaded rats did not alter renal function or endothelial cell morphology. It is suggested that in UN-induced ARF the morphological alterations in endothelial cells reduce the Kf of glomerular capillaries by reducing the filtration area.