A study of the intrarenal recycling of urea in the rat with chronic experimental pyelonephritis.

Abstract

A B S T R A C T The concentrating ability of the kidney was studied by clearance and micropuncture techniques and tissue slice analyses in normal rats with two intact kidneys (intact controls), normal rats with a solitary kidney (uninephrectomized controls), and uremic rats with a single pyelonephritic kidney. Urinary osmolality after water deprivation for 24 h and administration of antidiuretic hormone was 2,501+217 and 2,874±392 mosmollkg H20 in intact and uninephrectomized control rats, respectively, and 929±130 mosmol'kg H20 in pyelonephritic rats (P < 0.001 compared to each control group). Fractional water reabsorption and concentrating ability were significantly decreased in the pyelonephritic group, and, to achieve an equivalent fractional excretion of urea, a greater fractional excretion of water was required in the pyelonephritic rats than in the control rats.Whole animal glomerular filtration rate was 1.57 +0.19 ml/min and 1.39±0.18 ml/min in intact and in uninephrectomized controls, respectively, and 0.30 +0.07 ml/min in pyelonephritic rats (P < 0.001 compared to each control group). Single nephron glomerular filtration rate was 35.6±3.8 nl/min in intact control rats and was significantly increased (P < 0.05) in both uninephrectomized (88.0±10.8 nl/min) and pyelonephritic rats (71.5± 14.4 nl/min).

Effect of Febuxostat on the Progression of Renal Disease in 5/6 Nephrectomy Rats with and without Hyperuricemia

“…We do not have a definitive explanation for this behavior, however it is well known that urinary concentration decreases in response to a reduction of functioning renal mass [33], and this effect induces polyuria and increased water consumption. In this regard, it has been proposed that the disruption of medullary architecture due to interstitial fibrosis may contribute to the defect in urinary concentration by preventing the generation of a hypertonic medullary interstitium [34]. Because Fx treatment significantly reduced TI fibrosis in 5/6 Nx rats, it is possible that this effect may have had a salutary effect on the urine concentrating ability of the remnant kidney, resulting in normalized water consumption in Fx-treated animals.…”

Functional Profile of the Isolated Uremic Nephron

“…This abnormality is associated with an inability to concentrate the urine normally with failure to conserve free-water maximallv (9). Amonig the possible explanations for this phenomenon, anid one which could not be ruled out by the existing data was a diminished responsiveness to vasopression in the cortical collecting tubule.…”

“…This finding provides an important explanation for the observation that the diluting ability of the diseased kidney is well preserved long after the concentrating defect becomes overtly manifest (3,9). The ability of the diseased kidney to dilute the urine requires that the generation of' hypotonic fluid by the ascending limb is intact and that little or no equilibration occurs between this fluid and the hypertonic medullary interstitium in the collecting tubule.…”

“…The dif: fereniee between an absolute inability to concentrate the uirine above the osmolality of plasma (hyposthenitiria) and the ability to raise the urinary osmolality to a value slightly greater than that of' plasma is a (uiaintitative one only. If' it is accepted that the kidney in uremia can generate hypotonic tubular fluid (3,9) the absolute amount of water renmoved by the distal tubule and collecting tubule will determine the final urinie osmiiolality which mlay vary from hypo-to hypertonic. In the present study the resistanice to vasopressii was not complete.…”

“…We have recently described a disturbance of such urea recycling and failure to accumulate interstitial soluite in rats with chronic pyelonephritis (9). If vasopressin unresponsiveness is a component of the uremic state, it is highly likely that failure to abstract water from the cortical and outer medullary collecting tubules plays an important role in the failure of the diseased kidney to concentrate the urine normally.…”