Renal hemodynamics in acute renal failure.
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Biomedical subjects
Publications and source records attributed to J D Conger.
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Tubular fluid flow, urine osmolality, and pH were selectively altered to determine the relative protective roles of these factors in a rat model of acute urate nephrophathy. Various prehyper uricemic conditions were established in five groups of animals: (a) normopenic Wistar rats given no pretreatment (Group I); (b) Wistar rats given acetazolamide, 20 mg/kg, and isotonic NaHCO3 to produce urine alkalinization (Group II); (c) Wistar rats in which a moderate diuresis, similar to that observed in Group II but without urine alkalinization, was induced with furosemide, 2 mg/kg (Group III); (d) Wistar rats in which a high-flow solute diuresis was induced with furosemide, 15 mg/kg (Group IV); (e) Brattleboro rats, homozygous for pituitary diabetes insipidus, that had a spontaneous high-flow water diuresis (Group V). A comparable level of hyperuricemia (19.4+/-2.2 mg/100 ml) was achieved in all animals with intravenous urate infusion. Clearance and micropuncture studies were performed before and 1 h after induction of hyperuicemia. Group I rats had mean falls in renal plasma flow and glomerular filtration rate of 83 and 86%, respectively; nephron filtration rate decreased 66%, and tubular and microvascular pressures increased twofold. In Group II there were 45 and 47% declines in renal plasma flow and glomerular filtration rate, respectively, a 66% fall in nephron filtration rate, and a 30% increase in tubular and vascular pressures. Moderate amounts of urate were seen in the kidneys. Group III had changes in renal function identical to Group II suggesting that the moderate prehyperuricemic diuresis in the latter group and not urine alkalinization produced the partial protection observed. Groups IV and V were completely and comparably protected with renal function studies unchanged from controls. It is concluded that high tubular fluid flow, whether induced by a solute or water diuresis, is the primary mechanism of protection in acute urate nephropathy. At most, urine alkalinization plays a minor preventive role.
Autopsy protocols and microscopic slides of 56 dialyzed and 18 nondialyzed chronically uremic patients were reviewed to assess the presence, extent, and severity of extraosseous soft tissue calcification. Calcification was identified in 79% of the dialysis patients and 44% of the nondialysis patients (P iss less than .025). Soft tissue calcification most frequently involved the heart, lungs, stomach, and kidneys. Lesions were severe in 36% of the dialysis patients and, when strategically located within the myocardium, were life-threatening. The deaths of 6 dialysis patients were attributed to severe calcification of the cardiac conduction system and/or myocardium. The presence and severity of soft tissue calcification was not related to duration of dialysis, patients' age, degree of parathyroid gland hyperplasia, radiographic evidence of soft tissue calcification, serum calcium and phosphate levels, Ca X P products, or type or severity of metabolic bone disease.
1. Peritubular capillary microperfusion was used to examine the effects of protein-free and hyperoncotic homologous plasma on fluid reabsorption by proximal convoluted tubules in the hydropenic rat. 3H-labelled p-aminohippurate was added to perfusates for the purpose of estimating the extent to which tubules under study were bathed by the perfusates. [14C]Mannitol was added to perfusates in order to detect contamination of collected tubular fluid by perfusates. 2. Hydrostatic pressures were monitored in the peritubular microvasculature and adjacent proximal tubules during perfusion. Evidence for secretion of p-aminohippurate from perfusate into tubules under study was determined by collecting tubular fluid from both early and late puncture site. Fractional and absolute reabsorption were not affected by either the protein-free or the hyperoncotic plasma. 3. When acetazolamide was added to the perfusate both fractional and absolute reabsorptive rates decreased by an average of 36%, indicating that the techniques were capable of detecting a decrease in proximal tubular reabsorption. 4. It is concluded that under the conditions of this study changes in peritubular capillary protein concentrations have no detectable effect on the rate of proximal convoluted tubule fluid reabsorption.
Controversy has existed over apparent dissimilarities in the autoregulatory capacities of the rat and dog. A protocol was designed to evaluate both the effects of the anesthetic agents. Nembutal (used most commonly in dogs) and Inactin (most frequently employed in rats) and the species peculiarities of these two mammals on autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). With Nembutal autoregulation of RBF was present in both experimental animals. Inactin impaired RBF autoregulation similarly in both species. With impaired RBF autoregulation similarly in both species. With either anesthetic GFR was autoregulated well in both rat and dog. Comparison of the two species revealed a greater RBF per gram kidney weight and a higher renal perfusion pressure (RPP) at which autoregulation of both hemodynamic parameters was lost in the rat. It is concluded from these studies that 1) the frequent use of Inactin in the rat in large part accounts for the observed lack of autoregulation of RBF in this animal and 2) renal hemodynamic responses are qualitatively similar in rat and dog when the same anesthetic agents are used.
The early pathophysiological changes in acute urate nephropathy were investigated in a rat model using micropuncture, clearance, and morphologic methods. Plasma urate was increased from 1.2 +/- 0.6 to 20.1 +/- 3.1 mg/100 ml (P less than 0.001). Urinary urate rose from 24.3 +/- 5.1 to 142.2 +/- 21.0 mg/100 ml (P less than 0.001). Renal plasma flow and glomerular filtration rate fell to 17 and 14% of control values, respectively, and urine flow rate decreased from 11.3 +/- 4.8 to 4.2 +/- 2.2 mul/min (all P less than 0.005) Superficial nephron filtration rate fell less than that of the whole kidney (70 vs. 86%). Both proximal and distal tubular pressures were increased from 10.6 to 26.1 mm Hg and from 7.2 to 24.7 mm Hg, respectively (P less than 0.005). Efferent arteriolar and peritubular capillary pressures were increased twofold. Vascular resistance beyond the peritubular capillaries increased from 4.8 X 10(9) to 21.6 X 10(9) dynes s/cm5. Extensive deposits of uric acid and urate were found in the tubular system and vasa recti from the corticomedullary junction to the tip of the papilla. It is concluded from these experiments that not only tubular obstruction in the collecting ducts, but also obstruction of the distal renal vasculature, are the primary early pathogenetic events in acute urate nephropathy.
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A prospective study of 31 chronically hemodialyzed patients was made to investigate the incidence and pathology of pulmonary calcification and the relation of the latter to ventilatory function. Fifteen of the patients have died thus far; 9 had evidence of lung calcification. The lesions occurred predominately in alveolar septa and were associated with varying degrees of fibrosis and alveolar septal thickening. Only one patient had X-ray evidence of calcification. An X-ray diffraction analysis showed a predominant pattern of whitlockite (CaMg)3(Po4)2 in deposits. Patients with the severest pulmonary calcification had abnormalities of vital capacity, carbon monoxide diffusion, and Po2. Serum calcium levels were slightly higher in patients with calcification, but there was no measurable association with the duration of dialysis, serum phosphorus, calcium X phosphorus product, magnesium, bicarbonate, or arterial pH. These data show that pulmonary calcification occurs with high frequency in patients undergoing long-term hemodialysis and that such lesions are associated with restrictive and diffusion ventilatory defects.
Micropuncture techniques in the rat were used to reinvestigate the possibility that intraluminal flow rate per se may influence net volume reabsorption by the proximal tubule. An experimental design was devised which lowered intraluminal flow without affecting filtration rate of the nephron under study or without directly affecting other renal hemodynamics. In 11 rats flow of tubular fluid between early and late proximal tubular sites was reduced by partially collecting tubular fluid at the early puncture site. In 42 nephrons the rate of flow of tubular fluid was reduced an average of 45% without changing nephron filtration rate and there was an associated reduction in reabsorption between the two sites which averaged 29%. This indicated 63% balance between delivery of tubular fluid and the rate of reabsorption between two sites along proximal tubules. The results of these studies indicate that a reduction in delivery of normal filtrate along the proximal tubule is associated with a concordant reduction in the absolute rate of reabsorption. Since this relationship occurred in the absence of changes in renal hemodynamics or even a change in filtration rate of the nephron under study it is concluded that changes in intraluminal load per se play an important role in the phenomenon of glomerulotubular balance.
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