Richard W. Baehler

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

To further evaluate the mechanism of the oliguria of acute renal failure, a model was utilized in which intense and prolonged vasoconstriction produced the unilateral cessation of urine flow. The radioactive microsphere method was used to measure total and regional blood flow before and after the intrarenal infusion of norepinephrine, 0.75 mug/kg/min, for 2 h in the dog. In the control kidney, renal blood flow increased 32% 48 h after norepinephrine in association with a fall in the fractional distribution of flow to the outer cortex. In the experimental kidney, total renal blood flow fell from 190 ml/min before norepinephrine to 116 ml/min at 48 h (P < 0.025) with a uniform reduction in cortical blood flow. After the administration of 10% body wt Ringers solution, there was a marked redistribution of flow to inner cortical nephrons in both the control and experimental kidney. In addition, there was a marked increase in total blood flow in both kidneys. On the experimental side, flow rose to 235 ml/min, a value greater than in either the control period (P < 0.05) or at 48 h after norepinephrine (P < 0.001). However, in spite of this marked increase in blood flow, there was essentially no urine flow from the experimental kidney. In separate studies, the animals were prepared for micropuncture. In all studies, the surface tubules were collapsed, and there was no evidence of tubular obstruction or leakage of filtrate. Over 99% of the 15-muM spheres were extracted in one pass through the experimental kidney. An analysis of the forces affecting filtration suggested that an alteration in the ultrafiltration coefficient may be responsible, at least in part, for the anuria in this model. In this regard, transmission and scanning electron microscopy revealed a marked abnormality in the epithelial structure of the glomerulus. It is suggested that a decrease in glomerular capillary permeability may be present in this model of acute renal failure.

Studies on the pathogenesis of Bartter's syndrome

There is no agreement concerning the primary pathogenetic event leading to Bartters syndrome. Free water clearance and distal fractional chloride reabsorption were abnormally low in our patient with Bartters syndrome. This series of investigations in this patient with Bartters syndrome and hypomagnesemia was undertaken to determine if the defect in chloride transport in the ascending limb and the associated renal potassium wasting was specifically related to potassium depletion, increased prostaglandin production or magnesium depletion. Neither potassium repletion, indomethacin administration nor magnesium repletion had an effect on the defect in free water clearance or in distal fractional chloride reabsorption. However, magnesium infusion eliminated renal potassium wasting. These observations suggest that the proximate cause of Bartters syndrome in this patient is a primary defect in the reabsorption of sodium chloride in the ascending limb and not renal potassium wasting. however, hypomagnesemia may contribute to the renal potassium wasting seen in this syndrome.

The Radiolabeled Frog Red Blood Cell: A NEW MARKER OF CORTICAL BLOOD FLOW DISTRIBUTION IN THE KIDNEY OF THE DOG

The red cell of the bullfrog Bufo vulgaris was used to measure the intrarenal distribution of blood flow in the kidney of the dog. These cells were fixed in 1% glutaraldehyde and labeled with sodium pertechnetate (99MTc); they were 18 × 10μ in size and had a specific gravity of 1.076—a value close to that of the dog red blood cell. These cells had no discernible effect on systemic or renal hemodynamics after injection, did not agglutinate, were well mixed and evenly distributed throughout different areas of the renal cortex, and were completely extracted in one circulation through the kidney. When the renal cortex was divided into four equal zones, the fractional distribution of the frog red blood cells was 39, 33, 20, and 8% going from the outer to the inner cortex. These values were not significantly different from those obtained in the same dogs with radioactive microspheres—particles much denser than the frog red cells. In two other models involving intrarenal acetylcholine administration and hemorrhagic hypotension, there was no difference between the regional blood flow distribution measured with the frog red cell method and that measured with the microsphere method. However, with both acetylcholine infusion and hemorrhage, there was a redistribution of renal cortical blood flow to the inner cortex compared with the distribution determined by either method during hydropenia. Thus, a similar intrarenal distribution of blood flow was found with two indicators of different size, shape, and density. We suggest that the primary rheologic factor affecting a particle such as a frog red blood cell or a microsphere markedly diluted among circulating red cells is its interaction with these normal cells.

Failure of chronic sodium chloride loading to protect against norepinephrine-induced acute renal failure in dogs.

We previously have shown that chronic sodium chloride (NaCI) loading protects against HgCI2-induced acute renal failure (ARF) in dogs. To determine whether NaCI loading protects against an ischemic model of ARF, unilateral oliguric renal failure was produced by the infusion of norepinephrine (NE) into the renal artery of both saline-expanded (SE) and water-drinking (WD) dogs (n = 7). The renal renin content (30 U/g kidney) of SE dogs was suppressed (P < 0.001) compared to that of WD dogs (132 ± 18). Forty-eight hours after infusion of NE (1.5 fig/kg per min x 100 min), inulin clearances from the infused kidney of SE (6 ml/min ± 2) and WD dogs (7 ± 2) did not differ; in both groups, respective clearances from the noninfused kidney (43 ml/min ± 3) and (36 ± 5) also did not differ from each other. The percent fall in renal blood flow to the infused kidney 48 hours after NE in SE (44%) and WD dogs (38%) did not differ. Because of failure to demonstrate protection, a lower dose of NE (0.75μg/kg Per m +- n x 40 min) was infused into SE and WD animals (n = 6). Forty-eight hours after low dose NE, inulin clearances of the infused kidney of SE (17 ml/min ± 5) and WD dogs (17 ± 4) did not differ. Respective clearances in the noninfused kidney of SE (46 ml/min ± 6) and WD dogs (35 ± 4) did not differ. Therefore, despite suppression of renal renin content, NaCI loading failed to protect against this ischemic model of ARF. In conclusion, unlike HgCI2-induced ARF, it is unlikely that the renin angiotensin system contributes to the pathogenesis of this ischemic model of ARF.

Studies on the Natural History of the Norepinephrine Model of Acute Renal Failure in the Dog

Studies on the natural history of the norepinephrine (NE) model of acute renal failure (ARF) in the dog. Group I (n = 6) was infused with NE into the renal artery (0.75 microgram/kg/min x 80 min) and glomerular filtration rate (GFR) determined sequentially. 21 days post-NE infusion (I) the GFR of the I kidneys (20 + or - (SE) 5ml/min) remained less (p less than 0.001) than the pre-I control value (44 plus or minus 2.9). Group II (n = 7) was treated in an identical fashion except that a contralateral nephrectomy (CN) was done on day 7 and the animals were prepared for micropuncture on day 16. In the animals with residual nephron function at CN, the GFR increased (p less than 0.02) from 26 plus or minus 6.4 ml/min on day 7 to 38 plus or minus 6.6 ml/min on day 14. Considerable interanimal heterogeneity of single nephron GFR (SNGFR) was demonstrated and morphologic studies revealed a very patchy lesion. Therefore, the model is reversible, heterogeneity of SNGFR is present, and the residual functioning nephrons have the capacity to undergo an increase in GFR after CN.

Plasma renin and aldosterone in an abdominal pregnancy with toxemia

The first reported measurement of plasma renin and aldosterone in toxemia with an abdominal pregnancy is presented. In contrast to toxemia where plasma renin and aldosterone are either normal or low, extraordinarily high levels of both were found in this patient which returned to normal after delivery. The role of extrarenal renin in the hypertension of toxemia is discussed and the possibility raised that the elevated renin in this case was of placental origin.