Roy A. Axelsen

Spontaneous renal papillary necrosis in the gunn rat

Summary Homozygous animals of the mutant Gunn strain of Wistar rat have an unconjugated hyperbilirubinaemia, jaundice and an accumulation of unconjugated bilirubin in the renal papilla. In the older rats (i.e. those weighing over 200 grams), this syndrome is invariably associated with spontaneous papillary necrosis. The evolution of these lesions as seen by light microscopy is described.

Healed experimental renal papillary necrosis and cortical scarring in the rat from 2-bromoethylamine hydrobromide

Male Sprague-Dawley rats were each given a single subcutaneous injection of an aqueous solution of bromoethylamine hydrobromide (BEA) at dose levels of 80 mg/kg (16 rats), 125 mg/kg (15 rats) and 250 mg/kg (16 rats) or a single subcutaneous injection of water (controls, 15 rats). The dose levels were chosen so as to cause renal papillary injury varying from minor necrotic foci to necrosis and subsequent sloughing of the entire papilla. The animals were killed after 5 months and the kidneys were weighed and examined macroscopically and microscopically for the presence of RPN and cortical scarring. Macroscopically evident RPN occurred in 18 of 43 surviving BEA-treated rats, bilaterally in 16 and unilaterally in 2. Bilateral asymmetry of the extent of sloughing was evident. All kidneys with macroscopic RPN exhibited cortical scarring. Asymmetry of the extent of atrophy and scarring in some animals resulted in a significant unilateral reduction in renal weight and a significant contralateral compensatory hypertrophy. Twenty-three of the 25 BEA-treated rats without macroscopically evident RPN exhibited minor, histologically visible lesions of the renal papillae including necrosis of loops of Henle in the presence of intact collecting ducts. Only 2 of these animals exhibited tiny, unilateral cortical scars, and renal weights did not differ significantly from those of controls. It may therefore be concluded, contrary to certain published proposals: that experimental RPN may be followed by severe renal cortical scarring, reduction in renal size and (in the presence of asymmetrical lesions) compensatory renal hypertrophy, and that necrosis of thin limbs of loops of Henle does not appear to lead to frequent or severe cortical scarring.

Experimental renal papillary necrosis in the rat: the selective vulnerability of medullary structures to injury.

Acute renal papillary necrosis was produced in rats by the administration of ethyleneimine. Low doses resulted in necrosis of interstitial cells, thin limbs of the loops of Henle and vasa recta, while collecting ducts were spared (subtotal renal papillary necrosis). High doses resulted in necrosis of all elements of the papilla (total renal papillary necrosis). Although the ranges of the doses that produced these two patterns of necrosis overlapped, it is clear that there is a dose dependent selective vulnerability of renal medullary structures to injury by the toxic agent studied.

Localization of medullary functional abnormalities in experimental papillary necrosis

Summary Renal function was investigated in rats 3 d or 4 wk after an injection of 2‐bromoethylarnine hydrobromide (BEA) 40–125 mg/kg body weight. Animals developed necrosis of renal papillary structures other than collecting ducts (subtotal renal papillary necrosis) (RPN) or necrosis of all structures in the distal papilla, including collecting ducts (total RPN). Glomerular filtration rate (GFR) was reduced in animals with total RPN (667 SD 168 mUl/min/100 g body weight, n = 5) in comparison with controls (1065 103, n = 5; P <0.001) but was unimpaired in animals with subtotal RPN (1162 200, n = 4; P >0.3). Maximum urinary osrnolality (Umax) was significantly decreased in subtoatal RPN (1241 388 rnOsmlkg, n = 4) and in total RPN (626 f 293, n = 5) in comparison with controls (2216293, n = 5). Free water reabsorption (TcH2O) was impaired in animals with total RPN but was not significantly reduced in the presence of subtotal RPN. Total RPN did not affect free water formation (CH2O). It is concluded that impaired TCH2O occurs in RPN because of the damage to the collecting duct, and not because of necrosis of the thin limbs juxtarnedullary nephrons.

Renal function, cortical blood flow and morphometry in ischaemic acute renal failure in the rat

&NA; Unilateral post‐ischaemic acute renal failure (ARF) was produced in rats by occluding the left renal artery and vein for one hour. Left renal function was assessed 1 or 2 h after the end of the period of ischaemia and the kidneys fixed by arterial perfusion. ARF was characterized by increased urine flow (8.1 ± 1.2 SEM #/min/100 g body weight, n = 14; controls 1.0 ± 0.1, n = 11), decreased urinary osmolality (335 ± 12 m Osm/kg, n = 14; controls 1885 ± 97, n = 11), and markedly reduced 3H inulin urine/plasma ratio (3.98 ± 0.56, n = 14; controls 499 ± 60, n = 9) and 3H inulin clearance (32.9 ± 7.0 μml;l/min/100 g body weight, n = 14; controls 505 ± 45, n = 9). Renal cortical blood flow, determined by the hydrogen desaturation technique, was less in animals with ARF (4.2 ± 0.4 ml/min/ml of cortex, n = 8) than in controls (5.4 ± 0.6, n = 5), but not significantly so. In vivo stereomicroscopic examination of the left renal surface in ARF revealed dilated proximal convoluted tubules and delayed passage of intravenously injected dye (lissamine green) through these tubules. Histological examination also showed dilated proximal convoluted tubules and cellular debris impacted in the terminal straight portions of proximal tubules and thin limbs of the loops of Henle. Light microscopic morphometric studies demonstrated significant dilatation of proximal convoluted tubules and Bowmans spaces, and significant narrowing of the lumina of distal convoluted tubules and cortical collecting ducts. The data support the pathogenetic significance of tubular obstruction in a polyuric model of ischaemic ARF in the absence of a marked decrease in renal cortical blood flow, and demonstrate the value of morphometric studies in experimental ARF. The usefulness of the hydrogen desaturation technique for the determination of renal cortical blood flow, reported herein for the first time in ischaemic ARF, is emphasized.