Bernard J. Panner

Reversible uranyl fluoride nephrotoxicity in the Long Evans rat

Severity and duration of renal injury produced by low levels of uranyl fluoride (UO2F2) were examined in the rat. Rats received multiple ip injections of UO2F2 (cumulative dose: 0.66 or 1.32 mg U/kg body wt). Renal injury was characterized histologically by cellular and tubular necrosis of pars recta of proximal tubule (S2 and S3), with less severe cellular injury to thick ascending limb of loop of Henle and collecting tubule. Injury was evident when renal uranium levels were between 0.7 and 1.4 micrograms U/g wet kidney and was most severe when renal uranium burden was between 3.4 and 5.6 micrograms U/g. Repair of injury was rapid, with complete restoration within 35 days after exposure. Associated with injury were abnormalities in renal function, including impaired tubular reabsorption, proteinuria, and enzymuria, which appeared temporally related, to variable degrees, to progression of renal injury. Thus, reversible renal injury occurs in the rat at levels of uranium in kidney below the present Nuclear Regulatory Commission standard of 3 micrograms U/g kidney for renal injury in humans.

Effects of contrast media on renal function and subcellular morphology in the dog

The effects of intravenous contrast media (CM) on renal excretory function and subcellular morphology are examined in this animal investigation. A decrease in GFR (12.0 +/- 1.6 vs. control 30.2 +/- 2.5 ml/min) was observed when renal function was evaluated by means of the artero-venous extraction method with Tc99m DTPA and the anticipated inverse relationship to urinary flow (Vml/min) noted. An artifactual increase in GFR (43.5 +/- 10.0 vs. control 39.1 +/- 3.8 ml/min) was observed using the timed urinary clearance of inulin. V(ml/min) increased four-fold (0.6 +/- 0.16 control vs. 2.7 +/- 0.7 ml/min; P less than .05) over the first five minutes after injection of CM. Urine osmolality initially approached isotonicity and then returned toward preinjection values. Osmolal clearance (Cosm) rose 2.5 times (1.4 +/- 0.3 control vs. 3.7 +/- 1.0 ml/min; P less than .05). The fractional excretion of both Na+ (FENa+) and K+ (FEK+) increased. A comparison of urinary osmolality vs. time after injection of CM confirms a nonspecific osmotic effect on tubular (and hence total urine) flow. The hemodynamic effects of CM on the kidney via the i.v. route reflect a predominant and nonspecific osmotically mediated vasodilation. No significant light or electron microscopic changes were observed. These findings suggest that the major renal physiologic actions of hypertonic CM are a nonspecific response to agent osmolality.

Toxicity of sodium cyanurate

Abstract Sodium cyanurate fed to rats for 20 weeks and to dogs for 6 months was without evident adverse effects at a dietary concentration of 0.8%. Rats fed 8% of sodium cyanurate in the diet for 20 weeks showed consistent and characteristic histologic changes in the kidneys, consisting of dilatation of the distal collecting tubules and ducts of Bellini with focal areas of epithelial proliferation. Similar renal changes were observed in dogs fed 8% of sodium cyanurate in the diet for 16–24 months. Five milliliters of an 0.8% or 8% aqueous suspension of sodium cyanurate applied daily, 5 days/week, to the skin of rabbits for 3 months caused no adverse effects at the lower concentration. At the higher concentration, kidney changes similar to, but less marked than, those described in the rats and dogs were noted. No skin irritation was caused by either concentration. No eye irritation was observed in rabbits receiving 0.1 ml daily, 5 days/week, of an 8% aqueous suspension of sodium cyanurate instilled into one eye over a period of 3 months.

Acute Idiopathic Tubulointerstitial Nephritis: Report of Two Cases and Review of the Literature

Two patients who presented with severe renal failure and evidence of generalized proximal tubular dysfunction were found to have severe diffuse acute tubulointerstitial nephritis on renal biopsy. No etiology could be found in either case. Both patients had dramatic improvement in renal function following steroid therapy. In the first reported case of its kind, one patient relapsed when steroids were withdrawn, but improved again with reinstitution of steroid therapy. These cases, as well as others in the literature, show that steroids are effective and may be necessary to improve renal function in some patients with acute idiopathic tubulointerstitial nephritis. Evidence of proximal tubular dysfunction is a clue to the presence of this disorder.

Renal involvement in Refsum's disease

Renal hemodynamic and tubular functions were measured in a patient with Refsums disease before and after 12 weeks of twice-weekly plasmaphereses. Percutaneous renal biopsy was performed before initiation of plasmapheresis. These studies were performed to (1) define the nature of the renal lesions and the effects of phytanic acid accumulation on renal functions, and (2) assess the effects of lowering the plasma phytanic acid level on renal functions. The patient, a 39 year old woman, had lipiduria, glycosuria, cylindruria, minimal proteinuria and mild azotemia initially. Renal lesions consist of extensive vacuolization and mitochondrial changes of the tubular epithelial cells, vacuolization of the visceral epithelial cells of the glomeruli, and slight to moderate mesangial sclerosis. The impaired renal hemodynamic function and various tubular functions improved following plasmaphereses associated with reduction of plasma phytanic acid. Over-all clinical improvement was also evident.

Lysosomes in the Renal Papillae of Rats: Formation Induced by Potassium-Deficient Diet

Lysosomes appeared in the cytoplasm of cells of the renal papillae of rats fed on a potassium-deficient diet. The lysosomes were identified by their morphologic appearance when examined by electron microscopy, and by their acid phosphatase activity shown by both light and electron micro-scopic examination of Gomori-treated tissue.

Increased Plasma IgA, sIgA, and C3- and IgA-Containing Immune Complexes With Renal Glomerular Deposits in Diabetic Rats

Male Sprague-Dawley rats were fasted 18 h and given streptozocin (STZ; 60 mg/kg body wt i.p.). The resultant diabetes mellitus, not treated with insulin, was associated with persistent manifoldly increased plasma IgA levels, as measured by single-radial immunodiffusion after reduction with dithiothreitol and alkylation with iodoacetamide. Also observed were concurrent increases in plasma levels of secretory IgA (sIgA) and of C3- and IgA-containing immune complexes (C3-IgA-CIC). After 104 days without insulin treatment, six of the diabetic rats were given daily injections of 2 U of insulin for 11 days. Insulin treatment was associated with a precipitous decrease in plasma levels of IgA, sIgA, and C3-IgA-CIC. Cessation of insulin treatment resulted in restoration of greatly increased levels of all three IgA-containing species. Histoimmunofluorescence studies of kidneys from untreated rats with diabetes of 192–324 days revealed glomerular capillary wall and mesangial deposits reacting strongly with anti-IgA (α-chain-specific) antiserum. Kidneys from two of the diabetic rats (324 days) were tested with anti-rat C3 and anti-rat secretory component (SC) antisera, and they reacted positively. Control kidneys from normal rats examined simultaneously were negative. The concurrent changes in plasma levels of three IgA-containing species in the untreated STZ-induced diabetic rat and the demonstration of abnormal immunoreactive IgA-containing renal glomerular deposits make this experiment an attractive model for studying the possible role of disturbed IgA metabolism in the pathogenesis of diabetic nephropathy.

Spontaneous remission of the nephrotic syndrome in diabetic nephropathy

A 28 year old woman, with diabetes since age 18, had the nephrotic syndrome, hypertension and renal insufficiency. The initial renal biopsy specimen revealed diffuse glomerulosclerosis with early nodular changes. After an initial decline in renal function, her creatinine clearance progressively improved and has remained normal. Within 2 years she had a spontaneous remission of the nephrotic syndrome despite the presence of more pronounced nodular glomerular lesions. Although the renal hemodynamic functions were normal, certain tubular functions were impaired. Since we found no etiology for the nephrotic syndrome other than diabetic glomerulopathy, the complete remission of the nephrotic syndrome and improvement in renal function were very unusual events.

Glomerulonephritis and reversible renal failure resulting from osteomyelitis in a diabetic patient

W hen renal insufficiency develops in a diabetic patient, the usual diagnosis is diabetic nephropathy. However, if the clinical course deviates from the classical pattern of diabetic nephropathy, other potentially treatable causes of renal failure must be considered [1-4]. Here we describe a diabetic patient with osteomyelitis in whom acute renal failure developed from mesangiocapillary glomerulonephritis. Renal function improved significantly with eradication of infection. This association between osteomyelitis and glomerulonephritis has only been rarely reported [5,6].

Nephrotoxicity of Uranyl Fluoride and Reversibility of Renal Injury in the Rat

Recent accidental exposures of workers and members of the public to uranium hexafluoride (UF6) releases have reinforced interest in the nephrotoxic properties of uranium compounds (1). Additionally, a large industrial work force is engaged in several types of uranium production operations in which intermittent exposures frequently occur. Despite recent improvements in our understanding of the toxicology and biokinetics of uranium, there remain several important issues for which there are virtually no occupational or experimental data. Foremost of these issues is the time course and extent to which nephrotoxic actions of uranyl uranium are reversible, particularly after exposures at or near the socalled threshold for injury of 3 ug U/g kidney (2–5). More-over, better procedures for detecting uranium-induced renal injury need to be identified, particularly for injury associated with exposure to occupationally relevant uranium compounds. The objective of the present study was to examine severity and duration of renal injury produced in the rat from exposures to low levels of uranyl fluoride (UO2F2).