Severe Kidney Damage Research Articles

The effect of immediate and delayed treatment with 2,3-dimercaptopropane-1-sulphonate on the distribution and toxicity of inorganic mercury in mice and in foetal and adult rats.

The distribution and excretion of mercury were studied in mice and rats given a single injection of HgCl2 combined with chelation treatment. BAL-sulph (2,3-dimercaptopropane-1-sulphonate) given intravenously (500 mumol SH/kg) to mice 24 hrs after the mercury injection (2.0 mumol Hg/kg) reduced the kidney Hg-level significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. Severe kidney damage with oliguria was observed in pregnant as well as in non-pregnant rats after injection of 5 mumol/kg of HgCl2. The gross pathological changes could be avoided with immediate treatment with BAL-sulph (500 mumol SH/kg), and such treatment protect against the oliguric reaction. Treatment delayed for 24 hrs reduced the renal Hg-levels significantly, but was ineffective in preventing the kidney damage. This indicates that irreversible changes might have occurred in kidneys cells at this time. The Hg-levels in the brain were either unchanged or lowered in animals given BAL-sulph treatment. BAL-sulph is supposed to act by chelation Hg++, particularly in the extracellular space. The complexes formed appears to be rapidly excreted by healthy kidneys. Mercury poisoning with severe renal damage is, however, associated with a block in urinary Hg-excretion. The poisoned animals responded on the BAL-sulph treatment with a substantial raise of faecal mercury excretion.

Significance of urinary enzymes in gestosis.

The levels of five enzymes were examined in the urine and the serum of pregnant women. They included leucine aminopeptidase (LAP), alkaline phosphatase (AP), N-acetyl-beta-glucosaminidase (ABG), lactic acid dehydrogenase (LDH) and glutamic-oxaloacetic transaminase (GOT). After establishing the normal curve and upper confidence limits in healthy pregnant patients (138 examinations in 52 women), the the enzymes were examined in the urine and the serum of 21 severe and 23 mildly toxemic cases. The mean urinary levels of ABG, AP and LAP in the severe cases were significantly higher than in the normals, and by examining all three enzymes, at least one of them was found to be above the upper confidence limit in 95% of the severely ill women. The changes did not show up early enough to form a good diagnostic and prognostic sign in moderate pregnancy-induced hypertension, but severe kidney damage may be revealed earlier than by the regular kidney function tests, and patients with a bad remote prognosis can be singled out by this method.

Hereditary tyrosinemia - fumarylacetoacetase deficiency

Succinylacetone which has been isolated from urine from patients with hereditary tyrosinemia inhibits porphobilinogen synthase (EC 4.2.1.24) both in liver and erythrocytes. It accumulates together with succinylacetoacetate secondary to a low activity of fumarylacetoacetase (EC 3.7.1.2) in liver (0.09-2.3 U/g protein, n=9, ref. values 5-17 U/g protein, n=5). We suggest that this is the primary enzyme defect and that the severe liver and kidney damage arise secondary to accumulation of maleylacetoacetate and/or fumarylacetoacetase. This is supported by the following facts (1) maleylacetoacetate and fumarylacetoacetate react with SH-groups and are therefore potentially toxic metabolites, (2) injection of glutathione decreases S-succinylacetoacetate and S-succinylacetone probably by reacting with maleylacetoacetate and fumarylacetoacetate, (3) injection of homogentisate increases the tubular proteinuria, (4) among nine patients those with a more benign form of the disease had the lowest activity of 4-hydroxyphenylpyruvate dioxygenase in liver, i.e. accumulate less of maleylacetoacetate and fumarylacetoacetate, (5) 4-hydroxyphenulpyruvate dioxygenase (EC 1.13.11.27) is present only in the tissues seriously damaged in hereditary tyrosinemia. Oral treatment with SH-reagents like penicillamine and N-acetylcysteine has been evaluated in clinical trials in combination with dietary restriction of phenylalanine and tyrosine intake.

On the enzymic defects in hereditary tyrosinemia.

The activity of the enzyme porphobilinogen synthase (EC 4.2.1.24) in erythrocytes from patients with hereditary tyrosinemia was less than 5% of that in a control group and the activity in liver tissue was less than 1% of the reported normal activity. Urine from patients with hereditary tyrosinemia contained an inhibitor that was isolated and identified as succinylacetone (4,6-dioxoheptanoic acid) by gas/liquid chromatography-mass spectrometry. Fresh urine samples contained succinylacetoacetate (3,5-dioxooctanedioic acid) as well as succinylacetone. The inhibition of porphobilinogen synthase explains the high excretion of 5-aminolevulinate observed in hereditary tyrosinemia. Succinylacetone and succinylacetoacetate presumably originate from maleylacetoacetate or fumarylacetoacetate, or both, and their accumulation indicates a block at the fumarylacetoacetase (EC 3.7.1.2) step in the degradation of tyrosine. We suggest that the severe liver and kidney damage in hereditary tyrosinemia may be due to the accumulation of these tyrosine metabolites and that the primary enzyme defect in hereditary tyrosinemia may be decreased activity of fumarylacetoacetase.

The effect of Leptospira interrogans serotype pomona infection on some characteristics of Dia urine

Summary Urine samples were collected from two groups of pigs during a 10-week period of exposure to a natural infection of Leptospira interrogans serotype pomona. One group was protected against infection by immunization. No differences were observed between the degree of proteinuria in infected and protected, animals. However, urine from infected pigs was more dilute than that from protected pigs. This was reflected in the paler colour, lower refractive index and lower untraviolet absorbance of urine samples from infected pigs. Sodium and potassium ion concentrations correlated with the degree of dilution and did not show any increase as a result of infection. These findings suggest that infection of pigs with pomona does not lead to severe functional kidney damage.

Experimental studies on hematogenously induced renal damage in the rabbit due to Pseudomonas aeruginosa.

Chronic systemic infections of rabbits were established by intravenous inoculation of 4 times 10-8 P. aeruginosa cells in order to study the sequence of events leading to severe kidney damage. Renal lesions were detected by the fifth- to seventh-day postinfection, as were lesions in the liver and lungs. Progressive azotemia led to death by the 12th-16th day. Lesions in the kidneys, lungs and liver were characterized terminally by intense mononuclear cell infiltrates, hemorrhage, and microabscess formation. Mononuclear cells also appeared to be the predominant responsive cell early in infection. There appeared to be no difference in the susceptibility to infection or severity of renal lesions between rabbits with surgically induced unilateral ureteral obstruction and nonobstructed rabbits.

Chronic folic acid-nephropathy.

Investigations with a total of 169 male Wistar-rats led to the result that repeated injections of 250 mg folic acid per kilogram body weight in intervals of 3 weeks cause severe chronic kidney damages. After the 4th folic acid injection the outer surface of the kidneys is roughly granular due to circumscribed destructions of the parenchyma in the cortical area and turns into contracted kidneys, within the 48 weeks of the test. Lesions of tubules and of the interstice, particularly around distal nephron segments (convoluted portion of distal tubule, initial segment of collecting tubule and cortical collecting tubules) and focal atrophies of proximal tubules can be observed microscopically. Apart from this, a significant enlargement of all straight portions of the distal tubules in the outer medulla can be noticed. At the end of the 48 weeks serum urea and serum creatinine are twice as high as standard, the daily amount of urine is 4 times higher than the control value, the osmolarity of urine is reduced by 60–77%, experimental animals lose essentially more sodium with the urine than control animals.

Effect of a single small dose of inorganic cooper on the liver of sheep

The pathology of acute copper toxicity was studied in sheep given either 25 mg., 50 mg. or 100 mg. of copper, as copper sulphate, by intravenous injection. Liver biopsies taken 48 hours after injection from animals given 25 mg. or 50 mg. of copper revealed centrilobular necrosis which was associated with a leakage of liver specific enzymes into the blood. These changes had resolved one week later. Animals given 50 mg. of copper also showed markedly elevated blood urea levels during the first few days after injection and two which died had severe kidney damage. One animal given 100 mg. of copper died within two hours and a second was killed in extremis after six hours. Both these sheep showed intense congestion of the abomasum and duodenum at post-mortem examination. The results strongly suggest that the previously reported hepatotoxic effects of copper calcium EDTA are caused by the copper component of this compound.

Classical and Variant Avian Infectious Bronchitis Virus Strains

Infectious bronchitis (IB) is an acute and highly contagious respiratory disease of chickens. The disease is characterized by respiratory signs including gasping, coughing, sneezing, tracheal râles, and nasal discharge. In young chickens, severe respiratory distress may occur. In layers, respiratory distress, decrease in egg production, and loss of internal egg quality and egg shell quality are reported. Some strains of the virus cause severe kidney damage and may be associated with high mortality. This document is VM127, one of a series of the Veterinary Medicine-Large Animal Clinical Sciences Department, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida. Original publication date May 1, 2002.
 VM127/PS039: Infectious Bronchitis Virus: Classical and Variant Strains (ufl.edu)

Studies on the Carcinogenic Activity of Protein-Denaturing Agents: Hepatocarcinogenicity of Dioxane<xref ref-type="fn" rid="FN2">2</xref>

The carcinogenic activity of diethylformamide, diethylacetamide, N,N′-dimethyl-N,N′-dinitrosophthalamide, heptylamine, and dioxane, compounds selected both because of their potency to denature proteins and their structural resemblance to nitrosamine derivatives, was investigated. Dioxane, when administered orally, was found to be a hepatic carcinogen, producing hepatomas in 6 of 26 rats. Diethylacetamide ingestion produced a transitional cell carcinoma of the kidney in 1 of 30 rats. Dioxane, diethylacetamide, and N,N′-dimethyl-N,N′-dinitrosoph-thalamide caused severe kidney damage. The possible relationship between the carcinogenic activity of dioxane and its capacity to alter cellular metabolic control sites by virtue of its protein-denaturing ability is discussed.

The effect of hydrochlorothiazide on the kidney of the electrolyte-deficient rat.

In rats eating a normal diet, large doses of hydrochlorothiazide given for 6 weeks caused potassium depletion with only localized changes in the kidney. With an electrolyte‐deficient diet much smaller therapeutic doses of the drug caused severe kidney damage in 10 days. The severe type of lesion seemed less likely to be due to increased potassium depletion than to potentiation of its effect by other electrolyte deficiencies.Hydrochlorothiazide‐induced lesions had some features in common with potassium deficiency induced by other means, especially a striking enlargement of the intercalated cells of the first part of the collecting duct. This suggests that these cells may be concerned in the tubular secretion of potassium. Hydrochlorothiazide diminished the widespread epithelial hyperplasia of renal tubules caused by deoxycortone without reducing the enlargement of the intercalated cells which also followed steroid treatment. This may have been due to partial blockade of the tubular action of the deoxycortone.

A simple operation for the treatment of chronic coronary artery disease.

For the past 4 years we have been doing coronary ligation and cardiopericardiopexy in the dog; and to date we have performed the Thompson operation in 47 patients. INDICATIONS: 1. Angina on effort and definite evidence of coronary artery disease as confirmed by clinical and laboratory findings. 2. Coronary artery disease after recovering from an acute infarction (3 to 6 months). 3. Any chronic coronary heart disease showing no improvement following medical management. CONTRAINDICATIONS: 1. Congestive failure. 2. Active myocardial infarct or occlusion. 3. Severe liver or kidney damage. CONTRAINDICATIONS: 1. Age—up to 67 years. 2. Positive proof of coronary artery insufficiency. a. If angina—do EKG and positive Masters exercise test. b. If history of infarction, do only EKG. Do not do Masters exercise test, but wait 3 to 6 months for healing before considering surgery. 3. EKG readings on three alternating days must

Influence of dl-Methionine and Other Substances on the Nephrotoxic Action of dl-Serine

dl-SERINE introduced either by stomach tube or by intraperitoneal injection causes severe kidney damage in young rats1,2. In view of the probable interaction of serine and methionine in the rat3,4, the influence of methionine on the serine effect was studied. Male rats weighing approximately 100 gm. were given 100 mgm. dl-serine by stomach tube and killed 24 hours later. Litter mates received the same amount of serine, and in addition dl-methionine in amounts varying from 100 to 600 mgm. subcutaneously in several injections preceding and following the administration of serine. 24 rats given serine alone showed extensive renal necrosis localized in the region of the corticomedullary junction (see Fig. 1). Of 39 animals given methionine in addition, 30 showed no lesions or only minute lesions (see Fig. 2). Only in two rats was no protective effect seen.

Fatal reactions to administration of sulfonamide drugs

Abstract Five deaths are reported following the administration of sulfonamide drugs, three from granulocytopenia, one from hemolytic anemia, and one from liver and kidney damage. In a patient receiving 101 Gm. of sulfanilamide for scarlet fever, and in another patient receiving 64 Gm. of sulfanilamide for streptococcal sore throat, fatal granulocytopenia developed. A third case of fatal granulocytopenia occurred in a patient who was given 88.5 Gm. of sulfapyridine in the treatment of bacterial endocarditis. In two of these patients the bone marrow was examined at autopsy and showed maturation arrest of the myeloid series at the myelocyte level. A typical acute hemolytic anemia developed within three days in a patient treated for erysipelas with 25 Gm. of sulfanilamide. Interference with renal tubular function by precipitated hemoglobin derivatives was thought to be a major factor leading to death in this patient. The fifth case showed clinical evidence of severe liver and kidney damage developing after the administration of 34 Gm. of sulfanilamide for gonorrheal arthritis. Degeneration of liver cells and necrosis of renal tubular epithelium were found at autopsy.

FATAL HEMOGLOBINURIA WITH UREMIA FROM QUININE IN EARLY PREGNANCY

As it is not generally known to the physician that quinine, when employed in early pregnancy, may produce hemoglobinemia with severe kidney damage, we report a case of fatal quinine poisoning in a woman in the early stage of pregnancy, with hemoglobinuria and uremia. The case also stresses the importance of a thorough pathologic and toxicologic examination in any instance in which the clinical observations are not fully explained by the laboratory data. The urea nitrogen retention in the blood of this patient was the highest ever recorded in our laboratories. This, together with increasing oliguria, focused the clinical attention on the kidneys. Since mercury poisoning was ruled out by the analysis of the urine and a history of drug ingestion could not be obtained before the death of the patient, it remained for the postmortem examination to determine the nature and etiology of the anticipated severe renal damage. Here