Urinary Lactate Dehydrogenase Research Articles

Measurement of urinary lactic dehydrogenase isoenzyme 5 for the localisation of urinary-tract infection

Measurement of urinary lactic dehydrogenase isoenzyme 5 for the localisation of urinary-tract infection

Effects of inhaled chlorotrifluoroethylene and hexafluoropropene on the rat kidney

Male Fischer-344 rats were subjected to 4.0 hr inhalation exposure to chlorotrifluoroethylene (CTFE) concentrations ranging from 100 to 540 ppm, or hexafluoropropene (HFP) concentrations ranging from 380 to 1200 ppm. Within 2 days following exposure, the rats exhibited dose-related proximal tubular necrosis, diuresis, increases in urinary fluoride, urinary lactic dehydrogenase (LDH) activity, serum creatinine, and BUN. The toxicities of CTFE and HFP were similar except that (1) CTFE was the more potent renal toxin and (2) HFP produced necrosis of the pars recta and pars convoluta portions of the proximal tubule, while CTFE produced necrosis of only the pars recta. At the lowest exposure concentrations, diuresis was the most sensitive index of toxicity manifesting 50% increases in water intake and 25% decreases in urine osmolality. Increases in urinary LDH activity correlated with the degree of proximal renal tubular necrosis, with greater than 100-fold increases at the highest concentrations of CTFE and HFP. At 100 ppm, CTFE induced renal dysfunction (mild diuresis), but no significant increase in urinary LDH nor necrosis were apparent. All concentrations of HFP studied produced necrosis within 24 hr postexposure, with tubular cell regeneration apparent within 4 days.

Effect of sodium tetrathionate on the activities of some enzymes in kidney and urine.

The activities of lactate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase, beta-galactosidase, N-acetyl-beta-D-glucosaminidase, leucine aminopeptidase, gamma-glutamyltransferase and alkaline phosphatase in renal tissue and urine of rats treated with sodium tetrathionate were determined. A decrease of enzyme activities in renal tissue and an increase in urine were observed. The largest decrease in the glutamate dehydrogenase of renal tissue amounted to 0.7 times the control value, and was correlated with an appropriate increase in the urine. Increases in urinary enzyme activity were especially marked for beta-galactosidase and N-acetyl-beta-D-glucosaminidase (3 and 6 times the control values, respectively). The increase in enzyme activities was not accompanied by a corresponding change in the urinary protein. Characterization of urinary lactate dehydrogenase and N-acetyl-beta-D-glucosaminidase isoenzymes also indicates the renal origin of these enzymes. The abnormally high enzyme activities of the urine correlated with the nature and degree of renal damage shown by electron microscopy.

Effects of 4-dimethylaminophenol in rat kidneys, isolated rat kidney tubules and hepatocytes.

1. Addition of 4-dimethylaminophenol (DMAP) to suspensions of isolated rat kidney tubules increased extracellular lactate dehydrogenase (LDH) at concn. which did not markedly affect gluconeogenesis. ATP content was also decreased by DMAP but this did not occur until the membrane became permeable to LDH. There was no similar leakage of the mitochondrial enzyme glutamate dehydrogenase. 2. After i.v. injection of DMAP to rats in doses which did not inhibit gluconeogenesis, kidney glutathione was decreased and the urinary LDH was increased. DMAP was irreversibly bound to tissue in rat, with the highest binding in the kidney. The highest binding occurs in those tissues in which DMAP causes necrosis. 3. In isolated rat hepatocytes, DMAP caused toxic effects which were similar but less extensive than occur on addition of DMAP to kidney tubules. The formation of acid-soluble metabolites was higher in isolated rat hepatocytes (20 nmol/mg protein) than in rat kidney tubules (4 nmol/mg protein). DMAP-glucuronide and DMAP-sulphate comprised the major acid-soluble metabolites in both preparations; conjugates of DMAP with glutathione or cysteine were also found.

Comparison of Urinary Lactic Dehydrogenase with Antibody-Coated Bacteria in the Urine Sediment as Means of Localizing the Site of Urinary Tract Infection

Two noninvasive methods of localizing the site of urinary tract infection, urinary lactic dehydrogenase (LDH) isoenzymes and antibody coating of bacteria in the urinary sediment, have been prospectively compared with the bladder washout technique in a series of children with urinary tract infection. Fifteen children had infection localized in the upper tract. Urinary LDH isoenzymes correctly localized the infection in 14 children; however, the infection was correctly localized by the antibody coating of bacteria in only eight patients (P less than .02). Fourteen children had lower tract infection by the bladder washout technique. Urinary LDH isoenzymes localized the infection in all 14 children, whereas the antibody coating correctly localized the infection in ten children (P less than .05). This study shows the urinary LDH isoenzyme pattern to be a more accurate technique than the detection of antibody-coated bacteria for localizing the site of urinary tract infection.

Urinary lactic dehydrogenase isoenzyme IV and V in the differential diagnosis of cystitis and pyelonephritis

To ACCOMPLISH precise localization of the site of urinary tract infection, direct and indirect methods have been developed. The former include culture of kidney biopsy tissue or of ureteral urine, and the bladder washout test1; the latter include assessment of maximal urine concentrating capacity, determination of specific serum antibodies to the infiltrating organism, urinary enzyme assays such as catatase and fl-glucyronidase 2, and calculation of urinary leukocytes, leukocyte casts, or antibodycoated bacteria? The present investigation was undertaken to determine if urinary lactic dehydrogenase isoenzymes could be used to differentiate accurately between pyelonephritis and cystitis?

Ochratoxin a mycotoxicosis in the guinea-pig

Ochratoxin A dissolved in dimethylsulphoxide-50% ethanol (1:1, v/v) was administered to male and female guinea-pigs in doses of 5·6, 7·5, 10, 13·3 and 20mg/kg/day by gastric intubation for 14 days. Clinical, clinico-pathological, gross and histopathological observations were made. The 14-day LD 50 was 9·1 mg/kg for males and 8·1 mg/kg for females. The dose of 5·6 mg/kg was essentially a no-effect dose. Loss of body weight was the most consistent clinical change observed and was roughly proportional to the dose of the mycotoxin. Alterations in clinico-pathological values included increased total plasma protein, decreased serum potassium and chloride, proteinuria and increased serum and urinary lactic-dehydrogenase activities. Gross lesions were not striking, but included pale discoloration of the kidneys, fluid contents and petechiae in the caecum, gastric atony, and congested and enlarged lymph nodes. Major histological changes occurred in the kidneys, lymphoid tissues and gastro-intestinal tract. Renal alterations were degeneration and necrosis of the tubular epithelium, involving both straight and convoluted portions of the proximal tubules, together with tubular dilation and hyaline-cast formation. Congestion, necrosis and oedema involved lymphoid tissues such as lymph nodes, spleen, thymus and the submucosal lymphoid tissue of the gut. Gastro-intestinal lesions included mucosal hyperaemia, necrosis of mononuclear cells of the lamina propria, and caecal and gastric mucosal ulceration.

Toxic renal damage: Changes in enzyme levels

A study of rat urinary excretion of lactate dehydrogenase, alkaline phosphatase, and muramidase was carried out following the administration of a high dose (2 g/kg) of cephaloridine, a known nephrotoxic antibiotic (12–15). Urinary lactate dehydrogenase and muramidase levels were highly elevated 0–12 hr after the drug, while alkaline phosphatase levels did not alter considerably from the normal values. Kidney protein levels and lactate dehydrogenase and alkaline phosphatase activities were reduced 30 hr after the drug, while the serum proteins and enzyme levels did not show significant changes. Evidence was presented to show that the study of urinary enzyme excretion could prove a sensitive early indicator of kidney damage.

Influence of some Antirheumatic Drugs and Cytostatics on Urinary Enzyme Level

In experiments with rats, the influence of the treatment with sodium salicylate (350 mg/kg), phenylbutazone (100 mg/kg), cyclophosphamide (5 mg/kg), 6-mercaptopurine (25 mg/kg) and D-penicillamine (50 mg/kg), on urinary lactate dehydrogenase, leucine aminopeptidase and alanine aminopeptidase was investigated. All these drugs caused an increase in the enzyme levels in urine. In the case of sodium salicylate, the increase occurred only after the first administration of the drug; phenylbutazone caused a gradual increase of the enzymes. Cytostatic drugs caused an increase in the level of the investigated enzymes in urine with a maximum after 1 week of treatment.

Urinary lactic dehydrogenase isoenzyme 5 in the differential diagnosis of kidney and bladder infections

Urinary lactic dehydrogenase (U-LDH) isoenzyme assays were performed on ch2) as well as normal controls (N = 24). Docuemntation of bladder and kidney infection was accomplished by means of the bladder washout test, culture of ureteric urine (in patients with urinary diversion), kidney function studies including the maximal urine concentration test, clinical symptomatology and radiologic appearance of the urinary tract. Total U-LDH in normal children (10.8 +/- 1 mU/ml) was lower than in patients with bladder (27.0 +/- 3.9 mU/ml) or kidney (226 +/- 67.3 mU/ml) infections (P less than 0.005). In normal children isoenzymes 1 and 2 predominated (LDH-1 migrates fastest to anode -- fast zone pattern). In patients with bladder infections, the isoenzyme patterns varied but the concentration of isoenzyme 5 (3.1 +/- 0.8 mU/ml) was lower (P less than 0.005) than in patients with kidney infections (120 +/- 39 mU/ml). In the latter, isoenzymes 4 and 5 predominated (slow zone pattern). Since overlap between kidney and bladder infections regarding isoenzyme 5 concentrations (at 3 SD) occurred in only one individual (patient 37), a correct differential diagnosis using U-LDH-5 alone would have been possible in 94% of the children with pyelonephritis or 97% of the total patient population (kidney + bladder).

Studies on urinary isozymes of lactic dehydrogenase and beta-glucuronidase in patients with bladder tumors.

Isozymes of urinary lactic dehydrogenase (LDH) were studied in 55 subjects, including 17 patients with bladder tumors. Normal clear urine from healthy persons showed little activity of LDH5, but in 11 out of 17 patients with bladder tumors LDH5 was increased sufficiently to invert the ratio of LDH5/LDH1, although the urine was not contaminated appreciably with leucocytes. Studies on tissue LDH isozymes in 16 tumors specimens strongly suggested that increased LDH5 in the urine of patients with bladder tumors originated from the tumors themselves. beta-Glucuronidase (B-G) isozymes were studied in urine specimens from 10 normal subjects, and 10 patients with bladder tumors and in 5 specimens of normal epithelium and 5 of tumor tissue. Two or three distinct bands of beta-G were separated from specimens of urine and tumor tissue from patients with bladder tumors, but only a single band was found in specimens from normal subjects.

Early warning of rejection?

The urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), beta-galactosidase (GAL), beta-glucosidase (GLU), and alkaline phosphatase (AP) was studied in 83 patients with renal allografts. Thirty of these patients had stable graft function and their urinary enzyme levels provided a range of normal values. Urinary lactic dehydrogenase (LDH) was estimated in 29 normal subjects and in 11 patients with renal allografts. Serum values for the five enzymes were also obtained. Urinary NAG excretion was abnormally high in 16 out of 17 (94%) episodes of acute rejection. The other urinary enzymes were raised less frequently. In nine patients studied before the onset of rejection urinary NAG activity rose up to three weeks before changes in other tests of renal function. Serum enzyme levels were not found to be of value in the diagnosis of rejection.

The influence of gold salts on the urinary enzyme level.

The effect of Sanocrysin® (sodium aurothio-sulfate) in the dosage 1, 5, 12.5 and 25 mg/kg on urinary lactate dehydrogenase, leucine aminopeptidase and alanine aminopeptidase was investigated in rats in a 10 days’ experiment. During this experiment three injections of Sanocrysin® in these dosages were administered. The treatment with Sanocrysin® resulted in an increase of urinary enzymes. This increase correlated with the height of used doses. After the dosage of 5 mg/kg this increase occurred only after the first injection. The dosage of 12.5 and 25 mg/kg resulted in a two-phase increase after the first and third injection.

Kaliopenic nephrosis: protective action of l-ornithine- l-aspartate

In rats, renal changes in potassium depletion (kaliopenic nephrosis) were recorded by determinations of renal enzyme excretion (urinary lactate dehydrogenase, alkaline phosphatase, and “leucine aminopeptidase” activities). In animals which were treated with intraperitoneal injections of l-ornithine- l-aspartate (200 mg/kg), the increase in urinary lactate dehydrogenase and alkaline phosphatase activities was significantly lower than in untreated potassium-depleted controls. The mechanisms by which l-ornithine- l-aspartate could exert its protective action in kaliopenic nephrosis are briefly discussed.

Urinary lactic dehydrogenase activity. Posture dependent activity changes for the diagnosis of unilateral nephroptosis.

Measurements of urinary lactate dehydrogenase (LDH) activity in 25 patients with clinically significant unilateral nephroptosis demonstrated a posture-dependent change. While these patients were supine – overnight – the urinary LDH activity was normal. On assuming an erect posture, the LDH activity rose to abnormal level. Such ‘swinging’ changes in urinary LDH activity could not be detected in normal people and in patients having undergone nephropexy one year following the intervention. The LDH activity obtained by unilateral catheterization was shown to be higher on the affected side than on the normal.

Postural dependent activity changes of urinary LDH as a diagnostic aid in nephroptosis.

Measurements of urinary lactate dehydrogenase (LDH) activity in 20 patients with clinically significant unilateral nephroptosis demonstrated a posture-dependent change. While these patients were supine – over night – the urinary LDH activity was normal. On assuming an erect posture, the LDH activity rose to abnormal level. Such ‘swinging’ changes in urinary LDH activity could not be detected in normal people and in patients having undergone nephropexy 1 year following the intervention. The LDH activity obtained by unilateral catheterization was shown to be higher on the affected side than on the normal.

Relation of the activity of urinary lactate dehydrogenase to the activity of glomerulonephritis

In 84 patients with glomerulonephritis, the LDH activity in urine was examined. The results were statistically compared, using different parameters. Positive correlation was found with the activity of inflammatory processes in the kidney (determined by a score system) and with proteinuria. No correlation was observed with the degree of renal insufficiency and with erythrocyturia. Positive correlation with leukocyturia (or, rather, with the occurence off tubular cells in urine) was proved only in the whole group of patients, but this correlation was insignificant when 24 patients with nephrotic syndrome had been omitted from the study. The authors suppose that the LDH activity in urine may be considered as a measure of the activity of the disease in patients with glomerulonephritis.

The excretion of lacate dehydrogenase in human urine after he ingestion of aspiin.

1. Cells present in normal human urine contain 5-10% of the total lactate dehydrogenase excreted. The enzyme released from these cells by ultrasonication contained a distribution of isoenzymes similar to that found in the bulk of the urine and it is suggested that these cells are the main source of urinary lactate dehydrogenase. 2. Cells were thoroughly washed before examination so it is unlikely that the enzyme found in urinary sediment was simply adsorbed. In addition, full recoveries of added lactate dehydrogenase isoenzymes LDH(1) and LDH(5) showed that adsorption did not occur. 3. Most of the cells in normal urine are of the non-squamous epithelial type and their excretion is greatly increased after the ingestion by the subject of 3g. of aspirin. The possible origin of these non-squamous cells from the kidney is discussed. 4. Starch-block electrophoresis and relative activity measurements of lactate dehydrogenase excreted after the subject had taken aspirin show that the enzymes present in urine and cells are very similar, confirming the conclusion reached above (point 1). They have slightly more M subunits than the normal, shown particularly as an increase in isoenzyme LDH(2). The isoenzyme pattern is like that of the kidney medulla and the possible reasons for this are discussed in terms of the concentration of salicylic acid in various parts of the kidney. 5. The results confirm the previous suggestion that the kidney is the main source of urinary lactate dehydrogenase.

Urinary Lactic Dehydrogenase in Genitourinary Tract Diseases

Enzyme studies of urinary lactic dehydrogenase (LDH) have been carried out in a total of 263 patients with various diseases of the genitourinary tract seen at this institution. Almost half had bladder tumors, but patients with other diseases, both benign and malignant, were also included in the study. Elevation of urinary LDH enzyme levels is noted after catheterization and instrumentation. Elevation seems more related to the presence of pyuria, hematuria, and bacteriuria than to the presence of a specific, proved tumor. Only rarely does a patient with normal results of urinalysis have elevated LDH levels. Urinary LDH levels and results of cytologic studies of urinary sediment show a poor correlation. We have concluded that urinary LDH determinations are not useful as a routine diagnostic procedure in the study and follow-up of patients with malignant diseases of the genitourinary tract.

Urinary lactic dehydrogenase in genitourinary tract diseases

Urinary lactic dehydrogenase in genitourinary tract diseases