Urine profiles and kidney histology following intravenous diatrizoate and iohexol in the degeneration phase of gentamicin nephropathy in rats. Effects on urine and serum profiles.

Urine chemical profiles were followed for three or nine days after intravenous injection of diatrizoate, iohexol, or saline in 30 rats, where a tubulointerstitial nephropathy was induced by gentamicin given over an eight-day period. Another ten rats injected with saline served as controls. Compared to injection of saline, both iohexol and diatrizoate induced dysfunction. The excretion of the cytoplasmic enzyme lactate dehydrogenase was significantly greater following iohexol than following diatrizoate. No significant differences between the two media were shown by the various serum components examined. Among the gentamicin-treated rats, light microscopy showed prolonged occurrence of tubular necrosis and a more intensive round cell infiltration following iohexol than following diatrizoate and saline. Both contrast media induced further temporary renal dysfunction in rats with gentamicin nephropathy; iohexol induced more morphologic changes than diatrizoate.

Pretreatment with steroids before intravenous injection of diatrizoate or iohexol. Effects on urine and serum profiles.

The effects on urine and serum profiles of intravenous injection of diatrizoate, iohexol, or saline were studied in male rats pretreated with steroids or saline. Using urinary albumin, glucose, sodium, and the enzymes lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) as markers of glomerular and tubular function, it was found that diatrizoate caused temporary glomerular and tubular dysfunction; the effect was independent of the kind of pretreatment. Iohexol did not cause increased glomerular permeability in steroid- and saline-pretreated rats. When used following saline, iohexol induced increased excretion of three tubular components, whereas iohexol plus steroids caused increased excretion of all five tubular components. The dysfunctional effect of iohexol plus steroids was less than that of diatrizoate plus steroids. The serum components revealed no abnormalities induced by either contrast media or methylprednisolone. Pretreatment with steroids has no effect on the glomerular or tubular dysfunctional effect of diatrizoate, whereas it worsens the temporary tubular dysfunctional effect of iohexol in rats.

Do contrast media aggravate Fanconi's syndrome in rats? A comparison of diatrizoate, iohexol, and ioxilan.

Urine profiles (albumin, glucose, N-acetyl-beta-D-glucosaminidase [NAG], lactate dehydrogenase [LDH], L-gamma-glutamyltransferase [GGT], sodium, and phosphate) were followed for seven days after intravenous (IV) administration of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a tubular dysfunction induced by IV sodium maleate. Ioxilan and saline had a similar effect on albumin excretion, iohexol had an intermediate effect, and diatrizoate increased it significantly from day 2 to day 7. Glucosuria was significantly greater after diatrizoate than after the nonionic contrast media (CM) or saline. Diatrizoate delayed normalization of enzymuria, whereas iohexol and ioxilan did not. None of the CM affected urinary sodium or phosphate excretion. It is concluded that Fanconi's syndrome is significantly aggravated only by diatrizoate.

Urine profiles following intravenous diatrizoate, iohexol, or ioxilan in rats.

The effects of intravenous diatrizoate, iohexol, ioxilan, or saline on albumin, glucose, sodium and the enzymes N-acetyl-beta-D-glucosaminidase (NAG), lactate dehydrogenase (LDH), and L-gamma-glutamyltransferase (GGT) in the urine of 24 normal Wistar rats were followed for seven days. During the first two hours after administration of diatrizoate, all profile components changed markedly; the albumin excretion was significantly greater than following ioxilan and iohexol; glucose, LDH, and GGT excretions were significantly greater than following ioxilan. Iohexol and ioxilan caused a higher excretion of albumin, LDH, and GGT than saline. Iohexol also increased glucose and sodium levels. Glucose and GGT were significantly higher following iohexol than following ioxilan. Both high osmolar and low osmolar contrast media may cause temporary glomerular and tubular damage. Urine profile components are affected most by diatrizoate, less by iohexol, and least by ioxilan.

Urine profiles and kidney histologic findings after intravenous injection of mannitol and iohexol in the degeneration phase of gentamicin nephropathy in rats.

RATIONALE AND OBJECTIVES: Previous studies have shown that iodinated contrast media may cause further renal dysfunction in tubulointerstitial nephropathy induced by gentamicin. The current investigation was undertaken to study whether the dysfunction after intravenous injection of a low-osmolar contrast medium is due to a chemotoxic and/or an osmotic effect. METHODS: Urine profiles were followed for 3 or 9 days after intravenous injection of saline, mannitol, and varying dosages of iohexol (1, 2.5, 5, and 10 mL/kg body weight (BW); 350 mg I/mL) in 60 rats, in which intramuscular injection of 40 mg/kg BW gentamicin had been administered daily nine times. A seventh group of 10 rats was given 20 mg/kg BW gentamicin and 5 mL/kg BW of 350 mg I/mL iohexol. Another 10 rats injected with saline served as controls. RESULTS: Both mannitol and iohexol increased the excretion of albumin and the enzyme N-acetyl-B-D-glucosaminidase (NAG) temporarily; the effect was independent of the dose of iohexol. There was a dose-dependent effect on the transient increase in excretion of the enzymes lactate dehydrogenase (LDH), gamma glutamyltransferase (GGT), and alkaline phosphatase (ALK); mannitol did not increase the excretion of these enzymes. In the group given 20 mg/kg BW gentamicin, only the dose-dependent effects of iohexol were seen. Neither various plasma components nor light/electron microscopy showed any changes that could solely be related to the contrast medium. CONCLUSIONS: Iohexol produces transient renal effects in gentamicin nephropathy, which may be due to both chemotoxic and osmotic mechanisms.

Evaluation of quantitative methods for determination of protein in urine.

The automated immunoprecipitin reaction (A.I.P.) and the Laurell electroimmuno assay (rocket electrophoresis) are applied to unconcentrated overnight urines from patients hospitalised for various diseases, including both Albustix-positive and Albustix-negative samples. The results of both methods and the results of a quantitative determination of total protein are compared. The correlation coefficients between the two immunochemical methods are good, with a significance level of p less than 0.01 for all r-values. The correlation coefficient between the immunochemical methods and the quantitative determination of total protein is dependent on the amount of protein excreted in the urine. If urines should be examined for proteins we recommend a quantitative screening method or an immunochemical determination of albumin. For the latter we find that the A.I.P.-reaction is the method of choice, because it is fast, precise, sensitive, and specific.

The predictive value of specific protein clearances in detecting acute rejection episodes after renal transplantation.

The relative clearances of albumin, transferrin, haptoglobin, IgG, IgA, and IgM and the relative excretion of immunoglobin free lambda- and kappa light chains, lysozyme, and beta2-microglobulin were measured in 24 patients who had recently received renal transplants. Eleven out of 13 acute rejection episodes were predicted 1 to 5 days before the clinical diagnosis was made, and in 2 patients the clinical diagnosis of rejection and the prediction were made simultaneously. Successful antirejection therapy was followed by a decrease in protein excretion; in irreversible rejection episodes protein excretion continued to increase in spite of antirejection therapy. It is recommended that the relative clearances of IgG and haptoglobin be measured daily in patients recently treated by renal transplantation.

Urine profiles and kidney histology after intravenous injection of ionic and nonionic radiologic and magnetic resonance contrast media in normal rats.

RATIONALE AND OBJECTIVES: Previous studies showed that both high-osmolality and low-osmolality iodinated contrast media cause temporary albuminuria and enzymuria (presence of enzymes in urine) in normal rats. Whether the same is true with ionic high-osmolality and nonionic low-osmolality magnetic resonance (MR) contrast media is unknown. We studied urine profiles and histology after intravenous injection of four types of contrast media in rats with normal kidneys. METHODS: Urine profiles were monitored 4, 24, 48, and 72 hr after intravenous injection of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide (4.59 mmol/kg of body weight) in normal rats. Each group included 20 male rats. After sacrifice, both kidneys were removed for examination by light microscopy (LM) and electron microscopy (EM). RESULTS: All four contrast agents caused a temporary (< 22 hr) increase in the excretion of albumin (2-5 times) and of cytoplasmic (30-100 times) and brush border (10-100 times) renal enzymes when compared with saline. The degree of albuminuria correlated well (r = 0.90) with the osmolality of the injected media, whereas the increased level of enzymuria was unrelated to the osmolality. No major differences in the enzymuric effects of the four agents were noted. LM revealed vacuoles in all kidneys exposed to radiologic contrast media but not in kidneys exposed to MR contrast media or saline. Slight vacuolation was revealed by EM after the use of MR contrast media, and significant vacuolation was evident via EM after the use of radiologic contrast media. No difference between ionic and nonionic media within each drug group was detected by either LM or EM. CONCLUSIONS: Transient renal effects are induced by both ionic and nonionic high-osmolality and low-osmolality radiologic and MR contrast media in normal rats. Both osmotic (e.g., albuminuria) and chemotoxic (e.g., enzymuria) mechanisms seem to be involved. From a morphologic point of view, the chemotoxic mechanisms seem to be of major importance.

Urine profiles and kidney histology after ionic and nonionic radiologic and magnetic resonance contrast media in rats with cisplatin nephropathy.

RATIONALE AND OBJECTIVES: The nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcinoma frequently undergo examinations with contrast media. We examined whether ionic and nonionic radiologic and magnetic resonance contrast media would have any effect on cisplatin nephropathy in rats. METHODS: Urine and serum profiles were monitored for 24 days after intravenous (i.v.) injections of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (i.p.) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. Another 10 rats injected with both i.p. and i.v. saline served as control subjects. After euthanization, rats' kidneys were removed for examination by light microscopy and electron microscopy. RESULTS: Light and electron microscopy showed severe morphologic changes, including tubular dilatation, atrophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dimeglumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with i.v. saline in cisplatin nephropathy, whereas gadodiamide did not. Albuminuria was highest after diatrizoate injection. All four contrast media caused an immediate and transient significant increase in the excretion of the brush border enzymes alkaline phosphatase and gamma-glutamyltransferase (125-500 times) and the cytoplasmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-100 times). Compared with saline, the ionic agents significantly increased the excretion of both glucose (two times) and sodium (three to five times), whereas the nonionic agents did not. CONCLUSION: High doses of radiologic and magnetic resonance contrast agents cause temporary dysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.

[Use of prostate specific antigen. A review]. / Anvendelse af prostataspecifikt antigen. En oversigt.

Since it was first introduced, measurement of prostate specific antigen has gained increasing interest, and prostate specific antigen is regarded as being the best tumour marker available. The antigen lacks cancer specificity, limiting the usefulness in early diagnosis, The use of prostate specific antigen in early diagnosis, staging, and in monitoring patients with prostate cancer is reviewed.

Beta 2-microglobulin in urine and serum determined by ELISA technique.

A two-site solid-phase enzyme immunoassay for the determination of beta 2-microglobulin in serum and urine is established using polystyrene tubes as solid phase. Horseradish peroxidase-conjugated antihuman beta 2-microglobulin was used as labelled antibody. The technique is based on a general ELISA procedure and can be established without any specific equipment.

Urinary excretion of ten plasma proteins in patients with extrarenal epithelial carcinoma.

Urinary and serum proteins were studied in 55 patients with extrarenal epithelial carcinoma, using an automated immunopreciptin reaction. The 24 h excretion and renal clearance of 6 high molecular weight proteins: albumin, transferrin, haptoglobin, IgG, IgA, and IgM were significantly increased compared with a control group, implying a glomerular injury. The 24 h excretion of 4 low molecular weight proteins: free lambda and kappa light chains of immunoglobulin, lysozyme, and beta2-microglobulin was significantly increased in patients with disseminated carcinoma compared with patients with localized carcinoma. The serum concentrations of albumin and transferrin were significantly decreased and the serum concentration of haptoglobin significantly increased in patients with disseminated carcinoma compared with patients with localized tumours.

Urinary excretion of ten plasma proteins in patients with renal carcinoma.

Urinary and serum proteins were studied preoperatively in 48 patients with renal carcinoma, using an automated immunoprecipitin reaction. The 24 h excretion and the renal clearance of albumin, transferrin, haptoglobin, IgG, IgA, and IgM and the 24 h excretion of the immunoglobulin lambda and kappa free light chains and beta2-microglobulin were significantly increased compared with a control group. The excretion of lysozyme was also increased, but not significantly. Increased protein excretion was the most common urinary finding in patients with renal carcinoma. The protein excretion was predominantly of the glomerular type, implying a glomerular injury. The serum concentrations of albumin and transferrin were significantly decreased and the serum concentration of haptoglobin significantly increased in patients with stage III and IV tumours compared with patients with stage I and II tumours. Abnormal serum concentrations of albumin, transferrin, and haptoglobin were indicative for advanced renal carcinoma.

Urinary excretion of ten plasma proteins in patients with febrile diseases.

The 24-hour urinary excretion of albumin, transferrin, haptoglobin, IgG, IgA, IgM, free lambda and kappa light chains from immunoglobulin, lysozyme, and beta2-microglobulin has been investigated in 22 patients with febrile diseases, using an automated immunoprecipitin reaction. The average excretion of the 10 proteins was significantly increased in the patients compared with a control group. In patients with body temperature is greater than or equal to 38.5 degrees C the tubular type of proteinuria was significantly increased compared with those with body temperature is less than 38.5 degrees C. Sequential studies in 10 patients showed that the tubular type of proteinuria occurred in all, whereas the glomerular type was demonstrated in 8. when the fever had subsided, the tubular proteinuria disappeared rapidly i in all patients, while the glomerular proteinuria disappeared in only 4 out of 8. It was shown that tubular proteinuria was caused by fever per se, and it is suggested that glomerular prteinuria might be due to an immue response to antigens, derived from the infectious agents, producing a transient or permanent glomerular injury.

The 24-hour excretion of plasma proteins in the urine of apparently healthy subjects.

In 239 apparently healthy subjects the 24-h urinary excretion of albumin transferrin, haptoglobin, IgM, IgG, IgA, immunoglobulin-free lambda and kappa light chains, lysozyme, and beta-2-microglobulin was studied by means of an automated immunoprecipitin reaction. The 24-h excretion of the proteins showed a very uneven distribution. Albumin was excreted in the largest quantities, 1.6-34.2 mg/24 h (0.95 range), and beta-2-microglobulin in the smallest quantities, 0-0.14 mg/24 h (0.95 range). Seven of 10 proteins were excreted in significantly lower quantities in children than in adults.

Infiltrating renal collecting duct carcinoma associated with epithelial dysplasia of the renal pelvis.

A case of multifocal urothelial dysplasia in the renal pelvis and simultaneously occurring dysplasia in collecting ducts with invasion in the renal medulla is presented. The essential role of cytopathology in diagnosis is emphasized.

Urinary protein profiles following urography with iothalamate. A preliminary report.

Urinary protein profiles (IgG, albumin, beta 2-microglobulin) following urography with iothalamate were investigated in 5 patients with functionally and morphologically normal kidneys. In 4 of 5 patients an increased clearance of at least one of the proteins was found indicating disturbance in both glomerular and tubular function and the change was transient (up to 6 days). Albustix was always negative.

The urinary excretion of ten plasma proteins in long-term renal transplant patients.

Using an automated immunoprecipitin reaction, the urinary excretion of albumin, transferrin, haptoglobin, IgM, IgG, IgA, free lambda and kappa light chains from immunoglobulin, lysozyme and beta2-microglobulin has been investigated in 40 long-term bilaterally nephrectomized renal transplant patients. The excretion of the proteins, except lysozyme, was significantly increased in 21 of the paitents with Albustix-negative urine. In patients with glomerulonephritis prior to the transplantation, the excretion of albumin, transferrin, and IgG was significantly increased compared with the other patients. The IgM excretion was significantly increased in patients who had received C and D matches compared with those with A and B matches. Patients with severe surgical complications in the postoperative period had a tubular proteinuria, and in patients surviving more than 60 months after transplantation the excretion of several proteins was significantly increased compared with patients surviving less than 60 months.

Asynchronous metastasizing renal cell carcinoma associated with progressive immune complex glomerulonephritis and proteinuria.

A case of asynchronous renal carcinoma with a 15-year course is described. Right nephrectomy and left heminephrectomy were performed. Solitary metastases to pancreas and striated muscle were treated with total pancreatectomy and local excision, respectively. The patient died of renal failure due to progressive immune complex glomerulonephritis, which was documented histologically as well as by clinical observations of intensifying excretion of urinary protein with decreasing selectivity. The glomerular lesion is suggested to have been caused by deposition of tumour-related immune complexes arising from an immune response by the host to his tumour.