Real cause of high level of urinary beta 2-microglobulin after renal transplantation.
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Biomedical subjects
Publications and source records attributed to J Steinhoff.
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Serial serum determinations of the tumour associated antigens carcinoembryonic antigen, tissue polypeptide antigen, CA 19-9, CA 15-3 and CA 125 were performed on 70 patients who were undergoing, or had undergone renal transplantation. The period of observation ranged from 4 days pre-operative to 708 days post-operative, although daily monitoring was usually carried out during the first 14-35 days post-operatively. With the exception of tissue polypeptide antigen, which was analysed with an immunoluminometric assay, all analytes were measured with the Enzymun-Test System ES-300 using immunoenzymometric assays with colorimetric determination. The interassay coefficients of variation were less than 5% for the immunoenzymometric assays and 8.7% for tissue polypeptide antigen, all values being derived from 20 consecutive assays. Only 8/70 patients with no complications showed normal concentrations for all five analytes. 6/79 patients showed parallel changes of at least three markers. 7/70 patients had transient elevations of at least one marker, whereas 25/70 patients had a continual elevation of CA 125, 9/70 CA 19-9 and 1/70 CA 15-3, although no patient showed evidence of disease. Two patients, each with 2 rejection episodes, showed daily fluctuations up to 100% for all markers, with the exception of carcinoembryonic antigen. There was no correlation between elevated tumour markers and cytomegalovirus infection.
A prospective study was undertaken in 73 patients (24 women, 49 men; mean age 47.9 [21-64] years) after renal transplantation to discover whether the presence of C-reactive protein in urine (CRPu) and its serum concentration (CRPs) are of value in the differential diagnosis of abnormal function in the transplanted kidney. CRPu concentration was measured with a highly sensitive immunoluminometric assay (minimal threshold value 6 micrograms/l). CRPu was demonstrated in 36 histologically proven rejection episodes and 21 bacterial infections proven by culture. In contrast, no CRPu was demonstrated when the course was normal and in individual cases of cyclosporin renal toxicity, as well as in 27 of 34 cases of cytomegalovirus infection. In addition, the CRPs to CRPu ratio was a sensitive means of distinguishing between rejection (CRPs/CRPu less than 1) and bacterial infection (CRPs/CRPu greater than 1). Determining CRPu concentration thus proved to be useful in the initial monitoring of renal transplantation before starting any specific urinary protein diagnosis, as well as (together with CRPs) in the diagnosis of severe posttransplantation complications.
The frequency of cytomegalovirus infection was studied in a prospective study of 106 kidney recipients. The detection of cytomegalovirus-immediate-early-antigen and cytomegalovirus-immunoglobulin (IgM) antibodies in serum was used as the reference method and showed that 23.6% (25/106) of all patients were infected. In addition, four urinary proteins (IgG and transferrin as glomerular markers and alpha1-microglobulin and beta2-microglobulin as tubular markers) were quantitatively measured in 24-h urine samples from all of the patients using an immunoluminometric assay (ILMA). In all cytomegalovirus infection cases a pronounced but isolated increase of urinary beta2-microglobulin excretion was observed. In 20 of 25 infected patients, the beta2-microglobulinuria occurred 1-21 days (median 5.0) earlier than the appearance of the cytomegalovirus-immediate-early-antigen in blood. Thus, it can be seen that the quantitative measurement of beta2-microglobulin in urine is useful for the early detection of cytomegalovirus infection following renal transplantation.
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A 15-year-old girl of Turkish descent had for one year complained of severe recurrent fever-associated deep back pains. Since she was three years of age she had suffered from repeated attacks of fever and severe abdominal pain which ceased spontaneously in 1-3 days. On physical examination the sacrum and iliosacral joints were very painful to percussion, and she limped. Radiography revealed symmetric destructive sacroiliitis. Despite the unusual location of the arthritis, the triad of fever, abdominal pain and arthritis, as well as her belonging to an ethnic "at risk" group, pointed to the diagnosis of familial mediterranean fever (FML) or recurrent hereditary polyserositis. This diagnosis was confirmed by a positive metaraminol provocation test in that infusion of metaraminol reproduced the typical pains. Collagen diseases, rheumatic disease, acute porphyria and chronic infectious processes were excluded. The sacroiliitis quickly responded to long-term administration of colchicine, 0.5 mg twice daily. The patient also has Hageman factor deficiency whose significance remains unclear.
In a prospective study the occurrence of cytomegalovirus (CMV) infection was diagnosed by demonstrating CMV-immediate early antigen (IEA) in the blood in 13 out of 68 (19%) patients who had undergone renal transplantation (27 women, 41 men, mean age 46.3 [21-64] years). Twenty-four hour urine samples were collected at the same time for quantitative determination of selected marker proteins by immunoluminometric assays (IgG and transferrin as glomerular markers, alpha 1-microglobulin and beta 2-microglobulin as tubular markers). In all 13 confirmed cases of CMV infection there was an isolated rise in urinary beta 2-microglobulin excretion amounting to more than three times the normal. In 11 of the 13 cases the beta 2-microglobulinuria was noted before the CMV-IEA test became positive. This suggests that quantitative assay of beta 2-microglobulin in the urine may be of value in the early diagnosis of CMV infection--a matter of some prognostic importance--and may hence offer additional support for therapeutic decisions.
A 45-year-old Turk had a year ago noticed a submandibular and a retroauricular node-like swelling, about 2 cm in diameter each, firm and freely mobile. During the preceding two months he had polydipsia and polyuria. Recently he developed a nephrotic syndrome with lower-leg oedema and proteinuria (14 g albumin in 24-hour urine). The concentrations of IgE (250 IE/ml) and IgA (745 mg/dl) were raised, and there was eosinophilia of 14%. Renal needle biopsy revealed glomerulonephritis with minimal proliferation. Excision of part of the nodular tumour revealed histologically the typical signs of Kimura's disease (eosinophilic follicular lymphadenitis of the skin; subcutaneous angiolymphoid hyperplasia with eosinophilia). During treatment with prednisolone, 20 mg daily by mouth, the clinical and biochemical findings regressed within two weeks. But eight weeks later, after dose reduction to 10 mg daily, the nephrotic syndrome recurred so that the dosage had to be increased again to 20 mg prednisolone daily. On this treatment the patient has now been symptom-free for six months. This case demonstrates the unusual association of Kimura's disease with minimally proliferative glomerulonephritis.
The introduction of cyclosporin gave rise to an additional problem in the surveillance of renal transplant patients, namely the differentiation between cyclosporin toxicity and acute transplant rejection. The development of assays for specific proteins in urine has produced a non-invasive solution to this problem. In 55 renal transplant patients the following proteins were determined daily in 24 h-urine samples: IgG, transferrin (TF), albumin, beta 2-microglobulin (beta 2-MG), retinol binding protein (RBP), alpha 1-microglobulin (alpha 1-MG) and alpha 1-antitrypsin (alpha 1-AT). All proteins were determined quantitatively using immunoluminometric assays and 10 microliters urine in dilutions from 1:1-1:100. The urinary protein excretion was related to the actual creatinine clearance as this index gave the best differentiation between normal and abnormal status. In 24 h-urine, intraindividual peaks of IgG, TF and albumin were seen regularly in acute rejection episodes. However, a peak in the "tubular" proteins (RBP, beta 2-MG, alpha 1-MG) could not be detected. After effective treatment of the rejection episode, the renal function improved and the protein excretion returned to prerejection episode levels. In bacterial infection of the urogenital tract, urinary alpha1-AT levels rose. They returned to normal after successful antibiotic treatment. In two cases of cyclosporin toxicity neither glomerular nor tubular proteins were excreted in abnormal amounts when compared with transplant patients without complications, the only changes being an increase in serum creatinine as a result of reduced renal function.
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A 38-year old woman with serious nephrotic syndrome due to kidney amyloidosis in consequence of Crohn's disease was observed. The long-term prognosis of this illness is serious, but since in the literature several good results have been mentioned under treatment with immunosuppressives, in the present case an aggressive immunosuppression was carried out, which was started under the conception that, in consequence of elimination of preamyloid substances from the serum by plasmapheresis in combination with an additional inhibition of the reproduction of these substances by azathioprine, the clinical picture could be favourably influenced. During therapy with long-term intermittent plasmapheresis in combination with azathioprine a complete remission of the nephrotic syndrome was achieved.
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A progressive deterioration of renal anatomy and renal function with aging is inevitable. Glomeruli become sclerotic, renal mass declines, kidneys are shrinking and creatinine clearances decreases about 50% after the third decade of life. Renal aging in accelerated by risk factors of arteriosclerosis. The relationship of serum creatinine and creatinine clearance changes with age, since creatinine production is diminished. Old kidneys show a reduced ability to compensate stress, e.g., infection, medication, changes in blood pressure, and the risk of acute renal failure is increased. A glomerulonephritis in advanced age may be caused by a vasculitis; despite rapidly progressive course, early treatment can often improve renal function. The dosage of drugs eliminated by the kidneys has to be adapted in old patients. Despite only moderately elevated serum creatinine, renal function may be severely reduced in old persons and dialysis may be indicated. Dialysis and renal transplantation are possible therapeutic options despite advanced age.