Hypertension, erythrocyturia and proteinuria in childhood non-Hodgkin's lymphoma.

AIM: The objectives were to determine the prevalence and outcome of hypertension, significant microerythrocyturia and proteinuria among children with acute renal failure (ARF) due to Burkitt-type non-Hodgkin's lymphoma (BNHL). METHODS: A retrospective analysis of clinical and laboratory data of children with BNHL/ARF was undertaken. RESULTS: Nine of 23 (39.13%) BHNL/ARF children aged 5-14 years were found to have significant microerythrocyturia and proteinuria as urinary markers of glomerulonephritis (GN). Eight of nine were hypertensive with hypertensive encephalopathy (HTE) in three, and congestive heart failure (CCF)/pulmonary oedema in six. Three of nine patients (33.3%) died from these complications; two from CCF and one from a combination of CCF and HTE. A fourth death was due to uraemia. Treatments with cytotoxic drugs and anti-tumour lysis syndrome therapy resulted in normotension, improved clinical outcome and normalisation of laboratory features of ARF and GN in all five (55.6%) survivors. CONCLUSION: We conclude that all the children with BNHL/ARF had enlarged kidneys and evidence of glomerular disease. The mechanism of the glomerular disease is unclear. It is associated with a high mortality rate.

Urinary N-acetyl-beta-D-glucosaminidase activity in leukaemic children during high-dose methotrexate therapy.

Urinary N-acetyl-beta-D-glucosaminidase (NAG-ase) activity is a very sensitive parameter of kidney proximal tubular damage. Using urinary NAG-ase activity/urinary creatinine as the NAG index, the serum methotrexate (MTX) level and urinary pH were investigated simultaneously. These parameters were measured in 17 leukaemic children. During MTX treatment, NAG indices were normal in 5 children and only slightly elevated occasionally in 9 patients. Among them, transiently high serum MTX levels (Patient A) or low urinary pH (Patient B) were accompanied by high NAG indices. MTX toxicity has been diagnosed in 3 cases, when permanently high NAG indices were in accordance with other clinical signs.

New applications of urinary nucleoside markers.

In order to extend the usefulness of the quantitation of urinary nucleoside markers, studies were undertaken to explore the adaptability of such determinations for early detection in cancer-prone populations such as asbestos workers. Another study was aimed at exploring the usefulness of therapy in individual patients. During these studies, two heretofore unknown phenomena serendipitously emerged which expand the versatility of the marker determinations: (a) radiation damage in animals and humans causes an excretion of urinary BAIB which from preliminary studies appears to be proportional to the irradiation burden, and (b) lead poisoning in the human also produces BAIB excretion. Some of the practical uses of these determinations are self-evident. Among 13 asbestos workers without clinical symptoms, eight were found to have significant elevations of the marker levels. Nine asbestos workers with diagnosed mesothelioma all excreted two or more markers at high levels. Some of the psi levels were the highest seen. Currently the diagnosis of mesothelioma is difficult and painful, requiring a rib resection; however, an asbestos worker with such elevations--provided small cell carcinoma of the lung is ruled out--can be seriously suspected of having mesothelioma. In a study of the usefulness of the markers in following therapy of trophoblastic disease, these markers were determined in women with incipient invasive hydatidiform mole. After curettage, the nucleoside markers indicated absence of residual disease but the usual marker, HCG, was still markedly elevated. The women were followed up for 2 years and were found to remain symptom-free. Therefore the source of the nucleoside markers is cleared more rapidly than that of HCG.

Beta-aminoaciduria in patients with Burkitt's lymphoma.

The massive amounts of beta-aminoisobutyric acid (beta-AIBA) in the urine of Burkitt's lymphoma patients were measured along with other alpha-amino acids and beta-alanine present in normal and decreased levels. The ratios of the amount of beta-AIBA to beta-alanine, in mumoles/kg urine collected in 24 hours, were elevated for all patients. The degree of elevation of beta-AIBA excretion and the ratio of the two beta-amino acids appeared to be related to the amount of tumor mass present. These analyses may have possible value in monitoring patients with Burkitt's lymphoma during their disease course.

Potential biologic markers in Burkitt's lymphoma.

Specific biochemical molecules used as potential biologic markers, including modified nucleosides, polyamines, and pyrimidine catabolic end-products, were quantitatively measured in the urine of seven patients with Burkitt's lymphoma before, during, and after one or more courses of therapy. The results of this preliminary study demonstrated that patients with this disease frequently excrete significantly increased amounts oof modified nuceleosides (considered to be derived primarily from transfer ribonucleic acid), polyamines, and beta-aminoisobutyric acid during the course of their disease. With successful treatment and rapid destruction of tumor cells, a concomitant rise in these molecules occurs. Elevations were observed prior to chemotherapy and changes in levels associated with treatment or tumor progression appeared to correlate with disease status and to aid in assessing antitumor response. Periodic follow-up analysis of these molecules may be helfful in appraising relapse or recurrence of the malignancy prior to overt evidence of tumor by existing clincial means.

Excretion of immunoglobulins in Burkitt's lymphoma.

IgM was detected in the urines of 4 out of 17 patients with Burkitt's lymphoma. This IgM emerged from Sephadex G 200 column in two different peaks strongly suggesting sub-units of the intact molecule. IgM was not detected in any of the control urines. The total protein excreted in the urine of Burkitt's lymphoma patients is higher than in controls and may be due to renal involvement. Intact IgA and IgG as well as fragments of IgG were present in the urines of all Burkitt patients as well as in controls. Six of 16 Burkitt's lymphoma patients had reduced serum levels of IgG. Four of these also had reduced serum IgM. The low mean concentration of serum IgM confirms our previous studies.