Early diagnosis of endemic nephropathy.

Urinary alpha(1)-microglobulin as a tubular marker and albumin as a glomerular marker were measured in 373 subjects living in a typical endemic village of Kaniza, Croatia, previously classified as diseased, suspect, 'at risk' and others according to the criteria used for the diagnosis of endemic nephropathy. Based on the excretion pattern of alpha(1)-microglobulin and albumin and its extent, significant tubular with significant glomerular proteinuria was found in seven diseased subjects. Significant tubular proteinuria with slight glomerular proteinuria was found in one diseased subject, while another diseased subject had slight tubular with significant glomerular proteinuria. Significant tubular with significant glomerular proteinuria was found in only one suspect subject. Also, significant tubular proteinuria was established in one other subject.

Antibodies to Tamm-Horsfall protein in endemic nephropathy.

BACKGROUND: The aim of the study was to investigate the possible role of antibodies to Tamm-Horsfall protein (anti-THP) in the early diagnosis of endemic nephropathy (EN). METHODS: Anti-THP (IgA, IgM, IgG classes) antibodies were determined by direct ELISA in a random sample of 159 subjects from the endemic village of Kaniza who were divided into four groups according to the WHO criteria, i.e., 'diseased', 'suspect', 'at risk', and 'others'. These groups were compared to subjects from the non-endemic village of Klakar and healthy subjects from Zagreb. RESULTS: No differences for all the classes of antibody were observed among the groups of subjects from the endemic village of Kaniza (P>0.05) or between these subjects and those from the non-endemic village of Klakar (P>0.05). The values of IgM anti-THP antibodies exceeded those of the IgA and IgG classes in all groups of subjects (P<0.05). The values for all three classes of antibodies were higher in the rural than the urban population (P<0. 05). CONCLUSION: Determination of anti-THP antibodies was not found to be useful in the early diagnosis of endemic nephropathy. The results suggest that most of the anti-THP antibodies are 'natural' and/or cross reactive. The highest values observed in the rural population could probably be explained by exposure to some ubiquitous antigen or more likely they are consequences of fever.

Relation between urinary cytology abnormalities and cyclosporine A therapy in bone marrow transplant recipients.

The aim of the study was to determine the relationship, if any, between abnormalities in urinary cytology and the administration of cyclosporine A in bone marrow transplant recipients. Specific attention was given to the presence of tubular cells with round inclusions (TCRI). Two bone marrow transplant recipient groups were studied: one with allogeneic bone marrow transplantation (BMT) (20 patients) who were treated with cyclosporine A, and the other with autologous BMT (12 patients) who did not receive cyclosporine A. Urinary cytology showed TCRI in 41.66% of the patients after autologous BMT and in 80% of the patients after allogeneic BMT. In the group of patients treated with allogeneic BMT, the occurrence of TCRI was associated with a high incidence of glycosuria and was followed by an increase in the blood level of cyclosporine A, an increase in the serum creatinine concentration and a decrease in the creatinine clearance. These results demonstrated that TCRI, although related to, were not found to be exclusively specific to the administration of cyclosporine A.

Endemic nephropathy in Croatia.

Endemic nephropathy is a chronic renal disease with a high prevalence in a geographically limited area of Croatia. It has also been recorded in some parts of Bosnia, Serbia, Bulgaria and Romania. Despite numerous studies conducted to date, the etiology of this disease has not been clarified. Pathological studies of the kidney in the early stage of endemic nephropathy have shown renal tubules to be the primary sites of the pathologic process with an interstitial tissue reaction, whereas glomerular alterations are of a secondary character. Tubulointerstitial lesions can thus account for the symptoms of the disease, i.e. tubular proteinuria and reduced urine concentration capacity and urine acidification. Also, an increased incidence of malignant tumours of the urinary tract was found in the same geographic area.

Antibodies to Tamm-Horsfall protein in patients treated with extracorporeal shock wave lithotripsy (ESWL).

The aim of this study was to determine antibodies to Tamm-Horsfall protein in patients with nephrolithiasis treated with extracorporeal shock wave lithotripsy (ESWL). The values of antibodies to Tamm-Horsfall protein were determined by direct enzyme immunoassay. No statistically significant differences (P > 0.05) were observed for the IgG and IgM classes of antibodies between the groups of healthy subjects and patients with nephrolithiasis before, and 30 and 60 days after ESWL. The values of IgA class determined 30 days after treatment were significantly higher (P < 0.05) in patients, which could be due to the stimulation of the immune system. The highest values of antibodies to Tamm-Horsfall protein were obtained in both groups in the test with secondary antibodies directed toward IgM class, implicated at the presence of cross-reactive antibodies. Determination of antibodies to THP subunits isolated form urine of patients with nephrolithiasis should be performed.

Association between deletion polymorphism of the angiotensin-converting enzyme gene and cerebral atherosclerosis.

We investigated deletion polymorphism in the gene for angiotensin-converting enzyme in patients with angiographically verified cerebral atherosclerosis. Genotypes were determined by the polymerase chain reaction with oligonucleotide flanking of the polymorphic region of intron 16 of the angiotensin-converting enzyme gene. Results of angiotensin-converting enzyme genotyping showed 46% of 50 studied patients to be homozygous for the DD allele, whose prevalence was significantly increased as compared with a group of controls without atherosclerotic changes. In this control group, the following genotypes were observed (%): II = 24, ID = 52 and DD = 24. The frequency of the I and D alleles in the group of patients with cerebral atherosclerosis was 0.28 and 0.72, respectively, whereas in the group without atherosclerosis it was 0.50 for both. Furthermore, in the present study, the DD genotype was associated with a high level of serum angiotensin-converting enzyme activity, total and LDL-cholesterol and triacylglycerol. A newly established association between DD genotype and cerebral atherosclerosis, detected even in our small group, supports the view that angiotensin-converting enzyme polymorphism might be indicative of the development of cerebral atherosclerosis.

Effect of Tamm-Horsfall protein on calcium oxalate precipitation.

The effect of Tamm-Horsfall protein isolated from urine of healthy subjects on calcium oxalate precipitation was studied in model systems of precipitation. The study was performed using following conditions: concentrations of calcium chloride 10 mmol/l, sodium chloride 150 mmol/l, oxalic acid 300 mumol/l; pH 6.0, and temperature 310 K. The concentration of Tamm-Horsfall protein varied between 1-10 mg/l. The kinetics of calcium oxalate precipitation was observed by measuring the number and volume of particles in the suspension, and the precipitate composition by an optic microscope. In all the studied systems, the precipitate morphology corresponded to pure calcium oxalate monohydrate. Tamm-Horsfall protein was found to inhibit the growth of calcium oxalate monohydrate crystals and stimulate their aggregation in the given experimental conditions. Both effects were enhanced by increase in the concentrations of Tamm-Horsfall protein and were most pronounced at the concentration of Tamm-Horsfall protein of 10 mg/l.

Acute upper respiratory tract infections and indications for tonsillectomy in children. I. Immunoglobulin synthesis in the palatine tonsil tissue.

Current viewpoints and practice concerning indications for tonsillectomy are presented. The annual specific risk for upper respiratory infection in children aged up to 15 is 1.1. The risk is higher in the youngest age group, in whom it rises to 1.8, decreasing with age and being lowest among children aged 12-15 years (0.5). The proportion of tonsillitis among acute upper respiratory tract infections is highest in the age group up to 3 years (36.9%); at the age of 4-5 years it is 37.1%, and is lowest among children aged 12-15 years (21.9%). The risk of tonsillitis caused by streptococci is highest among children aged up to 5 years. Statistical significance of differences in the synthesis of immunoglobulins (G, M, A and sA) and lysozymes in the palatine tonsil tissue of tonsillectomized children and healthy volunteers was tested by non-parametric tests for independent samples. Significant differences of the above mentioned syntheses were found in all entities studied. Any contribution to the documentation on the nature and cause of each tonsillitis in childhood is of great clinical value, because it is the only basis for rational consideration of indications for tonsillectomy.

Urinary glycosaminoglycans in different phases of Balkan endemic nephropathy.

The relationship between glycosaminoglycans and beta 2-microglobulin, glycosaminoglycans and N-acetyl-beta-D-glucosaminidase as well as the relationship between the chondroitin sulfate/heparan sulfate ratio and SDS electrophoresis in the urine of subjects from the endemic area of Balkan nephropathy was studied in order to establish a method for early detection of this disease. The results show an unquestionable increase in urinary excretion of total glycosaminoglycans in subjects with or suspected of having Balkan endemic nephropathy while the chondroitin sulfate/heparan sulfate ratio was not statistically different between the groups studied. Thus, the chondroitin sulfate/heparan sulfate ratio cannot be used as a cheap and quick semiquantitative method for the diagnosis of early tubular damage in Balkan endemic nephropathy. However, the determination of total glycosaminoglycans in the urine of subjects from endemic areas proved to be valuable additional information helping with the diagnosis of Balkan endemic nephropathy.

Beta 2-microglobulin studies in endemic Balkan nephropathy.

The diagnosis of BEN and its differentiation from other chronic interstitial nephropathies are difficult because of the insidious onset as well as nonspecific morphological changes in the kidney. Early diagnosis of this disease is by clinical and laboratory findings which have not been universally accepted. This study was designed to determine if the frequency of increased urinary beta 2-microglobulin (U beta 2m) in village populations at risk to develop BEN was significantly higher than that seen in a control population. Individuals in the two population samples were classified in one of three categories: healthy, suspect or diseased. There were 23 individuals who met the criteria for the clinical diagnosis of BEN. Twenty (87%) of these had one or more positive tests for increased U beta 2m. The prevalence of kidney disease in the endemic village population sample was 13.4 times that for the control village population sample. The data show that the healthy individuals living in a village where BEN is endemic have 6.4 times greater chance of having tubular proteinuria than those living in a control area. The coincidence of the finding of U beta 2m in the urine of 87% of those sick with BEN and in 37 of the 342 (10.8%) people judged to be free of kidney disease suggests that a positive U beta 2m test is an early indicator of exposure to a nephrotoxic agent.

A fifteen year cohort based evaluation of beta 2-microglobulin as an early sign of Balkan endemic nephropathy.

The occurrence of elevated urinary beta 2-microglobulin (U beta 2m) has been established to be more common in village populations living in areas where BEN is endemic when compared to appropriate control population. In addition, beta 2-microglobulinuria is associated with BEN. It has been demonstrated that there is an increase in the U beta 2m in apparently healthy populations located in high risk areas. It is 15 years since the first systematic investigations of U beta 2m in the villages of Brod Posavina were conducted. The purpose of this study was to determine the value of a positive test for tubular proteinuria as defined by increased U beta 2m, in identifying individuals at risk to develop BEN. In these studies we followed two cohorts for 15 years: one group consisted of individuals who were positive for tubular proteinuria by U beta 2m testing in 1974; the second group was an age and sex matched group from the same village who were never positive after 12 testings in 1974. The results show that a positive test for U beta 2m is associated with 9.9 times greater relative risk of developing BEN when compared to controls that had no positive U beta 2m tests.

Relationship of anemia to Balkan endemic nephropathy.

Anemia has been reported to be an early sign of Balkan endemic nephropathy (BEN) occurring before the serum creatinine is elevated. This study was designed to determine if anemia occurred more frequently in an otherwise 'healthy' population living in an area where BEN is endemic when compared to a control population. Also, we wished to determine if any relationship existed between anemia and beta 2-microglobulinuria (beta 2mu) in these populations. The prevalence of anemia in the control village population was 7%, compared to 21.4% of the at-risk village population. These data suggest that anemia is a part of the pathophysiologic picture of endemic nephropathy, and that anemia can be found in an early, non-azotemic phase of the kidney disease.

[Quantitative evaluation of the immunoglobulin G, A and M in the human dental pulp]. / Kvantitativna evaluacija imunoglobulina G, A i M humane zubne pulpe.

The presence of immunoglobulins G, A and M was studied in human dental pulps using a quantitative method of radial immunodiffusion. Valid data on the amounts of IgG, IgA and IgM were obtained on the basis of measured concentrations of immunoglobulins in each pulp sample and their correlation with total protein concentrations. The results indicated IgG to be present in 100%, IgA in 15% and IgM in 8% of 13 pulp samples affected by chronic inflammation. The mean values of IgG, IgA and IgM thus determined were 84.3, 4.4 and 1.4 mg/g protein, respectively. In intact pulp tissue, however, no presence of immunoglobulins G, A and M could be detected using the same method as above. The results obtained suggested the possibility of local synthesis of immunoglobulins in chronically inflamed pulp tissue, indicated that nonspecific inflammatory reaction may have occurred concurrently with some specific immunologic reactions. The predominance of IgG pointed to immunologic reactions of early types II and III hypersensitivity.

[Serum acute phase proteins for determining disease activity of ulcerative colitis and Crohn disease]. / Akutphasenproteine im Serum zur Aktivitätsbeurteilung von Colitis ulcerosa und Morbus Crohn.

We studied the activity assessment of ulcerative colitis and Crohn's disease by 5 acute phase reactants: C-reactive protein (CRP), alpha 1-acid glycoprotein, alpha 1 antitrypsin, haptoglobin and fibrinogen. From a large register of patients with inflammatory bowel disease (IBD) we chose randomly 91 patients: 61 with ulcerative colitis and 30 with Crohn's disease. As a reference point in the disease activity assessment we used standard clinical indices. Statistical analysis was performed by non-parametric methods: the Kruskal-Wallis and Fisher's exact test. The disease activity assessment in patients with ulcerative colitis by the index according to Powell-Tuck indicated that the patients with active disease (N = 19) had significantly higher levels of all acute phase proteins mentioned above except fibrinogen (alpha less than 0.05 to 0.001) than patients in remission (N = 42). Analysis of the same data by Fisher's exact test indicated that there had been a probability for all the proteins measured to be higher than the normal values, particullary CRP (p less than 10(-8) and the other somewhat less. In patients with Crohn's disease, the disease activity assessment was performed by 2 indices. According to "The Crohn's Disease Activity Index" (CDAI), only alpha-1 acid glycoprotein and haptoglobin (alpha less than 0.05) were higher in patients with active disease (N = 4) than in patients with remission (N = 26).(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of C-reactive protein in the evaluation of activity in ulcerative colitis and Crohn's disease]. / Vrijednost C-reaktivnog proteina u procjeni aktivnosti ulceroznog kolitisa i Crohnove bolesti.

We studied a value of measuring the C-reactive protein (CRP) serum concentration in the assessment of ulcerative colitis and Crohn's disease activity. From a large register of patients with the inflammatory bowel disease (IBD), we have chosen randomly 91 patients: 61 with ulcerative colitis and 30 with Crohn's disease. As a reference point in the assessment of ulcerative colitis we have used the Powell-Tuck clinical index. Nineteen patients had an active disease, and 42 were in a remission. Patients with the active disease had significantly higher levels of the CRP then the patients in remission (chi 2 = 4.99; alpha less than 0.05). Serum CRP levels and the disease activity assessment by Powell-Tuck index were in a positive correlation, according to the Fisher's exact test (p less than 10(-8)). In the group of 30 patients with Crohn's disease, the disease activity was assessed by CDAI ("The Crohn's Disease Activity Index") and by van Hees index. According to CDAI, 26 patients were in a remission, and only 4 had an active disease. According to van Hees index, there was no patient in a complete remission, 17 patients had a partial remission and 13 had an active disease. Patients with the active disease had significantly higher CRP levels then the patients in remission, according to van Hees index (chi 2 = 7.863; alpha less than 0.01), but not according to CDAI (not significant). Meanwhile, the Fisher's exact test suggested a high positive correlation between the disease activity assessment with both indexes, either CDAI or van Hees, and the CRP serum values (alpha less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of long-term use of lithium on kidney function]. / Utjecaj dugotrajne primjene litija na bubreznu funkciju.

The effect of lithium and other antipsychotic drugs on the renal function in patients with manic-depressive disorders has been investigated. Thirty-four patients (5 males and 29 females) treated with lithium and 21 patients (6 males and 15 females) on other antipsychotic drugs were studied. A control group of 10 persons consisting of healthy subjects, all of whom were taking no medication was also studied. No significant differences in the treatment duration were present between the patients investigated. Although few patients on lithium had glomerular filtration reduced, no statistically significant difference in creatinine clearance was found between the groups. None of the patients had a disturbance in the reabsorption of glucose, amino acids (histidine, lysine, valine, glutamine, glycine, serine, taurine, threonine, alanine, isoleucine) and beta 2-microglobulin. Patients treated with lithium had a significantly reduced urine concentration and higher daily diuresis than did the other two studied groups. A significantly higher overnight elimination of alkaline phosphatase was found in a group of patients taking other antipsychotic drugs. The attained results suggest tubular lesions in patients with manic-depressive psychosis occurring in the association with the prophylactic use of lithium and, at same time, the possibility of the other in association with the other antipsychotic drugs.