Dubravka Čvorišćec

Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

Endemic nephropathy in Croatia.

Abstract 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.

Comparison of the values of basic fibroblast growth factor determined by an immunoassay in the sera of patients with traumatic brain injury and enhanced osteogenesis and the effects of the same sera on the fibroblast growth in vitro.

In patients with severe traumatic brain injury, the early healing of fractures is accompanied by hypertrophic callus formation or heterotopic ossifications, which might even result in ankylosis of the affected joints. Analysis of the sera of patients with traumatic brain injury revealed post-traumatic dynamic changes of basic fibroblast growth factor immunoreactivity, similar to those observed during fracture healing associated with enhanced osteogenesis. The aim of this study was to determine whether such changes in basic fibroblast growth factor concentrations could be related to the phenomenon of enhanced osteogenesis. Basic fibroblast growth factor immunoreactivity was determined (using an IEMA kit) in the sera of patients with traumatic brain injury and bone fractures (n = 8) and in the sera of patients with either traumatic brain injury alone (n = 10) or bone fractures alone (n = 7), and the effects of these sera on L929 fibroblast growth were analysed in vitro. The results did not prove a causative relationship between the changes of basic fibroblast growth factor immunoreactivity and in vitro growth promoting effects of the sera. However, it is apparent that, in addition to changes in the growth-promoting activity and basic fibroblast growth factor concentration of serum, other as yet unknown post-traumatic changes can cause enhanced osteogenesis.

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.

Relationship between Tubular and Tamm-Horsfall Proteinuria in Balkan Endemic Nephropathy

Excretion of low molecular mass proteins derived from blood plasma and Tamm-Horsfall protein, a specific renal protein, was determined in the subjects from the area of Balkan endemic nephropathy. A significantly higher excretion of Tamm-Horsfall protein was observed in the subjects with tubular type of proteinuria compared to the subjects with glomerular selective type proteinuria and the subjects with physiological type proteinuria.

Could Disappearance of Endemic (Balkan) Nephropathy Be Expected in Forthcoming Decades

Background/Aims: An epidemiological survey of endemic nephropathy (EN) was performed in endemic Croatian areas and the current prevalence was compared to that reported for the same villages several decades ago. Methods: A total of 2,487 adult farmers from 6 endemic villages and 3 non-endemic villages were enrolled. An extensive epidemiological questionnaire, clinical examination and laboratory analyses of blood and urine were performed. According to the modified WHO criteria, participants were classified into diseased, suspected of having EN, and those at risk of developing EN. Results: The overall prevalence of EN in the Croatian areas was 1.0%, ranging between 0.3 and 2.3% in different villages. Those suspected of having EN amounted to 3.9%. In the endemic villages a decreasing trend in the prevalence of EN was observed comparable to the results obtained in previous surveys. It is interesting to note that no EN patients were recorded in the endemic village of Dubočac. Conclusion: The prevalence of EN in the endemic Croatian areas appears to be decreasing. For the first time, we failed to detect any EN patients in a village that was previously considered endemic, which might indicate that EN is diminishing.

Biochemical markers of bone remodeling – review

Danas je u upotrebi niz biokemijskih biljega pregradnje kostiju, ukljucujuci biljege izgradnje i razgradnje kostiju. Oni pružaju klinicki korisne

Characteristics of proteinuria in endemic nephropathy

Subjects living in the endemic area of Posavina round Slavonski Brod have a significantly greater incidence of proteinuria (13.6%) than those living under the same conditions in the area where endemic nephropathy has not been observed (5.5%). Following determination of the grade and type of proteinuria, physiologic proteinuria was found in 36% of subjects from the endemic area. In nonphysiologic proteinuria the incidence of tubular proteinuria was 41%. A slight selective glomerular proteinuria was found in 51%, and other types of proteinuria in 8% of subjects. Tubular proteinuria was significantly higher in the endemic area than in the control area. The subjects with tubular proteinuria from the endemic area excrete significantly greater amounts of beta 2-microglobulin and light immunoglobulin chains.

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.

Tamm-horsfall protein determination in Balkan endemic nephropathy

SummaryData on the excretion of Tamm-Horsfall protein (THP) in subjects living in an area of Balkan endemic nephropathy (BEN) are reported. The study subjects were divided into groups as follows: diseased, suspect, “at risk” and others, according to previously adopted criteria. The THP excretion in “at risk” subjects was found to be significantly higher as compared to control subjects. The difference between these two groups could not be registered by any other clinical or laboratory diagnostic methods. No difference in the excretion of THP was observed between the groups of others and control subjects. According to the results obtained, the excretion of THP may be considered a possibly useful additional diagnostic test for the detection of subjects with the latent, early subclinical phase of BEN. On the other hand, the data obtained shed some more light on the still obscure pathogenesis and natural history of BEN.