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Balkan endemic nephropathy (BEN) is a chronic progressive kidney disease leading to renal insufficiency. The possible etiological role of some toxic factors was considered in this study by investigating the activity of erythrocyte delta-aminolevulinate dehydratase (ALA-D), an enzyme influenced by various environmental factors. We observed that ALA-D activity was markedly decreased in patients with BEN and in 32% of their healthy family members. Glutathione concentration was found normal in all the groups studied, however, it was possible to reactivate the enzyme in vitro by addition of exogenous glutathione. Percent activation was significantly higher in the groups with decreased ALA-D activity. Blood lead levels were within normal range. The results suggest a normal synthesis of ALA-D apoenzyme, and also the presence of some factors, environmental, metabolic, or genetic, which may affect the enzyme activity through binding to the reactive groups in the active center of this enzyme or by oxidation of the reactive groups. Additional studies are necessary to further elucidate the significance of decreased ALA-D activity in BEN and their healthy relatives.

We studied the urinary excretion of total protein and five other proteins in urine samples from a total of 831 children and adolescents. The characteristics of the children were: (1.) they resided in areas where Balkan nephropathy (BEN) is endemic and also had family members suffering from BEN; (2.) they resided in areas where BEN is endemic, but the families had no members suffering from the disease; (3.) they lived in nonendemic settlements; (4.) they lived in the city of Nis. Urinary excretion of total protein (TP), albumin (ALB), alpha 2-macroglobulin (alpha 2m), transferrin (TF), IgG, and beta 2-microglobulin (beta 2m) were measured. This study showed that urinary excretion of beta 2m and albumin in children from endemic settlements and from families affected with Balkan nephropathy were not different from the control rural settlements. However, children residing in the city of Nis had significantly increased urinary beta 2m and albumin excretion, over 1.5 to 2.6 times the excretion in the other three groups, although excretion of either protein remained within accepted normal ranges in all groups. The increased excretion of beta 2m and albumin in children from the city of Nis could probably be related to the different growth conditions and/or the effect of toxic environmental factors. These data could serve as a reference base for future comparative studies of urinary protein excretion in children as well as in BEN populations.

The role of lipid abnormalities has been also implicated in the progression of renal diseases. The search for lipid abnormalities in Balkan endemic nephropathy (BEN) has roused sporadic interest and has not been fully elucidated. This study was performed in 54 healthy subjects from the families affected with BEN (group A), 18 members from non-affected families living in the same location (group B), and 25 control subjects (group C). Lipid profiles and lecithin:cholesterol acyltransferase (LCAT) were determined in each subject. The most striking distinction between the groups was that of the LCAT activity, which was abnormally low in group A (39 +/- 2), significantly different (P less than 0.0001) from that of the other groups. Thirty individuals from group A were those accounting for the low LCAT activity (A1). This group had a significantly lower total cholesterol and free cholesterol than all of the other subjects. The entire group A subjects had a significantly lower percentage of free cholesterol than the other two groups. There was no significant difference in HDL cholesterol between any of the groups, but group A1 had significantly higher HDL than group C (P less than 0.04). What emerges from our study is that a certain proportion of subjects from BEN families have a peculiar form of lipid abnormalities associated with an abnormal LCAT activity. At present we have no explanation for these findings. We believe that these changes may have an important role in the pathogenesis of BEN.

In 97 patients with different stages of chronic renal failure prolactin serum level was determined, and its diurnal rhythm and dependence on haemodialysis treatment were studied. Diurnal rhythm was investigated in 6 men and 6 women with advanced chronic renal failure on diet and other symptomatic treatment. A normal diurnal rhythm of prolactin was recorded only in 3 patients, two of them being with elevated basal prolactin levels; an abnormal prolactin rhythm was documented in 8 patients. In 4 patients no evident diurnal changes in prolactin level were observed, though 3 of them had a normal basal prolactin level. In one patient slight fluctuations of the prolactin level were recorded, while in 4 other patients an abnormal type of diurnal rhythm was observed. Prolactin determinations in patients on maintenance haemodialysis showed increased values in 45 men (719 + 122 mIU/l) as well as 34 women (1251 + 171 mIU/l). The analysis of the influence of haemodialysis on cuprophane and polyacrylonitrile membrane was made in 6 patients and no difference was shown between predialysis and postdialysis serum prolactin values, as well as in values obtained for non-dialysis and dialysis days. The results obtained in this study showed an absent or abnormal diurnal rhythm of prolactin in 75% of patients with chronic renal failure. In patients on maintenance haemodialysis increased prolactin levels were found. Haemodialysis procedure on cuprophane and polyacrylonitrile membrane failed to affect the serum level of prolactin.

The paper deals with the study of cortisol and aldosterone plasma levels in patients with acute and chronic renal insufficiency. Various degrees of supranormal cortisol levels were found in all 6 examined patients with acute renal insufficiency in oligonauric phase of the disease. A gradual decrease was observed in diuretic stade. However, during the recovery period they were within normal limits. In 3 of 4 patients in whom acute changes changed to chronic renal insufficiency increased cortisol levels were registered. In one patient the elevated cortisol level achieved the upper limit of normal values. In both groups of examined patients, but not in all of them, moderately increased aldosterone plasma levels were found. The obtained results speak in favour of an important role of stress factors in patients with acute renal insufficiency.

Deranged adrenal cortical function was previously described in different stress situations. The aim of this work was to study the plasma cortisol and aldosterone levels in acute renal failure induced by the uranyl nitrate injection or bilateral ureteral ligation. In both groups of uremic dogs on the first day of uremia there was a significant elevation of the plasma cortisol level, being more pronounced and lasting longer after bilateral ureteral ligation. In sham operated controls a modest elevation was recorded. The plasma aldosterone level rose significantly from the first day in both groups of uremic animals. A further progressive elevation continued the following days and a highly elevated aldosterone levels remained until the end of the experiments. A minor but significant elevation of plasma aldosterone was also found in sham operated controls. This study has established increased plasma cortisol and aldosterone levels attributable to the operative stress and failing kidney function in acute uremia.

Plasma calcium regulation in uranyl nitrate-treated dogs was studied. A discrete hypercalcemia was observed without significant changes in the level of plasma ionized calcium. Serum phosphate increased markedly following uranyl nitrate treatment. A sharp rise of iPTH was demonstrated. Uranyl nitrate-induced acute renal failure in dogs was found to be a useful model for studying the mechanisms regulating calcium and phosphate metabolism.

In 30 uremic patients on chronic maintenance hemodialysis the sensory and motor fiber conduction and the motor distal latency were measured in the left tibial nerve, in order to evaluate if a correlation between their values and the serum IPTH or 1.25(OH)2D3 can be found. The sensory and motor fiber conduction velocities were found to be significantly lower in hemodialysis patients than in a group of healthy controls. The motor distal latency time did not differ significantly from that found in healthy persons. A markedly increased serum C-terminal and mid-region (44-68) iPTH, and a very low serum 1.25(OH)2D3 were found in uremic patients. Regression analyses demonstrated the significant negative correlations between the serum C-terminal iPTH and the sensory (r = -0.441, p less than 0.05) and motor nerve (r -0.471, p less than 0.01) conduction velocities. A significant positive correlation between serum 1.25(OH)2D3 levels and the motor distal latency time was also observed (r = 0.3639, p less than 0.05). The results obtained suggest a role of the increased concentration of IPTH fragments in the development of uremic polyneuropathy. A significant decrease of 1.25(OH)2D3 obviously has no negative effect upon the nerve conductance in patients on maintenance hemodialysis.