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Aim: To evaluate effects of corticosteroids, cytostatics, ACE inhibitors, Ang-II receptor blockers, HMG-CoA-reductase inhibitors on the levels of blood cholesterol in patients with progressive glomerulonephritis (PGN)., Material and Methods: The influence of medications which are used for treatment of chronic glomerulonephritis on the serum levels of total cholesterol (TCh) was investigated in 53 patients with chronic glomerulonephritis and persistent nephrotic syndrome (NS). All the patients with NS or nephrotic range proteinuria were divided into five groups depending on the type of therapy: corticosteroids, cytotoxic agents, ACE inhibitors, Ang-II receptor blocker, HMG-CoA-reductase inhibitors., Results: No negative change of serum TCh was revealed after the courses of treatment with corticosteroids and cytotoxic agents. Moreover, treatment with ACE inhibitors and Ang-II receptor blockers was accompanied with a significant reduction of the TCh level., Conclusion: ACE inhibitors and Ang-II receptor blockers affect some mechanisms of glomerulonephritis progression including hypercholesterolemia.

Objective: Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear and vestibular lumen as an end-stage sequelae to various pathologies. This study was designed to establish the sequence of events and chronology of the osteoneogenesis and calcification., Study Design: A prospective randomized double-blind study., Methods: By using serial application of different colored fluorochromes, which deposit in newly forming bone, the timing of bone deposition and bone remodeling can be established. Labyrinthitis ossificans was induced in six groups (n = 5) of gerbils by an intrathecal injection of live Streptococcus pneumoniae. Group 1 received no fluorochrome labels, group 2 received one label, group 3 received three labels, and groups 4, 5, and 6 received four labels. The temporal bones were harvested after 2 weeks (group 1), 1 month (group 2), 3 months (group 3), 4 months (group 4), 6 months (group 5), and 12 months (group 6)., Results: Sixteen of the 25 animals that received labels developed ossification, demonstrated with fluorescent microscopy. In the animals that developed labyrinthitis ossificans, newly formed disorganized bone began calcifying as early as 3 weeks (label 1) after S. pneumoniae injection. Osteoneogenesis continued as evidenced by the presence of the other labels when first applied at 6 weeks (label 2), and 10 weeks (label 3). Ossification, calcification, and remodeling proceeded through a 12-month course, wherein a reduction of labels was present at 6 months and total disappearance by 12 months., Conclusions: The use of fluorescent stains in this animal model provides a means to establish a timeline of the ossification seen in labyrinthitis ossificans.

Hypercholesterolemia and mesangial cell proliferation have been proposed to play a role in the progression of glomerulosclerosis in diabetic nephropathy and other renal diseases. Although LDL is mitogenic for and cytotoxic to mesangial cells, the effect of HDL on these cells is unknown. HDL stimulates fibroblast mitogenesis and is the principal cholesterol-bearing lipoprotein in the rat, the experimental model for studying the effect of hyperlipidemia on renal disease. Insulin is mitogenic in several cell systems, and its levels are increased in serum in non-insulin-dependent diabetes mellitus. This study investigates whether HDL acts as a growth factor in mesangial cells and whether it functions in parallel with insulin. It was found that HDL at protein concentrations between 10 and 500 microg/ml, both alone and in the presence of 100 nM insulin, increased DNA synthesis in mesangial cells (129 to 165% of control for HDL alone; 140 to 235% for HDL plus insulin), whereas HDL at 1000 microg/ml and greater inhibited mesangial cell proliferation. Insulin alone at 100 nM stimulated [3H]thymidine incorporation in the same cell system (145% of control); the mitogenic effect of insulin was additive to that of HDL. Purified apo A-I had a similar effect, but at significantly lower concentrations. Specific binding of HDL to mesangial cells was demonstrated (B(max) [binding constant] of 5.19 +/- 0.70 x 10(-7) micromol of HDL bound/mg cell protein and K(b) of 2.83 +/- 0.22 nM). Tetranitromethane alters apo A-I, preventing binding to its cognate receptor. Tetranitromethane-modified HDL did not bind to mesangial cells and had no effect on [3H]thymidine incorporation. Addition of HDL to mesangial cells caused an immediate transient increase in free intracellular calcium in several representative mesangial cells, similar to the response seen with platelet-derived growth factor. The mitogenic effect of HDL was not altered after attenuation of cellular protein kinase C activity, but the stimulatory effect of HDL alone and in combination with insulin on DNA synthesis was completely eliminated after inhibition of cellular tyrosine kinases by 24-h pretreatment with 0.25 microM herbimycin A. Thus, HDL binds to a specific apo A-I-dependent receptor, promotes DNA synthesis, and initiates second-messenger events by a tyrosine kinase-dependent and protein kinase C-independent mechanism.

The activity of gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), lactate dehydrogenase (LDG), N-acetyl-beta-D-glucosaminidase (NAG) was assessed in 53 patients with psoriasis (PS), 24 PS patients with affected kidneys, 50 patients with type 1 diabetes mellitus(DM). Enhanced activity of the enzymes occurred not only in nephropathy patients but also in those without proteinuria. AP and NAG were more active in PS, while LDG and NAG in DM. Both in PS and DM, NAG activity rose 3-4-fold compared to control. A direct correlation was found between enzymuria and uremia, glycemia (in hyperglycemia only) and cholesterolemia. An inverse relationship existed between enzymuria and uricosuria. The above changes in enzymic activity are attributed to impairment of tubules of the kidney induced by PS and DM. Diagnostic significance of enzymuria as a marker of early tubular involvement is confirmed by investigations of renal biopsies.

Inhibition of non-immune progression of renal insufficiency for control of glomerulonephritis was attempted via hemodynamic, metabolic and hypolipidemic means. Hemodynamic correction was conducted using inhibitors of angiotensin-converting enzyme capoten and renitek. The action on metabolic factors of progression was realized by lovastatin mevakor. Capoten and renitek exhibited in 57 patients with chronic nephritis not only a hypotensive effect, but also reduced intraglomerular hypertension and proteinuria. A long-term (7-12 months) hypolipidemic therapy (diet and lovastatin) in 20 patients with chronic glomerulonephritis with nephrotic syndrome resulted in lowering of serum cholesterol concentrations and proteinuria, raised serum albumin. 9 patients achieved remission of nephrotic syndrome. The highest effect occurred in non-inflammatory nephropathy: membranous nephropathy, focal-segmental glomerulosclerosis, nephrosclerosis.

In view of weak implication of immunoinflammatory mechanisms in pathogenesis of noninflammatory nephropathy one may expect the disease course improvement and more slow progression of renal dysfunction. The mechanism of this action can be realized through hypolipidemic effect. In recent research there are data on a direct lovastatin action on the mechanism underlying nephritis progression by means of inhibiting proliferation of mesangial cells.

An extracellular matrix (collagens I, III, IV) was studied in the glomeruli of patients demonstrating glomerular low density lipoproteins (LDL) and free of them. These two patients' groups were not found significantly different by age, nephropathy duration, blood pressure, serum concentrations of creatinine, triglycerides, HDL cholesterol. The LDL deposit group differed by longer duration of the nephrotic syndrome, higher 24-h proteinuria, lower serum albumin levels, higher total cholesterol in the serum and the proportion VLDL and LDL cholesterol to HDL cholesterol. They had noninflammatory nephropathies more frequently, collagen IV accumulated in the glomerulus more actively, there appeared interstitial collagens I and III. The discussion concerns the role of hypercholesterolemia with the above proportion of cholesterols, its duration, a type of cells dictating mesangial proliferation, in the development of LDL-deposit-induced glomerulosclerosis.

Boyden camera tests, chemiluminescence of urinary supernatant, passive hemagglutination tests were used in measuring chemotactic properties of the urine, intensity of free-radical processes, fibronectin urine concentrations, respectively, in 31 glomerulonephritis (GN) patients. The above parameters were closely related to nephritis activity. These were much lower in patients with nephritis remission, than in subjects with nephrotic syndrome or exacerbation of latent nephritis. Chemotactic activity and intensity of free-radical processes were unrelated to protein urea which, however, correlated with fibronectin concentrations (r = 0.35, p < 0.05). The authors discuss the role of the mediators' values in evaluation of local renal inflammation and feasibility of their use as criteria of nephritis activity and prognosis.

Twenty-nine patients with insulin-dependent diabetes mellitus with similarly manifest renal involvement were examined to elucidate the role of dyslipidemia in diabetic nephropathy progress. Clinico-laboratory parameters (urinary albumin excretion, blood serum levels of total cholesterol, triglycerides, low, very low, and high density lipoprotein cholesterol) and morphologic changes in renal tissue biopsy specimens were analyzed. An increment of the number of large lipid incorporations was observed in various cells of renal glomeruli and interstitium, as well as a high prevalence of low density lipoprotein deposition in glomerular basal membranes and canaliculi as the renal process augmented in severity. Since lipids accumulating in glomerular structures may stimulate mesangial cell proliferation and mesangial matrix hyperproduction, the authors believe that dyslipidemia in diabetes mellitus may be conducive to a more rapid progress of renal disease.

To determine the mechanisms underlying diabetic nephropathy (DN) onset, a clinical and morphological study was initiated of 14 diabetics with insulin-dependent disease free of clinical renal manifestations. The patients were examined for intraglomerular hypertension, blood lipid spectrum and renal tissue morphology. In high intraglomerular hypertension, i. e. in renal functional reserve depletion, there is dyslipidemia with a characteristic significant rise in the levels of very low density lipoprotein cholesterol and low density lipoprotein cholesterol, in the value of atherogenic index. Morphologically, renal tissue of the hypertensive and dyslipidemic patients experienced hyperperfusion and massive lipid infiltration in glomerular cells. In contrast, renal tissue underwent only minimal nonspecific changes when intraglomerular hemodynamics and lipidemia were normal. The findings suggest that associated effects of intraglomerular hypertension and dyslipidemia may promote DN onset.

Serum lipids were estimated in patients with renal amyloidosis (RA): 21 with familial Mediterranean fever (FMF) and 24 with secondary renal amyloidosis versus FMF patients without renal dysfunction or having chronic glomerular nephritis. All the RA patients had dyslipidemia of atherogenic nature the severity of which correlated with that of renal disorder. Our results showed the presence of dyslipidemia early during RA course. It is renal involvement that results in dyslipidemia observed in FMF patients.

A study was made of urine lipids and their fractions in chronic glomerulonephritis (CGN) and renal amyloidosis with nephrotic syndrome (NS). 91 patients suffering from NS were examined. 2 subgroups were distinguished among these patients: with CGN of the nephrotic type and with the nephrotic stage of renal amyloidosis. The reference groups were made up of patients with latent CGN and healthy subjects. Measurements were made in the blood and urine of total lipids (TL) and their fractions--phospholipids (LP), free cholesterol (FC), mono- and diglycerides, triglycerides (TG), and cholesterol esters (CE). The presence of the NS was attended by a rise in the blood of TL concentration, relative content of FC, TG and by a decline of RL and CE, with the decrease of the relative content being more manifest in amyloidosis. Nephrotic lipiduria was largely characterized by an increase of the concentration of TL and of the relative content of PL, with the changes of the latter parameter being mostly characteristic of CGN patients. Thus, NS was associated with a high excretion of lipids with urine which is likely to reflect their elevated filtration under nephrotic hyperlipidemia. Still, in nephropathies whose pathogenesis is determined by an important role of inflammatory and membrane-destructive processes, of definite role is also the local (renal) formation of PL.

The main classes of serum lipids (fatty acids, phospholipids, triglycerides, cholesterol) were studied and compared in 36 patients aged 20 to 41 years with the renal hypertensive syndrome of different etiology, in 25 patients aged 30 to 51 years with essential hypertension, and in 20 practically healthy subjects aged 20 to 42 years. The mechanism of changes in the content of serum lipids in different diseases associated with the hypertensive renal syndrome and in patients with essential hypertension allows an assumption that these changes are linked to a large degree with arterial hypertension.

A study was made of the content of blood lipids in patients with associated chronic nephritis and arterial hypertension (AH). It has been established that the reduction of arterial pressure as a result of hypotensive therapy (administration of central action drugs, vasodilators of direct action, calcium antagonists, blockers of the angiotensin-transforming enzyme) was followed by a decrease in the blood of the concentration of fatty acids, glycerin, triglycerides, low density lipoproteins, total cholesterol, free cholesterol, phospholipids, characteristics of lipid peroxidation and by the rise of cholesterol concentration in high density lipoproteins. The data obtained are of clinical importance in view of the possibility of correcting dyslipidemia in patients with associated chronic nephritis and arterial hypertension during hypotensive treatment.

The study involved 33 patients with chronic glomerulonephritis of hypertonic type (CGNHT), in their number 8 with the signs of a moderate renal failure, 25 with a latent form of the disease (CGNLF), 10 ones with hypertension, and 20 healthy age-matched subjects. Patients with CGNHT and hypertension patients were comparatively studies for the blood pressure values. Fatty acid, glycerine, malonic dialdehyde contents were investigated in all the examinees. Some patients were studied for the fraction composition of fatty acids as well. The majority of CGNHT and hypertensive patients demonstrated a significant increase in the levels of fatty acids, glycerine and malonic dialdehyde versus healthy and CGNLF subjects, whereas the content of polyunsaturated fatty acids was found to be decreased (exemplified by linoleic acid) and the content of monounsaturated ones increased (exemplified by myristic acid). The aforementioned changes were mostly pronounced in those CGNHT patients who had higher systolic pressure whereas the signs of renal failure were of no importance for the value variance. No differences were revealed in the parameters of hypertensive and CGNHT patients. Accounting for the role of fatty acids, polyunsaturated ones predominantly, which provide the energy consumption of myocardium (raised in those with higher blood pressure values) the authors suggested that arterial hypertension played a definite role in the aforementioned alterations. The results obtained could be of a certain clinical value for dietetic and medicamentous improvement of the deficiency in the levels of polyunsaturated fatty acids in the patients with CGNHT, possible normalization of fatty acid content and composition during the decrease of the blood pressure.