Manifestation Of Nephropathy Research Articles

THEEFFECT OF MELATONIN ON ELECTROLYTE AND WATER-RETENTION RENAL DYSFUNCTION IN CHRONIC ALCOHOL INTOXICATION ASSOCIATED WITH AUTOIMMUNE NEPHRITIS: AN EXPERIMENTAL RAT MODEL

Autoimmune nephritis represents one of the frequent types of kidney pathology. With rates of alcohol consumption being on the rise, it is crucial to study the effects of alcohol abuse on the manifestations of nephropathy. Since the activation of lipid peroxidation plays a significant role in the formation of autoimmune and alcoholic nephropathy, it appears relevant to investigate the potential positive effects of a natural antioxidant, melatonin. The aim of the study was to investigate the effect of melatonin on renal function in chronic alcohol intoxication associated with autoimmune nephritis. Material and methods. The characteristics of changes in electrolyte and water excretory functions of the kidneys in Wistar rats with chronic alcohol intoxication associated with autoimmune nephritis were examined. Experimental chronic alcohol intoxication was obtained by daily intragastric injection through an atraumatic tube of 40% ethanol solution and the administration of isovaleric acid amide solution for 30 days. The model of autoimmune nephritis was obtained via a single subcutaneous injection of an emulsion of complete Freund's adjuvant with an equal volume of a mixture of kidney cortical homogenate at five points. Melatonin was administered intragastrically at a dose of 10 mg/kg for one month. Results. Alcohol intoxication was found to increase the degree of renal dysfunction in autoimmune nephritis. The administration of melatonin as a preventative agent led to a significant reduction in manifestations of nephropathy. Conclusions. Alcohol intoxication may exacerbate the manifestations of autoimmune nephritis. The administration of melatonin in chronic alcohol intoxication associated with autoimmune nephritis leads to the reduction in the severity of pathological changes in the electrolyte-excretory function of the kidneys.

The state of the hemomicrocirculation system and predictive capacity of parameters characterizing it in patients with hypertensive nephropathy

Today the diagnostics of microcirculatory disorders in patients with hypertensive nephropathy (HN) is an extremely important issue. Aim. To evaluate the functional state of hemomicrocirculatory (HMC) system and to analyze predictive capacity of parameters characterizing it in patients with essential hypertension (EH) of II stage accompanied with manifestations of nephropathy. Methods and results. 155 patients were examined including two main groups of patients with stage II EH of second (n=31) and third (n=31) degree of arterial hypertension (AH) with early signs of nephropathy as well as three comparison groups including patients with essential hypertension stage II of the second (n=31) and third (n=31) degree of hypertension with preserved renal function, and practically healthy individuals (n=31). Albumin/creatinine ratio in urine greater that 30 mg/g was taken as the marker of kidney disorder. The function of HMC system was evaluated by means of laser Doppler flowmetry. It was found that it is typical for patients with HN to show the reduction in tissue perfusion, variability of peripheral blood flow, apparent dysfunctional disorders of the microvascular endothelium, significant neurogenic and myogenic tonus increase. The significant loss of elastic properties of microvessels and pronounced signs of stagnation of blood in the postcapillary segment of microvasculature were also noted. Patients with HN accompanied with the sharp reduction of normocirculatory microcirculation hemodynamic type (HTM) showed increase in the cases of spastic and stagnant-stasis HTM. Conclusions. Among the analyzed parameters which characterize HMC system, A max E and A max C appeared to be the most qualitative predictors of the HN in hypertensive patients and had a joint predictive potential.

High glucose-induced Galectin-1 in human podocytes implicates the involvement of Galectin-1 in diabetic nephropathy.

The diabetic milieu is believed to change the activity, or result in damage of podocytes-a key component of the glomerular filtration barrier and known to secrete matrix for glomerular basement membrane. This in turn contributes to diabetic nephropathy. However, how podocyte dysfunction is triggered in diabetic nephropathy remains ambiguous. Galectin-1 belongs to Galectin family that bind to β-galactoside residues of glycosylated proteins. We explored whether Galectin-1 is dysregulated in diabetic nephropathy using three different techniques, namely real-time polymerase chain reaction, western blotting, and immunofluorescent staining, to follow the expression of Galectin-1 under high glucose levels in podocytes. High glucose consistently induced Galectin-1 expression. Immunohistochemistry using a Galectin-1-specific antibody also showed elevated Galectin-1 in renal tissues of diabetic patients with manifestation of nephropathy, indicating a correlation of Galectin-1 overexpression with diabetic nephropathy. Upregulation of Galectin-1 is associated with loss of podocin, which is important for the physiological function of podocytes and decreases in the renal tissues of diabetic nephropathy. Increased Galectin-1 is a causal event for the high glucose-induced loss of podocin, since silencing Galectin-1 in podocytes increased podocin expression in the presence of 25 mM glucose. Thus expression of Galectin-1 in diabetic nephropathy may serve as a marker and contribute to disease progression by interfering with podocin expression.

Two cases of HIVAN in young AIDS patients

HIV associated nephropathy (HIVAN) is a quite frequent pathology among HIV infected patients with a high incidence in black people. Among the 800 patients from Western Romania, infected with HIV type 1, mostly subtype F, none were diagnosed based on renal biopsy with HIVAN until 2010, albeit several renal abnormalities have been described among HIV patients based on a complex etiology. We present two cases, both Caucasian, a 25 years old female and a 26 years old male, HIV infected in the early 1990`s with horizontal transmission. First case was diagnosed with HIV infection as late-presenter and staged C3 at the age of 10 when she was admitted in coma secondary to toxoplasmic encephalitis. The first manifestations of nephropathy were detected 6 years later with decreased creatinine clearance. The second case was HIV diagnosed at the age of 19, in 2007, during hospital admission for acute glomerulonephritis with secondary renal impairment, as a late-presenter staged also C3. The patient presented hepatitis B co-infection as well as chronic CMV infection. Renal biopsy was performed on both patients and revealed aspects of focal and segmental glomerulosclerosis, applicable for HIVAN. Both patients started HAART immediately after diagnosis, none of the medications used had been showed to induce renal impairment and both of them had creatinine clearance adjusted dosing of antiretroviral (ARV) treatment, but in spite of similar ARV and supportive treatment, the two cases had different outcome. One had a very slow rate of decrease in renal function while the second one (similar to literature data) had a rapid evolution towards chronic kidney disease, within 3 years dialysis had to be initiated. Compliance to antiretroviral treatment improves survival rate globally (with presumable late onset for chronic kidney disease). Renal biopsy remains the standard in order to diagnose HIVAN. As far as patients are aging with AIDS, renal manifestations may become more frequent and a comprehensive oversight is needed.

Early Manifestation of Nephropathy in Rats with Arterial Calcinosis

In vascular smooth muscle, calcium overload is a highly pathogenic event, which increases with advancing age. An increase in the calcium content of arterial wall may be produced in rats by treatment with vitamin D3. The aim of this study was to evaluate the renal clearance of sulfanilamide (a model organic anion, preferentially eliminated by the kidneys) and other parameters of global renal function in rats with arterial calcinosis. Arterial calcinosis was produced in adult rats by means of a single dose of vitamin D3 (300,000 UI/kg bw, i.m.) 5 days before the experiment. Treated rats showed a large increase in calcium content of aortic tissue and an increase in systolic arterial pressure. No modifications were observed in plasma calcium levels and in plasma lipid profiles. Statistically significant decrements were observed in renal clearance of sulfanilamide, in renal blood flow, in fractional excretion of sodium and potassium. A slight decrease, not statistically different, was observed in the glomerular filtration rate. Rats with arterial calcinosis also showed an increment of total calcium levels in renal tissue, in fractional excretion of calcium and in the expression of organic anion transporter 1 (OAT1). Histological studies revealed tubular alterations. In summary, modifications in hemodynamics and tubular parameters are early manifestations of nephropathy in rats with arterial calcinosis, some of which may account for the changes observed in organic anions renal depuration. It is important to mention that the decrease in clearance of organic anions were seen in spite of the increase in expression of OAT1.

Early manifestations of nephropathy in alloxan-treated rats

An early stage of diabetic nephropathy was studied. Rat renal function was evaluated by clearance techniques, 7 or 15 days after alloxan administration (groups A7 and A15). Significant diminutions of glomerular filtration rate (inulin clearance) and p-aminohippurate clearance were observed in alloxan-treated rats. Diabetic animals presented glucosuria and enhanced water excretion. A natriuretic response was only observed in A15-rats. Arterial pressure increased along time, and enlarged lipid deposits in glomeruli and vessels of A7-kidney sections were observed. Thus, a vascular compromise at this time was suggested. To better characterize the set up of the renal dysfunction, other studies were performed in A7-group. Urinary protein excretion remained unchanged while a higher level of glycosylation of urinary proteins was observed in A7-rats. Histological studies revealed a normal general morphology in kidneys from diabetic rats. Immunohistochemical analysis in renal sections showed enlarged deposits of fibronectin in glomeruli and interstitium of alloxan-treated rats. Higher myeloperoxidase activity was observed in renal cortex from diabetic animals indicating leukocytes infiltration.These results indicated that 7 days after hyperglycemia induction, the animals presented a renal dysfunction characterized by hemodynamic alterations associated with vascular and glomerular structural impairments, without modifications in tubular function. The higher level of protein glycosylation and the inflammatory process at this early stage could be responsible for the beginning of diabetic nephropathy.

Uremia in diabetics: the prognosis improves.

Chronic uremia caused by diabetic glomerulopathy accounts for about 25 percent of new patients treated by maintenance hemodialysis. At the onset of glucose intolerance, insulin dependent diabetics have larger than normal kidneys, with a markedly increased glomerular filtration rate. During the subsequent 15 to 20 years of insulin use, glomerulosclerosis progresses silently, until a clinically overt nephrotic syndrome becomes evident. Thereafter, the clinical manifestations of nephropathy appear rapidly with an exponential decline in creatinine clearance to less than 5 ml/min within one to five years. Putting together a life plan for a nephrotic and azotemic diabetic involves awareness, and coordinated management of not only renal but extrarenal vasculopathic complications of diabetes, especially proliferative retinopathy. Carefully made preparations for hemodialysis and/or renal transplantation with increase changes for at least a short-term favorable outcome, which can now be anticipated in a growing proportion of patients.