FederationIntroduction and Aims: Loss of podocytes in primary glomerulopathies is crucial for glomerulosclerosis progression which leads to end-stage renal failure in such patients. The mechanism of direct replacement of injured podocytes does not exist so the only way to compensate the integrity of glomerulus is change of cells shape to cover the glomerular tuft with a smaller number of podocytes. Foot process effacement is the typical morphological sign of podocyte respond to stress. Podocyte detachment (PD) from glomerular basement membrane (GBM) develops when podocyte hypertrophy is unsufficient. The aim of investigation was estimation of relationship between range of foot process width (FPW), PD and level of daily proteinuria in patients with primary variants of glomerulopathies. Methods: 42 patients with biopsy proven primary glomerulopathies were included in the study. According to the the results of light and electron microscopy 17 (40,5%) patients had membranous nephropathy, 8 (19,0%) -focal segmental glomerulosclerosis, 12 (28,6%) -minimal change disease and 5 (11,9%) -proliferative variants of glomerulonephritis (2-IgA-nephropathy, 3 -membrano-proliferative glomerulonephritis). Standart laboratory and instrumental investigations were perfomed. Samples of serum and urine were obtained in the day of byopsy. FPW and PD were measured using Image J software (NIH, 1997). FPW was counted as ratio of GBM length to amount of foot processes in every electronogramm using correction factor π/4 as described in previous works. PD was calculated as percentage of bare areas of GBM. Results: There were no statistically significant differences between FPW and PD in patients with different forms of glomerulopathies ( p>0,05). There was negative correlation between 31, p<0,05). Daily proteinuria rate positively correlated with FPW (r=0,52, p<0,05) while inverted relation with level of PD was found (r=-0,36, p<0,05). The same pattern was detected comparing groups of patients with and without nephrotic syndrome. The level of daily proteinuria was higher in patients with more expressed hyaline droplet degeneration of tubular epithelial cells. Conclusions: Unlike data published in recent works we found no difference of FPW and PD rate in patients with different forms of glomerulonephritis. Strong positive correlation of FPW with proteinuria range confirms the role of podocytes in development of high proteinuria and nephrotic syndrome, considering that there were no abnormalities in tubular reabsorbtion of protein. Interestingly the detachment of podocytes from GBM does not increase proteinuria range, more over inverse relationship was detected. Probably this fact can be explained by unknown mechanisms of transcellular transport of protein rather than directly through bare parts of GBM. Nagoya University Graduate School of Medicine, Nagoya, Japan Introduction and Aims: The clinicopathological characteristics of PLA2R-related membranous nephropathy (MN) in Japan remain unclear. Methods: We studied retrospectively the outcomes ...
Aim. To investigate the diagnostic value of biomarkers in assessing the severity of sclerotic and atrophic lesions in primary glomerulopathies. Materials and methods. One hundred patients were included in the study, according to the results of kidney biopsy in 9 (9%) cases minimal change disease was diagnosed, in 28 (28%) focal segmental glomerulosclerosis, in 26 (26%) membranous nephropathy and in 37 (37%) IgA nephropathy. The clinical course of nephropathy was evaluated, standard laboratory tests were performed, and urinary excretions of cystatin C, 1-microglobulin, 2-microglobulin and NGAL were measured. The degree of glomerulosclerosis was assessed quantitatively, tubulointerstitial sclerosis and tubular atrophy semiquantitatively. Results. According to the results of linear correlations and ROC-analysis, urinary excretion of cystatin C and 1-microglobulin had diagnostic value for early degree of tubulointerstitial sclerosis (cut-off value 319.9 and 10.94 mg/day, respectively). Urinary excretion of 2-microglobulin reflected the initial degree of tubalar atrophy (cut-off value of 0.224 mcg/day), as well as tubulointerstitial sclerosis of various degrees of severity (cut-off value 0.224 and 0.240 mkg/day). NGAL urinary excretion was the only marker of early degree of glomerulosclerosis with its excretion of more than 1445.4 ng/day and tubular atrophy, with a severity of 50% or more (cut-off value 4897.8 ng/day). Conclusion. A comprehensive assessment of sclerotic and atrophic lesions in the renal parenchyma, can be performed using a panel of traditional (GFR, proteinuria) and specific biomarkers (1-, 2-microglobulins, cystatin C, NGAL) to implement a comprehensive, personalized approach, as well as to assess the prognosis of nephropathy. In addition, the evaluation of the panel of different biomarkers can be used in those clinical situations where kidney biopsy can not be performed.
Background and Aims IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and is a frequent cause of end-stage renal disease. The best predictors of progression are histologic parameters. Nevertheless, there is a pressing need to identify suitable noninvasive biomarkers in IgAN, to aid with diagnosis, treatment decisions, and prediction of the disease progression. Our aim was to assess diagnostic value of urinary excretions of transferrin and IgG in prediction of morphological lesions in patients with IgAN. Method 37 patients [19 female, age Me 33 (25; 48) years] with biopsy proven IgAN and without acute kidney injury, infectious diseases, severe heart failure, respiratory insufficiency, cancer were included in the study. 24-hour urinary excretions of transferrin (uTr), IgG (uIgG) were measured by immunoturbidimetric method (Furuno CA-90, Furuno Electric Co., Ltd., Japan). Tubulointerstitial fibrosis (TIF) and tubular atrophy (TA) were assessed semi-quantitatively (0-lesions absent; 1-mild focal tubular and interstitial lesions; 2-moderate tubular and interstitial lesions; 3-diffuse tubular and interstitial lesions). All patients consistently were separated into two groups according to the degree of each morphological lesion (TIF or TA): “mild” (TIF or TA grade 0 or 1) and “severe” (TIF/TA grade 2-3). Results uTr, uIgG positively correlated (p<0,05) with TIF (r=0,38, r=0,43) and TA (r=0,38, r=0,45), respectively. We did not find correlations between uTr, uIgG and glomerulosclerosis. Using ROC-analysis all patients were separated in two groups using uTr or uIgG according to the degree of morphological lesions (“mild” or “severe) (Table 1,2; Figure 1). According to the results of ROC-analysis we also found that all cut-off values of uTr, uIgG corresponded to the level of urinary protein excretion not more than 1,25 g/24hour. Conclusion Our results show that uTr and uIgG can be used as markers of early tubulointerstitial lesions in patients with IgA nephropathy with mild protein excretion.
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