Ilona Idasiak-Piechocka

Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis

BACKGROUND The effects of tumor necrosis factor α (TNF α), a potent proinflammatory cytokine, in the kidneys are mediated by two membrane receptors (TNFR), TNFR1 and TNFR2. The expression of both TNF and TNFRs increases in several kidney diseases and is associated with the shedding of the receptors out of the cell membranes. In an experimental model of glomerulonephritis (GN), elevated concentrations of TNFRs in serum and TNFRs excretion in urine were demonstrated. The aim of this study was evaluation of urinary excretion of TNFR1 and its relationship with the clinical markers of kidney injury in patients with GN. The value of basal urinary TNFR1 excretion as a prognostic indicator of the progression of kidney function impairment was also assessed. MATERIAL AND METHODS Fifty-five patients with newly diagnosed, biopsy-proven primary GN were included in the study. In all patients, and in 20 healthy subjects, UTNFR1 was measured using an ELISA . In the patients, risk factors of the progression of impairment of kidney function (reduced eCcr, nephrotic syndrome, hypertension and intensity of morphological lesions in the kidneys) were evaluated. The appropriate treatment was then introduced and the patients were in follow-up for 4 years. The progression of kidney function impairment was defined as a reduction of eCcr > 5 mL/min/1.73 m2 /year during follow-up. The association of basal TNFR1 excretion with the progression was evaluated. RESULTS Urinary excretion of TNFR1 in the patients with GN (4039.2 ± 3801.5 pg/mgCr) was greater than in the healthy subjects (1358.9 ± 927.8 pg/mgCr, P < 0,00002). A significant negative correlation between TNFR1 excretion and eCcr (Sr=0.464, P < 0.01) and a positive correlation between TNFR1 excretion and proteinuria (Sr = 0,463, P < 0.01) were found. In 13 patients, a marked reduction of eCcr was observed during follow-up. Logistic regression analysis revealed that TNFR1 excretion > 3863.3 pg/mgCr predicts progression of renal function impairment along with advanced interstitial fibrosis in the kidney biopsy specimens at presentation. CONCLUSION Markedly elevated urinary TNFR1 excretion may be considered as a good marker of an activated TNFα-pathway in patients with newly diagnosed GN and as a potentially modifiable risk factor of progressive kidney function impairment.

Elevated Urinary Fibronectin Excretion Predicts Poor Outcome in Patients with Primary Chronic Glomerulonephritis

Background/Aims: Fibronectin (FN) is one of the major matrix proteins in the kidney. The accumulation of FN fragments in inflamed glomeruli could contribute to the progression of renal injury. In the present study, the urinary FN excretion (UFN) was measured for evaluation of its possible role as a prognostic marker in patients with newly diagnosed chronic glomerulonephritis (GN). Methods: In 55 patients with newly diagnosed biopsy-proven chronic GN, UFN was measured using an enzyme-immunossay kit. The progression of kidney disease was defined as a reduction of the estimated glomerular filtration rate (eGFR) ≧5 ml/min/year during the 4-year follow-up. Results: The mean UFN in patients with GN (245.0 ± 229.2 ng/mmol creatinine) was higher than in the 19 healthy subjects (100.7 ± 87.3 ng/mmol creatinine; p < 0.002). No correlations between the initial UFN and eGFR and proteinuria were found. We did not find any association between UFN and the severity of glomerular sclerosis or the intensity of interstitial fibrosis. The progressive fall of eGFR was recorded in 13 patients (progressors). The mean initial UFN was significantly higher in progressors than in nonprogressors (p < 0.01). In logistic regression analysis, the initial high UFN was identified as independent factor predicting kidney function deterioration. Conclusion: These results indicate that UFN measured before treatment could serve as an additional prognostic marker of a poor outcome in patients with newly diagnosed primary GN.

Efficacy and Safety of Low-Dose Chlorambucil in Nephrotic Patients with Idiopathic Membranous Nephropathy

Aim: This observational study aimed to evaluate the results of treatment with low-dose chlorambucil in combination with corticosteroids in patients with idiopathic membranous nephropathy (iMGN) and nephrotic syndrome. Methods: Thirty-two patients with nephrotic syndrome and biopsy-proven iMGN were included in the study. At presentation, 9 patients were found to be in stage 1, 13 patients in stage 2 and 10 patients in stage 3 chronic kidney disease. In all patients, i.v. methylprednisolone pulses (500 mg/day for 3 days) were administered, followed by oral prednisone at an initial dose of 1 mg/kg per day, tapered gradually after 8 weeks to the maintenance dose of 5 mg/day after 6 months, and chlorambucil 2 mg twice daily for 6 months. Results: Complete remission of nephrotic syndrome was obtained in 14 patients (47.3%) and partial remission in 16 patients (50%). Two patients relapsed after 1 year of treatment. We did not record any severe side effects in treated patients, except glucose intolerance in 4 subjects on high corticosteroid doses. Conclusion: Immunosuppressive treatment with corticosteroids and low-dose chlorambucil seems to be effective and well tolerated in nephrotic patients with iMGN.

Electron-microscopic and Immunohistochemical Study in Henoch-Schoenlein Nephritis

Henoch-Schoenlein nephritis (HSN) is the most common secondary childhood nephropathy, leading to end-stage renal disease in up to 20% of pediatric patients after long-term follow-up. Forty-four cases of HSN were reviewed (32 children, 12 adults). Electron microscopy (EM) was performed in 7 cases and immunohistochemistry for Ki-67, PCNA, and p27 in all. Light microscopy: grade II (18), III (15), IV (3), and VI (8). Glomerulosclerosis and interstitial fibrosis were important prognostic markers and coexisted with poor outcome. EM was performed mainly in grade VI and was useful in recognition of early glomerulosclerosis. No correlations were found between the Ki67 and PCNA mesangial expression and outcome. Progressive decrease in p27 podocyte expression was noted with more severe HSN grades.

Ghrelin as a potential molecular marker of adrenal carcinogenesis: In vivo and in vitro evidence

Adrenal tumours belong to one of the most prevalent neoplasms. It is a heterogeneous group with different aetiology, clinical manifestation and prognosis. Its histopathologic diagnosis is difficult and identification of differentiation markers for tumorigenesis is extremely valuable for diagnosis.