Andrzej Oko

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.

Association of aldosterone synthase (CYP11B2) gene −344T/C polymorphism with the risk of primary chronic glomerulonephritis in the Polish population

Introduction: We evaluate whether angiotensinogen AGT M235T (rs699), angiotensin-converting enzyme ACE (I/D) (rs4646994) and aldosterone synthase CYP11B2 –344C/T (rs1799998) polymorphisms can be genetic risk factors of chronic glomerulonephritis (GN) in the Polish population. Materials and methods: The study was conducted in 140 patients with primary chronic GN: mesangial proliferative GN (MesPGN) (n = 49), IgA nephropathy (IgAN) (n = 31), membranous nephropathy (MN) (n = 27), focal segmental glomerulosclerosis (FSGS) (n = 25), membranoproliferative GN (MPGN) (n = 4), and minimal change disease (MCD) (n = 4), and controls (n = 187). Genotypes were determined by HRM curve analysis for AGT M235T, by PCR and agarose gel separation for ACE (I/D), and by PCR-RFLP for CYP11B2 –344C/T. Results: We found a significant association of the CYP11B2 –344C/T polymorphism in the recessive model with all subtypes of GN (OR = 1.925 (95% CI = 1.152–3.219, p = 0.0118, pcorr = 0.0354)). We also observed that the CYP11B2 –344C/T polymorphism in the recessive model may also be an independent significant risk factor of IgAN (OR = 2.743 (95% CI = 1.219–6.172, p = 0.0122, pcorr = 0.0366)), FSGS (OR = 2.895 (95% CI = 1.200–6.985, p = 0.0145, pcorr = 0.0435)), and all proliferative GNs (MesPGN, IgAN, MPGN) (OR = 2.171 (95% CI = 1.211–3.894, p = 0.0084, pcorr = 0.0252)). Conclusion: Our results suggest that the CYP11B2 –344C/T polymorphism might be an independent risk factor of IgAN, FSGS and all proliferative chronic GNs.

Arterial hypertension due to perirenal and subcapsular hematoma induced by renal percutaneous biopsy.

In this study we report three patients, in whom arterial hypertension was induced by compression of the kidney parenchyma due to perirenal or subcapsular hematoma following percutaneous blind renal biopsy with use of Vim-Silverman type needle.

Influence of donor and recipient gender as well as selected factors on the five-year survival of kidney graft.

UNLABELLED The aim of the study was to determine the impact of the gender of renal allograft donor and recipient on the graft function over a 5-year follow-up period. MATERIAL AND METHODS The 154 kidney grafts from 77 donors transplanted into recipients of both genders. Two study groups were formed: one group consisted of male donors, while the other consisted of female donors. The recipients in each of the groups consisted of a pair, one male and one female. RESULTS 71% of grafts survived the five-year period in the group of male and female recipients when the donor was male; in case of female donors, the rate was 62.5%. Depending on the gender of the donor and the recipient, the rates of grafts with five-year survival were as follows: 79.2% for male donors and female recipients (MF); 62.5% for male donors and male recipients (MM). The difference between both groups was not statistically significant. In the case of female donors and male recipients (FM), the five-year survival rate was 58.3%, while in female donors and female recipients, the five-year survival rate was 64.1%. CONCLUSIONS Grafts from male donors show a trend towards better five-year survival compared to grafts from female donors. The highest five-year survival rate was observed when the donor was male and the recipient was female; the lowest rate was observed for female donors and male recipients.

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.

Dialysis vintage stratified comparison of body composition, hydration and nutritional state in peritoneal dialysis and hemodialysis patients

Introduction Body mass decomposition and hydration state imbalances affect patients on maintenance dialysis. We compared body composition, hydration and nutritional state of patients on peritoneal dialysis (PD) and hemodialysis (HD) based on dialysis vintage (DV). Material and methods Three hundred and fifty-nine prevalent patients on HD (n = 301) and PD (n = 58) were divided into 3 subgroups depending on DV: < 2 years HD (n = 41) and PD (n = 28), 2–4 years HD (n = 111) and PD (n = 17), > 4 years HD (n = 149) and PD (n = 13). Bioimpedance analysis delivered data including overhydration (OH), Lean (LTM) and adipose lipids mass (FAT). Other measurements included daily diuresis (DD), subjective global assessment (SGA) and serum albumin (alb), C-reactive protein (CRP) and total cholesterol (TChol), and hemoglobin (Hb). Results Dialysis vintage < 2 years. Hemodialysis patients were older (65.5 ±18.5 vs. 50.9 ±17.1; p < 0.01) with a higher mortality (28 vs. 1; p < 0.01) and OH (8.0 ±4.3 vs. 1.6 ±3.1; p < 0.001). Hemoglobin (10.6 ±1.5 vs. 11.8 ±1.7; p < 0.05), TChol (180.2 ±47.0 vs. 211.7 ±46.3; p < 0.05), DD (871 ±729 vs. 1695 ±960; p < 0.001) and LTM (46.5 ±12.9 vs. 53.8 ±14.4; p < 0.05) were lower on HD. Dialysis vintage 2–4 years: when compared to PD, HD patients had higher OH (11.7 ±5.9 vs. 2.1 ±3.2; p < 0.001) and lower Hb (10.8 ±1.5 vs. 11.9 ±1.4; p < 0.01). Dialysis vintage > 4 years: compared to PD, HD patients had higher LTM (44.3 ±11.7 vs. 38.6 ±7.9; p < 0.05) and lower FAT (34.4 ±11.1 vs. 42.8 ±6.4; p < 0.01). Conclusions Dialysis patients’ body composition depends on dialysis modality and DV. Dialysis vintage < 2 years is associated with better hydration, nutritional state, and survival in PD patients, but longer DV reduces these benefits. Dialysis vintage > 4 years associated with similar hydration and mortality in both PD and HD while body composition was better on HD.

The importance of hypoalbuminemiain peritoneal dialysis patients: Impact of gender

BACKGROUND High mortality in peritoneal dialysis (PD) patients is associated with the presence of nontraditional cardiovascular risk factors, such as malnutrition. However, hypoalbuminemia in patients undergoing PD may have gender-dependent consequences. OBJECTIVES The aim of the study was to evaluate the relationship between hypoalbuminemia, overhydration (OH), inflammation, and cardiovascular risk, depending on gender. MATERIAL AND METHODS The group studied consisted of 54 PD patients: 26 male (mean age: 59 ±19 years) and 28 female (mean age: 52 ±15 years) patients. Serum albumin levels were measured routinely by the hospital central laboratory. The degree of OH was assessed by bioelectrical impedance analysis (BIA). Serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6 were measured as inflammatory markers. Levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and troponin T (TnT) were used to assess cardiovascular risk. RESULTS Median serum albumin concentration was 3.9 g/dL (3.6-4.2 g/dL). Both genders were comparable regarding most parameters except body weight (79 ±16 kg vs 67 ±16 kg; p = 0.009), but no differences were observed in body mass index (BMI) (26.3 ±5.0 kg/m2 vs 26.2 ±5.9 kg/m2; non significant (NS)). There was also no difference in the prevalence of hypoalbuminemia between female and male PD patients (23% vs 21%; NS). In females, low serum albumin concentrations were associated with OH, inflammation and cardiovascular risk, while in males serum albumin levels correlated with the parameters of dialysis and cardiovascular risk. CONCLUSIONS The impact of hypoalbuminemia may be gender-dependent. It seems that hypoalbuminemia is more important for female patients. It is also possible that different mechanisms regulate serum albumin concentration in female and male PD patients.

Acute Progression of Adult-Onset Atypical Hemolytic-Uremic Syndrome due to CFH Mutation: A Case Report

Atypical hemolytic-uremic syndrome (aHUS), unlike typical HUS, is not due to bacteria but rather to an idiopathic or genetic cause that promotes dysregulation of the alternative complement pathway. It leads to hemolytic anemia, thrombocytopenia, and renal impairment. Although aHUS secondary to a genetic mutation is relatively rare, when occurring due to a mutation in Factor H (CFH), it usually presents with younger onset and has a more severe course, which in the majority ends with end-stage renal failure. Paradoxically to most available data, our case features acute aHUS due to a CFH mutation with late onset (38-year-old) and rapid progression to end-stage renal disease. Due to current data indicating a high risk of graft failure in such patients, the diagnosis of aHUS secondary to a genetic cause has disqualified our patient from a living (family) donor renal transplantation and left her with no other option but to begin permanent renal replacement therapy.