Quantitative evaluation of interstitial fibrosis with Sirius Red in IgA nephritis.

OBJECTIVE: Tubulointerstitial fibrosis is one of the strongest independent predictive factors in determining the prognosis in IgA nephritis. Recently, software-based quantitative measurement of interstitial fibrosis with Sirius Red staining has entered the practice. The objective of this study was to investigate the prognostic value of measurement of interstitial nephritis with this method in IgA nephritis. METHOD: Forty-three patients diagnosed with IgA nephritis with renal biopsy between the years 2005 and 2009 were included in this retrospective observational study. The diagnostic biopsies of 37 patients were examined. Basal data included age, gender, creatinine level, glomerular filtration rate (GFR), presence of proteinuria, hypertension, glomerulosclerosis, mesangial proliferation, and interstitial fibrosis and fibrosis index calculated by the measurement of computed images of Sirius Red positive areas. Final visit included evaluation of development of end-stage renal disease (ESRD), and GFR (whether = 60 mL/min or <60 mL/min). RESULTS: Numbers of patients with hypertension (75% vs. 34.5%; p = 0.050), ESRD development (62.5% vs. 20.7%, p = 0.035), GFR <60 mL/min (87.5% vs. 31%; p = 0.007) were greater; and basal GFR (34.25 ± 25.29 vs. 64.14 ± 35.34; p = 0.048) was lower in high-intensity interstitial fibrosis group (>1000 µm2) compared to low-intensity interstitial fibrosis group (≤1000 µm(2)). CONCLUSION: Quantitative analysis of computed imaging of areas of Sirius Red positive tubulointerstitial fibrosis might serve as an effective novel method to determine the prognosis in IgA nephritis.

Glomerular c4d staining can be an indicator of disease activity in lupus nephritis.

BACKGROUND: Abnormalities in complement activation and clearance of immune complexes by erythrocytes are the central pathogenic mechanisms in systemic lupus erythematosus (SLE). Serum C4d level, which is a degradation product of complement factor C4, was found to be a sensitive indicator of SLE activity. Our aim was to determine whether glomerular C4d staining could be a useful marker of disease activity in patients with lupus nephritis. METHODS: This retrospective study included all consecutive patients who underwent a renal biopsy at our center between January 2005 and December 2009. A total of 29 patients with IgA nephritis were enrolled, and renal biopsy specimens of 24 patients have been evaluated. We evaluated baseline age, sex, hypertension, serum creatinine level, glomerular filtration rate (GFR), urine protein, and glomerular C4d staining. The primary endpoint of this study was the onset of end-stage renal disease (ESRD) in the course of study. RESULTS: Fourteen (58%) patients were C4d+ and 10 (42%) patients C4d-. Urinary protein excretion was more elevated in C4d+ group (p = 0.0001). The renal biopsy showed that activity index score >12 was a higher proportion in C4d+ patients. The patients were followed up for 3.5 years. Four patients in the C4d+ group evolved to ESRD in the follow-up, but none of the patients in the C4d- group (p = 0.064). DISCUSSION: We found a relationship between glomerular C4d staining and activity of lupus nephritis. C4d staining may be a useful marker to predict the prognosis of lupus nephritis.

Prognostic value of NGAL staining in patients with IgA nephropathy.

BACKGROUND: Renal tubulointerstitial injury plays an important role in disease progression of IgAN. Neutrophil gelatinase-associated lipocalin (NGAL) is a stress protein released by tubular cells. NGAL is a promising biomarker of acute kidney injury. There is a growing literature suggesting that NGAL is also a marker of chronic kidney disease and severity. Our aim was to evaluate the prognostic value of NGAL staining in patients with IgAN. METHODS: This retrospective study included all consecutive patients who underwent a renal biopsy at our center between January 2005 and December 2009. Forty-five patients with IgA nephritis were enrolled, and renal biopsy specimens of 29 patients were evaluated. We evaluated baseline age, sex, hypertension, serum creatinine, glomerular filtration rate (GFR), urine protein, NGAL staining, glomerulosclerosis, interstitial fibrosis, and extracapillary proliferation. The primary endpoint of this study was doubling of baseline serum creatinine and/or the onset of ESRD in the course of the study. At the end of the follow-up, patients whose estimated GFR (eGFR) was ≤15 mL/min/1.73 m(2) and/or baseline serum creatinine doubled, were defined as the progressor group. RESULTS: Nineteen patients (65.5%) were NGAL positive and 10 patients (34.5%) were NGAL negative. Female gender and hypertension were associated with NGAL-positive staining. Urinary protein excretion and serum creatinine levels were more elevated in the NGAL-positive group, but the difference was not significant. We found NGAL-positive staining in major proportion in the progressor group (88.9%) than the non-progressor group (55%) (p = 0.076). CONCLUSION: NGAL staining can be a new histological marker in IgAN progression.

Deformation-Controlled Design of Metallic Nanocomposites.

Achieving the theoretical strength of a metallic alloy material is a demanding task that usually requires utilizing one or more of the well-established routes: (1) Decreasing the grain size to stop or slow down the dislocation mobility, (2) adding external barriers to dislocation pathways, (3) altering the crystal structure, or (4) combining two of the previous discrete strategies, that is, implementing crystal seeds into an amorphous matrix. Each of the outlined methods has clear limitations; hence, further improvements are required. We present a unique approach that envelops all the different strength-building strategies together with a new phenomenon-phase transition. We simulated the plastic deformation of a Zr-Nb nanolayered alloy using molecular dynamics and ab initio methods and observed the transition of Zr from hexagonal close-packed to face-centered cubic and then to body-cenetered cubic during compression. The alloy, which was prepared by magnetron sputtering, exhibited near-theoretical hardness (10.8 GPa) and the predicted transition of the Zr structure was confirmed. Therefore, we have identified a new route for improving the hardness of metallic alloys.

Prognostic value of glomerular C4d staining in patients with IgA nephritis.

INTRODUCTION: Mesangial IgA deposition is the initiative factor in the pathogenesis of IgA nephropathy (IgAN). Glomerular IgA depositon leads to activation local complement system. C4d positivity shows that complement activation occurs via alternative pathway. C4d positivity at the time of renal biopsy can be associated with poor prognosis in IgA nephropathy. We aimed to evaluate C4d deposition and renal outcome in patients with IgA nephritis. METHODS: Between January 2005 and December 2009, 40 patients with IgA nephritis were enrolled. Renal biopsy specimens of 33 patients have been evaluated. C4d immunohistochemical staining was performed 3-µm deparaffinized and rehydrated sections of formaldehyde-fixed renal tissues, using rabbit polyclonal anti-human C4d as the antibody. Baseline demographical, clinical and laboratory data were recorded retrospectively. RESULTS: Mean age of the patients was 35.9 ± 12.9 years and female/male ratio was 19/21. Mean duration of follow-up was 32.8 (12-60) months. Baseline glomerular filtration ratio (GFR) and proteinuria were 55.8 ml/min and 2.44 gr/day respectively at the time of renal biopsy. Eleven patients were C4d positive. Presence of hypertension (p=0.133), proteinuria (p=0.007), serum creatinine levels (p=0.056) and glomerulosclerosis (p=0.004), mesengial hypersellularity (p=0.0001) and interstitial fibrosis (p=0.006) at the time of renal biopsy were higher in C4d positive group rather than negative group. Evolution to renal failure were 63.6% in C4d positive group and 13.6% in negative group (p=0.006). Renal survival at 3 years was 39% in C4d-positive patients versus 66.7% in the C4d-negative patients (log rank- p=0.0072).

C-reactive protein in unstable angina pectoris and its relation to coronary angiographic severity and diffusion scores of coronary lesions.

OBJECTIVE: We aimed to assess the relationship between C-reactive protein (CRP) and the severity and diffusion of coronary artery lesions in patients with unstable angina pectoris (UAP) and the independent association of CRP with this clinical situation. METHODS: This cross-sectional, observational study included 50 patients. Classification by Braunwald was used for UAP. The severity and diffusion of angiographic coronary disease were graded according to Reardon's modified scoring system. Plasma CRP levels were quantified by immunoturbidimetry. Nonparametric tests were used for comparison of CRP and other risk factors, and logistic regression analysis for evaluation of independent association between CRP and unstable angina pectoris. RESULTS: The severity score was 46±18 points in class IIB1 UAP, 36±20 points in class IIB2 and 53±18 points in class IIIB2 (p=0.017, class IIIB2 vs IIB2). Respectively, CRP levels were 6.6 mg/L, 3.8 mg/L and 4.8 mg/L (p=0.371, class IIB1 vs IIB2 vs IIIB2). Lesions with diffusion score 4 revealed higher CRP values than lesions with diffusion score 1 (11.1 mg/L vs 3.1 mg/L, p=0.048). Adjusting age, sex and smoking, assessment of partial correlation analysis showed a positive, moderately powerful and significant association between CRP levels and the severity and diffusion scores of the coronary lesions (r=0.30; p=0.034 and r=0.31; p=0.030, respectively) in the whole study group. Multiple logistic regression analysis showed no appreciable independent association between CRP and UAP (OR: 1.63, 95%CI: 0.90-5.63, p=0.093). CONCLUSION: Although, CRP was correlated with the severity and diffusion of angiographic coronary disease in patients with UAP, there was no independent association between CRP and clinical severity of UAP.