Validation of QB stress test as a useful tool in the detection of native arteriovenous fistula stenosis: results after 22 months of follow-up.

BACKGROUND: Access flow (QA) surveillance is the best method recommended for early stenosis detection, but in native arteriovenous fistula (AVF), the literature is conflicting about the real need for monthly monitoring of QA, as suggested by the K-DOQI Guidelines. METHODS: From 1 January 2006 to 31 October 2007 (mean 18.0 +/- 4.9 months), we prospectively followed up 224 patients with monthly AVF monitoring by means of clinical examination and QB stress test (QBST). Suspected malfunctioning AVFs were referred to ultrasound dilution technique (UDT) and imaging techniques (Doppler ultrasonography, angiography), with eventually further percutaneous angioplasty (PTA) or surgical revision. RESULTS: We observed a good correlation between QBST and QA measurement obtained by the UDT. Patients with positive QBST had a lower QA than negative QBST subjects (433 +/- 203 vs 1168 +/- 681 ml/min, P < 0.0001). Fifty-four out of 224 (24%) patients were selected for possibly malfunctioning AVF. We found no stenosis in 13 out of 54 (24%) patients, inflow stenosis in 29 out of 54 (54%) patients and outflow stenosis in 12 out of 54 (22%) patients. The QBST positive predictive value for inflow stenosis was 76.3%. The interventional radiologist performed 38 PTA procedures in 33 patients (11 PTA per 100 patient-years) and we surgically created 13 new AVF (3.7 per 100 patient-years). Only five thrombosis episodes occurred in five patients during the follow-up (1.5 thromboses per 100 patient-years). CONCLUSIONS: QBST is a simple, low-cost, not time-consuming test, able to select, together with clinical evaluation, malfunctioning AVF with stenosis located specifically in the inflow tract. Our follow-up data demonstrated that it is possible to achieve a low AVF thrombosis rate by adding QBST in an AVF monitoring program, thus reducing the surveillance burden.

Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies.

BACKGROUND: In recent studies performed on cultured cells and experimental nephropathies, it has been hypothesized that tubular epithelial cells (TEC), via epithelial-mesenchymal transformation (EMT), can become collagen-producing cells. According to this theory, they should proceed through several activating steps, such as proliferation and phenotype changes, to eventually synthesize extracellular matrix (ECM). METHODS: To evaluate whether EMT operates in human TECs, 133 renal biopsies of different renal diseases were studied, analyzing by immunohistochemistry and in situ hybridization the possible expression of markers of proliferation (PCNA, Mib-1), cellular phenotype (vimentin, alpha-SMA, cytokeratin, ZO-1) and ECM production (prolyl 4-hydroxylase, HSP47, interstitial collagens). RESULTS: Independently of histological diagnosis, variable degrees of TEC positivity for PCNA (2.7 +/- 2.4 cells/field) and Mib-1 (1.9 +/- 2.3) were present. TECs expressing vimentin (1.4 +/- 4.7) and alpha-smooth muscle actin (alpha-SMA; 0.04 +/- 0.4) also were detected. It was possible to observe loss of epithelial antigens from 8 to 10% of the tubular cross sections. Moreover, TECs were stained by prolyl 4-hydroxylase (3.6 +/- 4.3), heat shock protein-47 (HSP47; 2.9 +/- 5.4), collagen type I (0.2 +/- 2.7) and type III (0.3 +/- 2.0). Collagen types I and III mRNAs were found in 0.8 to 1.4 cells/field. The number of TEC with EMT features were associated with serum creatinine and the degree of interstitial damage (P< or = 0.03), and even considering the 45 cases with mild interstitial lesions, the tubular expression of all markers remained strictly associated with renal function (P< or = 0.01). CONCLUSIONS: Our results suggest that, via transition to a mesenchymal phenotype, TEC can produce ECM proteins in human disease and directly intervene in the fibrotic processes. Moreover, the association of EMT features with serum creatinine supports the value of these markers in the assessment of disease severity.

Glomerular monocyte-macrophage features in ANCA-positive renal vasculitis and cryoglobulinemic nephritis.

Although it is widely known that many macrophages are present in glomeruli of antineutrophil cytoplasmic antibody (ANCA)-positive renal vasculitis (ANCA + RV) and are believed to contribute to necrotizing extracapillary damage, their precise role is not yet completely understood, especially in humans. The goal of this study was to provide evidence of glomerular macrophage properties in human vasculitis. Twenty-five renal biopsies of ANCA + RV and 18 cases of cryoglobulinemic glomerulonephritis (cryoGN), a disease characterized by massive glomerular macrophage infiltration but absence of necrotizing extracapillary lesions, were selected, and macrophage number, adhesion, acute activation, proliferation, and apoptosis were analyzed by immunohistochemistry and in situ hybridization. Accumulation of macrophages in ANCA + RV was found in areas of glomerular active lesions, whereas in cryoGN, they homogeneously occupied the entire glomerular tuft. Considering the areas of accumulation, comparable macrophage numbers were detected in both diseases. Glomerular vascular cell adhesion molecule-1 was found only in ANCA + RV and only in areas of active lesions. Acute macrophage activation (HLA class II, 27E10) and proinflammatory cytokine production (tumor necrosis factor-alpha, interleukin-1alpha) were prominent in ANCA + RV, whereas in cryoGN, 30% of glomerular macrophages seemed activated and cytokine expression was limited to a few glomerular cells (P: = 0.01). Moreover, only in ANCA + RV proliferative markers were shown on glomerular macrophages and apoptotic macrophages were found. From the data, it seems that ANCA + RV and cryoGN differ profoundly in macrophage properties, namely adhesion, proliferation, and apoptotic clearance. Moreover, acute activation and cytokine production seem to be present in a greater number of macrophages in ANCA + RV, giving this disease a stronger severity that could be taken into account for therapeutic strategies.