The Significance of Inflow Artery and Tourniquet Derived Cephalic Vein Diameters on Predicting Successful Use and Patency of Arteriovenous Fistulas for Haemodialysis.

OBJECTIVE: To investigate the significance of inflow artery and cephalic vein diameters on predicting patency of radiocephalic and brachiocephalic arteriovenous fistulas (AVFs). DESIGN: Single centre study with retrospective analysis of prospectively collected data between November 2010 and July 2015. METHODS: A detailed history and physical examination was undertaken, including age, gender, history and duration of haemodialysis, cause of chronic kidney disease, and the presence of comorbidities/risk factors. Pre-operative arterial and venous upper extremity mapping was performed and inner vessel diameter was recorded, using a tourniquet for the veins. Outcome measures included AVF use (functionality), primary, primary assisted, secondary, and functional secondary patency. RESULTS: One hundred and thirty five AVFs (57 and 78 radiocephalic and brachiocephalic AVFs, respectively) were constructed and followed up for 5 years. A cephalic vein diameter <4.3 mm (lower three quartiles) was the single independent predictor of inferior secondary and also functional secondary patency of radiocephalic AVFs (p = .02, HR 11.2, 95% CI 1.44-90.9). A brachial artery diameter ≤4.1 mm (lowest quartile) was an independent predictor of AVF functionality (57% vs. 83% for larger arteries, p = .017), and inferior primary, primary assisted, secondary, and functional secondary patency of brachiocephalic AVFs (primary assisted patency 21.9% vs. 55.9% at 3 years, p = .001/log-rank test, HR 3.1, p = .002/Cox regression). The presence of lower extremity PAD or use of dual antithrombotics was also independently associated with an inferior secondary patency. The number of risk factors (brachial artery diameter ≤4.1 mm, PAD, and use of dual antithrombotics) demonstrated risk stratification capabilities for functional secondary patency. CONCLUSIONS: Among patients undergoing radiocephalic AVFs, a tourniquet derived cephalic vein diameter <4.3 mm was the single independent predictor of inferior secondary and functional secondary patency. Among patients undergoing brachiocephalic AVFs, all patency rates were inferior in the presence of a brachial artery diameter ≤4.1 mm and secondary patency was inferior in the presence of multiple risk factors.

Urinary interleukin-6 (IL-6) and transforming growth factor (TGF-ß) levels in corticosteroidtreated patients with IgA nephropathy.

BACKGROUND: Interleukin-6 (IL-6) and transforming growth factor-ß (TGF-ß) are implicated in the progression of IgA nephropathy, which is usually treated with corticosteroids. PATIENTS AND METHODS: Urinary IL-6 and TGF-ß were measured in 21 proteinuric patients with IgA nephropathy, before and after treatment with corticosteroids, to estimate the activity of the disease after remission of proteinuria. RESULTS: Urinary IL-6 and TGF-ß levels at diagnosis were significantly higher in patients with IgA nephropathy compared to healthy subjects. TGF-ß levels, were significantly higher in patients with proteinuria > 1 g/24 h and/or severe mesangial proliferation. Although a significant reduction of proteinuria was observed with corticosteroid treatment, urinary IL-6 and TGF-ß levels remained elevated. Deterioration of renal function over a period of 5 years was observed in 3 patients. High urinary IL-6 levels at diagnosis represent a significant parameter distinguishing patients with progressive course in comparison to those with favorable clinical outcome (p = 0.01). CONCLUSION: Treatment of patients with IgA nephropathy with corticosteroids is followed by remission of proteinuria but still increased urinary IL-6 and TGF-ß excretion. This may be related to an ongoing inflammatory process within the kidney, and further research is required to estimate the value of urinary IL-6 and TGF-ß as markers of activity of the disease.

Expression of transgelin in human glomerulonephritis of various etiology.

BACKGROUND/AIMS: Activation of myofibroblasts occurs during kidney injury. Genomic and proteomic studies suggest that transgelin represents a protein that may be involved in renal injury. The purpose of this study was to estimate transgelin expression in the renal tissue of patients with glomerulonephritis. METHODS: Transgelin was identified in biopsy sections of 67 patients by immunohistochemistry and immunofluorescence. Its distribution was compared to that of α-smooth muscle actin (α-SMA), a marker of myofibroblast activation in the kidney. RESULTS: Transgelin and α-SMA expression was identified within glomeruli and interstitium. In patients with IgA nephropathy and focal segmental glomerulosclerosis, glomerular expression of transgelin was higher than that of α-SMA. The extent of transgelin immunostaining was related to mesangial proliferation (p = 0.034), glomerular sclerosis (p = 0.035), interstitial fibrosis (p = 0.047) and to the clinical course (p = 0.009). Colocalization studies showed that in some areas of kidney tissue both proteins were expressed with comparable intensity, whereas in other areas expression of either transgelin or α-SMA was predominant. CONCLUSION: Strong transgelin expression was observed in renal tissue of patients with glomerulonephritis. The observed differences in the pattern of transgelin and α-SMA expression suggest that either different subpopulations of myofibroblasts exist, or that these proteins are activated at different stages of renal injury/scarring.

The remission of nephrotic syndrome with cyclosporin treatment does not attenuate the progression of idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated by combination of corticosteroids with cytotoxic drugs. In cases resistant to this regimen, the use of cyclosporin A (CsA) is followed by frequent remissions of the nephrotic syndrome. AIM: The purpose of this study was to estimate the effectiveness of prednisolone and small doses of CsA as first-line treatment of nephrotic patients with IMN, in relation to the progression of the disease, based on functional and histological changes. PATIENTS AND METHODS: Sixteen patients, with nephrotic syndrome due to IMN and well-preserved renal function, were treated with prednisolone (starting dose: 0.5 mg/kg bw/day) and CsA (starting dose: 3 mg/kg bw/day) for 24 months. A repeat renal biopsy was performed after 18 months of treatment in 10 patients with remission of nephrotic syndrome, to estimate the activity of the disease and to identify any features of CsA toxicity. RESULTS: Remission of the nephrotic syndrome was observed in 14 out of 16 patients after 5 +/- 2 months of treatment. Complete remission was observed in 8 and partial remission in 6 patients (urinary protein was reduced from 6.9 +/- 3.4-0.2 +/- 0.06 g/24 h and 1.2 +/- 1.0 g/24 h, respectively, p < 0.01). The renal function was well preserved in 13 out of 16 patients over a 24-month period of treatment. Deterioration of renal function was observed in 3 patients (creatinine clearance reduced from 86 +/- 21-37 +/- 17 ml/min, p < 0.05) who had either persistent nephrotic syndrome or frequent relapses. Relapses of the nephrotic syndrome were observed in 5 of 14 patients. Repeat renal biopsies showed that glomerular sclerosis, tubulointerstitial injury, vascular hyalinosis and stage of the disease were deteriorated in most patients. Isometric vacuolization of tubular epithelial cells was observed in 2 of 10 patients. CONCLUSION: IMN nephrotic patients treated with prednisolone and low doses of cyclosporin A showed a high remission rate of nephrotic syndrome. However, progression of chronic histological lesions was found in repeat renal biopsies. This suggests that cyclosporin can frequently induce remission of nephrotic syndrome in IMN patients, but even low doses of the drug are not free of potential renal toxicity.

Endothelin-1 in the kidney and urine of patients with glomerular disease and proteinuria.

BACKGROUND: Endothelin-1 (ET-1) is a strong vasoconstrictive peptide that is involved in the pathogenesis of arterial hypertension. There is increasing evidence, based on studies in experimental animals, that endothelin-1 is produced by tubular epithelial cells in response to activation by filtered protein and is involved in the development of renal scarring. The aim of this study is to examine the distribution of ET-1 in the renal tissue of patients with heavy proteinuria and to estimate the changes in its urinary excretion after immunosuppressive therapy. PATIENTS AND METHODS: Twenty-four patients with severe proteinuria (7.5 +/- 6.5 g/24 h) due to different types of glomerular disease and normal renal function (creatinine clearance 91 +/- 14 ml/ min) were investigated. All patients underwent a renal biopsy and commenced on immunosuppressive therapy with corticosteroids and cyclosporin A. The localization of ET-1 in the renal tissue was examined by immunohistochemistry and compared to control renal tissue from 9 patients who underwent nephrectomies because of hypernephroma. In patients with proteinuria, endothelin-1 excretion in the urine at diagnosis was determined by radioimmunoassay and compared to that of 14 healthy subjects. A second measurement of urinary ET-1 excretion was performed after remission of proteinuria or 6 months after the initiation of treatment in patients with persistent nephrotic syndrome. RESULTS: ET-1 in renal tissue of patients and controls was localized within the cytoplasm of endothelial cells. In nephrotic patients, it was also localized within the cytoplasm of tubular epithelial cells. Urinary ET-1 levels were higher in nephrotic patients compared to healthy subjects (746 +/- 180 ng/24 h vs 410 +/- 112 ng/ml, p < 0.001). In 17 of 24 patients who showed remission of proteinuria with immunosuppressive therapy, the urinary ET-1 levels decreased (from 803 +/- 168 ng/24 h to 511 +/- 80 ng/24 h, p < 0.001) whereas in 7 patients with persistent proteinuria, urinary ET-1 excretion remained elevated. CONCLUSIONS: The increased urinary excretion of ET-1 in patients with severe proteinuria followed by a significant decrease after remission ofproteinuria with immunosuppressive treatment, along with its expression within tubular epithelial cells, suggests a possible relationship between proteinuria and renal ET-1 production.

Polymorphonuclear leukocyte rigidity is defective in patients with chronic renal failure.

BACKGROUND: The purpose of the study was to investigate the rigidity of polymorphonuclear leukocytes (PMNs) in non-dialysed chronic renal failure (CRF) and haemodialysis (HD) patients. METHODS: PMN rigidity as well as tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) plasma levels were assessed in 10 early-stage CRF, 10 late-stage non-HD, and 10 HD patients, before and during dialysis. In HD patients both cellulose acetate and polysulphone membranes were used. Ten healthy subjects served as controls. Rigidity was tested by counting the deformability in morphologically passive PMNs by the micropipette method. Cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: PMN rigidity was significantly increased in end-stage CRF patients regardless of HD but not in early-stage CRF. In HD patients PMN rigidity increased significantly 60 min after initiation of HD. There was an increase of TNF-alpha and IL-1beta levels in end-stage non-HD and HD patients and a further increase at 60 min after initiation of HD. The percentage of morphologically activated PMNs was increased only during dialysis. The nature of the HD membrane had no influence on rigidity, PMN activation, or cytokine production. CONCLUSIONS: The results indicate that PMN rigidity is defective in end-stage chronic CRF patients and is further increased 60 min after initiation of HD, regardless of the nature of the HD membrane used. PMN activation, increased TNF-alpha and IL-1beta levels, or a direct PMN impairment may cause the observed cell rigidity.

Myofibroblasts, predictors of progression of mesangial IgA nephropathy?

The limited knowledge of the cellular mediators of renal scarring hampers progress in the management of progressive chronic renal failure (CRF). We have studied 38 patients with biopsy-proven mesangial IgA nephropathy with emphasis on attempting to define the role of myofibroblasts (alpha-smooth muscle actin/SMA-positive cells) in renal scarring. In 18 untreated patients, correlations were undertaken between known histological parameters of progression as well as the presence of myofibroblasts in tissues and the clinical outcome. alpha-SMA staining by an avidin-biotin-peroxidase method was confined to a large extent to the vascular smooth muscle cells of normal kidneys but extended to the tubulointerstitium and periglomerular space in scarred kidneys. Mild glomerular staining was also noted. The interstitial immunostain followed a similar distribution to that of interstitial type III collagen. Morphometric analysis showed the interstitial alpha-SMA staining to be a reliable histological predictor of outcome as it discriminated between progressors and non-progressors (chi 2 = 4.923, P = 0.026). The intensity of the interstitial alpha-SMA staining correlated with renal functional outcome; inversely with the reciprocal of serum creatinine slopes (r = -0.466, P < 0.025) and positively with the serum creatinine value at the end of the observation period (r = 0.704, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)