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.

Microchimerism in peripheral blood and urine in renal transplant recipients: preliminary results.

The role of microchimerism in peripheral blood and urine of renal transplant recipients remains a matter of debate, depending on the sensitivity of the methods used for detection. We studied 17 female renal transplant recipients who had received renal allografts from male donors. Polymerase chain reaction (PCR) was applied to blood and urine for the microsatellite markers D1S80, DYZ1, TH01, and kalphai SE33. Detection of DYZ1 that is present only on the Y chromosome was considered proof for microchimerism. No microchimerism was detected in peripheral blood, whereas it could be detected in the urine of 8/17 (48%) patients. There were no differences between patients with and without microchimerism regarding patient age, dialysis vintage, immunosuppression, time post-transplantation, and allograft function as measured using serum creatinine, creatinine clearance, and proteinuria. Two patients in each group showed chronic allograft dysfunction. These findings raise questions regarding the role of microchimerism in renal transplantation.

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.