Aim.Recent evidence suggests that chronic subclinical inflammation plays a key role in the pathogenesis and progression of diabetic nephropathy. Aim of the present study was to investigate possible correlation between the presence and degree of microalbuminuria and markers of inflammation in patients with type 2 diabetes mellitus (DM).Patients-Methods.Eighty patients were enrolled and clinical and laboratory data were recorded. Albumin-creatinine ratio (ACR) was calculated in first-morning urine samples. Serum and urinary tumor necrosis factor-α(TNF-α) levels were determined by ELISA.Results.Forty-five patients had normoalbuminuria, 33 microalbuminuria, and 2 macroalbuminuria. Patients with microalbuminuria were older, with higher glycosylated hemoglobin levels (HbA1c) and they more frequently had diabetic retinopathy, neuropathy, and cardiovascular disease and were on treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). ACR was significantly correlated with the presence of cardiovascular disease, hypertension, and HbA1c levels and the administration of clopidogrel and ACEi or ARBs. ACR was not correlated with C-reactive protein, fibrinogen, or serum TNF-αlevels but had a strong correlation with urinary TNF-αlevels.Conclusions.In patients with type 2 DM, urinary, but not serum, TNF-αlevels are associated with the presence and severity of microalbuminuria.

The clinical course of primary focal segmental glomerulosclerosis (FSGS) varies and there is considerable controversy as to which factors are of importance in determining prognosis or response to therapy. The aim of this study was to identify clinical, pathological or immunohistochemical features at biopsy that could identify patients with progressive disease who might benefit from treatment, and predict long-term outcome. The clinical and pathological findings of 33 adult patients with primary FSGS were retrospectively analysed in order to identify features at biopsy that could be predictive of outcome or response to treatment. For this purpose an immunohistochemical study was also performed, using monoclonal antibodies against intracellular adhesion molecules-1, C5b-9, alpha 3 beta 1 integrin, alpha-smooth-muscle actin (SMA), and TGF-beta1. At biopsy 17 patients (51%) were nephrotic and 16 (49%) non-nephrotic. Of the nephrotic patients, 11 were treated and six received only symptomatic therapy. Initial treatment with prednisolone (Pred) for 6-12 months (average 9 months) resulted in remission in 64% of nephrotic patients. To those with partial or no response, cyclosporin (CsA) or cyclophosphamide was given. At the end of follow-up (mean 57 months) three nephrotic patients (28%) were in complete remission, six (54%) in partial remission, and two (18%) did not respond to the treatment. In the seven treated non-nephrotic patients, Pred induced a complete remission in two (28%), a partial remission in three (44%), while two patients (28%) did not respond. Plasma creatinine remained stable in nephrotic patients who responded and it almost doubled in non-responders. Plasma creatinine also remained unchanged in treated non-nephrotic patients who responded to Pred, while two non-responders reached end-stage renal disease (ESRD). In contrast, 50% of untreated nephrotic patients and 67% of untreated non-nephrotic patients progressed to ESRD. Multivariate analysis showed only age and plasma creatinine at biopsy to have an independent predictive value for renal survival in nephrotic patients. This analysis also demonstrated that only the severity of interstitial fibrosis predicted the response to the treatment. In addition, the tubulointerstitial but not the glomerular expression of C5b-9, alpha 3 beta 1 integrin, alpha-SMA, and TGF-beta1 was significantly more extensive in non-responders and correlated with renal function at biopsy. However, only tubulointerstitial expression of TGF-beta1 independently correlated with the degree of renal function impairment at biopsy, but none of the above markers independently predicted renal survival or response to therapy. Nephrotic patients with FSGS may benefit from a more prolonged course of Pred. Nephrotic patients responding to treatment have a significantly better renal survival than non-responders. Age and plasma creatinine at biopsy are independent risk factors leading to ESRD. The severity of tubulointerstitial fibrosis is predictive of response to therapy.