Ten-year prognosis of Puumala hantavirus-induced acute interstitial nephritis.

Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. There are, however, some reports about subsequent hypertension, glomerular hyperfiltration, and proteinuria after previous hantavirus infection. Therefore, we studied 36 patients 5 and 10 years after acute NE, with 29 seronegative controls. Office blood pressure, ambulatory 24-h blood pressure (ABP), glomerular filtration rate (GFR), and proteinuria were examined. Hypertensive subjects were defined as those patients having increased ambulatory or office blood pressure, or receiving antihypertensive therapy. Office blood pressure was used to define hypertension only if ABP was not determined. At 5 years, the prevalence of hypertension was higher among NE patients than in controls (50 vs 21%, P=0.020). At 10 years, the difference between the groups was no more significant (39 vs 17%, P=0.098). Five years after NE, patients showed higher GFR (121+/-19 vs 109+/-16 ml/min/1.73 m(2), P=0.012) and urinary protein excretion (0.19 g/day, range 0.12-0.38 vs 0.14 g/day, range 0.09-0.24, P=<0.001) than controls. At 10 years, there were no more differences in GFR or protein excretion between the groups (GFR: 113+/-20 vs 108+/-17 ml/min/1.73 m(2), P=0.370; proteinuria: 0.14 g/day, range 0.07-0.24 vs 0.13 g/day, range 0.06-0.31, P=0.610). In conclusion, the 10-year prognosis of NE is favorable, as glomerular hyperfiltration and slight proteinuria detected at 5 years disappeared during the longer follow-up. However, the possibility exists that NE may predispose some patients to the development of hypertension.

Altered levels of Smad2 and Smad4 are associated with human prostate carcinogenesis.

Alterations have been demonstrated in ligand and cognate receptor system of the transforming growth factor beta (TGF-beta) pathway in prostate cancer (PC). Still, little is known about changes in the activity of the intracellular Smad cascade of TGF-beta signaling during prostate carcinogenesis. We used immunohistochemistry to analyze phosphorylated Smad2 (p-Smad2), nuclear Smad4 and inhibitory-Smad7 in epithelial cells of normal, hyperplastic and malignant prostate. Specimens comprised 49 tissue cores of PC, 10 benign prostate hypertrophies and three normal prostates. Nuclear p-Smad2 (P<0.001) and nuclear Smad4 (P=0.023) were significantly decreased in PC with remarkable variations in cytoplasmic Smad7 levels. Substantial decreases in p-Smad2 and Smad4 levels were found in specimens with primary Gleason grades 3 and 4, whereas in grade 5, levels were markedly higher. Our results provide the first evidence for changes and reversible attenuation in the Smad system of the TGF-beta pathway during prostate carcinogenesis.