Background: Serum levels of C-reactive protein (CRP) increase during various atherosclerotic as well as kidney diseases. Whether CRP plays a pathophysiological role or rather serves as a marker is unknown. Here, we investigated the role of CRP in diabetic patients with chronic kidney disease.
Methods: Kidney biopsies from 20 diabetic patients, six with IgA nephropathy and six controls (absence of disease) were stained using a commercially available anti-CRP antibody (clone 8). We characterized this antibody by ELISA and found that it mainly recognized 'modified' CRP (mCRP), the conformational isoform of CRP that occurs after dissociation of the pentameric isomer.
Results: A specific CRP signal was observed in the cytoplasma of tubules in 17 out of 20 kidney biopsies from diabetic patients, while all glomeruli, vessels and interstitium stained CRP-negative. This signal was absorbed against the mCRP protein suggesting that the detected tissue-based antigen is more closely related to the mCRP conformer than to the native CRP conformer. Almost all patients (eight out of nine) with severe chronic kidney disease [glomerular filtration rate (GFR) <30 ml/min/1.73 m(2)] strongly stained for the mCRP antigen, whereas only four out of 11 patients with mild and moderate chronic kidney disease (GFR >/=30 ml/min/1.73 m(2)) demonstrated a strong CRP signal. Normal renal tissue and most biopsies with IgA nephropathy were mCRP negative. Severity of histologic changes as assessed by histology score and mCRP staining correlated significantly, but no correlation was evident between tubular mCRP staining and serum levels of CRP or proteinuria.
Conclusions: The present group of diabetic patients showed progressive tubular mCRP staining with declining renal function and increasing severity of histological lesions. Further studies in less proteinuric patients should clarify whether tubular mCRP expression constitutes a progression factor. It also needs to be demonstrated whether mCRP accumulates in tubuli to further stimulate interstitial fibrosis or is mandatory for the resolution of the process. Since mCRP staining was independent of proteinuria we suggest that mCRP is locally produced.