Heat shock protein (HSP) expression and proliferation of tubular cells in end stage renal disease with and without haemodialysis

Abstract

Background. Prolonged dialysis is associated with acquired cystic kidney disease (ACKD) and also higher incidence of renal cell carcinoma. Relationship among dialysis, tubular cell proliferation, development of cystic change and neoplastic transformation is not clearly known. Whether dialysis causes additional stress on tubular cells is also conjectural. Study of heat shock protein (HSP) expression which are rapidly synthesized in cells in response to a variety of stresses may be helpful in this regard. Methods. To evaluate dialysis induced early changes in end stage renal disease (ESRD), kidneys from eight adult autopsied patients were examined (group I) who were on weekly maintenance haemodialysis for 3-12 months. The heat shock protein (HSP 72/73) expression of tubular epithelial cells and their proliferating cell nuclear antigen (PCNA) labelling index (LI) were studied by immunohistochemistry using monoclonal antibodies. For comparison similar study was carried out in 10 cases of ESRD (Group II) of similar age and sex distribution who were not dialysed. The atrophic tubules were subtyped morphologically into (1) classic, (2) thyroid, (3) endocrine and (4) super tubules. Results. In the dialysed group (I) the percentage of hyperplastic super tubules (10.6 ± 4.1%) was significantly higher than in the non-dialysed group (II) (5.2 ± 1.3%) with a higher PCNA LI (6.8 ± 2.04%) (group II 4.9 ± 1.9%) (P < 0.01 to < 0.001). Though grossly not detected, but microscopic cysts and microadenoma like areas were seen in all the cases in group I with a mean diameter of 522.66 ± 315.25 μm and 494.85 ± 262.46 μm respectively. They were seen in one case of group II. PCNA LI of the cells in microadenoma (7.2 ± 3.1%) and microcysts (6.6 ± 2.6%) were similar to that of super tubules in group I. Quantitation of HSP expression by image analysis (optical density 2.309 ± 0.155) showed a positive correlation (r = 0.7555) (P < 0.001) with PCNA LI in super tubules indicating a higher induction in the dialysed group. Conclusions. This study suggests that haemodialysis may cause injury to tubular cells and aggravate stress on an already compromised situation of ESRD leading to increased cell proliferation and more hyperplastic supertubule formation which may be the forerunner of cyst formation as well as neoplastic transformation.