HEAT-SHOCK-PROTEIN (HSP) EXPRESSION AND PROLIFERATION OF TUBULAR CELLS IN END-STAGE RENAL-DISEASE WITH AND WITHOUT HEMODIALYSIS

Background. Prolonged dialysis is associated with acquired cystic kidn ey disease (ACKD) and also higher incidence of renal cell carcinoma. R elationship among dialysis, tubular cell proliferation, development of cystic change and neoplastic transformation is not clearly known. Whe ther dialysis causes additional stress on tubular cells is also conjec tural. Study of heat shock protein (HSP) expression which are rapidly synthesized in cells in response to a variety of stresses may be helpf ul 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 haemo dialysis for 3-12 months. The heat shock protein (HSP 72/73) expressio n of tubular epithelial cells and their proliferating cell nuclear ant igen (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 morphologic ally into (1) classic, (2) thyroid, (3) endocrine and (4) super tubule s. Results. In the dialysed group (I) the percentage of hyperplastic s uper tubules (10.6+/-4.1%) was significantly higher than in the non-di alysed group (II) (5.2+/-1.3%) with a higher PCNA LI (6.8+/-2.04%) (gr oup II 4.9+/-1.9%) (P<0.01 to <0.001). Though grossly not detected, bu t microscopic cysts and microadenoma like areas were seen in all the c ases in group I with a mean diameter of 522.66+/-315.25 mu m and 494.8 5+/-262.46 mu m 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) s howed a positive correlation (r=0.7555) (P<0.001) with PCNA LI in supe r tubules indicating a higher induction in the dialysed group. Conclus ions. This study suggests that haemodialysis may cause injury to tubul ar cells and aggravate stress on an already compromised situation of E SRD leading to increased cell proliferation and more hyperplastic supe rtubule formation which may be the forerunner of cyst formation as wel l as neoplastic transformation.