ELSEVIER Ann Anat 186 (2004): 277-282 http://www.elsevier.de ANI J S OF ANATOMY Low-dose radiation modifies the progression of chronic renal failure Marina Aunapuu 1, [)lie Pechter 2, Eduard Gerskevits 3, Margit-Maie Marjamfigi 3, Sirje Suuroja 4, Andres Arend 1, Ivo Kolts 1, Wolfgang Kiilmel 5, and Mai Ots 6 1Department of Anatomy, University of Tartu, Ravila 19, 51014 Tartu, Estonia, 2Depart- ment of Sport Medicine and Rehabilitation, 3Department of Radiology, 4Unified Centre of Laboratories, SDepartment of Internal Medicine, Tartu University Clinicum, L. Puusepa 6 a, 50406 Tartu, Estonia, and 6Institute of Anatomy, Medical University Ltibeck, Ratzeburger Allee 160, D-23538 Ltibeck, Germany Summary. Previous studies have indicated that the appli- cation of low dose radiation to an arterial ligation has the potential to subsequently reduce or eliminate restenosis caused by smooth muscle cell proliferation. Sufficient kid- ney irradiation causes a radiation nephropathy and often leads to renal failure. In order to evaluate the effect of low-dose irradiation on the kidney we hypothesized that this particular therapy modifies renal injury in rats with renal ablation and subsequently slows the rate of the pro- gression. For further clarification of the effect of irradiation at low doses, we determined proliferating cell nuclear anti- gen (PCNA) and monocyte chemoattractant protein-1 (MCP-1) expression in remnant kidneys after low-dose radiation. Adult Wistar rats (n = 10) were studied during the two weeks after renal ablation. The left kidney was ir- radiated 24 hours after an operation in anaesthetised ani- mals with 3 Grey in a single dose. Ablated rats without irradiation (n =9) served as nephrectomized animals group. Rats without surgery and without radiation (n = 10) served as healthy controls. Renal damage was assessed using the following parameters: urine protein excretion rate (UprotV, mg/day), awake systolic blood pressure (SBP, mm Hg), serum creatinine (SCr, pmol/1). The indirect immunofluorescence method was used for the detection of PCNA and MCP-1 expression. Glomeru- lar and tubular immunostaining was scored semiquantita- tively. Correspondence to: M. Aunapuu E-maih mariaun@ut.ee Numerous PCNA positive cells and MCP-1 expression were present in the glomerulus and tubulointerstitium in nephrectomized rat kidneys. Low-dose radiation applica- tion was associated with a significant reduction in PCNA and low MCP-1 expression. This study shows that the application of low-dose irradiation has the potential to modify the progression of chronic renal failure in rats. Key words: Rats - Proteinuria - Proliferating cell nuclear antigen - Monocyte chemoattractant protein-1 - Focal segmental glomerulosclerosis Introduction During last decades understanding of pathophysiological processes leading to the progression of chronic nephropa- thy has significantly changed (Ots et al. 2000). Irrespec- tive of the renal primary detractive mechanism, immune or non-immune, the remaining parts of the kidney under- go adaptive changes. Critical amount of nephrons are de- stroyed during the development of chronic renal failure, but the remaining ones show compensatory changes. These studies demonstrate that alterations in glomerular hemodynamics associated with renal ablation are accom- panied by structural lesions and suggest that sustained single nephron hyperfiltration may have maladaptive con- sequences by damaging remnant glomeruli (Hostetter et al. 1981; Brenner 1989). The five-sixths nephrectomy or remnant kidney model in rats is a very useful and widely studied model for the analysis of differences and progres- 0940@6021041186103-277 $30.00/0