Pathological Characteristics of the Kidney and Bone of Patients with Itai-Itai Disease (Chronic Cadmium Toxicity)
Koichi Tsuneyama, Megumi Yazaki, Takashi Minamisaka, Kohei Nagata, Hayato Baba, Tatsuhiro Tsuda, Keiko Aoshima. University of Toyama, Toyama, Japan; Hagino Hospital, Toyama, Japan
Background: Itai-itai disease (IID), which is recognized in Japan as a pollution-related illness, is caused by chronic exposure to the mineral cadmium (Cd). Excess Cd accumulation in the proximal renal tubules (PRT) causes renal atrophy and secondary osteomalacia. In the present study, we assessed kidney and bone specimens of IID patients and compared the degree of histopathological change in these specimens with Cd concentrations within organs.
Design: Autopsy specimens from 71 IID patients and 27 patients not exposed to Cd pollution were examined. Cd concentration was measured using fresh organs. H&E staining was performed in addition to specialized staining with Azan for detecting fibrosis, Yoshiki staining for osteoid recognition, and immunostaining for metallothionein (MT), which binds and detoxifies Cd, CD10, a marker of the PRT, and EMA, a marker of the distal renal tubules (DRT). Images were analyzed with WinRoof. Statistical analyses were performed using JMP.
Results: Cd accumulation in the organs of the IID patients was 5.2 (liver), 4.1 (pancreas), 4.9 (thyroid gland), 7.3 (muscle), 3.3 (rib), 0.38 (renal cortex), and 0.62 (renal medulla) times higher than that of the controls. More than 80% of the IID patients showed kidney atrophy, with the surface of the kidney having a sandpaper-like surface. Microscopically, marked atrophy of the PRT and interstitial fibrosis with inflammatory changes were commonly observed among the IID patients, but there was less damage to the DRT. The intensity and distribution of MT in the kidneys of the IID patients were weaker than those of the controls. In bone, severe osteomalacia was observed in all of the IID patients before their deaths and was diagnosed by X-ray. However, more than 80% of these patients had mild-to-moderate osteomalacia in remission at autopsy. The degree of renal damage and osteomalacia was not related to the Cd concentration.
Conclusions: Atrophy of the PRT with interstitial changes was commonly observed among the IID patients. Renal damage may be a primary event and intractable to treatment. In contrast, osteomalacia was improved in most of the IID patients because of recent progress in treatments. The volumes of MT and Cd were markedly reduced in the kidneys of the IID patients. A portion of the excess Cd may have moved to other organs. However, we hypothesized that a portion of the excess Cd may have spilled into the urine due to renal damage. Examination of urinal Cd concentration should be required as part of a medical check-up of residents in Cd-polluted areas.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 269, Wednesday Afternoon