case_images: PMC11309756_01
case_images: a Clinical time course of sCr levels of case 1. The renal biopsy was performed on day 12 after cessation of the RYR supplement (orange arrow). b-d Light microscopy and electron microscopy findings of the renal biopsy of case 1, performed on day 12 after cessation of the RYR supplement. PAS (b, c) and HE (d) staining show proximal tubular injury with flattening, diffuse loss of the brush border, and tubular dilatation with interstitial edema and mild fibrosis. Only a few inflammatory cell infiltrates are found. e Electron microscopy shows diffuse loss of microvilli and flattened proximal tubular cells. Bar in (b-d): 50 mum, (e): 10 mum.
case_images: cnd-2024-0014-0001-540258_F01.jpg
case_images: PMC11309756_01_cnd-2024-0014-0001-540258_F01.jpg
case_images: F1
case_images: February 2023 showed serum creatinine (sCr) levels of 0.61 mg/dL and 0.65 mg/dL, and blood urea nitrogen (BUN) levels of 20.6 mg/dL and 20.6 mg/dL, respectively, indicating satisfactory renal function. From January 2023, the patient began self-administering an RYR supplement, "         (R)" (Fig. 1a), 3 tablets per day. Light microscopy (Fig. 1b-d), which included 47 glomeruli with 6 showing global sclerosis, showed a severe proximal tubular injury, characterized by flattening of proximal tubular cells, dilatation of the tubular lumen, and diffuse loss of the brush border with moderate interstitial edema and mild interstitial fibrosis. Prominent flattening of the proximal tubules and loss of the brush border were marked, with no intracellular crystal formation detected (Fig. 1e).
case_images: PMC11309756_02
case_images: a Clinical time course of the sCr level of case 2. The renal biopsy was performed on day 19 after cessation of the RYR supplement (orange arrow). b-d Light microscopy and electron microscopy findings of the renal biopsy of case 2, performed on day 19 after cessation of the RYR supplement. PAS (b, c) and HE (d) staining show proximal tubular injury with flattening, partial loss of the brush border, and tubular lumen dilatation with interstitial edema and mild fibrosis. Only a few inflammatory cell infiltrates are found. e Electron microscopy shows partial loss of microvilli and moderately flattened proximal tubular cells. Bar in (b-d): 50 mum, (e): 10 mum.
case_images: cnd-2024-0014-0001-540258_F02.jpg
case_images: PMC11309756_02_cnd-2024-0014-0001-540258_F02.jpg
case_images: F2
case_images: In 2021, he was diagnosed with dyslipidemia, and from 2022 onward, he began self-administering an RYR supplement, the same tablets as in case 1, 3 tablets per day (Fig. 2a). Histopathology of the renal biopsy (Fig. 2b-d), similar to case 1, showed proximal tubular injury with diffuse and moderate flattening and loss of the brush border on light microscopy, but the degree of injury was relatively milder than in case 1. Electron microscopy (Fig. 2e) showed injured proximal tubules with flattening and loss of the brush border partially observed, but the degree of injury was relatively milder than in case 1.
case_images: Immunostaining of the 2 cases (case 1: a-f, case 2: g-l) using Abs against CD10 (a, d, g, j), a marker for proximal tubules, E-cadherin (b, e, h, k), a marker for distal tubules including the loop of Henle, and Ki-67 (c, f, i, l), a marker for cell proliferation. Low (a-c, g-i) and high magnification (d-f, j-l) fields are shown, respectively. CD10 expression is markedly decreased in the cytoplasm and expressed only in the brush border in case 1 (a, d). In comparison, in case 2, CD10 is expressed not only in the brush border, but also in the cytoplasm, although its expression pattern deviates significantly from the normal expression observed in proximal tubules (g, j). The expression of E-cadherin in both cases is preserved (b, e, h, k). Expression of Ki-67 is observed in both cases, but appears slightly more abundant in case 1 (c, f, i, l). Bar in (a-c) and (g-i): 50 mum. Bar in (d-f) and (j-l): 25 mum.
case_images: cnd-2024-0014-0001-540258_F03.jpg
case_images: PMC11309756_02_cnd-2024-0014-0001-540258_F03.jpg
case_images: F3
case_images: Renal biopsy tissue samples from both patients were examined immunohistochemically using anti-CD10 antibody (Ab) as a convoluted and straight proximal tubular marker, anti-E-cadherin Ab as loop of Henle, distal tubule, and collecting duct marker, and anti-Ki67 Ab as a cell proliferation marker (Fig. 3). In case 1, CD10 was expressed only in the brush border and not in the cytoplasm (Fig. 3a, d). In case 2, compared to case 1, CD10 was observed to be slightly but markedly more strongly expressed, with its distribution seen not only in the brush border, but also within the intracellular compartment (Fig. 3g, j). In comparison, the expression of E-cadherin was preserved in both cases (Fig. 3b, e, h, k). The proliferation marker, Ki-67, was slightly more frequently observed in case 1 than in case 2 (Fig. 3c, f, i, l).