A 74-year-old woman was started on antihypertensive therapy 1 year prior to admission when she was noted to have a mild renal impairment with a serum Cr level of 1.1 mg/dL. She was status post-appendectomy at 20 years of age, had a history of ulcerative colitis with rectal cancer at 61 years of age, and a cataract at 68 years of age. She had no family history of renal disease or dialysis. Although her blood pressure was well controlled, her serum Cr level rapidly increased to 1.5 mg/dL at 3 months after the start of antihypertensive therapy and 2.4 mg/dL at 5 months after the start of therapy. She was subsequently referred to our hospital for further evaluation and treatment.
On physical examination, her temperature was 36.5C, and her blood pressure was 150/79 mmHg. Her conjunctivae were pale and she had lower extremity edema. The following laboratory results were obtained: WBC count, 6,800 WBC/mm3; RBC count, 248x104 RBC/mm3; Hb, 7.3 g/dL; Ht, 21.7%; Plt, 18.2x104/mm3; TP, 7.1 g/dL; Alb, 4.1 g/dL; BUN, 30 mg/dL; Cr, 3.6 mg/dL; Na, 138 mEq/L; K, 5.3 mEq/L; Cl, 107 mEq/L; CRP, 0.21 mg/dL; plasma glucose, 107 mg/dL; HbA1c, 5.1%; IgG, 1,326 mg/dL; IgM, 76 mg/dL; IgA, 239 mg/dL; C3, 91 mg/dL; C4, 24.7 mg/dL; and CH50, 13 U/mL. Cryoglobulin was negative. ANA was negative, and MPO, PR3, ANCA, and anti-GBM were not detected. A urinalysis showed 1.23 g protein/g creatinine and 6 RBC/HPF. Urinary beta-2MG was 27,708 ng/mL.
Abdominal CT showed bilateral kidney enlargement that was not seen on an earlier CT exam 1 year previously. Serial CT images are shown in Fig. 3. Magnetic resonance images (MRI) are shown in Fig. 4. MRI, including coronal magnetic resonance images, did not reveal multiple microcysts in the enlarged kidneys, however, a careful observation revealed multiple cysts along the corticomedullary boundary.
A percutaneous renal biopsy was performed on day 2. Of seven glomeruli, two were globally sclerotic, one was segmentally sclerotic, and two showed glomerular cysts. The other glomeruli were essentially normal. The distal tubules were also dilated, consistent with MCKD, and there was mild interstitial fibrosis and inflammatory cell infiltration (Fig. 5). Electron microscopy revealed irregular layering, spheroidizing, thinning, and partial rupture of the TBM. The patient was treated with corticosteroids [prednisolone (PSL) 30 mg/day] in view of the significantly elevated urinary beta-2MG level and interstitial cell infiltration. Immediately after PSL administration, a slight reduction in the serum Cr level was noted and her anemia improved. However, the serum Cr level gradually increased and the Hb level gradually decreased 2 months later, when PSL was tapered. Three months after the start of PSL therapy, the patient developed gastrointestinal bleeding and was found to have a serum Cr level of 7 mg/dL. The gastrointestinal bleed may have been an adverse effect of PSL therapy. However, no apparent bleeding source was detected by gastroscopy, colonoscopy, or enteroscopy. Anemia was corrected with blood transfusions, however, the patient's renal function did not improve and she began hemodialysis therapy 5 months after referral.
We also performed immunohistochemical staining in both cases for CD10, cytokeratin 7 (CK7), epithelial membrane antigen (EMA), E-cadherin, and cytokeratin (34 beta E12) to identify the level of tubular dilatation (Fig. 6). In case 1, the dilated tubules were negative for CD10, a marker of proximal tubules. In contrast, immunostaining results for CK7, EMA, and E-cadherin, markers of the distal tubules and collecting ducts, were positive. Immunostaining results for CK (34 beta E12), a marker of collecting ducts, were also positive, indicating that the cysts predominantly arose from collecting ducts in case 1. In case 2, the dilated tubules were positive for CK7 and EMA and weakly positive for E-cadherin and CK (34 beta E12).