A 22-year-old Vietnamese woman was referred to the nephrology clinic for evaluation of elevated creatinine that was incidentally found on a laboratory check. She had a history of papillary thyroid cancer treated with a left thyroid lobectomy in 2017. She was currently in remission. She was found to have had hyperuricemia since high school. She said she was told by her primary care physician a few years previously that she has chronic kidney disease (CKD) and that her creatinine has been 0.9-1.0 mg/dL. However, laboratory tests performed 7 months prior to the nephrology clinic visit showed a serum creatinine level of 1.52 mg/dL. She denied any acute illnesses in the previous 7 months. Her only medication was febuxostat 40 mg once a day. She does not take nonsteroidal anti-inflammatory drugs or any other medication or supplements, including herbal supplements. Review of systems was negative for all systems.

The patient had a significant family history of hyperuricemia and CKD. Her father had hyperuricemia and CKD and is now on dialysis. Her paternal grandmother also had kidney disease and hyperuricemia. Her older brother had hyperuricemia but no history of kidney disease. There was no family history or personal history of kidney stones. 

Her physical examination was unremarkable, including normal blood pressure (110/55 mm Hg). A kidney ultrasound did not find any kidney cysts, stones, or any solid masses. An initial workup ordered at the clinic visit included the following:

  • Serum creatinine 1.4 mg/dL
  • Blood urea nitrogen (BUN) 22 mg/dL
  • Serum sodium 137 mmol/L, potassium 3.9 mg/dL, chloride 104 mmol/L, CO2 26 mmol/L, calcium 9.7 mg/dL
  • Plasma uric acid level 6.3 mg/dL
  • Hemoglobin 13.1 mg/dL
  • Hemoglobin A1c 5.5%
  • Complements C3, C4, and CH50 levels normal

The patient tested negative for antinuclear antibody (ANA), anti-double stranded DNA (dsDNA), antineutrophil cytoplasmic antibody (ANCA), hepatitis B and C, HIV, and syphilis.

Urinalysis results: specific gravity 1.020, pH 5.0, no blood or protein, WBC 5/hpf, and RBC 2/hpf. Urine microscopy showed no dysmorphic RBCs or any cellular casts. The urine albumin/creatinine ratio was 13 mg/g and protein/creatinine ratio was 0.1g/g.

A kidney biopsy showed mild arterial nephrosclerosis and mild acute tubular injury. There was a low degree of interstitial fibrosis and tubular atrophy (~10%). No urate crystals were observed. Interestingly, there were cytoplasmic inclusion bodies staining trichrome blue in the epithelial cells of the thick ascending limb of the loop of Henle (TALH) (Figure 1A). Immunohistochemistry confirmed the inclusions to be composed of Tamm–Horsfall glycoprotein (Figure 1B). Electron microscopy of the biopsy tissue revealed distal tubular cells containing hyperplastic endoplasmic reticulum (ER) with intervening mitochondria alternating with areas of dilated ER containing storage material.

This case was prepared by Yongen Chang, MD, PhD, assistant clinical professor, Division of Nephrology and Hypertension, University of California-Irvine, and Jonathan E. Zuckerman, MD, PhD, and Anthony E. Sisk, DO, both assistant clinical professors, Department of Pathology, University of California-Los Angeles.

Figure 1. Renal biopsy images of this patient. (A) Light microscopy showing cytoplasmic inclusion bodies staining trichrome blue in the renal tubular epithelial cells (solid arrow). Dotted arrow points to cell nuclei.
(B) Immunohistochemistry identified uromodulin inclusion bodies in the thick ascending limb of the loop of Henle (solid arrow).
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