The variable course of women with X-linked Alport Syndrome
A 36-year-old white female presented in 1990 at age 14 with microscopic hematuria and nonnephrotic proteinuria, and had a normal SCr of 0.8 mg/dL (70.7 μmol/L) (eGFR—98 mL/min/1.73 m2). A kidney biopsy demonstrated TBMN, but there was no other evidence of AS. Her urinalysis findings persisted, but her kidney function remained normal so no further work-up was pursued. The family history was negative for AS, TBMN, microscopic hematuria, proteinuria or renal disease. In 2007, she had proteinuria of 500 mg/day which by 2008 had progressed to 4 g/day with a SAlb of 3.6 g/dL (36 g/L) and a SCr of 0.8 mg/dL (70.7 μmol/L) (eGFR—84 mL/min/1.73 m2), and the urinalysis continued to demonstrate microscopic hematuria. A serological evaluation (rheumatoid factor, C3 and C4 levels, myeloperoxidase and proteinase 3 anti-neutrophil cytoplasmic antibody, hepatitis B surface antigen, hepatitis C antibody, HIV, anti-nuclear antibody, anti-Smith antibodies and anti-ribonucleoprotein antibodies) was negative. She had no history of gross hematuria, hearing difficulty or visual changes. She underwent a second kidney biopsy in 2008 for the evaluation of nephrotic-range proteinuria and microscopic hematuria.\nThe biopsy contained eight glomeruli by LM and two were globally sclerotic. The remaining six glomeruli appeared normal. Small foci of tubular atrophy and interstitial fibrosis affected 10% of the total cortex. IF demonstrated segmental/mosaic staining of the GBM and Bowman's capsule with the alpha 3 and alpha 5 chains of type IV collagen. There was no staining of the dTBM for either the alpha 3 or alpha 5 chains of type IV collagen. EM demonstrated variable thinning and thickening of the GBMs, averaging 265 (range 157–427) nm with no splitting or lamellation. Foot process effacement was focal.\nHeterozygous XLAS was diagnosed based on the ultrastructural findings and the segmental/mosaic IF staining of the GBM and Bowman's capsule and the lack of staining of the dTBM for the alpha 3 and alpha 5 chains of type IV collagen.\nShe was placed on an ACEi. Nonetheless, in 2012, her SCr had risen to 1.1 mg/dL (97.2 μmol/L) (eGFR—54 mL/min/1.73 m2), she remained nephrotic with proteinuria of 4–6 g/day and continued to have microscopic hematuria. Additionally, formal hearing test demonstrated high-frequency hearing loss and an ophthalmologic evaluation showed anterior lenticonus.