A 3-year-old male neutered Sphynx cat was referred for a history of progressively elevated liver enzymes, predominantly alanine aminotransferase and persistent glucosuria despite normoglycemia for several months. The patient had had lower urinary tract signs (pollakiuria) when 5 months old and underwent perineal urethrostomy at the age of 1.5 years. Lower urinary tract signs (LUTS) persisted but resolved after therapy with polysulfated glycosaminoglycan (5 mg/kg twice weekly for 4 weeks then once weekly; Adequan; Luitpold Animal Health). Polysulfated glycosaminoglycan was tapered down to once every 3 months as LUTS were less frequent. Multiple urinalyses showed proteinuria, glucosuria (despite normoglycemia) and no bacteriuria, although one previous urine culture (cystocentesis) grew Staphylococcus chromogenes (10–50 k/cfu), which was treated with cefovecin (8 mg/kg SC once; Convenia; Zoetis). The patient was referred 2 months later; physical examination revealed a grade III/VI parasternal heart murmur but was otherwise normal. Hematology was unremarkable at that visit. A point-of-care ELISA for feline leukemia virus antigen and feline immunodeficiency virus antibody (SNAP FeLV/FIV; IDEXX Laboratories) was negative. A summary of serial biochemical findings is provided in. Venous blood gas revealed hyperchloremic metabolic acidosis. Urinalysis showed urine specific gravity (USG) of 1.043, pH 6, 1+ protein and 2+ glucose. Urine culture was negative and urine protein:creatinine ratio (UPC) was 0.51. Leptospirosis real-time PCR on urine sample was negative and Leptospira species microscopic agglutination test for six serovars did not detect any antibodies. Abdominal ultrasound revealed irregular kidneys with loss of corticomedullary distinction. Urine metabolic testing at PennGen Laboratories was negative for ketones and cystine but revealed increased amino aciduria, adipic acid and glucosuria, suggesting Fanconi syndrome (FS). Polysulfated glycosaminoglycan was discontinued at this time; however, recheck urinalysis showed persistent glucosuria (despite normoglycemia) and proteinuria. Three months later, laparoscopic liver and kidney biopsies were obtained. Venous blood gas showed worsening hyperchloremic metabolic acidosis. Urinalysis showed a USG of 1.026, pH 6, 2+ protein and 3+ glucose. Serum cobalamin, folate, trypsin-like immunoreactivity and feline pancreatic lipase immunoreactivity were within the reference intervals (RIs). The coagulation panel revealed increased fibrinogen 263 (relapse incidence 124–170 mg/dl) but clotting times (prothrombin time and partial thromboplastin time) and antithrombin III were all within RIs and fine-needle aspiration of the left kidney showed marked tubular cell dysplasia. Urine sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE) was suggestive of primary mild-to-moderate tubular damage without concurrent glomerular damage (). Laparoscopic biopsies of the right kidney, liver and small intestine were obtained. Histopathology of the kidney revealed tubular injury characterized by tubular degeneration and mild multifocal necrosis. There was marked karyomegaly of the tubular epithelium with tubular atrophy elsewhere, mild-to-moderate chronic lymphoplasmacytic and histiocytic interstitial nephritis, and replacement fibrosis. Further histopathological analysis of the kidney was also performed at the Ohio State Renal Pathology Laboratory; immunofluorescence with IgG, IgM, IgA and lambda light chain were conducted with no evidence of glomerular immune-complex deposition. Global sclerosis, mild segmental effacement of podocyte foot processes and moderate interstitial fibrosis with interstitial and intrahistiocytic lipid was documented on transmission electron microscopy (TEM). Tubular abnormalities included loss of apical brush border and detachment of the epithelium from the basement membrane. Liver histopathology revealed moderate diffuse zone 1 hepatocellular atrophy, periportal fibrosis, biliary hyperplasia and karyomegaly in zones 2 and 3. Interrupted bands of amyloid were seen in the Disse space. Histopathology of the small intestines revealed a mild lymphoplasmacytic enteritis with rare crypt dilation and mild mucosal fibrosis. After surgery, the patient developed worsening hyperchloremic metabolic acidosis and hypernatremia that improved with intravenous fluids and bicarbonate therapy. The patient was discharged 3 days post-surgery with sodium bicarbonate (1 mEq/kg PO q12h; compounded), K citrate (50 mg/kg PO q12h; compounded), maropitant citrate (1 mg/kg PO q24h; Cerenia; Zoetis), mirtazapine (1.87 mg PO q48h; compounded) and pradofloxacin (7.5 mg/kg PO q24h; Veraflox, Bayer Healthcare) while pending liver culture. Two weeks later, bloodwork showed a non-regenerative normocytic normochromic anemia with a hematocrit (HCT) of 22.3% (RI 28.2–52.7%). Serum chemistry results are shown in. Urinalysis showed a USG of 1.020, pH 7, 1+ protein and 3+ glucose and UPC of 2.4. Three months later, the patient declined, despite the increased dosage of sodium bicarbonate (1 mEq/kg PO q8h), subcutaneous fluids and aluminum hydroxide (90mg/kg PO q12h). The patient became polyuric and polydipsic, lethargic and hyporexic. The patient remained anemic (HCT 19.6%). Recheck serum chemistry results are shown in. Urinalysis showed a USG of 1.014, pH 6.5, trace protein, 2+ glucose and a UPC of 1.3. Venous blood gas showed persistent metabolic acidosis pH 7.255 (RI 7.33–7.44) and low bicarbonate 12.2 (RI 24.0–28.0 mEQ/l). Two weeks later, the patient was euthanized owing to progressive decline and poor quality of life. On post-mortem examination, the kidneys were bilaterally small with mild capsular undulation. All other organs appeared grossly normal. Histopathology of the kidneys revealed severe chronic, multifocal interstitial fibrosis with tubular degeneration and atrophy, glomerulosclerosis, multifocal interstitial lymphoplasmacytic nephritis, amyloidosis and tubular epithelial cell karyomegaly. The liver revealed moderate diffuse zone 1 hepatocellular atrophy, periportal fibrosis, biliary hyperplasia and hepatocytic karyomegaly. No microorganisms were identified with periodic acid–Schiff or Grocott methenamine silver staining. Congo red staining revealed amyloidosis that was confined to the vascular walls in the kidney and liver ().