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A 50-year-old white woman was admitted to the hospital for new-onset anasarca. She has no prior history of chronic kidney disease (CKD). She had no history of recent non-steroidal anti-inflammatory drug use. She also had no hesistancy, urgency, dysuria, or gross hematuria. She further denied dyspnea, chest pain, or liver disease.
Past history includes asthma and hypertension. She is not on any medications. She had a 20-pound weight gain over past six weeks. Family history is negative for CKD or stone disease. On exam, blood pressure is 165/98 mm Hg, and lung fields are diminished bilaterally at the bases. Legs show 2+ edema to the thighs. There is also sacral pitting and evident distal arm swelling without any rash.
Labs include a creatinine of 1.4 mg/dL, hemoglobin of 15 g, platelets of 236,000, albumin of 1.3 g/dL, calcium of 7.9 mg/dL. Urinalysis shows SG 1.017, 600 protein, and 82 rbcs. Urine protein to creatinine ratio equals 12 grams. Total cholesterol is 387 mg/dL. Complement 3 and 4 are normal and ANA and anti DS-DNA antibodies are negative.
Serum and urine protein electrophoresis show no monoclonal spike. RPR, HIV, and hepatitis serology are negative. Ultrasound reveals no evidence of urinary obstruction and doppler study is negative for renal vein thrombus. .
Kidney biopsy is done and representative light micrographs are shown.
Submit your diagnosis to see full explanation.
FSGS is one of the more common causes of idiopathic nephrotic syndrome. Among non-diabetic adults with nephrotic syndrome in the U.S., it is implicated in over a third of biopsies. In African Americans, this number approaches 50%.
FSGS can be divided into different sub-types based on histologic findings. These subtypes include FSGS not otherwise specified (or classic variant), hilar variant, tip variant, cellular variant, and collapsing variant.
Tip lesion FSGS is characterized by pathology at the origin of the proximal tubule including foam cell accumulation and cellular adhesions. Tip lesions seem to be the most steroid responsive of the FSGS subtypes. A few small series indicate up to 50% of tip lesion patients respond completely to glucocorticoid therapy or spontaneously remit.
Those with collapsing variant are characterized by complete collapse of the glomerular tuft, a more rapid decline in glomerular filtration rate, and poor response to immunotherapies. Collapsing variant has been associated with HIV infection and with African American race. Classic FSGS is the type most commonly seen on renal biopsy.
The cellular variant of FSGS requires demonstration of glomerular capillary occlusion due to hypercellularity without tip or collapsing lesions. The perihilar variant requires a finding of hyalinosis with or without sclerosis near the glomerular vascular pole.
The diagnosis in this particular patient was FSGS tip variant. The sclerotic segments in the representative micrographs are notably in the region of the urinary pole. There are also adhesions to Bowman’s capsule and proliferation of parietal epithelial cells. The patient was started on steroids.
Answer: This FSGS histologic variant is most likely to be steroid responsive
This case was prepared by Kevin T. Harley, MD, Assistant Clinical Professor of Medicine and Philip Carpenter, MD, Professor of Clinical Pathology at the University of California in Irvine.
References
- D’Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 2004;43:368-382.
- D’Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med 2011;365:2398-2411
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