A 42-year-old Vietnamese man presented for evaluation of microscopic hematuria and apparent chronic kidney disease.
His serum creatinine had ranged from 1.4 to 1.6 mg/dL for at least the last 6 months. He had no medical history except mild hypertension for which he had recently been started on an ACE inhibitor. He had completed a non-contrast computed tomography scan of his abdomen and pelvis that revealed no stone disease. He was not a diabetic.
On exam, he had controlled blood pressure and no peripheral edema. Urinalysis showed 2+ protein and positive hemoglobin with 9 red blood cells. Urine sediment revealed dysmorphic RBCs. A 24-hour urine collection demonstrated 1.5 grams of protein.
A renal biopsy revealed moderate mesangial expansion and hypercellularity. The mesangium stained positive for IgA on immunofluorescence. Electron microscopy confirmed mesangial and paramesangial deposits. There was also evidence of thrombotic microangiopathy. Interstitial fibrosis was graded as mild. A presumptive diagnosis of IgA nephropathy was made. Representative micrographs are shown.
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IgA nephropathy is the most common cause of primary glomerulonephritis in many countries throughout the world. It afflicts Caucasians and Asians more than other racial groups. Typical clinical features include hematuria of the microscopic and macroscopic variety, variable proteinuria, and hypertension.
IgA may present with macroscopic hematuria following an upper respiratory syndrome, with microscopic hematuria on labs, or less commonly with acute kidney injury and rapid decline in glomerular filtration rate (GFR). IgA variants, with mesangial deposits, may also be found in other renal entities such as minimal change disease, focal segmental glomerulosclerosis, and even diabetic nephropathy. Renal IgA may also be part of systemic illness such as celiac disease, and Henoch-Schonlein purpura.
IgA nephropathy results in end-stage renal disease in about half of diagnosed patients. Assessment of increased likelihood of progressive loss of GFR is an important aspect of chronic management of IgA patients. As with other forms of chronic kidney disease, uncontrolled hypertension and increasing amounts of proteinuria are known to correlate with more rapid decline in GFR.
Higher serum levels of galactose-deficient IgA1 have been linked to more likely decline in GFR in at least one Chinese study. Other investigators have shown that higher number of fibroblast on renal biopsies and amount of interstitial fibrosis are predictors of worse renal outcomes.
As listed in multiple choice answer E, the Oxford criteria include endocapillary hypercellularity, mesangial cellularity, segmental sclerosis, and tubular atrophy/interstitial fibrosis. These histologic markers are scored during renal biopsy interpretation to and can predict poor renal outcomes.
Discovery of thrombotic microangiopathy in biopsies of IgA patient was recently retrospectively shown to predict a more likely decline in GFR, even in those with controlled hypertension.
Persistent isolated microscopic hematuria may be a predictor of worse renal prognosis in some cohorts. However, episodic macrohematuria without proteinuria has not been correlated with a more likely decline in GFR.
Answer: Persistent microhematuria and episodes of gross hematuria are independent indicators of worse renal prognosis in IgA nephropathy patients
This case was prepared by Kevin T. Harley, MD, assistant clinical professor of medicine, Division of Nephrology & Hypertension, and Philip Carpenter, MD, professor of clinical pathology at the University of California in Irvine.
- El Karoui K, Hill GS, Karras A, et al. A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy. J Am Soc Nephrol 2012;23:137-48
- Harada K, Akai Y, Yamaguchi Y, et al. Prediction of corticosteroid responsiveness based on fibroblast-specific protein 1 (FSP1) in patients with IgA nephropathy. Nephrol Dial Transplant 2008;23:3152-3159.
- Zhao N, Hou P, Lv J, et al. The level of galactose-deficient IgA1 in the sera of patients with IgA nephropathy is associated with disease progression. Kidney Int 2012;82:790-796.