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A.
Figure 1. Patient's kidney biopsy images. Light microscopy showed focal glomerulosclerosis (A) and meningeal and endocapilary proliferation (B). Electron microscopy showed electron dense deposits in the meningeal region (C). The podocyte foot processes are well preserved.
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B.
Figure 1. Patient's kidney biopsy images. Light microscopy showed focal glomerulosclerosis (A) and meningeal and endocapilary proliferation (B). Electron microscopy showed electron dense deposits in the meningeal region (C). The podocyte foot processes are well preserved.
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C.
Patient's kidney biopsy images. Light microscopy showed focal glomerulosclerosis (A) and meningeal and endocapilary proliferation (B). Electron microscopy showed electron dense deposits in the meningeal region (C). The podocyte foot processes are well preserved.
A 19-year-old Asian woman with no significant past medical history was referred to the nephrology clinic for hematuria. She noticed tea-colored urine 3 days after an upper respiratory illness. It lasted for 1 week. During that time, urinalysis showed 3+ blood, 1+ protein, >60 RBCs. Since then, she has had recurrent pink-tinged urine lasting a few days. Serial urinalyses showed persistent microscopic hematuria. There is no family history of kidney diseases or autoimmune diseases. She denies any dysuria, flank pain, swelling, joint pain, rash or Reynaud’s phenomenon. She does not take medications or herbal supplements. Her blood pressure is 120/64 mm Hg. Physical examination is unremarkable.
During the initial clinic visit, urinalysis was again positive for blood (2+) and protein (1+). Urine sediment shows 5-10 non-dysmorphic RBCs/hpf. Urine protein-to-creatinine ratio (uPCR) was 0.18g/g. Serum creatinine was 0.79 mg/dL. Anti-nucleic antibody (ANA) and anti-double stranded DNA are both negative. Complements C3 and C4 levels are normal. Renal ultrasound showed that the left kidney measured 9.8 cm in length and the right kidney measured 10.3 cm in length. Both kidneys have normal echogenicity. There are no stones or renal mass lesions.
She was followed in the nephrology clinic for the next 18 months with periodic monitoring of her blood pressure, renal function, and urine. Her creatinine remained at 0.7 to 0.8 mg/dL. However, her uPCR gradually increased to 0.8 g/g. A 24-hour urine collection revealed total urinary protein 1.3g/24 hours. A kidney biopsy was performed which showed 1) focal meningeal and endocapillary proliferative glomerulonephritis with focal cellular crescents; 2) predominant immunoglobulin A (IgA) deposits in the mesangium; 3) Mild global glomerulosclerosis (~8%) and mild interstitial fibrosis/tubular atrophy (5%-10%). The findings are consistent with IgA nephropathy with Oxford classification M0 E1 S1 T0 C1 (Figure 1).
She returned to the clinic for a follow-up visit after the biopsy. Her blood pressure was 130/65 mm Hg.
Submit your diagnosis to see full explanation.
This case was prepared by Yongen Chang, MD, PhD, Assistant Clinical Professor, Division of Nephrology and Hypertension, University of California-Irvine.
References
3 Rodrigues JC, Haas M, Reich HN. IgA Nephropathy. Clin J Am Soc Nephrol. 2017;12:677-686.
4 Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013;368:2402-2414.
Answer: F
IgA nephropathy was first described in 1968 by Berger and Hinglais,1 who described a cohort of 55 patients with hematuria, proteinuria, and no signs of systemic diseases. Major pathologic findings were predominance of IgA deposition in the meningeal regions of the glomeruli. IgA is more prevalent in those of Asian descent (~40% of all kidney biopsies in Asia). The classic clinical presentation of IgA nephropathy is hematuria concurrent with or within a few days of an upper respiratory illness, as in this case. The clinical course of IgA varies, with 25%-30% of patients progressing to end stage renal disease (ESRD) in the absence of therapeutic intervention. Prognostic factors predicting worse renal outcome include proteinuria, hypertension, and impaired glomerular filtration rate (GFR) at the time of diagnosis. Additionally, in 2009, the Oxford classification was published to further characterize IgA nephropathy based on histologic features on the kidney biopsy.2 Histologic features associated with progression to ESRD include meningeal hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), crescents (C). This patient’s kidney biopsy was classified as M0 E1 S1 T0 C1, meaning that there was a mild degree of endocapillary proliferation, segmental sclerosis, and crescents. Thus, she had 3 of 5 histologic risk factors for progression to ESRD.
Treatment of IgA nephropathy is based on patients’ ESRD risk profile. This patient has >1 g of proteinuria and histologic risk factors on her kidney biopsy. Therefore, monitoring alone (choice A) is incorrect. Among different therapeutic interventions, use of renin angiotensin system (RAS) blockade with an ACE inhibitor (or angiotensin receptor blocker, ARB) has the strongest support from clinical evidence. RAS blockade targeting blood pressure below 125 mm Hg systolic and 75 mm Hg diastolic has proven to be beneficial in many randomized controlled clinical trials (RCTs).3 It is recommended for IgA patients with proteinuria (>0.5-1 g/day) by KDIGO guidelines.4Therefore, choice F is the correct answer. Evidence for omega 3 fatty acid supplementation (choice B) and mycofenolate mofetil (choice E) is mixed, so use of these as first-line agents is not recommended.3Immunosuppression regimens such as glucocorticoids alone or in combination with cyclophosphamide (choices C and D) has been shown to be effective in RCTs for patients with >1 g/day proteinuria.3 However, limitation of these studies includes inconsistent use of ACE inhibitors or ARBs. Current guidelines recommend use of glucocorticoids in combination with cyclophosphamide for those with crescentic glomerulonephritis (>50% crescents on kidney biopsy) and rapid deterioration of GFR. The earliest large RCT showed that 3-day “pulse” IV methylprednisone alternating with oral prednisolone for a total of 6 months reduced the risk of progression of renal diseases.5 Therefore, it is reasonable to treat patients with glucocorticoids if they do not respond to ACE inhibitors or ARBs. Tonsillectomy has not been tested in large RCTs and is not recommended as standard of treatment.
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