Case Study: ANCA-negative Small Vessel Vasculitis

INTRODUCTION

Rapidly progressive (crescentic) glomerulonephritis clinically manifests as proteinuria, hematuria, and decline in kidney function during a short time period, typically within days to months. Pauci-immune necrotizing and crescentic glomerulonephritis is a subtype of common ANCA-positive renal-limited vasculitis. In this case study, an asymptomatic patient who was being evaluated by his primary care physician for a pre-procedural visit was found to have ANCA-negative pauci-immune necrotizing crescentic glomerulonephritis.

CASE PRESENTATION

A 70-year-old man with a history of hypertension, severe aortic stenosis, and dyslipidemia was referred to the community hospital emergency department (ED) by his primary care physician for acute kidney injury. The patient had lost 40 lbs in the past 6 months. Results of laboratory and diagnostic tests are shown:

Table 1. Laboratory Test Results From 5 months Ago

Test	Result
Serological analysis
Creatinine, mg/dL	2.86 (baseline: 0.82)
Potassium, mmol/L	5.4 (previously within the reference ranges)
Blood analysis
Hemoglobin, %	7.8

Table 2. Laboratory Test Results From the ED

Test	Result
Serologic analysis
C-reactive protein high sensitivity, mg/L	40 (N=8 to 10)
Complement C3, mg/dL	120 (N=88 to 201)
Complement C4, mg/dL	15 (N=15 to 45)
Glomerulonephritis serology	Negative
Blood analysis
Erythrocyte sedimentation rate, mm/hr	>120 (N=0 to 22)
Rheumatoid factor, IU/mL	45 (N=0 to 20)
Urinalysis
Red blood cell (RBC) count, RBC/HPF	3+
Urine protein creatinine ratio, g/g Cr	1 (N<0.2)

Table 3. Diagnostic Test Results

Test	Result
Electron microscopy	Negative for immune-type electron dense deposits
Esophagogastroduodenoscopy with biopsies	No malignancy
Immuno-fluorescent assay	Negative for immune complex glomerular disease
Rapid urease test	Negative

The patient was diagnosed with idiopathic focal segmental necrotizing and crescentic glomerulonephritis, pauci-immune type. Correlation with repeat ANCA serology testing was recommended and returned negative multiple times, confirming pauci-immune type. Rituximab was initiated for remission induction, along with prednisone and creatinine. The patient’s serum creatinine level stabilized at 1.3 to 1.6 mg/dL, while his urine RBC level ranged between 2 to 3 RBC/HPF.

DISCUSSION

Idiopathic crescentic glomerulonephritis is rare,¹ and ANCA-negative, pauci-immune renal vasculitis accounts for 5% to 10% of cases.² In ANCA-negative small vessel glomerulonephritis, complement activation appears to be more prominent.¹ However, this patient had normal complement levels. He was thought to be outside the average age at onset of the disease, which usually occurs at approximately 40 years.³  Because of the high risk for progression to end-stage renal disease with ANCA-negative pauci-immune crescentic glomerulonephritis compared with ANC-positive, rituximab with prednisone pulse therapy was initiated soon after diagnosis; this regimen induced remission.³ It was decided to continue the patient on a maintenance dose of rituximab given the similar response rates between ANCA-positive and ANCA-negative crescentic glomerulonephritis.⁴ In the future, ANCA levels should be monitored to detect seroconversion.

CONCLUSION

The presentation ofANCA-associated vasculitis (AAV) is varied and complex. Patients can be asymptomatic or have vague signs, such as this patient’s weight loss. As a result, AAV is prone to underdiagnosis. ANCA-negative pauci-immune crescentic glomerulonephritis is an important diagnosis to consider given high mortality in patients aged 65 years or older, which makes early diagnosis and treatment essential.⁵

References

1. R. Angangco, S. Thiru, V. L. M. Esnault, A. K. Short, C. M. Lockwood, D. B. G. Oliveira, Does truly ‘idiopathic’ crescentic glomerulonephritis exist?, Nephrology Dialysis Transplantation, Volume 9, Issue 6, 1994, Pages 630–636. doi:10.1093/ndt.9.6.630

2. Parmar MS, Bashir K. Crescentric Glomerulonephritis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022 Jan.

3. Min Chen, Feng Yu, Su-Xia Wang, Wan-Zhong Zou, Ming-Hui Zhao, Hai-Yan Wang. Antineutrophil cytoplasmic autoantibody–negative pauci-immune crescentic glomerulonephritis. JASN. Feb 2007, 18 (2) 599-605; doi:10.1681/ASN.200609102

4. Shah S, Hruskova Z, Segelmark M, et al. Treatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Ritixumab. Am J Nephrology. 2015;41:296-301. doi:10.1159/000431336

5. Sampathkumar K, Ramakrishnan M, Sah AK, Gowtham S, Ajeshkumar RN. ANCA negative pauci-immune glomerulonephritis with systemic involvement. Indian J Nephrol. 2010;20(1):43-47. doi:10.4103/0971-4065.62096