INTRODUCTION

Rapidly progressive (crescent) glomerulonephritis is clinically manifested by proteinuria, hematuria, and decline in renal function for a short period, usually within days or months. Pauciimmune 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 preoperative visit was found to have ANCA-negative pauciimmune necrotizing crescentic glomerulonephritis.

CASE PRESENTATION


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A 70-year-old man with a history of hypertension, severe aortic stenosis, and dyslipidemia was referred to the emergency department of a community hospital by his attending physician for acute kidney injury. The patient had lost 40 pounds in the past 6 months. The results of the laboratory and diagnostic tests are presented:

Table 1. Laboratory test results from 5 months ago

Test Results
Serological analysis
Creatinine, mg/dL 2.86 (reference: 0.82)
Potassium, mmol/L 5.4 (previously in reference ranges)
Blood test
Hemoglobin, % 7.8

Table 2. Emergency department laboratory test results

Test Results
Serological analysis
High sensitivity C-reactive protein, 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 test
Erythrocyte sedimentation rate, mm/h >120 (N=0 to 22)
Rheumatoid factor, IU/mL 45 (N=0 to 20)
Urine analysis
Red blood cell count (RBC), RBC/HPF 3+
Urinary protein-creatinine ratio, g/g Cr 1 (N

Table 3. Results of diagnostic tests

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

The patient was diagnosed with idiopathic focal segmental necrotizing glomerulonephritis and crescentic glomerulonephritis, pauciimmune type. Correlation with repeated ANCA serological tests was recommended and proved negative several times, confirming the pauci-immune type. Rituximab was initiated for induction of remission, along with prednisone and creatinine. The patient’s serum creatinine level stabilized between 1.3 and 1.6 mg/dL, while his urinary red blood cell count ranged between 2 and 3 red blood cells/hpf.

DISCUSSION

Idiopathic crescent glomerulonephritis is rare,1 and ANCA-negative pauci-immune renal vasculitis account for 5-10% of cases.2 In ANCA-negative small vessel glomerulonephritis, complement activation appears to be greater.1 However, this patient had normal complement levels. It was thought to be outside the average age of disease onset, which usually occurs around the age of around 40.3 Because of the high risk of progression to end-stage renal disease with ANCA-negative versus ANC-positive pauciimmune crescentic glomerulonephritis, rituximab with pulsed prednisone therapy was initiated soon after diagnosis; this diet induces remission.3 It was decided to continue the patient with 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 of ANCA-associated vasculitis (AAV) is varied and complex. Patients may be asymptomatic or have vague signs, such as this patient’s weight loss. As a result, AAV is prone to underdiagnosis. ANCA-negative pauciimmune crescentic glomerulonephritis is an important diagnosis to consider given the high mortality in patients aged 65 or older, making early diagnosis and treatment essential.5

References

1. R. Angangco, S. Thiru, VLM Esnault, AK Short, CM Lockwood, DBG Oliveira, Does “idiopathic” crescentic glomerulonephritis really exist?, Nephrology Dialysis Transplantation, Volume 9, Number 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. Anti-neutrophil cytoplasmic autoantibodies–negative pauci-immune crescentic glomerulonephritis. JASN. 2007 Feb, 18(2)599-605; doi:10.1681/ASN.200609102

4. Shah S, Hruskova Z, Segelmark M, et al. Treatment of severe renal failure in ANCA-positive and small-vessel-negative 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 pauciimmune glomerulonephritis with systemic involvement. Indian J Nephrol. 2010;20(1):43-47. doi:10.4103/0971-4065.62096