Two Patients with “Acute Kidney Injury” (AKI) and ANCA-Positive State

Acute kidney injury (AKI) is one of the common manifestations of kidney disease. It could be broadly classified according to its aetiology as pre-renal, intrinsic renal, and post-renal causes. It could be community-acquired or hospital-acquired AKI. Community-acquired AKI is commonly secondary to acute gastroenteritis, infection-related, glomerulonephritis, nephrotoxic drug-related etc. Hospital- acquired AKI is commonly due to sepsis, contrast agents, cardiac failure, drugs etc.

Recently we saw two patients with community-acquired AKI, and we share this experience here.

Patient No 1: Mr.HR, a 40-year-old gentleman, presented to his family physician with total painless hematuria of one-week duration. There was mild peripheral oedema, and he was detected to have mild increase in his blood pressure (160/100 mm Hg). Investigations revealed that he had azotemia (urea 60 mg% and creatinine 1.9 mg %), and urine analysis revealed proteinuria (1 gram per day) and microscopic hematuria. Ultra sonogram revealed normal-sized kidneys.

He was referred to us. Specific investigations included: his c ANCA was positive +++, both by ELISA and Immuno florescence, ANA and anti GBM antibodies were negative. Serology for HIV was positive – HIV p24 antigen and antibodies by ELISA and ICT ( Immunochromatography).

He underwent renal biopsy that revealed 11 glomeruli with endothelial and mesangial hyper cellularity. The Immuno florescence staining was positive for IgG (++) and C3 (+) deposits suggestive of infecton-related glomerulonephritis.

Fig 1. Renal biopsy showing mesangial and endothelial proliferation

There was no crescent formation, fibrinoid necrosis suggestive of vasculitis. There was no tuft collapse with sclerosis suggestive of HIVAN (HIV-associated nephropathy)

Patient no 2 : Mrs.A, aged 35 years, was admitted with history of low grade fever for 2 days and progressive drop in her urine output that culminated in anuria. There was no history of NSAID intake, vomiting, diarrhoea, skin rashes, or other constitutional symptoms. She was non diabetic and non hypertensive with background history of psychiatry illness on medications. Her ultra sonogram revealed normal-sized kidneys, and her vasculitis workup revealed c- ANCA was positive by IF and by ELISA method.

She became progressively drowsy and was admitted in a hemodynamically stable state. Investigations revealed severe renal failure (urea 140 mg % and creatinine was 5 mg %). She had leucocytosis with neutrophilic predominance – total count was 15,000 with 90 % polymorphs. Her blood culture revealed E.coli and was treated with appropriate antibiotics. She was dialysed that helped her to regain consciousness. Her renal functions recovered with infection control.

In these two patients with AKI, there were suggestions of infection – HIV and E.coli sepsis to account for the AKI. The patient with bacterial sepsis recovered with infection control, and the other patient is referred to the Infectious disease consultant for management of his HIV. Both the patients are positive for c ANCA that was not treated.

ANCA – Its clinical utility

Anti-neutrophilic cytoplasmic antibodies (ANCA) are auto-antibodies that are produced against the antigens in the cytoplasm of the neutrophils. There are two main types of antibodies – one located in the cytoplasm (cytoplasmic / c ANCA) and located around the nuclei (peri-nuclear / pANCA). They are directed against the proteinase3 and myeloperoxidase MPO respectively.

AAV (ANCA-associated vasculitis are group of disorders that are categorised as ‘small vessel vasculitis”. There are different subtypes of these vasculitic disorders.

1. Granulamatosis with polyangiitis GPA ( earlier called as Wegener’s granulamatosis)
2. Microscopic polyangiitis (MPA)
3. Eosinophilic granulamatosis with polyangiitis, previously known as Chrug–Strauss syndrome

These are systemic vasculitis, autoimmune in nature, and affect multiple organ systems. The renal involvement is clinically characterised by rapidly progressive glomerulonephritis and demands early identification and early institution of immunosuppressive therapy.

In any patient who presents with unexplained glomerulonephritis or AKI, screening for these groups of disorders becomes mandatory. A positive test guides towards the diagnosis of AAV.

But this should be interpreted with caution as this test report has to be taken in conjunction with the other clinical, laboratory or renal biopsy findings before starting the patient on immunosuppressive therapy.

False-Positive ANCA

There are sporadic case reports that suggest false-positive ANCA. It is being reported in various rheumatological disorders, including rheumatoid arthritis, infections including HIV, bacterial infections, tuberculosis, etc.

Both patients described here are ANCA-positive but had concurrent infections. Here the treatment is not  immunosuppressive but directed towards infection control. Before we decide to treat this group of patients, proper evaluation towards identifying an underlying infection becomes mandatory.