Infection-Related Glomerulonephritis Associated with West Nile Neuroinvasive Disease: A Case Report

Introduction

West Nile Virus (WNV), of the Flavivirus genus and the Japanese encephalitis antigenic complex of the Flaviviridae family, has emerged as a significant global health concern. In India, WNV has been circulating since at least 1952, with sporadic cases. The spread is supported by the country’s diverse ecological landscapes, which favor mosquito breeding and arbovirus transmission. WNV is primarily transmitted by Culex mosquitoes, with birds serving as natural reservoirs. Serological evidence of WNV antibodies in migratory and domestic birds underscores its ongoing presence in South Asia.^1-3 While most infections are asymptomatic, ∼20-40% present with mild symptoms, and 1% develop neuroinvasive disease, including meningitis and encephalitis, which carries a mortality rate of up to 10%.⁴ Renal involvement is usually limited to tubular injury, with glomerular pathology not being documented until now.¹ Here, we describe a unique presentation of acute proliferative glomerulonephritis (GN) associated with WNV meningoencephalitis, broadening the recognized clinical manifestations of the infection.

Case Report

A 21-year-old male presented with new-onset, generalized, tonic-clonic seizures and vomiting, following 48 hours of high-grade fever, bifrontal headache, myalgia, bilateral lower limb edema, periorbital puffiness, and frothy urine. His medical history included adequately treated childhood tuberculosis. Examination revealed a postictal state, fever (101°F), hypertension (140/100 mmHg), tachycardia (110 bpm), bilateral pedal edema, periorbital puffiness, and neck stiffness, with a normal fundus.

Initial laboratory investigations showed serum creatinine 1.5 mg/dL, nephrotic-range proteinuria (10,071 mg/day), and microscopic hematuria [Table 1]. Empirical therapy with intravenous ceftriaxone, vancomycin, acyclovir, antihypertensives (nifedipine), and antiepileptics (levetiracetam) was initiated. CT brain was normal; MRI revealed multifocal sulcal space hyperintensities, patchy cortical-subcortical T2 hyperintensities, and smooth dural thickening in the bilateral parieto-occipital region.

Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis (15 cells/µL), elevated protein (255 mg/dL), and normal glucose. CSF Gram stain, acid-fast bacilli stain, and cartridge-based nucleic acid amplification test (CBNAAT) were negative. The EEG was normal. Renal workup showed low C3 (15 mg/dL), normal C4 (30 mg/dL), and normal Anti-Streptolysin O (ASO) titer. Ultrasound abdomen showed normal-sized kidneys with increased echogenicity.

Infectious workup was negative except for positive serum WNV IgM antibodies, confirming the diagnosis of WNV infection. By the second week, the fever and seizures resolved, but the headache persisted. Repeat CSF analysis showed improvement (2 lymphocytes, glucose 60 mg/dL, protein 16 mg/dL). Antibiotics and antivirals were continued for 2 weeks, with gradual tapering of antiepileptics and antihypertensives. Repeat urinalysis showed 2+ protein, 4–6 pus cells/HPF, and numerous RBCs/HPF. Although creatinine initially improved to 0.9 mg/dL, it rebounded to 1.5 mg/dL. Repeat 24-hour urine protein decreased to 4,250 mg/day. By the fourth week, clinical improvement was evident, with normal BP, sub-nephrotic proteinuria (1.6 g/day), and creatinine (0.9 mg/dL), prompting discharge.

At the 5-week follow-up, serum creatinine rose to 1.6 mg/dL, C3 remained low (45 mg/dL), and urinalysis revealed persistent hematuria and 2+ proteinuria. Due to worsening renal function, a kidney biopsy was performed. Light microscopy showed enlarged glomeruli with diffuse mesangial hypercellularity, patchy capillary wall thickening, neutrophilic infiltration (8/18 glomeruli), interstitial fibrosis (15–20%), and acute tubular injury [Figure 1]. Immunofluorescence revealed 2+ granular C3 deposition in mesangium and capillary walls, minimal IgA/IgM, and negative IgG, C1q, C4, and fibrinogen. A diagnosis of diffuse proliferative GN (IRGN/C3 glomerulopathy) was made.

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Figure 1:

(a) Light microscopy – hematoxylin and eosin, original magnification ´40. The glomerulus is enlarged and displays diffuse mesangial (small black arrow) and segmental endocapillary hypercellularity, with abundant infiltrating neutrophils (long black arrow). (b) Light microscopy – periodic acid-Schiff, original magnification ×40. A glomerulus exhibiting mesangial hypercellularity (black circles) and endocapillary hypercellularity (long black arrow) with infiltrating neutrophils (small black arrow).

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At two months, creatinine improved to 1.17 mg/dL, with proteinuria decreasing to 162 mg/day and normal C3 (126.4 mg/dL). By four months, creatinine stabilized at 1.12 mg/dL, with minimal proteinuria (62 mg/day) and no albuminuria.

Discussion

Viral infections can cause kidney injury through direct cytopathic effects, immune complex deposition, or vasculitis. Well-recognized viral causes of glomerulopathies include hepatitis B, C, and E, HIV, dengue, and Hantavirus, while parvovirus, Epstein-Barr Virus (EBV), and Cytomegalovirus (CMV) have been linked to collapsing focal segmental GN (FSGS). In adults, IRGN is typically linked to bacterial infections from the skin, upper respiratory tract, heart, lungs, oral cavity, and urinary tract. Meningoencephalitis is a rare presenting infection site for IRGN.⁵

Renal involvement in WNV infection has previously been limited to tubular injury or interstitial nephritis.¹ In this patient, nephrotic-range proteinuria, hematuria, low complement C3, and biopsy-proven mesangial and endocapillary proliferation with dominant C3 deposition demonstrated glomerular injury. The clinical picture more closely resembled Staphylococcus-associated GN (SAGN) than post-streptococcal GN, given the heavy proteinuria, and histologically mirrored dengue-associated GN, suggesting possible shared flavivirus-associated pathways despite differences in systemic features. AKI was likely multifactorial, driven by GN, hypoalbuminemia, and potential drug-induced nephrotoxicity.

Animal studies have shown persistent WNV infection in renal tissue, and human data suggest a 40% risk of CKD in survivors, emphasizing the need for close renal monitoring in neuroinvasive WNV infection.^1,4 The strength of this report lies in the comprehensive diagnostic evaluation, including biopsy confirmation, while its limitation is the absence of viral PCR in renal tissue.

This case expands the clinical spectrum of WNV infection to include GN, underscoring the importance of recognizing viral triggers in infection-related glomerular diseases and the need for vigilant renal monitoring in neuroinvasive WNV cases.