Morphological Spectrum and Novel Necrotizing Crescentic Pattern in Microfilaria-Induced Renal Injury: A Case Series

Introduction

Microfilarial infections remain a major public health challenge in tropical and subtropical regions, with India contributing a significant global burden. Classical manifestations involve lymphatic and cutaneous disease, and renal injury attributable to microfilariae is distinctly uncommon, making diagnosis challenging in endemic areas.

The spectrum of renal pathology ranges from minimal change disease and focal segmental glomerulosclerosis to mesangioproliferative and diffuse proliferative glomerulonephritis. Isolated case reports have described immune-complex-mediated injury with IgG and C3 deposition. Most descriptions are limited to case reports and large series documenting the full morphological diversity of microfilarial glomerulopathy remain scarce.

We present a 6-year series of biopsy-proven cases of microfilaria-induced renal injury, describing the range of the morphological patterns of this entity.

Case Series

This retrospective study included cases of microfilaria-induced renal injury diagnosed over a period of 6 years at our center. Clinical, laboratory, histopathological, and follow-up data were retrieved from medical records.

Renal biopsies were processed for light microscopy using hematoxylin and eosin, periodic acid-Schiff, Jones methenamine silver, Congo red, and Masson trichrome stains. Direct immunofluorescence (DIF) was performed on frozen sections using FITC-conjugated antibodies against IgA, IgG, IgM, C3, C1q, ĸ, and λ.

Seven patients (three females) with a median age of 32 years (range 15-55) were identified. The presenting syndromes were acute nephritic syndrome (n=1), nephrotic syndrome (n=2), generalized edema with sub-nephrotic proteinuria (n=1), chyluria (n=2), rapidly progressive renal failure (n=1), and unexplained renal failure without a classic syndrome (n=1). Peripheral eosinophilia was documented in three cases (43%).

Table 1 shows the clinical and laboratory details of the cases. A circulating microfilaria antigen test was positive pre-biopsy in 1/7.

The histopathological spectrum [Figure 1] included non-proliferative glomerulopathy (n=3), membranous-pattern glomerulopathy (n=1), amyloidosis with non-proliferative GN (n=1), focal necrotizing and crescentic GN (n=1), and crescentic diffuse proliferative GN with neutrophil/eosinophil exudation (n=1). Microfilariae were identified in glomerular capillaries in six (86%) and peritubular capillaries in three (43%) cases.

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Figure 1:

Spectrum of microfilaria-associated renal pathology on light microscopy (all panels ´400). (a) Hematoxylin and Eosin (H&E), ×400. Peritubular capillary in cortex distended by a slender intraluminal microfilaria, with adjacent tubules preserved; mild peri-capillary edema (black arrow). (b) Periodic Acid–Schiff (PAS), ×400. Non-proliferative glomerulonephritis (GN) pattern with several glomerular capillary loops occluded by microfilariae; tuft architecture otherwise maintained and no obvious mesangial hypercellularity (black arrow). (c) H&E, ×400. Non-proliferative GN with microfilaria in a peritubular capillary alongside intact tubules; background interstitium without significant inflammation (black arrow). (d) PAS, ×400. Membranous-pattern GN showing diffuse capillary-wall thickening, with intraluminal microfilariae within glomerular loops contributing to luminal crowding (black arrow). (e) PAS, ×400. Diffuse proliferative GN with endocapillary hypercellularity and neutrophil/eosinophil-rich exudation; microfilariae are present within capillary loops contributing to segmental luminal obstruction (black arrow). (f) PAS, ×400. Focal necrotizing and crescentic GN with a cellular crescent partially encircling the tuft and compressing residual capillary loops; fibrin/karyorrhexis is suggested at the necrotic segment (black arrow).

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Immunoflorescence showed reactivity in 3 cases: IgG+++ capillary-wall granular (membranous pattern), C3 mesangial granular (focal necrotizing/crescentic GN), and combined IgG with coarse C3 (crescentic DPGN). The remaining 4 were DIF-negative.

All patients received diethylcarbamazine (DEC); three also received corticosteroids. Clinical response was complete in four and partial in three cases.

Discussion

Renal involvement due to lymphatic filariasis is uncommon on native-kidney biopsy, and the morphologic spectrum is broader than often appreciated. Microfilariae may be encountered incidentally or as contributors to disease across lesions that resemble primary or immune-complex glomerulopathies.¹ In our seven-case cohort from an endemic setting, the spectrum included non-proliferative and membranous patterns, a case with amyloidosis, and notably two crescentic lesions, expanding what is typically reported.²

We document coexistence of crescentic injury with microfilarial parasitemia. Two patients had crescents; both showed immune reactivity on DIF. Contemporary reports emphasize proteinuric phenotypes and immune-complex patterns, crescents are less frequently highlighted; our experience supports considering adjunct immunomodulation alongside anti-filarial therapy when crescents or marked endocapillary activity are present.³

Second, localization may track with phenotype. Microfilariae were identified in glomerular capillaries in six, and in peritubular capillaries in three cases. Both crescentic cases had intraglomerular organisms, whereas peritubular localization tended to accompany non-proliferative or membranous patterns, consistent with case descriptions of intravascular parasites in glomerular and peritubular beds.⁴ Although causality cannot be inferred, these observations suggest that intravascular parasitic burden and anatomic distribution may modulate the inflammatory phenotype.

Third, eosinophil-rich exudation is a practical signpost. One crescentic case displayed conspicuous eosinophils, which in an endemic region should prompt a deliberate search for intravascular worms on H&E/PAS and targeted deeper levels. This step can prevent misclassification as a primary crescentic GN and aligns with guidance to actively look for helminths when clinicopathologic cues (eosinophilia, chyluria, tropical exposure) are present.^1,4

Fourth, the spectrum includes secondary membranous nephropathy and can extend to amyloidosis. We observed a membranous pattern and one patient with amyloidosis. Recent reports describe filariasis-associated membranous nephropathy with negative PLA2R/THSD7A/exostosin panels improving after diethylcarbamazine (DEC), supporting targeted anti-filarial therapy when serology or tissue context implicates Wuchereria bancrofti.² These entities broaden the differential diagnosis for nephrotic-range proteinuria in endemic zones.

Fifth, pathogenesis is mixed. Contemporary guidance on parasitic kidney disease emphasizes immune-complex deposition and complement activation, but also non-immune factors such as vascular obstruction and direct antigen exposure.^3,5 Our DIF-positive crescents and membranous pattern fit the immune-complex paradigm, whereas non-proliferative lesions with intravascular worms underscore mechanical/antigenic contributions.

Our experience suggests the need for keeping microfilarial disease in the differential when faced with nephrotic syndrome, unexplained hematuria/chyluria, or proliferative/crescentic GN, especially if eosinophils are conspicuous in the exudate;^1,5 the need for actively hunting for parasites on LM in glomerular and peritubular capillaries; use routine stains first and perform DIF systematically.

In summary, this series broadens the recognized spectrum of microfilaria-associated renal disease to include aggressive crescentic GN, highlights localization-linked phenotypes, and affirms a morphology-guided therapeutic strategy in endemic settings.