Renal Lesions in Leprosy

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Leprosy is caused by Mycobacterium leprae, an intracellular organism that affects the skin and peripheral nerves. It causes chronic debilitating sequelae and systemic complications.¹ There are limited data on renal manifestations of M. leprae infection. Here, we describe the pathological findings in leprosy patients with renal involvement.

Sixteen renal biopsies of patients diagnosed with leprosy were retrieved from the biopsy database at Renopath, Center for Renal and Urological Pathology (2013-2025). Clinical and laboratory data at the time of biopsy was collected. For routine diagnostic evaluation, paraffin-embedded sections were cut and stained with hematoxylin and eosin, periodic acid-Schiff, Jones methenamine silver, and Masson’s trichrome. All cases were stained with Congo red and modified Ziehl-Neelsen. Biopsies underwent routine immunofluorescence staining for IgG, IgM, IgA, C3, C1q, and ĸ and λ light chains. Two pathologists (J.P.KS. and A.A.K) independently reviewed the histopathologic findings.

The cohort of patients with M. leprae infection who underwent kidney biopsy included 11 males and five females. The median age at the time of renal biopsy was 48.5 years (range: 33,63). Subnephrotic and nephrotic-range proteinuria were observed in six and seven patients, respectively. Nine patients presented with AKI, and two had hematuria. The mean serum creatinine at presentation was 3.15 ± 2.65 mg/dL. One patient required hemodialysis. Four patients had hypertension, and one had a history of diabetes mellitus.

The pathological diagnoses of the 16 cases have been enumerated in Table 1. Most patients had glomerular disease. Diagnoses included infection-associated glomerulonephritis (IRGN) (n=6), membranous nephropathy (MN) (n=3), C3 GN (n=1), AA amyloidosis (n=1), focal segmental glomerulosclerosis (FSGS) with concurrent acute tubular injury (ATI) (n=1), minimal change disease with concurrent acute interstitial nephritis (n=1), acute pyelonephritis (n=1), intravascular hemolysis-associated ATI (n=1), and necrotizing vasculitis (due to Lucio phenomenon, n=1). In patients with IRGN, immunofluorescence revealed C3 and IgG deposits in glomerular capillary loops and/or mesangium. Four biopsies revealed endocapillary proliferative GN [Figure 1a, 1b]. One case of resolving IRGN with mesangial hypercellularity was noted. IgA-dominant IRGN with C3 and IgA deposits was found in another. None of the biopsies exhibited crescents or necrotizing glomerular lesions. No biopsy showed granuloma formation. Interstitial fibrosis and tubular atrophy were absent to mild in most cases and of moderate degree in two biopsies. Necrotizing vasculitis and arteriosclerosis were present in one and four cases, respectively. In patients with membranous nephropathy, one was PLA2R positive [Figure 1c] and two were negative for PLA2R and NELL1.

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Figure 1:

(a) Endocapillary hypercellularity and neutrophilic infiltration in a patient with IRGN (40X, hematoxylin and eosin stain), (b) C3 immunofluorescence stain shows intense granular staining along the capillary loops and mesangium in a case of IRGN (40X, C3 immunofluorescence), (c) PLA2R immunostain is positive on the glomerular capillary loops in a granular pattern in a patient with membranous nephropathy (20X, PLA2R immunostain), (d) acute pyelonephritis with pus cell cast (blue arrow) in medullary tubules (10X, hematoxylin and eosin stain), (e) densely eosinophilic granular to globular tubular pigment cast (blue arrows) in a patient with rifampicin associated intravascular hemolysis (40X, hematoxylin and eosin stain), (f) immunohistochemical stain for hemoglobin is strongly positive on the pigment casts (blue arrows), confirming the diagnosis of intravascular hemolysis associated tubular injury (40X, hemoglobin immunohistochemical stain), (g) amyloid deposits (blue arrows) showing Congo red positivity (40X, Congo red stain) and (h) amyloid A immunohistochemical stain is positive (blue arrows) in the amyloid deposits (40X, amyloid A immunohistochemical stain).

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The patient with hemolysis-associated ATI had a history of rifampicin use, which was discontinued. Two patients were on multidrug therapy for multibacillary leprosy, and one for the paucibacillary form at the time of biopsy. Two patients were on steroids for erythema nodosum leprosum (ENL). One patient showed Lucio phenomenon with systemic vasculitis, mixed connective tissue disorder and severe pulmonary hypertension.

Renal involvement in patients with leprosy has been described from around the world.^1-3 Lepra bacilli are infrequently demonstrated in renal biopsies.⁴ Factors responsible for renal injury in leprosy include circulating immune complexes, infections, drug toxicity, disease duration, and lepra reactions.⁵

IRGN was the most common cause of renal failure in our cohort (n=6). Three of these patients had non-healing trophic ulcers of the feet. Infections and neoplastic conditions have been reported in association with GN in leprosy.⁴ However, many studies have observed GN more commonly in lepromatous leprosy and ENL. ENL, a type II lepra reaction, has an immune-mediated inflammatory pathogenesis.⁶ We found acute pyelonephritis [Figure 1d] and IgA-dominant IRGN in two patients with ENL.

Lucio phenomenon is a rare vasculonecrotic reaction occurring in untreated or inadequately treated leprosy. Endothelial injury due to a heavy bacterial load has been proposed as the cause of vasculitis or thrombosis in vessels. Histologically, endothelial proliferation, thrombosis, and vasculitis have been reported in dermal biopsies.⁷ Acid-fast lepra bacilli have been demonstrated in the endothelial cells of dermal vessels.⁸ The kidney biopsy in our patient with Lucio phenomenon showed necrotizing vasculitis. No acid-fast bacilli were identified on modified Ziehl-Neelsen staining.

Drug toxicity can cause renal failure. Rifampicin is known to cause hemoglobin casts due to intravascular hemolysis.⁹ One case had granular to ropy pigment casts with associated ATI [Figure 1e]. Immunostaining for hemoglobin was positive in the tubular casts [Figure 1f].

Amyloidosis associated with leprosy has been described by Nakayama et al.⁴ Repeated complications related to leprosy, such as lepra reactions and trophic ulcers, are considered possible triggers for amyloid fibril production [Figure 1g, 1h].

Three MN cases were reported in our series. Our spectrum also included one case each of minimal change disease and FSGS. These presented with proteinuria and AKI due to concurrent tubulointerstitial pathology [Table 1]. Podocytopathy and C3 GN in leprosy were less evident in the literature. Given the limited number of cases in our study, it remains difficult to interpret these as primary glomerular pathologies or lesions secondary to leprosy.

To conclude, the spectrum of renal lesions in leprosy is diverse. IRGN is the most common cause of renal failure.