Introduction

Post-infectious glomerulonephritis typically presents in children with hematuria, proteinuria, edema and hypertension following an infection.[1] Histologically, it is characterized by diffuse endocapillary proliferative glomerulonephritis with immune complex deposition.[1] Thrombotic microangiopathy, characterized by endothelial injury and microvascular thrombosis, is an uncommon finding in association with PIGN.[2] The coexistence of these two entities is rare and may influence prognosis and management.[2] We present a case of a 10 year-old male child who had PIGN with some glomeruli showing features of Thrombotic microangiopathy.

Case Report

A 10-year-old boy presented with swelling of the lower limbs and facial puffiness of a few days. There was no history of recent respiratory tract or skin infections. The patient reported a recent episode of loose stools. There was no significant past medical or family history of renal disease, and no known drug allergies.

On physical examination, the child had trace pedal edema. Blood pressure at presentation was 100/64 mmHg, with subsequent recordings reaching 130/83 mmHg. Anthropometric assessment showed an initial weight of 39.8 kg, later decreasing to 36.3 kg, with a body mass index ranging from 20.35 to 20.78 kg/m².

Urinalysis revealed 3+ proteinuria with numerous red blood cells and 6–8 white blood cells per high-power field. The spot urine protein-to-creatinine ratio was markedly elevated at 4.54, consistent with nephrotic-range proteinuria. The Anti-Streptolysin O was positive, platelet count was 6,96,000, hemoglobin was 10g/dl, hematocrit was 30.8. In view of the nephritic–nephrotic presentation, a native kidney biopsy was performed.

Light microscopic examination of multiple step serial sections stained with Hematoxylin and eosin(H&E), Periodic acid–schiff (PAS), Masson trichrome (MTS), and Jones silver stains (JMS) revealed 38 glomeruli, none of which were globally sclerosed. All glomeruli exhibited diffuse endocapillary hypercellularity with proliferation of endothelial and mesangial cells and prominent neutrophilic infiltration, resulting in obliteration of capillary lumina.(Figure 1a) Focal double-contoured basement membranes were noted. Three glomeruli showed fibrin thrombi with associated focal mesangiolysis.(Figure 1b &1c) The arteries demonstrated tunica media hyperplasia. Immunofluorescence microscopy performed on 19 viable glomeruli showed coarse granular deposits of IgG (3+) and C3 (3+) along the glomerular capillary walls and in the mesangium.(Figure 2a & 2b) Staining for IgA, IgM, and C1q was negative. Based on these findings, a diagnosis of Post-infectious glomerulonephritis with superimposed thrombotic microangiopathy was rendered.

Figure 1: a. Microscopic image showing diffuse endocapillary hypercellularity with proliferation of endothelial and mesangial cells and prominent neutrophilic infiltration, resulting in obliteration of capillary lumina. (PAS, 20x ) b. Microscopic image showing fibrin thrombi (PAS, 20x) c. Microscopic image showing fibrin thrombi (JMS, 20x)

Figure 2: a. Direct immunofluorescence image showing coarse, granular capillary basement membrane deposits of IgG b. Direct immunofluorescence image showing granular capillary basement membrane deposits of C3

The child was closely monitored with serial blood pressure measurements, renal function tests, and assessment of proteinuria along with supportive treatment with antihypertensive and oral steroids. On follow-up, the patient remained clinically stable, with no progression of edema or deterioration in renal parameters.

Discussion

Post-infectious glomerulonephritis (PIGN) is an immune complex–mediated glomerular disease occurring after infection, characterized by deposition of antigen–antibody complexes in the mesangial and subepithelial regions. These complexes activate the alternative complement pathway, leading to C3 consumption, endothelial injury, and diffuse endocapillary hypercellularity, with characteristic subepithelial “hump-like” deposits on ultrastructural examination. [1]

Thrombotic microangiopathy (TMA) comprises a group of disorders characterized by endothelial injury leading to platelet activation, fibrin deposition, and microvascular thrombosis within arterioles and capillaries. Renal involvement is marked by endothelial swelling, mesangiolysis, and fibrin thrombi in glomerular capillaries and arterioles, resulting in ischemic injury.[2]

The coexistence of PIGN and TMA is rare but pathologically possible, as immune complex–mediated inflammation and predominant alternative complement pathway activation in PIGN can induce glomerular endothelial injury, thereby triggering secondary TMA. Additional contributing factors may include infection-related systemic inflammation, cytokine release, hypertension or underlying abnormalities of complement regulation.[3]

Recognition of TMA in PIGN is clinically important, as its presence reflects severe endothelial damage and is associated with more aggressive renal involvement and poorer outcomes compared with isolated PIGN.[3] Identification of TMA necessitates exclusion of primary TMA syndromes and may influence therapeutic decisions, including intensified supportive care, blood pressure control, or selected use of immunomodulatory or complement-directed therapies.[3]

In the present case, TMA involvement was focal, and the patient demonstrated a favourable short-term clinical outcome with supportive management.

The coexistence of Post-infectious glomerulonephritis (PIGN) and Thrombotic microangiopathy (TMA) is rare, with only a few cases reported in the literature. Prior reports describe PIGN associated with hemolytic uremic syndrome, malignant hypertension–related TMA, and renal-limited or systemic TMA, highlighting the heterogeneity of underlying mechanisms. Proposed pathogenic links include immune complex–mediated endothelial injury, severe hypertension, and dysregulation of the alternative complement pathway, including possible toxin-mediated endothelial damage. Collectively, these findings support endothelial injury and complement activation as central mechanisms in this uncommon overlap. [3-6]

The present case is notable for the coexistence of classical histological features of post-infectious glomerulonephritis with superimposed focal thrombotic microangiopathy in a pediatric patient, in the absence of overt systemic manifestations of TMA. Awareness of this coexistence is important for accurate diagnosis, prognostication, and management. Early recognition and close follow-up can result in a favourable outcome, particularly when TMA involvement is limited.

References

1. Kambham N. Postinfectious glomerulonephritis. Adv Anat Pathol. 2012 Sep;19(5):338-47. doi: 10.1097/PAP.0b013e31826663d9.
2. Abou-Ismail MY, Kapoor S, Citla Sridhar D, Nayak L, Ahuja S. Thrombotic microangiopathies: An illustrated review. Res Pract Thromb Haemost. 2022 Apr 22;6(3):e12708. doi: 10.1002/rth2.12708.
3. Davin JC, Groothoff JW, Oosterveld M, Schriemer R, van de Kar N. Hemolytic Uremic Syndrome in Post-Infectious Glomerulonephritis: Possible Pathophysiological Mechanisms. J Nephrol Therapeutic S. 2014;11:2161-0959.
4. Siebels M, Andrassy K, Waldherr R, Ritz E. Hemolytic uremic syndrome complicating postinfectious glomerulonephritis in the adult. Am J Kidney Dis. 1995 Feb;25(2):336-9. Doi: 10.1016/0272-6386(95)90017-9.
5. Vankalakunti M, Malleshappa P, Hussain H, Marilingegouda A. Atypical presentation of post infectious glomerulonephritis as malignant hypertension and thrombotic microangiopathy. Indian J Nephrol. 2014 Mar;24(2):110-3. Doi: 10.4103/0971-4065.127900.
6. Malathi CV, Prema K S J, Aralapuram K, Krishnamoorthy V, Kurien AA. Rare Histologic Coexistence of Infection-Related Glomerulonephritis and Thrombotic Microangiopathy. Indian J Nephrol. 2025 Jan-Feb;35(1):109-110. doi: 10.25259/IJN_304_2024.