Infection Related Glomerulonephritis in Renal Allografts: A Case Series

Dear Editor,

Glomerulonephritis in renal allografts may occur de novo or as recurrence of native kidney disease. Infection-related glomerulonephritis (IRGN) is an immune complex-mediated injury that follows infection and is characterized by immune complex deposition, complement activation, and glomerular inflammation.¹ Although immunosuppression increases infection risk in transplant recipients, it also dampens immune responses, potentially reducing or masking the typical manifestations of IRGN. As a result, IRGN in renal allografts is rarely reported. We describe the clinicopathologic features of 12 renal allograft recipients with biopsy-proven IRGN.

Twelve renal allograft recipients were diagnosed with IRGN based on established diagnostic criteria,¹ including a combination of temporal association with infection, supportive clinical features, and characteristic histopathological findings [Table 1]. The cohort comprised 10 males and two females, with a median age of 47 years (16–75 years). The interval between transplantation and biopsy was <1 year in one patient, 1–5 years in eight patients, and >5 years in three patients. Ten patients had received live-donor transplants, while two had deceased-donor allografts.

All patients underwent kidney biopsy for evaluation of allograft dysfunction. The mean serum creatinine level at the time of biopsy was 2.36 ± 0.9 mg/dL. Subnephrotic proteinuria was observed in seven patients (58.3%), and nephrotic-range in four patients (33.3%). Blood and urine cultures were sterile in all six patients who were tested.

On histopathologic examination, all biopsies demonstrated endocapillary hypercellularity with prominent neutrophilic infiltration. Cellular crescents were identified in two cases. Immunofluorescence showed C3 and IgG deposition in 10 biopsies, while two biopsies exhibited C3 and IgA positivity, consistent with IgA-dominant IRGN. There was no evidence of acute or chronic rejection, and C4d staining was negative in all cases. One biopsy showed coexistent diabetic nephropathy, and one showed recurrent IgA nephropathy.

An infectious source was identified in nine patients. In three patients, no definite source of infection could be identified. Microbiological confirmation was available in a minority.

The incidence of recurrent glomerulonephritis following kidney transplantation varies between 3% and 15%, depending on the specific type and the duration of post-transplant follow-up. Recurrence is most frequently observed 3-5 years after transplantation.³ In a large South Asian cohort, post-transplant glomerulonephritis was identified in 177 of 3,630 patients (4.8%). IgA nephropathy accounted for the majority (52%).⁴

Although infectious complications are common after renal transplantation, IRGN is rare. Moroni et al.⁵ reported IRGN in only 3 of 827 renal transplant recipients, despite 65% experiencing significant bacterial infections during follow-up. Alsaad et al.⁹ identified just 11 cases in the literature. Immunosuppressive therapy limits immune activation and immune-complex formation, while routine post-transplant surveillance allows early infection treatment, reducing prolonged antigenemia.²

Patients typically present with nephritic syndrome, including hematuria, proteinuria, edema, hypertension, and variable renal dysfunction.¹ Clinical and pathological features are influenced by comorbidities, immunosuppressive therapy, and prior rejection. Immunosuppression may also mask systemic signs of infection.^2,3

Diabetes mellitus is an important predisposing factor. Plumb et al.⁶ reported type 1 diabetes in all three post-transplant IRGN cases, and four of twelve patients in our cohort had diabetes. Diabetes may increase susceptibility to IRGN, including cases caused by atypical pathogens such as Enterococcus.⁷

The differential diagnosis includes acute rejection, de novo or recurrent glomerulonephritis, transplant glomerulopathy, and thrombotic microangiopathy. Accurate diagnosis requires careful clinicopathologic correlation.^2,5

Although no standardized treatment guidelines exist, management centers on prompt eradication of infection with appropriate antimicrobial therapy and careful adjustment of immunosuppression. Poor prognostic factors include extensive crescent formation, severe interstitial fibrosis, and delayed diagnosis. Even after resolution of glomerular inflammation, irreversible interstitial damage may result in progressive allograft dysfunction.

A broad spectrum of infectious sources and pathogens has been implicated in IRGN after kidney transplantation. Review of published cases shows that infections of the urinary tract, skin and soft tissues, and vascular access sites are most commonly associated with Staphylococcus aureus, followed by Streptococcus species. Rare causes, including Salmonella enteritidis and polyomavirus, have also been reported.

In contrast, infections in our cohort most frequently involved the lower respiratory tract, suggesting that pulmonary infections may also trigger immune complex-mediated glomerular injury in immunosuppressed recipients. Additional sources included diabetic or fungal foot infections, post-streptococcal upper respiratory infection, scrotal cellulitis, and acute gastroenteritis. In three patients, no clear source or organism was identified, likely reflecting prior antimicrobial exposure and the diagnostic challenges posed by localized or subclinical infections in transplant recipients.

Follow-up data were available for 10 patients in our cohort, of whom only three recovered. The remaining patients had graft dysfunction or failure, and two died from complications related to the disease. Published reports [Supplementary Table] show variable clinical outcomes. While some patients achieved partial or complete recovery following infection control, graft dysfunction, loss, and progression to end-stage renal disease were frequent.^2,5-9,S1-S4 These findings highlight that IRGN in the allograft is associated with a poor prognosis, despite accurate diagnosis and aggressive treatment of the infection.

This study is limited by its small sample size and retrospective design. Microbiological confirmation of infection was not obtained.

In conclusion, IRGN is an important cause of graft dysfunction in kidney transplant recipients and is often associated with poor outcomes.