Infection-Related Glomerulonephritis in the Very Elderly: A Clinicopathological Analysis

Dear Editor,

Infection-related glomerulonephritis (IRGN), historically considered a pediatric disease with a generally favorable prognosis, is increasingly recognized in adults and older individuals.^1,2 In these populations, IRGN represents an important cause of acute kidney injury and is more frequently associated with incomplete renal recovery or progression to chronic kidney disease (CKD).¹ Among the very elderly, defined as individuals aged ≥80 years, concerns about biopsy-related risk and assumptions that renal injury is irreversible often limit comprehensive diagnostic evaluation. However, recent case series demonstrate that many such patients exhibit biopsy findings that may respond to targeted therapeutic interventions, highlighting the value of renal biopsy in guiding management decisions.²

In this study, we analyzed the clinicopathological features of 26 very elderly patients with IRGN, representing, to our knowledge, the largest biopsy-based series in this age group. Although IRGN is well described in adults and older populations, data specifically focused on patients aged ≥80 years remain limited.^2-5 This demographic subset is increasingly relevant as population longevity rises, underscoring the need for age-specific data to better inform diagnostic and therapeutic decision-making.

The mean age of the cohort was 81.9 (range 80-89) years. Of the patients, 20 (76.9%) were males and 6 (23.1%) were females. The mean serum creatinine at presentation was 4.5 mg/dL. For comparative analysis, the cohort was stratified into two groups based on histopathological findings: patients with crescents on renal biopsy (n = 13) and those without crescents (n = 13) [Table 1]. Crescent formation was observed in 50% of biopsies. Among these, four patients exhibited crescents in >50% of glomeruli, meeting criteria for crescentic glomerulonephritis. The remaining nine patients had crescents involving <50% of glomeruli, of whom seven showed cellular crescents, and two demonstrated fibrocellular crescents.

The male-to-female ratio in our cohort was 3.3:1, similar to our previous study in the very elderly, which reported a ratio of 2.7:1.² The mean age at presentation was 81.9 years. Clinical manifestations of IRGN vary with age, the underlying pathogen, and infection severity. In children, renal biopsy is rarely required because the presentation is characteristic and the prognosis is favorable. In adults, however, a biopsy is often necessary to confirm the diagnosis and exclude other conditions with similar features.¹

Declining glomerular filtration with ageing, cardiovascular comorbidities, polypharmacy, and cumulative nephrotoxin exposure all contribute to diagnostic uncertainty and poorer outcomes in the very elderly.^3,6 Additionally, diabetes, reduced immune function, and a high burden of healthcare-associated infections further increase susceptibility to severe or atypical presentations of IRGN.⁶

In our cohort, eight patients had diabetes mellitus, and all eight also had hypertension. Four of these individuals had concomitant diabetic nephropathy. Their outcomes were poor. Only one patient recovered renal function; one with a venous ulcer developed septic shock and died; another developed a lung infection with subsequent renal deterioration; and the fourth progressed to CKD. These findings reinforce earlier reports that underlying diabetic nephropathy portends a poor prognosis in IRGN.³

IgA-dominant IRGN was observed in one patient, an 81-year-old hypertensive male, non-diabetic, with a recent skin infection. He was treated with steroids and antibiotics and demonstrated clinical improvement, with a discharge serum creatinine of 2.7 mg/dL, consistent with reports that IgA-dominant IRGN often follows skin infections.^S1

Interstitial fibrosis and tubular atrophy (IFTA) were absent or mild in 80.8% of the biopsies, and moderate in 19.2%, with no severe cases, indicating relatively preserved tubulointerstitial architecture in much of the cohort. In contrast, arteriosclerosis was more prominent, with moderate and severe vascular sclerosis in 50% and 11.5% of patients, respectively. These findings suggest that while vascular chronicity was common in the very elderly, extensive parenchymal scarring was not universal, underscoring the value of biopsy in distinguishing reversible injury from end-stage damage.³

When patients with and without crescents were compared, clinical presentations were broadly similar, with rapidly progressive renal failure occurring at comparable frequencies in both groups. Comorbid conditions, including hypertension and diabetes mellitus, were also similarly distributed. Histopathologically, endocapillary proliferative glomerulonephritis was the predominant pattern in both groups. Indices of chronicity, including global glomerulosclerosis, IFTA, and arteriosclerosis, did not demonstrate marked differences between patients with and without crescents.

Among the 13 patients with follow-up, infection sources were diverse, and outcomes varied [Supplementary Table 1]. Urinary tract infections due to Escherichia coli were common and generally associated with recovery. In contrast, skin and soft-tissue infections resulted in severe outcomes, including Fournier’s gangrene, septic shock, and death. Respiratory, dental, and catheter-related infections were also noted, with outcomes ranging from full recovery to dialysis dependence. Central-line-associated septicemia and venous ulcers with Pseudomonas infection carried particularly poor prognoses. These findings highlight the variability of IRGN in the very elderly and the influence of infection source on renal outcomes.^S2

Two patients became dialysis-dependent, and crescents were present in both. One patient with catheter-related septicemia demonstrated diffuse crescent formation involving 100% of glomeruli, without significant chronic changes. The second patient, with a lung infection, showed only 9.4% crescents but had underlying diabetic nephropathy with moderate IFTA, indicating that pre-existing chronic injury contributed to the poor outcome. Three patients died during follow-up. One with leg cellulitis and 42.9% crescents developed Fournier’s gangrene and succumbed to sepsis. Another with a Pseudomonas-infected venous ulcer, without crescents, died of septic shock. The third, with a healed skin wound and 10% crescents, remained dialysis-dependent and died of myocardial infarction. Overall, mortality was driven predominantly by severe infectious and systemic complications.

Our findings demonstrate that IRGN in the very elderly is often severe and arises in patients with multiple comorbidities, particularly hypertension and diabetes mellitus. These conditions, together with age-related physiological vulnerability, are associated with high rates of incomplete renal recovery, dialysis dependence, and increased morbidity and mortality. Crescent burden and preexisting chronic parenchymal injury further worsen the outcome. Nevertheless, renal biopsy frequently reveals treatable inflammatory lesions, underscoring the value of histological confirmation and the need for early recognition and management of infectious triggers. Limitations include the retrospective design, small cohort size, and incomplete follow-up, which may affect the broader applicability of these results.