Acute Infection-Related Glomerulonephritis with Disseminated Gonococcal Infection in a 13-year-old Girl: A Case Study Report

Clinical Summary and Pathological Background of Gonococcal-Related Glomerulonephritis

Infection-related glomerulonephritis (IRGN) is a clinical condition resulting from the deposition of immune complexes within the glomeruli, triggered by a wide array of potential pathogens. While poststreptococcal glomerulonephritis (PSGN) remains the most widely recognized form of this disorder, other bacteria, viruses, fungi, and parasites can induce similar renal injury. This specific case, authored by Asif Noor, Leonard R. Krilov, Vivette D’Agati, and Manju Chandra (2018), details the first reported instance of acute infection-related glomerulonephritis associated with disseminated gonococcal infection (DGI) in a sexually active adolescents in the absence of endocarditis. The patient, a $13$-year-old girl, presented with classic features of DGI, including fever, hypotension, tenosynovitis, polyarthralgias, and petechiae, while simultaneously developing hypocomplementemic glomerulonephritis.

Renal involvement in this context was characterized by a diffuse endocapillary proliferative and exudative glomerulonephritis. Histological examination via renal biopsy demonstrated subepithelial electron-dense humps and granular glomerular capillary wall staining for $C3$ and $IgG$, which are hallmark findings of acute postinfectious glomerulonephritis. Following targeted antibiotic treatment and the resolution of the Neisseria gonorrhoeae infection, the patient's serum creatinine, complement levels, and urine sediment returned to normal ranges. The only lasting sequela recorded $16$ months post-infection was low-grade proteinuria.

Case Presentation: Clinical History and Physical Manifestations

The patient, a previously healthy $13$-year-old female, was admitted to the hospital with a $1$-day history of high-grade fever, reaching a temperature maximum of $105^{\circ}F$ ($40.5^{\circ}C$). Her symptoms included vomiting, pain in the ankles, wrists, and proximal right metacarpophalangeal joints, and a distinctive rash localized to the palms, soles, and distal legs. During the initial history, she denied experiencing a sore throat, headache, visual changes, vaginal discharge, dysuria, or urinary frequency. However, she disclosed having unprotected sexual intercourse with two male partners approximately $1$ month prior to the onset of symptoms.

Upon admission, physical examination revealed a temperature of $102.5^{\circ}F$ ($39.1^{\circ}C$), a heart rate of $110\,\text{beats/min}$, and a borderline low blood pressure of $95/65\,mmHg$. Her capillary refill time was less than $2\,s$. The skin examination was notable for painful petechiae over the palms, soles, and lower legs. Joint examination showed moderate swelling of both ankle joints, along with erythema and tenderness on the dorsum of the right foot, which was clinically attributed to acute tenosynovitis. There was an absence of periorbital or pedal edema, pharyngitis, cervical lymphadenopathy, or perianal/genital lesions.

Diagnostic Investigations and Laboratory Analysis

Initial laboratory testing indicated significant systemic inflammation and renal impairment. The patient's hematocrit was $31\%$, and her white cell count (WBC) was markedly elevated at $30.8 \times 10^9/L$, consisting of $65\%$ neutrophils and $24\%$ immature neutrophils. Inflammatory markers were high, with a C-reactive protein (CRP) of $180\,mg/L$ and an erythrocyte sedimentation rate (ESR) of $64\,mm/h$. Urinalysis revealed significant abnormalities: protein at $100\,mg/dL$, $41$ red blood cells (RBC) per high-power field (hpf), more than $182\,WBC/hpf$, and $4+$ WBC clumps.

Blood chemistry further defined the renal insult, showing a serum creatinine of $2.9\,mg/dL$ and a blood urea nitrogen (BUN) of $39\,mg/dL$. Serum albumin was $3.5\,g/dL$. Immunological testing showed a low complement $C3$ level of $12\,mg/dL$ (reference range: $70\text{--}225\,mg/dL$) and a low-normal $C4$ level of $14\,mg/dL$ (reference range: $14\text{--}55\,mg/dL$). Antinuclear antibody (ANA) was positive at a $1:320$ titer with a homogenous pattern, though specific antibodies such as antimyeloperoxidase, antiproteinase-3, and anti-DNA were negative. A rapid streptococcal antigen test from a throat swab was also negative.

Clinical Course and Therapeutic Management

The medical team initiated empiric treatment for presumed bacterial sepsis and potential tickborne infection using vancomycin, ceftriaxone, and doxycycline. On the second hospital day, the patient’s condition deteriorated as she became hypotensive and oliguric, requiring vasopressor support with dopamine despite receiving an infusion of $4\,L$ of normal saline ($0.9\%$). Infectious disease testing confirmed the presence of Neisseria gonorrhoeae DNA via urine PCR. Tests for syphilis, hepatitis C, and HIV were unremarkable, and the patient was immune to hepatitis B. Blood and urine cultures showed no bacterial growth, and an echocardiogram ruled out endocarditis (no vegetations observed).

By hospital day $3$, her blood pressure stabilized, her fever subsided, and her ankle pain improved. Serum creatinine decreased to $1.2\,mg/dL$, but the patient developed fluid overload manifested by anasarca, dyspnea, and a requirements for supplemental oxygen, which resolved with diuretic therapy. However, on day $5$, despite stable hemodynamics, the serum creatinine rose again to $2.3\,mg/dL$. Urinalysis at this time showed protein at $300\,mg/dL$, multiple RBCs, and mixed cellular casts, with a urine protein/creatinine ratio of $1.1\,mg/mg$ (normal $<0.2$). Further complement studies showed extremely low levels: $C3$ at $6\,mg/dL$, $C4$ at $9\,mg/dL$, $CH50$ at $10\,U/mL$, and $C5$ at $3\,mg/dL$. Serology for antistreptolysin O (ASO) was elevated at $860\,Todd\,units/mL$, but anti-DNAase B was normal ($<250\,U/mL$).

Pathological Findings from Renal Biopsy

A renal biopsy was performed on hospital day $6$ to investigate the cause of the deteriorating renal function. Light microscopy of $19$ sampled glomeruli revealed diffuse and global severe endocapillary proliferative and exudative glomerulonephritis. The specimen showed heavy infiltration of neutrophils and patchy interstitial edema/inflammation involving $15\%–20\%$ of the cortical parenchyma. Focal RBC and WBC casts were also identified. Immunofluorescence microscopy of $5$ glomeruli revealed dominant ($2−3+$) granular deposits of $C3$ in a "starry sky" pattern along the capillary walls and mesangium, accompanied by $1−2+\ IgG$.

Electron microscopy confirmed the diagnosis, showing marked global proliferation of mesangial and endothelial cells alongside numerous infiltrating neutrophils. Most notably, the biopsy exhibited abundant subepithelial hump-shaped electron-dense deposits. Foot process effacement was noted overlying these deposits. There were also scattered small segmental mesangial and subendothelial electron-dense deposits. These pathological features are classic for acute postinfectious glomerulonephritis, but in this instance, they were temporally linked to the active gonococcal infection.

Long-term Outcome and Follow-up

The patient completed a treatment regimen consisting of intravenous ceftriaxone for $10$ days and oral doxycycline for $7$ days. For management of hypertension, she was prescribed amlodipine ($5\,mg$ daily) for $3$ weeks and enalapril ($10\,mg$ daily) for $16$ months. Recovery of renal function and complement levels was gradual but steady. Serum $C4$ normalized within $10$ days of admission, while $C3$, $C5$, and $C8$ levels returned to normal ranges by $5$ weeks.

Serum creatinine improved to $0.7\,mg/dL$ by the sixth week after admission. The urine protein/creatinine ratio stabilized at approximately $0.22\,g$ after an initial period fluctuating between $0.3$ and $0.36$. At the final follow-up $16$ months after the initial illness, the patient's urinalysis showed stable low-grade proteinuria at $100\,mg/dL$ with minimal hematuria ($1−3\,RBC/hpf$). This suggests that while the acute inflammation resolved, some minor residual glomerular damage persisted.

Discussion: Pathophysiology and Differential Diagnosis

Disseminated gonococcal infection (DGI) typically accounts for only $0.5\%–3\%$ of all gonococcal infections. While Neisseria gonorrhoeae usually presents as cervicitis or urethritis, DGI manifests as an abrupt onset of malaise, tenosynovitis, and hemorrhagic skin lesions. This case is exceptional because the glomerulonephritis occurred synchronously with the active infection, unlike the latent period usually seen in PSGN. In PSGN, the latent period is typically $1−3$ weeks after pharyngitis or $2−4$ weeks after skin infection. The low levels of $C3$, $C4$, $C5$, and $C8$ in this patient suggest activation of both the classical and alternative complement pathways, whereas PSGN usually involves only the alternative pathway (low $C3$, normal $C4$).

The researchers postulate that certain strains of N. gonorrhoeae may possess nephritogenic properties similar to certain strains of group A Streptococcus. The diversity of gonococcal porin proteins (Por A and Por B), which include $26$ and $32$ serovars respectively, suggests that specific rare strains may be responsible for renal injury. Possible mechanisms for this injury include: (1) passive glomerular entrapment of circulating antigen-antibody complexes; (2) in situ binding of antibodies to cationic gonococcal antigens planted in the glomerular capillary wall; or (3) molecular mimicry, where antibodies against the bacteria cross-react with glomerular components.

Learning Points and Clinical Recommendations

Clinical practitioners should maintain a high index of suspicion for disseminated gonococcal infection in sexually active adolescents who present with fever, joint pain, and petechial rashes. Early recognition of concurrent glomerulonephritis is vital to ensure timely and appropriate management of fluid status and hypertension. The workup for infection-related glomerulonephritis should include comprehensive testing for common causes, such as Staphylococcus bacteremia, hepatitis B and C, and PSGN, while also excluding underlying host immunodeficiencies, particularly complement deficiencies ($C6$, $C7$, and $C8$).