Crescentic postinfectious glomerulonephritis in an adult patient with juvenile nasopharyngeal angiofibroma

Abstract

Crescentic glomerulonephritis is usually associated with an acute nephritic syndrome with rapidly declining renal function. Postinfectious cases usually have a higher possibility of recovery. Juvenile nasopharyngeal angiofibroma (JNA) is a rare, locally aggressive tumour affecting mostly young men. A 28-year-old man presented with recurrent JNA initially excised 2 years prior. The patient was initially managed as a case of airway obstruction and pneumonia. He developed tea-coloured urine, oedema and acute kidney failure requiring dialysis while awaiting surgery. Urine and immunological studies (low C3, negative antineutrophil cytoplasmic antibody and antinucleosomal antibody and high antistreptolysin O) suggested a nephritic aetiology. Nasopharyngeal swab cultures of the mass revealed gram-negative organisms. Kidney biopsy showed diffuse proliferative glomerulonephritis compatible with a postinfectious glomerulonephritis with 77% cellular crescents. The mass was excised with histopathology consistent with JNA. The patient was eventually discharged off dialysis.

Background

Severe cases of infectious-related glomerulonephritis (IRGN) like acute poststreptococcal glomerulonephritis (APSGN) may present with cellular crescents and necrosis in addition to the usual findings of endocapillary hypercellularity in the glomeruli affected.¹ Crescentic glomerulonephritis (GN) is usually associated with an acute nephritic syndrome with rapidly declining renal function.² Although prognosis is generally poor in most crescentic GN, postinfectious cases usually have higher possibility of recovery.² Juvenile nasopharyngeal angiofibroma (JNA) is a rare, benign but locally aggressive tumour with a propensity for local recurrence. It affects mostly young men, and due to its highly vascular nature, management usually involves embolisation of the tumour prior to surgical resection.³ We present herein a case of a young man diagnosed with JNA who developed renal insufficiency requiring haemodialysis whose kidney biopsy eventually showed crescentic APSGN.

Case presentation

A 28-year-old man with a history of gradually enlarging nasopharyngeal mass compatible with angiofibroma on biopsy underwent tracheostomy and had the mass excised after 2 years. He has no other known medical problems except for a history of methamphetamine use 5 years prior to the current admission. Family medical history is unremarkable. In the interim, the stoma was sutured, and a residual tumour was observed. Seven months prior to admission, the patient noticed the tumour to gradually increase in size associated with progressive dysphagia and anorexia. Development of dysphonia and dyspnoea prompted consult in our hospital.

The patient underwent urgent tracheostomy and was treated for obstructive pneumonia. Tracheostomy secretion culture grew Pseudomonas aeruginosa and Klebsiella pneumoniae, while the nasopharyngeal swab culture showed growth of gram-negative organisms (no speciation provided in actual report). There was no culture sample growing Streptococcus. During treatment, he was noted to develop tea-coloured urine and oliguria. Serum creatinine was 276 umol/L (kinetic estimated glomerular filtration rate (eGFR): 26 mL/min). Urinalysis showed haematuria with 99% dysmorphism, albuminuria and granular casts. Spot urine protein-to-creatinine ratio was elevated at 2031.60 mg/g. A diagnosis of postinfectious GN with possible progression to rapidly progressive GN was considered, which was consistent with serological findings of elevated antistreptolysin O titre and low C3. C4 level was not available at the hospital during that time. Ultrasound initially showed normal-sized kidneys and normal parenchymal echogenicity with good corticomedullary differentiation. The patient was prepared for kidney biopsy; however, the presence of bilateral perinephric fluid collections on subsequent scan precluded such procedure.

On his second month of admission, the patient developed pulmonary congestion unresponsive to diuretics and worsening pedal oedema and was initiated on haemodialysis. His serum creatinine at that time was 735 umol/L (kinetic eGFR: 7.8 mL/min). He continued his dialysis sessions for 3 weeks, undergoing necessary preoperative workup and optimisation prior to surgery. He underwent kidney biopsy after his follow-up scan showed resolution of the perinephric fluid, revealing crescentic GN. The patient was supposedly for methylprednisolone pulse therapy but was not cleared from an infectious standpoint due to ongoing nosocomial pneumonia. After resolution of infection, the patient underwent a successful staged procedure—four-vessel angiography with preoperative embolisation of the nasopharyngeal mass followed by excision—and experienced a remarkable improvement in urine output and serum creatinine in a span of 7 days postoperatively. No further haemodialysis was done postoperatively. Intraoperative findings showed 20×13×4 cm intraoral mass and 3×3×1 cm lip mass (figure 1), which on histopathology was consistent with JNA. The patient was discharged without need for further haemodialysis, his final serum creatinine improving to 92 umol/L (kinetic eGFR: 93.5 mL/min).

Figure 1.

Preoperative picture of patient with tumour extending from the nasopharyngeal area into the oral cavity (left). Mass excised from the patient (right).

Investigations

Urinalysis was remarkable for +3 albuminuria on dipstick, haematuria with 760 red blood cells per high-power field (HPF) with 99% dysmorphism, leucocyturia at 410 cells per HPF and a variety of casts suggesting actue kidney injury (hyaline, granular and epithelial cells). Urine chemistry showed spot urine creatinine of 31.01 mg/dL, total protein of 63 mg/dL and elevated spot urine protein-to-creatinine ratio at 2031.60 mg/g. Serological studies revealed antistreptolysin O titre of >400 IU/mL (normal value:<200 IU/mL) and C3 of 0.146 g/L (NV: 0.811–1.57 g/L). Antineutrophil cytoplasmic antibodies (ANCA) (both p-ANCA and c-ANCA) were negative. Antinucleosomal antibodies (ANA) were also negative. Ultrasound initially showed normal kidneys, the right kidney measuring 11.4×4.3×5.7 cm with cortical thickness of 1.3 cm while the left kidney measuring 10.8×4.2×5.5 cm with cortical thickness of 1.3 cm. On subsequent scan, perinephric fluid collections were seen surrounding both kidneys, 0.3 cm on the left and 0.2 cm on the right. Kidney biopsy revealed diffuse proliferative GN compatible with a postinfectious GN with 77% cellular crescents (33 of 43 glomeruli). All glomeruli show mesangial and endothelial cell proliferation. There are mononuclear cells, plasma cells, neutrophils and eosinophils in the interstitium with associated tubulitis (figure 2). Immunofluorescence showed the following: diffuse segmental granular mesangial and glomerular basement membrane staining to IgG (trace to 1+), focal segmental granular mesangial trace staining to IgM, diffuse granular mesangial staining (1+) and focal granular tubular basement membrane staining (1+) to C3, diffuse granular staining (1+ in the mesangium and 3+in the crescents) for fibrinogen and IgA and C1q that are both negative (figure 3). Electron microscopy studies showed scattered subepithelial deposits (humps) and widespread podocyte foot process effacement (figure 4).

Figure 2.

Light microscopy (H&E) showing mesangial proliferation (arrows) with associated inflammatory infiltrates in the interstitium and tubulitis (asterisk).

Figure 3.

Immunofluorescence slides. Clockwise: antihuman C1q, antihuman C3, antihuman IgA, antihuman IgG, antihuman fibrinogen and antihuman IgM.

Figure 4.

Electron microscopy slides showing scattered subepithelial humps (asterisk) and widespread podocyte foot process effacement (arrows).

Differential diagnosis

Prebiopsy diagnosis at that time was a rapidly progressive GN, highly considering poststreptococcal glomerulonephritis (PSGN). Another differential diagnoses that can present clinically as an acute nephritic syndrome with hypocomplementemia are lupus nephritis, cryglobulinemic GN, C3 glomerulopathy, IgA nephropathy (triggered by infection) and ANCA-associated pauci-immune GN. Given the benefit of the serological examinations in this case, as well as the background of a possible source of infection (oral cavity), PSGN is the most likely diagnosis.

Outcome and follow-up

The patient experienced abrupt improvement in his kidney function during the postoperative period. The patient was discharged without need for further haemodialysis, his final serum creatinine improving to 92 umol/L (kinetic eGFR: 93.5 mL/min). However, due to the coronavirus-19 disease (COVID-19) pandemic, the patient was lost to follow-up postoperatively.

Discussion

We have presented a case of an adult patient diagnosed with recurrent JNA who was referred to the nephrology service for rapidly deteriorating renal function resolving after removal of the mass. In a review of adult IRGN cases done in Europe, the teeth and gums accounted for 23% of the cases seen, and IRGN is usually associated with poor dental hygiene and alcoholism.^{4 5} Acute nephritic syndrome presenting in adults as IRGN should be biopsied because of the following: (1) to rule out other causes of hypocomplementemia especially if kidney function is rapidly declining and (2) to guide management especially if prompt immunosuppression is needed.⁶ Aside from standard immunological markers (ANA, ANCA and complement), other studies such as an echocardiogram to rule out endocarditis should also be done to rule out endocarditis-associated GN, which could present as crescentic and necrotising GN on biopsy.^{7 8} A positive ANCA panel can also be present in IRGN especially in the endocarditis-associated type.^7–9 Thus, in patients presenting with crescentic and necrotising GN, an echocardiography and ANCA panel should be part of the investigations that should be ordered. Despite the crescents on kidney biopsy, an echocardiogram done in our patient ruled out the presence of endocarditis, while ANCA panel was found to be negative. In a single-centre review of kidney biopsies, crescentic and necrotising GN, defined by the presence of crescents affecting ≥50% of glomeruli, was rare and made up only <5% of all biopsied patients suspected of having IRGN.⁸ Compared with children wherein complete remission comprises majority of cases, adults presenting with IRGN do not usually recover normal renal function due to the presence of multiple comorbidities,^{6 10 11} more so when presenting as crescentic GN on biopsy.^{2 12} Among the various causes of crescentic GN, postinfectious cases have better prognosis in terms of recovery of renal function.² There is no report yet of JNA directly causing kidney injury. In our patient, excision of the mass subsequently resulted in improvement in renal function most probably due to the removal of the infected mass. Other factors that increase risk of poor renal outcomes after an episode of IRGN are methicillin-resistant Staphylococcus aureus infection, unidentified source of infection, non-isolation of organisms, presence of interstitial fibrosis and tubular atrophy on biopsy and requirement for dialysis.¹¹ Immunosuppressive therapy in the treatment of IRGN in adults is currently not recommended.⁶ Observational studies showed positive outcomes after steroid administration^{13 14} while in studies that performed statistical analysis, it was not associated with a beneficial outcome.^{6 8 12} Our patient was not given steroids due to the presence of active infection at that time. Supportive therapy with haemodialysis and infection control via antibiotics and surgery was done instead. Lastly, following-up patients who had a crescentic type of IRGN should include periodic monitoring of serum creatinine, proteinuria and serum C3 especially in patients with risk factors for persistent renal dysfunction.¹⁵

Learning points.

• Evaluation of acute kidney failure in a previously well adult should corroborate key clinical and laboratory data with judicious performance of a kidney biopsy.

• Acute kidney injury from infectious-related glomerulonephritis (IRGN) usually resolves with removal of the infectious focus.

• Immunosuppression in IRGN is not recommended at present especially if infection is active.

• Crescentic glomerulonephritis (GN) associated with IRGN usually portends a good prognosis for renal recovery compared with other causes of crescentic GN.