Case Presentation: A 76-year-old woman presented with right flank pain and intermittent painless hematuria. Exam was unremarkable. Labs revealed a Cr of 2.35 mg/dL (0.50 – 1.20 mg/dL), BUN 54mg/dL (6.0 – 23.0 mg/dL), and urinalysis with 229 RBCs and >300 protein, but no casts. CT showed bilateral renal nephrolithiasis without hydronephrosis and a distended bladder. The patient was discharged with outpatient urology and nephrology follow-up, as well as a scheduled outpatient cystoscopy to evaluate hematuria. On discharge, her serum creatinine was 1.99 mg/dL. The patient presented 2 weeks later with shortness of breath. O2 saturation was 77% on room air and she had conjunctival pallor and bilateral crackles on pulmonary auscultation. Labs revealed Cr 2.56, Pro BNP 7000, and a hemoglobin of 6 mg/dL (baseline hemoglobin was 12mg/dL). Urinalysis redemonstrated hematuria and proteinuria. A chest X-ray showed bilateral diffuse airspace hazy opacities. Acute hypoxic respiratory failure was thought to be due to pneumonia or decompensated heart failure with preserved ejection fraction. Broad-spectrum antibiotics were initiated along with diuresis. Proteinuria work-up, including anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (anti-GBM) antibodies was sent. Four days later, the patient developed worsening hypoxia requiring high flow nasal cannula, and creatinine increased to 3.96 mg/dL. ANCA antibodies displayed reactivity to Myeloperoxidase (MPO). Pulmonary infiltrates were attributed to DAH secondary to ANCA-related pulmonary-renal syndrome. High dose steroids and rituximab were initiated, and hypoxic respiratory failure improved. A renal biopsy revealed crescentic glomerulonephritis. The patient remains critically ill and is receiving high dose steroids and continuous renal replacement therapy for management of acute renal failure.
Discussion: Pulmonary-renal syndrome (PRS) is defined as a clinical syndrome characterized by diffuse alveolar hemorrhage (DAH) combined with rapid progressive glomerulonephritis (RPGN). DAH is characterized by hemoptysis, low hematocrit, bilateral diffuse alveolar infiltrates, and hypoxemic respiratory failure. Up to 30% of patients with DAH do not demonstrate hemoptysis, as was the case in our patient. A variety of mechanisms are implicated in the pathogenesis of PRS, including ANCA- and anti-GBM-mediated injury, immune-complex-mediated vasculitis of small vessels, and drug-induced vasculitides. In our patient, the delayed recognition of PRS was multifactorial – her pre-existing nephrolithiasis was felt to be the etiology of her hematuria, and her advanced age put ANCA and anti-GBM vasculitis lower on the differential. On literature review, there are fewer than 5 case reports detailing first time presentations of ANCA/GBM-related disease in patients above the age of 70.
Conclusions: PRS is an urgent clinical problem which necessitates a high index of suspicion. ANCA-associated vasculitis and anti-GBM disease account for 70% to 90% of these cases. Effective management often requires multidisciplinary involvement of pulmonary, rheumatology, nephrology and critical care medicine physicians.