Biostatistics Case Studies

CASE 9: Cohort Study

Clinical History:

A 25-year-old military serviceman reports having respiratory difficulty along with red-tinged sputum, chest pain, chills, and fever for the past 2 days. He then passes dark urine. He goes to see the base physician. Vital signs are recorded as: T 37.9 C, P 83/min, RR 15/min, and BP 145/90 mm Hg. Physical examination findings include crackles over lung bases.

Urine dipstick examination shows 1+ protein and 4+ blood.

Additional laboratory findings include serum creatinine 2.8 mg/dL, urea nitrogen 30 mg/dL, glucose 74 mg/dL, total protein 6.1 g/dL, and albumin 3.6 g/dL

Two days later is serum creatinine is 4 mg/dL and urea nitrogen 43 mg/dL. Further history reveals that he works in a military fuel depot.

A renal biopsy on light microscopy shows crescents in the glomeruli, filling Bowman's space and compressing the residual glomerular tufts.

With immunofluorescence staining for fibrinogen, the crescents within Bowman's space stain for fibrinogen, consistent with severe glomerular injury leading to leakage of fibrinogen that stimulates epithelial cell proliferation and crescent formation.

The immunofluorescence show with staining for IgG shows a linear pattern of staining along the glomerular basement membrane with antibody to IgG. In most cases of Goodpasture syndrome with rapidly progressive glomerulonephritis there is linear staining with IgG, but staining with IgA and IgM can also be present.


  1. What is the differential diagnosis?

  2. Hemoptysis suggests a possible infectious disease such as tuberculosis or severe bacterial infection. Causes for nephrititic syndrome along with pulmonary involvement may include:

    • Goodpasture syndrome

    • Vasculitis (ANCA-associated granulomatous vasculitis, SLE, polyarteritis nodosa)

    • IgA nephropathy

  3. What is the pathogenesis?

  4. There is anti-glomerular basement membrane (anti-GBM) antibody. The target antigen is likely the non-collagenous domain of the alpha-3 chain of type IV collagen in the basement membrane. Since this antigen is present all along the basement membrane, the attached antibody will have a linear pattern when detected by immunofluorescence. The damage is often severe, leading to this rapidly pogressive form of glomerulonephritis.

  5. What is the treatment and prognosis?

  6. He can be given immunosuppresive therapy along with plasmapheresis. The pheresis removes the antibody while immunosuppression diminishes antibody production. Once remission is achieved and no more antibody is detected, the immunosuppressive therapy is tapered off. Infections and smoking are risk factors for recurrence, as well as re-exposure to substances (such as hydrocarbon solvents) that precipitated the disease.

  7. What long-term type of study can be undertaken to determine what risk factors, if any, play a role in development of this disease in persons working at this man's job?

  8. A cohort study follows initially disease free subjects over a period of time. During that time, some subjects are exposed to risk factors, such as hydrocarbon compounds, and the outcomes are measured. The cohort may be defined as persons born in a particular year (making them all the same age), persons who lived in a particular community, or persons who worked in a particular place such as this patient. The outcome may be a particular disease state (glomerulonephritis) or death. Cohort studies need large numbers of subjects studied for long periods of time to be valid.