Biostatistics Case Studies



CASE 10: Case Control Study


Clinical History:

A 26-year-old man with no major medical problems goes to his family physician for a checkup, which includes a urinalysis. The urinalysis findings are shown:

Urine dipstick examination shows 1+ blood. Urine microscopic examination reveals dysmorphic RBCs and RBC casts, but no WBC's.

Additional laboratory findings include serum creatinine 1.8 mg/dL, urea nitrogen 20 mg/dL, glucose 82 mg/dL, total protein 6.6 g/dL, and albumin 4.6 g/dL

Light microscopy of a renal biopsy shows mesangial cell proliferation. The glomerular capillaries and Bowman spaces appear normal. The immunofluorescence with staining for both IgA and C3 shows a predominantly mesangial deposition of IgA and C3. Staining for C1q, IgM, and IgG is negative.<

Urine microscopic examination shows dysmorphic red blood cells. This is an indicator for glomerular disease with a nephritic component.

Questions:

  1. What additional history do you want to know?

  2. There was no history of trauma. He had no dysuria. He had a recent "flu-like" illness. There is no family history of renal disease. One maternal uncle is deaf.

  3. What is the differential diagnosis based upon the history?

  4. He has a nephritic syndrome:

    • IgA nephropathy (also known as Berger disease)

    • Alport syndrome - but absence of thickening and thinning of basement membrane by electron micrscopy makes this unlikely

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

    • Urinary tract infection - but absence of WBCs makes this unlikely

  5. What additional laboratory tests could be ordered?

    • ANA - negative

    • ANCA - negative

    • Urine culture - negative

  6. What underlying disease(s) might be present? What diagnosis would you consider if the patient had presented with petechiae and purpura of the skin?

  7. IgA nephropathy is most often seen with onset in the 2nd and 3rd decades, more often in males, and most often in Caucasians. Since it is related to IgA derived from mucosal immunity, it has been seen in associationwith celiac disease. Respiratory tract infections may lead to increased IgA production. Persons with advanced liver disease from cirrhosis have impaired clearance of IgA containing immune complexes by hepatic Kupffer cells. Henoch-Schönlein purpura is the skin disorder associated with IgA nephropathy.

  8. What type of study would you perform to determine the risk for developing chronic renal failure in patients with this disease, compared to persons without this disease?

  9. In a "case control" study, one defines a population with a particular disease and then finds a suitable control group without the disease. One then compares the two using a particular risk factor for the disease. The cases and the controls may be matched for variables such as age, sex, and race, but they may be unmatched. Here is an example of an unmatched case control study comparing the risk for chronic renal failure:

    		Subjects with	Subjects without
    		Berger Disease	Berger disease
    
    CRF present	10 (a)		50 (b)
    CRF not present	10 (c)		1750 (d)
    
    Total		20		1800
    
    Odds Ratio = a X d / b X c = 35
    
    

    Unlike the cohort study, a relative risk is not used in a case-control study. Instead, an "odds ratio" is used. An odds ratio can give a reasonable estimate of the relative risk when the proportion of subjects with the disease is small. This example illustrates the observation that half of persons with IgA nephropathy (1 to 2% per year) may go on to chronic renal failure.