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The most appropriate test to diagnose the cause of abnormal kidney function, proteinuria, and intermittent gross hematuria is kidney biopsy.

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Hematuria can be caused by bleeding anywhere in the urinary tract from the glomeruli to the urethra. Therefore, the differential diagnosis is broad and includes glomerular disease, nephrolithiasis, urologic malignancy, renal papillary necrosis, prostate disorders, acute trauma, infection, hematologic disorders, and other forms of cystitis. Radiation to the pelvis may produce hemorrhagic cystitis, and patients who are excessively anticoagulated may develop hematuria without identifiable structural disease. Abdominal aortic dissection may have associated hematuria due to renal ischemia.

This patient has proteinuria and progressive chronic kidney disease in addition to the hematuria. Taken together, these findings suggest glomerular disease. Definitive diagnosis is obtained only by kidney biopsy and will help guide therapy.

In patients with nonglomerular hematuria, it is appropriate to evaluate the upper and lower urinary tract for causes of hematuria. A CT urogram is considered the study of choice for evaluating all types of nonglomerular hematuria originating in the upper tracts.

Cystoscopy would be the study of choice to evaluate the bladder in a patient with nonglomerular hematuria who was at risk for transitional-cell cancer. Risk factors for transitional-cell cancer include cigarette smoking (50% of cases), chemical exposures, drug exposures (cyclophosphamide, phenacetin), radiation, long urine dwelling times (such as in truck drivers), chronic urinary stone disease, chronic catheterization, chronic infections, and genetic mutations.

Urine cytology was previously recommended to evaluate the lower tract in patients at low risk for bladder cancer, but it is an insensitive study. Furthermore, malignancies that cause hematuria are not generally associated with proteinuria or a significant decline in renal function.

Doppler studies of the renal veins are used to detect renal-vein thrombosis. This entity is more common in the setting of nephrotic syndrome with heavy proteinuria or a hypercoaguable state from a malignancy. Patients may be asymptomatic or complain of flank pain. If there has been a thrombosis of one renal vein, this would not explain the rise in serum creatinine to the degree seen in this patient. Instead, causes of glomerular bleeding should be pursued.