Patients with severe nephrotic syndrome are predisposed to thrombotic events. One possible mechanism for hypercoagulability is loss of natural anticoagulants in the urine. Thromboses occur most commonly in the renal veins and deep veins of the lower extremities. Chronic renal vein thrombi are usually asymptomatic. (Acute renal vein thrombi often lead to renal infarction but are not typically seen in nephrotic syndrome.) Lower extremity deep vein thromboses can sometimes lead to pulmonary embolism. Patients with nephrotic syndrome are also at increased risk for venous clots in the cerebral veins and arterial clots in the cerebral or lower limb vasculature. The highest risk patients include those with underlying membranous nephropathy, serum albumin < 2.0 g/dl, and massive proteinuria. There is no clear evidence to support prophylactic anticoagulation for nephrotic syndrome.
This patient's isolated proteinuria on urinalysis is consistent with orthostatic proteinuria, a higher than normal protein excretion during the day (when upright) but normal protein excretion at night (when supine). Orthostatic proteinuria is the most common cause of proteinuria in adolescents (60%-75% prevalence) and rarely occurs after age 30. Possible mechanisms of proteinuria include an exaggerated normal response to upright posture, increased glomerular capillary pressure due to an exaggerated angiotensin II response with standing, subtle glomerular abnormality (eg, focal mesangial hypercellularity and/or basement membrane thickening), or left renal vein entrapment.
Diagnosis can be confirmed by comparing the urine protein-to-creatine ratio in urine samples collected in both the supine and standing positions. Another confirmatory test is to compare protein excretion in a split 24-hour urine collection divided between the daytime (after morning void until bedtime) and nighttime periods. Orthostatic proteinuria is confirmed in patients with a significant elevation in daytime protein excretion but a normal nighttime rate. Clinical features suggesting an alternate diagnosis include history of nephrotoxic agents, acute glomerulonephritis (eg, hypertension, hematuria, acute kidney injury), or nephrotic syndrome (eg, proteinuria >3-3.5 g/24 hr, hypoalbuminemia, edema).
Long-term studies have shown that orthostatic proteinuria in adolescents is a benign condition that usually resolves spontaneously and does not have a significant effect on renal function. As a result, patients do not require further diagnostic workup or treatment. Although very subtle glomerular abnormalities may be seen, orthostatic proteinuria has an excellent prognosis and does not predict development of significant glomerular pathology in the future. The patient should be reassured about the benign nature of orthostatic proteinuria and the tendency to resolve with age. He should be monitored periodically and have orthostatic proteinuria reconfirmed if he has persistent proteinuria.