Fever. Fever is the most common cause of proteinuria (up to 75% of febrile patients). If severe, it may be associated with an increase in hyaline casts (etiology unknown, possibly dehydration).

Cystitis-urethritis. Cystitis and urethritis are lower urinary tract infections, often hard to differentiate from renal infection. Clumping of WBCs is suggestive of pyelonephritis but only WBC casts provide absolute specificity. Necrotizing cystitis may cause hematuria. The two-glass urine test helps to differentiate urethritis from cystitis. After cleansing the genitalia, the patient voids about 10-20 ml into container number 1 and the remainder into container number 2. A significant increase in the WBC count of container number 1 over that of container number 2 suggests urethral origin.

Genitourinary tract obstruction. Neuromuscular disorders of the bladder, congenital urethral strictures and valves, intrinsic or extrinsic ureteral mechanical compressions, and intraluminal calculi produce no specific urinary changes but predispose to stasis and infection. Obstruction, partial or complete, is a frequent etiology for recurrent genitourinary tract infections.

Amyloidosis. Renal involvement usually leads to proteinuria. In a minority of cases, when the process severely affects the kidney there may be high proteinuria and sediment typical of the nephrotic syndrome. The urinary sediment, however, is not specific, and RBC casts are not present. Renal amyloidosis is usually associated with chronic disease, such as long-standing osteomyelitis or infection, or multiple sclerosis.

Urinary calculi. Urinary calculi often cause hematuria of varying degree and, depending on the composition of the stone, may be associated with excess excretion of calcium, uric acid, cystine, phosphates, or urates in the urine, even when calculi are not clinically evident. Frequent complications are infections or obstruction, and infection may occur even in the absence of definite obstruction. Ureteral stone passage produces hematuria, often gross. Intravenous pyelography is the best means of diagnosis. Some types of calculi are radiopaque, and others may be localized by finding a site of ureteral obstruction.

Sickle cell anemia. Hematuria frequently occurs due to kidney lesions produced by intra-capillary RBC plugs, leading to congestion, small thromboses, and microinfarctions. Hematuria is also frequent at times of hematologic crises. Hematuria may be present even without crises in sickle cell disease or sickle cell variants. Sickle cell patients may lose urine-concentrating ability for unknown reasons. This happens even with sickle cell variants but is less common.

Chronic passive congestion. One cause of renal congestion is inferior vena cava obstruction. It produces mild diffuse tubular atrophy and hyperemia, leads to proteinuria (usually mild to moderate) and hyaline casts, and sometimes also elicits epithelial casts and a few RBCs. Occasionally, but not commonly, severe chronic passive congestion (CPC) may simulate the nephrotic syndrome to some extent, including desquamated epithelial cells containing fat plus many casts of the epithelial series. In CPC of strictly cardiac origin without significant previous renal damage, there is decreased urine volume but usually retained urine-concentrating ability. No anemia is present unless it is due to some other systemic etiology.

Benign arteriosclerosis. Benign arteriosclerosis involves the renal parenchyma secondarily to decreased blood supply. In most cases in the earlier stages, there are few urinary findings, if any; later, there is often mild proteinuria (0.1-0.5 gm/24 hours) and a variable urine sediment, which may contain a few hyaline casts, epithelial cells, and perhaps occasional RBCs. If the condition eventually progresses to renal failure, there will be significant proteinuria and renal failure sediment with impaired renal function tests.

Weil’s disease. Weil’s disease is leptospiral infection (Chapter 15) and clinically presents with hepatitis and hematuria. Characteristically, there are also high fever and severe muscle aching, and there may be associated symptoms of meningitis.

Infectious mononucleosis. Renal involvement with hematuria occurs in 5%-6% of cases.

Purpura and hemorrhagic diseases. These diseases should be recognized as causes of hematuria, either by itself or in association with glomerular lesions. The Henoch-Schцnlein syndrome (anaphylactoid purpura) is a rare condition featuring gastrointestinal bleeding (Henoch) or skin purpura (Sch?nlein) that often is concurrent with hematuria and nephritis.

Hypersensitivities. Hypersensitivities may lead to proteinuria (usually slight) with hematuria and perhaps a moderate increase in casts. Kidney involvement may occur due to hypersensitivity to mercurials, sulfas, or other substances.

Fat embolism. Fat embolism commonly occurs after trauma, especially fractures. Cerebral or respiratory symptoms develop the second or third day after injury, usually associated with a significant drop in hemoglobin values. Fat in the urine is found in about 50% of patients. Unfortunately, a physician’s order for a test for fat in the urine will usually result in microscopic examination of the sediment. Whereas this is the correct procedure to detect fat in the nephrotic syndrome, in which fat is located in renal epithelial cells and casts, it is worthless for a diagnosis of fat embolism, in which free fat droplets must be identified. Since free fat tends to float, a simple procedure is to fill an Erlenmeyer (thin-neck) flask with urine up into the thin neck, agitate gently to allow fat to reach the surface, skim the surface with a bacteriologic loop, place the loop contents on a slide, and stain with a fat stain such as Sudan IV.

Hemochromatosis. This condition is suggested by hepatomegaly, gray skin pigmentation, and proteinuria in a diabetic patient. Proteinuria may exceed 1 gm/24 hours, but sediment may be scanty and fat is absent. In severe cases yellow-brown coarse granules of hemosiderin are seen in cells, in casts, and lying free. Prussian blue (iron) stains in this material are positive. Distal convoluted tubules are the areas primarily involved. Since hemochromatosis does not invariably involve the kidney until late, a negative urine result does not rule out the diagnosis. False positive results (other types of urine siderosis) may occur in pernicious anemia, hemolytic jaundice, and in patients who have received many transfusions.

Thyroid dysfunction.

Myxedema. Proteinuria is said to occur without other renal disease. Its incidence is uncertain, especially since some reports state that proteinuria is actually not common and usually persists after treatment.

Hyperthyroidism. The kidney may lose its concentrating ability so that specific gravity may remain low even in dehydration; this is reversible with treatment and a return to a euthyroid condition. Occasionally, glucosuria occurs in patients.