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  • Bland urine sediment (few if any cells or cellular casts).

  • Nephrotic syndrome manifestations:

    • –Heavy proteinuria (urine protein excretion greater than 3 g per 24 hours).

    • –Hypoalbuminemia (albumin less than 3 g/dL).

    • –Peripheral edema.

    • –Hyperlipidemia.

    • –Oval fat bodies may be seen in the urine.

In American adults, the most common cause of nephrotic spectrum glomerular disease is diabetes mellitus. Other causes include minimal change disease, FSGS, membranous nephropathy, and amyloidosis. Any of these entities can present on the less severe end of the nephrotic spectrum with a bland urinalysis and proteinuria, or with the most severe presentation of the nephrotic syndrome. Serum creatinine may be abnormal at the time of presentation, depending on the severity and acuity of the disease.

A. Symptoms and Signs

Patients with subnephrotic range proteinuria do not manifest symptoms of the kidney disease. In those with the nephrotic syndrome, peripheral edema is present and is most likely due to sodium retention and hypoalbuminemia-induced low plasma oncotic pressure. Edema may develop solely in dependent regions, such as the lower extremities, or it may become generalized and include periorbital edema. Dyspnea due to pulmonary edema, pleural effusions, and diaphragmatic compromise due to ascites can occur.

B. Laboratory Findings

1. Urinalysis

Proteinuria occurs as a result of effacement of podocytes (foot processes) and an alteration of the negative charge of the GBM. The urinary dipstick is a good screening test for proteinuria; however, it detects only albumin. The addition of sulfosalicylic acid to the urine causes total protein to precipitate, allowing for the possible discovery of paraproteins (and albumin). A spot urine protein to urine creatinine ratio gives a reasonable approximation of grams of protein excreted per day; a 24-hour urine sample for protein excretion is rarely needed.

Microscopically, the urinary sediment has relatively few cellular elements or casts. However, if marked hyperlipidemia is present, urinary oval fat bodies may be seen. They appear as “grape clusters” under light microscopy and “Maltese crosses” under polarized light.

2. Blood chemistries

The nephrotic syndrome results in hypoalbuminemia (less than 3 g/dL [30 g/L]) and hypoproteinemia (less than 6 g/dL [60 g/L]). Hyperlipidemia occurs in over 50% of patients with early nephrotic syndrome, and becomes more frequent and worsens in degree as the severity of the nephrotic syndrome increases. A fall in oncotic pressure triggers increased hepatic production of lipids (cholesterol and apolipoprotein B). There is also decreased clearance of very low-density lipoproteins, causing hypertriglyceridemia. Patients may also have an elevated erythrocyte sedimentation rate as a result of alterations in some plasma components such as increased levels of fibrinogen. Patients may become deficient in vitamin D, zinc, and copper from loss of binding proteins in the urine.

Laboratory testing to determine the underlying cause may include complement levels, serum ...

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