Fixed Proteinuria

The glomerular capillary wall consists of 3 layers: the fenestrated capillary endothelium, the glomerular basement membrane, and the podocytes (with foot processes and intercalated slit diaphragms). Glomerular proteinuria results from alterations in the permeability of any of the layers of the glomerular capillary wall to normally filtered proteins and occurs in a variety of renal diseases (Table 520-1). Glomerular proteinuria can range from <1 g to >30 g/24 hr.

Glomerular proteinuria should be suspected in any patient with a first morning urine protein : creatinine ratio >1.0, or proteinuria of any degree, accompanied by hypertension, hematuria, edema, or renal dysfunction. Disorders characterized primarily by proteinuria include idiopathic (minimal change) nephrotic syndrome, focal segmental glomerulosclerosis, mesangial proliferative glomerulonephritis, membranous nephropathy, membranoproliferative glomerulonephritis, amyloidosis, diabetic nephropathy, and obesity-related glomerulopathy. Other renal disorders that can include proteinuria as a prominent feature include acute postinfectious glomerulonephritis, immunoglobulin A nephropathy, lupus nephritis, Henoch-Schönlein purpura nephritis, and Alport syndrome.

Initial evaluation of a child with fixed proteinuria should include measurement of serum creatinine and electrolyte panel, first morning urine protein : creatinine ratio, serum albumin level, and complement levels. The child should be referred to a pediatric nephrologist for further evaluation and management. Renal biopsy is often necessary to establish a diagnosis and guide therapy.

In asymptomatic patients with low-grade proteinuria (protein : creatinine ratio 0.2-1.0) in whom all other findings are normal, renal biopsy might not be indicated because the underlying process may be transient or resolving or because specific pathologic features of a chronic kidney disease might not yet be apparent. Such patients should have periodic re-evaluation (every 4-6 mos unless the patient is symptomatic) consisting of a physical examination and blood pressure determination, urinalysis, and measurement of serum creatinine and first morning voided urine protein:creatinine ratio. Indications for renal biopsy include increasing proteinuria (protein:creatinine >1.0) and/or the development of hematuria, hypertension, or diminished renal function.

A variety of renal disorders that primarily involve the tubulointerstitial compartment of the kidney can cause low-grade fixed proteinuria (protein : creatinine ratio <1.0). In the healthy state, large amounts of proteins of lower molecular weight than albumin are filtered by the glomerulus and reabsorbed in the proximal tubule. Injury to the proximal tubules can result in diminished reabsorptive capacity and the loss of these low molecular weight proteins in the urine.

Tubular proteinuria (see Table 520-1) may be seen in acquired and inherited disorders and may be associated with other defects of proximal tubular function, such as the Fanconi syndrome (glycosuria, phosphaturia, bicarbonate wasting, and aminoaciduria). Tubular proteinuria is a consistent finding among patients with the X-linked tubular syndrome, Dent disease, caused by mutations of the renal chloride channel.

Asymptomatic patients having persistent proteinuria generally have glomerular rather than tubular proteinuria. In occult cases, glomerular and tubular proteinuria can be distinguished by electrophoresis of the urine. In tubular proteinuria, little or no albumin is detected, whereas in glomerular proteinuria the major protein is albumin.