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Glomerular diseases can be challenging to understand clinically because the glomerulus is a histologically complex structure (consisting of the epithelial cells [podocytes], basement membrane, capillary endothelium, and mesangium). The following are examples of injuries that can affect any or all of the constituents of the glomerulus: (1) overwork injury, as in CKD; (2) an inflammatory process, such as SLE; (3) a podocyte protein mutation, as in hereditary focal segmental glomerulosclerosis (FSGS); or (4) a deposition disease, as in diabetes or amyloidosis. When a glomerular disease is suspected, a kidney biopsy may be needed to clarify the etiology.

CLASSIFICATION

Clinically, a glomerular disease can be classified as being in one of two clinical spectra—either in the nephritic spectrum or the nephrotic spectrum (Figure 22–4). At the “least severe” end of the nephritic spectrum, the findings of asymptomatic glomerular hematuria (ie, dysmorphic red blood cells with or without some proteinuria [<1 g/day]) are characteristic. The nephritic syndrome, comprising glomerular hematuria, subnephrotic proteinuria (less than 3 g/day), edema, and elevated creatinine, falls in the mid-portion of the spectrum. The rapidly progressive glomerulonephridities (RPGNs), with systemic symptoms, are at the “most severe” and clinically urgent end of the nephritic spectrum. The nephrotic spectrum is comprised of diseases that present primarily with proteinuria of at least 0.5–1 g/day and a bland urine sediment (no cells or cellular casts). At the more severe end of the nephrotic spectrum is the nephrotic syndrome, consisting of nephrotic-range proteinuria (>3 g/day), hypoalbuminemia, edema, hyperlipidemia, and urinary oval fat bodies. Differentiating between a clinical presentation within the nephritic spectrum versus the nephrotic spectrum is important because it helps narrow the differential diagnosis of the underlying glomerular disease (Tables 22–7 and 22–8).

Figure 22–4.

Glomerular diseases present within one of the clinical spectra shown; the exact presentation is determined by the severity of the underlying disease and the pattern of injury. Nephritic diseases are characterized by the presence of an active urine sediment with glomerular hematuria and often with proteinuria. Nephrotic spectrum diseases are proteinuric with bland urine sediments (no cells or cellular casts). All glomerular diseases may progress to a chronic, scarred state. (Adapted, with permission, from Megan Troxell, MD, PhD.)

Table 22–7.Classification and findings in glomerulonephritis: nephritic spectrum presentations.

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