Minimal-Change Disease Workup

Updated: Nov 13, 2020
  • Author: Abeera Mansur, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Workup

Approach Considerations

Urinalysis findings are benign in minimal-change disease (MCD), but profound proteinuria and oval fat bodies may be observed. In children, the critical level for diagnosis is proteinuria of more than 40 mg/h/m2. In adults, the threshold is more than 3.5 g/d/1.73 m2.

A random albumin-to-creatinine concentration ratio is in excess of 5. Urine specific gravity is high because of proteinuria. A 24-hour urine measurement should be obtained for protein and creatinine clearance.

Hypoalbuminemia is an important marker of nephrotic syndrome. The level at which edema occurs varies, but it tends to be lower in children than in adults. Nephrotic syndrome in children is defined by a serum albumin of less than 2.5 g/dL. Hyperlipidemia also is a feature of a nephrotic state.

Other laboratory findings are as follows:

  • Kidney function usually is normal except in cases of undiagnosed focal segmental glomerulosclerosis (FSGS) or in those cases that progress to acute kidney injury

  • Serologic workup (including antinuclear antibodies, complements, and cryoglobulins) is normal

  • Hyponatremia is often observed and is in part a spurious finding secondary to the hyperlipidemic state; it also occurs from water retention caused by hypovolemia and antidiuretic hormone release

  • Elevated hemoglobin and hematocrit are consequences of plasma volume contraction

Renal sonogram results are normal in patients with MCD.

Because MCD accounts for 90% of all cases of idiopathic nephrotic syndrome in children, kidney biopsy is not part of the initial workup for MCD in that age group. Instead, biopsy is performed only in those children who fail to achieve remission with an empiric course of corticosteroids. In contrast, a kidney biopsy is performed in all adult patients with nephrotic syndrome, before the initiation of treatment for MCD.

Increasing interest centers on the possibility of using urinary levels of CD80 as a biomarker in MCD (see Pathophysiology and Prognosis). Elevated levels may help differentiate MCD from FSGS [7] and predict responsiveness to corticosteroids. [16, 17]

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Histologic Findings

Light microscopy

In patients with MCD, the glomerulus is, by definition, normal or nearly so when examined with the light microscope; however, the precise limits of normal are not clearly defined. This creates difficulty in differentiating the appearance of minimal change with mild mesangial proliferation from a mesangial proliferative glomerulonephritis. Diagnosis can be even more difficult because, at the peak age of onset (approximately 3 y), the mesangial and epithelial cells are more prominent. In adult patients, diagnosis is made more challenging by superimposed arterionephrosclerosis secondary to hypertension.

In children with frequently relapsing MCD, some involuted glomeruli may be present. These lesions are small and sclerotic but retain their podocyte and parietal epithelial cell constituents. The presence of these glomeruli is related to the duration of the disease.

The most common tubular lesion is protein and lipid droplets in epithelial cells due to increased reabsorption. The presence of areas of tubular atrophy and interstitial fibrosis should raise the suspicion of FSGS.

Immunohistology

These studies usually do not demonstrate significant glomerular deposition of immunoglobulins or complement components in patients with MCD. Some biopsy specimens may be positive for low-level IgM deposits not accompanied by mesangial dense deposits.

Electron microscopy

Retraction of the epithelial foot processes is observed consistently in patients with MCD. This is, at times, erroneously described as foot-process fusion and results from disordered epithelial cell structure with withdrawal of the dendritic process. This finding is not unique to MCD, and the diagnosis is one of exclusion of other diseases based on lack of other processes on light microscopy, immunohistology, or electron microscopy.

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