Case 8: Diagnosis & Conclusions

Case 8 Index

Diagnosis: Minimal Change Disease (MCD) 

Case Summary: Well done! Let’s take a closer look at this case of a young boy who presents with sudden onset of edema and proteinuria. From the history, we learn this child, who has a history of seasonal allergies, recently experienced a viral illness and now presents with significant edema. When patients of all ages present with new onset of edema, the differential diagnosis includes congestive heart failure, cirrhosis, and nephrotic syndrome.

Moving on to the labs, we find hypoalbuminemia and 4+ protein on the urine dipstick. Both are suggestive of nephrotic syndrome, though we should quantify the proteinuria before making this assessment. The urine protein to creatinine ratio (UPCR) confirms nephrotic range proteinuria, defined as greater than 3 to 3.5 grams of protein in a 24-hour urine collection, or a urine protein:creatinine ratio of greater than 3000 to 3500 mg/g. Together, proteinuria, significant edema, hypoalbuminemia, and often hyperlipidemia/lipiduria (lipids in the urine seen as fatty oval bodies with lipid droplets as we see in this patient’s urine) comprise nephrotic syndrome.

What is the differential diagnosis for nephrotic syndrome?
Primary causes of nephrotic syndrome
Focal segmental glomerulosclerosis (FSGS)
Membranous nephropathy
Minimal change disease
Secondary causes of nephrotic syndrome
Diabetes mellitus (most common)
Systemic lupus erythematosus (SLE)
Hepatitis B or C (more commonly HBV)
Nonsteroidal anti-inflammatory drugs
HIV
Amyloidosis
Multiple myeloma
Preeclampsia

Now that we have established a broad differential for nephrotic syndrome, let’s try to determine which etiology is most likely in our patient. The age of this patient makes many of these diagnoses less likely, though the biopsy will provide the highest yield information.

Our biopsy reveals a normal glomerulus on light microscopy with effacement of the podocytes on EM without evidence of dense deposits – leading us to the diagnosis of minimal change disease (MCD). MCD, previously known as “nil disease,” gets its name from the minimal changes seen on light microscopy.

 


In children, MCD likely represents a primary glomerular disease, but there are numerous secondary causes.
Drugs
NSAIDs, salazopyrin, D-penicillamine, mercury, gold, tiopronin, lithium tyrosine-kinase inhibitors, bisphosphonates, interferon
Infection
Viruses, parasites, Mycoplasma pneumoniae
Malignancy
More often hematologic malignancies (Hodgkin disease, non-Hodgkin lymphoma, leukemia, multiple myeloma), thymoma, bronchogenic cancer, colon cancer, eosinophilic lymphoid granuloma (Kimura disease)
Allergy/Immunizations
Pollen, dust, fungi, bee sting, cat fur, food allergens (cow’s milk, egg)
Autoimmune disease
SLE, diabetes mellitus , myasthenia gravis, autoimmune pancreatitis, celiac disease, allogeneic stem cell transplantation

Both B-cells and T-cells are thought to be important in the pathogenesis of minimal change disease. Interestingly, infection with measles (which leads to T-cell suppression) has been associated with disease remission. Though a percentage of patients may experience disease remission without treatment, the mainstay of therapy is daily or alternate-date corticosteroids (and treatment of the underlying disease may lead to remission in secondary MCD). 10-20% of patients will have steroid-resistant or relapsing disease, which can be treated with a variety immunosuppressive agents with varying efficacy including cyclophosphamide, calcineurin inhibitors (CNI), azathioprine, levisamole (in children), and ritixumab. Time of response to therapy is typically shorter in children.

For more, take a look at the references below:

  1. Glassock RJ: Secondary minimal change disease. Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. – Eur. Ren. Assoc. 18 Suppl 6: vi52-58, 2003
  2. Hogan J, Radhakrishnan J: The treatment of minimal change disease in adults. J. Am. Soc. Nephrol. JASN 24: 702–711, 2013
  3. Vivarelli M, Massella L, Ruggiero B, Emma F: Minimal Change Disease. Clin. J. Am. Soc. Nephrol. CJASN 12: 332–345, 2017

Case 8 Index

Case 8 Introduction
Case 8 Physical Exam
Case 8 Diagnostic Testing
Case 8 Pathology
Case 8 Additional Pathology
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