Swelling: Nephrotic Syndrome Review

In  our #AMreport today @WCHospital we reviewed an approach to leg edema and closed our discussion on a case of nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS). We also touched on HIVAN (HIV-Associated Nephropathy), which usually causes a collapsing variant of FSGS. See below for details.

1. This is a general approach to leg edema. Although not an exhaustive list it highlights more common causes as well as rare ones that can give rise to leg edema. Edema due to increased hydrostatic forces is one of the most common causes of leg edema.

Approach to edema
Increased hydrostatic pressure usually secondary to heart failure is one of the most common causes of leg edema given the ubiquity of cardiovascular disease. The other causes should be entertained in your differential diagnosis.

2.Nephrotic syndrome should be broken down into two (2) categories, primary and secondary. The primary causes are usually due to non-proliferative glomerolunephritis.

“Well what does non-proliferative GN mean?”

It means that there is not an increase or change in the number of cells within the glomerulus.

Non-proliferative GN
The most common causes of primary nephrotic syndrome in adults is FSGS. Whereas, in pediatric populations it is minimal change disease.

3. Remember that nephrotic syndrome is a constellation of clinical findings and laboratory abnormalities. Importantly if a clinical picture is suspicious for nephrotic syndrome collect the urine for 24 hours and ensure that you have ordered : 24 hr urine creatinine and protein. This is very important in determining whether your collection is appropriate. 

approach to nephrotic workup
In general practice it would be reasonable to organize the 24 hour urine collection for protein and creatinine. If it is >3.5 g/day then you have nephrotic range proteinuria. Given this can be caused by diabetes, SLE as well as light chain disease such as amyloidosis, it is reasonable to order an A1c, ANA, C3,C4 and SPEP. At this juncture it important to consult nephrology as the histopathology from renal biopsy is important for: treatment and prognostication.

Extra Take Home Points:

  • Patients with nephrotic syndrome have an increased incidence of arterial and venous thrombosis (typically deep vein and renal vein thrombosis) at about 10-40% compared to the general population. http://www.ncbi.nlm.nih.gov/pubmed/18158362
  • HIVAN (HIV-Associated Nephropathy) usually causes a collapsing variant of FSGS and the overall prognosis is poor as most patients progress to End-Stage Renal Disease (ESRD). Treating the HIV with HAART is the primary target in management (Grade 1B evidence).
    • HIVAN is more common in populations of Western African-descent with HIV infection as there is likely a “double hit phenomenon” from a genetic predisposition from the APOL1 gene polymorphisms.
    • APOL1 is believed to have conferred resistance to trypanosomiasis, also known as African sleeping sickness in those populations.