Nephrotic Syndrome

Nephrology Morning Report

The case involved a woman admitted with back pain who had a medical history of Sjogren’s disease and rheumatoid arthritis.  She was noted to have peripheral edema and periorbital edema, heavy proteinuria, a normal serum creatinine, and hypoalbuminemia of 18g/L.  She went on to receive a kidney biopsy which demonstrated immune complex deposition and some features consistent with cryoglobulinemia.  Her serum cryocrit was 1% (which is abnormal).  There is no final diagnosis as of yet, but her nephrotic syndrome is thought to be related to one of her existing autoimmune diagnoses.

There were multiple learning points discussed:

-There are different ways of quantifying proteinuria.  Firstly, a dipstick only measures albumin and is a point of care test.  A 24-hour urine collection for protein will give you an exact amount of all types of protein in the urine as well as an amount of creatinine (in mmol).  The normal excretion of creatinine in a 24-hour period is 5-15mmol.  A spot protein/creatinine ratio will quantify all types of protein against the number of mmol of creatinine, so it acts as a surrogate for a 24-hour collection when you estimate the amount of creatinine a person would excrete.

-The differential diagnosis of edema (whether dependent or independent of gravity) can relate to the Starling forces: cardiac pump failure (or any venous problem such as thrombosis) can increase venous pressure allowing filtration of fluid from the vascular to extravascular compartment.  Low oncotic pressure from hypoalbuminemia impairs the blood’s ability to retain fluid/sodium in the intravascular compartment and allows it to be filtered out.  Impaired lymphatic drainage can lead to edema.  Impairment in vascular tone caused by medications such as amlodipine can also lead to edema.  Finally, impaired filtration of salt/water as a result of renal insufficiency can also be a cause.

-We discussed nephrotic syndrome: it was broken down into primary renal lesions (which are typically at the glomerular level and include minimal change disease, focal segmental glomerulosclerosis, and membranous disease) and secondary causes (SLE, viruses such as the hepatitides, other autoimmune diseases, drugs such as penicillamine/gold/NSAIDs, malignancies such as lymphomas, amyloidosis).

-The hallmark features of nephrotic syndrome include proteinuria, lipiduria, coagulopathies as a result of loss of anticoagulant factors in the urine, hypoalbuminemia, and a preserved GFR.

-There are a number of ways that multiple myeloma (a clonal plasma cell dyscrasia in which B-cells secrete a monoclonal immunoglobulin) leads to renal disease.  Cast nephropathy (“myeloma kidney”) occurs as a result of filtered immunoglobulin light chains depositing in the tubules and impairing their function.  Monoclonal IgG deposition disease (MIDD or sometimes light chain deposition disease) occurs as a result of deposits of immunoglobulin in the basement membranes of renal tissue.  To distinguish from AL amyloidosis, MIDD deposits do not stain positively for typical amyloid stains (Congo Red).  AL amyloidosis involves deposition of amyloid plaques in renal basement membranes.  Other frequent causes in multiple myeloma include hypercalcemia and volume depletion.

-We did not discuss the hyponatremia, but patients with nephrotic syndrome can classically have one of the “hypervolemic” hyponatremia syndromes.

-Sjogren’s disease can lead to a tubulointerstitial problem, and both it and rheumatoid arthritis are associated with distal renal tubular acidosis.  These would typically be non-anion gap metabolic acidoses.

Further Reading:

Hebert, L. A., Parikh, S., Prosek, J., Nadasdy, T., & Rovin, B. H. (2013). Differential diagnosis of glomerular disease: a systematic and inclusive approach. American journal of nephrology, 38(3), 253-266.