Clinical Pearls & Morning Reports
Published April 19, 2017
In most cases, the estimated glomerular filtration rate is normal or near normal at the onset of the nephrotic syndrome, and only few clinical situations explain the concurrent presence of acute kidney injury and the nephrotic syndrome. Read the latest Case Record of the Massachusetts General Hospital.
Q. What are some of the primary and secondary causes of the nephrotic syndrome?
A. Primary nephrotic syndromes include minimal change disease and focal segmental glomerulosclerosis (which primarily affect podocytes), as well as membranous nephropathy. Secondary nephrotic syndrome can occur as a result of systemic illnesses, including diabetes mellitus, amyloidosis, and lupus nephritis (class V membranous lupus nephritis or lupus nephritis with podocytopathy).
Q. What other abnormalities often accompany the proteinuria, hypoalbuminemia, and peripheral edema that characterize the nephrotic syndrome?
A. The nephrotic syndrome affects both the biosynthesis and the clearance of lipoproteins and results in hyperlipidemia and alterations in the composition of lipoproteins; the severity of these effects is proportional to the degree of proteinuria. The nephrotic syndrome causes thrombophilia that results from an overall net increase in procoagulant factors due to a variety of different mechanisms.
Q: What characterizes the collapsing variant of focal segmental glomerulosclerosis?
A: Patients with the collapsing variant of focal segmental glomerulosclerosis often present with acute kidney injury in addition to the nephrotic syndrome. Collapsing focal segmental glomerulosclerosis is characterized by widespread podocyte injury with diffuse effacement of foot processes and severe proteinuria, as well as collapse and sclerosis of the entire glomerular capillary bed. This variant of focal segmental glomerulosclerosis contrasts with other variants, in which areas of mesangial collapse and sclerosis typically affect only a portion of the glomerular surface, sparing some glomeruli entirely and maintaining enough capillary surface area to preserve renal function during the early stages of this disease. The causes of collapsing focal segmental glomerulosclerosis are varied. Several infections are associated with collapsing focal segmental glomerulosclerosis; human immunodeficiency virus (HIV)–associated nephropathy is a classic form of this condition. It is thought that HIV directly infects podocytes, which leads to dedifferentiation, apoptosis, and widespread effacement of foot processes.
Table 3. Causes of Collapsing Focal Segmental Glomerulosclerosis.
A: HIV-associated nephropathy classically occurs in patients with chronic, uncontrolled HIV infection and is associated with a CD4 cell count of less than 250 per cubic milliliter, but on rare occasions, it can also be seen as a manifestation of acute HIV infection. HIV-associated nephropathy is also associated with characteristic histologic changes that affect each of the different renal compartments. The tubules classically develop microcystic dilatation; they fill with proteinaceous material and undergo cast formation, and a lymphocytic infiltrate and tubulitis are commonly seen. Because of the tubulointerstitial nephritis and the proteinaceous, cast-filled microcysts, the kidneys become enlarged and appear echogenic on renal ultrasonography. Approximately 50% of patients with HIV-associated nephropathy have progression to end-stage renal disease, and this highlights the need for a directed therapy for HIV-associated nephropathy that halts the progression of renal disease.