Clinical Pearls & Morning Reports
Published May 30, 2018
As compared with other causes of the nephrotic syndrome, membranous nephropathy has been associated with a particularly high risk of thrombophilia, even in a study that controlled for the degree of proteinuria. Read the latest NEJM Case Records of the Massachusetts General Hospital here.
Q: What proportion of cases of the nephrotic syndrome in the United States are due to membranous nephropathy?
A: In the United States, nearly one third of cases of the nephrotic syndrome can be ascribed to membranous nephropathy. In 25% of cases of membranous nephropathy, the disease is due to an underlying cause such as medication use or a systemic disorder (e.g., hepatitis B virus or hepatitis C virus infection, syphilis, thyroiditis, or cancer). The remaining cases are considered to be primary and of an unknown cause. Primary and secondary membranous nephropathy are indistinguishable on clinical grounds; they are both characterized by a gradual progression to the nephrotic syndrome over a period of months, often with preserved renal function and normal blood pressure.
Q: What is the role of serologic tests for anti-PLA2R antibodies in the diagnostic workup for membranous nephropathy?
A: The M-type phospholipase A2 receptor (PLA2R), which is a transmembrane receptor that is expressed in podocytes, has been identified as a major antigen in approximately 70% cases of primary (idiopathic) membranous nephropathy. The presence of this receptor is highly specific for primary membranous nephropathy because it is absent in patients with secondary cases and in those with other causes of the nephrotic syndrome. Serologic testing for anti-PLA2R antibodies has become a key component of the diagnostic workup for membranous nephropathy because of its noninvasive nature and very high specificity (99%). A positive serologic test may obviate the need for a kidney biopsy in many patients. The sensitivity of serologic testing for anti-PLA 2R antibodies (78%) is not sufficiently high for a negative test to completely rule out the diagnosis of membranous nephropathy, PLA 2R type.
A: On the basis of the natural history of membranous nephropathy, approximately one third of patients have spontaneous remission in the absence of specific therapy, another third remain nephrotic with stable renal function, and the remaining third have progressive renal failure. Therapeutic decisions should be based on certain clinical characteristics that help to predict the group in which the patient will be included. Favorable prognostic features include female sex, white race, normal blood pressure and renal function, an age of 30 to 50 years, and proteinuria with a urinary protein loss of less than 10 g per day, as well as an absence of fibrosis on renal biopsy, when such results are available.
A: When treating patients who have membranous nephropathy, clinicians weigh the risks and benefits of each treatment method. There is a strong consensus supporting the administration of lipid-lowering agents, particularly statins, when hyperlipidemia is present. Anticoagulation is administered to patients who have definite evidence of thromboembolic disease or to those who have severe hypoalbuminemia, since they have particularly high risk of the development of venous thrombi. The use of angiotensin-converting–enzyme inhibitors is also accepted widely, since it usually decreases the severity of proteinuria. Diuretics are commonly administered to help with the edema, but they are used with caution, since they are associated with an increased occurrence of acute kidney injury. The administration of immunosuppressive therapy in patients who are deemed to be at high risk for declining renal function is standard, but the choice of medication or combination of drugs and the dosing schedule are highly variable.