Clinicopathologic correlations in the nephrotic syndrome

The wide utilization of renal biopsy and the introduction of electron microscopic and immunohistologic methods has allowed better definition of the clinico-pathological conditions associated with the nephrotic syndrome (NS). Two major categories of facts can be differentiated. In the first one, diffuse lesions of glomeruli, either secondary to specific diseases, or apparently primary diseases such as membranous or membrano-proliferative glomerulonephropathy (GN) are responsible for the increased permeability of the glomerular capillaries. In most of these, there is evidence that immunological mechanisms play a role in the injury of the glomerular capillary. Any of the following clinical symptoms are suggestive of this category of NS: an acute nephritic onset, a moderate NS, macroscopic hematuria, marked hypertension and/or renal insufficiency, poorly selective proteinuria and decreased plasma C3 levels. Patients affected with any of these glomerulopathies usually do not respond to steroids. In the second one, usually referred to as the idiopathic nephrotic syndrome (INS) the mechanism of glomerular capillary alteration is unknown and the nephrotic syndrome is more marked. Minimal change NS (MCNS) accounts for the great majority of INS and is characterized in most cases by a selective proteinuria, the absence of hematuria, a good response to steroids and a good prognosis. However, in some instances, renal biopsy reveals either diffuse mesangial proliferation (DMP) or focal glomerular sclerosis (which may be superimposed on MCNS or on DMP). In both instances, hematuria may be present and 50--75% of patients do not respond to steroids and have a poor prognosis. There is still considerable controversy about the exact relationship between these 3 patterns. We believe that they are not distinct entities but represent variants of the same disease. In addition to these 2 major categories of NS, there are, in infancy, 2 conditions associated with a NS of poor prognosis: congenital NS of Finnish type and infantile mesangial sclerosis. Since steroid-sensitive nephrosis is by far the commonest cause of NS especially in young children up to 8 years, a renal biopsy should be performed only in 2 instances: (a) when the clinical symptoms suggest diffuse glomerular lesions, and (b) when steroid resistance has been demonstrated.