NONRENAL COMPLICATIONS OF THE NEPHROTIC SYNDROME

The nephrotic syndrome is a consequence of urinary loss of intermediate-sized plasma proteins and the resulting homeostatic responses to those losses. Plasma protein composition is changed greatly. Pathphysiologic changes are a consequence of the nature of the proteins lost and of the proteins that are increased in plasma to replace them. Plasma oncotic pressure (π) falls because of the replacement of relatively small plasma proteins by larger ones. Decreased π increases transudation of fluid into the interstitum and favors edema. This is exacerbated by causing renal insensitivity to atrial natriuretic factor (ANF), primary renal sodium retention, and plasma volume expansion. Many proteins lost in the urine, such as erythopoietin and IgG, are not defended by increased synthesis. Their loss may result in reduced immunity, anemia, and endocrinopathies. Albumin synthesis can be increased by dietary protein augmentation; however, urinary protein losses also increase, offsetting any palliative effect of increased albumin synthesis on albumin stores. The synthesis of many other proteins secreted by the liver is also increased, causing an elevation in plasma levels of several large proteins, including lipoproteins and elements of the coagulation cascade. This results in hyperlipidemia and, in conjunction with the urinary loss of smaller proteins that impede coagulation, a hypercoagulable state. Lipoprotein catabolism is also reduced as a consequence of proteinuria contributing to increased lipid levels.