Renal Vascular and Glomerular
The renal vasculature includes the renal artery and sits major branches, the specialized glomerular capillary bed, and the renal veins. Each of these vascular divisions may contribute to distinct clinical syndromes. Glomerular disease rarely causes local symptoms; it is more likely detected by the presence of either edema or hypertension, the cardiovascular complications of the disorder, or the presence of blood or protein in the urine. Deranged glomerular function either proteinuria consequent to increased glomerular capillary permeability to macromolecules, or a reduced GFR secondary to altered glomerular ultraﬁltration dynamics characterizes these diseases. Large vessel disease of the kidney may be associated with ﬂank or abdominal pain and cause alteration of both glomerular and tubular function.
Proteinuria in excess of 0.5 to 1 gm/24 hr is the hallmark of glomerular disease and indicates an impairment in the ability of the glomerular capillary to retain serum macromolecules (proteins). The second common sign of glomerular disease, red and white blood cells and cellular casts in the urinary sediment, is associated with glomerular inﬂammation. Regardless of the etiology of the glomerular injury, the clinical presentation and course of glomerular diseases converge on the following general patterns.
Nephrosis is a presentation of glomerular injury characterized predominantly by proteinuria with minimal or no cellular sediment in the urine. Nephrosis is expressed clinically as edema formation, normal to reduced blood pressure, and normal or slowly decreasing rates of glomerular filtration (GFR). The nephrotic syndrome is a clinical syndrome in which heavy proteinuria (usually >3 gm/24 hr) leads to a reduction in the serum albumin (usually <3.0 gm/dl) and in which edema formation, the expansion of the interstitial component of the extracellular fluid volume, occurs as a result of renal salt retention in the face of a reduced serum oncotic pressure. Hyperlipidemia and lipiduria are frequent findings in the syndrome.
Nephritis describes a presentation of glomerular injury in which hematuria or a prominent cellular urinary sediment occurs along with moderate to heavy proteinuria. Hypertension and/or heart failure occurs regularly in nephritic glomerulopathies as renal salt retention expands both the intravascular and interstitial components of the extracellular fluid volume. A reduced GFR is usually seen at an early stage in the course of nephritic diseases. Focal glomerulonephritis, which affects portions of some glomeruli, may present only with hematuria and proteinuria; the GPR and systemic hemodynamic functions may be little affected. Diffuse glomerulonephritis, which affects the entirety of most glomeruli, more often presents with clinical signs of ECF volume excess and azotemia in addition to hematuria and proteinuria.
Mechanisms of Injury
In most primary glomerular diseases, injury is, believed to occur through immunological processes. The principal indication of this association IS the regular; detection by immunofluorescent staining of immune, reactants (IgG, IgM, IgA, C3, or C4) within the glomeruli (Figure 1).
Three modes of antigen-antibody interaction have been described for the activation of complement within the glomerulus. Circulating immune complexes (CIC) form within the circulation and may be trapped in the glomerular capillary wall during ultraﬁltration. In situ immune complex formation takes place when circulating free antigen lodges within the glomerulus and antibody subsequently binds to the strapped antigen. Finally, anti-renal antibody (specifically, anti-glomerular basement membrane antibody) may form, bind to an element of the glomerulus, and activate injury pathways.
Attraction of polymorphonuclear leukocytes; (PMN’s) appears to be the most direct consequence of immune complex complement activation. However, injury does occur in immune deposit glomerular diseases in which PMN infiltration is minimal or absent. Moreover, in some common human glomerulopathies, immune reactants are absent. Glomerular injury in diseases such as diabetes mellitus and amyloidosis likely proceeds from metabolic derangements. Finally, hemodynamic insults to the glomerular capillary bed may lead to glomerular necrosis, as in the case of severe hypertension, or to sclerosis, as with sustained elevations of glomerular capillary pressure or ﬂow.
Figure 1. Patterns of immune deposits in glomeruli. A, normal capillary loop; B, sub-endothelial deposits; C, intramembranous deposits; D, sub-epithelial humps; E, fine epimembranous deposits; F, linear glomerular basement membrane deposits; G, mesangial deposits.
Dr. Afsaneh Jeddi