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The kidneys have several essential homeostatic functions. These functions include waste removal (NH3), fluid/electrolyte balance, metabolic blood acid-base balance, and the production/modification of hormones for blood pressure, calcium/potassium homeostasis, and red blood cell production. The renal corpuscle (filtration unit, which comprises the glomerulus and the surrounding the Bowman capsule) and tubules (reabsorption and excretion) of the kidney perform the majority of these functions. The primary function of the kidney, filtering blood, is in part due to its unique blood flow, with high perfusion autoregulation of flow across the glomerular capillaries over a range of pressures. The kidneys receive about 20% of the cardiac output, thereby enabling the filtration of large volumes of blood. Blood flow autoregulates across the filtration capillaries (glomeruli) due to the unique arrangement of blood vessels. The glomerulus, in contrast to the majority of other capillary beds, sits between 2 arterioles; receiving blood supply from the upstream afferent arteriole, and blood exiting downstream via the efferent arterioles (E for exit). This arrangement allows precise control of glomerular flow and filtration rate via autoregulatory changes in the diameters of these resistance arterioles (vasodilation/vasoconstriction). The primary function of the kidney is to filter blood and form urine. The histological structures of the kidney's filtering units (renal corpuscles) are crucial for this function. The renal corpuscles are located only in the kidney cortex, with about 1 million per kidney; variation by race is common. This unique filtration barrier comprises 3 histological structures: the capillary endothelium of the glomeruli, specialized cells called podocytes, and the fused basement membranes of these cells (Figure 1). This filtration barrier allows the filtration of small molecules, including water, ions, creatinine, and glucose, as well as small proteins (less than 90 kDa). This structure must prevent the filtration of large proteins present in the blood, such as albumin and immunoglobulins.

The primary function of the kidney is to filter blood and form urine. The histological structures of the kidney's filtering units (renal corpuscles) are crucial for this function. The renal corpuscles are located only in the kidney cortex, with about 1 million per kidney; variation by race is common. This unique filtration barrier comprises 3 histological structures: the capillary endothelium of the glomeruli, specialized cells called podocytes, and the fused basement membranes of these cells (Figure 1). This filtration barrier allows the filtration of small molecules, including water, ions, creatinine, and glucose, as well as small proteins (less than 90 kDa). This structure must prevent the filtration of large proteins present in the blood, such as albumin and immunoglobulins. Any aberrance of this filtration barrier leads to pathological conditions. Indeed, about 90% of end-stage kidney disease is due to glomerular diseases.[1] The primary concern is that once damaged, the kidneys have limited capacity for repair. Indeed, most forms of glomerular disease develop gradually, with symptoms only appearing after a significant proportion of the kidney's functional units are damaged.

There are several signs of glomerular dysfunction that can be used in diagnosis and to distinguish nephrotic from nephritic syndromes. Protein in the urine (proteinuria): This is a hallmark measure of renal disease, and the primary measure used to differentiate between nephrotic and nephritic syndromes. Protein in the urine can result from glomerular disease, which causes proteins to leak into the urine, or from a defect in protein reabsorption in the kidney tubules. Proteinuria may cause foamy urine. Generally, a very high protein concentration in the urine, or "nephrotic range" >200 mg/l, is associated with podocyte disruption, resulting in non-selective protein loss.[4] Loss of protein into the urine is typically associated with reduced protein or albumin in the blood (proteinuria or hypoalbuminemia). Blood in the urine (hematuria): The presence of hemoglobin from leaked red blood cells gives the urine a pink or light brown (cola-colored). This presentation is a typical symptom of nephritic syndrome, along with lower proteinuria, which is associated with nephritic syndrome attributable to a defect in the glomerular basement membrane. Edema: Protein loss from the blood reduces colloid oncotic pressure and increases capillary filtration, leading to excess, non-resorbed fluid accumulation within the intercellular spaces, causing swelling. This swelling due to edema is usually more noticeable in the hands, ankles, or periorbitally. Uremia: reduced glomerular filtration rate. Disruption of the barrier can also result in reduced filtration, leading to the accumulation of waste products. Creatinine and urea nitrogen in the blood. Acidosis: This is beyond the scope of a discussion of the glomerulus, but it still bears mentioning. Kidney tubules are involved in metabolic acid-base homeostasis, which regulates blood pH. Tables 1-3 and Legends

Uremia: reduced glomerular filtration rate. Disruption of the barrier can also result in reduced filtration, leading to the accumulation of waste products. Creatinine and urea nitrogen in the blood. Acidosis: This is beyond the scope of a discussion of the glomerulus, but it still bears mentioning. Kidney tubules are involved in metabolic acid-base homeostasis, which regulates blood pH. Tables 1-3 and Legends Table 1: Diseases with Nephritic syndromes. This syndrome is a set of symptoms generally attributed to inflammatory processes, and not a disease in itself. It involves disruption of the glomerular basement membrane, and common features include hypertension (salt retention), increased blood urea nitrogen (BUN), creatinine, oliguria, hematuria, and red blood cell casts. Proteinuria of less than approximately 3.5 g/day. References for diseases in table 1: Le et al 2019, First Aid for the USMLE, McGraw-Hill, pp. 583-5. Key: GBM= glomerular basement membrane, LM= light microscopy, IF= immunofluorescence, EM= electron microscopy, IgG= immunoglobulin G, C3= complement C3. Table 2: Diseases with Nephrotic syndromes. This syndrome is also a set of symptoms and not a disease in itself. It can occur with many diseases; thus, the basis of prevention is controlling the underlying causal diseases. This syndrome is generally due to podocyte disruption, which impairs the charge barrier. This syndrome is characterized by massive proteinuria > 3.5g/day with hypoalbuminemia, hyperlipidemia, and edema.[22] Also, there is an increased risk of venous thromboembolism in adults, especially of the renal vein. Edema is due to the loss of proteins. Dyslipidemia was originally thought to be due to increased albumin metabolism in the liver, but it may now be due instead to altered lipoprotein synthesis and cholesterol transport from peripheral tissues to the liver.[23][24] Thromboembolism is due to the loss of the clotting protein antithrombin III.[24] References for diseases in table 2: Le et al 2019 First Aid for the USMLE McGraw Hill pp 583-585.[1][22][1][25][26][27][28] Key: GBM= glomerular basement membrane, LM= light microscopy, IF= immunofluorescence, EM= electron microscopy, IgG= immunoglobulin G, C3= complement C3.

Table 2: Diseases with Nephrotic syndromes. This syndrome is also a set of symptoms and not a disease in itself. It can occur with many diseases; thus, the basis of prevention is controlling the underlying causal diseases. This syndrome is generally due to podocyte disruption, which impairs the charge barrier. This syndrome is characterized by massive proteinuria > 3.5g/day with hypoalbuminemia, hyperlipidemia, and edema.[22] Also, there is an increased risk of venous thromboembolism in adults, especially of the renal vein. Edema is due to the loss of proteins. Dyslipidemia was originally thought to be due to increased albumin metabolism in the liver, but it may now be due instead to altered lipoprotein synthesis and cholesterol transport from peripheral tissues to the liver.[23][24] Thromboembolism is due to the loss of the clotting protein antithrombin III.[24] References for diseases in table 2: Le et al 2019 First Aid for the USMLE McGraw Hill pp 583-585.[1][22][1][25][26][27][28] Key: GBM= glomerular basement membrane, LM= light microscopy, IF= immunofluorescence, EM= electron microscopy, IgG= immunoglobulin G, C3= complement C3. Table 3: Diseases with both Nephritic-nephrotic syndromes. Severe nephritic syndrome with profound glomerular basement membrane damage, resulting in a change of the charge barrier. Nephrotic range proteinuria (>3.5 g/day) and features of nephrotic syndrome. Reference for diseases in table 3: Le et al 2019 First Aid for the USMLE McGraw Hill pp 583-5.[22][25] Key: GBM= glomerular basement membrane, LM= light microscopy, IF= immunofluorescence, EM= electron microscopy, IgG= immunoglobulin G, C3= complement C3.