Distal nephron injury

Other enzymes (lactate dehydrogenase, LDH, and aspartate aminotransferase, AST) also indicate tubular injury when present in the urine but they cannot be localized to a specific nephron segment. Despite this, LDH is commonly used as a marker for distal tubular injury (Price 1982 Guder and Ross 1984 Clemo 1998). 

Proximal tubule Distal nephron Cellular injury ... 

Major functions of the distal nephron include the regeneration of bicarbonate, the excretion of acid (hydrogen ion), the secretion of potassium, and the reabsorption of water. Damage to this portion of the nephron may present as significant acidemia and either hypo-or hyperkalemia, depending on the mechanism of injury. For example, amphotericin B produces small pores in the luminal membrane of distal tubular cells. These pores allow small molecules such as potassium to leak out the molecules are then wasted in the urine. Consequently, amphotericin B nephrotoxicity is characterized by hypokalemia secondary to renal potassium wasting. ATN is associated with urinary sediment characterized by the presence of tubular cells, coarse granular casts, and rarely, RBC casts. 

Nouwen EJ, Verstrepen WA, Buyssens N, Zhu MQ, De Broe ME. Hyperplasia, hypertrophy, and phenotypic alterations in the distal nephron after acute proximal tubular injury in the rat. Lab Invest 1994 479-493. 

Among the various published observations for enzyme measurements, evidence has been provided for several enzymes however, none of these suggestions have been widely applied. These observations include the differing distributions of LDH and NAG isoenzymes along the nephron these have also been suggested as regional markers of nephron toxicity used to differentiate between proximal and distal tubular injury (Bombard et al. 1990 Morita et al. 1998). 

Toxic injury to the distal nephron is relatively uncommon, and injury to this area generally manifests as decreased urine concentrating ability or as defects in acid secretion resulting in metabolic acidosis (Khan et al., 2013). Injury to the renal papilla is most commonly seen with toxicants that impede blood flow to this normally poorly perfused area. Direct injury to renal papillae from renally excreted irritants (e.g., vesicants such as cantharidin) may also occur. 

Fourth, certain segments of the nephron have a capacity for metabolic bioactivation. For example, the proximal and distal tubules contain isozymes of the cytochrome P450 monooxygenase system that may mediate intrarenal bioactivation of several protoxicants. Additionally, prostaglandin synthetase activity in medullary and papillary interstitial cells may be involved in cooxidation of protoxicants, resulting in selective papillary injury. 

Therefore, the kidneys receive 25 % of cardiac output and filter large volumes of plasma. As the filtrate moves along the nephron, its components are concentrated greater than threefold in the proximal tubule and greater than 100-fold in the distal tubule and the collecting ducts. As a result, the renal tubular and interstitial cells are exposed to high concentrations of medications and their metabolites, which predispose the kidneys to injury (Choudhury and Ahmed 2006). 

FIGURE 43.2 Cartoon of the nephron and lower urinary tract showing sites of injury caused by various chemical and biological warfare agents (A, afferent arteriole G, glomerulus B, Bowman s capsule P, proximal tubule L, loop of Henle D, distal tubule C, collecting ducts R, renal pelvis UR, ureter UB, urinary bladder UA, urethra). 

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