Tubular obstruction

Additional studies of decalin exposure in rats have characterized the specific sequence of renal alterations first the variable occurrence of light-microscopically evident proximal convoluted tubule epithelial cell necrosis, presumably a reflection of cellular injury associated with excessive protein accumulation (hyaline droplets) then the occurrence of granular casts at the junction of the inner and outer bands of the outer zone of the medulla and finally, chronic nephrosis, occurring secondary to tubular obstruction by granular casts. It is not... 

The area of wedge-shaped contrast enhancement increased with the increase in serum creatinine level. When the serum creatinine level exceeded 5 or 6 mg/dl, diffuse contrast enhancement involved the entire kidney. However, even in patients with diffuse contrast enhancement, delayed CT confirmed patchy wedge-shaped contrast enhancement again when the serum creatinine level decreased to 1.2-3.5 mg/dl in the recovery phase (refer to Patient 2 in Fig. 59, Chap. 10, Sect. 1). This finding in the recovery phase cannot be explained by tubular obstruction. 

The mechanism by which these patients develop ALPE also remains to be clarified. However, two hypotheses have been put forward, and active oxygen/renovascular spasm or tubular obstruction may be involved. One hypothesis is that patients with renal hypouricemia are exposed to active oxygen because the level of an active oxygen... 

Radiocontrast-induced renal ischemia may have contributed to the pathogenesis of the dextran-induced renal insufficiency, as has been shown in animal studies. The mechanism of dextran-induced acute renal insufficiency may be multifactorial, with elements of hyperoncotic acute renal insufficiency, tubular obstruction, and direct tubular toxicity. Radiocontrast-induced acute renal insufficiency is unusual in patients with normal baseline creatinine concentrations. The ischemic effect of radiocontrast seemed to be important in this case. Renal function should be carefully monitored if the simultaneous administration of dextran and radiocontrast is necessary. If renal function deteriorates and oliguria or anuria occurs, plasmapheresis may be an appropriate and effective approach for clearing dextran. 

Crystal deposition Particularly important with acyclovir and indinavir, but also noted with sulfonamides, methotrexate and triamterene. This mechanism is becoming more recognized due to the rise in the incidence of tumor-lysis syndrome with AKI. Acute kidney injury caused by tubular obstruction can also occur with a number of drugs (Table 2), due to intratubular precipitation of the... 

As the glomerular filtrate proceeds down the tubule, the filtrate becomes increasingly concentrated and the pH of the filtrate becomes more acidic. Therefore chemicals with pH-dependent solubility have the potential to precipitate and cause tubular obstruction, resulting in local interstitial inflammation, granuloma formation, and fibrosis. Indinavir is a protease inhibitor used in the treatment of immunodeficiency virus that has been reported to cause renal toxicity. The solubility of indinavir is pH- and flow-dependent, and some patients treated with indinavir form urinary crystals that obstruct tubules, leading to inflammation or granuloma formation, resulting in renal failure [23]. 

From an epidemiological point of view, among the causes of AKI of a medical nature, drug-induced and toxic AKI are very important [77]. Nephrotoxic substances include a wide variety of compounds such as heavy metal ions, organic solvents, antibodies and natural toxins. Nephrotoxins induce AKI in humans by direct cellular toxicity, vasoconstriction, and crystal-mediated tubular obstruction. Acute interstitial inflammation is an important factor in pathogenesis of acute interstitial nephritis. In general, a decrement of... 

Rabbit Glycerol 7.5g/kg Tubular obstruction Proximal tubules [196]... 

Rat Gentamycin 40-120 mg/kg/day Decreased ultrafiltration coefficient Tubular obstruction Proximal convoluted tubule [197-199]... 

Neugarten J, Aynedjian HS, Bank N Role of tubular obstruction in acute renal failure due to gentamicin. Kidney Int 24 330-335, 1983... 

Examples angiotensin converting enzyme (ACE) inhibitors, cyclosporine, nonsteroidal antiinflammatory drugs (NSAIDs) Tubular obstruction... 

The excretion of contrast agent by the liver or the kidney is not exclusive when either of these organs is in a dysfunctional or diseased state, heterotopic excretion by the other organ will occur to compensate for the impediment (688,781, 783). In patients with renal failure or advanced renal disease, contrast media may still be used to produce nephrograms (689) if the tubular obstruction prevents the passage of urine along the nephron, back-diffusion of the contrast medium into the interstitial volume will occur (791,793,794). During the pe-... 

Mitochondrial dysfunction is believed to play a vital role in the pathogenesis of acute renal failure. In the face of inadequate production of mitochondrial ATP, sodium and calcium efflux from the cell, which requires ATP, is curtailed. This leads to the swelling of the cell and activation of the calcium-calmodulin complex. The latter may activate phospholipases, which in turn can damage the cell membrane and cause swelling of the cell, leading to its death. The cell debris serves as a substrate for tubular obstruction and supports the maintenance phase of acute renal failure. Complications of casts solidifying in the tubular lumen can be avoided by early measures to prevent cell death. 

Adverse effects tend to be mild GI effects—dyspepsia, constipation and flatulence. More serious effects, such as renal tubular obstruction, rhabdomyolysis and myopathy, have been reported. These are most likely to occur with concurrent therapy of other drugs that inhibit the metabolism of the drug (e.g., systemic anti-fungals or macrolide antibiotics) or with consumption of grapefruit. Elevated liver enzymes (e.g., transaminase) may also be present. 

The renal concentrating mechanisms can increase by the concentration of a neph-rotoxicant in the glomerular hltrate and/or lead to an accumulation of a compound within the proximal tubular cells, which can be several fold times the levels found in the plasma thus both or either of these factors can lead to cellular toxicity. These compounds, which are concentrated as they move down the nephron, can cause injury to the renal medulla and papilla (e.g., phenacetin). Some compounds may alter renal function by relatively simple processes, such as tubular obstruction by crystal formation (e.g., some antiviral compounds) (Izzedine, Launay-Vacher, and Deray... 

Clinical picture was consistent with tubular obstruction by U A and/or oxidized derivatives of adenine. Adenine is oxidized by xanthine oxidase to 2,8-dioxyadenine, a compound with a very low solubility and a definite toxic effect on kidney Therefore it is likely that dioxyadenine was the initiating factor... 

Tubular obstruction. The CFR can be diminished when obstructing casts, composed of hemoglobin or myoglobin pigments, necrotic tubule cells, and aystals, form in damaged renal tubules. 

The role of Dextran 40 (= low molecular weight dextran) in inducing acute renal failure has been reviewed (27), and its mechanism discussed. The recently reported acute glomerulonephritis appears to be mediated through a hypersensitivity phenomenon. Osmotic nephropathy is a well-known complication of dextran infusion. In dehydrated states Dextran 40 is concentrated in the proximal tubules, producing a viscid fluid which can cause tubular obstruction. 

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