Tubulointerstitial nephritis

Acute drug-related hypersensitivity reactions (allergic responses) may cause tubulointerstitial nephritis, which will damage the tubules and interstitium. These reactions are most commonly observed with administration of methicillin and other synthetic antibiotics as well as furosemide and the thiazide diuretics. The onset of symptoms occurs in about 15 days. Symptoms include fever, eosinophilia, hematuria (blood in the urine), and proteinuria (proteins in the urine). Signs and symptoms of acute renal failure develop in about 50% of the cases. Discontinued use of the drug usually results in complete recovery however, some patients, especially the elderly, may experience permanent renal damage. 

Tubulointerstitial disease Acute allergic interstitial nephritis Pamidronate Nephrocalcinosis... 

Mice exposed to 100 or 50 ppm 6 hour/day, 5 days/week for 2 or 4 weeks developed tubulointerstitial nephritis at the high dose kidney lesions were not observed in the mice exposed to 50 ppm, but histopathologic changes in the nasal mucosa were evident." ... 

Tubulointerstitial nephritis Reports of tubulointerstitial nephritis with medullary calcification and cortical atrophy have been observed in patients with asymptomatic severe leukocyturia (greater than 100 cells/high power field). 

Chronic tubulointerstitial nephritis with renal insufficiency without antineutrophil cytoplasmic antibodies has been attributed to propylthiouracil (55). 

Nakahama H, Nakamura H, Kitada O, Sugita M. Chronic drug-induced tubulointerstitial nephritis with renal failure associated with propylthiouracil therapy. Nephrol Dial Transplant 1999 14(5) 1263-5. 

Lithium-associated changes in kidney morphology include an acute, reversible, and possibly lithium-specific distal tubular lesion and a chronic, nonspecific, and tubulointerstitial nephritis (379). The differential diagnosis of the latter is extensive, and it is not clear if lithium is causative. Lithium received a brief mention in a review of tubulointerstitial nephritis (379). 

The main targets of heavy metal toxicity are the kidneys and central nervous system. In humans, occupational or environmental exposure of inorganic heavy metals is known to be nephrotoxic at relatively high levels of exposure, with numerous reports of tubulointerstitial nephritis possibly... 

A prerenal mechanism secondary to the vascular leak syndrome is commonly involved in the pathophysiology of acute renal insufficiency. In addition it has been suggested that a direct intrinsic intrarenal effect of aldesleukin with a higher than expected reduction in glomerular filtration rate or tubular dysfunction (85,89) is involved. Several isolated cases of acute interstitial or tubulointerstitial nephritis with predominant T lymphocjde infiltration of the kidneys (90-92) and the exacerbation of a subchnical IgA glomerulonephritis (93) suggested altered cell-mediated immunity. 

As more experience accumulates it appears clear that COX-2 inhibitors have a nephrotoxic potential similar to that of the non-selective NSAIDs. Sixteen cases of tubulointerstitial nephritis were reported to the manufacturers of celecoxib between the time when it was launched in 1999 and July 2001, but the diagnosis was not confirmed in 12 of these cases (10). Most of these renal adverse reactions occur in patients with susceptibility factors associated with prostaglandin-dependent renal function (11-13). 

In a report of acute tubulointerstitial nephritis in a patient receiving cefdinir, it was stated that among 41 kinds of cephalosporins available in Japan, this complication has been reported with 12 (129). 

The outcome of drug-induced acute tubulointerstitial nephritis can be life-long dialysis or renal transplantation if it is not adequately treated in time. The authors therefore concluded that it is important to look out for this complication when using any cephalosporin. 

A patient developed acute renal insufficiency after ciprofloxacin overdose. This was mediated by tubulointerstitial nephritis with distal nephron apoptosis, as evidenced by renal biopsy (39). 

Chronic tubulointerstitial nephritis has been reported with furosemide. 

A 25-year-old woman developed biopsy-proven chronic tubulointerstitial nephritis with accompanying distal renal tubular acidosis in association with furosemide abuse (up to 1.2 g/day for several months) (9). 

Park CW, You HY, Kim YK, Chang YS, Shin YS, Hong CK, Kim YC, Bang BK. Chronic tubulointerstitial nephritis and distal renal tubular acidosis in a patient with frusemide abuse. Nephrol Dial Transplant 2001 16(4) 867-9. 

Several reports have suggested that patients using indinavir may also develop a syndrome consisting of back or flank pain, accompanied by crystalluria, renal function abnormalities, and evidence of tubulointerstitial nephritis on renal biopsy, but without obvious renal calculus formation (15-17). 

Two reports have suggested that levofloxacin can cause tubulointerstitial nephritis (23). A case of nephrotoxicity and purpura associated with levofloxacin has also been reported allergic interstitial nephritis or vasculitis was believed to be the underlying pathologic process (24). 

Wood ML, Schlessinger S. Levaquin induced acute tubulointerstitial nephritis—two case reports. J Miss State Med Assoc 2002 43(4) 116-17. 

Rastegar A, Kashgarian M. The chnical spectrum of tubulointerstitial nephritis. Kidney Int 1998 54(2) 313-27. 

Acute tubulointerstitial nephritis has been reported in relation to various penicillins, including penicillin G, ampicillin, and amoxicillin (98-102), dicloxacillin (103), meticillin (104-109), nafcillin (110,111), oxacillin (107), and piperacillin (112-114). However, meticillin is the prototype that has caused this reaction more often than any other beta-lactam. 

Tanaka H, Waga S, Kakizaki Y, Tateyama T, Koda M, Yokoyama M. Acute tubulointerstitial nephritis associated... 

Rofecoxib 12.5 mg bd for arthritic pain was associated with biopsy-proven acute tubulointerstitial nephritis in a 67-year-old woman. 

Rocha JL, Fernandez-Alonso J. Acute tubulointerstitial nephritis associated with the selective COX-2 enzyme inhibitor, rofecoxib. Lancet 2001 357(9272) 1946-7. 

Tomita N, Kanamori H, Fujita H, Manila A, Naitoh A, Nakamura S, Ota Y, Nozue N, Kihara M, Ishigatsubo Y. Granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid. Anticancer Drugs 2001 12(8) 677-80. 

In five patients with prior normal renal function, zomepirac caused acute renal insufficiency, with varying degrees of uremia, proteinuria, and oliguria (5). All recovered either after withdrawal or with prednisone therapy. In another case renal biopsy showed a tubulointerstitial nephritis (6). 

The appearance in the urine of epithelial cells is most likely a result of tubular injury. These cells may be present alone or in casts and be indicative of either acute or chronic tubulointerstitial nephritis. Since casts may dissolve in alkaline urine, an acid urine sample is preferred for analysis. 

Viscosity of THP solutions increases markedly when the sodium chloride concentration is > 60 mM. Increasing the concentration of calcium and/.or a reduction in pH also increase viscosity and may account for the involvement of THP in the pathogenesis of cast nephropathy and tubulointerstitial nephritis. THP appears to have an inhibitory effect on urinary crystal arrgegation [154] and may play a role in preventing renal stone formation [155]. In some humans with calcium oxalate nephrolithiasis, a molecular abnormality of THP has been detected [156]. Other studies showed decreased urinary levels of THP in patients with nephrolithiasis [157, 158]. A relative deficiency in THP has been associated with impaired inhibition of crystal adhesion to renal epithelial cells instone formers [159]. 

Lee JW, Kim HJ, Sung SH, Lee SJ. A case of tubulointerstitial nephritis and uveitis syndrome with severe immunologic dysregula-tion. Pediatr Nephrol 2005 20 1805-1808. 

The classical symptoms of drug-induced hypersensitivity reactions include fever, rashes, arthralgias, eosinophilia, eosinophiluria. Hematuria, sterile pyuria, moderate proteinuria and renal failure are observed in patients with drug-induced immune tubulointerstitial nephritis (discussed in [72]). The interstitial inflammatory cells include eosinophils, lymphocytes, monocytes. 

Non-steroidal anti-inflammatory drugs are known to induce a nephrotic syndrome in addition to acute tubulointerstitial nephritis (discussed in [77]). Glomerulopathies include minimal change disease, focal glomerulosclerosis that could represent a continuum with the former entity and membranous glomerulopathy. A review of 97 patients with non-steroidal anti-in-... 

---