Nephrotic syndrome, with interstitial

Acute deterioration of renal function Salt and water retention The concept of "renal sparing" NSAIDs Nephrotic syndrome with interstitial nephritis Chronic renal failure/papillary necrosis Other NSAID-induced renal syndromes Renal effects of COX-2 inhibitors 424 428 430 431 432 434 435... 

The NSAID-induced abnormahties of renal function, in descending order of chnical frequency, are (i) fluid and electrolyte disturbances (ii) destabilizahon of con-troUed hypertension (hi) decompensated congestive heart failure (iv) acute deterioration of renal function (v) nephrotic syndrome with interstitial nephritis and (Vi) chronic renal failure/papillary necrosis [1, 3-5]. 

Aspirin and similar NSAIDs can cause other toxic side effects if used improperly or if taken by patients who have preexisting diseases. For instance, serious hepato-toxicity is rare with normal therapeutic use, but high doses of aspirinlike drugs can produce adverse changes in hepatic function in patients with liver disease.85,99 Likewise, aspirin does not seem to cause renal disease in an individual with normal kidneys,84 but problems such as nephrotic syndrome, acute interstitial nephritis, and even acute renal failure have been observed when aspirin is given to patients with impaired renal function, or people with decreased body water (volume depletion).35,102... 

Whether selective COX-2 inhibitors can cause the other types of renal toxicity that are associated with non-selective NSAIDs (that is acute interstitial nephritis, nephrotic syndrome with or without renal insufficiency) is not known. 

Renal papillary necrosis and interstitial nephritis with the nephrotic syndrome have been documented (27,28). Other cases of the nephrotic syndrome, with or without renal insufficiency, which were apparently due to minimal-change nephropathy (which is relatively more common in NSAID users), have been reported (29,30). The unusual feature of diclofenac-associated renal interstitial mucinosis has been described (SEDA-17, 109). 

A 57-year-old woman developed severe nephrotic syndrome after 3 months of interferon alfa re-treatment, and renal biopsy showed minimal change nephrotic syndrome with T cell-predominant interstitial nephritis (265). Proteinuria persisted despite interferon alfa withdrawal and resolved only after glucocorticoid treatment. 

NSAIDs can produce a spectrum of renal diseases functional renal insufficiency, nephrotic syndrome with or without interstitial nephritis, renal papillary necrosis and... 

Alper AB, Jr., Meleg-Smith S, Krane NK, Alper ABJ, Meleg-Smith S, Krane NK. Nephrotic syndrome and interstitial nephritis associated with celecoxib. American Journal of Kidney Diseases 2002 40 1086-1090. 

Renal effects Acute renal insufficiency, interstitial nephritis with hematuria, nephrotic syndrome, proteinuria, hyperkalemia, hyponatremia, renal papillary necrosis, and other renal medullary changes may occur. 

Rare reactions with long-term use include peptic ulcer disease, G1 bleeding, gastritis, severe hepatic reactions (cholestasis, jaundice), nephrotoxicity (glomerular nephritis, interstitial nephritis, nephrotic syndrome), and an acute hypersensitivity reaction (includingfever, chills, and join pain). 

Extensive literature has accumulated concerning other forms of renal dysfunction during long-term lithium therapy, including chronic interstitial nephritis and minimal-change glomerulopathy with nephrotic syndrome. Some instances of decreased glomerular filtration rate have been encountered but no instances of marked azotemia or renal failure. 

The concomitant administration of ibuprofen antagonizes the irreversible platelet inhibition induced by aspirin. Thus, treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin. Rare hematologic effects include agranulocytosis and aplastic anemia. Effects on the kidney (as with all NSAIDs) include acute renal failure, interstitial nephritis, and nephrotic syndrome, but these occur very rarely. Finally, hepatitis has been reported. 

A retrospective analysis of acute renal insufficiency related to NSAID therapy in France showed that clo-metacin was most frequently implicated. Cases of functional renal insufficiency and interstitial nephritis with nephrotic syndrome were reported (SEDA-12, 84). 

Ibuprofen can cause renal impairment, ranging from an insignificant reduction to an acute fall in creatinine clearance associated with a general hypersensitivity reaction, especially in patients with systemic lupus erythematosus or acute tubular necrosis (20). The nephrotic syndrome without renal insufficiency and acute interstitial nephritis without the nephrotic syndrome have been described after self-administration of over-the-counter ibuprofen (SEDA-12, 86). 

Phenindione can cause renal insufficiency and the nephrotic syndrome, usually preceded by fever and skin reactions. In such cases, renal biopsy shows interstitial edema with infiltration by eosinophils and plasma cells. Tubular necrosis has also been observed(9). 

Averbuch SD, Austin HA 3rd, Sherwin SA, Antonovych T, Bunn PA Jr, Longo DL. Acute interstitial nephritis with the nephrotic syndrome following recombinant leukocyte a interferon therapy for mycosis fungoides. N Engl J Med 1984 310(l) 32-5. 

Oliguric renal insufficiency with the nephrotic syndrome and active interstitial nephritis has been described in a young woman with systemic lupus erythematosus taking intermittent long-term naproxen (SEDA-15,102). 

Membranous nephropathy is rare and causes the nephrotic syndrome, usually with minimal-change glomerulopathy, with or without interstitial nephritis (SEDA-11, 85). A retrospective study provided more data on the frequency and clinical characteristics of membranous nephropathy associated with NSAIDs (158). It confirmed that it is rare (13 of 125 patients diagnosed during the last 20 years met the strict criteria for NSAID-associated membranous nephropathy), and the nephrotic syndrome is reversible after prompt withdrawal. The pathogenesis is unknown but seems to be immune-mediated, given the characteristic deposition of IgG and C3. 

It is worth emphasizing that the same drug is capable of inducing several types of renal injury, e.g. NSAIDs may lead to intrarenal hemodynamic disturbances as well as to acute tubular necrosis, acute interstitial nephritis with or without nephrotic syndrome, and sometimes to various glomerular and arteriolar diseases [50,51]. 

Makino H, HaramotoT, SasakiT, Hironaka K, Shikata K,Takahashi K, Ota Z Massive eosinophilic infiltration in a patient with the nephrotic syndrome and drug-induced interstitial nephritis. Am J Kidney Dis 1995 26 62-7. 

Cahan DH, UccI AA. Acute renal failure, interstitial nephritis, and nephrotic syndrome associated with captopril. Kidney Int 1984 25 160. 

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