Nephrotic syndrome NSAIDs

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... 

Loop diuretics induce renal prostaglandin synthesis, and these prostaglandins participate in the renal actions of these drugs. NSAIDs (eg, indomethacin) can interfere with the actions of the loop diuretics by reducing prostaglandin synthesis in the kidney. This interference is minimal in otherwise normal subjects but may be significant in patients with nephrotic syndrome or hepatic cirrhosis. 

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. 

Because the sulfide may be reoxidized to the inactive prodrug in the kidney, sulindac may inhibit renal COX less than other NSAIDs, though reversible renal failure and nephrotic syndrome have been observed with this drug. Among the more severe reactions, Stevens-Johnson epidermal necrolysis syndrome, thrombocytopenia, agranulocytosis, and nephrotic syndrome have all been observed. Like diclofenac, sulindac may have some propensity to cause elevation of serum aminotransferases it is also sometimes associated with cholestatic liver damage, which disappears or becomes quiescent when the drug is stopped. 

Acute renal failure, e.g. cuninoglycosides, cisplatin Nephrotic syndrome, e.g. penicillamine, gold, cap-topril (only at higher doses than now recommended) Chronic renal failure, e.g. NSAIDs Functional impairment, i.e. reduced ability to dilute and concentrate urine (lithium), potassium loss in urine (loop diuretics), acid-base imbalance (acetazolamide). 

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). 

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). 

Like many other NSAIDs, ketoprofen can cause acute interstitial nephritis (10). Renal insufficiency and the nephrotic syndrome due to membranous glomerulonephritis (an unusual cause of NSAID-induced nephrotic syndrome) have been described in an elderly patient taking long-term ketoprofen (SEDA-12, 86). 

Low-dose methotrexate is usually not regarded as nephrotoxic, and one report of nephrotic syndrome with minimal change disease on renal biopsy should be regarded with caution, since there was recovery after glucocorticoid treatment and withdrawal of concomitant NSAIDs (SEDA-22, 416). 

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

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. 

Sulindac may be less hkely to cause renal toxicity than other NSAIDs (32), at least when it is used in low dosages, but there is some disagreement on this point (33-35), and five cases of nephrotic syndrome and renal insufficiency have been described (36,37). 

In this case, end-stage renal disease with nephrotic syndrome and insulin-dependent diabetes mellitus were predisposing factors to the development of hyperkalemia, but a possible role of accumulated tolfenamic acid meta-bohtes could not be excluded. Patients with severe renal insufficiency should not receive NSAIDs. 

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]. 

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]. 

To summarize patient a risk of NSAID-induced AKI. Frequency will be greater in patient populations with restricted renal blood flow, e.g. CHF, cirrhosis, nephrotic syndrome, shock. However, for absolute numbers, the elderly are probably most at risk since they are the primary group who take NSAIDs for re-heve rheumatic complaints [3]. 

Risk factors for NSAID-induced nephrotic syndrome... 

The risk factors associated with NSAID-related nephrotic syndrome are not well identified. Underlying renal impairment does not appear to be a risk factor. Old age has been identified as a risk factor [33, 88], but this may also be a reflection of the usual... 

Nonsteroidal anti-inflammatory drugs (NSAIDs Group toxicity decreases renal function and platelet aggregati and stroke 3n may cause nephrotic syndrome, interstitial nephritis, hyperkalemia, sodium retention carries increased risk of CVD, Ml, ... 

Lithium carbonate 0.9-1.2gq.24hr Renal 100% 50-75% 25-50% Nephrotoxic adverse effects include nephrogenic diabetes insipidus, nephrotic syndrome, renal tubular acidosis, and interstitial fibrosis acute toxicity when serum levels > 1.2 mEq/L serum levels should be measured periodically 12 hr after dosing half life does not reflect extensive tissue accumulation plasma levels rebound after dialysis toxicity enhanced by volume depletion, NSAIDs, and diuretics Dose after dialysis NC Dose for GFR 10-50 ml/min... 

NSAID-induced acute renal failure is treated by discontinuation of therapy and supportive care. Renal failure may be severe, but recovery is usually rapid and dialysis is rarely necessary. Occasionally the hemodynamic insult is sufficiently severe to cause frank tubular necrosis, which can prolong recovery. The differential diagnosis of NSAID hemodynamically-mediated acute renal failure must include NSAID-induced acute interstitial nephritis, with or without the nephrotic syndrome, because steroid therapy may benefit this type of renal injury. 

NSAlD-induced AIN has a different clinical presentation than that seen with most other drugs. Patients are typically over age 50 (reflecting NSAID use for degenerative joint disease), the onset is delayed a mean of 6 months from initiation of therapy, and ex-trarenal symptoms are observed in only 10% of patients. Concomitant nephrotic syndrome (proteinuria >3.5 g/day) occurs inmorethan70% of patients. Eenoprofen-allergic interstitial nephritis is considered the prototype for NSAlD-induced AIN because it accounts for nearly 50% of cases. ... 

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