Acute interstitial nephritis due to pantoprazole

OBJECTIVE: To describe what is believed, as of November 4, 2003, to be the first case published in the literature of acute interstitial nephritis (AIN) due to pantoprazole. CASE SUMMARY: A 77-year-old white woman presented to the hospital with elevated serum creatinine, oliguria for the past 24 hours, arthralgia, fatigue, fever, and bilateral flank pain. The patient had initiated treatment with oral pantoprazole 40 mg/d for gastroesophageal reflux 2 months prior to admission. After 5 weeks of therapy, she stopped taking pantoprazole due to general malaise. Upon admission, all home medications, including pantoprazole, were reinitiated based on the patient's medication list. Serum creatinine increased to 6.1 mg/dL on day 4 of admission from a baseline of 1.0 mg/dL. Pantoprazole therapy was promptly discontinued, and prednisone 40 mg/d was initiated. Urinalysis revealed eosinophils, and a subsequent renal biopsy confirmed a diagnosis of AIN. The serum creatinine level gradually declined over 2 weeks, and the patient was discharged home with a serum creatinine level of 1.6 mg/dL. The Naranjo probability scale suggests a highly probable relationship between AIN and pantoprazole therapy in this patient. DISCUSSION: Drug hypersensitivity reactions are the most common cause of AIN. There have been several reported cases of omeprazole-induced AIN. Although there are very few prospective data on the efficacy of treatment of drug-induced AIN, corticosteroids may have a role in recovery of renal function. Prednisone doses of 1 mg/kg/d have been suggested. CONCLUSIONS: Physicians should be aware that drug-induced AIN can be associated with proton-pump inhibitors. Early detection of this rare adverse reaction may prevent acute renal insufficiency.     

Acute interstitial nephritis

The disease course and prognosis of work fitness were studied in 66 patients with acute interstitial nephritis (AIN). In 68 patients, the disease onset was preceded by antibiotic treatment. The main disease symptom consisted in creatininemia of varying degree, disappearing on the 5th-10th day of the disorder. Prognosis in AIN is favourable. The working capacity gets restored 2-4 months after the disease onset.     

Acute interstitial nephritis in childhood]

Acute tubulointerstitial nephritis (TIN) was diagnosed during a 10-year period in 6 previously healthy children (4 boys) with a mean age of 10 years (range 2.5-14 years). All presented with a non-specific history. First laboratory findings were nearly identical, with a raised erythrocyte sedimentation rate and non-oliguric renal failure; the urine contained protein, glucose, and leucocytes, but no bacteria. A serologically proven infection (streptococcal infection 2x; mononucleosis 1x) or drug-related TIN (penicillin) was present in 4 children; in one, both conditions could have been responsible. One girl suffered from idiopathic TIN with uveitis. Rapid progression of renal failure occurred in 3 children, but the response to steroid therapy was satisfactory. No dialysis was necessary and all patients showed a complete recovery. We think that acute TIN occurs more frequently than suggested previously. Many episodes are probably mild or subclinical and the rate of spontaneous remission is high. The results of initial laboratory evaluation in conjunction with acute renal failure and predominantly proximal tubular dysfunction, are sufficiently typical to arouse suspicion of acute TIN at an early stage, although they do not permit any conclusion as to the aetiology.     

Acute interstitial nephritis associated with moxifloxacin use

BACKGROUND: Moxifloxacin is a fluoroquinolone antimicrobial agent with proven efficacy against community-acquired respiratory pathogens. Common adverse effects associated with its use include gastro-intestinal symptoms, but nephrotoxicity has not yet been reported to the manufacturer or in the literature (based on a MEDLINE search [key words: fluoroquinolone, moxifloxacin, kidney, interstitial, and nephritis; years: 1970-2005]). OBJECTIVE: The purpose of this article was to describe a case of nephrotoxicity associated with moxifloxacin use. METHODS: A 68-year-old woman weighing 65 kg was referred to our nephrology clinic by her general practitioner because of an acute increase in serum creatinine concentration (SCC). In this patient, biopsyproven acute tubulointerstitial nephritis (ATIN) developed approximately 10 days after the end of moxifloxacin therapy for a nonspecific bronchial infection. The patient initially presented with nonspecific clinical symptoms, foaming of her urine, elevated erythrocyte sedimentation rate, and the acute increase in SCC. Urinalysis revealed signs of tubulointerstitial damage, including leukocyturia and proteinuria with a high concentration of alpha(1)-microglobulin. Oral corticosteroid therapy with prednisolone was started approximately 14 days after symptom development, beginning at 1 mg/kg body weight QD. RESULTS: After the initiation of therapy, renal function was gradually restored over 6 months, but mild proteinuria persisted. Although the exact pathogenesis of drug-induced ATIN remains unclear, an immune-mediated hypersensitivity reaction is the assumed mechanism. CONCLUSIONS: Fluoroquinolones might have a nephrotoxic effect. In this patient, ATIN was likely associated with moxifloxacin use. Because the course of ATIN is unpredictable and might lead to long-term dialysis, considering ATIN as a possible diagnosis in the scenario of systemic symptoms after moxifloxacin treatment is essential.     

Acute interstitial nephritis: immunologic and clinical aspects

Acute interstitial nephritis is a common renal syndrome that may be associated with a variety of infections and drug therapies or may develop without an identified cause. Three cases are presented to illustrate the three types of acute interstitial nephritis--drug related, infection related, and idiopathic. Cell-mediated immune mechanisms seem to be more important than humorally mediated mechanisms in the pathogenesis of acute interstitial nephritis. Frequently, eosinophils are identified as a component of the interstitial cellular infiltrate, and eosinophiluria and eosinophilia have been claimed to be helpful in the diagnosis of acute interstitial nephritis, especially the drug-induced type. Neither eosinophiluria nor the presence of increased urinary levels of eosinophil major basic protein, however, is specific for the diagnosis of acute interstitial nephritis. Patients with drug-induced interstitial nephritis frequently have symptoms and signs suggestive of a hypersensitivity syndrome and rarely have more dramatic anaphylactic manifestations. Systemic glucocorticoids have been shown to be beneficial in this type of acute interstitial nephritis.     

Acute interstitial nephritis observed with three different triggering agents

A 70‐year‐old female patient developed acute interstitial nephritis (AIN) after treatment with non‐steroidal anti‐inflammatory drugs (NSAIDs), proton pump inhibitors (PPI), and Bromhexine. Renal biopsy confirmed the diagnosis, and the patient was treated with oral prednisone. Careful attention to timing of acute kidney injury (AKI) is crucial to diagnosing AIN.     

Allergic interstitial nephritis possibly related to sunitinib use

Background: Sunitinib is an oral multitargeted inhibitor indicated for the treatment of renal cell carcinoma.Objective: This report describes a case of allergic interstitial nephritis possibly related to this agent.Case Summary: A 69-year-old female patient with a history of metastatic renal cell carcinoma after left radical nephrectomy presented to our nephrology clinic after completing 2 courses of sunitinib therapy. The patient was noted to have progressive kidney dysfunction with proteinuria, together with peripheral eosinophilia and eosinophiluria, which developed during the first of 2 cycles of sunitinib therapy. Her concomitant medications included atenolol, triamterene/hydrochlorothiazide, amlodipine, and multivitamin tablets, all of which she had been receiving at stable doses over the previous 2 years. There were no other over-the-counter medications involved and other possible causes of interstitial nephritis were excluded. The proteinuria, eosinophilia, and eosinophiluria worsened with the second course and resolved after sunitinib discontinuation, which resulted in initial stabilization followed by slight improvement in kidney function. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 7, indicating a probable association of the event with the drug. With clinical improvement after discontinuation of sunitinib and the presence of a solitary remaining kidney and thrombocytopenia, renal biopsy was not performed after discussion with the patient. When challenged with a related agent, sorafenib, the patient experienced worsening of serum creatinine and increasing eosinophilia, similar to that noted with sunitinib, suggesting that this event may be a class effect.Conclusions: Nephrologists and oncologists should be aware of allergic interstitial nephritis as an adverse effect related to this agent. Although there are no current recommendations for monitoring serum creatinine with sunitinib therapy, we recommend that serum creatinine and white cell count with differential be checked within 2 weeks of initiation of therapy with sunitinib to enable earlier diagnosis of this condition and avoid renal damage.     

Once more about interstitial nephritis

A comparative study was made of 25 patients (Group 2, control) with documented pyelonephritis and 55 patients (Group 1) who had a morphological picture of chronic interstitial inflammation without signs of abnormal urodynamics, bacteriuria, urographic and sonographic evidence of pyelonephritis. All the patients underwent life-time morphological study, their immunological spectrum (IgA, IgG, IgM, IgE) was explored. They had a test for sensitization of a peripheral blood mononuclear fraction to one or several drugs which had been given to the patients. The patients from Group 1 displayed significantly elevated IgE levels and a regularly detected sensitization of mononuclears to one or several drugs. Morphologically, there were signs of congenital renal tissue dysplasia in the presence of diffuse interstitial inflammation. Positive immunofluorescence findings were seen in the tubular wall of 10 (18%) patients. The findings made it possible to define diagnostic criteria for interstitial nephritis, a nosological entity.     

Cloxacillin-induced acute tubulo interstitial nephritis.

OBJECTIVE: To report a case of possible cloxacillin-induced acute tubulo interstitial nephritis (AIN). CASE SUMMARY: A 15-year-old male patient presented with hypertension, edema, lumbar pain, sterile pyuria, eosinophiluria (ten percent), and severe renal dysfunction three months after the ingestion of cloxacillin. A renal biopsy revealed diffuse edema and inflammatory infiltrate of the interstitium (five percent eosinophils). He received four sessions of peritoneal dialysis with dramatic improvement in urinary output and renal function. His biochemical parameters returned to normal values 21 days after admission, without the use of glucocorticosteroids. DISCUSSION: Published case reports on AIN induced by penicillin and related drugs are reviewed and compared. The role of interstitial edema in acute renal failure associated with drug-induced AIN is mentioned. CONCLUSIONS: AIN is a rare but significant complication of therapy with penicillin and related drugs. The clinical picture is similar for all of these drugs, but skin rash and fever are absent in AIN induced by cloxacillin and cloxacillin-related drugs. Dialysis improved the patient's urinary output and renal function. Beta-lactam antibiotics should be avoided in patients with cloxacillin-induced AIN.     

Suppression of interstitial nephritis by auto-anti-idiotypic immunity

Rats immunized with renal tubular antigens were protected from the development of interstitial nephritis by pretreatment with tubular antigen-reactive T lymphoblasts. Protected animals developed anti- idiotypic antibodies against idiotypes primarily within the antigen- binding region of monoclonal antitubular basement membrane antibodies. These studies extend the concept of auto-anti-idiotypic regulation to autoimmune disease, and they also provide an experimental basis for further efforts to develop biologically relevant mechanisms for attenuating the expression of other kidney diseases.     

Diagnosis and management of acute interstitial nephritis

Acute interstitial nephritis is an important cause of acute renal failure resulting from immune-mediated tubulointerstitial injury, initiated by medications, infection, and other causes. Acute interstitial nephritis may be implicated in up to 15 percent of patients hospitalized for acute renal failure. Clinical features are essentially those of acute renal failure from any cause, and apart from a history of new illness or medication exposure, there are no specific history, physical examination, or laboratory findings that distinguish acute interstitial nephritis from other causes of acute renal failure. Classic findings of fever, rash, and arthralgias may be absent in up to two thirds of patients. Diagnostic studies such as urine eosinophils and renal gallium 67 scanning provide suggestive evidence, but they are unable to reliably confirm or exclude the diagnosis of acute interstitial nephritis. Renal biopsy remains the gold standard for diagnosis, but it may not be required in mild cases or when clinical improvement is rapid after removal of an offending agent or medication. The time until removal of such agents, and renal biopsy findings, provide the best prognostic information for return to baseline renal function. Corticosteroids appear to provide some benefit in terms of clinical improvement and return of renal function, but no controlled clinical trials have been conducted to confirm this.     

Mechanisms of the development of chronic interstitial nephritis

Certain developmental mechanisms of chronic interstitial nephritis are discussed. The organism's sensitivity to various medicinal agents is supposedly of importance. Determination of the IgE content has been suggested as a diagnostic test.