Advertisement
Original Investigation Pathogenesis and Treatment of Kidney Disease| Volume 64, ISSUE 4, P558-566, October 01, 2014

Biopsy-Proven Acute Interstitial Nephritis, 1993-2011: A Case Series

      Background

      Acute interstitial nephritis (AIN) is an important cause of acute kidney injury, especially in hospitalized patients. The cause and outcome of AIN, particularly that due to drugs, is changing with prevalent medication use. The effectiveness of steroids for treatment of AIN is debated.

      Study Design

      Case series.

      Setting & Participants

      133 patients with biopsy-proven AIN from 1993 through 2011 at a single center.

      Outcomes

      Recovery of kidney function by 6 months, either complete, partial, or none. Complete recovery was defined as improvement in serum creatinine level to within 25% of baseline (or <1.4 mg/dL), and partial recovery, as a ≥50% decrease in serum creatinine level from its peak value but not reaching within 25% of its baseline value.

      Results

      Causes of AIN included drugs (70%), autoimmune diseases (20%), and infections (4%). Drug-induced AIN was due to antibiotics in 49%, proton pump inhibitors (PPIs) in 14%, and nonsteroidal anti-inflammatory drugs (NSAIDs) in 11%. Overall, the top 3 drug causes were omeprazole (12%), amoxicillin (8%), and ciprofloxacin (8%).  Patients with drug-induced compared to non-drug-induced AIN were older and had higher baseline kidney function, but more severe acute kidney injury. Patients with PPI-induced AIN were older, were less symptomatic, and had longer durations of drug exposure and longer delays in getting kidney biopsy and steroids than for antibiotic-induced or NSAID-induced AIN. At 6 months postbiopsy, 49% of patients with drug-induced AIN treated with steroids achieved complete recovery; 39%, partial recovery; and 12%, no recovery. Correlates of poor recovery included a longer duration of drug exposure (15 vs 30 vs 130 days for complete, partial, and no recovery, respectively; P = 0.04) and longer delay in starting steroid therapy (8 vs 11 vs 35 days, respectively; P = 0.05).

      Limitations

      Retrospective study, selection bias in patients who had kidney biopsy, single-center experience.

      Conclusions

      The cause of AIN may be shifting; PPIs are emerging as an important contributor to this disease. Delays in discontinuation of the culprit drug and in initiating steroid treatment adversely affect recovery of kidney function.

      Index Words

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Biermer A.
        Ein ungervohnlicher Fall von Scharlach.
        Virchows Arch Pathol Anat. 1860; 19: 537-545
        • Councilman W.T.
        Acute interstitial nephritis.
        J Exp Med. 1898; 3: 393-420
        • Councilman W.T.
        Acute interstitial nephritis.
        J Boston Soc Med Sci. 1898; 2: 189-192
        • More R.H.
        • McMillan G.C.
        • Duff G.L.
        The pathology of sulfonamide allergy in man.
        Am J Pathol. 1946; 22: 703-735
        • Baldwin D.S.
        • Levine B.B.
        • McCluskey R.T.
        • Gallo G.R.
        Renal failure and interstitial nephritis due to penicillin and methicillin.
        N Engl J Med. 1968; 279: 1245-1252
        • Rossert J.
        Drug-induced acute interstitial nephritis.
        Kidney Int. 2001; 60: 804-817
        • Michel D.M.
        • Kelly C.J.
        Acute interstitial nephritis.
        J Am Soc Nephrol. 1998; 9: 506-515
        • Schwarz A.
        • Krause P.H.
        • Kunzendorf U.
        • Keller F.
        • Distler A.
        The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis.
        Clin Nephrol. 2000; 54: 179-190
        • Perazella M.A.
        • Markowitz G.S.
        Drug-induced acute interstitial nephritis.
        Nat Rev Nephrol. 2010; 6: 461-470
        • Neilson E.G.
        Pathogenesis and therapy of interstitial nephritis.
        Kidney Int. 1989; 35: 1257-1270
        • Clarkson M.R.
        • Giblin L.
        • O'Connell F.P.
        • et al.
        Acute interstitial nephritis: clinical features and response to corticosteroid therapy.
        Nephrol Dial Transplant. 2004; 19: 2778-2783
        • Brewster U.C.
        • Perazella M.A.
        Proton pump inhibitors and the kidney: critical review.
        Clin Nephrol. 2007; 68: 65-72
        • Simpson I.J.
        • Marshall M.R.
        • Pilmore H.
        • et al.
        Proton pump inhibitors and acute interstitial nephritis: report and analysis of 15 cases.
        Nephrology (Carlton). 2006; 11: 381-385
        • Geevasinga N.
        • Coleman P.L.
        • Roger S.D.
        Rabeprazole-induced acute interstitial nephritis.
        Nephrology (Carlton). 2005; 10: 7-9
        • Geevasinga N.
        • Kairaitis L.
        • Rangan G.K.
        • Coleman P.L.
        Acute interstitial nephritis secondary to esomeprazole.
        Med J Aust. 2005; 182: 235-236
        • Ray S.
        • Delaney M.
        • Muller A.F.
        Proton pump inhibitors and acute interstitial nephritis.
        BMJ. 2010; 341: c4412
        • Raissian Y.
        • Nasr S.H.
        • Larsen C.P.
        • et al.
        Diagnosis of IgG4-related tubulointerstitial nephritis.
        J Am Soc Nephrol. 2011; 22: 1343-1352
        • Gonzalez E.
        • Gutierrez E.
        • Galeano C.
        • et al.
        Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis.
        Kidney Int. 2008; 73: 940-946
        • National Kidney Foundation
        K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.
        Am J Kidney Dis. 2002; 39: S1-S266
        • Mehta R.L.
        • Kellum J.A.
        • Shah S.V.
        • et al.
        Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.
        Crit Care. 2007; 11: R31
        • Farrington K.
        • Levison D.A.
        • Greenwood R.N.
        • Cattell W.R.
        • Baker L.R.
        Renal biopsy in patients with unexplained renal impairment and normal kidney size.
        Q J Med. 1989; 70: 221-233
        • Haas M.
        • Spargo B.H.
        • Wit E.J.
        • Meehan S.M.
        Etiologies and outcome of acute renal insufficiency in older adults: a renal biopsy study of 259 cases.
        Am J Kidney Dis. 2000; 35: 433-447
        • Goicoechea M.
        • Rivera F.
        • Lopez-Gomez J.M.
        Increased prevalence of acute tubulointerstitial nephritis.
        Nephrol Dial Transplant. 2013; 28: 112-115
        • Bomback A.S.
        • Markowitz G.S.
        Increased prevalence of acute interstitial nephritis: more disease or simply more detection?.
        Nephrol Dial Transplant. 2013; 28: 16-18
        • Mahevas M.
        • Lescure F.X.
        • Boffa J.J.
        • et al.
        Renal sarcoidosis: clinical, laboratory, and histologic presentation and outcome in 47 patients.
        Medicine (Baltimore). 2009; 88: 98-106
        • Baker R.J.
        • Pusey C.D.
        The changing profile of acute tubulointerstitial nephritis.
        Nephrol Dial Transplant. 2004; 19: 8-11
        • Forgacs I.
        • Loganayagam A.
        Overprescribing proton pump inhibitors.
        BMJ. 2008; 336: 2-3
        • IMS-Health-Report
        IMS National Prescription Audit.
        IMS, New Jersey2010
        • Ruffenach S.J.
        • Siskind M.S.
        • Lien Y.H.
        Acute interstitial nephritis due to omeprazole.
        Am J Med. 1992; 93: 472-473
        • Myers R.P.
        • McLaughlin K.
        • Hollomby D.J.
        Acute interstitial nephritis due to omeprazole.
        Am J Gastroenterol. 2001; 96: 3428-3431
        • Ricketson J.
        • Kimel G.
        • Spence J.
        • Weir R.
        Acute allergic interstitial nephritis after use of pantoprazole.
        CMAJ. 2009; 180: 535-538
        • Geevasinga N.
        • Coleman P.L.
        • Webster A.C.
        • Roger S.D.
        Proton pump inhibitors and acute interstitial nephritis.
        Clin Gastroenterol Hepatol. 2006; 4: 597-604
        • Sierra F.
        • Suarez M.
        • Rey M.
        • Vela M.F.
        Systematic review: proton pump inhibitor-associated acute interstitial nephritis.
        Aliment Pharmacol Ther. 2007; 26: 545-553
        • Torpey N.
        • Barker T.
        • Ross C.
        Drug-induced tubulo-interstitial nephritis secondary to proton pump inhibitors: experience from a single UK renal unit.
        Nephrol Dial Transplant. 2004; 19: 1441-1446
        • Raza M.N.
        • Hadid M.
        • Keen C.E.
        • Bingham C.
        • Salmon A.H.
        Acute tubulointerstitial nephritis, treatment with steroid and impact on renal outcomes.
        Nephrology (Carlton). 2012; 17: 748-753
        • Fogazzi G.B.
        • Ferrari B.
        • Garigali G.
        • Simonini P.
        • Consonni D.
        Urinary sediment findings in acute interstitial nephritis.
        Am J Kidney Dis. 2012; 60: 330-332
        • Pusey C.D.
        • Saltissi D.
        • Bloodworth L.
        • Rainford D.J.
        • Christie J.L.
        Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose steroid therapy.
        Q J Med. 1983; 52: 194-211
        • Buysen J.G.
        • Houthoff H.J.
        • Krediet R.T.
        • Arisz L.
        Acute interstitial nephritis: a clinical and morphological study in 27 patients.
        Nephrol Dial Transplant. 1990; 5: 94-99
        • Bhaumik S.K.
        • Kher V.
        • Arora P.
        • et al.
        Evaluation of clinical and histological prognostic markers in drug-induced acute interstitial nephritis.
        Ren Fail. 1996; 18: 97-104
        • Koselj M.
        • Kveder R.
        • Bren A.F.
        • Rott T.
        Acute renal failure in patients with drug-induced acute interstitial nephritis.
        Ren Fail. 1993; 15: 69-72
        • Chawla L.S.
        • Kimmel P.L.
        Acute kidney injury and chronic kidney disease: an integrated clinical syndrome.
        Kidney Int. 2012; 82: 516-524
        • Murugan R.
        • Kellum J.A.
        Acute kidney injury: what's the prognosis?.
        Nat Rev Nephrol. 2011; 7: 209-217
        • Chawla L.S.
        • Amdur R.L.
        • Amodeo S.
        • Kimmel P.L.
        • Palant C.E.
        The severity of acute kidney injury predicts progression to chronic kidney disease.
        Kidney Int. 2011; 79: 1361-1369
        • Preddie D.C.
        • Markowitz G.S.
        • Radhakrishnan J.
        • et al.
        Mycophenolate mofetil for the treatment of interstitial nephritis.
        Clin J Am Soc Nephrol. 2006; 1: 718-722