Approach Considerations

Corticosteroids have been a mainstay of therapy for tubulointerstitial nephritis, but mycophenolate mofetil may also have a role. Ultimately, however, treatment depends on the underlying etiology.^[2]

Most patients presenting with renal insufficiency, proteinuria, and/or acid-base electrolyte disorders require consultation with a nephrologist. These patients may require inpatient care until stabilization or resolution.

Hypertensive patients should be on a low-sodium diet. For all patients with early renal disease, recommend general guidelines for a healthy diet (ie, low-fat [low-cholesterol] diet rich in fresh fruits and vegetables such as the Dietary Approaches to Stop Hypertension [DASH] diet).

Provide patients with acute interstitial nephritis with follow-up care until resolution. Patients who do not recover renal function and those with chronic tubulointerstitial nephritis should receive long-term follow-up care to ensure that optimal control of blood pressure is achieved and to protect kidneys from further potentially nephrotoxic therapies and/or interventions.

Management of Acute Tubulointerstitial Nephritis

In cases of acute tubulointerstitial nephritis due to hypersensitivity reactions (allergic interstitial nephritis), early recognition and prompt discontinuation of the offending drug are helpful; cessation of the offending agent usually, but not always, results in complete recovery in patients. However, the rate of recovery is variable, and, in some patients, renal failure persists for many weeks before renal function improves. Some patients may progress to chronic renal insufficiency.

Obtain a thorough history of previously documented drug allergies before prescribing a new drug.

If no sign of improvement is observed within a few days of discontinuation of the offending agent, consider therapy with steroids. Although controlled trials are lacking, many authors suggest using prednisone at relatively high doses (eg, 1 mg/kg for 4-6 wks with rapid tapering of the dose). This intervention may improve the outcome, speeding renal recovery and reducing the requirement for dialysis.

A systematic review concluded that limited evidence does not support the use of corticosteroids in the treatment of drug-induced cases. The review included eight studies with 430 patients (300 of whom received corticosteroids and 130 of whom did not): four studies showed no difference in serum creatinine levels between the corticosteroid and comparator arms, while four studies found a benefit.^[28]

Management of Chronic Tubulointerstitial Disease

Treatment of chronic tubulointerstitial nephritis depends on the etiology and generally consists of supportive measures, such as adequate blood pressure control and management of anemia.

Analgesic nephropathy

Treatment of analgesic nephropathy is supportive and also includes discontinuation of analgesic use. Long-term follow-up studies have shown progression to end-stage renal disease (ESRD) requiring dialysis, and increased incidence of uroepithelial cancers is also observed in patients with analgesic nephropathy.

Cyclosporine/tacrolimus–induced renal failure

Reduce the cyclosporine/tacrolimus doses and target trough levels. Discontinuing these medications and/or switching to other immunosuppressives (eg, rapamycin), especially in those with more advanced renal failure, should also be considered.

Lead nephropathy

Body burden of lead and bone lead concentration can be reduced by extended chelation treatment using ethylenediaminetetraacetic acid (EDTA) (versenate). Chelation therapy is of proven value and must be implemented in acute lead poisoning. Although the oral chelating agent succimer (Chemet) has proved highly successful in treating children, it has not been widely used in adults. Nevertheless, it appears effective in reducing body lead stores.

Chelation therapy with EDTA may slow progressive renal insufficiency in patients with mild lead intoxication. Several studies from Taiwan have shown that chelation therapy in patients with modest increases in body lead burden (ie, 80-600 µg of lead) significantly slowed and/or reversed the rate of decline in the glomerular filtration rate (GFR) compared with placebo.^{[29, 30]}This was found in both diabetics and nondiabetics.^{[29, 30]}However, given that these studies took place in Taiwan, it is difficult to generalize these results. Further study is needed before this treatment can be recommended.

Because no effective therapy reverses the long-term consequences of lead poisoning, the best therapy is prevention and awareness of potential environmental and occupational sources for lead exposure. Therefore, implement environmental measures, such as removal of lead from indoor paint and gasoline, and eliminate other sources of exposure. Use caution with imported ceramics, particularly if glazed.

In patients with established lead nephropathy, treatment consists of management of hypertension, gout, and chronic renal insufficiency. Many patients with lead nephropathy progress to end-stage kidney failure and require dialysis.

Atherosclerotic kidney disease and cholesterol microembolic disease

No specific therapy is available for atherosclerotic kidney disease, but good control of hypertension, cessation of smoking, and vigorous control of dyslipidemia with diet and with statins are expected to result in improved outcomes. There is also no effective treatment available for cholesterol microembolic disease.

Immunoglobulin G (IgG)-4–related disease

McMahon and colleagues reported a case of a 58-year-old man initially misdiagnosed with chronic interstitial nephritis secondary to renal sarcoid and treated with repeated doses of prednisone. After his third relapse, a repeat renal biopsy confirmed a diagnosis of IgG4-tubulointerstitial nephritis. The patient had become refractory to treatment with prednisone but achieved sustained improvement in renal function after receiving rituximab. At 1 year post-treatment, serum creatinine remained at baseline and a reduction in his kidney size was observed with imaging.^[17]

Medication

Bhandari J, Thada PK, Arif H. Tubulointerstitial Nephritis. 2021 Jan. [QxMD MEDLINE Link]. [Full Text].
Joyce E, Glasner P, Ranganathan S, Swiatecka-Urban A. Tubulointerstitial nephritis: diagnosis, treatment, and monitoring. Pediatr Nephrol. 2017 Apr. 32 (4):577-587. [QxMD MEDLINE Link]. [Full Text].
Harris RC, Neilson EG. Toward a unified theory of renal progression. Annu Rev Med. 2006. 57:365-80. [QxMD MEDLINE Link].
Liu Y. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int. 2006 Jan. 69(2):213-7. [QxMD MEDLINE Link]. [Full Text].
Rangan GK, Wang Y, Tay YC, Harris DC. Inhibition of nuclear factor-kappaB activation reduces cortical tubulointerstitial injury in proteinuric rats. Kidney Int. 1999 Jul. 56(1):118-34. [QxMD MEDLINE Link].
Hadded S, Harzallah A, Chargui S, Hajji M, Kaaroud H, Goucha R, et al. [Etiologies and prognostic factors of acute interstitial nephritis]. Nephrol Ther. 2021 Apr. 17 (2):114-119. [QxMD MEDLINE Link].
Martínez-Valenzuela L, Draibe J, Fulladosa X, Gomà M, Gómez F, Antón P, et al. Acute Tubulointerstitial Nephritis in Clinical Oncology: A Comprehensive Review. Int J Mol Sci. 2021 Feb 26. 22 (5):[QxMD MEDLINE Link]. [Full Text].
De Broe ME, Elseviers MM. Over-the-counter analgesic use. J Am Soc Nephrol. 2009 May 7. [QxMD MEDLINE Link].
De Broe ME. Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity, aristolochic acid nephropathy. Kidney Int. 2012 Mar. 81(6):513-5. [QxMD MEDLINE Link].
Jelaković B, Dika Ž, Arlt VM, Stiborova M, Pavlović NM, Nikolić J, et al. Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid. Semin Nephrol. 2019 May. 39 (3):284-296. [QxMD MEDLINE Link]. [Full Text].
Maripuri S, Grande JP, Osborn TG, et al. Renal involvement in primary Sjögren''s syndrome: a clinicopathologic study. Clin J Am Soc Nephrol. 2009 Sep. 4(9):1423-31. [QxMD MEDLINE Link]. [Full Text].
Jain A, Srinivas BH, Emmanuel D, Jain VK, Parameshwaran S, Negi VS. Renal involvement in primary Sjogren's syndrome: a prospective cohort study. Rheumatol Int. 2018 Aug 23. [QxMD MEDLINE Link].
Slade N, Moll UM, Brdar B, et al. p53 mutations as fingerprints for aristolochic acid: an environmental carcinogen in endemic (Balkan) nephropathy. Mutat Res. 2009 Apr 26. 663(1-2):1-6. [QxMD MEDLINE Link]. [Full Text].
Salvadori M, Tsalouchos A. Immunoglobulin G4-related kidney diseases: An updated review. World J Nephrol. 2018 Jan 6. 7 (1):29-40. [QxMD MEDLINE Link]. [Full Text].
Mbengue M, Goumri N, Niang A. IgG4-related kidney disease: Pathogenesis, diagnosis, and treatment. Clin Nephrol. 2021 Jun. 95 (6):292-302. [QxMD MEDLINE Link].
Saeki T, Nishi S, Imai N, Ito T, Yamazaki H, Kawano M, et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010 Nov. 78(10):1016-23. [QxMD MEDLINE Link].
McMahon BA, Novick T, Scheel PJ, Bagnasco S, Atta MG. Rituximab for the Treatment of IgG4-Related Tubulointerstitial Nephritis: Case Report and Review of the Literature. Medicine (Baltimore). 2015 Aug. 94 (32):e1366. [QxMD MEDLINE Link]. [Full Text].
Inoue D, Yoshida K, Yoneda N, Ozaki K, Matsubara T, Nagai K, et al. IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 2015 Apr. 94 (15):e680. [QxMD MEDLINE Link]. [Full Text].
Mackensen F, Billing H. Tubulointerstitial nephritis and uveitis syndrome. Curr Opin Ophthalmol. 2009 Sep 11. [QxMD MEDLINE Link].
Patel S, Hossain MA, Ajam F, Patel M, Nakrani M, Patel J, et al. Dabigatran-Induced Acute Interstitial Nephritis: An Important Complication of Newer Oral Anticoagulation Agents. J Clin Med Res. 2018 Oct. 10 (10):791-794. [QxMD MEDLINE Link]. [Full Text].
Roy S, Awogbemi T, Holt RCL. Acute tubulointerstitial nephritis in children- a retrospective case series in a UK tertiary paediatric centre. BMC Nephrol. 2020 Jan 14. 21 (1):17. [QxMD MEDLINE Link]. [Full Text].
Clive DM, Vanguri VK. The Syndrome of Tubulointerstitial Nephritis With Uveitis (TINU). Am J Kidney Dis. 2018 Jul. 72 (1):118-128. [QxMD MEDLINE Link].
Kanno H, Ishida K, Yamada W, Shiraki I, Murase H, Yamagishi Y, et al. Clinical and Genetic Features of Tubulointerstitial Nephritis and Uveitis Syndrome with Long-Term Follow-Up. J Ophthalmol. 2018. 2018:4586532. [QxMD MEDLINE Link]. [Full Text].
Border WA, Holbrook JH, Peterson MC. Gallium citrate Ga 67 scanning in acute renal failure. West J Med. 1995 May. 162(5):477-8. [QxMD MEDLINE Link].
Linton AL, Richmond JM, Clark WF, Lindsay RM, Driedger AA, Lamki LM. Gallium67 scintigraphy in the diagnosis of acute renal disease. Clin Nephrol. 1985 Aug. 24(2):84-7. [QxMD MEDLINE Link].
Hettinga YM, Scheerlinck LM, Lilien MR, Rothova A, de Boer JH. The value of measuring urinary β2-microglobulin and serum creatinine for detecting tubulointerstitial nephritis and uveitis syndrome in young patients with uveitis. JAMA Ophthalmol. 2015 Feb. 133 (2):140-5. [QxMD MEDLINE Link].
Shi Y, Su T, Qu L, Wang C, Li X, Yang L. Evaluation of urinary biomarkers for the prognosis of drug-associated chronic tubulointerstitial nephritis. Am J Med Sci. 2013 Oct. 346(4):283-8. [QxMD MEDLINE Link].
Quinto LR, Sukkar L, Gallagher M. The effectiveness of corticosteroid compared to non-corticosteroid therapy for the treatment of drug-induced acute interstitial nephritis: A systematic review. Intern Med J. 2018 Aug 21. [QxMD MEDLINE Link].
Lin JL, Lin-Tan DT, Hsu KH, Yu CC. Environmental lead exposure and progression of chronic renal diseases in patients without diabetes. N Engl J Med. 2003 Jan 23. 348(4):277-86. [QxMD MEDLINE Link].
Lin JL, Lin-Tan DT, Yu CC, Li YJ, Huang YY, Li KL. Environmental exposure to lead and progressive diabetic nephropathy in patients with type II diabetes. Kidney Int. 2006 Jun. 69(11):2049-56. [QxMD MEDLINE Link].

Media Gallery

Tubulointerstitial nephritis: Kidney biopsy reveals acute interstitial nephritis. The renal cortex shows a diffuse interstitial, predominantly mononuclear, inflammatory infiltrate with no changes to the glomerulus. Tubules in the center of the field are separated by inflammation and edema, as compared with the more normal architecture in the right lower area (periodic acid–Schiff, 40 X).
Tubulointerstitial nephritis. On a kidney biopsy, the diagnosis of acute interstitial nephritis is based on the active inflammatory infiltrate on the right with unaffected glomeruli. Interstitial edema and fibrosis are present on the left side of the field, where some tubules show thickened basement membrane (hematoxylin and eosin, 20 X).
Tubulointerstitial nephritis. Kidney biopsy shows acute interstitial nephritis. The interstitium is expanded by mononuclear inflammatory infiltrate and edema. Acute tubular damage is present; some tubules are distended and contain granular casts (hematoxylin and eosin, 40 X).
Tubulointerstitial nephritis. Kidney biopsy shows acute crescentic glomerulonephritis. The glomerular tuft is compressed by the proliferation of epithelial cells, forming a crescent. In addition, the interstitium shows mononuclear inflammatory infiltrate and edema (periodic acid–Schiff, 40 X).
Tubulointerstitial nephritis. Kidney biopsy shows acute interstitial nephritis. The mononuclear inflammatory infiltrate contains abundant eosinophils, suggesting an allergic etiology. Severe tubular damage is observed (hematoxylin and eosin, 40 X).
Tubulointerstitial nephritis. Kidney biopsy shows acute interstitial nephritis. The inflammatory infiltrate forms an ill-defined granuloma, suggesting allergic or infectious etiologies. A partially destroyed tubule is present (periodic acid–Schiff, 40 X).
Tubulointerstitial nephritis. Kidney biopsy shows chronic tubulointerstitial nephritis. The interstitium is expanded by fibrosis, with distortion of tubules and periglomerular fibrosis. Glomeruli do not show pathologic changes (hematoxylin and eosin, 20 X).
Tubulointerstitial nephritis. Kidney biopsy in interstitial nephritis shows a cholesterol microembolism. The 2 arterioles in the center are occluded by elongated crystals (hematoxylin and eosin, 20 X).
Tubulointerstitial nephritis. Kidney biopsy in interstitial nephritis shows a cholesterol microembolism. The arteriole in the center of the field has a thickened wall. The lumen is occluded by elongated spaces, corresponding to dissolved crystals surrounded by cellular reaction. The 2 glomeruli flanking the arteriole are sclerotic and hardly recognizable (hematoxylin and eosin, 40 X).