Tubulointerstitial diseases

Last updated: July 20, 2023

Summarytoggle arrow icon

Tubulointerstitial diseases are conditions of inflammation of the renal tubules and interstitium that can lead to renal failure. Acute tubulointerstitial nephritis (ATIN) is the third most common cause of acute kidney injury (AKI) in hospitalized patients after acute tubular necrosis (ATN) and prerenal AKI, and it is most commonly caused by an allergic reaction to medications. ATIN commonly manifests with a slowly progressive, nonoliguric, intrinsic AKI. The classic triad of fever, morbilliform rash, and eosinophilia is seen in < 10% of cases. Laboratory study findings may suggest interstitial nephritis, but histological confirmation with renal biopsy is required for a definitive diagnosis. Early recognition, removal, or treatment of the suspected cause, and, in select cases, administration of glucocorticoid therapy, will result in complete or partial resolution for most patients, while a minority of patients experience irreversible kidney damage. Chronic tubulointerstitial nephritis (CTIN) is commonly due to the progression of ATIN, but it may also be caused by medications, infections, toxins, or systemic diseases. Treatment involves managing or eliminating the underlying cause and management of CKD. Crystal-induced nephropathy is a type of kidney damage that results from crystal deposition in the renal vasculature, the renal tubules, or the draining urinary tract and that may lead to crystal-induced AKI, crystal-induced CKD, or urolithiasis. Renal papillary necrosis, a necrosis of the renal medullary pyramids and papillae, is caused by ischemia (due to, e.g., sickle cell disease and sickle cell trait, acute pyelonephritis, or obstruction of the urinary tract). Patients often present with AKI with hematuria and sloughed papillae. Management should include treatment of the underlying cause, IV fluids to prevent blood clot formation and upper urinary tract obstruction, and management of further complications.

Acute tubulointerstitial nephritistoggle arrow icon


Acute tubulointerstitial nephritis (ATIN) is an acute inflammation of the renal interstitium and tubules that causes a decline in renal function over a period of days to weeks. [1]


  • Third most common cause of AKI in hospitalized patients [2]
  • Seen in ∼ 15% of biopsy samples obtained for unexplained AKI [3]


Etiology [1][5][6]

“Please RSVP:” Rifampin, Sulfa drugs and the V (5) Ps (Proton pump inhibitors, Pain killers (NSAIDs), “Pee pills” (diuretics), Penicillins, and Phenytoin) are the drugs that cause acute tubulointerstitial nephritis.

Clinical features [2]

The classic triad of fever, morbilliform rash, and eosinophilia is present in < 10% of patients with ATIN, but their presence can help to guide the diagnosis. [2][6]

Diagnostics [8][9]


ATIN typically manifests as slowly progressive, nonoliguric, intrinsic AKI. However, patients with severe disease may present with oliguria and the course may be rapidly progressive. [4]

Blood tests [2][3][6]

Urine studies [2][3][6]

Although frequently cited as a diagnostic clue, in clinical practice, urine eosinophils lack sensitivity and specificity for reliably confirming ATIN. [12]

Renal ultrasound [5]

Renal biopsy [6][13]

Differential diagnoses [5]

ATIN, atheroembolic disease, vasculitis, and DRESS syndrome can all manifest with AKI, skin lesions (e.g., livedo reticularis, purpura, or rash), and eosinophilia, and should be considered as differential diagnoses. [6]

Management [1][8][13]

Glucocorticoid therapy [6][14]

Chronic tubulointerstitial nephritistoggle arrow icon


Chronic tubulointerstitial nephritis (CTIN) is a condition of chronic inflammation of the renal tubules and interstitium and can progress to end-stage renal disease (ESRD) after months or years. [15]

Pathophysiology [11]

Epidemiology [11]

Etiology [5]

Clinical features [5][9]

CTIN typically follows an indolent course. Clinical features vary according to the etiology.

Analgesic nephropathy increases the risk of urothelial carcinoma and can progress to ESRD. [16]

Diagnostics [5][9][18]

Perform a diagnostic workup for CKD and evaluate for risk factors and exposures that suggest CTIN (see “Etiology”).

Laboratory findings in chronic tubulointerstitial nephritis have significant overlap with other causes of CKD and are neither sensitive nor specific.

Differential diagnoses

See “Etiology of chronic kidney disease.”

Treatment [18]

Treatment consists of management of CKD, including treatment of the underlying cause.

Crystalline nephropathiestoggle arrow icon

Overview of crystalline nephropathies [19][20]
Renovascular crystallopathy

Tubular crystallopathy


  • Crystal deposits → necroinflammation, tubular obstruction, or formation of granulomas
Clinical features
  • Crystals may be seen on urine microscopy.

Renal papillary necrosistoggle arrow icon


Renal papillary necrosis is ischemic, coagulative necrosis of the renal medullary pyramids and papillae and is a feature of various conditions.


  • Ischemia necrosis and sloughing of the papillae ureteral obstruction → possible scarring
  • Usually bilateral; can also affect a single papilla [21]


POSTCARDS: Pyelonephritis, Obstruction, Sickle cell disease, Tuberculosis, Cirrhosis, Analgesics (NSAIDs), Renal transplant rejection, Diabetes mellitus, and Systemic vasculitis are the causes of renal papillary necrosis.

Clinical features

Diagnostics [11][22]

Consider renal papillary necrosis as part of the differential diagnosis for patients presenting with hematuria, particularly if risk factors are present (e.g., sickle cell disease, diabetes, chronic oral analgesic use).

Laboratory studies

Imaging studies [21][22]

Obtain in all patients to assess for ischemic changes and exclude differential diagnoses or precipitating conditions (e.g., kidney tumors, pyelonephritis, nephrolithiasis).

Treatment [11]

Referencestoggle arrow icon

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  2. Nussbaum EZ, Perazella MA. Diagnosing acute interstitial nephritis: considerations for clinicians. Clinical Kidney Journal. 2019.doi: 10.1093/ckj/sfz080 . | Open in Read by QxMD
  3. Raghavan R, Eknoyan G. Acute interstitial nephritis - a reappraisal and update.. Clin Nephrol. 2014; 82 (3): p.149-62.doi: 10.5414/cn108386 . | Open in Read by QxMD
  4. Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nature Reviews Nephrology. 2010; 6 (8): p.461-470.doi: 10.1038/nrneph.2010.71 . | Open in Read by QxMD
  5. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical ; 2018
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  7. Salvadori M, Tsalouchos A. Immunoglobulin G4-related kidney diseases: An updated review. World J Nephrol. 2018; 7 (1): p.29-40.doi: 10.5527/wjn.v7.i1.29 . | Open in Read by QxMD
  8. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Updated: January 1, 2012. Accessed: September 19, 2020.
  9. Perazella MA. Clinical Approach to Diagnosing Acute and Chronic Tubulointerstitial Disease. Adv Chronic Kidney Dis. 2017; 24 (2): p.57-63.doi: 10.1053/j.ackd.2016.08.003 . | Open in Read by QxMD
  10. Moledina DG, Parikh CR. Differentiating Acute Interstitial Nephritis from Acute Tubular Injury: A Challenge for Clinicians. Nephron. 2019; 143 (3): p.211-216.doi: 10.1159/000501207 . | Open in Read by QxMD
  11. Gilbert, SJ; Weiner, DE. National Kidney Foundation's Primer on Kidney Disease. Elsevier Health Sciences ; 2017
  12. Ruffing KA, Hoppes P, Blend D, Cugino A, Jarjoura D, Whittier FC. Eosinophils in urine revisited.. Clin Nephrol. 1994; 41 (3): p.163-6.
  13. Fogo AB, Lusco MA, Najafian B, Alpers CE. AJKD Atlas of Renal Pathology: Acute Interstitial Nephritis. Am J Kidney Dis. 2016; 67 (6): p.e35-e36.doi: 10.1053/j.ajkd.2016.04.002 . | Open in Read by QxMD
  14. González E, Gutiérrez 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 (8): p.940-946.doi: 10.1038/ . | Open in Read by QxMD
  15. Joyce E, Glasner P, Ranganathan S, Swiatecka-Urban A. Tubulointerstitial nephritis: diagnosis, treatment, and monitoring.. Pediatr Nephrol. 2017; 32 (4): p.577-587.doi: 10.1007/s00467-016-3394-5 . | Open in Read by QxMD
  16. Uetrecht J. Adverse Drug Reactions. Springer Science & Business Media ; 2009
  17. Jayasumana C, Orantes C, Herrera R, et al. Chronic interstitial nephritis in agricultural communities: a worldwide epidemic with social, occupational and environmental determinants. Nephrol Dial Transplant. 2016: p.gfw346.doi: 10.1093/ndt/gfw346 . | Open in Read by QxMD
  18. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Updated: January 1, 2013. Accessed: July 18, 2021.
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  21. Sutariya HC. Renal Papillary Necrosis: Role of Radiology. J Clin Diagn Res. 2016.doi: 10.7860/jcdr/2016/15092.7091 . | Open in Read by QxMD
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