Tubulointerstitial diseases

Last updated: July 29, 2022

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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.

Definition

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]

Epidemiology

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

Pathophysiology

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]

Approach

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]

Definition

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.

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

Tubular crystallopathy

Urolithiasis

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

Definition

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

Pathophysiology

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

Etiology

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]

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