Acute tubulointerstitial nephritis

Introduction

Primary interstial nephropathies are a group of diseases that are associated with interstitial inflammation and subsequent damage to the tubulus cells and fibrosis. The conditions are traditionally divided into acute or chronic tubulointerstitial nephritis (TIN) based on the clinical course of the disease and morphology. Acute tubulointerstitial nephritis is characterised by acute inflammation of the interstitium together with edema, with a subsequent drop in GFR. Vascular and glomerular structures are spared and the progonsis is good if the patient receives adequate treatment. Acute TIN is found to be the cause of ca. 10-15% of reported acute kidney failures.

Causes

Acute TIN is generally a result of an immunological reaction to external influences such as medication and infectious agents. The list of medications that can induce acute TIN is long. In principal, all medications can result in a hypersensitivity reaction with acute TIN. The reaction is not dependent on dosage and usually occurs after repeated exposure to the same or related medications. Systemic autoimmune diseases can also result in acute TIN. A cause cannot be ascertained in a significant number of patients, these are labelled idiopathic. Acute TIN occurs in all age groups, but the incidence appears to increase with age. Direct inflammatoric responses (ascending UTI) or hypersensitivity reactions initiate local inflammation with edema and infiltration of leukocytes.

Table of the most common causes to acute tubulointerstitial nephritis

Causes Examples

Drugs NSAIDs

Antibiotics

Diuretics

Infections Systemic (viral, bakterial and others)

Infectious pyelonephritis

Immunomediated causes SLE

Sjogren

Sarcoidosis

Idiopathic

Causes	Examples
Drugs	NSAIDs
	Antibiotics
	Diuretics
Infections	Systemic (viral, bakterial and others)
	Infectious pyelonephritis
Immunomediated causes	SLE
	Sjogren
	Sarcoidosis
Idiopathic

Clinical presentation

During an ascending urinary tract infection (acute pyelonephritis), the patient can present with systemic symptoms of infection such as a feber and positive SIRS criteria, together with pyuria and tenderness or pain along the flank. Renally, an acute TIN will present with an acute fall in the GFR, like an acute kidney failure. Mild proteinuria is common, rarely more than 1 g/day. Abnormal function of the tubules can occur based on which part of the nephron is the most affected. An ultrasound of the kidneys will show either kidneys of a normal size or enlarged kidneys due to edema. NSAIDs can occasionally induce an acute TIN with nephrotic proteinuria. The glomeruli will then be affected and the patient will have histological changes similar to minimal change nephropathy in addition to acute tubulointerstitial changes. Immunological cross-reaction against glomerular structures can therefore be present in acute TIN induced by NSAIDs.

Urinalysis

Web microscoe with description of the elements.
erythrocytes
White blood cells, eosinophiles, and white blood cell casts
Pyuria

Histopathology

One can see interstitial edema and leukocyte infiltration

Prognosis and treatment

The spectrum of acute TIN ranges from a mild self-limiting disease to acute oliguric kidney failure that requires dialysis. Acute TIN is potentially reversible and the prognosis is generally good. The treatment is directed towards identifying and removing the trigger. Treatment with steroids to decrease inflammation is disputed and reserved for severe cases to prevent or reduce time with dialysis. Maybe future studies will document the effect of immunosuppressive treatment in more patients, as irreversible interstitial fibrosis is shown to appear as early as 10-14 days in acute TIN, but this is currently not an established form of treatment.