Chronic tubulointerstitial nephritis

Introduction

Primary interstial nephropathies are a group of diseases that are associated with interstial inflammation and subsequent damage to the tubulus cells and fibrosis. The conditions are traditionally divided into acute or chronic tubulointerstitial nephritis (TIN) based on clinical course of the disease and morphology. Chronic TIN is characterised by tubulointerstitial fibrosis and atrophy due to longterm low-level inflammation. Nephrones are damaged and over time, this leads to falling GFR and development of chronic kidney failure. About 15 % of the terminal kidney failure patients in Norway are due to chronic TIN.

Causes

Chronic TIN occurs in a number of a conditions, but most important is exposure to drugs and toxins. A hypothesis for the causal mechanism involves cross-reactions between drugs/toxins and endogenous renal antigens that initiate immune responses against the tubules and interstitium. Infections, obstructions of the urinary tract, congenital genetic disorders, metabolic disorders, immune-mediated diseases and hematological disorders can also cause chronic TIN.

Table of the most common causes of chronic tubulointerstitial nephritis.

Causes Examples

Drugs/Toxins Analgetics

Heavy metals (lead, cadmium)

Lithium

Naturopathic medicines

Cyclosporine A/Tacrolimus

Cisplatin

Infections Systemic

Renal

Obstruction Vesicoureteral reflux

Kidney stone

Tumors

Metabolic disorders Hypercalcemia

Hypokalemia

Hyperuricemia

Hyperoxaluria

Immune-mediated causes SLE, Sjogren, Sarcoidosis

Hematologic cause Sickle-cell anemia, dysproteinemia

Circulatory Hypertension, aging, ischemia

Idiopathic

Causes	Examples
Drugs/Toxins	Analgetics
	Heavy metals (lead, cadmium)
	Lithium
	Naturopathic medicines
	Cyclosporine A/Tacrolimus
	Cisplatin
Infections	Systemic
	Renal
Obstruction	Vesicoureteral reflux
	Kidney stone
	Tumors
Metabolic disorders	Hypercalcemia
	Hypokalemia
	Hyperuricemia
	Hyperoxaluria
Immune-mediated causes	SLE, Sjogren, Sarcoidosis
Hematologic cause	Sickle-cell anemia, dysproteinemia
Circulatory	Hypertension, aging, ischemia
Idiopathic

Clinical presentation

Since chronic tubulointerstitial nephritis is a slow progressive disease, the patient will present with systemic symptoms of underlying disorders or with symptoms of chronic kidney disease. Proteinuria is normal, but not at nephrotic levels. Microscopic hematuria is normal as well as pyuria. Depending on which part of the nephron is the most affected, the patient will present with different disturbances in tubular function. For example, damage to the proximal convoluted tubule will result in glycosuria, phosphaturia, and renal tubular acidosis of the proximal type. The kidney's ability to concentrate urine is affected, resulting in polyuria. Hypertension is normal, at least in the later stages when GFR is low. An ultrasound of the kidneys shows small kidneys with an uneven surface. Calcium deposits are normal in some forms of chronic TIN.

Urinalysis

Web microscope with descriptions of the elements
Cylinderuria
Tubule cells and white blood cells
Hematuria, not dysmorphic

Histopathology

One can see atrophy of the tubule and increase in interstitial tissue, eventually fibrosis around the glomerulus and glomerulosclerosis also appears..

Prognosis and treatment

The challenge with chronic TIN is to identify the condition early, and thereby remove exposure or treat the underlying systemic disorder early before fibrosis has developed too far. There are no available treatments for established fibrosis and loss of nephrons, treatment is then supportive and the goal is to limit further loss of GFR with the same principles that apply to all forms of chronic kidney failure. Chronic TIN is the cause of kidney failure in about 15 % of those with terminal kidney failure in Norway.