Chronic tubulointerstitial nephritis

Introduction

Primary interstitial nephropathies is a group of disorders associated with interstitial inflammation and subsequent damage of the tubular cells and the development of fibrosis. We share traditionally into acute and chronic tubulointerstitial nephritis (TIN), on the basis of clinical course and morphology. Chronic TIN is characterized by tubulointerstitial fibrosis and atrophy based on prolonged low-grade inflammation. Nephrons are destroyed, and over time this leads to declining GFR and development of chronic renal failure. Chronic TIN is the cause of terminal renal failure in approximately 15% of patients in Norway.

Causes

Chronic TIN occur at a variety of conditions, but most importantly exposure of drugs and toxins. One hypothesis for causal mechanism involving cross-reaction between the drug / toxin and endogenous renal antigens that initiate immune response against the tubules and interstitium. Infections, urinary tract obstruction, congenital genetic disorders, metabolic disorders, immune-mediated diseases and hematological disorders can also cause chronic TIN.

Table of common causes of chronic tubulointerstitial nephritis

Causes Examples
Drugs / Toxins Analgesics
Heavy metals (lead, cadmium)
Lithium
Natural Medicines
Cyclosporine A / Tacrolimus
Cisplatin
Infections Systemic
Renal
Obstruction Vesicouretral reflux
Nephrolithiasis
Tumours
Metabolic disorders Hypercalcemia
Hypokalemia
Hyperuricaemia
Hyperoxaluria
Immune-mediated causes SLE, Sjogren, Sarcoidosis
Hematologic causes Sidgcelle anemia, dysproteinemi
Circulatory Hypertension, aging, ischemia
Idiopathic

Causes	Examples
Drugs / Toxins	Analgesics
	Heavy metals (lead, cadmium)
	Lithium
	Natural Medicines
	Cyclosporine A / Tacrolimus
	Cisplatin
Infections	Systemic
	Renal
Obstruction	Vesicouretral reflux
	Nephrolithiasis
	Tumours
Metabolic disorders	Hypercalcemia
	Hypokalemia
	Hyperuricaemia
	Hyperoxaluria
Immune-mediated causes	SLE, Sjogren, Sarcoidosis
Hematologic causes	Sidgcelle anemia, dysproteinemi
Circulatory	Hypertension, aging, ischemia
Idiopathic

Clinical presentation

Since chronic tubulointerstitial nephritis is a slowly progressive disease presents patient with systemic symptoms of the underlying disease or with symptoms of chronic kidney disease. Proteinuria is common, but not in nephrotic range. Microscopic hematuria is common, and the same is pyuria. Depending on which part of nephrons that are most affected, the patient will be able to present various disorders of tubular function. For example, damage of proximal tubule give glucosuria and phosphaturia and renal tubular acidosis of proximal type. Kidney's ability to concentrate urine may be affected thereby giving polyuria. Hypertension is common, at least late appearance when GFR is low. Ultrasound of the kidneys show small kidneys with rough surface. Kalk Impact is common in some forms of chronic TIN.

Urinary Findings

Web microscope with descriptions of the items.
Sylinderuri
Tubule and white
Haematuria, not dysmorf

Histopathology

It is seen tubulusatrofi and interstitial connective tissue searching, eventually periglomerulær fibrosis and glomerulosclerosis.

Course and treatment

The challenge of chronic TIN is to detect the condition early, thus removing exposure or treat the underlying systemic disorder early before fibrosis have evolved too far. There is no available treatment for established fibrosis and nefrontap, treatment becomes supportive and goal to limit further loss of GFR by the same principles that apply to all forms of chronic renal failure. Chronic TIN is the cause of renal failure in approximately 15% of those receiving terminal kidney failure in Norway.