The kidney has several important functions including filtering out waste from the blood, regulating the water-electrolyte balance in the body and controlling the blood pressure. The basic functional unit of the kidney is the nephron which is made up of two main parts – the glomerulus and tubule. Firstly the head of the nephron, known as the glomerulus, collects fluid and substances that filter out from the blood capillaries next to it. Then the remainder of the nephron, the tubule, reabsorbs or secretes fluid and certain substances until the urine is formed and passed out of the kidney. This fluid and substances are either absorbed from, or passed out into the surrounding kidney tissue known as the interstitium. When the nephron is damaged, these mechanisms are severely disturbed. The damage may involve the entire kidney, or may be isolated to one part of the nephron like the glomerulus or tubule and/or surrounding tissue (interstitium). This ultimately disturbs the kidney’s functions to varying degrees.
What is tubulointerstitial nephritis?
Tubulointerstitial nephritis is a group of diseases that affect the tubule of the nephron and/or surrounding interstitial tissue. It should be differentiated from similar diseases that predominantly affect the glomerulus, known as glomerulonephritis. However, tubulointerstitial disease may sometimes be related to glomerulonephritis but in these cases, the glomerular damage is minimal causing a mild disturbance.
Acute and Chronic Tubulointerstitial Nephritis
Tubulointerstitial nephritis may be acute or chronic. The acute stages are characterized by rapid onset of inflammation of the renal tubule that compromises its function. This tubular dysfunction is usually temporary. Inflammation is also present in chronic tubulonephritis along with structural damage to the tubule and/or interstitium. The injury is often irreversible in chronic states. Tubulointerstitial nephritis is more commonly seen in women as the two most common causes, analgesic use and kidney infections, are more prevalent in females. However, it can affect men with the same risk factors equally.
The two most common mechanisms associated with tubulonephritis is cellular injury by bacteria (infection) and toxins, and drug hypersensitivity which leads to an inappropriate immune response. Acute tubulointerstitial nephritis is marked by inflammation with associated swelling of the affected area. Leukocyte inflitration of the renal tissue, particularly eosinophils and neutrophils, are prominent and in severe cases there is confined areas of cell death (necrosis).
Most cases of acute tubulointerstitial nephritis are largely reversible since the tubules can regenerate if the basement membrane is intact. With chronic tubulointerstitial nephritis, the long term inflammation and subsequent fibrotic scarring tends to lead to irreversible changes. If a small amount of the total nephrons are affected then kidney function is not severely compromised. However, it tends to lead to progressive chronic renal insufficiency.
Causes of Tubulointerstitial Nephritis
Infections of the upper urinary tract and kidney (pyelonephritis) accounts for a large number of cases of acute tubulointerstitial nephritis. Chronic pyelonephritis associated with reflux nephropathy may also be a cause. Most infections are bacterial in nature, although viruses (HIV, HBV, CMV), fungi (histoplasmosis) and parasites can also cause tubulointerstitial nephritis.
Drugs and Toxins
Drug hypersensitivity is largely responsible for acute tubulointerstitial nephritis and associated with drugs like NSAIDs, certain antibiotics, diuretics, anticonvulsants and proton pump inhibitors. It is known as acute-hypersensitivity interstitial nephritis. Chronic cases are more often associated with toxicity caused by long term and/or excessive use of drugs like analgesics and lithium.
Heavy metal toxicity, lead, mercury and cadmium poisoning may also be responsible for chronic tubulointerstitial nephritis but has decreased substantially with greater awareness of the toxicity associated with these metals. Other toxins may include fungal toxins like ochratoxin (possibly related to Balkan endemic nephropathy) or plant toxins like aristolochic acid (Chinese herb nephropathy).
A number of immunologic diseases can cause acute and chronic tubulointerstitial nephritis. This includes :
- Goodpasture syndrome
- Systemic lupus erythematosus (SLE)
- Sjogren syndrome
- Wegener’s granulomatosis
Acute transplant rejection and chronic transplant nephropathy also need to be considered in patients following a kidney transplant.
- Chronic urinary tract obstruction – stones or tumors
- Atherosclerosis – injury associated with reduced blood supply (ischemia)
- Multiple myeloma
- Metabolic diseases – hypercalcemia, hypokalemia, hyperoxaluria
- Genetic diseases – Alport syndrome, medullary cystic disease
- Idiopathic – unknown causes
Signs and Symptoms of Tubulointerstitial Nephritis
The clinical features of tubulointerstitial nephritis may be non-specific and it is difficult to differentiate with other kidney disorders. It can, however, be differentited from glomerulonephritis by the absence of nephrotic and nephritic syndrome as discussed under signs and symptoms of glomerulonephritis. The clinical presentation may also vary slightly depending on the causative factor and other underlying diseases.
The presentation in tubulointerstitial nephritis includes :
- Polyuria. Passing of large amounts of urine, seen as frequent urination and waking at night to urinate (nocturia).
- Hematuria (blood in the urine) may not be seen in every case of tubulointerstitial nephritis.
- Metabolic acidosis. Accumulation of acids in the body fluid due to decreased excretion.
- Changes in blood pressure – hypertension, hypotension or normal blood pressure.
- Congestive heart failure
- Vomiting and/or diarrhea
- Weight loss