What is nephritis? |

Causes and Symptoms

Nephritis means any inflammatory responses of the kidney, whether the cause is infectious or immunological. Generally, it involves mainly the glomeruli, where the initial formation of urine takes place. The term is therefore equivalent in meaning to glomerulonephritis. Pathological changes may also occur in the interstitium (the extravascular, extracellular domain in which the tubules are embedded) and affect tubular functions. This condition, referred to as tubulointerstitial nephritis, is associated with localized cellular infiltrates and the accumulation of fluid.

The classic cause of acute glomerulonephritis is an infection in the throat or of the skin by a nephritogenic strain of Group A streptococci. The clinical presentation can be dramatic and can be associated not only with a sore throat but also with headaches, shortness of breath, and swelling of the ankles. Physical examination may find hypertension, rales in the lungs, peripheral pitting edema, and changes in the retinal vessels. In the chronic form, the onset is usually insidious; an infection may have been forgotten or ignored, without specific complaints except for some ankle edema, tiredness, and perhaps pallor. The physical findings for chronic glomerulonephritis are similar to but less striking than in the acute form.

The diagnosis in each type of nephritis is presumed on the basis of urinalysis, with a finding of blood (hematuria) in the acute form; proteinuria (actually mainly albuminuria, although globulins may also be present); and a decreased glomerular filtration rate. Diagnosis is established on the basis of renal biopsy with examination by both light and electron microscopy. Throat cultures and streptococcal group determination are appropriate if an infection is suspected.

Both conditions may be followed by the development of nephrotic syndrome, which is characterized by major losses of albumin in the urine, decreased serum albumin concentrations (hypoalbuminemia), the retention of water and of sodium and chloride ions, and massive edema and ascites (fluid leakage from blood vessels into the abdomen). Nephrotic syndrome may also appear without any history or evidence of a preceding episode of acute glomerulonephritis. On renal biopsy, essentially no changes or only minimal changes may be noted on inspection by light microscopy (minimal change disease), although characteristic changes are found with electron microscopy affecting particularly the foot processes (podocytes) of the glomeruli.

Acute glomerulonephritis resolves spontaneously and rapidly in about 95 percent of cases, without detectable residual damage to kidney functions. Apart from control of hypertension, no specific treatment is available. The edema is rarely sufficient to warrant the use of diuretics. Antibiotics are not indicated unless there is evidence of an infection. Patients can be considered to be cured but should nonetheless be followed in the event of a reappearance of symptoms or manifestations.

In nonresolving acute glomerulonephritis and in chronic glomerulonephritis, there can be progression of damage to the glomeruli so that the number of functioning glomeruli (normally, about one million in each kidney) diminishes. This process may be gradual or may occur as a part of acute exacerbations that subside but leave the patient with diminished renal functions. As a result, glomerular filtration is decreased and the accumulation of metabolic end-products, particularly urea, occurs in the blood and tissue fluids. Abnormalities of acid-base regulation appear with decreased blood pH (acidemia), decreased serum bicarbonate concentration, and increased potassium concentration. Generally, a significant anemia exists, and renal blood flow is decreased so that the metabolic activities of the renal tubule
cells are affected. Renal insufficiency is established, and dietary control is instituted, with decreased intakes of protein and potassium. Paradoxically, with decreased glomerular function, proteinuria decreases, serum albumin increases, and edema decreases or disappears.

Unfortunately, the progression of glomerular dysfunction continues, and dietary measures provide insufficient control of metabolic abnormalities. Resort is then made to hemodialysis or peritoneal dialysis to control the metabolic abnormalities and lift dietary restrictions to some degree while the patient awaits kidney transplantation. During this waiting period, stimulants of the bone marrow, such as erythropoietin, are administered in the expectation of maintaining the red cell count and the hematocrit at a satisfactory level. Transplants will require the use of immunosuppressive agents to prevent rejection unless an identical twin is the donor.

Other diseases in which glomerular damage can occur include diabetes mellitus, amyloidosis, systemic
lupus erythematosus (SLE), Wegener’sgranulomatosis, Goodpasture’s syndrome, syphilis, and human immunodeficiency virus (HIV) infection. Common problems associated with glomerular damage of any etiology are hypertension, strokes, heart failure, pulmonary edema, arteriolar vasoconstriction and sclerosis, impaired vision from exudates, pericarditis, and pericardial effusions.

Treatment and Therapy

Acute glomerulonephritis is characterized by the disappearance of signs and symptoms, or at least their marked reduction, in most patients. In 90 to 95 percent of cases, there is no progression and no recurrence. In some patients, the problems may reappear after apparent complete remission, while in others the disease progresses, often to nephrotic syndrome. This phase, too, disappears as the disease worsens, reaching the stage where hemodialysis or peritoneal dialysis becomes necessary. A renal biopsy can aid in determining the appropriate treatment. For example, if the biopsy confirms that poststreptococcal nephritis is present, then no specific treatment is available. If progressive glomerulonephritis is the diagnosis, then steroids may be indicated.

Hemodialysis depends on an arteriovenous shunt being created, usually in the forearm, so that the patient’s blood can pass through a dialysis
machine, which functions in a manner similar to glomeruli. Usually, several sessions, two or three times per week for several hours at a time, are required. Peritoneal dialysis involves the introduction of large amounts of fluid into the peritoneal cavity and its withdrawal after adequate exchanges with body fluids across the peritoneal surfaces have occurred. Hemodialysis requires going to a hospital or specialized facility, while pertoneal dialysis can be performed at home. Both procedures require careful and frequent monitoring of the patient’s acid-base, electrolyte, and metabolic statuses.

While arrangements can usually be made for local dialysis, patients on dialysis lose a significant degree of mobility and independence. This independence can be regained to a considerable degree through kidney transplantation.
Kidneys may be obtained from cadavers, unrelated living donors, and related living donors, such as identical twins. Except with the latter group, rejection phenomena may occur. Infections can occur with the use of immunosuppressive agents. Rarely, malignancies can be introduced with transplanted kidneys.

A low protein intake is recommended in the later stages of glomerulonephritis because too high a protein intake may accelerate the progression of the disease. Lack of control of water intake may lead to edema. Anemia is common in the later stages and may require the administration of erythropoietin.

In the nephrotic phase and in minimal change disease, control of edema is sought through one or more of the following measures: salt restriction, diuretics, intravenous (IV) administration of concentrated human serum albumin, corticosteroids (such as prednisone, which is more likely to be effective in minimal change disease), and other immunosuppressive agents. Nephrotic syndrome may occur in the presence of other underlying diseases, such as lupus, diabetes mellitus, HIV infection, syphilis, amyloidosis, and microvascular angiopathies. Specific treatments should be used when applicable.

Perspective and Prospects

The monograph Reports of Medical Cases by Richard Bright, published in 1827, marks the first clear description of nephritis through clinical findings (edema), laboratory assessment (proteinuria), and gross structural changes in the kidneys at postmortem. For many years, nephritis was referred to as Bright’s disease. Apart from the measurement of blood constituents such as urea and creatinine, functional assessment was limited until the development, by Donald D. Van Slyke, of the clearance concept, defined as the amount of a given substance excreted in the urine per unit time relative to its concentration in plasma or blood. Van Slyke focused on the clearance of urea, while P. B. Rehberg in Denmark proposed that the clearance of creatinine could be used as a measure of the glomerular filtration rate. Glomerular fluid had been shown by Newton Richards to have the same composition as an ultrafiltrate of plasma. Accordingly, if creatinine was neither secreted nor reabsorbed by the tubules, then its clearance would be equivalent to the glomerular filtration rate.

The assumptions with respect to creatinine were shown to be incorrect, and inulin, a polyfructoside studied by Homer Smith, was found to be a reliable and correct indicator for measuring the glomerular filtration rate. Smith and his collaborators systematized and advanced knowledge of the kidney as a whole organ in a quantitative manner. Detailed understanding of the components of the whole organ progressed rapidly with the discovery of the significance of countercirculation in establishing the solute concentration gradient from cortex to medulla reported by H. Wirz and B. Hargitay. Functions of limited segments of the tubules (and later of individual cells) have provided additional important information on transport and metabolic processes in the kidneys.

On the clinical side, the introduction of renal biopsies and of hemodialysis (and later peritoneal dialysis) by way of an arteriovenous shunt made for more accurate diagnoses and longer life expectancies for patients with chronic renal disease. Further encouragement was provided by the development of techniques for successful renal transplants, first from identical twins, then from living donors and cadavers. Problems of rejection remain. Another major challenge is to find the means of delaying or arresting the progression of chronic renal disease before dialysis and transplants become necessary.

A study published in the Journal of Epidemiology and Community Health in May 2013 reported that half of over 1,100 adults treated for stroke in Boston, Massachusetts between 1999 and 2004 lived in close proximity to a major roadway. According to researchers, there is evidence that air pollution caused by traffic can cause harm to the arteries that supply blood to the kidneys.

Bibliography

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Cameron, J. Stewart, and Richard J. Glassock, eds. The Nephrotic Syndrome. New York: Marcel Dekker, 1988.

D’Amico, G., and C. Bazzi. “Pathophysiology of Proteinuria.” Kidney International 63 (2003): 809-825.

Eddy, A. A., and J. M. Symons. “Nephrotic Syndrome in Children.” The Lancet 362 (2003): 629-639.

Hricik, D. E., M. Chung-Park, and J. R. Sedor. “Glomerulonephritis.” New England Journal of Medicine 339 (1998): 888-899.

Lue, Shih-Ho. "Residential Proximity to Major Roadways and Renal function."  Journal of Epidemiology and Community Health. 10.1136 (2012). Print.