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Hereditary nephritis is a genetically heterogeneous disorder characterized by hematuria, impaired renal function, sensorineural hearing loss, and ocular abnormalities. Cause is a gene mutation affecting type IV collagen. Symptoms and signs are those of nephritic syndrome (ie, hematuria, proteinuria, hypertension, eventual renal insufficiency) often with sensorineural deafness and, less commonly, ophthalmologic symptoms. Diagnosis is by history, including family history, urinalysis, and biopsy (renal or skin). Treatment is the same as that of chronic kidney disease, sometimes including kidney transplantation.
Hereditary nephritis is a nephritic syndrome (see Overview of Nephritic Syndrome) caused by a mutation in the COL4A5 gene that encodes the α-5 chain of type IV collagen and results in altered type IV collagen strands. The mechanism by which collagen alteration causes a glomerular disorder is unknown, but impaired structure and function are presumed; in most families, thickening and thinning of the glomerular and tubular basement membranes occur, with multilamination of the lamina densa in a focal or local distribution (basket-weave pattern). Glomerular scarring and interstitial fibrosis eventually result.
The disorder is most commonly inherited in X-linked fashion, although autosomal recessive and dominant varieties exist. Patients may develop renal insufficiency between ages 20 and 30 yr (juvenile form) or after age 30 (adult form).
Because of X-linked transmission, women usually are asymptomatic and have little functional impairment. Most men eventually develop renal symptoms and signs similar to those of acute nephritic syndrome (eg, microscopic hematuria, hypertension, eventually gross hematuria with proteinuria) and progress to renal insufficiency between ages 20 and 30 (juvenile form).
Sensorineural hearing loss frequently is present, affecting higher frequencies; it may not be noticed during early childhood. Some men develop renal insufficiency after age 30 (adult form) with hearing loss that occurs late or is mild. Some patients have sensorineural hearing loss alone without renal disease but can transmit renal disease to their children.
Ophthalmologic abnormalities—cataracts (most common), anterior lenticonus (a regular conical protrusion on the anterior aspect of the lens due to thinning of the lens capsule), spherophakia (spherical lens deformation that can predispose to lens subluxation), nystagmus, retinitis pigmentosa, blindness—also occur but less frequently than hearing loss.
Other nonrenal manifestations include polyneuropathy and thrombocytopenia.
Diagnosis is suggested in patients who have microscopic hematuria on urinalysis or recurrent episodes of gross hematuria, particularly if an abnormality of hearing or vision or a family history of chronic kidney disease is present.
Urinalysis and usually renal biopsy are done. In addition to dysmorphic RBCs, the urine may contain protein, WBCs, and casts of various types. Nephrotic syndrome occurs rarely. No distinguishing histologic changes are seen on light microscopy. The diagnosis can be confirmed by any of the following:
Renal biopsy with immunostaining for the subtypes of type IV collagen
Characteristic disorganization of the lamina densa with variable thickening and thinning of the glomerular capillary seen using electron microscopy
Skin biopsy with immunostaining for the type IV collagen subtypes in a patient with a positive family history
A combination of immunostaining and electron microscopy is often needed to distinguish hereditary nephritis from some forms of thin basement membrane disease. Although not yet widely available, molecular techniques for evaluating DNA gene mutations or mRNA may become the diagnostic techniques of choice.
Treatment is indicated only when uremia occurs; its management is the same as that for other causes of chronic kidney disease (see Chronic Kidney Disease : Treatment). Anecdotal reports suggest that ACE inhibitors or angiotensin II receptor blockers may slow progression of renal disease. Transplantation has been successful, but anti-glomerular basement membrane antibody disease may occur in the transplanted kidney. Genetic counseling is indicated.
Consider hereditary nephritis if patients have hematuria plus a hearing and/or vision abnormality or a family history of chronic kidney disease.
Confirm the diagnosis by biopsy of the kidney or sometimes skin and immunostaining for type IV collagen subtypes.
Treat chronic kidney disease and consider transplantation.
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