IgA nephritis

IgA nephritis (also known as Berger's disease and synpharyngitic glomerulonephritis) is aform of glomerulonephritis ( inflammation of the glomeruli of the kidney ). It presents with hematuria and generally resolves spontaneously, but a proportion of patientsdevelops chronic renal failure . IgA is the antibody which accumulates in the kidney and probably plays a central role in thedisease.

Signs and symptoms

The classic presentation (in 40-50% of the cases) is frank hematuria whichstarts one or more days after an upper respiratory tract infection (sore throat). Flank pain can occur. The hematuriaresolves after a few days. These episodes occur on an irregular basis, and in most patients, this eventually stops (although itcan take many years).

A smaller proportion (20-30%) has microscopic hematuria and proteinuria (less than2 gram of protein per 24 hours). These patients can have mild symptoms and are only pickedup if a doctor decides to take a urine sample.

Very rarely (5% each), the presenting history is:

• Nephrotic syndrome (excessive protein loss in theurine)
• Acute renal failure (generally a complication of thehematuria)
• Chronic renal failure (no previous symptoms, presentswith anemia , hypertension andother symptoms of renal failure)

IgA-nephritis can occur in the context of liver failure , coeliac disease , rheumatoid arthritis , Reiter's disease , ankylosingspondylitis and HIV . Occasionally, there are simultaneous symptoms of Henoch-Schönlein purpura ; see below for more details onthe association.

Diagnosis

The history and association with respiratory infection can raise the suspicion IgAN. A urinary specimen can confirm thesuspicion ( red blood cells , sometimes in cylinders), but in order tocompletely determine the cause, a kidney biopsy is necessary (generally performed under local anaesthetic ). The biopsy specimen shows proliferation of the mesangium and occasional crescentic changes(see below).

Blood tests that are generally performed before the biopsy are: full blood count , coagulation ( APTT , PT ), CRP or ESR , electrolytes , renal function ( creatinine , urea ), total protein, albumin , LDH . Protein electrophoresis and immunoglobulin levels can show increased IgA1 in up to 30% of all patients. Complement levels can be decreased.

Ultrasound of the kidney is generally performed atsome stage in the diagnostic tract.

Differential diagnosis: other diseases that cause episodic hematuria are kidney stones , bladder cancer and Alport's disease . Post-streptococcal glomerulonephritis occurs longer after the throat infection andpresents differently (see there).

Pathophysiology

The disease derives its name from deposits of Immunoglobulin A (IgA) in ablotchy pattern in the mesangium (on immunofluorescence ), theheart of the renal glomerulus . As a rule, this affects the whole kidney. Thetissue changes gradually from being hypercellular to depositing extracellular matrix proteins, and finally fibrosis .

There is no clear known explaination for the accumulation of the IgA. Exogenous antigens for IgA have not been identified in the kidney, but it is possible that this antigen has been clearedbefore the disease manifests itself.

A recently advanced theory focuses on abnormalities of the IgA1 molecule. IgA1 is one of the two immunoglobulin subclasses(the other is IgD) that is O-glycosylated on a number of serine and threonine residues in a special proline -rich hinge region. Deficiency of these sugars appears to lead to polymerisation of the IgA molecule in tissues, especially the glomerular mesangium. A similarmechanism has been claimed to underly Henoch-Schönlein purpura (HSP), a vasculitis that mainly affects children and can feature renal involvement that is almost indistinguishable from IgA nephritis.

From the fact that IgAN can recur after renal transplant it can be postulated that the disease is caused by a problem in the immune system rather than the kidney itself. Remarkably, the IgA1 thataccumulates in the kidney does not appear to originate from the mucosa-associated lymphoid tissue (MALT), which is the site ofmost upper respiratory tract infections, but from the bone marrow . This, too,suggests an immune pathology rather than direct interference by outside agents.

Therapy

There is no curative therapy for IgAN. People with a known propensity often have their renal function monitored once every fewmonths, to identify chronic renal failure if this occurs. Tonsillectomy (to decrease the amount of infections) is not effective inslowing down any long-term kidney damage, although attack frequency decreases.

Proteinuria responds to ACE inhibitor therapy, and some studies indicate favorable response to prednisolone .

Genetics

Virtually all cases are sporadic, although a family in Kentucky has beendescribed where IgAN occurs in a familial pattern ( OMIM 161950 ).

Prognosis

Episodes of hematuria recur with variable frequency in most patients, but this generally resolves over a number of years. Thiscan take a long time: after 10 years, 30% has ceased having attacks. Strangely, the classic form (episodic hematuria) has a goodprognosis.

Up to 25% develops chronic renal failure within 20years of diagnosis. Unfortunately, the disease can recur after renal transplant , potentially damaging the graft.

Epidemiology

Males are affected three times as often as women. For an unknown reason, it occurs more often in Meditteranian and Pacificcountries than in Northern Europe and America. Kaukasians are most often affected, while Afro-Caribbeans and Polynesians rarelyare, even when they live in Westernised countries. This argues in favour of a genetic cause.

History

The disease was first described in French in 1968 : Berger J, Hinglais N. Les depots intercapillaires d'IgA-IgG. J Urol Nephrol 1968;74:694-5.

Sources

• Oxford Textbook of Medicine