Oral Glucocorticoids for Immunoglobulin A Nephropathy

What Is IgA Nephropathy?

Immunoglobulin A nephropathy (Berger’s disease) is a renal disease that results due to immunoglobulin A deposits accumulating in the kidneys, causing inflammation that destroys kidney tissues. IgA is an antibody, a protein built by the immune system to defend the body from foreign entities such as bacteria or viruses. Most people with IgA nephropathy need assistance from a nephrologist, a doctor who specializes in treating kidney disease.

IgA nephropathy involves the kidneys by damaging the glomeruli. The glomeruli are bunches of looping blood vessels in nephrons (the filtering units of the kidneys) that filter wastes and remove excess fluid from the blood. The buildup of IgA precipitates inflames and harms the glomeruli, resulting in the kidneys oozing blood and protein into the urine. The injury results in scarring of the nephrons that advances gradually over several years. Ultimately, IgA nephropathy can lead to end-stage renal disease, also called ESKD, which means the kidneys no longer work adequately to keep an individual healthy. When a person’s kidneys fail, a renal transplant or artificial blood-filtering treatment called dialysis is required.

What Causes IgA Nephropathy?

IgA nephropathy is an autoimmune renal disorder in which the body’s immune system damages the kidneys. People with IgA nephropathy have an elected blood level of IgA that includes less of a unique sugar, galactose, than normal. This galactose-deficient IgA is supposedly foreign by other antibodies circulating in the blood. As a result, these other antibodies bind to the galactose-deficient IgA and form a clot. This clot is also known as an immune complex. Some of the clots become attached to the glomerulus of the nephron and result in inflammation and injury. For some individuals, IgA nephropathy is familial. Recently, varied genetic markers that may play a function in the growth of the disease have been found. IgA nephropathy may also be associated with respiratory or intestinal infections and the immune system’s reaction to these infections.

What Is the Role of Glucocorticoids in Treating IgA Nephropathy?

• The record of corticosteroids in IgA nephropathy is lengthy. A study indicated a clear advantage of oral prednisone (40 milligrams per day tapered over one to two years) in the initial phase of the disease with (creatinine clearance of more than 70 millimeters per minute) and prevailing proteinuria of one to two grams per day, with a reduction in proteinuria and safety from functional deterioration at ten years follow-up.
• The results of using corticosteroids in IgA nephropathy at low doses and for a short duration are poor.
• The inflammatory behavior of IgA precipitates seemed, at this time, largely controversial.
• IgA is recognized to play a defensive role against pathogens in mucosal secretions, in evoking the inflammatory reaction by complement activation and mediators release. The mesangial cells act as glomerular capillary networks and highly reactive cells, proliferating and generating inflammatory mediators after contact with macromolecular IgA.
• Rather than passive mesangial engulfment of barely immunologically active immunoglobulins, IgA glomerular deposits turn out to be toxic resulting in mesangial cell activation, matrix production, proinflammatory cytokine release, and the endocapillary influx of inflammatory cells, which resulted in sclerosis.
• Therefore, IgA nephropathy is recognized as an inflammatory disease, providing a basis for corticosteroid therapy analyzing its pronounced anti-inflammatory consequences and instead weak immunosuppressive activity.
• The effects in patients administered with corticosteroids for six months are not appealing. At the same time, renin-angiotensin system blockers (RASB) are used in correcting renal hemodynamics, progression to sclerosis, and proteinuria, therefore, indicating a crucial role in postponing non-immune advancement of any renal disease, particularly when proteinuria is more than one gram per day.
• The Kidney Disease Improving Global Outcome (KDIGO) guidelines indicate providing corticosteroids to patients with GFR (glomerular filtration rate) more than 50 milliliter/minute per 1.73 meters square retaining persistent proteinuria more than one gram/day, despite three to six months of optimized supportive care with RASBs.
• The favorable outcomes are obtained with six-month corticosteroid regimens utilizing either a course of three intravenous pulses of one gram methylprednisolone and 0.5 milligram/kilogram oral prednisone on alternate days or a regimen of oral prednisone (0.8 to one milligram/kilogram per day) for two months, weaning over six months.
• Both strategies caused a reduction in disease advancement and proteinuria without serious side effects.

How Is IgA Nephropathy Treated?

The treatment of IgA nephropathy involves:

Supportive Care With Antiproteinuric and Antihypertensive Drugs -

Long-term ACE-I (angiotensin-converting enzyme inhibitor) and renin-angiotensin system blockers (RASB) treatment when proteinuria is needed when proteinuria is more than one gram/day, with up-titration of the drug based on blood pressure. Suggestions to up-titrate RASBs to be given until proteinuria less than one gram/day is achieved.

Corticosteroids -

Patients with persistent proteinuria of more than one gram per day, in spite of three to six months of optimized supportive care (with RASBs and blood pressure control) and GFR of more than 50 millimeters/minutes, should be given a six-month course of corticosteroid therapy.

Corticosteroid Regimens -

Intravenous injection of one gram Methylprednisolone for three days each at months one, three, and five followed by oral steroid (0.5 milligram per kilogram Prednisone) on 26 alternate days for six months.

Intravenous injection of one gram Methylprednisolone for three days each at months one, three, and five followed by oral steroid (0.5 milligram per kilogram Prednisone) on 26 alternate days for six months.

Oral Prednisone begins at 0.8 to one milligram/kilogram per day for two months and then decreased by 0.2 milligram per kilogram per day per month for the next 4 to 28 months.

Immunosuppressive Agents - Cyclophosphamide and Azathioprine are used in the treatment. The corticosteroids combined with Cyclophosphamide or Azathioprine in patients with IgA nephropathy are not used unless there is a crescentic IgA nephropathy with the quickly advanced course.

Conclusion:

IgA nephropathy is an autoimmune disease and requires immunosuppressive drugs for the treatment. The symptoms are the same as renal function impairment. The diagnosis is made based on the lab findings and imaging tests. The treatment involves corticosteroids and immunosuppressive drugs to prevent the immune system from attacking healthy renal tissues. The use of oral glucocorticoids helps in the prevention of inflammation of the renal tissues and renal function impairment.