Glucocorticoids - a "double-edged sword" for treating IgA nephropathy. 6 questions and 6 answers to help you use them clearly!

IgA nephropathy (IgAN) is a primary glomerular disease characterized by diffuse deposition of IgA or IgA-based immunoglobulins in the mesangial area of ​​renal tissue. It is also a common primary disease of chronic kidney disease in my country. Although there has been great progress in the understanding of the occurrence, development, diagnosis and treatment of the disease, its pathogenesis has not yet been clarified, and there is a lack of effective treatment methods to date [1]. Glucocorticoids are the most widely used immunomodulators in glomerular diseases, with anti-inflammatory, immunosuppressive and anti-allergic effects, but due to their many adverse reactions, there are still many limitations in clinical application. The editor summarizes 6 issues related to IgAN and glucocorticoids and shares them with everyone.

1. Do all IgAN patients need to be treated with glucocorticoids?

no.

For IgAN patients with normal renal function, if the urine protein is less than 1.0 g/d, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers can be used. In addition to lowering blood pressure, these two types of drugs also have the effects of lowering urine protein and protecting the kidneys. They are the basic drugs for chronic nephritis, especially those with combined proteinuria. It should be noted that only one of these two types of drugs can be selected, and it is not recommended to use them together.

2. When do IgAN patients need to be treated with glucocorticoids?

The KIDGO guidelines recommend [2] that patients receive 3 to 6 months of optimal supportive care (including angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and blood pressure control), but patients with persistent proteinuria >1 g/d and a glomerular filtration rate >50 ml/(min·1.73 m2) should receive 6 months of glucocorticoid treatment.

3. What are the principles for the use of glucocorticoids in patients with IgAN?

Glucocorticoid treatment of kidney disease should follow the principle of starting with sufficient dose, slowly reducing the dose, and maintaining the treatment for a long time. It should also follow the principle of individualized treatment: timely, appropriate, and individualized. The treatment cycle, dosage, and time of maintenance treatment should be determined based on the patient's age, etiology, pathology, treatment response, and whether the patient is prone to relapse.

4.What does hormone shock therapy for IgAN mean?

Hormone pulse therapy refers to oral or intravenous injection of high-dose glucocorticoids in a short period of time, which can quickly control the deterioration of the disease. The commonly used pulse treatment regimen for IgAN is: intravenous drip or intravenous push of methylprednisolone 1 g/d, for 3 consecutive days, once every other month, for a total of 3 times, combined with oral prednisone 0.5 mg/kg, once every other day, for a total of 6 months.

5.What are the adverse reactions of glucocorticoids?

Common adverse reactions to glucocorticoid treatment include secondary infection, sodium and water retention, osteoporosis, impaired glucose tolerance, gastrointestinal symptoms, neurological symptoms, etc. For patients with kidney disease, studies have shown that the lower the estimated glomerular filtration rate and the higher the blood creatinine, the higher the risk of glucocorticoid-related adverse events.

6. How to reduce the adverse reactions of glucocorticoids?

To reduce the adverse reactions of glucocorticoids, we must first choose hormones with less adverse reactions. Secondly, we must strictly control the dosage and time of medication, do not reduce the dosage without permission, and take medication according to the doctor's instructions. Finally, we need to change bad living habits in daily life, develop good habits of reasonable diet, regular work and rest, and strengthen exercise, so as to improve physical fitness and reduce the adverse reactions of glucocorticoids.

In addition, the combined use of immunosuppressants on the basis of glucocorticoid treatment, such as low-dose hormones combined with tacrolimus to treat IgAN, has a good therapeutic effect and fewer adverse reactions [3]. Other studies have found that the regimen of half-dose hormones combined with sulfonamides to prevent infection reduced the occurrence of serious adverse reactions by more than 80% without affecting the efficacy. At present, there are some progress in the research on reducing the adverse reactions of glucocorticoids: (1) Compared with the full glucocorticoid regimen, half-glucocorticoids + renin-angiotensin system blockers can reduce the occurrence of adverse events in IgAN patients and may be a better choice for the treatment of IgAN. (2) On the basis of optimizing the blockade of the renin-angiotensin system, the use of a new oral budesonide targeted release preparation, TRF-budesonide, can reduce serious systemic adverse reactions, but its tolerability and whether it improves renal outcomes still need further large-sample trials to demonstrate.

summary

As an effective means of treating IgAN, glucocorticoids have been used for a long time, in a wide range of areas, and have definite efficacy. However, the use of glucocorticoids has both risks and benefits. Many serious adverse reactions may occur during treatment. It can be said to be a "double-edged sword". In clinical applications, it is necessary to weigh its pros and cons and then develop individualized treatment plans for patients to minimize adverse factors for patients. In the future, it is still necessary to explore safer and more effective drugs to delay the progression of IgAN.

References:

[1] Liu Kaixiang, Gong Rong, Feng Jie, Xie Xisheng. Systematic review of glucocorticoids alone in the treatment of IgA nephropathy[J]. Chinese Journal of Integrated Traditional and Western Medicine Nephrology, 2020, 21(04):321-327.

[2]RADHAKRISHNAN J,CATTRAN D C. The Kdigo Practice Guideline on Glomerulonephritis: Reading between the (Guide) Lines-Application to the Individual Patient［J］. Kidney Int, 2012, 82: 840-856.

[3] Yang Lin. Observation on the effect of tacrolimus combined with low-dose hormone in the treatment of IgA nephropathy[J]. Chinese Practical Medical Journal, 2021, 48(09): 104-107.