For the initial treatment of lupus nephritis with glucocorticoids, should I choose a high dose or a medium dose?

Kidney damage secondary to systemic lupus erythematosus (SLE) is called lupus nephritis (LN).

More than 50% of SLE patients have kidney involvement clinically, and LN is one of the most common secondary kidney diseases in China.

Glucocorticoids are traditional medicines for relieving LN.
The three principles of "sufficiency, slow reduction and long-term maintenance" are usually followed in China.

Recently, a study from the Lupus Clinic of the University of Toronto made recommendations for the glucocorticoid medication regimen for newly-onset LN patients.
This recommendation is mainly for the "sufficient amount" and "slow reduction" of the traditional medication regimen.

1Research background The existing LN treatment guidelines recommend the use of glucocorticoids (usually the starting dose is prednisone 0.
3-1mg/kg/d or equivalent doses of other glucocorticoids) and immunosuppressive agents (such as mycophenolate mofetil) Esters, cyclophosphamide, etc.
).

The recommended dose of prednisone for LN patients in the New Nephrology Physician's Manual in my country is 1mg/kg/d or 40-60mg/d.

 However, recent studies have reported that lower doses of prednisone have non-inferiority compared to the above recommended doses of prednisone.

This study aims to evaluate the difference in the complete renal response rate between prednisone ≤ 30 mg/d and ≥ 40 mg/d.

Complete renal response is defined as proteinuria <0.
5g/d, and renal function has not deteriorated.

In addition, glucocorticoid-related damage was also assessed.

2Research Overview From 1970 to November 2019, the Lupus Clinic at the University of Toronto recruited 2,050 LN patients, matched propensity scores based on baseline data, and finally enrolled 206 newly diagnosed LN patients who had started treatment.

The participants were divided into two groups: high-dose group (prednisone ≥ 40 mg/d) and medium-dose group (prednisone ≤ 30 mg/d), followed up for at least 12 months.

The results showed that the high-dose group had a higher complete remission rate than the medium-dose group at 12 months (61.
8% vs 38.
2%, p=0.
024).

The average doses of the two groups were 48.
6±12.
3 mg/d and 24.
2±4.
6 mg/d, respectively.

In this study, patients in the high-dose group were more severely ill, such as higher blood creatinine at baseline, lower eGFR levels, and more patients with type 4 LN.

 In the second year of LN diagnosis, the complete remission rate was 67.
8% in the high-dose group and 39% in the medium-dose group (P=0.
002); in the third year, the complete remission rate was 64.
9% in the high-dose group and 49.
1% in the medium-dose group (P =0.
025).

 Although early use of high-dose glucocorticoid therapy can achieve good results, the related adverse events are worthy of attention.

There was no significant difference between the cumulative glucocorticoid dose and glucocorticoid-related damage two and three years after LN diagnosis.

In the late stage of LN, the damage in the two groups was more obvious, suggesting the need for rapid dose reduction or alternative treatment strategies.

 In conclusion, in patients with new-onset LN, a higher initial dose of prednisone (median 45 mg/d) can significantly increase the complete renal response rate at 12 months.

At the same time, considering the adverse effects of glucocorticoids, researchers believe that patients with new-onset LN are initially treated with a higher dose of prednisone, and the dose is reduced rapidly based on the patient's clinical response, and the effect is better.

References: 1.
Tselios K, GladmanDD, Al-Sheikh H, et al.
Medium versus high initial prednisone dose forremission induction in lupus nephritis: A propensity score matched analysis.
Arthritis Care Res (Hoboken).
04 Mar 2021.
2.
Shi Hongbin, Tang Liping , Zeng Qiao, et al.
Handbook of New Nephrology Physicians (Third Edition).
Beijing: Chemical Industry Press, 2019: 41-49.