Interpretation of multi-faceted guidelines, how to accurately apply hormones in the treatment of lupus nephritis?

It is only for medical professionals to read for reference.
To solve the "old problem" of lupus nephritis medication, nearly half of patients with systemic lupus erythematosus (SLE) are complicated by lupus nephritis (LN), LN is one of the common causes of end-stage renal disease (ESRD)
.

In recent years, with the progress of basic research and clinical research, the diagnosis and treatment of LN has also made progress, especially in the treatment and application of hormones
.

According to the guidelines, this article summarizes the precision medication for LN treatment as follows
.

 Comparison of three guideline hormone treatment programs.
Glucocorticoid is a traditional medicine to relieve LN
.
The three principles of "sufficiency, slow reduction and long-term maintenance" are generally followed in China .

In recent years, the three major guidelines have changed the treatment options for LN hormones and other immunosuppressive agents
.

 The 2012 Guidelines for Improving the Prognosis of Global Kidney Diseases (KDIGO) pointed out that for type II LN, if proteinuria is greater than 3 g/d, hormones or hormones combined with calcineurin inhibitors (CNI) can be added to induce remission
.

For the III/IV±V type of remission induction program, hormone combined with immunosuppressive agent, hormone 1mg/(kg·d)
.

The dose of prednisone in the maintenance phase is less than 10 mg/d, and the medication is maintained for at least 1 year
.

For type V LN, use the hormone 10mg/d in the maintenance phase, combined with the minimum effective dose of tacrolimus (TAC)
.

 The 2019 revision of the KDIGO guidelines reduced the amount of hormones in the maintenance phase to less than 5 mg/d instead of 10 mg/d; at the same time, the maintenance treatment time was extended from 1 year to 3 years
.

Studies have shown that the recurrence rate of LN in patients treated with this program is only 1.
5 times per year, which is much smaller than previous reports
.

 The "2019 European Union Against Rheumatism (EULAR) Recommendations and Recommendations on Systemic Lupus Erythematosus" refers to the induction remission program for Type III/IV±V LN, using 0.
5~2.
5g methylprednisolone pulse therapy, and then using hormone 20 ~30mg/d, maintenance sequential treatment, after 6 months, reduced to 7.
5mg/d, maintenance treatment with mycophenolate mofetil (MMF) or azathioprine (AZA)
.

For simple type V LN, intravenous injection of methylprednisolone 0.
5~2.
5g, 20mg/d to maintain sequential treatment, 3 months to reduce to 5mg/d and minimum effective dose of CNIs to maintain
.

 "2020 Chinese Systemic Lupus Erythematosus Guidelines" proposes to use methylprednisolone 500~750mg/d, shock therapy for 3 days, repeat if necessary, and accumulate 3~4.
5g
.

The maintenance dose of prednisone is 7.
5 mg recommended in China and 5 mg recommended in Europe and America
.

Table 1: The three major guidelines for type III and type IV LN treatment options are not difficult to see.
The new version of the guidelines recommends reducing the cumulative dosage and maintenance dose of hormones, and extending the maintenance time to reduce the incidence of LN recurrence and ESRD
.

 Some people in China have explored the effects of different prednisone acetate doses combined with CYC and Tripterygium wilfordii on irregular chemokine (FKN), cathepsin S and vascular endothelial adhesion factor-1 (VCAM-1) in elderly patients with LN
.

Grouped control treatment showed that when the dose of prednisone acetate is 0.
6mg/(kg·d), the therapeutic effect of combined CYC and Tripterygium wilfordii on elderly patients with LN is better than 0.
8mg/(kg·d) and 1.
0mg/( kg·d), the effect of regulating the expression levels of blood FKN, cathepsin S and VCAM-1 is more obvious
.

 Latest research report: Adjustment of the initial dose of hormones Recently, the Lupus Clinic of the University of Toronto released a research report on the glucocorticoid medication regimen for LN patients
.

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

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

In addition, glucocorticoid-related damage was also assessed
.

 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 type IV LN patients
.

 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)
.

  The researchers found that 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
.

 Summary of the application of hormones in the treatment of LN ■ Application in the induction treatment period Glucocorticoids are the most important drugs for the treatment of LN
.

Generally use intermediate-acting hormones, such as prednisone, prednisolone, or methylprednisolone.
The starting dose is usually 1mg/(kg·d) of prednisone
.

 After that, reduce the dose gradually, usually at a rate of 10% reduction every 10 days.
After the dose is reduced to less than 0.
5 mg/(kg·d) of prednisone, the rate of drug reduction should be further slowed down; if the condition permits, prednisone The dose should be less than 10mg/d as far as possible
.

 For those patients with acute renal failure, or LN patients whose blood creatinine level is still within the normal range, but a large number of cell crescent formations are found on renal pathological biopsy, hormone shock therapy can be considered, usually using methylprednisolone 500-1000mg intravenous infusion, Once a day, continuous use for 3-5 days is a course of treatment, if necessary, the shock treatment can be repeated after 1 week
.

 For the induction phase treatment of proliferative LN (type Ⅲ, Ⅳ, Ⅴ, and Ⅲ+Ⅴ and Ⅳ+Ⅴ LN), the combination of immunosuppressive agents can be used on the basis of glucocorticoids
.

 ■ Application in the maintenance treatment period After 6-12 months of induction therapy, the patient's SLE gradually stabilized, LN was relieved, and the patient's treatment entered the maintenance treatment phase
.

Maintenance treatment of LN requires at least 3-4 years
.

In the maintenance treatment stage, the hormone should be gradually reduced to the lowest effective dose to maintain the disease without recurrence.
After the condition continues to stabilize, the daily hormone therapy can be gradually transferred to the alternate day therapy
.

It should be noted that long-term use of hormones may cause adverse reactions, such as central obesity, elevated blood sugar, high blood pressure, induced infections, aseptic necrosis of the femoral head, and osteoporosis, etc.
The medication should be closely monitored and paid attention to.
Prevention
.

 In summary, the treatment of LN mainly depends on hormones or combined immunosuppressive agents
.

In the remission induction treatment stage, high-dose hormones or even methylprednisolone shock therapy are required.
For proliferative LN immunosuppressants, MMF is the first choice, with a dose of 1.
5-2g/d, divided into 2 to 3 times orally; in the maintenance treatment stage, Try to reduce the hormone dose to the lowest effective dose.
Immunosuppressants are still the preferred MMF (or AZA) to reduce the risk of adverse reactions
.

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Source: Medical Community Nephropathy Channel Author: Chang Yiyong Reviewer: Professor Li Qing, editor in charge: Cassette copyright statement