Arthritis Rheumatol: The relationship between urinary matrix metalloproteinase 7 and the pathogenesis of lupus nephritis

Purpose: The worsening of lupus nephritis (LN) is related to poor renal prognosis
.

One of the main management obstacles to LN deterioration is the lack of effective methods to identify high-risk patients early in the course of the disease

The worsening of lupus nephritis (LN) is related to poor renal prognosis

Results: The level of uMMP7 in patients with lupus nephritis was elevated
.

The higher the level of uMMP7 in LN, the stronger the histological activity of the kidney

Figure 1 The level of uMMP7 in LN patients was significantly increased; (A) LN patients (Phase I trial cohort, n=88), patients with extrarenal systemic lupus erythematosus (SLE, n=30), had minor changes in nephropathy on the day of biopsy (MCD, n=20) or uMMP7 levels in thin basement membrane nephropathy (TBMN, n=20), and healthy volunteers (control group, n=20)
.

The horizontal line represents the median and interquartile range

Figure 1 The level of uMMP7 in LN patients was significantly increased; (A) LN patients (Phase I trial cohort, n=88), patients with extrarenal systemic lupus erythematosus (SLE, n=30), had minor changes in nephropathy on the day of biopsy (MCD, n=20) or uMMP7 levels in thin basement membrane nephropathy (TBMN, n=20), and healthy volunteers (control group, n=20)

Figure 2 The increase of uMMP7 level during biopsy is related to the enhancement of LN renal histological activity; (A) Representative images of biopsy of LN patients showed active renal disease by PAS staining (Phase I trial cohort, n=88)
.

The level of uMMP7 and renal tissue activity index (AI) at the time of biopsy are displayed at the top of each image

Figure 2 The increase of uMMP7 level during biopsy is related to the enhancement of LN renal histological activity; (A) Representative images of biopsy of LN patients showed active renal disease by PAS staining (Phase I trial cohort, n=88)

Figure 3 uMMP7 levels are related to LN deterioration; in the whole cohort and subgroups of patients stratified according to the presence or absence of hypertension, the use or non-use of renin-angiotensin system (RAS) blockers, uMMP7 levels are associated with subsequent occurrences LN deterioration is related
.

The whisker plot shows the 95% confidence interval (95% CI) of the average hazard ratio

Figure 3 uMMP7 levels are related to LN deterioration; in the whole cohort and subgroups of patients stratified according to the presence or absence of hypertension, the use or non-use of renin-angiotensin system (RAS) blockers, uMMP7 levels are associated with subsequent occurrences LN deterioration is related

Figure 4 The increase in uMMP7 level during follow-up indicates that LN worsens before clinical examination; (A) Comprehensive patient value
.

The levels of uMMP7 in LN patients (n=15) were compared with routine clinical measures before, during and after the onset of LN

Figure 4 The increase in uMMP7 level during follow-up indicates that LN worsens before clinical examination; (A) Comprehensive patient value
.
The levels of uMMP7 in LN patients (n=15) were compared with routine clinical measures before, during and after the onset of LN
.
Deterioration is indicated as 0 time point
.
The data are expressed as mean ± SE
.
Mann-Whitney U test
.
*, P <0.
05; * *, P <0.
01; * * *, P <0.
001
.
(B) Measure the time point at which uMMP7 (defined as uMMP7 >2.
5 ng/mg creatinine) or proteinuria (defined as an increase of more than 0.
5 g/d) rises
.
An increase in uMMP7 indicates an early deterioration of the kidneys (median [interquartile range]; 3 [2-4] months) rather than an increase in proteinuria
.
Mann-Whitney U test
.
* * *, P <0.
001
.
(C) Comparison of uMMP7 level at the time of deterioration with uMMP7 level at the end of follow-up
.
When LN is in remission, the uMMP7 level decreases (left panel), and the uMMP7 level remains stable in patients who are not in remission (right panel)
.
Mann-Whitney U test
.
* * *, P <0.
001
.
Scr, serum creatinine
.

Figure 5 The level of uMMP7 in patients with LN is closely related to the histological activity of the kidney; (A) A typical image shows the expression of MMP7 in the kidney during diagnosis of LN (initial biopsy) and deterioration of LN (repeated biopsy)
.
The uMMP7 level and histological activity index (AI) at the biopsy site are displayed at the top of each image
.
The arrow indicates that the renal tubules are positive
.
The scale is 50µm
.
(BD), renal AI (B) uMMP7 level (C) and renal MMP7 expression (D) (blue circle) compared with LN onset (red circle) (n=5)
.

Figure 5 The level of uMMP7 in patients with LN is closely related to the histological activity of the kidney; (A) A typical image shows the expression of MMP7 in the kidney during diagnosis of LN (initial biopsy) and deterioration of LN (repeated biopsy)
.
The uMMP7 level and histological activity index (AI) at the biopsy site are displayed at the top of each image
.
The arrow indicates that the renal tubules are positive
.
The scale is 50µm
.
(BD), renal AI (B) uMMP7 level (C) and renal MMP7 expression (D) (blue circle) compared with LN onset (red circle) (n=5)
.

Conclusion: The level of uMMP7 in LN is related to renal histological activity
.
The increase of uMMP7 after renal remission is related to renal deterioration
.

The level of uMMP7 in LN is related to renal histological activity
.
The increase of uMMP7 after renal remission is related to renal deterioration
.

Original source:

Wang G,Wu L,Su H,Feng X,et al, Association of Urinary Matrix Metalloproteinase 7 Levels With Incident Renal Flare in Lupus Nephritis.
Arthritis Rheumatol 2021 02;73(2)

Association of Urinary Matrix Metalloproteinase 7 Levels With Incident Renal Flare in Lupus Nephritis.
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