J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 16, Number 2-3, March 2024, pages 106-117

Comparison of Clinical Features, Treatment and Outcomes of Lupus Nephritis Between Patients With Late- and Early-Onset Systemic Lupus Erythematosus: A Controlled Study

Figure 1. Flowchart showing the matching process. ACR: American College of Rheumatology; SLE: systemic lupus erythematosus.

Figure 2. Kaplan-Meier curve showing mortality rate among late- and early-onset SLE patients. SLE: systemic lupus erythematosus.

**Table 1.** Demographic Characteristics of Late- and Early-Onset SLE Patients With LN
Variables	Late-onset SLE (N = 33)	Early-onset SLE (N = 90)	P-value
Data are expressed as mean (95% CI) or n (%). ^aTransformed data. ^bAt SLE diagnosis. *Statistically significant. CI: confidence interval; LN: lupus nephritis; SLE: systemic lupus erythematosus.
Female	28 (84.85)	82 (91.11)	0.425
Body weight (kg)	47.31 (44.57 - 50.10)	50.81 (48.91 - 52.72)	0.052
Age at SLE diagnosis (years)	56.27 (54.79 - 57.75)	29.96 (28.06 - 31.86)	< 0.001*
Age at LN diagnosis (years)	56.78 (55.27 - 58.30)	31.52 (29.60 - 33.44)	< 0.001*
Duration of SLE (years)^a	3.87 (2.51 - 5.54)	6.46 (5.35 - 7.68)	0.011*
Duration of LN (years)^a	3.68 (2.33 - 5.34)	5.39 (2.33 - 5.34)	0.073
Year of LN diagnosis			0.629
1990 - 1999	0	2 (2.22)
2000 - 2009	13 (39.39)	31 (34.44)
2010 - 2020	20 (60.61)	57 (63.33)
Underlying disease^b
Hypertension	9 (27.27)	2 (2.22)	< 0.001*
Diabetes mellitus	3 (9.09)	1 (1.11)	0.059
Dyslipidemia	1 (3.03)	0	0.286
Chronic kidney disease	1 (3.03)	0	0.268
Thyroid disease	4 (12.12)	4 (4.44)	0.209
Cerebrovascular disease	1 (3.03)	0	0.268
Venous thromboembolism	0	1 (1.11)	1.000
Heart disease	3 (9.09)	2 (2.22)	0.119
Malignancy	0	1 (1.11)	1.000

Table 1. Demographic Characteristics of Late- and Early-Onset SLE Patients With LN

Variables

Late-onset SLE (N = 33)

Early-onset SLE (N = 90)

P-value

Data are expressed as mean (95% CI) or n (%). ^aTransformed data. ^bAt SLE diagnosis. *Statistically significant. CI: confidence interval; LN: lupus nephritis; SLE: systemic lupus erythematosus.

Female

28 (84.85)

82 (91.11)

0.425

Body weight (kg)

47.31 (44.57 - 50.10)

50.81 (48.91 - 52.72)

0.052

Age at SLE diagnosis (years)

56.27 (54.79 - 57.75)

29.96 (28.06 - 31.86)

< 0.001*

Age at LN diagnosis (years)

56.78 (55.27 - 58.30)

31.52 (29.60 - 33.44)

< 0.001*

Duration of SLE (years)^a

3.87 (2.51 - 5.54)

6.46 (5.35 - 7.68)

0.011*

Duration of LN (years)^a

3.68 (2.33 - 5.34)

5.39 (2.33 - 5.34)

0.073

Year of LN diagnosis

0.629

1990 - 1999

2 (2.22)

2000 - 2009

13 (39.39)

31 (34.44)

2010 - 2020

20 (60.61)

57 (63.33)

Underlying disease^b

Hypertension

9 (27.27)

2 (2.22)

< 0.001*

Diabetes mellitus

3 (9.09)

1 (1.11)

0.059

Dyslipidemia

1 (3.03)

0.286

Chronic kidney disease

1 (3.03)

0.268

Thyroid disease

4 (12.12)

4 (4.44)

0.209

Cerebrovascular disease

1 (3.03)

0.268

Venous thromboembolism

1 (1.11)

1.000

Heart disease

3 (9.09)

2 (2.22)

0.119

Malignancy

1 (1.11)

1.000

**Table 2.** Comparison of 1997 ACR Classification Criteria for SLE, SLE Disease Activity and Damage Score at SLE Diagnosis Between Late- and Early-Onset SLE Patients With LN
Variables	Late-onset SLE (N = 33)	Early-onset SLE (N = 90)	P-value
Data are expressed as mean (95% CI) or n (%) unless indicates otherwise. ^aTransformed data. *Statistically significant. ACR: American College of Rheumatology; ANA: anti-nuclear antibody; anti-dsDNA: anti-double stranded DNA antibody; anti-Sm: anti-Smith antibody; CI: confidence interval; LN: lupus nephritis; mSLEDAI-2K: modified systemic lupus erythematosus disease activity index-2000; n/N: number of positive tests/numbers of patients tested; SDI: ACR/Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) damage index; SLE: systemic lupus erythematosus.
Mucocutaneous manifestation	19 (57.58)	64 (71.11)	0.156
Malar rash	5 (15.15)	34 (37.78)	0.017*
Discoid rash	11 (33.33)	35 (38.89)	0.573
Oral ulcers	7 (21.21)	34 (37.78)	0.084
Photosensitivity	5 (15.15)	14 (15.56)	0.956
Nonerosive arthritis	10 (30.30)	54 (60.00)	0.003*
Serositis	13 (39.39)	13 (14.44)	0.003*
Pleuritis	8 (24.24)	10 (11.11)	0.068
Pericarditis	8 (24.24)	8 (8.89)	0.025*
Lupus nephritis	29 (87.88)	58 (64.44)	0.011*
Neurologic disorder	4 (12.12)	5 (5.56)	0.215
Seizures	2 (6.06)	2 (2.22)	0.288
Psychosis	2 (6.06)	3 (3.33)	0.497
Hematologic disorder	25 (75.76)	73 (81.11)	0.513
Hemolytic anemia	18 (54.55)	30 (33.71)	0.036*
Leukopenia	12 (36.36)	46 (51.11)	0.147
Lymphopenia	17 (51.52)	62 (68.89)	0.075
Thrombocytopenia	8 (24.24)	16 (17.78)	0.423
Positive ANA, n (%)	33 (100)	89/89 (100)
Immunologic disorder
Anti-dsDNA, n/N (%)	20/29 (68.97)	61/70 (87.14)	0.033*
Anti-Sm, n/N (%)	4/8 (50.00)	4/10 (40.00)	0.671
Anticardiolipin, n/N (%)	4/19 (21.05)	10/40 (25.00)	0.739
Lupus anticoagulant, n/N (%)	5/14 (35.71)	9/29 (31.03)	0.759
Number of ACR criteria	5.00 (4.58 - 5.42)	5.24 (4.95 - 5.53)	0.369
mSLEDAI-2K at SLE diagnosis^a	9.46 (7.43 - 11.72)	8.72 (7.46 - 10.07)	0.563
SDI at SLE diagnosis	0.94 (0.61 - 1.27)	0.13 (0.06 - 0.21)	< 0.001*

Table 2. Comparison of 1997 ACR Classification Criteria for SLE, SLE Disease Activity and Damage Score at SLE Diagnosis Between Late- and Early-Onset SLE Patients With LN

Variables

Late-onset SLE (N = 33)

Early-onset SLE (N = 90)

P-value

Data are expressed as mean (95% CI) or n (%) unless indicates otherwise. ^aTransformed data. *Statistically significant. ACR: American College of Rheumatology; ANA: anti-nuclear antibody; anti-dsDNA: anti-double stranded DNA antibody; anti-Sm: anti-Smith antibody; CI: confidence interval; LN: lupus nephritis; mSLEDAI-2K: modified systemic lupus erythematosus disease activity index-2000; n/N: number of positive tests/numbers of patients tested; SDI: ACR/Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) damage index; SLE: systemic lupus erythematosus.

Mucocutaneous manifestation

19 (57.58)

64 (71.11)

0.156

Malar rash

5 (15.15)

34 (37.78)

0.017*

Discoid rash

11 (33.33)

35 (38.89)

0.573

Oral ulcers

7 (21.21)

34 (37.78)

0.084

Photosensitivity

5 (15.15)

14 (15.56)

0.956

Nonerosive arthritis

10 (30.30)

54 (60.00)

0.003*

Serositis

13 (39.39)

13 (14.44)

0.003*

Pleuritis

8 (24.24)

10 (11.11)

0.068

Pericarditis

8 (24.24)

8 (8.89)

0.025*

Lupus nephritis

29 (87.88)

58 (64.44)

0.011*

Neurologic disorder

4 (12.12)

5 (5.56)

0.215

Seizures

2 (6.06)

2 (2.22)

0.288

Psychosis

2 (6.06)

3 (3.33)

0.497

Hematologic disorder

25 (75.76)

73 (81.11)

0.513

Hemolytic anemia

18 (54.55)

30 (33.71)

0.036*

Leukopenia

12 (36.36)

46 (51.11)

0.147

Lymphopenia

17 (51.52)

62 (68.89)

0.075

Thrombocytopenia

8 (24.24)

16 (17.78)

0.423

Positive ANA, n (%)

33 (100)

89/89 (100)

Immunologic disorder

Anti-dsDNA, n/N (%)

20/29 (68.97)

61/70 (87.14)

0.033*

Anti-Sm, n/N (%)

4/8 (50.00)

4/10 (40.00)

0.671

Anticardiolipin, n/N (%)

4/19 (21.05)

10/40 (25.00)

0.739

Lupus anticoagulant, n/N (%)

5/14 (35.71)

9/29 (31.03)

0.759

Number of ACR criteria

5.00 (4.58 - 5.42)

5.24 (4.95 - 5.53)

0.369

mSLEDAI-2K at SLE diagnosis^a

9.46 (7.43 - 11.72)

8.72 (7.46 - 10.07)

0.563

SDI at SLE diagnosis

0.94 (0.61 - 1.27)

0.13 (0.06 - 0.21)

< 0.001*

**Table 3.** Renal Manifestations and Response to Treatment of First LN Episode Between Late- and Early-Onset SLE Patients
Variables	Late-onset SLE (N = 33)	Early-onset SLE (N = 90)	P-value
Data are expressed as mean (95% CI) or n (%) unless indicates otherwise. *Statistically significant.^aHypertension was adjusted with underlying hypertension. ^bTransformed data. ^cUnavailable data in one. ^dDead in five and missing in one. ^eDead in five and unavailable data in two. ^fDead in three, unavailable data in two and study censor in one. ^gDead in three, unavailable data in one and study censor in four. LN: lupus nephritis; n: number of observations; n/N: number of positive tests or clinical manifestation/number of patients tested or had clinical manifestations; CI: confidence interval; eGFR: estimated glomerular filtration rate; RPGN: rapidly progressive glomerulonephritis; SLE: systemic lupus erythematosus; UPCR: urine protein-creatinine ratio.
Hypertensive episode during active LN^a, n/N (%) (n)	8/33 (24.24) (33)	9/90 (10.00) (90)	0.235
Serum creatinine (mg/dL)^b (n)	0.84 (0.71 - 1.01) (33)	0.83 (0.79 - 0.93) (90)	0.888
eGFR (mL/min/1.73 m²) (n)	81.43 (67.56 - 95.31) (33)	93.97 (86.49 - 101.45) (90)	0.096
< 30 mL/min/1.73 m², n/N (%)	2/33 (6.06)	4/90 (4.44)	0.712
UPCR^b (n)	2.57 (2.04 - 3.25) (33)	1.94 (1.63 - 2.31) (89)	0.078
UPCR ≥ 3.5, n/N (%)	12/33 (36.36)	23/89 (25.84)	0.254
Serum albumin (g/dL) (n)	2.30 (2.06 - 2.53) (33)	2.94 (2.79 - 3.09) (89)	< 0.001*
Low C3 level, n/N (%)	19/28 (67.86)	44/59 (74.58)	0.512
Low C4 level, n/N (%)	16/27 (59.26)	38/55 (69.09)	0.378
Anti-dsDNA, n/N (%)	19/29 (65.52)	50/58 (86.21)	0.025*
RPGN, n/N (%)	2/33 (6.06)	5/90 (5.56)	0.915
Treatment
Prednisolone (mg/day)	37.88 (34.22 - 41.53)	36.06 (33.46 - 38.65)	0.452
< 0.5 mg/kg/day	1 (3.03)	19 (21.11)	0.016*
≥ 0.5 mg/kg/day	32 (96.97)	71 (78.89)	0.016*
Intravenous methylprednisolone	2 (6.06)	5 (5.56)	0.915
Antimalarial drug	14 (42.42)	53 (58.89)	0.104
Immunosuppressive drug	18 (54.54)	53 (58.89)	0.666
Azathioprine	2 (6.06)	12 (13.33)	0.260
Cyclophosphamide	10 (30.30)	32 (35.56)	0.586
Intravenous cyclophosphamide	5 (15.15)	22 (24.44)	0.270
Oral cyclophosphamide	6 (18.18)	10 (11.11)	0.302
Mycophenolate mofetil	6 (18.18)	9 (10.00)	0.219
Renal outcomes
At 6 months, no. of events	27^d	84^f
Serum creatinine (mg/dL) (n)	0.99 (0.84 - 1.14) (27)	0.81 (0.76 - 0.85) (82)	0.019*
eGFR (mL/min/1.73 m²) (n)	74.02 (64.59 - 83.45) (27)	103.11 (97.52 - 108.71) (82)	< 0.001*
UPCR^b (n)	0.48 (0.27 - 0.85) (20)	0.48 (0.35 - 0.66) (65)	0.988
Serum albumin (g/dL) (n)	3.49 (3.20 - 3.79) (26)	3.81 (3.69 - 3.93) (77)	0.020*
Complete remission, n/N (%)	14/26 (53.85)	51/84 (60.71)	0.534
Partial remission, n/N (%)	4/26 (15.38)	6/84 (7.14)	0.201
No remission, n/N (%)	8/26 (30.77)^c	27/84 (32.14)	0.895
At 12 months, no. of events	26^e	82^g
Serum creatinine (mg/dL) (n)	1.08 (0.89 - 1.26) (25)	0.81 (0.76 - 0.86) (78)	0.008*
eGFR (mL/min/1.73 m²) (n)	69.36 (58.47 - 80.25) (25)	103.89 (96.81 - 110.98) (78)	< 0.001*
UPCR^b (n)	0.40 (0.24 - 0.69) (19)	0.49 (0.38 - 0.64) (61)	0.473
Serum albumin (g/dL) (n)	3.55 (3.22 - 3.88) (24)	3.90 (3.78 - 4.01) (73)	0.051
Complete remission, n/N (%)	15/26 (57.69)	49/82 (59.76)	0.852
Partial remission, n/N (%)	3/26 (11.54)	14/82 (17.07)	0.500
No remission, n/N (%)	8/26 (30.77)	19/82 (23.17)	0.436

Table 3. Renal Manifestations and Response to Treatment of First LN Episode Between Late- and Early-Onset SLE Patients

Variables

Late-onset SLE (N = 33)

Early-onset SLE (N = 90)

P-value

Data are expressed as mean (95% CI) or n (%) unless indicates otherwise. *Statistically significant.^aHypertension was adjusted with underlying hypertension. ^bTransformed data. ^cUnavailable data in one. ^dDead in five and missing in one. ^eDead in five and unavailable data in two. ^fDead in three, unavailable data in two and study censor in one. ^gDead in three, unavailable data in one and study censor in four. LN: lupus nephritis; n: number of observations; n/N: number of positive tests or clinical manifestation/number of patients tested or had clinical manifestations; CI: confidence interval; eGFR: estimated glomerular filtration rate; RPGN: rapidly progressive glomerulonephritis; SLE: systemic lupus erythematosus; UPCR: urine protein-creatinine ratio.

Hypertensive episode during active LN^a, n/N (%) (n)

8/33 (24.24) (33)

9/90 (10.00) (90)

0.235

Serum creatinine (mg/dL)^b (n)

0.84 (0.71 - 1.01) (33)

0.83 (0.79 - 0.93) (90)

0.888

eGFR (mL/min/1.73 m²) (n)

81.43 (67.56 - 95.31) (33)

93.97 (86.49 - 101.45) (90)

0.096

< 30 mL/min/1.73 m², n/N (%)

2/33 (6.06)

4/90 (4.44)

0.712

UPCR^b (n)

2.57 (2.04 - 3.25) (33)

1.94 (1.63 - 2.31) (89)

0.078

UPCR ≥ 3.5, n/N (%)

12/33 (36.36)

23/89 (25.84)

0.254

Serum albumin (g/dL) (n)

2.30 (2.06 - 2.53) (33)

2.94 (2.79 - 3.09) (89)

< 0.001*

Low C3 level, n/N (%)

19/28 (67.86)

44/59 (74.58)

0.512

Low C4 level, n/N (%)

16/27 (59.26)

38/55 (69.09)

0.378

Anti-dsDNA, n/N (%)

19/29 (65.52)

50/58 (86.21)

0.025*

RPGN, n/N (%)

2/33 (6.06)

5/90 (5.56)

0.915

Treatment

Prednisolone (mg/day)

37.88 (34.22 - 41.53)

36.06 (33.46 - 38.65)

0.452

< 0.5 mg/kg/day

1 (3.03)

19 (21.11)

0.016*

≥ 0.5 mg/kg/day

32 (96.97)

71 (78.89)

0.016*

Intravenous methylprednisolone

2 (6.06)

5 (5.56)

0.915

Antimalarial drug

14 (42.42)

53 (58.89)

0.104

Immunosuppressive drug

18 (54.54)

53 (58.89)

0.666

Azathioprine

2 (6.06)

12 (13.33)

0.260

Cyclophosphamide

10 (30.30)

32 (35.56)

0.586

Intravenous cyclophosphamide

5 (15.15)

22 (24.44)

0.270

Oral cyclophosphamide

6 (18.18)

10 (11.11)

0.302

Mycophenolate mofetil

6 (18.18)

9 (10.00)

0.219

Renal outcomes

At 6 months, no. of events

27^d

84^f

Serum creatinine (mg/dL) (n)

0.99 (0.84 - 1.14) (27)

0.81 (0.76 - 0.85) (82)

0.019*

eGFR (mL/min/1.73 m²) (n)

74.02 (64.59 - 83.45) (27)

103.11 (97.52 - 108.71) (82)

< 0.001*

UPCR^b (n)

0.48 (0.27 - 0.85) (20)

0.48 (0.35 - 0.66) (65)

0.988

Serum albumin (g/dL) (n)

3.49 (3.20 - 3.79) (26)

3.81 (3.69 - 3.93) (77)

0.020*

Complete remission, n/N (%)

14/26 (53.85)

51/84 (60.71)

0.534

Partial remission, n/N (%)

4/26 (15.38)

6/84 (7.14)

0.201

No remission, n/N (%)

8/26 (30.77)^c

27/84 (32.14)

0.895

At 12 months, no. of events

26^e

82^g

Serum creatinine (mg/dL) (n)

1.08 (0.89 - 1.26) (25)

0.81 (0.76 - 0.86) (78)

0.008*

eGFR (mL/min/1.73 m²) (n)

69.36 (58.47 - 80.25) (25)

103.89 (96.81 - 110.98) (78)

< 0.001*

UPCR^b (n)

0.40 (0.24 - 0.69) (19)

0.49 (0.38 - 0.64) (61)

0.473

Serum albumin (g/dL) (n)

3.55 (3.22 - 3.88) (24)

3.90 (3.78 - 4.01) (73)

0.051

Complete remission, n/N (%)

15/26 (57.69)

49/82 (59.76)

0.852

Partial remission, n/N (%)

3/26 (11.54)

14/82 (17.07)

0.500

No remission, n/N (%)

8/26 (30.77)

19/82 (23.17)

0.436

**Table 4.** Renal Manifestations and Response to Treatment of All Active Lupus Nephritis Episodes Between Late- and Early-Onset SLE Patients
Variables	Late-onset SLE (N = 33)	Early-onset SLE (N = 90)	P-value^†
Data are expressed as mean (95% CI) or n (%) unless indicates otherwise. ^aTransformed data. ^bHypertension also was adjusted with underlying hypertension. ^cSome patients received combination of immunosuppressive drugs. ^dLaboratory not available in one. ^eDead in five and unavailable data in one. ^fDead in five, unavailable data in two and study censor in one. ^gDead in four, unavailable data in four, and study censor in six. ^hDead in four, unavailable data in eight and study censor in 12. *Statistically significant. ^†P-value was adjusted with duration of lupus nephritis. LN: lupus nephritis; n: number of observations; n/N: number of positive tests or clinical manifestation/number of patients tested or had clinical manifestations; CI: confidence interval; eGFR: estimated glomerular filtration rate; RPGN: rapidly progressive glomerulonephritis; SLE: systemic lupus erythematosus; UPCR: urine protein-creatinine ratio.
Total active LN events	39	214
Duration of follow-up of LN (years)^a	3.68 (2.33 - 5.34)	5.39 (2.33 - 5.34)	0.073
Frequency of LN flare (time/person)	1.18 (0.84 - 1.61)	2.38 (2.07 - 2.72)	0.001*
Incidence of LN (per 100 person-years)	2.00 (0.75 - 5.33)	6.11 (4.32 - 8.64)	0.020*
Incidence rate of active LN (95% CI)/per 100 person-years)	5.78 (2.75 - 12.12)	18.28 (13.93 - 24.00)	0.001*
Hypertensive episode during active LN^b, n/N (%)	8/39 (20.51)	55/214 (25.70)	0.920
Serum creatinine^a (mg/dL) (n)	0.82 (0.71 - 0.98) (39)	0.83 (0.79 - 0.87) (213)	0.995
eGFR (mL/min/1.73 m²) (n)	79.33 (66.80 - 91.85) (39)	92.57 (88.24 - 96.90) (213)	0.016*
eGFR < 30, n/N (%)	3/39 (7.69)	7/213 (3.29)	0.168
UPCR^a (n)	2.58 (2.09 - 3.19) (39)	2.20 (1.98 - 2.44) (212)	0.238
UPCR ≥ 3.5, n/N (%)	13/39 (33.33)	58/212 (27.36)	0.499
Serum albumin (g/dL) (n)	2.43 (2.19 - 2.66) (39)	3.13 (3.04 - 3.23) (212)	< 0.001*
Low C3 level, n/N (%)	22/31 (70.97)	70/114 (61.4)	0.580
Low C4 level, n/N (%)	18/30 (60.00)	65/109 (59.63)	0.365
Anti-ds DNA, n/N (%)	21/32 (65.63)	87/101 (86.14)	0.011*
RPGN, n/N (%)	3/39 (7.69)	12/214 (5.61)	0.671
Treatment
Prednisolone (mg/day)	32.99 (31.28 - 34.70)	36.28 (32.88 - 39.68)	< 0.001*
< 0.5 mg/kg/day	3 (7.69)	84 (39.25)	< 0.001*
≥ 0.5 mg/kg/day	36 (92.31)	130 (60.75)	0.001*
Intravenous methylprednisolone	2 (5.13)	22 (10.28)	0.319
Antimalarial drug	16 (41.03)	98 (45.79)	0.196
Immunosuppressive drug^c	23 (58.97)	168 (78.50)	0.009*
Azathioprine	2 (5.13)	31 (14.49)	0.111
Cyclophosphamide	11 (28.21)	88 (41.12)	0.128
Intravenous cyclophosphamide	5 (12.82)	61 (28.50)	0.040*
Oral cyclophosphamide	7 (17.95)	27 (12.62)	0.369
Calcineurin inhibitor	1 (2.56)	5 (2.34)	0.932
Mycophenolate mofetil	10 (25.64)	55 (25.70)	0.994
Renal outcomes
At 6 months, events	33^e	200^g
Serum creatinine (mg/dL) (n)	1.01 (0.88 - 1.14) (33)	0.86 (0.81 - 0.91) (194)	0.011*
eGFR (mL/min/1.73 m²) (n)	72.93 (64.42 - 81.44) (33)	97.47 (93.53 - 101.42) (194)	< 0.001*
UPCR^a (n)	0.57 (0.34 - 0.95) (26)	0.71 (0.60 - 0.85) (170)	0.630
Serum albumin (g/dL) (n)	3.53 (3.29 - 3.78) (32)	3.72 (3.64 - 3.81) (186)	0.086
Complete remission, n/N (%)	17/32 (53.13)	83/200 (41.50)	0.494
Partial remission, n/N (%)	5/32 (15.63)	36/200 (18.00)	0.942
No remission, n/N (%)	10/32 (31.25)^d	81/200 (40.50)	0.491
At 12 months, events	31^f	193^h
Serum creatinine (mg/dL)^a (n)	0.95 (0.85 - 1.06) (30)	0.79 (0.76 - 0.82) (187)	0.001*
eGFR (mL/min/1.73 m²) (n)	70.73 (61.02 - 80.43) (30)	97.60 (93.32 - 101.88) (187)	< 0.001*
UPCR^a (n)	0.44 (0.28 - 0.70) (23)	0.65 (0.54 - 0.77) (163)	0.259
Serum albumin (g/dL) (n)	3.66 (3.38 - 3.94) (29)	3.83 (3.76 - 3.91) (181)	0.157
Complete remission, n/N (%)	18/31 (58.06)	92/193 (47.67)	0.452
Partial remission, n/N (%)	4/31 (12.90)	39/193 (20.21)	0.423
No remission, n/N (%)	9/31 (29.03)	62/193 (32.12)	0.873

Table 4. Renal Manifestations and Response to Treatment of All Active Lupus Nephritis Episodes Between Late- and Early-Onset SLE Patients

Variables

Late-onset SLE (N = 33)

Early-onset SLE (N = 90)

P-value^†

Data are expressed as mean (95% CI) or n (%) unless indicates otherwise. ^aTransformed data. ^bHypertension also was adjusted with underlying hypertension. ^cSome patients received combination of immunosuppressive drugs. ^dLaboratory not available in one. ^eDead in five and unavailable data in one. ^fDead in five, unavailable data in two and study censor in one. ^gDead in four, unavailable data in four, and study censor in six. ^hDead in four, unavailable data in eight and study censor in 12. *Statistically significant. ^†P-value was adjusted with duration of lupus nephritis. LN: lupus nephritis; n: number of observations; n/N: number of positive tests or clinical manifestation/number of patients tested or had clinical manifestations; CI: confidence interval; eGFR: estimated glomerular filtration rate; RPGN: rapidly progressive glomerulonephritis; SLE: systemic lupus erythematosus; UPCR: urine protein-creatinine ratio.

Total active LN events

214

Duration of follow-up of LN (years)^a

3.68 (2.33 - 5.34)

5.39 (2.33 - 5.34)

0.073

Frequency of LN flare (time/person)

1.18 (0.84 - 1.61)

2.38 (2.07 - 2.72)

0.001*

Incidence of LN (per 100 person-years)

2.00 (0.75 - 5.33)

6.11 (4.32 - 8.64)

0.020*

Incidence rate of active LN (95% CI)/per 100 person-years)

5.78 (2.75 - 12.12)

18.28 (13.93 - 24.00)

0.001*

Hypertensive episode during active LN^b, n/N (%)

8/39 (20.51)

55/214 (25.70)

0.920

Serum creatinine^a (mg/dL) (n)

0.82 (0.71 - 0.98) (39)

0.83 (0.79 - 0.87) (213)

0.995

eGFR (mL/min/1.73 m²) (n)

79.33 (66.80 - 91.85) (39)

92.57 (88.24 - 96.90) (213)

0.016*

eGFR < 30, n/N (%)

3/39 (7.69)

7/213 (3.29)

0.168

UPCR^a (n)

2.58 (2.09 - 3.19) (39)

2.20 (1.98 - 2.44) (212)

0.238

UPCR ≥ 3.5, n/N (%)

13/39 (33.33)

58/212 (27.36)

0.499

Serum albumin (g/dL) (n)

2.43 (2.19 - 2.66) (39)

3.13 (3.04 - 3.23) (212)

< 0.001*

Low C3 level, n/N (%)

22/31 (70.97)

70/114 (61.4)

0.580

Low C4 level, n/N (%)

18/30 (60.00)

65/109 (59.63)

0.365

Anti-ds DNA, n/N (%)

21/32 (65.63)

87/101 (86.14)

0.011*

RPGN, n/N (%)

3/39 (7.69)

12/214 (5.61)

0.671

Treatment

Prednisolone (mg/day)

32.99 (31.28 - 34.70)

36.28 (32.88 - 39.68)

< 0.001*

< 0.5 mg/kg/day

3 (7.69)

84 (39.25)

< 0.001*

≥ 0.5 mg/kg/day

36 (92.31)

130 (60.75)

0.001*

Intravenous methylprednisolone

2 (5.13)

22 (10.28)

0.319

Antimalarial drug

16 (41.03)

98 (45.79)

0.196

Immunosuppressive drug^c

23 (58.97)

168 (78.50)

0.009*

Azathioprine

2 (5.13)

31 (14.49)

0.111

Cyclophosphamide

11 (28.21)

88 (41.12)

0.128

Intravenous cyclophosphamide

5 (12.82)

61 (28.50)

0.040*

Oral cyclophosphamide

7 (17.95)

27 (12.62)

0.369

Calcineurin inhibitor

1 (2.56)

5 (2.34)

0.932

Mycophenolate mofetil

10 (25.64)

55 (25.70)

0.994

Renal outcomes

At 6 months, events

33^e

200^g

Serum creatinine (mg/dL) (n)

1.01 (0.88 - 1.14) (33)

0.86 (0.81 - 0.91) (194)

0.011*

eGFR (mL/min/1.73 m²) (n)

72.93 (64.42 - 81.44) (33)

97.47 (93.53 - 101.42) (194)

< 0.001*

UPCR^a (n)

0.57 (0.34 - 0.95) (26)

0.71 (0.60 - 0.85) (170)

0.630

Serum albumin (g/dL) (n)

3.53 (3.29 - 3.78) (32)

3.72 (3.64 - 3.81) (186)

0.086

Complete remission, n/N (%)

17/32 (53.13)

83/200 (41.50)

0.494

Partial remission, n/N (%)

5/32 (15.63)

36/200 (18.00)

0.942

No remission, n/N (%)

10/32 (31.25)^d

81/200 (40.50)

0.491

At 12 months, events

31^f

193^h

Serum creatinine (mg/dL)^a (n)

0.95 (0.85 - 1.06) (30)

0.79 (0.76 - 0.82) (187)

0.001*

eGFR (mL/min/1.73 m²) (n)

70.73 (61.02 - 80.43) (30)

97.60 (93.32 - 101.88) (187)

< 0.001*

UPCR^a (n)

0.44 (0.28 - 0.70) (23)

0.65 (0.54 - 0.77) (163)

0.259

Serum albumin (g/dL) (n)

3.66 (3.38 - 3.94) (29)

3.83 (3.76 - 3.91) (181)

0.157

Complete remission, n/N (%)

18/31 (58.06)

92/193 (47.67)

0.452

Partial remission, n/N (%)

4/31 (12.90)

39/193 (20.21)

0.423

No remission, n/N (%)

9/31 (29.03)

62/193 (32.12)

0.873

**Table 5.** Death and Cause of Death
Variables	Late-onset SLE (N = 33)	Early-onset SLE (N = 90)	P-value
P₁: P-value adjusted with duration of lupus nephritis. P₂: P-value adjusted with duration of lupus nephritis and underlying diseases at SLE diagnosis (hypertension and diabetes mellitus). *Statistically significant. ^†Adjusted with underlying diseases at SLE diagnosis (hypertension and diabetes mellitus). SLE: systemic lupus erythematosus.
Death (N, %)	9 (27.27)	6 (6.67)	0.014*	0.013*
Infection (N, %)	9 (100)	5 (83.33)	0.379	0.476
Associated with SLE (N, %)	3 (33.33)	3 (50.00)	0.554	0.265
Cardiovascular disease (N, %)	0	1 (16.67)	0.386	0.484
Incidence rate of death (95% CI)/100 person-years)	5.61 (2.92 - 10.78)	1.02 (0.46 - 2.26)	0.004*^†

Table 5. Death and Cause of Death

Variables

Late-onset SLE (N = 33)

Early-onset SLE (N = 90)

P-value

P₁

P₂

P₁: P-value adjusted with duration of lupus nephritis. P₂: P-value adjusted with duration of lupus nephritis and underlying diseases at SLE diagnosis (hypertension and diabetes mellitus). *Statistically significant. ^†Adjusted with underlying diseases at SLE diagnosis (hypertension and diabetes mellitus). SLE: systemic lupus erythematosus.

Death (N, %)

9 (27.27)

6 (6.67)

0.014*

0.013*

Infection (N, %)

9 (100)

5 (83.33)

0.379

0.476

Associated with SLE (N, %)

3 (33.33)

3 (50.00)

0.554

0.265

Cardiovascular disease (N, %)

1 (16.67)

0.386

0.484

Incidence rate of death (95% CI)/100 person-years)

5.61 (2.92 - 10.78)

1.02 (0.46 - 2.26)

0.004*^†