fc asoc a daño en nefritis lupica.pdf

8/9/2019 fc asoc a daño en nefritis lupica.pdf

1/7

Lupus (2014) 23, 436–442

http://lup.sagepub.com

LUPUS AROUND THE WORLD

A descriptive study of the factors associated with damagein Malaysian patients with lupus nephritis

SS Shaharir, AH Abdul Ghafor, MS Mohamed Said and NCT KongDepartment of Internal Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia

Introduction: Renal involvement is the most common serious complication in patients withsystemic lupus erythematosus (SLE). Objective: The objective of this article is to investigateand determine the associated factors of disease damage among lupus nephritis (LN)patients. Methods: Medical records of LN patients who attended regular follow-up for atleast one year in the Nephrology/SLE Clinic, Universiti Kebangsaan Malaysia MedicalCentre (UKMMC), were reviewed. Their Systemic Lupus International Collaborating

Clinics/American College of Rheumatology (SLICC/ACR) Damage Index scores werenoted. Univariate analysis and multivariable regression analysis were performed to determinethe independent factors of disease damage in LN. Results: A total of 150 patients wereincluded and their follow-up duration ranged from one to 20 years. Sixty (40%) LN patientshad disease damage (SDI 1). In the univariate analysis, it was associated with age, longerdisease duration, antiphospholipid syndrome (APS), higher maximum daily oral prednisolonedose (mg/day), lower mean C3 and C4, higher chronicity index and global sclerosis on renalbiopsies ( p< 0.05). Patients who received early (3 months after the SLE diagnosis) hydro-xychloroquine (HCQ), optimum HCQ dose at 6.5 mg/kg/day and achieved early completeremission (CR) were less likely to have disease damage ( p< 0.05). After adjustment for age,gender, disease duration and severity, multivariable regression analysis revealed that a highermaximum daily dose of oral prednisolone was independently associated with disease damagewhile early HCQ and CR were associated with lower disease damage. Conclusion: Highermaximum daily prednisolone dose predicted disease damage whereas treatment with earlyHCQ and early CR had a protective role against disease damage. Lupus (2014) 23, 436–442.

Key words: Antiphospholipid syndrome; lupus nephritis; systemic lupus erythematosus

Introduction

Systemic lupus erythematosus (SLE) is a systemicautoimmune disease that is characterized by a widespectrum of clinical manifestations and organinvolvement. The heterogeneous nature of the dis-ease, with unpredictable flares and remissions, may

eventually lead to permanent damage.Sociodemographic factors such as sex, race andethnicity play an important role in the incidenceof the disease, frequency of its manifestation andtherapeutic response.1

Lupus nephritis (LN) is one of the most seriousSLE complications since it is the major predictor of

poor prognosis. Asian lupus patients particularlyare at risk as the reported prevalence of renalinvolvement is high, up to 61% at diagnosis and82% over the time of the course of SLE.2 Variousfactors have been found to be significantly asso-ciated with poor prognosis in LN such as AfricanAmerican race,3 male sex,3 unfavorable histological

features (diffuse proliferative glomerulonephritis,presence of cellular crescents, fibrinoid necrosisand tubular atrophy)4,5 and treatment delay.6

The Systemic Lupus ErythematosusInternational Collaborating Clinics/AmericanCollege of Rheumatology (SLICC/ACR) DamageIndex (SDI) for SLE is a well-validated tool forassessing accumulated damage index (DI) fromthe onset of the disease.7 The damage includesnon-reversible changes in organs and systemsaffected by the disease process itself, its therapyor intercurrent illness. The SLICC/ACR damage

index is highly reproducible and has been shown

Correspondence to: Syahrul Sazliyana Shaharir, Department of

Internal Medicine, Universiti Kebangsaan Malaysia Medical Centre,

Jalan Yaacob Latiff, 56000, Kuala Lumpur, Malaysia.

Email: [email protected]

Received 19 August 2013; accepted 27 November 2013! The Author( s) , 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203313518624

at JOHNS HOPKINS UNIVERSITY on January 7, 2015lup.sagepub.comDownloaded from

http://lup.sagepub.com/http://lup.sagepub.com/http://lup.sagepub.com/http://lup.sagepub.com/


2/7

to have a good agreement with prospective andretrospective measurements of DI.8

Our study was aimed to evaluate the predictorsof disease damage among our multiracial cohortof LN patients.

Methodology

This was a retrospective study and the clinical rec-ords of LN patients who attended regular follow-up visits for at least one year in the Nephrology/SLE clinic, Universiti Kebangsaan MalaysiaMedical Centre (UKMMC), were reviewed. Allpatients fulfilled at least four criteria from theACR classification criteria for SLE of 19979 orhad renal biopsy consistent with LN. LN was diag-nosed by renal biopsy or by clinical and laboratorymanifestations that meet the ACR criteria (persist-ent proteinuria of more than 0.5 g per day and/or‘‘active urinary sediment’’ i.e. >5 red blood cells(RBCs)/high-power field (hpf), >5 white bloodcells (WBCs)/hpf in the absence of infection or cel-lular casts limited to RBC or WBC casts.10 Renalbiopsies were further classified according to theWorld Health Organization (WHO) 1982 orInternational Society of Nephrology/RenalPathology Society (ISN/RPS) Classification2003.11 The mean cumulative serum complement

levels (C3 and C4), which were calculated routinelyduring clinical follow-up, were also noted.

Clinical records noting the patients’ sociodemo-graphic and disease characteristics, duration of dis-ease (defined as duration from the date of SLEdiagnosis), renal biopsy class and histological indi-ces, and treatment information were recorded. Thetime to achieve complete remission (CR) was deter-mined from the time of induction treatment for LN.CR was defined by a serum creatinine of 1.4 mg/dland proteinuria of 0.33 g/day.12

As part of a standard protocol in our clinic, sur-

veillance for damage was performed regularly. Thisincludes bone mineral density measurement onceevery two years and screening for diabetes mellitus(DM) (fasting blood sugar and/or oral glucose tol-erance tests) at least every six months. As a referraltertiary center with multidisciplinary services, thepresence of other disease damage that was managedby other subspecialties was readily accessed fromthe medical records. Damage was measured byusing the SDI.13 This index documents cumulativeand irreversible damage, irrespective of its cause, in12 different organ systems. To be scored, each mani-

festation must be present for at least six months.

SLICC/ACR damage scores were determined atone year post-diagnosis and every five years untilthe day of enrollment in the study. The category of damage was also noted.

Information on the maximum daily prednisolone

dose (mg per day) during induction or after pulseintravenous (IV) methylprednisolone and the use of other immunosuppressive agents (cyclophospha-mide, mycophenolic acid (MMF), cyclosporine A(CyA) and azathioprine) were determined fromthe clinical records. Apart from that, the use of an immunomodulator, i.e. hydroxychloroquine(HCQ) and chloroquine, was also recorded. Inour clinical practice, the HCQ dose is usuallygiven at 200 mg daily to a maximum of 6.5 mg/kg/day. The dosage of HCQ at 6.5 mg/kg/day is usu-ally given up to three months and then it is subse-

quently reduced to 200 mg daily. These patientswere reviewed annually by the ophthalmologistfor screening of maculopathy.

Statistical analysis

Various parameters were compared between thosewith disease damage (SDI 1) and without diseasedamage (SDI¼ 0) using standard statistical tests.All normally distributed numerical data wereexpressed as meanSD and continuous variableswere analyzed with the Student’s t test. Non-nor-mally distributed data were expressed as

median interquartile range (IQR) and continuousvariables were analyzed using the Mann-Whitney Utest. The Chi-square test was used for categoricalvariables. Significance was indicated at p 0.05.Subsequently, multivariable regression analysiswas performed to determine the independent fac-tors associated with disease damage in LN. In theregression analysis, all factors that were found to besignificantly associated with disease damage( p< 0.05) on univariate analyses and possible con-tributing factors, i.e. age, disease duration andseverity (proliferative LN, presence of crescents,

global sclerosis on renal biopsy, CI and cyclophos-phamide use) were included in the regression ana-lysis. Statistical analyses were performed using theSPSS program version 18.0.

Results

A total of 150 LN patients were included in thestudy. Their duration of follow-up ranges fromone to 20 years, with mean of 10 5.6 years. Ourcohort consisted of a multiracial population of pre-

dominantly Malays (n¼

78, 52%), followed by

A descriptive study of the factors associated with damage in Malaysian patients with lupus nephritisSS Shaharir et al.

437

Lupus




3/7

Chinese (n¼ 64, 42.7%), Indians (n¼ 6, 4%) andothers (n¼ 2, 1.3%). Their mean age was35.6 10.5 years with mean disease duration of 11.7 6.1 years. The majority of them were females(n¼ 135, 90%) in keeping with the female predilec-tion for SLE.

A total of 133 patients had renal biopsy while theremaining 17 patients did not because of noncon-sent or contraindications for the procedure. Thedisease improved with the usual induction treat-ment of pulse methylprednisolone for active SLE/LN. The majority of them had Class IV LN (n¼ 61,40.7%), followed by Class III (n¼ 49, 32.7%),Class V (n¼ 15, 10%), Class II (n¼ 6, 4%) andClass VI (n¼ 2, 1.3%). Apart from renal involve-ment, 55.3% had musculoskeletal (MSK) andmucocutaneous manifestations, followed by hema-

tological (47.3%), neuropsychiatric (NP) lupus(10%) and serositis (8.7%).

Disease damage in LN

A total of 60 patients (40%) had disease damage(SDI 1) with a mean of onset of damage of 5.6 4.7 years from the diagnosis of SLE. Themedian SDI score was 1 (IQR 1).The highestorgan damage was renal (n¼ 18, 22.5%), followedby MSK damage (n¼ 14, 23.3%), steroid-inducedDM (n¼ 12, 20%) and NP at 17.7% (n¼ 10).Avascular necrosis accounted for approximately

two-thirds of MSK damage (n¼ 10). Only one-third of patients with NP damage had a cerebro-vascular accident, and almost one-half (40%, n¼ 4)of them had cognitive impairment or psychosis.The reported cardiovascular (CVS) damage was8.3% (n¼ 5).

Disease damage was significantly associated witholder age and longer disease duration ( p< 0.05,respectively). Among patients with secondary anti-phospholipid syndrome (APS) (n¼ 12), 11 (92%)had disease damage. Disease damage was also asso-ciated with a higher maximum oral daily dose of

prednisolone, higher CI and global sclerosis( p< 0.05). Meanwhile, early CR of less than oneyear was associated with lower disease damage( p 0.05).

Only 90 patients (60%) had ever received HCQ.Two of them initially were treated with chloroquinefor one year and 18 months. Patients who werestarted on HCQ early (started 3 months afterdiagnosis) and had ever received an optimumdose of 6.5 mg/kg/day were less likely to developdisease damage ( p 0.05).There were no reportedcases of visual or hearing damage secondary to

HCQ or chloroquine. Table 1 summarizes the

demographics and disease characteristics betweenLN patients with and without disease damage.

After adjustment of age, gender, disease durationand severity of LN (proliferative LN, presence of crescents, global sclerosis on renal biopsy, CI andcyclophosphamide use), multivariable logisticregression analysis revealed that the use of earlyHCQ and achievement of CR in less than a yearwere independently associated with lower diseasedamage. On the other hand, higher maximumdaily oral prednisolone dose was an independentfactor associated with disease damage. Table 2illustrates the regression analysis of the independ-ent predictors of disease damage among the LNcohort.

Discussion

With advances in the treatment and quality of careover the past few decades, there has been a tremen-dous improvement in the survival of lupus patients.Thus organ damage rather than patient survival hasbecome the standard measure for morbidity amonglupus patients. Because of differences in diseaseduration, disease manifestations and sociodemo-graphic background, the prevalence and accrualdamage in SLE patients in Asia has been reportedto vary between 38% and 76%.14 The highest

prevalence of 76% was reported in Pakistan.However, 45% of their patients had renal involve-ment (64% had WHO Class IV and 14% WHO IIILN).15 In Asian lupus patients, organ systems com-monly affected include renal, MSK and NP.15–17

Renal damage in LN has been well described butthere are scarce data for other organ/systemdamage. To the best of our knowledge, this is thefirst Malaysian study that reports disease damagein LN patients. Our study has demonstrated thatour LN cohort developed a slightly different pat-tern of organ system damage. Besides renal and

MSK damage, our cohort had a higher prevalenceof steroid-induced DM (20%), compared to lessthan 5% reported in other general lupus stu-dies.15–19 This could be attributed to a combinationof genetic predisposition and lifestyle changes. Ingeneral, Asian populations are genetically moresusceptible to develop DM and insulin resistanceas compared to Caucasians.20,21 Therefore, steroidtreatment in lupus may actually unmask theirunderlying DM.22 Lifestyle and dietary changeshave also certainly contributed to the increaseprevalence of DM in Malaysia almost two-fold

from 11.6% in 2006 to 22.6% in 2012.

23

This is


438

Lupus




4/7

because the increasing prevalence of DM parallelsthe increasing prevalence of obesity in Malaysia.24

The reported prevalence of avascular necrosis

(AVN) in our LN cohort was also high as it

accounted for more than two-thirds of overallMSK damage. A similar trend was also noted inthe Monash Lupus Clinic database whereby

there was a trend toward a higher risk of AVN

Table 1 Demographics and disease characteristics among lupus nephritis (LN) patients with and without disease

damage

Parameters

No disease damage,

SDI ¼ 0 (n¼ 90)

Disease damage,

SDI 1 (n¼ 60) p

Age (years), mean (SD) 32.39.0 35.9 10.5 0.03Duration (years), mean (SD) 7.9 5.1 11.7 6.1 0.01

Race, % 48.9% 56.7% 0.49

Malay (n¼ 78) 45.6% 38.3%

Chinese (n¼ 64) 3.3% 5.0%

Indian (n¼ 6) 2.2% 0.0%

Others (n¼ 2)

Gender, % 93.3% 85.0% 0.11

Female (n¼ 135) 6.7% 15.0%

Male (n¼ 15)

Age onset (years), mean (SD) 25.68.8 25.4 10.5 0.80

APS (n¼ 12), % 1.1% 19.0% 0.001

Maximum oral prednisolone (mg/day), mean (SD) 37.612.9 47.9 15.7 0.001

Hydroxychloroquine (n¼ 90), % 73.6% 43.3% 0.001

Early HCQ (


5/7

among Asians compared to non-Asian patients.25

However, it is still unclear whether this phenom-enon reflects the genetic predisposition or lupus dis-ease severity in Asians rather than corticosteroidsusage alone, as all of the LN patients were treated

with corticosteroids.On the other hand, our cohort of LN patients

had a lower prevalence of CVS damage as com-pared to Caucasians. The lower CVS morbidity inour LN cohort, however, is comparatively simi-lar to other lupus cohorts from Asian countries,as the reported prevalence ranged from 2% to4.5%.15,17,26,27 This is in contrast with Jewish28

and western cohorts,18,19,29 in which the reportedCVS damage was around 10% or more. Althoughthe proportion of NP damage in our cohort wassimilar to Hong Kong lupus patients, CVS was

the most frequent cause of NP damage in HongKong as it accounted for more than one-third.However, most of them had secondary APS andmultiple traditional CVS risk factors.30 Therefore,not surprisingly their cohort also reported a higherprevalence of CVS damage.16

In concordance with many studies, our cohortalso demonstrated significant associations betweendisease damage and older age,31 longer disease dur-ation32 and presence of APS.33,34 Mean cumulativeserum complement levels C3 and C4 were alsolower among those LN patients with diseasedamage. These findings imply that more severe ormore persistent active disease led to the develop-ment of disease damage.

Our study also showed that a higher CI on renalhistopathology is a strong predictor of diseasedamage. This further reinforces the results of pre-viously reported studies that showed that CI inrenal biopsy predicts not only renal damage inLN patients,35,36 but also overall patient survival.37

Of all the medications used, lower diseasedamage was associated with HCQ use. The mostimportant finding of our study was that early useof HCQ may protect against disease damage and it

independently may protect against disease damageamong LN patients. In the past decade, much evi-dence has accumulated to show that HCQ not onlyalleviates and prevents disease relapse, but alsoreduces the risk of damage accrual in SLEpatients.38,39 Its favorable effect on lipid profilesand potential role in thrombotic event preventionmay subsequently lead to the reduction in CVS riskamong SLE patients.39 Despite all the benefits of HCQ, its usage was still low in our cohort as well asin those seen in other epidemiological or majorrandomized trials in SLE. In general HCQ was

used in only about 50% of these patients.

39,40

Therefore HCQ should not be regarded as asecond-line treatment for SLE but should bestarted early at an optimum dose because of its potential role in protecting against diseasedamage.

Corticosteroids have been long recognized to bean independent predictor of disease damage inlupus.29,41 and in our study, a higher maximumdose of daily oral prednisolone was signifi-cantly associated with disease damage. However,a high daily dose of prednisolone may also reflectthe underlying severity of the disease that in turnconfers a higher risk of damage among SLEpatients.

The limitation of this study is our findings maynot suitably be extrapolated to other LN popula-tions since the treatment protocol of LN from our

center may be different from others. Apart fromthat, in view of the nature of the retrospectivestudy and the fact that SLE itself is a very heteroge-neous disease, there may still be other potential con-founding factors that may have contributed to thepresence of disease damage among patients withSLE. Moreover, a large variation of the follow-upduration with different points of time of damageoccurrence may not allow direct comparison of some other possible risk factors; for example, dur-ation and cumulative corticosteroid dose.Notwithstanding these limitations, our study is rele-vant as it further reinforces the evidence on theimportance of HCQ in the management of SLEand LN.

In conclusion, the prevalence of disease damagein a single urban Malaysian tertiary hospital LNcohort was comparatively similar to other stu-dies16–18,27 but with a different pattern of diseaseand organ damage involvement. A higher CI andglobal sclerosis on renal biopsy, higher age and dis-ease duration, APS and higher maximum oral pred-nisolone were the associated factors of diseasedamage in LN. However, in the multivariableregression analysis model, only higher maximum

daily prednisolone dose was the independentfactor of disease damage while the early use of HCQ and early CR potentially protect patientsagainst damage. Further, larger prospective trialsare needed to accurately delineate the specific riskof disease damage in LN.

Funding

This research received no specific grant from anyfunding agency in the public, commercial, or not-

for-profit sectors.


440

Lupus




6/7

Conflict of interest

The authors have no conflicts of interest to declare.

Acknowledgment

The authors thank Raymond Azman Ali, directorand dean of Universiti Kebangsaan MalaysiaMedical Centre.

References

1 Sa ´ nchez E, Rasmussen A, Riba L, et al . Impact of genetic ancestryand sociodemographic status on the clinical expression of systemiclupus erythematosus in American Indian-European populations.

Arthritis Rheum 2012; 64: 3687–3694.2 Jakes RW, Bae SC, Louthrenoo W, Mok CC, Navarra SV, Kwon

N. Systematic review of the epidemiology of systemic lupus erythe-matosus in the Asia-Pacific region: Prevalence, incidence, clinicalfeatures, and mortality. Arthritis Care Res (Hoboken) 2012; 64:159–168.

3 Korbet SM, Schwartz MM, Evans J, Lewis EJ. Severe lupus neph-ritis: Racial differences in presentation and outcome. J Am SocNephrol 2007; 18: 244–254.

4 Donadio Jr JV, Hart GM, Bergstralh EJ, Holley KE. Prognosticdeterminants in lupus nephritis: A long-term clinicopathologicstudy. Lupus 1995; 4: 109–115.

5 Mok CC, Wong RW, Lau CS. Lupus nephritis in SouthernChinese patients: Clinicopathologic findings and long-term out-come. Am J Kidney Dis 1999; 34: 315–323.

6 Faurschou M, Starklint H, Halberg P, Jacobsen S. Prognostic fac-

tors in lupus nephritis: Diagnostic and therapeutic delayincreases the risk of terminal renal failure. J Rheumatol 2006; 33:1563–1569.

7 Gladman D, Ginzler E, Goldsmith C, et al . The development andinitial validation of the Systemic Lupus InternationalCollaborating Clinics/American College of Rheumatologydamage index for systemic lupus erythematosus. Arthritis Rheum1996; 39: 363–369.

8 Thumboo J, Lee H-Y, Fong K-Y, et al . Accuracy of medical recordscoring of the SLICC/ACR Damage Index for systemic lupus ery-thematosus. Lupus 2000; 9: 358–362.

9 Hochberg MC. Updating the American College of Rheumatologyrevised criteria for the classification of systemic lupus erythemato-sus. Arthritis Rheum 1997; 40: 1725.

10 Tan EM, Cohen AS, Fries JF, et al . The 1982 revised criteria forthe classification of systemic lupus erythematosus. Arthritis Rheum

1982; 25: 1271–1277.11 Weening JJ, D’Agati VD, Schwartz MM, et al . The classificationof glomerulonephritis in systemic lupus erythematosus revisited.J Am Soc Nephrol 2004; 15: 241–250.

12 Chen YE, Korbet SM, Katz RS, Schwartz MM, Lewis EJ. Valueof a complete or partial remission in severe lupus nephritis. Clin J Am Soc Nephrol 2008; 3: 46–53.

13 Gladman DD, Urowitz MB, Goldsmith CH, et al . The reliabilityof the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patientswith systemic lupus erythematosus. Arthritis Rheum 1997; 40:809–813.

14 Kuan WP, Li EK, Tam LS. Lupus organ damage: What isdamaged in Asian patients? Lupus 2010; 19: 1436–1441.

15 Rabbani MA, Habib HB, Islam M, et al . Survival analysis andprognostic indicators of systemic lupus erythematosus inPakistani patients. Lupus 2009; 18: 848–855.

16 Mok CC, Ho CT, Wong RW, Lau CS. Damage accrual in south-ern Chinese patients with systemic lupus erythematosus.J Rheumatol 2003; 30: 1513–1519.

17 Sung YK, Hur NW, Sinskey JL, Park D, Bae SC. Assessment of damage in Korean patients with systemic lupus erythematosus.J Rheumatol 2007; 34: 987–991.

18 Alarco ´ n GS, McGwin G Jr, Bastian HM, et al . Systemic lupuserythematosus in three ethnic groups. VII [correction of VIII].Predictors of early mortality in the LUMINA cohort. LUMINAStudy Group. Arthritis Rheum 2001; 45: 191–202.

19 Gladman DD, Urowitz MB, Rahman P, Iban ˜ ez D, Tam LS.Accrual of organ damage over time in patients with systemiclupus erythematosus. J Rheumatol 2003; 30: 1955–1959.

20 Ma RCW, Chan JCN. Type 2 diabetes in East Asians: Similaritiesand differences with populations in Europe and the United States.Ann N Y Acad Sci 2013; 1281: 64–91.

21 Chan JC, Malik V, Jia W, et al . Diabetes in Asia:Epidemiology, risk factors, and pathophysiology. JAMA 2009;301: 2129–2140.

22 Simmons LR, Molyneaux L, Yue DK, Chua EL. Steroid-induceddiabetes: Is it just unmasking of type 2 diabetes? ISRN Endocrinol 2012; 2012: 910905.

23 Wan Nazaimoon WM, Md Isa SH, Wan Mohamad WB, et al .

Prevalence of diabetes in Malaysia and usefulness of HbA1c as adiagnostic criterion. Diabet Med 2013; 30: 825–828.

24 Mohamud WN, Musa KI, Khir AS, et al . Prevalence of overweightand obesity among adult Malaysians: An update. Asia Pac J ClinNutr 2011; 20: 35–41.

25 Golder V, Connelly K, Staples M, Morand E, Hoi A. Associationof Asian ethnicity with disease activity in SLE: An observa-tional study from the Monash Lupus Clinic. Lupus 2013; 22:1425–1430.

26 Al-Mayouf SM, Al Sonbul A. Influence of gender and age of onseton the outcome in children with systemic lupus erythematosus. ClinRheumatol 2008; 27: 1159–1162.

27 Thumboo J, Feng PH, Soh CH, Boey ML, Thio S, Fong KY.Validation of a Chinese version of the Medical Outcomes StudyFamily and Marital Functioning Measures in patients with SLE.Lupus 2000; 9: 702–707.

28 Molad Y, Gorshtein A, Wysenbeek AJ, et al . Protective effect of hydroxychloroquine in systemic lupus erythematosus.Prospective long-term study of an Israeli cohort. Lupus 2002; 11:356–361.

29 Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage insystemic lupus erythematosus and its association with corticoster-oids. Arthritis Rheum 2000; 43: 1801–1808.

30 Mok CC, To CH, Mak A. Neuropsychiatric damage in SouthernChinese patients with systemic lupus erythematosus. Medicine(Baltimore) 2006; 85: 221–228.

31 Lopez R, Davidson JE, Beeby MD, Egger PJ, Isenberg DA. Lupusdisease activity and the risk of subsequent organ damage and mor-tality in a large lupus cohort. Rheumatology (Oxford) 2012; 51:491–498.

32 Zonana-Nacach A, Camargo-Coronel A, Yán ˜ ez P, et al .Measurement of damage in 210 Mexican patients with systemiclupus erythematosus: Relationship with disease duration. Lupus

1998; 7: 119–123.33 Ruiz-Irastorza G, Egurbide MV, Martinez-Berriotxoa A, Ugalde

J, Aguirre C. Antiphospholipid antibodies predict early damage inpatients with systemic lupus erythematosus. Lupus 2004; 13:900–905.

34 Descloux E, Durieu I, Cochat P, et al . Paediatric systemic lupuserythematosus: Prognostic impact of antiphospholipid antibodies.Rheumatology (Oxford) 2008; 47: 183–187.

35 Hiramatsu N, Kuroiwa T, Ikeuchi H, et al . Revised classi-fication of lupus nephritis is valuable in predicting renaloutcome with an indication of the proportion of glomeruliaffected by chronic lesions. Rheumatology (Oxford) 2008;47: 702–707.

36 D’Agati VD, Appel GB. Lupus nephritis: Pathology and patho-genesis. In: Wallace DJ, Hahn BH (eds), Dubois’ lupus erythema-tosus, 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins,2007, p. 1105.


441

Lupus




7/7

37 Nossent HC, Henzen-Logmans SC, Vroom TM, Berden JH,Swaak TJG. Contribution of renal biopsy data in predicting out-come in lupus nephritis. Analysis of 116 patients. Arthritis Rheum1990; 33: 970–977.

38 Kasitanon N, Fine DM, Haas M, Magder LS, Petri M.Hydroxychloroquine use predicts complete renal remissionwithin 12 months among patients treated with mycophenolatemofetil therapy for membranous lupus nephritis. Lupus 2006; 15:366–370.

39 Fessler BJ, Alarco ´ n GS, McGwin G Jr, et al . Systemic lupus ery-thematosus in three ethnic groups: XVI. Association of

hydroxychloroquine use with reduced risk of damage accrual.Arthritis Rheum 2005; 52: 1473–1480.

40 Costedoat-Chalumeau N, Amoura Z, Hulot JS, Lechat P, PietteJC. Hydroxychloroquine in systemic lupus erythematosus. Lancet2007; 369: 1257–1258.

41 Petri M, Purvey S, Fang H, Magder LS. Predictors of organdamage in systemic lupus erythematosus: The Hopkins LupusCohort. Arthritis Rheum 2012; 64: 4021–4028.


442

Lupus
http://lup.sagepub.com/

fc asoc a daño en nefritis lupica.pdf

Documents

Transcript of fc asoc a daño en nefritis lupica.pdf