Original Article

Lupus nephritis in King Hussein Medical Center-Jordan Ausaylah Burgan, Ala Al-Hersh Rheumatology Unit, Department of Internal Medicine, King Hussein Medical Center Royal Medical Services, Amman-Jordan

ABSTRACT Objective To study characteristics of lupus nephritis in Jordan and compare our results with other studies. Patients and Methods We retrospectively reviewed the medical records and the renal histopathology slides of 74 patients with lupus nephritis seen in Rheumatology department at King Hussein Medical Center in Jordan, over a 14 year period (1996-2009). Sixty nine (93.24%) were females and 5 (6.75%) were males. The median age was 26 year. The indications for renal biopsy were the presence of proteinuria, defined as a 24 hr urinary protein excretion 1 gram and/or the presence of active casts in the urinary sediment. All patients had normal serum creatinine and all fulfilled at least four of the American College of Rheumatology (ACR) classification criteria for SLE; the renal biopsy specimens were studied by light and immunofluorescence microscopy. Results Diffuse proliferative glomerulonephritis (class IV) was the most frequent histopathologic finding and was seen in 48 (40.1%) patients. The frequencies of other findings were as follows: Class III (n=10, 13.5%), Class V (n =7, 9.5%), Class I (n =6, 8.1%), class II

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(n=1, 1.3%). All patients were treated with different combination of treatment, 58 (77%) patients had controlled disease on their last evaluation, 11(14%) still having active disease, 4 patients (5.3%) on chronic hemodialysis, one of them had kidney transplant, 2 (2.6%) died due to infection. Conclusion Diffuse proliferative GN class IV was the most frequent type of lupus nephritis in this study. The renal biopsy provides important information for the proper diagnosis and management of patients having lupus nephritis. (Rawal Med J 2011:36:31-33). Key words Lupus, glomerulonephritis, renal failure. INTRODUCTION Lupus nephritis is the renal manifestation of systemic lupus erythematosus (SLE) - A disease mainly affecting young women with substantial morbidity and mortality. Renal involvement is a serious feature of SLE, despite the great improvement in the management of lupus nephritis¹ and remains the most frequent cause of death.² Renal biopsy is used to confirm the diagnosis, evaluate disease activity, determine the prognosis and appropriate therapy.3 Urinalysis provides the best screening for indications for biopsy. The decision to institute immunosuppressive therapy is highly influenced by the results of renal biopsy and offers the prospect of achieving more favorable renal outcomes. Biopsies are classified according to the World Health Organization (WHO) system (Table 1). The renal biopsy should be reviewed jointly by pathologists and the clinicians caring for patients with lupus nephritis. Aim of this study was to review lupus nephritis

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diagnosed at King Hussein Medical Center (KHMC), Jordan and compared our findings with similar studies. PATIENTS AND METHODS We have retrospectively reviewed the medical records and the renal histopathogy slides of 74 patients with lupus nephritis seen in Rheumatology unit at KHMC, Jordan, over a 14 year period (1996-2009). Sixty nine (93.24%) were females and 5 (6.75%) were males. The female to male ratio was (13.8:1).The median age was 26 year. All patients were Jordanians. All patients fulfilled at least four of the American College of Rheumatology (ACR) classification criteria for SLE.4 The renal biopsy specimens were studied by light and immunofluorescence microscopy. The renal involvement, specifically the glomerular, was classified according to the WHO classification.5 This classification is practical and widely accepted system for defining renal lesions observed on biopsy of patients with lupus nephritis.. The immunofluorescence slides were prepared according to standard methods, from frozen sections of the kidney biopsy 6. Table 1. International Society Nephrology/Renal Classification of Lupus Nephritis Class I Minimal mesangial lupus nephritis

Class II

Light microscopy findings

Pathology

Society 2003

Normal

Immunofluorescence Mesangial immune deposits electron microscopy findings Clinical manifestations

Mild proteinuria

Light microscopy

Purely mesangial hypercellularity or mesangial

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Mesangial findings matrix expansion with mesangial immune deposits proliferative lupus nephritis Immunofluorescence Mesangial immune deposits; few immune deposits in electron microscopy subepithelial or subendothelial deposits possible findings

Class III

Clinical manifestations

Mild renal disease such as asymptomatic hematuria or proteinuria that usually does not warrant specific therapy

Light microscopy findings

Active or inactive focal, segmental, or global glomerulonephritis involving 50% of all glomeruli; subdivided into diffuse segmental (class IV-S) when >50% of involved glomeruli have segmental lesions (involving less than half of glomerular tuft) and diffuse global (class IV-G) when >50% of involved glomeruli have global lesions

Class III (C) Chronic inactive lesions - Focal sclerosing lupus Class IV Diffuse lupus nephritis

Class IV-S (A) Active lesions Diffuse segmental proliferative lupus Immunofluorescence Subendothelial immune deposits nephritis electron microscopy

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findings Class IV-G (A) Active lesions Clinical Diffuse global proliferative lupus manifestations nephritis Class IV-S (A/C) Active and chronic lesions Diffuse segmental proliferative and sclerosing lupus nephritis

Clinical evidence of renal disease including hypertension, edema, active urinary sediment, worsening renal function, and nephrotic range proteinuria in most cases; active extrarenal SLE in many patients

Class IV-G (A/C) Active and chronic lesions Diffuse global proliferative and sclerosing lupus nephritis Class IV-S (C) Chronic inactive lesions with scars - Diffuse segmental sclerosing lupus nephritis Class IV-G (C) Chronic inactive lesions with scars - Diffuse global sclerosing lupus nephritis Class V Membranous lupus nephritis

Light microscopy findings

Diffuse thickening of glomerular basement membrane without inflammatory infiltrate; possibly, subepithelial deposits and surrounding basement membrane spikes on special stains, including silver and trichrome; may occur in combination with class II or IV; may show advanced sclerosis

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Immunofluorescence Subepithelial and intramembranous immune deposits; electron microscopy subendothelial deposits present only when associated findings proliferative component is present

Class VI

Clinical manifestations

Clinical and laboratory features of nephrotic syndrome, usually without manifestations of active SLE

Light microscopy findings

Advanced glomerular sclerosis involving >90% of glomeruli, interstitial fibrosis, and tubular atrophy, all morphological manifestations of irreversible renal injury

Clinical manifestations

Significant renal insufficiency or end-stage renal disease in most cases; unlikely to respond to medical therapy

Advanced sclerosis lupus nephritis

Courtesy Dr. Lawrence H Brent, MD and Dr. Fadi Ahmad Hamed, MD. All the patients were treated with different combination of treatment which consisted of IV methylpredinsolone, oral prednisolone, IV cyclophosphamide,6 azothioprine, cyclosporine,

chloroquine

sulfate,

mycophenolate

mofetil,

plasmapheresis

and

immunoadsorption. RESULTS Articular manifestation was the most predominant clinical feature seen in all patients, followed by hematologic changes which were present in more than 95% of patients. Malar rash was the most frequent cutaneous manifestation (95% of patients) followed by oral ulcers (80%), photosensitivity (77%) and discoid lupus (70%). Serositis was seen in 34% and 20% had neuropsychiatric manifestations. ANA was detected in 98% of patients. The 24hr urinary protein excretion on presentation exceeded 3.5g/day in 7 patients only and the rest it was more than 0.5g/day.

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Table 2. Comparsion of the renal histopathologic findings in Kuwait,7 United Arab Emirates (UAE),8 Saudi Arabia,9 France,11 Netherlands,12 South Africa,13 Thailand14 and Taiwan.15 Jordan Kuwa it

UAE

Saudi Arabi a

Franc e

Nethe rlands

South Africa

Thailan d

Taiwa n

Class

n (%)

n (%)

n(%)

n (%)

n (%)

n (%)

n (%)

n (%)

n (%)

Class 1

6(8.1)

-

2(3.6)

2(4.9)

3(1.0)

1(1.4)

Class 11

1(1.3)

2(6))

2(10)

2(12.5 2(1.5) ) 1(1.5) 35(22)

15(36.6)

50(15.9)

14(20)

Class 111

19(54)

3(7.3)

11(3.5)

Class V

10(13. 5) 48(64. 9) 7(9.5)

10(18 ) 10(18 ) 28(50 ) 5(9)

ClassV1

2(2.6)

-

--

--

1(1)

1(1.8)

--

--

2(2.9)

Others

0(0)

--

--

--

-

--

8(2.5)

--

Total

74

50

35

16

10(6.5 ) 158

56

41

314

70

Class 1V

14(40) -

19(50 3(18.8 35(22) ) ) 14(10 1(6.2) 43(27) ) --32(20)

17(41.5) 4(9.8)

15(21. 4) 193(61. 29(41. 5) 4) 57(18.1) 9(12.9)

Diffuse proliferative glomerulonephritis (class IV) was the most frequent histopathologic finding seen in 48 patients (40.1%). The frequencies of other histopathologic findings were as follows: Class III (n=10, 13.5%), Class V (n =7, 9.5%), Class I (n =6, 8.1%), class II (n=1, 1.3%) (Table 2). All patients were followed for a period ranging from 1-14 year. Fifty eight (77%) patients had controlled disease on their last evaluation; 11(14%) still had active disease, four (5.3%) were on chronic hemodialysis, one underwent kidney transplant and two (2.6%) died due to infection.

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DISCUSSION Rheumatology Unit at KHMC is considered as a tertiary referral center in Jordan and treats patients from all regions in the country. Nephrotic range proteinuria was seen in 9.5% of our study on presentation and 3% had active urinary casts. Diffuse proliferative glomerulonephritis class IV was the most frequent histopathology finding, followed by class III which is similar to studies from France,11 Netherlands,12 South Africa,13 Thailand14 and Taiwan.15 .Unlike Jordan, in the three other Arab populations, studies from Kuwait,7 UAE8 and Saudi Arabia,9 the most frequent histopathologic abnormality was class III lupus nephritis which was the second most frequent type of lupus nephritis in our patients. Another finding is the similar incidence of class III lupus nephritis in our patients to the Saudi patients (1.5%). All patients received basically oral prednisolone and/or IV cyclophosphamide with satisfactory outcome. CONCLUSION Diffuse proliferative GN class IV was the most frequent type of lupus nephritis in our study and various areas in the world. As urinalysis findings or serological markers do not always reflect renal disease activity in patients with lupus nephritis, a renal biopsy provides critical information providing the basis for therapeutic decisions. Correspondence: Ausaylah Burgan, MD Tel: +962776512155. Email: [email protected] Received : September 9, 2010 Accepted: October 24, 2010

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