In the 12-year period between 1974 and 1985, 19 children aged between 8 and 12 years with systemic lupus erythematosus (SLE) were seen in the Department of Paediatrics, University Hospital, Kuala Lumpur. A preponderance of females (M:F = 1:2.8) and ethnic Chinese was evident. Renal biopsies revealed a wide Iange of renal morphology, including minimal change glomerulonephritis, focal proliferative glomerulonephritis, diffuse proliferative glomerulonephritis with varying degrees of severity and membranous glomerulonephritis. The majority (15) of patients had clinical SLE at the time of renal biopsy, of whom 4 were also grossly nephrotic. In the remaining 4 patients a diagnosis of SLE was made after further investigation for nephrotic syndrome (2) and acute nephritis (2). The pattern of renal pathology in childhood lupus nephritis appears not to differ significantly from adults.
Key words: Systemic lupus erythematosus, glomerulonephritis
Ki-67 expression in diffuse proliferative lupus nephritis, WHO Class IV, was compared against normal controls to establish that cellular proliferation is involved in the production of glomerular hypercellularity. Twenty-three histologically confirmed WHO Class IV lupus nephritis and 23 normal control renal tissue were immunohistochemically stained with a polyclonal antibody to Ki-67 (Dako) using the peroxidase labelled streptavidin bioitin kit (Dako). There were 20 females and 3 males, with 17 Chinese and 6 Malays in the WHO Class IV lupus nephritis group. Ages of patients ranged between 10-56 years with a mean of 31.9 years. The normal controls, 20 males and 3 females, and ethnically 9 Indians, 7 Malays, 2 Chinese, and 5 foreign nationals (4 Indonesians and 1 Bangladeshi), had an age range between 15-33 years (mean = 23.3 years). Sixteen (69.6%) WHO Class IV lupus nephritis and 8 (34.8%) normal controls demonstrated Ki-67 immunoreactivity in at least 1 glomerulus (p<0.05). Of the 256 WHO Class IV lupus nephritis non-sclerosed, glomeruli studied, 37 (14.5%) were Ki-67 immunopositive compared with normal controls where 16 (0.7%) of 2159 glomeruli demonstrated Ki-67 (p< 0.01). Cellular proliferative activity, as evidenced by Ki-67 expression, was significantly increased in WHO Class IV lupus nephritis confirming that cell proliferation contributes to glomerular hypercellularity.
OBJECTIVES: To determine the pattern of renal histology, clinical outcome of children with lupus nephritis and to identify any associated risk factors predicting renal failure in these children.
METHODS: Retrospectively, 27 children under 16 years of age with lupus nephritis who had renal biopsies done at Sultanah Aminah Hospital Johor, Malaysia from 1994 to 2002 were studied. The renal histology was graded according to WHO classification system (1982). The medical records, laboratory data and the clinical outcome of the patients were studied.
RESULTS: There were 24 cases of WHO Class IV, two cases of WHO Class II and a case of WHO Class V. Twenty children were in the good renal outcome group while six children progressed into the poor renal outcome group and required renal replacement. One child was lost to follow-up. All six children in the poor renal outcome group had WHO Class IV histology. The 5-year patient and renal survival rates were 84% and 75%, respectively. Age, sex, activity and chronicity indices in the renal histology, anaemia, elevated serum creatinine, depressed levels of C3 and C4, heavy proteinuria or presence of urinary active sediments were not associated with progression to renal failure.
CONCLUSIONS: Presently, children with lupus nephritis appeared to have better patient and renal survival rates. Assessment of renal histology in these children was important for diagnosis, treatment and probably prognosis. In this study, there was a 25% incidence of loss of renal function over 5 years in children with WHO Class IV renal histology.
Thirty-eight cases of lupus nephritis, all satisfying the American Rheumatism Association criteria for diagnosis of systemic lupus erythematosus (SLE), with renal involvement and biopsy were immunohistochemically studied for the expression of HLA-DR (DAKO: HLA-DR/alpha, TAL.1B5), one of the three known families belonging to the class II major histocompatibility complex (MHC), using a standard streptavidin-biotin-peroxidase method. 20 nephrectomies performed for renal trauma and tumours constituted the normal controls. Of the lupus nephritis cases, 34 were females and 4 males. Ethnically, 20 were Chinese, 13 Malay, 4 Indian and 1 of indigenous origin. Their ages ranged from 16 to 59 years (mean of 31 years). Histologically, 23 expressed World Health Organisation (WHO) class IV (diffuse proliferative), 10 WHO class V (diffuse membranous), 4 WHO class II (pure mesangiopathy) and 1 WHO class III (segmental and focal proliferative) nephritis. Activity scores ranged between 5 to 19 (mean = 8.6) and chronicity scored between 2 to 7 (mean = 3.2) on a standard scoring system. Similar to other studies, HLA-DR was expressed in the glomerular capillaries and peritubular capillaries of all and mesangium, tubules (proximal, distal and collecting), veins and arterioles of some normal controls. Interestingly, HLA-DR expression was noted in the arteries of 25% of the normal controls, a finding hitherto not reported. The frequency of lupus nephritis cases expressing HLA-DR in the various anatomical components did not differ significantly from the normal controls except that HLA-DR expression in arteries and arterioles was seen at a significantly increased frequency (p < 0.01) in lupus nephritis. This increased expression did not correlate with the WHO class, activity or chronicity scores. It therefore appears that MHC class II shows increased expression in the arterial system of lupus nephritis kidneys. The significance of this is unclear but could be related to heightened (gamma-interferon activation which may be a de novo phenomenon or result of T cell proliferation and activation in SLE.
Between 1980-1986, 219 renal biopsies were performed on patients with lupus nephritis (LN) presenting at the General Hospital, Kuala Lumpur. There were 172 (78.5%) females and 47 (21.5%) males. The ethnic distribution of 48.4% Malays, 46.1% Chinese and 5.5% Indians reflected their proportional composition in the general population. Peak incidence (40.6%) of cases occurred in the third decade of life (20-29 group) followed by 26.5% and 20.1% in the second and fourth decades respectively. The median age was 24 for females and 27 for males. In both sexes, nephrotic syndrome was the commonest mode of presentation (62.2%) followed by proteinuria (20.5%). Acute oliguric renal failure occurred in 11 patients (5%) and 8 of these showed crescentic glomerulonephritis with more than 50% crescents. The commonest histological picture was diffuse proliferative LN (WHO Stage IV-44.7%) which included 70% (19/27) of those with crescentic disease. This was followed by membranous LN (28.8%) of which 6 (all males) had crescentic disease. 7 (12.3%) of our patients had crescentic nephritis with a female to male distribution of 14: 13, suggesting either more aggressive disease or delayed diagnosis in males.
Key words - Renal biopsies, lupus nephritis, nephrotic syndrome, proteinuria.
Renal biopsy is essential in the management of renal parenchymal diseases. Thus far there is no publish report on the pattern of glomerulonephritis in Kelantan. We decided to establish the pattern of glomerulonephritis in Kelantan and use this information as our reference in future studies. Records of patients who had proven glomerulonephritis histologically were analysed. Their biological data, clinical presentation, etiology and clinicopathological pattern were studied. Where appropriate mean and standard deviation were calculated. A total of 74 biopsies were performed during the study period (between January 1991 and December 1993), out of which 72 biopsies (97.3%) were considered suitable for analysis. The male to female ratio was 1:1.1. Mean age at presentation was 27.6 +/- 12.2 years. Nephrotic syndrome was the commonest clinical presentation (65.3%). The main underlying cause was systemic lupus erythematosus (50%) followed by primary glomerulonephritis. Histologically, IgA nephropathy and minimal change disease were the main patterns among patients with primary glomerulonephritis while diffuse proliferative glomerulonephritis was the commonest pattern among patients with lupus nephritis. Hence the pattern of glomerulonephritis is similar to other reported series. The procedure is considered safe and has a high success rate.
AIM: The objectives of this study were to investigate the frequency of thickened carotid intima media thickness (CIMT) and atherosclerosis among lupus nephritis (LN) patients and to study their associated risk factors.
METHOD: In this cross-sectional study, carotid ultrasonography was performed on consecutive LN patients to determine CIMT and presence of carotid plaques. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex from the 'Carotid Atherosclerosis Progression Study'. The association between thickened CIMT with traditional cardiovascular risk factors and lupus characteristics were examined. A total of 83 patients with the mean age of 33.6 ± 10 years were recruited.
RESULTS: Fourteen patients (16.9%) had thickened CIMT and three (3.6%) had carotid plaques. On univariate analysis, traditional risk factors significantly associated with thickened CIMT (P < 0.05) were patient's current age, diabetes mellitus and waist circumference. Meanwhile, a lower serum C4 levels and higher serum C-reactive protein levels were the lupus-specific factors associated with thickened CIMT (P < 0.05, P < 0.05 and P < 0.01, respectively). In logistic regression analysis, the independent predictors of thickened CIMT were age of diagnosis, lower serum C4 levels and waist circumference (P < 0.05).
CONCLUSION: More lupus specific factors were independently associated with thickened CIMT, suggesting that a multi-targeted approach of treatment addressing both the lupus and traditional cardiovascular risks are very important. Larger prospective studies of these special risk factors are indicated.
BACKGROUND: The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.
METHODS: Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were randomly assigned to either mycophenolate mofetil (MMF) 2 g/day for 6 months or intravenous cyclophosphamide (IVC) 0.75-1 g/m(2) monthly for 6 months in addition to corticosteroids.
RESULTS: Remission occurred in 13 out of 25 patients (52%) in the IVC group and 11 out of 19 patients (58%) in the MMF group (P = 0.70). There were 12% in the IVC group and 26% in the MMF group that achieved complete remission (P = 0.22). Improvements in haemoglobin, the erythrocyte sedimentation rate, serum albumin, serum complement, proteinuria, urinary activity, renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups. Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups. The chronicity index increased in both groups but was only significant in the IVC group. Adverse events were similar. Major infections occurred in three patients in each group. There was no difference in gastrointestinal side-effects.
CONCLUSIONS: MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis.
Background: Malignancies are among the leading causes of death in Systemic Lupus Erythematosus (SLE)
patients with studies reporting a higher prevalence of malignancy in SLE patients compared to the general population.
We wanted to determine the frequency of cancer in a cohort of SLE patients and identify its associated risk factors.
Methods: Cross-sectional study involving SLE patients attending the nephrology outpatient clinic, Universiti
Kebangsaan Malaysia Medical Centre between January and June 2014. Results: We recruited 228 patients (207 female,
21 male), aged 40.48 ± 12.86 years with mean SLE duration of 11.65 ± 6.46 years. Majority (87%) had lupus nephritis
and were in remission with a median SLEDAI score 2 (0, 14). Majority (89%) were on corticosteroid with either a
steroid sparing agent like mycophenolate mofetil (15.4%), azathioprine (36.8%) or ciclosporin (15.4%). One hundred
and sixty (70.2%) patients were either receiving or had received intravenous cyclophosphamide with median dose
of 5,173.6 ± 3,242.4 mg. Seven female patients were diagnosed with cancer during the course of their SLE with 56
(34-78) years being median age at malignancy and SLE duration of 4 (0-12) years. Majority (5/7) had lupus nephritis
and all patients a median dose of prednisolone 10 (2.5, 10) mg with 10 (4-24) years of steroids. Two patients had a
family history of cancer with majority developing cancer after the diagnosis of SLE. Two patients received intravenous
cyclophosphamide prior to the development of cancer for their SLE compared to overall cohort of 160. Three patients
had colorectal cancer, 2 had cervical cancer, 1 had breast cancer, and one patient had germ cell tumour and one thyroid
cancer. All patients had their cancer successful treated with no signs of recurrence. Conclusion: We found a lower
occurrence of cancer in our SLE patients as compared with the reported literature.
OBJECTIVES: To investigate the prevalence of thickened carotid intima media thickness (CIMT) and its associated risk factors in patients with lupus nephritis (LN) who were in remission.
METHODS: This was a cross sectional study in which consecutive LN patients who were in remission and attending our Nephrology/SLE Clinic were included. Their demographic profile, traditional cardiovascular risk factors and treatment medications were evaluated by clinical interview and review of medical records. Carotid intima media thickness (CIMT) was measured using B Mode carotid ultrasonography. CIMT was considered to be abnormally thickened if it exceeded the 75th percentile matched for age-and sex-matched normal controls. The associated factors for thickened CIMT were examined.
RESULTS: A total of 39 patients with a mean remission duration of 29 ± 24.3 months and on a mean prednisolone dose of 9.10 ± 7.83 mg daily completed the study. Six patients (15.4%) had thickened CIMT. On univariate analysis, male gender, patient age, older age at diagnosis, higher serum CRP levels, greater proteinuria and higher mean cumulative azathioprine dose were associated with thickened CIMT (P<0.05). Lower mean cumulative doses of cyclosporine A (CyA) and mycophenolic acid (MPA) (P<0.05) each were associated with thickened CIMT. Using regression analysis, the associated factors of CIMT were older age at diagnosis and proteinuria.
CONCLUSIONS: Lupus factors particularly age at diagnosis and proteinuria were the associated factors of thickened CIMT. Larger prospective trials are indicated to confirm our findings.