A descriptive study of the factors associated with damage in Malaysian patients with lupus nephritis.

INTRODUCTION: Renal involvement is the most common serious complication in patients with systemic lupus erythematosus (SLE). OBJECTIVE: The objective of this article is to investigate and determine the associated factors of disease damage among lupus nephritis (LN) patients. METHODS: Medical records of LN patients who attended regular follow-up for at least one year in the Nephrology/SLE Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), were reviewed. Their Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index scores were noted. Univariate analysis and multivariable regression analysis were performed to determine the independent factors of disease damage in LN. RESULTS: A total of 150 patients were included and their follow-up duration ranged from one to 20 years. Sixty (40%) LN patients had disease damage (SDI ≥1). In the univariate analysis, it was associated with age, longer disease duration, antiphospholipid syndrome (APS), higher maximum daily oral prednisolone dose (mg/day), lower mean C3 and C4, higher chronicity index and global sclerosis on renal biopsies (p < 0.05). Patients who received early (≤3 months after the SLE diagnosis) hydroxychloroquine (HCQ), optimum HCQ dose at 6.5 mg/kg/day and achieved early complete remission (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 higher maximum daily dose of oral prednisolone was independently associated with disease damage while early HCQ and CR were associated with lower disease damage. CONCLUSION: Higher maximum daily prednisolone dose predicted disease damage whereas treatment with early HCQ and early CR had a protective role against disease damage.

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus: pooled analysis of the literature reviews and report of six new cases.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder which is increasingly recognized to occur in systemic lupus erythematosus (SLE). OBJECTIVE: The purpose of this study was to identify the characteristics of SLE patients with PRES and the associated factors of the poor outcome among them. METHODS: We investigated SLE patients who developed PRES between 2005-2011 at the Universiti Kebangsaan Malaysia Medical Centre. A comprehensive literature search was done to find all published cases of PRES in SLE. Pooled analysis was conducted to identify the factors associated with poor outcome. RESULTS: There were 103 cases of PRES in SLE published in the literature but only 87 cases were included in the analysis in view of incomplete individual data in the remaining cases. The majority of the cases were Asians (74.2%), female (95.4%) with mean age of 26.3 ± 8.8 years. PRES was highly associated with active disease (97.5%), hypertension (91.7%) and renal involvement (85.1%). We found that 79 patients had a full recovery (90.8%) with a mean onset of full clinical recovery in 5.6 ± 4.1 days. On univariate analysis and logistic regression analysis the predictors of poor outcome, defined as incomplete clinical recovery or death, were intracranial hemorrhage, odds ratio (OR) 14 (1.1-187.2), p=0.04 and brainstem involvement in PRES, OR 10.9 (1.3-90.6), p=0.003. CONCLUSION: Intracranial hemorrhage and brainstem involvement were the two important predictors of poor outcome of PRES. Larger prospective studies are needed to further delineate the risk of poor outcome among them.

Predictors of thickened carotid intima media thickness among well controlled lupus nephritis patients in a Malaysian tertiary centre.

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.

Acute renal failure following the use of rosiglitazone in a chronic kidney disease patient.

Drug-induced acute interstitial nephritis is a well-recognised and important reversible cause of acute renal failure. Peroxisome-proliferator activated receptor-gamma agonists, such as rosiglitazone, have been proven to be safe in chronic kidney disease patients. We describe a 65-year-old man with long-standing diabetes mellitus and hypertension, presenting with a five-day history of fluid overload and uraemic symptoms. There was no ingestion of analgesics, alternative medicine and other nephrotoxic drugs, the only new prescription being rosiglitazone, which was commenced during his last clinic follow-up two weeks prior to presentation. He required haemodialysis with minimal improvement in renal profile, despite cessation of the offending drug. Renal biopsy revealed findings consistent with acute interstitial nephritis. An episode of upper gastrointestinal bleeding with bleeding duodenal ulcer limited the use of steroids. He was treated with a course of mycophenolate mofetil which showed good gradual response and he remained stable with residual renal impairment.

Influences on bone mineral density in Malaysian premenopausal systemic lupus erythematosus patients on corticosteroids.

The aim of this study was to assess the bone mineral density (BMD) of premenopausal patients with systemic lupus erythematosus (SLE) on corticosteroids (CS) and to determine the influence of CS and other risk factors on BMD. A total of 98 premenopausal patients with SLE were recruited from outpatient clinics in two teaching hospitals. Risk factors for osteoporosis were determined, and BMD was measured using dual-energy x-ray absorptiometry. The mean age of the patients was 30.05 +/- 7.54 years. The mean dose of prednisolone at time of BMD measurement was 18.38 +/- 10.85 mg daily. Median duration of CS use was 2.5 years (range 0-20). Median cumulative dose of CS was 9.04 g (range 0.28-890.0). Six patients (6.1%) had osteoporosis, 41 (41.9%) had osteopenia and 51 (52.0%) had normal BMD. Lumbar spine T score correlated with cumulative CS dose (P = 0.019). Duration of CS intake correlated with femoral neck T score (P = 0.04) and trochanter T score (P = 0.008). There was no correlation between BMD and race, SLE Disease Activity Index score, smoking and self-reported calcium intake or exercise. Only 52% of these patients had normal BMD. The duration and cumulative dose of CS intake was significantly correlated to BMD, but not the other commonly assessed risk factors. These findings suggest that premenopausal patients with SLE on CS should have their BMD measured at regular intervals to fully assess their osteoporosis risk.

A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients.

Prehemodialysis and hemodialysis patients are at an increased risk of hepatitis B infection and have an impaired immune response to hepatitis B vaccines. We evaluated the immune response to the new adjuvant of hepatitis B vaccine AS04 (HBV-AS04) in this population. We measured antibody persistence for up to 42 months, and the anamnestic response and safety of booster doses in patients who were no longer seroprotected. The primary vaccination study showed that HBV-AS04 elicited an earlier antibody response and higher antibody titers than four double doses of standard hepatitis B vaccine. Seroprotection rates were significantly higher in HBV-AS04 recipients throughout the study. The decline in seroprotection over time was significantly less in the HBV-AS04 group with significantly fewer primed patients requiring a booster dose over the follow-up period. Solicited/unsolicited adverse events were rare following booster administration. Fifty-seven patients experienced a serious adverse event during the follow-up; none of which was vaccine related. When HBV-AS04 was used as the priming immunogen, the need for a booster dose occurred at a longer time compared to double doses of standard hepatitis B vaccine. Hence, in this population, the HBV-AS04 was immunogenic, safe, and well-tolerated both as a booster dose after HBV-AS04 or standard hepatitis B vaccine priming.

Outcome of bacteraemia in patients admitted to the adult medical wards of the UKM hospital.

The clinical outcome of bacteraemic patients is influenced by many factors. It is vital to know one's own local hospital epidemiological data so as to provide optimal care to the affected patients. This was a prospective, observational study carried out in the said patient population over a period of four months in the year 2005. One hundred and ninety one patients presented with bacteraemia over the study period. Fifty-two (27%) of the patients died. Mechanical ventilation, inappropriate empirical antibiotic usage, Chinese ethnicity and low serum albumin levels independently affected prognosis. These factors should alert physicians to those patients who require more intensive monitoring and care.

Case of severe refractory myasthenia gravis in HUKM.

A 20-year-old girl first notice bilateral ocular muscle weakness in 2001. Two months later, she developed acute muscle paralysis and respiratory failure which required ventilation. Serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation test was positive and consistent with myasthenia gravis (MG). CT scan thorax revealed thymic enlargement and she underwent a video assisted thymectomy (VATS). However, over the next three years, despite maximal doses of various immunosuppressive agents with plasmapheresis and intravenous immunoglobulin, she was admitted with recurrent myasthenic crisis without any obvious precipitant. She was then commenced on mycophenolate mofetil and together with regular plasmapheresis, cyclosporine and prednisolone, her symptoms have finally improved and brought under control.

Microalbuminuria prevalence study in hypertensive type 2 diabetic patients in Malaysia.

Microalbuminuria is the earliest indicator of diabetic kidney disease and generalised vascular endothelial dysfunction. The Microalbuminuria Prevalence (MAP) Study was carried out to assess the prevalence of macroalbuminuria, microalbuminuria and normoalbuminuria in Asian hypertensive patients with type 2 diabetes on usual care. This paper presents a subanalysis of data from patients in Malaysia. In 733 analysed patients, the prevalence of macroalbuminuria and microalbuminuria was 15.7% and 39.7%, respectively. The high prevalence of diabetic nephropathy in these high-risk patients is a cause for concern, and the Malaysian Health Care system should be prepared for a pandemic of end-stage renal disease due to diabetic nephropathy.

An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria Prevalence (MAP) Study.

AIM/HYPOTHESIS: Microalbuminuria represents the earliest clinical evidence of diabetic nephropathy and is a marker of increased cardiovascular morbidity and mortality. Its early detection allows the implementation of individualised and aggressive intervention programmes to reduce cardiovascular risk factors. There is limited information on the prevalence of microalbuminuria among hypertensive type 2 diabetic patients in Asia. METHODS: This cross-sectional epidemiological study aimed to assess the prevalence of microalbuminuria and macroalbuminuria among consecutively screened hypertensive type 2 diabetic adult patients in 103 centres in 10 Asian countries or regions. Predictive factors for microalbuminuria and macroalbuminuria were characterised using a stepwise logistic regression model. RESULTS: A total of 6,801 patients were enrolled and 5,549 patients constituted the per-protocol population (patients with bacteriuria and haematuria were excluded). The prevalence of microalbuminuria was 39.8% (39.2-40.5; 95% CI) and the prevalence of macroalbuminuria was 18.8% (18.2-19.3; 95% CI). Only 11.6% of the patients had systolic and diastolic blood pressure below the 130/80 mm Hg target. In the multivariate analyses, the predictive factors for the presence of microalbuminuria were age, BMI, systolic blood pressure and ethnic origin. The highlighted predictive factors for the presence of macroalbuminuria were age, sex, ethnic origin, BMI, duration of diabetes, presence of diabetic complications, intake of diuretics, intake of calcium channel blockers, diastolic and systolic blood pressure. CONCLUSIONS/INTERPRETATION: The high prevalence (58.6%) of micro or macroalbuminuria observed in these patients is alarming and indicates an impending pandemic of diabetic cardiovascular and renal diseases in Asia with its potential economic consequences.

Antibodies in systemic lupus antineutrophil cytoplasmic erythematosus: prevalence, disease activity correlations and organ system associations.

Systemic Lupus Erythematosus (SLE) is a disease with multiorgan involvement and multiple autoantibody production including antineutrophil cytoplasmic antibodies (ANCA). Despite its reported prevalence in more than one third of SLE patients, the role of ANCA in the pathogenesis or otherwise in SLE remains unresolved. 131 SLE patients had been previously studied for various serologic parameters of disease activity. Their cumulative organ involvement in the course of their disease had also been determined and the Lupus Activity Index (LAI) calculated. Their stored sera were then screened for the presence of ANCA by two methods viz Indirect immunofluorescence (IIF) and also enzyme-linked immunosorbent assay (ELISA). ANCA was present in 24.8% of these SLE patients. The atypical ANCA pattern was predominant and accounted for an overall of 20.6%. Anti-MPO and anti-PR3 were detected in 1.5% of patients respectively. No association was found between ANCA positivity and disease activity. There was also no association of ANCA with specific organ involvement. Despite the high prevalence of ANCA especially the atypical variant in SLE, they probably represent only one of the wide repertoire of autoantibodies found in this disease. Routine testing for ANCA in lupus patients is therefore not recommended.

Lupus band test in systemic lupus erythematosus.

The usefulness of the direct immunofluorescent antibody technique--lupus band test--for the diagnosis of systemic lupus erythematosus (SLE) has been well established. The aims of the study were to determine the prevalence of the LBT at various sites of the skin in a cross section of patients with SLE and its correlation with disease activity. The LBT was demonstrated in 64% of skin lesions, 63% in non-lesional sun-exposed (NLSE) skin and 25% in non-lesional sun-protected (NLSP) skin. The prevalence of the LBT in lesional and NLSE groups was significantly different from the NLSP group (p = 0.03 and 0.005 respectively). There was a significant correlation between the presence of a positive LBT in NLSE skin with the presence of the LE cell phenomenon (p = 0.04) and anti - ds DNA antibody (0.02). In addition, there was a significant correlation between IgG LBT in the NLSE skin with serum hypocomplementaemia (p = 0.03) and anti - ds DNA antibody (p = 0.04). Other than these, no significant correlation was detected between the LBT from the 3 sites with overall clinical activity, renal disease, active skin lesions, or other laboratory indices of activity. These findings suggest that the LBT is mainly indicated as a diagnostic tool and has little role in assessing disease activity.