Abdul Halim Abdul Gafor

Neutrophil Gelatinase-Associated Lipocalin as an Early Marker of Contrast-Induced Nephropathy After Coronary Angiography

We investigated whether serum neutrophil gelatinase-associated lipocalin (NGAL) was an early predictive biomarker of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (n = 100) undergoing coronary catheterization. Serum creatinine (SCr) levels were measured at baseline, 24 hours, and 48 hours post procedure. Serum NGAL was measured preprocedure, 4 hours, and 24 hours post procedure. The frequency of CIN was 11%. In patients with CIN, SCr achieved significance only at 48 hours (P = .006), whereas serum NGAL increased ≥25% from baseline at 24 hours in 7 of 11 patients with CIN (P = .04) but did not change in the other 4. However, serum NGAL also rose ≥25% in 12 of 89 non-CIN patients. This subgroup could have had “incipient CIN.” Serum NGAL delta value at baseline, 24 hours was superior to SCr for early diagnosis of CIN. In conclusion, serum NGAL is an early predictive biomarker for CIN.

Serum neutrophil gelatinase-associated lipocalin and cystatin C are early biomarkers of contrast-induced nephropathy after coronary angiography in patients with chronic kidney disease

We had previously reported on serum neutrophil gelatinase-associated lipocalin (NGAL) as an earlier biomarker of contrast-induced nephropathy (CIN) than serum creatinine (SCr) in 100 patients with chronic kidney disease undergoing coronary angiography.1 We then compared serum NGAL to serum cystatin C (CysC) in the same group of patients. The SCr, estimated glomerular filtration rate, serum NGAL, and serum CysC were measured at baseline and various time points as appropriate postprocedure. The frequency of CIN was 11% (n = 11). Serum NGAL increased ≥25% from baseline at 24 hours in 7 patients with CIN (P = .04). Serum CysC increased ≥25% from baseline at 24 hours in 4 patients with CIN (P = .008). Changes in serum NGAL and serum CysC from baseline at 24 hours (▵ values) could diagnose CIN 24 hours earlier than SCr with serum NGAL showing a superior performance.

Immunoadsorption and plasmapheresis are equally efficacious as adjunctive therapies for severe lupus nephritis

This was a prospective randomized controlled trial to evaluate the effects of immunoadsorption (IA) versus conventional PP (PP) as adjunctive therapy in the treatment of severe lupus nephritis (LN). Of 28 patients with biopsy-proven severe LN (ISN/RPS classes III or IV ± V), 14 underwent 36 sessions of PP and the other 41 sessions of IA in addition to our centers standard LN treatment protocol. Three patients in the PP group and 2 in the IA group experienced a transient, marked drop in platelets with the second session. Except for a higher pre treatment mean SLEDAI score in the PP group 17.4 ± 2.0 vs. 13.5 ± 4.8; p = 0.009 and a serum creatinine of 163 ± 7.9 vs. 81.7 ± 10.2; p = 0.33, there were no other baseline differences. Some differences did exist between the two therapies in the immediate post-treatment phase, at 1 and 3 months. Three in IA relapsed, none of PP in third months, whereas two patients relapsed in the PP and none of IA cohorts at 6 months. However, most of these parameters did not differ by 6 months. The pre- and post-therapy SLEDAI scores remained different 12.4 ± 4.5 vs. 9 ± 4; p = 0.04 at 1 month, and at 3 month 13.5 ± 4.7 vs. 7.7 ± 1.1; p = 0.012 but not at 6 months. We conclude that IA and PP were equally well tolerated and efficacious as adjunctive therapy for severe LN.

Intravenous calcitriol versus paricalcitol in haemodialysis patients with severe secondary hyperparathyroidism

Aim:  Secondary hyperparathyroidism (SHPT) is common among haemodialysis patients. Intensive treatment with calcitriol is often complicated by hypercalcaemia, hyperphosphataemia and elevated calcium phosphorus (Ca X PO4) product. Paricalcitol is a vitamin D analogue developed to overcome some of the limitations of calcitriol therapy. The study objectives were to compare the response of intact parathyroid hormone (iPTH) and the incidence of hypercalcaemia, hyperphosphataemia and elevated Ca X PO4 product in patients with severe SHPT treated with either i.v. calcitriol or i.v. paricalcitol.

Urine Monocyte Chemoattractant Protein-1 and Lupus Nephritis Disease Activity: Preliminary Report of a Prospective Longitudinal Study.

Objective. This longitudinal study aimed to determine the urine monocyte chemoattractant protein-1 (uMCP-1) levels in patients with biopsy-proven lupus nephritis (LN) at various stages of renal disease activity and to compare them to current standard markers. Methods. Patients with LN—active or inactive—had their uMCP-1 levels and standard disease activity markers measured at baseline and 2 and 4 months. Urinary parameters, renal function test, serological markers, and renal SLE disease activity index-2K (renal SLEDAI-2K) were analyzed to determine their associations with uMCP-1. Results. A hundred patients completed the study. At each visit, uMCP-1 levels (pg/mg creatinine) were significantly higher in the active group especially with relapses and were significantly associated with proteinuria and renal SLEDAI-2K. Receiver operating characteristic (ROC) curves showed that uMCP-1 was a potential biomarker for LN. Whereas multiple logistic regression analysis showed that only proteinuria and serum albumin and not uMCP-1 were independent predictors of LN activity. Conclusion. uMCP-1 was increased in active LN. Although uMCP-1 was not an independent predictor for LN activity, it could serve as an adjunctive marker when the clinical diagnosis of LN especially early relapse remains uncertain. Larger and longer studies are indicated.

The role of urinary neutrophil gelatinase-associated lipocalin in lupus nephritis

BACKGROUND Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been proposed as a potential biomarker for lupus nephritis (LN) activity. We determined the association between uNGAL with LN activity in systemic lupus erythematosus (SLE) patients compared to the current standard markers of SLE. METHODS A total of 100 SLE patients with biopsy-proven LN were recruited-47 with active and 53 inactive LN. uNGAL levels were measured. Renal function test, urinary parameters, lupus serology and calculated renal SLE Disease Activity Index-2K (renal SLEDAI-2K) were analyzed to determine their associations with uNGAL. RESULTS Normalized uNGAL levels (ng/mg creatinine) were significantly higher in patients with active LN compared to those with inactive disease (p=0.01). uNGAL and renal SLEDAI-2K were associated (r=0.32, p=0.001). Multiple logistic regression showed that only serum creatinine and renal SLEDAI-2K were independent predictors of uNGAL levels (p=0.03 and 0.02 respectively). Analysis of the receiver operating characteristic (ROC) curve showed that uNGAL was a potential biomarker for LN. CONCLUSIONS uNGAL was increased in active LN especially in LN flares. Serial measurements of uNGAL levels may be of value in monitoring response of LN to treatment and for predicting LN flares.

Urinary Monocyte Chemoattractant Protein and Lupus Nephritis Activity

Objective: Monocyte chemoattractant protein-1 (MCP-1) is reported to be associated with lupus nephritis (LN) activity. We therefore investigated urinary MCP-1 (uMCP-1) in patients with biopsy proven LN. Methods: This was a cross-sectional observational study in which uMCP-1 levels and the standard parameters of LN activity were measured in these patients. Results: One hundred patients were recruited: 47 with active and 53 inactive LN. uMCP-1 levels were increased in those with active LN [9,317.5 pg/mg creatinine (5,48.3-40,170)] compared to those with inactive LN [3,682 pg/ mg creatinine (0-23,866)] (p<0.001). uMCP-1 correlated with proteinuria (r=0.39, p=0.001), serum albumin (r=-0.35, p=0.001) and SLEDAI-2K (renal) (r=0.39, p=0.001). Area under receiver operating characteristic (AUROC) curve for uMCP-1 was 0.82 (p=0.001) compared with 0.50 (p=0.95), 0.37 (p=0.50), 0.43 (p=0.26) for anti-ds-DNA Ab, C3 and C4 respectively. AUROC for proteinuria was 0.94 (p<0.001) and for SLEDAI-2K (renal) was 0.96 (p<0.001). Only proteinuria and SLEDAI-2K (renal) were independent predictors of LN activity. Conclusions: uMCP-1 may provide further adjunctive evidence if the clinical diagnosis of LN activity remains uncertain and facilitate improved grading of renal disease activity in this complex disease thus leading to improved treatment and outcome. Serial measurements of uMCP-1 are indicated.

Steroid‐induced diabetes mellitus in systemic lupus erythematosus patients: analysis from a Malaysian multi‐ethnic lupus cohort

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and glucocorticoid is the mainstay of treatment in SLE. The reported incidence of steroid‐induced diabetes mellitus (SDM) ranged between 1–53%. We sought to investigate the prevalence and associated factors of SDM in patients with SLE.

Damage in the multiethnic Malaysian systemic lupus erythematosus (SLE) cohort: Comparison with other cohorts worldwide

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease and despite the improvement in the survival in the past few decades, the morbidity due to disease damage remains significant. The objectives of this study were to investigate the disease damagepattern and determine the associated factors of damage in the multi-ethnic Malaysian SLE patients. We consecutively 424SLE patients who attended a consistent follow-up at the National University of Malaysia Medical Centre and Putrajaya Hospital were recruited. Disease damage was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index (SDI) scores. Information on their demographics and disease characteristics were obtained from the clinical record. Univariate analysis was performed and the best model of independent predictors of disease damage was determined by multivariate logistic regression analysis. A total of 182 patients (42.9%) had disease damage (SDI ≥1). A significantly higher number of Indian patients had disease/organ damage and they predominantly developed steroid-induced diabetes mellitus (SDM). Patients with corticosteroid-induced osteoporosis (CIOP) were more likely to be Malayswhile majority of patients who developed malignancy were Chinese (p<0.05). In the univariate and multivariate analyses, disease damage was significantly associated with age, Indian ethnicity, lower mean cumulative C3 level, neuropsychiatry lupus (NPSLE), and antiphospholipid syndrome (APLS). Patients who had ever and early treatment with hydroxychloroquine(HCQ)were less likely to develop disease damage while more patients who had received oral prednisolone ≥1mg/kg daily over 2 weeks had disease damage (p<0.05). In conclusion, there were inter-ethnic differences in the damage pattern and risks among SLE patients.

The effects of calcitriol with calcium carbonate supplementation on inflammatory biomarkers in chronic kidney disease patients' with low vitamin D.

Introduction Chronic kidney disease (CKD) patients’ are at risk of low vitamin D and chronic inflammation. We studied the effect of 12 weeks calcitriol and calcium carbonate supplementation on inflammatory mediators serum; interleukin-6 (IL-6), interleukin-10 (IL-10) and highly sensitive C-reactive protein (hs-CRP). Material and methods A prospective randomized study in CKD stages 2-4 with serum 25-hydroxyvitamin D (25-OHD) levels < 30 ng/ml. Patients were randomized into the Vitamin D + Calcium (Vitamin D + C) or Calcium group. Serums were analyzed at baseline, week 6 and 12. Results Fifty patients, median age of 53 (13.5) years were recruited. Their median IL-10 was 13.35 (25.22) pg/ml. At week 12, serum IL-6 was reduced in both groups (p = 0.001), serum IL-10 was maintained in the Vitamin D + C group (p = 0.06) and was reduced in the Calcium group (p = 0.001). CKD-diabetic patients had reduced serum IL-6 in both study groups (p = 0.001) and a reduction was seen in the Vitamin D + C group of the non-diabetics counterparts (p = 0.005). Serum IL-10 was reduced in the Calcium group (p < 0.05) whereas serum 25-OHD rose in both groups, regardless of their diabetic status (p < 0.05). Conclusions Twelve weeks, calcitriol supplementation maintained IL-10, had no effects on hs- CRP and had no additional benefit compared to calcium carbonate in reducing serum IL-6 except in non-diabetics.