Displaying all 12 publications

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  1. Cader RA, Mohd R, Gafor HA, Kong NC
    EXCLI J, 2013;12:144-9.
    PMID: 26417223
    Post-transplant lymphoproliferative disorder (PTLD) is a recognized complication exclusive to solid organ transplant recipients and carries a high mortality. We retrospectively reviewed records of all renal transplant recipients under follow up at our institution over the last seven years (2005-2011). We reviewed the patient characteristics, immunosuppression regimen and risk factors for the development of PTLD and its outcomes in our transplant cohort. Four out of 63 patients were diagnosed with PTLD. PTLD was incidentally diagnosed on a transplant biopsy that was performed for an unexplained rise in serum creatinine in three patients. The fourth patient presented with left submandibular lymphadenopathy. Majority presented within 18 months of renal transplantation. After the diagnosis of PTLD on graft biopsy, all patients were fully investigated and two patients had systemic involvement. In the patients with systemic involvement, reduction of immunosuppression and anti B cell therapy with Rituximab was used with good success. The patient with submandibular lymphadenopathy received chemotherapy in addition to reduction of immunosuppression. Three PTLD cases were polyclonal and diagnosed early whereas the fourth case was monoclonal. PTLD can sometimes be incidentally diagnosed on an allograft biopsy performed for rejection. The incidence of PTLD in our centre is higher than reports from other centres but our outcome is good if recognised and treated early.
  2. Shaharir SS, Mustafar R, Mohd R, Mohd Said MS, Gafor HA
    Clin Rheumatol, 2015 Jan;34(1):93-7.
    PMID: 25373448 DOI: 10.1007/s10067-014-2802-0
    Arterial hypertension (HPT) burden up to two third of systemic lupus erythematosus (SLE) patients and contributes to accelerated atherosclerosis and cardiovascular (CV) risk. We aim to determine the prevalence of HPT among lupus nephritis (LN) patients who were in complete remission (CR) for a minimum of 6 months, with estimated glomerular filtration rate (eGFR) of >60 mL/min/1.73 m(2). This is a cross-sectional study of 64 LN patients who attended Nephrology/SLE Clinic at The National University of Malaysia Medical Centre (UKMMC). Persistent hypertension (blood pressure (BP) ≥140/90 mmHg for at least two occasions), CR for a minimum of 6 months and eGFR of >60 mL/min/1.73 m(2) were identified. Univariate and multivariate analyses were performed to determine the demographic and disease characteristics associated with HPT. Thirty-four of them (53.1 %) were hypertensive. Persistent HPT was associated with disease duration, acute kidney injury and high BP at the onset of LN, longer duration interval to achieve CR, number of relapses and cyclosporine A (CyA) use. There were no associations between histological classes, nephrotic range proteinuria, body mass index and waist circumference with HPT. Factors independently associated with HPT were disease duration OR 1.06 [95 %CI (0.91-1.24)], longer duration interval to achieve CR OR 1.104 [95 %CI (1.02-1.19)], number of relapses OR 2.53 [95 % CI (1.01-6.3)] and CyA use OR 5.3 [95 % CI (1.14-23.9)]. The prevalence of HPT among LN is high despite in remission. Aggressive treatment is important to achieve early CR and to prevent relapses.
    Study site: Nephrology/SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  3. Cader RA, Ibrahim OA, Paul S, Gafor HA, Mohd R
    Int Urol Nephrol, 2014 Jun;46(6):1209-15.
    PMID: 24307428 DOI: 10.1007/s11255-013-0615-8
    PURPOSE: Cardiovascular disease is the leading cause of mortality in dialysis patients with left ventricular hypertrophy (LVH) being an important predictor of mortality. We wanted to determine the prevalence of LVH in peritoneal dialysis (PD) patients and factors contributing to it.

    METHODS: This is a cross-sectional study assessing LVH using echocardiogram in PD patients. Left ventricular mass index (LVMI) was calculated to determine LVH. Chronic fluid overload (overhydration) was assessed using the body composition monitor, and blood pressure (BP) was measured using 24-h ambulatory BP monitoring.

    RESULTS: Thirty-one patients (21 females:10 males, 48.97 ± 14.50 years and dialysis vintage 40.0 ± 28.9 months) were studied. More than two-thirds (77.4 %) were hypertensive, and a third (35.5 %) were diabetic. Baseline data included mean serum albumin (37.34 ± 4.43 g/l), weekly Kt/V (2.02 ± 0.23), residual renal function of 68 (0-880) ml and ultrafiltration of 1,606.9 ± 548.6 ml. Majority of patients (80.6 %) had LVH on echocardiogram with LVMI of 136.5 ± 37.8 g/m(2) and overhydration of 2.23 ± 1.77 l. Average systolic BP, diastolic BP and mean arterial pressure were 141.2 ± 23.3, 90.8 ± 19.7 and 107.6 ± 19.6 mmHg, respectively. Patients with LVH had a lower serum albumin (p = 0.003), were more overhydrated (p = 0.010) and were on higher number of anti-hypertensive agents (p ≤ 0.001). Predictors of LVMI were overhydration (p = 0.002), the presence of diabetes (p = 0.008) and the number of anti-hypertensive agents used (p = 0.026). However, overhydration (p = 0.007) was the main predictor of LVH on multivariate analysis.

    CONCLUSION: Overhydration is strongly associated with LVH in PD patients.

  4. Nadira U, Cader RA, Kong NC, Mohd R, Gafor HA
    Am J Case Rep, 2012;13:160-2.
    PMID: 23569517 DOI: 10.12659/AJCR.883248
    BACKGROUND: Malignancies are more common in patients with systemic lupus erythematosus (SLE) than the general population. SLE patients are recognized to have higher prolactin levels. However, there are very few reported cases of SLE with pituitary adenomas.
    CASE REPORT: We report the second case of a pituitary adenoma in a patient with underlying SLE. A 51 year old lady presented with blurred vision and magnetic resonance imaging of the brain demonstrated a pituitary macroadenoma with mildly elevated serum prolactin levels. The diagnosis of a non functioning pituitary macroadenoma was confirmed histologically. The diagnosis of SLE was made on the basis of thrombocytopenia, antinuclear antibodies, anti double stranded DNA antibodies and lupus nephritis (confirmed on renal biopsy). The patient initially received medical therapy with carbegoline, followed by transsphenoidal neurosurgery for the pituitary macroadenoma. SLE with lupus nephritis was treated with steroids and low dose intravenous cyclophosphamide.
    CONCLUSIONS: Hyperprolactinaemia is prevalent in twenty to thirty percent of SLE patients but it is rarely due to a prolactinoma. The source of excessive circulating prolactin in SLE patients has not been fully determined.
    KEYWORDS: pituitary macroadenoma; prolactin; systemic lupus erythematosus
  5. Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE
    Br J Clin Pharmacol, 2015 Nov;80(5):1064-75.
    PMID: 25959850 DOI: 10.1111/bcp.12678
    AIMS: The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis.
    METHODS: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events.
    RESULTS: Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023).
    CONCLUSIONS: This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis.
    KEYWORDS: lupus nephritis; mycophenolic acid; pharmacodynamics; pharmacokinetics; prednisolone; treatment outcome
    Study site: Nephrology and SLE Clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  6. Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE
    Eur J Drug Metab Pharmacokinet, 2017 Dec;42(6):993-1004.
    PMID: 28536776 DOI: 10.1007/s13318-017-0420-3
    BACKGROUND AND OBJECTIVE: Mycophenolic acid (MPA) provides effective treatment for lupus nephritis patients. Owing to its large pharmacokinetic variability, it is questionable whether standard fixed dose therapy can achieve optimal MPA exposure. The aim of this study was to develop a population pharmacokinetic model of MPA and its metabolite, 7-O-MPA-β-glucuronide (MPAG), to identify important covariate influences and better predict patient dosing requirements.
    METHODS: MPA and MPAG concentration-time profiles were collected from 25 patients receiving mycophenolate mofetil (MMF) with or without cyclosporine (CsA) co-therapy. Samples were collected pre-dose and at 1, 2, 4, 6 and 8 h post-dose on one or two occasions.
    RESULTS: A total of 225 and 226 concentration-time measurements of MPA and MPAG, respectively, were used to develop the model, utilizing NONMEM® software. A two-compartment model with first-order absorption and elimination for MPA and a one-compartment model with first-order elimination and enterohepatic circulation (EHC) for MPAG best described the data. Apparent clearance of MPAG (CL/F MPAG) significantly decreased with reducing renal function and extent of EHC was reduced with concomitant CsA use. Simulations using the final model showed that a 70-kg subject with a creatinine clearance of 90 mL/min receiving concomitant CsA would require 1.25 g of MMF twice daily while a similar subject who did not receive concomitant CsA would require 0.75 g twice daily to achieve a MPA area under the concentration-time curve from 0 to 12 h (AUC0-12) of 45 mg·h/L.
    CONCLUSION: A 'tiered' dosing approach considering patient renal function and CsA co-therapy, rather than a 'one dose fits all' approach, would help individualize MMF therapy in adult lupus nephritis patients to ensure more patients have optimal MPA exposure.
    Study site: Nephrology and Systemic Lupus Erythematosus (SLE) Clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  7. Cader RA, Gafor HA, Mohd R, Ibrahim S, Wan Haslina WH, Bain A, et al.
    EXCLI J, 2012;11:116-24.
    PMID: 27366136
    Cardiovascular mortality is the leading cause of death in end stage renal disease. Despite being on continuous ambulatory peritoneal dialysis (CAPD), blood pressure (BP) remains poorly controlled. A higher pulse pressure and non dipping are associated with increased cardiovascular mortality. We studied BP control and the prevalence of non dipping in CAPD patients.
  8. Mohd R, Wahab ZA, Cader R, Gafor HA, Radzi AM, Shah SA, et al.
    J Clin Med Res, 2014 Aug;6(4):245-51.
    PMID: 24883149 DOI: 10.14740/jocmr1550w
    BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) accounts for a third of biopsy-proven primary glomerulonephritis in Malaysia. Pediatric studies have found the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene to be associated with renal disease progression. The aim of this study was to determine the prevalence of the ACE (I/D) genotypes in adult primary FSGS and its association with renal outcome on follow-up.

    METHODS: Prospective observational study involving primary FSGS patients was conducted. Biochemical and urine tests at the time of study were compared to the time of the diagnosis and disease progression analyzed. ACE gene polymorphism was identified using polymerase chain reaction amplification technique and categorized into II, ID and DD genotypes.

    RESULTS: Forty-five patients with a median follow-up of 3.8 years (interquartile range: 1.8 - 5.6) were recruited. The commonest genotype was II (n = 23, 51.1%) followed by ID (n = 19, 42.2%) and DD (n = 3, 6.7%). The baseline characteristics were comparable between the II and non-II groups at diagnosis and at study recruitment except that the median urine protein-creatinine index was significantly lower in the II group compared to the non-II group (0.02 vs. 0.04 g/mmol (P = 0.03). Regardless of genotypes, all parameters of renal outcome improved after treatment.

    CONCLUSION: The II followed by ID genotypes were the predominant ACE gene alleles in our FSGS. Although the D allele has been reported to have a negative impact on renal outcome, treatment appeared to be more important than genotype in preserving renal function in this cohort.

  9. Mustafar R, Mohd R, Ahmad Miswan N, Cader R, Gafor HA, Mohamad M, et al.
    Nephrourol Mon, 2014 Jan;6(1):e13381.
    PMID: 24719814 DOI: 10.5812/numonthly.13381
    Hypovitaminosis D (serum 25-OHD < 30 ng/mL) is common in patients with chronic kidney disease (CKD). Vitamin D is believed to involve in the regulation of renin-angiotensin system and may be renoprotective.
  10. Cader RA, Gafor HA, Mohd R, Kong NC, Ibrahim S, Wan Hassan WH, et al.
    J Clin Nurs, 2013 Mar;22(5-6):741-8.
    PMID: 23039369 DOI: 10.1111/j.1365-2702.2012.04298.x
    To assess the degree of overhydration in our peritoneal dialysis patients and to examine the factors contributing to overhydration.
  11. Sahathevan S, Se CH, Ng S, Khor BH, Chinna K, Goh BL, et al.
    Clin Nutr ESPEN, 2018 06;25:68-77.
    PMID: 29779821 DOI: 10.1016/j.clnesp.2018.04.002
    BACKGROUND AND AIMS: Poor dietary intake is commonly associated with malnutrition in the dialysis population and oral nutritional supplementation is strategized to redress dietary inadequacy. Knowledge on clinical efficacy of whey protein supplementation (WPS) as an option to treat malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients is limited.

    METHODS: This multicenter, parallel, open-label, randomized controlled trial investigated the clinical efficacy of WPS in 126 malnourished CAPD patients with serum albumin <40 g/L and body mass index (BMI) <24 kg/m2. Patients randomized to the intervention group (IG, n = 65) received protein powder (27.4 g) for 6 months plus dietary counseling (DC) while the control group (CG, n = 61) received DC only. Anthropometry, biochemistry, malnutrition-inflammation-score (MIS), dietary intake inclusive of dialysate calories, handgrip strength (HGS) and quality of life (QOL) were assessed at baseline and 6 months. Clinical outcomes were assessed by effect size (Cohen's d) comparisons within and between groups.

    RESULTS: Seventy-four patients (n = 37 per group) completed the study. Significantly more IG patients (59.5%) achieved dietary protein intake (DPI) adequacy of 1.2 g/kg per ideal body weight (p  0.05). A higher DPI paralleled significant increases in serum urea (mean Δ: IG = +2.39 ± 4.36 mmol/L, p = 0.002, d = 0.57 vs CG = -0.39 ± 4.59 mmol/L, p > 0.05, d = 0.07) and normalized protein catabolic rate, nPCR (mean Δ: IG = +0.11 ± 0.14 g/kg/day, p  0.05, d = 0.09) for IG compared to CG patients. Although not significant, comparison for changes in post-dialysis weight (mean Δ: +0.64 ± 1.16 kg vs +0.02 ± 1.36 kg, p = 0.076, d = 0.58) and mid-arm circumference (mean Δ: +0.29 ± 0.93 cm vs -0.12 ± 0.71 cm, p = 0.079, d = 0.24) indicated trends favoring IG vs CG. Other parameters remained unaffected by treatment comparisons. CG patients had a significant decline in QOL physical component (mean Δ = -6.62 ± 16.63, p = 0.020, d = 0.47). Using changes in nPCR level as a marker of WPS intake within IG, 'positive responders' achieved significant improvement in weight, BMI, skinfold measures and serum urea (all p  0.05).

    CONCLUSION: A single macronutrient approach with WPS in malnourished CAPD patients was shown to achieve DPI adequacy and improvements in weight, BMI, skin fold measures, serum urea and nPCR level. CLINICAL TRIAL REGISTRY: www.clinicaltrials.gov (NCT03367000).

  12. Sahathevan S, Se CH, Ng SH, Chinna K, Harvinder GS, Chee WS, et al.
    BMC Nephrol, 2015;16:99.
    PMID: 26149396 DOI: 10.1186/s12882-015-0073-x
    Poor appetite could be indicative of protein energy wasting (PEW) and experts recommend assessing appetite in dialysis patients. Our study aims to determine the relationship between PEW and appetite in haemodialysis (HD) patients.
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