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Fulltext Antineutrophil Cytoplasmic Autoantibody-Negative Pauci-Immune Crescentic Glomerulonephritis in a Patient with Systemic Lupus Erythematosus

Chan CE, Ng TJ, Ahmad MK, Mohamad Nor FS

Case Rep Nephrol Dial, 2022;12(3):201-206.
PMID: 36465575 DOI: 10.1159/000527248

Renal involvement in systemic lupus erythematosus is usually exhibited as lupus nephritis, which is a form of immune complex-mediated glomerulonephritis and one of the most severe organ manifestations of systemic lupus erythematosus. The pathogenesis involved glomerular immune complex deposition, which leads to glomerular inflammation and typically shows a "full-house" pattern on immunofluorescence microscopy. Other forms of glomerulonephritis are rarely observed in patients with systemic lupus erythematosus. Pauci-immune crescentic glomerulonephritis is the pattern of injury most commonly observed in patients with antineutrophil cytoplasmic autoantibody-associated glomerulonephritis. The characteristic histological feature of pauci-immune crescentic glomerulonephritis is focal necrotizing and crescentic glomerulonephritis with little or no glomerular staining for immunoglobulin by immunofluorescence microscopy. We report a rare case of antineutrophil cytoplasmic autoantibody-negative pauci-immune crescentic glomerulonephritis in a patient with systemic lupus erythematosus.
A national survey of renal replacement therapy prescribing practice for acute kidney injury in Malaysian intensive care units

Jamal JA, Mat-Nor MB, Mohamad-Nor FS, Udy AA, Lipman J, Roberts JA

Nephrology (Carlton), 2014 Aug;19(8):507-12.
PMID: 24802363 DOI: 10.1111/nep.12276

To describe renal replacement therapy (RRT) prescribing practices in Malaysian intensive care units (ICU), and compare this with previously published data from other regions.
Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: A randomised controlled trial of continuous infusion versus intermittent bolus administration

Jamal JA, Roberts DM, Udy AA, Mat-Nor MB, Mohamad-Nor FS, Wallis SC, et al.

Int J Antimicrob Agents, 2015 Jul;46(1):39-44.
PMID: 25881872 DOI: 10.1016/j.ijantimicag.2015.02.014

Here we describe the pharmacokinetics of piperacillin administered by continuous infusion (CI) versus intermittent bolus (IB) dosing in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and compare the frequency of pharmacodynamic/pharmacokinetic (PK/PD) target attainment with each dosing strategy. This was a prospective pharmacokinetic trial in 16 critically ill patients with severe sepsis or septic shock undergoing CVVH and randomised to receive either CI or IB administration of a standard daily dose of piperacillin/tazobactam (11.25g/day on Day 1 followed by 9g/day). Serial blood samples were measured on two occasions. Piperacillin pharmacokinetics were calculated using a non-compartmental approach. Blood concentrations were compared with established PK/PD targets. On occasion 1 (Days 1-3 of therapy), IB administration resulted in significantly higher piperacillin peak concentrations (169 vs. 89mg/L; P=0.002), whereas significantly higher steady-state concentrations were observed in CI patients (83 vs. 57mg/L; P=0.04). Total clearance and clearance not mediated by CVVH were significantly higher with CI administration [median (interquartile range), 1.0 (0.7-1.1) and 0.8 (0.6-1.0)mL/kg/min; P=0.001 and 0.001, respectively]. The estimated unbound piperacillin concentrations were four times above the target susceptibility breakpoint (16mg/L) for the entire dosing interval (100%fT>4xMIC) in 87.5% of patients receiving CI administration (sampling occasion 1), compared with 62.5% of IB patients achieving the desired target (50%fT>4xMIC). Compared with IB dosing, and despite similar CVVH settings, CI administration of piperacillin results in a pharmacokinetic profile that may optimise outcomes for less susceptible pathogens.
Pharmacokinetics of meropenem in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration

Jamal JA, Mat-Nor MB, Mohamad-Nor FS, Udy AA, Wallis SC, Lipman J, et al.

Int J Antimicrob Agents, 2015 Jan;45(1):41-5.
PMID: 25455853 DOI: 10.1016/j.ijantimicag.2014.09.009

The objective of this study was to describe the pharmacokinetics of meropenem, administered by continuous infusion (CI) or intermittent bolus (IB), in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and to evaluate the frequency of pharmacokinetic/pharmacodynamic target attainment with each dosing strategy. This was a prospective, randomised controlled trial in critically ill patients receiving CVVH and administered meropenem by CI or IB. Serial meropenem concentrations in plasma and ultrafiltrate were measured after administration of a standard total daily dose (4 g/day on Day 1, followed by 3g/day thereafter) on two occasions during antibiotic therapy. Meropenem pharmacokinetic parameters were calculated using a non-compartmental approach. Sixteen critically ill patients receiving CVVH concurrently treated with meropenem were randomised to CI (n = 8) or IB dosing (n = 8). IB administration resulted in higher maximum concentrations (C(max)) [64.7 (58.9-80.3) and 64.8 (48.5-81.8) mg/L, respectively] on both sampling occasions compared with CI (P < 0.01 and P = 0.04, respectively). CI resulted in a higher meropenem steady-state concentration (Css) on occasion 1 [26.0 (24.5-41.6) mg/L] compared with the minimum concentration (C(min)) observed for IB patients [17.0 (15.7-19.8)mg/L; P < 0.01]. CVVH contributed to ca. 50% of meropenem total clearance in these patients. The administered meropenem doses resulted in plasma drug concentrations that were >4× the targeted susceptibility breakpoint (2mg/L) for 100% of the dosing interval, for both groups, on both occasions. CI could be an alternative to IB for meropenem administration in critically ill patients receiving CVVH.
Fulltext Cost utility analysis of end stage renal disease treatment in Ministry of Health dialysis centres, Malaysia: Hemodialysis versus continuous ambulatory peritoneal dialysis

Surendra NK, Abdul Manaf MR, Hooi LS, Bavanandan S, Mohamad Nor FS, Firdaus Khan SS, et al.

PLoS One, 2019;14(10):e0218422.
PMID: 31644577 DOI: 10.1371/journal.pone.0218422

OBJECTIVES: In Malaysia, there is exponential growth of patients on dialysis. Dialysis treatment consumes a considerable portion of healthcare expenditure. Comparative assessment of their cost effectiveness can assist in providing a rational basis for preference of dialysis modalities.
METHODS: A cost utility study of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) was conducted from a Ministry of Health (MOH) perspective. A Markov model was also developed to investigate the cost effectiveness of increasing uptake of incident CAPD to 55% and 60% versus current practice of 40% CAPD in a five-year temporal horizon. A scenario with 30% CAPD was also measured. The costs and utilities were sourced from published data which were collected as part of this study. The transitional probabilities and survival estimates were obtained from the Malaysia Dialysis and Transplant Registry (MDTR). The outcome measures were cost per life year (LY), cost per quality adjusted LY (QALY) and incremental cost effectiveness ratio (ICER) for the Markov model. Sensitivity analyses were performed.
RESULTS: LYs saved for HD was 4.15 years and 3.70 years for CAPD. QALYs saved for HD was 3.544 years and 3.348 for CAPD. Cost per LY saved was RM39,791 for HD and RM37,576 for CAPD. The cost per QALY gained was RM46,595 for HD and RM41,527 for CAPD. The Markov model showed commencement of CAPD in 50% of ESRD patients as initial dialysis modality was very cost-effective versus current practice of 40% within MOH. Reduction in CAPD use was associated with higher costs and a small devaluation in QALYs.
CONCLUSIONS: These findings suggest provision of both modalities is fiscally feasible; increasing CAPD as initial dialysis modality would be more cost-effective.
Fulltext Health related quality of life of dialysis patients in Malaysia: Haemodialysis versus continuous ambulatory peritoneal dialysis

Surendra NK, Abdul Manaf MR, Hooi LS, Bavanandan S, Mohamad Nor FS, Shah Firdaus Khan S, et al.

BMC Nephrol, 2019 04 30;20(1):151.
PMID: 31039745 DOI: 10.1186/s12882-019-1326-x

BACKGROUND: Health related quality of life (HRQOL) is an important predictor of clinical outcomes for End Stage Renal Disease (ESRD) patients and to establish quality adjusted life years (QALYs) for economic evaluation studies. This study aims to measure the health utilities and to identify socio-demographic and clinical factors associated with HRQOL for haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) in Malaysia.
METHODS: A total of 141 patients (77 HD and 64 CAPD) from 1 federal and four state hospitals participated in this cross-sectional study. Patients were randomly selected from the National Renal Registry (NRR) using a stratified random sampling. The EQ-5D-3 L questionnaire was used to measure HRQOL. Variables investigated include dialysis modalities, sociodemographic characteristics, co-morbidities and biochemical markers. Utilities are measured on an ordinal scale of 0-1, where 1 indicates full health and 0 indicates death.
RESULTS: The mean utility scores were 0.854 ± 0.181 and 0.905 ± 0.124 (p > 0.05) and the mean Visual Analogue Scale (VAS) scores were 76.2 ± 12.90 and 77.1 ± 10.26 (p > 0.05) for HD and CAPD patients respectively. There was a significant difference in problems reported between HD (35.1%) and CAPD (15.6%) on usual activities dimension (p = 0.009). The proportion of patients having problems in the pain/discomfort domain in both modalities was high (34.0%). Haemoglobin (
Calcific Uremic Arteriolopathy (CUA) Among Malaysian Dialysis Patients: Clinical Characteristics, Treatment, and Outcomes

Lee YW, Tan MH, Bavanandan S, Bee BC, Lim CTS, Mohd R, et al.

Cureus, 2024 Nov;16(11):e73711.
PMID: 39677159 DOI: 10.7759/cureus.73711

Background Calcific uremic arteriolopathy (CUA) is a rare but debilitating disease affecting patients with kidney disease. Reported risk factors of CUA in the literature include female sex, obesity, diabetes mellitus, and vitamin K antagonists' (VKAs) usage. CUA prevalence in Malaysia is unknown and has not been reported before. Methods A multicenter observational study was conducted in 13 centers all over Malaysia to study the clinical characteristics, treatment, and outcomes of CUA. The data of patients confirmed with CUA between January 1, 2016, and December 31, 2021, was collected from medical records by each center's nephrologists. Results Out of 33 confirmed CUA cases, 69.7% were females, and 66.7% were Malay with a mean age of 47.33 ± 13.80 years old. The mean BMI was 25.66 ± 9.77 kg/m2, and 18.2% were classified as obese (BMI > 30). Two-thirds of the patients were on hemodialysis (HD), and the mean dialysis vintage was 6.2 ± 4.11 years. A majority (87.9%) have hypertension, 33.3% are diabetic, and 27.3% have coronary artery disease. Only 15.2% of the patients were on warfarin at the time of diagnosis. A total of 78.8% of patients were taking calcium-based phosphate binders during diagnosis. Investigation results showed calcium, 2.44 ± 0.29 mmol/L; phosphate, 2.18 ± 0.67 mmol/L; CaXPO4 = 5.41 ± 1.90; and parathyroid hormone, 181.14 ± 153.23 pmol/L. About half (54.5%) had skin biopsy confirmation done. Distribution of lesions was 57.6% peripheral and 30.3% central. For treatment of CUA, there were 57.6% usage of non-calcium-based phosphate binders, 48.5% cinacalcet, 30.3% sodium thiosulphate, and 33.3% had parathyroidectomy. Half (54.5%) of our CUA patients died within three months from diagnosis. The mean time from diagnosis to mortality was 4.12 ± 5.59 months. A majority (45.5%) died from septicemia caused by infections. Interestingly, there were a few rare presentations of CUA such as pulmonary calciphylaxis, heart and lung calcifications, liver and spleen calcifications, and genital lesions. One patient had resistant CUA and was given a trial of lipid apheresis for 10 sessions. Conclusion This is the first and largest multicenter study looking into the characteristics, treatment, and outcome of CUA in Malaysia. Majority of patients in Malaysia undergo HD as kidney replacement therapy; hence, our results correlate with this. The incidence of CUA was estimated to be 6.6 per 10,000 dialysis patients in this study and the mortality rate is very high. This is consistent with worldwide data which reported mortality as high as 60%.