METHODS: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil) or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day). Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN) and creatinine activities were measured.
RESULTS: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine.
CONCLUSION: RESULTS from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.
Materials and Methods: This retrospective cohort study extracted de-identified data from the Malaysian Registry of Intensive Care in four Malaysian tertiary ICUs between January 2010 and December 2014. The study was registered under the NMRR and approved by the ethics committee. AKI was defined as twice the baseline creatinine or urine output <0.5 ml/kg/h for 12 h.
Results: Of 26,663 patients, 24.2% had AKI within 24 h of admission. Patients with AKI were older and had higher severity of illness compared to those without AKI. AKI patients had a longer duration of mechanical ventilation, length of ICU, and hospital stay. Age, Simplified Acute Physiological II Score, and the presence of sepsis and preexisting hypertension, chronic cardiovascular disease independently associated with AKI. About 32.3% had sepsis. Patients with both AKI and sepsis had the highest risk of mortality (relative risk 3.43 [3.34-3.53]).
Conclusions: AKI is common in our ICU, with higher morbidity and mortality. Independent risk factors of AKI include age, the severity of illness, sepsis and preexisting hypertension, and chronic cardiovascular disease. AKI independently contributes to mortality. The presence of AKI and sepsis increased the risk of mortality by three times.
Methods: We evaluated commonly used surrogate and imputed baseline creatinine values against a "reference" creatinine measured during follow-up in an adult clinical trial cohort. Known AKI incidence (Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was compared with AKI incidence classified by (1) back-calculation using the Modification of Diet in Renal Disease (MDRD) equation with and without a Chinese ethnicity correction coefficient; (2) back-calculation using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation; (3) assigning glomerular filtration rate (GFR) from age and sex-standardized reference tables; and (4) lowest measured creatinine during admission. Back-calculated distributions were performed using GFRs of 75 and 100 ml/min.
Results: All equations using an assumed GFR of 75 ml/min underestimated AKI incidence by more than 50%. Back-calculation with CKD-EPI and GFR of 100 ml/min most accurately predicted AKI but misclassified all AKI stages and had low levels of agreement with true AKI diagnoses. Back-calculation using MDRD and assumed GFR of 100 ml/min, age and sex-reference GFR values adjusted for good health, and lowest creatinine during admission performed similarly, best predicting AKI incidence (area under the receiver operating characteristic curves [AUC ROCs] of 0.85, 0.87, and 0.85, respectively). MDRD back-calculation using a cohort mean GFR showed low total error (22%) and an AUC ROC of 0.85.
Conclusion: Current methods for estimating baseline creatinine are large sources of potential error in acute infection studies. Preferred alternatives include MDRD equation back-calculation with a population mean GFR, age- and sex-specific GFR values corrected for "good health," or lowest measured creatinine. Studies using surrogate baseline creatinine values should report specific methodology.
MATERIALS AND METHODS: An e-mail invitation to participate in an online survey was sent to hospital laboratories in Malaysia (n=140). Questions regarding methods for measuring creatinine, equations for calculating eGFR, eGFR reporting, the terminology used in reporting urine albumin, types of samples and the cut-off values used for normal albuminuria.
RESULTS: A total of 42/140 (30%) laboratories answered the questionnaire. The prevalent method used for serum creatinine measurement was the Jaffé method (88.1%) traceable to isotope-dilution mass spectrometry. eGFR was reported along with serum creatinine by 61.9% of laboratories while 33.3% of laboratories report eGFR on request. The formula used for eGFR reporting was mainly MDRD (64.3%) and results were reported as exact numbers even when the eGFR was <60 ml/min/1.73m2. The term microalbumin is still used by 83.3% of laboratories. There is a large heterogeneity among the labs regarding the type of sample recommended for measuring urine albumin, reference interval and reporting units.
CONCLUSION: It is evident that the laboratory assessment of chronic kidney disease in Malaysia is not standardised. It is essential to provide a national framework for standardised reporting of eGFR and urine albumin. Recommendations developed by the MACB CKD Task Force, if adopted by all laboratories, will lead to a reduction in this variability.
METHODS: A population-based study was conducted on a total of 890 respondents who were representative of the adult population in Malaysia, i.e., aged ≥18 years old. Respondents were randomly selected using a stratified cluster method. The estimated glomerular filtration rate (eGFR) was estimated from calibrated serum creatinine using the CKD-EPI equation. CKD was defined as eGFR
METHODS: A state-wide cross-sectional study was conducted. There were 336 native renal biopsies in 296 eligible patients from 1st January 2013 to 30th June 2016. All patients aged ≥12 years with sufficient sampling (≥8 glomeruli) for histopathological assessment were included. Graft kidney biopsies, protocol-based biopsies and patients with uncertain demographics were excluded. Demographics of patients, clinical data, laboratory parameters prior to biopsy, and histology findings of renal biopsies were collected from local unit database and recorded into a standardised data collection form. Descriptive statistical analyses were employed and factors associated with Lupus nephritis (LN) were explored using logistic regression.
RESULTS: The mean age during biopsy was 34.53 years (Standard Deviation 0.759). Primary glomerulonephritis (PGN) accounted for 42.6% (126) of all native renal biopsies. The commonest cause of PGN was minimal change disease (38.9%, 49) followed by focal segmental glomerulosclerosis (33.3%, 42) and IgA nephropathy (14.3%, 18). LN is the leading cause for secondary glomerulonephritis (SGN) (87.2%, 136). Younger age (Odds Ratio, OR 0.978; 95% Confidence Interval, 95%CI 0.960, 0.996); female gender (OR 17.53; p<0.001); significant proteinuria (OR 132.0; p<0.001); creatinine level at biopsy (OR 11.26; p=0.004); positive antinuclear antibody (ANA) (OR 46.7; p<0.001); and ANA patterns (OR 8.038; p=0.018) were significant in predicting the odds of having LN.
CONCLUSION: This is the first epidemiology study of glomerular diseases in Sabah. The predominance of LN suggests lower threshold for renal biopsy in patients with suspected glomerular disorders. We have identified significant predictors for early detection and treatment of LN.
Aim: To evaluate the nephroprotective activity of CAE and its fractions in cisplatin-induced nephrotoxicity and to assess whether they compromise the anticancer efficacy of cisplatin.
Materials and methods: Cisplatin-induced renal damage was induced in Ehrlich Ascites Carcinoma (EAC) bearing mice during mild phase of tumor growth. CAE and its butanol (BF) and aqueous (AF) fractions were administered orally from the 5th day for five days. Nephroprotective potential (serum urea, creatinine, renal histology) and effect of VC on cisplatin anticancer efficacy (tumor volume, viable tumor cells, percentage increase in life span (% ILS)) were calculated.
Result: CAE and its fractions significantly reversed the cisplatin-induced renal damage. CAE and BF treated animals showed regeneration of 50%-75% of proximal tubular cells. Compared to EAC control mice, the % ILS of the cisplatin-treated group was 244% and it was further extended to 379% after CAE administration. The % ILS in the CAE treated group was 1.6 times higher than the cisplatin alone treated group. GC-MS study showed the presence of astaxanthin and betulin.
Conclusion: CAE of VC reverses cisplatin-induced kidney damage as well as regenerates proximal tubular epithelial cells, without compromising the anticancer effect of cisplatin. When CAE was further fractionated, the nephroprotective activity was retained, but the beneficial anticancer effect of cisplatin was compromised.
Methods: In this cross-sectional study with retrospective record review, 403 established gouty arthritis patients were recruited to determine the incidence of UGIB and associated factors among gout patients who were on regular nonsteroidal anti-inflammatory drugs (NSAIDs).
Results: The mean age of the 403 gouty arthritis patients was 55.7 years old and the majority (n = 359/403; 89.1%) were male. The incidence of UGIB among gouty arthritis patients who were on NSAIDs was 7.2% (n = 29/403). Older age (p < 0.001), diclofenac medication (p = 0.003), pantoprazole medication (p = 0.003), end-stage renal failure (ESRF) (p = 0.007), smoking (p = 0.035), hypertension (p = 0.042) and creatinine (p = 0.045) were significant risk factors for UGIB among the gouty arthritis patients in univariable analysis. Older age (p = 0.001) and diclofenac medication (p < 0.001) remained significant risk factors for UGIB among the gouty arthritis patients in multivariable analysis.
Conclusions: Age and diclofenac were significantly associated with UGIB among patients with gouty arthritis on regular NSAIDs, indicating that these factors increased the risks of developing UGIB in gout patients. Hence, these high-risk groups of gouty arthritis patients should be routinely monitored to avoid the potential onset of UGIB. Our data also suggest that diclofenac should be prescribed for the shortest duration possible to minimize the risk of developing UGIB in gout patients.