Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals.
Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported.
Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.
MATERIALS AND METHODS: A total of 140 patients who had compatible ABO blood type with negative T-cell lymphocytotoxicity crossmatch were included in the study and 25% of them were spousal transplant donors. No remarkable differences in acute rejection rate, graft survival, patient survival and serum creatinine level were observed between the spousal and living-related donor groups.
RESULTS: The spousal donor group had a higher degree of HLA mismatch than the living-related donor group. HLA-A mismatch was associated with increased rejection risk at 6 months (odds ratio [OR], 2.75; P = 0.04), 1 year (OR, 2.54; P = 0.03) and 3 years (OR, 3.69; P = 0.001). It was also observed in the deleterious effects of HLA-B and HLA-DQ loci when the number of antigen mismatches increased. The risk was 7 times higher in patients with ≥1 mismatch at HLA-A, HLA-B and HLA-DR loci than those who did not have a mismatch at these loci at 6 months (P = 0.01), 1 year (P = 0.03) and 3 years (P = 0.003).
CONCLUSION: A good match for HLA-A, HLA-B, HLA-DR and HLA-DQ can prevent acute rejection risk in renal transplant patients. Consequently, spousal donor transplants could be a safe intervention in renal patients.
METHODS: PACKNOW was an open-label, randomized, controlled trial of acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen in Malaysian patients aged ≥5 years with knowlesi malaria of any severity. The primary end point was change in creatinine at 72 hours. Secondary end points included longitudinal changes in creatinine in patients with severe malaria or acute kidney injury (AKI), stratified by hemolysis.
RESULTS: During 2016-2018, 396 patients (aged 12-96 years) were randomized to acetaminophen (n = 199) or no acetaminophen (n = 197). Overall, creatinine fell by a mean (standard deviation) 14.9% (18.1) in the acetaminophen arm vs 14.6% (16.0) in the control arm (P = .81). In severe disease, creatinine fell by 31.0% (26.5) in the acetaminophen arm vs 20.4% (21.5) in the control arm (P = .12), and in those with hemolysis by 35.8% (26.7) and 19% (16.6), respectively (P = .07). No difference was seen overall in patients with AKI; however, in those with AKI and hemolysis, creatinine fell by 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .041). Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .041) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .027 and P = .002, respectively).
CONCLUSIONS: Acetaminophen did not improve creatinine among the entire cohort but may improve renal function in patients with severe knowlesi malaria and in those with AKI and hemolysis.
CLINICAL TRIALS REGISTRATION: NCT03056391.
METHODOLOGY: Eight (8) urine and serum samples each obtained from consenting healthy controls (HC), twenty-five (25) urine and serum samples each from first episode treatment naïve MDD (TNMDD) patients, and twenty (22) urine and serum samples each s from treatment naïve MDD patients 2 weeks after SSRI treatment (TWMDD) were analysed for metabolites using proton nuclear magnetic resonance (1HNMR) spectroscopy. The evaluation of patients' samples was carried out using Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Square- Discriminant Analysis (OPLSDA) models.
RESULTS: In the serum, decreased levels of lactate, glucose, glutamine, creatinine, acetate, valine, alanine, and fatty acid and an increased level of acetone and choline in TNMDD or TWMDD irrespective of whether an OPLSDA or PLSDA evaluation was used were identified. A test for statistical validations of these models was successful.
CONCLUSION: Only some changes in serum metabolite levels between HC and TNMDD identified in this study have potential values in the diagnosis of MDD. These changes included decreased levels of lactate, glutamine, creatinine, valine, alanine, and fatty acid, as well as an increased level of acetone and choline in TNMDD. The diagnostic value of these changes in metabolites was maintained in samples from TWMDD patients, thus reaffirming the diagnostic nature of these metabolites for MDD.
METHODS: Between 2010 and 2020, 79 of the 3180 KT recipients followed at Hamed Al-Essa organ transplant center received low-osmolality iodine-based contrast for radiological assessment for various indications. Preventive measures including holding metformin, intravenous hydration, sodium bicarbonate and N-acetylcysteine were given before contrast administration. CIN was defined as an increase in serum creatinine of 25% from the baseline within 72 hours.
RESULTS: The enrolled patients were divided into two groups: those who developed CIN (n = 7) and those with no increase in serum creatinine level (n = 72). The mean age of the patients was 52.1 ± 12.3 years; 44 of them were males, and the cause of end-stage kidney disease was mostly diabetic nephropathy. The pre-transplant demographics were comparable between the two groups. Fortyseven cases received contrast for coronary angiography, and 32 received it for a CT scan. The graft function deteriorated in group 1, but no significant difference was found between the two groups at the end of the study.
CONCLUSION: CIN is not uncommon in KT recipients receiving CM, especially with ischemic heart disease. Risk stratification, optimizing hemodynamics, and avoiding potential nephrotoxins are essential before performing CM-enhanced studies in KT recipients. DOI: 10.52547/ijkd.7165.
METHODS: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution.
RESULTS: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin).
CONCLUSIONS: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.
METHODOLOGY: A single-center cohort study was performed at Indus Hospital and Health Network, Karachi, Pakistan, between April 1, 2021, and October 31, 2021. This study included 333 hospitalized hypertensive COVID-19 patients and evaluated their clinical characteristics and survival outcomes. A multivariate logistic regression model was applied in IBM SPSS 27.0 to determine the predictors of mortality.
RESULTS: The majority of patients were females (54.7%), the median age was 62 [55-70] years, with co-existing diabetes (56.5%) and severely ill (52.6%). The independent predictors of mortality identified were age ≥ 65 years (aOR 20.89, 95% CI, 5.81-75.15; p < 0.001), pulse rate (aOR 1.03, 95% CI 1.01-1.63; p = 0.006), serum creatinine (aOR 1.34, 95% CI 1.11-1.63; p = 0.002), use of antibiotics (aOR 3.40, 95% CI 1.29-8.98; p = 0.014)), corticosteroid (aOR 49.68, 95% CI 1.83-1350.31; p = 0.020), and who needed high flow oxygen supply (aOR 13.08, 95% CI 1.70-100.54; p < 0.001), non-invasive mechanical ventilation (aOR 229.01, 95% CI 29.30-1789.71; p < 0.001) and invasive mechanical ventilation (aOR 379.54, 95% CI 36.60-3935.87; p < 0.001).
CONCLUSIONS: Our study suggests that older age, elevated pulse rate, serum creatinine, use of antibiotics and corticosteroids, and the need for mechanical ventilation predict mortality among hypertensive COVID-19.
Objective: To investigate the nephroprotective effect of quercetin (QT) against renal injury induced by titanium dioxide nanoparticles (NTiO2) in rats.
Methods: NTiO2-intoxicated rats received 50 mg/kg of NTiO2 for seven days. The QT + NTiO2 group was pretreated with QT for seven days before being administered NTiO2. Uric acid, creatinine, and blood urea nitrogen were considered to be biomarkers of nephrotoxicity. Catalase (CAT) and superoxide dismutase (SOD) activities and renal levels of malondialdehyde (MDA) were measured to assess the oxidative stress caused by NTiO2.
Results: NTiO2 significantly increased the plasma level of the biomarkers. It also significantly decreased the activities of CAT (P = 0.008) and SOD (P = 0.004), and significantly increased the MDA levels (P = 0.007). NTiO2 caused proximal tubule damage, the accumulation of red blood cells, the infiltration of inflammatory cells, and reduced the glomerular diameters, as well as induced apoptosis in the proximal tubules. Pre-treatment with QT attenuated the histological changes, normalised the plasma biomarkers, suppressed oxidative stress, ameliorated the activities of CAT (P = 0.007) and SOD (P = 0.006), and reduced apoptosis (P < 0.001).
Conclusion: QT was found to have a potent protective effect against nephrotoxicity induced by NTiO2 in rats. It also reduced apoptosis caused by NTiO2.
MATERIALS AND METHODS: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and 500 μg/day) groups of six animals each, and another group (n=6) treated with TAM 100 μg/day at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice.
RESULTS: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups.
CONCLUSIONS: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.