Displaying publications 221 - 240 of 1036 in total

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  1. Hiong LC, Voon KL, Abdullah NA, Sattar MA, Rahman NA, Khan AH, et al.
    Acta Pharmacol Sin, 2008 Apr;29(4):451-7.
    PMID: 18358091 DOI: 10.1111/j.1745-7254.2008.00772.x
    The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-beta1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF).
    Matched MeSH terms: Kidney/blood supply; Kidney/drug effects; Kidney/metabolism*; Kidney/pathology; Kidney Failure, Chronic/chemically induced; Kidney Failure, Chronic/physiopathology*
  2. Mallhi TH, Khan YH, Adnan AS
    Am J Trop Med Hyg, 2020 Dec;103(6):2164-2167.
    PMID: 33124548 DOI: 10.4269/ajtmh.20-0794
    Despite myriad improvements in the care of COVID-19 patients, atypical manifestations are least appreciated during the current pandemic. Because COVID-19 is primarily manifesting as an acute respiratory illness with interstitial and alveolar pneumonia, the possibility of viral invasions into the other organs cannot be disregarded. Acute kidney injury (AKI) has been associated with various viral infections including dengue, chikungunya, Zika, and HIV. The prevalence and risks of AKI during the course of COVID-19 have been described in few studies. However, the existing literature demonstrate great disparity across findings amid variations in methodology and population. This article underscores the propensity of AKI among COVID-19 patients, limitations of the exiting evidence, and importance of timely identification during the case management. The prevalence of AKI is variable across the studies ranging from 4.7% to 81%. Evidence suggest old age, comorbidities, ventilator support, use of vasopressors, black race, severe infection, and elevated levels of baseline serum creatinine and d-dimers are independent risk factors of COVID-19 associated with AKI. COVID-19 patients with AKI also showed unsatisfactory renal recovery and higher mortality rate as compared with patients without AKI. These findings underscore that AKI frequently occurs during the course of COVID-19 infection and requires early stratification and management.
    Matched MeSH terms: Kidney/pathology; Kidney/virology; Acute Kidney Injury/diagnosis; Acute Kidney Injury/epidemiology*; Acute Kidney Injury/pathology; Acute Kidney Injury/virology
  3. Ramly F, Mohamad NAN, Zahid AZM, Kasim NM, Teh KY
    Case Rep Womens Health, 2021 Jan;29:e00275.
    PMID: 33304832 DOI: 10.1016/j.crwh.2020.e00275
    Adult giant hydronephrosis in a normally sited kidney is unusual during pregnancy. The most frequent cause is congenital obstruction at the ureteropelvic junction. Ultrasound accompanied by magnetic resonance imaging (MRI) are valuable in reaching the diagnosis, especially when clinical assessment of an abdominal mass is inconclusive regarding aetiology. We report a case of giant hydronephrosis in a woman who presented at 23 weeks of gestation with abdominal distension. She was managed conservatively. Unfortunately, the pregnancy was complicated by severe pre-eclampsia at 32 weeks of gestation, necessitating delivery via emergency caesarean section. She had a smooth postpartum recovery, and subsequently standard imaging was performed before nephrectomy. The literature and previously reported cases of giant hydronephrosis in pregnancy are reviewed.
    Matched MeSH terms: Kidney; Kidney Pelvis
  4. Khai YT, Teck MT
    Med J Malaysia, 2020 05;75(3):240-245.
    PMID: 32467539
    INTRODUCTION: Laparoscopic nephrectomy is the standard of care for the removal of both non-functioning and tumourbearing kidneys. This study was conducted to compare the characteristics and outcomes follow-ing laparoscopic transperitoneal nephrectomy (TP) for tumour and nontumour disease.

    METHODS: We retro-spectively reviewed all TP nephrectomies performed in the Hospital Sultanah Bahiyah Alor Setar, Kedah between January 2016 and July 2017.

    RESULTS: A total of 36 eligible cases were identified, 10 of which were for renal tumours and the others for nonfunctioning kidneys. There were no statistically significant differ-ences between the two groups in terms of demographics and comorbidities. We also did not identify any sta-tistically significant differences between the two groups in terms of operating time, blood loss, need for transfusion, septic complications and postoperative recovery. The only significant difference between the groups was the postoperative rise in serum creatinine, which was higher in the tumour disease group (mean rise 23.4 vs 5.35µmol/l; p = 0.012).

    CONCLUSIONS: Our study showed that laparoscopic nephrectomy is both feasible and safe for the treatment of tumour and non-tumour renal disease with low complication rates in both groups.

    Matched MeSH terms: Kidney Neoplasms/surgery*
  5. Tang ASO, Wong QY, Pao Lin Ting I, Selvesten P, Yeo ST, Chew LP, et al.
    Am J Case Rep, 2021 Aug 06;22:e932923.
    PMID: 34354036 DOI: 10.12659/AJCR.932923
    BACKGROUND No cases of Fabry disease (FD) have been reported thus far in Malaysia. We aimed to report the demographic characteristics, clinical manifestations, molecular results, and treatment outcomes of 2 FD cases. This study was a retrospective review of 2 family clusters of FD on follow-up in Sarawak, Malaysia. CASE REPORT Two index patients were confirmed to have FD. Index patient 1, who had nephrotic-range proteinuria and cornea verticillata, carried a variant within exon 4 of the GLA gene: c.610 T>C (p.Trp204Arg). Agalsidase beta (Fabrazyme®) enzyme replacement therapy was initiated, with the absence of neutralizing antibody after 24 months. No hypersensitivity or adverse reactions were reported. The patient's proteinuria and renal function remained stable. Other family members who carried the same mutation were asymptomatic. Index patient 2, who had residual activity of alpha-galactosidase A and a normal globotriaosylsphingosine level, carried a novel GLA mutation of c.548-5T>A. He was diagnosed with end-stage renal disease on regular dialysis and had nonspecific headache with 1 episode of seizure a few years prior to FD genetic screening. One brother had chronic neuropathic pain but refused further investigations. Other family members who had the same mutation were asymptomatic. This mutation has never been reported in literature, and its pathogenicity warrants further studies. CONCLUSIONS It is of utmost importance to increase awareness of FD among clinicians, so that appropriate screening may be done to determine its true prevalence and prompt treatment can be initiated early.
    Matched MeSH terms: Kidney Failure, Chronic*
  6. Tan CH, Tan NH, Sim SM, Fung SY, Jayalakshmi P, Gnanathasan CA
    Toxicon, 2012 Dec 1;60(7):1259-62.
    PMID: 22975088 DOI: 10.1016/j.toxicon.2012.08.012
    Mice experimentally envenomed with Hypnale hypnale venom (1× and 1.5×LD₅₀) developed acute kidney injury (AKI) principally characterized by raised blood urea and creatinine. Prolonged blood clotting time and hemorrhage in lungs implied bleeding tendency. Pallor noted in most renal cortices was suggestive of renal ischemia secondary to consumptive coagulopathy. Intravenous infusion of Hemato polyvalent antivenom following experimental envenoming effectively prevented death and AKI in all mice, supporting its potential therapeutic use in envenoming cases.
    Matched MeSH terms: Acute Kidney Injury/prevention & control*
  7. Kirubakaran R, Stocker SL, Hennig S, Day RO, Carland JE
    Clin Pharmacokinet, 2020 11;59(11):1357-1392.
    PMID: 32783100 DOI: 10.1007/s40262-020-00922-x
    BACKGROUND AND OBJECTIVES: Numerous population pharmacokinetic (PK) models of tacrolimus in adult transplant recipients have been published to characterize tacrolimus PK and facilitate dose individualization. This study aimed to (1) investigate clinical determinants influencing tacrolimus PK, and (2) identify areas requiring additional research to facilitate the use of population PK models to guide tacrolimus dosing decisions.

    METHODS: The MEDLINE and EMBASE databases, as well as the reference lists of all articles, were searched to identify population PK models of tacrolimus developed from adult transplant recipients published from the inception of the databases to 29 February 2020.

    RESULTS: Of the 69 studies identified, 55% were developed from kidney transplant recipients and 30% from liver transplant recipients. Most studies (91%) investigated the oral immediate-release formulation of tacrolimus. Few studies (17%) explained the effect of drug-drug interactions on tacrolimus PK. Only 35% of the studies performed an external evaluation to assess the generalizability of the models. Studies related variability in tacrolimus whole blood clearance among transplant recipients to either cytochrome P450 (CYP) 3A5 genotype (41%), days post-transplant (30%), or hematocrit (29%). Variability in the central volume of distribution was mainly explained by body weight (20% of studies).

    CONCLUSION: The effect of clinically significant drug-drug interactions and different formulations and brands of tacrolimus should be considered for any future tacrolimus population PK model development. Further work is required to assess the generalizability of existing models and identify key factors that influence both initial and maintenance doses of tacrolimus, particularly in heart and lung transplant recipients.

    Matched MeSH terms: Kidney Transplantation*
  8. Al-Shibli S.M.
    MyJurnal
    As it is known; the majority of the human subjects has two renal arteries arising from the abdominal aorta; each will supply one kidney but in 30% of individuals, certain variations can be found. Accessory renal arteries constitute the most common and clinically important of these variations. For our case report, we are presenting one of these different variations that can be found in the blood supply of the kidneys. During dissecting the abdomen of an approximately 65 years-old male cadaver, multiple variations were found. There were double right renal arteries with prehilar branching of the upper renal artery. We found also that the right renal vein ascended upwards obliquely before ending in the lateral aspect of the inferior vena cava. Variation in the renal vessels is relatively common, especially multiple renal arteries, and can go smoothly without any abnormalities with the function of the kidney, but in some situations like renal transplantations, vascular reconstructions, and various surgical and radiological diagnostic techniques, the study of the anatomy of these variations is of crucial importance to decrease the patient morbidity during surgical procedures.
    Matched MeSH terms: Kidney; Kidney Transplantation
  9. Hiew KC, Sachithanandan A, Muhammad Nor MA, Badmanaban B, Jasid AM, Ismail F, et al.
    Med J Malaysia, 2016 Jun;71(3):126-30.
    PMID: 27495886 MyJurnal
    Acute kidney injury (AKI) following cardiac surgery is well established but the reported incidence is variable due to varying definitions and criteria. Furthermore there is a paucity of such data from Southeast Asia.
    Matched MeSH terms: Acute Kidney Injury*
  10. Park J, Lee SB, Cho SY, Jeong CW, Son H, Park YH, et al.
    Urol J, 2016 Aug 25;13(4):2759-64.
    PMID: 27576882
    PURPOSE: To evaluate the utility and safety of laparoendoscopic single-site surgery (LESS) in comparison with conventional laparoscopic (CL) surgery for the treatment of upper urinary tract stones.

    MATERIAL AND METHODS: Between June 2011 and May 2012, 20 patients with upper urinary tract stones were included in this prospective randomized study. The patients were assigned into the LESS group or CL group in a one-on-one manner using a random table. The clinical parameters were evaluated in the immediate postoperative period, and the stone clearance rate was evaluated via non-contrast computer tomography at one month postoperatively.

    RESULTS: There were no significant differences in patient demographics or preoperative stone sizes between the two groups. The perioperative parameters, including operative time, estimated blood loss, postoperative pain scores, length of hospital stay, and changes in renal function, were comparable. No transfusions or open conversions were required in either group. The incidence of residual stones was lower in the LESS group (1 case) than in the CL group (2 cases). However, this difference was not statistically significant.

    CONCLUSIONS: For large and impacted upper ureteral stones, the effectiveness and safety of LESS were equivalent to those of CL. Further randomized control trials with larger sample sizes are needed to strengthen the conclusions of this study.&nbsp.

    Matched MeSH terms: Kidney Calculi/surgery*
  11. Bhagavath P, Nayak BS, Monteiro NP, Kumar GP
    Kathmandu Univ Med J (KUMJ), 2016 7 18;13(52):369-71.
    PMID: 27423291
    Kidneys are the organs that remove the waste products of the metabolic activities. A smooth blood flow to the kidneys is essential to maintain their function. Abnormalities of the renal vasculature may result not only in impairing the renal function but can lead to conditions like varicocele. During an autopsy of an adult male, we observed renal vascular variations. The left renal vein had a retro-aortic course before its termination into the inferior vena cava. It was joined with the inferior vena cava at the level of inferior mesenteric artery with an acute angle. The left testicular vein joined the left renal vein with an acute angle. The right kidney was supplied by two renal arteries. The knowledge about retro-aortic course of the left renal vein may be important during renal transplantation. The oblique course of left renal vein and the termination of left testicular vein into it with an acute angle may increase the chances of left sided varicocele.
    Matched MeSH terms: Kidney/blood supply
  12. Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Gan SH
    PLoS One, 2018;13(2):e0192510.
    PMID: 29481564 DOI: 10.1371/journal.pone.0192510
    BACKGROUND: Despite myriad improvements in the care of dengue patients, acute kidney injury (AKI) remained least appreciated intricacy of dengue infection. Exiting literature does not provide any information on renal outcomes among dengue patients surviving an episode of AKI.

    METHODS: Dengue patients who developed AKI were followed up for post-discharge period of three months and renal recovery was assessed by using recovery criteria based on different thresholds of serum creatinine (SCr) and estimated glomerular filtration rates (eGFR).

    RESULTS: Out of the 526 dengue participants, AKI was developed in 72 (13.7%) patients. Renal recovery was assessed among AKI survivors (n = 71). The use of less (±50% recovery to baseline) to more (±5% recovery to baseline) stringent definitions of renal recovery yielded recovery rates from 88.9% to 2.8% by SCr and 94.4% to 5.6% by eGFR, as renal function biomarkers. At the end of study, eight patients had AKI with AKIN-II (n = 7) and AKIN-III (n = 1). Approximately 50% patients (n = 36/71) with AKI had eGFR primitive to CKD stage 2, while 18.3% (n = 13/71) and 4.2% (n = 3/71) patients had eGFR corresponding to advanced stages of CKD (stage 3 & 4). Factors such as renal insufficiencies at hospital discharge, multiple organ involvements, advance age, female gender and diabetes mellitus were associated with poor renal outcomes.

    CONCLUSIONS: We conclude that dengue patients with AKI portend unsatisfactory short-term renal outcomes and deserve a careful and longer follow-up, especially under nephrology care.

    Matched MeSH terms: Acute Kidney Injury/complications*
  13. Tey WK, Kuang YC, Ooi MP, Khoo JJ
    Comput Methods Programs Biomed, 2018 Mar;155:109-120.
    PMID: 29512490 DOI: 10.1016/j.cmpb.2017.12.004
    Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses. This study proposes an automated quantification system for measuring the amount of interstitial fibrosis in renal biopsy images as a consistent basis of comparison among pathologists. The system extracts and segments the renal tissue structures based on colour information and structural assumptions of the tissue structures. The regions in the biopsy representing the interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area and quantified as a percentage of the total area of the biopsy sample. A ground truth image dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated a good correlation in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification.

    BACKGROUND AND OBJECTIVE: Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses due to the uncertainties in human judgement.

    METHODS: An automated quantification system for accurately measuring the amount of interstitial fibrosis in renal biopsy images is presented as a consistent basis of comparison among pathologists. The system identifies the renal tissue structures through knowledge-based rules employing colour space transformations and structural features extraction from the images. In particular, the renal glomerulus identification is based on a multiscale textural feature analysis and a support vector machine. The regions in the biopsy representing interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area. The experiments conducted evaluate the system in terms of quantification accuracy, intra- and inter-observer variability in visual quantification by pathologists, and the effect introduced by the automated quantification system on the pathologists' diagnosis.

    RESULTS: A 40-image ground truth dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated an average error of 9 percentage points in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists involving samples from 70 kidney patients also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification.

    CONCLUSIONS: The accuracy of the proposed quantification system has been validated with the ground truth dataset and compared against the pathologists' quantification results. It has been shown that the correlation between different pathologists' estimation of interstitial fibrosis area has significantly improved, demonstrating the effectiveness of the quantification system as a diagnostic aide.

    Matched MeSH terms: Kidney Diseases/pathology
  14. Cooper DJ, Grigg MJ, Plewes K, Rajahram GS, Piera KA, William T, et al.
    Clin Infect Dis, 2022 Oct 12;75(8):1379-1388.
    PMID: 35180298 DOI: 10.1093/cid/ciac152
    BACKGROUND: Acetaminophen inhibits cell-free hemoglobin-induced lipid peroxidation and improves renal function in severe falciparum malaria but has not been evaluated in other infections with prominent hemolysis, including Plasmodium knowlesi malaria.

    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.

    Matched MeSH terms: Kidney/physiology
  15. Arsad FS, Hod R, Ahmad N, Ismail R, Mohamed N, Baharom M, et al.
    Int J Environ Res Public Health, 2022 Dec 06;19(23).
    PMID: 36498428 DOI: 10.3390/ijerph192316356
    BACKGROUND: This study aims to investigate the current impacts of extreme temperature and heatwaves on human health in terms of both mortality and morbidity. This systematic review analyzed the impact of heatwaves on mortality, morbidity, and the associated vulnerability factors, focusing on the sensitivity component.

    METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 flow checklist. Four databases (Scopus, Web of Science, EBSCOhost, PubMed) were searched for articles published from 2012 to 2022. Those eligible were evaluated using the Navigation Guide Systematic Review framework.

    RESULTS: A total of 32 articles were included in the systematic review. Heatwave events increased mortality and morbidity incidence. Sociodemographic (elderly, children, male, female, low socioeconomic, low education), medical conditions (cardiopulmonary diseases, renal disease, diabetes, mental disease), and rural areas were crucial vulnerability factors.

    CONCLUSIONS: While mortality and morbidity are critical aspects for measuring the impact of heatwaves on human health, the sensitivity in the context of sociodemographic, medical conditions, and locality posed a higher vulnerability to certain groups. Therefore, further research on climate change and health impacts on vulnerability may help stakeholders strategize effective plans to reduce the effect of heatwaves.

    Matched MeSH terms: Kidney Diseases*
  16. H'ng PK, Nayar SK, Lau WM, Segasothy M
    Singapore Med J, 1991 Apr;32(2):148-9.
    PMID: 2042077
    We report two cases of acute renal failure that followed the ingestion of jering. Features of jering poisoning included clinical presentation of bilateral loin pain, fever, nausea, vomiting, oligo-anuria, haematuria and passage of sandy particles in the urine. Blood urea (40.8 mmol/l; 21.9 mmol/l) and serum creatinine (1249 mumols/l; 693 mumols/l) were markedly elevated. With conservative therapy which included rehydration with normal saline and alkalinisation of the urine with sodium bicarbonate, the acute renal failure resolved.
    Matched MeSH terms: Acute Kidney Injury/etiology*
  17. Rohilla S, Singh M, Priya S, Almalki WH, Haniffa SM, Subramaniyan V, et al.
    PMID: 36734949 DOI: 10.1615/JEnvironPatholToxicolOncol.2022042088
    Melatonin is a serotonin-derived pineal gland hormone with many biological functions like regulating the sleep-wake cycle, circadian rhythm, menstrual cycle, aging, immunity, and antioxidants. Melatonin synthesis and release are more pronounced during the night, whereas exposure to light decreases it. Evidence is mounting in favor of the therapeutic effects of melatonin in cancer prevention, treatment and delayed onset in various cancer subtypes. Melatonin exerts its anticancer effect through modification of its receptors such as melatonin 1 (MT1), melatonin 2 (MT2), and inhibition of cancer cell proliferation, epigenetic alterations (DNA methylation/demethylation, histone acetylation/deacetylation), metastasis, angiogenesis, altered cellular energetics, and immune evasion. Melatonin performs a significant function in immune modulation and enhances innate and cellular immunity. In addition, melatonin has a remarkable impact on epigenetic modulation of gene expression and alters the transcription of genes. As an adjuvant to cancer therapies, it acts by decreasing the side effects and boosting the therapeutic effects of chemotherapy. Since current treatments produce drug-induced unwanted toxicities and side effects, they require alternate therapies. A recent review article attempts to summarize the mechanistic perspective of melatonin in different cancer subtypes like skin cancer, breast cancer, hepatic cancer, renal cell cancer, non-small cell lung cancer (NSCLC), colon oral, neck, and head cancer. The various studies described in this review will give a firm basis for the future evolution of anticancer drugs.
    Matched MeSH terms: Kidney Neoplasms*
  18. Zafar R, Rehman IU, Shah Y, Ming LC, Goh HP, Goh KW
    PLoS One, 2023;18(9):e0291417.
    PMID: 37773947 DOI: 10.1371/journal.pone.0291417
    INTRODUCTION: Chronic kidney disease (CKD) is a significant public health challenge due to its rising incidence, mortality, and morbidity. Patients with kidney diseases often suffer from various comorbid conditions, making them susceptible to potential drug-drug interactions (pDDIs) due to polypharmacy and multiple prescribers. Inappropriate prescriptions for CKD patients and their consequences in the form of pDDIs are a major challenge in Pakistan.

    AIM: This study aimed to compare the incidence and associated risk factors of pDDIs among a public and private sector hospital in Khyber Pakhtunkhwa, Pakistan.

    METHOD: A retrospective cross-sectional study design was conducted to compare pDDIs among public and private sector hospitals from January 2023 to February 2023. Patients profile data for the full year starting from January 1 2022 to December 302022, was accessed All adult patients aged 18 years and above, of both genders, who currently have or have previously been diagnosed with end-stage renal disease (ESRD) were included. For assessing pDDIs, patient data was retrieved and checked using Lexicomp UpToDate® for severity and documentation of potential drug-drug interactions.

    RESULTS: A total of 358 patients' data was retrieved (with n = 179 in each hospital); however, due to incomplete data, n = 4 patients were excluded from the final analysis. The prevalence of pDDIs was found to be significantly higher in private hospitals (84.7%) than in public hospitals (26.6%), with a p-value <0.001. Patients in the age category of 41-60 years (AOR = 6.2; p = 0.008) and those prescribed a higher number of drugs (AOR = 1.2; p = 0.027) were independently associated with pDDIs in private hospitals, while the higher number of prescribed drugs (AOR = 2.9; p = <0.001) was an independent risk factor for pDDIs in public hospitals. The majority of pDDIs (79.0%) were of moderate severity, and a significant number of patients (15.1%) also experienced major pDDIs, with a p-value <0.001. The majority of pDDIs had fair documentation for reliability rating in both public and private hospitals.

    CONCLUSION: The prevalence of pDDIs was higher among CKD patients at private hospitals, and most of the pDDIs were of moderate severity. A considerable number of patients also experienced major pDDIs. The risk of experiencing pDDIs was found to be higher in older patients and among those prescribed a higher number of drugs.

    Matched MeSH terms: Kidney Failure, Chronic*
  19. The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, et al.
    N Engl J Med, 2023 Jan 12;388(2):117-127.
    PMID: 36331190 DOI: 10.1056/NEJMoa2204233
    BACKGROUND: The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.

    METHODS: We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes.

    RESULTS: A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.

    CONCLUSIONS: Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).

    Matched MeSH terms: Kidney/physiopathology
  20. Albitar O, Harun SN, Ballouze R, Mohamed Noor DA, Sheikh Ghadzi SM
    Ther Drug Monit, 2022 Apr 01;44(2):282-289.
    PMID: 34334682 DOI: 10.1097/FTD.0000000000000916
    BACKGROUND: Cyclosporine is an essential component of many immunosuppressive regimens. However, its pharmacokinetic and pharmacodynamic (PKPD) modeling has not been widely investigated. This study aims to develop a time-dissociated PKPD model of cyclosporine in renal transplant patients.

    METHODS: Medical records of renal transplant patients at Penang General Hospital were retrospectively analyzed. A time-dissociated PKPD model with covariate effects was developed using NONMEM to evaluate renal graft function response, quantified as estimated glomerular filtration rate (eGFR), toward the cyclosporine cumulative exposure (area under the concentration-time curve). The final model was integrated into a tool to predict the potential outcome. Individual eGFR predictions were evaluated based on the clinical response recorded as acute rejection/nephrotoxicity events.

    RESULTS: A total of 1256 eGFR readings with 2473 drug concentrations were obtained from 107 renal transplant patients receiving cyclosporine. An Emax drug effect with a linear drug toxicity model best described the data. The baseline renal graft level (E0), maximum effect (Emax), area under the concentration-time curve achieving 50% of the maximum effect, and nephrotoxicity slope were estimated as 12.9 mL·min-1·1.73 m-2, 50.7 mL·min-1·1.73 m-2, 1740 ng·h·mL-1, and 0.00033, respectively. The hemoglobin level was identified as a significant covariate affecting the E0. The model discerned acute rejection from nephrotoxicity in 19/24 cases.

    CONCLUSIONS: A time-dissociated PKPD model successfully described a large number of observations and was used to develop an online tool to predict renal graft response. This may help discern early rejection from nephrotoxicity, especially for patients unwilling to undergo a biopsy or those waiting for biopsy results.

    Matched MeSH terms: Kidney Transplantation*
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