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Fulltext Risk factors associated with nosocomial infections among end stage renal disease patients undergoing hemodialysis: A systematic review

Abbasi SH, Aftab RA, Chua SS

PLoS One, 2020;15(6):e0234376.
PMID: 32569265 DOI: 10.1371/journal.pone.0234376

BACKGROUND: Profound healthcare challenges confront societies with an increase in prevalence of end-stage renal disease (ESRD), which is one of the leading causes of morbidity and mortality worldwide. Due to several facility and patient related factors, ESRD is significantly associated with increased morbidity and mortality attributed to infections.
AIMS AND OBJECTIVE: The aim of this study was to assess systematically the characteristics of patients and risk factors associated with nosocomial infections among ESRD patients undergoing hemodialysis.
METHODS: A systematic literature search was performed to identify eligible studies published during the period from inception to December 2018 pertaining to risk factors associated with nosocomial infections among hemodialysis patients. The relevant studies were generated through a computerized search on five databases (PubMed, EBSCOhost, Google Scholar, ScienceDirect and Scopus) using the Mesh Words: nosocomial infections, hospital acquired infections, healthcare associated infections, end stage renal disease, end stage renal failure, hemodialysis, and risk factors. The complete protocol has been registered under PROSPERO (CRD42019124099).
RESULTS: Initially, 1411 articles were retrieved. Out of these, 24 were duplicates and hence were removed. Out of 1387 remaining articles, 1337 were removed based on irrelevant titles and/or abstracts. Subsequently, the full texts of 50 articles were reviewed and 41 studies were excluded at this stage due to lack of relevant information. Finally, nine articles were selected for this review. Longer hospital stay, longer duration on hemodialysis, multiple catheter sites, longer catheterization, age group, lower white blood cell count, history of blood transfusion, and diabetes were identified as the major risk factors for nosocomial infections among hemodialysis patients.
CONCLUSION: The results of this review indicate an information gap and potential benefits of additional preventive measures to further reduce the risk of infections in hemodialysis population. Moreover, several patient-related and facility-related risk factors were consistently observed in the studies included in this review, which require optimal control measures.

Matched MeSH terms: Kidney Failure, Chronic/blood; Kidney Failure, Chronic/complications*; Kidney Failure, Chronic/therapy*
Fulltext Denosumab as the Treatment of Recalcitrant Tuberculous Pleural Effusion-Associated Hypercalcemia

Abd Jalil AA, Wan Muhamad Hatta SF, Mohamad AF, Abdul Rani MF

Case Rep Med, 2021;2021:5544848.
PMID: 33986809 DOI: 10.1155/2021/5544848

Denosumab is a human monoclonal antibody that binds to RANKL (receptor activator of nuclear factor-kappa B ligand). It has mainly been used in the treatment of osteoporosis for a variety of causes especially in situations refractory to bisphosphonates or when kidney function is impaired. It is also used in cases of malignancy-associated hypercalcemia. There are many causes of hypercalcemia, but only rarely it is associated with granulomatous diseases such as tuberculous pleural effusion. We report a case of hypercalcemia from tuberculous pleural effusion that was initially admitted with left medium abundance pleural effusion and a serum corrected calcium level of 3.48 mmol/L. The calcium level was successfully normalized within 72 hours of subcutaneous denosumab administration after other interventions have failed.

Matched MeSH terms: Kidney
Fulltext Acute renal failure following the use of rosiglitazone in a chronic kidney disease patient

Abdul Ghani R, Zainudin S, Kamaruddin NA, Kong NC

Singapore Med J, 2009 Jan;50(1):e32-4.
PMID: 19224067

Drug-induced acute interstitial nephritis is a well-recognised and important reversible cause of acute renal failure. Peroxisome-proliferator activated receptor-gamma agonists, such as rosiglitazone, have been proven to be safe in chronic kidney disease patients. We describe a 65-year-old man with long-standing diabetes mellitus and hypertension, presenting with a five-day history of fluid overload and uraemic symptoms. There was no ingestion of analgesics, alternative medicine and other nephrotoxic drugs, the only new prescription being rosiglitazone, which was commenced during his last clinic follow-up two weeks prior to presentation. He required haemodialysis with minimal improvement in renal profile, despite cessation of the offending drug. Renal biopsy revealed findings consistent with acute interstitial nephritis. An episode of upper gastrointestinal bleeding with bleeding duodenal ulcer limited the use of steroids. He was treated with a course of mycophenolate mofetil which showed good gradual response and he remained stable with residual renal impairment.

Matched MeSH terms: Kidney Failure, Chronic/complications; Acute Kidney Injury/chemically induced*; Acute Kidney Injury/drug therapy
Fulltext Nephroprotective effects of Zingiber zerumbet Smith ethyl acetate extract against paracetamol-induced nephrotoxicity and oxidative stress in rats

Abdul Hamid Z, Budin SB, Wen Jie N, Hamid A, Husain K, Mohamed J

J Zhejiang Univ Sci B, 2012 Mar;13(3):176-85.
PMID: 22374609 DOI: 10.1631/jzus.B1100133

Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. In this study, the effects of ethyl acetate extract of Zingiber zerumbet rhizome [200 mg per kg of body weight (mg/kg) and 400 mg/kg] on PCM-induced nephrotoxicity were examined. Rats were divided into five groups containing 10 rats each. The control group received distilled water while other groups were treated with extract alone (400 mg/kg), PCM alone (750 mg/kg), 750 mg/kg PCM+200 mg/kg extract (PCM+200-extract), and 750 mg/kg PCM+400 mg/kg extract (PCM+400-extract), respectively, for seven consecutive days. The Z. zerumbet extract was given intraperitoneally concurrent with oral administration of PCM. Treatment with Z. zerumbet extract at doses of 200 and 400 mg/kg prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (P<0.05) level of plasma creatinine, plasma and renal malondialdehyde (MDA), plasma protein carbonyl, and renal advanced oxidation protein product (AOPP). Furthermore, both doses were also able to induce a significant increment (P<0.05) of plasma and renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity. The nephroprotective effects of Z. zerumbet extract were confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. Moreover, Z. zerumbet extract administered at 400 mg/kg was found to show greater protective effects than that at 200 mg/kg. In conclusion, ethyl acetate extract of Z. zerumbet rhizome has a protective role against PCM-induced nephrotoxicity and the process is probably mediated through its antioxidant properties.

Matched MeSH terms: Acute Kidney Injury/chemically induced*; Acute Kidney Injury/metabolism; Acute Kidney Injury/pathology; Acute Kidney Injury/prevention & control*
Fulltext Adult female with acute renal failure and weight loss

Abdul-Rahman NA, Azman RR, Kumar G

Saudi Med J, 2016 May;37(5):584-6.
PMID: 27146625 DOI: 10.15537/smj.2016.5.15042
Matched MeSH terms: Acute Kidney Injury/diagnosis*; Acute Kidney Injury/physiopathology; Acute Kidney Injury/surgery
High-fructose feeding impacts on the adrenergic control of renal haemodynamics in the rat

Abdulla MH, Sattar MA, Johns EJ, Abdullah NA, Hye Khan MA, Rathore HA

Br J Nutr, 2012 Jan;107(2):218-28.
PMID: 21733307 DOI: 10.1017/S0007114511002716

The present study explored the hypothesis that a prolonged 8 weeks exposure to a high fructose intake suppresses adrenergic and angiotensin II (Ang II)-mediated vasoconstriction and is associated with a higher contribution of α1D-adrenoceptors. A total of thirty-two Sprague-Dawley rats received either 20 % fructose solution (FFR) or tap water (control, C) to drink ad libitum for 8 weeks. Metabolic and haemodynamic parameters were assessed weekly. The renal cortical vasoconstrictor responses to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II were determined in the presence and absence of BMY7378 (α1D-adrenoceptor antagonist). FFR had increased blood pressure, plasma levels of glucose, TAG and insulin. FFR expressed reduced renal vascular responses to adrenergic agonists and Ang II (NA: 50 %, PE: 50 %, ME, 65 %, Ang II: 54 %). Furthermore in the C group, the magnitude of the renal cortical vasoconstriction to all agonists was blunted in the presence of the low or high dose of BMY7378 (NA: 30 and 31 %, PE: 23 and 33 %, ME: 19 and 44 %, Ang II: 53 and 77 %), respectively, while in the FFR, vasoconstriction was enhanced to adrenergic agonists and reduced to Ang II (NA: 8 and 83 %, PE: 55 %, ME, 2 and 177 %, Ang II: 61 and 31 %). Chronic high fructose intake blunts vascular sensitivity to adrenergic agonists and Ang II. Moreover, blocking of the α1D-adrenoceptor subtype results in enhancement of renal vasoconstriction to adrenergic agonists, suggesting an inhibitory action of α1D-adrenoceptors in the FFR. α1D-Adrenoceptors buffer the AT1-receptor response in the renal vasculature of normal rats and fructose feeding suppressed this interaction.

Matched MeSH terms: Kidney/blood supply*; Kidney/drug effects
Evidence for the role of α1A-adrenoceptor subtype in the control of renal haemodynamics in fructose-fed Sprague-Dawley rat

Abdulla MH, Sattar MA, Johns EJ, Abdullah NA, Khan MA

Eur J Nutr, 2011 Dec;50(8):689-97.
PMID: 21373947 DOI: 10.1007/s00394-011-0180-9

AIM: To explore the hypothesis that high fructose intake results in a higher functional contribution of α1A-adrenoceptors and blunts the adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction.
METHODS: Twelve Sprague-Dawley rats received either 20% fructose solution [FFR] or tap water [C] to drink ad libitum for 8 weeks. The renal vasoconstrictor response to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II was determined in the presence and absence of 5-methylurapidil (5-MU) (α1A-adrenoceptor antagonist) in a three-phase experiment (pre-drug, low- and high-dose 5-MU). Data, mean ± SEM were analysed by ANOVA or Student's unpaired t-test with significance at P < 0.05.
RESULTS: FFR exhibited insulin resistance (HOMA index), hypertension and significant increases in plasma levels of glucose and insulin. All agonists caused dose-related reductions in cortical blood perfusion that were larger in C than in FFR while the magnitudes of the responses were progressively reduced with increasing doses of 5-MU in both C and FFR. The degree of 5-MU attenuation of the renal cortical vasoconstriction due to NA, ME and Ang II was significantly greater in the FFR compared to C.
CONCLUSIONS: Fructose intake for 8 weeks results in smaller vascular response to adrenergic agonists and Ang II. The α1A-adrenoceptor subtype is the functional subtype that mediates renal cortical vasoconstriction in control rats, and this contribution becomes higher due to fructose feeding.

Matched MeSH terms: Kidney/drug effects*; Kidney/physiopathology; Kidney Diseases/chemically induced; Kidney Diseases/drug therapy; Kidney Diseases/physiopathology
The contribution of α1B-adrenoceptor subtype in the renal vasculature of fructose-fed Sprague-Dawley rats

Abdulla MH, Sattar MA, Abdullah NA, Hye Khan MA, Anand Swarup KR, Johns EJ

Eur J Nutr, 2011 Jun;50(4):251-60.
PMID: 20882287 DOI: 10.1007/s00394-010-0133-8

PURPOSE: Fructose feeding induces a moderate increase in blood pressure, insulin resistance, and hyperinsulinemia. This study investigated the role of α(1B)-adrenoceptor subtype in the control of renal hemodynamic responses to exogenously administered angiotensin II (Ang II) and a set of adrenergic agonists in a model of high fructose-fed rats.
METHODS: Sprague-Dawley rats were fed for 8 weeks with 20% fructose in drinking water (FFR). The renal cortical vasoconstriction to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II in the presence and absence of chloroethylclonidine (CEC) (α(1B)-adrenoceptor antagonist) was determined. Data, mean ± SEM or SD were subjected to ANOVA with significance at p

Matched MeSH terms: Kidney/blood supply*; Kidney/drug effects; Kidney/physiopathology
Fulltext Effect of renal sympathetic nerve on adrenergically and angiotensin II-induced renal vasoconstriction in normal Wistar-Kyoto rats

Abdulla MH, Sattar MA, Abdullah NA, Khan AH, Anand Swarup KR, Rathore HA, et al.

Ups. J. Med. Sci., 2011 Mar;116(1):18-25.
PMID: 21047287 DOI: 10.3109/03009734.2010.526723

This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats.

Matched MeSH terms: Kidney/innervation*
Chronic treatment with losartan and carvedilol differentially modulates renal vascular responses to sympathomimetics compared to treatment with individual agents in normal Wistar Kyoto and spontaneously hypertensive rats

Abdulla MH, Sattar MA, Abdullah NA, Khan MA, Abdallah HH, Johns EJ

Eur J Pharmacol, 2009 Jun 10;612(1-3):69-74.
PMID: 19356722 DOI: 10.1016/j.ejphar.2009.03.064

This study set out to investigate the impact of chronic cumulative blockade of angiotensin II and adrenoceptors in WKY and SHR and to explore how the renovascular responses to adrenergic and angiotensin II receptor agonists may be interdependent. Rats were treated with either losartan, carvedilol or losartan+carvedilol for 7 days and on day eight, animals were pentobarbitone anaesthetized and prepared for renal haemodynamic study. Dose-response relationships were determined in terms of reduction/elevation in the magnitude of renal blood flow in response to intrarenal arterial injection of dopamine, phenylephrine and isoprenaline. Renal vascular responses were blunted in WKY and SHR treated with either losartan or carvedilol as compared to their untreated counterparts (P<0.05). In the combined treated rats, the vascular responses to isoprenaline and phenylephrine were restored to levels observed in the untreated rats, but the renal vasoconstrictor responses to dopamine decreased (P<0.05) in both WKY and SHR. There was a reduction of (P<0.05) in the magnitude of the isoprenaline induced renal vasodilation in all SHR as compared to WKY groups. The data obtained showed that the renal vascular action of dopamine, phenylephrine and isoprenaline depended on an intact renin-angiotensin system (RAS) in WKY and SHR. Treatment with losartan or carvedilol blunted the renal vasoconstrictor/vasodilator responses to sympathomimetics which was attenuated with the combined treatment. These observations using chronic blockade of adrenergic and angiotensin receptors demonstrated that there was a long standing interdependency between the RAS and sympathetic nervous system (SNS) in determining the responsiveness of the renal vasculature of normal and hypertensive rats.

Matched MeSH terms: Kidney/blood supply*; Kidney/innervation
Influence of sympathetic and AT-receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive rats

Abdulla MH, Sattar MA, Khan MA, Abdullah NA, Johns EJ

Acta Physiol (Oxf), 2009 Mar;195(3):397-404.
PMID: 19183357 DOI: 10.1111/j.1748-1716.2008.01895.x

This study investigated the influence of angiotensin II (Ang II) receptor and adrenergic blockade on the renal vasoconstrictions caused by Ang II and adrenergic agonists in spontaneously hypertensive rats (SHR).

Matched MeSH terms: Kidney/innervation
Inhibition of Ang II and renal sympathetic nerve influence dopamine-and isoprenaline-induced renal haemodynamic changes in normal Wistar-Kyoto and spontaneously hypertensive rats

Abdulla MH, Sattar MA, Abdullah NA, Hazim AI, Anand Swarup KR, Rathore HA, et al.

Auton Autacoid Pharmacol, 2008 Oct;28(4):95-101.
PMID: 18778332 DOI: 10.1111/j.1474-8673.2008.00422.x

1. This study was undertaken to elucidate the effects of inhibiting the renin-angiotensin system (RAS) with losartan, and acute unilateral renal denervation on renal haemodynamic responses to intrarenal administration of vasoconstrictor doses of dopamine and vasodilator doses of isoprenaline in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Acute unilateral renal denervation of the left kidney in rats was confirmed by a drop in the renal vasoconstrictor response to renal nerve stimulation (P < 0.05) along with diuresis and natriuresis. Rats were pretreated with losartan for 7 days and thereafter animals fasted overnight were anaesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and acute renal haemodynamic responses studied. 3. Dose-response curves were constructed for dopamine and isoprenaline that induced falls or increases in renal blood flow, respectively. It was observed that renal vascular responses were greater in the denervated as compared with rats with intact renal nerves (all P < 0.05). Dopamine-induced renal vasoconstrictor responses were markedly lower in losartan-treated denervated WKY and SHR compared with their untreated counterparts (all P < 0.05). It was also observed that in losartan-treated and denervated WKY rats the vasodilatory responses to isoprenaline were markedly lower compared with untreated rats (all P < 0.05). However, in SHR, under the same conditions, there was no difference in the renal response to isoprenaline whether or not rats were treated with losartan (P > 0.05). 4. The data obtained showed that the renal vasoconstrictor effect of dopamine depends on intact renal nerves and RAS in WKY and SHR. Isoprenaline responses were likewise sensitive to renal denervation and RAS inhibition in WKY rats but not SHRs. Our observations reveal a possible relationship between renal AT(1) receptors and alpha(1)-adrenoceptors in WKY and SHR. There is also evidence to suggest an interaction between renal beta-adrenoceptors and AT(1) receptors in WKY rats.

Matched MeSH terms: Kidney/blood supply; Kidney/innervation
Effect of acute unilateral renal denervation on renal hemodynamics in spontaneously hypertensive rats

Abdulla MH, Sattar MA, Salman IM, Abdullah NA, Ameer OZ, Khan MA, et al.

Auton Autacoid Pharmacol, 2008 Apr-Jul;28(2-3):87-94.
PMID: 18598290 DOI: 10.1111/j.1474-8673.2008.00421.x

1 This study was undertaken to characterize the renal responses to acute unilateral renal denervation in anaesthetized spontaneously hypertensive rats (SHR) by examining the effect of acute unilateral renal denervation on the renal hemodynamic responses to a set of vasoactive agents and renal nerve stimulation. 2 Twenty-four male SHR rats underwent acute unilateral renal denervation and the denervation was confirmed by significant drop (P < 0.05) in renal vasoconstrictor response to renal nerve stimulation along with marked diuresis and natriuresis following denervation. After 7 days treatment with losartan, the overnight fasted rats were anaesthetized (sodium pentobarbitone, 60 mg kg(-1) i.p.) and renal vasoconstrictor experiments were performed. The changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine, methoxamine and angiotensin II. 3 The data showed that there was significantly (all P < 0.05) increased renal vascular responsiveness to the vasoactive agents in denervated rats compared to those with intact renal nerves. In losartan-treated denervated SHR rats, there were significant (all P < 0.05) reductions in the renal vasoconstrictor responses to neural stimuli and vasoactive agents as compared with that of untreated denervated SHR rats. 4 The data obtained in denervated rats suggested an enhanced sensitivity of the alpha(1)-adrenoceptors to adrenergic agonists and possible increase of AT(1) receptors functionality in the renal vasculature of these rats. These data also suggested a possible interaction between sympathetic nervous system and renin-angiotensin system in terms of a crosstalk relationship between renal AT(1) and alpha(1)-adrenoceptor subtypes.

Matched MeSH terms: Kidney/blood supply; Kidney/innervation; Kidney/physiology*
The effect of losartan and carvedilol on renal haemodynamics and altered metabolism in fructose-fed Sprague-Dawley rats

Abdulla MH, Sattar MA, Abdullah NA, Johns EJ

J Physiol Biochem, 2012 Sep;68(3):353-63.
PMID: 22281695 DOI: 10.1007/s13105-012-0147-1

The aim of this study is to assess the effects of losartan and carvedilol on metabolic parameters and renal haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of fructose-fed rat. Thirty-six Sprague-Dawley rats were fed for 8 weeks either 20% fructose solution (F) or tap water (C) ad libitum. F or C group received either losartan or carvedilol (10 mg/kg p.o.) daily for the last 3 weeks of the study (FL and L) and (FCV and CV), respectively, then in acute studies the renal vasoconstrictor actions of Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. Data, mean±SEM were analysed using ANOVA with significance at P <0.05. Losartan and carvedilol decreased the area under the glucose tolerance curve of the fructose-fed group. The responses (%) to NA, PE, ME and Ang II in F were lower (P <0.05) than C (F vs. C, 17±2 vs. 38±3; 24±2 vs. 48±2; 12±2 vs. 34±2; 17±2 vs. 26±2), respectively. L had higher (P <0.05) responses to NA and PE while CV had blunted (P <0.05) responses to NA, PE and Ang II compared to C (L, CV vs. C, 47±3, 9±2 vs. 38±3; 61±3, 29±3 vs. 48±2; 16±3, 4±3 vs. 26±2), respectively. FL but not FCV group had enhanced (P <0.05) responses to NA, PE and ME compared to F (FL vs. F, 33±3 vs. 17±2; 45±3 vs. 24±2; 26±3 vs. 12±2), respectively. Losartan and carvedilol had an important ameliorating effect on fructose-induced insulin resistance. Losartan treatment could be an effective tool to restore normal vascular reactivity in the renal circulation of the fructose-fed rat.

Matched MeSH terms: Kidney/metabolism*
Prevalence of anaemia and associated risk factors amongst The Malaysian Cohort participants

Abdullah N, Ismail N, Abd Jalal N, Mohd Radin F, Othman R, Kamalul Arifin AS, et al.

Ann Hematol, 2020 Nov;99(11):2521-2527.
PMID: 32975589 DOI: 10.1007/s00277-020-04279-w

This study was aimed at determining the prevalence of anaemia amongst the Malaysian Cohort participants and the associated risk factors. This was a cross-sectional study that involved 102,388 participants from The Malaysian Cohort (TMC) aged between 35 and 70 years old recruited from April 2006 to September 2012. Venous blood was taken for the full blood count. The prevalence of anaemia was 13.8% with majority having the microcytic-hypochromic type (59.7%). Comparison between the ethnic groups showed that Indians have the highest prevalence of anaemia (19.9%), followed by Malays (13.1%), and Chinese (12.0%). The prevalence of anaemia was substantially higher in females (20.1%) compared to males (4.9%). Amongst the female participants, the prevalence of anaemia was highest amongst those who were younger than 49 years old and decreased as the age increased. In contrast, the prevalence of anaemia in males increased with age. Gender, ethnicity, age, marital status, presence of platelet disorders and kidney disease were significant risk factors associated with anaemia and contributed to 14.9% of the risk of developing anaemia in this population. The prevalence of anaemia amongst the Malaysian Cohort participants is 13.8% with the majority having the microcytic and hypochromic type implying iron deficiency as the main cause. It is important that those who have anaemia be further investigated and treated.
Study name: The Malaysian Cohort (TMC) project

Matched MeSH terms: Kidney Diseases
Predicting points of departure for risk assessment based on in vitro cytotoxicity data and physiologically based kinetic (PBK) modeling: The case of kidney toxicity induced by aristolochic acid I

Abdullah R, Alhusainy W, Woutersen J, Rietjens IM, Punt A

Food Chem Toxicol, 2016 Jun;92:104-16.
PMID: 27016491 DOI: 10.1016/j.fct.2016.03.017

Aristolochic acids are naturally occurring nephrotoxins. This study aims to investigate whether physiologically based kinetic (PBK) model-based reverse dosimetry could convert in vitro concentration-response curves of aristolochic acid I (AAI) to in vivo dose response-curves for nephrotoxicity in rat, mouse and human. To achieve this extrapolation, PBK models were developed for AAI in these different species. Subsequently, concentration-response curves obtained from in vitro cytotoxicity models were translated to in vivo dose-response curves using PBK model-based reverse dosimetry. From the predicted in vivo dose-response curves, points of departure (PODs) for risk assessment could be derived. The PBK models elucidated species differences in the kinetics of AAI with the overall catalytic efficiency for metabolic conversion of AAI to aristolochic acid Ia (AAIa) being 2-fold higher for rat and 64-fold higher for mouse than human. Results show that the predicted PODs generally fall within the range of PODs derived from the available in vivo studies. This study provides proof of principle for a new method to predict a POD for in vivo nephrotoxicity by integrating in vitro toxicity testing with in silico PBK model-based reverse dosimetry.

Matched MeSH terms: Kidney/drug effects*; Kidney/pathology
Fulltext Defining in vivo dose-response curves for kidney DNA adduct formation of aristolochic acid I in rat, mouse and human by an in vitro and physiologically based kinetic modeling approach

Abdullah R, Wesseling S, Spenkelink B, Louisse J, Punt A, Rietjens IMCM

J Appl Toxicol, 2020 12;40(12):1647-1660.
PMID: 33034907 DOI: 10.1002/jat.4024

Aristolochic acid I (AAI) is a well-known genotoxic kidney carcinogen. Metabolic conversion of AAI into the DNA-reactive aristolactam-nitrenium ion is involved in the mode of action of tumor formation. This study aims to predict in vivo AAI-DNA adduct formation in the kidney of rat, mouse and human by translating the in vitro concentration-response curves for AAI-DNA adduct formation to the in vivo situation using physiologically based kinetic (PBK) modeling-based reverse dosimetry. DNA adduct formation in kidney proximal tubular LLC-PK1 cells exposed to AAI was quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. Subsequently, the in vitro concentration-response curves were converted to predicted in vivo dose-response curves in rat, mouse and human kidney using PBK models. Results obtained revealed a dose-dependent increase in AAI-DNA adduct formation in the rat, mouse and human kidney and the predicted DNA adduct levels were generally within an order of magnitude compared with values reported in the literature. It is concluded that the combined in vitro PBK modeling approach provides a novel way to define in vivo dose-response curves for kidney DNA adduct formation in rat, mouse and human and contributes to the reduction, refinement and replacement of animal testing.

Matched MeSH terms: Kidney/drug effects*; Kidney/metabolism; Kidney/pathology
Fulltext Risk of acute kidney injury and hyponatremia in long-distance runners

Abdullah R., Wan Md Adnan W.A.H.

JUMMEC, 2018;21(2):4-9.
MyJurnal

Long-distance running has gathered some momentum among health-conscious participants. However, some
studies have revealed association between long-distance running and development of acute kidney injury.
Although the impact usually lasts only for a few days after the event, some participants have been admitted for
severe acute kidney injury, the minority of which require dialysis treatment. The mechanisms underlying the
injury may include dehydration, development of rhabdomyolysis, heat stroke and concomitant use of NSAIDS.
Unfortunately, there is no long-term follow-up study to determine the long-term effect on kidney function.
Acute hyponatremia may develop in a significant proportion of long-distance runners. Majority of them were
asymptomatic but a few fatal cases which were supposedly due to cerebral oedema have been reported.
Excessive intake of hypotonic drinks, excessive sweating and secretion of non-osmotic antidiuretic hormone
have been postulated to be the causes of hyponatremia. This mini review will discuss the pathophysiology of
the development of acute kidney injury and hyponatremia. It will also discuss the prevention and treatment
of both conditions.

Matched MeSH terms: Acute Kidney Injury
Beneficial effects of ginger (Zingiber officinale) on carbohydrate metabolism in streptozotocin-induced diabetic rats

Abdulrazaq NB, Cho MM, Win NN, Zaman R, Rahman MT

Br J Nutr, 2012 Oct;108(7):1194-201.
PMID: 22152092

Zingiber officinale (ZO), commonly known as ginger, has been traditionally used in the treatment of diabetes mellitus. Several studies have reported the hypoglycaemic properties of ginger in animal models. The present study evaluated the antihyperglycaemic effect of its aqueous extract administered orally (daily) in three different doses (100, 300, 500 mg/kg body weight) for a period of 30 d to streptozotocin (STZ)-induced diabetic rats. A dose-dependent antihyperglycaemic effect revealed a decrease of plasma glucose levels by 38 and 68 % on the 15th and 30th day, respectively, after the rats were given 500 mg/kg. The 500 mg/kg ZO significantly (P<0·05) decreased kidney weight (% body weight) in ZO-treated diabetic rats v. control rats, although the decrease in liver weight (% body weight) was not statistically significant. Kidney glycogen content increased significantly (P<0·05) while liver and skeletal muscle glycogen content decreased significantly (P<0·05) in diabetic controls v. normal controls. ZO (500 mg/kg) also significantly decreased kidney glycogen (P<0·05) and increased liver and skeletal muscle glycogen in STZ-diabetic rats when compared to diabetic controls. Activities of glucokinase, phosphofructokinase and pyruvate kinase in diabetic controls were decreased by 94, 53 and 61 %, respectively, when compared to normal controls; and ZO significantly increased (P<0·05) those enzymes' activities in STZ-diabetic rats. Therefore, the present study showed that ginger is a potential phytomedicine for the treatment of diabetes through its effects on the activities of glycolytic enzymes.

Matched MeSH terms: Kidney/drug effects; Kidney/pathology
Defining a threshold for tacrolimus intra-patient variability associated with late acute cellular rejection in paediatric kidney transplant recipients

Abu Bakar K, Mohamad NA, Hodi Z, McCulloch T, Williams A, Christian M, et al.

Pediatr Nephrol, 2019 12;34(12):2557-2562.
PMID: 31520127 DOI: 10.1007/s00467-019-04346-z

BACKGROUND: Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known.
METHODS: We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels

Matched MeSH terms: Kidney Transplantation/adverse effects

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