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Drug use and dosing in chronic kidney disease

Hassan Y, Al-Ramahi R, Abd Aziz N, Ghazali R

Ann Acad Med Singap, 2009 Dec;38(12):1095-103.
PMID: 20052447

One of the most important drug-related problems in patients with chronic kidney disease (CKD) is medication dosing errors. Many medications and their metabolites are eliminated through the kidney. Thus, adequate renal function is important to avoid toxicity. Patients with renal impairment often have alterations in their pharmacokinetic and pharmacodynamic parameters. The clearance of drugs eliminated primarily by renal filtration is decreased by renal disease. Therefore, special consideration should be taken when these drugs are prescribed to patients with impaired renal function. Despite the importance of dosage adjustment in patients with CKD, such adjustments are sometimes ignored. Physicians and pharmacists can work together to accomplish safe drug prescribing. This task can be complex and require a stepwise approach to ensure effectiveness, minimise further damage and prevent drug nephrotoxicity.

Matched MeSH terms: Kidney Diseases/physiopathology
Fulltext The effects of intermittent fasting during the month of Ramadan in chronic haemodialysis patients in a tropical climate country

Wan Md Adnan WA, Zaharan NL, Wong MH, Lim SK

PLoS One, 2014;9(12):e114262.
PMID: 25546434 DOI: 10.1371/journal.pone.0114262

Chronic kidney disease is an emerging problem in the majority Muslim countries. Despite the uncertainties of the risks involved, some Muslim patients undergoing chronic haemodialysis choose to observe intermittent fasting during the month of Ramadan. This study aims to investigate the effect of Ramadan fasting in haemodialysis patients residing in a tropical climate country.

Matched MeSH terms: Kidney Diseases/physiopathology*
Fulltext Ethnic disparities in prevalence and impact of risk factors of chronic kidney disease

Sabanayagam C, Lim SC, Wong TY, Lee J, Shankar A, Tai ES

Nephrol Dial Transplant, 2010 Aug;25(8):2564-70.
PMID: 20185856 DOI: 10.1093/ndt/gfq084

There is substantial heterogeneity in literature regarding the epidemiology for chronic kidney disease (CKD) in different Asian populations. We aimed to assess the prevalence and risk factors of CKD in a multi-ethnic Asian population in Singapore.

Matched MeSH terms: Kidney Diseases/physiopathology
Fulltext Acute protein loading in the assessment of renal reserve

Loo CS, Zaki M, Sulaiman AB, Sukanya AB, Voon YC, Kua SL

Med J Malaysia, 1994 Mar;49(1):36-43.
PMID: 8057988

Functional renal reserve is a measure of the capacity of the kidney to increase the glomerular filtration in response to the stimulus of a protein meal or amino acid infusion. The aim of this study was to evaluate the usefulness of protein meal test to measure functional renal reserve in normal subjects and various groups of renal patients. One hundred and twenty five subjects from the Nephrology Clinic, Kuala Lumpur General Hospital were subjected to a protein loading test to measure their renal reserve. Each subject had to eat a 100 gram cooked chicken meat and timed 2 hours urine collections before and after the test meal were done to measure the creatinine clearances. The 62 healthy subjects showed a mean renal reserve (creatinine clearance after protein loading-baseline creatinine clearance) of 31.0 ml/min. The 31 subjects with various kidney diseases showed a mean renal reserve of 13.5 ml/min. The 19 renal transplant recipients showed renal reserve of 13.2 ml/min. The 12 nephrectomised donors showed renal reserve of 5.4ml/min. Renal reserve may be used to assess suitability of living related transplant donor for nephrectomy.

Study site: Nephrology Clinic, Kuala Lumpur General Hospital

Matched MeSH terms: Kidney Diseases/physiopathology
Fulltext Historical development of the renal histopathology services in Malaysia

Looi LM, Cheah PL

Malays J Pathol, 2009 Jun;31(1):11-6.
PMID: 19694308 MyJurnal

Western-style medicine was introduced to Malaya by the Portuguese, Dutch and British between the 1500s and 1800s. Although the earliest pathology laboratories were developed within hospitals towards the end of the 19th Century, histopathology emerged much later than the biochemistry and bacteriology services. The University Departments of Pathology were the pioneers of the renal histopathology diagnostic services. The Department of Pathology, University of Malaya (UM) received its first renal biopsy on 19 May 1968. Hospital Universiti Kebangsaan Malaysia (HUKM) and Hospital Universiti Sains Malaysia (HUSM) started their services in 1979 and 1987 respectively. It is notable that the early services in these University centres caterred for both the university hospitals and the Ministry of Health (MOH) until the mid-1990s when MOH began to develop its own services, pivoted on renal pathologists trained through Fellowship programmes. Currently, key centres in the MOH are Kuala Lumpur Hospital, Sultanah Aminah Hospital Johor Bahru and Malacca Hospital. With the inclusion of renal biopsy interpretation in the Master of Pathology programmes, basic renal histopathology services became widely available throughout the country from 2000. This subsequently filtered out to the private sector as more histopathologists embraced private practice. There is now active continuing professional development in renal histopathology through clinicopathological dicussions, seminars and workshops. Renal research on amyloid nephropathy, minimal change disease, IgA nephropathy, fibrillary glomerulonephritis, lupus nephritis and microwave technology have provided an insight into the patterns of renal pathology and changing criteria for biopsy. More recently, there has been increasing involvement of renal teams in clinical trials, particularly for lupus nephritis and renal transplant modulation.

Matched MeSH terms: Kidney Diseases/physiopathology
Renal outcome following on- and off-pump coronary artery bypass graft surgery

Ooi JS, Abdul Rahman MR, Shah SA, Dimon MZ

Asian Cardiovasc Thorac Ann, 2008 Dec;16(6):468-72.
PMID: 18984756

A prospective study was carried out to compare the outcomes of patients with preexisting non-dialysis-dependent renal dysfunction who underwent coronary artery bypass grafting with or without cardiopulmonary bypass. Elective off-pump coronary artery bypass was performed in 29 patients with renal dysfunction. Their results were compared with those of a similar group of 35 patients who underwent the conventional on-pump coronary artery grafting. There was a significant deterioration in creatinine clearance in the on-pump group on days 1, 2, and 4 after surgery, while creatinine clearance in the off-pump group remained close to the baseline level. Both groups had improved to the preoperative creatinine clearance values on follow-up at 4 weeks. It was concluded that off-pump surgery provided better renal protection than the conventional on-pump technique in patients with preexisting non-dialysis-dependent renal dysfunction.

Matched MeSH terms: Kidney Diseases/physiopathology
Fulltext Estimating glomerular filtration rate in adult kidney transplant recipients in the Asian population

Kamaruzaman L, Mohd R, Zaki FM, Hod R, Aziz AA

Saudi J Kidney Dis Transpl, 2019 6 30;30(3):587-596.
PMID: 31249222 DOI: 10.4103/1319-2442.261331

Estimation of glomerular filtration rate (GFR) in renal transplant patients is often assessed by application of creatinine-based equations. The aim was to correlate the estimated GFR (eGFR) using creatinine-based equations [Cockroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Nankivell] with gold standard 51Cr-EDTA in kidney transplant patients in the Asian population. This is a single-center, cross-sectional study involving adult renal transplant patients. Background demographic data, medications, office blood pressure, and baseline investigations were taken. Correlations between measured GFR and eGFR were analyzed and Pearson's correlation coefficients, bias, and accuracy were assessed. Thirty-seven renal transplant patients with a mean age of 46 ± 13 years were recruited. Majority were Chinese (68%), Malay (24%), and Indian (8%). The median duration of the transplant was 84 (interquartile range 60,132) months. The mean measured GFR was 71 ± 21 mL/min/1.73 m2. Cockroft-Gault and CKD-EPI has the best correlation with 51Cr-EDTA with Pearson correlation coefficients of 0.733 (P <0.001) and 0.711 (P < 0.001), respectively. All formulae showed >80% accuracy with eGFR lies between 30% of the measured value. CKD-EPI and MDRD had the greatest accuracy with 89.2% each. Clinician may use any of these three serum creatinine-based equations to estimate GFR in kidney transplant recipients.

Matched MeSH terms: Kidney Diseases/physiopathology
Fulltext Alpha1B-adrenoceptors mediate adrenergically-induced renal vasoconstrictions in rats with renal impairment

Khan MA, Sattar MA, Abdullah NA, Johns EJ

Acta Pharmacol Sin, 2008 Feb;29(2):193-203.
PMID: 18215348 DOI: 10.1111/j.1745-7254.2008.00727.x

This study examined whether alpha1B-adrenoceptors are involved in mediating adrenergically-induced renal vasoconstrictor responses in rats with pathophysiological and normal physiological states.

Matched MeSH terms: Kidney Diseases/physiopathology*
Effect of antisense oligodeoxynucleotides for ICAM-1 on renal ischaemia-reperfusion injury in the anaesthetised rat

Kiew LV, Munavvar AS, Law CH, Azizan AN, Nazarina AR, Sidik K, et al.

J Physiol, 2004 Jun 15;557(Pt 3):981-9.
PMID: 15047774

An antisense oligodeoxynucleotide (As-ODN) to the 3' untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia-reperfusion injury in the rat. Wistar-Kyoto rats receiving i.v. either lipofectin-As-ODN (As-ODN group), lipofectin-reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three- to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia-reperfusion injury.

Matched MeSH terms: Kidney Diseases/physiopathology
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 Diseases/physiopathology
Fulltext Clinical efficacy and feasibility of whey protein isolates supplementation in malnourished peritoneal dialysis patients: A multicenter, parallel, open-label randomized controlled trial

Sahathevan S, Se CH, Ng S, Khor BH, Chinna K, Goh BL, et al.

Clin Nutr ESPEN, 2018 06;25:68-77.
PMID: 29779821 DOI: 10.1016/j.clnesp.2018.04.002

BACKGROUND AND AIMS: Poor dietary intake is commonly associated with malnutrition in the dialysis population and oral nutritional supplementation is strategized to redress dietary inadequacy. Knowledge on clinical efficacy of whey protein supplementation (WPS) as an option to treat malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients is limited.
METHODS: This multicenter, parallel, open-label, randomized controlled trial investigated the clinical efficacy of WPS in 126 malnourished CAPD patients with serum albumin <40 g/L and body mass index (BMI) <24 kg/m2. Patients randomized to the intervention group (IG, n = 65) received protein powder (27.4 g) for 6 months plus dietary counseling (DC) while the control group (CG, n = 61) received DC only. Anthropometry, biochemistry, malnutrition-inflammation-score (MIS), dietary intake inclusive of dialysate calories, handgrip strength (HGS) and quality of life (QOL) were assessed at baseline and 6 months. Clinical outcomes were assessed by effect size (Cohen's d) comparisons within and between groups.
RESULTS: Seventy-four patients (n = 37 per group) completed the study. Significantly more IG patients (59.5%) achieved dietary protein intake (DPI) adequacy of 1.2 g/kg per ideal body weight (p 0.05). A higher DPI paralleled significant increases in serum urea (mean Δ: IG = +2.39 ± 4.36 mmol/L, p = 0.002, d = 0.57 vs CG = -0.39 ± 4.59 mmol/L, p > 0.05, d = 0.07) and normalized protein catabolic rate, nPCR (mean Δ: IG = +0.11 ± 0.14 g/kg/day, p 0.05, d = 0.09) for IG compared to CG patients. Although not significant, comparison for changes in post-dialysis weight (mean Δ: +0.64 ± 1.16 kg vs +0.02 ± 1.36 kg, p = 0.076, d = 0.58) and mid-arm circumference (mean Δ: +0.29 ± 0.93 cm vs -0.12 ± 0.71 cm, p = 0.079, d = 0.24) indicated trends favoring IG vs CG. Other parameters remained unaffected by treatment comparisons. CG patients had a significant decline in QOL physical component (mean Δ = -6.62 ± 16.63, p = 0.020, d = 0.47). Using changes in nPCR level as a marker of WPS intake within IG, 'positive responders' achieved significant improvement in weight, BMI, skinfold measures and serum urea (all p 0.05).
CONCLUSION: A single macronutrient approach with WPS in malnourished CAPD patients was shown to achieve DPI adequacy and improvements in weight, BMI, skin fold measures, serum urea and nPCR level. CLINICAL TRIAL REGISTRY: www.clinicaltrials.gov (NCT03367000).

Matched MeSH terms: Kidney Diseases/physiopathology