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Papers by Robert Walker

The American Journal of Clinical Nutrition, 2010

Objectives: The survival time of red blood cells (RBCs) is commonly determined based on labelling... more Objectives: The survival time of red blood cells (RBCs) is commonly determined based on labelling experiments and an estimate of the mean RBC lifespan is obtained [1]. However, a better insight into the processes of RBC destruction would be desirable, especially in pathological states such as anaemia of chronic kidney disease (CKD), where the lifespan of RBCs is decreased [2] due to either an increase in random destruction or an accelerated senescence. A previously developed model for RBC survival that accounts for plausible processes of RBC destruction [3,4] was applied to clinical data, and differences in the RBC lifespan in anaemic CKD patients compared to healthy controls were investigated. Methods: RBC survival data using radioactive chromium as a random labelling method was available from 14 CKD patients receiving haemodialysis and 14 controls. The data were modelled based on two approaches: (1) a two-stage approach in MATLAB using generalized least squares; and (2) a full pop...

Nephrology Dialysis Transplantation, 1997

Introduction Background. Plasma cholesteryl ester transfer activity is increased in patients with... more Introduction Background. Plasma cholesteryl ester transfer activity is increased in patients with chronic renal failure on Transfer of cholesteryl esters from high-density lipodialysis who have elevated levels of apolipoprotein proteins (HDL) to other lipoproteins is catalysed by B (apoB)-containing lipoproteins. Simvastatin, a 3-hycholesteryl ester transfer protein in plasma and is part droxy-3-methylglutaryl coenzyme A (HMG CoA) of a pathway which returns cholesterol from peripheral reductase inhibitor, reduces levels of these lipoproteins tissues to the liver where the sterol can be excreted but the effect of treatment on cholesteryl ester transfer (reverse cholesterol transport). In this pathway, tissue activity in patients on dialysis remains to be cholesterol is bound by HDL, esterified by lecithin:chodetermined. lesterol acyltransferase (LCAT) activity and a substan-Methods. We measured serum newly synthesized choletial portion of the newly synthesized cholesteryl esters steryl ester transfer (NCET) activity, lecithin:cholesare transferred to apolipoprotein B(apoB)-containing terol acyltransferase (LCAT) activity and serum lipid, lipoproteins [1 ] which are removed from the circulation lipoprotein and apolipoprotein concentrations before by hepatic receptors. If this clearance is inefficient then and immediately after 6 months treatment with simvasplasma levels of apoB-containing lipoproteins increase tatin (10 mg daily, n=24) or placebo (n=29) in 53 and transfer of cholesteryl esters to these acceptors is patients with chronic renal failure receiving haemodiaaccelerated [2]. Thus treatment with drugs such as lysis or continuous ambulatory peritoneal dialysis 3-hydroxy-3-methylglutaryl Coenzyme A (HMG CoA) (CAPD). reductase inhibitors that up-regulate hepatic apoB,E Results. Simvastatin therapy significantly reduced receptor numbers and reduce plasma levels of apoBserum cholesterol, LDL cholesterol, apoB concentralipoproteins should also reduce plasma cholesteryl ester tions, and both NCET (P=0.001) and LCAT (P= transfer activity. 0.012) rates. The decrease in NCET activity was correl-The effect of HMG CoA reductase inhibitors on ated significantly with the corresponding decrease in plasma cholesteryl ester transfer activity has been apoB concentration (r=0.715, P<0.001) and LCAT documented in familial hypercholesterolaemia [2,3], activity (r=0.715, P<0.001) during simvastatin non-insulin-dependent diabetes mellitus [4 ] and in northerapy and was no longer significant when apoB molipidaemic subjects [5 ]. A decrease in plasma cholesconcentration (P=0.14) or LCAT activity (P=0.07) teryl ester mass transfer activity was observed in most were controlled. but not all [3 ] studies. In patients with familial hyperch-Conclusions. These data show that simvastatin therapy olesterolaemia the decrease in plasma cholesteryl ester reduces serum NCET rates, and suggest that this may transfer activity has been linked to the concomitant be linked to the concomitant decrease in levels of decrease in LDL particle acceptor concentration during apoB-containing lipoproteins which are acceptors of simvastatin therapy [2]. The effect of simvastatin transferred cholesteryl esters, and to the decrease in therapy on plasma cholesteryl ester transfer activity in serum LCAT rates in patients with chronic renal failure patients with chronic renal failure has not been studied. with treatment. In patients with chronic renal failure, plasma levels Key words: cholesteryl ester transfer; dialysis; of cholesteryl ester acceptor lipoproteins including simvastatin VLDL, intermediate density lipoprotein (IDL) and other remnants of triglyceride-rich lipoprotein metabolism, are frequently elevated and HDL levels are Correspondence and offprint requests to: Robert J. Walker, low [6-8]. We have previously documented increased

Australian and New Zealand Journal of Medicine, 1998

Anaesthesia and surgery alter renal function. Inhibition of prostaglandin synthesis by non-steroi... more Anaesthesia and surgery alter renal function. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs (NSAIDs) administered with anaesthesia may further compromise renal function. To study the effects of tenoxicam (NSAID) administered immediately prior to anaesthesia on renal function in normal individuals undergoing routine surgery. A randomised single blind placebo controlled study comparing tenoxicam (40 mg intravenously) with placebo was carried out in 20 healthy (ASA I) patients undergoing lower spinal surgery. Glomerular filtration rate (GFR) was determined by creatinine clearance and renal tubular function measured as osmolar and free water clearance. GFR fell by 60% at the end of surgery but returned to pre-operative values by six hours post-operatively. There was no difference between placebo or tenoxicam with regard to changes in GFR. Tubular function was not altered by tenoxicam. Current clinical practice of using NSAIDs for post-operative analgesia in low risk individuals appears to have no adverse effects on renal function.

Medicine & Science in Sports & Exercise, 1994

Nonsteroidal anti-inflammatory drugs (NSAID) are frequently used in sports medicine but few studi... more Nonsteroidal anti-inflammatory drugs (NSAID) are frequently used in sports medicine but few studies have documented their potential importance in modifying exercise-induced changes in renal function. The effects of indomethacin (50 mg orally every 8 h for 36 h) on renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in eight fit healthy males (age 21-42) before and after 30-min treadmill exercise at 80% VO2max and during 120-min recovery. Each volunteer served as their own control. There were no differences between control and indomethacin for the resting values of RBF, GFR, or renal vascular resistance (RVR). Using analysis of variance for repeated measures, indomethacin produced a significant reduction in RBF compared with control (P = 0.009) that was associated with a significant elevation in RVR (P = 0.027). Changes in GFR mirrored the changes in RBF but differences failed to reach statistical significance. These results suggest that with sustained exercise indomethacin can compromise renal function and potentiate the risk of developing acute renal failure. Indomethacin and other NSAID are widely used in the sports arena, and athletes should be warned of the potential danger of their use when renal function may be compromised.

Journal of Clinical Pharmacy and Therapeutics, 1995

Ciprofloxacin is a broad spectum quinolone antibiotic. Side effects reported include nausea and o... more Ciprofloxacin is a broad spectum quinolone antibiotic. Side effects reported include nausea and other gastrointestinal symptoms; skin and musculoskeletal side effects may also occur. No bleeding abnormalities or alteration in coagulation have been documented. We report a case where ciprofloxacin appeared to contribute to an idiosyncratic prolongation of bleeding time although a rechallenge 8 months later did not reproduce the effect. Moreover, subsequent investigation of the influence of ciprofloxacin on bleeding parameters in 10 healthy volunteers demonstrated no alterations in bleeding parameters.

Arteriosclerosis, Thrombosis, and Vascular Biology, 1999

Paraoxonase is an enzyme associated with HDL in human serum that hydrolyzes oxidized phospholipid... more Paraoxonase is an enzyme associated with HDL in human serum that hydrolyzes oxidized phospholipids and inhibits LDL oxidation, which is an important step in atherogenesis. In animals, addition of oxidized lipids to the circulation reduces paraoxonase activity, and diets rich in oxidized fat accelerate the development of atherosclerosis. The current randomized, crossover study was designed to compare the effect of a meal rich in oxidized lipids in the form of fat that had been used for deep-frying in a fast food restaurant and a control meal rich in the corresponding unused fat on postprandial serum paraoxonase (arylesterase) activity and peroxide content of LDL and its susceptibility to copper ion catalyzed oxidation in 12 healthy men. Four hours into the postprandial period, serum paraoxonase activity had decreased significantly after the used fat meal (Ϫ17%, Pϭ0.005) and had increased significantly after the meal rich in unused fat (14%, Pϭ0.005). These changes were significantly (Pϭ0.003) different. A time-course study indicated that serum paraoxonase activity remained lower than baseline for up to 8 hours after the used fat meal. Serum apoA1 concentration tended to decrease after the unused fat meal and tended to increase after the used fat meal. These changes were different at a marginal level of significance (Pϭ0.07). Also, a significantly (Pϭ0.03) greater decrease in apoA1 content of postprandial HDL was recorded after the unused fat meal. The peroxide content of LDL tended to decrease after the used fat meal and tended to increase after the control meal. These changes were significantly (Pϭ0.04) different. Susceptibility of isolated LDL to copper ion oxidation and plasma levels of malondialdehyde were unchanged during the study. These data suggest that in the postprandial period after a meal rich in used cooking fat, the enzymatic protection of LDL against accumulation of peroxides and atherogenic oxidative modification may be reduced, possibly due to factors associated with apoA1, without acutely affecting the intrinsic resistance of LDL to in vitro oxidation.

AJP: Regulatory, Integrative and Comparative Physiology, 2006

Exercise increases mean body temperature (T̄body) and cytokine concentrations in plasma. Cytokine... more Exercise increases mean body temperature (T̄body) and cytokine concentrations in plasma. Cytokines facilitate PG production via cyclooxygenase (COX) enzymes, and PGE2 can mediate fever. Therefore, we used a COX-2 inhibitor to test the hypothesis that PG-mediated pyrogenicity may contribute to the raised T̄body in exercising humans. In a double-blind, cross-over design, 10 males [age: 23 yr (SD 5), V̇o2 max: 53 ml·kg−1·min−1 (SD 5)] consumed rofecoxib (50 mg/day; NSAID) or placebo (PLAC) for 6 days, 2 wk apart. Exercising thermoregulation was measured on day 6 during 45-min running (∼75% V̇o2 max) followed by 45-min cycling and 60-min seated recovery (28°C, 50% relative humidity). Plasma cytokine (TNF-α, IL-10) concentrations were measured at rest and 30-min recovery. T̄body was similar at rest in PLAC (35.59°C) and NSAID (35.53°C) and increased similarly during running, but became 0.33°C (SD 0.26) lower in NSAID during cycling (37.39°C vs. 37.07°C; P = 0.03), and remained lower thro...

Diabetes Care, 2004

OBJECTIVE—Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased a... more OBJECTIVE—Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance. Vitamin E improves glycemic control in people with diabetes. We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS—Eighty overweight individuals (BMI >27 kg/m2) were randomly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months. The dose of vitamin E was increased to 1,200 IU per day for a further 3 months. RESULTS—Plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point. At 3 months, fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model ...

Nephrology Dialysis Transplantation, 2004

Journal of Cardiovascular Pharmacology, 2009

Cardiopulmonary bypass (CPB) is associated with a significant risk of postoperative renal dysfunc... more Cardiopulmonary bypass (CPB) is associated with a significant risk of postoperative renal dysfunction. We studied the utility of a novel biomarker in predicting acute kidney injury (AKI) in adult patients undergoing cardiac surgery. Blood and urine were obtained from 50 patients undergoing CPB-requiring surgery. Patients were divided into group A (n=41) with normal creatinine pre-bypass and post-bypass and group B (n=9) who developed an increase in serum creatinine of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.5 mg/dL within the first 48 hours post CPB. Plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL) was determined at baseline and 2 hours after CPB.Plasma levels of NGAL were higher in patients who developed AKI [214+/-16.7 ng/mL (95% CI 176.9-252.9)] compared with those who did not [149.5+/-13.5 ng/mL (95% CI 122.1-175.7); P=0.035]. Two hours after CPB, there was a significant increase (P=0.0003) in NGAL levels, greater in those patients who developed AKI [476.1+/-41.1 ng/mL (95% CI 380.6-571.6); P=0.0003] compared with those who did not [278.4+/-22 ng/mL (95% CI 233.9-323.0)]. In the AKI group, urinary NGAL increased from 7.13+/-2.30 ng/mL (95% CI 2.5-11.8) to 2924+/-786 ng/mL (95% CI 1110-4739). In the non-AKI group, there was an increase from 1.6+/-0.6 (95% CI 0.3-3.0) to 749+/-179 ng/mL (95% CI 386-1113). The post-CPB levels of urinary NGAL were significantly different in the AKI group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) such that a suitable threshold for use as a diagnostic test could be determined. Receiver operating characteristics were determined for plasma and urinary NGAL with area under the curve (AUC) of 0.80 and 0.96, respectively. For a threshold of 433 ng/mmol creatinine, the test had 90% sensitivity and 78% specificity for the detection of post-CPB renal dysfunction. Measurement of this novel biomarker in the urine or plasma of patients in the first hours after CPB is predictive of subsequent renal injury. Although the AUC for plasma NGAL seemed inferior to urine, even an AUC of 0.8 as reported compares very favorably to that for other &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;outstanding&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; biomarkers (eg, AUCs in the 0.7 range for troponin).

Journal of Endocrinology, 2000

This study was designed to determine the effect of menopause and hormone replacement therapy (HRT... more This study was designed to determine the effect of menopause and hormone replacement therapy (HRT) on plasma cholesteryl ester fatty acid (CEFA) composition and insulin sensitivity and the relationships between these variables in perimenopausal women (aged 40-55 years) including 49 who were premenopausal and 32 who were postmenopausal. Plasma cholesteryl ester proportions of dihomo-gamma-linolenic acid (20:3 n-6) were correlated significantly

Research communications in molecular …, 1996

1. Res Commun Mol Pathol Pharmacol. 1996 Mar;91(3):319-28. Altered cellular biosynthesis in human... more 1. Res Commun Mol Pathol Pharmacol. 1996 Mar;91(3):319-28. Altered cellular biosynthesis in human peritoneal mesothelial cells exposed to dialysis solutions. Bird SD, Walker RJ. Department of Medicine, Otago Medical School Dunedin, New Zealand. ...

In Vitro Cellular & Developmental …, 1994

The effect of a conventional antibiotic (penicillin/streptomycin) mixture on the widely used kidn... more The effect of a conventional antibiotic (penicillin/streptomycin) mixture on the widely used kidney epithelial cell line, LLC-PK 1, was investigated by measuring growth and intracellular free calcium. Free calcium concentration was the same in cells cultured for 3 to 7 wk with ("plus") and without ("minus") antibiotics both at rest and when challenged with high (14 mM) external calcium. When exposed to vasopressin, minus cells exhibited significantly smaller calcium transients than plus cells. A similar difference existed for transients elicited by a calcium ionophore, 4-br-A23187. After longer periods of culture (>20 wk), minus cells grew slower than plus cells but on reaching confluence (minus cells took 1 day longer) the morphologies and viabilities were indistinguishable. The finding that culture with penicillin/streptomycin reversibly modified some properties of LLC-PK1 cells, at least partly through altered calcium homeostasis, is of importance for workers using this cell model to study drug effects and raises the general possibility of similar effects on other cultured cells.

American Journal of Nephrology, 1995

A case of acute oliguric renal failure due to bilateral renal artery occlusion is described. The ... more A case of acute oliguric renal failure due to bilateral renal artery occlusion is described. The renal function was restored to normal 36 h after the embolic event by revascularization with streptokinase.

AJP: Renal Physiology, 2013

There is a lack of suitable animal models that replicate the slowly progressive chronic interstit... more There is a lack of suitable animal models that replicate the slowly progressive chronic interstitial fibrosis that is characteristic of many human chronic nephropathies. We describe a chronic long-term (6-mo) model of lithium-induced renal fibrosis, with minimal active inflammation, which mimics chronic kidney interstitial fibrosis seen in the human kidney. Rats received lithium via their chow (60 mmol lithium/kg food) daily for 6 mo. No animals died during the exposure. Nephrogenic diabetes insipidus was established by 3 wk and persisted for the 6 mo. Following metabolic studies, the animals were killed at 1, 3, and 6 mo and the kidneys were processed for histological and immunohistochemical studies. Progressive interstitial fibrosis, characterized by increasing numbers of myofibroblasts, enhanced transforming growth factor-β1 expression and interstitial collagen deposition, and a minimal inflammatory cellular response was evident. Elucidation of the underlying mechanisms of injury...

Kidney International Reports