Publications by authors named "Darin J Treleaven"

9 Publications

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Risk Factors for 1-Year Graft Loss After Kidney Transplantation: Systematic Review and Meta-Analysis.

Clin J Am Soc Nephrol 2019 11 20;14(11):1642-1650. Epub 2019 Sep 20.

Department of Health Research Methods, Evidence, and Impact and.

Background And Objectives: With expansion of the pool of kidney grafts, through the use of higher-risk donors, and increased attention to donor management strategies, the 1-year graft survival rate is subject to change. It is, therefore, useful to elucidate 1-year graft survival rates by dissecting the characteristics of the low-risk and high-risk kidney transplant cases. The objective of our study was to evaluate factors purported to influence the risk of 1-year graft loss in kidney transplant recipients.

Design, Setting, Participants, & Measurements: We searched bibliographic databases from 2000 to 2017 and included observational studies that measured the association between donor, recipient, the transplant operation, or early postoperative complications, and 1-year death-censored graft loss.

Results: We identified 35 eligible primary studies, with 20 risk factors amenable to meta-analysis. Six factors were associated with graft loss, with moderate to high degree of certainty: donor age (hazard ratio [HR], 1.11 per 10-year increase; 95% confidence interval [95% CI], 1.04 to 1.18), extended criteria donors (HR, 1.35; 95% CI, 1.28 to 1.42), deceased donors (HR, 1.54; 95% CI, 1.32 to 1.82), number of HLA mismatches (HR, 1.08 per one mismatch increase; 95% CI, 1.07 to 1.09), recipient age (HR, 1.17 per 10-year increase; 95% CI, 1.09 to 1.25), and delayed graft function (HR, 1.89; 95% CI, 1.46 to 2.47) as risk factors for 1-year graft loss. Pooled analyses also excluded, with a high degree of certainty, any associations of cold ischemia time, recipient race, pretransplant body mass index, diabetes, and hypertension with 1-year graft loss.

Conclusions: Recipient age, donor age, standard versus extended criteria donor, living versus deceased donor, HLA mismatch, and delayed graft function all predicted 1-year graft survival. The effect of each risk factor is small.
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http://dx.doi.org/10.2215/CJN.05560519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832056PMC
November 2019

A Mendelian Randomization-Based Approach to Identify Early and Sensitive Diagnostic Biomarkers of Disease.

Clin Chem 2019 03 18;65(3):427-436. Epub 2018 Oct 18.

Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada;

Background: Identifying markers of chronic kidney disease (CKD) that occur early in the disease process and are specific to loss of kidney function rather than other underlying causes of disease may allow earlier, more accurate identification of patients who will develop CKD. We therefore sought to identify diagnostic blood markers of early CKD that are caused by loss of kidney function by using an innovative "reverse Mendelian randomization" (MR) approach.

Methods: We applied this technique to genetic and biomarker data from 4147 participants in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial, all with known type 2 diabetes, impaired fasting glucose, or impaired glucose tolerance. Two-sample MR was conducted using variants associated with creatinine-based eGFR (eGFR) from the CKDGen Consortium (n = 133814) to estimate the effect of genetically decreased eGFR on 238 serum biomarkers.

Results: With reverse MR, trefoil factor 3 (TFF3) was identified as a protein that is increased owing to decreased eGFR (β = 1.86 SD per SD decrease eGFR; 95% CI, 0.95-2.76; = 8.0 × 10). Reverse MR findings were consistent with epidemiological associations for incident CKD in ORIGIN (OR = 1.28 per SD increase in TFF3; 95% CI, 1.18-1.38; = 4.58 × 10). Addition of TFF3 significantly improved discrimination for incident CKD relative to eGFR alone (net reclassification improvement = 0.211; = 9.56 × 10) and in models including additional risk factors.

Conclusions: Our results suggest TFF3 is a valuable diagnostic marker for early CKD in dysglycemic populations and acts as a proof of concept for the application of this novel MR technique to identify diagnostic biomarkers for other chronic diseases.

Clinicaltrialsgov Identifier: NCT00069784.
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http://dx.doi.org/10.1373/clinchem.2018.291104DOI Listing
March 2019

Risk of serious gastrointestinal bleeding in living kidney donors.

Clin Transplant 2014 May 11;28(5):530-9. Epub 2014 Apr 11.

Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada; Division of Nephrology, Department of Medicine, Western University, London, ON, Canada.

Individuals with moderate-to-severe reduced renal function have greater risk of gastrointestinal bleeding than those with normal renal function. We conducted a retrospective matched cohort study to assess whether living kidney donors share a similar risk. We reviewed pre-donation charts for living kidney donations from 1992 to 2009 in Ontario, Canada, and linked this information to healthcare databases. We selected healthy non-donors from the general population and matched ten non-donors to every donor. Of the 2009 donors and 20,090 matched non-donors, none had evidence of gastrointestinal bleeding prior to cohort entry. The cohort was followed for a median of 8.4 yr (maximum 19.7 yr; loss to follow-up <7%). There was no significant difference in the rate of hospitalization with gastrointestinal bleeding in donors compared to non-donors (18.5 vs. 14.9 events per 10,000 person-years; rate ratio 1.24; 95% confidence interval [CI] 0.85-1.81). Similar results were obtained when we assessed the time to first hospitalization with gastrointestinal bleeding (hazard ratio 1.25, 95% CI 0.87-1.79). In conclusion, we found living kidney donation was not associated with a higher risk of hospitalization with gastrointestinal bleeding. These results are reassuring for the safety of the practice.
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http://dx.doi.org/10.1111/ctr.12344DOI Listing
May 2014

Estimated GFR reporting influences recommendations for dialysis initiation.

J Am Soc Nephrol 2013 Nov 29;24(11):1737-42. Epub 2013 Aug 29.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada;

Automated reporting of estimated GFR (eGFR) with serum creatinine measurement is now common. We surveyed nephrologists in four countries to determine whether eGFR reporting influences nephrologists' recommendations for dialysis initiation. Respondents were randomly allocated to receive a survey of four clinical vignettes that included either serum creatinine concentration only or serum creatinine and the corresponding eGFR. For each scenario, the respondent was asked to rank his or her likelihood of recommending dialysis initiation on a modified 8-point Likert scale, ranging from 1 ("definitely not") to 8 ("definitely would"). Analysis of the 822 eligible responses received showed that the predicted likelihood of recommending dialysis increased by 0.55 points when eGFR was reported (95% confidence interval, 0.33 to 0.76), and this effect was larger for eGFRs >5 ml/min per 1.73 m(2) (P<0.001). Subgroup analyses suggested that physicians who had been in practice ≥13 years were more affected by eGFR reporting (P=0.03). These results indicate that eGFR reporting modestly increases the likelihood that dialysis is recommended, and physicians should be aware of this effect when assessing patients with severe CKD.
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http://dx.doi.org/10.1681/ASN.2013010035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810082PMC
November 2013

Acute dialysis risk in living kidney donors.

Nephrol Dial Transplant 2012 Aug 30;27(8):3291-5. Epub 2012 Jan 30.

Department of Medicine, Division of Nephrology, University of Western Ontario, London, Canada.

Background: Reduced kidney function confers a higher risk of acute kidney injury at the time of an inciting event, such as sepsis. Whether the same is true in those with reduced renal mass from living kidney donation is unknown.

Methods: We conducted a population-based matched cohort study of all living kidney donors in the province of Ontario, Canada who underwent donor nephrectomy from 1992 to 2009. We manually reviewed the medical records of these living kidney donors and linked this information to provincial health care databases. Non-donors were selected from the healthiest segment of the general population.

Results: There were 2027 donors and 20 270 matched non-donors. The median age was 43 years (interquartile range 34-50) and individuals were followed for a median of 6.6 years (maximum 17.7 years). The primary outcome was acute dialysis during any hospital stay. Reasons for hospitalization included infectious diseases, cardiovascular diseases and hematological malignancies. Only one donor received acute dialysis in follow-up (6.5 events per 100 000 person-years), a rate which was statistically no different than 14 non-donors (9.4 events per 100 000 person-years).

Conclusions: These results are reassuring for the practice of living kidney donation. Longer follow-up of this and other donor cohorts will provide more precise estimates about this risk.
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http://dx.doi.org/10.1093/ndt/gfr802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408936PMC
August 2012

Use of erythropoietins in patients with renal transplants.

BMJ 2009 Oct 23;339:b3825. Epub 2009 Oct 23.

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http://dx.doi.org/10.1136/bmj.b3825DOI Listing
October 2009

Risk factors for increased variability in dialysis delivery in haemodialysis patients.

Nephrol Dial Transplant 2003 Oct;18(10):2112-7

McMaster University, Department of Medicine, Hamilton, ON, L8N 1Y2 Canada.

Background: Numerous events may occur during a haemodialysis session, leading to variation in the quantity of dialysis received. The purpose of this study was to identify risk factors for variability in haemodialysis delivery.

Methods: Variability in dialysis delivery was expressed by the coefficient of variation (CV%) and calculated for the volume of blood processed (VBP) for all treatments and the monthly urea reduction ratio (URR) in each patient over an 8 month period. The univariate and multivariate relationships between various predictor variables and the URR and VBP CV% were determined.

Results: Eighty-nine patients were identified who met study criteria. The mean VBP and URR CV% were 10.3 +/- 4.7 and 5.4 +/- 3.8%, respectively. Patients with tunnelled catheters and total nursing-care patients had higher VBP and URR CV%, as evaluated by multivariate analysis. Patients with inadequate dialysis (mean URR <65%) had a higher VBP CV% than those patients with mean URR values > or =65% (14.8 +/- 5.4 vs 9.7 +/- 4.5%; P = 0.01). An accurate determination of the URR in 90% of patients required 14 measurements in patients with catheters vs three and two measurements in arteriovenous fistulae and polytetrafluoroethylene grafts, respectively.

Conclusions: This study demonstrated that the use of a venous tunnelled catheter and dialysis in a total nursing-care unit were the only factors independently associated with greater variability in both VBP and URR. Attention to individual dialysis sessions in patients with tunnelled catheters or in a total nursing-care unit is prudent, particularly when identifying reasons for under-dialysis.
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http://dx.doi.org/10.1093/ndt/gfg297DOI Listing
October 2003

Prognostic value of myocardial perfusion studies in patients with end-stage renal disease assessed for kidney or kidney-pancreas transplantation: a meta-analysis.

J Am Soc Nephrol 2003 Feb;14(2):431-9

Department of Medicine, Division of Nephrology, McMaster University, Hamilton, Ontario, Canada.

The prognostic utility of myocardial perfusion studies (MPS) such as thallium scintigraphy and dobutamine stress echocardiography (DSE) for stratifying cardiac risk among candidates for kidney or kidney-pancreas transplantation is uncertain. This study is a meta-analysis to determine the prognostic significance of MPS results on future myocardial infarction (MI) and cardiac death (CD) in patients with end-stage renal disease (ESRD) assessed for kidney or kidney-pancreas transplantation. MEDLINE was searched using combinations of MeSH headings and text words for transplantation, coronary artery disease, prognosis, end-stage renal disease, and noninvasive cardiac testing (nuclear scintigraphy and DSE) for primary studies. Studies were included if they reported MPS results and cardiac events in patients assessed for kidney or kidney-pancreas transplantation. Methodologic study quality and outcome data were independently abstracted in duplicate by two researchers. The relative risks (RR) of MI and CD were calculated using a random effects model. Twelve articles met all inclusion criteria; 12 studies reported CD, and 9 reported MI. In eight studies, thallium scintigraphy was used (four with pharmacologic stress, four with exercise stress), whereas four used DSE. When compared with negative tests, positive tests had a significantly increased RR of MI (2.73 [95% CI, 1.25 to 5.97]; P = 0.01) and CD (2.92 [95% CI, 1.66 to 5.12]; P < 0.001). Subgroup analyses of studies of diabetic patients indicated that positive tests were associated with a RR of CD 3.95 (95% CI, 1.48 to 10.5; P = 0.006) and a RR of MI 2.68 (95% CI, 0.95 to 7.57; P = 0.06) when compared with negative tests. In studies evaluating mixed populations of diabetic and nondiabetic patients, positive tests were associated with a RR of CD 2.52 (95% CI, 1.25 to 5.08; P = 0.01) and with a RR of MI 2.79 (95% CI, 0.85 to 9.21; P = 0.09) when compared with a negative test. The presence of reversible defects was associated with an increased risk of MI in diabetic patients and of CD in both subgroups; fixed defects were associated with an increased risk of CD but not MI. It is concluded that positive MPS are useful in identifying patients with significantly increased risk of future MI and CD in both diabetic and nondiabetic ESRD patients.
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http://dx.doi.org/10.1097/01.asn.0000047560.51444.3aDOI Listing
February 2003

Comparison of volume of blood processed on haemodialysis adequacy measurement sessions vs regular non-adequacy sessions.

Nephrol Dial Transplant 2002 Aug;17(8):1470-4

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Background: Knowledge that adequacy measures such as the urea reduction ratio (URR) or Kt/V(urea) are being measured on haemodialysis may influence the behaviour of patients or staff such that the treatment may be better on those days. This study therefore tested the hypothesis that mean volume of blood processed (VBP), utilized as a surrogate for adequacy, is higher on adequacy measurement days than non-measurement days.

Methods: Patients were identified who had been on haemodialysis over the preceding 8 months. Primary outcome was the difference in the mean VBP (in litres) on URR measurement compared with non-URR measurement days (DeltaVBP(U)(-N)). Univariate and multivariate correlates of mean VBP and DeltaVBP(U)(-N) were also determined.

Results: Eighty-nine patients were identified who met inclusion and exclusion criteria. Linear regression demonstrated a weak relationship between VBP and URR (r=0.24, P<0.02). This relationship was much stronger when VBP was adjusted for patient weight (mean VBP/weight; r=0.78, P<0.0001). The overall mean VBP was 87.4 l (+/-1.2 l) and the average DeltaVBP(U)(-N) was 1.1 l (+/-0.3 l) (P=0.001). Twenty per cent of patients had a clinically relevant DeltaVBP(U)(-N) of >3.6 l. Patients with a graft or fistula had a significantly higher DeltaVBP(U)(-N) than patients with a tunnelled catheter.

Conclusions: This study demonstrates that the average VBP is less on non-URR than on URR measurement days; this difference was clinically important in >20% of patients. Univariate analysis indicated that the use of a fistula or graft correlated with a higher DeltaVBP(U)(-N). This implies that our current method of assessing dialysis adequacy does systematically overestimate the average delivered dose of dialysis in a subset of patients.
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http://dx.doi.org/10.1093/ndt/17.8.1470DOI Listing
August 2002
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