In this prospective observational cohort study, we evaluate the change in cardiovascular risk parameters, with a focus on lipids, in live kidney donors 1 year post donation. Body mass index, systolic/diastolic blood pressure, kidney function (chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration) and lipid parameters were measured at baseline and 1 year. Data on 87 live kidney donors were collected. Body mass index increased from 26.5 ± 2.7 pre to 27.4 ± 3.0 kg/m post donation (p < 0.0001). Chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration decreased from 111.8 ± 20.0 pre to 72.1 ± 13.1 mL/min/1.73 m post donation (p < 0.0001). Serum triglyceride levels increased from 0.8 (interquartile range 0.6–1.3) pre to 1.0 mmol/L (interquartile range 0.7–1.6) post donation (p = 0.0004). Statin use increased from 11.5% pre to 21% post donation (p < 0.005). Low-density lipoprotein remained stable, and other lipids (high-density lipoprotein, apolipoprotein B and lipoprotein a) did not change post donation

Doucet, Brian

Hawley, Carmel

Isbel, Nicole

Kaiser, Omar

Kostner, Karam

University of Queensland eSpace

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doi: 10.1111/nep.12792 
 
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Live Donor Study – Implications of Kidney Donation on Cardiovascular Risk with a 
Focus on Lipid Parameters including Lipoprotein a  
Brian Doucet
1,2
, Karam Kostner
1,2
, Omar Kaiser
3
, Carmel Hawley
2,3,4,5
, Nicole  Isbel
2,3 
1
Department of Cardiology, Mater Misericordiae Hospital, Brisbane, Australia; 
2
School of Medicine, University of Queensland, Brisbane, Australia 
3
Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia 
4
Translational Research Institute, Brisbane, Australia 
5
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia 
 
 
Address for Correspondence: Nicloe Isbel, ARTS Building, Princess Alexandra Hospital, 237 
Ipswich rd, Woolloongabba, QLD 4102 
Nikky.isbel@health.qld.gov.au 
Ph 0404834705 
 
SUPPORT AND FINANCIAL DISCLOSURE DECLARATION 
Carmel Hawley has no conflicts to declare. 
Brian Doucet has no conflicts to declare. 
Nicole Isbel has no conflicts to declare. 
Karam Kostner has no conflicts to declare. 
Omar Kaiser has no conflicts to declare. 
  
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Abstract 
In this prospective observational cohort study we evaluate the change in cardiovascular risk 
parameters, with a focus on lipids, in live kidney donors one year post donation.  Body mass 
index (BMI), systolic/diastolic blood pressure, kidney function (51 Cr-EDTA eGFR), and 
lipid parameters were measured at baseline and one year.  Data on 87 live kidney donors was 
collected.  BMI increased from 26.5 ± 2.7 pre to 27.4 ± 3.0 kg/m
2
 post donation (p<0.0001).  
51 Cr-EDTA eGFR decreased from 111.8 ± 20.0 pre to 72.1 ± 13.1 ml/min/1.73m
2
 post 
donation (p<0.0001).  Serum triglyceride levels increased from 0.8 (IQR 0.6-1.3) pre to 1.0 
mmol/l (IQR 0.7–1.6) post donation (p=0.0004).  Statin use increased from 11.5% pre to 21% 
post donation (p<0.005).  LDL remained stable and other lipids (HDL, Apo B, Lp(a)) did not 
change post donation. 
KEYWORDS 
Living donor transplantation; Transplantation; Lipids; Lp(a); Cardiovascular risk 
 
 
 
 
 
 
 
 
 
  
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Introduction 
Living kidney donors take on immediate and long term risks for the benefits that are gained 
by the grafts’ recipients.  Recent studies suggest that live kidney donors are at a small but 
increased risk of progression to end stage kidney disease (ESKD) and cardiovascular events 
when compared to healthy matched donors (1, 2).  Other studies have shown increased 
uraemic toxin levels and small but significant increases in blood pressure and proteinuria in 
live donors (3-5).  These newly appreciated risks call for further investigation into kidney 
donor cardiovascular risk.   
Chronic kidney disease (CKD) is associated with cardiovascular disease risk that increases as 
kidney function declines (6).  Lipoprotein metabolism and function is altered in patients with 
CKD as the renal dyslipidaemic lipid profile demonstrates increased total cholesterol, 
triglycerides and Lp(a) with decreased high-density lipoprotein (HDL) levels (7).  The aim of 
this prospective observational cohort study is to examine cardiovascular risk parameters, with 
a focus on lipid profiles, in living kidney donors pre and post donation. 
Materials and Methods 
Participants and study design 
This study was conducted at a tertiary Australian hospital.  Prospective donors were deemed 
eligible according to the Queensland Renal Transplant Service protocol (8). Enrolment began 
in September 2007.  Participants provided informed consent and ethics approval was obtained 
through the institution’s Human Research Ethics Committee (HREC/2007/078). 
 
 
 
  
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Laboratory Assessment and statistical analysis 
Serum samples were collected from fasting participants before and one year after 
nephrectomy.  Serum total cholesterol, triglycerides, HDL, LDL, and creatinine were 
measured with standard laboratory methods.  The Sebia Hydrasys LC was used to measure 
Lp(a).  Apo A-1 and Apo B were measured with the Siemens BN2 Nephelometer.  Kidney 
function was measured with chromium-51 ethylenediaminetetraacetic acid (EDTA).  
Wedderburn SK-VET scales correct to 0.1kg were used to measure weight.  Height was 
measured using a wall-mounted stadiometer.  Body mass index (BMI) was calculated as 
weight (Kg)/height (m)
2
 and classified according to the World Health Organisation 
classification.  Statistical analysis was performed using Stata (version 12;2012;StataCorp, 
College Station, TX).  The null hypothesis was rejected at the 0.05 level.   
Results 
Baseline Characteristics 
Eighty-seven donors were recruited and followed-up at one year post donation.  Baseline 
Characteristics are listed in Table 1.  Mean donor age was above 51 years and 66% were 
female.  The mean BMI of the participants was 26.5 ± 2.7 Kg/m
2
.  Pre-existing 
cardiovascular disease (1%), anti-hypertensive use (10%), and statin use (11.5%) along with 
family history of hyperlipidaemia (15%) was self-reported by the donors.  51 Cr-EDTA 
eGFR reported the mean baseline eGFR of 111.8 ± 20.0 ml/min/1.73m
2
. 
Longitudinal Changes 
BMI increased following donation by 0.86 kg/m
2 
(0.54, 1.17) (p<0.0001) with an average 
weight gain of 2.43 Kg (1.55, 3.32) (p<0.0001).  The number of obese (BMI 30-35) donors 
increased from 8% to 15% (Figure 1).  No cardiovascular events were observed.  Post 
donation 51 Cr-EDTA eGFR was 72.1 ± 13.1 ml/min/1.73m
2
 with a mean decrease of 39.6 
  
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(42.23, 36.92) ml/min/1.73m
2
 (p<0.0001) (Table 2). There was no significant change in 
systolic or diastolic blood pressure (Table 2).  Statin use increased from 11.5% pre to 21% 
post donation (p<0.005).  Small but statistically significant increases in triglycerides and Apo 
A-1 were observed (Table 2). 
Discussion 
The live donor study is the first prospective study to evaluate cardiovascular risk parameters 
including extensive lipid profiles of kidney donors before and one year after donation.  This 
study identifies an increase in BMI and triglycerides post donation which may have 
implications for donor cardiovascular risk.  Statin use was increased post donation and in this 
setting there was no significant change in total cholesterol, LDL, HDL, Apo B, or Lp(a). 
BMI 
Increased kidney donor BMI of 0.86 kg/m
2
 was observed across this study (Table 2).  The 
percentage of obese donors more than doubled from 8% to 15% at follow-up (Figure 1).  
Previous retrospective studies have identified weight gain and progression to obesity in 
kidney donors (9,10).  This is a concerning finding as obesity is a risk factor for diabetes and 
hypertension and for the development and progression of kidney disease (11-13).  Obesity 
has been associated with the development and progression of renal failure in non-donation 
associated nephrectomy (14).  The observed increase in donor weight may reflect a regain of 
weight lost pre-donation, as specified weight targets are often advised according to unit 
criteria.  Better understanding of the risks of such practices is required.  Overall, weight gain 
and progression to obesity may be a contributor to poor long-term donor outcomes and 
requires further study. 
 
 
  
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eGFR 
Mean one year post donation 51 Cr-EDTA eGFR was 72.1 ml/min/1.73m
2
 (Table 2).  With 
the use of radiolabelled chromium, we report a decrease in donor eGFR of 39.6 
ml/min/1.73m
2
.  
Hypertension 
No change in systolic or diastolic blood pressure was observed and mean donor blood 
pressure remained well controlled post donation (table 2).  Increased blood pressure of 6 
mmHg systolic and 4 mmHg diastolic has been observed within 5 to 10 years post donation 
(4).  This suggests vigilant monitoring for hypertension is required years after donation. 
Lipids 
Concerning donor lipid profiles, median triglyceride levels increased from 0.8 mmol/L to 1.0 
mmol/L (Table 2).  There was no change in total cholesterol, HDL, LDL, or Apo B.  The 
observed increase in Apo A-1 of 0.09 g/L is not clinically significant.  Aside from the 
increase in triglycerides, we did not observe changes consistent with the renal dyslipidaemic 
profile despite the decline in renal function observed.  The mechanism of increased 
triglycerides in donors is not clear, however it may reflect dietary changes post-donation.  
Triglycerides are a well-established cardiovascular risk factor (15), however with the increase 
in median triglycerides to 1.0 mmol/L donors remain in the low risk category.   
Statin use 
Statin use increased from 11% to 21% post donation.  Statins act to decrease total cholesterol, 
decrease triglycerides, decrease LDL, increase HDL, increase Apo A-1 and decrease Apo B 
(16, 17).  No data was collected on the reason for statin commencement, however pre 
donation demographics predictive of starting a statin included total cholesterol, triglycerides, 
  
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LDL, and Apo-B (univariate logistic regression, data not shown).  In view of the small 
number of donors started on statins (n=8), multivariate logistic regression was not 
appropriate.  The increased statin use may have masked changes in other donor lipid 
parameters.         
Lp(a) 
This study helps clarify the role of the kidney in Lp(a) kinetics and the impact of kidney 
donation on Lp(a) related cardiovascular risk.  Lp(a) is believed to be influenced by GFR 
with previous studies reporting increasing Lp(a) levels across all stages of kidney disease 
(18).  The relationship between Lp(a) and GFR has appeared inversely proportional (18).  
Live kidney donors in this study sustained a substantial decrease in eGFR, however we 
observed no corresponding increase in serum Lp(a) levels (Table 2).  The mechanism of 
increased Lp(a) levels in individuals with kidney disease remains uncertain but this data 
suggests that reduced clearance (from 72-111 ml/min/1.73m
2
) may be a concomitant instead 
of causative factor.  Furthermore, individuals with serum Lp(a) levels above 30mg/dl have a 
1.75 fold risk of myocardial infarction (19).  The number of donors with serum Lp(a) levels 
greater than 30mg/dl (29 donors) did not change after donation.  Statins have no Lp(a) 
lowering effects (20) therefore the increased statin use is unlikely to account for these results. 
Limitations 
There are limitations to this study.  Donors are encouraged to achieve optimal weight before 
donation and the observed increased donor BMI may reflect a return to individual baseline.  
No data was collected on weight loss that occurred prior to referral to the transplant unit and 
this is an important area requiring further study.  Increased statin use post donation likely 
influenced lipid outcomes, however no record of factors considered when initiating statins are 
available as statins were commenced by patients’ General Practitioner.  This study presents 
  
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one year follow-up data while long-term follow-up would be better identify which donors 
progress to cardiovascular events and ESKD. 
Conclusions 
This is the first prospective observational cohort study to examine cardiovascular risk 
parameters with a focus on lipid parameters in living kidney donors pre and post donation.  
We found significant increases in BMI and statin use, but overall cardiovascular risk factor 
profiles remained well controlled. This is somewhat reassuring but warrants further longer 
term studies to delineate if there is any increase in cardiovascular risk associated with live 
donor nephrectomy.  
 
 
 
 
 
 
 
 
 
 
 
 
  
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References 
1. Muzaale AD, Massie AB, Wang MC, et al.  Risk of end-stage renal disease following 
kidney donation. JAMA. 2014; 311(6): 579-586. 
2. Mjoen G, Hallan S, Hartmann A, et al.  Long-term risks for kidney donors. Kidney 
Int. 2014; 86(1): 162-167. 
3. Rossi M, Campbell KL, Johnson DW, et al.  Uraemic toxin development in living 
kidney donors: A longitudinal study. Transplantation. 2014; 97(5): 548-554. 
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kidney donors. Ann Intern Med. 2006; 145(3): 185-196. 
5. Garg AX, Muirhead N, Knoll G, et al.  Proteinuria and reduced kidney function in 
living kidney donors: a systematic review, meta-anaylsis, and meta-regression. 
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6. Go AS, Chertow GM, Fan D, et al.  Chronic kidney disease and the risks of death, 
cardiovascular events, and hospitalisation. NEJM.2004; 351: 1296-1305. 
7. Kwan BC, Kronenberg F, Beddhu S, et al.  Lipoprotein metabolism and lipid 
management in chronic kidney disease. J Am Soc Nephrol. 2007; 18: 1246-1261. 
8. The Transplantation Society of Australia and New Zealand (TSANZ).  Kidney 
Protocol – The Allocation of Transplant Kidneys in Australia. TSANZ, Sydney, 
Australia: 2011. 
9. Reese PP, Feldman HI, Asch DA, et al.  Short-term outcomes for obese live kidney 
donors and their recipients. Transplantation. 2009; 88(5): 662-671. 
  
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10. Tavakol MM, Vincenti FG, Assadi H, et al.  Long-term renal function and 
cardiovascular disease risk in obese kidney donors. Clin J Am Soc Nephrol. 2009; 
4(7): 1230-1238. 
11. Afshinnia F, Wilt TJ, Duval S, et al.  Weight loss and proteinuria: systematic review 
of clinical trials and comparative cohorts. Nephrol Dial Transplant. 2010; 25(4): 
1173-1183. 
12. Bolignano D, Zoccali C.  Effects of weight loss on renal function in obese CKD 
patients: a systematic review. Nephrol Dial Transplant. 2013; 28(suppl 4): iv82-iv98. 
doi: 10.1093/ndt.gft302. 
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function and mortality: a cohort study. Lancet Diabetes Endocrinol. 2015; 3(9): 704-
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population based prospective studies. J Cardiovasc Res. 1996; 3: 213-219. 
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J Cardiol. 1998; 14 Suppl B:28B-38. 
17. Bard JM, Parra HJ, Douste-Blazy P, et al.  Effect of pravastatin, an HMG CoA 
reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein 
  
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particles defined by their apolipoprotein composition. Metabolism. 1990; 39(3): 269-
273. 
18. Kronenberg F.  Causes and consequences of lipoprotein (a) abnormalities in kidney 
disease. Clin Exp Nephrol. 2014; 18(2): 234-237. 
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Table 1. Baseline Characteristics 
Characteristic 
 
 
 
Age (years) 51.8 ± 10.4 
Female Gender (n) % 57 (66%) 
BMI (kilograms/meters
2
) 26.5 ± 2.7 
Weight (kilograms) 75.3 ± 12.1 
Cardiovascular Disease (n) % 1 (1%) 
Creatinine (micromoles/litre) 68.5 ± 13.8 
Kidney Function Cr51 EDTA eGFR 
(millilitre/minute/1.73metre
2
)  
111.8 ± 20.0 
Anti-hypertensive use (n) % 9 (10%) 
Systolic Blood Pressure (mmHg) 124.3  ± 11.7 
Diastolic Blood Pressure (mmHg)  76.5 ±8.5 
Family History of Hyperlipidaemia (n) % 13 (15%) 
Statin use (n) % 10 (11.5%) 
Total Cholesterol (millimoles/litre) 5.4 ±  1.1 
Triglycerides (millimoles/litre) 0.8 (0.6, 1.3) 
HDL (millimoles/litre) 1.4 ± 0.4 
LDL (millimoles/litre) 3.5 ± 0.9 
Apo A-1 (grams/litre) 1.6 ± 0.2 
Apo B (grams/litre)  0.98 ± 0.27 
Lp(a) (grams/litre) 0.18 (0.06, 0.46) 
Mean +/- standard deviation; Median (Interquartile Range).  BMI (Body Mass Index), 51 Cr-
EDTA eGFR (Chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration 
rate), Lp(a) (lipoprotein a), HDL (High-Density Lipoprotein), LDL (Low-Density 
Lipoprotein), Apo A-1 (apolipoprotein A-1), Apo B (apolipoprotein B). 
 
 
 
 
 
 
 
 
 
  
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Table 2. Change in characteristics at 1 year post kidney donation 
Characteristic Baseline 1 Year  Delta over one 
year 
P- Value 
Body Mass Index 
(kilograms/meters
2
) 
26.5 ± 2.7 27.4 ± 3.0  0.86 (0.54, 
1.17) 
P< 0.0001 
Weight 
(Kilograms) 
75.3 ± 12.1 77.7 ± 13.0 2.43 (1.55, 3.32) P< 0.0001 
Cardiovascular 
Disease 
1 (1%) 1 (1%) 0% P=N/S 
Kidney Function 
51 Cr-EDTA eGFR 
(ml/min/1.73m
2
) 
111.8 ± 20.0 72.1 ± 13.1 -39.6 (-42.23, -
36.92) 
P< 0.0001 
Ant-hypertensive 
use 
9 (10%) 10 (11%) 1.1% (-2.2, 4.5) P= 0.317 
Systolic Blood 
Pressure (mmHg) 
124.3 ± 11.7 124.8 ± 13.4 0.33 (-2.70, 
3.35) 
P=0.830 
Diastolic Blood 
Pressure(mmHg) 
76.5 ± 8.5 78.4 ± 7.8 1.84 (-0.01, 3.7) P=0.0516 
Statin Use 10 (11.5%) 18 (21%) 10.3% (2.0, 
16.4) 
P<0.005 
Total Cholesterol 
(millimoles/litre) 
5.4 ± 1.1 5.4 ± 1.0 -0.01(-0.18, 
0.16) 
P=0.873 
Triglycerides 
(millimoles/litre) 
0.8 (0.6, 1.3) 1.0 (0.7, 1.6)  P=0.0004 
HDL 
(millimoles/litre) 
1.4 ± 0.4 1.5 ± 0.4 +0.04 (-0.01, 
0.09) 
P=0.103 
LDL 
(millimoles/litre) 
3.5 ± 0.9 3.4 ± 1.0 -0.15 (0.29, 
0.002) 
P=0.0530 
Apo A-1 
(grams/litre) 
1.6 ± 0.2 1.7 ± 0.3 +0.09 (0.05, 
0.13) 
P=0.0001 
Apo B (grams/litre) 0.98 ± 0.27 0.99 ± 0.24 0.01 (-0.02, 
0.05) 
P=0.457 
Lp(a) (grams/litre) 0.18 (0.06, 
0.46) 
0.19 (0.06, 0.51)  P=0.072 
Mean +/- standard deviation, Median (Interquartile range).  BMI (Body Mass Index), 51-Cr 
EDTA eGFR (chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration 
rate), HDL (High-Density Lipoprotein), LDL (Low-Density Lipoprotein), Apo A-1 
(apolipoprotein A-1), Lp(a) (lipoprotein a), Apo B (apolipoprotien B). 
  
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Figure 1. BMI distribution before and after kidney donation; Normal (BMI 18.5-24.9 kg/m2),  
Pre-obese (BMI 25 to 29.9 kg/m2), Obese (BMI ≥ 30 kg/m2). 
 


Live donor study – implications of kidney donation on cardiovascular risk with a focus on lipid parameters including lipoprotein a

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Live donor study – implications of kidney donation on cardiovascular risk with a focus on lipid parameters including lipoprotein a

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