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Meta-Analysis: Risk for Hypertension in Living Kidney Donors

Neil Boudville, MD; G. V. Ramesh Prasad, MD; Greg Knoll, MD, MSc; Norman Muirhead, MD; Heather Thiessen-Philbrook, MMath; Robert C. Yang, MD; M. Patricia Rosas-Arellano, MD, PhD; Abdulrahman Housawi, MD; Amit X. Garg, MD, PhD, Donor Nephrectomy Outcomes Research (DONOR) Network*
[+] Article, Author, and Disclosure Information

From University of Western Ontario, London, Ontario, Canada; University of Western Australia, Perth, Australia; University of Toronto, Toronto, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; and McMaster University, Hamilton, Ontario, Canada.

Acknowledgments: The authors thank Jan Challis, MLIS, who provided administrative help; Nick Barrowman, PhD, Brian Haynes, MD, PhD, and Joel Ray, MD, MSc, for statistical and methodologic advice; and William Clark, MD, for his support. The authors also thank the 30 authors of included studies who generously confirmed and provided information and performed additional analyses for this review.

Grant Support: By the London Multi-Organ Transplant Program, the Canadian Institutes of Health Research, the Physicians Services Incorporated Foundation, and the Canadian Council for Donation and Transplantation. Dr. Garg was supported by a Canadian Institutes of Health Research Clinician Scientist Award, and Dr. Yang was supported by a Biomedical Fellowship from the Kidney Foundation of Canada.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Amit X. Garg, MD, PhD, Division of Nephrology, London Kidney Clinical Research Unit, Room ELL-101, Westminster Tower, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada; e-mail, amit.garg@lhsc.on.ca.

Current Author Addresses: Dr. Boudville: Division of Nephrology, University of Western Australia, Verdun Street, Nedlands, WA 6050, Australia.

Dr. Prasad: Division of Nephrology, University of Toronto, St. Michael's Hospital Health Centre, 61 Queen Street East, 9th Floor, Toronto, Ontario M5C 2T2, Canada.

Dr. Knoll: Division of Nephrology, University of Ottawa, The Ottawa Hospital, 1967 Riverside Drive, Ottawa, Ontario K1H 7W9, Canada.

Drs. Muirhead, Yang, Rosas-Arellano, Housawi, and Garg and Ms. Thiessen-Philbrook: Division of Nephrology, London Kidney Clinical Research Unit, Room ELL-101, Westminster Tower, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada.

Ann Intern Med. 2006;145(3):185-196. doi:10.7326/0003-4819-145-3-200608010-00006
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Background: The risk for hypertension after kidney donation remains uncertain.

Purpose: To see whether normotensive adults who donate a kidney develop higher blood pressure and risk for hypertension compared with nondonor adults acting as control participants.

Data Sources: MEDLINE, EMBASE, and Science Citation Index were searched from 1966 until November 2005 for articles published in any language. Reference lists of pertinent articles were also reviewed.

Study Selection: The authors selected studies involving 10 or more healthy normotensive adults who donated a kidney and in whom blood pressure was assessed at least 1 year later.

Data Extraction: Two reviewers independently abstracted data on study and donor characteristics, blood pressure measurements, outcomes, and prognostic features. Comparison data were abstracted from donor studies with control participants. Thirty primary authors provided additional data.

Data Synthesis: Forty-eight studies from 28 countries followed a total of 5145 donors. Before surgery, the average age of donors was 41 years, the average systolic blood pressure was 121 mm Hg, and the average diastolic blood pressure was 77 mm Hg for all studies. In controlled studies in which the average follow-up was at least 5 years after donation (range, 6 to 13 years), blood pressure was 5 mm Hg higher in donors than in control participants (the weighted mean for systolic blood pressure using 4 studies involving 157 donors and 128 control participants was 6 mm Hg [95% CI, 2 to 11 mm Hg], and the weighted mean for diastolic blood pressure using 5 studies involving 196 donors and 161 control participants was 4 mm Hg [CI, 1 to 7 mm Hg]). There was statistical heterogeneity among the 6 controlled studies that assessed hypertension; an increase in risk was noted in 1 study (relative risk, 1.9 [CI, 1.1 to 3.5]).

Limitations: Most studies were retrospective and did not include control groups that were assembled and followed along with donors. Approximately one third of the donors had incomplete follow-up information.

Conclusions: On the basis of the limited studies conducted to date, kidney donors may have a 5–mm Hg increase in blood pressure within 5 to 10 years after donation over that anticipated with normal aging. Future controlled, prospective studies with long periods of follow-up will better delineate safety and identify donors at lowest risk for long-term morbidity.

*For a list of DONOR Network Investigators, see the Appendix.


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Figure 1.
Meta-analysis of controlled studies of systolic blood pressure (SBP) and diastolic blood pressure (DBP) at least 5 years after kidney donation.

The size of each square is inversely proportional to the variability of the study estimate. NR = not reported. *Studies are arranged by the average number of years after donation. †A summary of various methods to assess blood pressure are presented in the Results section. ‡Study reported that a percentage of donors were taking antihypertensive medication but did not quantify the amount.

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Figure 2.
Controlled studies of hypertension risk after kidney donation.

Results were not mathematically pooled because of statistical heterogeneity between studies (chi-square, 10.1; P = 0.074; I2 = 50%). The size of each square is inversely proportional to the variability of the study estimate. *Studies are arranged by the average number of years after donation. †Definitions of hypertension and a summary of various methods to assess blood pressure are presented in the Results section.

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Figure 3.
Studies with a higher proportion of donors lost to follow-up.

These studies on average showed a higher increase in blood pressure after donation, explaining 72% of the between-study variability for a change in systolic blood pressure (SBP) after donation and 59% for a change in diastolic blood pressure (DBP) after donation. This association remained statistically significant after adjustment for duration of follow-up. The area of each circle is proportional to the number of donors in each study. Best-fit lines with 95% CIs are from meta-regression. See the Methods section.

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