Jonas Wadström

Fibrin Glue (TisseelR) Added with Sodium Hyaluronate in Microvascular Anastomosing

To test the effect on the handling properties of a two component fibrin glue, the viscosity was increased with sodium hyaluronate and the glue was applied to a microvascular anastomosis in rats. The femoral artery of each rat was anastomosed with three conventional sutures and then sealed with fibrin glue. Three glues with different viscosities were tested: original Tisseel fibrin glue (Immuno AG, Vienna); Tisseel with 0.9% sodium chloride added to the fibrinogen component; and Tisseel with a high molecular weight sodium hyaluronate (10 mg/ml, Healon, Pharmacia, Sweden) added to the fibrinogen component. The increased viscosity of the fibrin glue to which hyaluronate had been added resulted in a significantly higher patency rate 20 minutes after completion of the anastomosis (p < 0.01), and reduced the amount of fibrin that entered the vessels.

Kidney donors at increased risk? Additional studies are needed.

To the Editor: The recent article by Mj en et al.1 reports that former kidney donors have increased long-term risk of death, cardiovascular death, and end-stage renal disease (ESRD). The authors note the increased risk to be small, and conclude that they will continue to promote living donation. Yet, we are already aware of insurance companies citing these data (in the United States) when denying or charging increased rates for life and health insurance. Despite its strengths (comparing donors with healthy controls), there are weaknesses in the analysis: (1) all postdonation ESRD is in related donors; relatives of those with ESRD are known to have increased ESRD rates.2–4 (2) Most ESRD was due to immunologic disease, which would have affected both kidneys. (3) The statistical analysis is a concern due to the following: (a) 1901 donors are compared with 32,621 controls with much of the data imputed; (b) the reported hazard ratio for ESRD in donors was 11.38, yet only 0.47% of donors developed ESRD; (c) the donors were 8 years older than controls and, in the analysis adjusted for age, cardiovascular death was nonsignificant; (d) there is uncertainty about the randomness of imputed data, especially on key determinants of survival such as smoking; and (e) 9512 potential controls were eliminated because of ‘reduced general health’. (4) Rather than the entire country, the matched controls were from a relatively small, genetically homogenous geographic area. (5) The difference in mortality was about 5% and only seen after 15 years; the number at risk at or beyond this time point was not stated. (6) The donor cohort originated in the 1970s, whereas controls began observation between 1984 and 1988; in the interval, average lifespan increased. Clearly, Mj en et al. make important observations and future candidates need to be informed of the results. However, additional studies, addressing the limitations noted, are needed to validate these findings.

Kidney Donation and Risk of ESRD

To the Editor Dr Muzaale and colleagues 1 matched all US kidney donors from 1994 to 2011 with a cohort of selected participants from the Third National Health and Nutrition Examination Survey (NHANES III) and found an increased cumulative incidence and lifetime risk of end-stage renal disease (ESRD) among the donors. The Editorial by Drs Gill and Tonelli 2 highlighted several methodological factors that may have biased the findings in the direction of finding increased risk to donors, and we identify an additional factor.

Mid- and Long-Term Health Risks in Living Kidney Donors: A Systematic Review and Meta-analysis.

Living kidney donation is the gold standard treatment of end-stage renal disease (ESRD); more than 8000 living-donor kidney transplantations were done in 2013 in the United States, Brazil, and Japan alone (1). Although living donation is highly beneficial to recipients, it remains a complex ethical, moral, and medical issue. It is practiced with the expectation that risk for minimal short- and long-term harm to the donor is outweighed by the psychological benefits of altruism and improved recipient health (2). A short-term reduction in glomerular filtration rate after nephrectomy is a known consequence of kidney donation (3). However, the mid- and long-term health risks remain uncertain, despite their critical role in informing clinical guidelines for follow-up and supporting the process of informed consent (4, 5). Although narrative reviews (1, 6, 7) and individual studies have reported on the longer-term health risks of living kidney donation, most have not been systematically assessed and quantified. For example, the 3 previously published meta-analyses (each involving up to 6 studies comparing donors vs. a nondonor control group) focused only on a limited number of outcomes (such as hypertension and renal function) and involved only about half of the currently available data (3, 8, 9). Interpretation of the evidence has also been complicated by diverse selection criteria for nondonor control groups (for example, general population vs. based on donation criteria), follow-up durations, and analytic approaches (for example, different matching criteria or adjustment for potential confounders) (4, 10). To help quantify the mid- and long-term risks of living kidney donation, we conducted a systematic review and meta-analysis of observational studies comparing living kidney donors with control participants (nondonors) for a broad range of health outcomes. Methods Data Sources and Searches This review was done using a predefined protocol published in PROSPERO (CRD42017072284) and in accordance with MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. Studies published from April 1964 to 20 July 2017 were identified, without language restriction, through electronic searches using PubMed, Embase, Scopus, and PsycINFO. We supplemented this search by scanning reference lists of relevant articles (including studies as well as reviews and meta-analyses) and by backward and forward citation searching of all included studies. The computer-based searches combined terms related to living organ donation, health related quality of life, and epidemiological studies without health outcomes restriction (Supplement). Supplement. Supplementary Online Content Study Selection Studies were eligible for inclusion if they reported associations between living kidney donation and any health outcomes, disease traits, or health-related quality of life (HRQoL) using a validated instrument; had a mean follow-up after donation of at least 1 year; and provided a comparison group of control participants who had not donated a kidney. Outcomes evaluated in only 1 study (gout and kidney stones) were not included. Data Extraction and Quality Assessment Two investigators independently extracted data on the following characteristics using standardized protocols: sample size; study design; sampling population; location; year of publication; years of baseline survey (year of kidney donation); follow-up duration; participant sex, age range, and ethnicity; number of donors and control participants; selection criteria for control participants; outcomes recorded; outcome definitions and methods of ascertainment (Supplement Table 1); reported risk estimates; and degree of statistical adjustment used or, where relevant, mean level of disease traits and HRQoL assessment scores in donors and control participants. Discrepancies were resolved by discussion and adjudication by a third reviewer. We used the most up-to-date or comprehensive information when more than 1 article reported on the same study. Study quality was evaluated with the Newcastle-Ottawa Scale (NOS) (11), which uses a star system (maximum of 9 stars) to assess quality in the following 3 domains: selection of participants, comparability of study groups, and ascertainment of outcomes of interest. Studies with 4 stars or more were rated as medium or higher quality. We classified selection of control participants as +++ if they were eligible for nephrectomy based on medical status and assessment of renal function; ++ if they were eligible for nephrectomy based on medical status but without assessment of renal function, or if renal function was assessed but limited information on medical history was available; and + if limited screening or information on controls selection was available. Furthermore, we classified matching of donors with control participants as +++ if it was done according to age, sex, sociodemographic factors, or other factors potentially influencing the outcome of interest (for example, body mass index, blood pressure, medical history, and smoking history); ++ if it was based on age, sex, and sociodemographic factors; + if it was based only on age or sex; and null if no matching was done. Data Synthesis and Analysis Primary analyses involved only within-study comparisons to limit potential biases. We restricted primary analyses to studies with an NOS score of at least 4 and baseline recruitment period ending in or after 2000 to provide more reliable and contemporary summary estimates. Supplementary analyses involved all available studies. We used reported relative risks (RRs) or unadjusted RRs or odds ratios calculated from study-specific data to quantify the association between living kidney donation and each of the binary outcomes of interest. Hazard ratios and odds ratios were assumed to approximate the same measure of RR. Incidence rates per 1000 person-years in donors were extracted from studies or calculated as the ratio of events in donors and control participants over the number of person-years at risk. This number in each group was extracted from each study or estimated by multiplying the mean (or median) years of follow-up by the number of donors and control participants. For pregnancy outcomes, incidence of adverse outcomes per 100 pregnancies was calculated by dividing the number of adverse events by the number of pregnancies. We assessed continuous outcomes (disease traits and HRQoL outcomes) by comparing mean differences in living kidney donors with those in control participants for each study. Standardized mean difference (SMD) was calculated within each study as the mean difference between cases and control participants divided by the pooled SD (12). This estimate allows comparison among disparate outcome measures reported with different units. Summary RRs, incidence rates, and SMDs comparing donors with control participants were calculated for each outcome by pooling the study-specific estimates using the random-effects profile likelihood meta-analysis method (13). Consistency of findings across individual studies for outcomes reported in 3 or more studies was assessed by the I 2 statistic. Evidence of publication bias across studies was assessed for outcomes with more than 10 studies using funnel plots and the Egger test. All analyses were 2-sided, used a significance level of P< 0.05, and were done with Stata, version 14.2 (StataCorp). Role of the Funding Source None of the funding organizations were involved in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Results Overall, 52 unique studies from 17 countries involving 118426 donors and 117656 control participants met the inclusion criteria (Figure 1 and Appendix Table). Twenty-three studies were based in North America, 10 in Europe, 2 in Australia, 5 in South America, and 12 in other or several regions. Donors were primarily recruited from hospital registries: 39 studies recruited donors from hospitals and 11 from national or regional donor registries (2 studies did not report this information). The average follow-up ranged from 1 to 24 years, and 14 studies reported a mean or median follow-up of 10 years or more. Selection of the control population differed between studies, with 8 studies selecting control participants from population-based studies, 11 from the general population, 14 from siblings and other volunteers, and 19 from other sources. Twenty-seven studies used several characteristics to match the control and donor populations, and 17 excluded control participants with 2 or more contraindications for nephrectomy. Of these, only 5 selected the control population on the basis of completion of living donor screening or eligibility for nephrectomy based on medical status and renal function tests (Supplement Table 2). Twenty-eight studies were judged to have an NOS score of at least 4 (Supplement Table 3) and had a baseline recruitment period ending in or after 2000. Figure 1. Evidence search and selection. Appendix Table. Summary of 52 Included Unique Prospective Studies on Outcomes of Living Kidney Donation* Association With Disease Traits Twenty-six studies reported associations with disease traits, of which 17 reported information on blood pressure, 6 on metabolic markers, and 17 on markers of renal function (Appendix Table). In the primary analysis (up to 8 studies, 1040 donors, and 1032 control participants), living kidney donors had higher mean diastolic blood pressure (SMD, 0.17 [95% CI, 0.03 to 0.34]) and lower levels of high-density lipoprotein cholesterol than control participants (SMD, 0.29 [CI, 0.52 to 0.11]). Donors also had poorer renal function than control participants, with a lower mean estimated glomerular filtration rate (SMD, 1.59 [CI, 1.86 to 0.33]) and higher mean level of serum creatinine (SMD, 1.0

Single-centre long-term follow-up of live kidney donors demonstrates preserved kidney function but the necessity of a structured lifelong follow-up

Abstract Background. The increase of live kidney donation (LKD) demands that we scrutinize its long-term consequences. Socialized medicine in Sweden has allowed us to survey long-term consequences of LKD with a high response rate. Methods. Between 1974 and 2008, 455 LKDs were performed; 28 donors were deceased and 14 had moved abroad at the time of the survey. Of the remaining 413, 96% agreed to participate in a retrospective study with laboratory testing and answering a questionnaire. Results. Mean age at donation was 49 ± 10 years, and the mean time since nephrectomy was 11 ± 7 years (range 1–33). No death was of renal cause. S-creatinine at follow-up was 93 ± 18 μmol/L, 28% had treated hypertension, of whom only 52% had BP <140/90. Eleven per cent had spot microalbuminuria, and 1% were diagnosed with diabetes mellitus. Seventy-one per cent had check-ups at least every second year, but 14% had no check-ups. Eighty per cent would be willing to donate again if it were possible, and only 3% regretted the donation. Conclusion. Renal function is well preserved in the long term after donation, no case of end-stage renal disease was identified, and a large majority of our donors would donate again if it were possible. Although rates of microalbuminuria and hypertension were at expected levels, a significant number of donors demonstrated elevated blood pressure levels and inadequate antihypertensive treatment. A relatively large number of donors did not receive regular check-ups. Both of these issues demonstrate the need for a better-structured lifelong follow-up.

The Influence of Body Temperature on Traumatic Vasospasm

The effect of hypothermia on traumatically induced vasospasm was studied in an in vivo model of the rabbit ear artery. Spasm was induced by standardized compression of a 3.2 mm segment of the artery for 3 s. The internal diameter was continuously measured with the aid of an operating microscope during transillumination of the artery. Measurements were begun before spasm induction and continued until the spasm was completely resolved. Spasm was first induced at normothermia and then after reduction of the body temperature by 1.0 degrees C and 1.75 degrees C. The spasm was evaluated in terms of its duration, intensity (% reduction of initial diameter) and severity (area under the curve where diameter was plotted against time). The results were compared with those in a control group which was kept normothermic. Reduction of the body temperature caused a significant increase in the duration of the spasm and increased its severity, but did not influence its intensity.

Advancing transplantation: New questions, new possibilities in kidney and liver transplantation

Advancing Transplantation : New Questions, New Possibilities in Kidney and Liver Transplantation

Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes Over Time

Background We sought to study gender differences and differences over time with respect to demographics, relation to recipient, donor motives, and experiences of live kidney donation. Material/Methods In all, 455 consecutive live kidney donors, representing all of the donors at our center between 1974 and 2008 were considered for this study. There were 28 deceased donors and 14 donors who had moved abroad, leaving 413 donors; 387 (94%) agreed to participate in this study. A questionnaire was sent and the answers was analyzed for gender differences and, where relevant, for changes over time. Results In all sub-periods, female donors made up the majority (55–62%), except for sibling donors (45%) and child-to-parent donors (40%). No significant gender differences were seen in perceived information given before donation. For males, it was more common that the recipient took the initiative to donate. For females, the motivation for donating was more frequently to help the recipient and because others wanted them to donate. For males, it was more common to feel a moral obligation. Post-operatively, females more frequently felt sad and experienced nausea, and more frequently felt that the donation had a positive impact on their lifes. With the introduction of minimally invasive surgical techniques, donors experienced fewer problems from the operation, with no gender difference. Conclusions Females donate more frequently than males, a difference that did not change over time. Only a few gender differences were seen in donor motives and the donation experience; however, these differences may be relevant to address the gender imbalance in kidney donations.