Investigating kidney donation as a risk factor for hypertension and microalbuminuria: findings from the Swiss prospective follow-up of living kidney donors.

OBJECTIVES: To assess the role of nephrectomy as a risk factor for the development of hypertension and microalbuminuria. DESIGN: Prospective, long-term follow-up study. SETTING: Swiss Organ Living-Donor Health Registry. PARTICIPANTS: All living kidney donors in Switzerland between 1993 and 2009. INTERVENTIONS: Data on health status and renal function before 1 year and biennially after donation were collected. PRIMARY AND SECONDARY OUTCOME MEASURES: Comparison of 1-year and 5-year occurrences of hypertension among normotensive donors with 1-year and 5-year estimates from the Framingham hypertension risk score. Multivariate random intercept models were used to investigate changes of albumin excretion after donation, correcting for repeated measurements and cofactors such as age, male gender and body mass index. RESULTS: A total of 1214 donors contributed 3918 data entries with a completed biennial follow-up rate of 74% during a 10-year period. Mean (SD) follow-up of donors was 31.6 months (34.4). Median age at donation was 50.5 years (IQR 42.2-58.8); 806 donors (66.4%) were women. Donation increased the risk of hypertension after 1 year by 3.64 (95% CI 3.52 to 3.76; p<0.001). Those participants remaining normotensive 1 year after donation return to a risk similar to that of the healthy Framingham population. Microalbuminuria before donation was dependent on donor age but not on the presence of hypertension. After nephrectomy, hypertension became the main driver for changes in albumin excretion (OR 1.19; 95% CI 0.13 to 2.25; p=0.03) and donor age had no effect. CONCLUSIONS: Nephrectomy propagates hypertension and increases susceptibility for the development of hypertension-induced microalbuminuria.

Prospective Swiss cohort study of living-kidney donors: study protocol.

Background Offering living kidney donation raised the concern that donors are exposed to unknown risks. All Swiss transplant centres therefore decided to start a prospective cohort study of living kidney donors in Switzerland. This paper describes the rationale for and implementation of this cohort study. Methods/design All kidney donors in Switzerland are registered and examined before donation and biennially after donation starting in the first year after nephrectomy. Before each follow-up visit, the study centre sends a package to the kidney donor containing the health questionnaire, blood and urine tubes and a prepaid envelope for sending the samples to the central laboratory. The donor makes an appointment with their family physician, who examines the donor and reports findings such as pain and other complaints, blood pressure, creatinine, albumin, all major health events and the state of mental and social well-being to the study centre. The family doctor draws the blood sample and mails it with the urine sample in the prepaid envelope. All data are centrally managed. All abnormal findings in the follow-up of individual donors are regularly discussed with the principal investigator, and necessary clinical changes made and recorded in the database. The health insurance of the recipient covers all costs of the donor follow-up. The main outcomes are the occurrence of albuminuria, hypertension and renal insufficiency. The secondary outcomes are major somatic and social events such as death, cardiovascular disease, stroke and depression. Discussion This prospective cohort offers unique opportunities to assess the risks of living kidney donation and will allow us to examine the risks associated with the methods used for nephrectomy in Switzerland (various forms of open surgery and laparoscopic nephrectomy). The prospective collection of all clinically relevant data and the regular monitoring of donors will allow timely interventions at early stages before serious kidney and general health problems occur.

An easy to calculate equation to estimate GFR based on inulin clearance.

BACKGROUND: For the estimation of renal function on the basis of serum creatinine, either the Cockcroft-Gault (CG) equation or the MDRD formula is commonly used. Compared to MDRD (using power functions), CG has the advantage of easy calculability at the bedside. MDRD, however, approaches glomerular filtration rate (GFR) more precisely than CG and gives values corrected for a body surface area (BSA) of 1.73 m(2). We wondered whether CG could be adapted to estimate GFR rather than creatinine clearance without losing the advantage of easy calculability. In this prospective study, inulin clearance under well-defined conditions was taken as the gold standard for GFR. METHODS: In 182 living kidney donors, inulin clearance was measured under standardized conditions (protein, salt and water intake, overnight stay) before and after nephrectomy. Together with the serum creatinine level, and demographic and clinical data, 281 measurements of inulin clearance were used to compare the accuracy of different estimation equations. Using stepwise multiple regression, a new set of constants was defined for a CG-like equation in order to estimate GFR. RESULTS: The MDRD equation underestimated GFR by 9%, and the quadratic equation suggested by Rule overestimated GFR by 12.4%. The new CG-like equation, even when calculated with 'mental arithmetic-friendly' rounded parameters, showed significantly less bias (1.2%). The adapted equation is GFR[mL/min] = ((155 - Age[years]) x weight [kg]/serum creatinine [micromol/L]) x 0.85 if female. CONCLUSIONS: We propose the CG-like equation called IB-eGFR (Inulinclearance Based eGFR) to estimate GFR more reliably than MDRD, Rule's equation or the original Cockcroft-Gault equation. As our data represent a Caucasian population, the adapted equation is still to be validated for patients of other ethnicity.

40 projects in stem cell research, tissue engineering, tolerance induction and more (NRP46 "Implants and Transplants" 1999-2006).

Forty projects on stem cell research, tissue and matrix engineering, tolerance induction and other topics were supported by the Swiss National Research Program NRP46 (Implants, Transplants) from 1999-2006. The last project is devoted to developing stem cell lines from frozen surplus human embryos in Switzerland, which would otherwise have to be destroyed at the end of 2008. It is entitled JESP (Joint Embryonic Stem Cell Project) since it involves two Swiss universities, in vitro fertilisation centres and experts from the humanities (ethics and law) to handle this difficult problem. Over the years, stem cell transplantation and tissue/matrix engineering have drawn closer to each other and even developed synergies. Progress in stem cell research has been slower than anticipated, but a multitude of technical skills (phenotyping, isolation, transfection, induction of differentiation, labelling, expanding cells in culture, etc) were acquired. Understanding of stem cell biology has grown. The 7 projects on tissue and matrix engineering progressed closer to clinical applicability than the stem cell projects. Of 3 projects to implant encapsulated cells for the production of hormones (insulin, erythropoietin), one is close to clinical pilot studies with an advanced encapsulated device. Five projects were devoted to mechanisms of tolerance or the role of metzincins in chronic allograft nephropathy. Four studies in psychology and communication in transplantation were funded, as were 5 projects in ethics, law and the history of transplantation in Switzerland. The goal of NRP46 was to provide an impulse for research in these new fields and bring together experts from the humanities, biology and medicine to cope more effectively with the problems of regenerative medicine in the future. The majority of goals were attained, mainly in the basics.

Open and laparoscopic living donor nephrectomy in Switzerland: a retrospective assessment of clinical outcomes and the motivation to donate.

BACKGROUND: Laparoscopic living kidney nephrectomy is thought to be associated with reduced morbidity, when compared to open nephrectomy. The purpose of this study was to explore the impact of these techniques on donors' clinical outcomes, satisfaction and motivation to donate. METHODS: Clinical outcomes were retrospectively compared in 152 open (n = 71) or laparoscopic (n = 81) donor procedures. Donor satisfaction and motivation were assessed with a self-administered questionnaire. RESULTS: The complication rate was the same with both procedures and the majority of complications were mild. Laparoscopy was significantly less painful and resulted in an insignificantly faster return to active life. More than 80% of the donors volunteered to donate without pressure. Worries about future health status, pain or scars were not important in the decision to donate. Similarly, only 15% considered the surgical procedure as instrumental for their decision. Few donors currently worried about their health with one kidney and more than 95% of the donors in both groups stated that they would give their kidney again. CONCLUSIONS: Living donor nephrectomy is safe, regardless of the procedure used. Although the laparoscopic nephrectomy offers clear short-term benefits over the open nephrectomy, donors' satisfaction was excellent with both surgical approaches. Moreover, the type of procedure did not seem to influence their decision to donate.