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.

ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial.

BACKGROUND: Despite all the advantages in the immunosuppressive therapy, kidney transplantation in immunologically high risk patients remains a challenge. Ideally, an induction therapy should provide maximal graft protection, while adverse events rate and costs remain as low as possible. MATERIAL & METHODS: Immunologically high risk kidney recipients with CDC-PRA l 25% within the last 3 years, a positive B-cell CDC-crossmatch or graft loss due to rejection within 3 years following a prior transplantation, were randomized 1:1 to receive ATG-Fresenius (ATG-F) (9 mg/kg day 0; 3 mg/kg day 1-4) or Daclizumab therapy (1 mg/kg day 0, 14, 28, 42, 56) in a pilot study. Additional immunosuppression consisted of cyclosporine, mycophenolate mofetil, and steroids. 11 patients were included in each group. RESULTS: The patient (90% in ATG-F; 100% in Daclizumab) and graft survival (censored for death) (100% in ATG-F; 90% in Daclizumab) and the mean creatinine concentration at 24 months (139+/-68 mol/l in ATG-F; 176+/-103 mol/l in Daclizumab) were similar in both groups. More severe graft rejections (3 vascular rejections in Daclizumab) and adverse events (5.3/patient in ATG-F; 6.7/patient in Daclizumab) were observed in the Daclizumab group. The costs for hospitalization/ day within 24 months were lower in ATG-F (2.32+/-3.51 USD vs. 12.25+/-9.75 USD; p=0.02) resulting in an average cost-difference of more than 10'435 USD /patient. CONCLUSIONS: In this pilot trial, both treatments were comparably successful regarding graft and patient outcome.

Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete haemodialysis patients.

BACKGROUND: Haemodialysis patients need sustained treatment with intravenous iron because iron deficiency limits the efficacy of recombinant human epoetin therapy in these patients. However, the optimal intravenous iron maintenance dose has not been established yet. METHODS: We performed a prospective multicentre clinical trial in iron-replete haemodialysis patients to evaluate the efficacy of weekly low-dose (50 mg) intravenous iron sucrose administration for 6 months to maintain the iron status, and to examine the effect on epoetin dosage needed to maintain stable haemoglobin values in these patients. Fifty patients were enrolled in this prospective, open-label, single arm, phase IV study. RESULTS: Forty-two patients (84%) completed the study. After 6 months of intravenous iron sucrose treatment, the mean ferritin value showed a tendency to increase slightly from 405 +/- 159 at baseline to 490 +/- 275 microg/l at the end of the study, but iron, transferrin levels and transferrin saturation did not change. The haemoglobin level remained stable (12 +/- 1.1 at baseline and 12.1 +/- 1.5 g/dl at the end of the study). The mean dose of darbepoetin alfa could be reduced from 0.75 to 0.46 microg/kg/week; epoetin alfa was decreased from 101 to 74 IU/kg/week; and the mean dose of epoetin beta could be reduced from 148 to 131 IU/kg/week at the end of treatment. CONCLUSIONS: A regular 50 mg weekly dosing schedule of iron sucrose maintains stable iron stores and haemoglobin levels in haemodialysed patients and allows considerable dose reductions for epoetins. Low-dose intravenous iron therapy may represent an optimal approach to treat the continuous loss of iron in dialysis patients.

Why do kidney grafts fail?A long-term single-center experience.

Chronic allograft failure remains the main problem limiting long-term success after kidney transplantation. The aim of this retrospective analysis was to define clinical and histological parameters associated with favorable or poor 10-year outcome. To compare outcome we defined two groups of cadaveric-allograft recipients: a good-outcome group (GOG), composed of 145 cadaveric-kidney recipients who had lived with a functioning graft for at least 10 years and who were either still alive or had died with the functioning graft, and a poor-outcome group (POG) consisting of 86 cadaveric-kidney recipients who had had a functioning graft for at least 1 year and had returned to dialysis between 1 and 10 years after transplantation. The following factors were found to be statistically significant indicators of poor outcome: advanced donor age ( P=0.0001); a first biopsy-proven acute rejection episode within the 1st year ( P<0.0001); more than one acute rejection episode within the 1st year ( P<0.0001); acute vascular rejection, especially if occurring after the 3rd month ( P<0.0001); chronic sclerosing rejection ( P<0.0001); glomerulonephritis in the graft ( P=0.0001); and non-compliance and suboptimal medical treatment (15% of the POG). The mean plasma creatinine and mean urine protein-to-creatinine ratios were significantly lower at 1 month and 1 year in the GOG. In conclusion, advanced donor age, acute rejection episodes with vascular involvement, chronic sclerosing rejection, non-compliance, and suboptimal medical treatment are strong predictors of a poor long-term outcome. The plasma creatinine and protein-to-creatinine ratios at 1 year are the best predictors of good or poor long-term outcome.