A prospective controlled study of kidney donors: baseline and 6-month follow-up.

BACKGROUND: Most previous studies of living kidney donors have been retrospective and have lacked suitable healthy controls. Needed are prospective controlled studies to better understand the effects of a mild reduction in kidney function from kidney donation in otherwise healthy individuals. STUDY DESIGN: Prospective, controlled, observational cohort study. SETTING & PARTICIPANTS: Consecutive patients approved for donation at 8 transplant centers in the United States were asked to participate. For every donor enrolled, an equally healthy control with 2 kidneys who theoretically would have been suitable to donate a kidney also was enrolled. PREDICTOR: Kidney donation. MEASUREMENTS: At baseline predonation and at 6 months after donation, medical history, vital signs, measured (iohexol) glomerular filtration rate, and other measurements were collected. There were 201 donors and 198 controls who completed both baseline and 6-month visits and form the basis of this report. RESULTS: Compared with controls, donors had 28% lower glomerular filtration rates at 6 months (94.6 ± 15.1 [SD] vs 67.6 ± 10.1 mL/min/1.73 m(2); P < 0.001), associated with 23% greater parathyroid hormone (42.8 ± 15.6 vs 52.7 ± 20.9 pg/mL; P < 0.001), 5.4% lower serum phosphate (3.5 ± 0.5 vs 3.3 ± 0.5 mg/dL; P < 0.001), 3.7% lower hemoglobin (13.6 ± 1.4 vs 13.1 ± 1.2 g/dL; P < 0.001), 8.2% greater uric acid (4.9 ± 1.2 vs 5.3 ± 1.1 mg/dL; P < 0.001), 24% greater homocysteine (1.2 ± 0.3 vs 1.5 ± 0.4 mg/L; P < 0.001), and 1.5% lower high-density lipoprotein cholesterol (54.9 ± 16.4 vs 54.1 ± 13.9 mg/dL; P = 0.03) levels. There were no differences in albumin-creatinine ratios (5.0 [IQR, 4.0-6.6] vs 5.0 [IQR, 3.3-5.4] mg/g; P = 0.5), office blood pressures, or glucose homeostasis. LIMITATIONS: Short duration of follow-up and possible bias resulting from an inability to screen controls with kidney and vascular imaging performed in donors. CONCLUSIONS: Kidney donors have some, but not all, abnormalities typically associated with mild chronic kidney disease 6 months after donation. Additional follow-up is warranted.

Recipient outcomes of dual and multiple renal arteries following 1000 consecutive laparoscopic donor nephrectomies at a single institution.

PURPOSE: We examined outcomes of kidney transplant recipients from allografts harvested via laparoscopic donor nephrectomy (LDN) with various arterial anatomies. We examined the risk of slow graft function, delayed graft function (DGF), and postoperative urological complications in recipients of multi-vessel allografts. METHODS: Donor and recipient records for 1000 consecutive LDN were reviewed (1996-2005). Characteristics examined included donor demographics, intraoperative parameters and complications, recipient post-operative complications and short-term recipient allograft function. RESULTS: DGF was 5.3% for single; 5.2% for dual; and 9.8% for multiple (p = 0.05). Recipient creatinine (Cr) at one wk and one month was 1.9 + 1.5 and 1.6 + 0.8; 2.1 + 1.6 and 1.7 + 1.2; 2.8 + 2.3 and 1.7 + 0.8 respectively (p = 0.01). Recipient Cr at one year averaged 1.6 mg % with no significant differences between groups, with 48 ureteral complications (4.8%): 32/732 = 4.4% recognized in single arterial allograft recipients; 12/212(5.7%) for dual and 4/43 for multiple (9.3%) (p = 0.03). CONCLUSION: Complex vascular anatomy not a contraindication to LDN. Recipients of allograft with >2 arteries experience longer warm and cold ischemia times, greater incidence of DGF, and greater propensity for ureteral complications. Long term recipient outcomes remain excellent.

Cigarette smoking, kidney function, and mortality after live donor kidney transplant.

BACKGROUND: The role of smoking as a risk factor for adverse renal outcomes after kidney transplant has not been well studied. We therefore undertook this investigation to assess the association of smoking with transplant outcomes. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 997 consecutive laparoscopic live donor kidney transplant recipients at a tertiary-care transplant center. PREDICTOR: Smoking at the time of the transplant evaluation. OUTCOMES & MEASUREMENTS: Primary outcome is transplant survival. RESULTS: At the time of pretransplant evaluation, 329 participants had ever smoked and 668 participants had never smoked. Transplant survival was worse in ever smokers compared with never smokers (adjusted HR, 1.47; 95% CI, 1.08-1.99; P = 0.01), as was patient survival (adjusted HR, 1.60; 95% CI, 1.06-2.41; P = 0.02). First-year rejection-free survival was substantially worse (adjusted HR, 1.46; 95% CI, 1.05-2.03; P = 0.03) and risk of rejection on or before posttransplant day 10 was much higher (adjusted HR, 1.8; 95% CI, 1.10-2.94; P = 0.02) in ever smokers compared with never smokers. Glomerular filtration rate (estimated using the Modification of Diet in Renal Disease Study equation) at 1 year posttransplant was lower and poor early transplant function was more common in ever smokers on univariate, but not multivariate, analysis. LIMITATIONS: Lack of quantitation of smoking exposure and uncertainty about whether patients were still smoking at the time of transplant. CONCLUSIONS: Our results suggest that any history of smoking before transplant is associated with impaired transplant and patient survival and increases the risk of early rejection after live donor kidney transplant. Further study is needed to determine whether smoking may impart immunomodulatory and perhaps nephrotoxic effects.

Anemia after kidney transplantation; its prevalence, risk factors, and independent association with graft and patient survival: a time-varying analysis.

INTRODUCTION: Posttransplant anemia and its association with transplant outcomes have not been properly studied. METHODS: We examined 530 renal allograft recipients transplanted at our center and followed up for 31.0±14.1 months. Hemoglobin (Hb), serum bicarbonate, and creatinine; use of erythropoiesis-stimulating agent (ESA) and iron; and immunosuppressive regimen data were obtained at multiple time points during 24-month posttransplant. RESULTS: The overall prevalence of anemia was 89.4% at the time of transplant, dropping to 49.2% at 1 year and 44.3% at 2 years. ESA use decreased from 25.6% at 1 month to 8.23% at 24 months, only in 30.9% to 51.2% with severe anemia; 21.0% to 29.2% received iron supplements. Factors independently predictive of Hb included male gender (ß=0.64, P<0.001, confidence interval [CI]: 0.45-0.82), estimated glomerular filtration rate (ß=0.21 per 10 mL/min/1.73 m, P<0.001; CI: 0.16-0.27), bicarbonate (ß=0.4 per 10 mmol/L increase, P<0.001; CI: 0.31-0.85), using angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ß=0.36, P<0.001; CI: 0.16-0.55), African American race (ß=-0.34, P=0.001, CI:-0.54 to -0.14), iron (ß=-0.28, P=0.003, CI:-0.47 to -0.09) and ESA use (ß=-0.73, P<0.001, CI:-0.93 to -0.52), and prednisone (ß=-0.46, P<0.001, CI:-0.71 to -0.22 for >10 mg/day vs. none). Using a competing-risk regression model, Hb less than 9 in men and less than 8 in women, was associated with 5.25-fold higher risk of death-censored graft loss compared with no anemia (adjusted, P=0.005, CI: 1.7-16.7). Degree of anemia also remained significantly associated with risk of death (hazard ratio [HR]: 2.2, P<0.1, CI: 0.9-5.6 for grade 2; HR: 3.9, P=0.009, CI: 1.4-10.8 for grade 3; and HR: 4.8, P=0.08, CI: 1.5-15.4 for grade 4, all vs. grade 0). CONCLUSION: We showed that posttransplant anemia is common, and ESA/iron use remains suboptimal, and Hb is independently associated with graft failure and mortality.

A study of renal outcomes in obese living kidney donors.

BACKGROUND: Little is known about the long-term outcomes of obese living kidney donors (OLKDs). We undertook this study to describe renal outcomes of OLKDs several years after donation. METHODS: We invited 101 OLKDs for follow-up health evaluation. RESULTS: Thirty-six subjects (35.6%) completed evaluation at 6.8±1.5 years postdonation. The mean estimated glomerular filtration rate (eGFR) using the abbreviated modification of diet in renal disease (MDRD) equation (MDRD-eGFR) at follow-up was 72.1±16.3 (range: 42-106) mL/min per 1.73 m, and 47.2% of subjects had an MDRD-eGFR of 30 to 59. The absolute decrease in MDRD-eGFR from the time of donation to follow-up was 27.2 ± 13.1 mL/min per 1.73 m (P<0.001 on paired t test), which represents a 29.2% drop in the serial MDRD-eGFRs. Seven subjects (19.4%) had microalbuminuria (30-300 µg/mg creatinine). Subjects with microabuminuria were more likely to have MDRD-eGFR of less than 60 mL/min per 1.73 m (P=0.021). Subjects whose body mass index was greater than or equal to 35 kg/m (n=14) were found to have an absolute decrement in MDRD-eGFR similar to those with body mass index less than 35 kg/m (31.5 ± 15.6 and 24.7 ± 11.0 mL/min/1.73 m, respectively; P=not significant). Fifteen (41.6%) were hypertensive at follow-up. CONCLUSIONS: On medium-term follow-up, a large proportion of OLKDs will have a MDRD-eGFR of less than 60 mL/min per 1.73 m, and the likelihood increases markedly among those who develop microalbuninuria. This raises concern for hyperfiltration injury. Furthermore, OLKDs experience a substantial incidence of hypertension. Caution is advised in selecting OLKDs pending further data on long-term outcomes.

The independent association between serum uric acid and graft outcomes after kidney transplantation.

BACKGROUND: Improving long-term outcomes of kidney transplantation depends on identifying novel risk factors that lead to poor outcomes. We sought to evaluate the predictive value of mean uric acid (UA) level during the first 6 months posttransplant for graft survival and function. METHODS: Two hundred twelve recipients of living donor kidneys transplanted during January 2000 to December 2001 were included. The study outcome included graft and patient survival and graft function at 1 year posttransplant. Regression models were used to adjust for the confounding variables including graft function during first 6 months. RESULTS: During 68.3 + or - 27.2 months follow-up, UA level (mg/dL) and hyperuricemia (n=45) were associated with graft loss (hazard ratio [HR]=1.26, P=0.026, 95% confidence interval [CI]=1.03-1.53, and HR=1.92, P=0.029, 95% CI=1.1-3.4, respectively) independent of graft function and other confounders. UA also seemed to be associated with risk of death with borderline significance (HR=1.2, P=0.096, 95% CI=0.97-1.46). Examining the predictive value for graft function, UA level and hyperuricemia were independent predictors of 1-year serum creatinine (beta=0.10, P=0.013, 95% CI=0.02-0.18, and beta=0.25, P<0.04, 95% CI=0.01-0.49, respectively). Similarly, both were associated with 1-year estimated glomerular filtration rate (beta=-3.9, P<0.001, 95% CI=-5.7 to -1.5 for UA, and beta=-7.6, P<0.02, 95% CI=-13.6 to -1.5 for hyperuricemia). Notably, these associations were all independent of renal function during first 6 months. CONCLUSION: The results of this study suggest that mean UA level during the first 6 months posttransplant is an independent predictor of long-term graft survival and short-term graft function. Further investigations are needed to evaluate its causal association with chronic allograft injury and cardiovascular disease.

A study of renal outcomes in African American living kidney donors.

BACKGROUND: Little is known about the long-term outcomes of African American living kidney donors (AALKDs). We undertook this study to describe renal outcomes of AALKDs several years after donation. METHODS: We invited 107 AALKDs to come for follow-up health evaluation. RESULTS: Thirty-nine subjects (36.4%) completed evaluation at a mean of 7.1+/-1.6 (range, 3.9-10.2) years postdonation. The mean estimated glomerular filtration rate using the abbreviated Modification of Diet in Renal Disease equation [eGFR(MDRD)] at follow-up was 72.1+/-16.3 (range, 42-106) mL/min/1.73 m2, and 18% of subjects had an eGFR(MDRD) of 30 to 59. The mean absolute and relative decrease in eGFR(MDRD) from the time of donation to follow-up was 30.5+/-16.4 mL/min/1.73 m2 and 28.8%, respectively. Subjects whose body mass index was more than or equal to 35 kg/m2 (n=8) were found to have a greater decrement in e(MDRD) than those with body mass index less than 35 kg/m2 (40.1+/-7.3 and 28.3+/-17.1 mL/min/1.73 m2, respectively; P=0.009). Sixteen (41%) were hypertensive at follow-up, as defined as treatment with antihypertensive medications (n=8) or average blood pressure of more than or equal to 140 systolic or 90 mm Hg diastolic (n=10, of whom two were on antihypertensive medications). One subject had macroalbuminuria (>300 microg/mg creatinine), and six (15.4%) had microalbuminuria (30-300 microg/mg creatinine). CONCLUSIONS: AALKDs experience a substantial incidence of hypertension and a modest drop in eGFR(MDRD) postdonation, and obesity may increase the magnitude of renal decline. Further study is urgently needed to determine the long-term risks of AALKDs.

Transplant recipient renal function is donor renal mass- and recipient gender-dependent.

The effect of both donor renal mass and gender on renal function, in both gender recipients, was examined. Qualifying consecutive living-donor renal transplants (n = 730) were stratified into 4 donor-recipient groups: female-female (n = 177), male-female (n = 151), female-male (n = 240), male-male (n = 162). Groups were equivalent in age, race, body mass index (BMI), match, ischemia time, operative time, and estimated glomerular filtration rate (eGFR). Female recipients had lower serum creatinine (Cr(s)). Male recipients had higher Cr(s) wherever they received a female allograft. Male recipients of male kidneys had a higher eGFR than all other groups for 3 years. Renal function of the recipient correlated with the renal mass of the donor within each group. Male and female kidneys functioned equivalently in the female-recipient environment. Large nephron-mass male donor kidneys function more poorly in female recipients. The male kidney loses 15-20 ml/min eGFR in the female host. The diminished graft function may be related to androgen deprivation. Female and male donor kidneys function equivalently in the male recipient if adjusted for renal mass transplanted. Female kidneys improve eGFR by 7-10 ml/min by being transplanted into a male environment. Donor renal mass and gender affect recipient graft function Expectations of ultimate recipient renal function should take into account both the gender and mass disparity of the donor-recipient pair.

A single center comparison of long-term outcomes of renal allografts procured laparoscopically versus historic controls procured by the open approach.

We have previously reported that renal allografts procured by the laparoscopic live donor nephrectomy (lapNx) demonstrate worse early renal outcomes but noninferior 1-year renal function as compared to those procured by the standard open nephrectomy (openNx). We undertook this study to examine whether the apparent early dysfunction will impair long-term renal allograft survival. We retrospectively updated the status of the first 132 consecutive adult left lapNx recipients at our center and the preceding 99 adult openNx recipients. With a mean follow-up of 5.8+/-2.0 years in lapNx and 8.7+/-3.3 years in openNx, we found that death-censored renal allograft survival was identical on univariate and multivariate analysis. Patient survival was worse (log rank P-value=0.048) in lapNx, but this finding did not persist in multivariate analysis. Combined graft-patient survival as well as 1-year mean serum creatinine levels were similar on univariate and multivariate analyses. We conclude that, despite having suffered early renal dysfunction, the lapNx cohort of renal allograft recipients enjoys similar long-term renal allograft survival as compared to openNx.

Pancreas transplant alone as an independent risk factor for the development of renal failure: a retrospective study.

BACKGROUND: Pancreas transplant alone (PTA) is a controversial procedure. Without clearly demonstrated patient survival, recipients report improved quality of life. Nephrotoxic immunosuppression (IS) may exacerbate diabetic renal injury post-PTA. METHODS: A single institution retrospective review of patients receiving PTA over a 14-year period was completed. Patient and donor demographics, surgical outcomes, rejection, and patient or graft survival were analyzed. Pre- and Postoperative estimated glomerular filtration rates (eGFR) were calculated based on the modification of diet and renal disease. Multivariate analysis was performed. RESULTS: One hundred twenty-three patients undergoing 131 PTAs had an average age of 40.0 years. Seven patients were retransplanted and one received a third pancreas. Mean graft survival was 3.26 years (0-11.3 years) with 21 patients (17%) lost to follow-up. One- and 5-year patient survivals were 96.6% and 91.5%, respectively (mean, 7.15 year). Seventeen patients had an eGFR less than 50 mL/min/1.73 m preoperatively, whereas 64 patients did so post-PTA and 24 had an eGFR less than 30 mL/min. Mean eGFR pretransplantation was 88.9 vs. 55.6 posttransplantation (P<0.0001) with mean follow-up of 3.68 years. All but 16 (12%) patients showed a decrease in eGFR. Mean decrement was 32.1 mg/min/1.73 m. Thirteen developed end-stage renal disease chronic kidney disease (CKD 5) requiring kidney transplantation (KT) at a mean of 4.36 years. Eighty-three patients had an episode of rejection. In post-PTA RF, graft survival was 3.2 vs. 2.4 years (P=0.13). In those requiring KT, graft survival was 7.9 vs. 2.9 years (P<0.0001). Cold ischemia times, donor age, and preoperative eGFR for those with and without RF-requiring KT were not significant. Body mass index was statistically significant. Leukocyte-depleting agents was evaluated, but was not significant. All patients received calcineurin inhibitor IS. CONCLUSIONS: Patients who undergo PTA may be at increased risk for RF. After comparing patient and donor demographics, IS, and human leukocyte antigen mismatch, it seems that PTA is an independent risk factor for the development of renal failure. Patients with more successful pancreatic grafts demonstrated lower eGFR. Patients should be made aware of the risks of long-term IS. Only the most appropriate patients should be chosen for PTA.