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

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. Prospective, controlled, observational cohort study. 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. Kidney donation. 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. 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. Short duration of follow-up and possible bias resulting from an inability to screen controls with kidney and vascular imaging performed in donors. Kidney donors have some, but not all, abnormalities typically associated with mild chronic kidney disease 6 months after donation. Additional follow-up is warranted.

Kasiske BL ，Anderson-Haag T ，Ibrahim HN ，Pesavento TE ，Weir MR ，Nogueira JM ，Cosio FG ，Kraus ES ，Rabb HH ，Kalil RS ，Posselt AA ，Kimmel PL ，Steffes MW ... -  《-》

A prospective controlled study of living kidney donors: three-year follow-up.

There have been few prospective controlled studies of kidney donors. Understanding the pathophysiologic effects of kidney donation is important for judging donor safety and improving our understanding of the consequences of reduced kidney function in chronic kidney disease. Prospective, controlled, observational cohort study. 3-year follow-up of kidney donors and paired controls suitable for donation at their donor's center. Kidney donation. Medical history, vital signs, glomerular filtration rate, and other measurements at 6, 12, 24, and 36 months after donation. At 36 months, 182 of 203 (89.7%) original donors and 173 of 201 (86.1%) original controls continue to participate in follow-up visits. The linear slope of the glomerular filtration rate measured by plasma iohexol clearance declined 0.36±7.55mL/min per year in 194 controls, but increased 1.47±5.02mL/min per year in 198 donors (P=0.005) between 6 and 36 months. Blood pressure was not different between donors and controls at any visit, and at 36 months, all 24-hour ambulatory blood pressure parameters were similar in 126 controls and 135 donors (mean systolic blood pressure, 120.0±11.2 [SD] vs 120.7±9.7mmHg [P=0.6]; mean diastolic blood pressure, 73.4±7.0 vs 74.5±6.5mmHg [P=0.2]). Mean arterial pressure nocturnal dipping was manifest in 11.2% ± 6.6% of controls and 11.3% ± 6.1% of donors (P=0.9). Urinary protein-creatinine and albumin-creatinine ratios were not increased in donors compared with controls. From 6 to 36 months postdonation, serum parathyroid hormone, uric acid, homocysteine, and potassium levels were higher, whereas hemoglobin levels were lower, in donors compared with controls. Possible bias resulting from an inability to select controls screened to be as healthy as donors, short follow-up duration, and dropouts. Kidney donors manifest several of the findings of mild chronic kidney disease. However, at 36 months after donation, kidney function continues to improve in donors, whereas controls have expected age-related declines in function.

Kasiske BL ，Anderson-Haag T ，Israni AK ，Kalil RS ，Kimmel PL ，Kraus ES ，Kumar R ，Posselt AA ，Pesavento TE ，Rabb H ，Steffes MW ，Snyder JJ ，Weir MR ... -  《-》

Bone and mineral metabolism and fibroblast growth factor 23 levels after kidney donation.

Living kidney donation offers a unique setting to study changes in phosphate and vitamin D homeostasis attributable to mild isolated decreases in estimated glomerular filtration rate (eGFR). Cross-sectional study. 198 living kidney donors and 98 nondonor controls from 9 transplant centers across 3 countries. For donors, median time after donation was 5.3 years. At assessment, donors had a lower eGFR than controls (73 vs 98 mL/min/1.73 m(2)). Living kidney donation (mildly decreased eGFR). Biochemical markers of chronic kidney disease-mineral and bone disorder. Serum creatinine, total serum calcium, serum and urine inorganic phosphate, plasma intact parathyroid hormone, serum calcidiol and calcitriol, renal fractional excretion of inorganic phosphate, and intact serum fibroblast growth factor 23 (FGF-23). Serum FGF-23 levels were significantly higher in donors (38.1 vs 29.7 pg/mL; P < 0.001). For every 10-mL/min/1.73 m(2) decrease in eGFR, FGF-23 level was higher by 3.2 (95% CI, 2.0-4.4) pg/mL. Compared with controls, donors showed higher renal tubular fractional excretion of inorganic phosphate (17.8% vs 12.3%; P < 0.001), lower serum phosphate (0.97 vs 1.02 mmol/L; P = 0.03), and lower serum calcitriol values (63 vs 77 pmol/L; P < 0.001). Serum calcium levels were not significantly different between the 2 groups. Plasma intact parathyroid hormone levels were significantly higher in donors (5.7 vs 5.0 pmol/L; P = 0.03), but were not correlated with FGF-23 or calcitriol levels. Enrollment of a small proportion of past donors at participating centers; assessment of only postdonation values; unable to assess seasonal variation or other temporal patterns in biochemical markers; assessment of kidney function was based on eGFR, not measured GFR. The FGF-23 pathway may be activated in living kidney donors who show early biochemical changes compatible with chronic kidney disease-mineral and bone disorder. Whether these changes influence bone mineral density and fracture rates warrants consideration.

Young A ，Hodsman AB ，Boudville N ，Geddes C ，Gill J ，Goltzman D ，Jassal SV ，Klarenbach S ，Knoll G ，Muirhead N ，Prasad GV ，Treleaven D ，Garg AX ，Donor Nephrectomy Outcomes Research (DONOR) Network ... -  《-》

Assessment of renal function in living kidney donors before and after nephrectomy: A Japanese prospective, observational cohort study.

To investigate the utility of estimated glomerular filtration rate for assessing kidney function in living kidney donors before and after nephrectomy. A total of 101 donors underwent inulin clearance measurements before and 1 year after nephrectomy. The mean of three inulin clearance values was used as the measured glomerular filtration rate. Estimated glomerular filtration rate based on serum creatinine and cystatin C levels was calculated using the Japanese estimated glomerular filtration rate equation, Chronic Kidney Disease Epidemiology Collaboration formula and new full age spectrum equation. Age-adjusted chronic kidney disease was defined as glomerular filtration rate <75 mL/min/1.73m2 for donors aged <40 years, <60 mL/min/1.73m2 for donors aged 40-65 years and <45 mL/min/1.73m2 for donors aged >65 years. The postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rate were 36.0% and 27.0%, respectively. In younger donors (aged <50 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rates were 5.3% and 26.3%, respectively. In older donors (aged >70 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rates were 75.0% and 33.3%, respectively. Donor age and measured glomerular filtration rate were significant predictors of postoperative measured glomerular filtration rate. The Japanese estimated glomerular filtration rate equation based on creatinine and cystatin C showed the strongest correlation with measured glomerular filtration rate. However, the Japanese estimated glomerular filtration rate equation based on creatinine overestimated the prevalence of measured glomerular filtration rate <60 mL/min/1.73m2 , whereas the Japanese estimated glomerular filtration rate based on cystatin C underestimated it. Aged donors might have an increased risk of lower glomerular filtration rate after donor nephrectomy; post-surgery, long-term monitoring of renal function is recommended. Measurement of glomerular filtration rate should be carried out for donors, especially pre-surgery. A more precise glomerular filtration rate equation is required in the future.

Kakuta Y ，Imamura R ，Okumi M ，Horio M ，Isaka Y ，Ichimaru N ，Takahara S ，Nonomura N ，Tanabe K ... -  《-》

A prospective controlled study of metabolic and physiologic effects of kidney donation suggests that donors retain stable kidney function over the first nine years.

While there have been numerous studies of living kidney donors, most have been retrospective without suitable controls and have yielded conflicting results. To clarify this we studied 205 living donor candidates and 203 controls having no medical conditions precluding donation. Before and at six months, one, two, three, six, and nine years after donation we measured iohexol glomerular filtration rate, clinic blood pressure, urine protein excretion and metabolic parameters reported to be affected by kidney function. We measured 24 hour ambulatory blood pressure at three, six, and nine years and at six and nine years blood pressure after treadmill exercise, carotid-femoral pulse wave velocity and arterial elasticity. Between six months and nine years, the mean (95% confidence interval) change in glomerular filtration rate was significantly different among 133 donors 0·02 (-0·16-0·20) mL/min/1·73m2/year versus -1·26 (-1·52--1·00) mL/min/1·73m2/year in 113 healthy controls. Blood pressure, urine protein, urine albumin, glucose, hemoglobin A1c, insulin, and lipoproteins were not different in controls versus donors; but parathyroid hormone, homocysteine and uric acid remained higher at nine years. At six and nine years carotid-femoral pulse wave velocity was not different, but the mean small artery elasticity was significantly lower in 141 donors 6·1 mL/mmHg x100, versus 113 controls 7·1 mL/mmHg x100, and 6·1 mL/mmHg x100 in 137 donors versus 7·6 mL/mmHg x100 in 112 controls at six and nine years, respectively [significant adjusted difference of 1·1 mL/mmHg x100]. Thus, donors remain healthy with stable kidney function for the first nine years, but differences in metabolic and vascular parameters could be harbingers of adverse outcomes requiring future interventions.

Kasiske BL ，Anderson-Haag TL ，Duprez DA ，Kalil RS ，Kimmel PL ，Pesavento TE ，Snyder JJ ，Weir MR ... -  《-》