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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 401-420
Short- and long-term follow-up of living kidney donors


1 Nephrology, Dialysis and Transplantation Department, Sahloul University Hospital of Sousse, Tunisia
2 Urology Department, Sahloul University Hospital of Sousse, Tunisia

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Date of Submission13-Feb-2018
Date of Acceptance18-Mar-2018
Date of Web Publication23-Apr-2019
 

   Abstract 


Living-donor kidney transplantation is a well-established treatment of end-stage renal disease in Tunisia. Over the years, concerns have increased about the harmlessness of kidney donation. This longitudinal single center study was carried out to evaluate the safety of nephrectomy as well as further medical and surgical outcomes among donors. We collected and analyzed clinical, biological, biochemical and kidney size data at the time of nephrectomy and at M1, M3, M6, Y1, Y2, and Y4 after donation measured by ultrasound. All donor nephrectomies performed in the nephrology and transplantation unit of Sahloul Hospital of Sousse since October 2006 were included. Criteria of exclusion were lost to follow-up or lack of complete data. Of the 106 donors (66 females and 40 males), 92 donors were included in the follow-up analysis after following exclusion criteria. The mean age at the time of nephrectomy was 42.8 ± 10 years with the sex ratio 0.6. and 27% of our donors were mothers. Twenty-two percent of the donors were obese and 4% were hypertensive. The median initial glomerular filtration rate (GFR) was 105 mL/min/1.73 m2. The surgical approach was costal lumbotomy in 96% of cases and laparoscopy for four cases. The kidneys were removed from the left side in 93% of cases. Postoperative mortality was zero and early postoperative morbidity was low. The median duration of hospital stay was nine days. During follow-up, 14% attended all recommended visits. The median follow-up duration was 26 months. After two years post donation, the prevalence of HTN was 28% and obesity was 26%. The prevalence of GFR decline (50–59 mL/min) was 14% using formula by modification of diet in renal disease. None of our donors reached stage 4 or 5 CKD. Twelve had proteinuria and one donor had diabetes, a comparable prevalence of morbidities to the general population.

How to cite this article:
Abdellaoui I, Azzabi A, Sahtout W, Sabri F, Hmida W, Achour A. Short- and long-term follow-up of living kidney donors. Saudi J Kidney Dis Transpl 2019;30:401-20

How to cite this URL:
Abdellaoui I, Azzabi A, Sahtout W, Sabri F, Hmida W, Achour A. Short- and long-term follow-up of living kidney donors. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jul 17];30:401-20. Available from: http://www.sjkdt.org/text.asp?2019/30/2/401/256848



   Introduction Top


Living kidney donor (LKD) transplantation is a well-established treatment of choice for the ever-increasing number of patients with endstage renal disease (ESRD), offering longer survival and a better quality of life at a lower cost than dialysis.[1],[2]

Since LKD transplantation is performed when the donor and the recipient are in optimum medical conditions, compared to cadaveric donors, recipients of living donor kidney grafts enjoy greater long-term graft survival and a better quality of life than do recipients of cadaveric kidney grafts.[3] In addition, it reduces the number of patients on the wait list for a cadaveric kidney. This is particularly important because the gap between the number of cadaveric donors and the number of patients on the waiting list is increasing.[4] An increase in the number of living donors (including living-unrelated donors) may ameliorate this trend.[5]

A randomized controlled American study (3698 donors) has shown no significant difference in mortality and in chronic kidney disease (CKD) occurrence in donors compared to general population over 30-year follow-up.[6] However, a Chinese meta-analysis published in 2016 (including 62 study and 19 country) concluded to a prevalence of CKD of 1.1% and mortality (all causes included) of 3.8%. Moreover, renal-related mortality occurred only after 10 years of follow-up.[7] These contradictions in donors’ outcomes led to many interrogations about the future of donors. Therefore, the harmlessness of kidney donation seems to be questioned. This is more relevant in an Arab Muslim developing country like Tunisia, where lack of cadaveric donors is continuously leading to an increase in living donor numbers.

The aim of this study is to evaluate the the safety of nephrectomy as well as medical and surgical outcomes among LKDs, both short and long terms.


   Subjects and Methods Top


Study population

This is a longitudinal monocentric study, involving a cohort of 106 LKDs in which nephrectomies were performed between November 2007 and April 2015. All the donors were chosen following the Amsterdam consensus recommendations,[8] and the nephrectomies were performed respecting the Istanbul consensus.[9]

In April 2016, the data of followed up donors were collected. To ascertain long-term outcomes, we attempted to contact nonobservant donors and ask about their current physical status. Criteria of exclusions were lost to follow-up donors or lack of complete data at the time of donation or in follow-up. The 92 donors that attended their follow-up visits after donation as per the European Renal Best Practice group recommendations by the European Renal Disease Association were included.[10] Because of the irregularity of visits, we defined visits as follows: M1 = from hospital discharge to the 3rd month, M3 = from the 3rd month to 6th month, M6 = from the 6th month to the 1st year, Y1 = from the 1st year to 2nd year, Y2 = from the 2nd year to the 4th year, and Y4 = 4 years and more. At the time of evaluation, we looked for the presence or history of renal events (i.e., elevation of serum creatinine level or proteinuria). We also detected by periodical checkup the presence or history of other physical or biological affections such as the presence of hypertension (HTN), diabetes mellitus (DM), sugar intolerance, hyperlipidemia, or hyperuricemia [Table 1].
Table 1: Data collection

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HTN was defined as systolic blood pressure (SBP) of ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg on more than one occasion.[11] Proteinuria was defined as protein excretion ≥300 mg over 24 h. Diabetes was diagnosed according to the WHO criteria, and obesity was defined as a body mass index (BMI) of >30 kg/m2 and overweight as a BMI of 25–30 kg/m2.[12] Metabolic syndrome was defined as the American Diabetes Association definition.[13] The glomerular filtration rate (GFR) was estimated using three methods: Modification of diet in renal disease (MDRD), Cock-croft and Gault formula (C&G), and formula (U*V/P). The kidney size was measured by its length in centimeters using ultrasound standard examination.


   Statistical Analysis Top


Data were statistically analyzed by Statistical Package for the Social Sciences software version 20.0 (IBM, Armonk, NY, USA). Categorical variables were presented as percentages, continuous variables as mean if data are normally distributed (±ET) and median if not (quartiles Q1, Q4). We used paired t-test sample in comparing mean values between visits. We used Pearson Chi-squared test to analyze associations between normally distributed independent variables. We studied the prevalence of HTN, obesity, DM, proteinuria, GFR decrease, prediabetes, hyperlipidemia, and hyperuricemia. For all analyses, P <0.05 was considered to indicate statistical significance.


   Results Top


Data at the time of donation

In this study, of the106 nephrectomies performed for donation (66 female and 40 male), 92 were assessed at M1, M3, M6, Y1, Y2, and Y4 after donation and met the criteria of inclusion. Sixty-seven donors (72%) attended the third follow-up visit – M6. Forty-nine donors (54%) attended the 5th follow-up visit Y2 (2st–4th year after donation). The median follow-up was 4.8 years (range 3.5–8.5 years). The mean age was 42.8 ± 10.6 years (range 21–68 years); 56.6% of the donors were between 40 and 60 years and 4.8% were ≥60 years at the time of donation. Donors were 27% mothers, 9% fathers, 15% spouses, and 33% siblings (17% brothers and 16% sisters) [Table 2].
Table 2: The main characteristics before donation. Part 1 (Demographic parameters), Part 2 (Clinico-biological parameters).

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The educational level of donors was as follows: 12% had no formal education, 43% had primary education, 32% had secondary education, and 13% had university education. Their marital status was as follows: 79% were married, 16% were single, widowed in four cases, and divorced in one case. The occupational classification was as follows: 42% had a fulltime job, 39% were homemakers, 15% had part-time job, students in two cases, retired in one case, and unemployed in one case. The social conditions were as follows: 71% had health insurance and 21% had free healthcare [Table 2].

One donor had a history of HTN, three donors were diagnosed having HTN at donation time, four had dyslipidemia (3.7%), eight had history of allergy (7.5%), seven had history of cystitis, four had anemia, and one case had hypothyroidism. A total of 30 cases (28%) had a family history of HTN, 27 cases (25%) had a family history of diabetes, seven cases (6.6%) had a family history of cardiovascular diseases, and nine cases (8.4%) had a family history of kidney diseases [Table 2].

The median SBP was 120 mm Hg, and the mean DBP was 70 mm Hg.

The mean BMI was 26.4 ± 4 (range, 16.6–26.2): 25.8 ± 3.5 among men and 26.9 ± 4.4 among women. The BMI was higher in donors aged more than 40 years of age (25.8 ± 3.5 among those aged <40 and 26.9 ± 4.4 among those aged more than 40 years) (P = 0.005). There was no significant difference between men and women in BMI. The distribution of BMI was as follows: 39 donors (37%) had a normal BMI, 45 donors (41%) had overweight, 20% had obesity OMS Stage 1, and in 2 cases, the BMI was more than 35 kg/m2 [Table 2].

The mean serum creatinine level at the time of donation was 65 ± 14 μmol/L: 78 ± 11 μmol/L for men and 57 ± 10 for women. The median GFR estimation with MDRD formula was 105 mL/min/1.73 m2 (105 mL/min/1.73 m2 for men and 110 mL/min/1.73 m2 for women). The median GFR estimation with Cockcroft and Gault formula was 117 mL/min: 124 mL/ min for men and 121 mL/min for women. There is no significant difference in gender of the estimated GFR no matter the estimation method. The majority of donors (more than 95%) had estimated GFR with MDRD greater than 80 mL/min/1.73 m2 and all of them had an estimated GFR greater than 65 mL/min/ 1.73 m2. The mean GFR (MDRD) was not significantly different whether donor was aged more than 40 years or <40 years (P = 0.06–0.09), or was a man or woman (P = 0.2), or had HTN or not (0.0.07), or was obese or not (P = 0.2). Of the 92 donors studied, no one had proteinuria and 6 donors had a microalbuminuria between 30–150 mg/24 h. [Table 2].

The median Fasing blood sugar (FBS) rate was 5.1 mmol/L (4.7; 5.7). The mean total cholesterol (TC) was 4.36 ± 0.8 mmol/L, mean low-density lipoprotein-cholesterol (LDL-Cho) was 2.84 ± 0.7 mmol/L, and the mean triglycerides (TG) was 0.79 ± 0.5 mmol/L. Mean uric acid blood rate was 273 ± 65 μmol/L, and the median creatine phosphokinase (CPK) was 86 (64; 125) mmol/L. Nine donors had metabolic syndrome.

The mean of the right kidney sizes was 10.6 ± 0.75 cm, and the mean of the left kidney sizes was 10.72 ± 0.84 cm. The mean size in men was 10.77–10.87 cm and in women was 10.52–10.62 cm in the right and left, respectively. There were no significant differences between sides and gender. The comparison in both left and right side of kidney sizes showed a difference between donors aged <30 years and donors aged 30–40 years (P = 0.05) and between donors aged <30 and donors aged more than 40 years (P = 0.04). In 86% of cases, donors have one artery and 16% had two arteries in the right kidney. In 79% of cases, donors had one artery, 20% had two arteries, and two donors had three arteries in the left kidney [Table 2].

Data in perioperative period

In 93% of cases, nephrectomy was performed on the left kidney. Right side nephrectomy occurred in five donors because of the arteries number (2 arteries in 3 cases and 3 arteries in 2 cases) and because of left renal lithiasis in one case. The operation procedure was subcostal lobotomy in 102 donors (96%) and laparoscopic nephrectomy in four donors. Complications during the operation were encountered in few cases: one case of cardiovascular collapses due to hemorrhagic incident, three cases of ventilation trouble, and seven cases of pleural wound without pneumothorax. No cases of anaphylactic reaction, bronchospasm, or death were noted.

The median length of hospital stay after nephrectomy was nine days. Only one donor was reoperated 15 days after nephrectomy due to lymphedema. This length of stay was significantly different in obese donors (P = 0.05) (BMI ≥30 kg/m2) and in those aged more than 40 years (P = 0.04). There was no significant difference in surgical method used.

In the postoperative period, some clinical events were encountered in 44% of donors and included the following: bronchopulmonary tract infection in 23% of cases, cystitis in 21% of cases, surgical site infection in 10 cases, myo-cardial infarction in one case, pulmonary embolism in one case, and transitory HTN in six cases. Some biological events were noted such as transitory acute kidney failure in five cases and rhabdomyolysis in 38% of cases. The mean values of serum creatinine (P = 0.0009), eGFR (MDRD, C&G) (P = 0.0009, P = 0.0002), and hemoglobin (P = 0.0004) before and after nephrectomy were significant, but was not significant for GFR estimated with U*V/P (P = 0.61), creatinine kinase (P = 0.89), and lactate dehydrogenase (P = 0.9). None of the study patients died.

Data after donation

The median follow-up was 4.8 years (ranges 3.5–8.5 years). Only 14% of the donors attended regularly their follow-up visits as recommended. The median of visit numbers was 4 (2; 5): 13 donors (14%) attended only once. However, six donors had more than six visits. The number of donors being lost to the follow-up increased every visit: 18% at M1 to 41% at Y1 and 52% at Y2. The number of donors attending the visits and their percentages (donors attending the visit/donors supposed to attend the visit) were, respectively, as follows: M1 (75; 82%), M3 (71; 78%), M6 (67; 74%), Y1 (57; 63%), Y2 (49; 59%), and Y4 (27; 48%).

Short- and long-term follow-up outcomes The mean BMI was stable during follow-up: a slight elevation was noted after M3 but the mean value remained between 25 and 30 kg/m2.

The mean BMI at Y2 was 28 kg/m2 [Figure 1]. The comparison of BMI mean values between before donation and the different follow-up visits after donation had shown a significant slight elevation only in A1 (27.2 vs. 28.09 kg/m2; P = 0.02). However, it had shown no significant increase in BMI in M1 (P = 0.37), M3 (P = 0.35), M6 (P = 0.15), Y2 (27.5 vs. 28.09 kg/m2; P = 0.08), and Y4 (27.23 vs. 27.7 kg/m2; P = 0.28) [Table 3].
Figure 1: Evolution of BMI, SBP and DBP mean values during the follow-up.
BMI: Body mass index, SBP: Systolic blood pressure, DBP: Diastolic blood pressure.


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Table 3: The mean value comparisons of clinical parameters (before vs. after donation).

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The prevalence of obesity was 22% before donation and 26% at Y2 (2 years after donation). The prevalence of obesity was higher among women before and after donation [Table 4].
Table 4: The prevalence of the main cardiovascular diseases and metabolic disturbance in LKD 2 years after donation (Y2).

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SBP and SBP: An increase in the mean SBP was noted immediately after nephrectomy; then, it remained stable all along the follow-up (inferior to 140 mm Hg). The mean value of DBP was seen increasing all along the follow-up but remaining below 90 mm Hg [Figure 1]. The comparison of mean values of BP before and the different visits had shown a significant increase in DBP in follow-up visits M1 (P = 0.001), M2 (P = 0.001), M6 (P = 0.017), Y2 (71.5 vs. 77 mm Hg; P = 0.007), and Y4 (69 vs. 75 mm Hg; P = 0.03). However, it had shown no significant increase in SPB in all follow-up visits: M1 (P = 0.27), M2 (P = 0.74), M6 (P = 0.96), Y1 (P = 0.95), Y2 (118 vs. 119.5 mm Hg; P = 0.84), and in Y4 (114.7 vs. 120.2 mm Hg; P = 0.08) [Table 3].

HTN: The prevalence of HTN in male donors two years after donation was 8%, and it was 20% in female donors. The prevalence of HTN in this study was 28% and was inferior to the prevalence of HTN in general population. The mean period between donation and HTN occurrence was 16 months [Table 4]. No case of gestational HTN or eclampsia was noted in female donors after donation.

The mean creatinine blood rate (CBR) increased immediately after nephrectomy from 64 μmol/L to 105 μmol/L and decreased progressively during follow-up to reach 84.7 μmol/L at the 5th visit A2. The mean clearance (MDRD) decreased from 108 to 71 mL/min/1.73 m2 but remained superior to 70 and increased progressively to 81 mL/min/1.73 m2 four years after nephrectomy [Figure 2].
Figure 2: Evolution of CBR and clearance mean values during the follow-up.
CBR: Creatinine blood rate, MDRD: Modification of the Diet in Renal Disease.


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The immediate elevation in serum creatinine levels as well as the immediate lowering in GFR estimation with both formulas in postoperative period were statistically significant (respectively creatinine level (P = 0.0009), MDRD (P = 0.0009) and C&G (P = 0.0002). The mean CBR at the visit A2 was 84.7 μmol/L, and the mean GFR estimation at the visit A2 were 79.2 mL/min/1.73 m2 (MDRD), 96.3 mL/min (C&G), and 131 mL/min (U*V/P). The comparison of the mean values between before donation and the different follow-up visits after donation had shown a significant elevation in CBR at all the visits M1 (P = 0.0001), M3 (P = 0.0001), M6 (P = 0.0001), Y1 (P = 0.0001), Y2 (P = 0.0001), and Y4 (P = 0.001) and a significant decrease in GFR estimations at M1, M3, M6, Y1, Y2, and Y4 with MDRD, respectively (P = 0.0001; P = 0.0001; P = 0.0001; P = 0.007; P = 0.0001; P = 0.0001), with C&G (P = 0.0001; P = 0.0001; P = 0.0001; P = 0.008; P = 0.0001; P = 0.0001), and with U*V/P (P = 0.0001; P = 0.0001; P = 0.0001; P = 0.001; P = 0.0017; P = 0.017) [Table 5].
Table 5: The comparison of mean values of biological parameters: renal function (creatinine blood rate, glomerular filtration rate estimations with (MDRD, U*V/P, C&G), proteinuria, and microalbuminuria.

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The prevalence of GFR decrease (50–59 mL/min) was varying between 4 and 14% at A2 (2 years after donation). This prevalence depends on calculation method [Figure 3]. No donor reached a decline in GFR less than CKD Stage 3 or 4 and no donor required dialysis for ESRD eight years after donation (as the longest period of follow-up reached in the study population). The mean proteinuria of 24H (Pu24H) increased immediately after nephrectomy and reached 0.73 g/L then decreased progressively during follow-up to 0.09 g/L at the 6th visit Y4. The mean microalbuminuria (MALB) increased progressively since the first visit M1 from 0.13 mg/L to 45 mg/L at M3 then 63 mg/L at Y2 and 16 mg/L at Y4 [Figure 4]. The comparison of the mean values of Pu24H and MALB between before donation evaluation and the different follow-up visits after donation had shown no significant elevation at all the visits except for in MALB at M1 (0.08 vs. 0.12; P = 0.037) [Table 5].
Figure 3: The prevalence of GFR decrease (50–59 mL/min) 2 years after donation.
GFR: Glomerular filtration rate, MDRD: Modification of diet in renal disease, C&G: Cockcroft and Gault.


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Figure 4: Evolution of proteinuria (Pu24H) and microalbuminuria mean values during the follow-up.

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The prevalence of proteinuria (PU24H ≥0.3 g/L) was 24% and the prevalence of MALB (≥30 mg/ 24H) was 24% at Y2 post-donation. The prevalence of proteinuria was equivalent in both gender (12.2%), and the mean period between donation and its occurrence was 11 months. The prevalence of MALB was greater in women (6% vs. 18.3% in men), and the mean period between donation and its occurrence was 12 months [Table 4].

The mean fasting blood sugar (FBS) rate remained stable all along the follow-up between 5.2 g/L and 5.3 g/L. The mean TC rates increased immediately after nephrectomy from 4.3 mmol/L to 4.8 mmol/L but still lower than pathological rates and reached 4.7 mmol/L at Y4. The mean TG rates remained stable between 0.9 mmol/L and 1.1 mmol/L. The highest TG rate was 1.4 at M1 after nephrectomy. The evolution of mean high-density lipoprotein cholesterol (HDL-Cho) and LDL-cholesterol was steady with no important variation between before and four years after donation Y4, respectively (HDL-Cho from 1.19 mmol/L to 1.3 mmol/L and LDL-Cho from 2.9 mmol/L to 2.9 mmol/L) [Figure 5].
Figure 5: Evolution of metabolic profile (mean values of FBS, TC, HDL-Cho, LDL-Cho, and TG rates) during the follow-up.
FBS: Fasting blood sugar, TC: Total cholesterol, TG: Triglycerides, HDL-Cho: High-density lipoprotein cholesterol, LDL-Cho: Low-density lipoprotein cholesterol.


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The mean UA rate was increasing progressively from 273 μmol/L (before donation) to attain the highest value at Y1 (316 μmol/L) then decreased to 306 μmol/L at Y4 (still <320 μmol/L).

The comparison of the mean values of metabolic rates between before donation and the different follow-up visits after donation had shown no significant elevation in mean FBS, mean HDL-Cho, and mean CPK rates at all the visits. A significant increase was found in the comparison of mean TC, mean TG, and mean UA rates, respectively, at M1 (0,002; P = 0.0001; P = 0.0001), M3 (P = 0.007; P = 0.025; P = 0.0001), M6 (P = 0.047; P = 0.0001; P = 0.0001), Y1 (P = 0.013; P = 0.003; P = 0.0001), Y2 (P = 0.043; P = 0.045; P = 0.0001), and Y4 (P = 0.017; P = 0.02; P = 0.0001). This difference was significant in both short and long terms. The comparison of mean LDL-Cho rates was significant only in short term at M1 (P = 0.09) and M3 (P = 0.014). However, the increase in mean LDL-Cho rates was nonsignificant at M6 (P = 0.3), Y1 (P = 0.11), Y2 (P = 0.16), and Y4 (P = 0.3) [Table 6].
Table 6: The comparison of mean values of biological parameters: metabolic profile (before vs. after donation).

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Diabetes mellitus occurred in one donor 72 months after donation. The donor was a woman aged more than 40 years and had obesity and HTN before nephrectomy. The prediabetes appeared in 40% two years after donation of donors with a mean period of occurrence 22 months. It was more frequent in women (26.5 vs 14.2%). The hyperuricemia happened in 4% equally in both sexes two years after donation with a mean period of occurrence – 14 months. The prevalence of hyperlipidemia in donors at Y2 (2 years of donation) was 61% and was greater in women (38.7% vs 22.4%), and the mean occurrence period was 12 months. The stroke occurred in one donor 22 months after donation. No case of myocardial infarction and no case of death were documented in the donors during a maximum follow-up of eight years [Table 4].

A progressive increase in the remaining kidney mean size was noted since M3 from 10.93 cm at baseline to 11.5 cm then reached 12.2 cm at Y1 and remained same all along the follow-up (12.3 cm at Y4). The ultrasound morphological notes among the 106 donors were found in <5% of cases: in the short-term follow-up, a residual collection in nephrectomy loge in three cases and infiltrated nephrectomy loge in one case. In the long-term follow-up, renal lithiasis occurred in one case and a simple cyst in the inferior pole in two cases. An asymptomatic benign prostatic hypertrophy without posturination residue was noted in two male donors after more than four years of follow-up. The comparison of the remaining kidney mean size measures between baseline and the different follow-up visits after donation had shown a significant elevation in three visits out of six: at M3 (P = 0.03), Y1 (P = 0.0001), and Y4 (P = 0.002). The increase was statistically insignificant at Y2.

Before donation, the microscopic hematuria was noted in four donors (3.7%); an aseptic leukocyturia was found in four cases and lower urinary tract infection with  Escherichia More Details coli germs was treated in two female donors. The cause of hematuria was investigated and the nutcracker syndrome (NCS) (left renal vein compression syndrome) was found in the CT angiogram. Two years after donation (at the visit Y2), 29 donors (61%) had performed a cyto-bacteriological examination of urine and was normal in 25 cases (86%). A urinary tract infection was diagnosed in ten cases all along the follow-up, and the mean period between infection and nephrectomy was one month. The infection was not severe, and no pyelonephritis was noted. At Y2, only one donor had confirmed hematuria. He was a 43-year-old man; he had a normal cyto-bacteriological examination of urine before donation, a normal ultrasound examination of bladder, prostate, and kidney had a GFR of 85 mL/min/1.73 m2 In this case it was the right kidney that was taken. Two years after nephrectomy, he had a GFR of 58 mL/ min/1.73 m2 and no lithiasis in the remaining kidney in the ultrasound examination. The follow-up of the four female donors that had NCS at the donation time had shown that three of them had no hematuria all along the follow-up and their GFR remained higher than 73 mL/ min/1.73 m2 at Y2 and one of them had a GFR = 57 mL/min/1.73 m2 with obesity, HTN, and hyperlipidemia occurring after donation but no hematuria with a normal ultrasound examination of the remaining kidney.


   Discussion Top


The donor’s age is an important parameter in the grafts outcomes.[14] The mean age of kidney donors in this study was similar to many other studies.[15] However, it was younger than many donors’ cohorts such as Gossmann et al,[16] Demir et al,[17] and de Yazawa et al.[18] It was higher than the mean age in Goecke et al.‘s study.[19] In this study, the percentage of donors (28%) aged more than 50 years was similar to many studies.[15] During the two past decades, this percentage is increasing (doubling) all over the world. An older donor was associated to worse outcomes of recipients’ grafts.[20] A medium-aged donor is preferable and is associated with a better graft survival in many studies but there are no definite recommendations by the North American and European transplantation associations.[21]

The sex ratio in this donor’s population was 0.6 with a proportion of 62%. The feminine predominance was noted in another Tunisian study[22] as well as many studies all over the world.[15],[16],[19],[23] In a large French study, the female predominance was found (sex ratio = 0.7) whatever the donor/recipient relationship was.[24] The female predominance was stable during the two last decades in the American studies.[25] However, male predominance was found in a Turkish study published by Demir et al.[17] In this study, like in other Tunisian and worldwide series, the most frequently noted donor/recipient relationships were as the following in decreasing order: mother/child, brothers and sisters, and spouses.[19],[22],[26] A higher percentage of spouses (38.2%) was reported by Wiedebusch et al.[27] The proportion of smokers in the largest North American donor series published was similar to ours (25%–35%), but the proportion of alcohol use was higher among the North American donors (more than 20%).[22],[28] The proportion of donors diagnosed with HTN before donation in this study was 3.6%. It was lower than in North African studies (11%–15%) and worldwide. It reached 17% for the North American series and 18% in the French studies.[22],[24],[29] Reese et al[30] and Briançon et al[31] attributed this variability to the differences in transplant center habits depending on the geographic location, donors’ availability, predominant age of the population, and transplantation activity frequency. The KDIGO 2014 guidelines recommended that DM is a contraindication for kidney donation, except under exceptional circumstances (1D).[21] No diabetic donors were reported in the Tunisian series as well as in this study,[18] although the proportion of non-insulin-dependent diabetics were 7%–11% in the American series and was 4.4% in France.[29],[32],[33]

In North American studies as well as in our study, the mean BMI was varied between 26 and 28 Kg/m2.[30] Similarly, the proportion of donors being obese Stage 1 of OMS classification in this study was similar to the proportion found in the American donors’ register (21%–22%).[30] In other Tunisian studies, this proportion was found to be increasing through the years. Comparing our donors’ outcomes with those of another Tunisian study that was conducted between 1986 and 2009, their proportion was 15%.[22] The prevalence of obesity among donors of another Tunisian study increased after nephrectomy (from 21% to 34%).[22] However, the stability of BMI after donation noted in this study was similar to some Japanese studies.[18],[34] The prevalence of obesity moving from 22% to 24% in two years after donation was superior to Ferreira-Filho et al’s finding[35] but remained inferior to El-Agroudy et al’s study.[23] Accordingly, kidney donation seems not to be exposing to obesity. Interestingly, the prevalence of obesity was less frequent in donors, two years after donation, than in the general Tunisian population, respectively, both in men (5% vs. 6.4%) and women (16.9% vs. 22.7%).[36] Some authors have concluded that preoperative obesity was a risk factor for GFR decrease and proteinuria after donation.[37] This fact has not been approved in the short term by Reese et al.[38] However, Rook et al have noted that the remaining kidney’s function was preserved in donors independently of the initial BMI.[39]

Before donation, the proportion of donors having HTN was 4%. Moreover, Segev et al have found a higher proportion of HTN among donors before nephrectomy (7%).[40] The proportion of donors having a SBP between 120 and 139 mm Hg was 51%. It was lower compared to an American cohort (40%). During donors’ follow-up, many studies did not find an increase in SBP and DBP after donation.[18],[41],[42] However, other studies have shown an increase in SBP and in DBP.[6],[43] Surprisingly, Yazawa et al had found a decrease in DBP after donation.[18] In this study, the prevalence of HTN went from 4% to 28% two years after donation. Furthermore, only one of five studies (249 donors with a follow-up duration varying between 2 and 28 years) found an increase of HTN prevalence after donation.[44],[45],[46] In the cohort of Tunisian donors, the prevalence of HTN two years after nephrectomy in both male (14.7%) and female donors (23.3%) was significantly lower than in the general population (35.9% and 46.2%, respectively).[36] Garg et al have found that gestational HTN and preeclampsia were noted among female donors in 8% to 11% in their Canadian study.[47] In our study, two female donors did have a history of preeclampsia but no case was reported after donation.

The follow-up of creatinine blood levels in this study had shown an increase by 20%, four years after donation compared to baseline. At A4, the GFR was at 72% of the baseline GFR (MDRD). In a retrospective Egyptian study that included 339 living donors, the GFR estimated 10 years post-donation was 73% of the baseline value.[23] The author considered that the renal function of donors was preserved.[23] The decrease in GFR of donors noted in this study (regardless of the estimation method) was found by other studies[48] In the short term, as in this study, some authors agreed that the GFR declines three to six months after nephrectomy and then improves beyond one year.[42],[48] In the contrary, others have found an earlier improvement in the function of the remaining kidney after three months of sampling.[49] Similarly, Goldfarb et al found that the serum creatinine elevation 25 years after donation was significant and still in the normal ranges.[43] Therefore, Ramcharan and Matas did not find significant difference in GFR 37 years after donation.[50] Surprisingly, Borchhardt et al noted a GFR improvement in the long term (137% of GFR expected regarding the age). This improvement was attributed to the compensatory hypertrophy and hyperfiltration in the remaining kidney.[51] During the follow-up, the mean Pu24H increased slightly in the short term then decreased in the long term. Although in the literature, there is no confirmed association between nephrectomy for donation and glomerular protein selectivity, Borchhardt et al recalled that theory in kidney donors.[51] In the studies of Ramesh Prasad et al and Samhan et al, no changes in 24-h urinary protein excretion were noted, respectively, in three and six months postdonation.[41],[42] In a review that included 48 studies and more than 5000 living donors, the mean 24-h urinary protein excretion was 0.154 g/L seven years after nephrectomy.[48] It is a higher value than this study with similar follow-up duration. In this same review of the literature, controlled studies concluded that urinary protein excretion was superior in donors compared to a matched control group of the general population.[48] In our study, the prevalence of proteinuria was 24%, two years after donation. Gossmann et al[16] concluded to a higher rate (65%). However, it was 12% according to Garg et al.[48] In our study, the MALB was noted in 24% of donors two years after nephrectomy. The prevalence of MALB in kidney donors was zero in the cohort of Gracida et al[52] and was varying between 10% and 20% in other studies such as studies by Gossmann et al and Yazawa et al[16],[18] and was 36% in the cohorts of Goldfarb et al.[37],[43]

The metabolic profile of the donors was not changed remarkably. It has long been argued that loss of renal mass may lead to glucose intolerance.[41] This has been confirmed experimentally by Sui et al.[53] Unlike our study, it has been shown by other authors that the modification in sugar blood rates was detected six months after nephrectomy.[54] In our study, DM occurred in one donor six years after donation, a lower prevalence than other studies.[18],[23],[50],[55] Furthermore, it was less than the prevalence of DM in the general Tunisian population both in male (13.6%) and female (15%).[36] According to El-Agroudy et al, the occurrence of DM was not correlated with age at the time of donation, nor with the number of years after nephrectomy.[23] The same study showed that DM was more frequent among donors who became obese after nephrectomy.[23] In this study, the prevalence of glucose intolerance increased from 30% at the time of donation to 40% two years after. However, this rate is still similar to its prevalence in the general Tunisian population.[36] The presence of glucose intolerance increases the risk of developing diabetes by 5%-10% per year in the general population.[53] However, other factors were imputed such as ethnicity, lipid profile, BMI, and family history of DM. But, it was described that disturbances in FBS rate and postprandial sugar blood rate are associated with increased risk of cardiovascular complications. These consequences seem to be more pronounced after nephrectomy.[48] Demographic changes in the US donor population including the increasing of older donors and the high-risk ethnic background proportions (more African American, Native American, and Hispanic) have influenced the prevalence of glucose intolerance, DM, and HTN among donors compared to the last two decades.[56] Nevertheless, the same study has shown that nephrectomy does not expose the donor to an increased risk.[56] Okamoto et al described in a study published in 2009 that donors with glucose intolerance and non-degenerative DM have the same risk of developing CKD as the general Japanese population.[57]

In our study, we noted an increase in mean TC and TG rates in both short and long term after donation. Concerning HDL-Cho, there was a decrease throughout the follow-up. But, in a prospective cohort study, Prasad et al[41] did not note any metabolic changes in donors six months after nephrectomy except the elevation of mean TG rates. Moreover, in the randomized controlled trial of Demir et al,[17] they concluded to a greater increase in TC and TG in donors compared to a matched control group in the general population during the same follow-up period. As in our study, they noted a decrease in HDL-Cho which is known as a protective factor against cardiovascular risk.[17] Sixty-two percent of our donors (22% of men and 38.7% of women) had hyperlipidemia two years after donation. This prevalence, despite being high, was comparable to the Japanese studies like the prevalence 48% noted by Yazawa et al[18] but it exceeded the prevalence of dyslipidemia in an Egyptian study.[23] By examining the changing in lifestyle of donors and its relationship with their weight and lipid status, Demir et al concluded that hyperlipidemia was significantly associated with weight gain and reduced physical activity.[17] In our study, the variation of uricemia after nephrectomy was a progressive and constant elevation. This increase was significant in both short and long term. Indeed, Kasiske et al described in their series that kidney donation was followed by an elevation of mean uric acid blood rates that could last up to three years after nephrectomy.[54] This elevation appeared inconsequential and was considered the expected result of nephrectomy.[54] According to Rossi et al,[58] mean hyperuricemia would increase significantly starting from the 1st and 2nd year postdonation, without reaching a pathological level. Like in our study, these same outcomes have been described by Undurraga et al.[59] and Hida et al.[60] The prevalence of hyperuricemia in our donors was low (4%) and similar to several studies.[58],[60]

In this study, the increase in the mean size of the remaining kidney was gradual and significant in both short and long term. It was independent of donor’s sex, age, and BMI at the time of donation. The compensatory renal hypertrophy has been reported by Chang et al.[61] They found that hypertrophy was similar in both sexes and inversely correlated to initial BMI. Furthermore, it was significantly greater in donors younger than 40 years.[61] During follow-up, two donors (2.1%) developed lithiasis, one donor had a single simple cyst (Bosniak type1) on the remaining kidney, and two donors had benign prostatic hypertrophy without bladder residua. The occurrence of renal lithiasis in LKDs was reported in the literature with comparable low rates.[22],[23],[43]

In our study, perioperative mortality was zero. Many author findings concluded to a low rate of perioperative mortality related to the donation between 0 and 0.03%.[62],[63] Segev et al in their study of 80347 living donors from the American national registry found that the postoperative mortality was around 3.1 per 10,000. This mortality rate has not changed over the last 15 years (from 1994 to 2009) despite changes in donor selection criteria and surgical nephrectomy techniques. This perioperative mortality was higher in male, Afro-American, and hypertensive donors.[40] During the follow-up, no deaths were recorded in our study. For long-term mortality, the same study compared mortality among donors with an age- and comorbidities-matched control group (a sample of the general population randomly chosen from participants in the American NHANES national study). The study found a similar risk of death among donors and the general population, regardless of age, gender, and ethnicity for a median follow-up of 6.3 years.[40] Another American-controlled study in 2010 did not show a higher risk of mortality after nephrectomy for donation, compared to the general population.[64] In a Chinese meta-analysis that included 62 studies in 19 countries, the postdonation morbidities were analyzed in 114,783 donors. These studies covered periods of six months, five years, 10 years, and more than 10 years. The prevalence of ESRD was 1.1% and all-cause mortality was 3.8%. The kidney-related mortality occurred 10 years of follow-up after nephrectomy.[7]

The main surgical complications encountered in the literature are pneumothorax, pleural effusion, and wound abscess.[62],[65],[66],[67] The postoperative complications rate was low but varied in different studies. This rate was estimated <10%, with 2% major complications and 8% minor complications according to Johnson et al, in a study of 871 donors operated by lobotomy.[62] The postoperative complications were more frequent, occurring in 14% of cases according to Wiesel et al[44] and in 25% in other studies.[4],[63],[68] Pneumothorax and pleural effusion complications were described by Okamoto et al in a Japanese mono-centric study enrollling 601 donors and occurred in <1% of cases, like in our study.[57] Other surgical complications were not found in our study but described in other studies including deep retroperitoneal suppuration after nephrectomy,[66] paralytic ileus,[62] and acute retention of urine.[6] Like in our study, bronchopulmonary and lower urinary tract infections were commonly reported during hospitalization.[62],[66],[67] Like in our study, deep venous thrombosis, myocardial infarction, and pulmonary embolism were rarely reported in various studies.[62],[65],[66] Other scarce medical complications have been reported in the literature such as unexplained fever, drug anaphylactic reaction, and pseudo-membranous colitis.[62],[65] Like in our study, Duque et al[69] found that 5.8% of donors reported significant discomfort due to the lumbar incision scar. In a French national report, 23% of donors complained of uncomfortable pain related to the nephrectomy during the first postoperative months.[30] According to Young et al,[52] the risk of postoperative complications related to nephrectomy for donation was not higher in elderly donors. However, Dols et al found a higher rate in elderly and obese donors.[70] In a cohort of 871 donors, the risk factors of surgical complications found by Johnson et al[62] were gender (male) and obesity (weight ≥100 kg).

The outcomes of eight years in living kidney donation care providing showed the complications related to the procedure of nephrectomy were rare. Our results are strong arguments for harmlessness of renal donation but emphasize the importance of a careful and science-based selection process. Post donation follow-up, seemingly insufficient in our study, is the only guarantor of short- and long-term safety for donors and therefore helps to encourage the act of donating in other potential donors. This follow-up has to be prolonged beyond 10 years. Further studies on risk factors of the reported complications and factors influencing donor adherence to follow-up would be of interest. The establishment of a Tunisian national registry of LKDs has become a necessity. In addition, the emerging interest of transplant teams around the world for other particularly genetic factors is urging us to update the donor selection process. The use of a calculated score, that predicts CKD with projection in 25 years after nephrectomy in donating candidates (GFR <60 mL/min/1.73 m2), is a valuable way to optimize the safety of this noble act.

Conflict of interest: None declared.



 
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Correspondence Address:
Imen Abdellaoui
Nephrology, Dialysis and Transplantation Ward, Sahloul Hospital, University of Medicine, Sousse
Tunisia
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DOI: 10.4103/1319-2442.256848

PMID: 31031377

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    Abstract
   Introduction
   Subjects and Methods
   Statistical Analysis
   Results
   Discussion
    References
    Article Figures
    Article Tables
 

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