Objectives: Donor kidney measurements may affect outcomes of transplanted allografts. We tested allograft and recipient measurements on kidney allograft outcomes. In this study, we compared the effects of kidney allograft volumes, which were measured using computed tomographic angiography before transplant, and allograft weight, which was measured during surgery, in relation to the recipient’s body weight and body mass index on kidney function at 6 and 12 months after transplant.
Material and Methods: We included 74 patients (40 female and 34 male patients, mean age of 50.42 ± 9.75 y) in this study.
Results: Intraoperative allograft weight was 182.68 ± 40.33 g (range, 104-266 g). The allograft volume measured using computed tomographic angiography scanning was 123.34 ± 24.26 mL (range, 78-181 mL). The estimated glomerular filtration rates of the recipients at 6 and 12 months after transplant correlated negatively with age and recipient body mass index but correlated positively with allograft volume/recipient body weight, allograft volume/recipient body mass index, allograft weight, allograft weight/recipient body weight, and allograft weight/recipient body mass index values, as concluded by univariate analyses. From multivariate analyses, we found variables of interest presumed to significantly affect the 12-month estimated glomerular filtration rates, including recipient age, allograft volume/recipient body weight, allograft volume/recipient body mass index, allograft weight, allograft weight/recipient body weight, and allograft weight/recipient body mass index.
Conclusions: Transplanted allograft and recipient body values may be used as predictors of estimated glomerular filtration rates 6 and 12 months after transplant.
Key words : Body mass index, Kidney allograft volume, Kidney allograft weight, Kidney function, Transplantation
The best treatment option for patients with end-stage renal disease is kidney transplant.1 Living-donor kidney transplant has become more favored recently due to shortages in grafts from deceased donors.2 Immunologic and nonimmunologic factors affect graft survival after kidney transplant. Although advances in immunosuppressive therapies for acute immunologic complications have resulted in improved short-term graft survival, long-term survival has not been as successful. Renal function within the first year has also been reported to be an important factor contributing to long-term graft outcomes.3 To improve the long-term graft survival rate, attention has shifted to research concerning the effects of nonimmunologic factors. Donor age, sex, and kidney function are the typical nonimmunologic factors that affect long-term graft outcomes and have recently drawn the attention of researchers.4
Animal studies have suggested that the nephron supply is also an important determinant of long-term allograft outcomes.5 The concept of nephron dosing, which refers to the proper dosing of the nephron supply in accordance with the recipient’s needs, influences posttransplant outcomes, as hypothesized by Brenner and associates and confirmed in other previous studies.6 Graft survival is improved if the volume of the donated kidney is appropriate for the recipient’s body mass. The dominant kidney should ideally remain within the donor, according to the nephron mass hypothesis. The smaller number of nephrons present in a smaller kidney, when transplanted to the patient, may face hyperfiltration injury due to the higher filtration demands in the recipient.7 Donor nephron dosing assessments are performed using various analyses of 24-hour urinary specimens and renal scintigraphic studies. Moreover, nephron dosing is also accomplished by weighing the allograft during the operation and by performing preoperative radiologic studies. Computed tomographic angiography (CTA) is a routine radiologic scan used in the preoperative evaluation of kidney donors. Computed tomographic angiography provides the surgical team with information about the number of renal arteries and veins in each kidney. In addition, three-dimensional CTA allows the direct measurement of kidney volume before transplant.8 Transplanting a donor kidney with greater volume was previously shown to be associated with improved outcomes of the transplanted kidney in the recipient.9-12 Nephron dosing can be roughly estimated by weighing the kidneys of the donor during the operation.13 A small number of studies that directly weighed the mass of the kidney using an electronic weighing scale investigated the survival rate of the renal graft.14 In summary, transplanting an adequately sized kidney is important to compensate for the metabolic demands of the recipient.9,14 In some previous studies, the recipient’s age, sex, body weight, and body mass index (BMI), as well as nephron dosing, were all found to be independent predictors of renal allograft survival.15 A limited number of studies have compared the combined effects of allograft weight or allograft volume/recipient body weight, recipient BMI, donor body weight, and donor BMI on graft survival.
In this study, we compared allograft volumes, which were measured using CTA before transplant, and the weight of the donated kidney, which was measured during surgery, in relation to the recipient’s body weight and BMI values and its effects on recipient kidney function 6 and 12 months after transplant.
Materials and Methods
This study was carried out between September 2010 and November 2015 at the Baskent University Hospital (Istanbul, Turkey). The study group included 74 (40 female/34 male) kidney transplant recipients, with mean age of 50.42 ± 9.75 years.
Recipient and donor characteristics, such as age, sex, height (m), body weight (kg), BMI (body weight/height2), past medical history, physical examination findings, and follow-up information, were retrieved from the medical databases of our center. The presence of donor-specific antibodies and human leukocyte antigen matching were assessed preoperatively. Serum urea nitrogen, creatinine, and electrolyte levels were determined with the use of either a C8000 system (Abbott Laboratories, Abbott Park, IL, USA) or a Cobas e-411 (Roche, Germany) autoanalyzer. The creatinine clearance rate of each donor was calculated using a 24-hour urinary specimen before surgery.
All of the patients were 18 years or older, ABO compatible, and first time kidney recipients who were followed for at least 1 year after transplant. The primary aim was to preserve the better functioning kidney of the donor while transplanting the other kidney to the recipient.
We excluded the possible effects of immunologic and nonimmunologic factors on graft function and excluded recipients with systemic or local infection, surgical complications, rejection episodes, posttransplant ischemic graft injuries, and drug toxicities, which resulted in functional decreases of the kidney graft.
The recipients’ follow-up clinical and laboratory examinations were performed
6 and 12 months after transplant. Age, sex, and serum creatinine values that
were applied to the Modification of Diet in Renal Disease16 formula were
obtained at each follow-up visit (at 6 and 12 months). Estimated glomerular
filtration rates (eGFR; mL/min/1.73 m2) was calculated as follows:
1⁄4(186 × [serum creatinine]-1.154 × [age]-0.203 × 0.742
The immunosuppression protocol used at our institution consists of an antithymocyte globulin and methylprednisolone induction regimen followed by maintenance therapy with mycophenolate mofetil, prednisolone, and a calcineurin inhibitor (tacrolimus, cyclosporine). Acute rejection was considered if biopsy proven and classified according to Banff criteria, and delayed graft function was defined as the need for dialysis treatment in the first 7 days after transplant.
This study was conducted according to the Helsinki Declaration, and the study protocol was approved by the local institute’s Committee on Human Research (our local ethics body). All of the patients gave their informed consents.
Computed tomographic angiography was utilized for the preoperative evaluation of kidney donors. A radiology specialist surveyed the renal volume on CTA. The specialist had 7 years of experience in computed tomography and was blinded to the donor’s radionuclide renography findings and the creatinine-based glomerular filtration rate results. Patients underwent scanning with a Siemens Sensation 64-slice multidetector computed tomography scanner (Siemens AG, Munich, Germany). Our multidetector computed tomography protocol includes an unenhanced scan, which primarily helps to detect nephrolithiasis and serves as the baseline for diagnosing foci of abnormal enhancement. An arterial or corticomedullary phase scan is acquired using the bolus tracking method, with a scan delay of approximately 24 to 48 seconds from the time of commencement of contrast injection. The craniocaudal coverage extends from the level of the dome of the diaphragm to the pubic symphysis. Subsequently, venous or nephrographic phase acquisition is completed after a scan delay of approximately 70 seconds. The arterial and venous phase scans are useful for delineating the regional anatomy, including the vascular system. A delayed or pyelographic phase scan is performed after an interval of 5 to 15 minutes. This scan is useful for the morphologic evaluation of the pelvicaliceal system and the ureter. We did not use low-dose protocols in the arterial and venous phases, primarily because of the suboptimal evaluation of veins. Linear renal dimensions (length, lateral diameter, and anterior-posterior diameter) were measured. The renal length was calculated from axial slices by multiplying the slice thickness by the number of slices between the superior and inferior tips of the kidneys. The slice represented the greatest cross-sectional area for the width and thickness measurements. The lateral diameter was measured from the lateral extent of the kidney to the renal sinus, and the anterior-posterior diameter was measured perpendicular to the lateral diameter. The prolate-ellipsoid method was used to estimate kidney volume (volume [cm3] = length × width × thickness × π/6), excluding the renal sinus area and renal cysts.
The weight of the donated kidney was measured up to 1 decimal point in grams using a digital scale (Seca 22089, Hamburg, Germany) immediately after the cold flush during the surgery. The kidney included the renal mass, the renal pelvis, the renal capsule, the ureter, the renal artery, and vein and its lymphatic system while weighing.
Statistical analyses were performed with SPSS software (SPSS Inc., version 13.0, Chicago, IL, USA). Results are presented as means ± standard deviation for continuous variables and frequency and percent values for categorical variables. Mean values among groups were compared with either the t test when the distribution was normal or the Mann-Whitney U test when the distribution was not normal. Simple linear regression was performed to estimate the effect of the parameters and ratios, including donor age, recipient age, allograft weight/recipient body weight, allograft weight/recipient BMI, allograft volume/recipient body weight, allograft volume/recipient BMI, recipient BMI, donor BMI, and donor BMI/recipient BMI on eGFR measured at 6 and 12 months after transplant. Multiple linear regression analyses were performed to estimate the effects of variables, such as recipient age, donor age, recipient sex, donor sex, HLA mismatch, cold ischemia time, allograft volume, allograft weight, donor BMI, recipient BMI, allograft weight/recipient body weight, allograft weight/recipient BMI, allograft volume/recipient body weight, allograft volume/recipient BMI, and donor BMI/recipient BMI on eGFR at 12 months after transplant. The inclusion of variables was assessed using the forward method. A P value of < .05 was considered significant.
Among the 96 patients who received a living-donor kidney transplant and were included in the study, 1 patient was lost to follow-up in the posttransplant period and a number of posttransplant patients had to be excluded from the study due to BK virus nephropathy (4 patients), cellular or humoral rejection episodes (14 patients), posttransplant ischemic injury (2 patients), and calcineurin inhibitor toxicity (1 patient). Hence, 74 patients met the study criteria and were included in the final statistical analyses.
Characteristics of donors and recipients, as well as their 6- and 12-month posttransplant creatinine levels, are shown in Table 1. Tacrolimus was administered to 75.6% of patients, whereas 97.3% of patients received mycophenolate mofetil.
The intraoperatively measured allograft weight was 182.68 ± 40.33 g (range, 104-266 g). The allograft weight correlated with both the donor body weight (r = 0.563; P < .001) and donor BMI (r = 0.342; P = .02). As expected, male kidney weights were greater than female kidney weights, with mean kidney weights of 199.80 ± 42.13 g (range, 134-266 g) for men and 170.00 ± 34.47 g (range, 104-224 g) for women (P = .014).
The allograft volume measured using CTA scan was 123.34 ± 24.26 mL (range, 78-181 mL). The allograft volume correlated statistically with allograft weight (r = 0.649; P < .001), donor body weight (r = 0.646; P < .001), and donor BMI (r = 0.471; P < .001). We failed to detect any significant sex-related differences (P = .086) in the mean allograft volumes between men (130.42 ± 21.82 mL [range, 96-181 mL]) and women (117.96 ± 25.05 mL [range, 78-171 mL]).
The eGFR of the recipients that was calculated using the Modification of Diet in Renal Disease formula at 6 months after transplant correlated negatively with age and recipient BMI but correlated positively with allograft volume/recipient body weight, allograft volume/recipient BMI, allograft weight, allograft weight/recipient body weight, allograft weight/recipient BMI, and recipient BMI values, as concluded by univariate analyses (Table 2).
The eGFR of the recipients that was calculated using the Modification of Diet in Renal Disease formula at 12 months after transplant correlated negatively with age and recipient BMI but correlated positively with the allograft volume/recipient body weight, allograft volume/recipient BMI, allograft weight, allograft weight/recipient body weight, allograft weight/recipient BMI, recipient BMI, and donor BMI/recipient BMI values, as concluded by univariate analyses (Table 2).
We also measured the correlation between sex and renal size posttransplant but found no statistically significant results.
Factors such as age, donor, recipient sex, recipient BMI, donor BMI, donor BMI/recipient BMI, allograft volume, allograft volume/recipient body weight, allograft volume/recipient BMI, allograft weight, allograft weight/recipient body weight, and allograft weight/recipient BMI, which were presumed to affect the 12-month eGFRs that were calculated using the Modification of Diet in Renal Disease formula, were tested using multivariate analyses. Among these factors, age, allograft volume/recipient body weight, allograft volume/recipient BMI, allograft weight, allograft weight/recipient body weight, and allograft weight/recipient BMI were found to have significant effects on the 12-month eGFR values (Table 3 and Figure 1).
Several donor- and recipient-related factors were suggested to act on kidney graft function after transplant. As reported before, donor body weight, graft weight or volume, and body surface area, or in combination, with allograft weight/recipient body weight, body surface area/recipient body weight, allograft volume/recipient body weight, and allograft volume/recipient body surface area; hence, these factors predict the graft survival rate.
In the present study, the ratios between the recipients’ body measurements and renal volume and the weight of the donated kidneys were found to affect eGFR, which was calculated based on creatinine levels at 6 and 12 months after transplant.
As shown in both animal and human studies, the nephron mass of the transplanted kidney independently influences posttransplant outcomes.5,17 The kidney that is to be transplanted should include enough nephron dosing to meet the metabolic demands of the recipient. Body measurements, such as weight, height, and BMI, of recipients are the main determinants of the metabolic demands on the donated kidney according to Kwon and associates.18 If the transplanted kidney nephron dosing fails to meet the metabolic demands of the recipient, the resulting hyperfiltration will negatively affect graft survival.19 Because we cannot measure the number of nephrons in a kidney in vivo, the renal weight or volume appears to be the best marker for estimating renal mass.13 Kidney weight is highly correlated with the mean glomerular volume and the number of glomeruli per kidney.6
Several studies also investigated the effects of kidney weight on posttransplant follow-up parameters. In a multicenter study from Giral and associates, 1189 patients receiving deceased-donor kidney transplants were investigated, and a mismatch between kidney weight and recipient weight was found to be an independent predictor of long-term graft survival.20 Giral and associates found that a lower ratio of donated kidney weight to recipient body weight was associated with a 55% increased risk of allograft failure 2 years after transplant. A study performed by Hwang and associates revealed that the allograft weight-to-recipient body weight ratio significantly affected long-term graft survival rates and early graft function in a 10-year follow-up of their patients after renal transplant.21 The kidney weight-to-recipient body weight ratio was found to be a reliable predictor of recipient eGFR in a study performed by Amante and associates.22 In another study by Douverny and associates that investigated 123 living-donor kidney recipients, the donor kidney weight was found to correlate positively with the donor’s BMI and the recipient’s 12-month posttransplant creatinine clearance rate.23 Kidney weight measurements from deceased donors may have value in the selection of a recipient for better graft survival. Interestingly, in univariate analyses of our findings, the kidney weight measurement alone was found to be a positive influencing factor for posttransplant kidney function at 6 and 12 months after surgery.
In the literature, some studies failed to find any relation between kidney weight measurements and graft survival rate. Giral and associates reported no effect of allograft weight-to-recipient weight ratio on graft survival rate at the end of a 32-month follow-up.14 In another study performed by Vianello and associates in 112 first-time deceased-donor kidney recipients, recipient allograft-to-recipient weight ratio had no significant effect on either kidney graft function or survival during short- to medium-term follow-up.24 According to Tent and associates, an adaptive change in the size of the transplanted kidney occurs in accordance with the recipient’s body size, without any consequent negative effect on function or survival rates.25 In our study, the mean graft weight (182.68 ± 40.33 g) was similar to reported data in other studies.23
Another marker of the nephron number in the kidney has been shown to be renal volume.26 Renal volume estimated using radiologic studies correlates strongly with direct anatomic measurements of kidney volume, as shown previously.27 We measured living-donor renal volumes using CTA. The three-dimensional volume data provided by CTA also includes congenital or acquired anatomic defects of the kidneys in the measurements. Pretransplant estimated renal volume and function may be crucial for determining the graft survival rate in kidney recipients. In a study by Poggio and associates, the renal volume was found to be strongly correlated with living-donor kidney function; hence, this parameter was an independent determinant of posttransplant kidney function.9 Saxena and associates reported that the ratio of renal volume measured using magnetic resonance imaging to the recipient’s body weight is a predictor of graft function.10 Allograft kidney volume estimated using computed tomography scans, donor age, and recipient body surface area were correlated with graft function according to a study by Hugen and associates.11 In a study by Juluru and associates, the ratio of renal cortical volume determined using CT scanning to the recipient’s pretransplant weight was found to correlate with the 12- and 24-month eGFR values.28 In their study, Sikora and associates divided their patients into 3 groups based on the ratio of renal volume to recipient body weight. At the end of the 12th month, the first and the last tertile groups of patients were found to differ significantly in renal function depletion rates.29 However, in a study from Chen and associates with a small sample size, renal volume estimated based on computed tomography scans and eGFR values were not found to be related. The lower renal volume measurements reported in this study are probably due to the ethnic origin of the sample population.30
In our study, several factors presumed to affect posttransplant graft survival rate, including age, recipient sex, donor sex, allograft volume/recipient body weight, allograft volume/recipient body mass index, allograft weight/recipient body weight, allograft weight/recipient body mass index, and donor body mass index/recipient body mass index, were investigated. In multivariate analyses, all of the above-mentioned parameters were found to have significant effects on the 12-month eGFR values except allograft volume measurements. In our search of the literature, we identified a study that investigated both renal volume and kidney weight measurements. In this study performed by Lee and associates, body surface area was used instead of BMI, and the 1- and 6-month eGFR values were compared among groups.31 In our study, we did not include the eGFR values at 1 month after transplant to avoid drug effects. Lee and associates reported that only the allograft volume-to-body surface area ratio had a significant effect on 6-month posttransplant eGFR values. Although a number of studies have investigated the effects of renal weight-to-BMI ratio on eGFR, we did not encounter any study that investigated the effects of the allograft volume-to-BMI ratio on graft survival rate. In our study, none of the factors except renal volume was observed to significantly affect eGFR 12 months after transplant. However, our study differs from that of Lee and associates in that our study also presented findings related to the effects of factors on eGFR at 12 months after transplant. Our study depicts the importance of both renal volume and weight as factors that contribute to eGFR values at 6 and 12 months after transplant.
In several previous studies, it was observed that the ratios of allograft volume and kidney weight to the recipients’ body measurements are significant predictors of long-term graft survival. However, these studies have some drawbacks in their patient selection criteria. Patients with acute rejection episodes were not excluded. The eGFR values of patients with or without acute rejection episode were analyzed together. Acute rejection has an incidence of 10% to 30% after renal transplant. In many previous studies, it was shown that acute rejection rates and posttransplant graft function are affected by graft size. In a study by Poggio and associates in patients with lower kidney weights, the rates of acute rejection episodes were found to be higher.9 Acute rejection is one of the factors that influence long-term graft survival rates. Including patients with acute graft rejection bears the risk of overestimating the decrease in the eGFR of the study population. In our study, patients who developed either humoral or cellular rejection were excluded.
In our study, we observed a negative correlation between recipient age and eGFR values at both the 6- and 12-month evaluations. Our study confirmed the findings of previous studies concerning the relation between the recipient age and eGFR values.21,32,28 However, some studies reported that age has no effect. In our study, we did not observe any effect of donor age on eGFR values at the 6- and 12-month evaluations. In some studies, the age of the donor was reported to affect eGFR values to a certain degree. In a study by Toma and associates, the most important risk factor affecting long-term graft survival rate 5 years after transplant was a donor age greater or equal to 60 years.33
Our study has some limitations. It is likely that the differences are sufficiently small that donor selection would rarely be affected by these parameters, except perhaps when multiple suitable living donors are available. A longer follow-up may also reveal further effects of donor-recipient kidney size mismatches on graft survival. In addition, renal volumes measured using CTA were not confirmed by intraoperative measurements.
Transplanted allograft and recipient body values may be used as predictors of eGFR values at 6 and 12 months after transplant.
Volume : 16
Issue : 3
Pages : 266 - 273
DOI : 10.6002/ect.2015.0353
From the 1Department of Nephrology, the 2Department of
General Surgery, and the 3Department of Radiology, Baskent University
School of Medicine, Uskukar/Istanbul, Turkey; and the 4Division
of Transplantation, Baskent University School of Medicine, Ankara, Turkey
Acknowledgements: The authors have no conflicts of interest to disclose and had no funding to support this study.
Corresponding author: Eyup Kulah, Baskent University Istanbul Hospital Oymaci Sok. No: 7, 34662 Uskudar, Istanbul, Turkey
Phone: +90 216 554 1500
Table 1. Overall Characteristic of Donors and Recipients
Table 2. Factors Affecting the 6- and 12-Month Estimated Glomerular Filtration Rates Based on Univariate Analyses
Table 3. Factors Affecting the 12-Month Estimated Glomerular Filtration Rates Based on Multivariate Analyses
Figure 1. Correlations Between Allograft and Body Measurements and 6- and 12-Month Modification of Diet in Renal Disease Formula Values