Impact of Obesity in Kidney Transplantation

A Prospective Cohort Study From French Registries Between 2008 and 2014

Clarisse Grèze; Bruno Pereira; Yves Boirie; Laurent Guy; Clémentine Millet; Guillaume Clerfond; Cyril Garrouste; Anne-Elisabeth Heng

Disclosures

Nephrol Dial Transplant. 2022;37(3):584-594.

Abstract and Introduction

Abstract

Graphical Abstract

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Background: The access of obese patients to kidney transplantation is limited despite several studies showing that obese transplant recipients had a better survival rate than those undergoing dialysis. The aim of this study was to compare patient and graft survival rates and post-renal transplant complications in obese patients and non-obese patients and to assess the effect of pre-transplant weight loss in obese patients on transplant outcomes.

Methods: We carried out a prospective cohort study using two French registries, the Renal Epidemiology and Information Network and CRISTAL, on 7270 kidney transplant patients between 2008 and 2014 in France. We compared obese patients with non-obese patients and obese patients who lost more than 10% of weight before the transplant (obese WL and obese nWL).

Results: The mean BMI in our obese patients was 32 kg/m². Graft survival was lower in obese patients than in non-obese patients {hazard ratio (HR) = 1.40, [95% confidence interval (95% CI) 1.09; 1.78], P = 0.007}, whereas patient survival was similar [HR = 0.94, (95% CI 0.73; 1.23), P = 0.66]. Graft survival was significantly lower in obese WL than in obese nWL [HR = 2.17, (1.02; 4.63), P = 0.045], whereas patient survival was similar in the two groups [HR = 0.79, (0.35; 1.77), P = 0.56].

Conclusion: Grade 1 obesity does not seem to be a risk factor for excess mortality after kidney transplantation and should not be an obstacle to having access to a graft. Weight loss before a kidney transplant in these patients should not be essential for registration on waiting list.

Introduction

Since the early 2000s, the prevalence of obesity in the Western world has been increasing annually.^[1] Obesity and its complications, in particular cardiovascular and metabolic disorders, increase the risk of chronic kidney disease.^[2–5] The prevalence of the disease in France in 2015 was 22% in dialysis patients^[6] versus 17% in the general population.^[7] The access of these obese patients to kidney transplantation is limited despite several studies showing that obese transplant recipients had a better survival rate than those undergoing dialysis.^[8–12] In France, although the High Authority for Health recommends offering renal transplants to patients with a body mass index (BMI) greater than 50 kg/m²,^[13] most transplant teams prefer potential recipients to have a BMI lower than 35 kg/m². Hence, obese patients are encouraged to lose weight before receiving a graft or being placed on a transplant waiting list.

Most relevant studies have shown that obese renal transplant recipients have more complications postoperatively and during the first year of graft than non-obese patients.^[14–27] However, obese patient and graft survival rates differ between reports.

Of the few studies investigating the effect of weight loss before transplantation on graft outcome in obese patients, most were performed in the USA.^[31–33] A preliminary study based on data from a French transplant centre showed that obesity and weight loss pre-transplant had no effect on graft outcome and patient survival.^[34]

The aim of this new study was to compare patient and graft survival rates and post-renal transplant complications in obese patients and non-obese patients and to assess the effect of pre-transplant weight loss in obese patients on transplant outcomes using data from French national registries.

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Table 1. Baseline characteristics: obese versus non-obese
	Obese (n = 1502)	Non-obese (n = 5768)	P
Male, n (%)	843 (56.1)	3789 (65.7)	<0.001
Mean age at the time of transplant ± SD, years	57 ± 11	53 ± 14	<0.001
Maximum weight before transplant, kg	91.4 ± 12.8	69.8 ± 13.2	<0.001
Maximum BMI before transplant, kg/m²	32.7 ± 3.3	24.3 ± 3.7	<0.001
Weight at transplant, kg	89.2 ± 12.4	67.4 ± 12.6	<0.001
BMI at transplant, kg/m²	32.0 ± 3.3	23.5 ± 3.5	<0.001
Weight loss before transplant (IQR), %	−1.4 (−6.2; 2.5)	−1.5 (−5.8; 2.4)	0.71
Initial nephropathy, n (%)			<0.001
Diabetic nephropathy	331 (22.1)	578 (10.0)	*
Vascular nephropathy	243 (16.2)	736 (12.8)	*
Glomerulopathy	263 (17.5)	1358 (23.5)	*
Polycystic kidney disease	179 (11.9)	957 (16.6)	*
Other	325 (21.6)	1421 (24.6)
Unknown	161 (10.7)	718 (12.5)
Time of dialysis ± SD, months	42.8 ± 29	41.4 ± 32	0.002
Time on waiting list ± SD, months	24.6 ± 20	24.1 ± 19	0.46
Time between start of dialysis and registration on the list ± SD, months	22.7 ± 25.8	21.6 ± 27.6	<0.001
Past medical history, n (%)
Diabetes	494 (32.9)	823 (14.3)	<0.001
Dyslipidemia	663 (44.1)	1498 (26.0)	<0.001
Chronic heart failure	54 (3.6)	138 (2.4)	0.09
Hypertension	937 (62.4)	3097 (53.7)	<0.001
Ischaemic cardiopathy	92 (6.2)	245 (4.2)	0.008
Coronary arterial disease	169 (11.3)	434 (7.5)	<0.001
Cardiac arrhythmia	76 (5.1)	203 (3.5)	0.006
Stroke	59 (3.9)	201 (3.5)	0.64
Peripheral vascular disease	78 (5.2)	176 (3.1)	<0.001
Smoking	564 (37.5)	2114 (36.7)	0.11

IQR, interquartile range; SD, standard deviation. Bold type indicates statistically significant difference.
*P < 0.05.

Table 2. Transplantation characteristics: obese versus non-obese
	Obese (n = 1502)	Non-obese (n = 5768)	P
Serum albumin levels ± SD, g/L	38.1 ± 4.6	38.3 ± 5.0	0.23
Donor type, n (%)			<0.001
Living donor	61 (4.0)	385 (6.7)	*
Donation after circulatory death donors	32 (2.1)	150 (2.6)
Deceased donor with standard criteria	625 (41.6)	2817 (48.9)	*
Deceased donor with expanded criteria	784 (52.3)	2416 (41.8)	*
Age of the donor ± SD, years	57 ± 15	53 ± 16	<0.001
Cold ischaemic time (IQR), h	16 (12; 20)	15 (12; 19)	0.001
Warm ischaemic time (IQR), min	50 (36; 67)	43 (33; 60)	0.001
Mismatch HLA-A, n (%)			0.34
0	204 (13.6)	841 (14.6)
1	787 (52.4)	3069 (53.2)
2	511 (34.0)	1858 (32.2)
Mismatch HLA-B, n (%)			0.92
0	120 (8.0)	449 (7.8)
1	653 (43.5)	2539 (44.0)
2	729 (48.5)	2780 (48.2)
Mismatch HLA-DR, n (%)			0.04
0	422 (28.1)	1475 (25.6)
1	848 (56.4)	3270 (56.7)
2	232 (15.5)	1023 (17.7)
HLA antibodies ± SD, %	4.7 ± 15	4.0 ± 13	0.12

HLA, human leukocyte antigen; IQR, interquartile range. Bold type indicates statistically significant difference.
*P < 0.05.

Table 3. Post-transplant complications: obese versus non-obese
	Obese (n = 1 502)	Non-obese (n = 5 768)	P (univariate)	OR (95% CI) (multivariate)	P (multivariate)
Primary graft failure, n (%)	108 (7.2)	336 (5.8)	0.05	1.19 (0.77; 1.84)	0.77
Delayed graft function, n (%)	370 (24.6)	709 (12.3)	<0.001	2.39 (1.96; 2.91)	<0.001
Length of hospital stay (IQR), days	15 (11; 21)	14 (10;19)	0.001	0.93a (0.06; 1.79)	0.04
Ureteral complication, n (%)	102 (6.8)	367 (6.4)	0.55	1.41 (0.83; 2.41)	0.21
Vascular graft complication, n (%)	136 (9.1)	460 (8.0)	0.17	0.93 (0.61; 1.41)	0.74
Graft haemorrhage, n (%)	34 (2.3)	120 (2.1)	0.66	1.15 (0.67; 1.97)	0.61

Bold type indicates statistically significant difference.
^aRegression coefficient.

Table 4. Post-transplant complications: obese versus non-obese
	HR (95% CI) (univariate)	P (univariate)	HR (95% CI) (multivariate)	P (multivariate)
Acute rejection	1.12 (0.94; 1.34)	0.06	0.45 (0.16; 1.30)	0.14
Bacterial infection	1.10 (0.98; 1.22)	0.12	1.06 (0.60; 1.87)	0.85
Fungal infection	1.02 (0.70; 1.49)	0.11	0.89 (0.60; 1.33)	0.57
Cardiovascular complication	1.24 (1.06; 1.45)	0.06	1.04 (0.86; 1.25)	0.70
Post-transplant diabetes	1.77 (1.38; 2.30)	<0.001	1.68 (1.30; 2.18)	<0.001
Digestive complication	1.10 (0.9; 134)	0.36	0.93 (0.75; 1.20)	0.67

Bold type indicates statistically significant difference.

Table 5. Baseline characteristics: obese WL versus obese nWL
	Obese WL (n = 218)	Obese nWL (n = 1 284)	P
Male	117 (53.7)	726 (56.5)	0.43
Mean age at the time of transplant ± SD, years	54 ± 13	57 ± 11	0.001
Maximum weight before transplant, kg	96.8 ± 13.9	90.5 ± 12.3	<0.001
Maximum BMI before transplant, kg/m²	34.6 ± 3.7	32.4 ± 3.2	<0.001
Weight at transplant, kg	81.6 ± 12.0	90.5 ± 12.0	<0.001
BMI at transplant, kg/m²	29.1 ± 3.3	32.4 ± 3.1	<0.001
Weight loss before transplant (IQR), %	−14.1 (−17.8; −11.9)	0 (−3.8; 3.4)	<0.001
Initial nephropathy, n (%)			0.57
Diabetic nephropathy	44 (20.2)	287 (22.4)
Vascular nephropathy	37 (17.0)	206 (16.0)
Glomerulopathy	43 (19.7)	220 (17.1)
Polycystic kidney disease	21 (9.6)	158 (12.3)
Other	46 (21.1)	279 (21.8)
Unknown	27 (12.4)	134 (10.4)
Time of dialysis (IQR), years	4 (3; 6)	3 (2; 4)	0.001
Time on waiting list ± SD, months	26.4 ± 21.6	23.8 ± 19	0.12
Time between start of dialysis and registration on waiting list ± SD, months	32.4 ± 34.8	21 ± 23.5	<0.001
Past medical history, n (%)
Diabetes	67 (30.1)	427 (33.3)	0.69
Dyslipidémia	94 (43.1)	569 (44.3)	0.55
Chronic heart failure	9 (4.1)	45 (3.5)	0.20
Hypertension	125 (57.3)	812 (63.2)	0.33
Ischaemic cardiopathy	10 (5.0)	82 (6.7)	0.39
Coronary arterial disease	21 (9.6)	148 (11.5)	0.57
Cardiac arrhythmia	12 (5.5)	65 (5.1)	0.65
Stroke	9 (4.1)	50 (3.9)	0.77
Peripheral vascular disease	10 (5.0)	68 (5.3)	0.77
Smoking	73 (33.5)	491 (38.2)	0.28

IQR, interquartile range; SD, standard deviation. Bold type indicates statistically significant difference.
*P < 0.05.

Table 6. Transplantation characteristics: obese WL versus obese nWL
	Obese WL (n = 218)	Obese nWL (n = 1284)	P
Serum albumin levels (g/L)	37.8 ± 4.6	38.2 ± 4.2	0.22
Donor type, n (%)			0.55
Living donor	9 (4.1)	52 (4.0)
Donation after circulatory death donors	7 (3.2)	25 (2.0)
Deceased donor with standard criteria	95 (43.6)	530 (41.3)
Deceased donor with expanded criteria	107 (49.1)	677 (52.7)
Age of the donor, ± SD, years	54 ± 16	57 ± 14	0.03
Cold ischaemic time (IQR), h	16 (13; 20)	16 (12; 20)	0.31
Warm ischaemic time (IQR), min	47 (31; 70)	50 (37; 67)	0.07
Mismatch HLA-A, n (%)			0.27
0	23 (10.6)	181 (14.1)
1	123 (56.4)	664 (51.7)
2	72 (33.0)	439 (34.2)
Mismatch HLA-B, n (%)			0.62
0	20 (9.2)	100 (7.8)
1	89 (40.8)	564 (43.9)
2	109 (50.0)	620 (48.3)
Mismatch HLA-DR, n (%)			0.79
0	62 (28.4)	360 (28.0)
1	119 (54.6)	729 (56.8)
2	37 (17.0)	195 (15.2)
HLA antibodies ± SD, %	6.6 ± 17.7	4.4 ± 13.9	0.10

HLA, human leukocyte antigen; IQR, interquartile range. Bold type indicates statistically significant difference.

Table 7. Post-transplant complications: obese WL versus obese nWL
	Obese WL (n = 218)	Obese nWL (n = 1 284)	P (univariate)	OR (95% CI) (multivariate)	P (multivariate)
Primary graft failure, n (%)	20 (9.2)	88 (6.9)	0.22	1.58 (0.62; 4.00)	0.33
Delayed graft function, n (%)	49 (22.5)	321 (25.0)	0.86	1.02 (0.62; 1.66)	0.95
Length of hospital stay (IQR), days	17 (12; 27)	15 (11; 20)	0.001	5.49^a (3.26; 7.73)	<0.001
Ureteral complication, n (%)	16 (7.3)	86 (6.7)	0.73	1.05 (0.30; 3.72)	0.94
Vascular graft complication, n (%)	25 (11.5)	111 (8.6)	0.18	0.60 (0.18; 2.03)	0.41
Graft haemorrhage, n (%)	6 (2.8)	28 (2.2)	0.60	0.31 (0.04; 2.38)	0.26

Bold type indicates statistically significant difference.
^aRegression coefficient.

Table 8. Post-transplant complications: obese WL versus obese nWL
	HR (95% CI) (univariate)	P (univariate)	HR (95% CI) (multivariate)	P (multivariate)
Acute rejection	0.97 (0.45; 1.32)	0.4	1.62 (1.01; 2.61)	0.04
Bacterial infection	0.94 (0.71; 1.25)	0.69	1.04 (0.17; 6.37)	0.97
Fungal infection	2.73 (0.65; 11.40)	0.17	0.40 (0.95; 1.69)	0.21
Cardiovascular complication	1.26 (0.84; 1.92)	0.27	0.79 (0.47; 1.32)	0.36
Post-transplant diabetes	1.67 (0.81; 3.37)	0.17	0.56 (0.27; 1.16)	0.12
Digestive complication	0.86 (0.54; 1.39)	0.55	1.29 (0.76; 2.18)	0.34