Variability in the leptin receptor gene and other risk factors for post-transplant diabetes mellitus in renal transplant recipients

Figures & data

Table 1. Clinical and demographic parameters of the study population.

		One week	One month	5 Months	One year
Age of recipient (years)	47.58 ± 13.52	–	–	–	–
Age of donor (years)	45.77 ± 17.44	–	–	–	–
Males	196 (62.2)	–	–	–	–
Females	119 (37.8)	–	–	–	–
Patients (Tacrolimus)	249 (79)	–	–	–	–
Dose (mg/kg)		0.13 ± 0.06	0.12 ± 0.05	0.08 ± 0.05	0.13 ± 0.92
Trough concentrations (ng/ml)		12.50 ± 19.33	11.35 ± 3.66	9.62 ± 3.46	8.66 ± 5.24
CDR (ng/ml per mg/day per kg body weight)		101.9 ± 69.74	122.13 ± 91.27	149.90 ± 83.45	169.88 ± 110.8
Patients (Cyclosporine)	66 (21)
Dose (mg/kg)		8.10 ± 2.11	6.6 ± 1.98	4.44 ± 1.58	3.58 ± 1.21
Trough concentrations (ng/ml)		460.93 ± 302.9	448.70 ± 298.2	281.06 ± 164.4	229.98 ± 157.7
CDR (ng/ml per mg/day per kg body weight)		60.19 ± 44.81	71.77 ± 56.52	69.66 ± 44.78	68,64 ± 49.74
PTDM	57 (18.1)	–	–	–	–
Time on dialysis (years)	4.3 ± 4.03	–	–	–	–
History of CV events	24 (7.6)	–	–	–	–
Weight (years) (kg)		69.58 ± 13.55	70.3 ± 14.07	73.26 ± 14.21	74.36 ± 14.90
BMI		25.85 ± 5.24	26.03 ± 4.75	27.19 ± 4.71	27.67 ± 5
Hypertension	235 (74.6)	–	–	–	–
Hyperlipidaemia	88 (27.9)	–	–	–	–
Smoking	53 (16.8)	–	–	–	–
HLA mismatch
0–2	94 (29.84)	–	–	–	–
3–4	206 (65.4)	–	–	–	–
5–6	15 (4.76)	–	–	–	–
Delayed graft function	80 (25.4)	–	–	–	–
Acute rejection	45 (14.3)	–	–	–	–
Graft loss	62 (19.7)	–	–	–	–
Cold ischemia time (hours)	16.91 ± 10.83	–	–	–	–
Creatinine serum concentration (mmol/l)		0.19 ± 0.14	0.15 ± 0.07	0.14 ± 0.06	0.13 ± 0.06
Creatinine clearance (ml/min) (MDRD)	63.23 ± 25.02	–	–	–	–
MMF	261 (82.9)	–	–	–	–
Basiliximab	133 (42.2)	–	–	–	–

Mean values ± standard deviation or count and percentages (in parenthesis) are shown.

CDR: trough concentration to dose ratio; MMF: mycophenolate mofetil; BMI: body mass index; PTDM: post-transplant diabetes mellitus; CV: cardiovascular.

Table 2. Genotypic and allelic frequencies in 315 renal transplant recipients.

Polymorphism	N	%	MAF	HWEp
LEPR Lys109Arg
Lys/Lys	181	57.5	0.241	.876
Lys/Arg	117	37.1
Arg/Arg	17	5.4
LEPR Gln223Arg
Gln/Gln	100	31.7	0.422	.353
Gln/Arg	164	52.1
Arg/Arg	51	16.2
LEPR Lys656Asn
Lys/Lys	211	67.0	0.181	1
Lys/Asn	94	29.8
Asn/Asn	10	3.2

N: number of subjects; MAF: minor allele frequency; HWEp: p value for Hardy–Weinberg equilibrium.

Table 3. Crude analyses for the association between polymorphisms in the LEPR gene with the development of post-transplant diabetes mellitus (PTDM) in renal transplant recipients.

Genotype	NO PTDM		PTDM		OR (CI)	p
	N	%	N	%
Lys109Arg
Lys/Lys	152	58.91	29	50.88	Ref.
Lys/Arg-Arg/Arg	106	41.09	28	49.12	1.38 (0.78–2.46)	.27
Gln223Arg
Gln/Gln	88	34.11	12	21.05	Ref.
Gln/Arg-Arg/Arg	170	65.9	45	78.95	1.94 (0.98–3.86)	.058
Lys656Asn
Lys/Lys	169	65.5	42	73.68	Ref.
Lys/Asn-Asn/Asn	89	34.5	15	26.32	0.68 (0.36–1.29)	.24

OR (CI): odds ratio with 95% confidence intervals; Ref.: reference.

Table 4. Multivariate logistic regression analysis for the risk of post-transplant diabetes mellitus in renal transplant recipients.

	B	SE	Wald	OR	CI	p Value
LEPR 223Arg	1.181	0.449	6.92	3.26	1.35–7.85	.009
Age	0.056	0.016	12.147	1.06	1.03–1.09	<.001
Creatinine clearance	0.018	0.008	5.056	1.02	1.00–1.04	.025
Delayed graft function	0.707	0.41	2.968	2.03	0.91–4.536	.085
HCV	−0.19	0.741	0.066	0.83	0.19–3.53	.798
Rejection	0.715	0.499	2.048	2.04	0.77–5.44	.152
BMI	0.047	0.039	1.429	1.05	0.97–1.13	.232
Cold ischemia time	−0.071	0.031	5.058	0.93	0.88–0.99	.025
Tacrolimus vs. Cyclosporine	0.549	0.493	1.244	1.73	0.66–4.55	.265
ADPKD	0.287	0.447	0.414	1.33	0.56–3.20	.52

B: regression coefficient; SE: standard error; OR: odds ratio; CI: 95% confidence interval; HCV: Hepatitis C virus; BMI: body mass index; ADPKD: Autosomal Dominant Polycystic Kidney Disease.

Figure 1. Distribution of the age of the recipient across four different population groups according to post-transplant diabetes mellitus (PTDM) and 223Arg status. **p = .002; ***p = .0004; NS: non-significant. Note: Analyses of differences between the first and third groups, and between the second and fourth groups produced non-significant results.

Figure 2. Body mass index (BMI) at transplant and increment of BMI during the first year after transplant, in renal transplant recipients with and without post-transplant diabetes mellitus (PTDM). *p < .00001.

Figure 3. Average body mass index (BMI) in the first year after transplant for carriers and non-carriers of the 223Arg variant. *p < .05.