Incidence, risk factors and survival outcomes of post-transplant tertiary hyperparathyroidism in kidney recipients

Table 1 Characteristics of the study cohort according to the occurrence of post-transplant tertiary hyperparathyroidism, n (%)

Characteristics	PT-tHPT (n = 125)	Non-tHPT (n = 762)	Total (n = 887)	P value
Demographics
Age (years), mean (SD)	50.5 (13.2)	47.0 (15.5)	47.5 (15.2)	0.016
Sex				0.617
Male	74 (59.2)	469 (61.5)	543 (61.2)
Female	51 (40.8)	293 (38.5)	344 (38.8)
Ethnicity				0.028
White	110 (88.0)	609 (79.9)	719 (81.1)
Asian	11 (8.8)	125 (16.4)	136 (15.3)
Black	4 (3.2)	12 (1.6)	16 (1.8)
Other	0 (0.0)	16 (2.1)	16 (1.8)
Pretransplant body mass index, mean (SD)	27.4 (5.0)	27.0 (8.3)	27.1 (7.9)	0.634
Donor characteristics
Donor type category				0.006
Deceased donor	101 (80.8)	523 (68.7)	624 (70.4)
Living donor	24 (19.2)	238 (31.3)	262 (29.6)
Total human leucocyte antigen mismatch, median (IQR)	3.0 (2.0-3.0)	3.0 (2.0-3.0)	3.0 (2.0-3.0)	0.425
Total ischaemia time, mean (SD)	14.1 (7.1)	12.5 (7.7)	12.7 (7.6)	0.037
Recipients’ characteristics
Primary renal disease				0.033
Adult polycystic kidney disease	12 (9.6)	104 (13.6)	116 (13.1)
Glomerulonephritis	32 (25.6)	207 (27.2)	239 (26.9)
Diabetic kidney disease	9 (7.2)	99 (13.0)	108 (12.2)
Hypertensive kidney disease	8 (6.4)	52 (6.8)	60 (6.8)
Reflux/chronic pyelonephritis	28 (22.4)	90 (11.8)	118 (13.3)
Unknown	21 (16.8)	130 (17.1)	151 (17.0)
Other	15 (12.0)	80 (10.5)	95 (10.7)
Dialysis vintage (pre-emptive transplants excluded), median (IQR)	39.0 (20.0-63.0)	23.0 (11.0-38.0)	25.0 (12.0-44.0)	< 0.001
Pretransplant diabetes	20 (16.0)	136 (17.8)	156 (17.6)	0.615
Transplant number, mean (SD)	1.2 (0.5)	1.1 (0.4)	1.1 (0.4)	0.013
Pre-emptive transplant	24 (19.8)	246 (34.2)	270 (32.1)	0.002
Pre-transplant calcium (mmol/L), median (IQR)	2.5 (2.4-2.5)	2.3 (2.2-2.4)	2.3 (2.2-2.4)	< 0.001
Pre-transplant phosphate (mmol/L), median (IQR)	1.6 (1.4-1.9)	1.6 (1.3-1.9)	1.6 (1.4-1.9)	0.153
Pre-transplant PTH (ng/L), median (IQR)	415.8 (232.0-717.9)	185.0 (97.8-307.8)	202.0 (107.0-360.0)	< 0.001
Post-transplant PTH (ng/L), median (IQR)	135.8 (107.6-240.1)	83.7 (58.3-119.9)	88.4 (61.7-138.1)	< 0.001
Smoking history				0.073
Non-smoker	110 (92.4)	604 (86.5)	714 (87.4)
Current smoker	9 (7.6)	94 (13.5)	103 (12.6)
Immunosuppression regime
Main immunosuppression				0.557
Tacrolimus	110 (88.7)	674 (90.1)	784 (89.9)
Mammalian target of rapamycin inhibitor	3 (2.4)	9 (1.2)	12 (1.4)
Cyclosporin	11 (8.9)	65 (8.7)	76 (8.7)
Antimetabolite				0.739
None	14 (11.3)	80 (10.7)	94 (10.8)
Mycophenolic acid	97 (78.2)	571 (76.3)	668 (76.6)
Azathioprine	13 (10.5)	97 (13.0)	110 (12.6)
Steroid regime				0.016
< 6 monhs of glucocorticoid	54 (45.4)	405 (57.2)	459 (55.5)
> 6 months of glucocorticoid	65 (54.6)	303 (42.8)	368 (44.5)
Other
Baseline eGFR (mL/minute/1.73 m2), median (IQR)	50.0 (37.2-62.2)	51.0 (40.8-65.0)	51.0 (40.0-64.0)	0.373
History of acute rejection	20 (16.5)	78 (10.9)	98 (11.7)	0.074
The eGFR slope (mL/minute/year), median (IQR)	1.4 (3.20.0)	0.8 (2.70.5)	0.9 (2.70.5)	0.027

Continuous variables: Presented as mean (SD) or median (interquartile range) and compared using the independent t-test test or Wilcoxon’s sign-rank test. Categorical variables: Presented as n (%) and compared using Pearson’s χ² test. eGFR: Estimated glomerular filtration rate; IQR: Interquartile range; PTH: Parathyroid hormone; PT-tHPT: Post-transplant tertiary hyperparathyroidism; tHPT: Tertiary hyperparathyroidism.

Table 2 Univariable and multivariable logistic regression analysis of the predictors of post-transplant tertiary hyperparathyroidism

Variables	Univariable analysis				Multivariable model
	n	OR	95%CI	P value	OR	95%CI	P value
Age (per decade)	887	1.17	1.03-1.33	0.016	1.36	1.15-1.62	< 0.001
Gender: Female	887	1.10	0.75-1.62	0.62
Ethnicity	871			0.033	-	-	-
White		1	-		-	-	-
Asian1		0.49	0.24-0.89		0.33	0.14- 0.70	0.006
Black		1.85	0.51-5.41		0.79	0.16-3.02	0.75
Other		0.00	0.00-0.00		0.00	0.00-0.00	0.98
Pretransplant body mass index	887	1.00	0.98-1.03	0.71	-	-	-
Primary renal disease	887			0.044	-	-	-
Adult polycystic kidney disease		1	-		-	-	-
Glomerulonephritis		1.34	0.68-2.81		-	-	-
Diabetic kidney disease		0.79	0.31-1.94		-	-	-
Hypertensive kidney disease		1.33	0.50-3.43		-	-	-
Reflux/chronic pyelonephritis		2.70	1.32-5.79		-	-	-
Unknown		1.40	0.67-3.06		-	-	-
Other		1.63	0.72-3.73		-	-	-
Pre-emptive transplant	887	0.50	0.31-0.78	0.002
Pretransplant diabetes	887	0.88	0.51-1.44	0.61	-	-	-
Donor type: Living donor	887	0.52	0.32-0.82	0.004	-	-	-
Total human leukocyte antigen mismatch	887	1.05	0.92-1.20	0.44	-	-	-
Immunosuppression	887			0.75	-	-	-
Tacrolimus		1	-		-	-	-
Mammalian target of rapamycin inhibitor		1.68	0.37-5.47		-	-	-
Cyclosporin		0.98	0.48-1.84		-	-	-
Antimetabolite	887			0.68	-	-	-
None		-	-		-	-	-
Mycophenolic acid		0.96	0.54-1.83		-	-	-
Azathioprine		0.74	0.33-1.68		-	-	-
Corticosteroid regime	887			0.023	-	-	-
< 6 months of glucocorticoid		-	-		-	-	-
> 6 months glucocorticoid		1.55	1.06-2.28		-	-	-
Total ischaemia time	887	1.03	1.00-1.05	0.038	1.03	1.00-1.07	0.048
Dialysis vintage	887	1.19	1.12-1.26	< 0.001	1.12	1.04-1.20	0.002
Baseline eGFR (per 10 mL/minute increase)	887	0.98	0.90-1.05	0.66	-	-	-
History of acute rejection	838	1.62	0.93-2.72	0.086	2.37	1.19-4.60	0.012
The eGFR slope	887	0.93	0.89-0.97	0.001	0.91	0.87-0.96	0.001
Median pretransplant calcium (per decile increase)	887	1.35	1.25-1.46	< 0.001	1.38	1.26-1.51	< 0.001
Median pretransplant phosphate (per decile increase)	887	1.05	0.99-1.12	0.13	-	-	-
Median pretransplant parathyroid hormone (per decile increase)	887	1.26	1.17-1.36	< 0.001	1.31	1.20-1.43	< 0.001
Posttransplant diabetes	831	1.50	0.91-2.39	0.11	-	-	-
Smoking history	816			0.077			0.070
None-smoker		-	-		-	-
Current smoker		0.53	0.24-1.02		0.48	0.20-1.02

¹Ethnicity was treated as a categorical variable with "White" as the reference group, and other groups (Asian, Black, other) were included as dummy variables in the logistic regression model.

Table 2 shows the unadjusted odds ratio with 95%CI of the factors associated with post-transplant tertiary hyperparathyroidism (PT-tHPT) by the univariable and multivariable logistic regression model. The independent predictors of higher odds of PT-tHPT include age at transplantation, dialysis vintage, history of acute rejection, negative estimated glomerular filtration rate slope, higher pretransplant serum adjusted calcium and higher pretransplant serum parathyroid hormone. Asian ethnicity was associated with lower odds of PT-tHPT. eGFR: Estimated glomerular filtration rate; OR: Odds ratio.

Table 3 Characteristics and outcomes of recipients with post-transplant tertiary hyperparathyroidism stratified by treatment modalities, n (%)

Variables	Conservative management (n = 40)	Calcimimetics (n = 42)	parathyroidectomy (n = 41)	Total (n = 123)	P value
Age (years), mean (SD)	52.1 (14.2)	50.4 (11.6)	49.6 (12.8)	50.7 (12.8)	0.679
Duration of pre-transplant renal replacement therapy (months), median (IQR)	24.0 (6.0-54.0)	48.5 (24.0-66.0)	24.0 (1.5-50.0)	31.0 (7.0-57.0)	0.049
Baseline eGFR (mL/minute/1.73 m2), median (IQR)	50.4 (37.0-59.2)	53.5 (43.0-71.8)	48.0 (38.0-59.0)	50.8 (39.0-62.5)	0.174
Median pre-transplant calcium (mmol/L), median (IQR)	2.5 (2.4-2.5)	2.4 (2.3-2.5)	2.5 (2.4-2.6)	2.5 (2.4-2.6)	0.184
Median pre-transplant phosphate (mmol/L), median (IQR)	1.6 (1.4-1.9)	1.7 (1.4-2.0)	1.6 (1.4-1.8)	1.6 (1.4-1.9)	0.621
Median pre-transplant parathyroid hormone (pmol/L), median (IQR)	295.0 (138-478)	643.5 (340-1163)	374 (190-599)	374 (216-719)	< 0.001
The eGFR slope (mL/minute/year), median (IQR)	-1.02 (-1.94 to 0.38)	-1.78 (-3.80 to 0.01)	-1.09 (-3.21 to -0.18)	-1.27 (-3.67 to -0.09)	0.378
History of acute rejection	4 (10.5)	5 (12.5)	10 (24.4)	19 (16.0)	0.186

eGFR: Estimated glomerular filtration rate; IQR: Interquartile range.