Mineral and bone disorder and longterm survival in a chronic kidney disease grade 3b-4cohort

Figures & data

Figure 1. Algorithm of the Uruguayan National Renal Healthcare Program (NRHP-UY) population and the distribution of the studied groups. eGFR: estimated glomerular filtration rate; Ca: calcium; P: phosphate; iPTH: intact parathyroid hormone; vitamin D : 25(OH) vitamin D.

Figure 2. Hazard ratio (HR) and 95% confidence interval (CI) for the death risk associated with mean serum calcium ranges (Model 1).

Figure 3. Hazard ratio (HR) and 95% confidence interval (CI) for the death risk associated with mean serum phosphate ranges (Model 1).

Figure 4. Hazard ratio (HR) and 95% confidence interval (CI) for the death risk associated with mean serum parathyroid hormone (iPTH) ranges (Model 1).

Figure 5. Hazard ratio (HR) and 95% confidence interval (CI) for the death risk associated with mean serum 25(OH) vitamin D ranges (Model 1).

Table 1. Baseline data.

	Global	PTH-data group	No PTH-data group	p
Number	6473	2013	4460
Age (years) (median, pc 25–75)	73.7 (65.9–79.6)	71.5 (63.1–77.8)	74.6 (67.0–80.3)	<.001^a
Sex (male), n (%)	3628 (56.0)	1141 (56.7)	2487 (55.8)	.254^a
CKD etiology
Vascular, n (%)	3388 (52.3)	973 (48.3)	2415 (54.1)	<.001^b
Diabetic, n (%)	789 (12.2)	204 (10.1)	585 (13.1)
Tubulo-interstitial/Obstructive, n (%)	364 (5.6)	105 (5.2)	259 (5.8)
Glomerulopathies, n (%)	181 (2.8)	67 (3.3)	114 (2.6)
CKD Grade 3b	3558 (55.0)	951 (47.2)	2607 (58.5)	<.001^b
CKD Grade 4	2915 (45.0)	1062 (52.8)	1853 (41.5)
Comorbidities
Diabetes, n (%)	2447 (37.8)	740 (36.8)	1707 (38.3)	.128^b
Smoking, n (%)	382 (5.9)	105 (5.2)	277 (6.2)	.124^b
Cardiovascular events (1 or more)	2242 (34.6)	618 (30.7)	1624 (36.4)	<.001^b
SBp < 120 mmHg, n (%)	1148 (17.7)	372 (18.5)	776 (17.4)	.573^b
120–139 mmHg, n (%)	2654 (41.0)	826 (41.0)	1828 (41.0)
140–159 mmHg, n (%)	1845 (28.5)	554 (27.5)	1291 (28.9)
≥160 mmHg, n (%)	826 (12.8)	261 (13.0)	565 (12.7)
DBp < 80 mmHg), n (%)	3231 (49.9)	1030 (51.2)	2201 (49.3)	.469^b
80–89 mmHg, n (%)	2125 (32.8)	645 (32)	1480 (33.2)
90–99 mmHg, n (%)	783 (12.1)	231 (11.5)	552 (12.4)
≥100 mmHg, n (%)	334 (5.2)	107 (5.3)	227 (5.1)
BMI (kg/m^2) (<21), n (%)	229 (4.6)	63 (3.9)	166 (4.9)	.272^b
BMI (kg/m^2) [21–25], n (%)	948 (18.9)	289 (18.0)	659 (19.3)
BMI (kg/m^2) (>25), n (%)	2590 (75.9)	1253 (78.1)	3843 (76.6)
eGFR (ml/min/1.73 m^2) (median, pc 25–75)	31.5 (23.9–37.9)	29.3 (22.5–36.2)	32.4 (24.9–38.5)	<.001^a
Proteinuria (data n = 6228)				.312^b
No	4748 (73.4)	1503 (74.7)	3245 (72.8)
<300 mg/d (o PCR < 300 mg/g), n (%)	524 (8.1)	162 (8.0)	362 (8.1)
300–1000 mg/d (o PCR 300–1000 mg/g), n (%)	726 (11.2)	215 (10.7)	511 (11.5)
≥1000 mg/d (o PCR < 1000 mg/g), n (%)	475 (7.3)	133 (6.6)	342 (7.7)
BSRA, n (%)	4665 (72.1)	1446 (71.8)	3219 (72.2)	.399^b

SBP: systolic blood pressure; DBP: diastolic blood pressure; BMI: body mass index; eGFR: estimated glomerular filtration rate.

^aMann–Whitney test.

^bChi² test.

Table 2. CKD-MBD data.

	Global	PTH-data	No PTH-data	p
Patients (n)	6473	2013	4660
Frequencies KDIGO ranges
Serum calcium^a
≤8.40 mg/dl, n (%)	325 (5.0)	62 (3.1)	263 (5.9)	<.001^b
8.41–10.00 mg/dl, n (%)	5625 (86.9)	1805 (89.7)	3820 (85.6)
>10.00 mg/dl, n (%)	523 (8.1)	146 (7.3)	377 (8.5)
Serum phosphate^a x
≤8.40 mg/dl, n (%)	537 (8.3)	149 (7.4)	388 (8.7)	<.001^b
3.01–4.50 mg/dl, n (%)	5077 (78.4)	1667 (82.8)	3410 (76.5)
>4.50 mg/dl, n (%)	859 (13.3)	197 (9.8)	662 (14.8)
iPTH (data n = 1943)^a
≤35.0 pg/ml, n (%)	–	87 (4.3)	–
35.1–70.0 pg/ml, n (%)	–	397 (19.7)	–
70.1–105.0 pg/ml, n (%)	–	451 (22.4)	–
>105.0 pg/ml, n (%)	–	1078 (53.5)	–
Frequencies Model 1 mortality risk ranges
Serum calcium^a ≤9.00 mg/dl, n (%)	1682 (26.0)	430 (21.4)	1252 (28.1)	<.001^b
9.01–10.25 mg/dl, n (%)	4519 (69.8)	1508 (74.9)	3011 (67.5)
>10.25 mg/dl, n (%)	272 (4.2)	75 (3.7)	197 (4.4)
Serum phosphate^a ≤2.75 mg/dl, n (%)	235 (3.6)	61 (3.0)	174 (3.9)	<.001^b
2.76–4.00 mg/dl, n (%)	4289 (66.3)	1401 (69.6)	2888 (64.8)
>4.0 mg/dl, n (%)	1949 (30.1)	551 (27.4)	1399 (31.3)
Serum 25(OH) vitamin D (data n = 1248)^a ≤10 ng/ml, n (%)	120 (9.6)	85 (8.8)	35 (12.3)	.078^b
>10 ng/ml, n (%)	1128 (90.4)	879 (91.2)	249 (87.7)
iPTH (data n = 2013)^a ≤105 pg/ml, n (%)	–	935 (46.4)	–
>105 pg/ml, n (%)	–	1078 (53.6)	–
Serum levels
Serum calcium (mg/dl) (median, pc 25–75)	9.33 (9.00–9.66)	9.36 (9.05–9.64)	9.30 (9.00–9.67)	.023^c
Serum phosphate (mg/dl) (median, pc 25–75)	3.70 (3.34–4.13)	3.70 (3.37–4.05)	3.70 (3.30–4.20)	.214^c
Serum iPTH (pg/ml) (median, pc 25–75)	–	112 (72–176)	–
Serum 25(OH) vitamin D (ng/ml) (data n = 1248) (median, pc 25–75)	25.5 (17.0–33.0)	25.7 (17.2–33.0)	25.1 (15.9–33.5)	.645^c
Treated 25(OH) vitamin D^d (data n = 5215), n (%)	1294 (24.8)	919 (45.6)	375 (11.7)	<.001^b
Treated1, 25(OH)2 vitamin D^e (data n = 5215), n (%)	710 (13.6)	512 (25.4)	198 (6.2)	<.001^b

iPTH: intact parathyroid hormone.

^aMean values.

^bChi² test.

^cMann–Whitney test.

^dTreated 25(OH) vitamin D: 20.6% on CKD G3b vs. 30.2% on CKD G4 (Chi² test p < .05).

^eTreated 1,25(OH)₂ vitamin D: 10.2% on CKD G3b vs. 18.0% on CKD G4 (Chi² test p < .05).

Table 3. Evolution data.

CKD grade 3b-4	Global	PTH-data	No PTH-data
Number	6473	2013	4460
Death, n (%)	2426 (37.5%)	469 (23.3%)	1957 (43.9%)
KRT, n (%)	618 (9.5%)	181 (9.0%)	437 (9.8%)
Follow-up time (sum) (patient–year)	38,030	13,850	24,180
Follow-up time (months) (med pc 25–75)	65.5 (33.2–102.1)	81.5 (47.9–113.6)	59.0 (28.2–95.1)
Incidence rate death (events/100 patient–year)	6.38	3.39	8.09
Incidence rate KRT (events/100 patient–year)	1.62	1.31	1.81

KRT: kidney replacement therapy.

Follow-up time, incidence rates (KRT and death).

Table 4. (Model 2) Death risk.

Death risk (Model 2)	HR	CI 95%	p
Serum calcium (mg/ml)
9.01–10.25 mg/dl [reference]			.005
≤9.0 mg/dl	1.391	1.127–1.707	.002
>10.25 mg/dl	1.449	0.904–2.322	.123
Serum phosphate (mg/dl)
2.76–4.0 mg/dl [reference]			.012
≤2.75 mg/dl	1.137	0.616–2.099	.680
>4.00 mg/dl	1.387	1.118–1.720	.003
Serum iPTH (pg/ml) [reference ≤105 pg/ml]
Serum iPTH > 105 pg/ml	1.275	1.049–1.550	.015

iPTH: intact parathyroid hormone.

Cox regression multivariate analysis, adjusted to sex, age, diabetes, smoking, CKD etiologies, CV comorbidities, eGFR, initial systolic and diastolic blood pressure, proteinuria, RASB, 25(OH) and 1,25(OH)₂ vitamin D treatments, serum calcium, serum phosphate, and serum iPTH (n = 2013).

Table 5. (Model 3) Death risk.

Death risk (Model 3)	HR	CI 95%	p
Serum calcium (mg/ml)
9.01–10.25 mg/dl [reference]			.132
≤9.0 mg/dl	1.265	0.891–1.794	.188
>10.25 mg/dl	1.944	0.865–4.369	.108
Serum phosphate (mg/dl)
2.76–4.0 mg/dl [reference]			.009
≤2.75 mg/dl	0.828	0.258–2.649	.750
>4.00 mg/dl	1.668	1.201–2.317	.002
Serum iPTH (pg/ml) [reference ≤105 pg/ml]
Serum iPTH > 105 pg/ml	1.386	1.012–1.898	.042
Serum 25(OH) vitamin D (ng/ml) [reference >10 ng/ml]
Serum 25(OH) vitamin D ≤10 ng/ml	1.958	1.238–3.098	.004

iPTH: intact parathyroid hormone. Cox regression multivariate analysis, adjusted to sex, age, diabetes, smoking, CKD etiologies, CV comorbidities, eGFR, initial systolic and diastolic blood pressure, proteinuria, RASB, 25(OH) and 1,25(OH)₂ vitamin D treatments, serum calcium, serum phosphate serum iPTH, and serum 25(OH) vitamin D levels (n = 964).

Data availability statement

Upon request, data set could be available as a Supplemental online archive.