What is the optimal level of vitamin D in non-dialysis chronic kidney disease population?

Table 1 Baseline patient characteristics (n = 470), as a function of vitamin D status

	All	25(OH)D < 20 ng/mL	25(OH)D 20-29 ng/mL	25(OH)D ≥ 30 ng/mL	P
n	470	252 (53%)	154 (33%)	64 (14%)
Age (yr)	66.1 ± 12.9	65.8 ± 13.1	65.9 ± 11.9	68.1 ± 12.1	0.421
Male sex (%)	309 (66%)	162 (64%)	101 (66%)	46 (72%)	0.303
High blood pressure (%)	444 (95%)	242 (96%)	144 (94%)	58 (91%)	0.072
Dyslipidemia (%)	311 (66%)	168 (68%)	101 (66%)	42 (66%)	0.646
Diabetes mellitus (%)	183 (39%)	114 (45%)	53 (34%)	16 (25%)	0.001
Ischemic heart disease (%)	104 (22%)	60 (24%)	33 (22%)	11 (17%)	0.224
Chronic heart failure (%)	43 (9%)	33 (13%)	7 (5%)	3 (5%)	0.005
Stroke (%)	52 (11%)	30 (12%)	15 (10%)	7 (11%)	0.668
Peripheral arterial disease (%)	93 (20%)	59 (24%)	22 (14%)	12 (19%)	0.117
Stage of CKD (%)
3 (eGFR = 30-59 mL/min per 1.73 m2)	221 (47%)	103 (41%)	84 (54%)	34 (53%)	0.002
4 (eGFR = 15-29 mL/min per 1.73 m2)	205 (44%)	105 (46%)	64 (42%)	26 (41%)
5 (eGFR < 15 mL/min per 1.73 m2)	44 (9%)	34 (13%)	6 (4%)	4 (6%)
Etiology of CKD (%)
Hypertension	108 (23%)	54 (21%)	40 (26%)	14 (22%)	0.039
Diabetes mellitus	108 (23%)	72 (29%)	29 (19%)	7 (11%)
Tubulointerstitial disease	65 (14%)	24 (10%)	25 (16%)	16 (25%)
Glomerulonephritis	47 (10%)	26 (10%)	15 (10%)	6 (10%)
Unknown/others	142 (30%)	75 (30%)	44 (29%)	20 (32%)
Smoking (%)1
Never	231 (53%)	124 (52%)	82 (58%)	25 (44%)	0.494
Ex-smoker	144 (33%)	81 (34%)	44 (31%)	19 (33%)
Active	64 (14%)	35 (14%)	16 (11%)	13 (23%)
Blood pressure (kPa)
Systolic	19.0 ± 2.9	19.3 ± 2.9	18.6 ± 2.8	19.0 ± 3.1	0.085
Diastolic	10.2 ± 1.5	10.2 ± 1.6	10.1 ± 1.4	10.3 ± 1.7	0.617
Pulse pressure (kPa)	8.8 ± 2.5	9.1 ± 2.5	8.5 ± 2.5	8.7 ± 2.5	0.098
Body mass index (kg/m2)	28.6 ± 5.1	28.8 ± 5.5	28.6 ± 4.6	27.7 ± 4.4	0.294
Underweight ( ≤ 18.5)	6 (1%)	4 (2%)	1 (1%)	1 (2%)	0.353
Normal (18.6-24.9)	96 (20%)	50 (20%)	30 (19%)	16 (25%)
Overweight (25.0-29.9)	210 (45%)	111 (44%)	68 (44%)	31 (48%)
Obesity (> 29.9)	158 (34%)	87 (34%)	55 (36%)	16 (25%)
Waist (cm)
Males	102.2 ± 12.0	102.1 ± 13.0	102.2 ± 10.6	102.4 ± 11.5	0.989
Females	97.8 ± 13.5	98.3 ± 14.7	97.7 ± 12.2	95.7 ± 11.4	0.760
ABPI	1.01 ± 0.21	0.98 ± 0.20	1.04 ± 0.21	1.05 ± 0.22	0.013
Abnormal ABPI2	194 (41%)	100 (41%)	66 (44%)	28 (44%)	0.539
Abnormal Kauppila score3	107 (29%)	52 (27%)	35 (29%)	20 (36%)	0.183
Abnormal Adragao score4	121 (32%)	66 (33%)	38 (30%)	17 (29%)	0.474
Vitamin D supplementation (%)	43 (9%)	16 (6%)	17 (11%)	10 (16%)	0.012
Use of phosphate binders (%)	72 (15%)	47 (19%)	16 (11%)	9 (14%)	0.105
Use of ACEI/ARB (%)	365 (78%)	196 (79%)	121 (82%)	48 (76%)	0.947
Use of diuretic (%)	287 (61%)	173 (70%)	88 (58%)	26 (42%)	< 0.001
Use of ESA (%)	124 (26%)	77 (31%)	31 (20%)	16 (25%)	0.015

¹Data available in 439 patientes;

²< 0.9 or > 1.3;

³> 6 data available in 370 patients;

⁴≥ 3 data available in 383 patients. If not indicated otherwise, results are presented as mean ± SD, or number (percent). ABPI: Ankle-brachial pressure index; ACEI: Angiotensin-converting-enzyme inhibitor; ARB: Angiotensin II receptor blocker; eGFR: Estimated glomerular filtration rate; ESA: Erythropoietin-Stimulating agents; 25(OH)D: 25-hydroxivitamin D.

Table 2 Baseline laboratory values, as a function of vitamin D status

	All (n = 470)	25(OH)D < 20 ng/mL (n = 252)	25(OH)D 20-29 ng/mL (n = 154)	25(OH)D ≥ 30 ng/mL (n = 64)	P
25-hydroxivitamin D (nmol/L)	52 ± 21	36 ± 9	61 ± 7	90 ± 16	< 0.001
1,25(OH)2 vitamin D (pmol/L)	103 ± 28	97 ± 27	111 ± 28	107 ± 23	< 0.001
Caalb (mmol/L)	2.40 ± 0.20	2.40 ± 0.15	2.42 ± 0.23	2.45 ± 0.23	0.163
P (mmol/L)	1.10 ± 0.26	1.10 ± 0.26	1.10 ± 0.26	1.07 ± 0.26	0.517
iPTH (ng/L)1	91 (85-97)	106 (96-116)	81 (73-91)	64 (55-74)	< 0.001
Creatinine (μmol/L)	221 ± 97	239 ± 106	212 ± 88	212 ± 88	0.017
eGFR (MDRD, mL/min per 1.73 m2)	29.4 ± 11.5	28.1 ± 11.9	30.8 ± 10.8	30.5 ± 11.1	0.049
Urine protein excretion (g/24 h)12	0.592 (0.502-0.697)	0.699 (0.573-0.853)	0.448 (0.321-0.626)	0.448 (0.271-0.742)	0.034
hsCRP (nmol/L)1	36.2 (29.5-39.1)	37.1 (33.3-41.0)	36.2 (31.4-41.0)	32.4 (26.7-39.1)	0.506
Albumin (g/L)	40 ± 5	39 ± 5	41 ± 5	40 ± 5	0.011
Total proteins (g/L)	77 ± 12	77 ± 11	77 ± 13	76 ± 14	0.877
Total cholesterol (mmol/L)	4.7 ± 1.1	4.7 ± 1.1	4.7 ± 1.0	4.8 ± 1.1	0.603
HDL cholesterol (mmol/L)	1.3 ± 0.4	1.3 ± 0.3	1.3 ± 0.4	1.3 ± 0.4	0.973
LDL cholesterol (mmol/L)	2.7 ± 0.9	2.7 ± 0.9	2.7 ± 0.9	2.9 ± 0.8	0.344
Hemoglobin (g/L)	130 ± 16	129 ± 16	132 ± 16	132 ± 18	0.058
Ferritin (pmol/L)1	225 (207-245)	227 (202-252)	216 (187-252)	247 (191-319)	0.635
Transferrin (μmol/L)	3.0 ± 1.2	2.9 ± 1.2	3.0 ± 1.2	3.1 ± 1.3	0.289
Glucose (mmol/L)	6.3 ± 2.2	6.3 ± 2.3	6.4 ± 2.4	5.9 ± 1.5	0.241

¹24 h urine proteinuria obtained in 237 (50%) patients;

²Skewed values are presented as geometric mean with 95%CI. Ca_alb: Calcium adjusted for albumin levels; eGFR: Estimated glomerular filtration rate; HSCRP: High-sensitive C reactive protein; iPTH: Intact parathyroid hormone; MDRD: Modification of diet in renal disease; P: Phosphorous; 25(OH)D: 25-hydroxivitamin D. If not indicated otherwise, results are presented as mean ± SD.

Table 3 Adjusted Cox proportional hazards models of patient survival (events = 46)

Model	Covariates controlled for	Adjusted HR (95%CI)	P
0 (Unadjusted)	25-hydroxivitamin D levels (mg/dL)	0.95 (0.91-0.99)	0.009
1	25-hydroxivitamin D levels (mg/dL) + age	0.95 (0.91-0.99)	0.009
2	Model 1 + diabetes mellitus, ischemic heart disease, chronic heart failure	0.96 (0.92-0.99)	0.028
3	Model 1 + peripheral arterial disease, abnormal ABPI1, phosphorous (mg/dL)	0.95 (0.92-0.99)	0.023
4	Model 1 + DBP (mm Hg), 1,25(OH)2 vitamin D (pg/mL), estimated GFR (mL/min per 1.73 m2)	0.96 (0.92-0.99)	0.020
5	Model 1 + vascular calcification [Kauppila score (log), Adragao score (log)], CKD stage 5	0.95 (0.91-1.00)	0.050
6	Model 1 + obesity, hemoglobin (g/L), albumin (g/dL)	0.95 (0.92-0.99)	0.019

¹< 0.9 or >1.3. ABPI: Ankle-brachial pressure index; DBP: Diastolic blood pressure; GFR: Glomerular filtration rate.

Table 4 Multivariate Cox regression analysis in relation to renal end point (events = 156)

	HR (95%CI)	P value
25-hydroxivitamin D (ng/mL)	0.97 (0.95-0.99)	0.004
Age (yr)	0.99 (0.97-1.00)	0.044
Male sex	2.20 (1.47-3.30)	< 0.001
Estimated GFR (mL/min per 1.73 m2)	0.93 (0.91-0.95)	< 0.001
ABPI (mmHg)	0.23 (0.10-0.53)	0.001
Hemoglobin (g/L)	0.84 (0.78-0.94)	0.001

ABPI: Ankle-brachial pressure index; GFR: Glomerular filtration rate.