A total of 33 patients with ESKD were enrolled in the study, comprising 13 patients (39.3%) on HD and 20 patients (60.7%) on PD. The age of the patients ranged from 0.82 to 18 years, with a mean age of 5.49 years. Among them, 14 were males (42.4%), and 19 were females (57.6%). The median follow-up time for the patients was 3.1 years (with a range of 6.7 years), and the median duration of dialysis was 2.1 years (with a range of 3.7 years) (Table 1). The causes of ESKD were hypodysplasia in six patients, focal segmental glomerulosclerosis in four patients, neurogenic bladder in three patients, cystinosis in two patients, nephrophitisis in two patients, Joubert syndrome in two patients, hemolitic uremic syndrome (HUS) in two patients, posterior uretral valve (PUV) in two patients, Alport syndrome in one patient, diffuse mesangial sclerosis (DMS) in one patient, Wilms tumor in one patient, primary hyperoxaluria in one patient, autosomal recessive polycystic kidney disease (ARPKD) in one patient and vesicoureteral reflux (VUR) nephropathy (solitary kidney) in one patient (Table-1).
Table 1
Baseline characteristics of the patients
Age, years | 0.82-18 ± 5.49 |
Sex, n (%) Girls Boys | 19 (%57.6) 14 (%42.4) |
•Duration of follow-up, years, median (IR) | 3.1 (6.7) |
•Duration of dialysis, years, median (IR) | 2.1 (3.7) |
Type of RRT PD, n (%) HD, n (%) | 20 (60.7%) 13 (39.3%) |
Diagnosis Hypodysplasia, n (%) FSGS, n (%) Neurogenic bladder, n (%) Cystinosis, n (%) Nephronophitisis, n (%) Joubert syndrome, n (%) HUS, n (%) PUV, n (%) Alport Syndrome, n (%) DMS, n (%) Wilms tumor, n (%) Primary hyperoxaluria, n (%) ARPKD, n (%) VUR Nephropathy(solitary kidney), n (%) Others, n (%) | 6 (%18.1) 4 (%12.1) 3 (%9) 2 (%6) 2 (%6) 2 (%6) 2 (%6) 2 (%6) 1 (%3) 1 (%3) 1 (%3) 1 (%3) 1 (%3) 1 (%3) 4 (%12.1) |
Types of ESA used Epoetin alfa, n (%) Darbepoetin alfa, n (%) | 22(%66.6) 11 (%33.4) |
Use of ACEIs, n (%) | 12(%36.3) |
Parameters which have homogeneous distrubution are presented by mean values and standart deviations, •Parameters which have non homogeneous distrubution are presented by median values (interquarter range). RRT, renal replacement theraphy; PD, peritoneal dialysis; HD, hemodialysis; FSGS, focal segmental glomerulosclerosis; HUS, hemolytic uremic syndrome; PUV, posterior urethral valve; DMS, diffuse mesangial sclerosis; ARPKD, autosomal recessive polycystic kidney disease; VUR, vesicoureteral reflux; ESA; erythropoiesis stimulating agent, ACEIs, angiotensin- converting enzyme inhibitors |
The mean ERI value was 15.7 IU/kg/w/g/dL. All patients were categorised into the low ERI group (ERI ≤ 16 IU/kg/w/g/dL) and the high ERI group (ERI > 16 IU/kg/w/g/dL) based on the mean ERI value. Among the patients, 22 (66.6%) received epoetin alfa, and 11 (33.4%) received darbepoetin alfa (Table 1). In the low ERI group, 14 patients received epoetin alfa, while three patients received darbepoetin alfa (a ratio of 4.6:1). In the high ERI group, eight patients received epoetin alfa, and eight patients received darbepoetin alfa (a 1:1 ratio). This was statistically significant with a p value of 0.049 (Table-2). However, in correlation analysis, we did not demonstrate a significant association between ERI and EPO subtypes (p = 0.18) (Table-3). The mean Hb value was 10.47 mg/dl and was lower in high ERI group (p:0.00) (Table-2). Hb concentration exhibited a negative correlation with ERI (p = 0.00, r=-0.75) (Table-3). There was no significant difference between WBC, platelet, Fe, TSAT, TIBC, folic acid, vitamin B12 levels and ERI groups (p > 0.05) (Table-2). The mean albumin level was lower in low ERI group compared to high ERI group, it was not statistically significant (3.93 ± 0.13 and 5.28 ± 1.65 respectively, p = 0.367) (Table-2). CRP levels were negative in all patients.
The mean serum phosphorus levels were significantly higher in the high ERI group compared to the low ERI group (6.61 ± 1.67 vs. 5.14 ± 1.14 mg/dL, respectively, p = 0.007) (Table 2). Furthermore, correlation analysis revealed a significant positive association between serum phosphorus levels and ERI (p = 0.016, r = 0.41) (Table 3). The mean PTH levels were higher in the high ERI group, approaching statistical significance (599 ± 351 vs. 392 ± 320 pg/mL, p = 0.088). Mean calcium levels were lower in the high ERI group compared to the low ERI group, although this difference did not reach statistical significance (7.66 ± 0.96 vs. 9.54 ± 0.27, p = 0.263, respectively)
Table 2
Comparison of demographic, clinical and biochemical characteristics of patients with high and low ERI groups
Variables | Overall (n:33) | Low ERI Group (n:17) | High ERI Group (n:16) | *p value |
ERI (IU/kg/w/g/dL) | 15.7 ± 6.7 | < 16 | > 16 | |
Age (years) | 10.7 ± 5.5 | 12 ± 4.7 | 9.4 ± 6.1 | 0.18 |
Sex (male/female) (%) | 14(42.4%)/19(57.6%) | 8/9 | 6/10 | 0.57 |
•Duration of dialysis (years) | 2.1 (3.7) | 2.1(4.3) | 3.1 (3.9) | 0.27 |
•Duration of follow-up (years) | 3.1 (6.7) | 2.84 (7.7) | 3.15 (4.9) | 0.95 |
BMI (kg/m2) | 16.9 ± 2.6 | 17.5 ± 3.1 | 16.3 ± 1.7 | 0.17 |
Hb (mg/dl) | 10.5 ± 1.6 | 11.6 ± 1.2 | 9.2 ± 1.1 | 0.00 |
WBC (×109) | 6882.8 ± 2723.4 | 6647 ± 2771 | 7132 ± 2739 | 0.61 |
•PLT (×109) | 264.000 (137.000) | 252.000 (108.250) | 354.000 (133.000) | 0.22 |
•Ferritin (ml/ng) | 335.6 (416.5) | 382.5 (273.00) | 329.4 (517.80) | 0.74 |
•Fe (mg/dl) | 84 (41.5) | 88.5 (41.7) | 84.4 (52.2) | 0.84 |
TIBC (mg/dl) | 247.2 ± 56.2 | 263.8 ± 50 | 229.6 ± 58.6 | 0.82 |
•TSAT (%) | 30.5 (20.7) | 30.5 (14.7) | 30 (32.5) | 0.33 |
•Folic acid (nmol/L) | 7 (10.6) | 6.4 (9.6) | 7.4 (14.4) | 0.86 |
•Vitamin B12 (pg/ml) | 457 (518) | 432 (812) | 580 (389) | 0.46 |
•Albumin (gr/dl) median mean | 3.8 (1) 4.5 ± 4.6 | 3.9 (0.7) 3.9 ± 2.6 | 3.6 (1.6) 5.3 ± 6.6 | 0.36 |
PTH(pg/mL) | 493.1 ± 346.8 | 392 ± 320 | 599 ± 351 | 0.08 |
•ALP (U/L) | 199 (219.5) | 168 (210) | 263.5 (257.5) | 0.48 |
P (mg/dl) | 5.8 ± 1.5 | 5.1 ± 1.1 | 6.6 ± 1.7 | 0.007 |
•Ca (mg/dL) median mean | 9.5 (1.1) 8.6 ± 2.9 | 9.5 (1.1) 9.5 ± 1.1 | 9.4 (1.6) 7.6 ± 3.8 | 0.26 |
•Vitamin 25-(OH) D3 (ng/ml) | 25 (16.7) | 28.5 (19.9) | 21.8 (13.8) | 0.34 |
Magnesium (mg/dl) | 2.6 ± 0.4 | 2.6 ± 0.4 | 2.6 ± 0.4 | 0.92 |
Hypertension (n) (%) | 22/33 (66.6%) | 9/17 (52.9) | 13/16 (81.2) | 0.085 |
≥ 2 antihypertensive drugs; (n) | 12/22 | 5/9 | 7/13 | 0.89 |
Use of ACEIs; (n) (%) | 12/33 (36.3) | 5/17 (29.4) | 7/13 (53.8) | 0.39 |
EPO subtypes (epoetinalfa/darbepoetin alfa) (n) | 22/11 | 14/3 | 8/8 | 0.049 |
•Overhydration (liter/kg) | 0.01 (0.9) | 0.1 (2.1) | 0.01 (0.04) | 0.78 |
LVH (n) (%) | 15/33 (45.4) | 6/17 (35.2) | 9/16 (56.2) | 0.22 |
Parameters which have homogeneous distrubution are presented by mean values and standart deviations, |
•parameters which have non homogeneous distrubution are presented by median values (interquarter range). |
*Significant difference between the low ERI group and the high ERI group, p < 0:05. ERI: erythropoietin |
resistance index; BMI: body mass index; Hb: serum hemoglobin concentration; WBC: white blood cell count; |
PLT: platelet count; Fe: serum iron level; TIBC: total iron binding capacity; TSAT: transferrin saturation; |
PTH: serum parathyroid hormone; ALP: serum alkaline phosphatase; P: serum phosphorus; Ca: serum |
calcium; LVH: left ventricular hypertrophy; ACEIs: anjiotension converting enzyme inhibitors; EPO: erythropoietin |
Table 3
Correlations between ERI and parameters ∗The correlation was statistically significant, p < 0:05.ERI: erythropoietin resistance index; Hb: serum hemoglobin concentration; WBC: white blood cell count; PLT: platelet count; Fe: serum iron level; TIBC: total iron binding capacity; TSAT: transferrin saturation
| Age | Duration of follow up | Duration of dialyses | Hb | WBC | PLT | Fe | TSAT | TIBC | Ferritin | Folic acid | Vitamin B12 | Albumin |
ERI r p | -0.29 0.09 | -0.1 0.58 | 0.75 0.67 | 0.75* 0.00* | -0.05 0.78 | 0.12 0.49 | 0.09 0.60 | 0.18 0.30 | -0.26 0.13 | 0.09 0.58 | 0.09 0.59 | 0.10 0.57 | -0.02 0.25 |
| Ca | P | Mg | ALP | Vitamin 25-(OH) D3 | PTH | BMI | Overhydration (liter/kg) | HT | LVH | ACEI | EPO subtypes |
ERI r p | -0.19 0.27 | 0.41* 0.016* | 0.16 0.36 | 0.15 0.40 | 0.07 0.67 | 0.077 0.67 | -0.2 0.26 | -0.15 0.39 | 0.32* 0.06* | 0.16 0.29 | 0.18 0.29 | 0.23 0.18 |
∗The correlation was statistically significant, p < 0:05. ERI: erythropoietin resistance index; BMI: body mass index; PTH: serum parathyroid hormone; ALP: serum alkaline phosphatase; P: serum phosphorus; Ca: serum calcium; HT: Hypertension; LVH: left ventricular hypertrophy; ACEIs: anjiotension converting enzyme inhibitors; EPO: erythropoietin |
No significant differences were observed in Mg, ALP and vitamin 25-(OH) D levels (p > 0.05) (Table-2). Correlations between ERI and all of the other parameters related to CKD bone mineral disease were also evaluated, no significant correlations were found (Table-3).
The prevelance of hypertension was higher in high ERI group compared to the low ERI group (p = 0.085) in the presence of comparable body fluid volumes of two groups (Table-2). An association, close to the statistical significance, was found between ERI and hypertension in correlation analysis, which supports this relationship (p = 0.06, r = 0.32) (Table-3).
There was no significant correlation between body fluid volume (overhydration) measured by bioimpedance spectroscopy and ERI (p = 0.39). Among the hypertensive patients, twelve of them were using more than one antihypertensive drug, with seven in the high ERI group (Table 2). Left ventricular hypertrophy was identified in 15 out of 33 patients, with six in the low ERI group and nine in the high ERI group; however, this difference did not reach statistical significance (p = 0.227) (Table 2). Of the patients, 12 (36.3%) received ACEIs, with five in the low ERI group and seven in the high ERI group; however, this was not statistically significant (p = 0.39) (Table 2), and there was no significant correlation between ERI and the use of ACEIs (p = 0.29) (Table-3).