Estimating the Fraction of First-Year Hemodialysis Deaths Attributable to Potentially Modifiable Risk Factors: Results from the DOPPS

Figures & data

Table 1 Patient Characteristics by Time on Dialysis (Vintage)

	Dialysis Vintage at Study Entry
Patient Characteristic	<60 Days	>1 Year
N patients (%)	15,891 (18%)	51,565 (58%)
Characteristics
Age (years)	63.4 ± 15.1	62.2 ± 14.8
Sex (% men)	60%	57%
Race (% black)	16%	18%
Vintage (months)	0.4 (0.0, 1.1)	48 (27, 88)
HD-related characteristics
No reported RUV (%)	26%	*
No pre-ESRD nephrology care (%)	24%	*
Central venous catheter use (%)	57%	15%
Treatment time (min)	209 ± 38	231 ± 38
Blood flow rate (mL/min)	308 ± 89	343 ± 97
Lab and biometric measurements
Pre-dialysis SBP (mm Hg)	147 ± 23	145 ± 23
Body mass index (kg/m^2)	26.4 ± 6.3	25.6 ± 6.4
Serum Creatinine (mg/dL)	6.9 ± 3.0	9.2 ± 3.1
Serum Albumin (g/dL)	3.4 ± 0.6	3.8 ± 0.5
WBC count (10^3 cells/mm^3)	7.8 ± 3.0	6.8 ± 2.3
Serum Calcium (mg/dL)	8.6 ± 0.9	9.1 ± 0.8
Serum Phosphorus (mg/dL)	5.2 ± 1.8	5.4 ± 1.7
PTH (pg/mL)	246 (132, 446)	236 (116, 432)
Serum Potassium (mEq/L)	4.5 ± 0.8	5.0 ± 0.8
Hemoglobin (g/dL)	10.0 ± 1.6	11.0 ± 1.5
Serum Ferritin (ng/mL)	207 (100, 405)	448 (192, 769)
Comorbid conditions (%)
Coronary artery disease	41%	40%
Cancer (non-skin)	13%	10%
Other cardiovascular disease	27%	32%
Cerebrovascular disease	15%	16%
Heart failure	34%	29%
Diabetes	50%	42%
Gastrointestinal bleeding	6%	5%
Lung disease	12%	11%
Neurologic disease	9%	10%
Psychiatric disorder	19%	16%
Peripheral vascular disease	23%	22%
Recurrent cellulitis, gangrene	6%	9%

Notes: Mean ± SD, Median (IQR), or % shown. *Pre-ESRD care data were only available for incident patients and RUV was assumed to be minimal for patients on dialysis >1 year.

Abbreviations: HD, hemodialysis; ESRD, end-stage renal disease; SBP, systolic blood pressure; WBC, white blood cell; PTH, parathyroid hormone; RUV, residual urine volume.

Table 2 Attributable Fractions for Mortality Risk-Factors, by Baseline Vintage

Risk Factor	Vintage <60 Days (N=15,891)			Vintage >1 Year (N=51,565)
	% Pts	HR (95% CI)	AF (95% CI)	% Pts	HR (95% CI)	AF (95% CI)
Catheter use	57%	1.52 (1.37–1.71)	22% (17–27%)	15%	1.22 (1.13–1.31)	4% (2–5%)
Albumin <3.5 g/dL	51%	1.51 (1.35–1.68)	19% (14–24%)	22%	1.80 (1.70–1.90)	15% (14–17%)
Creatinine <6 mg/dL	43%	1.32 (1.18–1.48)	12% (7–16%)	14%	1.30 (1.22–1.43)	5% (4–7%)
Lack of pre-ESRD care	26%	1.38 (1.24–1.56)	9% (6–12%)	–	–	–
No reported RUV	32%	1.32 (1.18–1.50)	9% (5–12%)	–	–	–
SBP >160 mm Hg	27%	0.87 (0.78–0.99)	8% (4–12%)	25%	1.01 (0.93–1.09)	8% (5–10%)
SBP <130 mm Hg	23%	1.51 (1.35–1.70)		25%	1.37 (1.26–1.43)
Phosphorus >5.5 mg/dL	39%	1.20 (1.06–1.36)	7% (2–11%)	41%	1.23 (1.16–1.30)	8% (5–10%)
Phosphorus <3.5 mg/dL	13%	1.12 (0.96–1.31)		11%	1.12 (1.03–1.22)
Hemoglobin >12 g/dL	9%	1.04 (0.87–1.27)	6% (1–11%)	23%	0.91 (0.85–0.98)	3% (1–5%)
Hemoglobin <10 g/dL	50%	1.14 (1.02–1.29)		22%	1.28 (1.18–1.36)
WBC count >10,000/μL	19%	1.30 (1.17–1.46)	5% (3–8%)	9%	1.31 (1.21–1.43)	3% (2–4%)
Ferritin >800 ng/mL	8%	1.35 (1.14–1.63)	2% (1–4%)	22%	1.07 (0.99–1.14)	1% (0–3%)
Calcium >9.5 mg/dL	13%	1.09 (0.92–1.27)	0% (0–4%)	30%	1.14 (1.06–1.21)	5% (3–8%)
Calcium <8.4 mg/dL	38%	0.96 (0.86–1.08)		16%	1.15 (1.06–1.26)
PTH >300 pg/mL	39%	0.88 (0.76–1.01)	0% (0–1%)	38%	1.11 (1.03–1.19)	5% (2–9%)
PTH <150 pg/mL	33%	0.92 (0.77–1.04)		34%	1.07 (0.99–1.14)
Combined AF
Malnutrition*	–	–	29% (23–35%)	–	–	20% (18–22%)
Inflammation*	–	–	8% (5–10%)	–	–	4% (2–6%)
MBD abnormality*	–	–	0% (0–10%)	–	–	17% (13–21%)
All risk factors	–	–	65% (59–71%)	–	–	46% (41–50%)

Notes: Cox models for 12 risk factors chosen a priori, stratified by DOPPS phase and country, adjusted for all other variables in table, plus age, sex, black race, BMI, and 12 comorbidities listed in Table 1. *Malnutrition variables include low albumin and low creatinine; inflammation variables include high WBC and high ferritin; MBD variables include high or low calcium, phosphorus and PTH; note pre-ESRD care data were only available for incident patients and RUV was assumed to be minimal for patients on dialysis >1 year; 95% CI: 2.5th and 97.5th percentiles from 1000 runs: 100 bootstrapped samples combined across 10 imputations; negative values of AF could be obtained when the observed HR was less than 1, and we report the negative AFs and/or CI bounds as 0% to convey that no excess mortality risk was attributable to the exposure.

Abbreviations: HR, Hazard Ratio of 1 year mortality; AF, Attributable Fraction; ESRD, end-stage renal disease; SBP, systolic blood pressure; WBC, white blood cell; MBD, mineral and bone disorder; RUV, residual urine volume.

Table 3 Attributable Fractions for Mortality Risk-Factors Among Incident (<60 Days Vintage) Patients, by Region

Risk Factor	North America (N=8972)			Europe/ANZ (N=5278)
	% pts	HR (95% CI)	AF (95% CI)	% pts	HR (95% CI)	AF (95% CI)
Catheter use	71%	1.46 (1.27–1.69)	22% (14–29%)	45%	1.50 (1.22–1.83)	18% (9–26%)
Albumin <3.5 g/dL	54%	1.54 (1.32–1.78)	20% (13–26%)	46%	1.45 (1.16–1.82)	17% (7–26%)
Creatinine <6 mg/dL	49%	1.33 (1.15–1.52)	13% (6–18%)	39%	1.30 (1.05–1.64)	10% (2–19%)
Lack of pre-ESRD care	30%	1.34 (1.18–1.57)	8% (5–13%)	21%	1.39 (1.10–1.74)	8% (2–13%)
No reported RUV	41%	1.37 (1.19–1.59)	11% (6–17%)	18%	1.22 (0.94–1.53)	3% (0–8%)
SBP >160 mm Hg	28%	0.88 (0.76–1.03)	9% (3–14%)	23%	0.84 (0.66–1.09)	6% (0–13%)
SBP <130 mm Hg	24%	1.56 (1.35–1.77)		23%	1.44 (1.16–1.79)
Phosphorus >5.5 mg/dL	37%	1.22 (1.05–1.42)	7% (1–12%)	42%	1.12 (0.90–1.38)	5% (0–14%)
Phosphorus <3.5 mg/dL	14%	1.09 (0.90–1.31)		13%	1.14 (0.84–1.50)
Hemoglobin >12 g/dL	10%	1.05 (0.84–1.28)	3% (0–9%)	11%	1.06 (0.75–1.44)	14% (5–23%)
Hemoglobin <10 g/dL	48%	1.07 (0.93–1.23)		46%	1.39 (1.15–1.73)
WBC count >10,000/μL	22%	1.23 (1.07–1.40)	4% (1–7%)	17%	1.42 (1.12–1.78)	6% (2–10%)
Ferritin >800 ng/mL	9%	1.27 (1.02–1.58)	2% (0–4%)	7%	1.50 (1.09–2.03)	3% (1–6%)
Calcium >9.5 mg/dL	10%	1.12 (0.89–1.37)	0% (0–5%)	20%	1.04 (0.78–1.37)	0% (0–9%)
Calcium <8.4 mg/dL	38%	0.97 (0.84–1.11)		31%	0.98 (0.78–1.25)
PTH >300 pg/mL	43%	0.87 (0.74–1.03)	0% (0–3%)	35%	0.88 (0.69–1.14)	0% (0–5%)
PTH <150 pg/mL	30%	0.92 (0.77–1.10)		35%	0.90 (0.71–1.16)
Combined AF
Malnutrition*	–	–	31% (23–38%)	–	–	26% (15–35%)
Inflammation*	–	–	6% (3–10%)	–	–	9% (4–14%)
MBD abnormality*	–	–	0% (0–11%)	–	–	0% (0–16%)
All risk factors	–	–	66% (58–73%)	–	–	62% (49–72%)

Notes: Cox models stratified by DOPPS phase and country, adjusted for all other variables in table, plus age, sex, black race, BMI, and 12 comorbidities listed in Table 1; analyses within Japan and countries new to DOPPS in Phase 5 were not reported due to the very small number of deaths; *Malnutrition variables include low albumin and low creatinine; inflammation variables include high WBC and high ferritin; MBD variables include high or low calcium, phosphorus and PTH; 95% CI: 2.5th and 97.5th percentiles from 1000 runs: 100 bootstrapped samples combined across 10 imputations; negative values of AF could be obtained when the observed HR was less than 1, and we report the negative AFs and/or CI bounds as 0% to convey that no excess mortality risk was attributable to the exposure.

Abbreviations: HR, Hazard Ratio of 1 year mortality; AF, Attributable Fraction; ESRD, end-stage renal disease; SBP, systolic blood pressure; WBC, white blood cell; MBD, mineral and bone disorder; RUV, residual urine volume.