Burden of illness for patients with non-dialysis chronic kidney disease and anemia in the United States: review of the literature

Figures & data

Figure 1. Flow chart for identification of studies in the systematic review: economics.

Table 1.  Economic burden literature included.

	Citation	Patient population	Study design and number of patients	Included in cost calculation
Economic impact of anemia in CKD patients	Ershler et al., 2005^9	Not specified CKD stage not reported Anemia defined using ICD-9 codes: 280.X, 285.2X, 281.9, 285.9, 284.8. Comparison groups: Anemic vs. Non-anemic	Claim database analysis n = 123,037	Direct costs (payments for inpatient hospital, ER, outpatient hospital, physician office visits, and pharmacy). Indirect costs (absenteeism and short-term disability)
	Lefebvre et al., 2006^10	Non-dialysis CKD stages 3–5, with subanalysis for stage 3 patients (GFR 30 to <60 ml/min) Anemia: Hb <11 g/dL Comparison groups: Untreated anemia vs. non-anemia	Claim database analysis n = 2,001	Outpatient and inpatient services and pharmacy cost
	Rasu et al., 2007^14	Not specified CKD stage not reported Anemia defined using ICD-9 codes for anemia and NDC codes for relevant prescriptions Comparison groups: None (all anemic patients)	Survey study n = 2,234 unweighted CKD-related visits in outpatient office representing 92 million weighted outpatients visits.	Not applicable
	Wish et al., 2009^13	Non-dialysis CKD stage not reported Anemia defined by at least 2 relevant claims Comparison groups: Anemia vs. non-anemia; treated anemia vs. untreated anemia	Claim database analysis n = 37,105	Direct (inpatient and outpatient and drug)
Cost burden of treating anemia	London et al., 2002^15	Non-dialysis CKD stage not reported Anemia status not specified Comparison groups: EPO vs. non-EPO treated anemia	Claim database analysis n = 1,936	Facility (inpatient hospital, outpatient hospital, and emergency room care), professional, laboratory services and outpatient pharmacy services
	Maddux et al., 2007^18	Non-dialysis CKD stage not reported Anemia defined using ICD-9 codes for anemia Comparison groups: EPO vs. untreated anemia	Claim database analysis on ESA n = 8,188	Admission, emergency room, ambulatory and laboratory
	Moyneur et al., 2008^19	Non-dialysis CKD stage not reported Anemia defined using ICD-9 codes: 280, 281, 283, 284, 285 Comparison groups: EPO vs. non-EPO treated anemia	Claim database analysis of ESA use n = 395 (EPO = 199, Non-EPO 196)	Direct (inpatient and outpatient and drug) and indirect (sick leave and disability) costs
	Papatheofanis et al., 2008^20	Non-dialysis CKD stage not reported Anemia: Hb <11 g/dL Comparison groups: Pre-EPO use vs. post-EPO use	Claim database analysis of ESA n = 152	Work productivity
	Perkins et al., 2007^21	Non-dialysis CKD stage not reported Anemia: Hb <12 g/dL Comparison groups: EPO vs. untreated historical control	Chart review/medical records for a management treatment plan CKD in anemia clinic n = 27, Control group CKD n = 22	Not applicable
	Provenzano et al., 2004^22	Non-dialysis CKD stages 1–5 Anemia: Hb <10 g/dL Comparison groups: None (all EPO-treated anemia)	nRCT n = 1,338	Transfusions avoided *Note: Study also appears in Table 2 and is counted with the HRQL papers, as it was identified in that search. Not applicable

CKD, chronic kidney disease; GFR, glomerular filtration rate; ICD, International Classification of Diseases; NDC, national drug code; EPO, erythropoietin; ESA, erythropoiesis-stimulating agents; nRCT, non-randomized controlled trial.

Figure 2. Flow chart for identification of studies in the systematic review: quality of life.

Table 2.  Health-related quality of life literature.

	Citation	Patient population	Study design and number of patients	HRQL measures
Generic measures of HRQL in anemic CKD patient	Odden et al., 2004^40	Not specified CKD stages 3–5 (GFR < 60 ml/min) Anemia: Hb < 12 g/dL Comparison groups: Anemia without CKD vs. anemia with CKD vs. CKD without anemia	Observational study n = 228 (anemic patients n = 90, CKD + anemia n = 45)	Patient Health Questionnaire (PHQ) Seattle Angina Questionnaire (SAQ) – measures limitations on daily activities due to symptoms of coronary disease
	Revicki et al., 1995^34	Non-dialysis CKD stage 5 (Baseline GFR ∼ 10 ml/min) Anemia: hematocrit ≤ 30% Comparison groups: EPO-treated vs. untreated anemia	RCT n = 83 (EPO = 43, control = 40)	SIP, MOS, Life Satisfaction Scale, Center for Epidemiologic Studies Depression Scale, 5-item measure of sexual dysfunction
Generic and disease specific measures of HRQL in anemic CKD patients	Abu-Alfa et al., 2008^28	Non-dialysis CKD stages 3–5 (GFR < 60 ml/min) Anemia: Hb < 11 g/dL Comparison groups: None (all EPO treated patients)	nRCT n = 277	SF-12, KDQOL-CRI
	Agarwal et al., 2006^29	Non-dialysis CKD stages 3–5 (GFR < 60 ml/min) Anemia: Hb < 12 g/dL Comparison groups: IV iron-treated vs. oral iron-treated anemia	RCT n = 75 (n = 36 intravenous iron group, n = 39 oral iron group)	SF-12, KDQOL
	Alexander et al., 2007^23	Non-dialysis CKD stage not reported Anemia: Hb ≤ 10 g/dL Comparison groups: None (all EPO treated patients)	nRCT n = 48	SF-36, FACT-An, FACT-F, ADL, IADL, KDQOL
	Finkelstein et al., 2009^12	Non-dialysis CKD stages 3–5 (GFR < 60 ml/min) Examined a variety of Hb ranges: < 11, 11– < 12, 12– < 13, ≥ 13 Comparison groups: Patients in 4 different hemoglobin levels	Survey n = 1,186	KDQOL and SF-36
	Lefebvre et al., 2006^33	Non-dialysis CKD stage not reported Anemia: Hb < 10 g/dL Comparison groups: None (all EPO treated patients)	nRCT open label n = 1,326	100 mm LASA scales for energy level, ability to perform daily activities, and overall quality of life KDQ
	Provenzano et al., 2004^22	Non-dialysis CKD stages 1–5 Anemia: Hb < 10 g/dL Comparison groups: None (all EPO-treated anemia)	nRCT n = 1,338	100 mm LASA of energy level, ability to perform daily activities, and overall HRQL KDQ
	Singh et al., 2006^27 (CHOIR study)	Non-dialysis CKD stages 3–4 (GFR 15–50 ml/min) Anemia: Hb < 11 g/dL Comparison groups: EPO treated with high Hb target vs. EPO treated with low Hb target	RCT n = 1,432 high hemoglobin group (target: Hb 13.5g/dL) n = 715, low hemoglobin group (target Hb 11.3g/dL) n = 717)	LASA, KDQ, SF-36
Utility measures in anemic CKD patients	Muirhead et al., 1994^26	Not specified CKD stage not reported Anemia: Hb 55–95 g/L Comparison groups: None (all EPO-treated anemia)	nRCT n = 40	SIP Transplant Disease Questionnaire (TDQ), an instrument consisting of 26 questions in 5 dimensions: physical symptoms, fatigue, uncertainty/fear, appearance, and emotions TTO measure of treatment utility
	Revicki D. A., 1992^25	Not specified CKD stage not reported Anemia: Hematocrit ≤ 30% Comparison groups: EPO-treated vs. placebo-treated anemia	RCT n = 37 (Placebo = 34, EPO = 39)	Health status: A structured interview including: SIP Home Management, Alertness Behavior and Social Interaction scales, MOS energy, health distress, and physical functioning scales, life satisfaction, sexual dysfunction Health Utility: Patient preferences were measured for current health and 3 hypothetical health states using standard gamble and categorical preference ratings, as measured by the Feeling Thermometer
Impact of treatment on anemic CKD patients	Benz et al., 2007^31	Non-dialysis CKD stages 2–4 (GFR 10–60 ml/min) Anemia: Hb < 11 g/dL Comparison groups: None (all CKD-anemia patients)	nRCT n = 67	SF-36, LASA
	Drueke et al., 2006^30 (CREATE Study)	Not specified CKD stages 3–4 (GFR 15–35 ml/min) Anemia: Hb 11–12.5 g/dL Comparison groups: EPO-treated at study start vs. EPO-treated initiated at Hb < 10.5 g/dL	RCT n = 603 (Group 1: treatment with EPO triggered by decrease in Hb to < 10.5 g/dL, n = 301 Group 2: EPO treatment administered at start of study, n = 302. More than 92% of total sample had CVD)	SF-36
	Kleinman et al., 1989^35	Non-dialysis CKD stage not reported Anemia: hematocrit ≤ 30% Comparison groups: EPO-treated vs. placebo-treated anemia	RCT n = 14	3 question QOL assessment related to energy level, ability to work, and overall QOL VAS scale
	Provenzano et al., 2005^32 (PROMPT Study)	Non-dialysis CKD stage not reported Anemia: Hb ≥ 11 g/dL (stable) Comparison groups: 4 treatment groups; baseline and endpoint values	RCT n = 130 (ESA QD) n = 131 (ESA every 2 weeks) n = 132 (ESA every 3 weeks) n = 126 (ESA every 4 weeks)	LASA, KDQ
Other	Lindgren C., 2003^41	Not specified Comparison groups: None (all CKD-anemia patients)	Survey	Survey covered symptoms and awareness of anemia. No information provided about development or validation of the survey

HRQL, health-related quality of life; CKD, chronic kidney disease; GFR, glomerular filtration rate; RCT, randomized controlled trial; EPO, erythropoietin; SIP, Social Impact Perception; MOS, Mean Opinion Scale; nRCT, non-randomized controlled trial; SF-12, Short Form-12 Health Survey; KDQOL-CRI, kidney diseases quality of life – chronic renal insufficiency; KDQOL, kidney diseases quality of life; SF-36, Short Form-36 Health Survey; FACT-An, functional assessment of cancer therapy – anemia; FACT-F, functional assessment of cancer therapy - fatigue; ADL, activities of daily living; IADL, instrumental activities of daily living; LASA, linear analog scale assessment; KDQ, Kidney Diseases Questionnaire; CHOIR Study, Correction of Hemoglobin Outcomes in Renal Insufficiency Study; TTO, time trade off; CREATE Study, Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta study; QOL, quality of life; VAS, visual analogue scale.

Table 3.  Average SF-36 and SF-12 Scores: patients with CKD-related anemia and normative US general population*.

SF-36, SF-12 scales	SF-36 US population normative score (percentile)^§			CKD-related anemia patients
				Abu-Alfa et al. (2008)[28]	Agarwal et al. (2006)[29]	Alexander et al. (2007)[23]	Singh et al. (2006)[27]
	25	50	75
PCS^†	45.5	53.2	57.1	36.5	35.9
MCS^‡	45.5	52.8	57.0	46.5	49.8
Physical function	46.5	54.9	57.0			40.9	42.4
Bodily pain	41.8	51.1	55.4			62.8	58.0
Role physical	47.1	54.4	56.9			25.5	32.5
General health	44.8	52.0	57.7			40.4	42.6
Vitality	45.9	52.1	58.3			38.4	36.6
Social role	54.9	56.9	56.9			61.5	63.7
Role emotional	48.1	55.9	55.9			54.9	57.2
Mental health	44.4	52.8	58.5			69.8	70.2

* blank spaces indicate that data was not reported.

^†PCS, Physical Component Summary.

^‡MCS, Mental Component Summary.

^§From: Ware et al. 2000 How to Score Version Two of the SF-36 Health Survey[42].

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