Clinical management of anaemia in a patient with chronic kidney disease not-on-dialysis Jolanta Malyszko, MD Department of Nephrology and Transplantology Medical University of Bialystok, Poland © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Objectives Focus on anaemia in CKD and DM, including prevalence and outcome Case report: Diagnosis of anaemia Treatment: Iron supplementation and ESA therapy Hb variability: Practical considerations Safety issues with ESA therapy CKD: chronic kidney disease; DM: diabetes mellitus; Hb: haemoglobin; ESA: erythropoiesis-stimulating agent © Springer Healthcare, a part of Springer Science+Business Media; 2010.

CKD anaemia: A common complication Anaemia associated with CKD is a major complication even in early stages Hb decreases progressively with the degree of renal impairment1 CKD anaemia occurs earlier in patients with type 2 diabetes2 CKD: chronic kidney disease; Hb: haemoglobin 1. Jungers. Nephrol Dial Transplant 2002; 17:1621-27, 2. Joss, et al. QJM 2007;100:641-47 © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Multiple choice question 1 Which of the following statements are true? Anaemia associated with CKD is a major complication even in its early stages. Haemoglobin remains stable despite the degree of renal impairment. Among patients with diabetes, CKD anaemia occurs earlier than among non-diabetics. A: 1 B: 1 & 3 C: All of the above D: None of the above CKD: chronic kidney disease © Springer Healthcare, a part of Springer Science+Business Media; 2010.

CKD anaemia with diabetes Correlates with eGFR Stage 4+ 60 Stage 3 macroalbuminuria 45 Stage 2 Prevalence anaemia (%) 30 Stage 1 microalbuminuria 15 normoalbuminuria >90 60-90 30-60 <30 eGFR (mL/min/1.73m2) eGFR: estimated glomerular filteration rate Adapted from Thomas, et al. Nephrol Dial Transplant 2004; 19:1792-97 © Springer Healthcare, a part of Springer Science+Business Media; 2010.

DM: diabetes mellitus; tid: 3 times a day; qd: once a day Case report Caucasian female born in 1956, high-school teacher Type 2 DM diagnosed at 33 years of age, treated with metformin (850 mg tid) and glimepiryde (3 mg qd) Surgery for ovarian abscess at 44 years of age Problems with blood pressure control at 45 years of age Under diabetologist care DM: diabetes mellitus; tid: 3 times a day; qd: once a day © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Nephrology findings 1st nephrology consultation at 50 years of age (Oct 2006) owing to poor blood pressure control Creatinine: 1.07 mg/dL; Hb: 12.6 g/dL, Hct: 38%; total cholesterol: 233 mg/dL Other medications: Indapamide SR; simvastatin 20 mg bedtime; quinalapril 5 mg ABPM: Mean SBP 162 mgHg; mean DBP 91 mmHg; non dipper Urinary protein excretion: 3.4 g/d ABPM: ambulatory blood-pressure monitoring; SBP: systolic blood pressure; DBP: diastolic blood pressure © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Additional findings and recommendations Leg oedema Urinary glucose: 0.26g/L Potassium: 5.46 mmol/L; sodium: 141 mmol/L TSH: 1.449 mIU/L Quinapril: ↑10 mg qd Add telmisartan: 80 mg qd Furosemide: 40 mg qd Refused insulin therapy TSH: thyroid-stimulating hormone; qd: once a day © Springer Healthcare, a part of Springer Science+Business Media; 2010.

1st nephrology hospitalisation 51 years of age (Dec 2007), owing to nephrotic syndrome, UAE- 8 g/d; albumin: 2.6 g/dL; protein: 5.5 g/dL Fasting glucose: 255 mg/dL; 2h post-meal: 280 mg/dL; urinary glucose: 250-1454 mg/dL; creatinine: 1.26 mg/dL; eGFR (MDRD): 48 mL/min Hb: 10.5 g/dL; Hct: 30.7%; MCV: 84.8 fl CRP: 1.3 mg/L Chol: 200 mg/dL; TG: 177 mg/dL Simple diabetic retinopathy Antihypertensives continued, insulin therapy refused Oral iron started UAE: urinary albumin excretion; eGFR: estimated glomerular filtration rate; MDRD: modification of diet in renal disease; Hb: haemoglobin; MCV: mean corpuscle volume; CRP: c-reactive protein; TG: triglyceride © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Outpatient unit March 2008: Hb 10.8 g/dL; oral iron June 2008: Iron: 56 μg/mL; TIBC: 263 μg/mL; TSAT: 21%; Ferritin: 241.41 ng/mL; Hb: 9.0 g/dL; Hct: 26.4%; plt: 464 x 103/mL; WBC: 11.26x106/mL; CRP: 0.2 mg/L; creatinine: 1.88 mg/dL; eGFR: 34 mL/min Darbepoetin (20 μg) Q2W then 40 μg QM Hb rose to 9.8 g/dL then 10.5 g/dL after 4 months Hb: haemoglobin; TIBC: total iron binding capacity; TSAT: transferrin saturation; Hct: haematocrit; eGFR: estimated glomerular filteration rate; Q2W: once every 2 weeks; QM: once a month; CRP: C-reactive protein; WBC: white blood cells; Hct: haematocrit © Springer Healthcare, a part of Springer Science+Business Media; 2010.

2nd nephrology hospitalisation Dec 2008: fall in Hb despite ESA therapy Hb: 8.5 g/dL; Hct: 25.6 % Ferritin: 104 ng/mL; TSAT: 21%; CRP: 2.2 mg/L; creatinine: 1.96-3.28 mg/L; eGFR (MDRD): 16-28 mL/min; urinalysis protein: 100 mg/dL; glucose: 363 mg/dL; albumin: 3.4 g/dL; tprotein: 6.7 g/dL IV iron and ESA continued ESA: erythropoiesis-stimulating agent, eGFR: estimated glomerular filteration rate, MDRD: modification of diet in renal disease; tprotein: total protein; CRP: C-reactive protein; Hct: haematocrit; Hb: haemoglobin; TSAT: transferrin saturation © Springer Healthcare, a part of Springer Science+Business Media; 2010.

3rd nephrology hospitalisation Feb 2009: Hb 10.2 g/dL; April Hb: 11.5 g/dL; darbepoetin alfa: 40 μg/month May 2009: 3rd nephrology hospitalisation Hb: 9.2 g/dL; CRP: 0.4 mg/dL; Fe: 35 μg/dL; TSAT: 14%; ferritin: 131 ng/mL; CEA: 2.5 ng/mL (N: 0-3 ng/mL); Ca-125: 237 mIU/mL; (N: 0-35 mIU/mL), tprotein: 7.1 g/dL; creatinine: 4.21 mg/dL Insulin therapy introduced Ascites, ovarian tumour: surgery Ovariectomy and hysterectomy: ovarian cystadenoma Hb: haemoglobin, CRP: C-reactive protein, Fe: iron, TSAT: transferrin saturation, CEA: carcinoembryonic antigen, Ca: calcium © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Post-surgical course IV iron supplementation Creatinine: 2.1-2.92 mg/dL; eGFR: 18-26 mL/min Hb: 9.8 g/dL; after 1 g of IV iron ESA reintroduced in June 2009 Creatinine stable 2.56-2.80 mg/dL Hb rose to 11.5 /dL (August 2009), then 12.2 g/dL; darbepoietin alfa dose 20 μg/month, then Hb 11.7 g/dL (Oct 2009), continue ESA 20 μg/month Hb stable: 11.9-11.8 g/dL Hb: haemoglobin; ESA: erythropoiesis-stimulating agent; eGFR: estimated glomerular filteration rate © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Multiple choice question 2 The patient’s haemoglobin has reached 13.2 g/dL; she asks her physician whether her ESA therapy should be continued. Your possible answer is: A: As her quality of life has improved, I would continue ESA therapy B: I would lower the dose of ESA by 25% C: I would discontinue ESA therapy D: None of the above © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Safety considerations Cystadenoma: Continue with ESA? IV iron without an ESA results in a fall in Hb Continue with careful gynaecological monitoring ESA: erythropoiesis-stimulating agent © Springer Healthcare, a part of Springer Science+Business Media; 2010.

Conclusions ESA therapy is effective in the clinical management of CKD Darbepoetin alfa administered monthly was effective and Hb levels were stable In patients with a history of malignancy, periodic monitoring is warranted ESA: erythropoiesis-stimulating agent; CKD: chronic kidney disease; Hb: haemoglobin © Springer Healthcare, a part of Springer Science+Business Media; 2010.