What we are missing 2012 KDIGO guideline

Anemia

Diagnosis and evaluation  Hb measurement - CKD patient with anemia  CKD 3-5ND, CKD 5PD : at least every 3months  CKD 5HD : at least monthly  Initial evaluation of the anemia  Complete blood count  Reticulocyte count  Serum ferritin level  Serum transferrin saturation  Serum vitamin B 12, folate level

Use of iron to treat  Untreated iron deficiency is an important cause of hyporesponsiveness to ESA treatment  For adult CKD patients on ESA therapy who are not receiving iron supplementation, we suggest a trial of IV iron (or in CKD ND patients alternatively a 1–3 month trial of oral iron therapy)  TSAT ≤ 30% and ferritin ≤ 500 ng/ml  CKD ND, CKD PD : oral or IV  CKD 5HD : IV iron → greater increase in Hb, lower ESA dose  Course of IV iron amounting to approximately 1000 mg (VENOF 100mg, 10 회 )  Initial dose of IV iron administered, we recommend that patients be monitored for 60 minutes after the infusion  Avoid administering IV iron to patients with active systemic infections

Use of ESAs and other agents  Address all correctable causes of anemia (iron deficiency, inflammatory states) prior to initiation of ESA therapy  Caution : active malignancy, history of stroke, malignancy  CKD ND  Hb ≥ 10 g/dl : ESA therapy not be initiated  Hb < 10g/dl : initiate ESA therapy be individualized  CKD 5D  ESA therapy be used to avoid having the Hb < 9 g/dl  ESAs not be used to intentionally increase the Hb >13 g/dl  Stroke, hypertension, vascular access thrombosis ↑

ESA dosing and maintenance  Initial ESA dose : Hb concentration, body weight, clinical circumstances  Epoetin-alfa or epoetin-beta : IU/kg, 3 times/week  Darbepoetin-alfa : 0.45 mg/kg, once weekly (SC or IV) or 0.75 mg/kg, every 2 weeks (SC)  CERA : 0.6 mg/kg, every 2 weeks (SC or IV), or 1.2 mg/kg, every 4 weeks (SC)  Lower dose : history of CVD, thromboembolism, seizures, high blood pressure  Rise in Hb of greater than 2.0 g/dl over a 4-week period should be avoided  CKD ND, CKD 5PD : SC  CKD 5HD : IV or SC (efficacy : SC > IV)

ESA hyporesponsiveness  ESA hyporesponsiveness  No increase in Hb concentration from baseline after the first month of ESA treatment on appropriate weight-based dosing  Avoiding repeated escalations in ESA dose beyond double the initial weight-based dose

Pure red cell aplasia  Patient receiving ESA therapy for more than 8 weeks  Sudden rapid decrease in Hb concentration at the rate of g/dl per week or requirement of transfusions at the rate of approximately 1-2 per week  Normal platelet and white cell counts  Absolute reticulocyte count < 10,000/ml  We recommend ESA therapy be stopped in patients who develop antibody-mediated PRCA  We recommend peginesatide (synthetic, peptide-based erythropoietin-receptor agonist) be used to treat patients with antibody-mediated PRCA

Red cell transfusion to treat anemia in CKD  Managing chronic anemia, we recommend avoiding red cell transfusions  In patients eligible for organ transplantation, we specifically recommend avoiding  Indication  ESA therapy is ineffective (e.g., hemoglobinopathies, bone marrow failure, ESA resistance)  The risks of ESA therapy may outweigh its benefits (e.g., previous or current malignancy, previous stroke)

Red cell transfusion to treat anemia in CKD  HLA sensitization  post-leukodepletion era still continues to pose a significant risk of sensitization  Urgent treatment of anemia  Rapid correction of anemia is required to stabilize the patient’s condition (e.g., acute hemorrhage, unstable coronary artery disease)  When rapid pre-operative Hb correction is required  Considered if the Hb < 7 g/dl

CKD-MBD

Diagnosis of CKD–MBD  Monitor serum levels of calcium, phosphorus, PTH, alkaline phosphatase activity beginning in CKD stage 3  CKD stage 3  Ca/P : 6–12 months  PTH : based on baseline level and CKD progression  CKD stage 4  Ca/P : 3–6 months  PTH : 6–12 months  CKD stages 5, 5D  Ca/P : 1–3 months  PTH : 3–6 months  CKD stages 4–5D  ALP : 12 months, or more frequently in the presence of elevated PTH

Diagnosis of CKD–MBD  CKD stages 3–5D  25(OH)D (calcidiol) levels might be measured  Vitamin D deficiency and insufficiency should be corrected

Diagnosis of CKD–MBD: bone  CKD stages 3–5D : perform a bone biopsy  Unexplained fractures, persistent bone pain, unexplained hypercalcemia, unexplained hypophosphatemia, possible aluminum toxicity, prior to therapy with bisphosphonates in patients with CKD–MBD  Gold standard for the diagnosis of renal osteodystrophy  Provide measurements of bone turnover, mineralization, volume  Help to assess bone quality and the underlying physiology  CKD stages 3–5D : we suggest that BMD testing not be performed routinely  BMD does not predict fracture risk as it does in the general population  BMD does not predict the type of renal osteodystrophy

Diagnosis of CKD–MBD: vascular calcification  CKD stages 3–5  Lateral abdominal radiograph → vascular calcification  Echocardiogram → valvular calcification Bellasi A. et al. Kidney Int 70:1623–1628, 2006

Treatment of CKD–MBD  CKD stages 3–5D  Ca, P : normal range  Dialysate calcium concentration between mEq/l  Hyperphosphatemia : use phosphate-binding agents  HyperP with hyperCa : restrict calcium-based phosphate binders, calcitriol, vitamin D analog  HyperP with arterial calcification, adynamic bone disease, low serum PTH : restrict calcium-based phosphate binders  Avoid the long-term use of aluminum-containing phosphate binders

Treatment of abnormal PTH levels in CKD–MBD  CKD stages 3–5 not on dialysis, the optimal PTH level is not known  We suggest that patients with levels of intact PTH above the upper normal limit of the assay are first evaluated for hyperphosphatemia, hypocalcemia, and vitamin D deficiency  In patients with CKD stage 5D : iPTH levels - 2-9xUNL  no RCTs showing that treatment to achieve a specific PTH level results in improved outcomes

Treatment of abnormal PTH levels in CKD–MBD  CKD stage 5D : iPHT ↑  Calcitriol, vitamin D analogs, calcimimetics be used to lower PTH  HyperCa/P : calcitriol or another vitamin D sterol be reduced or stopped  HypoCa : calcimimetics be reduced or stopped  Intact PTH levels < 2xUNL : calcitriol, vitamin D analogs, calcimimetics be reduced or stopped  CKD stages 3–5D with severe hyperparathyroidism who fail to respond to medical/pharmacological therapy, we suggest parathyroidectomy

Evaluation and treatment of kidney transplant bone disease  In patients in the immediate post-kidney-transplant period, we recommend measuring serum calcium and phosphorus at least weekly, until stable  CKD stages 1–3T  Ca/P : 6-12 months  PTH : once with subsequent intervals depending on baseline level and CKD progression  CKD stage 4T  Ca/P : 3–6 months  PTH : 6–12 months  CKD stage 5T  Ca/P : 1–3 months  PTH : 3–6 months  CKD stages 3–5T  ALP : annually or more frequently in the presence of elevated PTH

Evaluation and treatment of kidney transplant bone disease  CKD stages 1–5T  25(OH)D (calcidiol) levels might be measured  Vitamin D deficiency and insufficiency be corrected  eGFR > 30 ml/min/1.73m 2  Measure BMD in the first 3 months after kidney transplant if they receive corticosteroids or have risk factors for osteoporosis as in the general population  Low BMD : treatment with vitamin D, calcitriol/alfacalcidol, or bisphosphonates be considered  CKD stages 4–5T  BMD testing not be performed routinely

1month lab

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12 month

What we are missing?  25(OH)vitD  VitaminB 12, folate  Lateral abdominal radiograph  Echocardiography  Measure BMD in KT patient  Measure Ca/P immediate post-kidney-transplant period, at least weekly