CHRONIC KIDNEY DISEASE

KDOQI GUIDELINES

CKD AND ANEMIA

Anemia

is the clinical manifestation of a decrease in circulating red blood cell mass and usually is detected by low blood hemoglobin (Hb) concentration

WHO: Hb level less than 13.0 g/dL in adult men and less than 12 g/dL in adult women.

Stage and cause of CKD:

Hb testing should be carried out in all patients with CKD, regardless of stage or cause.

Frequency of testing for anemia:

Hb levels should be measured at least annually.

Diagnosis of anemia:

diagnosis of anemia should be made and further evaluation should be undertaken at the following Hb concentrations: <13.5 g/dL in adult males. <12.0 g/dL in adult females.

The purpose of specifying Hb level thresholds to define anemia is to identify patients who are most likely to show pathological processes contributing to a low Hb level and who therefore are most likely to benefit from further anemia evaluation.  

Patients with diabetes are more prone to both develop anemia and develop anemia at earlier stages of CKD than their nondiabetic counterparts

Anemia in patients with CKD is not always caused by erythropoietin deficiency alone. Initial laboratory evaluation therefore is aimed at identifying other factors that may cause or contribute to anemia or lead to ESA hyporesponsiveness.

Initial assessment of anemia should include the following tests:

1. complete blood count (CBC

2. Absolute reticulocyte count.

3. Serum ferritin to assess iron stores.

4. Serum TSAT or content of Hb in reticulocytes (CHr) to assess adequacy of iron for erythropoiesis.

 

Lower limit of Hb:

In patients with CKD, Hb should be 11.0 g/dL or greater. (MODERATELY STRONG RECOMMENDATION)

when comparing higher with lower Hb targets—QOL is a sufficient and, apparently, the sole determinant of treatment benefit.

Upper limit of Hb:

there is insufficient evidence to recommend routinely maintaining Hb levels at 13.0 g/dL or greater in ESA- treated patients.

For most patients, the known risks outweigh the known benefits of treating to higher Hb level.

The term ESA applies to all agents that augment erythropoiesis through direct or indirect action on the erythropoietin receptor. Currently available ESAs include epoetin alfa, epoetin beta, and darbepoetin.

Frequency of Hb monitoring:

the frequency of Hb monitoring in patients treated with ESAs should be at least monthly.

provide sufficient surveillance information to assist in achieving and maintaining target Hb levels safely and expeditiously during ESAtherapy. The minimum interval between ESA dose adjustments is 2 weeks because the effect of most dose changes will not be seen within a shorter interval.  

ESA DosingThe initial ESA dose and ESA dose adjustments should be determined by the patient’s Hb level, the target Hb level, the observed rate of increase in Hb level, and clinical circumstances.

In general, the objective of initial ESA therapy is a rate of increase in Hb levels of 1 to 2 g/dL per month.

ESA doses should be decreased, but not necessarily withheld, when a downward adjustment of Hb level is needed.

Withholding ESA doses, particularly for long periods, may lead to a delayed decrease in Hb levels to less than target range which may initiate periodic cycling of Hb levels at greater than and less than the target Hb range.  

Should ESA doses be withheld in an ESA-dependent patient, a prolonged loss of erythropoietic precursors may result.

ESA DosingScheduled ESA doses that have been missed should be replaced at the earliest possible opportunity.

missed doses of ESA, like held doses, may lead to a delayed decrease in Hb levels to less than target range 

ESA administration in ESA-dependent patients should continue during hospitalization.

Hypertension, vascular access occlusion, inadequate dialysis, history of seizures, or compromised nutritional status are not contraindications to ESA therapy.

discourage the practice of withholding ESA therapy in the presence of conditions potentially linked to anemia treatment. If these disorders arise in the course of anemia therapy with ESA, they should be treated appropriately with specific measures. There is no evidence that withholding ESA therapy improves patient outcomes in these settings.

Route of administration

the route and frequency of ESA administration should be determined by the CKD stage, treatment setting, efficacy, safety, and class of ESA used. subcutaneous (SC) administration in non–HD-CKD

patients. intravenous (IV) administration in HD-CKD patients.

Anemia therapy in patients with CKD requires effective use of iron agents, guided by appropriate testing of iron status. The goals of iron therapy are to avoid storage iron depletion, prevent iron-deficient erythropoiesis, and achieve and maintain target Hb levels.

Targets of iron therapy: HD-CKD: Serum ferritin>200 ng/mL AND TSAT >20%, or CHr >29

pg/cell. ND-CKD and PD-CKD: Serum ferritin>100 ng/mL AND TSAT

>20%.

Route of administration: HD-CKD: IV NDCKD or PD CKD: IV or oral

No single Hb concentration justifies or requires transfusion. In particular, the target Hb

recommended for chronic anemia management should not serve as a transfusion trigger.

  If red blood cell transfusions are deemed necessary for the

immediate treatment of patients with chronic anemia, the goal should be to attain an Hb concentration that will prevent inadequate tissue oxygenation or cardiac failure. When red blood cell transfusions are considered for the long-term treatment of patients with chronic anemia, treatment goals (other than to maintain a certain Hb concentration) should be determined in advance and assessed serially to ascertain whether the goals are being met.

CKD AND DIABETES

Screening and Diagnosis of DKD

CKD in patients with diabetes may or may not represent DKD. In the absence of an established diagnosis, the evaluation of patients with diabetes and kidney disease should include investigation into the underlying cause(s).

Patients with diabetes should be screened annually for DKD. Initial screening should commence:

5 years after the diagnosis of type 1 diabetes; (A) from diagnosis of type 2 diabetes.

Screening should include: Measurements of urinary albumin- creatinine ratio (ACR) in a

spot urine sample; Measurement of serum creatinine and estimation of GFR.

Screening and Diagnosis of DKD

An elevated ACR should be confirmed in the absence of urinary tract infection with 2 additional first-void specimens collected over the next 3 to 6 months. Microalbuminuria is defined as an ACR between 30-300 mg/g. Macroalbuminuria is defined as an ACR > 300 mg/g. 2 of 3 samples should fall within the microalbuminuric or

macroalbuminuric range to confirm classification.

In most patients with diabetes, CKD should be attributable to diabetes if: Macroalbuminuria is present; or Microalbuminuria is present in the presence of diabetic retinopathy, in

type 1 diabetes of at least 10 years’ duration. (A)

Management ofHyperglycemia & General Diabetes CareHyperglycemia, the defining feature of diabetes, is a

fundamental cause of vascular target- organ complications, including kidney disease. Intensive treatment of hyperglycemia prevents DKD and may slow progression of established kidney disease.

Target HbA1c for people with diabetes should be < 7.0%, irrespective of the

presence or absence of CKD. (A)

Management of Hypertension

Most people with diabetes and CKD have hypertension. Treatment of hypertension slows the progression of CKD.

Hypertensive people with diabetes and CKD stages 1-4 should be treated with an ACE

inhibitor or an ARB, usually in combination with a diuretic. (A)

Target blood pressure in diabetes and CKD stages 1-4 should be < 130/80 mm Hg. (B)

Management of Dyslipidemia

Dyslipidemia is common in people with diabetes and CKD. The risk of CVD is greatly increased in this population. People with diabetes and CKD should be treated according to current guidelines for high-risk groups.

Management of Dyslipidemia

Target low-density lipoprotein cholesterol (LDL-C) in people with diabetes and CKD stages 1-4 should be < 100 mg/dL; <70 mg/dL is a therapeutic option. (B)

People with diabetes, CKD stages 1-4, and LDL-C > 100 mg/dL should be treated with a statin. (B)

Treatment with a statin should not be initiated in patients with type 2 diabetes on maintenance hemodialysis therapy who do not have a specific cardiovascular indication for treatment. (A)

Nutritional Management in Diabetes and CKDDietary modifications may reduce the progression of

CKD.

Target dietary protein intake for people with diabetes and CKD stages 1-4 should be the RDA of 0.8 g/kg body weight per day. (B)

Treatments that decrease urinary albumin excretion may slow the progression of DKD and improve clinical outcomes, even in the absence of hypertension.

Nutritional Management in Diabetes and CKDTreatments that decrease urinary albumin excretion may

slow the progression of DKD and improve clinical outcomes, even in the absence of hypertension. However, most people with diabetes and albuminuria have hypertension.

Normotensive people with diabetes and albuminuria (micro/macro) should be treated with an ACE inhibitor or an ARB. (C)

Albuminuria reduction may be considered a treatment target in DKD. (C)

CKD AND HYPERTENSION

Goals of Antihypertensive Therapy in CKD Hypertension is common in CKD and is a risk factor for

faster progression of kidney disease and development and worsening of cardiovascular disease (CVD). Some antihypertensive agents also slow the progression of kidney disease by mechanisms in addition to their antihypertensive effect.

Antihypertensive therapy should be used in CKD to: Lower blood pressure (A); Reduce the risk of CVD, in patients with or without

hypertension (B); Slow progression of kidney disease, in patients with or

without hypertension (A)

Goals of Antihypertensive Therapy in CKD

Modifications to antihypertensive therapy should be considered based on the level of proteinuria during treatment (C)

Antihypertensive therapy should be coordinated with other therapies for CKD as part of a multi-intervention strategy (A).

If there is a discrepancy between the treatment recommended to slow progression of CKD and to reduce the risk of CVD, individual decision-making should be based on risk stratification (C).

Dietary and Other Therapeutic Lifestyle ChangesDietary and other therapeutic lifestyle modifications are recommended

as part of a comprehensive strategy to lower blood pressure and reduce CVD risk in CKD.

Dietary sodium intake of less than 2.4 g/d (less than 100 mmol/d) should be recommended in most adults with CKD and hypertension (A).

Other dietary recommendations for adults should be modified according to the stage of CKD (B).

Lifestyle modifications recommended for CVD risk reduction should be recommended as part of the treatment regimen (B).

Referral to a registered dietitian should be considered to help patients achieve dietary recommendations (C).

Pharmacological Therapy: Use of Antihypertensive Agents in CKD

All antihypertensive agents can be used to lower blood pressure in CKD. Multi-drug regimens will be necessary in most patients with CKD to achieve therapeutic goals. Patients with specific causes of kidney disease and CVD will benefit from specific classes of agents.

Patients with CKD should be considered in the "highest-risk" group for CVD for implementing recommendations for pharmacological therapy, irrespective of cause of CKD (A).

Target blood pressure for CVD risk reduction in CKD should be <130/80 mm Hg (B).

Pharmacological Therapy: Use of Antihypertensive Agents in CKD

Antihypertensive agents should be prescribed as follows, when possible: Preferred agents for CKD should be used first (A); Diuretics should be included in the antihypertensive

regimen in most patients (A). Choose additional agents based on cardiovascular disease-

specific indications to achieve therapeutic and preventive targets and to avoid side-effects and interactions (B).

Pharmacological Therapy: Use of Antihypertensive Agents in CKD

The antihypertensive regimen should be simplified as much as possible (B). Long-acting (once-daily agents) should be used when

possible (B). Two agents, either as separate prescriptions or as a fixed-

dose combination containing preferred agents, may be considered as initial therapy for SBP >20 mm Hg above goal according to the stage of CKD and CVD risk (C).

Fixed-dose combinations may be used for maintenance therapy after the antihypertensive regimen has been established (B).

Pharmacological Therapy: Diabetic Kidney Disease

Diabetes mellitus is the most common cause of kidney failure in the United States. Diabetic kidney disease is characterized by the early onset of albuminuria, hypertension, and a high risk of coexistent or subsequent CVD.

Target blood pressure in diabetic kidney disease should be <130/80 mm Hg

Patients with diabetic kidney disease, with or without hypertension, should be treated with an ACE inhibitor or an ARB

Pharmacological Therapy: Nondiabetic Kidney Disease

Nondiabetic kidney diseases include glomerular diseases other than diabetes, vascular diseases other than renal artery disease, tubulointerstitial diseases, and cystic disease.

Target blood pressure in nondiabetic kidney disease should be <130/80 mm Hg

Patients with nondiabetic kidney disease and spot urine total protein to creatinine ratio ≥ 200 mg/g, with or without hypertension, should be treated with an ACE inhibitor or ARB

Use of ACE Inhibitors and ARB in CKD

ACE inhibitors and ARBs can be used safely in most patients with CKD.

ACE inhibitors and ARBs: should be used at moderate to high doses, as used in

clinical trials) (A). should be used as alternatives to each other, if the

preferred class cannot be used (B). can be used in combination to lower blood pressure or

reduce proteinuria (C).

Use of ACE Inhibitors and ARB in CKD

Patients treated with ACE inhibitors or ARBs should be monitored for hypotension, decreased GFR, and hyperkalemia (A). The interval for monitoring blood pressure, GFR, and serum

potassium depends on baseline levels (B).

In most patients, the ACE inhibitor or ARB can be continued if: GFR decline over four months is <30% from baseline value (B); Serum potassium is <5.5 mEq/L (B). ACE inhibitors and ARBs should not be used or used with

caution in certain circumstances

Use of Diuretics in CKD

Diuretics are useful in the management of most patients with CKD. They reduce ECF volume, lower blood pressure, potentiate the effects of ACE inhibitors, ARBs, and other antihypertensive agents and reduce the risk of CVD in CKD. Choice of diuretic agents depends on the level of GFR and need for reduction in ECF volume.

Most patients with CKD should be treated with a diuretic (A). Thiazide diuretics given once daily are recommended in patients with GFR ≥ 30

mL/min/1.73 m2 (CKD Stages 1-3) (A); Loop diuretics given once or twice daily are recommended in patients with GFR

<30 mL/min/1.73 m2 (CKD Stages 4-5) (A); Loop diuretics given once or twice daily, in combination with thiazide diuretics,

can be used for patients with ECF volume expansion and edema (A). Potassium-sparing diuretics should be used with caution:

○ In patients with GFR <30 mL/min/1.73 m2 (CKD Stages 4-5) (A);○ In patients receiving concomitant therapy with ACE inhibitors or ARBs (A);○ In patients with additional risk factors for hyperkalemia (A).

Guideline 12: Use of Diuretics in CKD

Patients treated with diuretics should be monitored for: Volume depletion, manifest by hypotension or decreased GFR

(A); Hypokalemia and other electrolyte abnormalities (A).

Long-acting diuretics and combinations of diuretics with other antihypertensive agents should be considered to increase patient adherence (B).

CKD and BONE METABOLISM

EVALUATION OF CALCIUM AND PHOSPHORUS METABOLISM

Serum levels of calcium, phosphorus, and intact plasma parathyroid hormone (PTH) should be measured in all patients with CKD and GFR<60 mL/min/1.73m2. The frequency of these measurements

should be based on the stage of chronic kidney disease.

ASSESSMENT OF BONE DISEASE ASSOCIATED WITH CKD

2.1 The most accurate diagnostic test for determining the type of bone disease associated with CKD is iliac crest bone biopsy with double tetracycline labeling and bone histomorphometric nalysis. However, not necessary to perform bone

biopsy in most cases

EVALUATION OF SERUM PHOSPHORUS LEVELS

In CKD patients Stages 3 and 4: serum phosphorus:

2.7 mg/dL - 4.6 mg/dL (0.87 mmol/L -1.49 mmol/L)

In CKD Stage 5 and in those undergoing dialysis:Serum phosphorus:

3.5 - 5.5 mg/dL (1.13-1.78 mmol/L).

RESTRICTION OF DIETARY PHOSPHORUS

Dietary phosphorus should be restricted to 800 to 1,000 mg/day:serum phosphorus levels:

○ Stage 3 & 4: >4.6 mg/dL (1.49 mmol/L)○ Stage 5: >5.5 mg/dL (1.78 mmol/L)

plasma levels of intact PTH are elevated above target range of the CKD Stage

USE OF PHOSPHATE BINDERS Stages 3 and 4 phosphorus or intact PTH levels cannot be controlled within

the target range, despite dietary phosphorus restriction phosphate binders should be prescribed. Calcium-based phosphate binders are effective in lowering serum

phosphorus levels and may be used as the initial binder therapy.

Kidney Failure (Stage 5) Both calcium-based phosphate binders and other noncalcium-,

nonaluminum-, and nonmagnesium- containing phosphate-binding agents are effective in lowering serum phosphorus levels and either may be used as the primary therapy.

In dialysis patients who remain hyperphosphatemic despite use of phosphate binders, a combination of both should be used.

USE OF PHOSPHATE BINDERS total dose of elemental calcium provided

by the calcium-based phosphate binders: ≤1,500 mg/day

total intake of elemental calcium (including dietary calcium): ≤ 2,000 mg/day

USE OF PHOSPHATE BINDERS Calcium-based phosphate binders should not be

used in dialysis patients who are hypercalcemic or whose plasma PTH levels are <150 pg/mL (16.5 pmol/L) on 2 consecutive measurements.

Noncalcium-containing phosphate binders are preferred in dialysis patients with severe vascular and/or other soft-tissue calcifications.

In patients with serum phosphorus levels >7.0 mg/dL (2.26 mmol/L), aluminum-based phosphate binders may be used as a short-term therapy (4 weeks)

PREVENTION AND TREATMENT OF VITAMIN D INSUFFICIENCY AND DEFICIENCY Stages 3 and 4: If the serum level of 25-hydroxyvitamin D is

<30 ng/mL, supplementation with vitamin D2 (ergocalciferol) should be initiated

Stage 5: Therapy with an active vitamin D sterol

(calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) should be provided if the plasma levels of intact PTH are >300 pg/mL.

METABOLIC ACIDOSIS

Stages 3, 4, and 5:total CO2 >22 mEq/L (22 mmol/L).

○ Sodium bicarbonate Gr X tab = 7 mEq/tab○ Dose: 2-4 g/d or 25-50 mEq/d

CKD AND DYSLIPIDEMIA

All adults and adolescents with CKD should be evaluated for dyslipidemias. (B)a complete fasting lipid profile with total

cholesterol, LDL, HDL, and triglycerides. (B)

Stage 5 CKD patients with dyslipidemias should be evaluated for remediable, secondary causes. (B)

Stage 5 CKD and fasting triglycerides >500 mg/dL (>5.65 mmol/L) that cannot be corrected by removing an underlying cause:therapeutic lifestyle changes (TLC) and a

triglyceride- lowering agent should be considered. (C)

Hyperuricemia Reduction in the efficiency of urate excretion Hyperuricemia is of no clinical importance with

respect to CKD until serum urate levels exceed at least 13 mg/dL (773 µmol/L) in men, and 10 mg/dL (595 µmol/L) in women.

Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate CKD.

Helps preserve kidney function during 12 months of therapy compared with controls

Nutrition

Serum albumin is a valid and clinically useful measure of protein-energy nutritional status in maintenance dialysis patients.

The recommended daily energy intake is 35 kcal/kg/d for those who are less than 60 years of age and 30-35 kcal/kg/d for individuals 60 years or older.

Nutrition

The recommended DPI for clinically stable HD patients is 1.2 g/kg/d. At least 50% of the dietary protein should be of high biological value.

For individuals who are not undergoing maintenance dialysis, the institution of a planned low-protein diet providing 0.60 g protein/kg/d (up to 0.75 g protein/kg/d) should be considered.

Renal Replacement Therapy Severe metabolic acidosis Hyperkalemia Pericarditis Encephalopathy Intractable volume overload Failure to thrive and malnutrition Peripheral neuropathy Intractable gastrointestinal symptoms GFR <10 mL/min