Chronic Kidney Disease Guidelines

Step 1: Identify high risk

Step 2: Case finding

Step 3: Evaluation and staging

Step 4: Determine cause

Step 5: Care objectives

Practice Points

References

About This Document

Step 1: Identify high-risk populations

Identify patients at risk of kidney disease based upon a directed medical and surgical history including comorbidities (e.g. diabetes, cardiovascular disease), as well as dietary, social, demographic, and cultural factors, a review of symptoms, and physical examination.

High-risk populations include those:

· with diabetes

· with hypertension

· with a diagnosis of hypertension +/- vascular disease

· with autoimmune disease.

· with a family history of kidney disease

· belonging to specific high-risk ethnic groups: First Nations and Pacific Islanders.

Note: Age greater than 60 years is associated with an increased risk of impaired kidney function. However, there is insufficient evidence at this point to recommend screening all individuals over 60 solely on the basis of age.

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Step 2: Screen high-risk populations

Screen high-risk populations every 1-2 years depending upon clinical circumstances (e.g. yearly for persons with diabetes) using serum creatinine and random urine tests (also see Notes).

The estimated Glomerular Filtration Rate (eGFR), computed from the serum creatinine value, is the best laboratory marker for kidney disease. Most laboratories in BC now automatically report eGFR when a serum creatinine is ordered.

• Persistent eGFR values < 60 ml/min indicate substantial reduction in kidney function.

• Urine test abnormalities, even with persistent eGFR values =/<60 ml/min, indicate abnormal kidney function, either as an isolated condition or as a symptom of a systemic disease.

Random urine tests for macroscopic and microscopic urinalysis and albumin/creatinine ratio (ACR)

· Significant abnormalities include the presence of persistent white blood cells or red blood cells in the absence of infection or instrumentation. The presence of any cellular casts is always pathological.

· In diabetes, elevation of ACR (> 2.0 mg/mmol males; > 2.8 mg/mmol females) on 2 out of 3 serial tests, performed between 1 week and 2 months apart, indicates micro-vascular disease +/- glomerular disease requiring ACEI/ARB therapy.

· In hypertension, patients with ACR > 30 should be treated with ACEI/ARB’s. Lower levels of protein excretion should be treated with standard antihypertensives.

If test results are normal, repeat every 1-2 years and monitor blood pressure. If test results are abnormal, confirm the abnormality, then evaluate as described in Step 3.

Notes:

1. “Persistent” = present for > 3 months.

2. GFR estimates based on serum creatinine measurements may be unreliable in patients with very large or small body habitus, those on specific diets (very high or very low protein) and in patients receiving medications that interfere with the measurement or excretion of creatinine (e.g. trimethoprim and sulfamethoxazole, ciprofloxacin, fenofibrate).

3. 24-hour urine collections are not necessary in most cases.

4. ACR is also referred to as the test for microalbumin. “Microalbuminuria” refers to urinary albumin excretion above the normal range, but below the detection limit of tests for urinary total protein. Note that this guideline uses the thresholds adopted by the Canadian Diabetes Association for the detection of microalbuminuria. As methods improve and further data become available, these cutoffs may be revised. Serial ACR tests can normally be incorporated into the routine visit schedule.

5. Exercise, diet and/or hydration status may affect kidney function estimates or the degree of albuminuria/proteinuria. If baseline tests are abnormal or subsequent tests are significantly different from baseline, confirmation by repeat testing is warranted.

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Step 3: Evaluate patients with abnormal screening test results in absence of other systemic illness.

Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. Chronic kidney disease is defined as either kidney damage or GFR < 60 ml/min for =/> 3 months.

If chronic kidney disease is present, determine the stage of CKD based on eGFR, urinalysis and ACR. The following staging system, designed by the National Kidney Foundation (US) with international input, is recommended to facilitate assessment and management of kidney disease.

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Staging of Patients with Kidney Disease

Rec = Link to Recommendations for Management

Consider both stage and results of urinalysis and ACR testing

Stage	Features	eGFR	Complications
1 Rec	Kidney damage, N or ^ GFR	>/= 90	None
2 Rec	Mild v GFR	60-89	some ^ PTH some hypertension
3 Rec	Moderate v GFR	30-59	v Ca absorption v PO4 excretion Hyperparathyroid v Lipoprotein activity Malnutrition Onset LVH Onset anemia Hypertension
4 Rec	Severe v GFR	15-29	TG rise ^ PO4 Malnutrition Met. acidosis Onset ↑ K Hypertension
5 Rec	Kidney Failure	15 or Dialysis	Azotemia Heart failure and volume overload Hypertension

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Stage 1 and 2:

1. Urinalysis normal but ACR equivocal (2-20 M, 2.8-28 F)

· Consider kidney ultrasound

· Annual urinalysis and creatinine

· Nephrology referral if urine protein increasing or eGFR declining >10% annually.

2. Abnormal urinalysis or abnormal ACR (>20 M, >28 F)

· Kidney ultrasound to assess need for urgent referral

· Nephrology referral

· Urology referral for hematuria even if US normal

Stage 3:

1. Urinalysis normal or ACR equivocal (2-20 M, 2.8-28 F)

· Consider kidney ultrasound

· Every 6 mo. urinalysis and creatinine

· Nephrology referral if urine protein increasing or eGFR declining >10% annually.

2. Abnormal urinalysis or abnormal ACR (>20 M, >28 F)

· Kidney ultrasound to assess need for urgent referral

· Nephrology referral

· Urology referral for hematuria even if US normal

Stage 4:

Regardless of other results, refer to a nephrologist.

Stage 5:

Regardless of other results, urgent referral to a nephrologist.

Even if a primary cause seems obvious, the possibility of a serious underlying cause like vasculitis, lupus or other conditions must be considered in patients with:

• abnormal urinalysis (proteinuria, hematuria, cellular casts or combination thereof)

• rapid decline in kidney function (change in GFR > 10%/year)

• repeated impairment of kidney function even in the absence of risk factors

• constitutional symptoms suggesting systemic illness

• sudden or severe onset of symptoms (e.g. edema unrelated to heart disease or liver disease).

Refer to a specialist for further evaluation if etiology cannot be determined.

Note: Occasionally a screening test will identify a serious systemic disease or early stage of an acute illness. In those patients with active urine sediments (RBC casts, cellular casts +/- protein), constitutional symptoms or unexplained severity of kidney dysfunction, prompt consultation with a specialist and/or re-evaluation of tests is indicated.

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Step 5: Identify care objectives (also see Practice Points)

Identify care objectives for all patients with CKD In your practice. Depending on the level of kidney function and complexity of therapy required, these care objectives may be more or less difficult to achieve without help from a specialized team of health care professionals, including a nephrologist. Treatment goals must therefore be tailored to the individual.

Blood pressure:

1. Measure and record at diagnosis and at every visit thereafter.

2. BP target less than130/80

3. In presence of ACR > 30, use of ACEI/ARB recommended in addition to other drugs.

4. Renovascular hypertension treated the same as nondiabetic nonproteinuric chronic renal disease. Use caution with ACEI/ARB’s because of risk of acute renal failure.

Kidney function: Obtain regular measurements of serum creatinine for estimates of GFR (at least q 6 mths) and after any change in medications, medical interventions or clinical status.

Aim for stability of kidney function or measurements < 10% decline in GFR annually.

Proteinuria:

1. ACR (microalbumin) regularly (at least q 6 mths). Reduce abnormal values by 50% or more from baseline

2. Use of ACEI/ARBs recommended for treatment of proteinuria.

3. Diabetics with ACR > 2.0 mg/mmol for men, > 2.8 mg/mmol for women should receive ACEI/ARB to delay progression of CKD.

4. Protein controlled diet and wt. reduction may help in reducing proteinuria.

Cardiovascular disease risk assessment and lipid profiles:

1. Calculate & record cardiovascular risk and manage in accordance with relevant guidelines.

2. Check fasting lipids yearly once target values achieved, more frequently in patients on lipid lowering medication.

3. Lipid targets for stage 1-3 disease are the same as for the general population.

4. Lipid targets for stage 4 disease: LDL < 2.0 and Chol/HDL ratio < 4.0.

5. Gemfibrozil is safe for use in chronic renal disease. Other fibrates are not.

6. Statins and fibrates should not be combines in stage 4 disease because of high risk of rhabdomyolysis.

7. Serial monitoring of CK and ALT are not required for asymptomatic patients if stain dosage is lower than 20 mg. of atorvastatin or equivalent.

8. Serial monitoring of CK and ALT are recommended in stage 4 disease every 3 months if statin dosage exceeds 20 mg. of atorvastatin or equivalent.

Treatment of Anemia in stage 3-5 Disease:

1. Defined as < 135 g/L for men, < 120 g/L for women.

2. Check hematology profile, transferrin saturation and ferritin.

3. If iron stores adequate, consider erythropoiesis-stimulating agents if Hb falls below 100 g/L. Consider consultation.

4. Target Hb 110 g/L (range 100-120).

5. Oral iron should be administered to maintain a level of ferritin > 100 ng/ml and transferrin saturation > 20%.

6. IV iron use only if targets not met on oral therapy.

Mineral Metabolism:

1. Calcium, phosphate and PTH levels should be measured in stage 4 and 5 disease and in those with stage 3 disease with progressive decline in function.

2. Calcium and phosphate levels should be maintained at normal values. PTH will probably be elevated. Target levels are not known.

3. Dietary phosphate restriction for hyperphosphatemia. If this fails, use of phosphate binders (ca carbonate or ca acetate) if calcium levels normal.

4. If hypercalcemia develops, calcium-containing binders and Vit D analogues should be reduced. Remember to correct for albumin.

5. Correct symptomatic hypocalcemia if symptomatic or if associated with increased PTH.

6. Use Vit D analogues in consultation with a nephrologist if PTH > 53 pmol/L. Discontinue of hypercalcemia, hyperphosphatemia or PTH < 10.6

Diabetes:

1. Measure A1C every 3 months. Goal </= 7.0% (0.07)

2. Metformin recommended in stage 1 and 2 patients with unchanged renal function over 3 months.

3. Metformin can be continued in stable stage 3 disease.

4. Lactic acidosis is a risk with metformin in acute renal failure. Use with caution in dehydration, hypoxia, or in presence of IV contrast, NSAIDS, ACE/ARB’s or diuretics. Sulfonylureas, if used, should be short-acting (eg., gliclazide).

Lifestyle Management:

1. Record weight & BMI on each visit for comparison. Maintenance of adequate nutrition and BMI near ideal (18.5-24.9)

2. Salt restriction to <100 mmol/day to prevent hypertension; < 65-100 mmol/day if hypertension present.

3. Protein control of 0.80-1.0 grams/day recommended for all CKD. Further restriction should include monitoring for markers of nutritional deficiency.

4. Alcohol restricted to 2 drinks or less/day.

5. Aerobic exercise 30-60 min/day, 4-7 days/week.

6. Stop smoking

Hepatitis B screening: Identify seronegative patients; offer vaccination. Prevention of Hepatitis B (Seroconversion rate higher if immunized early)

Influenza vaccine: Immunize annually.

Pneumococcal vaccine: Immunize every 10 years.

Limit exposure to nephrotoxins: Reduce risk of acute or chronic deterioration of kidney function. Avoidance of aminoglycosides, NSAIDs, COX-2 inhibitors, intra-venous or intra-arterial radiocontrast studies.

Psychosocial health:

1. Identify depression and grief reaction often associated with chronic disease.

2. Identify and address psychosocial problems that affect the illness.

3. Advanced care planning should be done.

4. Coordinated end of life care should be anticipated.

● Reduction of proteinuria can be facilitated by the use of ACEI/ARBs. This has been shown to reduce the rate of progression of chronic renal insufficiency in hypertensive patients with diabetes or chronic glomerulonephritis.

● In patients with severe kidney disease (GFR < 15ml/min), weight loss may indicate a catabolic state and possibly the need for dialysis.

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Practice Points:

When setting goals with your patient, consider the following:

1. Exercise, diet and/or hydration status may affect kidney function estimates or the degree of albuminuria/proteinuria. If baseline tests are abnormal or subsequent tests are significantly different from baseline, confirmation by repeat testing is warranted

2. Rigorous control of blood pressure has been shown to reduce the risk of complications and mortality rates. In particular, the inhibition of the renin angiotensin system with ACE inhibitors or ARBs has been shown to be very effective. Target BP is < 130/80 mmHg. Most patients will need 3 or more medications. Diuretics and salt restriction are very useful, and if needed, consider furosemide BID dosing when eGFR < 30 ml/min/1.73m².

3. Every adult with kidney disease is at high to very high risk of cardiovascular disease (CV risk >> ESRD risk). Use risk factor modification.

4. Nephrotoxic medication (e.g. NSAIDs, COX-2 inhibitors, aminoglycosides) should be avoided or used with caution in patients with even mild kidney impairment (eGFR 60-90 ml/min), and kidney function should be monitored if they are used.

5. Intra-venous or intra-arterial radiocontrast use poses a high risk of acute kidney failure in CKD patients with Stage 4 or 5 CKD and a moderate risk in patients with Stage 3 disease. If imaging is required, alternate imaging techniques, including MRI angiography, should be considered for these patients. If no alternative exists and the procedure is medically necessary, the patient should give written informed consent and protection with IV hydration and N-acetyl cysteine should be used according to a published protocol.

6. Review medication list, identify those excreted by the kidneys and dose adjust as appropriate. Three examples include metformin, digoxin and lithium.

7. Referral to a nephrologist is recommended for:

a. Acute kidney failure

b. eGFR < 30 ml/min/1.73m². (CKD stage 4 and 5)

c. Progressive or rapid decline of eGFR

d. Urine protein/creatinine ratio (PCR) > 100 mg/mmol (~900 mg/24 hours) or urine albumin to creatinine ratio (ACR) > 60 mg/mmol (~500 mg/24 hr)

e. Inability to achieve treatment targets

8. Preparation for kidney replacement treatment requires a minimum of 12 months. Referral for consideration of kidney replacement should take this into account.

9. Many patients with CKD also have diabetes and/or heart disease. Explaining the linkage between these conditions and how treating one condition benefits others may lessen the psychological impact of several separate diagnoses.

10. Target urine protein/creatinine ratio (mg/mmol) is < 60 (< ~ 500 mg/day) or target urine albumin/creatinine ratio (mg/mmol) is < 40. ACEI and/or ARB are first line therapies in patients with albuminuria or proteinuria.

11. Consider reversible factors, such as medications, intercurrent illness, volume depletion, or obstruction. An abdominal ultrasound may be indicated when eGFR <60 ml/min/1.73m².

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References:

1. Guidelines and Protocols Advisory Committee. Identification, evaluation and management of patients with chronic kidney disease. BC Health Services 2004. Available from: www.healthservices.gov.bc.ca/msp/protoguides/gps/ckd.pdf

2. Position Paper of the Canadian Society of Nephrology. Care and referral of adult patients with reduced kidney function. 2006. Available from: www.csnscn.ca

3. Craven NH. Management of chronic kidney disease in the primary care setting. BC Medical Journal 2005; 47(6): 296-299.

4. Levin A, et al. Guidelines for the management of chronic kidney disease. CMAJ 2008; 179(11): 1154-1162.

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