Chronic Kidney Disease - Identification, Evaluation and Management of Adult Patients

Effective Date: October 30^th, 2019

Recommendations and Topics

• Scope
• Key Recommendations
• Background
• Definition
• Etiology
• Risk Factors and Screening
• Diagnosis
• Referral Recommendations
• Management
• Lifestyle and Self-Management
• Complex Scenarios
• Abbreviations
• Resources
• Appendix A: Potential complications of CKD
• Appendix B: Interpretation of urine ACR values to assess albuminuria and proteinuria
• Appendix C: Recommended drug modifications in presence of CKD and in acute kidney injury (AKI)

 

Scope

This guideline provides recommendations for the investigation, evaluation, and management of adults at risk of or with known chronic kidney disease (CKD). These recommendations and treatment targets may not be appropriate in all cases because many patients with CKD are complex due to older age and comorbidities. Communication between primary care providers and specialists is strongly encouraged.

Key Recommendations

• Identify high-risk patient groups for evaluation of CKD: diabetes, hypertension, cardiovascular disease, family history, high risk ethnicity (Indigenous peoples, Pacific Islanders, African, Asian, and South Asian descent), history of acute kidney injury (AKI)
• Screen high-risk patients using eGFR and uACR. Confirm abnormal test results with a repeat measurement and obtain urinalysis
• Determine likely cause of kidney disease where possible. The cause of CKD has important implications for the risk of end stage renal disease (ESRD) and other complications
• The three dimensions of Cause, eGFR and Albuminuria (CGA) are all important in developing a management plan
• Prompt advice from local internists, local nephrologists or the RACE Line is available to assist in determining the need for and timing of referral

Figure 1. Prognosis and recommendations for frequency of monitoring based on eGFR and uAC*

* Adapted from ckdpathway.ca and Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013;3:1–150

Background

CKD is associated with other common chronic diseases such as diabetes, hypertension, and cardiovascular disease (CVD)¹ and an estimated 1:10 British Columbians has some form of significant kidney disease².

CKD markedly increases the risk of: cardiovascular disease, adverse drug reactions, acute kidney injury and prolonged hospital admissions^{4-10, 13-14}. Patients with CKD have a risk of progression to end stage renal disease (ESRD), often requiring dialysis or kidney transplantation^{6, 9, 11-14}. Most patients with chronic kidney disease die from other comorbidities before they progress to kidney failure. The outcome of many patients who go on to dialysis remains poor with 10 percent annual mortality; the overall 5 year survival rate is worse than that of most cancers³.

Evidence clearly indicates that control of hypertension and proteinuria can prevent or postpone kidney function decline^4–12. This underscores the importance of early detection, evaluation and management of individuals with kidney disease.

Figure 2. CKD prevalence by health service delivery area, 2016/2017.

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Definition

CKD is defined as an abnormality of kidney structure or function that is present for greater than 3 months¹³.

The two key parameters for classification are estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (uACR). eGFR is the best marker for kidney function and is calculated from creatinine. All labs in British Columbia (BC) automatically report eGFR when creatinine is ordered. Note: the recommended equations for eGFR may change over time and are estimates only. Refer to page 3 for more information.

For diagnostic purposes, other evidence of kidney damage includes: urine abnormalities such as hematuria; structural problems on imaging studies e.g. polycystic kidneys on ultrasound; histological findings on kidney biopsy.

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Etiology

The two most common causes of CKD are hypertension and diabetes and they often co-exist¹³. Even if the cause seems obvious (e.g., diabetes), the possibility of a serious underlying primary renal disorder (e.g. glomerulonephritis) must be considered in patients with:

• Abnormal urinalysis, (e.g. proteinuria, hematuria, cellular casts). Note: hyaline casts are normal.
• Rapid sustained decline in kidney function (change in eGFR > 10-15%/year) despite remedy of reversible

precipitants (e.g. volume contraction, febrile illness, medications).

• Constitutional symptoms suggesting systemic illness.
• Sudden or severe onset of symptoms (e.g. edema unrelated to heart or liver disease).

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Risk Factors and Screening

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Diagnosis

CKD cannot be diagnosed with one isolated abnormal measurement of eGFR or urine ACR.

Estimated GFR (eGFR) Values and Interpretation

• Values of > 60 mL/min per 1.73m² without other markers of kidney disease (albuminuria, hematuria, structural abnormalities) do not indicate CKD
• Values of < 60 mL/min per 1.73m² which are persistent (present for ≥ 3 months) are diagnostic of CKD
• A single isolated measurement < 60 mL/min does not satisfy diagnostic criteria for CKD, but could reflect reduced kidney function and requires confirmatory testing
• In patients with a new unexpected finding of reduced eGFR, the test should be repeated to establish stability or rapid deterioration

Caveats of eGFR

• eGFR is an estimated value that assumes a steady state of creatinine generation
• eGFR may be unreliable in extremes of muscle mass or with certain diets (e.g., very high or very low protein). Some medications can interfere with the excretion of creatinine (e.g., trimethoprim, fenofibrate^{14, 15}
• In hospitalized patients or patients with AKI the fluctuations in creatinine make eGFR unreliable. In these circumstances, creatinine values should be used to guide management
• As a general rule, the eGFR can be used as a guide to outpatient drug dosing, even if the references use creatinine clearance (eCrCl). More caution is required for drugs with significant potential toxicity or a narrow therapeutic window (e.g. chemotherapy)

Urinalysis and ACR Values and Interpretation

• Significant abnormalities include persistent white blood cells or red blood cells in the absence of infection or instrumentation, and the presence of cellular casts
• Urine ACR (uACR) is the preferred method to screen for protein in the urine
  • uACR quantifies albuminuria in a range which is not detected by dipstick urinalysis
  • The term microalbumin has historically been used. Recent guidelines and consensus from laboratories have recommended abandoning this term and to quote the uACR value instead¹³
  • uACR elevation (>3.0 mg/mmol) on serial testing is abnormal
  • In patients without diabetes, no specific treatment is recommended for isolated uACR values between 3 and 30 mg/mmol. These individuals remain at risk of CKD progression and cardiovascular disease, therefore surveillance is warranted
  • uACR may be unreliable in some patients due to acute illness, vigorous exercise, poorly controlled hypertension or poorly controlled blood glucose. Repeat testing should be done when in doubt
• Urine test abnormalities, even with persistent eGFR values ≥ 60 mL/min per 1.73m² suggest kidney disease
• 24-hour urine collections are not necessary in most cases
• For equivalence of dipstick protein measurements, uACR and protein/creatinine ratios (PCR), see Appendix

Renal Imaging

• Renal ultrasound should be undertaken to assess structural abnormalities and aid in diagnosis. Renal ultrasound should be performed in the following cases:
  • Obstructive urinary symptoms
  • Unexplained microscopic or macroscopic hematuria
  • Unclear etiology of CKD, especially in young patients
  • Patients with suspicion of benign prostatic hypertrophy (BPH)
  • Family history of structural renal disease (e.g.  cystic kidney disease)

Staging of CKD

Risk staging of kidney disease is important for care planning and patient management. Risk is determined based on Cause, eGFR, and uACR, or CGA. Refer to Figure 1. Further details on risk determination are available on the Kidney Disease Improving Global Outcomes (KDIGO) CKD management guideline at kdigo.org/home/guidelines¹³.

Risk Calculators

The Kidney Failure Risk Equation (KFRE) is an equation designed to estimate probability of requiring dialysis within 2 or 5 years. The equation is derived from 4 variables and can be calculated using QxMD: qxmd.com.  Risks of > 10 -20% indicate high risk (analogous to Framingham risk scores). The KFRE is a useful tool for prognostication, however its role has yet to be established in routine clinical practice.

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Referral Recommendations

Indications for referral to specialist/nephrologist^22 †

Very high risk kidney disease (urgent communication needed)

• Presence of active urine sediments (red blood cell casts or cellular casts ± protein), especially when associated with reduced eGFR
• AKI in absence of readily reversible cause (e.g. volume depletion, NSAIDs)
• Abrupt sustained fall in eGFR in a patient with known CKD
• eGFR < 15
• Nephrotic syndrome

High risk kidney disease (patient to be seen within a timely fashion)

• GFR < 30^†
• Unexplained persistent uACR >30 mg/mmol (regardless of eGFR) e.g. in absence of diabetes or HTN
• Progressive CKD, with eGFR decline > 5 ml/min/year^†
• Diabetes and evidence of CKD with eGFR <45, urine ACR >30

Low to moderate risk kidney disease (patients that could be seen within a longer time interval, e.g. within 6 mos)

• Persistent abnormalities of serum potassium
• Hereditary kidney disease
• CKD, eGFR 30-45
• CKD and difficult to treat hypertension

Recommended history and tests to include in referral package

• Comorbidities (especially cardiovascular)
• Medications
• Complete blood count (CBC)
• Electrolytes (Na, K, Cl, HCO3), calcium
• Creatinine/eGFR (include current value and any historical values available)
• Urinalysis (urine microscopy)
• Urine ACR
• If older than age 40: serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP)
• Renal ultrasound – not required prior to referral, but should be arranged with result sent to specialist when completed

Please use for referral

• Use Pathways to see the list of specialists in your region and their wait times
• Use the BC Renal website to locate nephrologist in your region: bcrenalagency.ca/kidney-services
• Real-time communication with local specialists (or RACE line if uncertain) can provide rapid advice for urgent cases and facilitate the most appropriate mechanism of referral
• Patients benefit from inclusion in multidisciplinary clinics for prevention, education and management, including by telehealth^16–18

A urology consult is more appropriate than nephrology in the following scenarios

• Renal mass, enlarged prostate, obstruction, and large symptomatic or obstructing kidney stone

^†Time to first consultation will vary based on individual circumstances. Discussion with your local nephrologist as to timing of referral for specific individuals is encouraged if in doubt.

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Management

Refer to Figure 1 (page 1) for recommended follow-up intervals.

Customization of management plan

• Many patients with CKD have multiple comorbidities. In some situations, universal fixed targets may not be applicable and may even be harmful. Clinical judgment and individualized targets are recommended
• Communication with specialists is encouraged if appropriateness of any of the targets is in question

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Lifestyle and Self-Management

Support patient self management with the means available in your community. Patients with CKD benefit from multidisciplinary renal teams who can support patients to make beneficial changes in diet, smoking and physical activity, and to understand medications, and the uncertainty and emotional distress that can be seen in those with chronic conditions. Denial, often associated with grief, is common in patients with chronic disease affecting a vital organ.

Encourage patients with CKD to consider advance care planning and their goals for future care, including for the end of life.

• Provincial advance care planning resources are available at http://www.bcrenal.ca/resource-gallery/Documents/Recommendations%20to%20Support%20Renal%20Patients%20at%20End%20of%20Life.pdf
• BC Guidelines on palliative care are available at https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/palliative-care
• BC Renal Agency information about end of life care is available at bcrenalagency.ca/healthcare-professionals/end-life-resources

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Complex Scenarios

The following common complex scenarios benefit from discussion with a specialist:

• Whether to change the approach to a patient when eGFR goes down to 30 or lower
  • Example: A 60 year old woman with type 2 diabetes mellitus has a change in eGFR from 32 to 29. Should her metformin be stopped?
• Deciding whether to stop diuretic therapy when the creatinine goes up or eGFR goes down
  • Example: A 70 year old man with congestive heart failure requires escalation of diuretic therapy and experiences a deterioration in creatinine. Should his diuretics be discontinued?
• Difficult-to-treat hypertension
• Anticoagulation in patients with CKD

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Abbreviations

• AKI: acute kidney injury
• CKD: chronic kidney disease
• CVD: cardiovascular disease
• eGFR: estimated glomerular filtration rate
• ESRD: end stage renal disease
• uACR: urine albumin to creatinine ratio

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Resources

Diagnostic code: 585 (chronic renal failure)

Associated Documents

• Chronic Kidney Disease Flow Sheet
• List of Contributors 

Appendices

• Appendix A: Potential complications of CKD
• Appendix B: Interpretation of urine ACR values to assess albuminuria and proteinuria
• Appendix C: Recommended drug modifications in presence of acute kidney injury (AKI)

 

 

 

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Appendix A: Potential complications of CKD

Potential Complications of CKD^* (listed alphabetically)

* Listed complications are not specific to CKD but tend to occur with increasing frequency and are more directly attributable to more severe reduction in kidney function. If complications are noted at an early stage of CKD, investigation of alternative causes is recommended (e.g., profound anemia at eGFR of 55 mLl/min is likely not attributable to low kidney function alone). Kidney damage is defined as pathological abnormalities (e.g., kidney biopsy results) or markers of damage including abnormalities in blood or urine tests (e.g., protein/albumin in the urine, red blood cells, white blood cells or casts) or imaging studies.¹³

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Appendix B: Interpretation of urine ACR values to assess albuminuria and proteinuria

Categories	uACR (mg/mmol)	Protein reagent strip	PCR (mg/mmol)
Normal to mildly increased	< 3.0	Negative to trace	< 15.0
Moderately increased	3.0 – 30.0	Trace to +	15.0 – 50.0
Severely increased	> 30.0	+ or greater	> 50.0

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Appendix C: Recommended drug modifications in presence of CKD and in acute kidney injury (AKI)^§

Medication	Pathophysiology	Recommendation in CKD	Hold in AKI?
NSAIDS	Decreases renal perfusion, Interstitial nephritis	Use with caution in CKD.	Yes
ACEI, ARB, or any medication containing those compounds	Protective in proteinuric CKD, diabetes, and heart failure but can cause decreased renal perfusion and hyperkalemia	ACEI or ARB should be held in hypovolemia, and if receiving IV contrast.	Yes
Potassium sparing diuretics (spironolactone, eplerenone, and amiloride)	Volume depletion and hyperkalemia	In CKD (other than in AKI), dose and frequent monitoring is essential if eGFR < 50 mL/min.	Yes
Metformin	Increased risk of metformin associated lactic acidosis (MALA)	Avoid if GFR <30	Yes
SGLT-2 Inhibitors	Protective in diabetic nephropathy and cardiovascular disease but can cause decreased renal perfusion in the setting of volume depletion	Hold temporarily in the setting of volume depletion, or prior to administering contrast dye.	Yes
Diuretics: furosemide and thiazides	Volume depletion and electrolyte abnormalities	N/A	Yes, unless volume overloaded
Opioids (e.g. hydromorphone, fentanyl, methadone (for pain), oxycodone)	Metabolites can accumulate	Reduce dose in CKD For opioids that are considered safer in CKD, and opioids to avoid in CKD, consult: Preferred Medications Pain Medicines	Consider dose reduction
Pregabalin and gabapentin	Accumulation	Reduce dose and monitor for adverse effects In severe renal failure, dose should not exceed 300 mg gabapentin per day.	Consider dose reduction
Digoxin	Hyperkalemia Accumulation with side effects (bradycardia, confusion)	Reduce dose in CKD and monitor potassium and drug levels Consider alternative therapy in the setting of renal failure.	Adjust dose
Acyclovir	Risk of crystal nephropathy Drug accumulation and side effects (risk of seizures/confusion)	Encourage hydration. Dose adjust for GFR	No. Ensure hydration.
Statins	Risk of rhabdomyolysis	Consider dose reduction in CKD. Hold if rhabdomyolysis or unexplained / persistent muscle pain.	No
Phenytoin	Risk of accumulation and toxicity	Monitor levels and also adjust level for serum albumin	No
Lithium	Accumulation and increased risk of side effects Risk of nephrogenic diabetes insipidus Risk of chronic interstitial nephritis	Monitor lithium and electrolyte levels Encourage hydration Refer to a nephrologist if eGFR declines.	No
Hypoglycemics (sulfonylureas, insulin, meglitinides, thiazolidinediones)	Accumulation can increase risk of hypoglycaemia	Avoid long acting preparations in moderate-severe CKD. May require dose adjustments.	No
Trimethoprim and co-trimoxazole	Risk of hyperkalemia Reduces tubular secretion of creatinine so leads to a rise in serum creatinine without renal injury	Reduce dose when eGFR <30 mL/min, monitor GFR and potassium	No
Colchicine	Risk of accumulation and serious toxicity (GI, CNS)	Use lower dose and consider other agents (e.g. Steroids)	No
Proton pump inhibitors	Risk of interstitial nephritis	Clarify indication and consider other agent (e.g. H2 blocker)	No

For more information on dosing of DOACs in kidney disease please visit the 2018 European Heart Rhythm Association Guidelines (Figure 4). Available from academic.oup.com/eurheartj/article/39/16/1330/4942493

For more information on common prescribing questions for patients with CKD, consult:
http://www.bcrenal.ca/resource-gallery/Documents/Recommendations%20to%20Support%20Renal%20Patients%20at%20End%20of%20Life.pdf

Further information about drug dosage adjustments in chronic kidney disease is available from: rxfiles.ca/rxfiles/uploads/documents/ltc/HCPs/CKD/SDIS.Renal_newsletter.pdf

^§Adapted from: Acute Kidney Injury – potentially problematic drugs and actions to take in primary care. “Think Kidneys” initiative by the UK Renal Registry in partnership with NHS England. Available from: thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/07/Primary-Care-Advice-for-medication-review-in-AKI-.pdf

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This guideline is based on scientific evidence current as of the Effective Date.

This guideline was developed by the Guidelines and Protocols Advisory Committee, approved by the British Columbia Medical Association, and adopted by the Medical Services Commission.

For more information about how BC Guidelines are developed, refer to the GPAC Handbook available at BCGuidelines.ca: GPAC Handbook.

The principles of the Guidelines and Protocols Advisory Committee are to: encourage appropriate responses to common medical situations recommend actions that are sufficient and efficient, neither excessive nor deficient permit exceptions when justified by clinical circumstances. Contact Information Guidelines and Protocols Advisory Committee PO Box 9642 STN PROV GOVT Victoria BC V8W 9P1 E-mail:  hlth.guidelines@gov.bc.ca Web site: BCGuidelines.ca

 

Disclaimer The Clinical Practice Guidelines (the "Guidelines") have been developed by the Guidelines and Protocols Advisory Committee on behalf of the Medical Services Commission. The Guidelines are intended to give an understanding of a clinical problem and outline one or more preferred approaches to the investigation and management of the problem. The Guidelines are not intended as a substitute for the advice or professional judgment of a health care professional, nor are they intended to be the only approach to the management of clinical problems.  We cannot respond to patients or patient advocates requesting advice on issues related to medical conditions. If you need medical advice, please contact a health care professional.