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Chronic Kidney Disease Learning Zone

Diagnosing CKD

Read time: 80 mins
Last updated:26th Apr 2022
Published:22nd Oct 2021

Explore the diagnosis of chronic kidney disease (CKD) and find:

  • Expert interviews with Professor Hiddo Heerspink, Professor Vlado Perkovic and Dr George Bakris on the need for earlier diagnosis of chronic kidney disease and management of comorbidities
  • Why early diagnosis of CKD is important to optimal care
  • The importance of CKD screening in patients with comorbid conditions such as diabetes and hypertension
  • Strategies for CKD diagnosis and screening that may help improve your patient’s quality of life

The need for early chronic kidney disease diagnosis

Professor Vlado Perkovic from Australia stresses that early diagnosis of chronic kidney disease (CKD) is critical to slowing disease progression

Chronic kidney disease (CKD) is a significantly burdensome condition that substantially impacts people around the world through increased morbidity as well as cardiovascular and all-cause mortality1.

As the burden of CKD is immense, highly prevalent, and disproportionately impactful on people of lower socioeconomic status, strategies for identifying and treating CKD at the earliest stages are essential1.

Is chronic kidney disease underdiagnosed?

As CKD is a progressive disease that leads to a gradual loss of kidney function, people living with CKD can be unaware of the disease until it advances to later stages (Figure 1)2. Indeed, up to 82% of people with CKD stage 3 (moderately decreased kidney function) have not received a diagnosis of CKD (Figure 1)3.

T2 CKD_Fig1.png

Figure 1. Proportion of patients with diagnosed and undiagnosed chronic kidney disease across disease stages in adult patients with type 2 diabetes (Adapted4). aPercentage of study population at each indicated CKD stage. CKD, chronic kidney disease.

Approximately half of people with CKD remain undiagnosed by stage 4–5 when CKD symptoms begin to develop3

Late diagnosis drives up annual healthcare costs from nearly double at stage 2–3, to around four-fold with progression to stage 4–55. This is especially detrimental to people with a lower socioeconomic status who have limited access to appropriate treatment and consequently face poorer outcomes1. The adverse consequences of later treatment, such as the loss of employment due to the need for dialysis, also discourages patients from seeking treatment. This inevitably leads to preventable morbidity and death6.

Why is chronic kidney disease underdiagnosed?

Despite clear rationales and guidelines for early detection, risk stratification, treatment of CKD, and timely management with evidence-based strategies have not been universally adopted1.

Just over half of governments around the world recognise kidney failure (58%) and CKD (51%) as health priorities, and even fewer (43%) have national strategies for improving CKD care7

Even in countries where guidelines and interventions have been established, various obstructions can reduce the effective implementation of these strategies, including8–10:

  • Inadequate delivery of kidney care
  • Poor understanding of CKD and its risk factors among primary care physicians
  • Low patient awareness
  • Absence of locally appropriate or adapted guidelines

Moreover, unlike other chronic diseases, there is no consensus on early identification and intervention for CKD despite the potential beneficial impact on treatment outcomes1. This could be due to low policymaker awareness with few countries having policies or public programmes aimed at CKD prevention and control11.

How does early diagnosis impact chronic kidney disease treatment?

The early identification and management of patients can reverse, delay, or prevent progression of CKD and is a central aspect of international initiatives in kidney disease. The goals of early diagnosis and management include12:

  1. Provision of specific therapy based on diagnosis
  2. Slowing/arresting CKD progression
  3. Evaluation and management of comorbid conditions
  4. Prevention and management of cardiovascular disease
  5. Identification, prevention, and management of CKD-specific complications (such as malnutrition, anaemia, bone disease, acidosis)
  6. Planning and preparation for renal replacement therapy (such as the choice of modality, access-placement and care, pre-emptive transplantation)
  7. Psychosocial support and provision of conservative care and palliative care options where required
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Chronic kidney disease comorbidities: diabetes and hypertension

 

What are the recommendations for managing comorbidities in patients with chronic kidney disease?

Recommendations for managing comorbid conditions in patients at risk of chronic kidney disease

4

Professor Vlado Perkovic and Dr George Bakris discuss the recommendations for managing comorbid conditions in patients with or at risk of chronic kidney disease (CKD).

As hypertension, diabetes, or cardiovascular disease are well defined risk factors for CKD, it is recommended that people with these conditions be screened for CKD. Moreover, implementation of early CKD detection should first be implemented in people with established CKD risk factors, given the higher level of prevalence associated with these individuals1.

Why is it important to diagnose diabetes and hypertension early?

At the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) conference, the consensus was that CKD screening should be based on comorbidities and individualised risk assessment rather than specific age1. However, as previously noted by healthcare professionals, CKD can be a difficult condition to treat due to the wide and complex range of comorbidities (Figure 2) that patients can have associated with their disease16.

T2 CKD_Fig2.png

Figure 2. Venn diagram of the complex range of key comorbidities associated with chronic kidney disease patients from NPS MedicineWise’s MedicineInsight dataset (Adapted17). CVD, cardiovascular disease.

Of the range of possible comorbidities, intensively lowering blood pressure is known to reduce cardiovascular events and all-cause mortality in non-diabetic CKD18. Recent evidence is also revealing that intensive glucose control may help reduce the risk of kidney events; however, this benefit should be weighed against the risk of using agents that may cause hypoglycaemia1.

How do you monitor glycaemic control in patients with diabetes and CKD?

According to the 2020 KDIGO clinical practice guideline for diabetes management in CKD, haemoglobin A1c (HbA1c) monitoring of glycaemic control in patients with diabetic kidney disease (DKD) is recommended19.

For patients with diabetes, it is also recommended to monitor long-term glycaemic control by HbA1c twice per year, although HbA1c can be measured as often as four times per year if the glycaemic target is not met or following a change in anti-hyperglycaemic therapy19.

The accuracy and precision of HbA1c measurement declines in patients with advanced CKD (G4–G5), particularly among patients on dialysis where HbA1c measurements have low reliability19

In diabetic patients with CKD, who are not treated with dialysis, an individualised HbA1c target range of <6.5%– <8.0% is recommended depending on a variety of patient factors (Figure 3)19.

T2 CKD_Fig5.png

Figure 3. Factors guiding decisions on individual HbA1c targets (Adapted20). CKD, chronic kidney disease; G1, estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m2; G5, eGFR <15 ml/min/1.73 m2; HbA1c, glycated haemoglobin.

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Chronic kidney disease diagnostic strategies

 

Professor Hiddo Heerspink from the Netherlands stresses that early diagnosis of chronic kidney disease is critical to slowing disease progression, delaying dialysis, and prevention of cardiovascular events.

Chronic kidney disease (CKD) diagnosis is a controversial topic, as it has been posited that it may be over-diagnosed among older adults, and could require an age-adapted definition22. However, underdiagnosis also has a range of consequences; CKD impacts physical and cognitive function, medication safety, and cardiovascular prognosis1.

Despite the potential negative consequences associated with overdiagnosis, appropriate early diagnosis and risk stratification are needed for reducing CKD-related morbidity and mortality1.

How do you detect and diagnose chronic kidney disease?

CKD can be detected during health assessments, as part of an evaluation of individuals at risk of CKD, due to incidental findings in abnormal laboratory values, while investigating symptoms and/or signs relating to the kidneys, or through a screen programme23.

Regardless of the method of detection, two essential biochemical parameters used in the KDIGO matrix define CKD (Figure 4)2:

  • Glomerular filtration rate (GFR)
  • Albuminuria

In addition to these parameters, the addition of an aetiological diagnosis is recommended by the 2012 KDIGO clinical practice guidelines as a part of the cause/GFR/albuminuria (CGA) classification system2. This allows for the underlying conditions to be treated first to halt the progression of CKD2.

A number of tests can be used to confirm a CKD diagnosis as well as identify its cause; however a diagnosis of CKD will require persistence or progression of the abnormality for ≥3 months2.

T2 CKD_Fig3.png

Figure 4. Heat map diagram highlighting chronic kidney disease risk in increasing colour intensity (Adapted2). CKD, chronic kidney disease; GFR, glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes.

Alone, a GFR value or albuminuria result will not be sufficient for a diagnosis of CKD and may even lead to a high rate of false-positives24. Progression is defined by changes in the estimated GFR (eGFR)2.

How do you estimate and measure GFR to assess chronic kidney disease?

The assessment of GFR requires measuring the concentration of serum creatinine, under steady-state conditions, and using one of a number of formulae for estimating GFR23. A variety of factors may however influence the results of this assessment including25,26:

  • Changes in muscle (atrophy or hypertrophy)
  • Dietary intake of cooked red meat
  • Alterations in tubular secretion of creatinine caused by exposure to drugs, such as trimethoprim and sulfamethoxazole

An alternative approach that uses serum cystatin C concentrations has been proposed to minimise these influences. However, the cystatin C­based formulae for eGFR are instead influenced by27:

  • Inflammation
  • Obesity
  • Thyroid disease, diabetes
  • Steroid administration

Demographic variables, such as age and sex, may be used to correct for differences in creatinine generation. However, these may obfuscate prognostic inferences that can be made from measuring an eGFR23

More recent eGFR formulae utilise serum creatinine, cystatin C, or combine the assessment of both to increase the accuracy of the assessment28,29.

Considered a gold standard, measured GFR (mGFR) assessments can also be made in certain circumstances; for example, using urinary clearance methodology or following the removal of a kidney. However, these methods can be cumbersome and expensive30–32.

How do you measure proteinuria to assess chronic kidney disease?

In cases of CKD where GFR appears normal, it becomes necessary to test for the abnormal excretion of albumin or total protein33. This is determined through a variety of methods, including34,35:

  • Simple dipstick qualitative methods
  • Point of care urinary albumin concentration tests
  • Assessment of the urine protein to creatinine ratio (UPCR) or urine albumin to creatinine ratio (UACR) through random urine samples
  • Timed 24­hour urine collections to measure absolute protein or albumin excretion
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Chronic kidney disease screening strategies

Professor Hiddo Heerspink from the Netherlands points to guideline recommendations for chronic kidney disease screening, and some of the risk factors to look out for, including diabetes and hypertension.

The early identification and intervention of chronic kidney disease (CKD) was a hot topic at the 2021 KDIGO conference. At the KDIGO conference, the consensus was that a combination strategy of CKD screening, risk stratification, and treatment should be implemented immediately for people at high-risk of CKD in a primary or community care setting1.

Why is screening for chronic kidney disease important?

The early screening and risk-stratification of CKD has numerous benefits for patients with the disease, including40:

  • Early detection of the largely asymptomatic disease
  • Early medical and lifestyle intervention, which may slow progression of disease
  • Early treatment to reduce morbidity and mortality

This includes treatment of common coexisting comorbidities, such as diabetes and hypertension, in addition to the initiation of preventive medication and lifestyle modifications41.

Most guidelines recommend targeting high-risk populations, as it is advantageous to decrease the number of people needed to detect a single case42

The benefits of screening have been highlighted in several targeted screening programmes, such as the Kidney Early Evaluation Program (KEEP) in the United States (N = 72,963), and the See Kidney Disease (SeeKD) program in Canada (N = 5,194). In the KEEP and SeeKD, a high prevalence of undiagnosed or unrecognised CKD was reported at 28.7% and 18.8%, respectively43.

Point-of-care testing by the First Nations Community Based Screening to Improve Kidney Health and Prevent Dialysis (FINISHED) project (N = 1,700) was also shown to be efficacious in Canadian rural indigenous communities. Notably, while 25.5% showed signs of CKD, it was reported that 28.3% of people who were found to have CKD would have been missed if screening had only been offered to individuals with diabetes or hypertension44.

Integrating preventive, risk-based care approaches into routine clinical practice could therefore enhance CKD surveillance and potentially improve management of underlying health conditions as a result40.

What types of CKD screening strategies are there?

The screening of CKD can be carried out in two forms: opportunistic screening, through which a healthcare professional can carry out screening during encounters for other medical reasons; or population screening, through which samples are taken from specific populations23.

Population-based screening can be further sub-divided into general population screening or targeted screening of high-risk population groups23. General population screening is not currently recommended as the benefits and harms are poorly understood45–47.

Opportunistic testing and targeted screening are considered to be useful strategies when risk factors, such as diabetes, hypertension, or a family history of CKD, are used to demarcate the screened population23.

Management of CKD should focus on identifying people who are at high risk of adverse outcomes for more intensive treatment and referral to a specialist48

In older people with CKD stage G3, that have been detected by screening, the prognosis over five years has been shown to be improved48.

In a prospective cohort study of outcomes, a population with CKD stage 3 in primary care that did not meet criteria for referral to a nephrologist (N = 1,741) were assessed and managed. A low rate of ESRD (0.2%) and stable CKD or CKD remission was seen in 53% of older people after 5 years of follow up48.

In these populations, screening should be carried out through measurements of eGFR and albuminuria, UACR, or UPCR23.

Is there consensus for a specific CKD screening strategy?

At the 2021 KDIGO conference, it was concluded that CKD screening, together with risk stratification and treatment, should be implemented for high-risk individuals in a primary care setting1.

After a comprehensive review of topics, a consensus was reached to recommend a broad and proactive strategy for CKD screening, risk stratification, and treatment, with the aim of reducing the global burden of kidney disease (Figure 5)1.

T2 CKD_Fig4.png

Figure 5. Conceptual framework of a CKD screening, risk stratification, and treatment programme (Adapted1). CKD, chronic kidney disease.

Moreover, preferably in primary or community-care settings, it was suggested that CKD screening coupled with risk stratification and treatment should be immediately implemented for high-risk individuals1.

What are the challenges with CKD screening?

General population screening and targeted screening for CKD have a number of challenges that need to be overcome. These strategies create logistic difficulties due to the need for re-evaluation at defined intervals to fulfil the KDIGO duration requirement for diagnosis and staging of CKD23.

Individual one-off tests of eGFR or proteinuria produce high false-positive detection and diagnosis rates and introduce further inaccuracies due to the use of non-age sensitive eGFR thresholds23.

This can lead to a variety of issues, such as23:

  • Excessive follow-up diagnostic procedures
  • Unnecessary referral of erroneously diagnosed individuals
  • Anxiety causes by the possibility of having CKD
  • Potential impacts on insurability in some countries
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References

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