Staging of Chronic Kidney Disease (CKD) and principles of CKD management

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ACHAIKI IATRIKI | 2023; 42(1):28–32

Review

Lamprini Balta1,2

1Department of Nephrology and Kidney Transplantation, University Hospital of Patras, Patras, Greece.
2General Hospital of Preveza

Received: 08 Apr 2022; Accepted: 04 Oct 2022

Corresponding author: Lamprini Balta, Seleukeias 2, Preveza, 48 100, Tel.: +30 2682361 221, e-mail: lianabalta@gmail.com

Key words: Chronic kidney disease, proteinuria, estimated glomerular filtration rate

 

Abstract

Chronic Kidney Disease (CKD) is a multistage condition accompanied by a wide variety of health implications impairing patients’ quality of life and adding to the financial burden of health-care systems. Diabetes mellitus (DM) and hypertension are the main causes of CKD, thus special care is required to ensure that they are properly managed. Advances in patient classification enable clinicians to early recognize those at risk and aid the process of decision-making. CKD is classified into 5 stages according to the estimated glomerular filtration rate (eGFR) and into 3 stages according to albuminuria. Notably, CKD progression is neither given nor linear, since only a minority of patients develops stage 5 CKD. Although, patients should be carefully evaluated during every stage, evidence suggest that stage 3b acts as a crucial threshold where several issues must be promptly addressed in order to mitigate the risk for kidney function deterioration and cardiovascular events. Overall, the prerequisites for achieving optimal outcomes for CKD patients include the willingness of patients to adopt the appropriate lifestyle changes and the commitment of clinicians to diligently and collaboratively deal with the challenges rising in every step of the disease.

INTRODUCTION

Chronic Kidney Disease (CKD) is most common among people over 70 years old. People with CKD are 16-40 times more likely to die from other causes before they reach end-stage CKD (ESCKD). Patients with CKD have significantly higher rates of morbidity, mortality, hospitalization, and healthcare utilization [1]. The prevalence of CKD in the general adult population worldwide is 11-13% [2]. The prevalence of CKD stages 2–5 continues to rise since 1988. Diabetes mellitus (DM) and hypertension account for approximately 40% and 25% of CKD cases, respectively, while they are responsible for the majority of ESCKD cases. Meanwhile, these diseases are expected to increase in the future thus augmenting the burden for healthcare [3]. Early diagnosis and monitoring can prevent kidney disease progression. Patients with CKD can be classified depending on their level of kidney function, or eGFR, and the amount of protein present in urine. This information forms the basis of CKD staging and helps to risk stratify patients. The higher the stage (G1→G5) and the greater the amount of protein present in urine (A1→A3), the more “severe” the CKD. Optimal management of patients with CKD requires appropriate interpretation and use of the markers and stages of CKD, early disease recognition, and close collaboration between primary care physicians and nephrologists.

CKD definition

CKD is defined as abnormalities in kidney function (estimated glomerular filtration rate (eGFR)< 60 ml/min/1,73m2) or structure, present for more than three months, with implications for health. Markers of kidney disease may include the following:

albuminuria: albumin to creatinine ratio (ACR) > 30mg/g

hematuria: microscopic hematuria or red-blood cell casts

renal histological abnormalities

electrolyte disorders (due to tubular disorders)

structural abnormalities (polycystic kidney disease, reflux nephropathy, small kidney size, medullary sponge kidney)

history of kidney transplantation

CKD staging

CKD is classified based on eGFR and the level of proteinuria. CKD staging helps planning patients’ follow-up and management. The traditional 5 stages of CKD (Table 1) rely solely on eGFR and were adopted up to 2002 [4]. However, according to the latest KDIGO (The Kidney Disease: Improving Global Outcomes) 2012 Clinical Practice Guidelines for the evaluation and management of CKD, patients are classified as G1- G5 (Table 2), based on eGFR, and A1-A3 (Table 3) based on the ACR [5]. This change was primarily introduced to indicate the increase in cardiovascular risk and risk of further progression associated with stage 3b as demonstrated by several clinical studies [6,7]. It is important to note that patients with eGFR of >60 ml/min/1.73m2 should not be classified as having CKD unless they have other markers of kidney disease [8]. eGFR is primarily. determined by serum creatinine (SCr), and the preferred method for estimating GFR is the CKD-Epidemiology Collaboration (CKD-EPI) Equation [9] based on SCr, age, gender, and ethnicity according to the following formula:

eGFR = 141 * min (SCr/κ,1)α* max(SCr/κ, 1)-1.209* 0.993Age* 1.018 [if female] * 1.159 [if black]

Proteinuria

ACR (or PCR) measurements are usually performed on a random urine sample preferably the first morning sample. ACR is more sensitive to detect low levels of proteinuria and is the recommended method for screening and measuring proteinuria in patients with DM. For the quantification and monitoring of higher levels of proteinuria (eg, ACR > 700 mg/g), PCR or albumin measurement in a 24-hour urine collection is preferred. A PCR of 1000 mg/g, or ACR of 700 mg/g, is approximately equal to 1 g of protein per 24 hours.

Patients with proteinuria are at increased risk of developing cardiovascular disease (CVD), in addition to progressive kidney disease [10]. Therefore, strategies should be employed to re duce the cardiovascular risk for these patients such as: smoking cessation, physical exercise, reduce body weight to optimal goals and antilipidemic therapy [11]. Regarding antilipidemic therapy, the following instructions should be followed:

In adults over 50 years and eGFR ≥ 60 ml / min / 1.73m2, initiate statin treatment

In adults over 50 years and eGFR < 60 ml / min / 1.73m2, initiate statin or statin/ezetimibe combination

In adults under 50 years, with a known history of CVD, Myocardial Infarction, DM or Systematic Lupus Erythematosous (SLE), initiate statin treatment

Randomized trials on proteinuria-lowering treatment emphasize the importance of intervention in slowing CKD progression and reducing the development of cardiovascular events.

Antihypertensive agents that interfere with the renin angiotensin system (RAS), including angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), have been consistently shown to reduce proteinuria and the rate of renal function deterioration in patients with diabetic and non-diabetic kidney disease, independently of blood pressure (BP).

It should be noted that in the background of DM, albuminuria is a crucial feature for the progression of CKD. As a general guideline, in diabetic patients, serum ACR and SCr should be measured at least annually followed by referral to a nephrologist when necessary. Moreover, the presence of albuminuria (ACR> 30 mg/g) is a strong indication for the initiation of RAS block therapy, aiming at a BP target of less than 130/80mmHg [12].

Blockade of the RAS is also recommended for adults with a urine ACR of at least 300 mg/ per 24 hours. Dual therapy with an ACE-I and an ARB is generally avoided, given the associated risks of hyperkalemia and acute kidney injury.

Recently, sodium-glucose cotransporter 2 inhibitors (SGLT2i) were introduced as a therapeutic choice for DM. Mechanistically, these agents function by blocking glucose entry into the renal proximal tubule cells, facilitated by the SGLT2 transporter, thus leading to enhanced urinary glucose excretion [13]. A number of studies in patients with type 2 diabetes (T2D) have demonstrated that SGLT2i display renoprotective effects in manners independent of its glucose-lowering effects [14,15]. It appears that SGLT2i cause reduction of renal hyperfiltration thus mitigating the subsequent albuminuria [16]. Moreover, their natriuretic effect causes a decrease in BP. Taken together, these data suggest that SGLT2i may have a place in standard therapy of CKD.

Management of CKD stages G1 and G2

Initial assessment for most of these patients should be undertaken in the context of primary healthcare. The major aim of this assessment is to determine which patients are at risk of developing progressive renal disease. For this reason, all patients should be subjected to ACR, SCr and BP measurements, while they should also undergo urine analysis to check for blood and/or protein. The necessity for BP measurement is well justified given the bidirectional connection between CKD and hypertension, since CKD can be a complication of hypertension while CKD (of any etiology) can be associated with hypertension. Special care should be given at patients displaying a high risk of developing end-stage renal disease (stage G5) as these patients should be referred to a nephrologist [17]. Indicators for the devel opment of kidney disease include proteinuria (in patients without diabetes if ACR> 300mg/g), hematuria of glomerular origin, rapidly deteriorating renal function, family history of renal failure, difficult-to-control hypertension.

Management of CKD stage G3

Patients falling in this stage should also be assessed by primary health-care practitioners. The goal here, also, is to determine which patients are at increased risk of developing kidney disease and should be referred to a nephrologist. Markers of renal disease progression are the same as described at stages G1 and G2.

The patient should be subjected to thorough clinical assessment and ultrasound imaging of kidney, bladder and prostate (if men), while an overview of prescribed medication should be performed (i.e., to exclude the use of nephrotoxic drugs). Additionally, a careful recording of personal history could reveal the presence of severe comorbidities (DM, hypertension, multiple myeloma, connective tissue disease) and family history of CKD.

Long-term monitoring of renal function, proteinuria and blood pressure should be performed, with the aim of identifying a minority of patients with stage CKD G3 who will progress to end- stage renal disease and the detection of CKD complications. Renal function should be monitored at least annually. For patients with significant proteinuria (i.e., A3) renal function should be checked at least twice yearly. A brief guide to abide by is the following:

Anemia: Non-renal causes must be ruled out first. Significant anemia due to CKD is rare before the G3b stage. For patients with hemoglobin levels below 10.0 g/dL special interventions should be considered (iron administration, initiation of erythropoietin) [8].

Cardiovascular risk: smoking cessation, exercise, initiation of statin or statin/ezetimibe combination for primary and secondary prevention of CVD.

Immunization: against influenza virus and pneumococcus

Drug review: to minimize the exposure to nephrotoxic drugs (especially NSAIDs) and ensure that medication doses are appropriate for the level of kidney function [18]

Management of CKD stage G4 and G5

Patient monitoring at these stages must be performed by a specialist Nephrologist. Managing patients with G4 and G5 requires addressing several aspects of CKD. Efforts should focus on the need to slow down CKD progression while maintaining alertness in order to identify and treat possible CKD complications. Meanwhile, special care should be given to help reduce the incidence of CVD and to allow timely and informed decision-making regarding the management of ESCKD. Typically, patients should be assessed on a 1-2 monthly basis. Factors to be monitored and addressed include:

Hyperkalemia: a diet low in potassium should be followed, manage medication- induced hyperkalemia [19].

Metabolic acidosis: Treatment with bicarbonate supplement aiming at HCO3 > 22mEq/L.

Anemia: exclusion of other causes of anemia. When Hb <10.0 g / dL, special interventions should be considered (iron administration, initiation of erythropoietin). The goal of treatment is to maintain Hb levels 11.5 g/dL.

Calcium and phosphate disorders: restriction of dietary phosphates, orally supply “activated” (1α-hydroxylated) vitamin D and phosphate-binding factors.

Blood pressure: Target BP<130/80 mm Hg. A SBP target <120mmHg is suggested, if tolerated (KDIGO BP Guidelines 2021) [20].

Cardiovascular risk: smoking cessation, exercise, initiation of statin treatment or statin/ ezetimibe combination for primary and secondary CVD prevention [21].

Fluid balance: salt and water retention are common in patients with impaired renal function. Deterioration of fluid retention may require the initiation or increase of diuretics and may accelerate the need to initiate renal replacement therapy.

Immunization: Influenza and pneumococcal vaccinations should be given. Patients who may need renal replacement therapy should be vaccinated against hepatitis B.

Drug review: minimize exposure to nephrotoxic drugs (especially NSAIDs) and ensure that medication doses are appropriate for the level of kidney function. Metformin should be avoided in patients with CKD stage G4 and G5.

Patients in these stages should be educated about treatment options. Kidney transplanta tion is considered the optimal therapy for ESKD, with living donor kidney transplantations performed before or shortly after hemodialysis initiation. Alternative therapies for ESKD may include in-center hemodialysis and peritoneal dialysis. The KDIQO guidelines recommend that access creation should occur when eGFR is between 15 and 20 mL/min/1.73 m2.

COMMENTS

Stratification of CKD into 5 stages helps clinicians focus on CKD management aspects.

Notably, the majority of CKD stage 3 or 4 patients will not develop CKD Stage 5 / kidney failure (~1% risk).

Early examination and intervention in patients at risk for CKD are necessary because progressive CKD is associated with adverse clinical outcomes, including ESKD, CVD, and increased mortality.

Appropriate clinical measures should be performed, to manage the risk and increase the safety of patients with CKD.

Co-management and referral of patients to specialist Nephrologists, when appropriate, in order to improve the results in CKD.

Conflict of interest disclosure

None to declare

Declaration of funding sources

None to declare

Author contributions

LB was responsible for conception, writing, data interpretation and review of the final draft of the article.

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