Chronic kidney disease (CKD) is a common condition. Its prevalence in England is estimated to be 13%. The risk of CKD increases with age and comorbidities such as hypertension, diabetes, and cardiovascular disease (CVD). It is often not recognized, since it does not usually have specific symptoms.
A significant minority of patients with CKD will develop end-stage renal disease and, in this group, late application of renal replacement therapy increases morbidity and mortality.
However, the greatest importance of CKD is that it represents an independent, powerful and potentially modifiable risk factor for CVD.
CKD is also closely associated with other major adverse effects, such as acute kidney injury, frailty, and mortality. CKD is a growing health challenge. Its timely diagnosis and treatment can prevent or delay its progression, and reduce the development of complications.
| Scope and purpose |
This summary guideline highlights the key recommendation of the National Institute of Health Care Excellence (NICE) guideline and the Guideline for the Care of Chronic Kidney Disease in Adults: Assessment and Treatment, 2014.
| recommendations |
Information and education
People with CKD should receive education and information, tailored to the severity and cause of CKD, complications and risk of progression.
Diagnosis of chronic kidney disease
CKD is defined as an abnormality of kidney function and/or structure, lasting more than 3 months.
This includes people with:
• Markers of kidney damage: albuminuria, urinary sediment abnormalities, electrolyte abnormalities and other abnormalities, caused by tubular disorders, histological and structural abnormalities (on images), and, history of kidney transplantation.
• Glomerular filtration rate (GFR) <60 ml/min / 1.73 m2, on at least 2 separate occasions, for at least 90 days (with or without kidney damage).
Clinical laboratories should use the CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) creatinine equation to estimate creatinine GFR. However, in people with extreme muscle mass, measurements should be interpreted with caution. , since reducing muscle mass will lead to an overestimation while increasing muscle mass will lead to underestimation of the GFR.
Cystatin C-based GFR measurement is indicated to make the initial diagnosis and confirm or rule out CKD in people with:
• GFR creatinine d 45-59 ml/min/1.73 m2, sustained for at least 90 days and
• no proteinuria (ACR <30 mg/g).
The diagnosis of kidney disease is not possible in people with:
• IFG cystatin C >60 ml/min/1.73 m2 and
• IFG cystatin C >60 mL/min/1.73 m2 and
• no other markers of kidney disease.
When highly accurate GFR determination is required, such as during chemotherapy monitoring or evaluation of renal function in potential living donors, consider a reference standard measurement (inulin, chromium complexed with ethylenediaminetetracetic acid, iohexol, or 125I-iothalamate ).
To identify proteinuria when its level is low, the urinary ACR is preferred to the protein/creatinine ratio (PRC), due to its greater sensitivity. An ACR ≥30 mg/g indicates clinically significant proteinuria. Alternatively, to quantify and monitor higher levels of proteinuria (ACR: ≥700 mg/mmol). RPC can be used.
Who should be tested for CKD and who should be referred to a specialist for evaluation ?
| Who should be tested for CKD and who should be referred to a specialist for evaluation ? | |
| Who to test (using IFG and RAC)? | Who to refer to the specialist for evaluation? |
| Mellitus diabetes | GFR <30 mL/min/.73 m2 with or without diabetes |
| Hypertension | ACR ≥700 mg/mmol, unless CKD is caused by diabetes and appropriately treated |
| Acute kidney injury | ACR ≥300 mg/g together with hematuria |
| Cardiovascular disease | Sustained decrease in GFR ≥25% and a change in GFR category or, sustained decrease in GFR ≥15 ml/min/1.73 m2 or more, in 12 months. |
| Structural renal tract disease | Poorly controlled hypertension despite receiving at least 4 agents at therapeutic doses |
| Multisystem disease with potential renal involvement, e.g. THEM | Rare or genetic causes of CKD, known or suspected |
| Opportunistic detection of hematuria | |
| SLE: systemic lupus erythematosus | |
Acute kidney injury is common, affecting 20% of emergency admissions, and is an important risk factor for the development of CKD.
The development or progression of CKD should be monitored for at least 2-3 years following an episode of kidney injury, even if serum creatinine has returned to baseline values. To ensure that patient follow-up can be done in the community, fluid communication between primary care physicians and specialists is important.
> Classification of chronic kidney disease
Decreased GFR and increased ACR are associated with a higher risk of adverse outcomes (progression, end-stage CKD, acute kidney injury, CVD, and mortality), independently of each other and of traditional cardiovascular risk factors. This forms the basis of the classification system, which can be used to decide treatment, determine the intensity of follow-up, and tailor patient education.
| Pharmacotherapy |
Therapeutic strategies for CKD are aimed at reducing the risk of CVD, slowing the progression of CKD, addressing complications and, when possible, treating the underlying cause.
> Blood pressure control
It is widely accepted that the progression of CKD is related, in part, to common secondary factors, independent of the underlying cause of CKD. These factors are: intraglomerular hypertension, glomerular hypertrophy, proteinuria with adaptive hyperfiltration, glomerular scarring and interstitial fibrosis.
Numerous meta-analyses have shown that, in patients with proteinuric CKD, lowering blood pressure, through intensive treatment, reduces the progression of CKD. This result does not occur in those without proteinuria. Intensive treatment of hypertension is also associated with increased risk of adverse outcomes. Therefore, it is recommended to respect the target blood pressure ranges.
| Target blood pressures for patients with chronic kidney disease | |
| Chronic kidney disease | Blood pressure 120–139/<90 mmHg |
| Chronic kidney disease and diabetes | 120–129/<80 mmHg |
| Chronic kidney disease and ACR ≥6 mg/mmol | 120–129/<80 mmHg |
The role of renin-angiotensin system antagonists (RAS) in diabetes associated with proteinuria is well established. ARBs also have effects on diabetic non-proteinuric CKD, independent of blood pressure control, reducing proteinuria and CKD progression. The effect is greater in those with higher levels of proteinuria.
| Indications for ARA in chronic kidney disease |
| Diabetes and ACR ≥30 mg/g Hypertension and ACR ≥300 mg/g ACR ≥700 mg/mmol (620 mg/g) regardless of whether hypertension or CVD is present |
| ARA: antagonists of the renin angiotensin system. CVD: cardiovascular disease. ACR: albumin/creatinine ratio. |
Before starting treatment with ARA, potassium and eGFR should be measured. These measurements should be repeated 1 to 2 weeks after starting said treatment and after each dose increase.
If pre-treatment potassium is >5.0 mEq/L; Do not routinely prescribe ARAs to patients with CKD. If potassium is ≥6.0 mEq/l, ARBs should be discontinued, as well as other medications that cause hyperkalemia.
The combination of ARA is not indicated in people with CKD. Hypertension in people with CKD. Non-diabetics, or with an ACR ≥300 mg/g, should be treated in accordance with the therapeutic recommendations of the NICE guideline.
> Other kidney protection strategies
There is some evidence that treatment of chronic metabolic acidosis with oral sodium bicarbonate may delay progression to end-stage CKD. The authors recommend considering oral sodium bicarbonate supplementation for individuals presenting with the following parameters (both).
• GFR <30 ml/min/1.73 m2 and
• serum bicarbonate concentration <20 mEq/l.
It is well established that glycemic control in patients with diabetes mellitus can delay the onset of albuminuria and the progression of CKD. There is also more recent evidence that, in patients with type 2 diabetes, sodium-glucose cotransporter-2 inhibitors promote the reduction of proteinuria and slow the progression of CKD,
> Reduction of cardiovascular risk
Reducing lipids is important in CKD to reduce cardiovascular risk. For primary and secondary prevention, the guideline recommends prescribing atorvastatin to all people with CKD. For secondary prevention of CVD, antiplatelet agents are also indicated, but the increased risk of bleeding in this population must be taken into account.
The authors prefer apixaban to waerfarin for patients with non-valvular atrial fibrillation, with an eGFR of 30-50 ml/min/1.73 m2, and the following risk factors:
• Previous stroke or transient ischemic attack
• age >75 years
• hypertension
• Mellitus diabetes
• symptomatic heart failure.
| Bone metabolism and osteoporosis |
Calcemia, phosphatemia, and parathyroid hormone and vitamin D levels should not be routinely measured in people with an GFR ≥30 ml/min/1.73 m2; but they should be measured in those with an GFR <30 ml/min/1.73 m 2.
For the prevention and treatment of osteoporosis, bisphosphonates are used, if the patient has an GFR ≥30 ml/min/1.73 m 2.
> Vitamin D supplements
Vitamin D supplements should not be routinely prescribed to control or prevent bone and mineral disorders of CKD. In the presence of hypovitaminosis D in patients with CKD, cholecalciferol or ergocalciferol are indicated.
If hypovitaminosis has been corrected and symptoms of CKD-related bone or mineral disorders persist, along with an GFR <30 ml/min/1.73 m2, alfacalcidol or calcitriol are indicated. In these cases, calcium and phosphate levels should be monitored regularly.
> Anemia
The hemoglobin (Hb) level in people with an GFR <45 mL/min/1.73 m2 allows the identification of anemia (Hb <110 gr/l).
| Limitations |
Several areas have been identified for future research:
• Self-care: impact of education and support interventions for people with CKD on clinical outcomes.
• Antiplatelet therapy: clinical efficacy and cost-effectiveness of low-dose aspirin compared with placebo for the primary prevention of CVD in people with CKD. This is the objective of the ATTACK study.
• Antagonists of the renin-angiotensin system: clinical and cost-effectiveness of these agents in people >75 years of age with CKD.
• Uric acid-reducing agents: their clinical features and profitability in the progression of CKD
• Vitamin D supplements in the treatment of mineral and bone disorders of CKD: the impact of treatment with vitamin D or vitamin D analogues on patient-related outcomes.
| Implications for implementation |
The NICE guidance identifies 3 areas that can have a significant impact on practice, or be difficult to implement.
> Calculation of estimated GFR based on creatinine
The use of the CKD-EPI equation more than the one used until now, the equation of the MDRD study (N. del T.: Modification of diet in renal disease), has generated the need for laboratories to modify their practice, which makes it difficult the adoption of the GKD-EPI creatinine equation. One difficulty is that it may become problematic to follow up on people whose previous eGFRs were calculated with other equations.
> Use of eGFR calculated using cystatin C
The eGFR cystatin C is an additional tool that can reduce the overdiagnosis of CKD, allowing a fairly accurate diagnosis in primary care. It is not yet widely available and laboratories must adapt their practice.
Despite its cost, it is considered profitable due to savings during the management of the disease. Because it is a new recommendation, doctors may not be familiar with it yet.
> Classification of chronic kidney disease
Evaluation of IFG and RAC may add additional burden and cost to the diagnosis and follow-up of CKD. The addition of the RAC increases the complexity of the classification and clinicians will need to be informed and advised, taking into account its clinical importance, along with other planned developments in guideline updates.
