Chronic kidney disease: An overview

Chronic Kidney Disease (CKD, also called kidney failure or renal failure) is a condition in which the kidneys lose some of their ability to remove waste products and excess fluid from the bloodstream. As waste products and fluids build up in the body, other body systems are affected, which can be harmful to human health. A person who has the most severe form of CKD, kidney failure (also known as end-stage kidney disease), usually requires a kidney transplant or dialysis to survive.

Causes
The most common causes of CKD are diabetes and high blood pressure. In the early stages of CKD, there are no symptoms. The disease can progress to complete kidney failure, also called end-stage kidney disease. This occurs when kidney function has worsened to the point that dialysis or kidney transplantation is required to maintain good health and even life, which is typically when kidney function is approximately 10 percent or less of the normal kidney function.

Symptoms
Most people may not have any severe symptoms until their kidney disease is advanced. However, you may notice that you:

• Feel more tired and have less energy
• Have trouble concentrating
• Have a poor appetite
• Have trouble sleeping
• Have muscle cramping at night
• Have swollen feet and ankles
• Have puffiness around your eyes, especially in the morning
• Have dry, itchy skin
• Need to urinate more often, especially at night

Chronic kidney disease: Risk factors
A number of factors can increase the risk of developing CKD, including:

• Diabetes mellitus
• High blood pressure
• A family history of kidney disease
• African-American and other ethnic minorities
• Obesity
• Smoking
• Older age
• Having protein in the urine
• Having autoimmune diseases such as lupus

Evaluation and Diagnosis
A healthcare provider may use several tests to diagnose CKD and determine if there is a treatable underlying cause. These include the following:

Kidney function tests – The Glomerular Filtration Rate (GFR) gives an approximate measure of the overall filtering abilities of the kidneys. Measuring true (actual) GFR is difficult and not practical in the care of most patients. Instead, GFR is usually estimated. The most common way to estimate GFR in adults is by measuring the creatinine level in the blood stream and then using this number in a formula to calculate an estimated GFR (eGFR) level. The eGFR gives an estimate of kidney function, but actual kidney function can be higher or lower than this estimate.

• A reduction in GFR implies either worsening of the underlying kidney disease or the development of another, occasionally reversible kidney problem.
• An increase in GFR, on the other hand, indicates improvement in kidney function.
• A stable GFR in people with CKD implies stable disease.

Urine tests – The presence of albumin or protein in the urine (called albuminuria or proteinuria) is a marker of kidney disease. Even small amounts of albumin in the urine may be an early sign of CKD in some people, particularly those with diabetes and high blood pressure.

Imaging studies – Imaging tests (such as Computed Tomography [CT] or ultrasound) may be recommended to determine if there are any obstructions (blockages) of the urinary tract, kidney stones, or other abnormalities, such as many large cysts seen in a genetic disease called polycystic kidney disease.

Kidney biopsy – With a kidney biopsy, a small piece of kidney tissue is removed and examined under a microscope. The biopsy helps to identify abnormalities in kidney tissue that may be the cause of kidney diseases.

Management of Patients with CKD
The main goal of treatment is to prevent the progression of CKD to complete kidney failure. The best way to do this is to diagnose CKD early and control the underlying cause.

Reducing the Risk of Cardiovascular Disease: The prevalence of the cardiovascular disease is markedly higher among individuals with CKD compared with those without CKD. Therefore, a major component of CKD management is the reduction of cardiovascular risk. It is recommended that patients aged 50 years or older with CKD be treated with a low- to moderate-dose statin regardless of low-density lipoprotein cholesterol level. Smoking cessation should also be encouraged.

Management of Hypertension: Many guidelines provide algorithms detailing which agents should be used to treat hypertension in people with CKD. The presence and severity of albuminuria should be evaluated. Blockade of the renin-angiotensin-aldosterone system with either an Angiotensin-Converting Enzyme inhibitor (ACE-I) or an Angiotensin II Receptor Blocker (ARB) is recommended for adults with diabetes and a urine Albumin-to-Creatinine Ratio (ACR) of at least 30 mg per 24 hours or any adult with a urine ACR of at least 300 mg per 24 hours.

Management of Diabetes Mellitus: Optimal management of diabetes is also important. First, glycemic control may delay the progression of CKD, with most guidelines recommending a goal hemoglobin A1c of ~7.0%. Second, dose adjustments in oral hypoglycemic agents may be necessary. In general, drugs that are largely cleared by the kidneys (e.g., glyburide) should be avoided, whereas drugs metabolized by the liver and/or partially excreted by the kidneys (e.g., metformin and some Dipeptidyl Peptidase 4 [DPP-4] and sodium-glucose cotransporter-2 [SGLT-2] inhibitors) may require dose reduction or discontinuation, particularly when eGFR falls below 30 mL/min/1.73 m². Third, use of specific medication classes such as SGLT-2 inhibitors in those with severely increased albuminuria should be considered.

Nephrotoxins: All patients with CKD should be counseled to avoid nephrotoxins. Although a complete list is beyond the scope of this review, a few warrant mentioning. Routine administration of NSAIDs in CKD is not recommended, especially among individuals who are taking ACE-I or ARB therapy.

Dietary Management: The KDIGO guidelines recommend that protein intake be reduced to less than 0.8 g/kg per day (with proper education) in adults with CKD stages G4-G5 and to less than 1.3 g/kg per day in other adult patients with CKD at risk of progression. Lower dietary acid loads (e.g., more fruits and vegetables and less meats, eggs, and cheeses) may also help protect against kidney injury. Low-sodium diets (generally <2 g per day) are recommended for patients with hypertension, proteinuria, or fluid overload.

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