Chronic Kidney Disease Nursing CE Course for APRNs

in the US have CKD, with many cases undiagnosed. In 2019, kidney diseases were listed as the 8th leading cause of death in the US. Diabetes and hypertension are the leading causes of CKD, accounting for 75% of all new cases. Every day in the US, 360 people are diagnosed with CKD. Treating CKD can be costly. In 2019, Medicare paid out $87.2 billion to treat CKD, or $24,453 per beneficiary over 65; an additional $37.3 billion, or $86,400 per beneficiary, was spent on end-stage renal disease (ESRD) treatment (Centers for Disease Control and Prevention [CDC], 2022; Heron, 2021).  

Anatomy and Physiology 

Structures of the Renal System      

Six organs comprise the urinary system, including two kidneys, two ureters, the urinary bladder, and the urethra. The kidneys are in the posterior region of the abdominal cavity. They are located behind the peritoneum on either side of the vertebral column between T12 and L3 (see Figure 1 below). Due to liver placement, the right kidney is located slightly lower than the left kidney. Each kidney measures approximately 11 cm long and 6 cm wide. The kidneys are considered the body's purification system since they remove wastes, including toxins, from the blood. They are protected by the renal capsule and a fatty layer. The capsule and fatty layer are covered with a double layer of renal fascia that adheres the kidneys to the abdominal wall. The outer layer of the kidney is called the cortex (see Figure 2 below). The cortex contains all the glomeruli, most of the proximal tubules, and some distal tubule segments. The inner portion of the kidney is called the medulla and contains the tubules and collecting ducts that drain into the calyces. The calyces join and form the renal pelvis, which is continuous with the upper end of the ureter (McCance & Huether, 2019).   

The nephron is the functional unit of the kidney and forms urine. The nephron comprises the glomerulus, proximal tubule, loops of Henle, distal tubule, and collecting duct (see Figure 3 below). Each kidney contains approximately 1.2 million nephrons. There are three types of nephrons: superficial cortical nephrons, which make up 85% of all nephrons, mid cortical nephrons, and juxtamedullary nephrons, essential for urine concentration. The glomerulus contains loops of capillaries contained in the Bowman capsule. The walls of the capillaries serve as a filtration membrane for urine formation. An anion charge across the filtration membrane restricts the filtration of negatively charged molecules such as proteins. Juxtaglomerular cells secrete renin and are located around the afferent arteriole. They are also connected to the sodium-sensing macula densa cells of the distal convoluted tubule. The proximal tubule is lined with microvilli to increase surface area and reabsorption. The loops of Henle selectively transport solutes and water, which contributes to the medulla's hypertonic state, essential for concentrating urine. The collecting duct contains principal cells that facilitate sodium and water reabsorption and the excretion of potassium and intercalated cells that secrete hydrogen, bicarbonate, and potassium. Once the urine is produced and concentrated, it flows through the ureters into the bladder. Once the amount of urine in the bladder reaches 250-300 mL, mechanoreceptors respond to the stretching and stimulate the micturition (urination) reflex (McCance & Huether, 2019). 

Renal Blood Flow 

To fully understand CKD, it is critical to review the blood pathway through the kidneys (see Figure 4 below). Blood enters the kidney via the aorta to each renal artery à arterial branches àafferent arterioles à glomerulus à leaves through efferent arterioles à then divides into two networks: peritubular capillaries & vasa recta (which rejoin to form the venous branches) à exit via the renal vein à empties into the inferior vena cava. Renal blood flows at approximately 1000-1200 mL/min or 20% to 25% of the total cardiac output. Blood flow through the glomerular capillaries is maintained at a set rate (i.e., autoregulation) despite various changes to systemic arterial pressures. The GFR is the plasma filtration per unit of time and is directly related to renal blood flow (i.e., perfusion pressure). The sympathetic noradrenergic nerves that regulate vasoconstriction innervate the renal blood vessels. The autoregulation of renal blood flow and sympathetic regulation of vasoconstriction maintain a constant GFR (Hinkle et al., 2021; McCance & Huether, 2019). 

There are hormones and other factors also regulating renal blood flow. These hormones and other mediators alter the resistance of the renal vasculature by stimulating either vasodilation or vasoconstriction. The renin-angiotensin-aldosterone system (RAAS) is a central hormonal regulator of renal blood flow. Renin is an enzyme formed and stored in the granular cells of the afferent arterioles. Renin release is stimulated by decreased blood pressure, reduced sodium chloride concentrations, and sympathetic nerve stimulation of beta-adrenergic receptors. When renin is released, it causes the production of angiotensin I, which is inactive. Angiotensin I is converted into angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II stimulates the adrenal cortex to release aldosterone, stimulates the release of antidiuretic hormone (ADH), and acts as a vasoconstrictor leading to increased blood pressure in the kidneys. Natriuretic peptides released by the myocardium inhibit the RASS. When fluid volume expands, the heart dilates, and releases natriuretic peptides which inhibit sodium and water reabsorption, inhibit the secretion of renin and aldosterone, dilate the afferent arterioles, and constrict the efferent arterioles resulting in increased urine formation and decreased blood volume and blood pressure (McCance & Huether, 2019).  

Kidney Function  

As discussed above, the primary function of the nephron is urine formation, a complex process involving glomerular filtration, tubular reabsorption, and tubular secretion and excretion. In addition to urine formation, the kidneys have specific functions such as: 

• regulation of electrolytes, specifically calcium and phosphorus 

• regulation of fluid volume and blood pressure 

• control of acid-base balance 

• secretion of prostaglandins 

• erythropoiesis (the production of red blood cells [RBCs]) 

• conversion of vitamin D into the active form 

• excretion of substances such as medications, poisons, and food additives (McCance & Huether, 2019) 

Pathophysiology 

CKD decreases filtration and tubular functions with the effects manifested throughout the body. The kidneys can adapt to nephron loss. Systemic changes occur due to increased creatinine, urea, and potassium. Salt and water alterations are not apparent until less than 25% of kidney function remains. Different hypotheses explain how kidney function can be maintained despite nephron loss. One theory is the intact nephron hypothesis. This hypothesis theorizes that nephrons are capable of compensatory hypertrophy and expansion or hyperfunction. Because of this, the kidneys can maintain the rate of filtration, reabsorption, and secretion to regulate solute and water levels despite a declining GFR. Although the urine of a patient with CKD may contain higher than normal protein levels and red and white blood cells, the overall urine concentration is like that of an individual without CKD. Since the kidney is a very complex organ, the location of the damage also influences the severity of the disease. Although the factors contributing to CKD are complex and involve the relation of many different processes, two factors are thought to advance CKD: increased levels of angiotensin II and proteinuria. The extended pressure on the efferent arterioles from the increase of Angiotensin II increases permeability, contributing to proteinuria: the presence of excess protein in the urine. Proteinuria promotes tubulointerstitial injury when protein accumulates in the interstitial space, activating the immune response and leading to inflammation and progressive fibrosis. Angiotensin II may also promote inflammation and growth factors, further contributing to fibrosis and scarring (McCance & Huether, 2019).  

Risk Factors 

The most common diseases associated with CKD include diabetes and hypertension; however, many factors increase a patient's risk of developing CKD (National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK], n.d.). The risk factors associated with CKD are described in Table 1 below.  

Signs and Symptoms  

Patients with CKD stages 1-3 are often asymptomatic. It is not until CKD reaches stages 4 or 5 that patients begin to have signs and symptoms related to metabolic changes and disturbances in water and electrolyte levels. Some effects of CKD are included in Table 2 below. Many of the signs and symptoms are directly related to metabolic acidosis, uremia, anemia, and the alterations in the ability of the kidney to maintain water and electrolyte balance within the circulatory system. As CKD progress, more symptoms may arise (Arora, 2021a; CDC, 2022).  

Diagnosis 

The decision to screen a patient for CKD should be individualized. Patients that are asymptomatic with a low risk of developing CKD should not be routinely screened. All patients diagnosed with hypertension or NIDDM should be screened. Evaluating GFR and albuminuria allow for a complete evaluation of CKD. If kidney disease is suspected, there are numerous testing options to determine the cause and severity of kidney disease. In addition to a thorough physical examination and medical history, there are diagnostic tests and procedures to help the healthcare provider (HCP) diagnose kidney disease (Department of Veterans Affairs, 2019; Lambert, 2014; Moyer, 2012; NKF, 2022d). Examples of diagnostic options to determine kidney function are discussed below.  

Blood Tests 

Blood Urea Nitrogen (BUN)  

Urea nitrogen is a waste product of the breakdown of dietary protein. A typical BUN result is between 7 and 20 mg/dL. As kidney function decreases, the BUN level in the blood increases. An increased BUN result can also be attributed to dehydration, urinary tract obstruction, severe burns, a high-protein diet, congestive heart failure, or a recent heart attack. Due to these other causative factors that can increase BUN, it is not used alone to diagnose kidney failure. The ratio between BUN and creatinine can determine if BUN elevation is due to prerenal or renal causes. When renal disease is present, the ratio of BUN to creatinine is close to 10:1 (Gounden et al., 2021; NKF, 2022d).  

Serum Creatinine 

Serum creatinine (SCr) measures the amount of creatinine in the blood. Creatinine is a waste product of creatine phosphate in the muscles. Creatinine levels vary depending on age, gender, and body size (muscle bulk), but it is released constantly. Creatinine is cleared almost entirely by the kidneys. When kidney function decreases, creatinine begins to build up in the blood. A serum creatinine level above 1.2 for women or 1.4 for men can indicate that the kidneys are not functioning correctly. As kidney disease progresses and kidney function deteriorates, the creatinine level rises in the blood. Many patients are diagnosed with CKD based on a GFR calculated using the patient's SCr level. However, using the SCr level may not accurately reflect kidney function since it measures both urinary excretion and any SCr production from muscle turnover. Measuring cystatin C levels is an alternative method of determining estimated kidney function (Department of Veterans Affairs, 2019; Gounden et al., 2021; NKF, 2022d).  

Cystatin C 

Cystatin C is a low-molecular-weight protein constantly produced by all cells in the body with a nucleus and filtered by the kidneys. Serum cystatin C levels are inversely related to GFR, like creatinine; however, the kidneys filter cystatin C using a different process than creatinine. Once the kidneys filter cystatin C, it is reabsorbed and metabolized by the proximal renal tubules, which differs from creatinine. The advantage of testing cystatin C is that the results are less impacted by patient age, sex, race, and muscle mass relative to SCr levels; however, cystatin C results can be affected by cancer, thyroid disease, and current smoking history. It is recommended that cystatin C is measured at least once to confirm a diagnosis of CKD or refine staging (Department of Veterans Affairs, 2019; Gounden et al., 2021). 

Glomerular Filtration Rate (GFR) 

GFR measures how well the kidneys remove waste and excess fluid from the blood. It is a calculation based on SCr, cystatin C, or both and considers the patient's age and gender. Since age is included in the GFR calculation, the rate can decrease as age increases. A GFR of less than 60 indicates that the kidneys are not functioning correctly. Once the GFR drops below 15, the patient and HCP must discuss aggressive treatment options like dialysis and kidney transplantation (NKF, 2022d). There are a variety of equations that HCPs can use to determine a patient's GFR. These equations are shown in Tables 3, 4, and 5 below. GFR value and staging of CKD are shown in Table 6 below.  

Urine Tests 

Urinalysis 

A urinalysis includes a microscopic evaluation of the urine and a dipstick test. The dipstick is chemically treated to react when in contact with specific components not typically found in urine, including protein, blood, pus, bacteria, and sugar. A urinalysis is not a specific test for CKD; however, certain components in the urine can indicate a problem with the kidneys, indicating that further testing is warranted (NKF, 2022d).  

A urine protein test can be done as part of the urinalysis or a stand-alone dipstick test. For a random urine sample, the expected protein value in the urine is 0-14 mg/dL. When a dipstick test is positive for protein, a more specific dipstick test such as an albumin-specific dipstick test or a quantitative measurement such as an albumin-to-creatinine ratio test is indicated for further evaluation. The more sensitive dipstick test can detect albuminuria (i.e., albumin in the urine). The clinician places a dipstick, or strip of chemically treated paper, into the urine sample for this test. If the paper turns color, then albumin is present in the urine. Patients with diabetes or hypertension should have an albuminuria test or albumin-to-creatinine ratio (ACR) test (discussed below) at the time of diagnosis and then annually. Patients with other risk factors, including cardiovascular disease, advanced age, obesity, and a family history of CKD, should be screened based on patient presentation. There is limited data on the benefits versus risk of screening for CKD in asymptomatic adults. Proteinuria and albuminuria are not interchangeable and do not describe the same thing. Proteinuria indicates that some sort of protein is present in the urine, while albuminuria is very specific to the abnormal loss of albumin in the urine (Gaitonde et al., 2017; NKF, 2022d; University of California San Francisco, 2019). 

Albumin-to-Creatinine Ratio (ACR)  

The ACR is a urine test to evaluate kidney function. The ACR is determined by dividing the amount of albumin by the creatinine in the urine. There are three stages of albuminuria: A1, A2, and A3 (see Table 7 below). The ACR and GFR determine CKD staging (NKF, 2022d).  

Creatinine Clearance  

Creatinine clearance (CrCl) is the volume of blood cleared of creatinine per unit of time. This test determines how much waste products the kidneys filter out of the blood each minute. CrCl is measured by comparing the creatinine in the blood versus the urine. A 24-hour urine collection and a single blood sample must be obtained to determine CrCl. Once the 24-hour urine results are analyzed, the creatinine level in the urine is compared to the level in the blood. The serum sample must be obtained within 24 hours of the urine collection. The Cockcroft-Gault formula determines the estimated creatinine clearance rate (eCCR). The formula is as follows: eCCR = (140 - Age) x Mass (kg) x [0.85 if female]/ 72 x [SCr (mg/dL)]. A normal CrCl is 110-130 mL/min in females and 110-150 mL/min in males (NKF, 2022d; Shahbaz & Gupta, 2021).  

Imaging Tests  

Imaging tests such as ultrasounds and computed tomography (CT) scans can be used to visualize the kidneys. A renal ultrasound uses sound waves to determine if there are any size or shape abnormalities or improper placement of the kidneys. An ultrasound can also identify kidney obstruction due to a stone, cyst, or tumor. A CT scan can be used to find structural abnormalities or obstructions. A CT scan must often be performed with contrast to get the best results; however, contrast dye in patients with decreased kidney function may be contraindicated (NKF, 2022d).  

Biopsy 

There are many reasons why a kidney biopsy may be performed. A renal biopsy allows the HCP to identify the underlying disease process causing the renal impairment. This procedure also allows the HCP to identify and implement the most effective treatments. A kidney biopsy can also give the HCP a better understanding of the extent of the kidney damage, which may influence treatment options. For patients who have received a transplanted kidney, a biopsy can give the HCP information about why the organ is no longer functioning properly (NKF, 2022d).  

Guidelines 

CKD staging is classified based on the cause (C), GFR category (G, see Table 6 above), and albuminuria category (A, see Table 7 above). This is collectively referred to as CGA staging. To diagnose CKD requires a decreased GFR of less than 60 mL/min/1.73 m2 (stage G3a-G5) or markers of kidney damage that have been present for over three months. GFR is used since it is accepted as the best overall index of kidney function. The duration criterion of three months is necessary to distinguish CKD from acute kidney injury (AKI; KDIGO, 2013). Markers of kidney damage are described in Table 8 below.

End-stage Renal Disease (ESRD)  

CKD may progress until the kidneys begin to permanently fail, known as ESRD (CKD stage 5). More than 500,000 individuals in the US suffer from ESRD. When kidney function becomes this impaired, the patient will not survive without intervention. The HCP must initiate some type of renal replacement therapy (RRT) and, if a good candidate, seek a kidney donor for transplant. Starting dialysis or receiving a kidney transplant can increase life expectancy in patients with ESRD. RRT can increase life expectancy by 5-10 years. Receiving a kidney from a deceased donor can increase life expectancy by 10-15 years. Receiving a kidney from a living donor can increase life expectancy by 15-20 years. Supportive care and symptom management are the primary treatment goals for patients who choose not to pursue RRT or kidney donation. Due to the debilitating nature of ESRD and the time commitment and disruption in daily life that occurs with RRT, patients diagnosed with ESRD are eligible for Medicare coverage regardless of age (Benjamin & Lappin, 2021; Centers for Medicare & Medicaid Services [CMS], 2021). 

Treatment and Management 

Conservative Management  

For patients not interested in RRT, conservative management should be considered. All healthcare team members should be able to assist the patient with advanced care planning and recognize when there is a need for end-of-life care. End-of-life care should focus on symptom management and psychological and spiritual support for the patient and family members (KDIGO, 2013).  

Pharmacological Management 

When managing patients with CKD, the GFR must be considered when dosing medications. When precision dosing is necessary due to a narrow therapeutic index, it is recommended that the measurement of GFR be based on cystatin C. Patients with CKD taking nephrotoxic medications should have their GFR, electrolytes, and drug levels monitored regularly. Patients with CKD should not take herbal remedies and consult their HCP or pharmacist before taking any OTC medications (KDIGO, 2013).  

Diabetes  

The target hemoglobin A1c (HbA1c) to prevent or delay CKD progression is 7%. If a patient has comorbidities, a limited life expectancy, or is at increased risk for hypoglycemia, the target HbA1c should be above 7%. Metformin (Glucophage) is recommended as a first-line treatment to manage NIDDM in patients with CKD stages 1-3. Metformin (Glucophage) works by decreasing the hepatic production and intestinal absorption of glucose and increasing insulin sensitivity. Metformin (Glucophage) does not slow the progression of CKD. A sodium-glucose co-transporter 2 (SGLT2) inhibitor can be used as an add-on treatment for NIDDM in patients with CKD stages 1-3 to slow the progression of the disease and decrease the risk of cardiovascular events (this is discussed further below). Metformin (Glucophage) as monotherapy reduces the risk of hypoglycemia versus independent treatment with insulin. Metformin (Glucophage) is also easier for patients to administer, is less expensive, and is more convenient than insulin. Metformin (Glucophage) is contraindicated in patients with a GFR below 30 mL/min/1.73m2. Metformin (Glucophage) can be utilized at the standard dose in patients with a GFR above 45 mL/min/1.73m2. When the GFR is between 30 and 45 mL/min/m2, the HCP must determine if the benefits of continuing metformin outweigh the potential risks. Adverse effects of using metformin (Glucophage) in patients with decreased GFR include lactic acidosis and gastrointestinal effects such as diarrhea (Department of Veterans Affairs, 2019; KDIGO, 2013). 

The initial dose of the immediate-release formulation of metformin (Glucophage) should be 500 mg twice a day or 850 mg once daily. The dose can be titrated in 500 mg increments weekly or 850 mg increments every two weeks. The initial dose for the extended-release formulation is 500 to 1000 mg once daily. If needed, the dose can be titrated weekly by 500 mg. Metformin (Glucophage) can cause hypoglycemia, nausea, diarrhea, vomiting, dizziness, weakness, and a slow and irregular heart rate; it is contraindicated in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis (DKA; Vallerand & Sanoski, 2017).  

The US Food and Drug Administration (FDA) has approved an SGLT2 inhibitor, dapagliflozin (Farxiga), to slow CKD progression. Dapagliflozin (Farxiga) also reduces the risk of death due to cardiovascular disease and hospitalization for heart failure in patients with CKD. The medication works by decreasing glucose absorption from the proximal renal tubule and increasing the amount of glucose excreted through the urine. Standard dosing is based on GFR. When used for glycemic control in patients with a GFR of 45 mL/min/1.73m2 or more, the starting dose is 5 mg orally daily with a maximum of 10 mg. The recommended starting dose is 10 mg orally daily for all other indications. When GFR is between 25 and 45 mL/min/1.73m2, the recommended dose is 10 mg orally daily. If GFR decreases to less than 25 mL/min/1.73m2, dapagliflozin (Farxiga) should not be initiated; however, if the patient is already taking the medication, treatment can be continued. Dapagliflozin (Farxiga) is contraindicated in patients with IDDM, on dialysis, or who have experienced a previous allergic reaction to any of the drug's ingredients. Adverse effects include ketoacidosis, dehydration, urinary tract infections, hypoglycemia, and vaginal yeast infections (AstraZeneca, 2021; FDA, 2021).  

Hypertension  

Managing hypertension is a priority when treating patients diagnosed with or at risk for CKD. Target blood pressure (BP) results should be individualized according to patient demographics such as age, past medical history, and response to treatment. When treating hypertension in patients with CKD, it is essential to monitor the patient for postural dizziness and hypotension. It is recommended that adults with CKD and an ACR greater than 30 mg/g be treated to maintain systolic blood pressure (SBP) less than 130 mmHg and diastolic blood pressure (DBP) less than 80 mmHg. Systolic BP control is considered more important than diastolic BP control. In patients with diabetes and an ACR of 30 - 300 mg/day or a non-diabetic patient with an ACR above 300 mg/day, a renin-angiotensin-system (RAS) blocker (i.e., an angiotensin receptor blocker [ARB] or angiotensin-converting enzyme [ACE] inhibitor) is the first-line treatment (KDIGO, 2013).  

ACE inhibitors prevent the production of angiotensin II, leading to vasodilation and decreased blood pressure. ACE inhibitors include benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), and lisinopril (Prinivil, Zestril), to name a few. Recommended dosing for ACE inhibitors in CKD is as follows:  

• benazepril (Lotensin) starting at 5 mg daily with a maximum dose of 40 mg/day; 

• captopril (Capoten) starting dose is 25 mg two to three times daily with a maximum dose of 450 mg/day;  

• enalapril (Vasotec) initial dose in patients with CKD is 2.5 mg once daily with a maximum dose of 40 mg/day; and  

• lisinopril (Prinivil, Zestril) initial dose is 2.5 mg or 5 mg once daily depending on creatinine clearance, with a maximum dose of 40 mg once daily.  

Common side effects of ACE inhibitors include a dry nagging cough, hyperkalemia, fatigue, dizziness, headaches, and loss of taste. In rare cases, ACE inhibitors may cause angioedema (swelling of the lips, tongue, or face), requiring discontinuation. ACE inhibitors are contraindicated in patients with hyperkalemia, renal artery stenosis, or angioedema (KDIGO, 2013; Vallerand & Sanoski, 2017).  

Switching to an ARB may be beneficial if patients report a cough using ACE inhibitors. ARBs include irbesartan (Avapro), valsartan (Diovan), olmesartan (Benicar), losartan (Cozaar), telmisartan (Micardis), and candesartan (Atacand). ARBs decrease blood pressure through competitive antagonist activity at angiotensin II receptor sites. All ARBs are dosed once daily; however, if BP is not controlled, losartan (Cozaar) may be dosed twice daily. Recommended dosing for ARBs is as follows:  

• irbesartan (Avapro) 150 mg with a maximum dose of 300 mg;  

• valsartan (Diovan) 80 or 160 mg with a maximum dose of 320 mg;  

• olmesartan (Benicar) 20 mg with a maximum dose of 40 mg;  

• losartan (Cozaar) 25 to 50 mg with a maximum dose of 150 mg;  

• telmisartan (Micardis) 40 mg with a maximum dose of 80 mg;  

• candesartan (Atacand) 4 to 8 mg with a maximum dose of 32 mg.  

Side effects include dizziness, headache, hyperkalemia, angioedema, nausea, vomiting, severe diarrhea, and weight loss. ARBs are contraindicated in patients with a life-threatening reaction to ARBs, SBP less than 80 mmHg, hyperkalemia, or renal artery stenosis (KDIGO, 2013; Vallerand & Sanoski, 2017).  

ACE inhibitors or ARBs should be continued if the patient tolerates the medication regimen. The patient should be monitored closely during treatment for further renal deterioration and electrolyte imbalances, including hyperkalemia. With every dose change, SCr should be obtained. If the patient's SCr increases by more than 30% from baseline after adding an ACE inhibitor or ARB, the medication should be discontinued. RAS blockers are also contraindicated in patients with advanced CKD, renal artery stenosis, and those with only a solitary kidney (Arora, 2021b).  

Anemia  

Anemia is a complication associated with CKD due to inadequate erythropoietin production by the kidneys. Anemia in any patient over 15 with CKD occurs when the hemoglobin level drops below 13.0 g/dl in males and 12.0 g/dl in females. Hemoglobin (Hgb) should be assessed only when clinically indicated in patients with a GFR above 60 ml/min/1.73 m2; at least annually in patients with a GFR of 30-59 ml/min/1.73m2; and at least twice per year in patients with a GFR less than 30ml/min/1.73m2 (KDIGO, 2013). Folic acid and ferrous sulfate (iron) may increase healthy red blood cell production. Hgb that drops below 10 g/dL should be treated with an erythropoiesis-stimulating agent (ESA) such as epoetin alfa (Procrit, Epogen) or darbepoetin alfa (Aranesp). These medications stimulate the bone marrow to produce more red blood cells (RBCs). The goal of treatment is to raise Hgb to 10-12 g/dL since the normalization of Hgb levels in patients with CKD stages 4 and 5 has been associated with severe effects, including cardiovascular reactions, stroke, and death. Before initiating treatment with ESAs, the patient's iron store levels should be checked. The goal is to maintain an iron saturation of 30-50% and a ferritin level of 200-500 ng/mL (Arora, 2021b). 

Epoetin alfa (Procrit, Epogen) should be initiated at 50-100 units/kg intravenously (IV) or subcutaneously (SQ) three times weekly, with the IV route preferred in patients on hemodialysis. Adverse effects include hypertension, arthralgia, muscle spasms, dizziness, and upper respiratory infection. For patients on dialysis, darbepoetin alfa (Aranesp) should be started at 0.45 mcg/kg IV or SQ weekly or 0.75 mcg/kg IV or SQ every two weeks with the IV route preferred. The recommended starting dose for patients not on dialysis is 0.45 mcg/kg IV or SQ every four weeks. Adverse effects include hypertension, dyspnea, peripheral edema, cough, and an increased risk of seizures. Epoetin alfa (Procrit, Epogen) and darbepoetin alfa (Aranesp) are both contraindicated in patients with hypertension, pure red cell aplasia following treatment with ESAs, or a history of allergic reaction to the medication (Vallerand & Sanoski, 2017).  

Blood transfusions may be needed in patients with acute blood loss or severe, symptomatic anemia (Hinkle et al., 2021). 

Bone Health  

Due to the risk of metabolic bone disease, serum calcium, phosphate, parathyroid hormone (PTH), and alkaline phosphatase should be checked once the GFR drops below 45 ml/min/1.73m2 (stages G3b-G5). Individuals with an elevated PTH should be evaluated for hyperphosphatemia, hypocalcemia, and vitamin D deficiency. Unless there is a documented deficiency in vitamin D, vitamin D supplements should not be utilized to decrease elevated PTH levels in patients with CKD not currently on dialysis. Bisphosphonate treatment is not recommended in patients with GFR less than 30 ml/min/1.73m2 (KDIGO, 2013). 

Paricalcitol (Zemplar) is a synthetic vitamin D analog used to prevent and treat secondary hyperparathyroidism associated with CKD stages 3 and 4 and patients with CKD stage 5 that are currently being treated with hemodialysis or peritoneal dialysis. It can also decrease the amount of protein excreted by the kidneys in patients with CKD stages 2-5. For patients with CKD stages 3 and 4 and a PTH level less than or equal to 500 pg/mL, initial dosing is 1 mcg orally daily or 2 mcg orally three times per week. If the PTH level is greater than 500 pg/mL, initial dosing is 2 mcg orally daily or 4 mcg orally three times per week. For patients with CKD stage 5 on dialysis initial dose in mcg is equivalent to the patient's PTH level divided by 80, administered three times a week. Adverse effects include diarrhea, vomiting, nausea, dizziness, hypertension, and peripheral edema. Contraindications include hypercalcemia and vitamin D toxicity. To avoid hypercalcemia in patients with CKD stage 5, initiation of paricalcitol (Zemplar) should not occur until serum calcium level has been decreased below 9.5 mg/dL (Arora, 2021b; Vallerand & Sanoski, 2017).  

Phosphate binders can be given with meals to eliminate excess phosphorus from the body. A phosphate binder works by binding the phosphorus in the stomach, preventing it from being absorbed into the bloodstream, and excreting it through the stool. These medications must be taken 5-10 minutes before or immediately after each meal, including snacks (Aurora, 2021b). There are different categories of phosphate binders, including the following (Vallerand & Sanoski, 2017):  

• Calcium-based phosphorus binders include calcium acetate (PhosLo) and calcium carbonate (Tums). Calcium-based phosphorus binders have widely replaced aluminum-based binders. They also function as a calcium supplement. Calcium acetate (PhosLo) coupled with dietary modifications is the first-line treatment of hyperphosphatemia. There is a risk of hypercalcemia due to the number of phosphate binders the patient must take throughout the day, which requires frequent monitoring of serum calcium levels. These medications are contraindicated in patients with hypercalcemia or adynamic bone disease. Adverse effects of calcium-based binders include nausea, diarrhea, vomiting, and constipation. Adult dosing of calcium acetate (PhosLo) is 1334 mg orally with meals with a maximum of 2668 mg per meal. The dose can be adjusted to maintain a phosphate level above 6 mg/dL.  

• Aluminum-free, calcium-free phosphorus binders do not contain aluminum or calcium and trap phosphorus in the gastrointestinal tract through ion exchange and hydrogen bonding. These medications include sevelamer (Renagel) and sevelamer carbonate (Renvela). These medications should be considered over calcium-based binders in patients with complicated diabetes mellitus, vascular or valvular calcification history, or persistent inflammation. Common side effects of aluminum and calcium-free binders include vomiting, nausea, diarrhea, abdominal pain, flatulence, and constipation. Bicarbonate and chloride blood levels should be monitored with these medications. Serious adverse effects include gastrointestinal bleeding, ulcer, colitis, bowel obstruction, necrosis, or perforation. The initial dose of sevelamer carbonate (Renvela) is 800 to 1600 mg orally three times per day with meals. The dose may be titrated by 0.8 g per meal in two-week increments based on serum phosphorus level.  

Metabolic Acidosis  

Managing metabolic acidosis in patients with CKD may improve protein levels and bone metabolism. Patients with CKD with a serum bicarbonate concentration of less than 22 mmol/l should be treated with oral sodium bicarbonate (Neut). Studies have shown that serum bicarbonate levels less than 22 mmol/l can increase the risk of CKD progression and death. Sodium bicarbonate (Neut) is an antacid commonly used to relieve heartburn and indigestion. Standard oral dosing is 325 to 2000 mg 1-4 times daily. Common side effects include dry mouth, increased thirst, and polyuria. Sodium bicarbonate (Neut) is contraindicated in patients with hypocalcemia, receiving diuretics, or patients with chlorine loss due to vomiting or continuous gastrointestinal suction. Sodium bicarbonate is removed by both peritoneal and hemodialysis; however, it is also commonly used in dialysate (KDIGO, 2013; Vallerand & Sanoski, 2017).  

Renal Replacement Therapy (RRT) 

RRT refers to the use of life-supporting treatment for renal failure. RRT can replace the nonendocrine-related functions of the kidneys. There are different types of RRT, including intermittent hemodialysis, continuous hemofiltration and hemodialysis, and peritoneal dialysis (Arora, 2021b). RRT should be initiated when one or more of the following are present:  

• signs and symptoms of renal failure, including pruritus (itching), abnormal electrolyte levels, acid-base imbalance, or serositis  

• inability to control blood volume or blood pressure 

• deterioration in nutritional status 

• pericarditis 

• intractable gastrointestinal symptoms  

• GFR between 5 and 10 ml/min/1.73m2 (Arora, 2021b; KDIGO, 2013) 

Although the goal of RRT is to mimic the function of the kidneys and filter the patient's blood, no form of RRT is equivalent in efficiency to a healthy, functioning kidney.  

Hemodialysis 

Hemodialysis is a treatment used for patients with ESRD to filter wastes and water out of the blood. Hemodialysis can help manage blood pressure and electrolyte balance, including potassium, sodium, and calcium. As previously stated, hemodialysis increases the life expectancy of patients with ESRD, but it is not a cure. During hemodialysis, the patient's blood is removed from their body via an intravenous (IV) catheter, graft, or fistula and pumped through a filter known as a dialyzer, commonly referred to as an artificial kidney. For patients with a dialysis catheter, one lumen connects to an artery and the other to a vein. If the patient has a fistula or graft, one needle is inserted into the fistula or graft's arterial side and one into the fistula or graft's venous side. The dialysis machine pumps the blood through the dialyzer into very thin, hollow fibers and back into the patient's body (see Figure 5 below). While flowing through the fibers, a dialysis solution, known as dialysate, passes in the opposite direction, and waste products move from the blood into the dialysate via osmosis (NIDDK, n.d.).  

Hemodialysis can be performed in different settings and at various frequencies. Many patients have hemodialysis performed at a dialysis center three days per week (Monday, Wednesday, and Friday, or Tuesday, Thursday, and Saturday). Some dialysis centers offer overnight hours to accommodate patients with other commitments during the day. Treatment occurs while the patient is sleeping, leaving their days free. Another option is home dialysis. This option allows patients to have longer or more frequent (i.e., 3-7 days per week) dialysis treatments better mimicking the work of the kidneys. Completing more frequent treatments also allows the patient to maintain a fluid intake amount closer to normal and decreases the need for antihypertensives. This increased frequency also reduces some side effects of traditional hemodialysis in a dialysis center, including muscle cramps, high or low blood pressure, and hyperphosphatemia (NIDDK, n.d.).  

Peritoneal Dialysis  

Peritoneal dialysis is a treatment for ESRD that uses the patient's peritoneum to filter their blood inside the body. A catheter is inserted surgically into the peritoneum to utilize peritoneal dialysis. During peritoneal dialysis, a specifically formulated dialysate is instilled into the abdomen. Once the solution is instilled, the patient can disconnect, cap the catheter, and engage in normal daily activities. Peritoneal dialysis is completed on a schedule dictated by the patient's nephrologist, usually 4-6 times daily. Once the prescribed dwell time is reached, the patient drains the dialysate fluid into an empty drainage bag and instills fresh dialysate into the abdomen (see Figure 6). The patient exchanges the dialysate regularly throughout the day, known as continuous ambulatory peritoneal dialysis (CAPD). Alternatively, they can use a machine known as a cycler to complete the process overnight while they sleep, known as automated peritoneal dialysis. Like hemodialysis, peritoneal dialysis increases the patient's life expectancy and decreases symptoms; however, it is not a cure for ESRD (NIDDK, n.d.).  

One of the most severe complications related to peritoneal dialysis is infection. It is possible to get an infection of the skin surrounding the catheter site or the peritoneum (i.e., peritonitis). Signs of a catheter site infection include purulent drainage, erythema, swelling, tenderness, or bulging of the site. Topical mupirocin (Bactroban) or gentamicin (Garamycin) can be applied to the site daily to prevent or treat catheter or exit site infections. Signs of peritonitis include abdominal pain, fever, nausea, and vomiting. The patient may also notice cloudiness or unusual color of the used dialysate fluid or the cuff of the catheter beginning to emerge from the insertion site. When the clinical presentation suggests an infection, the outflowed peritoneal dialysis fluid should be collected for a cell count, differential count, gram stain, and culture. Antibiotics can be added directly to the dialysate to treat peritonitis. For gram-positive bacterial infections, cefazolin (Ancef) or vancomycin (Vancocin) are the treatments of choice. For gram-negative bacterial infections, 3rd generation cephalosporins or aminoglycosides are the treatments of choice. Dosing recommendations are outlined in table 9 below. Another complication of peritoneal dialysis includes a hernia, an area of weakness in the abdominal muscles. Hernia risk is increased due to the surgical opening in the abdominal muscles and the considerable weight of the dialysate during indwelling. Hernias often occur in the umbilical area, near the catheter site, or the groin (Li et al., 2018; NIDDK, n.d.).  

Transplant 

Of the over 120,000 Americans on the nation's organ transplant registry awaiting an organ transplant, more than 98,000 are awaiting a kidney. Due to the shortage of donor organs, not every patient on the transplant registry will receive a kidney transplant. Kidney donation can occur from deceased or living donors. Placing a patient on the organ transplant registry should be done preemptively for most patients with CKD G4 or G5 (GFR less than 30 ml/min/1.73 m2, with clinical data indicating irreversible progression of the CKD over the preceding 6-12 months. Transplantation from a living donor is the preferred treatment for transplant-eligible patients. Once the GFR drops below 10 ml/min/1.73 m2 (or earlier if symptoms are present), transplantation with either a living or deceased donor is recommended (Chadban et al., 2020; KDIGO, 2013; NKF, 2022a).  

Patients with multiple myeloma, amyloidosis with extensive prerenal involvement, decompensated cirrhosis, severe irreversible obstructive or restrictive lung diseases, severe untreatable and symptomatic cardiac disease deemed by a cardiologist to preclude the patient from transplantation, and progressive central neurodegenerative disease should not be referred for kidney alone transplant evaluation; those with cirrhosis should be considered for a combined liver-kidney transplant (Chadban et al., 2020; KDIGO, 2013; NKF, 2022a). Evaluation for kidney transplantation should be delayed in patients with the following conditions until they are appropriately managed. 

• unstable psychiatric conditions that affect decision making  

• ongoing substance abuse disorder 

• nonadherence to treatment 

• active infection (excluding hepatitis C) 

• active malignancy; except for low-grade cancers (i.e., prostate cancer) 

• active symptomatic cardiac disease (i.e., angina, arrhythmia) 

• active symptomatic peripheral arterial disease  

• recent stroke or transient ischemic attack (TIA); kidney transplantation should be delayed at least 6 months following a stroke and 3 months following a TIA 

• active symptomatic gastrointestinal disease (i.e., peptic ulcer disease, diverticulitis, pancreatitis, gallbladder disease or gallstones, inflammatory bowel disease) 

• tobacco use 

• diabetes 

• obesity 

• hematologic disease (i.e., thrombophilia, sick-cell disease, thalassemia)  

• bone and mineral disorders (i.e., severe hyperparathyroidism; Chadban et al., 2020) 

 Testing of a potential transplant candidate is extensive and includes: 

• laboratory testing: blood chemistries; liver function tests; complete blood count (CBC); infectious profile (hepatitis A, B, and C; Epstein-Barr virus; Cytomegalovirus; Varicella-zoster virus; HIV); urinalysis and urine culture  

• cardiac evaluation: 12-lead EKG; chest x-ray; exercise stress test; echocardiogram 

• immunologic evaluation: ABO blood group determination; human leukocyte antigen typing; crossmatching (Chhabra, 2022)  

Following kidney transplantation, the patient required life-long immunosuppression therapy to prevent an alloimmune rejection response. The treatment goals are to prevent acute or chronic rejection and achieve the highest possible patient and graft survival rate. There are different categories of rejection. Hyperacute rejection occurs within hours of the transplant. Acute rejection occurs within the first 6 months of transplantation and accounts for 15% of rejection cases. Chronic rejection occurs more than 1 year following transplantation and results in allograft loss. Potential complications following transplantation include recurrence of kidney disease, renal artery thrombosis or stenosis, infection, and ureteral stenosis and obstruction (Chhabra, 2022). See the Organ Donation Nursing CE course for more information on organ donation. 

Non-Pharmacological Management

Dietary Modifications  

Nutritional sodium, potassium, and protein restrictions may be necessary, so the APRN must be prepared to educate the patient about diet and nutrition. Daily protein intake should be less than 1.3 g/kg to slow CKD progression. Protein intake should be decreased further to 0.8 g/kg/day in adults with diabetes or those with a GFR less than 30 ml/min/1.73m2 (stage G4-G5). Salt intake should be limited to less than 2 g/day. When a patient has CKD, potassium and phosphorus can build up in the cardiovascular system. Calcium can be leached from the bones when phosphorus is high to balance phosphorus levels. This makes the bones weak, brittle, thin, and prone to fractures. When phosphorus levels become too high, the patient may experience pruritis and bone/joint pain. Therefore, patients should be instructed to avoid foods high in phosphorus. Foods high in phosphorus include meat, poultry, and fish; bran cereals and oatmeal; dairy; beans, lentils, nuts; dark-colored sodas, and canned or bottled iced teas. Instead, patients should be encouraged to eat fresh fruits and vegetables; bread, pasta, rice; rice milk; corn and rice cereals; and light-colored sodas or homemade iced tea. CKD allows potassium to build up in the bloodstream, with profound cardiac implications, including arrhythmias. Potassium should be limited in the diet by avoiding foods such as oranges, bananas, and orange juice; potatoes and tomatoes; brown and wild rice; bran cereals; dairy foods; whole-wheat bread and pasta; and beans and nuts. By contrast, foods low in potassium include apples and peaches; carrots and green beans; white bread and pasta; white rice; rice milk; cooked rice and wheat cereals and grits; and apple, grape, or cranberry juices. Since the kidneys also excrete magnesium, patients with CKD are at an increased risk of developing hypermagnesemia. In severe cases, patients should avoid foods high in magnesium, such as quinoa, spinach, whole wheat, nuts (almonds, cashews, and peanuts), dark chocolate, and black beans (KDIGO, 2013; NIDDK, n.d.).  

Electrolyte Monitoring  

Consistent Physical Activity 

Individuals with CKD should be encouraged to engage in physical activity appropriate for their cardiovascular health. The goal is 30 minutes of moderate activity five times per week. Patients with renal failure on dialysis should engage in aerobic exercises, improving fitness, strength, and quality of life. Resistance training can be beneficial in patients with earlier stages of CKD. Physical activity can also help patients maintain a healthy weight. Patients with CKD should aim for a BMI of 20-25 (KDIGO, 2013; NIDDK, n.d.).  

Adequate Sleep  

The goal is for patients to get 7-8 hours of sleep per night. Sleep is an essential factor in overall physical and mental health. Adequate and restful sleep can also decrease blood pressure and help patients achieve blood glucose goals (NIDDK, n.d.).  

Smoking Cessation 

Smoking can further damage the kidneys making CKD worse. Smoking cessation can also positively affect blood pressure, which is beneficial to kidney function. Patients that successfully quit smoking also decrease their risk of experiencing a heart attack or stroke (NIDDK, n.d.).  

Patient Monitoring 

For patients with ESRD, the HCP must monitor the patient for hypertension, tachycardia, dysrhythmias, and tachypnea. Daily weights are a good indicator of fluid loss or gain, so the APRN should educate the patient to weigh themselves at the same time using the same scale every day. If one kg (two to three pounds) of weight gain is noted in a day, the patient is retaining approximately 1000 mL of extra fluid. Fluid restrictions may be required if the patient is experiencing symptoms of fluid volume overload. Further, the HCP should expect to monitor for metabolic acidosis, proteinuria, hematuria, and urinary casts in patients with ESRD (Hinkle et al., 2021).  

Neurological assessment is critical, so the HCP should closely monitor the patient's level of consciousness as uremia can lead to confusion or coma. Since patients with ESRD are also at higher risk of developing infections, the HCP must monitor the patient's complete blood count (CBC) and vital signs for leukocytosis (elevation of white blood cells [WBCs] above 11.0x109 /L) or fever. Furthermore, patients with ESRD tend to be oliguric or anuric (see Table 2 above), so the APRN should monitor urine output and symptoms of fluid volume overload such as wheezing, rhonchi, edema, peripheral swelling, hypertension, tachycardia, and jugular venous distention (JVD). Frequent oral care will help prevent stomatitis and decrease discomfort. A buildup of urea can lead to uremic frost and pruritus, so appropriate skincare with medicated creams and lotions may be required (Hinkle et al., 2021; Mank & Brown, 2022). 

Patients with ESRD often develop hyperkalemia, hypermagnesemia, or hyperphosphatemia as the kidneys can no longer excrete excess potassium, magnesium, and phosphorus. The HCP should expect to monitor serum potassium (reference range 3.5-5 mEq/L), magnesium (reference range 1.7-2.2 mg/dL), and phosphorus (reference range 2.5-4.5 mg/dL) in these patients regularly. Hyperkalemia above 6 mEq/L can cause peaked T waves, flat P waves, widened QRS complexes, and prolonged PR intervals, so continuous cardiac monitoring is advised. Hyperkalemia can be treated by administering polystyrene sulfonate (Kayexalate) orally, an infusion of 50% dextrose, regular insulin, and calcium gluconate IV, or during hemodialysis. For hypermagnesemia, the HCP should be prepared to administer loop diuretics and calcium to lower magnesium levels and address resulting cardiac problems. Patients should be encouraged to avoid antacids, laxatives, or enemas containing magnesium. Hypertension can be improved with adherence to fluid and sodium restrictions and administering diuretics and antihypertensives regularly or as needed. Hypervolemia often occurs in ESRD, although it can be prevented by complying with the prescribed fluid restriction and avoiding excess intravenous fluids. The patient should be encouraged to avoid antacids or cold medications containing sodium bicarbonate. A diuretic such as furosemide (Lasix) may be necessary. The APRN should encourage frequent rest periods and advise the patient to avoid large crowds and sick people to reduce infection risk (Hinkle et al., 2021).   

Future Research 

Diabetes is the leading cause of kidney damage. However, recent research highlights that only half of primary health care providers discuss CKD with their diabetic patients. Therefore, it is critical to increase awareness amongst primary care providers and encourage early screening for CKD in patients with diabetes. Future research on CKD prevalence in adults with NIDDM is needed to optimize their care. To this end, the NKF has launched a multi-site, cross-sectional study, Awareness, Detection, and Drug Therapy in Type 2 Diabetes Mellitus and Chronic Kidney Disease (ADD-CKD). The researchers aim to assess how CKD is identified and managed in NIDDM patients in the primary care setting, using a survey of 10,000 adult patients and their 500 primary HCPs (NKF, 2022c). 

There is also an NKF-funded project underway using the contributions of leading investigators in the field to create and analyze the world's largest dataset of patient outcomes at each stage of CKD. Since CKD is a progressive spectrum disease, patients experience varying symptoms and complications within each stage. This research examines how these various complications at each stage of CKD impact patient prognosis (NKF, 2022c).  

Further research is needed on how to predict the progression of CKD through the various stages and eventually ESRD. Although there are factors associated with CKD progression, and those that are modifiable should be addressed, there is no current ranking of known risk factors to determine which is the most predictive of CKD progression. In addition, further research is needed to determine which mathematical formula is most predictive of a patient's likelihood of experiencing complications, such as cardiovascular events and progressive disease (KDIGO, 2013).  

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