By the end of this section, you should be able to:
- 34.1.1 Discuss fluid volume excess and its impact on renal system disorders.
- 34.1.2 Explain the implications of diuretic use for fluid volume excess with renal system disorders.
Fluid Volume Excess and the Renal System
The renal system normally contributes to the homeostasis of extracellular fluid volume by regulating the glomerular filtration rate (GFR), which is the rate at which the kidneys filter blood, and the reabsorption of sodium and water. Successful maintenance of this balance depends on both intrinsic (internal) renal mechanisms and extrinsic (external) systemic mechanisms.
Intrinsic Renal Response to Fluid Volume Excess
Increased fluid volume triggers an intrinsic response from the kidneys, referred to as renal autoregulation. Autoregulation depends on two physiologic processes: the myogenic response and tubular glomerular feedback. When cardiovascular fluid volume increases, the smooth muscle of the renal blood vessels stretches, stimulating the myogenic response. This response causes afferent arterioles to contract in response to increased volume. In turn, this action decreases the GFR by reducing the blood flow to the renal vessels. The tubuloglomerular feedback process decreases the GFR through the macula densa by reducing sodium reabsorption and inhibiting renin production. These actions by the kidneys are effective only when the pressure in the arterioles is 80–180 mm Hg (Dalal et al., 2022).
Extrinsic Renal Response to Fluid Volume Excess
Outside of the kidneys when there is excess fluid volume, the circulating blood volume increases, stretching the walls of the right atrium and thereby triggering atrial natriuretic peptide (ANP) secretion and reducing secretion of antidiuretic hormone (ADH). The ANP activation dilates afferent arterioles and constricts efferent arterioles, which increases the GFR. The ANP also decreases sodium reabsorption in the collecting duct and inhibits the renin–angiotensin–aldosterone system (RAAS) response to promote vasodilation and sodium excretion. Each nephron segment has a specific sodium entry mechanism that dictates the effect of decreased ADH secretion. In the loop of Henle, the sodium transporting cells respond to decreased ADH levels by reducing the reabsorption of sodium, potassium, and chloride. Decreased ADH secretion also decreases sodium and water reabsorption in the proximal and distal tubules. Under normal circumstances, these actions increase urinary output and decrease fluid volume and blood pressure.
Diuretic Use and the Renal System
Diuretic therapy decreases circulating blood volume to reduce blood pressure and resolve interstitial edema. Diuretic drugs inhibit either the specific sodium reentry mechanism for the nephron segments that regulate sodium, potassium, and chloride or water reabsorption in the proximal and distal tubules. As noted in Figure 34.2, loop diuretics affect sodium, potassium, and chloride levels or reabsorption in the thick ascending loop of Henle. Osmotic diuretics inhibit water reabsorption in the proximal convoluted tubule and the collecting duct. Potassium-sparing diuretics inhibit sodium reabsorption in the collecting tubule, and thiazide and thiazide-like diuretics decrease sodium reabsorption in the distal convoluted tubule. Different diuretics are often used in combination to take advantage of the complementary effects of individual drugs.
Barriers to Effective Treatment
The effectiveness of a specific diuretic is related to its active site in the nephron, its bioavailability, the dosing schedule, and the client’s daily salt intake. Under normal circumstances, the kidney quickly reestablishes a balance between sodium intake and sodium and water excretion, so effective diuretic therapy must be appropriately timed. In addition, two compensatory renal responses to diuretic therapy can limit a drug’s effectiveness: diuretic resistance and diuretic braking (Wilcox et al., 2020). Diuretic resistance occurs when the maximum dose of a loop diuretic fails to produce the anticipated effect on fluid volume status because the successive doses of the drug trigger hypertrophy of the distal tubule, which increases sodium reabsorption. Diuretic braking is a progressive decrease in urinary output after repeated doses of loop diuretics. This renal response is due in part to increased sodium reabsorption in the nephron. Chronic diuretic administration also results in decreased fluid volume, which stimulates the RAAS system and increases aldosterone secretion.
Diuretic Therapy for Acute Kidney Injury
Loop diuretics are most frequently prescribed for clients with acute kidney injury (AKI) to decrease the risk of additional kidney damage and the development of hypervolemia, or fluid overload (Hegde, 2020). Diuretic therapy is not recommended for preventing AKI, and the effectiveness of the therapy is limited in clients with hypoalbuminemia. Hypoalbuminemia commonly occurs in individuals with AKI because loop diuretics are protein bound, meaning they are not filtered by the glomeruli but are delivered directly to the proximal tubules and then secreted into the lumen of the nephrons. Effective diuretic therapy requires administering doses that meet the minimum or threshold dose for the specific drug but do not exceed the ceiling doses, the point at which the drug is no longer effective.
Diuretic Therapy for Chronic Renal Disease
Diuretics are used to treat chronic renal disease (CRD), also referred to as chronic kidney disease (CKD), to regulate fluid volume, increase the effectiveness of other antihypertensive drugs, and lower blood pressure. Standard practice has been to use thiazide and thiazide-like diuretics when the GFR is at or above 30 mL/hour and loop diuretics when the GFR is less than 30 mL/hour (Jo et al., 2023). However, research is being conducted that challenges this practice. Recent research indicates that thiazide and thiazide-like diuretics are safe and effective in clients with chronic renal disease (Teles et al., 2023).
Diuretic Therapy for Nephrotic Syndrome
Nephrotic syndrome is a disorder associated with proteinuria, edema, and hypertension. There is not a consensus regarding the use of diuretic therapy to treat edema secondary to sodium retention and hypoalbuminemia associated with nephrotic syndrome. Loop diuretics are largely protein bound, which means that delivery of the drug to the nephron is less efficient and clearance of the diuretic is increased in those with nephrotic syndrome. Results of research investigating the administration of albumin prior to, or in combination with, loop diuretics to improve delivery of the loop diuretic to the active site in the tubule in clients with hypoalbuminemia are inconclusive. A recent meta-analysis revealed coadministration of albumin with furosemide might enhance diuresis, but further research is needed (Lee et al., 2021). Angiotensin-converting enzyme (ACE) inhibitor drugs or angiotensin II receptor blocker drugs may be used to decrease the renal excretion of albumin, thereby improving the action of the diuretics. Loop diuretics are often used with thiazide or thiazide-like drugs to reduce edema because the combined action may be more effective than either drug type by itself. As noted above, as the GFR declines, the effectiveness of diuretic therapy also declines.
Link to Learning
Nephron Structure
The kidney plays an integral role in many body functions. Within the kidney, the nephron is the functional unit carrying out these tasks. Depending on their type, diuretics exert their effects on different parts of the nephron. This Pixorize animation reviews the structure and function of the nephron.
Commonly Assessed Laboratory Tests
Routine blood and urine tests can measure kidney function and indicate kidney damage. A chemistry panel measures several electrolytes and includes tests that indicate renal function.
Sodium
The therapeutic serum sodium level is 136–145 mEq/L (Padilla & Abadie, 2022). Higher or lower levels can have serious adverse effects. Lower levels, referred to as hyponatremia, can cause a range of symptoms. Mild hyponatremia can cause nausea and malaise. Moderate to severe hyponatremia can cause progressive neurologic alterations, including headache and lethargy progressing to seizures, coma, and death. Pulmonary edema unrelated to cardiac events has also been reported. Thiazide diuretic therapy can result in severe hyponatremia, especially in older adults who also consume large amounts of water. Hypernatremia, serum sodium levels above the therapeutic range, can cause cognitive dysfunction ranging from lethargy and confusion to seizures. Other signs and symptoms include orthostatic blood pressure changes, tachycardia, oliguria, and dry mucous membranes. Osmotic diuretic administration creates a diuresis that contains water losses in excess of sodium losses.
Potassium
The therapeutic serum potassium level is 3.5–5.0 mEq/L (Padill & Abadie, 2022). Higher or lower levels can have serious negative effects. Hypokalemia, or serum potassium levels that are lower than therapeutic, causes muscle weakness. The severity of manifestation depends on the potassium value and the cause and duration of the deficit. Potassium levels around 3.0 mEq/L cause mild to moderate muscle weakness. Potassium levels less than 2.5 mEq/L produce severe muscle weakness, including effects on respiratory muscles and life-threatening electrocardiogram (ECG) changes. Clients taking loop diuretics or thiazide diuretics are at risk for hypokalemia because these medications cause loss of potassium along with sodium. Hyperkalemia, or serum potassium levels that are higher than therapeutic, can develop with the use of potassium-sparing diuretics. Mild and moderate hyperkalemia can be asymptomatic, but life-threatening cardiac symptoms or paralysis can occur at levels greater than 6.5 mEq/L. The rate at which the potassium level shifts is more important than the level itself. Clients with chronically elevated potassium levels are less likely to have symptoms, whereas sudden increases are more likely to cause severe symptoms in clients with previously normal potassium levels (Simon et al., 2023).
Blood Urea Nitrogen
The amount of urea nitrogen in the blood, which is one type of waste product in the blood, varies inversely with the estimated GFR (eGFR; see below). However, the blood urea nitrogen (BUN) is also influenced by the client’s fluid volume status. The BUN is not identified as a critical indicator of the effectiveness of diuretic therapy. The therapeutic range is 8–20 mg/dL (Padilla & Abadie, 2022).
Creatinine
Serum creatinine is the waste product of muscle tissue metabolism. It is completely cleared by the kidneys, which means that creatinine levels can be used to assess kidney function. Significant renal impairment may occur before the creatinine level increases. The serum creatinine value is used to calculate eGFR. Therapeutic levels vary: 0.5–1.0 mg/dL in females and 0.7–1.2 mg/dL in males (Padilla & Abadie, 2022). Dietary intake of red meat affects creatinine levels.
Serum creatinine and urine creatinine can be compared to estimate renal function; however, the relationship between the two values changes as the GFR falls, and this comparison requires collecting urine over 24 hours as directed. As a result, it is more common to use the serum creatinine level alone. Accurate results from a 24-hour urine collection depend upon the client’s ability to follow the protocol for urine collection (Shahbaz & Gupta, 2023).
Glomerular Filtration Rate
The GFR provides the most accurate laboratory assessment of renal function but is not easily measured. The eGFR is calculated based on the client’s serum creatinine level, age, sex, and weight. The value is expressed as the filtration rate in milliliters per minute per average body surface area. The therapeutic range in adults is 120–130 mL/minute/1.73 m2 but can decline with age to about 75 mL/minute/1.73 m2 at age 70 (Maddukuri, 2022). Levels greater than 180 mL/minute/1.73 m2 indicate hyperfiltration, which may be the initial sign of diabetes. Decreased filtration rate is associated with advancing age and declining renal function. An eGFR value less than 60 mL/minute/1.73 m2 for 3 consecutive months indicates chronic renal disease, and an eGFR value less than 15 mL/minute/1.73 m2 indicates kidney failure or end-stage renal disease (ESRD).
Lipid Profile
Loop diuretics and thiazide and thiazide-like diuretics may increase serum levels of cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides. All these components are measured in a lipid profile laboratory test.
Uric Acid
Uric acid is a waste product of purine metabolism. It is excreted largely by the kidneys and the gastrointestinal system. Elevated uric acid levels are associated with gout, which is associated with joint and soft tissue injury, most commonly in the big toe. Thiazide and thiazide-like diuretics increase reabsorption of this waste product in the proximal renal tubules. Uric acid is measured in a separate laboratory test. The therapeutic uric acid level is 2.5–8.0 mg/dL (Padilla & Abadie, 2022).
Urinalysis
A urinalysis can detect signs of kidney disease. In addition to measuring creatinine, urine tests determine the presence of uric acid, glucose, and albumin in the urine. Urine osmolality and output are also measured. Therapeutic urine output is 30 mL/hour; an individual is considered oliguric if their urine output is less than 0.5 mL/kg/hour (Berry, 2022).
Client Teaching Guidelines
The client taking a diuretic should:
- Take all diuretics as prescribed by their health care provider.
- Take a baseline pulse and blood pressure measurement before starting the diuretic.
- Monitor and record their pulse and blood pressure regularly to share with their health care provider, reporting any significant changes as defined and directed by the health care provider.
- Maintain adequate intake of fluids as prescribed by their health care provider.
- Follow a low-sodium diet as prescribed by their health care provider.
- Elevate their feet and legs or walk, if they are able, to reduce swelling.
- Take the drug early in the day to avoid nocturia.
- Weigh themselves before starting the diuretic and every day at the same time of day. When weighing themselves, clients should use the same scale and wear the same amount of clothing. They should record their weights for review by the health care provider and to be able to track changes.
- Report weight increase of more than 2–3 pounds per day or more than 5 pounds in 1 week.
- Immediately report any concerning symptoms, including difficulty breathing, chest pain, lightheadedness, dizziness with position change, muscle weakness, confusion, significant decrease in urinary output, or irregular heart rate.
- Avoid orthostatic hypotension by changing position slowly and using assistive devices as necessary.
The client taking a diuretic should not:
- Change the dose or discontinue the medication without consulting their health care provider.
- Take over-the-counter medications or supplements without consulting their health care provider or pharmacist.
Unfolding Case Study
Part A
Read the following clinical scenario to answer the questions that follow. This case study will evolve throughout the chapter.
Gordon Jefferson is a 74-year-old client who presents to his health care provider’s office reporting a recent weight gain and lower leg swelling for approximately 1 week.
History
Chronic renal disease
Hypertension
Current Medications
Losartan 50 mg orally daily
Dapagliflozin 10 mg orally daily
| Vital Signs | Physical Examination | |
|---|---|---|
| Temperature: | 97.8°F |
|
| Blood pressure: | 178/92 mm Hg |
|
| Heart rate: | 76 beats/min | |
| Respiratory rate: | 20 breaths/min | |
| Oxygen saturation: | 98% on room air | |
| Height: | 5'9" | |
| Weight: | 201 lb | |