CHAPTER 16 Kidney Disorders
I. Background
A. The kidneys are responsible for removing toxins, chemicals, and waste products from the blood; regulating acid concentration; and maintaining water and electrolyte balance in the body by excreting urine.
Table 16-1 National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI™) Staging System for Chronic Kidney Disease
| Stage | Description | Glomerular Filtration Rate (GFR) (mL/min/1.73 m2) |
|---|---|---|
| 1 | Kidney damage with normal or increased GFR | ≥90 |
| 2 | Kidney damage with a mild decrease in GFR | 60–89 |
| 3 | Moderate decrease in GFR | 30–59 |
| 4 | Severe decrease in GFR | 15–29 |
| 5 | Kidney failure | <15 (or dialysis) |
Reprinted from American Journal of Kidney Diseases, 39(2):35, 2002, with permission from Elsevier.
II. Common Types and Causes of Kidney Disorders
A. Fanconi syndrome
1. Definition: The tubes in the kidneys do not work properly.
a) Unable to reabsorb glucose, amino acids, small proteins, water, calcium, potassium, magnesium, bicarbonate, and phosphate, making the blood overly acidic
b) May be caused by inherited disorders such as cystinosis, galactosemia, glycogen storage disease, hereditary fructose intolerance, Lowe syndrome, Wilson’s disease, tyrosinemia, medullary cystic disease, and vitamin D dependency; exposure to heavy metals, certain drugs, chemicals (e.g., toluene), or dietary supplements (e.g., lysine); and may even result from kidney transplantation
B. Glomerulonephritis
1. Definition: an acute or chronic kidney disease that occurs when the kidneys are unable to properly remove waste and excess fluids from the body. This occurs when there is glomerular damage from immune or inflammatory reactions and lesions.
2. It can occur by itself or in conjunction with other diseases such as lupus, Goodpasture syndrome, diabetes, immunoglobulin A (IgA) nephropathy, polyarteritis, Wegener granulomatosis, or infection with streptococcus, HIV, hepatitis B or C
3. Signs and symptoms: dark-colored urine, foamy urine, high blood pressure, fluid retention that causes swelling, fatigue, and less-frequent urination
4. Treatment
a) The goal of treatment is to reduce the decline of kidney function and control blood pressure. Corticosteroids are often used to reduce kidney inflammation. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor agonists (ARB), calcium channel blockers, or beta blockers may be used.
C. Focal segmental glomerulosclerosis (FSGS)
1. Definition: A type of glomerular disease that can cause permanent kidney disease in children and adults by attacking the glomeruli, the tiny structures inside the kidneys where blood is filtered. The most common sign of FSGS is the nephrotic syndrome, which is characterized by fluid in the body tissues that causes swelling, excess protein in the urine, hypoalbuminemia, and high cholesterol.
2. Signs and symptoms
b) Patients develop nephrotic syndrome, which is characterized by fluid retention that causes swelling and weight gain of 15 to 20 pounds or more, foamy urine, abnormally low levels of albumin in the blood, hypertension, and high cholesterol. Fluid in the lung cavity, abdomen, and in the sac that surrounds the heart may build-up and fill the cavities.
D. Kidney stones: Kidney stones (also called renal calculi, urinary calculi, urolithiasis, or nephrolithiasis) usually develop when the urine becomes too concentrated. As a result, minerals and other substances in the urine form hard crystals on the inner surfaces of the kidneys. Over time, these crystals may combine to form a small, hard mass, or stone.
1. Calcium stones are the most common type of kidney stones, accounting for 80% of cases. Calcium stones develop when there are high levels of calcium (hypercalcemia) and oxalate in the blood.
2. Struvite stones are usually caused by chronic urinary tract infections. The bacteria that cause these infections release enzymes that increase the amount of ammonia in the urine. This excess ammonia may form large, sharp stones that can potentially damage the kidneys.
3. Cystine stones develop in patients who have an inherited disorder called cystinuria. This disorder causes the kidneys to release too many amino acids, which then form stones.
4. Signs and symptoms
a) Patients may experience intense pain that comes and goes, lasting 5 to 15 minutes at a time. Pain usually begins in the lower back and moves to the abdomen, groin, or genital areas as the stone moves from the kidney toward the bladder. Other symptoms include blood in the urine, cloudy or foul-smelling urine, nausea, vomiting, and constant urge to urinate
5. Treatment
a) Calcium stones: Thiazide diuretics lower urine calcium in idiopathic hypercalciuria and are effective in preventing the formation of stones.
b) Uric acid stones: The two goals of treatment are to raise urine pH and to lower excessive urine uric acid excretion to less than 1 g per day. Supplemental alkali, 1–3 mmol/kg of body weight per day, should be given in three or four evenly spaced, divided doses, one of which should be given at bedtime.
c) Cystine stones: high fluid intake, even at night. Daily urine volume should exceed 3 L. Raising urine pH with alkali is helpful, provided the urine pH exceeds 7.5.
d) Struvite stones: Complete removal of the stone and subsequent sterilization of the urinary tract is the treatment of choice for patients who can tolerate the procedures. Irrigation of the renal pelvis and calyces with hemiacidrin, a solution that dissolves struvite. For patients who are not candidates for surgery, acetohydroxamic acid, and inhibitor of urease, can be used.
E. Nephrotoxicity
F. Diabetic nephropathy
1. Kidney disease that develops as a result of diabetes mellitus (DM); most common cause of kidney failure in the United States, accounts for more than one third of all patients who are on dialysis
2. Approximately 25% to 40% of patients with DM type 1 ultimately develop diabetic nephropathy (DN), which progresses through five predictable stages.
b) Stage 2 (developing diabetes): GFR remains elevated or has returned to normal, but glomerular damage has progressed to significant microalbuminuria (small but above-normal level of the protein albumin in the urine).
c) Stage 3 (overt, or dipstick-positive diabetes): Glomerular damage has progressed to clinical albuminuria.
d) Stage 4 (late-stage diabetes): Glomerular damage continues, with increasing amounts of protein albumin in the urine. The kidneys’ filtering ability has begun to decline steadily, and blood urea nitrogen (BUN) and serum creatinine (SCr) has begun to increase. The GFR decreases approximately 10% annually. Almost all patients have hypertension at stage 4.
G. Nephrotic syndrome
1. Nephrotic syndrome is a disorder of the glomeruli (clusters of microscopic blood vessels in the kidneys that have small pores through which blood is filtered) in which excessive amounts of protein are excreted in the urine (proteinuria). This typically leads to accumulation of fluid in the body (edema), low levels of the protein albumin (hypoalbuminemia), and high levels of fats (hyperlipidemia) in the blood.
2. Causes: DM, systemic lupus erythematosus, amyloidosis certain viral infections, glomerulonephritis, nonsteroidal anti-inflammatory drugs (NSAID), allergies to insect bites and to poison ivy or poison oak, hereditary
3. Signs and symptoms: loss of appetite, a general feeling of illness (malaise), puffy eyelids and tissue swelling, abdominal pain, wasting of muscles (atrophy), frothy urine, swollen abdomen, shortness of breath, swelling of the knees and, in men, the scrotum, shock. Blood pressure is generally low in children and may fall when the child stands up. Adults may have low, normal, or high blood pressure, urine production may decrease, and kidney failure may develop if the leakage of fluid from blood vessels into tissues depletes the liquid component of blood and the blood supply to the kidney is diminished. Other signs and symptoms are in nutritional deficiencies, growth may be stunted, calcium loss from bones, brittle nails and hair, hair loss
H. Drug-induced glomerular disease: Various drugs damage the glomerular filtration barrier and induce proteinuria and nephritic syndrome. Drugs that may cause glomerular disease include NSAID, recombinant interferon A, rifampin, penicillin, ampicillin, amoxicillin, gold, penicillamine, trimethadione, captopril, chlormethiazole, ciprofloxacin, hydralazine, allopurinol, sulfonamides, thiazides, warfarin, carbimazole, heroin, and amphetamines
1. Acute renal failure (ARF): a syndrome characterized by rapid decline in glomerular filtration rate (hours to days), retention of nitrogenous waste products, and perturbation of extracellular fluid volume and electrolyte and acid-base homeostasis. Discontinuation of the offending agents such as NSAID and hydration can be used to treat ARF.
I. End-stage renal disease (ESRD): End-stage kidney disease is a complete or near complete failure of the kidneys to function to excrete wastes, concentrate urine, and regulate electrolytes. End-stage kidney disease occurs when the kidneys are no longer able to function at a level that is necessary for day-to-day life. It usually occurs as chronic renal failure worsens to the point where kidney function is less than 10% of normal. At this point, the kidney function is so low that without dialysis or kidney transplantation, complications are multiple and severe, and death occurs from accumulation of fluids and waste products in the body.
1. Treatment of renal disease
a) Diuretics
(1) Loop diuretics (furosemide, torsemide, and bumetanide) inhibit the body’s ability to reabsorb sodium at the ascending loop of Henle, which leads to a retention of water in the urine because water normally follows sodium back into the extracellular fluid (ECF).
(2) Thiazides such as hydrochlorothiazide act on the distal tubule and inhibit the sodium-chloride symporter leading to retention of water in the urine as water normally follows penetrating solutes. Metolazone is not a true thiazide, but it is a sulfonamide derivative such as thiazides, and its site of action is similar. Metolazone is an oral quinazoline diuretic for the management of edema and hypertension.
b) Albumin: Exogenous administration of albumin increases the oncotic pressure of the intravascular system, pulling fluids from the interstitial space, thereby decreasing edema and increasing the circulating blood volume.
c) Antihypertensives (ACE inhibitors, ARB): reduces the amount of protein in the urine by reducing the amount of pressure and resistance on blood as it circulates through the body. Patients who cannot tolerate ACE inhibitors may use an ARB (e.g., losartan, valsartan). Both ACE inhibitors and ARB can cause hyperkalemia (abnormally high level of potassium in the blood) in patients with chronic renal failure.
2. Dosing Adjustments: Dosages of renally excreted drugs may need to be adjusted according to kidney function. Dose adjustment can be based on serum creatinine level, subsequent creatinine clearance estimation, and dosage calculation. Cockcroft-Gault equation or the Modification of Diet in Renal Disease (MDRD) study equations may be used for routine estimation of GFR.
a) Drugs that may require dosage adjustments include ACE inhibitors, beta blockers, diuretics, antimicrobial agents, some hypoglycemic agents (metformin is not recommended for use in patients with kidney failure), some antimicrobial agents (e.g., azole antifungals, acyclovir, carbapenems, cephalosporins, penicillins, quinolones), analgesics, statins, and others.
3. Dialysis
a) Dialysis works on the principles of the diffusion of solutes and convection of fluid across a semipermeable membrane. Blood flows by one side of a semipermeable membrane, and a dialysate or fluid flows by the opposite side. Smaller solutes and fluid pass through the membrane. The blood flows in one direction and the dialysate flows in the opposite direction. The concentrations of undesired solutes (e.g., potassium, calcium, and urea) are high in the blood, but low or absent in the dialysis solution, and constant replacement of the dialysate ensures that the concentration of undesired solutes is kept low on this side of the membrane. The dialysis solution has levels of minerals such as potassium and calcium that are similar to their natural concentration in healthy blood. For another solute, bicarbonate, dialysis solution level is set at a slightly higher level than in normal blood, to encourage diffusion of bicarbonate into the blood, to neutralize the metabolic acidosis that is often present in these patients.
b) There are two primary types of dialysis: hemodialysis and peritoneal dialysis.
(1) In hemodialysis, the patient’s blood is pumped through the blood compartment of a dialyzer, exposing it to a semipermeable membrane. The cleansed blood is then returned via the circuit back to the body.
(2) In peritoneal dialysis, a sterile solution containing minerals and glucose is run through a tube into the peritoneal cavity, the abdominal body cavity around the intestine, where the peritoneal membrane acts as a semipermeable membrane. The dialysate is left there for a period of time to absorb waste products, and then it is drained out through the tube and discarded. This cycle or “exchange” is normally repeated 4 to 5 times during the day or sometimes more often overnight with an automated system.
c) Continuous veno-venous hemofiltration (CVVH): a short-term treatment, used in patients with kidney failure. The kidney failure may be new or already present. Hemodialysis (kidney dialysis) is usually done for kidney failure. However, if a patient has low blood pressure, CVVH may be needed. As in dialysis, in hemofiltration one achieves movement of solutes across a semipermeable membrane. However, solute movement with hemofiltration is governed by convection rather than by diffusion. With hemofiltration, dialysate is not used. Instead, a positive hydrostatic pressure drives water and solutes across the filter membrane from the blood compartment to the filtrate compartment, from which it is drained. Solutes, both small and large, get dragged through the membrane at a similar rate by the flow of water that has been engineered by the hydrostatic pressure. Convection overcomes the reduced removal rate of larger solutes (due to their slow speed of diffusion) seen in hemodialysis.
J. IgA nephropathy is a common kidney disease that progresses very slowly. It often leads to decreased kidney function and ultimately to kidney failure. The cause of this disease is not known, although most people with the disease have abnormalities in their immune system. Patients with IgA nephropathy treated with immunosuppressive drugs, such as steroids, may be less likely to develop kidney failure.
PATIENT PROFILE
Allergies: No known drug allergies (NKDA)
Diabetes type 2 for 10 years, has been insulin dependent for 3 years
Alcohol use: Occasional beer on weekends
Employment: Postal carrier, job requires several miles of walking daily for deliveries
Medications before this admission:
Furosemide 40 mg PO once daily
Humulin N insulin 20 units SQ in morning and 10 units in evening
Insulin aspart, SQ sliding scale with meals; amount adjusted based on carbohydrate intake
Calcium acetate 667 mg, 2 tablets PO three times daily at meals
PATIENT PROFILE QUESTIONS
1. All of the following are some of the potential complications of chronic renal failure and end-stage renal disease (ESRD) EXCEPT:
2. AM has edema on admission. What would be an appropriate diuretic to add to AM’s existing regimen to reduce edema?
4. Later in the week, AM develops symptoms consistent with a Staphylococcus infection at the catheter site. The decision is made to begin vancomycin until blood culture results are known. Which of the following represents an appropriate initial dose of vancomycin at this time?
REVIEW QUESTIONS
(Answers and Rationales on page 364.)
1. A 60-year-old patient is admitted for surgical correction of a femoral fracture. Postoperative laboratory evaluation revealed severe metabolic acidosis (ph 7.0). What is the most appropriate therapy for the metabolic acidosis?
2. Which of the following is a primary strategy used in management of patients with acute glomerulonephritis?
4. A 58-year-old patient with renal failure secondary to diabetes mellitus has anemia secondary to renal disease. After an initial epoetinalfa dose of 75 U/kg, three times per week, the patient’s hematocrit increases from 22% to 30%. What is the next appropriate step in management of this patient?
6. JP is 57-year-old male that presents with fatigue and the lab work shows advanced renal failure. Which finding would help you determine if his renal failure is chronic?
8. KL is a 58-year-old female with a history of cirrhosis and small-cell lung cancer. Her routine bloodwork reveals a sodium level of 120 mEq/L. Which laboratory test is most useful in determining which of these diseases as the cause of hyponatremia?
9. WW is a 60-year-old male with chronic renal failure. The patient develops abdominal cramping, nausea, and vomiting from food poisoning. Laboratory examination reveals: sodium 143, potassium 4.1, chloride 94, and bicarbonate 24. What is your conclusion?
10. A patient with chronic renal failure was started on erythropoietin for anemia. The hospital protocol follows the manufacturer’s guidelines. The starting dose was 75 U/kg three times a week and the patient’s hematocrit was 25%. One month later, the patient’s hematocrit is reported at 30%, and the patient is asymptomatic. The hemoglobin is 10 g/dL. Which of the following should the pharmacist do?
