Chapter 22Renal disorders:

The kidneys play a major role in controlling blood pressure, regulating red blood cell (RBC) production,
breaking down drugs, metabolizing hormones, synthesizing vitamin D, managing electrolytes, and
balancing pH of the bloodstream. Although kidney dysfunction is seen in all ethnic groups, African
Americans have the greatest incidence of kidney disease. The kidneys receive 20% to 25% of the body’s
cardiac output. The glomerulus filters approximately 90 to 120 mL/min of blood, which is pushed
through Bowman’s capsule because of high hydrostatic pressure. The renal blood filtered per unit of
time, known as the glomerular filtration rate (GFR), is directly related to renal perfusion.

Peak function of the kidneys occurs at age 30 years; for each year after, GFR decreases by 1 mL/minute
until, by age 70 years, GFR is 70 mL/min.

The Nephron
Renal blood flow through the glomerulus requires high hydrostatic pressure to push blood through the
filtration process. As blood flows through the glomerulus and a membranous cap called Bowman’s
capsule, water and electrolytes leave the blood and pass into the proximal tubule. At this point, the
glomerular filtrate is very dilute and contains a high amount of electrolytes, glucose, and metabolic
waste products. At the proximal tubule, approximately 60% of water is reabsorbed back into the
bloodstream.

As the tubule fluid travels through the various parts of the nephron, water and electrolytes such as
sodium and potassium move to and from tubule fluid and blood. Within the next section of the nephron,
called the loop of Henle, urea is secreted into the tubule fluid. Urea is a composite of nitrogenous waste
that needs to be excreted.

At this juncture within the nephron, the tubule fluid, which contains urea, starts to resemble the
finished product: urine. Overall, the loop of Henle reabsorbs about 25% of filtered electrolytes, such as
sodium, chlorine, potassium, calcium, and bicarbonate, and 15% of the filtered water.

At the distal tubule, aldosterone acts to reabsorb more sodium and water into the bloodstream and
secrete potassium into the tubule fluid. Here again, tubule fluid is further concentrated and the body
saves water.

Finally, at the collecting duct under the influence of antidiuretic hormone, the last amount of water
needed by the body is reabsorbed from the tubule fluid back into the bloodstream. At this last stage, the
highly concentrated tubule fluid is urine.
Acid-Base Balance

Normal body function is dependent upon acid-base balance, and the kidneys play a major role through
regulation of bicarbonate and hydrogen reabsorption or secretion. Acids are produced during normal
metabolic processes, requiring the physiologic response of buffering to maintain the physiologic pH of
7.35 to 7.45. The kidneys’ role in maintaining acid-base balance involves excretion of excess hydrogen
ions [H+] and formation of bicarbonate ions [HCO3 –].

Waste Elimination

During the cell’s metabolic activity, waste products are accumulated. These waste products include such
substances as urea, uric acid, creatinine, and drug metabolites. If not excreted in the urine, waste
products become toxic to body tissues, particularly breakdown products of drugs. A reduction in renal
function can prolong the effect of some medications, which can lead to adverse effects or toxicity.
secretory Functions

The kidney has several unique secretory functions that are triggered by certain conditions in the body.
Hypoxia and low blood volume are two such conditions.

Control of Blood Pressure

The major mechanism whereby the kidneys influence systemic blood pressure and blood volume is the
renin-angiotensin-aldosterone system (RAAS). The RAAS contributes to sodium and water reabsorption
into the bloodstream at the renal tubules and potassium excretion. A specialized region of the nephron
called the juxtaglomerular apparatus is sensitive to sodium. These cells sense low sodium and, in
response, secrete renin. Other triggers for renin secretion include decreased renal perfusion and
increased sympathetic nervous system activity. The net effects of the RAAS activity are sodium and
water reabsorption, potassium excretion, and arterial vasoconstriction.

Red blood cell production:

The kidneys secre erythropoietin, which stimulates RBC’s production in the bone marrow, it is also
released in response to low oxygen levels in the arterial blood, also secreted in response to anemia and
reduced renal blood flow.

CLINICAL CONCEPT
Individuals who have chronic hypoxia, such as those with chronic obstructive lung disease, often
have higherthan-normal hemoglobin and hematocrit levels because of constant secretion of
erythropoietin. Conversely, patients with renal failure have lower hemoglobin and hematocrit
levels because of deficient erythropoietin.

Vitamin D Synthesis and Calcium Balances:

Kidneys synthesize components that compromise vitamin D, without kidney function vitamin D is
inactive, which affects the calcium absorption in the gastrointestinal tract which facilitates absorption of
calcium. When calcium absorption is diminished, disrupts calcium balance in the blood stream.

Glucose homestasis:

Renal tubules reabsorb glucose from the glomerular filtrate up to the renal threshold of glucose which is
180 mg/dL. If the blood glucose is higher the excess is excreted in the urine. Also kidneys can synthetize
glucose from amino acids in the process of gluconeogenesis for prolonged fasting or starvation. Kidneys
also are responsible for insulin degradation, that’s why patients with renal failure have a high insulin or a
decreased insulin clearance.

The kidneys are at risk for injury because they require a large blood flow in order to function and they
process potentially toxic waste products. For the nephrons to work, the blood entering at the
glomerulus needs to have high hydrostatic pressure. The kidneys are susceptible to ischemic injury if not
provided with high blood flow. All tubule fluid from the nephrons must travel toward the renal pelvis
and out the ureter. The nephrons need high pressure pushing tubule fluid out of the kidney without any
stasis or backflow. The tubule fluid contains waste products that can be toxic to the fragile nephron
cells. Many drug metabolites are particularly nephrotoxic. The nephron cells are at risk if urine outflow is
not maintained. Any obstruction to urine outflow, also called obstructive uropathy, can cause urine to
back up from the ureter into the renal pelvis and cause cellular injury.

the causes of kidney dysfunction are divided into three categories based upon the mechanism of injury:

1. prerenal dysfunction: caused by decreased blood flow and perfusion to the kidney.

2. intrarenal dysfunction: develops secondary to actual injuries to the kidney itself.

3. postrenal dysfunction: related to obstruction of urine outflow from the kidneys.

Pre-renal dysfunction: are process that affect glomeraluar filtration rate and is related to blood flow and
renal perfusion. Any condition that affects renal perfusion may lead to prerenal dysfunction. Reduced
cardiac output or deVere hypovolemia, during any kind of shock patient is vulnerable to prerenal
dysfunction. Mantainace of sufficient high blood pressure is necessary for kidney function and GFR
requires high hydrostatic pressure, large loss of blood from the body can cause kidney injury due to
ischemia.

Intrarenal dysfunction: direct damage to renal tissue, as in trauma or toxic injury causes nephron
damage, caused by nephrotoxic medications, renal infections or systemic illnesses. Common examples
NSAIDS use, and poststreptococcal glomerulonephritis.

Postrenal injury: is caused by obstruction of urine pathway, for example kidney stones, BPH, can cause
hydronephrosis which is a fluid filled swollen kidney. Urine is toxic for the nephron and urine stagnation
can cause infection.

Acute Tubular Necrosis

Ischemia and hypoxia can damage the renal tubules and result in acute tubular necrosis (ATN), the most
common cause of acute kidney injury (AKI). With ischemia there is sloughing of the cells of nephron
tubules into the tubular lumen, when the lumens gets blocked it prevents fluid from flowing through
them as consequence reducing urine formation, with the schemia there is additional damage to
intrarenal, unless this process is reversed renal failure with permanent injury to the kidney will occur.

Assessment: determining exposure to any medications or substances that would be nephrotoxic.

systemic illnesses or infections associated with renal damage need to be identified, such as hypertension
and diabetes are important causes of renal damage. Patients need to be asked about their urine patten,
excrection and the character of the urine.

Common questions to assess:

Does the urine have an unusual odor or color?

• Is the urine foamy? Is the urine very dark or tea-colored? • Is there blood in the urine? • Is there
pain or burning on urination? Is there abdominal or flank pain on urination?
• Have you noticed any change in the amount of urine or the frequency of urination?
ALERT! Long-term DM and HTN often lead to renal failure.

Risk Factors

Exposure to nephrotoxic agents is one of the greatest risks for the development of renal disorders.
The patient needs to describe the duration of the disorder, medications involved, and management of
the disorders. the patient should be asked about a recent streptococcal infection because
poststreptococcal glomerulonephritis can occur. Patients who have had major surgery are at risk for
altered renal function. Major surgery can reduce renal blood flow and lead to kidney injury. A reduction
in renal blood flow is also a concern for patients who have had an acute myocardial infarction or heart
failure. Renal ischemia commonly is a complication of severe heart failure.

Sings and symptoms: The symptoms can include fatigue, weakness, nausea, constipation, abdominal
pain, and confusion. Patients with renal calculi may have abdominal or flank pain in addition to
hematuria.

Costovertebral angle (CVA) tenderness is a classic sign of a kidney disorder, particularly infection

The presence of blood or protein in the urine is apparent to the patient, looks red, foamy, teacolored
urine indicates bilirubin as occurs in jaundice. All of this signs indicate further testing.
CLINICAL CONCEPT: Hematuria is most often a sign of renal calculi or an infection.

Normal total protein excretion does not usually exceed more than 150 mg/ day. Excess protein in the
urine is abnormal and is usually an indication of glomerular injury. when injured they demonstrate extra
permeability. Glomerular injury can occur in such disorders as glomerulonephritis, diabetes, and HTN.

Diagnosis:Renal function can be evaluated through examination of the urine and blood. Imaging studies
can be performed to evaluate the anatomy of the kidneys and renal blood flow and visualize renal
calculi, tumors, or cysts.

Urinalysis: basic examination, description and character of the urne as well as biochemical microscopic
analysis. the color varies according to the concentration of solutes and water content of the urine. For
example, a dehydrated person has an amber-colored urine, whereas a well-hydrated person has a light
yellow urine. hepatitis will cause a dark brown, tea-colored urine, caused by bile pigments.

Urine PH is neutral close to PH 7, but it can vary from acidic to basic. Specific gravity is from 1.001 when
dilute to 1.030 when highly concentrated, all of the reagent strips should be negative in healthy
individuals if any of these test are positive they are suggestive of a variety of illness.

TABLE 22-1. Urine Analysis Using Reagent Strips

Test Normal Common Etiology
value

GLUCOSE negative If positive: hyperglycemia,

diabetes
KETONES negative If positive: starvation or
diabetic ketoacidosis
PROTEIN negative Minimal: exercise or
or infection
trace Moderate: polycystic
kidney disease (PKD),
infection, heart failure,
diabetic kidney disease
Marked: PKD,
glomerulonephritis,
diabetic kidney disease,
nephrosis, lupus
nephritis
BLOOD negative If positive: infection or
kidney stone
BILIRUBIN negative If positive: hemolysis or
liver disease
UROBILINOGEN minimal If high: liver disease
 NITRITE negative If positive: urinary tract
infection
LEUKOCYTE negative If positive: urinary tract
ESTERASE infection
The presence of glucose and ketones is indicative of diabetic ketoacidosis. A positive leukocyte esterase
measures the amount of enzyme secreted by WBCs; a high amount is indicative of either a bladder or
kidney infection. Crystals are often seen in the urine of patients with renal calculi. Casts are substances
that are secreted into the nephron tubules and retain the shape of the tubules. They are made of
protein or fats and can be benign or signify kidney disease.

Blood Urea Nitrogen

Azotemia is the increase of blood urea nitrogen (BUN) within the bloodstream. The normal level for BUN
is 5 to 20 mg/dL. An elevated BUN can occur when there is a decrease in the GFR, which leads to
accumulation of nitrogenous waste products in the blood. Dehydration can also have high BUN levels
due to the concentration the urea in the urine.

In extremely muscular individuals, there is high nitrogen in the bloodstream because of high muscle
breakdown. The muscle cell proteins break down into amino acids, which are nitrogen compounds.
Another cause of high BUN occurs in persons on high protein diets, as the large load of protein
breakdown into amino acids raises nitrogen in the bloodstream. Because of the possible elevation of
BUN with nonrenal conditions such as dehydration, the clinician should not rely on BUN alone as an
indicator of renal dysfunction.

Serum creatinine: is a muscle breakdown product that is completelyfiltered at the glomerulus, normal
range is 0.5 to 1.5mg mg/dL. After it is filtered out of the bloodstream its not reabsorbed by the
nephron tubules. Accumulation fo serum creatinine indicates decreased filterinf of creatinine at the
glomerulus. Because serum creatinine is based on muscle tissue breakdown, serum creatinine can vary
depending on the patient’s muscle mass. A person who has an increased amount of muscle breakdown
daily may have an abnormally high serum creatinine, whereas a frail individual will have a low amount of
serum creatinine daily.

CLINICAL CONCEPT: Serum creatinine is a reliable indicator of kidney function.

ALERT! Nephrotoxic antibiotics include the aminoglycosides. Whenever these are administered, serum
levels of the medication and serum creatinine levels must be monitored.

Creatinine Clearance: sometimes assess the glomerular filtration rate, this test requires a measurement
of both blood and urine creatinie and 24 hour urine volume. The amount of creatine filtered at the
glomerulus is the total amount of creatinine that appears in the urine. A decreased creatinie clearance
indicates decreased GFR and impaired renal function. Caused by conditions such as renal disease, lack of
blood circulating to the kidnes, hypotension, heart failure and shock. Increased creatinine clearance
indicats more in the urine than normal it is common in pregnant women, patients with DM or those with
large protein intakes.
Imaging Studies

Visualization of the kidneys through various imaging studies can provide valuable information about
renal size and function. Renal ultrasound is used to determine the size of both kidneys. It can also be
used in the diagnosis of hydronephrosis, renal cysts, tumors, and calculi. Renal biopsy can be performed
if cancer is suspected but is not preferable because the kidney is a highly vascular organ and a great
amount of bleeding can occur.

ALERT! IV contrast-enhanced imaging studies should be avoided in patients with renal impairment
because radiopaque dye can cause renal failure. Dehydration markedly increases this risk.

Treatment: In treating renal disease, regardless of the etiology, all of the functions regulated by the
kidney need to be maintained. It is important to maintain fluid, electrolyte, and acid-base levels; control
blood glucose; control blood pressure; and monitor RBC production. sodium bicarbonate can help
control metabolic acidosis, whereas beta blocker medications can control blood pressure. Epogen is a
synthetic form of erythropoietin that can be used to stimulate RBC production. Diuretics can be used to
stimulate water loss from the body. However, when these medications cannot reverse the imbalances of
renal failure, dialysis is necessary. Indications for dialysis include persistent hyperkalemia,
uncompensated metabolic acidosis, and fluid volume excess that is unresponsive to diuresis. In relative
healthy individuals renal transplant may be considered.

Peritoneal Dialysis

In peritoneal dialysis (PD), the patient’s peritoneum is filled with a dialysis solution that pulls wastes and
extra fluid from the blood into the abdominal cavity. The dialysis solution, called the dialysate, contains
certain electrolytes that cause diffusion of solutes and ultrafiltration of fluid from the blood to cross the
peritoneal membrane. The principle of diffusion is employed due to substances waters tend to move
from an area of high concentration to an area of low concentration. After fliud is installed in the
peritoneal cavity for a period of time about fours hours called dwell time, the solution is drained from
and discarded. The process of draining and filling takes about 30 to 40 minutes. A typical schedule of PD
requires approximately four exchanges a day, each with a dwell time of 4 to 6 hours.

Hemodialysis is a treatment during which the patient’s blood is drawn out of the body at a rate of 200
to 400 mL/minute and passed through a device called a dialyzer. Commonly, a patient has an arterial-
venous fistula created in the arm that can facilitate this process. The blood is then returned to the body
via the cephalic vein. The dialysis solution is a sterile solution of electrolytes. Urea and other waste
products, such as potassium and phosphate, diffuse into the dialysis solution. During the treatment, the
patient’s entire blood volume (about 5,000 mL) circulates through the machine every 15 minutes.
Electrolytes, serum albumin, BUN, and serum creatinine are normalized during the dialysis procedure.
The procedure is usually required at least three times a week for 4 to 6 hours each session.

Continuous renal replacement therapy (CRRT) is similar to hemodialysis; however, it is a slower process
used for patients who are hemodynamically unstable and fluid overloaded. This continuous process
takes smaller volumes of blood from the patient and filters it through a dialyzer over 24 hours.
Acute glomerulonephritis (AGN) is a renal disorder in which an immunological mechanism triggers
inflammation that damages the membranes of the glomerulus. It can lead to significant illness because
the glomerulus is the critical, initial region of every nephron unit that filters the blood. Damage to the
glomerular capillaries causes a loss of vital substances, such as albumin, from the blood. AGN is the
cause of 25% to 30% of all cases of ESRD. In cases that progress to ESRD, the disease course is fairly
rapid. End-stage renal failure may occur within weeks or months of the onset of AGN. Most cases of
AGN occur in patients aged 5 to 15 years; only 10% occur in patients older than 40 years. It
predominantly affects males with a 2:1 male-to-female ratio.

Etiology: Poststreptococcal infection is the most common cause of AGN. Acute infection with group A
beta-hemolytic streptococcus (GABHS) usually begins as pharyngitis and then causes a secondary
immunological reaction at the glomeruli. AGN can also occur after a skin infection with GABS known as
impetigo, AGN can also arise from bacterial, virus and fungal infections, rubella, mumps, Epstein barr
virus, or cytomegalovirus. Also autoimmune disorders such as lupus causes AGN, acute can advance to
chronic, it is gradual and silent, by the time of diagnosis patient is in the early stages of ESRD.

Pathophysiology: AGN begins with an antigen-antibody reaction. An antigen, such as streptococcus,

enters the body and stimulates antibody synthesis. the antigen-antibody complexes damage the
structure of the glomeruli and cause nephron dysfunction throughout the kidneys. Glomerular injury
causes hyperpermeability of the capillaries, which allows loss of albumin and RBCs in the urine. The
large loss of albumin from the bloodstream causes proteinuria, also called microalbuminuria. Because
albumin content of the bloodstream decreases, diminished colloid oncotic pressure (COP) occurs
throughout the body. According to Starling’s Law of Capillary Forces, the decrease of COP causes an
imbalance in hydrostatic and oncotic pressure. The low COP is overcome by hydrostatic pressure, which
causes edema. Also due to diminished glomerular filtration of the blood, there is diminished urine
production, causing oliguria, develops as GFR decreases, the patient becomes hypovolemic and
edematous and blood pressure rises.

CLINICAL CONCEPT
A certain amount of urine production is necessary to excrete waste products. An inadequate
amount of urine is termed oliguria. Oliguria is less than 400 mL of urine output per day or fewer
than 20 mL of urine per hour.

Clinical presenation: sudden edema, hematuria, proteinuria and HTN, onset is 7-21 days after
streptococcal infection. This time is consistent with the time need to produce antibodies. Puffiness of
the eyelids, facial edema, urine is dark with RBCs described as cola-colored. Weakness, fever abdominal
pain and malaise, patient may complain of costovertebral angle tenderness.
 CLINICAL CONCEPT
Edema in kidney disease is most prevalent in the periorbital region.

CLINICAL CONCEPT
Costovertebral angle tenderness is a classic symptom of kidney infection.

Diagnosis: Serum creatinine and BUN will be elevated because of kidney dysfunction and should be
monitored during the course of treatment. Routine analysis will show low specific gravity of diluted
urine, caused by no concentration of urine by the kidneys. UA will show large amount of protein and
blood in the urine, creatinine clearance will be low because of dysfunctional kidneys do not excrete
nitrogenous wastes. Creatinine accumulates in the blood. Additionally, serum studies that are
diagnostically definitive include an elevated antistreptolysin O titer; a drop in C3 complement (an
immune mediator); and cryoglobulins, which are large immune complexes. Serum albumin will be low
because glomeruli are filtering albumin out of the blood into the tubules, then into the urine.

TReatment:The management of AGN is largely based upon clinical presentation and symptoms.
Antibiotics, antipyretics, and analgesics are needed. With systematic manifestations, such as edema and
elevated blood pressure, diuretics and antihypertensive agents may be indicated. Dietary restrictions of
sodium and protein are also advised. Plasmapheresis may be used to rid the blood of antiglomerular
antibodies. Immunosuppressants are also used in the treatment of AGN.

Nephrotic syndrome is a combination of clinical findings that occur when the glomerulus is damaged.
When glomeri are damaged they become hyperpermeable to proteins and other substances in the
bloodstream. Blood becomes depleted of albumin as they enter the nephron and get excreted with the
urine. Common causes of nephrotic syndrome include glomerulonephritis, DM and autoimmune
disease.

Epidemiology: Diabetic nephropathy is the most common type of nephrotic syndrome, with an
incidence of 50 to 100 cases per million population per year. Native Americans, Latino Americans, and
African Americans have a higher incidence than do Caucasians. There is a male predominance in the
occurrence of nephrotic syndrome, as there is for chronic kidney disease in general. However, nephrotic
syndrome secondary to systemic lupus erythematosus is more common in women.

Etiology Three systemic diseases—DM, amyloidosis, and systemic lupus erythematosus (SLE)—are
implicated in more than 90% of all cases of nephrotic syndrome. Other causes include immune-complex
deposition disease, vasculitis, allergies, pre-eclampsia, morbid obesity, malignant HTN, and infections
such as bacterial endocarditis and tuberculosis.

Pathophysiology: Glomerular damage occurs as a primary insult or secondary to one of the causes
described. Structural changes that occur in the glomerulus include injury to the endothelial cells,
derangement of the basement membrane, and damage to the epithelium. Massive albuminuria is a
consequence of the glomerular damage. As albumin is lost in the vascular space, edema forms because
of decreased colloidal osmotic pressure.
Clinical Presentation: Patients have albuminuria with consequent edema. Edema of the face is common,
especially in the periorbital region. With severe albumin loss, edema of the lower extremities, pleural
effusion, and ascites can develop. Patients also often present with hematuria and HTN.

Diagnosis: The workup for nephrotic syndrome includes urinalysis and blood tests for albumin, BUN, and
serum creatinine. Urinalysis usually shows proteinuria and hematuria. Elevations in BUN and serum
creatinine occur and are followed to assess renal function. The serum albumin level is classically low in
nephrotic syndrome, below its normal range of 3.5 to 4.5 g/dL. Also should test for Hep B, HIV, Lupus,
including ANA, antidouble stranded deoxyribonucleic acid antibodies. (anti-dsDNA), all of this exams are
commonly done when nephrotic syndrome etiology is unclear. In immunological etiologies of nephrotic
syndrome, complement is decreased in the bloodstream.

A 24 hour hour urine sample is collected for analysis the urine can contain up to 3grams of protein in a
when its normal level is fewer than 150mg per day.

Treatment: The patient with nephrotic syndrome needs to be vigilant of nutritional needs. The diet
should provide adequate energy (caloric) intake and adequate protein (1 to 2 g/kg/d). However,
supplemental dietary protein is of no proven value because it will be excreted. A low-sodium diet (fewer
than 1,500 g/day) will help to limit fluid overload. Adequate fluid intake is essential but overhydration
should be avoided. Because albumin levels are low, it is important to recognize that there are less-
binding sites for drugs. This will increase the amount of free active drug in the bloodstream. Also in
nephrotic syndrome, immunoglobulins are lost to the urine as well. This increases susceptibility to
infection. Medication regimens commonly include diuretics, anti-inflammatory agents, and, in certain
cases, immunosuppressants, ace inhibitors are used to control hyptertension
Complications: as nephrotic syndrome progresses, hyperlipidemia may be developed secondary to
increased lipoprotein synthesis in the liver. As the liver increases synthesis of albumin to replenish whay
its lost in the urine, it also hyper synthesizes lipids. There is an elevation of LDL and triglycerides.
Hyperlipidemia requires drugs that decrease liver synthesis of lipids such as statins. Also with increased
loss of protein in the urine, there is loss of antithrombin III and plasminogen the body’s natural
thrombolytic substances, there is increased risk of thromboembolism, patient may require
anticoagulants.

Nephrolithiasis: is the formation of stones, also called calculi, in the kidney. Although stones can
develop in other areas of the urological system, such as the ureter or bladder, kidney stones are most
common. Although pain is a presenting sign with all types of renal calculi, characteristics vary based
upon the stone’s location.

Epidemiology: In the United States, the lifetime risk of developing nephrolithiasis is approximately 12%
for men and 7% for women. Kidney stones most commonly develop in adults aged 20 to 49 years, with a
peak incidence at age 35 to 45 years old. A family history doubles the risk of kidney stones. Recurrence
of nephrolithiasis is common. After suffering a kidney stone, individuals have a 52% chance of suffering
another stone within 10 years.

Etiology: The exact cause of nephrolithiasis is unknown, but about 90% of patients who present with
clinical manifestations have at least one metabolic risk factor: hypercalcemia, hyperoxaluria,
hyperuricemia, hyperparathyroidism, or gout. In addition, low fluid intake is a significant risk factor
because dehydration enhances kidney stone formation. Hypercalciuria and low fluid content of the urine
are the most common predisposing factors that lead to nephrolithiasis

Excessive bone resorption caused by immobility, bone disease, hyperparathyroidism, and renal tubular
acidosis are all predisposing risk factors to calcium stone formation. Indinavir is a drug used for HIV
infection that predisposes to calcium stones. UTI and alkaline urine can predispose individuals to struvite
stones, which are usually large.

CLINICAL CONCEPT: Struvite stones commonly cause staghorn calculi, which can fill the entire renal
pelvis.

Pathophysiology

The formation of renal calculi involves many different factors that include dietary and intestinal
absorption factors, endocrine abnormalities, crystalline components in the blood, constituents of
urine, pH of urine, urinary tract structures, and heredity.

BOX 22-1. Predisposing Factors of Nephrolithiasis

There are a wide number of predisposing factors for nephrolithiasis. Nephrolithiasis is usually caused
by a number of different conditions that act together to cause precipitation of calculi in the kidney.

• Age greater than 40 years

• Male gender

• Certain medications (e.g., Sulfonamides, Indinavir, Acetazolamides)

• Dietary factors (e.g., purines, calcium, oxalate)

• Gastric bypass surgery

• Geographic location (hot, arid climates)

• Hypercalciuria

• Hyperparathyroidism

• Hyperuricemia

• High sodium diet

• Inflammatory bowel disease

• Inherited conditions (e.g., polycystic kidney disease, renal tubular acidosis)

• Low hydration/low urine volume

• Obesity

• Proteus urinary tract infection

The most common renal calculi are:

• calcium stones

• struvite (magnesium ammonium phosphate) stones

• uric acid stones

• cystine stones.

Seventy-five percent of renal calculi consist of calcium; most are composed of calcium oxalate. The
cause for these stones is attributed to hyperabsorption of calcium and oxalate from the gastrointestinal
tract.

Struvite stones account for 15% and are associated with chronic urinary tract infection and specific urine
pH. Usual organisms include Proteus, Pseudomonas, and Klebsiella species; urine pH is typically alkaline,
greater than 7.

Uric acid stones account for 6% of renal calculi and are associated with high purine intake, malignancy,
and gout. Purines are derived from the DNA of animal cells or cancer cells. High purine levels in the
bloodstream occur with high ingestion of meats or whenever there is high cellular breakdown, as in
treatment of malignancy. Approximately 25% of patients with uric acid stones have gout, which is
caused by hyperuricemia.

Cystine stones account for 2% of renal calculi and arise because of failure of renal tubular reabsorption
of cystine, an amino acid, into the blood. Urine becomes supersaturated with cystine, with resultant
crystal deposition.
Regardless of etiology or composition, a renal calculus flows into the ureter, becomes impacted, and
causes an obstruction. As the stone travels down the ureter, it scrapes against the ureter’s membrane,
causing minor bleeding into the urine and intense pain. The ureter spasms around the stone, causing a
colicky type of pain. Obstruction of urine can lead to increased pressure within the kidney. Based upon
the degree of obstruction, the stone can cause backpressure into the renal pelvis, a condition called
hydronephrosis. Hydronephrosis occurs when edema and distention of the renal pelvis interferes with
renal blood flow and function. Prolonged hydronephrosis causes compression of the kidney tissue,
ischemia, and irreversible kidney damage.

Clinical Presentation: Pain is the major symptom of nephrolithiasis. The pain is described as renal or
ureteral colic because it occurs in waves. It is also described as acute, excruciating pain in the flank and
upper outer quadrant of the abdomen on the affected side, and it is often accompanied by radiating
pain into the lower abdomen and groin (see Fig. 22-8). The patient is commonly bent over and cannot
find a comfortable position. Pain related to distention of the renal pelvis and calyx causes a dull, deep
ache in the flank or back that may vary in intensity. This type of pain is often associated with increased
intake of fluids that distends the calyx. Because of the intensity of the pain, the patient often presents
with cool, clammy skin; nausea; and vomiting. Hematuria is often noted because of damage caused by
obstruction or movement of the stone.

CLINICAL CONCEPT: Flank pain with radiation into the groin, hematuria, and crystalluria are classic signs
of nephrolithiasis.

Routine urine analyses are conducted, along with analysis of any stone fragments. Urinalysis provides
data related to hematuria, infection, urine pH, and presence of crystals. Additional diagnostic studies
that may be indicated include x-rays, intravenous pyelography, abdominal ultrasonography, retrograde
urography, and CT scanning.

Treatment: The approach to definitive treatment is based upon symptom management, as well as the
type and composition of the renal calculi. Pain relief is a priority because of the excruciating nature of
the pain that interferes with activities of daily living. Antibiotics may be necessary if urinary tract
infection is present. Most renal stones will pass spontaneously with administration of large amounts of
fluid to increase urine volume. Patients are instructed to drink at least 3 liters of fluid a day and strain all
urine. If the patient cannot pass the stone, lithotripsy is often used. In lithotripsy, sound waves break up
the stone into smaller particles to facilitate passage. If lithotripsy is unsuccessful, cystoscopic surgery
may be necessary. A major treatment goal is the patient is to prevent recurrence and is dependednt
upon determining the stone composition. Dietary changes may be necesseray, alteration of PH, Meat
and cranberry juice can keep the pH of urine acidic. A diet rich in citrus fruits, legumes, and vegetables
raises the pH and produces urine that is more alkaline.

Complications: Infection is one complication that may develop related to damage to renal tissue and
urinary stasis. With a urinary tract infection, there is a risk for pyelonephritis or urosepsis. Although
uncommon, with bilateral stones, renal damage caused by scarring from stone formation may lead to
acute or chronic renal failure (CRF). Hydronephrosis is a serious complication that occurs because of
complete obstruction of urine outflow that causes urine to back up into the renal pelvis and destroy
kidney tissue.
Pyelonephritis: is an infection of the renal pelvis and interstitium. It can be either acute or chronic, and
is most often secondary to bacteria, fungus, or virus. The incidence is high in young women related to
UTI, also increased in older male attributed to increased incidence of prostatis, 20-30% of pregnant
women develop pyelonephritis.

Etiology: There are numerous causes of pyelonephritis, and many of them are related to an obstruction
somewhere in the renal system, also referred to as an obstructive uropathy. Any kind of obstruction
predisposes the individuals to UTI. Staganation, of urine is a medium for bacterial growth which can
ascend to into the kidneys and cause pyelonephritis. An anatomic abnormality called vesicoureteral
reflux is a common predisposing factor for pyelonephritis. Reflux of urine occurs from the bladder into
the ureter. Neurogenic bladder is another condition that predisposes individuals to ascending bacterial
infection and pyelonephritis. Neurogenic bladder occurs in patients with conditions such as multiple
sclerosis, spinal cord injury, or transection of pelvic parasympathetic nerves. Because of the lack of
neurological control of the bladder, there is an inability to completely empty the bladder and urine
retention is common. Another risk for infection is the use foley catheters or cystoscopes, lastly
pregnancy risk for infection due to obstruction by the enlarged uterus and ureteral relaxation secondar
to to elevated progesterone levels.

The pathophysiology of pyelonephritis varies based upon whether the condition is acute or chronic.
With acute pyelonephritis, an inflammatory process develops, usually secondary to infection. Most
often the infection ascends from the lower urinary tract and is associated with gram-negative bacteria.
Less frequently, the infection is from the bloodstream, and is most often secondary to a staphylococcus
aureus infection. Chronic pyo is due to repeated kidney infection, recurrent inflammatory processes,
permanent damages develop in the renal tissue that increases chances for UTI.

The clinical presentation of acute pyelonephritis includes fever, chills, flank or groin pain, costovertebral
angle tenderness, urinary frequency, and dysuria. Flank or costovertebral angle pain can be mild or
severe, but the patient usually feels a general malaise. Nausea and vomiting commonly accompany this
disorder. Hematuria is present in 30% to 40% of patients. The patient may or may not present with signs
of lower urinary tract infection such as dysuria, urgency, and frequency. Symptoms can develop
gradually and can be present for weeks before the patient seeks health care. In patients with chronic
pyelonephritis, the clinical manifestations may be more subtle; Chronic pyelonephritis may present
more insidiously, particularly with unilateral involvement. As renal function declines because of this
disorder, polyuria, nocturia, and proteinuria are common.

CLINICAL CONCEPT: Costovertebral tenderness, fever, and pyuria are classic signs of pyelonephritis.

Diagnosis: In both acute and chronic processes, urine cultures are important in the diagnosis of
pyelonephritis. The most common bacteria that cause acute pyelonephritis is uropathogenic Escherichia
coli. Others include Staphylococcus saprophyticus, Proteus mirabilis, and Klebsiella pneumoniae. A
positive leukocyte esterase test is found with presence of WBCs in the urine. The nitrite test can be used
for bacteriuria and is usually positive, though it may be falsely negative in the presence of diuretic use,
low dietary nitrate, or organisms that do not produce nitrate reductase, such as Enterococcus,
Pseudomonas, or Staphylococcus. Gross hematuria usually does not occur in pyelonephritis and is more
common with cystitis, calculi, cancer, glomerulonephritis, tuberculosis, trauma, and vasculitis.
Proteinuria is expected (up to 2 g/day). When it exceeds 3 g/day, glomerulonephritis should be
considered.
Imaging studies such as intravenous pyelogram (IVP) are preferably ordered after acute pyelonephritis
has resolved. An IVP can be used to identify urinary tract abnormalities that can predispose the patient
to infection. CT scan and ultrasound imaging studies may or may not demonstrate findings. CT
urography is becoming a useful test that outlines the detailed structure of urological organs. Urological
procedures such as cystoscopy can demonstrate bladder and urethral disorders. In females, pelvic exam
should be done to rule out gynecological problems.

Treatment: Acute pyelonephritis is usually treated with 2 weeks of antibiotic therapy based upon
identification of the specific microorganism by urine culture. If symptoms recur, repeat urine cultures
are recommended at 1 and 4 weeks after completion of the antibiotic regimen. During exacerbations of
chronic pyelonephritis, antibiotics are administered. If some type of obstruction is found to be the
underlying cause of the recurrent infections, the obstruction must be relieved for cure. Treatment of
chronic pyelonephritis includes management of an infectious process and prevention of further renal
function deterioration.

Complications: with appropriate treatment long term complications are rare, it is estimated that 10 to
20% of ESRD is secondary to chronic pyelonephritis.

Polycystic kidney disease: is a genetic disorder that affects the kidneys and other organs. Because of the
development of cysts in the renal tissue, renal function is impaired. Cysts also develop in other organs of
the body, such as the liver.

The most common type is autosomal dominant polycystic kidney disease (ADPKD), one of the most
common inherited disorders. It is the most common hereditary cause of renal disease in adults and
accounts for 6% to 8% of patients on dialysis in the United States. Almost all people who inherit the
ADPKD gene will develop renal cysts by the age of 30 years.

The disease can also be inherited because of a recessive gene; this form is referred to as autosomal
recessive polycystic kidney disease (ARPKD). This is a much less common form because both parents
must carry the gene in order for an individual to develop the disorder. There is a 5% to 10% incidence of
ARPKD with no family history, and this is attributed to a sporadic type of gene mutation. The disease
caused by ARPKD is less severe than ADPKD, and the mean age of renal failure in affected patients is 74
years.

Etiology: Autosomal dominant polycystic kidney disease is categorized as either ADPKD 1 or ADPKD 2,
depending on the mutation of either of two genes. The majority of cases are ADPKD 1 caused by the PKD
1 gene mutation located at 16p13.3, which encodes for a protein called polycystin 1. The less common
type is ADPKD 2, which involves a mutation at 4q21-22 called the PKD 2 gene, which encodes for a
protein called polycystin 2. Both polycystin 1 and 2 are involved in renal epithelial cell cycle regulation
and intracellular transport of calcium. ADPKD 1 is a more severe disease than ADPKD 2.

Pathophysiology: Polycystic kidney disease leads to formation of fluidfilled cysts in both kidneys. The
renal epithelial cell cycle becomes dysfunctional, leading to hyperplasia of renal epithelial cells. The
hyperplastic cells cause an outpocketing of the nephron tubule walls, with the formation of cysts that fill
with fluid derived from glomerular filtrate.

The cystic structures have continual hyperplastic growth and proliferate within the kidney. Glomerular
filtrate accumulates in the cysts, and the surrounding normal renal tissue is compressed and damaged.
As cysts increase in number and size, the kidneys enlarge. Fibrotic changes occur in the kidneys with
time. The cystic structures also develop blood vessels. The blood vessels are extremely fragile and
susceptible to rupture, which causes leakage of blood into the cysts. With the entry of blood, the cystic
walls stretch, causing excruciating pain. Cysts often rupture into the renal calyces, causing gross
hematuria.

Aside from cystic kidneys, patients with PKD are also susceptible to disorders of other organs. Cysts can
form in the liver, pancreas, and spleen. Diverticula, which are saccular structures that form in the
intestinal wall, often occur in the colon. Heart valve problems such as mitral valve prolapse commonly
develop, causing heart murmur. The patient with PKD also has a susceptibility to cerebral aneurysms,
which are weak pouches that form in the walls of the cerebral arteries. The cerebral aneurysms often
rupture, causing hemorrhagic stroke, which is often fatal. Polycystic kidney disease also increases
susceptibility to renal carcinoma.

Clinical Presentation: Patients with PKD usually present with pain caused by the pressure associated
with fluid accumulation in the cysts. Because of stagnation of fluid within the cysts, uric acid and calcium
crystals can precipitate and renal calculi can develop, which cause obstruction. The patient presents
with the pain of renal colic and hematuria in these cases. Stagnation of fluid also increases susceptibility
to infection. Costovertebral angle tenderness, fever, and pyuria occur if pyelonephritis develops. In
addition, cysts place pressure on kidney blood vessels, which activates the RAAS. In this situation, the
patient will present with hypervolemia and HTN. If cerebral aneurysm is present, HTN can trigger a
hemorrhagic stroke. The patient with PKD can demonstrate various symptoms, depending on the
involvement ofother organs, such as the colon, liver, spleen, and pancreas. Thoracic aortic aneurysm is
also a common problem in patients with PKD.

Diagnosis: Ultrasonography and abdominal CT scans are used to diagnose PKD. In 80% to 90% of people
with PKD, cysts are detectable via CT scanning by the age of 20 years. Magnetic resonance imaging (MRI)
is the best diagnostic study that can visualize cysts in the kidneys and extrarenal organs. MRI can also
rule out renal carcinoma. Genetic testing can be used to determine the type of disease. Serum chemistry
profiles should include calcium and uric acid levels. Urinalysis shows microalbuminuria. Magnetic
resonance angiography should be used to investigate the possibility of cerebral aneurysms.

Treatment: Because there is no definitive treatment for management of PKD, treatment is primarily
supportive, with the goal to delay disease progression. Control of associated urinary tract infections and
HTN are integrated into the treatment plan. Angiotensin-converting enzyme (ACE) inhibitors or
angiotensin receptor blockers are commonly used to control blood pressure. Reversing metabolic
imbalances associated with ESRD is necessary. Such conditions as hyperkalemia, hypocalcemia, and
metabolic acidosis require treatment. Urinary tract infections are common in PKD and antibiotic
treatment is needed. Large cysts of the kidney can be surgically decompressed if the patient endures
severe pain. Hemodialysis is necessary because of ESRD. Patients are usually eligible for kidney
transplant. Development of cysts in the liver, hepatomegaly, and liver failure can occur in PKD. Patients
may require liver transplant.