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Nephrolithiasis specifically refers to calculi in the kidneys, but renal calculi and ureteral
calculi (ureterolithiasis) are often discussed in conjunction. The majority of renal calculi
contain calcium. The pain generated by renal colic is primarily caused by dilation, stretching,
and spasm because of the acute ureteral obstruction.
Stones obstructing ureteropelvic junction: Mild to severe deep flank pain without
radiation to the groin; irritative voiding symptoms (eg, frequency, dysuria);
suprapubic pain, urinary frequency/urgency, dysuria, stranguria, bowel symptoms
Stones within ureter: Abrupt, severe, colicky pain in the flank and ipsilateral lower
abdomen; radiation to testicles or vulvar area; intense nausea with or without
vomiting
Distal ureteral stones: Radiate into groin or testicle (men) or labia majora (women)
Stones passed into bladder: Mostly asymptomatic; rarely, positional urinary retention
Diagnosis
The diagnosis of nephrolithiasis is often made on the basis of clinical symptoms alone,
although confirmatory tests are usually performed.
Examination in patients with nephrolithiasis includes the following findings:
Tachycardia
Hypertension
Microscopic hematuria
Testing
The European Association of Urology recommends the following laboratory tests in all
patients with an acute stone episode[2] :
Urinary sediment/dipstick test: To demonstrate blood cells, with a test for bacteriuria
(nitrite) and urine culture in case of a positive reaction
Serum creatinine level: To measure renal function
Serum and urinary pH level: May provide insight regarding patients renal function
and type of calculus (eg, calcium oxalate, uric acid, cystine), respectively
Microscopic urinalysis
Imaging studies
The following imaging studies are used in the evaluation of nephrolithiasis:
Plain abdominal radiograph (flat plate or KUB): To assess total stone burden, as well
as size, shape, composition, location of urinary calculi; often used in conjunction with
renal ultrasonography or CT scanning
IVP (urography) (historically, the criterion standard): For clear visualization of entire
urinary system, identification of specific problematic stone among many pelvic
calcifications, demonstration of affected and contralateral kidney function
Retrograde pyelography: Most precise imaging method for determining the anatomy
of the ureter and renal pelvis; for making definitive diagnosis of any ureteral calculus
Management
Supportive care and pharmacotherapy
Medical treatment of nephrolithiasis involves supportive care and administration of agents,
such as the following:
IV hydration
Nonnarcotic analgesics (eg, APAP)
Alkalinizing agents (eg, potassium citrate, sodium bicarbonate): For uric acid and
cysteine calculi
morphine
sulfate,
Surgical option
Stones that are 7 mm and larger are unlikely to pass spontaneously and require some type of
surgical procedure, such as the following:
Stent placement
Percutaneous nephrostomy
Ureteroscopy
Percutaneous nephrostolithotomy
Open nephrostomy
Pathophysiology
Development of renal colic pain and renal damage
The colicky-type pain known as renal colic usually begins in the upper lateral midback over
the costovertebral angle and occasionally subcostally. It radiates inferiorly and anteriorly
toward the groin. The pain generated by renal colic is primarily caused by the dilation,
stretching, and spasm caused by the acute ureteral obstruction. (When a severe but chronic
obstruction develops, as in some types of cancer, it is usually painless.)
In the ureter, an increase in proximal peristalsis through activation of intrinsic ureteral
pacemakers may contribute to the perception of pain. Muscle spasm, increased proximal
peristalsis, local inflammation, irritation, and edema at the site of obstruction may contribute
to the development of pain through chemoreceptor activation and stretching of submucosal
free nerve endings.
The term "renal colic" is actually a misnomer, because this pain tends to remain constant,
whereas intestinal or biliary colic is usually somewhat intermittent and often comes in waves.
The pattern of the pain depends on the individuals pain threshold and perception and on the
speed and degree of the changes in hydrostatic pressure within the proximal ureter and renal
pelvis. Ureteral peristalsis, stone migration, and tilting or twisting of the stone with
subsequent intermittent obstructions may cause exacerbation or renewal of the renal colic
pain.
The severity of the pain depends on the degree and site of the obstruction, not on the size of
the stone. A patient can often point to the site of maximum tenderness, which is likely to be
the site of the ureteral obstruction
In summary, by 24 hours after a complete ureteral obstruction, the renal pelvic hydrostatic
pressure has dropped because of (1) a reduction in ureteral peristalsis; (2) decreased renal
arterial vascular flow, which causes a corresponding drop in urine production on the affected
side; and (3) interstitial renal edema, which leads to a marked increase in renal lymphatic
drainage.
Etiology
A low fluid intake, with a subsequent low volume of urine production, produces high
concentrations of stone-forming solutes in the urine. This is an important, if not the most
important, environmental factor in kidney stone formation. The exact nature of the tubular
damage or dysfunction that leads to stone formation has not been characterized.
Most research on the etiology and prevention of urinary tract stone disease has been directed
toward the role of elevated urinary levels of calcium, oxalate, and uric acid in stone
formation, as well as reduced urinary citrate levels.
Hypercalciuria is the most common metabolic abnormality. Some cases of hypercalciuria are
related to increased intestinal absorption of calcium (associated with excess dietary calcium
and/or overactive calcium absorption mechanisms), some are related to excess resorption of
calcium from bone (ie, hyperparathyroidism), and some are related to an inability of the renal
tubules to properly reclaim calcium in the glomerular filtrate (renal-leak hypercalciuria).
Magnesium and especially citrate are important inhibitors of stone formation in the urinary
tract. Decreased levels of these in the urine predispose to stone formation.
The following are the 4 main chemical types of renal calculi, which together are associated
with more than 20 underlying etiologies:
Calcium stones
Struvite (magnesium ammonium phosphate) stones
Cystine stones
Calcium stones
Calcium stones account for 75% of renal calculi. Recent data suggest that a low-protein, lowsalt diet may be preferable to a low-calcium diet in hypercalciuric stone formers for
preventing stone recurrences.[6] Epidemiological studies have shown that the incidence of
stone disease is inversely related to the magnitude of dietary calcium intake in first-time stone
formers.
Calcium oxalate, calcium phosphate, and calcium urate are associated with the following
disorders:
Hyperoxaluria - Treated with dietary oxalate restriction, oxalate binders, vitamin B-6,
or orthophosphates
Cystine stones
Cystine stones account for 2% of renal calculi. They arise because of an intrinsic metabolic
defect resulting in failure of renal tubular reabsorption of cystine, ornithine, lysine, and
arginine. Urine becomes supersaturated with cystine, with resultant crystal deposition.
Cystine stones are treated with a low-methionine diet (unpleasant), binders such as
penicillamine or a-mercaptopropionylglycine, large urinary volumes, or alkalinizing agents. A
24-hour quantitative urinary cystine determination helps to titrate the dose of drug therapy to
achieve a urinary cystine concentration of less than 300 mg/L.
Epidemiology
International statistics
Nephrolithiasis occurs in all parts of the world. The incidence of urinary tract stone disease in
developed countries is similar to that in the United States; the annual incidence of urinary
tract stones in the industrialized world is estimated to be 0.2%. Stone disease is rare in only a
few areas, such as Greenland and the coastal areas of Japan. A lifetime risk of 2-5% has been
noted for in Asia, 8-15% for the West, and 20% for Saudi Arabia.
In developing countries, bladder calculi are more common than upper urinary tract calculi;
the opposite is true in developed countries. These differences are believed to be diet-related.
An initial stone attack after age 50 years is relatively uncommon. Nephrolithiasis in children
is rare; approximately 5-10 children aged 10 months to 16 years are seen annually for the
condition at a typical US pediatric referral center.
Prognosis
Approximately 80-85% of stones pass spontaneously. Approximately 20% of patients require
hospital admission because of unrelenting pain, inability to retain enteral fluids, proximal
UTI, or inability to pass the stone.
The most morbid and potentially dangerous aspect of stone disease is the combination of
urinary tract obstruction and upper urinary tract infection. Pyelonephritis, pyonephrosis, and
urosepsis can ensue. Early recognition and immediate surgical drainage are necessary in these
situations.
The usually quoted recurrence rate for urinary calculi is 50% within 5 years and 70% or
higher within 10 years, although a large, prospective study published in 1999 suggested that
the recurrence rate may be somewhat lower at 25-30% over a 7.5-year period. Recurrence
rates after an initial episode of ureterolithiasis have also been reported to be 14%, 35%, and
52% at 1, 5, and 10 years, respectively.
History
Patients with urinary calculi may report pain, infection, or hematuria. Small nonobstructing
stones in the kidneys only occasionally cause symptoms. If present, symptoms are usually
moderate and easily controlled. The passage of stones into the ureter with subsequent acute
obstruction, proximal urinary tract dilation, and spasm is associated with classic renal colic.
Acute onset of severe flank pain radiating to the groin, gross or microscopic hematuria,
nausea, and vomiting not associated with an acute abdomen are symptoms that most likely
indicate renal colic caused by an acute ureteral or renal pelvic obstruction from a calculus.
Renal colic pain rarely, if ever, occurs without obstruction.
Patients with large renal stones known as staghorn calculi (see the image below) are often
relatively asymptomatic. The term "staghorn" refers to the presence of a branched kidney
stone occupying the renal pelvis and at least one calyceal system. Such calculi usually
manifest as infection and hematuria rather than as acute pain.
Important historical features are as follows:
Complications
Serious complications of urinary tract stone disease include the following:
Abscess formation
Serious infection of the kidney that diminishes renal function
Ureteral perforation
Extravasation
Urosepsis
Infected hydronephrosis is the most deadly complication because the presence of infection
adjacent to the highly vascular renal parenchyma places the patient at risk for rapidly
progressive sepsis and death.
Ureteral obstruction from a stone occurs in the presence of a urinary tract infection
(UTI), fever, sepsis, or pyonephrosis.
Surgical Care
In general, stones that are 4 mm in diameter or smaller will probably pass spontaneously, and
stones that are larger than 8 mm are unlikely to pass without surgical intervention. With MET,
stones 5-8 mm in size often pass, especially if located in the distal ureter. The larger the
stone, the lower the possibility of spontaneous passage (and thus the greater the possibility
that surgery will be required), although many other factors determine what happens with a
particular stone.
Dietary Measures
In almost all patients in whom stones form, an increase in fluid intake and, therefore, an
increase in urine output is recommended. This is likely the single most important aspect of
stone prophylaxis. Patients with recurrent nephrolithiasis traditionally have been instructed to
drink 8 glasses of fluid daily to maintain adequate hydration and decrease chance of urinary
supersaturation with stone-forming salts. The goal is a total urine volume in 24 hours in
excess of 2 liters.
As a rule, dietary calcium should be restricted to 600-800 mg/d in patients with dietresponsive hypercalciuria who form calcium stones. This is roughly equivalent to a single
high-calcium or dairy meal per day.
Prevention of Nephrolithiasis
The most common causes of kidney stones are hypercalciuria, hyperuricosuria,
hyperoxaluria, hypocitraturia, and low urinary volume. Each of these major factors can be
measured easily with a 24-hour urine sample using one of several commercial laboratory
packages now available. Kidney stone preventive therapy consists of dietary adjustments,
nutritional supplements, medications, or combinations of these.
Strongly encourage patients who have a stone at a young age (ie, < 25 y), multiple
recurrences, a solitary functioning kidney, or a history of prior kidney stone surgery to obtain
a 24-hour urine collection for stone prevention analysis, especially if they are motivated to
comply with a long-term stone prevention program. These 24-hour urine collection kits can
be obtained from a number of commercial medical laboratories.
Long-Term Monitoring
Patients who do not meet admission criteria may be discharged from the ED in anticipation
that the stone will pass spontaneously at home. Arrangements should be made for follow-up
with a urologist in 2-3 days. Patients should be told to return immediately for fever,
uncontrolled pain, or vomiting. Patients should be discharged with a urine strainer and
encouraged to submit any recovered calculi to a urologist for chemical analysis.
UTI female
Practice Essentials
Urinary tract infections (UTIs) are common in females, accounting for over 6 million patient
visits to physicians per year in the United States. Cystitis (bladder infection) represents the
majority of these infections (see the image below). Related terms include pyelonephritis,
which refers to upper urinary tract infection; bacteriuria, which describes bacteria in the
urine; and candiduria, which describes yeast in the urine.
Dysuria
Suprapubic tenderness
Flank pain and costovertebral angle tenderness (may be present in cystitis but suggest
upper UTI)
Bloody urine
Fevers, chills, and malaise (may be noted in patients with cystitis, but more frequently
associated with upper UTI)
Diagnosis
Diagnostic studies for UTI consist of dipstick, urinalysis, and culture. No imaging studies are
indicated in the routine evaluation of cystitis.
Current emphasis in the diagnosis of UTI rests with the detection of pyuria, as follows:
A positive nitrate test is highly specific for UTI, but it occurs in only 25% of patients
with UTI
Urine culture remains the criterion standard for the diagnosis of UTI. Consider obtaining
urine cultures in patients with probable cystitis if any of the following is present:
Immunosuppression
Recent urinary tract instrumentation
Recurrent infection
Advanced age
Definitions of UTI in women, based on culture results in clean-catch urine specimens, are as
follows:
Management
Oral therapy with an empirically chosen antibiotic that is effective against gram-negative
aerobic coliform bacteria (eg, Escherichia coli) is the principal treatment intervention in
patients with cystitis. The first-choice agents for treatment of uncomplicated acute cystitis in
women include the following:
Nitrofurantoin monohydrate/macrocrystals
Trimethoprim-sulfamethoxazole (TMP-SMX)
Fosfomycin
Clinicians may wish to limit use of TMP-SMX, to reduce the emergence of resistant
organisms
Duration of antibiotic treatment for acute, uncomplicated cystitis in women who are not
pregnant is as follows:
The vast majority of women with UTI present on an ambulatory basis and can be treated as
outpatients. Hospital admission may be indicated for some patients with complicated UTI.
Complicating factors include the following:
Impaired host defenses (eg, HIV infection, current chemotherapy, underlying active
cancer)
Background
Urinary tract infections (UTIs) are common in females, and cystitis (bladder infection)
represents the majority of these infections. Related terms include pyelonephritis, which refers
to upper urinary tract infection; bacteriuria, which describes bacteria in the urine; and
candiduria, which describes yeast in the urine. Very ill patients may be referred to as having
urosepsis.
UTI is defined as significant bacteriuria in the setting of symptoms of cystitis or
pyelonephritis. These infections account for a significant number of emergency department
(ED) visits,[3] and 20% of women develop at least one UTI. (See Epidemiology.)
Escherichia coli causes the majority of uncomplicated cystitis cases. Among the pathogens
responsible for the remainder are Staphylococcus saprophyticus, Proteus mirabilis, Klebsiella
pneumonia e, or Enterococcus faecalis. (See Etiology.)
Pathophysiology
The urinary tract is normally sterile. Cystitis represents bladder mucosal invasion, most often
by enteric coliform bacteria (eg, Escherichia coli) that inhabit the periurethral vaginal
introitus and ascend into the bladder via the urethra.
In recurrent E coli UTIs, peak colonization rates of the periurethral area 2-3 days prior to the
development of the symptoms of acute cystitis range from 46-90%. During this same period,
asymptomatic bacteriuria rates increase from 7% to 70%.[6]
Because sexual intercourse may promote this migration, cystitis is common in otherwise
healthy young women. Generally, urine is a good culture medium. Factors unfavorable to
bacterial growth include a low pH (5.5 or less), a high concentration of urea, and the presence
of organic acids derived from a diet that includes fruits and protein. Organic acids enhance
acidification of the urine.
If the defense mechanisms of the lower urinary tract fail, upper tract or kidney involvement
occurs and is termed pyelonephritis. Host defenses at this level include local leukocyte
phagocytosis and renal production of antibodies that kill bacteria in the presence of
complement. In general, there are 3 main mechanisms responsible for UTIs:
Periurogenital spread
Etiology
E coli causes 70-95% of both upper and lower UTIs. Various organisms are responsible for
the remainder of infections, including S saprophyticus, Proteus species, Klebsiella species,
Enterococcus faecalis, other Enterobacteriaceae, and yeast. Some species are more common
in certain subgroups, such as Staphylococcus saprophyticus in young women.
The most important risk factor for bacteriuria is the presence of a catheter. [8] Eighty percent of
nosocomial UTIs are related to urethral catheterization, while 5-10% are related to
genitourinary manipulation. Catheters inoculate organisms into the bladder and promote
colonization by providing a surface for bacterial adhesion and causing mucosal irritation. For
more information on this topic, see the Medscape Reference article Catheter-Related Urinary
Tract Infection.
Sexual intercourse contributes to increased risk, as does use of a diaphragm and/or
spermicide. Routine pelvic examinations are also associated with an increased risk of a UTI
for 7 weeks post procedure.[9] Women who are elderly, are pregnant, or have preexisting
urinary tract structural abnormalities or obstruction carry a higher risk of UTI.
UTIs are the most common type of infection following renal transplantation. Susceptibility is
especially high in the first 2 months following transplantation. Triggering factors include
vesicoureteral reflux and immunosuppression. Corynebacterium urealyticum (ie, CDC group
D2) has been reported to cause encrusted pyelitis and cystitis in these patients.
Calculi related to UTIs most commonly occur in women who experience recurrent UTIs with
Proteus, Pseudomonas, and Providencia species.
Candiduria is defined as more than 1000 CFU/mL of yeast from 2 cultures. Candida
albicans, which is germ tube positive, is the usual culprit. Germ tubenegative Candida
species (tropicalis, parapsilosis, glabrata, lusitaniae, krusei) are less common.
Risk factors for candiduria include diabetes mellitus, indwelling urinary catheters, and
antibiotic use. Candiduria may clear spontaneously or may result in (or from) deep fungal
infections.
Epidemiology
Age- and sex-related demographics
Uncomplicated UTIs are much more common in women than men when matched for age. A
study of Norwegian men aged 21-50 years showed an approximate incidence of 0.00060.0008 infections per person-year, compared with approximately 0.5-0.7 per person-year in
similarly aged women in the United States.
The largest group of patients with UTI is adult women. The incidence of UTI in women tends
to increase with increasing age. Several peaks above baseline correspond with specific
events, including an increase in women aged 18-30 years (associated with coitusso-called
honeymoon cystitisand pregnancy).
Rates of infection are high in postmenopausal women because of bladder or uterine prolapse
causing incomplete bladder emptying; loss of estrogen with attendant changes in vaginal flora
(notably, loss of lactobacilli), which allows periurethral colonization with gram-negative
aerobes, such as E coli; and higher likelihood of concomitant medical illness, such as
diabetes.
Of neonates, boys are slightly more likely than girls to present with UTI as part of a gramnegative sepsis syndrome. The incidence in preschool-aged children is approximately 2% and
is 10 times more common in girls. UTI occurs in 5% of school-aged girls, but it is rare in
school-aged boys.
Prognosis
Younger patients have the lowest rates of morbidity and mortality. Factors associated with an
unfavorable prognosis include the following:
Old age
General debility
Recent hospitalization
Diabetes mellitus
Chronic nephropathy
Underlying cancer
Intercurrent chemotherapy
History
The classic symptoms of urinary tract infection (UTI) in the adult are primarily dysuria with
accompanying urinary urgency and frequency. A sensation of bladder fullness or lower
abdominal discomfort is often present.
Because of the referred pain pathways, even simple lower UTI may be accompanied by flank
pain and costovertebral angle tenderness. In the emergency department, however, assume that
the presence of these symptoms represents upper UTI.
Bloody urine is reported in as many as 10% of cases of UTI in otherwise healthy women; this
condition is called hemorrhagic cystitis. Fevers, chills, and malaise may be noted in patients
with cystitis, though these findings are associated more frequently with upper UTI (ie,
pyelonephritis).
A history of vaginal discharge suggests that vaginitis, cervicitis, or pelvic inflammatory
disease is responsible for symptoms of dysuria; therefore, a pelvic examination must be
performed. Important additional information includes a history of prior sexually transmitted
disease (STD) and multiple current sexual partners.
Physical Examination
The patient appears uncomfortable but not toxic. The presence of toxic fever, chills, nausea,
and vomiting suggests pyelonephritis rather than cystitis; however, immunosuppressed and
even immunocompetent patients with pyelonephritis may exhibit few, if any, of these
symptoms. In elderly women, 50% of cases of cystitis also involve the upper tracts.[13]
The clinician may appreciate signs of dehydration, such as dry mucous membranes and
tachycardia. Clammy extremities and symptomatic orthostasis suggest poor vascular tone due
to gram-negative bacteremia rather than simple cystitis.
Most adult women with simple lower UTI have suprapubic tenderness. Pelvic examination
should be performed to exclude vaginitis, cervicitis, or pelvic tenderness (eg, cervical motion
tenderness, which suggests pelvic inflammatory disease).
Approach Considerations
Urinalysis
The most accurate method to measure pyuria is counting leukocytes in unspun fresh urine
using a hemocytometer chamber; greater than 10 white blood cells (WBCs)/mL is considered
abnormal. Counts determined from a wet mount of centrifuged urine are not reliable
Urine Culture
Urine culture remains the criterion standard for the diagnosis of UTI. Collected urine should
be sent for culture immediately; if not, it should be refrigerated at 4C. Two culture
techniques (dip slide, agar) are widely used and accurate.
If a Gram stain of an uncentrifuged, clean-catch, midstream urine specimen reveals the
presence of 1 bacterium per oil-immersion field, it represents 10,000 bacteria/mL of urine. A
specimen (5 mL) that has been centrifuged for 5 minutes at 2000 rpm and examined under
high power after Gram staining will identify lower numbers. In general, a Gram stain has a
sensitivity of 90% and a specificity of 88%.
The WBC count may or may not be elevated in patients with uncomplicated UTI, but it is
usually elevated in patients with complicated UTIs. Patients with complicated UTIs may have
anemia; for example, anemia is observed in 40% of patients with perinephric abscesses.
Adjunctive Therapy
Patients with intense dysuria may obtain symptomatic relief from a bladder analgesic, such as
phenazopyridine, to be used for 1-2 days. Do not prescribe phenazopyridine if the patient has
a sulfa allergy. Avoid long-term use, as this agent may mask symptoms of therapeutic failure
or recurrence. Many authors advise stressing the intake of plenty of fluids to promote a dilute
urine flow.
Diet
Hydration to accentuate unidirectional clearance of bacteriuria is recommended, especially if
an obstruction was relieved recently. Drinking cranberry juice (10 oz/day) or taking cranberry
tablets may offer some benefit in reducing recurrent UTI and does not appear to be harmful.
[34, 35]
Cranberries contain type A proanthocyanidins. This compound and its urinary metabolites
interfere with the adhesiveness of uropathogenic bacteria to the bladder epithelium. [36] Their
effect is not as significant as antibiotics, but they do not induce bacterial resistance. Because
of their variable intestinal absorption, it is difficult to design a valid study comparing them
head-to-head with antimicrobials.[34]
UTI MALE
Practice Essentials
Urinary tract infections (UTIs) are rare in adult males younger than 50 years but increase in
incidence thereafter. Causes of adult male UTIs include prostatitis, epididymitis, orchitis,
pyelonephritis, cystitis, urethritis, and urinary catheters. Owing to the normal male urinary
tracts many natural defenses to infection, many experts consider UTIs in males, by
definition, to be complicated (ie, more likely to be associated with anatomic abnormalities,
requiring surgical intervention to prevent sequelae).
Dysuria is the most frequent chief complaint in men with UTI. The combination of dysuria,
urinary frequency, and urinary urgency is about 75% predictive for UTI, whereas the acute
onset of hesitancy, urinary dribbling, and slow stream is only about 33% predictive for UTI.
Relevant clinical history includes the following:
Previous UTI(s)
Nocturia, gross hematuria, any changes in the color and/or consistency of the urine
Prostatic enlargement
Diagnosis
Perform a thorough physical examination in males presenting with genitourinary complaints.
Focus particularly on the patients vital signs, kidneys, bladder, prostate, and external
genitalia.
Examination findings may include the following:
Fever
Tachycardia
Prostatic tenderness
Inguinal adenopathy
Laboratory testing
The workup of male UTI is dependent on the suspected diagnosis.
Routine laboratory studies include urine studies, such as urinalysis, Gram staining, and urine
culture. The threshold for establishing true UTI includes finding 2-5 or more white blood
cells (WBCs) or 15 bacteria per high-power field (HPF) in a centrifuged urine sediment.
Note that a positive nitrite test is poorly sensitive but highly specific for UTI; false-positives
are uncommon. Proteinuria is commonly observed in UTIs, but it is usually low grade. More
than 2g of protein per 24 hours suggests glomerular disease.
Imaging studies
Consider imaging and urologic intervention in patients with the following:
Ultrasonography
Contrasted computed tomography (CT) scanning or helical CT scanning (currently
preferred by most experts)
Management
In general, all male UTIs are considered complicated. Consider the potential for renal
involvement when planning treatment strategies.
Inpatient management is recommended for patients with the following features:
Appear toxic
Have obstructive uropathy or stones
Analgesics
Other medications used in the management of male UTIsor etiologic conditions such as
prostatitis; epididymitis; pyelonephritis; or cystitis/urethritisinclude the following:
Broaden the antimicrobial coverage and add an antipseudomonal agent in patients with risk
factors associated with an unfavorable prognosis (eg, old age, debility, renal calculi, recent
hospitalization or instrumentation, diabetes, sickle cell anemia, underlying carcinoma, or
intercurrent cancer chemotherapy).
Surgery
Surgical intervention may be required in the patients with the following conditions:
Complications
Complications of acute bacterial prostatitis include bacteremia, septic shock, prostatic
abscess, epididymitis, seminal vesiculitis, and pyelonephritis. Suspect a prostate abscess if
fever does not resolve within 48 hours; if confirmed, add anaerobic coverage and arrange for
drainage. (See Prognosis.)
neuropathic pain. Chronic bacterial prostatitis often produces few or no symptoms related to
the prostate, but it is probably the most common cause of relapsing UTI in men.
Epididymitis
Epididymitis is a clinical syndrome caused by infection or inflammation of the epididymis.
This condition is the most common cause of acute scrotum in adult male populations. Longterm complications include abscesses, infarction, recurrence, chronic pain, and infertility
Orchitis
Because of the widespread use of mumps vaccination, orchitis is no longer a common
infection in the United States. Orchitis is one of the few genitourinary infections to result
from a viral pathogen.
Mumps orchitis occurs in 18% of postpubertal boys infected with the mumps virus. Other
viruses that can cause the disease include coxsackie B, mononucleosis, and varicella. Unlike
the majority of genitourinary infections, viral particles are spread to the testicle by the
hematogenous route. Granulomatous orchitis is rare and results from hematogenous
dissemination of tuberculosis, fungi, and actinomycosis.
Pyelonephritis
Pyelonephritis is an infection of the renal parenchyma. Infection usually occurs in a
retrograde, ascending fashion from the bladder, but it may occur hematogenously. The
ureteral orifice becomes edematous and loses its one-way valve function during infection.
Retrograde flow of bacteria into the upper urinary tracts and into the renal parenchyma results
in clinical symptoms.
Bacterial cystitis
Bacterial cystitis without concomitant infection in other portions of the genitourinary tract is
believed to be a rare event in males. The abrupt onset of irritative voiding symptoms (eg,
frequency, urgency, nocturia, dysuria) and suprapubic pain are clinically diagnostic.
Most cases of bacterial cystitis occur by an ascending mechanism. Bacterial cystitis in the
male is uncommon in the absence of anatomic abnormality, defect in bladder emptying
mechanism, or urethral catheterization (eg, poor bladder emptying from prostatic obstruction
or dysfunctional voiding). Elevated postvoid residuals allow bacteria to multiply to critical
levels. High voiding pressures and poor bladder compliance diminish the natural uroepithelial
resistance to infection.
Urethritis
Urethritis has been described for thousands of years. The term gonorrhea (gonus meaning
seed, rhoia meaning flow) was coined by Galen. The urethral nonsquamous epithelium can
be penetrated by N gonorrhoeae, resulting in periurethral microabscesses. Necrotic debris is
sloughed into the urethra lumen, producing a milky penile discharge.
Etiology
Risk factors for UTI and bacterial causes of prostatitis, epididymitis, orchitis, pyelonephritis,
cystitis, and urethritis are discussed in this section.
Risk factors
Obstruction from any cause is a major risk factor for the development of UTI, as are
instrumentation of the urinary tract, catheterization, and urologic surgery.
In males older than 50 years, prostatic hypertrophy with partial obstruction is the main
contributor to the increase in UTI. Risk factors observed more commonly in elderly or
institutionalized males include cognitive impairment, fecal or urinary incontinence, and the
use of catheters.
Catheter-associated bacteriuria risk factors include female sex, significant comorbid
conditions (especially diabetes mellitus), age older than 50 years, lack of systemic
antibiotic(s), and a serum creatinine level greater than 2mg/dL.
Risk factors for bacteremia secondary to catheter-associated UTI (CAUTI) are male sex, UTI
caused by Serratia marcescens, older age, underlying urologic disease, and an indwelling
catheter.
In young men, risk factors for acute cystitis include homosexual behavior with anal
intercourse, intercourse with a female infected or colonized with a uropathogen, lack of
circumcision, and human immunodeficiency virus (HIV) infection with CD4 counts of
200/L or less.
Prostatitis
Gram-negative uropathogens (eg, Enterobacteriaceae, such as E coli, Klebsiella, and
Pseudomonas) are acknowledged pathogens of the prostate. Probable pathogens include
Enterococcus and S aureus, and possible pathogens include coagulase-negative
Staphylococcus, Chlamydia, Ureaplasma, anaerobes, Candida, and Trichomonas.
Acknowledged nonpathogens of the prostate include diphtheroids, lactobacilli, and
Epididymitis
Chlamydia trachomatis and N gonorrhoeae are the most common pathogens in patients
younger than 35 years with UTI, whereas Enterobacteriaceae and gram-positive cocci are
frequent pathogens in older patients.
Orchitis
Orchitis is one of the few genitourinary infections resulting from viral pathogens, such as the
mumps, coxsackie B, Epstein-Barr (EBV), and varicella (VZV) viruses.
Urethritis
N gonorrhoeae is the most common cause of urethritis in males; nongonococcal causes of
urethritis include C trachomatis (in up to 50% of cases), Ureaplasma urealyticum,
Trichomonas vaginalis, and herpes simplex virus (HSV). The role of Mycoplasma in
urethritis is controversial.
Catheter-associated bacteriuria
Short-term catheters are placed for a mean duration of 2-4 days. The usual indications are for
acute illnesses, output measurement, perioperative routine, and acute retention.
Approximately 15% of patients develop bacteriuria, usually with a single organism (E coli).
Catheter-associated bacteriuria usually resolves after the catheter is removed; however, one
third of patients may have symptoms, and bacteremia is the most serious complication.
Approximately 10-30% of patients develop a fever, and the risk of postoperative wound
infection associated with bacteriuria is increased.
Epidemiology
The incidence of UTI in men approaches that of women only in males older than 60 years; in
men aged 65 years or older, 10% have been found to have bacteriuria, as compared with 20%
of women in this age group.
Internationally, there is a similar incidence in developed countries; however, in developing
countries where men have shorter life spans, the incidence of UTI due to prostatic
hypertrophy is lower.
The incidence of true UTI in adult males younger than 50 years is low (approximately 5-8 per
year per 10,000). In this population, the symptoms of dysuria or urinary frequency are usually
due to sexually transmitted disease (STD)related infections of the urethra (eg, gonococcal
and nongonococcal urethritis) and prostate.[5]
In men older than 50 years, the incidence of UTI rises dramatically (range, 20-50%
prevalence), because of enlargement of the prostate, prostatism, debilitation, and subsequent
instrumentation of the urinary tract. The spectrum of causative agents is also somewhat
broader in these older men.
History
In men, the most frequent chief complaint related to urinary tract infection (UTI) is dysuria.
In fact, complaints of dysuria, urinary frequency, and urgency are approximately 75%
predictive for UTI, whereas the acute onset of hesitancy, urinary dribbling, and slow stream
are only approximately 33% predictive for it. Other aspects to inquire about include the
following:
Previous UTI(s)
Nocturia, gross hematuria, any changes in the color and/or consistency of the urine
Prostatic enlargement
In a younger man, the presence of UTI is often associated with anatomic abnormality. In the
absence of this history, a detailed sexual history may implicate activities such as sex with a
new partner, sex with multiple partners, or other risk-taking behavior associated with sexually
transmitted disease (STD)-related urethritis, prostatitis, or epididymitis that may lead to UTI.
Physical Examination
Physical findings of UTI may include the following:
Fever
Tachycardia
Meatal discharge
Prostatic tenderness
Inguinal adenopathy
Prostatitis Syndromes
These syndromes tend to occur in young and middle-aged men. Symptoms may include pain
(in the perineum, lower abdomen, testicles, or penis or with ejaculation), bladder irritation,
and, sometimes, blood in the semen.
Orchitis
The most common presentation of orchitis is in a patient in the later stages of epididymitis. In
this situation, inflammation has spread to the adjacent testicle and results in a tender, warm,
and swollen hemi-scrotal mass. Patients have the characteristic history and urinary findings
of epididymitis.
Of patients with orchitis resulting from tuberculosis, 70% have other genitourinary or
pulmonary symptoms of this disease.
Viral orchitis is notable for the symptoms of the viral syndrome. Orchitis occurs in
approximately 18% of postpubertal boys infected with the mumps virus; symptoms usually
begin within 1 week of parotitis. Up to 30% of cases are bilateral, and sterility develops in up
to 10% of cases.
Pyelonephritis
Patients with pyelonephritis appear ill; have fever, chills, and flank pain; and may have
hypotension. Although fever is very suggestive of pyelonephritis, it has also been
demonstrated in some males with simple cystitis. Note that 30-50% of pyelonephritis cases
may be silent, without clinical symptoms.
In the older male, prostate enlargement along with delayed presentation are the primary
causes of pyelonephritis. Other historical risk factors include nephrolithiasis, neurogenic
bladder, prostatitis, or symptom duration greater than 5 days.
Classic findings with pyelonephritis include fever, chills, and flank pain/costovertebral angle
tenderness that follow the symptoms of UTI; these findings are combined with pyuria and
bacteriuria. Occasionally, the urinalysis and urine culture findings are negative, such as when
an obstruction of the upper urinary tract is present due to stone disease.
Urethritis
The incubation period of gonococcal urethritis is 2-6 days. Occasionally, 2 weeks may elapse
before symptoms such as dysuria; thick, milky discharge; and pruritus occur.
The incubation period of nongonococcal urethritis (NGU) is 2-6 weeks. The symptoms are
less severe and the discharge may be clearer than with gonococcal urethritis. Patients are
likely to have a higher level of education (ie, 90% of urethritis cases in college health
services is NGU) and fewer sexual contacts.
Because patients with urethritis have a thick, milky discharge, the underpants may be
impressively stained. Typically, patients with gonorrhea have a thicker, more copious
discharge, but significant overlap with chlamydial urethritis is not uncommon.
Dietary considerations
Keeping the patient well hydrated is important, especially if an obstruction was recently
relieved.
Drinking cranberry juice offers little benefit. Although it appears to inhibit E coli from
adhering to human uroepithelium, the amounts of bacteriostatic hippuric acid that are present
are unlikely to be clinically effective.
For complicated UTIs associated with struvite calculi, foods and vitamin supplements rich in
phosphorus and magnesium are advised. Remember that divalent cations (eg, magnesium)
can chelate oral fluoroquinolones, preventing their absorption from the gut.
Activity considerations
Bedrest and avoiding certain activities (eg, bike riding) may be beneficial in patients with
prostatitis. For patients with category IIIB (chronic, noninflammatory, abacterial) prostatitis,
bedrest for 2 weeks has been advocated. Sitting on ring cushions can be a simple way to
minimize symptoms.
In urethritis, sexual activity may be resumed when both partners have completed treatment;
barrier methods are encouraged. No one knows for certain when sexual activity may be
resumed for the other topics discussed in this article.
UTI Prevention
Preprocedure prophylaxis, condom use, and appropriate use of urinary catheters can reduce
the risk of infections and complications.[21]
GN AKUT
Background
Acute glomerulonephritis (GN) comprises a specific set of renal diseases in which an
immunologic mechanism triggers inflammation and proliferation of glomerular tissue that
can result in damage to the basement membrane, mesangium, or capillary endothelium. Acute
poststreptococcal glomerulonephritis (PSGN) is the archetype of acute GN. Acute nephritic
syndrome is the most serious and potentially devastating form of the various renal
syndromes.
Etiology
The causal factors that underlie acute GN can be broadly divided into infectious and
noninfectious groups.
Infectious
The most common infectious cause of acute GN is infection by Streptococcus species (ie,
group A, beta-hemolytic). Two types have been described, involving different serotypes:
Nonstreptococcal postinfectious GN may also result from infection by other bacteria, viruses,
parasites, or fungi. Bacteria besides group A streptococci that can cause acute GN include
diplococci, other streptococci, staphylococci, and mycobacteria. Salmonella typhosa,
Brucella suis, Treponema pallidum, Corynebacterium bovis, and actinobacilli have also been
identified.
Cytomegalovirus (CMV), coxsackievirus, Epstein-Barr virus (EBV), hepatitis B virus
(HBV),[4] rubella, rickettsiae (as in scrub typhus), and mumps virus are accepted as viral
causes only if it can be documented that a recent group A beta-hemolytic streptococcal
infection did not occur. Acute GN has been documented as a rare complication of hepatitis A.
[5]
Noninfectious
Multisystem systemic diseases that can cause acute GN include the following:
Polyarteritis nodosa - This causes nephritis from a vasculitis involving the renal
arteries.
Primary renal diseases that can cause acute GN include the following:
Guillain-Barr syndrome
Irradiation of Wilms tumor
Serum sickness
Epidermal growth factor receptor activation, [6] and possibly its inhibition by
cetuximab[7]
Epidemiology
International statistics
Worldwide, Berger disease is the most common cause of GN.
With some exceptions, the incidence of PSGN has fallen in most Western countries. PSGN
remains much more common in regions such as Africa, the Caribbean, India, Pakistan,
Malaysia, Papua New Guinea, and South America. In Port Harcourt, Nigeria, the incidence of
acute GN in children aged 3-16 years was 15.5 cases per year, with a male-to-female ratio of
1.1:1; the current incidence is not much different.[8]
Geographic and seasonal variations in the prevalence of PSGN are more marked for
pharyngeally associated GN than for cutaneously associated disease.[8, 9, 10]
Prognosis
Most epidemic cases follow a course ending in complete patient recovery (as many as 100%).
The mortality of acute GN in the most commonly affected age group, pediatric patients, has
been reported at 0-7%.
Sporadic cases of acute nephritis often progress to a chronic form. This progression occurs in
as many as 30% of adult patients and 10% of pediatric patients. GN is the most common
cause of chronic renal failure (25%).
In PSGN, the long-term prognosis generally is good. More than 98% of individuals are
asymptomatic after 5 years, with chronic renal failure reported 1-3% of the time.
History
A thorough history should be obtained, focusing on the identification of an underlying
systemic disease (if any) or recent infection. Most often, the patient is a boy, aged 2-14 years,
who suddenly develops puffiness of the eyelids and facial edema in the setting of a
poststreptococcal infection. The urine is dark and scanty, and the blood pressure may be
elevated. Nonspecific symptoms include weakness, fever, abdominal pain, and malaise.
Ask the patient about the onset and duration of the illness. Symptom onset is usually abrupt.
In the setting of acute postinfectious glomerulonephritis (GN), a latent period of up to 3
weeks occurs before onset of symptoms. However, the latent period may vary; it is typically
1-2 weeks for postpharyngitis cases and 2-4 weeks for cases of postdermal infection (ie,
pyoderma). The onset of nephritis within 1-4 days of streptococcal infection suggests
preexisting renal disease.
Identify a possible etiologic agent (eg, streptococcal throat infection [pharyngitis], skin
infection [pyoderma]). Recent fever, sore throat, joint pains, hepatitis, travel, valve
replacement, and/or intravenous drug use may be causative factors. Rheumatic fever rarely
coexists with acute PSGN.
Inquire about symptoms of acute glomerulonephritis, including the following:
Shortness of breath or dyspnea on exertion - This may occur secondary to heart failure
or pulmonary edema; it is usually uncommon, particularly in children.
Physical Examination
The following description does not address all of the physical findings that can be associated
with the nonnephrotic features of an infectious process, renal disorder, or systemic disease
that causes acute GN; to do so would be beyond the scope of this article.
Patients often have a normal physical examination and blood pressure; most frequently,
however, patients present with a combination of edema, hypertension, and oliguria.
The physician should look for the following signs of fluid overload:
Arthritis
Pharyngitis
Impetigo
Respiratory infection
Pulmonary hemorrhage
Scarlet fever
Weight gain
Abdominal pain
Anorexia
Back pain
Oral ulcers
Complications
Progression to sclerosis is rare in the typical patient; however, in 0.5-2% of patients with
acute GN, the course progresses toward renal failure, resulting in kidney death in a short
period.
Abnormal urinalysis (ie, microhematuria) may persist for years. A marked decline in the
glomerular filtration rate (GFR) is rare.
Pulmonary edema and hypertension may develop. Generalized
hypoalbuminemia may develop secondary to severe proteinuria.
anasarca
and
A number of complications that result in relevant end-organ damage in the central nervous
system (CNS) or the cardiopulmonary system can develop in patients who present with
severe hypertension, encephalopathy, and pulmonary edema. Those complications include the
following:
Hypertensive retinopathy
Hypertensive encephalopathy
Rapidly progressive GN
Nephrotic syndrome
Approach Considerations
Urinalysis and sediment examination are crucial in the evaluation of patients with acute
nephritic syndrome. Look for the following:
Protein
Blood
Dysmorphic RBCs
Acanthocytes
Granular casts
In some instances, marked sterile pyuria is present. The presence of RBC casts is almost
pathognomonic of glomerulonephritis (GN). Urine electrolyte, urine sodium, and fractional
excretion of sodium (FENa) assays are needed to assess salt avidity.
Streptozyme testing may be useful. Imaging studies are helpful in some patients, for
assessment of clinical signs suggesting extrarenal involvement or for structural evaluation of
the kidneys.
Histologic Findings
Diffuse endocapillary proliferative changes are found. The most common histologic patterns
are diffuse (72.1%), focal (12.8%), and mesangial (8.1%) proliferative GN in adults. [3] In
postinfectious GN, the glomerulus is hypercellular with marked cellular infiltration (ie,
polymorphonuclear neutrophils, monocytes)
Approach Considerations
Treatment of acute poststreptococcal glomerulonephritis (PSGN) is mainly supportive,
because there is no specific therapy for renal disease. When acute glomerulonephritis (GN) is
associated with chronic infections, the underlying infections must be treated.
Sodium and fluid restriction should be advised for treatment of signs and symptoms of fluid
retention (eg, edema, pulmonary edema). Protein restriction for patients with azotemia should
be advised if there is no evidence of malnutrition.
Bed rest is recommended until signs of glomerular inflammation and circulatory congestion
subside. Prolonged inactivity is of no benefit in the patient recovery process.
GN KRONIK
Background
Nearly all forms of acute glomerulonephritis have a tendency to progress to chronic
glomerulonephritis. The condition is characterized by irreversible and progressive glomerular
and tubulointerstitial fibrosis, ultimately leading to a reduction in the glomerular filtration
rate (GFR) and retention of uremic toxins. If disease progression is not halted with therapy,
the net results are chronic kidney disease (CKD), end-stage renal disease (ESRD), and
cardiovascular disease. Chronic glomerulonephritis is the third leading cause and accounts for
about 10% of all causes of CKD.
In accordance with this definition, the NKF developed guidelines that classify the progression
of renal disease into five stages, from kidney disease with a preserved GFR to end-stage
kidney failure. This classification includes treatment strategies for each progressive level, as
follows:
Stage 4 This stage is characterized by a severe decrease in the GFR (to 15-29
mL/min); the action plan is preparation for renal replacement therapy
Stage 5 This stage is characterized by kidney failure; the action plan is kidney
replacement if the patient is uremic
Pathophysiology
Reduction in nephron mass from the initial injury reduces the GFR. This reduction leads to
hypertrophy and hyperfiltration of the remaining nephrons and to the initiation of
intraglomerular hypertension. These changes occur in order to increase the GFR of the
remaining nephrons, thus minimizing the functional consequences of nephron loss. The
changes, however, are ultimately detrimental because they lead to glomerulosclerosis and
further nephron loss.
In early renal disease (stages 1-3), a substantial decline in the GFR may lead to only slight
increases in serum creatinine levels. Azotemia (ie, a rise in blood urea nitrogen [BUN] and
serum creatinine levels) is apparent when the GFR decreases to less than 60-70 mL/min. In
addition to a rise in BUN and creatinine levels, the substantial reduction in the GFR results in
the following:
Etiology
Progression patterns may be summarized as follows:
IgA nephropathy About 10% of patients with IgA nephropathy progress to CRF and
ESRD in 10 years[3]
Lupus nephritis Overall, about 20% of patients with lupus nephritis progress to CRF
and ESRD in 10 years; however, patients with certain histologic variants (eg, class
IV) may have a more rapid decline
History
The history should begin by focusing on cause-specific symptoms to determine the source of
the chronic kidney disease (CKD) if this is unknown. Recognition of such symptoms
facilitates the planning of further workup and management of the disease (if systemic).
The next step is to look for symptoms related to uremia to determine if renal replacement
therapy is needed. The following symptoms suggest uremia:
Pruritus
Peripheral neuropathy
Seizures
Tremors
The presence of edema and hypertension suggests volume retention. Dyspnea or chest pain
that varies with position suggests fluid overload and pericarditis, respectively. Leg cramps
may suggest hypocalcemia or other electrolyte abnormalities. Weakness, lethargy, and fatigue
may be due to anemia.
Physical Examination
Cause-specific physical examination findings are discussed elsewhere, in articles describing
the specific causes (see Etiology). Uremia-specific physical findings include the following:
Hypertension
Jugular venous distention (if severe volume overload is present)
Tenderness in the epigastric region or blood in the stool (possible indicators of uremic
gastritis or enteropathy)
Complications
The presence of the following complications generally indicates a need for urgent dialysis:
Metabolic acidosis
Pulmonary edema
Pericarditis
Uremic encephalopathy
Uremic neuropathy
Hyperkalemia
Laboratory Studies
Urinalysis
The presence of dysmorphic red blood cells (RBCs), albumin, or RBC casts suggests
glomerulonephritis as the cause of renal failure. Waxy or broad casts are observed in all forms
of chronic kidney disease (CKD), including chronic glomerulonephritis. Low urine-specific
gravity indicates loss of tubular concentrating ability, an early finding in persons with CKD.
See Urinalysis.
Renal ultrasonography
Obtain a renal ultrasonogram to determine renal size, to assess for the presence of both
kidneys, and to exclude structural lesions that may be responsible for azotemia. Small
kidneys often indicate an irreversible process.
Pharmacologic Therapy
Blood pressure management
The target blood pressure for patients with proteinuria in excess of 1 g/day is less than 125/75
mm Hg; for patients with proteinuria of less than 1 g/day, the target pressure is less than
130/80 mm Hg.
Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used and are usually the
first choice for treatment of hypertension in patients with chronic kidney disease (CKD).
NEFROPATI MEMBRANOSA
Background
Membranous nephropathy (MGN) is one of the more common forms of nephrotic syndrome
in the adult population. It can be idiopathic or secondary (30%). The two can be distinguished
by clinical, laboratory, and histological features.
Epidemiology
Biopsy reveals an underlying glomerular lesion in 25% of adults with nephrotic syndrome.
However, in patients older than 60 years, the incidence rate is 35%.
In the pediatric population, membranous nephropathy is rare but serious. Membranous
nephropathy accounts for approximately 3% of renal biopsies.
Race
The incidence of secondary forms may be influenced by the prevalence of hepatitis and
malaria in certain areas.
No increased incidence is reported in African Americans.
Sex
Membranous nephropathy has a predilection for males over females, with a male-to-female
ratio of 2:1.
Age
History
Onset is insidious.
Approximately 80% of patients describe edema.
Patients may present with nonspecific complaints of anorexia, malaise, and fatigue.
Physical
Ascites and pericardial and pleural effusions are uncommon, unless the nephrotic
syndrome is severe.
Causes
Causes of membranous nephropathy can be idiopathic or secondary. Often, distinguishing
between idiopathic and secondary causes is not possible based on clinical evidence alone. In
secondary membranous nephropathy, such as lupus and hepatitis, concomitant mesangial or
subendothelial deposits may be present. De novo membranous glomerulopathy (DNMG) can
develop post transplant. This can be in the context of a donor-specific alloantibody (DSA)
directed against HLA DQ7.[5]
Autoimmune diseases
o Ankylosing spondylitis
o
Dermatomyositis
Graves disease
Hashimoto disease
Rheumatoid arthritis
Sjgren syndrome
Systemic sclerosis
Infectious diseases
o
Enterococcal endocarditis
Filariasis
Hepatitis C
Hydatid cyst
Leprosy
Malaria
Schistosomiasis
Syphilis
Leukemia
Lymphoma
Melanoma
Drugs
o
Captopril
Gold
Lithium
Mercury-containing compounds
Penicillamine
Probenecid
Miscellaneous
o
Diabetes (uncommon)
Kimura disease
Sarcoidosis
Systemic mastocytosis
Laboratory Studies
Urine microscopy: Urine sediment is typically nephrotic, with oval fat bodies and
fatty casts; however, in mild cases, the urinalysis may reveal proteinuria without
formed elements in the sediment.
Serum creatinine
Serum albumin
Proteinuria (quantitative) with a 24-hour urine collection: A ratio of spot urine protein
to creatinine is easier to obtain, and the findings may be sufficient for screening
purposes.
Creatinine clearance
Antinuclear antibodies
Syphilis serology
Complement levels
Lipid profile
Urinary C5b-9
Imaging Studies
Sonogram
Procedures
Renal biopsy: Definitive diagnosis is made based on findings from a renal biopsy.
Histologic Findings
Pathologic features can be observed using light microscopy, immunofluorescence
microscopy, and electron microscopy.
Medical Care
Search for an underlying cause. Successful treatment of the underlying cause may be curative
in secondary forms.
A low-salt diet is key to reducing anasarca. Protein restrictions may or may not be
useful in reducing the rate of progression of chronic renal failure.
Diuretics help control edema. Loop diuretics are used most often.
NSAIDs help to decrease the proteinuria. These have been largely supplanted by
angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers
(ARBs).
ACE inhibitors decrease proteinuria and control hypertension; use ARBs for patients
intolerant of ACE inhibitors.
Hepatic 3-methylglutaryl
hypercholesterolemia.
Therapy with immunosuppressive agents is indicated in those patients who have the
following:
coenzyme
reductase
inhibitors
help
Progressive disease
Thromboembolism
Persistent nephrotic syndrome, male sex, and age older than 50 years
treat
Surgical Care
Transplantation is indicated if the patient progresses to ESRD. Some risk of recurrence in the
allograft is recognized.
Diet
Activity
Complications
Hypovolemia, with the possibility of acute renal failure, may occur in patients who
are overdiuresed. Hypovolemia exacerbates the adverse renal effects of ACE
inhibitors, ARBs, and NSAIDs.
Prognosis
The outcome depends on the renal function at the time of diagnosis and the amount of
proteinuria, ranging from remission without medication to ESRD.
MINIMAL CHANGE
Background
Minimal-change disease (MCD), also known as lipoid nephrosis or nil disease, is the most
common single form of nephrotic syndrome in children. It refers to a histopathologic lesion
in the glomerulus that almost always is associated with nephrotic syndrome. It typically is a
disease of childhood, but it also can occur in adults.
Epidemiology
Frequency
In preadolescents, minimal-change nephrotic syndrome (MCNS) makes up 85-95% of all
cases of nephrotic syndrome. In adolescents and young adults, the prevalence is 50%, while
in adults, MCNS accounts for 10-15% of primary nephrotic syndrome cases. The incidence
of nephrotic syndrome is 2-7 new cases annually per 100,000 children, and the prevalence is
15 cases per 100,000 children.
History
Facial edema is noted first. Edema may be preceded by an upper respiratory tract infection,
an allergic reaction to a bee sting, the use of certain drugs, or malignancies.
Malaise and easy fatigability can occur. Weight gain often is an additional feature.
The patient also may present with one or more of the following:
Hypovolemia
Hypertension
Thromboembolism
Infection
Causes
Almost all cases are idiopathic, but a small percentage of cases (approximately 10-20%) may
have an identifiable cause. Secondary cases may be due to any of the following:
Physical Examination
The blood pressure usually is normal in children [6] but may be elevated in adults. (In addition,
the plasma creatinine in adults is often slightly elevated at presentation.)
Dependent edema is the most prominent sign. The retina has a wet appearance. Subungual
edema with horizontal lines (called Muehrcke lines) also may occur.
Hernias may be found, and the elasticity of the ears may be decreased.
Heavy proteinuria over an extended period of time leads to a state of protein depletion with
muscle wasting, thinning of the skin, and growth failure.
Pleural and ascitic fluid can accumulate. Rarely, cellulitis, peritonitis, or pneumonia may be
the first indication of an underlying nephrotic syndrome.
Children may have growth failure.
Histologic Findings
Light microscopy
In children with frequently relapsing MCD, some involuted glomeruli may be present. These
lesions are small and sclerotic but retain their podocyte and parietal epithelial cell
constituents. The presence of these glomeruli is related to the duration of the disease.
The most common tubular lesion is protein and lipid droplets in epithelial cells due to
increased reabsorption. The presence of areas of tubular atrophy and interstitial fibrosis
should raise the suspicion of FSGS.
Approach Considerations
Urinalysis findings are benign in minimal-change disease (MCD), but profound proteinuria
and oval fat bodies may be observed. In children, the critical level for diagnosis is proteinuria
of more than 40 mg/h/m2. In adults, the threshold is more than 3.5 g/d/1.73 m2.
Hypoalbuminemia is an important marker of nephrotic syndrome. The level at which edema
occurs varies, but it tends to be lower in children than in adults. Nephrotic syndrome in
children is defined by a serum albumin of less than 2.5 g/dL. Hyperlipidemia also is a feature
of a nephrotic state.
Other laboratory findings are as follows:
Approach Considerations
Because of the high prevalence of minimal-change disease (MCD) in children with nephrotic
syndrome, an empiric trial of corticosteroids commonly is the first step in therapy.
Corticosteroids are the treatment of choice, leading to complete remission of proteinuria in
most cases. Approximately 90% of children respond within 2 weeks to prednisone at a dose
of 2 mg/kg/day (not to exceed 80 mg/day). After the remission of proteinuria, prednisone is
continued for another 6 weeks, at lower doses.
An adequate dietary protein intake, in accordance with the recommended daily allowance
(RDA) is necessary. No evidence suggests that hepatic albumin synthesis is elevated with
protein intake that is higher than the RDA.
Dietary sodium restriction helps forestall the progression of edema and also is prudent in the
management of hypertension.
Mobilization, rather than bed rest, is indicated to avoid thromboembolic complications.
Complications
The most common complications are the adverse effects of medications. Additional
complications may include peritonitis, infections, and acute renal failure. Acute renal failure
occurs because of either acute tubular necrosis or acute tubulointerstitial nephritis.
Patients with nephrotic syndrome have an increased incidence of arterial and venous
thromboemboli, particularly deep vein and renal vein thrombosis.
Hypercholesterolemia and hypertriglyceridemia can lead to accelerated atherosclerosis and
perhaps cause progressive glomerular injury.
Prognosis
Use of antibiotics and glucocorticoids and better-organized schedules of management have
substantially reduced the mortality rates associated with MCD. Deaths still occur from
disease complications.
Relapses eventually cease. Only approximately 5% of children continue to have steroidresponsive relapses when older than 18 years.
Adults have a similarly good prognosis. Survival rates of 85-90% are observed 10 years or
more after disease onset.
Chronic renal failure is extremely rare in patients who are steroid responsive. If chronic renal
failure occurs, the possibility that the pathologic lesion is different or has evolved must be
considered.