INFECTIONS

Urinary Tract Infection

Overview

Snapshot
A 23-year-old woman presents to her primary care physician due to pain with urination and
increased urinary frequency. She reports that her symptoms began approximately 3 days ago
and has not noticed any abnormal smell, vaginal discomfort, or vaginal discharge. The patient is
otherwise healthy and states that she has been having sexual intercourse more frequently with
her partner. She infrequently uses condoms and is on oral contraception. Her vital signs and
physical examination is unremarkable. She is started on oral nitrofurantoin for 5 days. (Acute
uncomplicated cystitis)

Introduction
 Clinical definition
o urinary tract infections (UTI) can either be asymptomatic or symptomatic and
encompasses
asymptomatic bacturia (ASB)

there is bacteria in the urinary tract; however, the patient has no symptoms
typically patients do not require treatment
pregnant women require screening and treatment
this is because ASB in pregnancy is associated with
pre-term birth
perinatal death
pyelonephritis in the mother
cystitis
prostatitis
pyelonephritis
o it is important to distinguish between uncomplicated and complicated UTI
uncomplicated UTI
this describes acute cystitis or pyelonephritis in outpatient women who
are not pregnant and do not have anatomic abnormalities or
instrumentation within the urinary tract
complicated UTI
this describes UTI that is not uncomplicated
Epidemiology
o incidence
50-80% of women acquire at least 1 UTI
20-30% of women with 1 UTI have recurrent infections
o demographics
more common in women, elderly, and infants
o location
bladder
prostate
 kidneys
o risk factors
female
benign prostatic hyperplasia
frequent sexual intercourse
history of UTI
incontinence
diabetes mellitus
vasicoureteral reflux
spermicide use
Pathogenesis
o in most cases bacteria ascends from the urethra to the bladder (cystitis)
bacterial organisms can further ascend through the ureter and infect the kidney
causing a renal parenchymal infection (pyelonephritis)
note that infection and symptom development depends on the
host
e.g., genetic background, behavioral factors, and underlying disease
pathogen
environmental factors
e.g., vaginal microflora, medical devices (e.g., indwelling catheters),
and urinary retention
for example, voiding and the host's innate immune response eliminates
bacterial colonization in the bladder after sexual intercourse
however, an indwelling catheter, stone, or any other foreign body
provides a surface where bacteria can colonize
hematogenous spread to the urinary tract can also result in a UTI; however, this is
rare
e.g., Salmonella, S. aureus, and Candida
Prognosis
o ASB in elderly or catheterized patients does not increase the risk of death
o recurrent UTI in children and adults does not result in chronic pyelonephritis or
renal failure
this is true when there are not anatomic abnormalities

Microbiology of Urinary Tract Infections

Microbe Findings Comments
Green metallic sheen on EMB
Most common cause of UTI
E. coli agar

Second most common cause in

S. saprophyticus - sexually active women

Large mucoid capsule and viscous

Third most common cause
K. pneumoniae colonies
 Red pigment production by select
S. marcescens strains -

Typically a nosocomial infection

Enterococcus - that is drug-resistant

"Swarming" appearance on agar

Urease positive
P. mirabilis Can result in struvite stone -
formation

Typically a nosocomial infection

Blue-green pigment
P. aeruginosa that is drug-resistant

Presentation
Symptoms/physical exam/findings
o ASB
asymptomatic patient with an incidental finding of bacteruria on urine culture
o cystitis
dysuria
urinary frequency
urgency
nocturia
suprapubic discomfort
gross hematuria
o prostatitis
dysuria
frequency
pain in the prostatic pelvic or perineal area
bladder outlet obstruction
fever and chills
o pyelonephritis
fever
this is the main feature that distinguishes pyelonephritis from cystitis
costovertebral angle pain
may be absent in mild pyelonephritis
obstructive uropathy in patients with diabetes
this is secondary to acute papillary necrosis that results in the papillae to
slough and subsequently obstruct the ureter
emphysematous pyelonephritis in patients with diabetes
gas is produced in the renal and perinephric areas

Studies
Labs
o urine dipstick
nitrite positivity suggests an E. coli infection or other infection of the
Enterobacteriaceae family
leukocyte esterase positive
urease positivity suggests an S. saprophyticus, Proteus, or Klebsiella infection
 o urinalysis
> 10 white blood cells (WBCs)/mL
> 1000 CFU/mL
white blood cell casts
a diagnostic finding of an upper urinary tract infection (e.g., pyelonephritis)
o urine culture
gold standard for diagnosing UTI
Histology
o chronic pyelonephritis
"thyroidization" of tubules due to eosinophilic casts contained in the tubules

Differential
Acute hemorrhagic cystitis
o can be caused by adenovirus
Urethritis
Nephrolithiasis
Genitourinary malignancy

Treatment
Medical
o TMP-SMX or nitrofurantoin
indications
first-line for uncomplicated UTI
second-line agents include a fluoroquinolone or -lactam
nitrofurantoin, ampicillin, and cephalosporins can be used in the treatment of
UTI in pregnant women
parenteral -lactam with or without aminoglycosides is used in
pregnant women with pyelonephritis
sulfonamides should not be used due to its possible teratogenic
effects (in first trimester) and kernicterus development (near term)
fluoroquinolones should also be avoided in pregnancy due to its
negative effect on the development of fetal cartilage
TMP-SMX or a fluoroquinolone is used in the treatment of prostatitis
o fluoroquinolones (e.g., ciprofloxacin)
indication
first-line for acute uncomplicated pyelonephritis
o fluconazole
indication
first-line treatment for Candida-related UTI
Operative
o nephrectomy
indications
treatment for xanthogranulomatous pyelonephritis
o percutaneous drainage
indications
treatment for emphysematous pyelonephritis and it may be followed by
elective nephrectomy

Complications
 Uncomplicated UTI
o complications are uncommon
Complicated UTI
o bacteremia
o urosepsis
o systemic inflammatory response syndrome (SIRS)
o renal and perinephric abscess
o emphysematous pyelonephritis
o xanthogranulomatous pyelonephritis
associated with long-term urinary tract obstruction and infection
this results in chronic destruction of the renal parenchyma via a
granulomatous process
o malakoplakia
o renal papillary necrosis
UTI in pregnancy
o pyelonephritis
o sepsis
o chorioamnionitis
o preterm labor
o low birth weight
o hypertension and pre-eclampsia
UTI in men
o acute or chronic prostatitis
o urethritis
o acute epididymitis
o orchitis

Urethritis
Snapshot
A 22-year-old man presents to his primary care physician due to pain with urination and a
burning sensation. The patient was in his usual state of health until 3 days prior to presentation.
He reports to having unprotected sex for the past few weeks. On physical examination, there is
purulent discharge at the urethral meatus. The patient receives a single intramuscular injection of
ceftriaxone with a 1 day course of oral azithromycin.

Introduction
Clinical definition
o urethritis describes inflammation of the urethra
Epidemiology
o incidence
gonococcal urethritis
second most commonly reported cause of sexually transmitted
infections (STI) in men
the most commonly reported is chlamydia
nongonococcal urethritis
the most common cause is chlamydia
o demographics
 most commonly occurs in sexually active young men
N. gonorrhoeae and C. trachomatis are commonly identified
o risk factors
sexual activity
Etiology
o microbial infection such as
N. gonorrhoeae
C. trachomatis
M. genitalium
o viruses such as
herpes simplex virus
Pathogenesis
o bacterial invasion results in an inflammatory response
Prognosis
o favorable for gonococcal or nongonococcal urethritis when treated appropriately

Presentation
Symptoms
o dysuria
o pruritis
o burning sensation
Physical exam
o discharge from the urethral meatus
o urethral meatus may appear inflamed

Studies
Labs
o first-void or first-catch urine
a positive leukocyte esterase on urine dipstick or having 10 WBC/hpf on
microscopy is suggestive of urethritis
nucleic acid amplification tests allows for the specific identification of the offending
organism such as
N. gonorrhoeae
C. trachomatis
M. genitalium
o Gram stain
2 WBC/hpf
organisms may or may not be present
lack of organisms suggests a nongonococcal urethritis
gram-negative diplococci suggests gonococcal urethritis

Differential
Cystitis
Epididymitis
Prostatitis

Treatment
Medical
 o intramuscular ceftriaxone and oral azithromycin
indications
this is initial therapy for men with urethritis
who have gonococcal urethritis supported by microscopic evidence
e.g., gram-negative intracellular diplococci
when there is high clinical suspicion of having a gonococcal infection
e.g., patient had sexual intercourse with someone with
known N. gonorrhoeae infection
note this combination covers nongonococcal urethritis caused by C.
trachomatis
o oral azithromycin or doxycycline
indications
first-line treatment for nongonococcal urethritis in the absence of
microscopic, laboratory, or clinical findings suggestive of N.
gonorrhea infection
note that treatment is directed against C. trachomatis and azithromycin also
covers M. genitalium

Complications
Gonococcal urethritis
o gonococcal prostatitis and pharyngitis
o acute epididymitis
o disseminated gonococcal infection
o infectious conjunctivitis
Nongonococcal urethritis
o acute epididymitis
o postinflammatory reactive arthritis (formerly known as Reiter's arthritis)
triad
urethritis
conjunctivitis
arthritis

GENETIC DISORDERS

Renal Cyst Disorders

Snapshot

A 26-year-old man presents to his primary care

physician with abdominal and lower back pain. He reports to also seeing blood in his
urine. Medical history is non-contributory. Family history is significant for his father
 requiring hemodialysis at a young age. Vitals signs are significant for a blood pressure
of 162/112 mmHg. A renal ultrasound is performed and shown. (Adult polycystic
kidney disease)

Adult Polycystic Kidney Disease (ADPCKD)

Clinical definition
o an inherited disorder that results in expansion of multiple renal cysts which
ultimately leads to end-stage renal disease
Epidemiology
o incidence
the most common inherited cause of kidney disease
o demographics
30 years of age
o risk factors
family history
Pathogenesis
o PKD1 or PKD2 mutations results in abnormal cell signaling that results in
cystogenesis
expansion of cysts results in progressive loss of nephrons
Genetics
o inheritance pattern
autosomal dominant
o mutations
PKD1 (on chromosome 16) or PKD2 (on chromosome 4)
PKD1 encodes polycystin-1
PKD2 encodes polycystin-2
Associated conditions
o cyst development in other organs such as
liver (most common extra-renal cyst type)
pancreas
seminal vesicle
note, that kidneys appear normal at birth
o vascular abnormalities such as
intracranial aneurysm
coronary artery aneurysm
o cardiovascular abnormalities
mitral valve prolapse
left ventricular hypertrophy
o diverticulosis
Prognosis
o with age the number and size of the cyst increases
Presentation
o symptoms
abdominal or flank pain
low back pain
hematuria
 urinary tract infection

Juvenile Polycystic Kidney Disease (ARPCKD)

Clinical definition
o a congenital fibrocystic disorder that results in renal and hepatic manifestations
Epidemiology
o incidence
1 in 20,000 live births
Pathogenesis
o PKHD1 gene mutation leads to abnormal production of fibrocystin and polyductin which
results in defects of the
renal tubular structures
dilatation and elongation of collecting ducts
bile duct structures
cystic dilatation of intra- and extra-hepatic bile ducts
Genetics
o inheritance pattern
autosomal recessive
o mutation
PKHD1 gene on chromosome 6
Associated conditions
o Potter sequence
Presentation
o symptoms/physical exam
bilateral abdominal mass in infants and children
hepatomegaly in infants and children
hypertension

Medullary Cystic Disease

Clinical definition
o an autosomal dominant inherited disorder that results in tubulointerstitial fibrosis of the
kidney
o medullary cystic disease is characterized by
autosomal dominant inheritance pattern
progressive and slow impairment in renal function that ultimately results in end-
stage renal disease
no or minimal proteinuria with a bland urine sediment
medullary cysts on renal ultrasound
in most cases medullary cysts are not present
can see shrunken kidneys on ultrasound

Horseshoe Kidney
Overview
Snapshot

A 2-year-old boy is referred by his pediatrician to a

nephrologist for recurrent urinary tract infections. He was born at 39 weeks and appeared
healthy at birth; however, he has developed significantly more urinary tract infections than
expected for a child of his age. Physical exam reveals increased fullness in the abdomen and an
MRI scan is obtained. Urine cultures are obtained and empirical antibiotics are started pending
culture results.

Introduction
Clinical definition
o congenital malformation of the renal system resulting in fused kidneys
Epidemiology
o common malformation found in 1/400 live births
o twice as common in males
Pathogenesis
o fusion of the lower poles of the kidneys (most common)
o trapping of the fused kidneys under the inferior mesenteric artery
o arrest of the normal retroperitoneal ascent of the kidneys
Associated conditions
o Turner syndrome
o trisomy 18 (Edwards syndrome)
Prognosis
o typically very good
o most patients remain asymptomatic
Presentation
Symptoms
o asymptomatic (most common)
o increased rate of urinary tract infections
o hydronephrosis due to
ureteropelvic junction obstruction
o renal stones
Physical exam
o abdominal fullness upon palpation

Imaging
Kidney ultrasound
o indications
initial evaluation of symptomatic patients
Voiding cysturethrogram
o indications
further evaluation of abnormal anatomy
o findings
fusion of kidney poles trapped under the inferior mesenteric artery
Intravenous pyelogram
o indications
for evaluation of symptomatic kidney stones
o findings
filling defect at the level of the obstruction

Differential
Unilateral renal agenesis
Posterior urethral valves
Multicystic dysplastic kidney
Duplex collecting system

Treatment
Conservative
o no treatment for asymptomatic patients
Medical
o antibiotics
indication
urinary tract infections
outcomes
very good

Complications
Postrenal kidney failure due to kidney stones
o rare since most cases are asymptomatic
o treatment
removal of kidney stones
Hydronephrosis if obstruction is left untreated
Congenital Bladder Disorders
Snapshot
A 2-year-old boy is brought to his pediatricians office for evaluation of a wet umbilicus. His
parents report noticing a persistently wet belly button since birth, and attributed that to healing
after birth. However, now that he is 2-years-old and starting to interact with other children, they
are concerned that he may be bullied for having a wet umbilicus. His past medical history is only
significant for a large umbilicus at birth. On physical exam, clear liquid is leaking from his
umbilicus without erythema or purulence. He is scheduled for an ultrasound later that
week.(Patent urachus)

Exstrophy of the Bladder

Clinical definition
o failure of caudal fold closure of ventral abdominal wall to close around the bladder
Epidemiology
o incidence
3-5 per 100,000
o demographics
males > females
more frequent in first-born children
Caucasian > other ethnicities
Associated conditions
o often associated with epispadias (congenital defect of penis)
often part of exstrophy-epispadias complex (EEC)
o inguinal hernia
Presentation
o phyical exam
low set umbilicus
open bladder plate and exposed urethra
inguinal hernia
may have genital abnormalities
Imaging
o prenatal ultrasound
indications
routine prenatal care
findings
absence of bladder filling
diminutive genitalia
o MRI
indications
to confirm findings of ultrasound
 Treatment
o reconstructive surgery
Complications
o risk of adenocarinoma

Urachal Disorders
Clinical definition
o congenital bladder disorder that results from a failure to obliterate the urachus
urachus is the duct between fetal bladder and the umbilicus
Epidemiology
o incidence
1% or less of boys
Classification
o patent urachus
complete failure of urachus to obliterate
presentation
physical exam
giant umbilical cord at birth
persistent urine discharge from umbilicus
complications
urinary tract infections
o urachal cyst
failure of urachus to completely obliterate
results in persistence of fluid-filled cavity between umbilicus and bladder
presentation
physical exam
umbilical mass
infection with tenderness and erythema below the umbilicus
complications
adenocarcinoma
o vesicourachal diverticulum
failure of urachus to completely obliterate
to a lesser extent than that in urachal cyst
presentation
physical exam
outpouching of the bladder
ureteral obstruction
Imaging
o ultrasound
initial imaging
Treatment
o surgical resection
indication
for correction of urachal cyst and patent urachus
RENAL FAILURE

Acute Tubular Necrosis

Snapshot

A 52-year-old man with a past medical history of diabetes mellitus

presents with fever and acute onset left lower quadrant abdominal pain. CT scan with contrast
shows acute diverticulitis. He is started on broad-spectrum antibiotics. The next day, daily labs
reveal a rise in creatinine from 0.7 mg/dL to 2.0 mg/dL. Urinalysis is obtained and a significant
amount of muddy brown casts is found. He is immediately started on intravenous normal saline.

Introduction
Clinical definition
o intrinsic acute kidney injury (AKI) to the kidneys from ischemia and/or toxins
Epidemiology
o incidence
US incidence
most common cause of AKI in hospitalized patients
o risk factors
pre-existing kidney disease
Etiology
o ischemia
hypovolemia
sepsis
o nephrotoxic injury
drugs
aminoglycosides
contrast for imaging
heavy metals
crystals
calcium oxalate crystals from ethylene glycol
urate crystals from tumor lysis syndrome
myoglobinuria
hemoglobinuria
Pathogenesis
o decreased renal blood flow results in ischemia
this results in death of renal tubular cells

in particular the proximal convoluted tubule and thick ascending limb are affected
o nephrotoxicity leads to damage in renal tubules
in particular proximal convoluted tubule is affected
Prognosis
o 3 stages of disease
inciting event
oliguric (maintenance) phase
1-3 week duration
risk of electrolyte abnormalities
hyperkalemia
metabolic acidosis
uremia
polyuric (recovery) phase
BUN and creatinine return back to normal
re-epithelialization of tubules
risk of hypokalemia
o prognostic variable
negative
requiring dialysis
o survival with treatment
over half of patients fully recover
5-11% require long-term dialysis
50% mortality in those needing dialysis

Classification of Acute Renal Failures

Urinary Indices Pre-Renal Intrinsic Renal Post-Renal
Urine osmolality > 500 < 350 < 350
(mOsm/kg)
< 20 > 40 > 40
Urine Na (mEq/L)
> 20 < 15 < 15
Serum BUN:creatinine
FENa (%)
< 1% > 2% > 2%
(fractional excretion of
Na)
FEUrea (%) (fractional < 35% 50-65 % -
excretion of urea)

Presentation
Symptoms
o primary symptoms
signs of acute renal failure
vomit
diarrhea
blood loss
shock
altered mental status
oliguria or polyuria
 Physical exam
o signs of volume overload
edema
jugular venous distention
decreased breath sounds in pulmonary edema

Imaging
Ultrasound
o indications
if an obstruction needs to be ruled out (post-renal cause of AKI)
best initial test
o findings
can see hydronephrosis or stones

Studies
Labs
o serum potassium
hyperkalemia during oliguric phase
hypokalemia during polyuric phase
o anion gap metabolic acidosis
o BUN
o creatinine
BUN:creatinine ratio < 15
Urinalysis with microscopy and sediment analysis
o granular casts
muddy brown from sloughing of tubular cells
Diagnostic criteria
o diagnosis of AKI
serum creatinine of 0.3 mg/dL within 48 hours
serum creatinine of 1.5 fold from baseline
o signs of acute tubular necrosis
urine osmolality < 350-500 mOsm/kg
muddy brown casts on urine sediment analysis
fractional excretion of sodium > 2%
decreased BUN:creatinine ratio

Differential
Prerenal azotemia
o BUN:creatinine ratio > 20
Post-renal azotemia
o source of obstruction found on imaging
e.g., stones or congenital abnormality

Treatment
Conservative
o supportive care
remove nephrotoxic agent
intravenous hydration
close electrolyte and fluid level monitoring
indications
 for all with suspected acute tubular necrosis
Medical
o renal replacement therapy (dialysis)
indications
signs of fluid overload
toxic electrolyte levels

Complications
Electrolyte abnormalities
o hypokalemia
o hyperkalemia
Volume overload

Renal Papillary Necrosis

Snapshot
A 50-year-old man with a history of diabetes mellitus presents to the emergency room for gross
amounts of blood in his urine. He denies any pain with urination and has never had hematuria
before. He has no family history of cancer and does not smoke. Physical exam is unremarkable.
His urinalysis reveals hematuria, proteinuria, and necrotic tissue.

Introduction
Clinical definition
o necrosis and sloughing of renal papillae
Epidemiology
o demographics
middle-aged adults
uncommon in children, except in those with sickle cell disease or trait
o risk factors
sickle cell disease or trait
acute severe pyelonephritis
analgesics such as NSAIDs
one of the most common and preventable risk factors
phenacetin
diabetes mellitus
tubulointerstitial nephritis
kidney stones causing obstruction
indinavir (anti-retroviral drug)
Pathogenesis
o due to ischemia
o in sickle cell trait or disease
sickling is promoted in the renal medulla
due to low oxygen tension, low pH, and high osmolality (pulling water out of
red blood cell and increasing concentration of hemoglobin S)
increased blood viscosity leads to infarcts and causes papillary infarcts
o in analgesic use
NSAIDs inhibit prostaglandin synthesis (remember that prostaglandins vasodilate)
this predisposes patients to renal hypoperfusion and ischemia, especially in those
with pre-existing renal disease or any other risk factors for renal papillary necrosis
Prognosis
 o prognostic variable
negative
concomitant diabetes
older age

Presentation
Symptoms
o primary symptoms
fever and chills
sudden onset flank or abdominal pain
o may be asymptomatic
o hematuria
o pyelonephritis
Physical exam
o tenderness to palpation in the flank or abdomen

Imaging

Radiographs
o indications
if obstruction, such as kidney stones, is suspected
not diagnostic
o recommend views
kidneys, ureters, and bladder (KUB)
o findings
hydronephrosis from obstruction
may visualize kidney stones
CT
o indications
typically performed if patients present with hematuria, even if renal papillary
necrosis is suspected, as hematuria can indicate malignancy in the bladder
o views
CT of abdomen and pelvis
o findings
hydronephrosis
kidney stones
ring shadows in medullae
loss of papillae
Intravenous urography (IVU)
 o indications
if CT scan is inconclusive and suspicious for renal papillary necrosis remains high
if there is no suspicion of obstruction but suspicion of renal papillary necrosis
remains high
o findings
ring shadow from desquamated papillae - ring sign

Studies
Labs
o serum creatinine
if there is a sudden rise in creatinine, consider renal papillary necrosis in patient
with diabetes or chronic urinary obstruction
Urinalysis
o hematuria
o pyuria
o proteinuria

Differential
Nephrolithiasis
o kidney stone seen on imaging without evidence of renal papillary necrosis
Tubulointerstitial nephritis
o often presents with rash, arthralgias, and eosinophilia in the urine

Treatment
Medical
o supportive care with fluid resuscitation
indications
for all patients

Complications
Chronic pyelonephritis
Sepsis

Acute Kidney Injury

Snapshot
A 56-year-old man presents with lower abdominal pain. His symptoms have progressively
worsened over the course of the day. Medical history is significant for benign prostatic
hyperplasia on tamsulosin. His blood pressure is 144/106 mmHg (normally, his blood pressure is
120/80 mmHg). On physical examination he has bladder distension. Laboratory testing is
significant for a creatinine of 2.4 mg/dL (last serum creatinine was 0.7 mg/dL.) (Post-renal acute
kidney injury likely secondary to benign prostatic hyperplasia)

Introduction
Clinical definition
o acute reduction in glomerular filtration rate (GFR)
recall that GFR represents the sum of the filtration rates of nephrons
therefore, GFR reflects functioning renal mass
Epidemiology
 o risk factors
hypertension
chronic kidney disease
dehydration and volume depletion
diabetes
chronic liver or lung disease
Etiology
o prerenal causes
decreased renal perfusion (e.g., hemorrhage, congestive heart failure, and diuretic
use)
o intrarenal causes
acute tubular necrosis
ischemia and toxic causes
interstitial nephritis
glomerulonephritis
vasculitis
hemolytic uremic syndrome
o postrenal causes
urinary flow obstruction (e.g., benign prostatic hyperplasia and nephrolithiasis)
Pathogenesis
o based upcome etiology (look at etiology)
Prognosis
o lower rates of recovery in patients > 65 years of age
o increased risk of end-stage renal disease, chronic kidney disease, and mortality

Presentation
Symptoms
o may be asymptomatic
o oliguria
o anuria
o polyuria
o confusion
Physical exam
o hypertension
o edema
o decreased urine output

Imaging
Renal ultrasound
o indication
initial imaging study for assessing acute kidney injury
can assess for renal size and hydronephrosis
to assess for postrenal obstruction

Studies
Labs
o increase in serum creatinine by 0.3 mg/dL within 48 hours
o blood urea nitrogen (BUN):creatinine ratio
o urinalysis
dipstick
 to assess for protein, glucose, leukocyte esterase, hemoglobin and
myoglobin, and specific gravity
microscopy
for example
red dysmorphic cells suggests a glomerular etiology
(e.g., glomerulonephritis)
muddy brown casts suggests tubular necrosis
white blood cell casts suggest pyelonephritis or acute interstitial
nephritis
o fractional excretion of Na+ (FeNa+)
if patient is on diuretics use FeUrea
o urine osmolality and Na+

Studies To Assess For Prerenal, Intrarenal, and Postrenal Acute Kidney Injury (AKI)
Studies Prerenal AKI Intrarenal AKI Postrenal AKI
> 500 < 350 < 350
Urine osmolality (mOsm/kg)
< 1% in mild cases
< 1% > 2%
FeNa +
> 2% in severe cases

< 20 > 40 > 40

Urine Na+ (mEq/L)
> 20:1 < 15:1 Variable
Serum BUN/Cr

Differential
Acute gastrointestinal bleeding
Rhabdomyolysis
Medication-induced impairment of creatinine secretion
o cimetidine
o trimethoprim
o pyrimethamine

Treatment
Treatment is dependent on the etiology of AKI and its consequences
o for example
a patient who is hyperkalemic and not responding to medical treatment should be
dialyzed
a patient with a history of excessive fluid loss (e.g., diarrhea and vomiting) should
be given intravenous fluid

Complications
Hyperkalemia
Metabolic acidosis
Uremic encephalopathy and platelet dysfunction
Anemia
Chronic kidney disease
 GLOMERULAR DISEASE

Nephritic Syndrome
Snapshot
A 14-year-old boy presents with hematuria, problems with vision, and deafness.
Approximately 2 weeks prior to symptom development, he recovered from a viral
upper respiratory tract infection. Family history is significant for deafness and early
initiation of lisinopril in his father. His temperature is 99F (37.2C), blood pressure
is 140/90 mmHg, pulse is 75/min, and respirations are 18/min. Physical examination
is signifcant for anterior lenticonus and sensorineural hearing loss. Urinalysis
demonstrates dysmorphic red blood cells and red blood cell casts. (Alport syndrome)

Introduction
Clinical definition
o renal disease secondary to an inflammatory process injuring the glomerulus
this results in damage involving the
basement membrane
capillary endothelium
mesangium
Presentation
o symptoms
hypertension
hematuria
oliguria
headache
o physical exam
edema
can be peripheral and/or periorbital
Diagnosis
o studies
complete blood cell count
anemia may be noted
azotemia
complement levels
C3, C4, and CH50 should be obtained
urinalysis
dysmorphic red blood cells (RBCs)
suggests hematuria is of glomerular origin
RBC casts
subnephrotic range proteinuria (< 3.5 g/day)
if the nephritic syndrome is severe enough it can lead to nephrotic
range proteinuria (> 3.5 g/day)
o renal biopsy
may be necessary to arrive to a definitive diagnosis and to determine prognosis
Nephrotic Syndrome
Snapshot
A 6-year-old boy is brought to the emergency department by his mother due to swelling around
his eyes and legs. The mother reports that the patient recently recovered from an upper
respiratory tract infection. Physical exam is significant for periorbital and lower extremity edema.
Laboratory testing is significant for hypoalbuminemia and normal complement levels. Urinalysis
demonstrates 4+ protein. A presumptive diagnosis of minimal change disease is made and the
patient is started on steroid therapy.

Introduction
Clinical definition
o a type of kidney disease that results in proteinuria, peripheral edema, hyperlipidemia, and
hypoalbuminemia
Epidemiology
o incidence
annually there are 3 cases per 100,000 adults
Etiology
o primary glomerular disease
focal segmental glomerulosclerosis
membranous nephropathy
minimal change disease
o secondary causes
diabetic nephropathy
systemic lupus erythematosus
amyloidosis
Pathogenesis
o the glomerulus becomes permeable to large molecules (e.g., albumin)
this loss of albumin (proteinuria) results in hypoalbuminemia and edema
associated with a hypercoagulable state
pathophysiology unclear but may be due to loss of antithrombin and
plasminogen proteins
increased lipid synthesis secondary to proteinuria
this in turn results in hypercholesterolemia and hyperlipidemia
Associated conditions
o chronic kidney disease
Prognosis
o depends on the underlying cause
e.g., patients with minimal change disease typically respond well to steroid therapy

Presentation
Symptoms
o edema
periorbital, lower extremity, and genital edema
o frothy urine
o ascites
o weight gain
o fatigue
o shortness of breath
Physical exam
 o hypertension
o edema
o leukonychia
suggestive of a low albumin state and presents as white streaking on the
fingernails

Studies
Labs
o hypoalbuminemia (serum albumin of < 2.5 g/dL)
o hyperlipidemia
Urine studies
o proteinuria > 3-3.5 g/day
or > 300-350 mg/mmol on spot urine protein to creatinine ratio
o fatty casts with "maltese cross" sign
TUBULOINTERSTITIAL DISEASE

Renal Tubular Acidosis (RTA)

Snapshot
A 36-year-old woman presents to the emergency department with left-sided back pain that
radiates to her left groin. Medical history is significant for Sjogren syndrome. On physical exam
there is left-sided costovertebral angle tenderness. Laboratory testing is notable for
hyperchloremic and normal anion gap metabolic acidosis and hypokalemia. Non-contrast
computerized tomography (CT) of the abdomen demonstrates urolithiasis. She is started on
ibuprofen and intravenous fluids. Once the calculi passed it was found to be a calcium phosphate
stone. (Type I renal tubular acidosis)

Introduction
Clinical definition
o renal tubular dysfunction that results in a hyperchloremic and normal anion gap metabolic
acidosis
there is a relatively normal glomerular filtration rate
Acute Interstitial Nephritis
Snapshot

A 60-year-old man presents to the emergency room with a 1-

day history of fever and a new skin rash. He is taking methicillin for a soft tissue infection. On
physical exam, he has costovetebral tenderness, and a diffuse maculopapular rash over his
trunk. His serum creatinine is elevated at 3 mg/dL. Urinalysis reveals white blood cells. Further
testing with Wright stain is positive for eosinophils in the urine.

Introduction
Clinical definition
o acute interstitial nephritis (AIN), also known as tubulointerstitial nephritis, is an acute
immune-mediated interstitial inflammation of the kidneys
Epidemiology
o demographics
middle-aged adults
Etiology
o drug-induced hypersensitivity (majority of cases)
typically developed between 1 week to 9 months
5 Ps
Pee (diuretics, especially sulfa ones)
Pain-free (NSAIDs)
Penicillins and cephalosporins
Proton pump inhibitors
rifamPin
o systemic infections
o autoimmune diseases
systemic lupus erythematosus
sarcoidosis
Pathogenesis
o type IV hypersensitivity reaction
o T-cell-mediated attack on tubular cells
Prognosis
o typically resolves after withdrawal of inciting agent

Presentation
Symptoms
o primary symptoms
fever
hematuria
arthralgia
 can be asymptomatic
Physical exam
o rash
maculopapular
o flank/costovertebral angle tenderness

Studies

Labs
o serum eosinophilia
o elevated serum creatinine
Urinalysis with microscopy and sediment analysis
o white blood cell casts
o hematuria
o eosinophiluria
seen with Hansel or Wright stain
Renal biopsy
o not usually indicated
Histology
o severe tubular damage
o interstitial edema
o T-cell and eosinophilic infiltration
Diagnostic criteria
o elevated creatinine
o urinalysis with white cell casts and eosinophiluria

Differential
Acute tubular necrosis from NSAIDs
o no rash or eosinophils
Renal atheroemboli
o also presents with eosinophiluria, eosinophilia, and skin rash
o rash is typically livedo reticularis with digital infarcts and not maculopapular

Treatment
Conservative
o discontinue inciting drug
indications
for all drug-induced hypersensitivity cases
Medical
o glucocorticoids
indications
 if creatinine continues to rise after stopping drugs

Complications
Renal failure requiring dialysis

Fanconi Syndrome
Snapshot
A 10-year-old girl with a past medical history of epilepsy presents to the emergency room after
sustaining a fall on the playground. She was fatigued and confused after the event and
complained of pain in her wrist. On review of systems, she endorsed polyuria and
polydipsia. Relevant medications included valproic acid, started 6 months ago, for her
epilepsy. On physical exam, her right wrist was erythematous, swollen, and
tender. Laboratory evaluation revealed hypokalemia, hypocalcemia, hypophosphatemia, and
a mild metabolic acidosis.

Introduction

Clinical definition
o a type of renal tubular acidosis (type 2)in the proximal convoluted tubules (PCT)
Epidemiology
o incidence
hereditary forms occur in 1:40,000
o demographics
hereditary forms affect Caucasian children
Etiology
o hereditary conditions
cystinosis
most common genetic cause
Wilson disease
tyrosinemia
galactosemia
o multiple myeloma
o drugs
cisplatin
 tenofovir
valproic acid
expired tetracyclines
ifosfamide
o heavy metal poisonings
Pathogenesis
o defect in PCT causes problems in reabsorption of almost all amino acids, glucose,
bicarbonate, phosphate, and potassium
this causes all of the above to be excreted in the urine
excretion of bicarbonate causes a metabolic acidosis
o defect is due to
direct injury to PCT
in genetic cases there is often a defective enzyme in nutrient metabolism that
causes damage to the PCT
light chains form crystals in PCT, causing damage
Associated conditions
o osteomalacia/rickets
chronic phosphate and insufficient synthesis of vitamin D
o hypokalemia
due to early Na+ reabsorption leading to K+ exchange
Prognosis
o depends on etiology of Fanconi syndrome
o prognostic variable
negative
hereditary diseases

Presentation
Symptoms
o primary symptoms
renal disease
polyuria
polydipsia
bone disease
bone pain in the backs and hips
pathologic fractures
constitutional
myalgias
weight loss
fatigue
hereditary abnormalities
failure to thrive
developmental delay
Physical exam
o signs of rickets
bowed legs
scoliosis
teeth abnormalities

Studies
Labs
o electrolyte panel
 hyponatremia
hypokalemia
hypocalcemia
hypophosphatemia
o serum creatinine
o metabolic acidosis
Urine studies
o aminoaciduria
o glycosuria
o phosphaturia
o urine pH < 5.5
defect in bicarbonate reabsorption leads to increased excretion of bicarbonate in
urine
urine is then acidified by the intercalated cells in collecting tubule
Diagnostic criteria
o no specific criteria, but these findings could suggest Fanconi syndrome
increased excretion of amino acids, phosphates, and bicarbonate in the urine
metabolic acidosis

Differential
Distal renal tubular acidosis (type 1)
o urine pH > 5.5
Hyperkalemic renal tubular acidosis (type 4)
o hyperkalemia and urine pH < 5.5

Treatment
Conservative
o supportive care with fluid and electrolyte repletion
indications
if any metabolic derangements are found
especially if hypokalemia or hypophosphatemia are found
Medical
o vitamin D (active form, cholecalciferol. or ergocalciferol)
indications
if osteomalacia is present
o bicarbonate
indications
metabolic acidosis

Complications
Bone disease (osteomalacia, osteopenia, and osteoporosis)
Renal insufficiency

Liddle Syndrome
Snapshot
A 3-year-old boy is brought to the pediatrician for a wellness visit. The mother reports that he has
been sleeping and feeding well. She does not have any active concerns. Family history is
 significant for hypertension. His blood pressure is 110/90 mmHg. Laboratory testing is significant
for hypokalemia and metabolic alkalosis.

Introduction

Clinical definition
o a renal tubular disorder affecting the collecting tubules characterized by
hypertension
hypokalemia
metabolic alkalosis
o also known as pseudohyperaldosteronism
Epidemiology
o incidence
rare
o demographics
young children
suspected if there is early onset hypertension
may not be detected until adulthood
o risk factors
family history of early onset hypertension or hypokalemia may suggest Liddles
Pathogenesis
o gain of function mutation involving the epithelial Na+ channel (ENaC) resulting in
increased Na+ reabsorption in the collecting tubules
this causes the lumen to be electronegative
which causes a gradient that favors secretion of K+ into the lumen
this results in decreased serum K+
mimics hyperaldosteronism
recall that aldosterone increases the number of open luminal Na+ channels
Genetics
 o inheritance pattern
autosomal dominant
o mutations
chromosome 16p12
Prognosis
o very good with treatment

Presentation
Symptoms
o triad presenting at a young age
hypertension
hypokalemia
metabolic alkalosis
Physical exam
o hypertension

Studies
Labs
o hypokalemia
o metabolic alkalosis
o aldosterone
o renin
o genetic testing
most definitive diagnosis

Differential
Primary hyperaldosteronism
Congenital adrenal hyperplasia
Treatment
Medical
o potassium-sparing diuretics
indication
for all patients with Liddle syndrome
recall that these medications directly block Na+ channels in the collecting
tubules
drugs
amiloride
triamterene

Complications
Cardiac arrhythmia due to hypokalemia
Gitelman Syndrome
Snapshot
An 8-year-old girl is brought to the pediatrician for evaluation of increased urinary frequency. She
has muscle cramps and fatigue. She is found to be normotensive. Laboratory exam reveals
hypomagnesemia, hypokalemia, and a mild metabolic alkalosis.

Introduction

Clinical definition
o a renal tubular defect affecting the distal convoluted tubules characterized by
mild hypokalemia
mild metabolic alkalosis
significant hypomagnesemia
normal blood pressure
Epidemiology
o incidence
rare
1:40,000
o demographics
detected in young children but can be detected in adulthood
o risk factors
consanguinity
Pathogenesis
o mutation involving NaCl cotransporter (NCTT) which results in
impaired Na+ reabsorption in distal convoluted tubule
Genetics
o inheritance pattern
autosomal recessive
 o mutations
chromosome
SLC12A3 gene

Presentation
Symptoms
o polyuria
o polydipsia
o muscle weakness or cramp
o fatigue
o paresthesias
o abdominal pain
o vomiting
Physical exam
o growth is often normal but can be delayed

Studies
Labs
o hypokalemia (lower than in Bartters)
o hypomagnesemia
o metabolic alkalosis
o genetic testing
most definitive diagnosis
Urine studies
o Ca2+

Differential
Bartters syndrome
o normal serum magnesium
Treatment
Conservative
o optimize electrolytes with diet or supplements
indications
those with hypokalemia or hypomagnesemia
Medical
o nonsteroidal anti-inflammatory drugs (NSAIDs)
indications
for patients who require medical therapy beyond dietary supplements
drugs
indomethacin
celecoxib
o potassium-sparing diuretics
indications
to treat hypokalemia and metabolic alkalosis
drugs
amiloride
 eplerenone

Complications
Cardiac arrhythmia due to hypomagnesemia and hypokalemia
Chondrocalcinosis

Bartter Syndrome
Snapshot
A 3-year-old boy is brought to the pediatrician due poor growth and increased urinary frequency.
According to the mother, the child appears to be very thirsty. He was born prematurely and the
mother states she was found to have polyhydramnios on ultrasonograpahy while pregnant.
Laboratory testing is significant for hypokalemia, hypochloremia, mild hypomagnesemia, and
metabolic alkalosis.

Introduction

Clinical definition
o a renal tubular disorder characterized by
 hypokalemia
hypochloremia
metabolic alkalosis
normotension
elevated plasma renin level
Epidemiology
o incidence
rare
precise incidence is unknown
o demographics
neonatal cases
can be suspected before birth and diagnosed soon after birth
classic cases
begins around 2 years of age or younger
no race or sex predilection
o risk factors
family history
Pathophysiology
o pathobiology
mutation involving the Na+/K+/Cl- cotransporter (NKCC2) results in salt and water
loss resulting in
activation of the renin-angiotensin-aldosterone system secondary to volume
depletion
renal vasoconstriction due to angiotensin II and hypokalemia leads to an
increase in prostaglandin E (PGE)
Genetics
o inheritance pattern
autosomal recessive
Prognosis
o can slowly progress to interstitial fibrosis resulting in chronic renal failure

Presentation
Symptoms
o failure to thrive
o increased thirst
o polyuria
o polydipsia
o vomiting
Physical exam
o clinical volume depletion
o maternal polyhydramnios
o growth retardation

Studies
Labs
o plasma renin and aldosterone
o serum potassium and chloride
o urine prostaglandin E
o genetic testing

Differential
 Diuretic abuse
Gitleman syndrome
Surreptitious vomiting
Mineralocorticoid excess
Cystic fibrosis

Treatment
Medical
o nonsteroidal anti-inflammatory drugs (NSAIDs)
indication
for patients with Bartter syndrome
drugs
indomethicin
celecoxib
o potassium-sparring diuretics
indication
to treat hypokalemia and metabolic alkalosis in Bartter syndrome
 drugs
spironolactone
eplerenone
amiloride
o potassium and magnesium supplementation
indication
to help improve potassium and magnesium levels in Bartter syndrome

Complications
Cardiac arrhythmia due to severe hypokalemia

Syndrome of Apparent Mineralocorticoid Excess (SAME)

Snapshot
A 1-year-old girl is brought to the pediatricians office for failure to thrive and muscle
weakness. Her parents deny any problems with feeding. On physical exam, her blood
pressure is elevated for her age. Laboratory tests reveal hypokalemia, metabolic
alkalosis, and low serum aldosterone and renin.

Introduction

Clinical definition
o Syndrome of Apparent Mineralocorticoid Excess (SAME) is a hereditary defect in 11-
hydroxysteroid dehydrogenase causing
 hypertension
hypokalemia
metabolic alkalosis
o these findings are similar to those in primary aldosteronism
Epidemiology
o demographics
early childhood onset
o risk factors
family history
Etiology
o hereditary deficiency
o acquired disorder
ingestion of glycyrrhetinic acid (licorice)
Pathogenesis
o genetic loss-of-function mutation in 11-hydroxysteroid dehydrogenase (kidney isoform)
11-hydroxysteroid dehydrogenase usually converts cortisOL to cortisONE
cortisOL can activate mineralocorticoid receptors (with similar affinity with
aldosterone)
cortisone is inactive
deficiency results in excess cortisol
this will increase activation of mineralocorticoid receptor
o glycyrrhetinic acid inhibits 11-hydroxysteroid dehydrogenase and reduces gene
expression
Genetics
o inheritance pattern
autosomal recessive
o mutations
chromosome 16
11-HSD2 gene

Presentation
Symptoms
o infants
low birth weight
failure to thrive
Physical exam
o muscle weakness due to hypokalemia
o hypertension

Studies
Labs
o hypokalemia
o metabolic alkalosis
o aldolsterone level
o renin activity
o may have creatinine
Urine
o hypercalciuria
o free cortisol to free cortisone ratio on 24-hour urine collection

Differential
 Liddle syndrome
o urine cortisol to cortisone ratio is normal
Primary aldosteronism
o elevated aldosterone

Treatment
Conservative
o remove licorice from diet
indications
for those with acquired SAME from licorice ingestion
Medical
o mineralocorticoid receptor blockade
indications
for those with hereditary SAME
drugs
spironolactone
eplerenone
amiloride
triamterene
o corticosteroids
indications
if mineralocorticoid blockade is not effective or tolerated
o thiazides
indications
hypercalciuria

Complications
Cardiac arrhythmia from hypokalemia
Nephrocalcinosis

VASCULAR DISEASE

Renal Infarction
Snapshot
A 68-year-old man presents to the emergency room with a 2-day history of abdominal pain,
nausea, and vomiting. He denies any urinary frequency or urgency and denies any recent
changes in his diet. His temperature is 100.4F (38C) and pulse is 104/min. He has a past
medical history significant for type II diabetes mellitus and coronary artery disease. He has had
two stents in the past three years. On physical exam, there is bilateral flank tenderness upon
palpation. A non-contrast computerized tomography (CT) scan without contrast is negative for
urolithiasis. A CT scan with contrast reveals a wedge shaped perfusion defect in both kidneys.

Introduction
 Clinical definition
o complete occlusion of main renal artery or segmental branch
Epidemiology
o incidence
very rare
0.7-1.4% found on autopsies
o risk factors
cardiovascular disease
Etiology
o cardioemboli
cardiomyopathy
endocarditis
artificial valves thrombi
o renal artery injury and thrombosis
Marfan syndrome
trauma
polyarteritis nodosa
other vasculitidies
o hypercoagulable states
hereditary thrombophilia
antiphospholipid syndrome
Pathogenesis
o complete occlusion of main renal artery or segmental branch artery
Associated conditions
o atrial fibrillation
Prognosis
o 11-12% mortality in first month after diagnosis
renal infarction occurs in patient populations with significant morbidity and
mortality, such as atrial fibrillation
o patients are at risk for future repeat renal infarctions

Presentation
Symptoms
o acute onset abdominal or flank pain
o nausea
o vomiting
Physical exam
o fever
o acute elevation in blood pressure
may be mediated by renin release
o tenderness to palpation of abdomen or flank
o other signs of extrarenal embolization
 focal neurologic deficits

Imaging
Spiral CT without contrast
o indications
initial test for flank pain to evaluate for renal calculi
CT with contrast
o indications
if there are no calculi seen on initial imaging
to evaluate for renal infarction
o findings
wedge-shaped perfusion defect
o 80% sensitivity

Studies
Labs
o creatinine
but it can also be normal if embolus is unilateral
o lactate dehydrogenase (> 2-4x upper limit of normal)
o little or no in serum aminotransferases
Urine studies
o hematuria
o proteinuria
Electrodiagnostics
o electrocardiogram to evaluate for atrial fibrillation
Diagnostic criteria
o in the correct clinical context, the combination of elevated lactate dehydrogenase and
normal serum aminotransferase is strongly suggestive of renal infarction
note, this combination is also seen in transplant rejection, late myocardial
infarction, and hemolysis, but these are clinically distinct from renal infarction

Differential
Renal atheroemboli
o incomplete occlusion of distal vessels
o will likely have eosinophilia, eosinophiluria, and hypocomplementemia
Nephrolithiasis
o stones seen on imaging
o lactate dehydrogenase is normal

Treatment
Medical
o anticoagulation
indications
atrial fibrillation
hypercoagulable state
delayed diagnosiss
anticoagulation therapy is prophylactic to prevent future events
drugs
heparin followed by warfarin
Percutaneous endovascular therapy
o thrombolysis and thrombectomy
 indications
in patients who are diagnosed early
if diagnosed early, viable tissue may be saved with thrombolysis

Complications
Repeat thromboembolic events
Renal failure

Hypertensive Nephrosclerosis
Snapshot
A 42-year-old African American woman presents to her physicians office for an annual visit. She
has a long-standing history of hypertension and is currently not on any medication. On routine
laboratory examination, she is found to have a creatinine of 1.5 mg/dL. Urine studies reveal mild
proteinuria. Her physician prescribes lisinopril for her hypertension and likely renal disease.

Introduction
Clinical definition
o this represents renal sclerosis
nephrosclerosis is associated with chronic hypertension
this is distinct from malignant hypertension or malignant nephrosclerosis
Epidemiology
o demographics
common in people of African descent
o risk factors
hypertension
chronic renal disease
Pathogenesis
o involves the vasculature, glomeruli, tubules, and interstitium of the kidney
chronic hypertension causes medial and intimal hypertrophy
this causes narrowed vessels and ischemia
ischemic damage to kidneys also can cause glomerulosclerosis
vessel walls are further damaged by hyaline-like material
deposition
interstitial nephritis is often found on biopsy and the exact mechanism is unknown

Presentation
Symptoms
o hypertension precedes proteinuria or renal insufficiency
Physical exam
o typically benign

Studies
 Labs
o creatinine
o blood urea nitrogen
o uric acid
Urinalysis
o few casts
o typically benign
o mild proteinuria (< 1 g/day)
Gross specimen
o cobblestone appearance
Diagnostic criteria
o hypertension precedes proteinuria or renal insufficiency
o no other causes of renal disease
o biopsy is not necessary

Differential
Malignant nephrosclerosis

Treatment
Medical
o angiotensin converting enzyme (ACE) inhibitors
indications
for all patients with hypertension-associated nephrosclerosis
o angiotensin II receptor blockers
indications
if ACE inhibitors are contraindicated

Complications
Renal failure
o typically only occurs in patients with concomitant other renal disease
Diffuse Cortical Necrosis
Snapshot
A 35-year-old G1P1 woman recently delivered a boy via normal spontaneous vaginal delivery.
As she holds her baby, she feels lightheaded and weak. An exam quickly reveals blood pooling
below her vagina. Her uterus is immediately massaged and oxytocin is given. A few hours later,
she reports having flank pain and seeing a significant amount of blood in her urine. Her
creatinine is found to be elevated at 2 mg/dL.

Introduction

Clinical definition
o diffuse necrosis of bilateral renal cortex
Epidemiology
o incidence
rare in developed countries
1-2% of all acute kidney injuries
Etiology
o obstetric catastrophes
abruption placentae
amniotic fluid embolism
postpartum hemorrhage
o septic shock
Pathogenesis
o pathogenesis is likely a combination of diffuse intravascular coagulation and renal
ischemia
hemorrhagic or septic shock causes endothelial damage and fibrin deposition,
causing necrosis
endothelial damage normally releases nitric oxide to minimize thrombi
formation
however, if the endothelia are damaged, nitric oxide release is
impaired which leads to increased thrombi formation and ischemia

Presentation
Symptoms
o sudden onset oliguria or anuria after an obstetric catastrophe
o gross hematuria
o flank pain
Physical exam
o hypotension
Imaging
Ultrasound
o findings
hyperechoic or hypodense areas in renal cortex

Studies
Urinalysis
o gross hematuria

Differential
Acute kidney injury in the setting of other obstetric catastrophe
o acute fatty liver of pregnancy
o pregnancy-triggered, thrombotic thrombocytopenic purpura

Treatment
Conservative
o supportive care
Medical
o dialysis

Complications
Renal failure

Sickle Cell Nephropathy

Snapshot
An 18-year-old African American man with a history of sickle cell trait presents with 1 week of
painless gross hematuria. On review of systems, he endorses a 10 pound weight loss within the
past 2 months. Physical exam reveals a left-sided abdominal mass. His serum creatinine is
found to be elevated. He is sent to the emergency room for urgent CT imaging. (Renal medullary
carcinoma secondary to sickle cell trait).

Introduction
Clinical definition
o nephropathy associated with sickle cell disease or trait
vaso-occlusion
renal medullary carcinoma
Epidemiology
o incidence
proteinuria
20-25% in sickle cell disease
renal insufficiency
5-30% in sickle cell disease
o risk factors
vaso-occlusion
sickle cell disease > trait
renal medullary carcinoma
sickle cell trait > disease
 patients of African ancestry
Pathogenesis
o normal O2 tension in the renal medulla is low enough to induce RBC sickling
o sickling of red blood cells in medulla capillaries cause increased viscosity
o increased viscosity causes ischemia and infarction in renal medulla
o this can lead to renal infarcts and papillary necrosis
Prognosis
o prognostic variable
negative
renal failure
o increased mortality risk for those with renal failure, regardless of treatment
o prognosis is < 1 year for renal medullary carcinoma
commonly very aggressive and metastasizes early

Presentation
Symptoms
o vaso-occlusion
nausea
vomiting
nocturia
polyuria
painless hematuria
history of urinary tract infections
o renal medullary carcinoma
gross painless hematuria
weight loss
Physical exam
o vaso-occlusion
flank or abdominal pain
hypertension
renin-mediated
o renal medullary carcinoma
abdominal mass

Imaging

Ultrasound
o indications
to exclude other abnormalities such as nephrolithiasis
o recommend views
 renal
o findings
can detect renal papillary necrosis
CT
o indications
if renal medullary carcinoma is suspected (young patient with sickle cell trait and
gross hematuria)
o findings
mass in kidney

Studies
Labs
o electrolyte abnormalities
impaired distal H+ and K+ secretion can cause a renal tubular acidosis
hyperkalemia
metabolic acidosis
o creatinine
Urinalysis
o proteinuria
o low specific gravity and osmolarity
indicates loss of urine concentrating ability
Diagnostic criteria
o generally, this is a diagnosis of exclusion

Differential
Nephrolithiasis
o seen on imaging

Treatment
Conservative
o hydration and blood transfusions as needed
indications
isolated hematuria
hydration can dislodge blood clots
Medical
o dialysis
indications
end-stage renal disease
Operative
o renal transplant
indications
end-stage renal disease not responsive to dialysis

Complications
End-stage renal disease
Renal medullary carcinoma with metastases
Renal Artery Stenosis
Snapshot
A 23-year-old woman with no significant past medical history presents to her primary care
physician for an annual physical exam. She was found to have a blood pressure of 156/94
mmHg. She has never had any episodes of high blood pressure in the past and she has no
family history of hypertension. She is prescribed captopril. After two weeks, she presents to the
emergency room with hypertensive urgency. Captopril was immediately stopped and after
stabilizing her blood pressure, an ultrasound revealed bilateral renal artery stenosis.

Introduction
Clinical definition
o renal artery stenosis (RAS) occurs when one or both of the renal arteries are narrowed
this often causes renovascular hypertension
Epidemiology
o prevalence
7% in the United States
present in up to 1/3 of patients with malignant or resistant hypertension
o demographics
atherosclerotic disease
patients > 50 years of age
fibromuscular dysplasia
young women
o risk factors
atherosclerosis and its risk factors (e.g., smoking and fatty diet)
fibromuscular dysplasia
in kidney transplant patients
high calcium or phosphorous levels
high low-density lipoprotein cholesterol levels
Pathogenesis
o narrowing of artery lumen due to
atherosclerosis
fibromuscular dysplasia
narrowed arteries lead to reduced renal perfusion
reduced perfusion leads to activation of renin-angiotensin system
increased renin hypertension, hypokalemia, and hypernatremia
bilateral renal stenosis can lead to volume overload
heart failure
pulmonary edema
Associated conditions
o other manifestations of atherosclerotic disease
carotid artery disease
lower extremity artery disease
coronary heart disease
Prognosis
o prognostic variable
negative
elevated serum creatinine
comorbid heart disease
comorbid chronic obstructive pulmonary disease (COPD)
o survival with treatment
 91% at 1 year
67% at 5 years
41% at 10 years

Presentation
History
o hypertension before 30 years of age
if abrupt onset in a young women, consider fibromuscular dysplasia
o resistant or malignant hypertension
o worsening renal function after taking an ACE inhibitor or angiotensin receptor blocking
(ARB) agent
may indicate bilateral renal artery stenosis (RAS) because ACE inhibitors and
ARBs further decrease glomerular filtration rate and worsen renal function
o sudden unexplained volume overload (heart failure or pulmonary edema)
Physical exam
o extremities
may have edema if volume overloaded
o abdomen
abdominal or flank bruit through systole and diastole
o vitals
hypertension

Imaging
Ultrasound
o indications
often initial imaging in those < 60 years of age in patients with suspected RAS
o sensitivity and specificity
sensitivity 88-93%
specificity 82-89%
CT angiography
o indications
in patients with normal renal function and suspected RAS
o sensitivity and specificity
sensitivity 90%
specificity 94%
MR angiography
o indications
in patients with renal insufficiency and suspected RAS
o sensitivity and specificity
sensitivity 75-97%
specificity 64-93%

Studies
 Labs
o serum creatinine to assess renal function
elevated creatinine may indicate atherosclerosis-associated RAS
normal creatinine may indicate fibromuscular dysplasia-associated RAS
o urine protein to assess renal function
typically below nephrotic range (< 3.5 g in 24 hours)
Invasive catheter angiography
o gold standard for diagnosis
o only indicated if high suspicion of disease but inconclusive imaging or if revascularization
is planned
Histology
o fibromuscular dysplasia
medial fibroplasia
Diagnostic criteria
o reduction of diameter of > 60%
o string-of-beads appearance on angiography in fibromuscular dysplasia

Differential
Essential hypertension
o typically responsive to therapy
Primary hyperaldosteronism
o high levels of aldosterone
Obstructive sleep apnea
o lethargy and fatigue

Treatment
Medical
o ACE-inhibitors or ARBs
indications
persistent hypertension
contraindicated in bilateral RAS or RAS in patients with single kidney
o calcium channel blockers or -blockers
given if patients do not respond to ACE-inhibitors or ARBs
Operative
o revascularization
indications
severe complications of RAS
unexplained heart failure
unexplained pulmonary edema
chronic kidney disease
inadequately controlled hypertension
 outcomes
may not improve outcomes in those with atherosclerotic RAS
cures up to 58% of hypertension in patients with fibromuscular dysplasia-
associated RAS
complications
contrast-induced acute kidney injury or allergic reaction (< 3%)
bleeding, hematoma, or arteriovenous fistula

Complications
Renal dysfunction can progress to end-stage renal disease
o incidence
4% in one study of 68 adults over 39 months
o treatment
dialysis and kidney transplant

ELECTROLYTE DISORDERS

Potassium Shifts
Snapshot
A 22-year-old man presents to the emergency department after a crush injury to his lower
extremities. He reports muscular pain, weakness, and palpitations and noticed that his urine is
"tea-colored." On physical exam, there is tenderness upon palpation of his lower extremities and
4-/5 power in the same area. Urinalysis is heme positive. Laboratory testing is significant for a
potassium level of 6.5 mEq/L and creatinine kinase level of 1,500 units/L. An electrocardiogram
is shown. (Rhabdomyolysis resulting in hyperkalemia)

Introduction
The major intracellular cation is potassium and magnesium
o cells contain approximately 98% of the body's potassium
o the sodium-potassium-ATPase (Na+/K+ -ATPase) pump within the cellular membrane
maintains this potassium distribution between the intracellular and extracellular
compartments
o potassium is the major determinant of the resting membrane potential across the cell
membrane
normal potassium homeostasis is essential for proper action potential generation in
muscle and neural tissue
Normal potassium homeostasis
o determined by
potassium intake
 intracellular and extracellular potassium distribution
urinary excretion of potassium
mainly accomplished by principal cells in the nephron
Disruptions in potassium homeostasis can result in hyperkalemia or hypokalemia
o these disruptions can have a number of clinical consequences
hyperkalemia
defined as a potassium level in the blood that is > 5.0-5.5 mEq/L
muscle and cardiac dysfunction
muscular symptoms
myalgias
muscle paralysis
chest pain
cardiac symptoms
arrhythmias and palpitations
nausea and vomiting
parasthesias
hypokalemia
defined as a potassium level in the blood that is < 3.5 mEq/L
muscle and cardiac dysfunction
muscular symptoms
abdominal cramping
muscle weakness and cramping
cardiac symptoms
palpitations
parasthesias
nausea and vomiting

Factors that Influence Potassium Shifts

Shifts out of Cells (Hyperkalemia) Shifts into Cells (Hypokalemia)
Insulin deficiency
2-adrenergic antagonists
Acidosis
o cells attempt to buffer excess hydrogen ions to
shift these ions into the cells
insulin
in exchange for this intracellular uptake of
Hyperglycemia
hydrogen, potassium is transferred out the
o this stimulates endogenous
cell
insulin secretion from the
this attempts to achieve
pancreas in normal conditions
electroneutrality
2-adrenergic agonists
Digitalis
Alkalosis
o secondary to dose-dependent Na+/K+ -
Hyposmolality
ATPase pump inhibition
Cell lysis (e.g., rhabdomyolysis)
Exercise
Hyperosmolarity
Succinylcholine
Electrolyte Disturbances
Snapshot
A 22-year-old man is brought to the emergency department by his friend after witnessing him fall
to the ground and shaking his upper and lower extremities. His friend reports that he prevented
the patient from hitting his head. Prior to developing this symptom the patient felt numbness in
his hands and feet, muscle cramps, and mild palpitations. Medical history is significant for
DiGeorge syndrome. On physical exam, there is facial muscle twitching with ipsilateral tapping of
the facial nerve anterior to the ear. An electrocardiogram shows QTc prolongation. Laboratory
testing is significant for an ionized calcium level of 4.0 mg/dL. (Provoked seizure secondary to
hypocalcemia)

Introduction
UROLOGY

Urinalysis
Snapshot
A 22-year-old woman presents with dysuria, pyuria, and increased urinary frequency. She
reports her symptoms began approximately 2 days prior to presentation. She has had similar
symptoms 5 months ago. She is sexually active and uses condoms inconsistently. Physical
examination is unremarkable. Urinalysis is positive for pyuria and bacteruria. Urine culture
demonstrates 100,000 colony forming units (CFU) /mL. (Urinary tract infection)

Introduction
Process
o a fresh urine specimen is obtained and subsequently centrifuged
the supernatant is placed in a separate tube
a urine dipstick is placed in the supernatant to analyze for
pH
normal is between 5-6.5
clinical correlate
urine pH >7.5 can suggest a urinary tract infection (UTI)
secondary to urea-splitting microbe
glucose
clinical correlate
urine glucose can be detected in the urine in poorly
controlled diabetes mellitus
ketones
clinical correlate
urine ketones can be seen in poorly controlled diabetes
mellitus
nitrite
clinical correlate
can be a reasonably good screening test for UTI
heme
clinical correlate
typically indicative of blood in the urine
however, the urine can be heme positive in the
setting of intravascular hemolysis and
rhabdomyolysis
protein
clinical correlate
elevated protein in the urine can suggest a nephrotic
syndrome
specific gravity
reflects the weight of a solution compared to the weight of distilled
water
the solution and distilled water must be of equal volume
when the urine contains large solutes (e.g., glucose) the
specific gravity increases
urine osmolality
 measures the amount of dissolved particles per unit of water found in
urine
the sediment should be resuspended and then transferred to a slide for analysis
urine casts
these represent protein and cell precipitates generated within the
tubular lumen
red blood cells (RBCs)
red cell morphology
dysmorphic RBCs
suggests glomerular bleeding
round and uniform RBCs
suggests extrarenal bleeding (e.g., ureter and
bladder)
white blood cells (WBCs)
seeing WBCs in the urine is termed pyuria and suggests an infection
or inflammatory process in the urinary tract
neutrophils are more commonly seen
eosinophiluria can be see in drug-induced acute intestitial
nephritis
epithelial cells
crystals

Urine Casts
Casts Associated Conditions
Glomerulonephritis
Vasculitis
RBC casts
Malignant hypertension

Tubulointerstitial inflammation
Acute pyelonephritis
WBC casts
Transplant rejection

Nephrotic syndrome
Fatty casts "Maltese cross" sign

Acute tubular necrosis

Granular casts
End-stage renal disease
Waxy casts Chronic renal failure

Non-specific
Hyaline casts
Hydronephrosis
Snapshot
A 48-year-old woman presents to the emergency department due to severe back pain. Her
symptoms began approximately 3 hours ago and says the pain is in her left mid-back. She
describes the pain as sharp and 9/10. The pain radiates to her left groin. On physical exam,
there is left-sided costovertebral angle tenderness. A non-contrast computerized tomography
(CT) scan of the abdomen demonstrates left-sided urolithiasis and hydronephrosis. She is
started on a nonsteroidal antiinflammatory drug (NSAID) and intravenous normal
saline. (Nephrolithiasis resulting in hydronephrosis)

Introduction
Clinical definition
o renal calyx and pelvis distension secondary to an obstruction in urine flow distal to the
renal pelvis
dilation of the ureter describes hydroureter
Epidemiology
o demographics
age
calculi is the most common cause of hydronephrosis and hydroureter in
young adults
sex
pregnancy and gynecologic causes are more common causes in women
prostatic hyperplasia and cancer are a major cause of hydronephrosis in
men
Etiology
o pregnancy
normal finding
there may be a more prominent dilation on the right ureter and renal pelvis than the
left
o benign prostatic hyperplasia
o calculi
o ureteral narrowing secondary to surgery
o malignancy
e.g., ureteral, cervical, and prostate
o congenital defects between the kidney, ureter, and bladder junction
o ureteropelvic junction obstruction
o retroperitoneal fibrosis
 Pathogenesis
o pathologic or anatomic processes interupt urine flow which leads to
a decline in glomerular filtration rate
impaired ability to concentrate, dilute, and transport sodium, potassium, and
hydrogen ions
o chronic hydronephrosis results in gross changes to the kidney such as
renal papillae compression
renal septa and calyx coalescence
peri-calyx renal parenchymal thinning
Prognosis
o variable as it is dependent on the underlying cause

Presentation
Symptoms
o depends on whether the obstruction is acute or chronic
asymptomatic
pain secondary to bladder, collecting system, or renal capsule distention
anuria
Physical exam
o palpable kidney in severe cases
o costovertebral angle tenderness
o distended bladder in lower urinary tract obstruction (e.g., benign prostatic hyperplasia)

Imaging
 Renal ultrasonography
o indication
imaging test of choice for evaluating urinary tract obstruction
Computerized tomography (CT) scan of the abdomen
o indication
used when results are equivocal on renal ultrasound

Studies
Labs
o urinalysis
to evaluate for infection, stone, or tumor
o serum chemistry
BUN and creatinine

Differential
Pyelonephritis
Peripelvic cyst
Calyceal diverticula

Treatment
Conservative
o bladder catheterization
indication
performed initially if the clinical presentation is suggestive of a bladder neck
obstruction such as
suprapubic pain
palpable bladder
Treatment ultimately depends on the underlying cause of hydronephrosis
o e.g., oral alkalinization therapy for patients with uric acid stones

Complications
Postobstructive diuresis
Nephrolithiasis
Snapshot

A 36-year-old woman presents to th e emergency department

with severe and colicky left flank pain that radiates to the left groin. She reports increased urinary
frequency and urgency. She is sexually active with multiple men and uses condoms
inconsistently. On physical exam, there is left-sided costovertebral angle tenderness and lower
abdominal tenderness.

Introduction
Clinical definition
o calculi (stones) affecting the kidneys; however, these stones can also affect the
ureter
Epidemiology
o prevalence
12% in men and 7% in women
o risk factors
hyperparathyroidism
hypocitraturia
sarcoidosis
hyperoxaluria
renal tubular acidosis type I
nephrocalcinosis
cystic fibrosis
hyperuricosuria
indwelling catheter
urinary tract infections
malabsorption (e,g., Crohn disease)
horseshoe kidney
obesity
low fluid intake
gout
medications
e.g., allopurinol, indinavir, acetazolamide, and topiramate
Pathogenesis
 o substance precipitation affecting the kidney and ureter
e,g., hypercalciuria and low urine volume forms calcium cystals
Prognosis
o small stones are more likely to spontaneously pass
Presentation
Symptoms
o colicky flank pain
pain may radiate to the groin or lower abdomen
o dysuria
o urgency and frequency
Physical exam
o low abdominal tenderness
o costovertebral angle (CVA) tenderness

Imaging
Renal ultrasound
o indication
in patients who are pregnant and children who are suspected to have
nephrolithiasis
o modality
abdomen and pelvis to visualize the kidney and bladder
Non-contrast computerized tomography (CT)
o indication
preferred imaging for most adults presenting with signs and symptoms concerning
for nephrolithiasis
o modality
abdomen and pelvis

Studies
Labs
o serum
creatinine, uric acid, and ionized calcium should be obtained
o urine studies
urinalysis/dipstick
in order to check for red and white blood cells, nitrites, and urine pH
urine culture
o stone composition analysis
perform in patients who developed their first stone
straining the urine
Diagnostic criteria
o based on clinical presentation and confirmed by imaging

Differential
Urinary tract infections
Acute pyelonephritis
 Groin hernia

Complications
Ureteral obstruction
Ureteral stricture
Urinary tract infection
Renal deterioration

Urinary Incontinence
Snapshot
A 42-year-old woman presents to her primary care physician due to involuntary
passage of urine. She reports to voiding small amounts of urine throughout the day
and night. She says that this occurs without warning. Medical history is significant for
multiple sclerosis treated with ocrelizumab. Physical examination is notable for a
distended bladder. (Overflow incontinence secondary to multiple sclerosis)

Introduction
Clinical definition
o involuntary urinary leakage
Diagnostic studies
o all patients with urinary incontinence should have a urinalysis
o if symptoms are concerning for a urinary tract infection obtain a urine culture