CPC
July 8th, 2013
A 65 y/o female with
uncontrolled hypertension and
acute kidney injury
Melanie Braganza, MD, MPH
Holly Rosencranz, MD
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65 Y/O F
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Worsening shortness of breath with orthopnea and
paroxysmal nocturnal dyspnea for 1 week
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Non-specific fatigue for several weeks
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Nausea and vomiting
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Decreasing urine output
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Severe neck pain with tingling and numbness in 2nd
and 3rd fingers of right hand
H&P
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Breast cancer, ER/PR positive stage 4 with metastatic
disease to cervical spine, received radiotherapy and
was on anastrazole Aug 2012
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Recent addition of Fulvestrant for newly noted
cervical spine disease
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Recurrent pleural effusions, non-malignant
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Pericardial effusion with tamponade s/p emergent
pericardiocentesis in Nov 2012
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HTN
Past Medical History
Appendectomy
• Hysterectomy
• Pacemaker placement
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Past surgical history
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Benazepril
Furosemide
Potassium chloride
Carvedilol
Anastrozole (Arimidex)
Fulvestrant (Faslodex)
Home medications
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Vitals: BP: 239/124 mmHg, HR: 114/min, O2: 99% 100% on 2 L nasal cannula, T 36.6 C/ 97.9 F
General: alert
ENT: unremarkable, no icterus
Resp: crackles to middle of chest bilaterally, wheezes
in upper lobes
CV: JVP to jaw, no murmur, RRR, S3, 2 +pitting
edema
Abdomen: no organomegaly
Neurological: alert/oriented, normal strength, tone,
reflexes and coordination
Skin: no petechiae, no bruising
Physical examination
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CBC: WBC: 8.99 (4-11)
Hgb: 11.6 (3/2013)-> 10.1 (4/1/2013)-> 8.1 (4/18/2013)
Platelets: 100-130 (3/2013) -> 80(4/18/2013)
RDW=17.3
Calcium 7.7 (8.5-10.1)
Phos 2.8 (2.5-4.9)
Glucose 85
Na 143
K 4.6 (3.5-5.1)
CL 106 (98-107)
CO2 29 (21-32)
LDH 660 (84-246)
Haptoglobin 14.1 (30-200)
Creatinine 0.77 (3/2013)->1.82 (4/1/2013)->4.69 ( 4/18/2013)
Laboratory tests
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COLOR
Latest Range: COLORLESS-YEL.
APPEARANCE
Latest Range: CLEAR
SP. GRAVITY
Latest Range: 1.003-1.033
PH
Latest Range: 5.0-8.0
PROTEIN
Latest Range: NEGATIVE mg/dl
GLUCOSE
Latest Range: NEGATIVE mg/dl
KETONE
Latest Range: NEGATIVE mg/dl
BILIRUBIN
Latest Range: NEGATIVE
BLOOD
Latest Range: NEGATIVE
NITRITE
Latest Range: NEGATIVE
UROBILINOGEN Latest Range: <2.0 mg/dl
LEUKOCYTE ESTERASE Latest Range:
RBC Latest Range: 0-20 /ul
WBC Latest Range: 0-25 /ul
SQUAMOUS EPI Latest Range: 0-30 /ul
HYALINE CASTS Latest Range: 0-5 /ul
LT YELLOW
HAZY (A)
1.010
6.0
100 (A)
NEGATIVE
TRACE
NEGATIVE
MODERATE (A)
NEGATIVE
NORMAL
LARGE (A)
123 (H)
958 (H)
19
0
Urine analysis with microscopy
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CT Brain : IMPRESSION: Minimal cerebral
atrophy. Moderate chronic small vessel
ischemic change. Otherwise negative with no
evidence of acute finding.
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CXR: Bibasilar atelectasis and pleural fluid.
Pleural fluid is increased in the left base
compared with 11/20/13. Decreased right
base pleural fluid. Left anterior chest with
CCD with lead tips in right atrium and right
ventricle. No other change.
Imaging
CXR
65 y/o female with metastatic breast
cancer with hypertensive crisis, new onset
renal failure, anemia, thrombocytopenia
 Volume overload with elevated JVD and
chest X ray picture suggestive of vascular
congestion
 UA with proteinuria, hematuria and pyuria
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Summary
The RIFLE criteria consists of various graded levels of kidney injury
based upon percent rise in serum creatinine, urine output and
outcome measures.
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Risk: 1.5-fold increase in the serum creatinine or GFR decrease
by 25 percent or urine output <0.5 mL/kg per hour for six hours
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Injury: Twofold increase in the serum creatinine or GFR decrease
by 50 percent or urine output <0.5 mL/kg per hour for 12 hours
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Failure: Threefold increase in the serum creatinine or GFR
decrease by 75 percent or urine output of <0.5 mL/kg per hour
for 24 hours, or anuria for 12 hours
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Loss: Complete loss of kidney function (eg, need for renal
replacement therapy) for more than four weeks
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ESRD: Complete loss of kidney function (eg, need for renal
replacement therapy) for more than three months
Acute Kidney Injury (AKI)
The AKIN (Acute Kidney Injury Network) criteria are a
modification of the RIFLE criteria and include both diagnostic
and staging system.
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Stage 1. Increase in serum creatinine 0.3 mg/dl or 1.5 to 2
fold increase from baseline or urine output less than 0.5
mL/kg per hour for more than 6 hours
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Stage 2. Increase in serum creatinine >2-3 folds from
baseline or urine output less than 0.5 mL/kg per hour for
more than 12 hours
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Stage 3. Increase in serum creatinine >3 fold from baseline or
serum creatinine of 4.0 mg/dl with an acute rise of at least
0.5 mg/dl or urine output less than 0.3 mL/kg per hour for 24
hours or anuria for 12 hours.
AKI definition
Etiology of AKI
Causes
Pre renal azotemia
Poor fluid intake, fluid loss
(vomiting, diarrhea, hemorrhage),
NSAIDS, ACEI and ARBS, evidence
of volume depletion, heart failure,
decreased effective circulatory
volume (cirrhosis, heart failure)
Sepsis associated AKI
Sepsis, sepsis syndrome, septic
shock
Ischemia associated AKI
Systemic hypotension, age, CKD
Nephrotoxin associated AKI
(endogenous)
Rhabdomyolysis, hemolysis, tumor
lysis syndrome, multiple myeloma,
contrast nephropathy
Nephrotoxin associated AKI
(exogenous)
Tubular injury from medications,
interstitial nephritis
AKI
Etiology of AKI
Causes
Glomerulonephritis/ vasculitis
Good Pasteur’s disease,
Microscopic polyangitis,
granulomatous polyangitis
Non drug associated interstitial
nephritis
Tubuluinterstitial nephritis uveitis
syndrome, Legionella infection
Thrombotic microangiopathy
TTP/HUS
Atheroembolic disease
Recent vascular procedures :
cardiac catheterization
Post Renal AKI
Kidney stones, prostate
hypertrophy, obstructed bladder
catheter
AKI
Urine sediment
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Accounts for 40-55% of all cases of acute renal injury
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Volume responsive- Hemorrhage (traumatic,
gastrointestinal, surgical), gastrointestinal losses
(vomiting, diarrhea, nasogastric suction), renal losses
(overdiuresis, diabetes insipidus), and third spacing
(pancreatitis, hypoalbuminemia)
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Volume unresponsive - Cardiogenic shock, septic
shock, cirrhosis, hypoalbuminemia, and anaphylaxis
all decrease effective arterial circulating volume,
independent of total body volume status, and result
in reduced kidney blood flow
Pre renal azotemia
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Hypoperfusion activates baroreceptors and activates a
cascade of neural and humoral responses
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Increase in antidiuretic hormone and renal adrenergic
activity
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Increase in angiotensin II activity which causes afferent
arteriolar constriction that reduces renal plasma flow, GFR,
and the filtration fraction, and markedly augments
proximal tubular sodium reabsorption in an effort to
restore plasma volume
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Severe and untreated hypoperfusion predisposes the
kidney to ischemic acute tubular necrosis (ATN) and
nephrotoxic AKI
Pathophysiology
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BUN/Creatinine ratio >20
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FeNa <1%
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Hyaline casts in urine sediment
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Urine specific gravity >1.018
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Urine osmolality >500 mOsm/kg
Laboratory studies
Upper urinary tract
Extrinsic
Upper urinary tract
intrinsic
Lower urinary tract
Retroperitoneal
space-lymph nodes,
tumors
Nephrolithiasis
Prostate- BPH,
Carcinoma, infection
Pelvic or
intraabdominal
tumors
Strictures
Bladder- calculi, neck
obstruction, cancer,
infection
Fibrosis
Edema
Functional
Ureteral
ligation/surgical
trauma
Debris, blood clots,
sloughed papillae,
fungal ball
Urethral – posteriors
urethral valves,
strictures, trauma
Granulomatous
disease
malignancy
Hematoma
Post renal AKI
Accounts for less than 5% of AKI
 Pain and oliguria are non specific findings
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Post renal AKI
Intrinsic AKI
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Ischemic insult causes proximal tubule cell injury
and dysfunction
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Profound drop in GFR through afferent arteriolar
vasoconstriction
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Mediated by tubular glomerular feedback and
proximal tubular obstruction
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Sloughed tubule cells, brush border vesicle
remnants and cellular debris in combination with
Tamm-Horsfall glycoprotein form the classical
muddy brown granular casts
Acute Tubular Necrosis (ATN)
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Regeneration can occur after removal of the
insult
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Minimally injured cells will repair themselves
without dedifferentiation
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Severely injured cells will undergo
dedifferentiation with proliferation of viable
cells which spread across the denuded
basement membrane and convert back into
normal tubular cells
ATN
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Muddy brown granular or tubular
epithelial cell casts
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FeNa >1%
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UNa >20 mEq/L
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Specific gravity ~ 1.010
Laboratory findings
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Systemic allergic response
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Leukemia, lymphoma, sarcoidosis, bacterial
infections, viral infections
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Rash, fever, eosinophilia, pyuria with
eosinophiluria (in NSAID related AIN
lymphocytes predominate)
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Inflammatory infiltrates in interstitium in deep
cortex and outer medulla with edema
Acute interstitial nephritis (AIN)
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The kidneys are vulnerable to toxicity due to
their high blood flow, and they are the major
route for metabolizing and eliminating drugs and
toxins
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Concentration of drugs within the tubular lumen
and the interstitium leads to higher exposure
rates
Nephrotoxic AKI
Nephrotoxic ATN -AKI
Intrinsic AKI
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The nephrotic syndrome is defined by the relatively
acute onset of edema, nephrotic range proteinuria (defined
as greater than 3.5 g/d per 1.73 m2 of body surface area),
hypoalbuminemia, hyperlipidemia, and lipiduria, all of
which occur with minimal impairment of the glomerular
filtration rate (GFR).
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The acute nephritic syndrome in its full-blown form is
characterized by edema; hypertension; azotemia with the
variable presence of oliguria; and a ‘‘nephritic’’ urinary
sediment marked by the presence of erythrocytes (red
blood cells [RBCs]), leukocytes (white blood cells [WBCs]),
cellular casts (especially RBC casts), and mild to moderate
proteinuria.
Glomerular injury
Acute Nephritic syndrome
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All age groups might be affected though more
common in children and young adults and occurs
more often in boys and men
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Characteristic presentation for IgAN is recurrent
episodes of macroscopic hematuria (usually
brown in color without blood clots) that may be
associated with flank pain and typically coincide
with or closely follow an upper respiratory tract
infection
Ig A nephropathy
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Granulomatous polyangiitis and microscopic
polyangiitis
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Systemic small-vessel vasculitides that typically
affect multiple organ systems and are associated
with nonspecific features of inflammation, such
as fever, malaise,myalgia, arthralgia, and weight
loss, with a peak age of onset in the seventh and
eighth decades
ANCA associated
glomerulonephritis
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The renal features of ANCA-associated vasculitis
are oliguria, hematuria, and proteinuria with RBC
casts
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Serum creatinine may or may not be elevated on
initial presentation but generally increases
rapidly over days to weeks without treatment
ANCA associated
glomerulonephritis
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Diffuse pulmonary infiltrates on chest
radiographs and a microcytic anemia are
suggestive of concurrent alveolar hemorrhage
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Antibodies directed against proteinase 3 are
usually associated with c-ANCA and with GP,
whereas antibodies against myeloperoxidase,
generally seen in MPA and renal-limited disease,
give a p-ANCA pattern
ANCA associated
glomerulonephritis
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The disease has two peaks of occurrence, the
first in younger men and the second in elderly
women, but it can occur at any age and in either
sex
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Extra renal findings- pulmonary hemorrhage,
arthralgias, fevers, chills, hepatosplenomegaly
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Renal presentation is a typical nephritic
syndrome
Anti- GBM syndrome
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Idiopathic type 1 MPGN is most often seen in
adolescents and young adults as a renal-limited
disorder presenting with severe proteinuria or
nephrotic syndrome and accompanying nephritic
features, particularly hematuria and RBC casts
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Azotemia and hypertension may be present
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The clinical presentation is similar in adults; however,
the disease is usually secondary to a chronic or
subacute infectious process, systemic autoimmune
disorder, or lymphoma
Membranoproliferative GN
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Thrombotic microangiopathy (TMA) in the form
of Hemolytic uremic syndrome (HUS) and
Thrombotic thrombocytopenic purpura (TTP) is a
disease of multiple etiologies manifesting as nonimmune hemolytic anemia, thrombocytopenia,
varying degrees of encephalopathy, and renal
failure due to platelet thrombi in the
microcirculation of the kidneys
Thrombotic microangiopathy
(TMA)
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HUS develops in children with hemorrhagic colitis
from infection by verotoxin-producing
Escherichia coli associated with ingestion of
undercooked meat
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Idiopathic TTP is usually seen in adult women
with encephalopathy as the predominant clinical
feature
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Both arise from endothelial cell dysfunction and
cause a similar clinical and laboratory picture
Thrombotic microangiopathy
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TTP classically manifests with the pentad of
thrombocytopenia, microangiopathic hemolytic
anemia, fever, neurologic dysfunction, and renal
dysfunction
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Thrombocytopenia is diagnostic; most patients
present with values below 60,000/μL
TTP
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Laboratory findings include elevated indirect
bilirubin and lactate dehydrogenase levels,
depressed serum haptoglobin values, and
schizocytes on peripheral blood smear
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The characteristic renal lesion consists of vessel
wall thickening in capillaries and arterioles, with
swelling and detachment of endothelial cells from
the basement membranes and accumulation of
subendothelial fluffy material
Thrombotic microangiopathy
Drugs
Immunosuppressive
Agents
Malignancy
Hematopoietic cell
transplantation
Mitomycin C
Cyclosporin
Gastric Ca
Bone marrow
transplant
nephropathy
Cisplatin
Tacrolimus
Breast Ca
Radiation
nephropathy
Bleomycin
Rapamycin
Lung Ca
Gemcitabine
TMA in cancer patients
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Rapidly progressive BP elevations with target
organ injury including retinal hemorrhages,
encephalopathy, and declining kidney function
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If untreated, patients with target organ injury
including papilledema and declining kidney
function suffered mortality rates in excess of
50% over 6–12 months, hence the designation
“malignant”
Malignant hypertension
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Renal abnormalities typically include rising serum
creatinine and occasionally hematuria and
proteinuria
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Biochemical findings may include evidence of
hemolysis (anemia, schistocytes, and
reticulocytosis) and changes associated with
kidney failure
Malignant hypertension
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Renal vein thrombosis (RVT) presents with flank pain,
tenderness, hematuria, rapid decline in renal
function, and proteinuria
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Homocystinuria, endovascular intervention, surgery,
dehydration, compression and kinking of the renal
veins from retroperitoneal processes such as
retroperitoneal fibrosis and abdominal neoplasms,
antiphospholipid antibody syndrome, nephrotic
syndrome, proteins C and S, antithrombin deficiency,
factor V Leiden, disseminated malignancy, and oral
contraceptives
Renal vein thrombosis
Intrinsic AKI
Urine sediment
History
 h/o chemotherapy
 h/o infections, fevers
 OTC medication use
Exam
 Previous BP readings, orthostats
Laboratory tests
 CBC with differential and RBC indices
 Hepatic function panel with bilirubin
 Fractional excretion of sodium
Extra information for diagnosis
1.
2.
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5.
Thrombotic thrombocytopenic purpura
Malignant hypertension
Renal vein thrombosis
ANCA associated vasculitis
ATN- nephrotoxins/ischemic
Differential Diagnosis

Taal: Brenner and Rector’s the kidney; 9th Ed. 2011-Saunders, an
imprint of Elseviers, accessed through MD consult

Harrison’s online: Harrison’s principles of Internal Medicine, 18
Ed. Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L.
Hauser, J. Larry Jameson, Joseph Loscalzo, Eds. Accessed through
Access Medicine

Beck, L.H., Salant, D.J. (2008) Glomerular and tubulointerstitial
diseases. Primary Care Clinical Office Practice. Vol. 35: 265–296
References