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Board Review 2009
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Hypo/Hyper natremia
mixed acid/base disturbances
Nephrotic Syndrome
Glomerulonephitis
RTAs
Calcium/Phosphate homeostasis
renal vasculitis
pictures of urine sediment
ATN
AIN
CKD staging and principles of management
Indications for renal transplant
Below is a list of topics that our residents did not do well on during the In-Training exam:
diagnosis of primary hyperaldosteronism in metabolic alkalosis
diagnose type 4 rta
diagnose psychogenic polydipsia
diagnose mixed acid/base disturbances
diagnose membranous GN
evaluate PCKD
diagnose IgA nephropathy
manage proteinuria in CKD
Question 1
A 65 y.o. male is referred for evaluation of edema and proteinuria. He
complains of fatigue, but otherwise is asymptomatic. On exam the
BP is 150/80. There is 1+ ankle edema. Labs show hemoglobin 10
(MCV 74, RDW 20); urine protein:creatinine ratio is 4.4 mg/gm,
serum creatinine is 1 mg/dL, and cholesterol is 320 mg/dL. Serum
complement levels are normal. Urinalysis shows 3+ protein,
hyalofatty casts and oval fat bodies.
Which of the following is the most likely cause of this patient’s renal
symptoms?
A.
B.
C.
D.
E.
Minimal change glomerulopathy
FSGS
Membranous glomerulopathy
IgA nephropathy
ANCA-associated GN
Question 2
A 19 y.o. female is evaluated for sudden onset periorbital and pretibial
edema. 3 weeks ago she was diagnosed with an URI that has
since resolved. On PE the BP is 150/100. A soft S3 gallop is
present. There are crackles at both lung bases. The liver is
enlarged and tender. There is bilateral pitting pretibial edema.
There is no rash. Labs show creatinine 1.5, albumin 3.8. C3 and C4
are low. Urinalysis shows rare dysmorphic red cells and trace
protein.
Which of the following is the most likely diagnosis?
A. IgA nephropathy
B. Goodpasture's syndrome
C. ANCA vasculitis
D. Postinfectious GN
E. SLE nephritis
Question 3
A 19 y.o. female presents with a several month history of symmetric
arthralgias, Raynaud’s phenomenon, and a Coomb’s positive
hemolytic anemia. On physical exam she has a malar rash that
crosses the nasal labial folds. The heart and pulmonary exams are
unremarkable. Her abdomen is benign. There is 1 + leg edema.
Urinalysis shows red cell casts and 2+ protein. A kidney biopsy
shows immune complex focal proliferative glomerulonephritis.
Which if the following tests provides the most additional diagnostic
information?
A. Low C 3 and C4
B. Positive ANA
C. Positive ss-DNA
D. Positive anti-Smith antibody
E. Positive ds-DNA
Question 4
A 51-year-old man with a history of chronic lymphocytic leukemia with transformation to
prolymphocytic leukemia is hospitalized for chemotherapy with R-CHOP (cyclophosphamide
doxorubicin vincristine prednisone rituximab).
On physical examination, he is afebrile, pulse rate is 98/min, respiratory rate is 16/min, and blood
pressure is 134/78 mm Hg. There is lymphadenopathy involving the cervical and submental
chains and supraclavicular areas bilaterally, as well as bulky axillary and inguinal
lymphadenopathy. Cardiac and pulmonary examinations are normal. The spleen is palpable
approximately 3 cm to 4 cm below the left costal margin, and there is no hepatomegaly. There is
no edema, cyanosis, or clubbing of the extremities.
Labs show hematocrit 22%, leukocyte count 110,000/µL, platelet count 19,000/µL, BUN 63 mg/dL, uric
acid 19 mg/dL, creatinine 1.3 mg/dL, potassium 5.5 meq/L, bicarbonate 17 meq/L, albumin 4.2
g/dL, calcium 7.5 mg/dL, phosphorus 5 mg/dL, urinalysis pH 5, numerous finely granular
casts/hpf, no uric acid crystals
In addition to hospitalization for intravenous hydration, which of the following is the most appropriate
next step in this patient’s management?
A. Furosemide
B. Rasburicase
C. Allopurinol
D. Probenecid
Tumor Lysis Syndrome
• Acute oliguric renal failure associated with urate levels > 15
mg/dl and hyperphosphatemia
• Associated with overproduction and excretion of urate and cell
lysis resulting in increased release of potassium and
phosphorus in patients undergoing chemotherapy or with a
heavy tumor burden
• Urine urate/creatinine > 1
• Prevention: allopurinol 600-900 mg/d + NS (uo > 2.5 l/d)
• Urinary alkalinization may worsen calcium phosphate
precipitation and NS is as effective as urinary alkalinization
alone
• Early dialysis indicated for oliguric ARF to decrease urate
burden
Risk Stratification for TLS
Risk
Type of cancer
High
Intermediate
Low
NHL
Burkitt's, lymphoblastic, B-ALL
DLBCL
Indolent NHL
ALL
WBC ≥100,000/microL
WBC 50,000-100,000/microL
WBC
≤50,000/microL
AML
WBC ≥50,000/microL,
monoblastic
WBC 10,000-50,000/microL
WBC
≤10,000/microL
CLL
WBC 10,000-100,000/microL
treated with fludarabine
WBC
≤10,000/microL
Other
hematologic
malignancies
(including CML
and multiple
myeloma) and
solid tumors
Rapid proliferation with expected
rapid response to therapy
Remainder of
patients
*From Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the
management of pediatric and adult tumor lysis syndrome: an evidence-based
review. J Clin Oncol. 2008; 26:2767-78.
Prevention of TLS
• If there is a concern about tumor lysis, as predicted by an elevated
serum LDH, serum uric acid, or heavy tumor burden, the patient
should be admitted for hydration and close monitoring of kidney
function, serum potassium, phosphorus and uric acid.
• Patients with a preexisting reduction in GFR, oliguria and/or acidic
urine, and volume depletion should also be hospitalized for
hydration and observation.
• High-risk patients should be hospitalized for aggressive intravenous
hydration and prophylactic rasburicase.
• Intermediate risk patients should receive allopurinol rather than
rasburicase for prophylaxis in the absence of pretreatment
hyperuricemia.
• Patients at low risk for TLS should receive hydration, but do not
require hypouricemic therapy.
Question 5
A 64-year-old woman is evaluated for progressive weakness, nausea, dyspnea, and acute renal failure
of several weeks’ duration. Her creatinine level is 4.6 mg/dL (last creatinine is 1.3 mg/dL 2 months
ago). She has a history of type 2 diabetes mellitus and hypertension treated with metoprolol and
hydrochlorothiazide. Other medications include aspirin and glipizide.
On physical examination, the blood pressure is 110/70 mm Hg. Fundoscopic examination reveals
arteriovenous nicking but no evidence of diabetic retinopathy. Cardiac examination shows a
laterally displaced PMI and a grade I holosystolic murmur at the apex. On pulmonary examination,
the lungs are clear to auscultation. There is no pedal edema.
Hemoglobin 12.8 g/dL, leukocyte count 8000/µL, platelet count 311,000/µL, BUN 48 mg/dL, uric acid
11.6 mg/dL, creatinine 4.6 mg/dL, sodium 140 meq/L, potassium 4.3 meq/L, chloride 110 meq/L,
bicarbonate 26 meq/L, total protein 8.4 g/dL, albumin 3.8 g/dL, calcium 10.5 mg/dL, phosphorus
5.6 mg/dL, lactate dehydrogenase 634 U/L; Urinalysis pH 6.5, trace protein, trace blood, 2
leukocytes/hpf, amorphous crystals. Urine sodium 60 meq/L, urine creatinine 90 mg/dL, urine
protein–creatinine ratio 3 mg/mg
Renal ultrasound shows enlarged hyperechoic kidneys bilaterally measuring 14 cm in length. Chest
radiograph reveals mild cardiomegaly but is otherwise unremarkable.
Which of the following is the most likely diagnosis?
A. Uric acid nephropathy
B. Thiazide-induced acute renal failure
C. Primary amyloidosis
D. Myeloma cast nephropathy
E. Lymphomatous infiltration of the kidneys
Question 6
A 38 y.o. man with a history of chronic liver disease secondary to hepatitis C is
treated with a 24-wk course of pegalated IFN combined with ribavarin.
Four weeks after completing treatment he complains of proximal muscle
weakness. On PE the BP is 120/80, pulse 110, RR 18. His general exam
is unremarkable. On neurologic exam he has symmetric proximal
weakness 3/5. Labs show Na 142, K 2.1, Cl 104, HCO3 20, creat 1. Urine
Na 100, urine K 10, urine Cl 110, urine osm 585, urine pH 5.3.
Which of the following is the most likely diagnosis?
A.
B.
C.
D.
E.
F.
Distal renal tubular acidosis (type I)
Vomiting
Diuretic abuse
IFN complication
Hypomagnesemia
Diarrhea
Question 7
A 34 year old woman who underwent elective laparoscopic cholecystectomy develops
severe headache and nausea the next morning. During the surgery, D5½NS was
started and continued postoperatively at 125 mL/hr. She remained in recovery until
late afternoon because she was too sedated to be discharged. Intravenous
meperidine is administered with adequate relief of her pain. On physical exam the
blood pressure is 130/80. She is afebrile. The heart and lung exams are normal.
There is no peripheral edema. Neurologic exam is remarkable only for lethargy.
Laboratory studies show sodium 128, potassium 3.4, chloride 86, bicarbonate 28, BUN
10, creatinine 0.8, glucose 86. Urine sodium 46, urine osmolality 453.
Which of the following should be done next?
A.
B.
C.
D.
E.
NS 200 mL/hr + furosemide
3% saline at 1 ml/kg/hr + furosemide
Emergent head CT
Naloxone
Observation
Symptomatic Hyponatremia:
Recommendations for Management
• 3% saline at average rate of 1 mL/kg/hr over
first 24 hours + furosemide if urine osm >
300 mOsm/kg or risk of CHF
• Stop therapy when symptoms resolve
• Measure the serum sodium every 1-2 hours
for the first 6 hours and then every 4 hours
• Do not exceed 10 mEq/L in 24 hours or 18
mEq/L in 48 hours in a symptomatic patient
with chronic hyponatremia
Hyponatremia: Recommendations for
Management
• Do not use fluid restriction alone in the symptomatic
patient
• If the serum sodium increases too rapidly, interrupt
the increase by starting hypotonic fluids and/or
dDAVP 4 micrograms s.c.
• Do not use 0.9% NaCl for symptomatic patients
with SIADH, especially when the urine osm is > 300
mOsm/kg
• Do not use vaptan therapy for symptomatic patients
Question 8
A 46 y.o. male is hospitalized for severe necrotizing pancreatitis. He is placed on NG
suction and over the first 24 hours of hospitalization he receives 6 liters of NS and
then NS at 100 mL/hour. Over the next 24 hours his urine output increases to > 3
liters per day and his plasma sodium concentration rises from 145 meq/L on
admission to 153 meq/L.
On exam the blood pressure is 140/90. Chest is clear . There is no edema.
Labs show sodium 153, potassium 3, chloride 112, bicarbonate 24, BUN 49, creatinine
1.1, urine sodium 50, urine potassium 20, urine osmolality 500 mosm/kg.
Which of the following is the most likely cause of this patient’s polyuria?
A.
B.
C.
D.
Central diabetes insipidus
Nephrogenic diabetes insipidus
Post obstructive diuresis
Solute diuresis
Polyuria
• Urine output exceeding 3 L per day
• Etiology
– Water diuresis
• diabetes insipidus
– central
– nephrogenic
• primary polydipsia
– Solute diuresis
Evaluation of Polyuria
Urine Osmolality
< 250 mosm/kg
Water Diuresis
> 300 mosm/kg
Solute Diuresis
Urine and Plasma Osmolality
in Disorders of Water Balance
1000
Normal
Water
Deprivation
dDAVP
800
Primary polydipsia
600
Central DI
400
Nephrogenic DI
200
280
285
290
295
Posm(mosm/kg)
300
Question 9
A 58-year-old woman with a history of chronic alcohol abuse is admitted to the hospital
for evaluation of abdominal pain and vomiting. A diagnosis of recurrent pancreatitis is
made on the basis of the history of alcoholism, the presence of diffuse abdominal
tenderness and decreased bowel sounds, and elevated serum amylase and lipase
levels.
Therapy is begun with intravenous fluids (0.9% saline and 5% dextrose in water at
75 mL/hr) and nasogastric drainage, which produces copious amounts of fluid. After
five days of therapy, the patient's symptoms resolve and the following laboratory
studies are obtained:
BUN 21 mg/dL, serum creatinine 1.4 mg/dL, plasma glucose180 mg/dL, serum sodium
140 mEq/L, potassium 2.6 mEq/L, chloride 86 mEq/L, bicarbonate 38 mEq/L, urine
pH 7.0, urine sodium 50 mEq/L, urine chloride 5 mEq/L
Which of the following best explains the hypokalemia in this patient?
(A) Renal potassium losses derived from decreased proximal tubule reabsorption
(B) Potassium loss in the gastric aspirate
(C) Intracellular redistribution of potassium is a major determinant of the hypokalemia
(D) Increased aldosterone and distal nephron bicarbonate delivery causing renal
potassium losses
Metabolic Alkalosis
BP
Volume status
BP Normal or Low
 Effective circulating volume
Loss of HCl
Loss of Volume (Na+/H20)
Loss of Gastric secretions
(vomiting, NG suction)
Diuretics
Bartter syndrome
Gitelman syndrome
BP High
 ECF
Primary
Hyperaldosteronism
Metabolic Alkalosis: Loss of Gastric
Secretions-Generation Phase
H+ ClParietal
Cell
K+
H+
Generation of
NaHCO3
Cl-
H2CO3
HCO3-
K+
Na+
HCO3-
Loss of HCl
from Stomach
Na+ ClCl-
Na+
ClNa+ K+
Cl- Cl-
Na+
Cl-
Kidney
Na+
ClK+
Na+
Na+
HCO3
HCO3-
-
1. Elimination of chloride from
the urine
2. Excretion of NaHCO3 and
KHCO3 in Urine
Na+
HCO3K+
HCO3-
Metabolic Alkalosis: Loss of Gastric
Secretions-Maintenance Phase
Volume Contraction
Reabsorption of sodium,
chloride, and bicarbonate
along the nephron
Secondary increase
in aldosterone
Metabolic alkalosis
Paradoxical
aciduria
Elimination of sodium,
chloride, and bicarbonate
from the urine
Increased H+
Excretion
Question 10
A 42 y.o. female is evaluated for minimal edema and a urinary protein excretion
of 5 gm/24 hours. As a child she had frequent urinary tract infections and
underwent a surgical procedure to reimplant the ureters to prevent reflux.
On PE the BP is 140/95. There is trace peripheral edema. Labs show
creatinine 1.5, albumin 3.4, Urinalysis shows 3 + protein and oval fat
bodies.
Chest x-ray is normal. Renal US shows a normal left kidney and the right
kidney small and difficult to visualize.
Which of the following is the most likely cause of the proteinuria?
A.
B.
C.
D.
Minimal change disease
Membranous nephropathy
FSGS
Membranoproliferative GN
Focal Segmental Glomerulosclerosis (FSGS)
•Most common cause for nephrotic syndrome in
African-Americans
•Occurs as a primary (idiopathic) glomerular
disease and also secondary to recognized causes
(such as obesity, HIV infection, and inherited
genetic defects)
•This is a pathologically and clinically
heterogeneous category of disease that includes
multiple structural variants with different
demographics, clinical presentations and outcomes
Different Structural Variants of FSGS
Perihilar
Tip Lesion
Collapsing
Cellular
PRIMARY (IDIOPATHIC) FSGS
SECONDARY FSGS
VIRUS-ASSOCIATED
HIV-1 (“HIV-associated nephropathy”)
Parvovirus B-19
FAMILIAL FSGS
Mutations in α-actinin 4 gene
Mutations in NPHS2 gene for podocin
Mutations in TRPC6 gene for a cation channel
DRUG TOXICITY
Heroin (“Heroin nephropathy”)
Pamidronate
Interferon-α
MEDIATED BY ADAPTIVE STRUCTURAL RESPONSES
Reduced renal mass
Obesity
Cyanotic congenital heart disease
Sickle cell anemia
Question 11
A 44 y.o. female with cirrhosis is admitted with fever and abdominal
pain. Medications include spironolactone, furosemide, and
lactulose. On exam the BP is 74/55, HR 72, T 38.3, RR 24. She is
cachectic. The abdomen is tense and diffusely tender. There is 1+
leg edema.
Labs show Serum sodium 128, potassium 5.1, chloride 104,
bicarbonate 12, BUN 20, creatinine 1.3, glucose 84, albumin 1.4.
ABG pH 7.25, pCO2 28, pO2 78.
Which best describes the acid-base status of this patient?
A. Mixed anion gap metabolic acidosis and respiratory alkalosis
B. Mixed anion gap metabolic acidosis and respiratory acidosis
C. Anion gap metabolic acidosis
D. Hyperchloremic acidosis
E. Mixed anion gap metabolic acidosis and hyperchloremic acidosis
Question 11 Analysis
1. What is the overriding disorder?
Metabolic acidosis
2. What is the anion gap?
128-104-12 = 12, increased AG met acidosis (Normal anion
gap is ~5.5 in this case due to the hypoalbuminemia- For every 1
gm/dL fall in the albumin from 4 gm/dL, the anion gap expected
anion gap decreases 2.5 mEq/L).
3. What is the expected bicarbonate with pure AG metabolic acidosis?
25-(12-5.5) = 18.5 Meas bicarb is 12,  concurrent hyperchloremic
metabolic acidosis
4. What is the expected pCO2 with normal respiratory compensation?
Expect PCO2 = 12 + 15 = 27. Meas PCO2 is 28, normal resp
comp
Answer = Mixed AG met acid, hyperchloremic met acidosis
Question 12
23-year-old Caucasian female referred for further evaluation of hypokalemic acidosis.
She was in her usual state of excellent health with normal growth and development
until her second month of pregnancy. She had a spontaneous miscarriage, and
was found to have a serum potassium of 3.2 mEq/L and a bicarbonate level of 19
mEq/L during a hospitalization for a D and C. She was treated with oral potassium
and bicarbonate supplements and then weaned these off after 4 months of therapy.
Six weeks later, she developed myalgias and collapsed due to profound weakness.
She was found to have a serum bicarbonate level of 14 mEq/L with a serum
potassium of 1.9 mEq/L.
140 114 13 Calcium 9.1
1.9 14 1 Phosphorus 3.5
ABG-pH 7.29, PCO2 30, pO2 100
Urine K 46 Urine Na 36 Urine Cl 42 Urine Osm 580
UA ph 6.8 trace protein No casts 10-15 white cells per high power field
Which of the following is the correct diagnosis?
A.
Type IV RTA
B.
Diarrhea
C.
Type I RTA
D.
Renal tubular alkalosis
E.
Proximal RTA
Practical Approach
(Hyperchloremic metabolic acidosis)
Urinary Anion Gap
Negative
Positive
Type 2 RTA
Diarrhea
DKA/Toluene
HCl (Hyperalimentation)
Urine pH and Plasma K
Urine pH < 5.5, K 
Urine pH > 5.5, K nl/low
Urine pH > 5.5, K 
Type 4
Type 1 (secretory defect
or back-leak)
Type 1 (voltage)
Type I Classic Distal RTA-Mechanism 1
Tubular lumen Na+
Na+
Peritubular
Capillary
3Na+
ATPase
(-)
(-)
K+
K+ Wasting
ClUrine pH > 5.5
Ca-P stones
H 2O
(-)
R-Aldo
3Na+
ATPase
T
2K+
OH- + CO2 HCO3-
K+
(-)
H+
ATPase
2K+ H+
Retention
Cl-
ATPase
H+
Type I Classic Distal RTA-Mechanism 2
Tubular lumen Na+
Na+
Peritubular
Capillary
3Na+
ATPase
(-)
(-)
K+
K+ Wasting
ClUrine pH > 5.5
Ca-P stones
H 2O
(-)
R-Aldo
3Na+
ATPase
T
2K+
OH- + CO2 HCO3-
K+
(-)
H+
ATPase
2K+ H+
Retention
Cl-
ATPase
H+
Type I Distal RTA-Mechanism 3
Tubular lumen Na+
Na+
Peritubular
Capillary
3Na+
ATPase
(-)
(-)
K+
K+ Wasting
ClUrine pH > 5.5
H+
Ca-P stones
R-Aldo
Backleak of H+
H+
ATPase
H 2O
(-)
OH- + CO2
K+
(-)
2K+
3Na+
ATPase
T
2K+
HCO3Cl-
ATPase
H+
H+
Retention
Question 13
A 32 y.o. male presents with paresthesias, perioral numbness, and
generalized weakness. He is not on any medications. The BP is
120/88, and the physical exam is remarkable for dental caries.
Earlier in the day he had attended a birthday party for his nephew.
Labs show Na 139, potassium 2.8, chloride 90, bicarbonate 38.
Urine sodium 28, urine potassium 38, urine chloride < 10, urine
pH 6.2, urine calcium:creatinine ratio 0.2 (mmol/mmol).
Is this:
A. Barrter syndrome
B. Vomiting
C. Gitelman syndrome
D. Hypokalemia periodic paralysis
E. Licorice ingestion
Urine Na+ and Cl- in the
Differential Diagnosis of Metabolic
Alkalosis and Hypokalemia
Condition
Vomiting
Alkaline urine
Acidic urine
Diuretic
Drug active
Remote use
Hyperaldosteronism
Urine Electrolytes
Na+
Cl(meq/L)
>15
<15
<15
<15
>15
<15
>15
<15
>15
>15
Question 14
You are asked to evaluate a 42 year old woman because of hyponatremia. She has a
history of schizophrenia and is currently hospitalized because of suicidal and
homicidal ideation. Her admission laboratory studies obtained during a psychiatric
hospitalization were normal. Current medications are haloperidol and benztropine
mesylate.
Physical exam shows pulse 92 supine, 100 standing, BP 112/82 supine and 108/88
standing. Occasional involuntary movements of the tongue and lips are noted. There
is no edema.
Labs show sodium 120 mEq/L, potassium 4.2 mEq/L, chloride 85 mEq/L, bicarb 27
mEq/L, BUN 8 mg/dL, creatinine 0.8 mg/dL, serum osmolality 250 mOsm/kg, TSH
3.8 microunits/mL, uric acid 3.2 mg/dL; Urine sodium 12, urine potassium 3, urine
chloride 10, urine osmolality 55.
Which of the following is the most likely cause of this patient’s hyponatremia?
A. Primary polydipsia
B. Mineralocorticoid deficiency
C. Reset osmostat
D. Diuretic abuse
E. SIADH
Question 15
A 49 y.o. female is admitted to the hospital because of severe right sided abdominal pain
requiring administration of narcotic analgesics. The patient is unable to provide a
complete medical history, but reports that she has had seizures for as long as she
can remember.
Physical exam reveals papular skin lesions in the malar area. Bilateral flank masses are
noted. There is a 2-cm periungual nodular lesion on the right great toe.
Hematocrit is 25%. Serum creatinine is 5.5 mg/dL. CT of the abdomen without contrast
reveals enlarged kidneys with bilateral renal cysts of varying size in the cortex and
the medulla; several variably sized masses with densities identical to perinephric fat
are also detected in areas not involved with cysts.
Which if the following is the most likely diagnosis?
A. ADPCKD
B. Von Hippel-Lindau disease
C. Medullary cystic kidney disease
D. Tuberous sclerosis
E. Bilateral renal dysplasia
Question 16
A 66-year-old man comes for a follow-up
examination for elevated blood pressure.
1 week ago
He has a history of chronic kidney
disease and hypertension well controlled
Potassium
4.5 meq/L
with hydrochlorothiazide. One week
ago, he was evaluated in the office after
Creatinine
1.2 mg/dL
obtaining several home blood pressure
Urine
measurements averaging 145/90 mm
albumin:creatinine
Hg. Enalapril was added at that time.
200 mg/g
ratio
He has felt well and has no history of
cough, lower-extremity edema, or
dyspnea. He also takes low-dose
aspirin.
On physical examination today, temperature is
normal, blood pressure is 126/70 mm
Hg, respiration rate is 18/min, and pulse
rate is 78/min and regular. On cardiac
examination, the point of maximal
impulse is laterally displaced and an S4
gallop is heard. There is no edema.
In addition to dietary potassium restriction, which of the following is the most
appropriate next step in this patient’s management?
A.
B.
C.
D.
Add diltiazem
Discontinue enalapril; switch to metoprolol
Repeat creatinine and potassium measurement in 1 week
Kidney arteriography
Today
5.2 meq/L
1.5 mg/dL
Question 17
A 55 y.o. male with stage 3 chronic kidney disease
presents for routine follow up. Laboratory
studies show calcium 9.2 mg/dL, phosphorus
2.8 mg/dL, PTH 215 pg/mL, 25-OH vitamin D
10 ng/mL, 1,25-(OH)2-vitamin D 19.
Which one of the following would you recommend?
A. Restrict dietary phosphorus to 600 mg daily
B. Start sevelamer 800 mg three time daily with
meals
C. Start calcitriol 0.25 mcg once daily
D. Start ergocalciferol 50,000 units once weekly
Time Course of Physiologic Alteration in Calcium,
Phosphorus, Vitamin D and PTH in CKD
Stage 1
Stage 2
Stage 3
Stage 4
Stage 5
 25-OH-vitamin D
 1,25-(OH)2-vitamin D
Transient Post-prandial Hypocalcemia
Hypocalcemia
Hyperphosphatemia
Increased PTH secretion
90
80
70
60
50
40
30
GFR (mL/min/1.73 m2)
20
<15
Question 18
A 59 y.o. female presents with 2 weeks of R hip pain. The
past history is significant for end stage renal disease
due to stone disease complicating type I distal renal
tubular acidosis now on peritoneal dialysis, s/p bilateral
nephrectomy, s/p living donor kidney transplant 5
years ago with loss of allograft function after 3 years
from chronic rejection, gout, and hypothyroidism.
Medications include levothyroxine 0.15 mg p.o. daily,
allopurinol 150 mg p.o. daily, aspirin 81 mg p.o. daily,
erythropoietin 10,000 units subcutaneously weekly,
colchicine 0.6 mg p.o. daily, sevelamer 800 mg three
times daily with meals, multivitamin one daily, and
calcitriol 0.25 mcg once daily. There is no history of
exposure to aluminum containing medications.
Question 18
On physical exam there is tenderness over the lateral
trochanteric bursa and pain with internal and external
rotation of the hip. Labs show calcium 9.1 mg/dL,
phosphorus 5.6 mg/dL, intact PTH 21 pg/mL, 1,25dihydroxy-vitamin D 52 pg/mL (reference range 15-75);
25-hydroxy-vitamin D 25 ng/mL (reference range 1557), alkaline phosphatase 86 U/L (reference range 38126). TSH is normal at 2.5 microIU/mL (reference range
0.6-3.3). Plain films of the right hip show diffuse
osteopenia and an area of lucency along the medial
aspect of the femoral neck on the right consistent with
stress fracture.
Question 18
Which of the following is the most likely
diagnosis?
A. Adynamic bone disease
B. Beta-2 microglobulin associated amyloidosis
C. Osteomalacia
D. Osteitis fibrosa cystica
Disorder
Turnover
Mineralization
Clinical Features
Adynamic bone disease
Low
Decreased
Fractures
Bone pain
Osteopenia
Low PTH
Hypercalcemia with calcium loading
Osteitis fibrosa cystica
High
 Resorption
 Formation
Fractures
Mixed sclerosis and osteopenia
Bone pain
Proximal myopathy
High PTH
Elevated alkaline phosphatase
Subperiosteal reabsorption
Brown tumors (rare)
Osteomalacia
Low
Low
Fractures
Osteopenia
Bone pain
Proximal myopathy
Looser zones on x-ray
High PTH related to secondary
hyperparathyroidism
Usually related to aluminum
accumulation
Mixed uremic osteodystrophy
Mixed
Variable
PTH and bone alkaline phosphatase
variable
Osteoporosis
Low
Decreased
Osteopenia
CKD specific risk factors
-heparin
-steroids
-Hypogonadism
-Poor nutrition
-Vitamin D deficiency
-Metabolic acidosis
Amyloid
Variable
Variable
Due to accumulation of beta-2
microglobulin
Bone pain
Cystic bone lesions
Transplant ameliorates bone pain
Question 19
A 64-year-old woman is referred for evaluation
of a rising serum creatinine level. She had
been recently diagnosed with severe reflux
esophagitis for which she was treated with
omeprazole. Over the past several weeks she
had noted onset of generalized malaise,
fatigue, and anorexia. Screening laboratory
studies revealed that the serum creatinine
level had risen to 2.5 mg/dL (0.221 mmol/L)
compared with a previous value of 1.2 mg/dL
(0.106 mmol/L) 6 weeks ago.
Question 19
On physical exam the blood pressure was 120/60 mm
Hg. There was no rash or edema.
Laboratory studies showed sodium 138 mmol/L,
potassium 4.7 mmol/L, chloride 103 mmol/L, total
carbon dioxide 17 mmol/L, BUN 43 mg/dL (15.3
mmol/L), creatinine 2.5 mg/dL (0.221 mmol/L),
hemoglobin 11 gm/dL (110 gm/L), white count 8,200
mm3 without eosinophilia. Serologic studies
including ANA and ENA all returned negative.
Urinalysis revealed trace protein and 35 white blood
cells per high-power field without casts.
Question 19
What is the most likely diagnosis?
A. Ischemic acute tubular necrosis
B. Acute interstitial nephritis
C. Myeloma cast nephropathy
D. Pyelonephritis
E. Obstruction due to kidney stones
Etiology of Acute Interstitial Nephritis (AIN)
Etiology
Drugs
Frequency
71%
Penicillins and cephalosporins
NSAIDs, including COX-2
inhibitors
Rifampin
Sulfonamides
Quinolones
Allopurinol
Proton pump inhibitors
Indinavir
5-aminosalicylates (e.g. mesalamine)
H-2 blockers
Infection
15%
Tubulointerstitial
5%
nephritis and uveitis
Sarcoidosis
1%
Baker RJ and Pusey CD. Nephrol
Dial Transplant 2004;19:8-11.
Medication
Frequency
Antibiotics
Cephalosporins
Quinolones
Penicillins
56%
15/34
12/34
7/34
NSAIDs
37%
Other
Allopurinol
Omeprazole
Ranitidine
Pimozide
7%
González E, et al. Kidney
Int 2008; 73: 940–946.
Clinical Features of AIN
Clinical Feature
Leukocyturia
Microhematuria
Fever
Eosinophilia
Rash
Oliguria
Frequency
82%
67%
42%
34%
23%
23%
González E, et al. Kidney Int 2008; 73: 940–946.
Corticosteroid Treatment for AIN
Serum creatinine (mg/dL)
7
6
5
P<0.05
4
No steroids
3
2
Steroid-treated
1
0
Baseline SCr (NS)
Peak SCr (NS)
Final SCr (p<0.05)
• Chronic dialysis in 44% with no steroids vs 3.8%
with steroids (Small study-52 patients treated with
steroids, 9 managed with drug withdrawal alone)
• Trend toward more fibrosis on biopsy when steroids
withheld and when started later (NS)
González E, et al. Kidney Int 2008; 73: 940–946.
Proton Pump Inhibitors (PPI) and
AIN
• 95 million prescriptions written for PPI
in the United States in 2005
• PPI’s are the most common cause of
drug induced interstitial nephritis (32%)
in an adverse drug reaction registry in
New Zealand (Simpson et al.
Nephrology 2006;11:381-385).
Estimated GFR
(ml/min)
Clinical Features of PPI-associated AIN
Finding
Frequency
Pyuria
72%
Fatigue and nausea
39%
Eosinophilia
33%
Weakness
22%
Fever
10%
Rash
<10%
40
30
20
10
0
Baseline
Presentation
3 months
Geevasinga N, et al. Clin Gastroenterol Hepatol 2006;4:597-604.
6 months
Question 20
A 56 y.o. male with a history of hypertension and
gout is seen for routine follow up by his primary
care physician. Medications include metoprolol,
colchicine, aspirin and meloxicam.
On PE the BP is 130/80, HR 86, RR 16, T 36.1.
The heart exam shows an S4 gallop. The
remainder of the exam is benign.
Question 20 Labs
Serum
ABG
Sodium
140
pH
7.35
Potassium
5.9
pCO2
35
Chloride
110
pO2
106
Bicarbonate
18
BUN
18
Sodium
26
Creatinine
1.1
Potassium
22
Glucose
76
Chloride
28
Urine
Urinalysis shows pH 5.2, (-) glucose, (-) blood, no casts. Urine P/C = 0.052.
Which of the following is the most likely
cause for the laboratory abnormalities?
A.
B.
C.
D.
E.
Increase potassium intake
Rhabdomyolysis
Proximal RTA
Adverse effect of meloxicam
Adverse effect of colchicine
Question 20 Analysis
1. What is the overriding disorder?
Metabolic acidosis
2. What is the anion gap?
140-110-18 = 12, Hyperchloremic metabolic acidosis
3. What is the expected pCO2 with normal respiratory compensation?
Expect PCO2 = 18 + 15 =33. Meas PCO2 is 35, normal resp comp
4. Net urine charge = 26+22-28= 20
Answer = Hyperchloremic met acidosis, distal RTA, type IV
Aldosterone Deficiency or Resistance
(Type IV RTA)
Na+
Tubular lumen
Na+
Peritubular
Capillary
3Na+
Na+
ATPase
Na+
K+
Na+
2K+
 Aldo
R-Aldo
Cl-
Urine pH < 5.5
Defect in H+ excretion
is mild
NH4+
H+ +
NH3
H+
ATPase
K+ retention
H+ retention
3Na+
ATPase
H2O
OH- + CO2
K+
T
2K+
HCO3Cl-
ATPase
H+
NH3
Causes of Type IV Distal RTA
•
•
•
•
•
Diabetic nephropathy
Tubulointerstial disease
Cyclosporine and tacrolimus
Transplant rejection
Adrenocorticoid
insufficiency
• Drugs
– NSAIDS, Cox 2 inhibitors
– ACE inhibitors
– Heparin
• Obstructive uropathy*
• Sickle cell nephropathy*
*Probably due to “voltage
dependent” type I RTA which
has a similar clinical picture
(hyperkalemia, non-gap acidosis)
Inhibitors of the Renin-AngiotensinAldosterone System
Question 21
A 26 year old female presents with a history of intermittent tea-colored
urine, often becoming apparent a day or two after onset on upper
respiratory tract infections. On exam the blood pressure is 140/90
mmHg, heart and lungs normal, and there is no peripheral edema.
There is no rash or synovitis.
Urinalysis reveals trace protein and 5-10 dysmorphic red cells per high
power field. The serum creatinine concentration is 0.6 mg/dL. Antinuclear antibodies and anti-neutrophil antibodies return negative.
Serum complement levels are normal.
Which one of the following represents the most likely diagnosis?
A.
B.
C.
D.
membranoproliferative glomerulonephritis
membranous nephropathy
IgA nephropathy
post-infectious glomerulonephritis
Question 22
A 35-year-old woman who is pregnant with her third child is
evaluated for right upper quadrant abdominal pain. She
has no significant medical history. Her father died of
cerebral aneurysm. She takes no medication.
On physical examination, temperature is normal, pulse rate
is 88/min, and blood pressure is 140/90 mm Hg. Cardiac
and pulmonary examinations are normal. Abdominal
examination is unremarkable. There is no edema.
Creatinine level is 0.8 mg/dL (70.74 μmol/L).
On abdominal ultrasound, the right kidney is 14 cm and the
left kidney is 13 cm. There are multiple cysts in both
kidneys and the liver. No hydronephrosis, solid masses,
or stones are present.
Question 22
Which of the following is the most likely
diagnosis in this patient?
A. Autosomal recessive polycystic kidney
disease
B. Acquired cystic kidney disease
C. Autosomal dominant polycystic kidney
disease
D. Nephronophthisis
Question 23
46 y.o. female with a history of alcohol abuse presents with
progressive nausea, confusion and labored breathing
over 5 days. The past medical history is significant for
chronic migraines and hypertension. Medications include
enalapril 10 mg daily, Premarin 0.625 mg daily and
Darvocet N-100 as needed for pain. She was a
vegetarian.
Physical exam showed respiratory distress and postural
hypotension.
Question 23 Labs
Serum
ABG
Sodium
131
pH
6.88
Potassium
4.0
pCO2
28
Chloride
90
pO2
145
Bicarbonate
8
BUN
40
White count
20
Creatinine
2.0
Hemoglobin
10.1
Glucose
106
Platelets
230
AST
2200
ALT
900
GGT
1100
CK
159
CBC
Question 23 Labs
Toxicology
Serum Ketones
Negative
Urine opioids
Positive
Urine cocaine
Negative
Serum salicylate
< 3 mg/dL
Serum
acetaminophen
6.8 mcg/mL
Alcohol screen
Negative
Lactic acid
15 mmol/L
From http://www.merck.com/mmpe/sec21/ch326/ch326c.html
Question 23
Treatment with intravenous fluids and supportive care
produced overall improvement and resolution of the
lactic acidosis. However, the anion gap remained high at
30 mmol/L over the next 3 days and the metabolic
acidosis persisted.
What is your diagnosis?
5-Oxoproline (Pyroglutamic Acid)
Related Acidosis
• Due to disruption of the gamma-glutamyl
cycle
– Inherited defect
– Acquired
•
•
•
•
•
Chronic acetaminophen use (decreases cysteine)
Malnutrition
Pregnancy
Vegetarian diet (decreased glycine)
Liver disease (depleted glutathione stores)
The {Gamma}-Glutamyl Cycle
Fenves, A. Z. et al. Clin J Am Soc Nephrol 2006;1:441-447