Board Review 2009

• 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 1A 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. Minimal change glomerulopathyB. FSGSC. Membranous glomerulopathyD. IgA nephropathyE. ANCA-associated GN

Question 2A 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 nephropathyB. Goodpasture's syndromeC. ANCA vasculitisD. Postinfectious GNE. 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 C4B. Positive ANAC. Positive ss-DNAD. Positive anti-Smith antibodyE. Positive ds-DNA

Question 4A 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. FurosemideB. RasburicaseC. AllopurinolD. 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

Type of cancer

Risk

High Intermediate Low

NHL Burkitt's, lymphoblastic, B-ALL DLBCL Indolent NHL

ALL WBC ≥100,000/microL WBC 50,000-100,000/microLWBC ≤50,000/microL

AMLWBC ≥50,000/microL, monoblastic

WBC 10,000-50,000/microLWBC ≤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 5A 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 nephropathyB. Thiazide-induced acute renal failureC. Primary amyloidosisD. Myeloma cast nephropathyE. Lymphomatous infiltration of the kidneys

Question 6A 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. Distal renal tubular acidosis (type I)B. VomitingC. Diuretic abuseD. IFN complicationE. HypomagnesemiaF. Diarrhea

Question 7A 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. NS 200 mL/hr + furosemideB. 3% saline at 1 ml/kg/hr + furosemideC. Emergent head CT D. NaloxoneE. 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 8A 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. Central diabetes insipidusB. Nephrogenic diabetes insipidusC. Post obstructive diuresisD. 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 > 300 mosm/kg

Water Diuresis Solute Diuresis

Urine and Plasma Osmolality in Disorders of Water Balance

1000

800

600

400

200

280 285 290 295 300Posm(mosm/kg)

Uo

sm(m

osm

/kg)

Normal

Primary polydipsia

Central DI

Nephrogenic DI

WaterDeprivation dDAVP

Question 9A 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

BPVolume status

BP Normal or Low Effective circulating volume

BP High ECF

Loss of HClLoss of Volume (Na+/H20)

Loss of Gastric secretions(vomiting, NG suction)DiureticsBartter syndromeGitelman syndrome

Primary Hyperaldosteronism

Metabolic Alkalosis: Loss of Gastric Secretions-Generation Phase

K+ Na+

H2CO3

K+

H+

H+

HCO3-

HCO3- Cl-

Cl-

Cl-

ParietalCell

Na+

HCO3-

Na+

HCO3-

Na+ Cl-

HCO3-

K+

Na+

HCO3-

K+

Loss of HClfrom Stomach

Generation ofNaHCO3

1. Elimination of chloride from the urine2. Excretion of NaHCO3 andKHCO3 in Urine

Kidney

Cl-

Cl-

Na+

Na+

Na+ K+

Cl- Cl-

Na+ Cl-

Metabolic Alkalosis: Loss of Gastric Secretions-Maintenance Phase

Volume Contraction

Reabsorption of sodium,chloride, and bicarbonate

along the nephron

Elimination of sodium, chloride, and bicarbonate

from the urine

Secondary increasein aldosterone

Increased H+

Excretion

Metabolic alkalosis

Paradoxicalaciduria

Question 10A 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. Minimal change diseaseB. Membranous nephropathyC. FSGSD. 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

Perihilar Tip Lesion Collapsing Cellular

Different Structural Variants of FSGS

PRIMARY (IDIOPATHIC) FSGSSECONDARY FSGS

VIRUS-ASSOCIATEDHIV-1 (“HIV-associated nephropathy”)Parvovirus B-19

FAMILIAL FSGSMutations in α-actinin 4 geneMutations in NPHS2 gene for podocin Mutations in TRPC6 gene for a cation channel

DRUG TOXICITYHeroin (“Heroin nephropathy”)PamidronateInterferon-α

MEDIATED BY ADAPTIVE STRUCTURAL RESPONSESReduced renal mass ObesityCyanotic congenital heart diseaseSickle cell anemia

Question 11A 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 alkalosisB. Mixed anion gap metabolic acidosis and respiratory acidosisC. Anion gap metabolic acidosisD. Hyperchloremic acidosisE. 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 1223-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 9.11.9 14 1 Phosphorus 3.5ABG-pH 7.29, PCO2 30, pO2 100Urine 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 RTAB. DiarrheaC. Type I RTAD. Renal tubular alkalosisE. Proximal RTA

Practical Approach (Hyperchloremic metabolic acidosis)

Urinary Anion Gap

Negative PositiveType 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 Type 1 (voltage)

or back-leak)

Type I Classic Distal RTA-Mechanism 1

ATPase

ATPase

ATPase

Tubular lumenPeritubularCapillary

K+

H+

OH- + CO2 HCO3-

T

Cl-

H2O

H+ 3Na+

2K+

Cl-

K+

Na+

ATPase

3Na+

2K+

R-Aldo

(-)

(-)

(-)

(-)H+

RetentionK+ WastingUrine pH > 5.5Ca-P stones

Na+

Type I Classic Distal RTA-Mechanism 2

ATPase

ATPase

ATPase

Tubular lumenPeritubularCapillary

K+

H+

OH- + CO2HCO3-

T

Cl-

H2O

H+ 3Na+

2K+

Cl-

K+

Na+

ATPase

3Na+

2K+

R-Aldo

(-)

(-)

(-)

(-)H+

RetentionK+ WastingUrine pH > 5.5Ca-P stones

Na+

Type I Distal RTA-Mechanism 3

ATPase

ATPase

ATPase

Tubular lumenPeritubularCapillary

K+

H+

OH- + CO2HCO3

-

T

Cl-

H2O

H+ 3Na+

2K+

Cl-

K+

Na+

ATPase

3Na+

2K+

R-Aldo

(-)

(-)

(-)

(-)

H+Retention

K+ WastingUrine pH > 5.5Ca-P stones

Na+

H+

Backleak of H+

Question 13A 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 syndromeB. VomitingC. Gitelman syndromeD. Hypokalemia periodic paralysisE. Licorice ingestion

Urine Na+ and Cl- in the Differential Diagnosis of Metabolic

Alkalosis and Hypokalemia

Urine ElectrolytesNa+ Cl-

Condition (meq/L)

VomitingAlkaline urine>15 <15Acidic urine <15 <15

DiureticDrug active >15 >15Remote use <15 <15

Hyperaldosteronism >15 >15

Question 14You 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 polydipsiaB. Mineralocorticoid deficiencyC. Reset osmostatD. Diuretic abuseE. SIADH

Question 15A 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. ADPCKDB. Von Hippel-Lindau diseaseC. Medullary cystic kidney diseaseD. Tuberous sclerosisE. Bilateral renal dysplasia

Question 16A 66-year-old man comes for a follow-up

examination for elevated blood pressure. He has a history of chronic kidney disease and hypertension well controlled with hydrochlorothiazide. One week ago, he was evaluated in the office after obtaining several home blood pressure measurements averaging 145/90 mm Hg. Enalapril was added at that time. 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.

1 week ago Today

Potassium 4.5 meq/L 5.2 meq/L

Creatinine 1.2 mg/dL 1.5 mg/dL

Urine albumin:creatinine ratio 200 mg/g

In addition to dietary potassium restriction, which of the following is the most appropriate next step in this patient’s management?

A. Add diltiazemB. Discontinue enalapril; switch to metoprololC. Repeat creatinine and potassium measurement in 1 weekD. Kidney arteriography

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 dailyB. Start sevelamer 800 mg three time daily with

mealsC. Start calcitriol 0.25 mcg once dailyD. Start ergocalciferol 50,000 units once weekly

GFR (mL/min/1.73 m2)

90 80 70 60 50 40 30 20 <15

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

Time Course of Physiologic Alteration in Calcium, Phosphorus, Vitamin D and PTH in CKD

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, 1,25-dihydroxy-vitamin D 52 pg/mL (reference range 15-75); 25-hydroxy-vitamin D 25 ng/mL (reference range 15-57), alkaline phosphatase 86 U/L (reference range 38-126). 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 FracturesBone painOsteopeniaLow PTHHypercalcemia with calcium loading

Osteitis fibrosa cystica High Resorption Formation

FracturesMixed sclerosis and osteopeniaBone painProximal myopathyHigh PTHElevated alkaline phosphataseSubperiosteal reabsorptionBrown tumors (rare)

Osteomalacia Low Low FracturesOsteopeniaBone painProximal myopathyLooser zones on x-rayHigh PTH related to secondary hyperparathyroidismUsually related to aluminum accumulation

Mixed uremic osteodystrophy Mixed Variable PTH and bone alkaline phosphatase variable

Osteoporosis Low Decreased OsteopeniaCKD specific risk factors

-heparin-steroids-Hypogonadism-Poor nutrition-Vitamin D deficiency-Metabolic acidosis

Amyloid Variable Variable Due to accumulation of beta-2 microglobulinBone painCystic bone lesionsTransplant 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)

González E, et al. Kidney Int 2008; 73: 940–946.

Baker RJ and Pusey CD. Nephrol Dial Transplant 2004;19:8-11.

Etiology FrequencyDrugs 71% Penicillins and cephalosporins NSAIDs, including COX-2 inhibitors Rifampin Sulfonamides Quinolones Allopurinol Proton pump inhibitors Indinavir 5-aminosalicylates (e.g. mesalamine) H-2 blockersInfection 15%Tubulointerstitial 5%nephritis and uveitisSarcoidosis 1%

Medication Frequency

Antibiotics

Cephalosporins

Quinolones

Penicillins

56%

15/34

12/34

7/34

NSAIDs 37%

Other

Allopurinol

Omeprazole

Ranitidine

Pimozide

7%

Clinical Features of AIN

González E, et al. Kidney Int 2008; 73: 940–946.

Clinical Feature Frequency

Leukocyturia 82%

Microhematuria 67%

Fever 42%

Eosinophilia 34%

Rash

Oliguria

23%

23%

Corticosteroid Treatment for AIN

0

1

2

3

4

5

6

7

Baseline SCr (NS) Peak SCr (NS) Final SCr (p<0.05)

Ser

um

cre

atin

ine

(mg

/dL

)

Steroid-treated

No steroids

• 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.

P<0.05

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).

Clinical Features of PPI-associated AIN

Geevasinga N, et al. Clin Gastroenterol Hepatol 2006;4:597-604.

010203040

Baseline Presentation 3 months 6 months

Est

imat

ed G

FR

(m

l/m

in)

Finding Frequency

Pyuria 72%

Fatigue and nausea 39%

Eosinophilia 33%

Weakness 22%

Fever 10%

Rash <10%

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 LabsSerum

Sodium 140

Potassium 5.9

Chloride 110

Bicarbonate 18

BUN 18

Creatinine 1.1

Glucose 76

ABG

pH 7.35

pCO2 35

pO2 106

Urine

Sodium 26

Potassium 22

Chloride 28

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. Increase potassium intake

B. Rhabdomyolysis

C. Proximal RTA

D. Adverse effect of meloxicam

E. 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 acidosis3. 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)

ATPase

ATPase

ATPase

Tubular lumen PeritubularCapillary

K+

H+

OH- + CO2 HCO3-

T

Cl-

H2O

H+ 3Na+

2K+

Cl-

K+

Na+

ATPase

3Na+

2K+

R-Aldo

NH3NH3H+ +

NH4+

Na+

Aldo

Na+

Na+

Na+

K+ retentionH+ retentionUrine pH < 5.5

Defect in H+ excretion is mild

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-Angiotensin-Aldosterone System

Question 21A 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. Anti-nuclear antibodies and anti-neutrophil antibodies return negative. Serum complement levels are normal.

Which one of the following represents the most likely diagnosis? A. membranoproliferative glomerulonephritisB. membranous nephropathy C. IgA nephropathy D. 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 LabsSerum

Sodium 131

Potassium 4.0

Chloride 90

Bicarbonate 8

BUN 40

Creatinine 2.0

Glucose 106

AST 2200

ALT 900

GGT 1100

CK 159

ABG

pH 6.88

pCO2 28

pO2 145

CBC

White count 20

Hemoglobin 10.1

Platelets 230

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)

Fenves, A. Z. et al. Clin J Am Soc Nephrol 2006;1:441-447

The {Gamma}-Glutamyl Cycle