Nephrology Board Review

Christopher McFadden, MD

May 20, 2008

Outline

• Highlights of MKSAP• Testable Points• Multi-center Trials• Questions throughout• Questions please

Hypertension

• Prevalence– 20% adults– 60% > 65

• Natural history• SBP correlates

better than DBP

Chobanian: Hypertension, Volume 42(6).December 2003.1206-1252

HTN

• Nephropathy now a risk factor• 70% aware of diagnosis, 53% on meds,

and 27% controlled (NHANES)• Initial eval:

Duration, risk factor stratification, and signs of TOD

Goal: <140/90, <130/80 w/ DM or CKD

7

Chobanian: Hypertension, Volume 42(6).December 2003.1206-1252

Chobanian: Hypertension, Volume 42(6).December 2003.1206-1252

Initial Management per JNC 7

Chobanian: Hypertension, Volume 42(6).December 2003.1206-1252

HTN- Major Trials

• ALLHAT- thiazides = amlodopine/ ACE• AASK- ACE renoprotective w/ proteinuria

in AA patients; CCB not• SHEP- isolated SBP > 160 in elderly pts

– Limited evidence for stage I HTN• RENALL/ IDNT- ARBs beneficial in DM II• LIFE- ARB > Beta-blocker w/ LVH

• Question 1

HTN- Secondary Causes

FeaturesAge < 30 & > 55Abrupt onset/ resistantTODHypokalemia, PCKD, family hx of renal disease, abdominal bruit (particularly diastolic), ACE assoc ARF

RVD vs RAS70% criticalDoppler: 90% sensRenal Scan: 85%MRA: preferred: 90% ostial

Mgmt:Some BP improvememnt- rarely correctsRenal outcomes limitedBetter response in FMD patients

• A 45-year-old woman is referred for evaluation for a blood pressure measurement of 150/94 mm Hg. Her husband is a nurse and regularly measures her blood pressure at home. Her usual home blood pressure measurement is between 110/76 mm Hg and 120/80 mm Hg. She does not smoke cigarettes. Her mother has hypertension.

• On physical examination, her average blood pressure is 148/98 mm Hg. Results of laboratory studies, including the creatinine level, are normal.

• In addition to counseling regarding lifestyle modifications, which of the following is the most appropriate management for this patient? – A Begin hydrochlorothiazide – B Begin enalapril – C Perform ambulatory blood pressure monitoring – D Continue home blood pressure measurement

HTN Measurement

• Resting comfortably, arm at heart level• Palpate for loss of arterial impulse• Cuff bladder 80% arm circumference

– Cuff too small elevates BP• Inflate cuff 20 mm above level of BP loss• Reduce BP 2 mm/sec• Up to 30% people have white coat HTN

Kidney Function Assessment

• Creat clearance overestimates GFR• Creat lowered in malnourished diseases• MDRD estimates GFR accurately up to

60-90 ml/min

Proteinuira

• > 150 mg/ 24 hours• Normally: albumin 30%; large proportion

Tamm- Horsfall proteins• Exercise induced• Orthostatic

Hematuria

• >3 erythrocytes/ hpf on centrifuged urine• W/U: urine cytology or cysto and upper

tract imaging

Risk factors: >40, smoking, analgesic use, benzene exposure

Sometimes repetitive evaluations

Pigmenturia

• Endogenous: Bilirubin, Myoglobin, Hemogloblin, Porphyrins

• Foods: Beets, Fava Beans, Rhubarb• Drugs: Rifampin, Nitrofurantoin,

Sulfonamides, Quinine, and others

Casts

• Formed by Tamm-Horsfall mucoprotein secreted by distal tubules

• RBC casts- glomerular disease• WBC casts- inflammation or infection• Granular casts- tubular injury and death

Granular & RBC casts

Glomerulus

Nephrotic Syndrome

Proteinuria > 3.5 g

Hyperlipidemia

Edema

Hypercoagulability

Sec hyperpara

Low thyroxine (nl TSH)

• Question 3

• Questin 16

Nephrotic Diseases

• PrimaryMinimal Change

FSGS

Membranous

Membranoproliferative• Treatment

? Immuno + supportive tx

• Secondary

FSGS

Membranous

MPGN

Amyloid

• TreatmentSupportive: ACE/ HMG/ HTN control

Membranous & Amyloid

• Case 8

Acute GN

• Hematuria- often RBC casts• HTN• Possible reduced GFR

Glomerulonephritis (cont)

• IgA- synpharyngitic hematuriaSecondary dz associated w/ liver dz

Treatment controversial; 30% reach ESRD

– Henoch-Schonlein purpura: IgA deposits• Post-strep: 2-3 weeks after infection

Treatment conservative

GN (cont)

• SLE- TreatmtentStage 1(nl) and 2 (mesangial)- supportive

3 (FPGN) and 4 (DPGN)- Cytoxan/ Pred

5 (Membranous)- controversial

6 Scarred

SLE Nephritis

RPGN

• ANCA associated (pauci-immune)Wegener’s

Microscopic Polyangitis/ Churg Strauss• Anti GBM

Goodpastures, Idiopathic• Immune Complex

SLE, Post infection, Cryo, HSP

• Question 6

GN Case (# 7)

• 28 yo w/ arthralgias, cough, hemoptysis, and dark urine for 2 weeks

• PMH negative• BP elevated; exam w/ basilar rales• UA 30 RBC, 2 + protein• Creat 2.3 mg/ dL, Hgb 9.8 g/ dL• Serologic wu: anti GBM positive• Renal biopsy: crescents and linear GBM

staining

RPGN

• Question 7

Tubulointersitial Disease

• Inactive Sediment• Cause- injury by

infection, crystals, medications, ischemia, immunologic including sarcoid/ sjogrens

• Triad of eosinophilia, fever, rash limited to PCN AIN

• Medications– Analgesics– Aristocholic Acid– Lithium– Amphotericin B– Cisplatinum

• Question 15

Acute Interstitial Nephritis

Myeloma Kidney Analgesic Nephropathy

• Light chains in urine toxic insult (LCDD), cast nephropathy, amyloidLamda chains: amyloidKappa chains: LCDDDipstick NOT adequate

• Long duration/ combo• Lobulated• Transitional cell CA of GU tract

Case 8

• 65 yo w/ cc fatigue & back pain• New onset nocturia, polyuria• Vitals normal, thoracic back pain• Ca 12.8 mg/ dL, Creat 2.6 mg/dL• UA: trace protein, no cells

PCKD AD >> AR AD 1:1000 Cerebral aneurysmsHepatic cysts; Valvular dz

Alports X linked Collagen defect Men- Renal failureHet women- hematuria

Benign Familial Hematuria

AR Hematuria; not renal failure

Barter’s/ Gitelman’s

AR Tubular d/o (CL transport; nl bp, low K

B- worse, hypercalciuriaG- subtler, lower serum magnesium

Fabry’s Disease X-linked Alpha-galactosidase

Progressive systemic dz

Hyperoxaluria AR Glyoxalate aminotransferase

Liver disease

Genetic Renal Disorders

PCKD

• Abx penetrating the cystsTMP/SXT

Chloramphenicol

Ciprofloxacin

• Question 14

Fluid/ Electrolytes- Formulas

Body= 60% water, 2/3 intracellular, 1/3 extracellular

Expected dec Na= 1.6 x (plasma gluc- 100)/100

AG= Na – (Cl + HCO3)

Delta/ Delta= [AG change/ hco3 change] w/ nl 1-2

Winter’s Formula= 1.5 (HCO3) + 8 +/- 2 = pCO2

Plasma osmol= 2x Na + BUN/ 2.8 + gluc/ 18

Unmeasured anion if calcul vs meaured > 10

Fluid/ Electrolytes- Pearls

• Hyponatremia- treat vol statusIf euvolemic, check TSH, cortisol levels

Drugs causing SIADH: cyclophosphamide, chlorpropamide, vincristine, carbamazepine, haldol, fluoxetine, hctz, and other cns agents

Max correction rate- 12 meq/ L in 24 hours

• Hypernatremia- acquired NDI from lithiun, foscarnet, hypokalemia, hypercalcemia

Fluid/ Electrolytes- Pearls

• Hypokalemia- urine K (20 meq/24 hrs) to differentiate high loss (met alkalosis or RTA) vs GI loss/ shift/ poor intake

• Hypophosphatemia- redistribution common w/ refeeding, insulin to control hyperglycemia, acute resp alk

• Hypomagnesemia- renal tubular loss due to cisplatinum, ampho B, aminoglycosides,

Fluid/ Electrolytes- Pearls

• Met acidosis- urine contacting GI tract Cl absorption and K/ HCO3 excretion

• Ethylene glycol associated w/ Ca oxalate crystals

• Formic acid (methanol) assoc w/ blindnesss

• RTAProximal (2)- variable urine pHDistal (1)- low K, high urine pHDistal (4)- high K, high urine pH

• Met acidosis and resp alkalosisEval for sepsis or saliclylate intoxication

Acute Renal Failure

• ACE-I- efferent vasodilation• NSAIDs- afferent vasoconstriction• FENA- (U Na/ P Na)/ (U Cr/ P Cr) * 100

Less than 1% in oliguric pre-renal patients

Renal Replacement Therapy

• CVVHD not proven to be more effective than intermittent HD

• Increased ultrafiltration w/ CVVH better outcomes

• Daily dialysis better outcomes in single center study

• “Renal dose” dopamine not effective

Contrast Nephropathy

• Creat peaks 4-5 days after exposure• Acetyl-cysteine has varying results• Limiting risk- decreased contrast volume,

use of isotonic contrast, and vol expansion pre-procedure

ARF- Other causes

• Aminoglycosides: 1-2 weeks; lower troughs!• Amph B: 2 grams cumulative dose; risk w/ vol

depletion, elderly, & CSA use• Cisplatinum: may have NDI; often recovers• MTX: ATN and tubular obstruction• Mitomycin C: consider HUS

• HIV: Indinavir crystals obstruction• HRS: low FENa• Rhabdo: rapid Cr increase (trauma, cocaine, HMG-

CoAs);Dipstick incosistent

• Cancer: r/o obstruction!Uric acid crystallization (allopurinol/ bicarb)Radiation (> 23 Grays)

ARF Case (# 15)

• 61 yo w/ ascites and edema• Longstanding etoh abuse• BP 96/70, P 112 w/ distened abdomen,

edema• Na 122, K 3.1, Cl 102, CO2 20, Cr 1.2• Urine Na 6, osmol 670 mosm/ kg H20• Previous creat 0.6

Indinavir Crystals

CV Risk Reduction

Complications

Prepare for RRT

RRT

Cause of ESRD: 40% DM, 27% HTN, 10% GN

• Question 9

• Question 12

CKD- Internist Managment

• Refer Cr > 1.5 (women) or >2.0 (men)• HTN

AASK- control w/ ACE better

• DM control• Protein Restriction• Anemia management: goal Hgb 11-12• ROD: Phosphorus restriction/ Binders/ Vitamin D

analogues (monitor Ca and Phos)

• A 54-year-old woman is evaluated for a creatinine level of 1.3 mg/dL (114.95 μmol/L); 18 months ago, this value was 0.9 mg/dL (79.58 μmol/L). She has a 5-year history of type 2 diabetes mellitus; hyperlipidemia; and hypertension well controlled with lisinopril, hydrochlorothiazide, and atenolol. She also uses glipizide and simvastatin. Laboratory studies reveal a normal hemoglobin level.

• Which of the following diagnostic studies is most appropriate for this patient?– A 24-Hour urine collection for proteinuria– B Kidney ultrasonography – C Measurement of urine microalbumin – D Serum protein electrophoresis – E Measurement of hemoglobin A1c

• Question 11

• Question 19

ESRD

• Poor survival• 20-40 % at 5 years (DM vs non)• PD vs HD• Main cause of death: CVD & Infection• Historically, ESRD worse response w/

PTA; stent effect unclear

• Question 5

Transplant

• Better Survival

LRRT 5ys: 90%

CRT 5ys: 81%

DM 5ys: 50%

• CSA: HTN, nephrotoxicity hirsutism, gum hypertrophy

• Tacrolimus: HTN, nephrotoxicity, DM

• MMF: diarrhea and leukopenia

• Aza: reduce dose of allopurinol!

Question 2

• A 60-year-old woman with a history of type 1 diabetes mellitus and stage 4 chronic kidney disease comes for a routine follow-up examination. She asks about modalities of renal replacement therapy.

• Which of the following is the best option for this patient?• A 0-Antigen-mismatched deceased donor kidney transplantation • B Peritoneal dialysis • C Hemodialysis • D Living donor kidney transplantation after a course of dialysis • E Preemptive living donor kidney transplantation

t

• Question 18

Nephrolothiasis

• Most patients: hypercalciuria– Tx: low salt, low protein, thiazides– NO calcium restriction (increases oxalate)

• Struvite stones: chronically infected; staghorn• Uric acid- radiolucent

– Tx- alkalinize urine and allopurinol• Cystine: metabolic (AR) defect

– Tx- volume, alkalinize, d-penicillamine or alpha mercaptoppropionyl glycine (more soluble cysteine disulfide compound)

Nephrolothiasis Images

Nephrolothiasis Images

Nephrolothiasis

• Work-up• Initial: chemistry, UA, stone analysis (if

available), and imagingHydration!!! 50% recurrence at 10 years

• Recurrent stones: metabolic/ 24 hr urinesDiarrhea think IBD with ca oxalate stones

Renal Disease in Pregnancy

• Tx asymptomatic bacteriuria• Chronic HTN- present before pregnancy or dx

before 20 weeks• Gestational HTN- dx after 20 weeks; “transient

HTN of pregnancy”• Preeclampsia

If before 20 weeks- consider hydatiform mole

Tx HTN when DBP 100-110 or symptomatic

Meds: 1st line- Methyldopa, Hydralazine

Renal Disease in Pregnancy

• Higher risk w/ proteinuria and Creat > 1.4• Mild hydro common- difficult to determine

signficance

Emphysematous Pyelonephritis

• Similar to pyelo• Majority pts have DM• Gas in renal/ perirenal

tissues• Drainage mild-

moderate cases; nephrectomy if severe

• CT if pyelo pts not getting better!

HTN Case (# 3)

• 76 yo for fu; several elevated BP recently• PMH negative; No medications• No etoh, tobacco use• BP 178/68, no orthostasis• No volume overload• Creat 1.0

HTN Case cont.

• Evaluation

BP change recently?

Ideal 1st line agent:

JNC 6: CCB or diuretics

JNC 7: Stage 2: combination

Auto regulation