ABIM Certification Exam: Nephrology

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Department of Medicine

ABIM Certification Exam: Nephrology

July 2015 UCSF CME Meyeon Park, MD MAS

Assistant Professor

Division of Nephrology


NEPHROLOGY


Disclosures

§  I am site PI for the REPRISE study evaluating efficacy of tolvaptan in autosomal dominant polycystic kidney disease (Otsuka pharmaceuticals)

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NEPHROLOGY


Roadmap for today

§  Acute kidney injury ---------Scheduled 15 min break-------

§  Glomerulonephritis §  Secondary hypertension §  Common electrolyte abnormalities §  Acid-base §  A few odds and ends

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NEPHROLOGY


Case A 57-yr-old man is admitted after a motor vehicle accident. He has sustained multiple fractures and blunt chest and abdominal trauma. A left hemothorax is treated with a chest tube, an abdominal lavage reveals only minimal blood, and a noncontrast computed tomography (CT) scan of the abdomen is negative. He is volume-resuscitated with approximately 15 L of crystalloid. Twenty-four hours after admission, he is noted to have marked abdominal distension and low urine output.

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NEPHROLOGY


Case

Physical Exam: Tm 37.2 BP 135/86 HR 86 RR 16 UOP 100 cc/12h CVP 18 Bladder pressure 28 Intubated, sedated Decreased breath sounds at bases Regular heart sounds, no m/r/g Abdomen distended and firm, hypoactive BS


NEPHROLOGY


Case

Labs: §  Na 135 §  K 5.8 §  Cl 103 §  HCO3 24 §  BUN 46 §  Cr 2.3 §  Imaging: Small retroperitoneal hematoma, normal sized

kidneys without hydronephrosis, marked ascites.

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NEPHROLOGY


Case Question 1

Which of the following would be the most appropriate next step?

A.  Abdominal decompression B.  Fluid resuscitation C.  Placement of bilateral ureteral stents D.  Initiation of renal replacement therapy


NEPHROLOGY


Acute Renal Failure/Kidney Injury

§  Pre-Renal = Decreased kidney perfusion §  Intra-Renal = Intrinsic kidney disease §  Post-Renal = Obstructive nephropathy

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NEPHROLOGY


Pre-Renal: Kidney Hypoperfusion §  Dehydration, overdiuresis, hypovolemia

–  Abdominal compartment syndrome: Typically occurs after massive volume resuscitation

§  Hemorrhage §  Hemodynamic effect: ACE/ARB and NSAIDs §  Heart failure

–  Cardiorenal syndrome

§  Cirrhosis/End-stage liver disease –  Hepatorenal syndrome


NEPHROLOGY


Pre-Renal: Kidney Hypoperfusion §  Diagnosis

–  +/- Oliguria –  High BUN:Creatinine ratio > 20 –  Bland urine sediment, normal kidney US –  Low FENa < 1% and low urine Na <10 mEq/L –  High specific gravity, high urine osmolality –  Rapid renal recovery with resuscitation

§  Therapy: Restore renal perfusion §  Prognosis: Good, often rapid renal recovery

–  Exceptions: Cardiorenal and hepatorenal syndromes

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NEPHROLOGY


Fractional Excretion of Sodium (FeNa) §  percent of filtered sodium that is excreted in the

urine §  FeNa = (UNa * PCr)/(PNa * Ucr) * 100 §  <1% consistent with pre-renal state §  Only useful when patient is oliguric (< 400 cc

urine output/24 hours) §  Confounded by use of diuretics


NEPHROLOGY


Case A 40-yr-old man with end-stage liver disease secondary to alcohol abuse is admitted to the hospital with altered mental status. Home meds: Propranalol/rifaximin/lactulose/lasix/ spironolactone Physical exam: T 37.4 BP 90/50 HR 80 RR 16 O2 sat 95% RA No JVD appreciated Bibasilar rales + abdominal distension + fluid wave 1-2+ LE edema

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NEPHROLOGY


Case

Labs: §  Na 135 §  K 5.1 §  Cl 103 §  HCO3 24 §  BUN 46 §  Cr 2.3 §  U/A: 1.025/7/neg heme/gluc/nit/LE/prot §  Imaging: Normal sized kidneys without

hydronephrosis, marked ascites.


NEPHROLOGY


Case Question 2


A.  Abdominal decompression B.  Fluid resuscitation C.  Placement of bilateral ureteral stents D.  Initiation of renal replacement therapy

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NEPHROLOGY


Pre-renal: Hepatorenal Syndrome §  Severe end-stage liver disease patients §  Intense renal vasoconstriction §  Diagnosis of exclusion

–  Oliguria –  Low urine sodium < 10 mEq/L, low FENa < 1% –  Hyponatremia –  Bland urine sediment –  Normal US (no hydronephrosis) –  No other identifiable cause –  Lack of response to volume expansion


NEPHROLOGY


Pre-renal: Hepatorenal Syndrome §  Treatment

–  Splanchnic vasoconstrictors (terlipressin, ornipressin), midodrine, octreotide

–  TIPS (transjugular intrahepatic portosystemic shunt) –  Dialysis as bridge to liver transplant –  Liver transplant

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NEPHROLOGY


Case A 39-yr-old woman with stage 4 ovarian

carcinoma with bulky pelvic and retroperitoneal disease is admitted with complaints of shortness of breath and decreasing urine output.

Physical exam: T 37.4, BP 130/90, HR 76, RR 16, UOP 35cc/6h

+ jugular venous distension Bibasilar rales + abdominal distension 1-2+ LE edema


NEPHROLOGY


Case

Labs §  Na 135 §  K 5.7 §  Cl 107 §  HCO3 16 §  BUN 60 §  Cr 3.1 §  PO4 6.9 §  Uric acid 12.4

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NEPHROLOGY


Case

Imaging

§  Abdominal ultrasound (outpatient study, 2 weeks ago): moderate right-sided hydronephrosis, normal left kidney

§  Repeat ultrasound demonstrates moderate calyceal dilation on the left, with no dilation on the right but persistent hydronephrosis. Kidney size is normal bilaterally.


NEPHROLOGY


Case Question 3


A.  CT scan with contrast B.  Allopurinol and urinary alkalinization C.  Emergent hemodialysis D.  Percutaneous nephrostomy

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NEPHROLOGY


Post-Renal: Obstruction

§  Urinary tract obstruction –  Renal pelvis, ureters, bladder, prostate, urethra –  Congenital and acquired lesions, BPH –  Neurogenic bladder, medication effects

§  Nephrolithiasis §  Malignancy

–  GI cancers –  Prostate cancers –  Uterine, cervical, ovarian cancers

§  Lymphadenopathy §  Retroperitoneal fibrosis


NEPHROLOGY


Post-Renal: Obstruction

§  Clinical –  Oliguric or non-oliguric –  Can have type 4 RTA, metabolic acidosis –  Foley does not definitively rule out obstructive

nephropathy –  Hydronephrosis on US, although negative US does

not rule out obstructive nephropathy

§  Therapy –  Correct obstruction; can see post-obstructive diuresis

from urinary concentrating defect –  Urology consultation –  Interventional radiology consultation: nephrostomy

tubes

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NEPHROLOGY


Case

A 65 year-old woman is admitted to the hospital with newly diagnosed diffuse B cell lymphoma for induction chemotherapy. 24 hours after induction chemotherapy, she is noted to be oliguric.

Physical exam T 38.4, BP 95/60, HR 94, RR 24 Heart is normal Lungs are clear, though she is mildly tachypneic Trace-1+ pitting edema


NEPHROLOGY


Case

Labs §  Na 138 §  K 6.0 §  Cl 95 §  HCO3 19 §  BUN 43 mg/dL §  Creatinine 3.4 mg/dL §  Ionized Ca 0.79 mmol/L §  PO4 9.9 mg/dL §  Uric acid 11.1 mg/dL

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NEPHROLOGY


Case Question 4

What is the most likely diagnosis? A.  Rhabdomyolysis B.  Tumor lysis syndrome C.  Cisplatin nephrotoxicity D.  Sepsis associated ATN


NEPHROLOGY


Intra-Renal: Acute Tubular Necrosis (ATN) §  Etiology

–  Ischemic = hypotension, sepsis, shock, hemorrhage –  Toxic

• Exogenous: intravascular radiocontrast, aminoglycosides, amphotericin, cisplatin, oxalate (ethylene glycol/anti-freeze ingestion)

• Endogenous: rhabdomyolysis (myoglobin), hemolysis (hemoglobin), tumor lysis (urate)

§  Diagnosis –  Muddy brown/pigmented casts in urine sediment –  Elevated FENa > 1-2% –  High urine Na > 20 mEq/L

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NEPHROLOGY


Intra-Renal: Acute Tubular Necrosis (ATN) §  Prognosis

–  Mortality: 40-70% in ICU if dialysis-requiring AKI –  Slower recovery

§  Therapy –  Supportive care –  Dialysis as needed –  Fluid and electrolyte management –  Medication dosing adjustment for GFR –  No proven therapies –  No benefit: mannitol, furosemide, dopamine, ANP,

thyroxine


NEPHROLOGY


Intra-Renal: Radiocontrast Nephropathy §  Etiology

–  Iodine-based radiocontrast –  Intravenous or intraarterial injection –  CT, angiography, cardiac catheterization

§  Risk factors –  Pre-existing chronic kidney disease –  Proteinuria –  Age –  Diabetes mellitus –  Multiple myeloma –  Dehydration

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NEPHROLOGY


Intra-Renal: Radiocontrast Nephropathy §  Presentation

–  Rise in creatinine 24-48 hours post-exposure –  Patient with risk factors –  Low FENa < 1% –  Bland sediment (mild forms with vasoconstriction) or

muddy brown casts of ATN (severe forms with toxic injury)

§  Prognosis –  Mild cases resolve within 2-5 days, likely

vasoconstriction mediated ARF –  Severe cases resolve slowly over days to weeks,

require dialysis, and may be irreversible due to toxin-induced ATN


NEPHROLOGY


Intra-Renal: Radiocontrast Nephropathy §  Prevention

–  Avoid radiocontrast (US, nuclear medicine) –  Minimize dose of radiocontrast –  Use iso-osmolar or hypo-osmolar contrast (as

opposed to hyperosmolar contrast) –  IVF: Isotonic sodium bicarbonate vs. normal saline –  N-Acetylcysteine (KDIGO yes, AHA no) –  Hold diuretics peri-contrast, avoid hypovolemia –  No clear benefit of post-contrast dialysis

§  Many meta-analyses –  Brar, CJASN 2009 –  Kshirsagar, JASN 2004

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NEPHROLOGY


Gadolinium based MRI agents – a word of caution §  Nephrogenic systemic fibrosis

–  Syndrome associated with MRI-based gadolinium administration

–  Patients with both acute renal failure/kidney injury and chronic kidney disease (especially) are at risk

–  Studies to ascertain incidence are ongoing –  Rarer than radiocontrast nephropathy, but can be

debilitating and fatal –  Post-contrast hemodialysis is recommended

§  Recent reviews –  Perazella Clin Journal Amer Soci Neph 2009


NEPHROLOGY


Case

§  A 24-yr-old construction worker has his legs pinned under a pile of rubble in a construction accident. He is extricated after 5 h. Upon arrival to the emergency department, he is found to have a CK of 23,000 U/L and a serum creatinine of 2 mg/dL.

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NEPHROLOGY


Case Question 5

Which ONE of the following treatments would be associated with a decreased risk for AKI in this patient?

A.  Intravenous crystalloid, initiated before hospital arrival

B.  Mannitol C.  Dopamine D.  Furosemide


NEPHROLOGY


Intra-Renal: Rhabdomyolysis §  Etiology

–  Crush injury, muscle trauma/ischemia/inflammation –  Prolonged immobilization: coma, ethanol, earthquake

victims –  Fevers/rigors, seizures –  Toxic injury: statins, cocaine, reverse transcriptase

inhibitors –  Metabolic: Hypokalemia, hypophosphatemia –  Genetic: McArdle disease

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NEPHROLOGY


Intra-Renal: Rhabdomyolysis §  Diagnosis

–  High serum uric acid, phosphate, potassium –  Hypocalcemia –  Elevated serum CK (along with AST/ALT) –  Dipstick heme+ from myoglobinuria –  UA negative for RBCs –  Urine sediment with ATN, muddy brown casts

§  Treatment –  Aggressive and early hydration –  Alkalinization of urine vs. NS hydration alone? –  Stop offending medications


NEPHROLOGY


Case

§  A 36-yr-old IV drug user is admitted to the hospital for intravenous antibiotic treatment of a large forearm abscess. Cultures grow MSSA, and he is treated with nafcillin. 9 days later, his creatinine is noted to have risen from 0.9 mg/dL at admission to 1.9 mg/ dL. Urinalysis is notable for white blood cell casts.

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NEPHROLOGY


Case Question 6

Which ONE of the following is not typical of this patient’s diagnosis?

A.  Fever B.  Rash C.  Eosinophilia D.  Arthralgias E.  Altered mental status


NEPHROLOGY


Intra-Renal: Acute Interstitial Nephritis (AIN) §  Etiology

–  Medications = antibiotics (beta lactams), NSAIDs, diuretics, PPIs, others

–  Infections = bacterial, fungal, viral, others –  Immune disorders = SLE, Sjogren’s, sarcoidosis

§  Presentation –  Fever (27%), drug rash (15%), eosinophilia (23%) –  Minority of patients have complete triad (10%) –  Arthralgias –  NSAID-AIN may have proteinuria from concomitant

minimal change disease –  AIN is often occult, should be suspected if no other

apparent etiology of AKI or if new medication started – time frame very variable

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NEPHROLOGY


Intra-Renal: Acute Interstitial Nephritis (AIN) §  Diagnosis

–  Sterile pyuria, WBC casts, eosinophilia –  Clinical diagnosis; kidneys improve after stopping

offending drug (which may be a chronic medication or one tolerated safely in the past)

–  Kidney biopsy –  Skin biopsy (leukocytoclastic vasculitis)

§  Therapy –  Stop offending drugs –  Treat underlying infection –  Consider oral steroids (e.g., prednisone 60 mg PO

daily), lack of large randomized controlled trials showing efficacy


NEPHROLOGY


Case

§  A 72-yr-old man with diabetes, hypertension, and hypercholesterolemia undergoes coronary artery bypass grafting. He has an uncomplicated post-operative course until POD #9, when he develops acute renal failure.

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NEPHROLOGY


Case Question 7

What is this patient’s MOST LIKELY diagnosis?

A.  Prerenal azotemia associated with heart failure

B.  Acute tubular necrosis C.  Atheroembolic renal disease (cholesterol

emboli) D.  Post-obstructive renal failure due to recent

foley removal


NEPHROLOGY


Intra-Renal: Atheroembolic Disease §  Etiology

–  Spontaneous/idiopathic –  Anticoagulation –  Instrumentation: aortic surgery/cross-clamping,

CABG, angiography, cardiac catheterization

§  Presentation –  Stuttering, inexorable rise in serum creatinine –  Livedo reticularis, stigmata of embolism –  Triad: precipitating event, subacute/acute AKI, skin

findings –  Non-specific urine sediment –  Often occult, should be considered if no obvious

etiology

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NEPHROLOGY


Intra-Renal: Atheroembolic Disease §  Diagnosis

–  Often clinical diagnosis, embolic skin findings –  Low complements C3 and C4 –  Eosinophilia and eosinophiluria –  Retinal embolization (Hollenhorst plaques) –  Skin biopsy, kidney biopsy

§  Therapy –  Supportive. Stop anticoagulation?

§  Prognosis –  Poor, generally irreversible –  Heavy burden of cardiovascular disease


NEPHROLOGY


Diagnostics in AKI

§  Urine sediment –  Muddy brown casts à ATN –  White cell casts à AIN, pyelonephritis –  Red cell casts and/or dysmorphic RBCs à GN

§  Fractional Excretion of Sodium (FENa) –  Only useful in oliguric patients –  The FENa asks, “Why is this patient oliguric?” –  FENa < 1%, pre-renal –  FENa > 1-2%, intra-renal/post-renal –  Many causes of intrinsic AKI with low FENa

(rhabdomyolysis, contrast nephropathy, acute GN) –  FENa does not replace a good history/physical

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NEPHROLOGY


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NEPHROLOGY


Diagnostics in AKI

§  BUN:Creatinine Ratio –  BUN:Cr > 20 pre-renal –  Many causes of azotemia/elevated BUN (steroids,

hypercatabolic states, total parenteral nutrition) –  Overused

§  Renal Ultrasound –  Never wrong to R/O obstruction –  Safe, fast, and cheap –  Small kidneys suggest element of chronic kidney

disease (AKI on CKD vs. CKD)

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NEPHROLOGY


Diagnostics in AKI

§  24 Hour Urine for CrCl and Proteinuria –  Not helpful if serum creatinine not stable –  Estimate proteinuria with spot urine protein:creatinine

§  Predictive formulas (CrCl, eGFR) should not be used if Cr is not at steady state!

§  Serologies and Kidney Biopsy –  Usually not necessary with careful history, physical,

and urine sediment exam –  Serologies are low yield: ANA, ANCA, anti-GBM,

ASO, cryoglobulins, HIV, HCV, HBV –  Biopsy will often find occult atheroembolic disease or

AIN


NEPHROLOGY


GLOMERULONEPHRITIS

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NEPHROLOGY


Case

A 65 year-old man admitted to the hospital for AKI and palpable purpura. He has a history of recurrent enterococcal UTIs. Over the past two weeks, he noticed a lower extremity rash.

Physical exam T 38.4, BP 170/98, HR 82 Heart and chest are normal No hepatosplenomegaly Petechial purpuric rash on lower extremities No edema


NEPHROLOGY


Case Question 8

Which one of the following studies is most appropriate?

A.  ANCA B.  Anti-GBM antibodies C.  Echocardiogram and blood cultures D.  Spiral CT scan

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NEPHROLOGY


Case

Labs §  CBC Normal §  Electrolytes Normal §  BUN 68 mg/dL §  Creatinine 3.4 mg/dL §  HCV, cryos Negative §  C3 ↓ 75 mg/dL (normal 88-252 mg/dL) §  C4 ↓ 10 mg/dL (normal 12-72 mg/dL) §  UA 2+ proteinuria, many dysmorphic RBCs,

occasional RBC casts


NEPHROLOGY


Glomerulonephritis: Signs and Symptoms §  Hematuria, tea-colored urine §  HTN §  +/- Edema §  +/- Rapid loss of GFR §  Active urine sediment

–  Dysmorphic red blood cells –  Red cell casts

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NEPHROLOGY


Hematuria: Glomerular versus non-glomerular §  Favoring glomerular bleeding:

–  Red cell casts: virtually diagnostic –  Red cell morphology: dysmorphic red cells –  Proteinuria: > 500 mg/day

•  1 mL blood in 1 liter of urine = color change but will only add 35 mg of protein

–  Urine color: smoky brown/”Coca cola” color

§  Favoring extraglomerular bleeding: –  Blood clots –  No proteinuria –  Urine color: red/pink

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Nephritic Nephrotic Diffuse (RPGN or severe GN) Chronic Hematuria Membranous Immune Complex GNs Benign Hematuria Focal Segmental (complements are low) IgA Nephropathy glomerulosclerosis Alport’s Minimal Change Dz Post-infectious GN SLE Diabetes mellitus Endocarditis Amyloidosis Membranoproliferative GN

Hepatitis C Virus related GN SLE Anti-GBM (complements are nl) ANCA (complements are nl)

CLASSIFICATION OF MAJOR GLOMERULAR DISEASES

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NEPHROLOGY


Rapidly Progressive Glomerulonephritis (RPGN) §  Diagnosis

–  Clinical diagnosis = loss of 50% GFR in less than one month from glomerular disease

–  Not a pathological diagnosis, does not always correlate with crescents on kidney biopsy.

–  Red cell dysmorphia and RBC casts

§  3 major categories –  Pauci-immune / ANCA Disease –  Anti-GBM Disease –  Immune Complex Disease

Rapidly progressive glomerulonephritis

Serologic analysis

Anti-neutrophil cytoplasmic autoantibodies (ANCA)

Anti-GBM autoantibodies

Immune complex disease markers

No extrarenal disease Renal limited vasculitis

Systemic necrotizing arteritis

Microscopic polyangiitis

Pulmonary Asthma necrotizing and granulomas eosinophilia Granulo- Churg- matosis Strauss with syndrome polyangitis

Lung hemorrhage Goodpasture's syndrome

No lung hemorrhage Anti-GBM GN

Anti-DNA autoabs Lupus GN

Anti-pathogen abs Post-strep GN/peri- infectious

Cryoglobulins/ HCV Cryo- globulinemic GN

IgA MPGN

Others

Immune complex GN Anti-GBM GN ANCA GN (‘pauci-immune’)

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Rapidly progressive glomerulonephritis

ANCA Caucasians:AA (7:1)

Anti-GBM Rare in AA

Immune complex SLE common in AA

40-80% 2-20% 15-50%

Mean Age Mean Age Mean Age 54 yo 20 - 30 yo Postinfx strep, 6-7 yo

HCV-MPGN, 46 yo IgA, 30 yo SLE, 27-32 yo idiopath MPGN, 3-30 yo Endocarditis, 48 yo


NEPHROLOGY


RPGN: Pauci-Immune/ANCA Disease §  Diagnosis: ANCA +, normal complements, no

immune complexes on renal bx §  Microscopic polyangiitis (p-ANCA)

–  Necrotizing vasculitis; no granulomas

§  Granulomatosis with polyangiitis (c-ANCA) –  Lung disease, upper airway disease, granulomas –  Formerly known as Wegener’s granulomatosis

§  Churg-Strauss Disease (p-ANCA) –  Eosinophilia, asthma, sinus disease, peripheral

neuropathy, granulomas

§  Treatment: Steroids, cyclophosphamide (+/- pheresis if hemoptysis, GPA)

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NEPHROLOGY


RPGN: Anti-GBM Disease

§  Autoimmune disease –  Auto-antigen on type IV collagen –  Renal limited: Anti-GBM Disease –  Pulmonary renal syndrome: Goodpasture’s

Syndrome

§  Clinical Features –  RPGN +/- hemoptysis/pulmonary hemorrhage –  Young Caucasian men, recent URI or smoking hx

§  Diagnosis: Anti-GBM titer, kidney biopsy §  Rx: Pheresis, steroids, cyclophosphamide


NEPHROLOGY


RPGN: Immune Complex (Hypocomplementemic) Disease §  Post-infectious/Strep GN

–  2-3 weeks after pharyngitis or skin infection –  Strep: elevated ASO and anti-DNase B antibody –  No direct therapy available

§  SLE nephritis –  ANA, anti-dsDNA, anti-Smith antibodies –  Immunosuppression:

• Steroids • Mycophenolate (CellCept) or cyclophosphamide •  +/- Plasmapheresis

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NEPHROLOGY


RPGN: Immune Complex (Hypocomplementemic) Disease §  IgA nephropathy (normal complements)

–  Synpharyngitic hematuria (simultaneous URI with hematuria, compared to post-infectious GN where hematuria occurs 1-2 weeks after URI sxs)

–  Henoch-Schonlein Purpura (HSP) = Abdominal pain, diarrhea, often seen in kids, rarely in adults

–  Rx: steroids, fish oil(?) in selected patients with more severe disease, ACE/ARB

§  MPGN/cryoglobulinemia –  Highly associated with HCV infection –  Cryos: arthralgias, purpura, livedo reticularis –  Rx: Underlying HCV à interferon and ribavirin


NEPHROLOGY


IgA and SLE: Chameleons Both IgA Nephropathy and SLE can be… §  Indolent or rapidly progressive §  Crescentic GN §  Nephritic and/or nephrotic IgA Nephropathy §  More common in Asians and Hispanics §  Episodic macrohematuria SLE §  More common in Asians, Hispanics, African Americans §  Up to 75% with SLE have renal disease; usually presents

with proteinuria

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NEPHROLOGY


AKI: Disease Associations Pulmonary Renal Syndromes §  Pneumonia with ATN §  Vasculitis §  SLE nephritis §  Anti-GBM Disease/Goodpasture’s Syndrome

With thrombocytopenia §  Common: ATN with DIC/sepsis §  SLE nephritis §  HUS/TTP (thrombotic microangiopathy)

Renal-Dermatological Syndrome §  SLE nephritis §  Henoch-Schonlein Purpura/IgA nephropathy §  HCV-related cryoglobulinemia §  ANCA vasculitis


NEPHROLOGY


Case

A 60 year-old woman with chronic low back pain has an elevated creatinine on routine annual evaluation. She has had polyuria and nocturia over the past few years.

She has no other medical history. She does not

use any prescription medications. Physical exam is unremarkable.

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NEPHROLOGY


Case, continued

Labs §  CBC normal §  Electrolytes normal §  BUN 35 mg/dL §  Creatinine 2.9 mg/dL §  UA 5-10 WBC/hpf, no protein or blood Renal US small kidneys

possible papillary necrosis


NEPHROLOGY


Case Question 9

What is the next step in management? A.  Nephrology referral for renal biopsy. B.  Ophthalmology referral for retinal exam. C.  Ask the patient about over-the-counter

medications. D.  Urine culture for Mycobacterium

tuberculosis.

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NEPHROLOGY


Interstitial Kidney Disease

§  Often asymptomatic –  May not have the fever, rash, and arthralgias of acute

interstitial nephritis

§  Minimal proteinuria/hematuria §  Sterile pyuria §  Urine sediment: +/- WBC, WBC casts §  Late manifestations: hypertension and

anemia


NEPHROLOGY



§  Tubular abnormalities –  Urinary concentrating defects and nephrogenic

diabetes insipidus à polyuria, nocturia –  Fanconi syndrome

•  Impaired tubular reabsorption: amino acids, bicarbonate, phosphate, glucose in urine

• Glucosuria with normal serum glucose • Proximal (type 2) RTA/metabolic acidosis from

bicarbonate spilling • Distal (type 1) RTA/metabolic acidosis from

inability to acidify urine

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NEPHROLOGY


DDx (CKD without proteinuria, asymptomatic) §  Chronic tubulointerstitial diseases

–  Occupational exposures, lead and heavy metals –  Medications = analgesics, lithium –  Traditional medicines: Aristolochic acid nephropathy –  Metabolic = hyperCa, hypoK, oxalosis, cystinosis –  Medullary cystic kidney disease –  Immune disorders = SLE, Sjogren’s, sarcoidosis –  Myeloma and lymphoproliferative disease

§  Proteinuric kidney disease with suppressed proteinuria from ACE/ARB

§  Urinary tract obstruction §  Polycystic kidney disease §  Hypertensive nephropathy


NEPHROLOGY



§  Definitive diagnosis by kidney biopsy –  Diagnosis often made clinically –  Biopsy may not alter therapy

§  Treatment –  Eliminate or treat underlying cause –  Mainly supportive therapy –  Steroids NOT used for chronic interstitial nephritis

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NEPHROLOGY


Analgesic Nephropathy (AN)

§  Phenacetin –  Previously widely available outside United States –  Incidence of AN dropped after taken off market

§  Acetaminophen –  Metabolite of phenacetin –  Conflicting data on nephrotoxicity

§  Aspirin –  Potentiates toxicity of phenacetin and acetaminophen


NEPHROLOGY


Analgesic Nephropathy (AN)

§  Usually seen in women §  History of chronic back pain or headaches §  Radiology findings

–  IVP: Papillary necrosis in severe cases –  Ultrasound: Atrophic kidneys –  CT: Papillary calcifications, atrophic kidneys with “bumpy" or lobulated/irregular contours

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NEPHROLOGY


NSAIDs and Kidney Disease

§  AKI: Hemodynamic acute renal failure –  Prostaglandins vasodilate afferent arteriole

§  AKI: Acute interstitial nephritis +/- minimal change disease

–  Sterile pyuria with proteinuria

§  CKD: Analgesic nephropathy –  Cumulative nephrotoxicity, high doses over years

§  CKD: Membranous nephropathy –  Heavy proteinuria, nephrotic syndrome –  Hypercoagulability


NEPHROLOGY


Case

A 72 year-old woman is admitted to the hospital for new onset nephrotic syndrome. She had been healthy until the past year when she noticed a decrease in appetite, constipation, and a ten pound weight loss. Over the past month, she has noticed face, arm, and leg swelling.

Physical examination reveals a chronically ill-appearing woman with anasarca.

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NEPHROLOGY


Case, continued

Labs §  Hematocrit 29% with MCV 72 fL §  BUN 54 mg/dL §  Creatinine 3.1 mg/dL §  HBV, HCV, cryo negative §  Complements normal §  UA 4+ protein, no hematuria §  24-hr urine 4.5 g protein Renal US: Normal sized kidneys with mild echogenicity Renal Bx: Thickened glomerular capillary walls with subepithelial

deposits consistent with membranous nephropathy


NEPHROLOGY


Case Question 10

Which of the following studies are most appropriate in light of the renal biopsy results?

A.  ANCA antibodies B.  Anti-GBM antibodies C.  ANA and double-stranded DNA antibodies D.  Echocardiogram E.  Colonoscopy

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NEPHROLOGY


Nephrotic Syndrome

§  Proteinuria > 3.5 g/day §  Dyslipidemia §  Edema §  Hypoalbuminemia §  Lipiduria (oval fat bodies in urine, Maltese cross

with polarized light) §  Associated Feature: Hypercoagulability Caveat:

–  Many patients do not have all 5 features, i.e. nephrotic-range proteinuria without nephrotic syndrome


NEPHROLOGY


Nephrotic Diseases: DDx

§  Focal Segmental Glomerulosclerosis (FSGS) –  More common in African-Americans, and in those <

40 y/o

§  Membranous Nephropathy (MN) –  Tend to be Caucasian and > 40 y/o

§  Minimal Change Disease (MCD) –  <15 y/o, BUT 10% adults

§  Amyloidosis §  Diabetic nephropathy §  Others = SLE, IgA nephropathy, MPGN

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NEPHROLOGY


Serologies in Nephrotic Syndrome §  Serologies are suggestive, not definitive

–  C3/C4: low vs. normal complements –  ANA: vaguely rheumatologic vs. non-rheumatologic –  SPEP/UPEP/IFE: multiple myeloma and MGUS –  Other serologies based on clinical suspicion

§  Still require kidney biopsy for diagnosis In contrast to nephritic diseases, where serologies and

clinical hx can be more definitive –  SLE (ANA, anti-DS DNA) –  ANCA-related disease (ANCA) –  Anti-GBM disease (anti-GBM) –  Post-infectious (ASO/antiDNase)

§  Kidney bx for prognosis as well as diagnosis


NEPHROLOGY


Nephrotic Disease: Membranous Nephropathy §  Idiopathic/Primary §  Secondary

–  Malignancy •  Typically solid (colon, lung, breast), also non-

Hodgkin’s •  5-10% have malignancy, but <1-2% are occult

–  Chronic infections, HBV > HCV, syphilis –  SLE (10-20% of lupus nephritis) and autoimmune/

connective tissue diseases –  Drugs: NSAIDs, gold, penicillamine (think of this in

pts with RA treated with these agents)

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NEPHROLOGY


Nephrotic Disease: Membranous Nephropathy §  Clinical

–  Renal vein thrombosis and hypercoagulability –  Secondary prophylaxis with warfarin –  Malignancy and age-appropriate cancer screening

§  Prognosis: Mixed –  Third get better, third stay same, third get worse

§  Treatment: –  Carefully selected patients with poor prognostic

features (older age, men, chronic kidney disease, symptomatic proteinuria/nephrotic syndrome)

–  Immunosuppression: steroids AND (cyclophosphamide or chlorambucil)


NEPHROLOGY


Nephrotic Disease: Focal Segmental Glomerulosclerosis (FSGS) §  Idiopathic/Primary

–  Can be treated with steroids –  Can recur explosively post-kidney transplant

§  Secondary –  HIV-associated nephropathy (HIVAN), almost

exclusively in African-Americans, large kidneys –  Chronic kidney disease, reduced nephron mass,

hyperfiltration injury –  Heroin, morbid obesity, drugs (lithium, pamidronate) –  Sickle cell disease –  Typically not steroid responsive

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NEPHROLOGY


Nephrotic Disease: Minimal Change Disease (MCD) §  Idiopathic/Primary

–  Second peak in 60-70 year old patients –  More steroid resistance/dependence and higher

relapse rate in adults than in children

§  Secondary –  Drugs –  NSAID-induced AIN with MCD, pyuria with

proteinuria –  Infections –  Neoplasm, Hodgkin’s and others –  Allergy and toxins (bee stings, mercury, lead)

§  Rx: Steroids typically first-line


NEPHROLOGY


Nephrotic Disease: Amyloidosis

§  Pathology –  β pleated structure that forms 8-10 nm fibrils –  Congo Red stain has apple-green birefringence with

polarized light

§  Classification –  ~ 20 unique amyloidoses –  AL (primary) amyloidosis

• myeloma and monoclonal gammopathies –  AA (secondary) amyloidosis

•  chronic infections, inflammatory states (inflammatory bowel disease, rheumatoid arthritis, familial Mediterranean fever)

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NEPHROLOGY



§  Clinical findings –  Renal involvement is common in amyloidoses –  Large kidneys and massive proteinuria –  Multi-organ involvement

• Periorbital hemorrhage (raccoon sign), macroglossia

• Cardiac deposits • GI involvement, hepatomegaly • Carpal tunnel syndrome, neuropathy • Shoulder pad sign = amyloid deposits in deltoids

–  Cardiac and kidney disease are poor prognostic signs


NEPHROLOGY



§  Treatment –  AA Amyloidosis: Treat underlying infection or

inflammation, colchicine for Familial Mediterranean Fever

–  AL Amyloidosis: Treat underlying myeloma, melphalan, prednisone, stem-cell transplant

–  Adjuvant therapy: ACE/ARB, blood pressure control, diuretics, sodium/water restriction

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NEPHROLOGY


Kidney Disease in Multiple Myeloma

§  Amyloidosis –  Lambda > kappa light chains

§  Light chain deposition disease –  Kappa > lambda light chains

§  Cast nephropathy §  Hypercalcemia and vasoconstrictive AKI §  Hypercalcemia and nephrogenic DI with pre-

renal AKI §  ATN from sepsis


NEPHROLOGY


Diabetic Nephropathy

§  Common cause of proteinuria §  Unusual cause of nephrotic syndrome §  Early hyperfiltration phase usually with

preserved creatinine and large kidneys §  Diagnosis

–  Usually clinical diagnosis without kidney biopsy –  Compatible clinical history

• Duration and severity of DM • Evidence of end-organ disease from DM

(retinopathy, neuropathy) • No suspicious features for alternative diagnosis

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NEPHROLOGY


Diabetic Nephropathy

§  Untreated DM patients will lose GFR at rate of 1 mL/min/month or 12 mL/min/year

§  Rapid deterioration of function and/or unexplained rise in proteinuria can suggest non-diabetic disease


NEPHROLOGY


Adjuvant Rx in Nephrotic Syndrome

§  HTN control –  Goal BP < 130/80 mm Hg or even 125/75

§  Proteinuria suppression –  ACE inhibitors / ARB –  Goal urine protein:creatinine ratio < 0.5 –  Dietary protein restriction à controversial

§  Loop diuretics for edema §  Sodium/fluid restriction §  No clear role for primary prophylaxis with

anticoagulation for hypercoagulability

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NEPHROLOGY


Case

A 32 year-old African-American man with a recent diagnosis of HIV presents with nausea and vomiting for 2 months. He notes frothy urine for 6 months.

He is afebrile with blood pressure 100/62 and

heart rate 72. Physical exam is normal without pedal edema.


NEPHROLOGY


Case, continued

Labs §  Hematocrit 32% §  BUN 104 mg/dL §  Serum Cr 14.2 mg/dL §  CD4 132/mm3 §  U/A 3+ protein, no hematuria §  24-hr urine 12 gm protein Renal US large kidneys with marked echogenicity He starts hemodialysis and has a kidney biopsy.

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NEPHROLOGY


Case Question 11 Kidney biopsy shows focal segmental

glomerulosclerosis of the collapsing variant, interstitial inflammation, and tubular microcyst formation.

Which of the following is the most appropriate

therapy for this patient’s disease? A.  Pulse IV methylprednisolone B.  Cyclophosphamide C.  Cyclosporine D.  Antiretroviral therapy


NEPHROLOGY


DDx Enlarged Kidneys

§  Hydronephrosis/Obstruction §  Polycystic kidney disease §  Infiltrative disease (lymphoma) §  HIVAN §  Amyloidosis §  Early diabetic nephropathy

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95

Common Etiologies of AKI in HIV infected Patients

(History PE Urinalysis US)

Pre-renal Renal Obstruction (PE, FENA) (US, RBC, Crystals)

dehydration Sulfadiazine NSAID HUS Acyclovir

Indinavir Acute Tubular Necrosis Glomerular lesion Acute Interstitial Nephritis (RTC, Gran. casts) (Proteinuria, +/-RBC) (Pyuria, WBC casts) Hypotension/Sepsis HIVAN Trimethoprim- Aminoglycosides HIVIC Sulfamethoxazole Pentamadine NSAID (proteinuria) Acyclovir Rifampin Foscarnet Amphotericin B Tenofovir

HIV may be coincident with: HBV: Membranous > MPGN HCV: MPGN, cryoglobulinemia

> Membranous


NEPHROLOGY


Typical Presentation: HIVAN

•  Asymptomatic •  Nephrotic-range proteinuria, bland urinary

sediment, absence of serologic markers of renal disease

•  Rapid deterioration of renal function •  Distinct lack of hypertension and edema •  Normal or enlarged kidney size, echogenic

texture on ultrasound •  Treatment: ART +/- ACE/ARB therapy

96

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NEPHROLOGY


SECONDARY HYPERTENSION

97


NEPHROLOGY


Case §  62-yo man referred to you for evaluation and

management of right-sided renal artery stenosis (approx 75%) that was identified incidentally during CT angio obtained for evaluation of claudication.

§  History of CAD, hypertension §  Meds: lisinopril, metoprolol, aspirin, atorvastatin §  BP 126/78, P 64 §  Decreased pedal pulses on left, otherwise

normal exam §  SCr 1.1 (last year was 1.0) §  CT: kidney size normal and similar on both sides

98

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NEPHROLOGY


Case Question 12

Which ONE of the following describes the most appropriate course of action at this time? A. No change in management B. Lisinopril should be d/c’ed C. Surgical (open bypass) revascularization D. Angioplasty with stenting E. Addition of warfarin

99


NEPHROLOGY


Renal Artery Stenosis/Disease

§  Clinical Features –  Secondary HTN –  Flash pulmonary edema –  Kidney size asymmetry > 1.5 cm –  AKI after initiation of ACE inhibitor/ARB

§  Diagnosis –  CTA, MRA, conventional angiography –  Ultrasound: highly operator/institution dependent

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NEPHROLOGY


Renal Artery Stenosis/Disease

§  Atherosclerosis –  Men and women, age > 50 –  Proximal/ostial lesions –  Complete occlusion and renal atrophy are common –  Medical management

§  Fibromuscular Dysplasia –  Women, younger, 15-40 –  Mid-vessel disease, can affect multiple vessels –  String of beads appearance on angiography –  Complete occlusion and renal atrophy are rare –  Often reversible with angioplasty


NEPHROLOGY


Primary hyperaldosteronism

§  11% of resistant hypertension cases §  Bilateral idiopathic hyperaldosteronism (hyperplasia)

(60-70%) §  Aldosterone-producing adenomas (30-40%) §  Hypertension with volume expansion and suppressed

renin §  Hypokalemia not required §  Lack of edema (“aldosterone escape”) §  Rx: spironolactone / eplerenone §  Other: diuretic and/or K-sparing diuretic §  Rx unilateral adenoma: surgery

102

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NEPHROLOGY


ELECTROLYTE ABNORMALITIES

103


NEPHROLOGY


Case

83 year-old woman falls and fractures her right hip. Medical history includes hypertension and diabetes.

Medications include an ACE inhibitor. On physical exam, she is slightly confused. BP

140/90, HR 80. JVP is 8 cm, normal heart sounds, and clear chest exam. No hepatosplenomegaly. No pedal edema. Deep tendon reflexes are normal.

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NEPHROLOGY


Case, continued

Labs CXR Normal §  WBC 5000/uL §  Hematocrit 39% §  Platelets 122,000/uL §  Sodium 115 mEq/L §  Potassium 3.8 mEq/L §  Chloride 85 mEq/L §  Bicarbonate 23 mEq/L §  BUN 12 mg/dL §  Creatinine 1.0 mg/dL §  Serum osms 240 mosm/kg §  Urine Na 42 mEq/L §  Urine osms 680 mosm/kg


NEPHROLOGY


Case Question 13

Which of the following is the most likely cause of hyponatremia in this patient?

A.  Extracellular fluid volume depletion B.  Congestive heart failure C.  Syndrome of inappropriate antidiuretic

hormone (SIADH) D.  Addison’s disease E.  Cirrhosis

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NEPHROLOGY


Hyponatremia

§  Serum Osmolality –  High: Translocational, mannitol and glucose –  Normal: Pseudohyponatremia, triglycerides and

paraproteinemias –  Low: Majority of hyponatremia cases

§  Volume status for hypo-osmolar patients

Exam: HYPOVOLEMIC Urine Na+ < 25 mEq/L

Exam: EUVOLEMIC

Exam: HYPERVOLEMIC Urine Na+ <25 mEq/L

True Volume Depletion GI Losses Renal Losses Skin Losses Thiazide diuretics

SIADH (urine Na+ usually high) Primary polydipsia / beer potomania (dilute urine with low urine Na+ due to dilute urine – ADH appropriately suppressed) Hypothyroidism (evidence of hypothyroidism on exam) Cortisol deficiency (evidence of cortisol deficiency on exam) Decreased GFR

Decreased effective circulating volume heart failure cirrhosis nephrotic syndrome

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NEPHROLOGY


Hyponatremia: Key physiology

§  Think about water, not salt! §  Water and sodium balance are interrelated, but

regulated by separate mechanisms –  ADH regulates osmolality (water balance) –  Aldosterone regulates sodium balance

109


NEPHROLOGY


Hyponatremia

§  Treatment –  Free water restriction; increase solute intake –  Hypovolemic: Saline IVF, suppress ADH excretion –  Euvolemic: Free H2O restriction –  Hypervolemic: Diuretics and/or dialysis

§  Hypertonic Saline (3% NaCl) –  Rarely indicated –  Risk of osmotic demyelination/pontine myelinolysis –  Used for severely symptomatic patients –  Infusion rate typically 0.5 to 1 mL/kg/hour

§  Correction rate –  Approximately 10-12 mEq/L per day

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NEPHROLOGY


SIADH: Syndrome of Inappropriate Antidiuretic Hormone §  Common cause of hyponatremia §  Low serum osmolality §  Clinically euvolemic §  DDx

–  CNS: head trauma, infection, CVA, tumors, others –  Pulmonary: Small cell lung cancer, pneumonia, lung

abscess, pneumothorax –  Drugs: Chlorpropamide, tricyclic antidepressants,

haloperidol, SSRIs –  Neoplasm –  Pain, nausea


NEPHROLOGY


SIADH: Syndrome of Inappropriate Antidiuretic Hormone §  Findings

–  Urine osms > serum osms –  Urine Na > 20 mEq/L

§  Diagnosis of exclusion –  Rule-out hypothyroidism and adrenal insufficiency

§  Treatment more specific for SIADH –  Sodium tablets and water restriction –  Demeclocycline is rarely used, nephrotoxic (induces

nephrogenic diabetes insipidus) –  Vasopressin receptor antagonists (vaptans) –

liberalize fluid intake if on vaptan!

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NEPHROLOGY


Hypernatremia

§  Clinical –  CNS symptoms: lethargy, weakness, irritability,

altered mental status, seizures, coma –  Thirst usually protects against hypernatremia;

impaired access to free water

§  DDx –  Renal water loss: DM and glucosuria, diabetes

insipidus (central or nephrogenic), post-obstructive or post-ATN diuresis

–  Extra-renal water loss: insensible losses, GI losses –  Excess Na+ retention: AKI


NEPHROLOGY


Hypernatremia

Free water deficit = 0.5 x Wt (kg) x [(plasma Na – 140)/140]

–  Free water deficit typically at least 2 L –  Intravenous D5W vs. water NG/PO –  If hypovolemic, resuscitate with NS first. –  Correction rate: 12 mEq/L per 24 hours?

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NEPHROLOGY


Hyperkalemia: Etiology

§  Dietary ingestion §  Decreased excretion

–  AKI/CKD –  Decreased RAAS (ACE/ARB, NSAIDs, cyclosporine,

type 4 RTA) –  Hypoaldosteronism (Addison’s disease) –  Aldosterone resistance (trimethoprim, pentamidine,

amiloride)

§  Extracellular K shift: metabolic acidosis, insulin deficiency, beta-blockers, tumor lysis, digoxin overdose, succinylcholine, hyperkalemic periodic paralysis


NEPHROLOGY


Hyperkalemia: Work-up

§  EKG findings –  Loss of P waves, QRS widening, T wave

peaking, V tach/fib –  EKG findings correlate poorly with severity

of hyperkalemia §  Transtubular Potassium Gradient (TTKG)

–  TTKG = (UK/PK) / (Uosm/Posm) –  TTKG < 6 à renal hyperkalemia –  TTKG > 10 à appropriate renal response

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NEPHROLOGY


Hyperkalemia Treatment

§  Stabilization of membrane = Fast –  Calcium gluconate IV

§  Shift potassium = Fast –  Beta-agonists (albuterol) –  Insulin/glucose –  NaHCO3 (may not work in ESRD)

§  Removal of potassium = Slow –  Diuretics, Dialysis –  Sodium polystyrene (Kayexalate – avoid in

peri-operative pts, ileus/SBO)


NEPHROLOGY


Hypokalemia

§  Clinical, typically K < 2.5-3 mEq/L –  Weakness, rhabdomyolysis, arrhythmias

§  DDx –  Low dietary K intake –  Intracellular shift: alkalemia, increased insulin,

increased beta-activity, periodic paralysis (classically with thyrotoxicosis)

–  Increased excretion: • GI: diarrhea, vomiting • Kidney: diuretics, hypomagnesemia,

mineralocorticoid excess (aldosteronism, Cushing’s, European licorice, hyperreninemia, syndrome of apparent mineralocorticoid excess), Bartter, Gitelman

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NEPHROLOGY


Hypokalemia

Diagnostics §  Transtubular Potassium Gradient (TTKG)

–  TTKG < 2 à GI losses, TTKG > 4 renal loss

§  24 hr urine –  < 25 mEq/day à extrarenal loss –  > 25 mEq/day à renal losses


NEPHROLOGY


ACID-BASE

120

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NEPHROLOGY


Case

68 year-old man with chronic kidney disease due to type 2 diabetes is evaluated in clinic for nausea, vomiting, and fatigue for the past several weeks. His symptoms started several days after a cardiac catheterization which demonstrated two-vessel coronary artery disease. Physical examination is remarkable for bibasilar crackles, a regular cardiac rhythm, and 2+ peripheral edema.

121


NEPHROLOGY


Case

§  Laboratory studies: §  BUN 110 mg/dL §  Serum Cr 14.0 mg/dL §  Serum sodium 135 mEq/L §  Serum potassium 5.5 mEq/L §  Serum chloride 80 mEq/L §  Serum bicarbonate 23 mEq/L §  Arterial blood gas (room air):

pH 7.39 PCO2 38 mmHg PO2 72 mmHg Bicarbonate 23 mEq/L

122

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NEPHROLOGY


Case Question 14

Which of the following describes this patient’s acid-base status?

A.  No acid-base abnormality B.  Metabolic acidosis and respiratory

alkalosis C.  Metabolic acidosis with respiratory

compensation D.  Metabolic acidosis and metabolic

alkalosis

123


NEPHROLOGY


Acid base disorders: systematic approach is key! §  Identify Primary Disorder §  Calculate the anion gap and learn the use of

delta gap §  Know 1 set of compensation method and apply §  Finalize the acid base disturbance and

generate a differential diagnosis for each problem identified

124

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NEPHROLOGY


Blood gases: a simple approach

Primary disorder Normal ABG range Primary disorder

Acidemia pH 7.35-7.45 Alkalemia

Respiratory alkalosis pCO2 35-45 mm Hg Respiratory acidosis

Metabolic disturbance

HCO3 22-26 mmol/L Metabolic disturbance

125


NEPHROLOGY


Metabolic disturbances

1)  Metabolic acidosis 2)  Metabolic alkalosis 3)  Gap metabolic acidosis 4)  Gap metabolic acidosis AND nongap

metabolic acidosis (!!!) ß2 completely different disorders

5)  Gap metabolic acidosis AND metabolic alkalosis

126

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NEPHROLOGY


Metabolic Acidosis: Increased Anion Gap §  Increased Anion Gap

–  MUDPILES (methanol, uremia, DKA, paraldehyde, isoniazid, lactic acidosis, ethylene glycol, salicylate)

–  AG > 20 implies metabolic acidosis regardless of serum bicarbonate or pH

Serum Anion Gap = Na – Cl – HCO3

Normal AG < 12 §  Corrected AG – add 2.5 to the AG for every 1 g/

dL drop in albumin


NEPHROLOGY


Aside: DDx Decreased Anion Gap

§  Extra Positive (+) charges –  Immunoglobulins (myeloma) –  Lithium –  Potassium –  Magnesium –  Calcium

§  Decreased Negative (-) charges –  Albumin

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NEPHROLOGY


Compensation and combined metabolic disturbances §  Respiratory compensation is rapid:

–  Several formulas, including Winter’s formula: • Expected pCO2 = 1.5* [HCO3-] + 8 +/- 2

§  Several ways to look for combined disorders: –  ∆Anion gap/∆ plasma HCO3-

• Usually not 1:1 since up to 50% of acid is buffered intracellular.

• A value below 1:1 suggests combined high and normal anion gap acidosis

• A value above 2:1 suggests a concurrent metabolic alkalosis

• Here, anion gap = 32, ∆anion gap = 20, serum bicarbonate = 23, ∆bicarbonate= 1, so ∆:∆ = 20

129


NEPHROLOGY


Compensation and combined metabolic disturbances §  Several ways to look for combined

disturbances: –  ∆Anion gap + actual serum bicarbonate

•  If it is < 24, there is a concomitant non-gap metabolic acidosis

•  If it is > 30, there is a concomitant metabolic alkalosis

–  Here: anion gap = 32, ∆anion gap = 20, serum bicarbonate = 23,

•  23 + 20 = 43 •  Therefore there is concomitant metabolic alkalosis

130

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NEPHROLOGY


Osmolar Gap

Osmolar Gap = Measured Osms – Estimated Osms

Estimated osms =

2Na + BUN/2.8 + glucose/18 + EtOH/4.6 Normal Osmolar Gap < 10


NEPHROLOGY


Osmolar Gap

Major Conditions with increased osmolar gap §  Increased AG metabolic acidosis (MUDPILES)

–  Conditions = uremia, DKA, alcoholic ketoacidosis, lactic acidosis

–  Ingestions = methanol, paraldehyde, formaldehyde, ethylene glycol

§  Normal AG, no metabolic acidosis –  Exogenous = isopropanol, diethyl ether, mannitol –  Artifact = hyperproteinemia, hypertriglyceridemia

(artificial lowering of serum sodium concentration)

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NEPHROLOGY


Metabolic acidosis: Normal Gap (non-gap) §  Normal anion gap metabolic acidosis

–  Also called hyperchloremic met. acidosis –  GI: Diarrhea with bicarbonate loss

• Negative urine anion gap –  Renal: Renal tubular acidosis (RTA)

• Positive urine anion gap Urine Anion Gap = Na + K – Cl

Normal UAG in acidosis is negative RTA = Urine K is high = UAG becomes

positive


NEPHROLOGY


Case

§  A 22 yo woman with a history of Sjogren’s syndrome presents with a 1 week history of progressive weakness

§  Exam: Diffuse muscle weakness, normal DTRs

134

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NEPHROLOGY


Case

§  Laboratory studies: §  BUN 20 mg/dL §  Serum Cr 0.7 mg/dL §  Serum sodium 140 mEq/L §  Serum potassium 2.2 mEq/L §  Serum chloride 120 mEq/L §  Serum bicarbonate 12 mEq/L §  Arterial blood gas (room air):

pH 7.1 PCO2 40 mmHg PO2 72 mmHg

§  Urine pH 6.5 §  Urine Na 95 K 32 Cl 90 (UAG = 37)

135


NEPHROLOGY


Case Question 15

Which of the following describes this patient’s acid-base status?

A.  No acid-base abnormality B.  Metabolic acidosis and respiratory

acidosis C.  Metabolic acidosis with respiratory

compensation D.  Metabolic acidosis and metabolic

alkalosis

136

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NEPHROLOGY


Case Question 16

Does this patient have a renal tubular acidosis? A. Yes B. No

137

Renal tubular acidosis – non gap met acid Type 1 Distal

Type 2 Proximal

Type 4

Defect ↓ distal acidification

↓proximal HCO3 reabsorption

Aldosterone deficiency or

resistance

Urine pH > 5.3 > 5.3 early < 5.3 late

Usually < 5.3

Plasma K Low or normal, can be high

Low or normal High

Dose of bicarbonate

Low High Low

Complications Nephrocalcinosis Nephrolithiasis

Rickets or osteomalacia

None

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NEPHROLOGY


Non-gap Metabolic Acidosis: Stepwise Analysis §  Examine serum K

–  If high, then type 4 RTA –  If normal, then type 1 or type 2

§  Urine pH –  If urine pH > 5.5, then Type 1 Distal –  If urine pH < 5.0, then Type 2 Proximal

§  If type 2 Proximal RTA –  Confirm with evidence of proximal tubular dysfunction

• Glucosuria, low-grade proteinuria, phosphaturia


NEPHROLOGY


Case

A 22 year-old woman comes to the emergency room with paresthesias and generalized weakness.

She has no significant medical history and does

not take any medications. Her blood pressure is 120/72 and physical exam

is unremarkable.

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NEPHROLOGY


Case, continued

Labs Urine §  Sodium 138 mEq/L pH 6.0 §  Potassium 2.4 mEq/L Na 16 mEq/L §  Chloride 90 mEq/L K 20 mEq/L §  Bicarbonate 36 mEq/L Cl < 5 mEq/L §  BUN 14 mg/dL §  Creatinine 1.0 mg/dL §  Magnesium 1.9 mg/dL §  Calcium 9.0 mg/dL


NEPHROLOGY


Case Question 17

Which of the following is the most likely diagnosis?

A.  Surreptitious vomiting B.  Surreptitious active diuretic use C.  Gitelman syndrome D.  Bartter syndrome E.  Liddle syndrome

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NEPHROLOGY


Major Causes of Metabolic Alkalosis

§  GI hydrogen loss –  NG suction, vomiting –  Chloride-losing diarrhea (villous adenoma, laxatives)

§  Renal hydrogen loss –  Aldosteronism –  Loop and thiazide diuretics, Bartter and Gitelman –  Post-hypercapnic alkalosis –  Milk-alkali syndrome (calcium carbonate loading)

§  Intracellular shift of hydrogen (hypokalemia) §  Administration of bicarbonate §  Contraction alkalosis


NEPHROLOGY


Maintenance of Metabolic Alkalosis

Reduced renal bicarbonate excretion §  Effective circulating volume depletion

–  Reduction in the filtered load of HCO3 –  Secondary aldosteronism (paradoxical aciduria)

§  Chloride depletion –  Vomiting and diuretics

§  Hypokalemia –  Intracellular shifting of potassium and hydrogen ions

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NEPHROLOGY


Urine Chloride in Metabolic Alkalosis

§  Vomiting and long term diuretic use –  Depleted body chloride stores –  Kidneys will conserve/reabsorb chloride –  Urine Cl < 15 mEq/L –  Urine Cl will be elevated with ACTIVE diuretic use

§  Primary aldosteronism –  Volume expanded –  Urine Cl > 20 mEq/L


NEPHROLOGY


Saline and Alkalosis

§  Saline Responsive = Low urine Cl < 15 –  Vomiting or nasogastric suction –  Diuretics –  Post‑hypercapnic alkalosis –  Low dietary chloride intake

§  Saline Unresponsive = High urine Cl > 20 –  Mineralocorticoid excess –  Severe hypokalemia –  Edematous disorders, e.g. CHF

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NEPHROLOGY


Acid base formulas

§  Metabolic Acidosis –  1.2 mmHg fall in PCO2 per 1 meq/L decrease in

plasma [HCO3-] –  (Winters formula pCO2 =(1.5 x HCO3-) + 8 +/- 2)

§  Metabolic Alkalosis –  0.6 mmHg rise in PCO2 per 1 meq/L elevation in

plasma [HCO3-]


NEPHROLOGY


Acid base formulas

Respiratory Acidosis §  Acute:

–  1 meq/L increase in plasma [HCO3-] per 10 mmHg rise in PCO2

–  ∆[H+] = 0.8 ∆PCO2 §  Chronic:

–  3.5 meq/L elevation in plasma [HCO3-] per 10 mmHg increase in PCO2

–  ∆[H+] = 0.3 ∆PCO2

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NEPHROLOGY


Acid base formulas

Respiratory Alkalosis §  Acute:

–  2 meq/L decrease in plasma [HCO3-] per 10 mmHg decrease in PCO2

–  ∆ [H+] = 0.8 ∆PCO2 §  Chronic:

–  4 meq/L decrease in plasma [HCO3-] per 10 mmHg decrease in PCO2

–  ∆ [H+] = 0.4 ∆PCO2


NEPHROLOGY


Predictive formulas for kidney function §  Cockcroft-Gault Formula

–  Estimates Creatinine Clearance (mL/min) eCrCl = 140 – age x mass (kg) x 0.85 (female)

72 –  Inaccurate for non-whites, women, patients at

extremes of age/weight?

§  MDRD Formula –  Estimates GFR (mL/min/1.73 m2) –  Does not incorporate weight

§  CKD-EPI Formula –  More accurate at higher eGFR than MDRD

Levey, AS et al Ann Int Med 2009; Stevens LA et al. NEJM 2006; Cockcroft DW, Gault MH. Nephron 1976.

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NEPHROLOGY


Estimating Proteinuria

§  24-hour urine collection –  Time consuming, inconvenient –  Inaccurate/inadequate urine collections –  Difficult to follow serially

§  Spot Urine Protein:Creatinine ratio –  Ratio correlates to grams/day/1.73 m2 of proteinuria –  Quick, easy to follow serially –  Assess response to therapy, e.g. ACE inhibitors/ARB –  Recommended by NKF


NEPHROLOGY


Answers to cases

§  1 A §  2 B §  3 D §  4 B §  5 A §  6 E §  7 C §  8 A §  9 C

§  10 E §  11 D §  12 A §  13 C §  14 D §  15 B §  16 A §  17 A

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Documents

ABIM Certification Exam: Nephrology