7/9/15
ABIM Certification Exam: Nephrology
Division of Nephrology Department of Medicine July 2015
Meyeon Park, MD MAS UCSF CME Assistant Professor
NEPHROLOGY
Disclosures Department of Medicine
Division of § I am site PI for the REPRISE study evaluating Nephrology efficacy of tolvaptan in autosomal dominant polycystic kidney disease (Otsuka pharmaceuticals)
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NEPHROLOGY
Roadmap for today Department of Medicine
Division of § Acute kidney injury Nephrology ------Scheduled 15 min break------§ Glomerulonephritis § Secondary hypertension § Common electrolyte abnormalities § Acid-base § A few odds and ends
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NEPHROLOGY
Case Department of Medicine A 57-yr-old man is admitted after a motor vehicle Division of Nephrology 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 Department of Medicine
Division of Physical Exam: Nephrology 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 Department of Medicine Labs: Division of Nephrology § 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 Department of Medicine
Division of Which of the following would be the most Nephrology 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 Department of Medicine
Division of § Pre-Renal = Decreased kidney perfusion Nephrology § Intra-Renal = Intrinsic kidney disease § Post-Renal = Obstructive nephropathy
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NEPHROLOGY Pre-Renal:
Department Kidney Hypoperfusion of Medicine
Division of § Dehydration, overdiuresis, hypovolemia Nephrology – 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:
Department Kidney Hypoperfusion of Medicine
Division of § Diagnosis Nephrology – +/- 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
Department (FeNa) of Medicine
Division of § percent of filtered sodium that is excreted in the Nephrology 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 Department of Medicine A 40-yr-old man with end-stage liver disease secondary to alcohol abuse is admitted to the Division of Nephrology 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 Department of Medicine
Division of Labs: Nephrology § 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 Department of Medicine
Division of Which of the following would be the most Nephrology appropriate next step? 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:
Department Hepatorenal Syndrome of Medicine
Division of § Severe end-stage liver disease patients Nephrology § 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:
Department Hepatorenal Syndrome of Medicine
Division of § Treatment Nephrology – 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 Department of Medicine A 39-yr-old woman with stage 4 ovarian Division of Nephrology 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 Department of Medicine Labs Division of Nephrology § 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 Department of Medicine Imaging Division of Nephrology § 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 Department of Medicine
Division of Which of the following would be the most Nephrology appropriate next step? A. CT scan with contrast B. Allopurinol and urinary alkalinization C. Emergent hemodialysis D. Percutaneous nephrostomy
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NEPHROLOGY
Post-Renal: Obstruction Department of Medicine § Urinary tract obstruction Division of Nephrology – 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 Department of Medicine § Clinical Division of Nephrology – 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 Department of Medicine
Division of A 65 year-old woman is admitted to the hospital Nephrology 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 Department of Medicine Labs Division of Nephrology § 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 Department of Medicine
Division of What is the most likely diagnosis? Nephrology A. Rhabdomyolysis B. Tumor lysis syndrome C. Cisplatin nephrotoxicity D. Sepsis associated ATN
NEPHROLOGY Intra-Renal:
Department Acute Tubular Necrosis (ATN) of Medicine
Division of § Etiology Nephrology – 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:
Department Acute Tubular Necrosis (ATN) of Medicine § Prognosis Division of Nephrology – 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:
Department Radiocontrast Nephropathy of Medicine § Etiology Division of Nephrology – 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:
Department Radiocontrast Nephropathy of Medicine
Division of § Presentation Nephrology – 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:
Department Radiocontrast Nephropathy of Medicine § Prevention Division of Nephrology – 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
Department word of caution of Medicine § Nephrogenic systemic fibrosis Division of Nephrology – 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 Department of Medicine
Division of § A 24-yr-old construction worker has his legs Nephrology 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 Department of Medicine
Division of Which ONE of the following treatments would Nephrology 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:
Department Rhabdomyolysis of Medicine
Division of § Etiology Nephrology – 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:
Department Rhabdomyolysis of Medicine
Division of § Diagnosis Nephrology – 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 Department of Medicine
Division of § A 36-yr-old IV drug user is admitted to the Nephrology 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 Department of Medicine
Division of Which ONE of the following is not typical of Nephrology this patient’s diagnosis? A. Fever B. Rash C. Eosinophilia D. Arthralgias E. Altered mental status
NEPHROLOGY Intra-Renal:
Department Acute Interstitial Nephritis (AIN) of Medicine § Etiology Division of Nephrology – 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:
Department Acute Interstitial Nephritis (AIN) of Medicine
Division of § Diagnosis Nephrology – 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 Department of Medicine
Division of § A 72-yr-old man with diabetes, hypertension, Nephrology 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 Department of Medicine What is this patient’s MOST LIKELY Division of Nephrology 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:
Department Atheroembolic Disease of Medicine
Division of § Etiology Nephrology – 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:
Department Atheroembolic Disease of Medicine
Division of § Diagnosis Nephrology – 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 Department of Medicine
Division of § Urine sediment Nephrology – 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
Department of Medicine
Division of Nephrology
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NEPHROLOGY
Diagnostics in AKI Department of Medicine
Division of § BUN:Creatinine Ratio Nephrology – 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 Department of Medicine
Division of § 24 Hour Urine for CrCl and Proteinuria Nephrology – 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
Department of Medicine
Division of Nephrology
GLOMERULONEPHRITIS
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NEPHROLOGY
Case Department of Medicine
Division of A 65 year-old man admitted to the hospital for AKI Nephrology 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 Department of Medicine
Division of Which one of the following studies is most Nephrology appropriate? A. ANCA B. Anti-GBM antibodies C. Echocardiogram and blood cultures D. Spiral CT scan
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NEPHROLOGY
Case Department of Medicine Labs Division of Nephrology § 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:
Department Signs and Symptoms of Medicine
Division of § Hematuria, tea-colored urine Nephrology § 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-
Department glomerular of Medicine
Division of § Favoring glomerular bleeding: Nephrology – 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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CLASSIFICATION OF MAJOR GLOMERULAR DISEASES
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)
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NEPHROLOGY Rapidly Progressive
Department Glomerulonephritis (RPGN) of Medicine
Division of § Diagnosis Nephrology – 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 Anti-GBM Immune complex autoantibodies (ANCA) autoantibodies disease markers
No extra- Lung Anti-DNA Anti-pathogen Others Systemic Pulmonary Asthma renal hemorrhage autoabs abs Cryoglobulins/ necrotizing necrotizing and disease HCV arteritis granulomas eosinophilia No lung
hemorrhage
Renal Goodpasture's Lupus GN Post-strep Cryo- IgA Microscopic Granulo- Churg- limited syndrome GN/peri- globulinemic MPGN polyangiitis matosis Strauss vasculitis infectious GN with syndrome Anti-GBM polyangitis GN
ANCA GN Anti-GBM GN Immune complex GN (‘pauci-immune’)
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Rapidly progressive glomerulonephritis
40-80% 2-20% 15-50% ANCA Anti-GBM Immune complex
Caucasians:AA (7:1) Rare in AA SLE common in AA
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:
Department Pauci-Immune/ANCA Disease of Medicine § Diagnosis: ANCA +, normal complements, no Division of Nephrology 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 Department of Medicine
Division of § Autoimmune disease Nephrology – 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
Department (Hypocomplementemic) Disease of Medicine
Division of § Post-infectious/Strep GN Nephrology – 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
Department (Hypocomplementemic) Disease of Medicine
Division of § IgA nephropathy (normal complements) Nephrology – 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 Department of Medicine Both IgA Nephropathy and SLE can be… Division of § Indolent or rapidly progressive Nephrology § 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 Department of Medicine Pulmonary Renal Syndromes Division of § Pneumonia with ATN Nephrology § 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 Department of Medicine
Division of A 60 year-old woman with chronic low back pain Nephrology 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 Department of Medicine Labs Division of Nephrology § 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 Department of Medicine
Division of What is the next step in management? Nephrology
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 Department of Medicine
Division of § Often asymptomatic Nephrology – 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
Interstitial Kidney Disease Department of Medicine
Division of § Tubular abnormalities Nephrology – 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,
Department asymptomatic) of Medicine § Chronic tubulointerstitial diseases Division of Nephrology – 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
Interstitial Kidney Disease Department of Medicine
Division of § Definitive diagnosis by kidney biopsy Nephrology – 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) Department of Medicine
Division of § Phenacetin Nephrology – 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) Department of Medicine
Division of § Usually seen in women Nephrology § 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 Department of Medicine
Division of § AKI: Hemodynamic acute renal failure Nephrology – 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 Department of Medicine
Division of A 72 year-old woman is admitted to the hospital Nephrology 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 Department of Medicine Labs Division of Nephrology § 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 Department of Medicine
Division of Which of the following studies are most Nephrology 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 Department of Medicine
Division of § Proteinuria > 3.5 g/day Nephrology § 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 Department of Medicine § Focal Segmental Glomerulosclerosis (FSGS) Division of Nephrology – 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 Department of Medicine § Serologies are suggestive, not definitive Division of Nephrology – 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:
Department Membranous Nephropathy of Medicine § Idiopathic/Primary Division of Nephrology § 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:
Department Membranous Nephropathy of Medicine
Division of § Clinical Nephrology – 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
Department Glomerulosclerosis (FSGS) of Medicine § Idiopathic/Primary Division of Nephrology – 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:
Department Minimal Change Disease (MCD) of Medicine § Idiopathic/Primary Division of Nephrology – 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 Department of Medicine
Division of § Pathology Nephrology – 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
Nephrotic Disease: Amyloidosis Department of Medicine § Clinical findings Division of Nephrology – 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
Nephrotic Disease: Amyloidosis Department of Medicine
Division of § Treatment Nephrology – 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 Department of Medicine
Division of § Amyloidosis Nephrology – 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 Department of Medicine § Common cause of proteinuria Division of Nephrology § 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 Department of Medicine
Division of § Untreated DM patients will lose GFR at rate of Nephrology 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 Department of Medicine § HTN control Division of Nephrology – 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 Department of Medicine
Division of A 32 year-old African-American man with a recent Nephrology 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 Department of Medicine Labs Division of Nephrology § 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 Department of Medicine Kidney biopsy shows focal segmental Division of glomerulosclerosis of the collapsing Nephrology 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 Department of Medicine
Division of § Hydronephrosis/Obstruction Nephrology § Polycystic kidney disease § Infiltrative disease (lymphoma) § HIVAN § Amyloidosis § Early diabetic nephropathy
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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 HIV may be coincident with: Tenofovir HBV: Membranous > MPGN
HCV: MPGN, cryoglobulinemia > Membranous 95
NEPHROLOGY
Typical Presentation: HIVAN Department of Medicine
Division of • Asymptomatic Nephrology • 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
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NEPHROLOGY
Department of Medicine
Division of Nephrology
SECONDARY HYPERTENSION
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NEPHROLOGY
Case Department of Medicine § 62-yo man referred to you for evaluation and
Division of management of right-sided renal artery stenosis Nephrology (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
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NEPHROLOGY
Case Question 12 Department of Medicine Which ONE of the following describes the Division of Nephrology 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
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NEPHROLOGY
Renal Artery Stenosis/Disease Department of Medicine
Division of § Clinical Features Nephrology – 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 Department of Medicine § Atherosclerosis Division of Nephrology – 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 Department of Medicine § 11% of resistant hypertension cases Division of Nephrology § 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
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NEPHROLOGY
Department of Medicine
Division of Nephrology
ELECTROLYTE ABNORMALITIES
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NEPHROLOGY
Case Department of Medicine
Division of 83 year-old woman falls and fractures her right Nephrology 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 Department of Medicine Labs CXR Normal Division of Nephrology § 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 Department of Medicine
Division of Which of the following is the most likely cause Nephrology 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 Department of Medicine
Division of § Serum Osmolality Nephrology – High: Translocational, mannitol and glucose – Normal: Pseudohyponatremia, triglycerides and paraproteinemias – Low: Majority of hyponatremia cases § Volume status for hypo-osmolar patients
Exam: Exam: Exam: HYPOVOLEMIC EUVOLEMIC HYPERVOLEMIC Urine Na+ < 25 mEq/L Urine Na+ <25 mEq/L
True Volume SIADH (urine Na+ usually Decreased Depletion high) effective GI Losses circulating volume Renal Losses Primary polydipsia / heart failure Skin Losses beer potomania (dilute cirrhosis urine with low urine Na+ due to
dilute urine – ADH nephrotic syndrome Thiazide diuretics appropriately suppressed)
Hypothyroidism (evidence of hypothyroidism on exam)
Cortisol deficiency (evidence of cortisol deficiency on exam)
Decreased GFR
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NEPHROLOGY
Hyponatremia: Key physiology Department of Medicine
Division of § Think about water, not salt! Nephrology § Water and sodium balance are interrelated, but regulated by separate mechanisms – ADH regulates osmolality (water balance) – Aldosterone regulates sodium balance
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NEPHROLOGY
Hyponatremia Department of Medicine § Treatment Division of Nephrology – 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
Department Antidiuretic Hormone of Medicine
Division of § Common cause of hyponatremia Nephrology § 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
Department Antidiuretic Hormone of Medicine
Division of § Findings Nephrology – 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 Department of Medicine
Division of § Clinical Nephrology – 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 Department of Medicine
Division of Free water deficit = Nephrology 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 Department of Medicine
Division of § Dietary ingestion Nephrology § 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 Department of Medicine § EKG findings Division of Nephrology – 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 Department of Medicine
Division of § Stabilization of membrane = Fast Nephrology – 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 Department of Medicine § Clinical, typically K < 2.5-3 mEq/L Division of Nephrology – 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 Department of Medicine Diagnostics Division of Nephrology § 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
Department of Medicine
Division of Nephrology
ACID-BASE
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NEPHROLOGY
Case Department of Medicine
Division of 68 year-old man with chronic kidney disease due Nephrology 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.
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NEPHROLOGY
Case Department of Medicine § Laboratory studies: Division of Nephrology § 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
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NEPHROLOGY
Case Question 14 Department of Medicine
Division of Which of the following describes this patient’s Nephrology 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
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NEPHROLOGY Acid base disorders: systematic
Department approach is key! of Medicine
Division of § Identify Primary Disorder Nephrology § 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
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NEPHROLOGY
Blood gases: a simple approach Department of Medicine
Division of Primary disorder Normal ABG range Primary disorder Nephrology
Acidemia pH 7.35-7.45 Alkalemia
Respiratory alkalosis pCO2 35-45 mm Hg Respiratory acidosis
Metabolic HCO3 22-26 mmol/L Metabolic disturbance disturbance
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NEPHROLOGY
Metabolic disturbances Department of Medicine 1) Metabolic acidosis Division of Nephrology 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
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NEPHROLOGY Metabolic Acidosis:
Department Increased Anion Gap of Medicine
Division of § Increased Anion Gap Nephrology – 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 Department of Medicine
Division of § Extra Positive (+) charges Nephrology – Immunoglobulins (myeloma) – Lithium – Potassium – Magnesium – Calcium § Decreased Negative (-) charges – Albumin
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NEPHROLOGY Compensation and combined
Department metabolic disturbances of Medicine § Respiratory compensation is rapid: Division of Nephrology – 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
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NEPHROLOGY Compensation and combined
Department metabolic disturbances of Medicine
Division of § Several ways to look for combined Nephrology 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
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NEPHROLOGY
Osmolar Gap Department of Medicine Osmolar Gap = Division of Nephrology Measured Osms – Estimated Osms
Estimated osms = 2Na + BUN/2.8 + glucose/18 + EtOH/4.6
Normal Osmolar Gap < 10
NEPHROLOGY
Osmolar Gap Department of Medicine Major Conditions with increased osmolar gap Division of Nephrology § 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
Department (non-gap) of Medicine § Normal anion gap metabolic acidosis Division of Nephrology – 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 Department of Medicine
Division of § A 22 yo woman with a history of Sjogren’s Nephrology syndrome presents with a 1 week history of progressive weakness § Exam: Diffuse muscle weakness, normal DTRs
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NEPHROLOGY
Case Department of Medicine § Laboratory studies: Division of Nephrology § 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)
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NEPHROLOGY
Case Question 15 Department of Medicine
Division of Which of the following describes this patient’s Nephrology 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
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NEPHROLOGY
Case Question 16 Department of Medicine
Division of Does this patient have a renal tubular Nephrology acidosis? A. Yes B. No
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Renal tubular acidosis – non gap met acid Type 1 Type 2 Type 4 Distal Proximal Defect ↓ distal ↓proximal HCO3 Aldosterone acidification reabsorption deficiency or resistance Urine pH > 5.3 > 5.3 early Usually < 5.3 < 5.3 late
Plasma K Low or normal, Low or normal High can be high
Dose of Low High Low bicarbonate
Complications Nephrocalcinosis Rickets or None Nephrolithiasis osteomalacia
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NEPHROLOGY Non-gap Metabolic Acidosis:
Department Stepwise Analysis of Medicine
Division of § Examine serum K Nephrology – 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 Department of Medicine
Division of A 22 year-old woman comes to the emergency Nephrology 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 Department of Medicine Labs Urine Division of Nephrology § 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 Department of Medicine
Division of Which of the following is the most likely Nephrology 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
Department of Medicine § GI hydrogen loss Division of Nephrology – 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 Department of Medicine
Division of Reduced renal bicarbonate excretion Nephrology § 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
Department of Medicine
Division of § Vomiting and long term diuretic use Nephrology – 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
Department of Medicine
Division of § Saline Responsive = Low urine Cl < 15 Nephrology – 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 Department of Medicine
Division of § Metabolic Acidosis Nephrology – 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 Department of Medicine
Division of Respiratory Acidosis Nephrology § 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 Department of Medicine
Division of Respiratory Alkalosis Nephrology § 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
Department of Medicine § Cockcroft-Gault Formula Division of – Estimates Creatinine Clearance (mL/min) Nephrology 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 Department of Medicine
Division of § 24-hour urine collection Nephrology – 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 Department of Medicine
Division of § 1 A § 10 E Nephrology § 2 B § 11 D § 3 D § 12 A § 4 B § 13 C § 5 A § 14 D § 6 E § 15 B § 7 C § 16 A § 8 A § 17 A § 9 C
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