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Acute Kidney Injury in the Out patient setting

Fidel Barrantes M.D

Renal Medicine Associates Presbyterian Transplant Center

Objectives

• Definition of Acute Kidney Injury (AKI) • Recognize types of Acute Kidney Injury • What tests to order? • What interventions can be applied? • When to call specialist or refer to hospital? • Common scenarios in Primary Care Setting and kidney

injury? • Common associations • What to focus on after patient returns from hospital?

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Roles of the Kidneys

What is Acute Kidney Injury?

• Abrupt reduction in GFR ( glomerular filtration rate) • Change in creatinine within certain period of time ( AKIN:

change in creatinine 0.3 mg/dl within 48 hrs), Serum creatinine >/= 1.5 x baseline within 7 days, urine volume < 0.5 ml/6 hrs

• Accumulation of nitrogenous waste, retention of urea, change in electrolytes, volume status and acid-base.

Clinical Consequences of AKI

• Retention of Nitrogen >>> Azotemia and uremia • Retention of Sodium >>> Volume overload, Hypertension • Retention of Water >>> Hyponatremia • Retention of Acids >>> Acidosis, low bicarbonate (CO2) • Retention of Potassium >>> Hyperkalemia • Retention of Phosphate >>> Hyperphosphatemia, hypocalcemia

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Types of AKI

www.medic.scientist.com

Pre renal AKI – Inadequate blood flow to the kidneys

True Intravascular Depletion

• Hypovolemia

-Renal Losses

-Blood Losses

-GI losses

-Third spacing

-Severe Sweating

Effective Intravascular depletion

• Impaired Cardiac function (CM, pulmonary, CHF HTN,etc)

• Impaired Liver Function (Hepato renal , Cirrhosis)

• Impaired Systemic Vascular Tone (Sepsis, Medication, autonomic failure)

Pre renal AKI – Inadequate blood flow to the kidneys

Renal Artery Disease

• Main Renal Artery disease

• Small renal vessels disease ( Hypertensive arteriolo nephrosclerosis)

Altered Renal Hemodynamics

• Afferent Arteriolar Vasoconstriction ( NSAIDs,CNI,Hypercalcemia)

• Efferent Arteriolar Vasdilatation ( ACEI inhibitors, ARB)

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Intrinsic Renal Kidney Injury

Vasculature

• Artery (thrombosis, dissection, renal vasculitis)

• Arteriole (Atheroembolic, vasculitis, scleroderma, fibrinoid necrosis, septic emboli )

• Venous (Thrombosis)

Glomerulus

• Acute proliferative glomerulonephritis

• Thrombotic microangiopathy

• Monoclonal Immunoglobulins deposition disease

www.uncnephropathology.org

Intrinsic Renal Kidney Injury

Tubules

• Acute Tubular Injury ( Ischemic,nephrotoxic)

• Pigment

• Crystal

• Osmotic

• Cast nephropathy

Interstitium

• Allergic interstitial nephritis

• Infection

• Systemic disease

• Malignant Interstitial infiltration

• Idiopathic interstitial

www.uncnephropathology.org

Post Renal AKI

• Retroperitoneal disease (tumor, LN,fibrosis) • Papillary Necrosis • Lithiasis • Fungus ball • Blood clots • Strictures

• Stones • Blood clots • Tumor • BPH • Functional CVA DM Spinal Cord Injury Drugs Neuropathic dz

Uretero calyceal obstruction Bladder Urethra

• Urethritis

• Urethral stricture

• Blood clots

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Approach to patient with AKI

History

Physical exam

Laboratory

Urine

Imaging

Biopsy

Approach I

• History

• Volume status

• Physical exam –What to look for?

Volume status-Orthos,edema Lungs Heart Abdomen-portal HTN, bladder distention Skin-rash Infection-PNA,Diarrhea Autoimmune-Arthritis, rash

Approach II

• Comorbidities- HTN, Ca, Liver Dz, Infectious, etc

• Recent Urgen Care and hospital visits • Medications ( prescribed, OTC, call

pharmacy) • Drugs synthetic • Creatinine trend • Electrolytes • CBC, Hb, PLT, eosinophils • Ca, CO2,Na • UA and sediment

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Urinalysis and Microscopic of the urine sediment

• Protein : Glomerular dz; Highly sensitive for albumin but less so for globulins Trace---5-20 mg/dl 1+-------30 mg/dl 2+-------100 mg/dl 3+-------3000 mg/dl 4+-----2000 mg/dl • Glucose • Blood dipstick: False Positive-Povidone-iodine,hypochlorite, bacterial peroxidase. + Blood but not RBC

suspect myglobinuria or hemoglobinuria

• WBC: GU tract Inflammation, AIN, periureteral inflammation • RBC : >2-3 /HPF Pathologic. Dysmorphic : coming from the renal parenchyma; monomorphic- GU tract • Casts : Granular (ATI, Glomerulonephritis, Tubulo interstitial disease) • Red Blood Cell casts: Intraparenchymal bleeding, GN • WBC casts: Pyelonephritis

What Tests to Order?

• Prerenal– CBC w/diff, CMP, cultures

• Renal—Infections, serologies (ANA, ANCA, SPEP, free light chains)

• Post renal-Renal Bladder US , CT abd/pelvic without contrast.

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Tests and AKI

Tests to Order When to order conditions

ANCA, Anti-GBM Suspect vasculitis Vasculitis, GoodPasture

Increased ASO titer Recent infection and GN clinical picture

Post strep GN

Elevated creatine kinase level, elevated myoglobin level, dipstick positive for blood but negative for red blood cells

Recent trauma, muscle injury Rhabdomyolysis

Elevated prostate-specific antigen level

Older men with symptoms suggestive of urinary obstruction

Prostate hypertrophy, prostate cancer

Elevated uric acid level History of rapidly proliferating tumors, recent chemotherapy

Malignancy, tumor lysis syndrome

Am Fam Physician. 2012 Oct 1;86(7):631-639.

Tests and AKI Tests to Order When to order conditions

Eosinophiluria Fever and rash, new med exposure

Allergic interstitial nephritis

Evidence of hemolysis (schistocytes on peripheral smear, decreased haptoglobin level, elevated ind bilirubin level, elevated LDH)

Fever, anemia, thrombocytopenia, neurologic signs

HUS, TTP, SLE or autoimmune dz

Hydronephrosis on renal ultrasonography

Obstruction Malignancy, prostate hypertrophy, uterine fibroids, nephrolithiasis, ureterolithiasis

Increased anion gap with increased osmolar gap

Suspected poisoning, unresponsive patient

Ethylene glycol or methanol poisoning

Low complement level Suspected acute glomerulonephritis

Systemic lupus erythematosus, endocarditis, postinfectious glomerulonephritis

Am Fam Physician. 2012 Oct 1;86(7):631-639.

Tests and AKI

Tests to Order When to order conditions

Monoclonal spike on serum protein electrophoresis

Anemia, proteinuria, acute kidney injury in older patients

Multiple myeloma

Positive antinuclear antibody, double-stranded DNA antibody

Proteinuria, skin rash, arthritis Autoimmune diseases, systemic lupus erythematosus

Positive blood cultures Intravenous drug use, recent Endocarditis

Am Fam Physician. 2012 Oct 1;86(7):631-639.

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Treatment of AKI

• Require identification of etiology and pathogenesis

• Emergency ( HyperK, Acidosis, Pericarditis)

• Specialist referral

• Hospital referral

Patient WM • Referred for abnormal

creatinine -2.7mg/dl in 07/2011

• c/o fatigue, tired, low energy

• 10/2010- Normal creatinine

• He denied the use of NSAIDs. During 10-2010 to 7/2011, he was on lisinopril 20mg/d, sulfazalazine 1g, omeprazole , Doxazosin 2mg, glucosamine, Vit C 500mg/d, Fosamax 70mg/wk.

• GI, Hematology – Not etiology of his problem • BP 137/77

1) Travatan Z - 0.004 % QD 2) simvastatin - 40 mg QD 3) lisinopril - 10 mg QD 4) Fosamax - 70 mg Q WEEK 07/15/2011

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Patient FK 1) lisinopril - 40 mg 1 QD 2) albuterol – 3) Advair Diskus - 500 mcg-50 mcg 1 PUFF BID 4) Cymbalta - 60 mg 1 QD 5) lactulose - 10 g/15 mL 1 OZ QD 6) Vitamin C - 1000 mg 2QD 7) Jentadueto - 2.5 mg-1000 mg 1 QD 08/28/2012 8) Atenolol - 50 mg 1 QD 9) metolazone - 10 mg AS 10) Avodart - 0.5 mg 1 QD 11) Senna - 15 mg 12) vitamin A - 10000 units 1 QD 13) Vitamin D3 - 2000 intl units 1 QD 14) ferrous sulfate - 324 mg 1 QD 15) furosemide - 20 mg 1/2 tab Q AM 16) CeleBREX - 200 mg 1 QD 17) glyBURIDE - 2.5 mg 1 QD 18) traMADol - 50 mg 1 tiD 19) meprazole - 20 mg 1 QD 20) hydrochlorothiazide - 25 mg 1 QD 21) aspirin - 81 mg 1 QD 22) lovastatin - 40 mg 1 BID 23) Flomax - 0.4 mg 1 Q HS 24) MetFORMIN - 1000 mg 1 BID 25) AmLODIPine - 5 mg 1 QD 26) Terazosin - 10 mg 1 QD

Ordering Provider

Barrantes-Ramire, Thelmo Fid

Collect Date & Time Date of Service

10/13/2012 8:30 am 10/13/2012 9:27 am FINAL

Status Signed

12287613184

Req. Number

Diagnostic Test / Results Results Out of Range Flag Units Range Site Stat

fidelb

10/15/2012

RENAL FUNCTION PANEL [Final]

Notes Patient Fasting? YesPatient Fasting? Yes

Patient Fasting? Yes

Glucose 60-99mg/dL FH131 WEST

Blood Urea Nitrogen 6-29mg/dL FN WEST15

Creatinine 0.70-1.40mg/dL FN WEST1.15

eGFR Male FWEST>=60

\RRGFR2GFR CLASSIFICATION eGFR (mL/min/1.73m2)

\RRGFR2Moderately decreased GFR 30 - 59

\RRGFR2Severley decreased GFR 15 - 29

\RRGFR2Kidney Failure <15 or receiving dialysis

\RRGFR2The creatinine method is correlated to the isotope dilution mass

\RRGFR2spectrometry (IDMS). Standardization of method calibration, as

\RRGFR2recommended by the National Kidney Disease Education Program, will

\RRGFR2reduce the interlaboratory bias in results and yield more accurate

\RRGFR2estimated glomerular filtration rates (eGFR) using the IDMS-traceable

\RRGFR2MDRD Study Equation. The GFR calculation has been revised to include

\RRGFR2this NKDEP standardization. Values are age and gender dependent.

\RRGFR2Note: eGFR calculated assuming the patient is non-African American. If

\RRGFR2patient is African American, multiply the eGFR by 1.21

Sodium 136-145mmol/L FN WEST139

Potassium 3.5-5.1mmol/L FN WEST4.5

Chloride 98-109mmol/L FN WEST102

Carbon Dioxide 21-32mmol/L FH34 WEST

Anion Gap 7-16mmol/L FL3 WEST

Calcium 8.5-10.1mg/dL FN WEST9.0

Albumin 3.4-5.0g/dL FN WEST3.7

Phosphorus 2.5-4.9mg/dL FN WEST3.8

Tests Performed at Labs / Sites

2.2 e-Medsys - EHR 8.0.18.d 1Lab/HL7 Version 3/26/2016 9:14:18PM Page:Date:

525786698HL7 Patient: JARAMILLO, FRANK R 09/30/1938DOB: SSN: Client:

Patient MF

• 65 yo woman with Progressive renal renal dysfunction, difficult to treat HTN and skin changes ( tight skin)

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Ordering Provider

Barrantes-Ramirez, Thelmo Fidel

Collect Date & Time Date of Service

2/25/2016 12:51 pm 2/25/2016 1:28 pm FINAL

Status Signed

163200

Req. Number

Diagnostic Test / Results Results Out of Range Flag Units Range Site Stat

fidelb

03/01/2016

Renal Function Panel [Final]

Sodium 134-144mmol/L FX139

Potassium 3.5-5.1mmol/L FX4.6

Chloride 98-111mmol/L FX103

CO2 20-30mmol/L FX23

Anion Gap 6-14 FX13

Glucose 60-100mg/dL FX94

BUN 7-31mg/dL FX14

Creatinine 0.50-1.40mg/dL FX1.04

eGFR non-African Am >60mL/Min/1.73M2 FL53 X

GFR Comment FXEstimated GFR values are not

accurate in acute kidney failure,

inpatients on IV

fluids, obese (BMI>34) or underweight (BMI<20) people,

the very old or very young, races other than Caucasian, people with acute

illnesses, or amputations.

Calcium 8.4-10.4mg/dL FX9.6

Phosphorus 2.3-5.6mg/dL FX4.0

Albumin 3.4-4.7gm/dL FX4.3

Tricore Reference Laboratories

1001 Woodward Pl NE, Albuquerque, NM 87102

Tests Performed at Labs / Sites

2.2 e-Medsys - EHR 8.0.18.d 1Lab/HL7 Version 3/26/2016 9:39:14PM Page:Date:

103387170HL7 Patient: FOLINO, MARY ANN 09/21/1946DOB: SSN: Client: Acute Kidney and ACEI, ARB, Aldosterone

Antagonists

Pearls • -How old my pt? • -What comorbidities does the pt

have? • -Target BP? • -Is the patient taking ACEI and /or

ARB? • -Is the patient taking ACEI/ARB and

aldosterone ant? • Did creatinine has changed after

ACEI, ARB or aldosterone ant started. Increment 25-30% is tolerable.

Acute Kidney Injury by PPI

• Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications

• 25% and 70% of these prescriptions do not have an appropriate indication.

• In 1992, a sentinel case report idenfied the possible association of Omeprazole and AIN ( Acute interstitial Nephritis)

• Multiples studies have shown the association of PPI with AKI, CKD and hypomagnesium

Pearls: • Always ask does my patient need

PPI? • Can I try non medication approach

for GERD? • Can I substitute for an H2 blocker? • Has the creatinine changed after

PPI was started?

CMAJ. 2015 Apr-Jun; 3(2): E166–E171.

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Acute Kidney Injury by NSAIDs

• NSAID-induced hemodynamic injury: NSAIDs are inhibitors of prostaglandin synthesis. NSAIDS and ACEI, ARB

• NSAID-induced acute interstitial nephritis (AIN): These patients present with the classic findings of AIN: sterile pyuria, WBC casts, and eosinophils in the urine or blood.

• NSAID-induced nephrotic syndrome: this may take the form of either minimal change disease, or membranous nephropathy.

• Acute renal papillary necrosis

Pearls : • Does my pt need an NSAID? Can I get by

with acetaminophen and PT? rheumatology eval?, steroid injection? -How old is my patient? >65yo

• Does my patient have DM, HTN, HF? • Is my patient s using ACEI, ARB, Diuretics,

Aldosterone antagonists (aldactone)? • Has creatinine changed after NSAIDs

started? • Is the patient taking OTC NSAIDs?

Kidney Injury and Acetaminophen

• Acetaminophen induced ATN-Reported with very high doses

• Analgesic nephropathy-cause chronic interstitial nephritis

• Metabolic gap acidosis secondary to 5-Oxoproline accumulation

Pearls:

• Ask about pain med use

• How many pills/day? How long?

• Can other interventions be made to reduce acetaminophen use?

Kidney Injury and Bactrim

• TMP inhibits proximal tubular secretion of creatinine

• Can cause interstitial nephritis

• Hyperkalemia

• Aso cause crystal nephropathy

• Dangerous when used in older with NSAIDs and ACEI or ARB

Pearls:

• Does the pt need an antibiotic?

• What is the the GFR, K?

• Is patient taking NSAIDs, ACEI or ARB?

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AKI and Synthetic Cannabinoids

Pearls:

• CDC is reporting increasing frequency of synthetic cannabinoids and AKI

• Case reports: Oxalate nephropathy, AIN , ATI

• Unexplained AKI in the young

AKI and Oxalate: Oxalate Nephropathy

Pearls:

• Post Bypass Metabolic surgery

• High doses of Vitamin C

• Rhubarb

• Start fruit

Adverse Kidney and Metabolic Effects Associated with Oral Sodium Phosphate Bowel Preparation

Absolute contraindications

-Estimated glomerular filtration rate <60 ml/min -Significant kidney disease with preserved GFR (e.g.,

nephrotic syndrome)

-Preexisting hyperphosphatemia of any cause

-Clinically significant congestive heart failure or

cardiomyopathy -Clinically significant cirrhosis and/or ascites

-Hypersensitivity to the ingredients

Relative contraindications

-Age <18 or >60 to 70 or clinically significant debilitation

-Use of diuretics, angiotensin-converting enzyme inhibitors,

angiotensin receptor blockers, or nonsteroidal anti-

inflammatory drugs, especially if in combination

-Dehydration or risk for dehydration (e.g., nausea, vomiting, diarrhea, low salt diet, inability to take adequate oral fluids).

-Uncorrected electrolyte abnormalities

-Pregnancy or nursing a child, as per package labeling.

Heher et al, CJASN 2008

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AKI and Obstruction: Normal or increased urine flow does not rule out obstruction

-Symptom onset can be acute ( Nephrolithiasis) or chronic (BPH, Prostate Ca) -Older Male patients -Urinary symptoms-frequency, decreased stream, nocturia, hematuria , post void dribbling) . -Pelvic mass-Cervical Ca -Diabetic with neuropathy -Retroperitoneal fibrosis

Pearl: Renal US with PVR is the most useful test to dx Urinary tract obstruction

AKI and Malignancy

• Pre renal- Volume depletion

• Renal- Cancer infiltration, drug side effects, tumor lysis syndrome (rhabdo)

• Post renal- Blockage

Drugs:

Iodinated Contrast

Pamidronate

Gemcitibine

Cisplatin

Methotrexate

Bevacizumab

Interferon-α

Ifosphamide

Contrast media

Strategies to prevent AKI

• Avoid nephrotoxic meds if possible • Revise OTC meds list ( vitamin C, NSAIDs, etc) • Be familiar the renal side effects of newer drugs (i.e Invokana) • Dose meds for appropriate GFR • Avoid dangerous combinations ( ACEI and ARB, ACEI/ARB and

aldosterone/eplerenone, ACEI/ARB and NSAIDs, ACEI/ARB and Bactrim, Bactrim and NSAIDs, etc)

• Maintain hemodynamics ( BP 120-140/70-90mmhg) • Avoid iodinated IV contrast when possible or use measures to decrease

risk of contrast induced nephropathy • Liver patients- recognize ascites, refer to specialists • Heart patients- master volume status exam

Am Fam Physician. 2012 Oct 1;86(7):631-639.

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Conclusions

• Evaluate creatinine trend

• Thorough History and PE

• Assess rise of creatinine in the setting of patient history ( HF, cirrhosis) .

• Ask About OTC

• Is this pre renal, renal or post renal?

• Do I need to refer to Hospital? Call Nephrologist? Or can I manage it?

• Repeat Labs in 1-2 weeks

• Look at the med list several time, what need to be changed/removed?

• Re-dose meds to kidney function level?

• Ask for pharmacist help when in doubt