Edward L. Barnes, MD Chief Resident Conference July 5, 2012 Acute Kidney Injury Edward L. Barnes, MD Chief Resident Conference July 5, 2012

Outline for Today Workup Pre-Renal Intrinsic Post-Renal Tubulointerstitial Disease Glomerular Disease Post-Renal 9/22/2018

Initial Work Up Attempt to define the problem What is the reason for the Acute Kidney Injury? Typically broken down into where the etiology is occurring Pre-Renal Intrinsic Disease Post-Renal 9/22/2018

Acute Kidney Injury Which situation is worse Creatinine 1.1 1.6 Creatinine 2.8  3.3 Is a Cr of 1 always normal? 80 yo woman, frail with BMI 18 25 yo man, muscular with BMI 25 9/22/2018

Serum Creatinine vs. GFR Remember this is a non-linear relationship 9/22/2018

Case #1 A 65-year-old man is admitted to the hospital because of fever and dysuria. Laboratory studies show a leukocyte count of 12,000/µL, a blood urea nitrogen level of 24 mg/dL, a serum creatinine concentration of 1.4 mg/dL, and pyuria. Empiric treatment with trimethoprim-sulfamethoxazole is started. Three days later, the pyuria and fever have resolved. The leukocyte count is 10,000/µL, blood urea nitrogen level is 24, and serum creatinine is 1.8 mg/dL. Urinalysis shows no leukocytes, casts or crystals. What are some potential causes of the increase in Cr from 1.4 to 1.8? 9/22/2018

Case #1 Which of the following is the most likely explanation for the rise in serum creatinine from 1.4 mg/dL to 1.8 mg/dL? Acute interstitial nephritis Acute pyelonephritis Acute tubular necrosis Obstructive uropathy Drug effect with reduced creatinine excretion Many medications can alter the kidney’s excretion of creatinine itself WITHOUT causing damage or decrease in kidney function. Cimetidine can do this as well. Part of defining the problem is ensuring that it’s really a problem. 9/22/2018

Case #2 What else do you want to know? A previously healthy 74-year-old man is hospitalized with cough and chest pain. On physical examination, the blood pressure is 148/92 mm Hg, heart rate is 75/min, respiration rate is 18/min, and temperature is 37.8 °C (100 °F). The left lower lung field has scattered basilar crackles. The hematocrit is 34% and leukocytosis is present. The serum creatinine concentration is 2.3 mg/dL. Urinalysis shows a pH of 6.0, 1+ proteinuria, and no hematuria or ketonuria. What else do you want to know? 9/22/2018

Case #2 Which of the following is most useful in distinguishing acute from chronic renal failure in this patient? A. A previous hematocrit B. Previous serum creatinine concentration C. Blood urea nitrogen to creatinine ratio D. Microscopic urinalysis E. Renal ultrasonography 9/22/2018

Acute Kidney Injury Step One: Define the Problem (History) Prior Creatinine Measurements All Medications, New Medications, Herbal Medications, Illicit Drug use Recent contrast exposure May have to explicitly ask about imaging Volume loss, dehydration, decreased po intake Flank Pain Hematuria, Dysuria, Anuria 9/22/2018

Acute Kidney Injury Step Two: Physical Exam Evaluate for dehydration Flank Pain Edema Tender, lower abdominal mass Rash Sinus abnormalities 9/22/2018

Acute Kidney Injury Step Three: Labs and Diagnostic Studies Urinalysis: the liquid kidney biopsy Urine “Lytes” Sodium Creatinine Urea (if on diuretics) Serum Chemistry Fractional Excretion of Na (FENa) Urine Na x Plasma Cr Urine Cr x Plasma Na Renal US allows you to evaluate for obstruction, as indicated by hydronephrosis 9/22/2018

Acute Kidney Injury Fractional Excretion of Na (FeNa) Urine Na x Plasma Cr Urine Cr x Plasma Na FeNa <1 = Pre-Renal FeNa >2 = Intrinsic FeUrea <35% = Pre-Renal FeUrea >35% = Intrinsic Disease 9/22/2018

Acute Kidney Injury Other Labs to consider: Urine Protein/Creatinine Ratio ANA, ANCA HIV, RPR Hepatitis Panel Complement Levels: C3, C4 SPEP/UPEP Hansel Stain 9/22/2018

Urinalysis red - myoglobin / hemoglobin brown - can be same as above, or ATN White - infection or chyle Green - medication induced Black - alkaptonuria Other colors - probably a metabolic disorder low - dilute ~ excess water intake or DI high - dehydrated with appropriate response or hyperosmolars (contrast, mannitol) pH- normal is acidic. alkaline ~ RTA (if acidosis is present), or infection with Ureaplasma, proteus or pseudomonas (split urease) “Pro” = albumin. no other proteins are measured on a UA. So you can have “negative protein” with multiple myeloma Glucose - threshold of serum 180 before it appears in the urine (or myeloma and faulty membrane) Ketones - DKA, alcoholism, starvation LE / Nitrites ~ infection. Negative for both of these makes a UTI fairly unlikely. LE = WBCs, so it can occur in AIN as well. Nitrites ~ ecoli, proteus, pseudomonas, klebsiella Bilirubin should never be in the urine of a healthy person. suggests liver failure / biliary obstruction Urobilinogen ~ hemolysis and hepatic necrosis (not obstruction) Too many squams? View with caution. 9/22/2018

Color Rhabdomyolysis (myoglobinuria) Alkaptonuria Alkaptonuria: Urine turns a dark brown or black color when exposed to air 9/22/2018

Color Pseudomonas Lee J. N Engl J Med 2007;357:e14. 9/22/2018

Urinalysis: Protein Only accounts for albumin You may need to test for other proteins Bence Jones protein in suspected Light Chain Disease or Multiple Myeloma 9/22/2018

Looking at the Urine 9/22/2018

Red Blood Cell Casts Looking at the Urine Indicates glomerulonephritis 9/22/2018

Dysmorphic Red Blood Cells Looking at the Urine Dysmorphic Red Blood Cells 9/22/2018

Calcium Oxalate Crystals Looking at the Urine Uric Acid Crystals Calcium Oxalate Crystals 9/22/2018

Putting it All Together 9/22/2018

Case #3 48 yo woman with PMH significant for HTN (treated with Lisinopril) presents with a chief complaint of vomiting and weakness. Baseline Cr is 0.8. Laboratory Studies are shown below: Na 140 Urine Na 7 K 3.8 Urine Cr 65 BUN 38 Cr 1.6 What type of Acute Kidney injury does this patient have? 9/22/2018

Case #3 FeNa = 0.12% Pre-Renal Acute Kidney Injury 9/22/2018

Pre-Renal Acute Kidney Injury Causes: Dehydration Shock Acute Volume Loss (bleeding) Abdominal Compartment Syndrome Decompensated Heart Failure End Stage Liver Disease (Hepatorenal syndrome) Renal Artery Thrombosis Anything that decreases blood flow to the kidney 9/22/2018

Urinalysis Urinalysis should be relatively normal If patient is dehydrated, you may see Hyaline Casts Urine Sediment will otherwise be bland 9/22/2018

Treatment Correct the underlying perfusion abnormality if possible 9/22/2018

How would you treat this patient? Case #3 48 yo woman with PMH significant for HTN (treated with Lisinopril) presents with a chief complaint of vomiting and weakness. Baseline Cr is 0.8. Laboratory Studies are shown below: Na 140 Urine Na 7 K 3.8 Urine Cr 65 BUN 38 Urine Urea 135 Cr 1.6 How would you treat this patient? 9/22/2018

Pre-Renal Acute Kidney Injury 48 yo woman with PMH significant for HTN presenting with: Severe abdominal pain Guarding on exam Bladder pressure as measured by foley catheter is 34 mmHg Cr is 1.9 (baseline 0.8) Urine sediment is bland What is the diagnosis? 9/22/2018

Pre-Renal Acute Kidney Injury 48 yo woman with PMH significant for HTN presenting with: Altered mental status Hypotension Blood cultures positive for Pseudomonas aeruginosa Cr is 2.7 (baseline 0.8) Urine sediment is bland What is the etiology of the acute kidney injury? 9/22/2018

Pre-Renal Acute Kidney Injury 48 yo woman with PMH significant for HTN, cirrhosis secondary to HCV presenting with: Altered mental status Hypotension Anasarca FeNa 0% (very low), Urine Na <5 Cr is 2.7 (baseline 0.8) Urine sediment is bland What is the etiology of the acute kidney injury? 9/22/2018

How would you treat this patient? Case #4 48 yo woman with PMH significant for HTN (treated with Lisinopril and HCTZ) presents with a chief complaint of vomiting and weakness. Baseline Cr is 0.8. Laboratory Studies are shown below: Na 140 Urine Na 85 K 3.8 Urine Cr 65 BUN 38 Urine Urea 135 Cr 2.6 How would you treat this patient? 9/22/2018

Pre-Renal Acute Kidney Injury Case #4 This patient is on chronic diuretic therapy, thus you must calculate the FeUrea: Urine Urea x Plasma Cr Urine Cr x Plasma Urea FeUrea= 14.21% Pre-Renal Acute Kidney Injury 9/22/2018

What is the etiology of this patient’s Acute Kidney Injury? Case #5 48 yo woman with PMH significant for HTN (treated with Lisinopril and HCTZ) presents with a chief complaint of vomiting and weakness. Baseline Cr is 0.8. Laboratory Studies are shown below: Na 140 Urine Na 65 K 3.8 Urine Cr 45 BUN 38 Urine Urea 265 Cr 2.5 What is the etiology of this patient’s Acute Kidney Injury? 9/22/2018

Intrinsic Acute Kidney Injury Etiology of Intrinsic AKI: Acute Tubular Necrosis (ATN) Contrast Induced Nephropathy (CIN) Rhabdomyolysis (Pigment Induced Nephropathy) Acute Interstitial Nephritis (AIN) Glomerulonephritis (multiple etiologies) Cholesterol Emboli Thrombotic Microangiopathy and more… 9/22/2018

What do you want to do next? Case 23 yo man with no PMH, but was recently treated for Strep Throat presents with fatigue and overall feeling poorly. Physical Exam is normal. Cr 2.5 FeNa 2.3% What do you want to do next? 9/22/2018

Post-Streptococcal Glomerulonephritis Case Continued Post-Strep Glomerulonephritis What is your diagnosis? Post-Streptococcal Glomerulonephritis 9/22/2018

Glomerulonephritis Defined by Red Blood Cell Casts in the urine sediment Multiple etiologies of Glomerulonephritis exist, will be covered in detail elsewhere Associations to remember: Most Common: IgA Nephropathy GN + Hemoptysis: ANCA or anti-GBM (Goodpasture’s Syndrome) GN + Purpura: Think Vasculitis 9/22/2018

Case #6 54 yo man with PMH significant for HTN, Hyperlipidemia, presented to the MICU after being found down and resuscitated for approximately 20 minutes. After 3 days, patient has now been extubated and is doing well, however his Creatinine continues to rise. Creatinine on admission was 1.2, now 3.5 this morning. Cr 3.5 FeNa 3.5% 9/22/2018

What is your diagnosis? Case #6 Continued You spin his urine and find… Acute Tubular Necrosis, Muddy Brown Casts Esson ML, Shrier RW. Diagnosis and Treatment of Acute Tubular Necrosis. Ann Intern Med. 5 November 2002;137(9):744-752 9/22/2018

Acute Tubular Necrosis Risk Factors: Prolonged Hypotension Nephrotoxic Agents Classic description: “muddy brown casts” Treatment Remove inciting etiology (resuscitate, remove suspected medication) If patient improves, suspect post ATN diuresis to occur (may take up to 1-3 weeks) Some patients may progress to End Stage Renal Disease 9/22/2018

What is the suspected diagnosis? Case #7 68 yo man with PMH significant for HTN and Hyperlipidemia, admitted for a STEMI. Patient received PCI with stent to the Right Coronary Artery. Patient is doing well, but on day 3 of admission, Creatinine is noted to be elevated at 1.9. Baseline Creatinine was 0.9. No new medications other than Plavix. FeNa: 2.5% What is the suspected diagnosis? 9/22/2018

Contrast Induced Nephropathy At Risk Patients: Diabetes Mellitus Chronic Kidney Disease Occurs in approximately 3% of the population Typically occurs 24-48 hours following contrast administration Typically transient, improving over 1-3 weeks; however there is potential for progression to ESRD Prevention Hydration Hold nephrotoxic agents (NSAIDs) Treatment supportive 9/22/2018

Case #8 68 yo man with PMH significant for HTN and Hyperlipidemia, admitted for a STEMI. Patient received PCI with stent to the Right Coronary Artery. Patient is doing well, however overnight, Cr increases from baseline (0.9) to 2.1 and the patient develops a new rash. No new medications other than Plavix. 9/22/2018

Case #8 What is this “rash”? Livedo Reticularis What is the diagnosis? Cholesterol emboli syndrome Livedo Reticularis What is the diagnosis? Cholesterol Emboli Syndrome 9/22/2018

Case #9 22 yo man with no PMH presents with nausea, vomiting, and fatigue. The patient is a member of the wrestling team at UNC. Denies taking any new medications or supplements. Cr 2.9 (baseline 0.8) FeNa 2.6% Urine dipstick performed in your office indicates 3+ blood. You examine the urine, and the sediment is bland, no RBC or WBC are seen. What other labs would you want to know? What is the diagnosis? 9/22/2018

What is the next test that you want to order? Case #10 78 yo man with PMH significant for HTN, and Benign Prostatic Hypertrophy. He has been taking over the counter allergy medications. Over the past 24 hours he has developed lower abdominal pain, decreased urine output. On laboratory studies: Cr 2.3 (baseline 1.0) FeNa 2.5% Urine Sediment is bland What is the next test that you want to order? 9/22/2018

Presence of Hydronephrosis indicates post-renal Acute Kidney Injury Renal Ultrasound Presence of Hydronephrosis indicates post-renal Acute Kidney Injury 9/22/2018

Post-Renal Acute Kidney Injury Hydronephrosis and Acute Kidney Injury is an Emergency You must relieve the obstruction Foley Catheter Nephrostomy Tubes Next you must identify the cause of the obstruction 9/22/2018

The End Acute Kidney Injury Pre-Renal Intrinsic Post-Renal 9/22/2018