Perelman School of Medicine at the University of Pennsylvania

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Renal Pearls

Acute Kidney Injury (AKI)

What is the definition of acute kidney injury (AKI)?

  • According to the KDIGO criteria in 2012, AKI can be diagnosed with any one of the following:
    • Creatinine increase of 0.3mg/dL in 48 hours
    • Creatinine increase to 1.5 times baseline within last 7 days
    • Urine volume < 0.5mL/kg/hour for 6 hours
  • 2012 KDIGO (Kidney Disease Improving Global Outcomes) guidelines on AKI: http://kdigo.org/home/guidelines/acute-kidney-injury/

What are the three main categories of acute kidney injury?

  • Pre-renal: related effective blood flow to the kidney
  • Intrinsic renal: damage to the kidney itself
  • Post-renal: urinary tract obstruction

What are the typical FeNa values for each type of AKI?

  • Pre-renal: <1%
  • Intrinsic renal > 2%
  • Post-renal: >4%
  • Keep in mind that pre-renal includes both total body volume depletion and also intravascular depletion while total body overloaded (thus not all pre-renal patients should get fluid)

What are the typical BUN/creatinine ratios for each type of AKI?

  • Pre-renal > 20:1
  • Intrinsic renal < 10:1
  • Post-renal or normal 10-20:1
  • Of note there is some variability of the exact cutoffs for each category

When would you use a FeUrea instead of FeNa?

  • Patients who get diuretics may have a higher urinary concentration of sodium due to the diuretic, falsely elevating the fractional excretion of sodium.
  • In these patients use a FeUrea instead since it is relatively unaffected by diuretics.
  • This is most notable in patients with CHF or cirrhosis.

What are the common causes of a pre-renal AKI?

  • Total body fluid depleted: dehydration (including poor PO intake, diarrhea, overdiuresis, insensible losses), bleeding, sepsis
  • Intravascular depletion and renal blood vessel changes: heart failure, cirrhosis, nephrotic, sepsis, renal artery stenosis, cholesterol embolism after cardiac catherization.

What are the common causes of an intrinsic renal AKI?

  • Acute tubular necrosis (includes prolonged pre-renal state, contrast nephropathy)
  • Acute interstitial nephritis
  • Rhabdomyolysis
  • Tumor lysis syndrome
  • Nephritic/nephrotic syndrome

What are some common medications that cause acute kidney injury via direct tubular effects?

  • Antibiotics: aminoglycosides, amphotericin
  • Blood pressure medications: ACEI/ARBs (though 30% creatinine rise is allowed)
  • Chemotherapeutics: cyclophosphamide, methotrexate
  • Immunosuppressants: tacrolimus, cyclosporine
  • Pain medications: NSAIDs
  • Psychiatric medications: lithium

What medications can cause acute kidney injury via acute interstitial nephritis?

  • Beta-lactam antibiotics
  • NSAIDs
  • Proton-pump inhibitors
  • Rifampin
  • Sulfa-drugs
  • Fluoroquinolones
  • Many others

For acute interstitial nephritis, what is the utility of checking for blood and urine eosinophils?

What is post-ATN diuresis?

  • During acute tubular necrosis, there is significant tubule cell damage and cell death related to an ischemic or toxic event.
  • In the maintenance phase of ATN there is a sustained severe reduction of GFR.
  • During the recovery phase, when tubular function is being restored, there can be a significant increase in urine volume (sometimes requiring fluid replenishment) as the BUN and serum creatinine return to pre-injury levels.

What are the common causes of a post-renal AKI?

  • Benign prostatic hyperplasia
  • Nephrolithiasis
  • Urinary retention or bladder outlet dysfunction
  • Obstructed urinary catheter
  • Mass (malignancy of kidney, ureter, or bladder)

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Chronic Kidney Disease (CKD) / End-Stage Renal Disease (ESRD)

How is AKI differentiated from CKD?

  • To be chronic kidney disease, kidney damage must occur for three or more months

How is CKD classified based on grade?

  • Grade 1: GFR > 90
  • Grade 2: 60-89
  • Grade 3a: 45-59
  • Grade 3b: 30-44
  • Grade 4: 15-29
  • Grade 5: < 15

How is CKD classified based on stage?

  • Stage 1: GFR > 90
  • Stage 2: 60-89
  • Stage 3: 30-59
  • Stage 4: 15-29
  • Stage 5: < 15

What are the AEIOUs of emergent dialysis indications?

  • A: acidosis
  • E: electrolytes
  • I: intoxications, ingestions
  • O: volume overload
  • U: uremia

What are some common manifestations of uremia?

  • Progressive weakness and fatigue
  • Loss of appetite with nausea/vomiting and metallic taste
  • Itching or uremic frost
  • Muscle atrophy
  • Tremors
  • Altered mental status

What is dialysis disequilibrium syndrome?

  • This occurs in patients after the start of new hemodialysis.
  • Aggressive solute removal worsens the risk of developing DDS.
  • Cause is not completely understood but current theories involve brain cells adapting to chronic high levels of urea and reverse osmosis. When dialysis begins cerebral edema may occur related to osmotic effects of high urea gradients.

What are the four main complications of CKD that require medications?

  • Hyperphosphatemia: phosphate binders
  • Hypocalcemia: calcium supplements (includes calcitriol)
  • Hyperparathyroidism: calcitriol or Vitamin D
  • Anemia: iron replacement or erythropoiesis-stimulating agents

 

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Electrolytes: Hypocalcemia

What is the formula for “corrected calcium”?

  • Corrected calcium = Serum calcium + (0.8) x (4.0 – serum albumin)

What signs and symptoms are associated with hypocalcemia?

  • Perioral numbness and tingling
  • Tetany (includes Chvostek’s sign and Trousseau’s sign)
  • Seizures
  • Long QT
  • Chvostek’s sign

What is Chvostek’s sign in hypocalcemia?

  • It is a sign of nerve hyperexcitability (tetany)
  • Tapping the cheek causes contraction of the face toward the stimulated side (includes deviation of the nasolabial fold)
  • Only 29% sensitive for hypocalcemia
  • NEJM article and video of Chvostek’s sign: https://www.ncbi.nlm.nih.gov/pubmed/22970971

What is Trousseau’s sign in hypocalcemia?

  • It is a sign of nerve hyperexcitability (tetany)
  • Inflating and maintaining blood pressure cuff  above systolic for three minutes leads to occlusion of the brachial artery
  • The wrist and MCP joints flex and the DIP/PIP joints extend
  • 94% sensitive for hypocalcemia
  • NEJM article and video of Trousseau’s sign: https://www.ncbi.nlm.nih.gov/pubmed/22970971

What are the most common causes of hypocalcemia?

  • Hypoparathyroidism
  • Vitamin D deficiency
  • Chronic kidney disease
  • Tumor lysis syndrome
  • Less commonly:
    • Nutritional deficiencies (eating disorders, vomiting) or magnesium overload
    • Hypercalcemia treatments (calcitonin, bisphosphonates)
    • Chelation therapy (EDTA)

 

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Electrolytes: Hypercalcemia

What are the most common causes of hypercalcemia?

In which ways does malignancy cause hypercalcemia?

Which malignancies are known to produce PTHrP

  • Squamous cell carcinomas (especially of the lung)
  • Breast cancer
  • Renal cell carcinoma
  • Ovarian/endometrial cancer
  • Breast cancer
  • Papillary thyroid carcinoma
  • Pancreatic cancer
  • Rhabdomyosarcoma

Which medications can cause hypercalcemia?

​​What is the definition of severe hypercalcemia?

  • When calcium >=14 or
  • When calcium >=12 with symptoms (stones, bones, abdominal moans, psychiatric overtones)

What is the formula for “corrected calcium”?

  • Corrected calcium = Serum calcium + (0.8) x (4.0 – serum albumin)

When using IV fluids to treat hypercalcemia, what is the time of onset and expected calcium decrease?

  • IV fluids: works immediately, causes 1-2mg/dL decrease in calcium

When using calcitonin to treat hypercalcemia, what is the time of onset and expected calcium decrease?

When using bisphosphonates to treat hypercalcemia, what is the time of onset and expected calcium decrease?

  • Bisphosphonates (for patients with CrCl>30): works in 2-4 days, can cause 30% decrease in calcium
  • Pooled analysis of two trials showing zoledronate was more effective than pamidronate in hypercalcemia of malignancy: https://www.ncbi.nlm.nih.gov/pubmed/11208851

Why are loop diuretics (like furosemide) no longer a standard treatment for hypercalcemia?

  • Loop diuretics theoretically cause excretion of calcium but can exacerbate tenuous renal function from volume depletion
  • Volume depletion can worsen hypercalcemia
  • Original 1970 NEJM article about using furosemide to treat hypercalcemia: https://www.ncbi.nlm.nih.gov/pubmed/5458033

 

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Electrolytes: Hypokalemia

What are the most common causes of hypokalemia?

  • Low PO intake or poor nutrition
  • GI or skin losses (diarrhea, sweating)
  • Urinary losses (diuretics, hyperaldosteronism, Cushing’s syndrome, Bartter syndrome, Gitelman’s syndrome)
  • Intracellular shifts (beta agonists, insulin, epinephrine)
  • Paper on mortality associated with hospitalized patients with hypokalemia: https://www.ncbi.nlm.nih.gov/pubmed/25107385

How does DKA (diabetic ketoacidosis) cause hypokalemia?

  • Polyuria
  • Volume contraction (holds onto Na, then sends K into urine)
  • Intracellular potassium movement after insulin treatment
  • Potassium is the cationic partner of negatively charged beta-hydroxybutyrate
  • Paper on incidence of significant hypokalemia related to DKA treatment with insulin: https://www.ncbi.nlm.nih.gov/pubmed/26970890

What signs and symptoms are seen in severe hypokalemia?

  • Muscle weakness and cramps, which can progress to flaccid paralysis
  • Tremor
  • Constipation
  • Hyporeflexia
  • Rhabdomyolysis
  • Respiratory depression from impairment of skeletal muscle function

Which EKG findings are associated with hypokalemia?

  • Flattened or inverted T waves
  • U waves
  • ST depressions
  • Wide PR intervals
  • Prolonged QT interval

Which foods can be used for potassium supplementation?

  • Oranges/orange juice
  • Bananas
  • Leafy green vegetables
  • Avocados
  • Tomatoes
  • Potatoes
  • Coconut water

 

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Electrolytes: Hyperkalemia

What are the most common causes of hyperkalemia?

  • Pseudohyperkalemia (related to phlebotomy)
  • Excessive intake (iatrogenic from potassium containing supplements)
  • Intracellular release (rhabdomyolysis, tumor lysis, hemolysis, blood transfusion, acidosis, beta blockers, low insulin levels, digoxin)
  • Reduced elimination (medications such as ACEI/ARBs/spironolactone/Bactrim/ tacrolimus/NSAIDs, hypoaldosteronism, Type IV renal tubular acidosis)

What EKG changes are associated with hyperkalemia, in order of appearance?

What are the temporary treatments for hyperkalemia?

What are the permanent elimination treatments for hyperkalemia?

In the treatment for hyperkalemia, how quickly does Insulin/D50 work?

  • Works within 30 minutes and lasts up to 6 hours

In the treatment for hyperkalemia, how quickly do beta agonists work?

  • Works within 30 minutes but needs to be 10-20mg nebulized (most nebulizers contain 2.5mg)
  • Can decrease K by up to 1.0mEq/L

 

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Electrolytes: Hyponatremia

How many mEq/L of sodium are in each of the following types of fluid?

  • Lactated Ringer’s: 130mEq/L
  • 0.9% normal saline: 154mEq/L
  • 3% hypertonic saline: 513mEq/L

What are the common causes of hyponatremia categorized by volume status?

  • Hypovolemic: low intake, vomiting/diarrhea, overdiuresis, Addison’s
  • Euvolemic: SIADH, hypothyroidism
  • Hypervolemic: cirrhosis, CHF, nephrotic
  • Other: beer potomania, primary polydipsia

Which three molecules in blood can cause pseudohyponatremia?

  • Elevated triglycerides
  • Paraproteinemia (includes immunoglobulins)
  • Hyperglycemia

What is the maximum rate of hyponatremia correction?

  • 8 mEq of sodium over 24 hours
  • Faster correction increases the risk of central pontine myelinolysis
  • May need to give vasopressin to slow the overcorrection

What are the treatments for SIADH?

  • Correct the underlying issue
  • Fluid restriction
  • Salt tablets and furosemide (Lasix)
  • Vasopressin receptor antagonists
  • Hypertonic saline
  • Expert Panel recommendations on hyponatremia treatment: https://www.ncbi.nlm.nih.gov/pubmed/17981159

Which type of lung cancer is associated with SIADH?

  • Small cell lung cancer due to ectopic creation of ADH or other tumor mechanisms that cause the pituitary to make more ADH
  • In small cell lung cancer patients, 38% had increased levels of ADH, 14% had lab-only manifestations of SIADH, and 4% had clinical symptoms associated with SIADH as seen in: http://www.ncbi.nlm.nih.gov/pubmed/1656520

 

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Electrolytes: Hypernatremia

What is the balance of free water and sodium in a hypernatremic patient?

  • Hypernatremia is generally not from sodium excess but rather a relative deficit of free water.
  • Water may be lost from sweating, insensible losses related to breathing, or urine/feces.
  • If the net balance of free water in and out leads to a deficit, the plasma sodium will rise.

What are the common causes of hyponatremia categorized by volume status?

  • Hypovolemic: low free water intake (those who can’t ask for water), urinary/diarrhea losses of water (including diuretics), osmotic diuresis (hyperglycemia)
  • Euvolemic: diabetes insipidus (central or nephrogenic)
  • Hypervolemic: following hypertonic fluid (concentrated sodium bicarbonate, ingesting seawater, salt poisoning)
  • Family Medicine paper on diagnoses and treatment of hypo- and hypernatremia: http://www.ncbi.nlm.nih.gov/pubmed/25822386

How do you calculate the free water deficit in hypernatremia?

  • Free water deficit = (0.6) x (weight in kg) x ((Na/140) – 1))

In hypernatremia, what are the two ways to give free water to a patient?

  • Oral free water: for those with nasogastric or orogastric access you can use free water flushes
  • IV fluids: D5W infusion
  • ICU paper on hypernatremia in critically ill patients: Family Medicine paper on diagnoses and treatment of hypo- and hypernatremia: http://www.ncbi.nlm.nih.gov/pubmed/25822386

Why do we worry about overcorrecting hypernatremia?

  • Rapid overcorrection of hypernatremia can lead to water entering brain cells causing swelling and cerebral edema. This can then result in seizures.

What are the acceptable correction rates of acute and chronic hypernatremia?

  • If the hypernatremia occurred rapidly (less than 24 hours) then correct it rapidly (2-3mEq/L/hour for 2-3 hours with maximum 12mEq/L/day)
  • If the hypernatremia occurred slowly (more than 48 hours) then correct it slowly (0.5mEq/L/h with total 8-10mEq/day)

 

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Hematuria

What are the two major classifications of hematuria severity?

  • Microscopic hematuria (only detectable on urine examination)
  • Macroscopic hematuria (grossly visible as red or brown urine)

How much blood does it take to cause a change in urine color?

  • 1mL of blood per liter of urine

What three situations can cause a positive urine dip for blood but negative microscopy?

  • Myoglobinuria from rhabdomyolysis
  • Semen present in the urine after ejaculation can cause a positive urine dipstick blood test
  • Alkaline urine with pH>9 or contamination with oxidizing agents to clean the perineum

If a patient presents with asymptomatic microscopic hematuria, what risk factors require evaluation for malignancy?

  • According to the American Urological Association:
    • Age > 35 years
    • Smoking
    • History of occupational exposures (especially benzenes or aromatic amines) in printers, painters, and chemical plant workers
    • History of gross hematuria
    • History of chronic cystitis or irritative voiding symptoms
    • History of pelvic irradiation
    • History of cyclophosphamide exposure
    • History of analgesics which can be associated with renal carcinoma
    • https://www.ncbi.nlm.nih.gov/pubmed/11306356

What are the most common causes of hematuria?

  • Urinary infection
  • Nephrolithiasis
  • Benign prostatic hyperplasia
  • Vigorous exercise
  • Trauma (even from bicycle saddle)
  • Cancer (renal cell, ureteral, prostate, bladder)
  • Polycystic kidney disease
  • Less commonly: Schistosomiasis (Schistosoma haematobium), prostatitis/urethritis, glomerulonephritis, AV malformations, paroxysmal nocturnal hemoglobinuria)

Which two urologic imaging modalities should be considered in both microscopic and macroscopic hematuria?

  • CT urogram
  • Cystoscopy
  • Other possibilities can include intravenous pyelogram, retrograde pyelogram, ultrasound

 

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Nephritic/Nephrotic Syndrome

What is the definition of nephritic syndrome?

  • Hematuria (especially with dysmorphic erythrocytes)
  • Proteinuria (variable but generally less than 3500mg/day)
  • Oliguria
  • Can also be associated with renal failure and hypertension.

What are the three main categories of nephritic syndrome based on immune response?

  • Anti-GBM antibodies (anti-GBM antibody disease)
  • Pauci-immune glomerulonephritis with few immune deposits (granulomatosis with polyangiitis aka Wegener granulomatosis, eosinophilic granulomatosis with polyangiotis aka Churg-Strauss syndrome, microscopic polyangiitis)
  • Immune complex deposition with low complement levels (IgA vasculitis aka Henoch-Schonlein purpura, IgA nephropathy, lupus nephritis, infection-related glomerulonephritis such as post-streptococcal, membranoproliferative glomerulonephritis, cryoglobulinemia)

Why is nephritic syndrome associated with hypertension?

  • Nephritic syndrome causes inflammatory damage to the glomerular cells
  • Reaction to this inflammation causes a decrease in kidney blood flow and decrease in urine production
  • Renin-angiotensin system gets activated due to the decreased perfusion of the kidney
  • RAAS leads to hypertension.

What is the definition of nephrotic syndrome?

  • Urine protein excretion > 3500mg/24hrs or spot urine protein/creatinine ratio of > 3500mg/g
  • Edema, hypoalbuminemia, and hyperlipidemia may also be present

What are the four most common causes of nephrotic syndrome?

  • Minimal change glomerulopathy
  • Diabetic nephropathy
  • Membranous glomerulopathy
  • Focal segmental glomerulosclerosis

Why is a patient with nephrotic syndrome prone to clots?

  • Antithrombin’s normal function is to bind to thrombin to form a thrombin-antithrombin complex which results in anticoagulation.
  • Under normal circumstances heparin enhances antithrombin III’s activity so a patient with antithrombin III deficiency and also requiring heparin may need higher doses of heparin
  • Antithrombin III may be lost in the urine

 

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Nephrolithiasis/Kidney Stones

What is the classic presentation of renal colic?

  • Excruciating pain from the flank to the groin or inner thigh
  • Intermittent pain usually 20-60 minutes at a time caused by peristaltic contractions of the ureter trying to expel the stone

Which stones can or can’t be seen on a KUB (abdominal X-ray)?

  • Calcium stones: can generally be seen on Xray
  • Cystine stones: faintly seen on Xray
  • Uric acid stones: generally not seen on Xray

In what position is a patient placed when getting a CT kidney stone protocol?

  • The CT begins with the patient laying face up (supine)
  • If a stone is detected in the ureterovesical junction or bladder, the patient lays face down during the noncontrast helical CT scan (stones in the junction will fall out of place and be more visible when proned)

What are the advantages and disadvantages of using ultrasound to look for kidney stones?

  • Advantages: less radiation, suitable for children and pregnant women
  • Disadvantages: may miss small stones (especially ureteral stones) or other serious disorders causing symptoms that a CT would find
  • 2014 NEJM paper validating ultrasound as acceptable first-line test for nephrolithiasis: https://www.ncbi.nlm.nih.gov/pubmed/25229916

What size of kidney stone would be expected to pass?

  • Kidney stone with diameter less than 5mm without significant pain

What are the nonsurgical interventions for kidney stones?

 

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Urinary Tract Infections (UTI)

Who requires asymptomatic bacteriuria treatment?

  • Only treat asymptomatic bacteriuria for the following groups:
    • Pregnancy
    • About to or recently had urologic procedure
    • Renal transplant
  • Meta-analysis of nine trials showing no reduction of symptomatic UTIs by treating asymptomatic bacteriuria (http://www.ncbi.nlm.nih.gov/pubmed?term=25851268)

What is the differential diagnosis of dysuria?

  • Urinary tract infection
  • Nephrolithiasis
  • Vaginitis (Candida, bacterial vaginosis, trichomonas)
  • Pelvic inflammatory disease
  • Urethritis (gonorrhea, Chlamydia)
  • Structural urethral abnormality (urethral diverticula, stricture)

What are the empiric treatment choices for an uncomplicated UTI?

What are the empiric treatment choices for pyelonephritis?

What are the criteria to be called a complicated UTI?

  • Complicated UTI criteria (one of the following):
    • Hospital acquired infection
    • Symptoms for 7 days before seeking care
    • Renal failure, urinary tract obstruction
    • Indwelling urinary catheter or stent or nephrostomy tube
    • Functional abnormality of urinary tract
    • Renal transplant
    • Immunosuppression
    • Pregnancy, diabetes

What are the empiric treatment choices for a complicated UTI?

  • Oral therapy: levofloxacin
  • IV therapy: cefepime (less preferably levofloxacin)

 

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