PANCE Blueprint Renal System (5%)

Lessons

1. PANCE Renal System Content Blueprint

2. PANRE & PANRE-LA Renal System Content Blueprint

   PANRE & PANRE-LA (NCCPA™) Renal System Blueprint Interactive Study Guide and PANRE-LA Smart Search
3. Renal Diseases (PEARLS)
4. Renal System Flashcards and Cheat Sheet

5. Brian Wallace PA-C Podcast: The Kidney

   28 mins

   Brian Wallace PA-C
6. Acid/Base Disorders (PEARLS)

   Average values "24/7 40/40"

   • 24 (HCO3, base) / 7.40 (pH) / 40 (CO2, acid)

   Respiratory Acidosis:

   • pH < 7.35, pCO2 > 45, HCO3 > 26
   • Lungs fail to excrete CO2 (Breathing too slow (holding onto CO2), pulmonary disease, neuromuscular disease, drug-induced hypoventilation - opiates, barbiturates)

   Respiratory Alkalosis:

   • pH > 7.45, pCO2 < 35, HCO3 < 22
   • Excessive elimination of CO2 (Breathing too fast (blowing of CO2), pulmonary embolism, fever, hyperthyroid, anxiety, salicylate intoxication, septicemia )

   Metabolic Acidosis

   • pH <7.35, pCO2 < 35, HCO3 < 22
   • Need to calculate anion gap: Anion Gap = Na – (Cl + HCO3-) = 10-16
   • Increased ion gap (>16): Addition of hydrogen ions (lactic acidosis (think metformin), diabetic ketoacidosis, aspirin overdose)
     •  MUDPILES:
       • Methanol
       • Uremia
       • Diabetic Ketoacidosis
       • Paraldehyde
       • Infection
       • Lactic Acidosis
       • Ethylene Glycol
       • Salicylates
   • Low anion gap (<16): Loss of bicarbonate (diarrhea, pancreatic or biliary drainage, renal tubular acidosis)

   Metabolic Alkalosis:

   • pH > 7.45, pCO2 > 45, HCO3 > 26
   • Loss of hydrogen (vomiting), bulimia, overdose of antacids, addition of bicarbonate (hyperalimentation therapy)
7. Acute Disorders (PEARLS)
   1. Glomerulonephritis (Lecture)

      Immune-mediated glomerular inflammation results in glomerular damage which results in urinary protein and RBC loss

      • Proteinuria, HTN, azotemia, oliguria (<400 ml urine/day), hematuria (RBC casts) hallmark, edema is not as much as nephrotic syndrome
      • Urinalysis: proteinuria < 3.5 grams per day, hematuria, RBC casts
      • Biopsy: hypercellular, immune complex deposition

      Etiologies of acute glomerulonephritis:

      • IgA Nephropathy (Berger disease): most common cause of acute glomerulonephritis worldwide - often affects young males within days  (24-48 hours) after URI or GI infection.
      • Postinfectious - Group A strep: 10-14 days after infection - diagnosed with ASO titers and low serum complement.
      • Membranoproliferative glomerulonephritis: due to SLE, viral hepatitis.
      • Rapidly progressive glomerulonephritis - crescent formation on biopsy due to fibrin and plasma protein deposition.
        • Goodpasture's syndrome: (+) anti-GBM antibodies, dx linear IgG deposits, treat with high dose steroids, plasmapheresis + cyclophosphamide.
        • Vasculitis: lack of immune deposits (+) ANCA antibodies.

   2. Nephrotic syndrome (ReelDx + Lecture)

      12 mins

      Glomerular damage results in increased urinary protein loss

      • Proteinuria, hypoalbuminemia, edema, hyperlipidemia, edema is predominant feature, transudative pleural effusion
      • Urinalysis: proteinuria > 3.5 grams on 24-hour urine, fatty casts, oval fat bodies
      • Biopsy: hypo-cellular minimal change disease loss of podocytes on microscopy

      The most common primary causes are:

      • Membranous nephropathy: most common in non-diabetic adults associated with malignancies.
      • Minimal change disease: 80% of nephrotic syndrome in kids. Responds to corticosteroids.
      • Focal segmental glomerulosclerosis:  obese patients, heroin, and HIV black males.

      The most common secondary causes are:

      • Lupus: both nephritic and nephrotic.
      • Diabetes: common cause of nephrotic syndrome and subsequent renal failure.
      • Preeclampsia

   3. Pyelonephritis (Lecture)

      Pyelonephritis is an infection of the renal pelvis and kidney parenchyma, typically ascending from a lower urinary tract infection.

      • Fever, chills, and flank pain are hallmark symptoms
      • Costovertebral angle tenderness (CVA)
      • May present with nausea, vomiting, and malaise
      • Dysuria, frequency, and urgency may be present if concurrent lower urinary tract infection
      • Diagnosed with urinalysis, showing pyuria, bacteriuria, and possibly white cell casts. Urine culture confirms the diagnosis and guides antibiotic therapy.
      • Common pathogens include Escherichia coli (most common), Proteus, Klebsiella, and Enterococcus
      • Treated with oral antibiotics (e.g., ciprofloxacin or trimethoprim-sulfamethoxazole) for mild cases; IV antibiotics (e.g., ceftriaxone or gentamicin) for severe cases or complicated infections
      • Imaging (e.g., ultrasound or CT scan) may be indicated in complicated cases or if abscess is suspected
8. Acute kidney injury (ReelDx + Lecture)

   Acute kidney injury (AKI) is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without a reduction in the amount of urine output.

   • Symptoms of AKI include fatigue, confusion, decreased urine output, and swelling in the legs and feet.

   Per the KDIGO Clinical Practice Guideline for Acute Kidney Injury, AKI is defined as any of the following:

   • Increase in the serum creatinine value of ≥ 0.3 mg/dL (26.52 micromol/L) in 48 hours
   • Increase in serum creatinine of ≥ 1.5 times baseline within the prior 7 days
   • Urine volume < 0.5 mL/kg/hour for 6 hours

   There are three mechanisms of acute kidney injury:

   • Prerenal: kidney hypoperfusion (50%)
   • Postrenal: urinary tract obstruction distal to the kidneys (5%)
   • Renal: direct effects on the kidneys - Glomerular (AGN), Tubular (ATN), Interstitial (AIN) (45%)

   Summary of the 3 types of renal causes of AKI 1. Acute tubular necrosis (ATN) (85%)

   • Etiology: Kidney ischemia or toxins
   • Urinalysis: Muddy brown casts. Renal tubular epithelial cells + High Urine Osmolality
   • FENa > 2%

   2. Acute Tubulointerstitial Nephritis (AIN) (10-15%)

   • Etiology: Immune-mediated response
     • Drugs: PCN, sulfa, NSAIDs, phenytoin, etc.
     • Immunologic and infectious disease: strep, SLE, CMV, Sjogren's, Sarcoidosis
   • Urinalysis: WBC casts and eosinophils

   3. Glomerulonephritis (AGN)

   • Etiology: IGA Nephropathy (Berger disease), postinfectious, membranoproliferative
   • Urinalysis: Oliguria, hematuria, and RBC casts

   Diagnosis of AKI is suspected when urine output falls or serum BUN and creatinine rise

   • Evaluation should determine the presence and type of acute renal failure and seek a cause: (prerenal (e.g., kidney hypoperfusion), renal (e.g., direct effects on the kidney), or postrenal (e.g., urinary tract obstruction distal to the kidneys)
   • Blood tests generally include CBC, BUN, creatinine, and electrolytes (including Ca and phosphate)
   • Urine tests generally include Urinary sediment (casts) and FENa
   • Postvoid residual bladder volume if postrenal cause suspected
   • ATN can be differentiated from prerenal AKI by urine indices
     • ATN (renal AKI): FENa (Fractional Excretion of Sodium is going to be GREATER than 2%), Granular and cellular casts
       • In intrinsic AKI (ATN, AIN, GN), the kidney loses its ability to retain sodium. Therefore, sodium is wasted in the urine, cannot be reabsorbed, and results in a high FENa
     • Prerenal AKI: (Fractional Excretion of Sodium is going to be Less than 1%), ↑ urine osmolality, ↑↑ BUN
       • The kidney has decreased perfusion, which results in ↑ aldosterone and NA+ retention to increase pressure. The kidney is still able to concentrate urine

   Treatment of AKI depends on the cause :

   • Immediate treatment of pulmonary edema and hyperkalemia
   • Dialysis as needed to control hyperkalemia, pulmonary edema, metabolic acidosis, and uremic symptoms
   • Adjustment of drug regimen for degree of renal dysfunction
   • Usually, restriction of water, sodium, phosphate, and potassium intake, but provision of adequate protein
   • Possibly phosphate binders (for hyperphosphatemia) and intestinal potassium binders (for hyperkalemia)
   1. Intrinsic (Renal) acute kidney injury (AKI)

      Intrinsic (Renal) AKI results from direct kidney damage, impairing filtration and renal function

      • Can be divided into FOUR major categories based on the location of the injury:
        • Acute tubular necrosis (ATN): Most common, caused by ischemia (e.g., shock) or nephrotoxins (e.g., aminoglycosides, contrast agents)
        • Acute interstitial nephritis (AIN): Immune-mediated, often from drugs (e.g., NSAIDs, antibiotics)
        • Glomerulonephritis: Immune complex deposition, linked to autoimmune diseases (e.g., lupus)
        • Vascular causes: Thrombotic microangiopathies, renal artery/vein thrombosis
      • Oliguria or anuria, edema, hypertension, symptoms of underlying cause (e.g., rash in AIN, hematuria in glomerulonephritis)
      • Urinalysis:
        • ATN: Muddy brown casts
        • AIN: WBC casts, eosinophils
        • Glomerulonephritis: RBC casts, proteinuria
      • Blood tests: Elevated BUN and creatinine, BUN:Cr ratio <15:1
      • FENa: >2% in ATN
      • Kidney biopsy: For unclear cases
      • Treat the cause: Stop nephrotoxic agents, corticosteroids for AIN or glomerulonephritis, manage ischemia or vascular issues
      • Supportive care: Optimize volume status, diuretics for fluid overload (no outcome benefit), dialysis for severe complications (e.g., hyperkalemia, acidosis, uremia)
   2. Prerenal acute kidney injury (AKI)

      Prerenal AKI is caused by reduced renal perfusion, leading to decreased glomerular filtration rate (GFR) WITHOUT direct damage to the kidney parenchyma

      • Common causes include:
        • Hypovolemia: Dehydration, hemorrhage, gastrointestinal or urinary fluid losses
        • Decreased cardiac output: Heart failure, cardiogenic shock
        • Systemic vasodilation: Sepsis, anaphylaxis
        • Renal vasoconstriction: NSAIDs, ACE inhibitors, ARBs, or severe liver failure (hepatorenal syndrome)
      • Oliguria (reduced urine output), signs of hypoperfusion (e.g., dry mucous membranes, tachycardia, hypotension), or symptoms related to the underlying cause (e.g., heart failure or sepsis)
      • Laboratory findings:
        • Elevated BUN:Cr ratio >20:1, due to increased urea reabsorption
        • Low fractional excretion of sodium (FENa <1%), indicating preserved tubular function
      • Urinalysis: Bland sediment with few or no casts
      • Response to fluids: Improvement in urine output and renal function after volume resuscitation confirms prerenal etiology
      • Management involves restoring renal perfusion, addressing the underlying cause, and preventing progression to intrinsic AKI
   3. Postrenal acute kidney injury (AKI)

      Postrenal AKI is caused by obstruction of urinary flow, leading to increased intratubular pressure, decreased glomerular filtration rate (GFR), and potential kidney damage if untreated

      • Common causes include:
        • Urethral obstruction (most common): Benign prostatic hyperplasia (BPH), prostate cancer
        • Bladder dysfunction or obstruction: Neurogenic bladder, bladder stones, or tumors
        • Ureteral obstruction: Urolithiasis, retroperitoneal fibrosis, or malignancy (e.g., cervical, colon, or bladder cancer)
        • External compression: Pelvic masses or abdominal tumors
      • Flank or lower abdominal pain, difficulty urinating, oliguria or anuria (complete obstruction), hematuria
      • Renal ultrasound: Detects hydronephrosis or bladder distension
      • CT scan: Sensitive for stones or malignancies
      • Post-void residual (PVR): Confirms urinary retention
      • Labs: Early normal BUN:Cr ratio; later stages show elevated BUN/creatinine and hyperkalemia
      • Treat by relieving obstruction via bladder catheterization (lower tract) and percutaneous nephrostomy or ureteral stent (upper tract)
      • Surgery, lithotripsy, or alpha-blockers (e.g., for BPH)
      • Watch for post-obstructive diuresis, correct fluids/electrolytes
9. Chronic kidney disease

   CKD is a progression of ongoing loss of kidney function (GFR) defined as < 60 mL/min/1.73 m² or presence of kidney damage (proteinuria, glomerulonephritis or structural damage from polycystic kidney disease) for > 3 months.

   • Measurement of GFR is the gold standard - The Cockcroft - Gault formula (requires age, body weight, and serum creatinine) or Modification of Diet in Renal Disease equation
   • Etiology: Diabetes, hypertension, glomerulonephritis
   • Findings: Fatigue, pruritus, Kussmaul respirations, asterixis (flapping tremor), muscle wasting, broad waxy casts
10. End Stage Renal Disease (ESRD)

    End-stage renal disease (ESRD) is defined as a complete loss of kidney function for more than 3 months and is the last stage of chronic kidney disease

    • Stage 5 kidney failure GFR < 15 mL/min/1.73 m2
    • Low erythropoietin levels, no reticulocyte response occurs, typically a normochromic and normocytic anemia
    • Treatment includes dialysis and kidney transplant
    • Generally, dialysis is initiated when GFR < 10–15 mL/min
    • High serum parathyroid hormone
    • Low serum calcium
    • High serum phosphate
    • High serum potassium
    • Waxy casts with very low urine flow are findings in end-stage renal disease
    • Hypertension due to salt and water retention, and increased renin in response to low GFR
    • Metabolic acidosis ↑ K+, ↑ phos, ↓ Na+, ↓ HCO3, ↓ Ca2+
    • Pericarditis is a cardiac complication that requires urgent dialysis
    • Loop diuretics are the preferred addition to the management of edema associated with hypertension due to chronic kidney disease
11. Congenital or structural renal disorders (PEARLS)
    1. Horseshoe kidney

       Horseshoe kidney, also known as renal fusion or super kidney, is a congenital disorder affecting about 1 in 500 people that is more common in men, often asymptomatic, and usually diagnosed incidentally

       • Congenital disorder affecting about 1 in 600 people, more common in men
       • Kidneys fuse together to form a horseshoe shape during development in the womb
       • Often asymptomatic, though persons affected by this condition may experience nausea, abdominal discomfort, kidney stone, and urinary tract infections
       • The prevalence of horseshoe kidneys in females with Turner syndrome is about 15%
       • Commonly diagnosed incidentally on abdominal imaging -  it can be confirmed with US, CT, MRI, or intravenous pyelogram
       • Increased risk of renal cancer
       • No treatment is required. May treat complications such as UTIs or kidney stones
    2. Hydronephrosis

       Urine outflow obstruction causes renal distention

       • Treat underlying cause

    3. Polycystic kidney disease (Lecture)

       Autosomal dominant genetic disorder presents as back and flank pain

       • Ultrasound will demonstrate many fluid-filled cysts
       • Associated with cerebral aneurysms, no cure, treatment is supportive, BP control

12. Fluid and Electrolyte Disorders (PEARLS)
    1. Dehydration

       Dehydration is caused by not drinking enough fluid or when body fluids are lost from the extracellular compartment at a rate that exceeds intake

       • Fluid can be lost from the GI tract (diarrhea, vomiting), kidneys (urinating), or skin (sweating, fever), third spacing in the abdomen (ascites), or from injured tissues (burns)
       • Mild volume depletion can cause increased heart rate, fatigue, and muscle cramps
       • Moderate fluid loss causes dizziness and hypotension when standing
       • Severe hypovolemia results in general hypotension, signs of ischemia and shock, and lethargy and confusion
       • On physical exam look for a delayed capillary refill, dry mucous membranes, and elevated pulse rate
       • Hematocrit and serum albumin may be increased in volume-depleted patients
         • Urinary sodium decreases and urine osmolality increases 
         • Urea increases (secondary to urine stasis in the nephron), but there is little change in serum creatinine
         • Serum bicarbonate is the most useful laboratory test to assess the degree of dehydration in children
       • Treatment depends on the level of dehydration
         • Mild: oral rehydration for patients with
         • Moderate: Administering 50 mL to 100 mL of oral rehydration solutions per kilogram per body weight during two to four hours to replace the estimated fluid deficit, with additional oral rehydration solution, administered to replace ongoing losses
         • Severe Dehydration
           • Rapid restorations of fluids are required - start with 20 ml/kg boluses of normal saline
           • Multiple boluses may be needed for children in hypovolemic shock
    2. Hyperkalemia/hypokalemia (Lecture)

       Hyperkalemia

       • Definition: serum potassium of > 5-5.5 mEq/L
       • Presentation: Peaked T waves, prolonged QRS, muscle fatigue
       • Treatment: Insulin, sodium bicarbonate, and glucose (drive potassium back into the cell). Calcium gluconate (antagonize effect of potassium on heart)

       Hypokalemia

       • Definition: serum potassium of < 3.5 mEq/L
       • Presentation: Muscle cramps, constipation, flattened/inverted T waves, U waves
       • Treatment: Potassium repletion - DO NOT use dextrose-containing fluids as this will stimulate insulin release and shift potassium within the cell which worsens the hypokalemia. Replace magnesium in magnesium deficiency
    3. Hypervolemia

       Hypervolemia, also known as fluid overload, is the medical condition where there is too much fluid (plasma) in the blood

       • Hypervolemia can be caused by failure of the heart, kidney, or liver, or by a high-salt diet
       • Symptoms include weight gain, swelling, and shortness of breath
       • The cause of hypervolemia may be apparent based on patient history (e.g. CKD, CHF, Cirrhosis)
         • Urine dipstick for protein, and measure serum creatinine, serum albumin, prothrombin time, liver function tests, and TSH
         • EKG, echocardiogram, ultrasonography
         • Chest X-Ray
       • Treatment depends on the cause, dietary sodium and fluid restriction, diuretics (furosemide), dialysis (ultrafiltration)
       • Monitor urine output and daily weights, and consider Swan–Ganz catheter placement depending on the patient’s condition
    4. Hyponatremia

       Hyponatremia / Hypervolemia: serum sodium of < 135 mmol/L

       • Presentation: Muscle cramps and seizures
         • Hypervolemic hyponatremia – CHF, nephrotic syndrome, renal failure, cirrhosis
         • Euvolemic hyponatremia – SIADH (Picmonic), steroids, hypothyroid
         • Hypovolemic hyponatremia – sodium loss (renal, non-renal)
       • Serum Na should be corrected slowly—by ≤ 10 mEq/L over 24 h to avoid osmotic demyelination syndrome
13. Neoplastic Diseases of the Renal System (PEARLS)
    1. Renal cell carcinoma (Lecture)

       Classic triad of flank pain + hematuria (blood in urine) + painless abdominal/renal mass

       • Renal clear cell carcinoma is the most common type (80%)
       • Transitional cell is the second most common type (20%)
       • Smoking is the most significant risk factor
    2. Wilms tumor (ReelDx + Lecture)

       Child with painless, unilateral abdominal mass with no other signs of symptoms, also known as nephroblastoma.

14. Renal vascular disease

    Narrowing of one or both of the renal arteries, most often caused by atherosclerosis or fibromuscular dysplasia.

    • Renal Arteriography is Gold Standard for diagnosis
    • May hear a renal artery bruit on auscultation
    • Percutaneous transluminal angioplasty (PTA) plus stent placement or with surgical bypass of the stenotic segment
15. Rhabdomyolysis (Lecture)

    Rhabdomyolysis is acute skeletal muscle breakdown causing release of myoglobin, creatine kinase (CK), and potassium into the bloodstream, leading to acute kidney injury (AKI).

    • Caused by trauma, prolonged immobilization, crush injury, extreme exertion, statins, alcohol, cocaine, or heat stroke
    • Presents with a triad of muscle pain, weakness, and dark “tea-colored” urine (although this triad is present in less than 10% of patients)
    • Creatine kinase (CK) >5× normal is the key diagnostic finding
    • Urinalysis shows heme-positive urine with no RBCs (from myoglobin)
    • Leads to acute tubular necrosis due to myoglobin-induced renal toxicity
    • Electrolyte abnormalities include hyperkalemia, hyperphosphatemia, and hypocalcemia
    • Diagnosis is confirmed with markedly elevated CK and renal function testing
    • Immediate treatment is aggressive IV fluids to prevent kidney failure
    • Urine alkalinization may help reduce myoglobin nephrotoxicity
    • Dialysis is required for severe AKI or life-threatening hyperkalemia