Renal Questions

Overview of the Urinary Tract

• The flow of urine is kidneys, to the ureter, to the bladder, and out the urethra
• The urinary tract maintains fluid balance and filters toxic substances from blood
• The ureters use smooth muscle contractions to propel urine
• The bladder can hold between 500cc-1L of urine

Urinary Bladder

• The detrusor muscle contracts during micturition and is controlled by the parasympathetic nervous system
• The internal urethral sphincter provides constriction to prevent urinary leakage and is controlled by the sympathetic nervous system

Urethra

• In men, the urethra can be compressed by benign prostatic hyperplasia (BPH)

Kidney Functions

• Kidneys are composed of nephrons, which are the functional units
• Production of urine
• Excretion of waste products
• Regulation of electrolytes, serum osmolality, and acid-base balance
• Hormone production and secretion including EPO, renin, calcitriol, and prostaglandins

The Nephron

• The nephron is the functional unit made of the renal corpuscle and renal tubule, and approximately 1 million exist in each kidney
• The renal corpuscle filters fluid from the blood to create an ultrafiltrate
• The glomerulus is a tuft of capillaries making up the vascular pole
• The Bowman capsule makes up the urinary pole
• The Bowman space is continuous with the renal tubule
• The Bowman capsule is separated from the capillaries by the glomerular filtration barrier, which consists of a fenestrated endothelium, GBM, and podocyte layers

Glomerular Filtration Barrier (GFB)

• Water, electrolytes, and small molecules can cross the GFB
• Cells and large or negatively charged molecules cannot cross the GFB
• The renal tubule resorbs and secretes substances from the ultrafiltrate

Renal Tubule Process

• Afferent arteriole regulates blood flow
• The proximal convoluted tubule (PCT) resorbs most ultrafiltrate including glucose (via SGLT2), amino acids, sodium, and phosphate
• Thin descending loop of Henle is impermeable to Sodium, increasing concentration for passive reabsorption of water
• Thick ascending loop of Henle is impermeable to water, decreasing concentration for passive reabsorption of Sodium and Potassium; loop diuretics
• Distal convoluted tubule resorbs ions including sodium; thiazide diuretics
• Collecting duct resorbs Sodium, secretes Hydrogen, and resorbs water via ADH (vasopressin)
• ACE inhibitors block Angiotensin II synthesis in the efferent arteriole
• ARBs block Angiotensin II receptors, inhibiting constriction of efferent arterioles, which leads to decreased glomerular filtration rate (GFR)

Hormone Synthesis

• Erythropoietin (EPO) stimulates red blood cell proliferation in bone marrow
• EPO binds to receptors of RBC precursor cells and is triggered by anemia and hypoxia
• Reduced EPO in CKD causes anemia
• Calciferol is produced by PCT cells
• PCT cells facilitates conversion of vitamin D3 from inactive to active form or calcitriol via 1-alpha hydroxylase; increases Calcium absorption in the small bowel
• Prostaglandins vasodilate afferent arterioles to increase renal blood flow
• NSAIDs block prostaglandins and cause afferent arterioles to constrict and decrease GFR
• Low doses of dopamine increase renal blood flow by dilating afferent/efferent arterioles
• High doses of dopamine acts as a vasoconstrictor

Renin Production

• Reninconverts angiotensinogen to angiotensin I, which is then converted to angiotensin II, by angiotensin converting enzyme (ACE).
• Angiotensin II vasoconstricts and increases secretion of aldosterone, which increases reabsorption of sodium and water.

Diagnostics of Renal Function

• Renal function and kidney flow rate
• Includes glomerular filtration rate (GFR) and creatinine clearance
• Urinalysis
• Includes urine dipstick and urine sediment
• Changes in micturition
• Includes dysuria, nocturia, polyuria, and oliguria
• Changes in urine
• Includes proteinuria, bacteriuria, and hematuria

Glomerular Filtration Rate (GFR)

• GFR is the volume of urine filtered by the kidneys over a period of time per body surface area
• Normal GFR is > 90 ml/min/1.73m2
• GFR helps estimate kidney function and stage CKD
• Creatinine clearance is an indirect indicator of renal function and measures the rate of renal clearance of creatinine
• Creatinine is produced in muscle at a constant rate and entirely removed by filtration without reabsorption
• Creatinine clearance is used to calculate GFR
• Direct calculation of creatinine in urine uses the Cockroft-Gault equation
• Trend serum creatinine which is normally ~1.0

Urinalysis (UA)

• Assesses urine color and turbidity, where cloudiness indicates infection
• Urine dipstick is used for quick screening of pH, blood, proteinuria, glucosuria, ketonuria, leukocyte esterase, and nitrite
• Urine microscopy provides more detailed information and requires urine to be centrifuged and looked at under a microscope for cells (WBCs and RBCs), casts, crystals, and culture

Urine Dipstick

• Ketonuria indicates DKA, DM1 complication
• Leukocyte esterase (an enzyme produced by WBC)
• Nitrite is formed by gram-negative (GN) bacteria

Urine Microscopy

• Cells present indicate WBCs and RBCs
• WBCS indicate infection
• RBCs indicate hematuria
• Casts are tubular structures indicative of renal tubule or glomerular disease
• Crystals are the result of urinary calculi, calcium, ammonium, uric acid, and cystine
• Provides bacterial or yeast culture indication

Urinary Casts

• Hyaline casts are common and indicate dehydration or CKD
• Granular casts that are muddy brown indicate degenerated cells and acute tubular necrosis (ATN)
• RBC casts indicate accumulated RBCs, Glomerulonephritis, and hypertensive emergency
• WBC casts indicate accumulated WBCs indicative of infection, cystitis, and pyelonephritis

Changes in Urination

• Dysuria indicates pain or discomfort, lower UTI (urinary tract infection)
• Nocturia indicates waking up to urinate, CHF, and bladder outlet obstruction due to enlarged prostate
• Polyuria indicates lots of urine (>3L/day), diabetes mellitus, and diabetes insipidus
• Oliguria/anuria indicates decreased or no urine output, AKI, shock, and obstruction

Changes in Urine

• Ketonuria indicates ketones in the urine from diabetic ketoacidosis (DKA), starvation ketoacidosis, and alcohol ketoacidosis
• Proteinuria indicates >150mg/day, DM+HTNsive kidney disease, and glomerulonephritis
• Bacteriuria needs >100,000 units to be significant for a UTI
• Pyuria indicates WBCs in urine due to UTI, glomerulonephritis, and acute tubulointerstitial nephritis (AIN)
• Hematuria indicates RBCs in the urine due to UTI, kidney stones, BPH, and glomerulonephritis

Acute Kidney Injury (AKI)

• AKI is a sudden loss of renal function with rise in serum creatinine
• AKI causes can be pre-renal, intrinsic, or post-renal
• Most common cause of AKI: Pre-renal which is decreased perfusion
• Intrinsic is direct damage to the kidneys
• Post-renal is obstruction
• Diagnosed by increase in Creatinine and/or decrease in urine output
• Clinically asymptomatic along with a decrease in urine output

Etiology breakdown for AKI

• Pre-renal most common: 60% of AKI, caused by hypovolemia and/or hypotension
• Hypovolemia is caused by GI losses, diuretics
• Hypotension is caused by sepsis
• Intrinsic occurs 35% of the time, and is damage to the vascular/tubular component of the nephron itself
• Acute tubular necrosis (ATN) is 85% of intrinsic AKIs, due to ischemia or nephrotoxic agents
• Acute interstitial nephritis (AIN) is the inflammation of renal interstitium, and causes decline in renal function over days to weeks
• Glomerulonephritis

Postrenal

• Accounts for 5% of AKI cases by outflow obstruction causes increased pressure in renal tubules causing decreased GFR
• Due to BPH, B/l stones, and acute urinary retention

Approach to Diagnosing

• Determine if Creatinine is higher than baseline
• Determine most likely mechanism based on patient background and physical exam
• Obtain creatinine, electrolyte, CBC, and UA study
• If history/physical seems to fit, consider a trial of fluids and look for Creatinine (Cr) improvement
• Perform a bladder and renal ultrasound to rule out post-renal AKI

Approaches for Care

• Prerenal: Increase fluid intake if history suggests dehydration or hypotension
• Postrenal: Relieve urinary obstruction; placement of foley catheter
• Intrinsic: Hold nephrotoxic agents, Nephrology consultation and supportive care while monitoring Creatinine and Urine Output (UOP)

Chronic Kidney Disease (CKD)

• CKD is a permanent decline in renal function over >3 months
• About 37 million Americans (15%) have CKD; 726,000 have end-stage CKD (CKD 5 requiring dialysis)
• Etiology breakdown is Diabetic nephropathy, Hypertensive nephropathy, Glomerulonephritis, Other
• Diabetic Nephropathy ~47%
• Hypertensive Nephropathy ~28%
• Glomerulonephritis ~7%
• Other ~15% including polycystic kidney disease, NSAID overuse, amyloid

CKD Clinical Features

• Often asymptomatic until later stages due to exceptional compensatory mechanisms of kidneys
• Sodium/water retention causes hypertension, volume overload, and CHF
• Uremia results in accumulation of toxic substances that causes many symptoms

Uremia

• Causes fatigue, N/V, pruritus, uremic pericarditis, pleuritic chest pain), uremic encephalopathy (somnolence, coma), uremic coagulopathy (platelet dysfunction)

CKD Treatment

• Suspect CKD/ESRD with uptrending Creatinine
• Refer to Nephrology to determine when dialysis is necessary in non-acute settings
• Prescribe renally-dosed medications
• Optimize ASCVD risk with BP <130/80 and statins

Renal Replacement Therapy (Dialysis)

• It can be administered acutely or chronically (ESRD)
• Indications for dialysis (“AEIOU"): Acidosis, Electrolyte abnormality, Intoxication, Overload, Uremia
• Acidosis which has a metabolic pH <7.0
• Electrolyte abnormalites which includes refractory hyperkalemia and hypercalcemia
• Intoxication from lithium, metformin, ethylene glycol
• Overload characterized by refractory volume overload
• Uremia that affects a patient via encephalopathy, neuropathy, and/or pericarditis
• Uses diffusion to remove solutes from blood across a semipermeable membrane
• Hemodialysis uses a central venous catheter or AV fistula
• Four-hour sessions are performed 3x/week at Fresenius or DaVita

AV Fistula

• Anastomosis created by connecting an artery and a vein to pull arterial blood into the dialyzer, then pushes clean blood back into the vein
• Usually takes 4-6 weeks to mature

Diabetic Kidney Disease

• Chronic hyperglycemia damages the kidneys, which worsens GFR
• Occurs in up to 40% of adults with diabetes
• Major cause of ESRD
• Affects patients with type 1 and type 2

DM1 and DM2 on kidneys

• Type 1 DM: Nephropathy occurs 10 years after diagnosis
• Type 2 DM: Nephropathy may be present at time of diagnosis

Pathophysiology

• Glycation of the basement membrane as a result of chronic hyperglycemia
• Increased permeability & thickening of the basement membrane causes stiffness of the efferent arteriole, hyperfiltration, progressive glomerular hypertrophy and scarring, and worsening filtration

Diabetic Kidney Disease Treatment

• A1c <7-8
• BP <130/80
• Albuminuria independently predicts mortality and CKD progression.

Glomerular Disease

• Damage to the glomeruli which results in disruption to the glomerular filtration barrier (fenestrated endothelium, basement membrane, podocytes) can lead to nephritic or nephrotic syndrome

Nephrotic

• Damage to podocytes; massive proteinuria, generalized edema (hypoalbuminuria), with hyperlipidemia and fatty casts

Nephritic

• immune-mediated inflammatory damage to basement membrane results in hematuria
• RBC casts
• Decreased GFR
• Oliguria
• Increased renin and hypertension
• Can lead to acute or chronic kidney disease

Nephrotic Syndrome Examples

• Diabetic glomerulonephropathy is the most common cause defined by nodular glomerulosclerosis (Kimmelstiel-Wilson Lesions)

Other nephrotic diseases to be aware of

• Focal Segmental Glomerulosclerosis (FSGS): idiopathic or 2/2 HIV, sickle cell, obesity, effacement of podocytes
• Membranous nephropathy: 2/2 Phospholipase A2 receptor or NSAIDs, infections, immune complex deposition “Spike and dome” appearance

Nephrotic Syndrome Management

• sodium restriction, fluid restriction, diuretics, ACEI/ARB, statin, prophylactic anticoagulation (10-40% VTE risk 2/2 loss of coag proteins)

Nephritic Syndrome examples

• Rapidly progressive glomerulonephritis (RPGN) results in rapid rise in BUN/Cr, and decreased Urine output weeks after onset
• Anti-GBM Disease (Goodpasture dz) is caused by autoantibodies against renal and pulmonary capillary basement membranes
• IgG deposition can be viewed via renal biopsy
• IgA Nephropathy (Berger dz): peak 20s-30s patients and forms immune complexes and deposit in renal from upper respiratory or GI infection

IgA Nephropathy/ Berger's Treatment

• Management relies on steroids, plasmapheresis, and immunosuppressants

Acid-Base Disorders

• Acidosis is an elevated hydrogen (H+) concentration
• Alkalosis is a decreased hydrogen (H+) concentration
• pH measures acidity/alkalinity and normal values are 7.35-7.45, obtained through a blood gas (ABG/VBG)
• pH < 7.35 indicates acidemia
• pH > 7.45 indicates alkalemia

Types of Acid/Base Disorders

• Respiratory Acidosis: pCO2 > 44mm Hg, caused by hypoventilation, increased CO2, decreased respiratory rate, oversedation, inability to expel CO2, and COPD exacerbation.
• Metabolic Acidosis: HCO3 < 20 mEq/L
• Respiratory Alkalosis: CO2 < 36 mm Hg, caused by hyperventilation, decreased CO2, anxiety, pulmonary embolism.
• Metabolic Alkalosis: HCO3 > 28 mEq/L, caused by vomiting, diuretics, laxatives
• Lungs and Kidneys work together to balance pH and compensate for each other
• Respiratory compensation occurs in hours, while renal compensation occurs over 2-3 days

Intravenous Fluid Therapy (IVF)

• Crystalloids include Normal Saline or Lactated Ringers, and free water (D5W)
• Colloids: albumin and blood products
• Crystalloids are the most commonly used fluids
• Isotonic solutions such as Normal Saline (NS) and Lactated Ringer's (LR) are for fluid resuscitation and maintenance fluids
• Hypotonic solutions such as 1/2 NS and Dextrose in water help correct free water deficit (hypernatremia), hypoglycemia, and maintenance fluids
• Hypertonic solutions such as 3% saline treat severe hyponatremia

Ordering IV Fluids

• Fluid choice should depend on resuscitation or maintenance
• Resuscitation rate: bolus (500cc-1L at a time; if h/o CHF or elderly, 250-500cc) over 15-30 mins
• Maintenance rate: only if effectively NPO; 2 cc/kg/hr (100-150cc/hr)
• Always add a stop time to the administration
• Add dextrose if there is a risk for hypoglycemia or maintenance fluids
• Can add 20 or 40mEq KCl

IVF Tips

• For extended periods of isotonic fluid, use LR over NS
• NS can cause hyperchloremic metabolic acidosis
• LR contains small amounts of potassium and lactate
• Watch for fluid overload in elderly patients with a history of CHF and CKD
• Monitor for signs of hypovolemia (fluid deficit): tachycardia, low blood pressure, cool extremities, low urine output (oliguria), and acute kidney injury (with BUN/Cr ratio >20:1)

Sodium Disorders

• Sodium is the most important osmotically active particle in the extracellular space, closely linked to the body’s fluid balance
• Sodium disorders are the most common electrolyte disorder, occurring up to 30% of hospitalized patients
• Normal serum sodium is 135-145
• Always correct sodium for hyperglycemia using MDCalc
• Hyponatremia is when Na < 135
• With severe hyponatremia, Na < 125, symptoms include nausea, confusion, coma, and seizures
• Hyponatremia Etiology: hypovolemia, CHF, and psychogenic polydipsia
• Hyponatremia Treatment: treat the underlying cause, trial IVF if hypovolemia is likely
• Hypernatremia is when Na > 145
• With severe hypernatremia, Na > 165, symptoms include irritability and coma
• Hypernatremia Etiology: caused by inadequate fluid intake or diabetes insipidus
• Hypernatremia Treatment: D5W or free water intake (water, gatorade, juices, soda)

Potassium Disorders

• Characterized by muscle cramps, weakness, arrhythmias, U waves, and flattened Tw
• In order to raise K from 2.4 to 3.0, you’d need 60mEq KCI
• Replenish magnensium; K+ will fail to correct if Mg is low
• Hyperkalemia is a potentially life-threatening disorder
• Usually when severe (>6.0), muscle cramps/weakness, paresthesia, wide QRS and peaked T waves, conduction delay (CHB, sinus arrest), arrhythmia (>8.0; VT/VF, asystole)
• Main Etiology: AKI or rhabdomyolysis

Calcium Disorders

• Hypercalcemia is high serum Ca levels (>10.5; severe >14)
• The symptoms include stones (nephrolithiasis), bones (arthralgias), thrones (polyuria), groans (constipation, abdominal pain), psychiatric overtones (anxiety, depression, fatigue), and cardiac arrhythmia (QTc shortening)
• The etiology is often a sign of dehydration; primary hyperparathyroidism, malignancy (~90%)
• Hypocalcemia is low serum Ca levels (<8.5; severe <7.5)
• Consists of tetany (increased neuromuscular excitability), paresthesias (“pins and needles"), twitching of facial mm after tapping facial nerve (Chovstek sign), hand spasms with BP cuff (Trousseau sign), seizures, QTc prolongation,
• Correct hypomagnesemia

Magnesium Disorders

• Hypomagnesemia can causes hypokalemia and hypocalcemia
• Common effect is EKG changes (Mg <0.5; QTc prolongation, VT/Torsades de pointes)
• Hypermagnesemia can be identified by decreased reflexes, lethargy, bradycardia, hypotension
• Renal insufficiency is a common etology

Phosphate Disorders

• Hypophosphatemia is when < 3.0 mg/dL
• Hyperphosphatemia is when > 4.5 mg/dL

Rhabdomyolysis

• Involves the breakdown of skeletal muscle tissue that releases intracellular contents (myoglobin, potassium, phosphate, creatinine kinase) into the blood
• Common symptoms include myalgia, generalized weakness, and darkened tea-colored urine
• Elevated serum CPK is the primary indicator
• CPK and myoglobin damages renal tubules resulting in AKI