Pt Care 4: Module 7 - 9: Introduction to the Renal System, Renal Failure and Disease, Infectious Diseases of the Kidney

Module 7: Introduction to the Renal System

Module 7: Introduction to the Renal System

Lab Values

• Sodium: 135-145 mEq/L

• Potassium: 3.5-5.0 mEq/L

• Chloride: 98 - 107 mmol/L

• Bicarbonate (HC)3): 22-26 mmol/K

• PO2: 35 - 45

• Total Calcium: 8.6 - 10.3 (total or "corrected") or 1.05 - 1.3 mmol/L ionized (reflects true available calcium status)

• Magnesium: 1.5-2.8 mg/dL

• Phosphorus: 2.7 - 4.5 mg/dL

• BUN: 6-20 mg/dL

• Equivalent hydrogen concentration: 16 - 120 nEq/L

• Normal Creatinine Clearance:

- 95 +/- 20 mL/min

- 120 +/- 25 mL/min

• Creatinine:

- 0.6 - 1.0 mg/dl in women

- 0.8 - 1.3 mg/dl in men

• Serum Osmolality: 280 - 300 mOsm/kg

• Albumin: 3.5 - 5 (like potassium)

• PTH - < 600 pg/mL (with treatment, the goal is < 300 pg/mL)

What is persistent AVP release caused by?

1.) Depletion of the effective circulating volume

2.) The syndrome of inappropriate antidiuretic hormone (SIADH)

These then promote hyponatremia

What plays a more essential role in increasing water intake in hypernatremia?

Thirst does, rather than an increase in AVP

Polyuria

• Excessive production of urine

• Caused by:

1. Osmotic diuresis

2. Water diuresis (AVP production issue or response issue)

- Central diabetes insipidus: AVP production issue

- Nephrogenic diabetes insipidius: AVP response issue

▪ Chronic lithium ingestion

▪ Hypercalcemia

- Decreased AVP production

caused by excessive water intake (primary polydipsia)

How does insulin affect potassium?

It promotes the cellular uptake of K+

What does hypomagnesemia affect potassium?

It increase K+ excretion

Metabolic alkalosis causes _________ and metabolic acidosis causes _________.

hypokalemia; hyperkalemia

Would diuretics cause metabolic alkalosis or acidosis?

Alkalosis since it causes H+ loss

What is the most sensitive part of the Creatinine vs. GFR curve?

The CrCl 1.0 to 1.5 mg/dl indicates a large fall in GFR from 120 to 80 mL/min

Creatinine: 0.8 to 1.3 mg/dl in men and 0.6 to 1.0 mg/dl in women (i.e. lower muscle mass)

Uremic Symptoms

• Symptoms: Pericarditis (inflammation of the pericardium), altered mental status, peripheral neuropathy

• Inadequate potassium and sodium excretion leading to hyperkalemia and edema

• Loss of functioning nephrons also impairs hormonal function of the kidneys. This can be manifested as bone disease (due to decreased calcitriol) and anemia (due to reduced erythropoietin)

To see symptoms of renal failure

90% of the nephrons may need to be destroyed before significant functional impairment is seen clinically

What are the balanced chloride solutions?

• LR (109) and Plasmalyte (98)

• Down with the chloride

• Normal Chloride - 98 - 107 mmol/L

Complications of crystalloid therapy

• Pro-inflammatory neutrophil activation – i.e. AcuteRespiratory Distress Syndrome (ARDS)

• Dilutional Coagulopathy

- Since you dilute our clotting factors and everything else in the blood

• Interstitial fluid accumulation (pulmonary/peripheral edema/abdominal compartment syndrome)

- Fluid inside the vascular space and not inside cells

• Hyperchloremia and hypernatremia from large volume NaCl solutions leading to acidosis

Colloids

Large molecules dispersed in a solution that do not usually cross membranes due to pore size (e.g. albumin, hetastarch, dextran)

Crystalloids

Can form solutions and pass freely between semipermeable membranes (e.g. normal saline, lactated ringers)

Oncotic vs Osmotic Pressure

• Oncotic pressure – pressure gradient created by proteins (mostly albumin) aka colloids

• Osmotic pressure – force that drives water from area of low concentration to area of high concentration aka crystalloids

What is hetastarch (hespan, hextend, voluven) CI in?

Renal failure - it is a type of colloid solution containing albumin

Complications of colloid therapy

• Infection – Albumin since it is human derived

• Renal damage – Hetastarch (CI)

• Allergic reactions – Albumin since it is human derived

• Some clearance through the reticuloendothelial system – Starches and can affect our immune response

• Cost - $$

Distribution of Water in Humans

• Adults: 45 - 60%

- Young men: 60%

- Elderly men, and young women: 50%

- Elderly women: 45%

– Premature infants: 80%

– Term infant: 70 - 75%

– Children: 60%

• ICF: 2/3

• ECF: 1/3

- Vascular space: 1/4

- Interstitial: 3/4

Fluid Distribution

(See Image)

• 0.9% Saline, Lactated Ringers, Plasmalyte: 25%

• Albumin 5%, Starches (Hetastarch): 75%- 100%

• 3% Saline: 75%

• 7.5 % Saline: 200%

• Albumin 25%: 500%

• 5% Dextrose in water: 8.3%

Distribution: Dextrose 5%

• Distributes everywhere equally and is considered "free water"

• Slightly hypotonic

• Not a good choice if goal is to increase vascular volume (e.g. hypovolemic/septic shock, dehydration)

Distribution: Sodium Chloride 0.9% (NS)

• Distributes ONLY into ECF so 1/4 in vascular space and 3/4 in interstitial space

• Na/K pump keeps Na outside cells

• Isotonic crystalloid solution

• Reasonable choice if goal is to increase vascular volume (e.g. hypovolemic /septic shock, dehydration)

Distribution: Sodium Chloride 0.45% (NS)

• Treat as 1/2 NS and 1/2 free water

• Hypotonic crystalloid solution

• Often used as maintenance IV fluid in patients with hypernatremia

Distribution: 5% Albumin

• Mostly stays in the vascular space

• Large protein molecule suspended in NS

• Iso-oncotic colloid solution; isotonic solution

• Very efficient if goal is to replete vascular volume (e.g. hypovolemic /septic shock, dehydration

*Note does have ~ 154 meq/L Na

Distribution: 25% Albumin

• Stays in the vascular space and pulls water in as well

• Large protein molecule suspended in NS

• Hyper-oncotic colloid solution; isotonic solution

• Very efficient if goal is to replete vascular volume (e.g. hypovolemic /septic shock, dehydration

*Note does have ~ 154 meq/L Na

Maximum and Minimum Osmolality of IV Solutions

• Max: 600 - 900 mOsm/L

• Minimum (to avoid hemolysis): 154 mOsm/L

Osmolality

mOsm/L

Calculated Osm

= 2Na + Glu/18 + BUN/2.6

Osmol gap = Osm(serum) - Osm(cal)

Normal Serum Osm = 280 - 300

What can an osmol gap stem from?

• Alcohols: methanol, ethanol, ethylene glycol, propylene glycol (e.g. lorazepam)

• Mannitol

• Osmol gap is usually < 10 mOsm/kg

Fluid Output

~ 2.5 L/day

– Urine ~ 1.5 liters/day

– Insensible losses 500 – 1000mL/day

• Skin

• Lungs

• Secretions

Maintenance Fluid Requirements:

• 1.5 L/day first 20 kg

• 20 mL/kg for each additional kg

• 2.5 L for 70 kg person = 1.5 L + 1L

What do you use for maintenance fluids?

• D5W1/2Ns

• D5W1/4NS

• +/- Potassium

• Volume and fluid component required can vary or need to be adjusted based on

– Renal/cardiac function

– Insensible loss variation

What do you NOT use for resuscitation/replacement?

D5W or 1/2 or 1/4 NS

What do you use for resuscitation?

• Balanced crystalloids (LR + Plasmalyte) for initial resuscitation

• For large volume resuscitations may consider alternative fluids later in the resuscitation process

Types of Hyponatremia

• Hypertonic Hyponatremia

• Hypovolemic Hypotonic Hyponatremia

• Hypervolemic Hypotonic Hyponatremia

• Euvolemic Hypotonic Hyponatremia

▪ Can CAUSE DEATH

Hypertonic Hyponatremia

• (serum Osm > 280 mOsm/L)

• Non-sodium “osmoles” pull fluid into vascular space

- Glucose

- Mannitol

• Excess fluid in the vascular space NOT depleted Na

• Treatment: Reduce non-sodium osmols

Ex. Decrease plasma glucose

Hypovolemic hypotonic hyponatremia

• Na and water loss, losing more Na than water

• Examples - diarrhea / vomiting (severe cases), blood loss, cerebral salt wasting, dehydration/excessive sweating, thiazide diuretics)

• urine Osm > 450 mOsm/L AVP stimulated, trying to concentrate urine, urine Na < 20 mmols/L trying to retain Na to retain water

• Treatment: Replace volume loss with sodium contain fluids, d/c thiazide diuretics

▪ Sodium chloride-containing solution (typically NS); hypertonic saline (usually 3%) if severe symptoms (i.e. seizures)

• Serum Osm < 280 mOsm/L

Hypervolemic hypotonic hyponatremia

• Examples: HF, cirrhosis, renal failure

• Retaining more water than Na+

• Treatment: Manage heart failure (water and sodium restriction, loop diuretics)

• Urine Na < 20 mmols/L abnormally retaining Na due to underlying condition

• Serum Osm < 280 mOsm/L

Euvolemic hypotonic hyponatremia

• Examples: SIADH, primary polydipsia, adrenal insufficiency, MDMA

• urine Na > 40 mmols/L, urine Na concentrated due to the inappropriate retention of water (AQs concentrate the urine )

• Treatment: discontinue medications causing SIADH, water restriction (polydipsia), steroids (adrenal insufficiency)

▪ Typically fluid restriction but if severe hypertonic saline, salt tablets, or demeclocycline* may be needed (NS will worsen hyponatremia)

• Serum Osm < 280 mOsm/L

• Demeclocycline reduces responsiveness to ADH

Demeclocycline

Reduces responsiveness to ADH and used in euvolemic hypotonic hyponatremia that occurs due to SIADH

When should you give NS for hypotonic hypernatremia? When would you not give NS?

For hypovolemic hypotonic hypernatremia, it will actually worsen euvolemic hypotonic hypernatremia (would use a hypertonic saline or salt tablets for euvolemic)

Causes of SIADH

• Medications and non-medication causes

• SIADH causes Euvolemic hypotonic hyponatremia

Max increase and max decrease of hyponatremia

8 mmol to increase and 10 mmol to decrease in 24 hrs

• Increase slowly or can cause osmotic demyelination syndrome

• Decrease slowly or can cause brain swelling

Vasporessin receptor antagonists

• Indicated for euvolemic or hypervolemic hyponatremia

- Blocks ADH

• Conivaptan (IV only)

• Tolvaptan

Hypernatremia Causes

• Na-containing IV fluids (hypertonic saline, sodium bicarbonate, etc.)

• Loop / osmotic diuretics (ex. furosemide / mannitol)

- Note this is different than what is seen with thiazide diuretics

▪ With loop diuretics you lose more water than Na+ so you have hypernatremia, but for thiazide diuretics, there is more Na+ loss than water, so you ahve hypovolemic hypotonic hyponatremia.

▪ This would make sense since loop diuretics are used for edema

• Lithium (“Li” causes “DI”) – inhibits adenylate cyclase and inhibits expression on aqua porin channel which resorbs water

• Vasopressin receptor antagonists (conivaptan, tolvaptan)

• Demeclocycline – blocks the binding of AD

__________ diuretics cause hypernatremia whereas __________ diuretics cause hypovolemic hypotonic hyponatremia.

Loop; thiazide

Hypernatremia

• Causes

- Na-contain IV fluids

- Loop/osmotic diuretics

- Lithium

- Vasopressin receptors antagonists (conivaptan, tolvaptan)

- Demeclocycline

• Symptoms/Signs

- Muscle weakness

- CNS: altered mental status, confusion, coma

- Severe: brain shrinkage, brain damage, death

• Treatment

- Correct underlying cause

- Replace free water

- Discontinue contributing Medications (e.g. loop/osmotic diuretics, lithium, etc.)

• Maximum rate of correction: decrease by 10 mEq/L per 24 hrs

Chloride (Cl)

• Normal: 98 - 107 mmol/L

• Na/Cl

HYPOcholermia

• Often accompanies hyponatremia

• Causes

– Thiazide and Loop Diuretics

– Vomiting, NG suctioning

• Effects

– Can lead to hypochloremic metabolic alkalosis (‘contraction alkalosis’)

• Treatment

– Discontinue offending medications

– Address underlying medical conditions

HYPERcholermia

• Causes

– Dehydration

– Infusion of Cl-containing solutions

• Effects

– Can lead to non-anion gap, metabolic acidosis

• Treatment

– Rehydration

– Discontinue offending medication

Hypochloremia leads to ____________________ while hyperchloremia can lead to __________________.

hypochloremic metabolic alkalosis (‘contraction alkalosis’) ; non-anion gap, metabolic acidosis

HYPOkalemia

• K Normal Range: 3.5 - 5 mmol/L

• K/Mg - hypomagnesia causes hypokalemia

• **Majority of K is intracellular so serum K concentrations typically reflect K shifts rather than total body K conc.**

• Causes (pumps K+ in):

- Alkalosis

- Medications: Beta-agonists + Insulin

- Hypothermia

- Vomiting, diarrhea, excessive laxative use

- Diuretics

- Amphotericin

- Hypomagnesemia

• Symptoms

- Cardiac arrhythmias

- Muscle weakness

• Treatment

- Check Mg and correct as needed (**kidneys preferentially reabsorb Mg first**)

- Oral treatment preferred unless severe or symptomatic hypokalemia

▪ Then IV: 10 – 20 mEq/hr (typical max 60 mEq and central vein required for 20 mEq/hr)

HYPERkalemia

• K > 5.0 mEq/L

• **Majority of K is intracellular so serum K concentrations reflect K shifts rather than total body K conc.**

• Causes of Potassium shift

– Acidosis (e.g. DKA)

– Cell lysis (rhabdomyolysis, tumor lysis, crush injury) - which is why you need to make sure serum K+ is not reported from a hemolyzed sample

– Common Medications

▪ Succinylcholine

▪ ARAs, ACEi, ARBs

▪ Bactrim

▪ B-blocker

▪ Calcineurin inhibitors

▪ NSAIDs

- Renal failure

• Symptoms

– Arrhythmias (classic "peaked" T-waves)

- Muscle weakness/paralysis

• Treatment

– IF arrhythmia present or considered imminent due to extremely high K+ (> 6.5 mEq/L)

▪ Stabilize cardiac membranes to effects of potassium with:

★ Calcium chloride preferred if central line (3x elemental Ca vs gluconate)

★ Calcium gluconate if peripheral access

★ BOTH do not decrease K+ concentration

▪ To shift K+ intracellularly

★ Insulin 10 units with dextrose (if BS < 250)

★ High DOSE B-2 Agonist

★ Sodium bicarbonate

▪ Remove K+ from body

★ Sodium polystyrene

★ Loop diuretics; increase renal K+ excretion

★ Dialysis; if renal failure

▪ Chronic hyperkalemia (CKD)

★ Patiromer (Veltassa)

★ Zirconium cyclosilicate

_________ potentiates digoxin toxicity.

Hypokalemia and hypomagnesia

Hypomagnesia

• Mg Normal Range: 1.5 - 2.8 mmol/L

• Primarily intracellular cation; regulates movement of Ca into muscle cells (important in maintaining vascular tone and cardiac contractility)

• K+ / Mg+ and Ca+ / Mg+ are partners

• Causes

- Medications

- Alcoholism

- Diarrhea

- Uncontrolled diabetes

• Symptoms/signs

– Tremor, weakness, delirium

– Hypocalcemia (competes with calcium for entrance into cells, so when Mg is low, Ca is more likely to be transported intracellularly)

– Hypokalemia

– Arrhythmias: prolonged PR interval, widened QRS complex, prolonged QT interval/Torsades de pointes, atrial fibrillation (post-op, ICU)

• Treatment (typical goal is ≥ 2.0 mg/dL in hospitalized patients)

– Usual IV dose: Mg sulfate 1 – 2 grams over 1 hour (1g = 100mg elemental Mg)

– Oral: Magnesium oxide 800 – 1600 mg/day

Hypermagnesia

• Mg Normal Range: 1.5 - 2.8 mmol/L

• K+ / Mg+ and Ca+/ Mg+ are partners

• Causes

- Renal failure

- Mg-contain antacids

- Mg-infusion (e.g. eclampsia, subarachnoid hemorrhage)

• Symptoms/signs (dose-dependent)

– 4.8 – 7.1 mg/dL: nausea, flushing, H/A, lethargy, diminished deep tendon reflexes

– 7.2 – 11.9 mg/dL: somnolence, bradycardia ,loss of deep tendon reflexes, hypotension, hypocalcemia (hypermagnesemia can suppress the release of parathyroid hormone, leading to a decrease in Ca concentration)

– ≥ 12 mg/dL: muscle paralysis/respiratory failure, heart block/cardiac arrest

• Supportive Treatment:

– Discontinue Mg,

– IV calcium (can also antagonize muscular and cardiovascular symptoms)

• Decrease magnesium

– Loop diuretic

– hemodialysis if severe

Calcium

• Ca++ normal range

– 8.6 – 10.3 mg/dL (total or “corrected”)

– 1.05 – 1.3 mmol/L ionized (reflects true available calcium status)

• Calcium is highly bound to albumin so if albumin is low, serum total calcium may not reflect ionized or free calcium which is the active calcium so we have to correct.

– Total Ca corrected = Serum Ca + 0.8 (Normal Albumin {4.0} – Patient Albumin)

in other words serum total Ca falls ~ 0.8 mg/dL per 1 mg/dL decrease in albumin

• Involved in bone/tooth formation, clotting, cardiac and neurologic function, hormone regulation

• Calcium is inverse partner with Phosphorus and similar partner with Magnesium

Hypocalcemia

• Ca++ normal range

– 8.6 – 10.3 mg/dL (total or “corrected”)

– 1.05 – 1.3 mmol/L ionized (reflects true available calcium status)

• Causes

▪ Medications

- Loop diuretics – Increase Ca excretion

- Cinacalcet – shuts down signaling from parathyroid (PTH) to create Ca

- Bisphosphonates – Prevents Ca release from bone lowering Ca levels

- Aminoglycosides – Renal wasting of Ca

- Cisplatin causes Mg wasting. Mg is PTH co-factor so if Mg low, PTH low

▪ Hypomagnesemia - required for PTH production

▪ Citrate from blood transfusions binds CA

▪ Alkalemia (increasing protein binding on albumin, decreasing ionized Ca)

▪ Hyperphosphatemia/chronic kidney disease (decrease Ca absorption and increased binding to phosphorus)

• Symptoms/signs

– Tetany / hyperreflexia

– Seizures

– Hypotension, decrease cardiac output, ectopy

• Treatment

– Calcium chloride/gluconate 1 – 2 grams over 1 hour

– Calcium chloride preferred for severe symptoms (e.g. seizures, arrhythmias) as Ca available right away (gluconate has to be hepatically metabolized to release)

– Central line required for calcium chloride (osmolality=2040 mOsm/L)

Hypercalcemia

• Ca++ normal range

– 8.6 – 10.3 mg/dL (total or “corrected”)

– 1.05 – 1.3 mmol/L ionized (reflects true available calcium status)

• Causes

– Malignancy (primary)

– Hyperparathyroidism

– Medications

• Thiazide diuretics – increase tubular reabsorption of Ca

• Lithium (long term) – resets level of Ca needed to inhibit PTH secretion

• Calcium Containing products (ex. Tums)

• Symptoms/signs

• GI: N/V, constipation, ileus

• CV: hypovolemia, hypotension

• Renal: polyuria

• Neurologic: confusion, altered mental status, coma

• Treatment

– Asymptomatic or mild symptoms (e.g. constipation) with Ca < 12 mg/dL

• No aggressive measures

• Adequate hydration, avoid precipitants (e.g. thiazide diuretics, Ca intake)

– Asymptomatic or mild symptoms (e.g. constipation) with chronic Ca 12 – 14 mg/dL

(same as above)

– Severe symptoms or Ca > 14 mg/dL

• NS infusion at 200 – 300 mL/hr

• Calcitonin

• Zoledronic acid or pamidronate

• Steroids effective in some malignancies

Phosphate

• Phosphate normal range 2.7 – 4.5 mg/dL

• Measure phosphate as a surrogate for body stores of phosphorus

• Reflects a small percentage of total body phosphorus

• Essential in cellular processes such as glycolysis, ATP production (think: ATP-hosphate)

• Ca and phosphorus-P (phosphate-PO4) are inverse partners

Hypophosphatemia

• Phosphate normal range 2.7 – 4.5 mg/dL

• Causes

– Intracellular shift (insulin facilitates movement into cell with glucose and K+)

– Medications

• Phosphate binders

• Sucralfate – binding properties

– Renal replacement therapy (e.g. continuous renal replacement therapy, CRRT)

– Re-feeding syndrome – increased utilization

• Symptoms/signs

– Decreased cardiac output

– Muscle weakness / respiratory muscle weakness

– Decrease in tissue oxygen release by hemoglobin

• Treatment

– Oral (preferred):• A variety of products available

• Not all have the same Phos content

– IV: 15 – 30 mmol NaPhos or K-Phos

• Decision between Na or K-containing product depends on other electrolytes

• Usually reserved for severe hypophosphatemia (<1 mg/dL)

Hyperphosphatemia

• Phosphate normal range 2.7 – 4.5 mg/dL

• Causes

– Renal failure

– Cell lysis (e.g. tumor lysis syndrome, rhabdomyolysis)

– Medications (Phosphate-containing laxatives, especially if renal failure {Fleet’s Phospho-Soda®})

• Symptoms/signs

– Ca/Phos precipitation in arteries, joints, soft tissue, organs; can lead totissue ischemia

• Treatment

– Dietary restriction

– Phosphate binders

▪ Calcium containing - CaCO3, Ca-acetate (ex. Phoslo, Tums)

▪ Aluminum-containing antacids (ex. Amphogel, Alternagel)

▪ Aluminum and calcium free (ex. Sevelamer, Fosrenal)

Refeeding syndrome

• Mechanism: chronic malnutrition leads to relative hypo-insulinemic state; introduction of carbohydrates causes insulin surge which drives glucose and electrolytes into cells

• Can cause hypophosphatemia

Electrolyte "pairs"

Na/DeCl, K/Mg, Ca/Phos, Ca/Mg

Definitions/Abbreviations

(See Image)

Hypoventilation causes _____________ and hyperventilation causes _____________.

respiratory acidosis; respiratory alkalosis

Lung vs Kidney Compensation for Metabolic Acid-Base Disorders

The kidneys work much slower (3 - 5 days for full compensation), so there is a formula for partial compensation and full compensation, and the lungs work immediately (within minutes)

Diagnosing Acid-Base Disorders

• Step 1: Obtain arterial blood gases (ABGs) and basic metabolic panel (BMP) for serum electrolytes

• Step 2: Compare HCO3 on ABG (calculated) to CO2 on BMP (measured); should be within 1 – 2 mEq/L

• Step 3: Look at the pH (a normal pH does not rule out an acid-base disorder!)

▪ Normal pH: 7.35 - 7.45

▪ Normal HCO3: 22 - 26 mEq/L

▪ Normal PCO2: 35 - 45 mmHg

• Step 4: Look at the PCO2 and HCO3 (determine primary disorder)

• Step 5: Calculate expected compensation

• Step 6: Calculate anion gap

Anion Gap

• Based on assumption that there is a net charge of “0” in the extracellular space

• Formula = Na + unmeasured cations (UC) = (Cl + HCO 3) +unmeasured anions (UA)

(rearranging) Na – (Cl + HCO3) = UA – UC = anion gap (AG)

• Normal AG = 3 – 11 mEq/L

Anion Gap Formula

= Na - (Cl + HCO3) = anion gap (AG)

Normal AG = 3 - 11 mEq/L

Metabolic Acidosis

• Primary problem is decreased HCO3 concentration

• Lungs compensate by increasing respiratory rate (leads to ↓ PCO2)

• Characterized as:

- Elevated anion gap (increased acid generation)

▪ M - methanol, metformin

▪ U - uremia (i.e. elevate BUN)

▪ D - diabetic ketoacidosis

▪ P - paraldehyde/propylene glycol/profol

▪ I - iron, INH, infection (sepsis)

▪ L - lactic acidosis

▪ E - ethylene glycol, ethanol

▪ S - salicylates

- Non-anion gap (loss of bicarbonate/hyperchloremia)

▪ U - ureteral diversion (fistula)

▪ S - sodium chloride administration

▪ E - exogenous acid

▪ D - diarrhea

▪ C -carbonic anhydrase inhibitors - CA is used to make bicarbonate, so lack of bicarb means acidosis

▪ A - ammonium chloride

▪ R- renal tubular acidosis

• Treatment:

- May consider alkali therapy if pH < 7.20

What can hyperchloremia cause?

Non-anion gap metabolic acidosis since the body reduces the amount of bicarbonate in the maintain charge neutraility

Metabolic Alkalosis

• Primary problem is increase in HCO3

• Lungs compensate by decreasing respiratory rate (leads to ↑ PCO2)

• Causes

– Contraction alkalosis due to loop diuretic use (most common)

▪ Loss of water leading to increase in HCO3 concentration

▪ Loss of chloride leading to reabsorption of HCO3 (hypochloremic metabolic alkalosis)

• Goal is to treat underlying cause

– Hold or decrease dose of diuretics

– Hydration with chloride-containing solutions (i.e.NS)

– Anti-emetics for vomiting

• In patients with metabolic alkalosis but ongoing evidence of fluid overload, may consider carbonic anhydrase inhibitor

– Acetazolamide 500 mg IV once

• Increases renal excretion of HCO3 , potassium, sodium and water

• Potassium-wasting diuretic (monitor K+)

What is the most common type of metabolic alkalosis?

Contraction hypochloremic alkalosis due to loop diuretic use (moCst common)

Carbonic anhydrase

An enzyme present in erythrocytes (as well as in other places) that catalyzes the conversion of CO2 and H2O into carbonic acid (H2CO3) and make bicarbonate.

Inhibitors of this will cause non-anion gap metabolic acidosis

Respiratory Acidosis

• Primary problem is PCO2 retention

• Expected compensation is reabsorption of HCO3 in the kidneys (remember,

this can take days for compensation to complete)

– Acute respiratory acidosis (compensation not fully completed)

– Chronic respiratory acidosis (compensation fully completed)

• Causes

– Decreased respiratory drive (sedatives, drug overdose)

– Asthma, COPD, pneumonia

– Neurologic injuries (e.g. cervical spinal cord injury)

– Ventilator-induced (i.e. mechanical ventilation rate too low)

– Cardiac arrest

• Goal is to treat underlying cause

– Bronchodilators for COPD, antibiotics for Pneumonia

– Decrease dose or reverse sedative medications (e.g. naloxone for opiate-induced respiratory depression)

– Increase mechanical ventilation rate

– Typically avoid

• Alkali therapy may worsen acidosis (e.g. cardiac arrest)

• Carbonic anhydrase inhibitors may worsen acidosis

Respiratory Alkalosis

• Primary problem is decrease in PCO2

• Expected compensation is increased excretion of HCO3 in the kidneys (remember, this can take days for to complete)

– Acute respiratory alkalosis (compensation not fully completed)

– Chronic respiratory alkalosis (compensation fully completed)

• Causes

– Hyperventilation (anxiety, pain, fever, altitude sickness)

– Drug overdose (salicylates)

– Mechanical ventilation (e.g. hyperventilation for increase intracranial pressure)

• Goal is to treat underlying cause

– Sedatives for anxiety (or breathe into paper bag)

– Analgesics for pain

– Decrease mechanical ventilation rate

– Treatment of salicylate toxicity

– Acetazolamide for altitude sickness

Mixed Acid Base Disorders

Typically consider when:

- pH is normal but either HCO3 or PCO2 are abnormal (based on the principle that compensation by lungs or kidneys typically does not fully correct pH)

- HCO3 and PCO2 are both abnormal in the opposite direction

- AG is elevated regardless of blood gas values

- Compensation for primary acid-base disorder is more or less than calculated expected values

Cystatin C

• Cystatin C, though influenced by other patient characteristics, is NOT influenced by changes in muscle mass

• Factors that may influence Cystatin C

- Obesity

- Inflammation

- Smoking status

- Exogenous steroids

- Thyroid disease

Gender Suggestions for CrCl Calculations

< 6 months of gender affirming hormone therapy: Consider using sex assigned at birth alone for CrCl

≥ 6 months of gender affirming hormone therapy: Consider using gender identity alone for CrCl

When is eGFR used to dose adjust?

Metformin, SGLT-2 inhibitors, allopurinol

For time-dependent antibiotics, adjust ______ and for concentration-dependent antibiotics adjust _______.

mg; frequency

Module 8: Renal Failure and Disease

Module 8: Renal Failure and Disease

Acute Kidney Injury (AKI)

• A clinical syndrome defined by an abrupt decease in kidney function

• Results in changes in:

– Serum creatinine (SCr)

▪ Normal: 0.6 - 1.3 mg/dL

– Blood urea nitrogen (BUN)

▪ Normal : 6 - 20

– Urine output (UOP)

▪ Decreases with injury

• Affects > 50% of patients in the intensive care unit (ICU)

• Associated with worse morbidity and mortality

– Need for renal replacement therapy (RRT)

– Development of CKD with or without chronic

dialysis

– Increased hospital length of stay/cost/ventilator days

What two parameters are used as diagnostic criteria for acute kidney injury?

SCr and UOP

(SCr increase are delayed compared to changes in UOP)

______ increase are delayed compared to changes in UOP.

SCr (lags behind 1 - 2 days behind GFR decline)

Kidney Disease Improving Global Outcomes (KDIGO) AKI Definition

• Presence of one of the following:

★ Increase in SCr ≥ 0.3mg/dL within 48 hours

★ Increase in SCr to ≥ 1.5 times baseline, within the prior 7 days

★ UOP < 0.5 ml/kg/h for 6 hours

(Basically the KDIGO Criteria for Stage 1)

AKI vs AKD vs CKD

AKI

• Lasts less than 7 days

• Rapidly reversible AKI resolves within 48 hours (is usually due to a med or volume status)

Acute Kidney Disease (AKD)

• Kidney impairment beyond 7 days

• May or may not include AKI

• Can lead to chronic kidney disease

Chronic Kidney Disease (CKD)

• AKD persisting > 3 months

• Patients with CKD can present with AKI or not

AKI lasts less than ___ days, AKD lasts beyond ___ days and CKD is AKD that persists for greater than ___ months.

7; 7; 3

Rapidly reversible AKI resolves within ____ hours (is usually due to a med or volume status)

48

Urine Output Definitions

• Anuria - absence of urine

▪ < 50 mL/day

• Oliguria - diminished urine

▪ < 500 mL/day

• Nonoliguria - poor quality (little waste products) but adequate volume

▪ > 500 mL/day

What is the most commonly used staging system for AKI?

KDIGO (Stage 3 is the most severe stage)

KDIGO Staging Criteria

(For each stage, patient only needs to meet one criteria)

Stage 1:

• SCr Criteria: Increase ≥ 0.3 mg/dL OR 1.5 - 1.9 times from baseline

• Urine Output Criteria: Increase < 0.5 mL/kg/hr for 6 - 12 hrs

Stage 2:

• SCr Criteria: 2 - 2.9 times from baseline

• Urine Output Criteria: Increase < 0.5 mL/kg/hr ≥ 12 hours

Stage 3:

• SCr Criteria: SCr ≥ 4 mg/dL OR 3 times from baseline OR need for RRT or eGFR < 35 mL/min/1.73 m² in patients < 18 years

• Urine Output Criteria: Anuria ≥ 12 hrs

Prerenal vs Intrinsic vs Postrenal

Prerenal:

• Decreased renal perfusion

• Causes:

▪ Hypovolemia

▪ Decreased cardiac output

▪ Decreased effective circulating volume

▪ Impaired renal autoregulation (NSAIDs, ACEi, ARBs)

Intrinsic:

• Structural kidney damage

• Causes:

▪ Acute glomerulonephritis (ex. autoimmune disorder)

▪ Tubular damage (ex. toxins, contrast dyes, ischemic damage from hypotension and sepsis)

▪ Vascular damage (ex. thrombosis)

Postrenal:

• Obstruction of urine downstream from the kidney

• Causes:

▪ Bilateral ureteropelvic obstruction

▪ Bladder outlet obstruction (ex. BPH)

Causes of AKI

Exposure

• Sepsis

• Critical illness

• Hypotension

• Burns

• Trauma

• Cardiac surgery

• Major surgery

• Nephrotoxic drugs

• Radiocontrast agents

• Toxins

Susceptibility

• Dehydration/volume depletion

• Age

• CKD

• Chronic diseases (heart failure, diabetes, liver disease, heart disease)

• Hypoalbuminemia

Prerenal AKI

• Hypoperfusion of undamaged renal parenchyma ± hypotension

• Causes

– Hypovolemia

• GI losses

• Hemorrhage

– Decreased circulating blood volume

• Sepsis

• Liver failure

• Decreased cardiac output

• Decreased renal autoregulation may increase risk of prerenal injury

– “triple whammy” – concurrent use of NSAIDs, ACEI/ARB, and a diuretic

▪ NSAIDs reduce PGE2 which means there is less vasodilation of the afferent arteriole

▪ ACEi/ARBs reduce Ang II which means there is less vasoconstriction of the efferent arteriole

▪ Diuretic can cause hypovolemia and decrease circulating volume

• Urine Studies

▪ Urine sediment - Hyaline casts or normal

▪ Specific gravity - > 1.018

▪ RBCs - None

▪ WBCs - None

▪ Urine Na - < 20 (due to RAAS activation)

▪ FEna (%) - < 1

• Treatment

▪ Volume replacement w/ IV isotonic crystalloid fluids

▪ Hemodynamic support

▪ Treat underlying cause (ie. N/V/D etc..)

Intrinsic AKI

• Damage to the kidney

– Vasculature

– Glomeruli

– Tubules

– Interstitium

• Causes:

- Vascular damage

▪ Bilateral renal artery occlusion

▪ Vasculitis

- Glomerular damage

▪ Autoimmune disease (i.e. lupus)

- Acute interstitial nephritis

▪ Hypersensitivity immune reaction usually due to drugs (NSAIDs, antibiotics)

▪ Infection (pyelonephritis), idiopathic, autoimmune

- Acute tubular necrosis (most common)

▪ Renal ischemia

▪ Nephrotoxic drugs/contrast dyes

• Urine Studies

▪ Urine sediment - Granular casts, cellular debris

▪ Specific gravity - < 1.012

▪ RBCs - 2-4+

▪ WBCs - 2-+

▪ Urine Na - > 40

▪ FEna (%) - > 2

• Treatment

▪ Discontinue cause (i.e., medications)

▪ Supportive care

Acute Tubular Necrosis

• Most common cause of intrinsic AKI that causes tubular epithelial damage

• Possible causes of ischemia that can lead to ATN (i.e. tubular injury/damage)

– Hypovolemia

– Diuretics

– Heart failure

– Cirrhosis

– Sepsis

– Anaphylaxis

• Drugs may cause direct renal injury

– Aminoglycosides

– Amphotericin B

– Contrast dyes

- Cisplatin, carboplatin

- Cyclosporine, tacrolimus

- Adefovir, cidofovir, tenofovir

- Pentamidine

- Forscarnet

- Zoledronate

• Four phases

1. Initation: Ischemic injury→ Renal tubular epithelial cell injury → Decrease in GFR, increase in SCr/BUN

2. Extension: Ongoing hypoxia & Inflammation → GFR continues to decrease

3. Maintenance: Cell repair and reorganization + Blood flow returns

4. Recovery: Continuation of maintenance phase + Improving renal function

Postrenal AKI

• Least common (< 5% of cases) compared to prerenal and intrinsic AKI

• Obstruction of urine → upstream pressure → decrease GFR

• Bladder outlet obstruction

– Prostate enlargement in males (hypertrophy, cancer, infection)

• Improperly placed urinary catheter/remove blockage

- Would need to replace foley to fix

• Urine Studies

▪ Urine sediment - Cellular debris

▪ Specific gravity - Variable

▪ RBCs - Variable

▪ WBCs -Variable

▪ Urine Na - > 40

▪ FEna (%) - Variable

• Postrenal

▪ Remove cause of obstruction

▪ Place foley catheter

Phases of Acute Kidney Disease

1. Initiation (Hours to Days)

2. Maintenance (7 to 14 days or longer)

3. Recovery (months to 1 year)

A prerenal AKI can progress to _________ AKI if there is prolonged sepsis or hypotension.

intrinsic