Renal replacement therapy (RRT) is a process of removing waste products and excess free water from the blood during renal failure and critical illness.
Common indications for RRT can be remembered with the mnemonic AEIOU:
- (Metabolic) Acidosis
- Electrolyte abnormalities (especially severe hyperkalemia)
- Ingestions/toxins (aspirin, lithium, methanol, ethylene glycol)
- (Volume) Overload
There are many different variations of RRT, but the main principles behind it can be quite simple.
In hemodialysis, diffusion is responsible for removing unwanted solutes and water. The setup involves a semipermeable membrane that can allow water and some water-soluble molecules to pass. Blood will flow on one side of the membrane, under pressure, while the dialysate (contains glucose and some electrolytes) generally flows on the other side in the opposite direction. This creates a suitable concentration gradient for unwanted molecules to pass into the dialysate, while excess water is forced across the membrane based on the amount of pressure is applied by the dialysis circuit.
In hemofiltration, blood is pushed across a semipermeable membrane, under pressure. Most of the plasma water is able to pass through the membrane, while unwanted molecules get stuck in the membrane (convection). A substitution fluid may be added back to the blood, in order to dilute out waste molecules (e.g., urea), replace useful molecules (e.g., bicarbonate), and to avoid losing too much fluid from the patient’s circulation.
Some modes of RRT will involve both hemodialysis and hemofiltration. Others only use one of these mechanisms.
- Butcher BW, Liu KD. 2013. Renal replacement therapy and rhabdomyolysis. In: Critical Care Secrets (Parsons and Wiener-Kronish, Eds.) Mosby, Philadelpia PA.
- Hoste E, Vanommeslaeghe. 2017. Renal replacement therapy. In: Textbook of Critical Care (Vincent, Abraham, Moore, Kochanek, and Fink, Eds.) Elsevier, Philadelphia PA.
- Ricci Z, Romagnoli S, Ronco C. 2015. Extracorporeal support therapies. In: Miller’s Anesthesia (Miller, Ed.) Elsevier/Saunders, Philadelphia PA.
The nephron is composed of distinct areas that are specific to regulating different electrolytes.
An overview of nephron anatomy
Loop diuretics: blocks the sodium/potassium/chloride transporter in the ascending loop of Henle, potassium-wasting
Thiazide diuretics: blocks the sodium/chloride transporter in the distal tubule, potassium-wasting
Amiloride: directly blocks sodium channels in the collecting duct, potassium-sparing
Spironolactone: blocks the aldosterone receptors in the cortical collecting duct. This causes a decrease in sodium and water reabsorption and decreases potassium secreting (therefore is potassium-sparing)
The nephron is divided into 6 distinct parts
- Proximal (covoluted) tubule
- Descending loop of Henle
- Ascending loop of Henle
- Distal (convoluted) tubule
- Cortical collecting duct
- Distal collecting duct
Each of these sections has a main function in adjusting the amount and kind of solutes in the urine. Different drugs and diuretics work at distinct areas, which is why some diuretics are potassium sparing while others (like Lasix/furosemide) are potassium wasting.
This is the general way to approach an acid-base disturbance. They’re not really as bad as they seem at first. You just need to remember that CO2 is acidic and HCO3- is basic. So an increase in CO2 makes the body acidotic and an increase in HCO3- makes the body alkalotic.
It’s also good to remember to calculate the anion gap when doing these calculations.
AG = Na – (Cl- + HCO3-) it’s just the cations minus the anions. If this gap between the cations and anions is large, it means that the anions are stacking their team and have an extra anion helping out.
The classic mnemonic is MUDPILES
- Diabetic ketoacidosis
- Isopropyl alcohol
- Lactic acidosis
- Ethylene glycol
If the anion gap is big, it’s good to look at the ratio between the change in the gap and the change in the HCO3-.
- Increase in AG < decrease in HCO3- = coexisting non-anion gap metabolic acidosis
- Increase in AG > decrease in HCO3- = coexisting metabolic alkalosis
GFR should be ~100 mL/min
(140 – age) x lean body weight (kg) / sCr (umol/L)
What determines GFR
- Renal blood flow: effective circulating volume, cardiac output
- Resistance to flow: vascular tone of afferent and efferent arterioles
- Permeability of glomerular basement membrane
Drugs that increase GFR
- Prostaglandin: vasodilator (afferent > efferent)
- Angiotensin II: vasoconstrictor (efferent > afferent)
- Norepinephrine: vasoconstrictor, increases blood pressure
- ANP: afferent vasodilator, efferent vasoconstrictor
Drugs that decrease GFR
- NSAIDs: afferent vasoconstriction
- ACE Inhibitors: decrease efferent vasoconstriction
- Angiotensin Receptor Blockers (ARBs): decrease efferent vasoconstriction
Calcium homeostasis is largely controlled by the parathyroid glands (tucked away underneath the thyroid). I’ve included a little bit of the vitamin D synthesis pathway as well, though D3 (the form that is absorbed in the intestines) is also synthesized in the skin as long as you’re getting a little bit of sunlight.
- Hyperparathyroidism: usually an adenoma
- Malignancy: PTH-related peptide released by tumor (squamous cell, renal, breast, bladder)
- Vitamin D excess: granulomas (sarcoidosis, TB, Wegener’s)
- Increased bone turnover: hyperthyroidism, Paget’s
- Familial hypocalcuric hypercalcemia: mutation in the calcium-sensing receptor in parathyroid and kidney
- Hypoparathyroidism: sporadic, caused by thyroid surgery, Wilson’s, hypomagnesemia
- Pseudo-Hypoparathyroidism: PTH end-organ resistance
- Vitamin D deficiency: no sunlight, GI disease
- Chronic renal failure: decreased 1,25(OH)D production, increased phosphate
- Calcium sequestration: acute phosphate increase
Acute kidney injury can be caused by problems directly in the kidney, before the kidney or after the kidney. If you think about it that way, it’s much easier to develop a differentiate and establish a treatment.
The RIFLE criteria define the relative damage to the kidney and the outcome.
RIF = Severity in terms of serum creatinine (sCr), glomerular filtration rate (GFR) and urine production. Though for simplicity I only included serum creatinine since that is most likely what you’ll be looking at on initial blood work.
LE = Outcome variables (temporary or permanent)
First – look to see what the person’s sodium is
Second – what is their volume status
The most important thing about hyponatremia is don’t correct more than 8 to 12 mmol/L per day!!!
Also, the paper titled “The Syndrome of Inappropriate Antidiuresis” by Ellison and Berl (N Engl J Med 2007;356:2064-72) is very useful.