W2 Acute Kidney Injury Flashcards
The kidneys are a key player in enzymatic conversion of what to what?
The kidneys are the key player in enzymatic conversion of an “inactive” form of Vitamin D3 (calcifediol) → the biologically “active” form Vitamin D3 (calcitriol)
**To remember which to which, think «calciferous» which is old and inactive
Active” Vitamin D3 (aka calcitriol) synthesis pathway
summary: Serum cholecalciferol (an inactive precursor of Vitamin D obtained either per PO intake of cholecalciferol itself, or via intra-epithelial synthesis of cholecalciferol (from ergocalciferol) in the setting of skin UVB exposure) → travels to the liver, where it is first enzymatically hydroxylated (hepatically) into calcifediol (aka, 25 dihydroxycholecalciferol, another inactive precursor
to active vitamin D3), then serum calcifediol → travels to the kidney, where it is again enzymatically hydroxylated (renally) into the active form of vitamin D3 (aka 1,25-dihydroxycholecalciferol, in practice called “calcitriol” ).
Calcitriol (active vitamin D3) is super important for which physiologic processes in the body? Think electrolyte regulation from a GI and Renal perspective… and subsequent Calcitriol ( “active” effects on other organs of the body…
Vitamin D3)
Patients who have chronic kidney disease have hypocalcemia.
What is a simple life cycle of the RBC and EPO
What does the kidney sense
What does the kidney release
The serum RBC Life Cycle is about 90 - 120 days (variable, however typically favoring the later).
Eventually, the RBC has grown old and frail and has decreased capacity to carry O2 and decreased compliance to get through small vessels.
These elderly red blood cells are identified by the liver, spleen, and RBM and targeted for RBC death and phagocytosis (gets eaten and broken down).
This transient drop in serum RBC leads to a transient net state of mild hypoxia, which is then recognized by the endothelium of the renal vasculature.
In response the renal pericytes produce and release erythropoietin.
Which level do we use to evaluate kidney function (AKI)
What about for CKD?
Creatinine — release by skeletal muscles, during breakdown. It exists in all cell types. Elevations in the serum creatinine level is an extremely helpful early indicator of acute changes in general renal function = creatinine clearance
GFR is the best overall measure of kidney function = i.e for CKD
EGRF is directly impacted by blood flow into the glomerulus
Presence of _______ or ______ in urine could be indicative of renal disease
What are the three shapes of RBCS and what could they indicate?
What about the difference between acute and chronic hematuria
Presence of protein (sensitive and pretty specific) or blood (sensitive, but not very specific - as blood could come from anywhere in urinary tract) in the urine may be indicative of of renal disease
Isomorphic — normal shaped RBC, true urinary tract bleed
Dysmorphic — RBCs coming from renal parenchyma
RBC cast — also dysmorphic but attached to protein
Microscopic hematuria: more commonly acute AKI, particularly intra-renal
Gross hematuria: BAD intra-renal AKI
Slide 18 review
Acute Kidney Injury
What is the general definition ?
Formal definition
AKI General Definition:
AKI is a broad umbrella term for a clinically significant acute change in a patient’s renal function, typically with focus on an acute change in the kidney’s ability to:
● Filter the serum of toxins and waste products (including byproducts of metabolism like creatinine )
● Appropriately participate in volume status regulation (intravascular & total body)
● Contribute to serum ionic balance regulation (ion homeostasis - i.e Na+, K+, Ca++, Mg++, Phos—, etc)
● Contribute to serum pH regulation (acid / base homeostasis - i.e H+ reabsorption / secretion & bicarb reabsorption / secretion)
- The most useful and important factor in early identification of AKI is an acute change in sCr from the pt’s b/l [ other renal injury syndromes like CKD take into account various other factors (notably GFR - b/c it’s the best way to measure overall kidney fxn chronically across all renal dz states), however for early identification of AKI, always look for changes in sCr ] *
AKI is formally defined as meeting at least 1 of the following three objective clinical criteria (which note are based on serum creatinine):
- Increase in sCr by >0.3 mg/dl within 48 hours *
- Increase in sCr to ≥1.5x b/l sCr over course of 1 wk
- Urine volume <0.5 ml/kg/hr for duration of >6 hrs *
there is variation here because every patient has a different baseline
Any patient presenting with OLIGURIA (low urine volume output) or ANURIA (NO urine volume output), AKI should immediately be on the menu (differential) for your patient.
What other two (non-nephro) processes that we’ve already discussed should be on your minds in patients presenting with oliguria or anuria? urinary retention
Comparison between AKI and CKD
AKI
—has more definitive criteria (see previous slide, there are 3 criteria)
—if remedied w/i 48 hours (creatinine elevation), usually patients can improve back to prior baseline. If it doesn’t, patient will likely need closer monitoring, or development of chronic picture
CKD
—more broadly defined and patient dependent.
— #s 1, 2, or 3 from AKI, but over weeks to months to years (rather than AKI which is more days to week(s).
AKI staging
Difference between pre, intra and post renal AKI
Examples for each
Pre-renal:
—hypotension (related to sepsis)
—renal artery stenosis
Intra-renal
—injury to the glomerulus, nephron or surrounding tissue or lining
—infection, medication, contrast
Post-renal
—urine backup, increases the pressure in renal parenchyma
—back up and decreased profusion
—kidney stones, malignancy, strictures, BPH, retention
Fix within 48 hours
Which metric is helpful when determining where the problem is for AKI, for example intra-renal?
Fractional excretion of Sodium (FeNa) = usually intra-renal
● The FeNa is a measurement of the kidney’s ability to functionally excrete (and really retain) sodium.
if Na+ is being kept inside, the kidneys are likely functioning well = lower FeNa
● Determining the FeNa gives insight into if the kidney is still able to do it’s other main function (aside from clearing
Cr of course… is the kidney still able to hold onto Na well?
● A non-injured kidney will usually reabsorb 99% of the Na+ that was initially secreted into the nephron, which easily enough is how you can remember “normal” and “abnormal” FeNa % #s:
○ If the FeNa is still normal (<1%), then this usually means that the kidney tissue itself is still functioning ok and
able to perform it’s role of retaining / reabsorbing sodium
○ If the FeNa is HIGH (ex FeNA > than 1% in AKI, this means that the kidney tissue itself is globally / intrinsically injured enough that it now cannot hold onto Na+ well.)
● Best part about the FeNa: it’s cheap, easy, & ~fast …. (well, kinda fast… it does involve both serum and urine studies, the urine studies may be a little more difficult and take more time to obtain, but in most cases if you take the time to place your orders for BMP + UA w/ Micro + Urine Lytes EARLY, you would have the info you need within a few hours)
○ However, pts w/ AKI need to start being treated ASAP too - this is where clinical prowess comes in :)
● FeNa does however have its drawbacks, and times when it is not useful…. Can you all think of examples? if they’re on diuretics
Joey says he never orders a FeNa ha! But good to know
<1 % pre-renal*, >1% intrinsic, >4 % post renal
● FeNa calculator link: https://www.mdcalc.com/fractional-excretion-sodium-fena
AKI algorithms for reference
Pre-renal: FeNa is <1
—hypoperfusion
—systemic hypotension (shock)
Pre-renal AKI
What will the work up involve?
● Prerenal AKIs are AKIs that result from a decrease in renal perfusion (more so perfusion globally from a whole kidney standpoint, not focal area / subunit)
● Prerenal AKIs are the most common type of AKI (c/t Intrarenal & Postrenal), accounting for over 50% of AKIs
● Given how commonly AKIs are prerenal, you’ll find that it’s often easy to preemptively start putting the clinical pieces of the puzzle together in one’s head for a likely cause of
a patient’s AKI if there are presenting with enough s/sx, recent history to suggest a prerenal etiology (think exs like recent < PO fluid intake for a week, recent. hemorrhagic events, recent / current sepsis picture), however sometimes (often) AKIs are multifactorial, and subcategories of AKI even like to cause each other (let’s not go there yet), so it’s important to still do your standard initial AKI workup:
○ In (sole) prerenal AKIs, the FeNa will still be <1%
○ In (sole) prerenal AKIs, the RBUS will not demonstrate hydronephrosis (dilation of renal parenchyma and pelvis) because this isn’t a post renal problem, an obstruction or something backing up into the kidney
○ The UA micro w/ sediment should be normal/bland/at pt’s b/l because there isn’t renal parenchyma injury
Causes of PRE-renal AKI
● True Hypovolemia: Low serum sodium and water leading to < intravascular pressure and < renal perfusion, leading to the prerenal AKI
○ Ex1: Hypovolemia 2/2 <PO fluid (and sodium) intake, - (note that dehydration is low H20 only, while hypovolemia is low H20 and Na+) ○ Ex 2: Hemorrhagic Shock is a notable cause of true hypovolemia
● Shock 2/2 Sepsis: Even if in theory the total serum volume is normal (pt is intravascularly euvolemic), vasodilatory impacts from sepsis may lead to profound decrease in ability to perfuse the kidney (not enough pressure)
● Shock 2/2… Anything Else:
○ Anaphylaxis, acute blood loss (AAA rupture patients rapidly lose ability to perfuse kidneys, among everything else), cardiogenic / acute heart failure
Pre-renal AKI
More causes
Appropriate intraglomerular / bowman’s capsule pressure (not too high, not too low) is needed for appropriate serum filtration and nephron function
Appropriate intraglomerular / bowman’s capsule pressure is normally achieved by optimizing (increasing) afferent blood flow into BC, and prevention of too much efferent blood flow via:
1. Afferent arteriole dilation (medicated by many systems, sometimes via ⭐️prostaglandin associated vasodilation)
2. Efferent arteriole vasoconstriction (also mediated by many systems, but w/ significant input f/⭐️ AT2-associated vasoconstriction)
● Medications (several, notables ones listed below):
○ ACE-is & ARBs
■ Why would this be ? * Think RAAS & AT2
○ NSAIDs (& all non selective COX 2 inhibitors), can cause COX inhibition → <PG synthesis (PG normally promotes afferent arteriole vasodilation) → less input for afferent arteriole vasodilation → net afferent arteriole vasoconstriction — decreased blood flow, and then intraglomerular pressure drops
■ Why do you think afferent arteriole vasoconstriction would lead to AKI?
■ Do you think this MOA of NSAID-induced AKI would lead to a change in eGFR, or not? yes, decrease it because reduced PGs = vasoconstriction
○ Anesthesias, Sedatives, EtOH, etc: may cause systemic vasodilation which leads to impaired renal blood flow, may → prerenal AKI
Chronic state of _____ can lead to pre-renal AKI
States of Chronic Hypoalbuminemia:
Regardless of primary etiology, any chronic state of hypoalbuminemia / low serum TP may lead to changes in intravascular oncotic pressure, resulting in H2O molecule third spacing (water leaving the vessels and going into areas classically associated w/ lower relative oncotic pressures c/t the serum like the peritoneum, the pleural space, etc), decreasing available intravascular volume. This decrease in intravascular volume leads to < renal perfusion, leading to the prerenal AKI.
○ Ex1: Hepatorenal Syndromes:
Cirrhosis associated chronic impairment of albumin production, leading to < serum albumin, when then follows the algorithm laid out above
○ Ex2: Anorexia
may also lead to chronic hypoalbuminemia, leads to a similar process as outlined above
● Other States of Chronic Protein Loss / Decreased Intravascular Oncotic Pressure:
○ Ex 3: Chronic renal protein spilling ⭐️(ex. nephrotic syndromes ! put pts at higher risk for AKIs - tho rare
to get AKI from nephrotic syndrome alone)
■ Chronic protein spilling may lead to third spacing of intravascular volume via mechanism similar
to loss of serum proteins in HRS described above
■ And / or may cause excessive volume loss via polyuria (as the H20 molecules may follow the protein into the intraluminal aspects of the nephron as a component of the urine filtrate, then stay there (not get re-absorbed) from the protein-associated increased osmotic pressure within
the lumen of the nephron), leading to polyuria and loss of H20 that way, may → intravascular hypovolemia, may → prerenal AKI
