6. AKI and CKD Flashcards
Acute Kidney Injury
• Loss of renal function, usually measured by a decline in the ____ ( rise in serum creatinine) that develops over a period of hours to days.
• Affects up to 5% hospitalized patients; 10-30% patients in ICU settings
• Often ____
• High mortality- up to 50% in some series
• Creatinine is a byproduct of muscle breakdown ○ Most commonly used indicator of kidney function in GFR • Complete kidney failure and require dialysis > high mortality despite advances in dialysis and critical care ○ Even if full kidney funciton in hospital; still risk of AKD, CKD and high mortality
GFR
reversible
AKI Classification
• Schemes that try to stage AKD • Biggest challenge in studying/reading research; lack of \_\_\_\_ defintion of AKD ○ Develop standardized shcemes; most are based on: § Changes in \_\_\_\_ § Changes in \_\_\_\_ • Not used \_\_\_\_, but in reported literature you'll see it
uniform
serum creatinine
urine output
Beyond creatinine: injury markers
• Changes in serum creatinine level; when it's rising and GFR is dropping > represents fairly advanced stage of kidney injury ○ Identify markers of \_\_\_\_ damage § \_\_\_\_ biomarkers shown to be indicators of early injury § Not ready for use yet, but in the future will be important
early
urinary
Causes of Acute Kidney Injury
• Most important slide she shows • Divides AKD into etiology ○ Prerenal § Situation where AKD due to decreased BF into the kidney (decrease \_\_\_\_ pressure into the kidney) ○ Postrenal § Situation where AKD due to \_\_\_\_ of urinary flow out of the kidney ○ Intrinsic § Direct damage to the various compartments to the renal parenchyma □ Compromised of: small vessels, arterioles, glomeruli and tubules and interstitium ® Pathologic processes that occur anywhere that cause AKD ○ Most common causes of AKD: \_\_\_\_ failure and \_\_\_\_ injury (acute tubular necrosis [intrinsic] due to ischemia or toxins)
perfusion
obstruction
prerenal
direct tubular
Renal Tissue Hypoxia
• Kidney is vascular • Sees 25% of CO • BF distribution within kidney is not even; most of the blood/oxygen is going to the \_\_\_\_ (glomeruli, filtration occurring here) ○ Much higher O2 tension in the cortex than the \_\_\_\_ ○ Tubules still in the medulla; \_\_\_\_ activity occurring here (ATP consumption) § Straight portion of \_\_\_\_; DAL (Na transport occurs) § Very vulnerable to decreased BF § Damage in setting of ATN or renal ischemia • Blood O2 level determined \_\_\_\_ ○ Lights depending on level of deoxy hemoglobin ○ Deeper levels are red/yellow § In \_\_\_\_ portions as opposed to the cortex
cortex medulla metabolic PT MRI medullary
Prerenal Failure- Causes
____ Depletion
- excessive diuresis, hemorrhage, GI losses, transcellular fluid accumulation (ascites, pancreatitis, burns)
Low ____
- cardiomyopathy, MI, pericardial tamponade, pulmonary embolism
Low ____Resistance - sepsis, liver failure
Increased ____
- liver failure, nsaids, calcineurin inhibitors, renal artery stenosis,
renal vein thrombosis
• Very common • Decreased perfusion into the kidneys, following a drop in BP • Septic shock ○ Vasodilation ○ \_\_\_\_
ECF volume cardiac output systemic vascular resistance renal vascular resistance hypotension
AUTOREGULATION
• Kidneys are good at AR • Drops in arterial BP > kidney maintains renal \_\_\_\_ and GFR to an extent ○ Has to do with mediators causing vasocon and vasodil at these aff/eff arteriolar beds that surround the glomerulus • Via AR > maintain renal BF and GFR to a point • But once arterial pressure drop below \_\_\_\_ > AR mechanisms fail > drop in renal BF and drop in GFR > \_\_\_\_ failur
BF
80
prerenal
Pathophysiology
dec RBF
dec flow of filtrate
inc Na reabsorption
dec GFR
inc reabsorption urea > creatinine
inc BUN/creat
• Rapidly \_\_\_\_ if restore renal BF • No damage to the tubules ○ Evidence by looking at urine sodium (will be \_\_\_\_), or a \_\_\_\_ BUN/creat ratio • Reestablish renal BF > raise BP, renal BF, GFR rapidly corrects
reversible
low
high
Postrenal Failure- Causes
• \_\_\_\_ • Urinary tract obstruction from renal pelvis down to the uretetha ○ Top down • Two functioning kidneys; unilateral obstruction > contralateral kidney can \_\_\_\_ > may not lead to AKD because of filtration/GFR in ongoing kidney ○ For AKD in obstruction: need \_\_\_\_ obstruction, or obstruction of a \_\_\_\_ functioning kidney
obstruction
compensate
bilateral
solitary
Postrenal Failure- Obstruction
Hydronephrosis seen on ____
• Renal ultrasound • Classic finding on a US: hydronephrosis ○ Calyxs are \_\_\_\_ and \_\_\_\_ bc of urine ○ Obstructive nephropathy can be rapidly \_\_\_\_ as long as you relieve the obstruction • Enlarge \_\_\_\_ is an e xample
ultrasound black dilated reversible prostate
Chronic Obstruction
• If obstruction goes on for long time > chronic \_\_\_\_ disease ○ Cortical loss of functioning renal \_\_\_\_ • This is with someone with CKD now
irreversible
parenchyma
AKI- Intrinsic Renal Disease
- glomeruli
- tubules/interstitium
- vessels• Pathophysiologic processes that can cause acute injury due to direct toxicity/inflam/damage to many parts of kidney
• Glomerular nephritis
○ ____
○ Lupus/vasculitis
• Small renal vessel
○ ____
○ Onion skinning
○ AKD in setting of malignant ____
§ Acute vascular injury in setting of high BP
• Tubular interstitial compartment
○ Lots of ____ cells > lymphos
§ Interstitial nephritis
§ Infalm disorder > seen in ____ reaction to medication
○ Acute tubular necrosis
§ Tubules that are injured > see in tubular CS > loss of cells, naked BM, debris, ____ cells into the tubular lumen
inflamed hyperplasia hypertension dark allergic apoptotit/necrotic
Intrinsic Renal Failure- Causes
Acute tubular injury (ATN)
-____: hypovolemic, cardiogenic, septic shock -Toxins: ____, contrast, myoglobin ~35%
Acute glomerulonephritis
- ____, Anti-GBM, ANCA associated diseases
Acute tubulointerstitial nephritis
- ____, intrarenal precipitation (uric acid, light chains)
Acute vascular nephropathy
-____, malignant hypertension, ____, thrombotic microangiopathy
• ATN most \_\_\_\_ cause of intrinsic AKD • Ischemia is the most common • Toxins can cause AKD ○ IV \_\_\_\_ ○ Myoglobin - endogenous toxin § Rhabdo: trauma with muscle crush § MG filtered by kidneys and cause toxic damage
ischemia aminoglycosides immune complex drug reaction vasculitis atheroembolism common contrast
Causes of Ischemic ATN
Generalized or localized reduction in renal BF
- Intravascular volume ____ and hypotension:
GI, renal, and dermal losses, hemorrhage
- congestive ____
- sepsis
- l____ failure
- Renal vascular dz-
renal artery thrombosis/ embolism/cross-clamping
- Medications-
____/ARB, NSAIDS, Calcineurin inhibitors
> > > ischemic ____ renal failure
• Causes of ischemic ATN ○ All same things that cause prerenal failure § Decreased perfusion into the kidneys □ Volume depletion □ HF □ Sepsis □ Liver failure § If insult is prolonged enough > can transition to ischemic damage of kidneys > \_\_\_\_ § Not clear where a patient lies on the \_\_\_\_ of prerenal to ATN
depletion heart failure liver ACEI acute
ATN
spectrum
Ischemic ATN- Pathophysiologic Processes
• Vascular Effects – \_\_\_\_ alterations – \_\_\_\_ cell injury • \_\_\_\_ Cell Injury • \_\_\_\_
hemodynamic
endothelial
epithelial
inflammation
Effects of AKI on arteriolar tone
• Vasculature in kidney that's damaged by prllonged ischemia ○ \_\_\_\_renal vasoconstriction in setting of hypoperfusion ○ IN normal > renal perf decreases > \_\_\_\_ of renal aff arterioles in order to maintain GFR ○ If kidney is ischemic bc of hypotension going on for long time > in setting of dec perf > increase renal \_\_\_\_ (opposite) § Increase \_\_\_\_ in SMC cells > inc sens to vasocontrictors § It perpetuates the problem > the \_\_\_\_
paradoxical dilation vasoconstriction Ca ischemia
Endothelial Injury in Ischemic ATN
• Sludging ○ CS of peritubular capillary and a tubule ○ In the PTC of ischemic kidney > upregulation of \_\_\_\_ molecules > sludging of \_\_\_\_ and RBCs > vascular \_\_\_\_ > perpetuates the\_\_\_\_ that causes further damage in kidney injury
adhesion
neutros
congestion
ischemia
Tubular Effects
• Tubular epithelium is \_\_\_\_ ○ Transporters on basal membrane, and different on the apical > \_\_\_\_ is critical in order for normal transport of all stuff the kidney must transport § Na, Bicarb, protons ○ NaK ATPase is ubiq expressed on \_\_\_\_ membrane ○ Integrins which keep epi on BM (\_\_\_\_membrane) ○ Ischemia reperfusion > disruption of cytoskeleton in cells and all proteins show in places they \_\_\_\_ be ○ Loss of \_\_\_\_ in tubular epithelium > impairment of Na reabsorption > inappropiate \_\_\_\_ (urine rich in Na) in setting of hypotension/prerenal failure ○ Tubule are damaged, cannot hold on Na, and lack of normal transport ○ Bc intergins arent anchoring cells > cells that shed off the BM and some are necrotic > induction of \_\_\_\_ § Some are viable cells that shed into tubular lumen and the ischemic kidney
basolateral basolateral shouldn't polarity wasting apoptosis
ATN
• \_\_\_\_ BM • Cells in \_\_\_\_ • Some tubular epi cells also look \_\_\_\_ ○ \_\_\_\_ phenomenom
naked
lumen
normal
patchy
Urine Sediment in ATN
• Urinalysis with someone with ATN ○ \_\_\_\_ casts ○ Cell debris that is filled in tubular lumens of nephron and excreted into the urine ○ Can see \_\_\_\_ casts (renal tubular \_\_\_\_ cells; intact) that are excreted in form of casts ○ Discrete solitary tubular epi cells into the urine
muddy brown granular
cellular
epi
Inflammation in Ischemic ATN
* Upregulation of \_\_\_\_ in ischemic ATN * Damaged epi release proinfl \_\_\_\_ > recruit inflam cells > cause further cell death
inflam
cytokines
Pathophysiology of Ischemic ATN
CHEKC ME OUT!
ya
The Repair Phase
• Kidney is good at \_\_\_\_ itself ○ If residual cells left bheind after insult > these viable cells can \_\_\_\_ and reproliferate and repop the tubular epi and regain \_\_\_\_ and function again ○ Can see full \_\_\_\_ in AKD
healing
dedifferentiate
polarity
recovery
Natural History of AKI
• Best case: ○ Full recovery ○ Patient has AKD > GFR recovers ○ \_\_\_\_ for some reason > high risk pop for further events • Red - worst case ○ Complete kidney failure > \_\_\_\_ • Variation in between ○ Someone had recovery but not as good as baseline > now has CKD > following a diff \_\_\_\_ • Or had CKD to begin with, and acute insult > \_\_\_\_ kidney disease
vulnerable
ESRD
trajectory
acute-on-chronic
Approach to the patient with AKI
• History and Physical Exam
– Hx: Events leading to changes in ____ or hemodynamic
status, exposures to ____
– PE: Volume and ____ status, ____, stigmata of emboli, ____ bladder
• Diagnostic Tests
– ____ indices , urinalysis – Radiographic studies
– ____
• Management
• \_\_\_\_ are most important ○ Rash > interstitial \_\_\_\_ due to drug ○ Bladder is full > large prostate and need a catheter
volume medications/toxins cardiovascular rash distended
blood + urine
biopsy
history/physical
nephritis
Urinalysis
- ____
- ____ stick
• Eachpadcontains reagents for a distinct chemical reaction• Most important test for AKD after physical/hisotry > ____
○ Cheap, quick
○ Sample of urine, and typical urinalsysi composed of two parts:
§ Dipstick
□ Tabs impregnated with various ____: tells blood in urine, leukos, blood, etc.
§ Spin the urine and examine what comes out in pellet
□ Look at the ____
□ What it looks like is hekpful: esp in ruling in the ____ renal processes
• Prerenal failure > hypotensive > give bag of IV fluid > GFR improves > urine will be ____ and not a lot of activity
○ Epi cell from skin in urine > not ____
○ Hyaline cast > not indicative of ____
§ Seen in volume depleted individuals
• RBC in urine sediment
○ Typical finding in ____(lupus, vasculitis, goodpasture)
• Cast of inside tubule
○ All have proteins that can form a matrix, start shedding cells > form casts
• Cast filled with WBC
○ Finding in someone with ____ due to a drug allergy
• Typical finding in ATN
○ ____ casts
○ And renal tubular ____ cells
micrscopy
dipstick
urinalysis
chemical
sediment
intrinsic
bland pathogneumoic patholgoy acute glomerular nephritis interstitial nephritis granular epi
Examples of Urine Sediments
Hyaline casts= ____
RBC CASTS + RBCS = ____
Granular casts/tubular epithelial cells= ____
WBC Cast +WBCS = ____
normal/prerenal
GN
ATN
in nephritis
AKI- Diagnostic Tests
- Radiographic Studies= Renal ____
- Biopsy:
Consider when there is concern for ____ disease, tubulointerstitial nephritis, vasculitis, or cause ____
• Not often used • But used in situations where the urinealsysis indicates issues • Local \_\_\_\_, needle, get some tissue etc. • Renal ultrasound ○ Rule out \_\_\_\_
ultrasound glomerular uncertain anesthesia obstruction
AKI- Treatment
- ____
- Support- optimize ____ status, maintain blood pressure, treat infection, provide nutrition, dose drugs appropriately, dialysis if necessary
- Specific therapy?• No ____
○ For ischemic ATN > no specific therapy; prevent from happening
§ Keep people volume replete; prevent hypotension; don’t give kidney toxic ____ or ____ die if already have some degree of kidney failure
○ In setting of ATN > support patient and hope things get better
§ Dialsysis until kidney function recovers
□ Acute dialysis catheter in the ____
□ Used for AKI
prevention volume specific therapy medications IV contrast jugular vein
AKI -Conclusions I
• AKI refers to loss in renal function that occurs over ____ to days
• AKI is often ____ but is associated with high ____ and may lead to ____.
• The causes of AKI can be classified as pre- renal, intrinsic renal, and post-renal
• ____ failure and ____ renal failure due to ATN are the most common causes of AKI in hospitalized patients
hours reversible mortality CKD pre-renal intrinsic
AKI- Conclusions II
- Ischemic ATN is a dynamic process involving the vasculature and the tubules in a complex interaction that is eventually followed by a ____ process that can restore normal morphology and function.
- The cause of AKI can usually be as certained by performing a careful ____, physical and urinalysis along with urine ____ and renal ultrasound.
- Management of AKI due to ATN remains primarily ____.
repair
history
chemistries
supportive
Chronic Kidney Disease- Definition
• Abnormalities of kidney structure or function, present for >____ months
Markers of Kidney Damage o \_\_\_\_ o Urine sediment abnormalities o \_\_\_\_ and other abnormalities due to tubular disorders o Abnormalities detected by histology o\_\_\_\_ abnormalities detected by imaging
Diminished GFR
o GFR CKD
3 albuminuria electrolyte structural 60 GFR
CKD or “CKDs”
• CKD is a ____ and not a single disease – Analogous to ____
• While the traditional definition of CKD is based on structural and/or functional changes, they can be the result of many varied pathogenic pathways such as:
– ____ diseases
– Glomerular diseases
– ____ diseases
– Obstruction
• SO many things can lead to CKD ○ The things for \_\_\_\_ can lead to CKD also
syndrome heart failure tubulointerstitial vascular AKD
Tools to Assess for CKD
• Focus on changes in \_\_\_\_ and filtration/clearance function of kidney ○ Serum creatinine marker of kidney filtration § Most commonly take this and the level is inserted into a formular that takes into account person age and gender > estimated \_\_\_\_ ○ Can measure true GFR via \_\_\_\_ tests § Cumbersome ○ 24 hour urines § Collect creatinine and compare to creatinine in blood > clearance calculation > use as indicator of what \_\_\_\_ is □ Creatinine is not a \_\_\_\_ marker of filtration rate • Barrier abnormalities ○ \_\_\_\_ § Albumin/protein in urine
GFR GFR isotope GFR perfect proteinuria
Glomerular pathology
- normal glomerulus
- glomerulosclerosis
• Glomerulosclerosis ○ More \_\_\_\_ ○ Scar ○ Losing normal capillary \_\_\_\_ § Fibrosis surrounding ○ Sign of chronic damage § High \_\_\_\_, damage, etc
pink
lumen
BP
Interstitial pathology
- normal interstitial compartment
- tubular atrophy with interstitial fibrosis
- CKD where lose a lot of ____
- ____ tissue in between
- Tubules are ____
- Tubules have ____ out
- Classic finding of CKD
tubules
fibrotic
atrophic
dropped
Radiographic Imaging
* \_\_\_\_ kidneys and \_\_\_\_ * Would rarely biopsy bc it would look like prior slides > doesn't tell us how patient got there * Manifestation of chronic, irreverisble KD
small
atrophic
NKF CKD Clinical Stages
• 1-5 determined by estimated GFR is • Any indication of kidney damage • Normal GFR (>\_\_\_\_ ) but evidence of \_\_\_\_ (proteinuria, cystic kidneys) ○ Stage I • Decreased GFR (\_\_\_\_ ) with markers of dmagae ○ Stage II • Stage III ○ GFR bt \_\_\_\_ • If GFR less than 60 for >3 mo you have CKD - don't have to see \_\_\_\_ in urine or any other damages • Stage IV ○ GFR bt \_\_\_\_ • Stage V ○ GFR
90 kidney damage 60-89 30-60 protein 15-30 15
The Burden of CKD in the US
• More than 10% of adults in the US, more than 20 million people, may have CKD*
• The prevalence of CKD grows with age
– By age 60 the percentage of Americans with
CKD exceeds ____%
• Very common • As people get older > more \_\_\_\_ • Stage 5 ○ ESRD ○ Just the tip of the \_\_\_\_ • People with other stages > in the millions ○ Why don't we have millions > \_\_\_\_ is so high so they're not living to get stage 5
20
prevalent
icerberg
mortality
Endstage Renal Disease- ESRD
CKD sufficiently severe to require replacement of renal function ( usually GFR ~ ____ cc/min)
• ____
• Peritoneal dialysis
• ____
• ESRD > kidney replacement therapy > stage 5 ○ Refer to people who need dialysis or kidney transplants • GFR of 15 that don't require \_\_\_\_
10
hemodialysis
transplantation
kidney transplantation
Causes of ESRD
Diabetes is, by far, the leading cause of ESRD
• \_\_\_\_ and \_\_\_\_ most common causes • Cystic is most common \_\_\_\_ form of kidney disease -- lowest \_\_\_\_ rate • Rate of rise has \_\_\_\_ down; but actual number (people living \_\_\_\_) > more people that have adv kidney failure from diabetes and HTN
diabetes HTN inherited affect slowed longer
Expected Remaining Lifetime: General Population vs Dialysis vs Transplant
• Life expectancy after surgical resection for colon cancer ~ ____ yrs; • Life expectancy after resection for lung cancer ~ ____ yrs
• Short lifespan • Red is dialysis • Green is transplant • Blue is US pop • Young person on dialaysis has same predicted lifespan as someone in their \_\_\_\_ ○ Middle aged person on dilaysis > better to get diagnoses of certain \_\_\_\_ then have diagnosis of ESRD and require renal replacement therapy • Transplatn gives better longevity • More to gain in \_\_\_\_ years • Transplatn vs dialsyis becomes less obvious with people of \_\_\_\_ age
7
6
70-80
cancers
younger
advanced
Consequences of CKD- Uremic Syndrome
- ____
- Cardiovascular Disease
- Hematologic Abnormalities- ____ and Bleeding
- Gastrointestinal Disease and Malnutrition
- ____
- Sexual Dysfunction and Infertility
- ____ Disorders
HTN
anemia
metabolic acidosis
bone and mineral
Hypertension a Cause and
Consequence of CKD Develops
Early in the Course of Disease
* \_\_\_\_ is a cause of kidney disease * In setting of kidney failure we see worsening \_\_\_\_ * Once GFR gets to stage IV/V > every patient has \_\_\_\_ no matter the cause of their kidney failure * Controlling HTN can \_\_\_\_ down progression of disease
HTN
HTN
HTN
slow
eGFR and CVD Events
• \_\_\_\_ is common in CKD ○ #\_\_\_\_cause of death • By GFR ○ Even people with moderate damage (GFR \_\_\_\_) § 4x more likely to have CV event than soemoen wtihout kidney failure ○ CV events \_\_\_\_ as GFR decliens
CVD
1
30-60
increase
Cardiovascular Mortality in Dialysis Patients and the General Population
* ESRD > very \_\_\_\_ CV mortality * Higher than the general pop * Young person on dialysis has just as high of a risk of a CV event as someone in their \_\_\_\_
high
80’s
Cardiovascular Diseases in Patients with CKD
- ____ disease
- Left ventricular hypertrophy(50-75%)
- ____(70-100%)
- Congestive heart failure
- ____
- Sudden death
- ____(6-10%)
- Pericardial fusion
- Infective ____• LVH
○ Very common in CKD population > ____ HF
ischemic coronary artery HTN arrhytmias pericarditis endocarditis hypertensive
Risk Factors for Cardiovascular Diseases
Traditional • \_\_\_\_ • Hyperlipidemia • \_\_\_\_ • Tobacco use • Physical \_\_\_\_ • Menopause • \_\_\_\_ age • Metabolic syndrome
Unique to CKD • \_\_\_\_ • increased Homocysteine • \_\_\_\_ factors • Obesity • Intake of \_\_\_\_ • Hyperparathyroidism • \_\_\_\_ toxins • Inflammatory state • \_\_\_\_ dz
HTN
hyperglycemia
inactivity
older
anemia thrombogenic calcium uremic periodontal
Calcium Deposition at Left Main Coronary Artery
• CAT scan of a heart • Seen in kidney patient • \_\_\_\_ artery ○ Not contrast, it's calcium! ○ Can play in a role in poor CV outcomes that we see
calcified coronary
Gastrointestinal System
- Loss of appetite > less protein intake, ____ loss
- Taste: altered ____, ____ taste in the mouth
- Mouth ulcers: mucosal irritation due to ____
- Uremic fetor: bacterial conversion of urea to ____ in the oral cavity
- Esophagitis and motility problems-alteration in ____
- GI bleeding: ____ mucosal abnormalities, ____ of the GI tract, peptic ulcer
- ____ disease and constipation• Most common thing we see as renal fucntion declines > loss of ____
• Dysgeusia > food tastes poorly
• Uremic fetor
○ Ammonia smell of breath
○ Urea converted to ammonium by bacteria in mouth
• GI bleeding is common
○ Angiodysplasia > GI bleeding that contributes to ____
weight sensation metallic ammonia ammonium peristalsis superficial angiodysplasia diverticular
appetite
anemia
Relationship Between Nutritional Status and GFR
• Trend in albumin ○ Commonly used nutritional indices ○ As GFR declines > trend in \_\_\_\_ albumin ○ Higher in \_\_\_\_ (solid)
decrease
males
Anemia in CKD
Decreased production of ____
- ____ growth factor produced in the kidney that is primary stimulus for erythropoiesis
____ erythrocyte life span
____ of erythropoiesis accumulating in
uremia/EPO resistance
Secondary causes- ____, B12, ____ deficiency, blood loss, inflammation
• Not as common due to increased treatment • Multifactorial ○ Primary cause: decreased production of \_\_\_\_ • Uremic \_\_\_\_ > shortened erythrocyte life span
erythropoietin (EPO) glycoprotein shortened inhibitors iron folate EPO toxins
Consequences of Anemia in CKD • \_\_\_\_/dizziness/dyspnea • Left ventricular dilatation and diastolic dysfunction • Increased \_\_\_\_ • Cognitive impairment • Intractable \_\_\_\_ • Impairment of sexual function
* Uremia symptoms were more anemia symptoms * A lot of itching > \_\_\_\_ * Decreased \_\_\_\_ and infertility
fatigue hospitalizations itching priritis libito
Treatment of Anemia in CKD
• Erythropoiesis Stimulating Agents -recombinant human ____: epogen,
procrit, aranesp, etc
• Iron ____
• B12/folate
• Transfusions- try to avoid if patient is ____candidate
• ESA were available in 80's ○ Before 80's patients were being transfused all the time ○ Now these are commonly in people with predialysis who end up anemic § Usually people in \_\_\_\_ CKD develop anemia § Once on dialysis > always get an \_\_\_\_ § Avoid transfusions now > \_\_\_\_ risk, also bc the patients can get sensitized > patient can develop ab's and make it challenging for person to get kidney in future • Iron deficiency ○ GI bleeding ○ Dialysis look a lot of \_\_\_\_ in tubing ○ Once on ESA > consume a lot of \_\_\_\_
erythopoieint supplements transplant stage 3 ESA infection blood iron
Hematopoietic System in CKD: Increased Bleeding
- ____: main determinant of altered bleeding in uremia
- Dysfunction of platelet ____
- Dialysis of uremic serum appears to remove “some ____” that causes the binding defect of the ____ platelet membrane glycoprotein receptor complex• Easy bleeders for CKD
○ Not due to coagulation, but due to platelet ____
• Receptors on platelets, the uremic mileu interferes with the binding of the GP receptors on surface of platelet with vWF which is on surface of epi > impaired ____ and activation of platelets that contirbute to bleeding risk
platelets aggregation compound IIb-IIIa dysfunction adhesion
reatment Options for Uremic Bleeding Disorders
• Correction of anemia with rHU-EPO
– ____ and vascular-endothelial cell effects
– RBCs express glycoproteins on their cell surface that are involved in hemostasis
• DDAVP- increased endothelial cell release of ____
• Conjugated estrogens
• Transfusions of ____
• Dialysis: removing “toxins”
• Someone with profound anemia > rheologic anemia > laminar flow is affected • DDAVP = \_\_\_\_ ○ Increase the release of VWF by endo cells ○ Given to someone who gets all their teeth and won't stop \_\_\_\_ ○ Won't help repeatedly due to \_\_\_\_ § Helps in \_\_\_\_ management of bleeding • Adequately \_\_\_\_ patients won't bleed as much
rheologic VWF cryoprecipitate vasopressin bleeding tachyphylaxis acute dialyzed
Sexual Dysfunction in CKD
Female Patients • Delayed sexual \_\_\_\_ • Amenorrhea • \_\_\_\_ • Conception rare • Spontaneous \_\_\_\_ • Decreased libido
Male Patients • Delayed sexual maturation • Decreased \_\_\_\_ • Partial or total impotence • \_\_\_\_ • Atrophic testes • \_\_\_\_ or azoospermia • Priapism
• Advanced CKD dialysis patients have lower libido and have low fertility • Complicated for women on dialysis to carry babies to full term • With more adequate dialysis > now that we have \_\_\_\_ dialyzing and anemia treated > better fertility ○ Compared to the \_\_\_\_ times a week dialysis > the standard regimen in the US
maturation
meorrhagia
abortion
libido
gynecomastia
oligospermia
consistent
3
Pregnancy in Women with CKD
• Preeclampsia (____, proteinuria, ____ and sometimes coagulation and liver abnormalities) and fetal growth ____ occur more frequently than in normal individuals
• Prematurity, low ____ birth and congenital anomalies leading to increased perinatal morbidity and mortality
* Risky for the mother and fetus * Risk gets higher as renal function is \_\_\_\_ * More rapid deteriation of renal function in setting of pregnancy
hypertension edema retardation weight worse
CKD-Mineral and Bone Disorder
• Abnormalities of calcium, phosphorus, PTH
and vitamin D metabolism
• Abnormalities of bone ____, mineralization, volume, linear growth and strength
• V____ and soft tissue calcification
* Increased risk of \_\_\_\_ * \_\_\_\_calcification (coronaries) is part of this mineral-bone disorder
turnover
vascular
fractures
extravascular
Pathophysiology of Secondary Hyperparathyroidism
• Hormonal changes in CKD • As GFR goes down: ○ Accumulation of \_\_\_\_ ○ Kidney is final step where vitamin D is activated > less active \_\_\_\_ ○ Both of things contribute to low \_\_\_\_++ in blood • High phos, low Ca++, low vitamin D levels > feeding back on parathyroid > increasing \_\_\_\_ ○ Secondary hyperparathyroidism ○ High PTH tries to compensate for these things; but ultimately high levels of PTH > negative consequence (systemic) > \_\_\_\_ issues
phosphate vitamin D Ca PTH skeletal
Secondary Hyperparathyroidism
• Hand x-ray ○ Radial surface of digits is being eaten away due to high PTH § Stimualtes \_\_\_\_ activity and increases bone turnover • \_\_\_\_ spine ○ Trabecular bone within vert bodies gets eaten away > \_\_\_\_ edges • Aorta ○ C\_\_\_\_ ○ Vascular manifestations of imparied mineral manifestation • \_\_\_\_ tumor ○ Long bone > \_\_\_\_ > hole from all resorption > increased fracture risk
OC jersey rugby scleoritc calcified brown osteoclatoma
Treatment of CKD-MBD
- Phosphate Binders- ____, sevelamer, lanthanum , ferric citrate
- Vitamin D analogs- ____, paricalcitol, doxercalciferol
- Calcimimetics- ____
- Parathyroidectomy• Constantly measuring phosphate, PTH, Ca and keeping things within a certain range
• Phosphate binders
○ Comprised of calcium, or can be ____ that bind phosphate within the food > not reabsorbed into BS and don’t get ____
○ Phosphate in everything
§ More so in ____ products
§ Less in brown sodas, chocholate, nuts
§ A lot of preservatives too
§ AS approach dialysis > everyone msut be on ____ binders > compliance is ____
□ Must take a lot of tablets while eat
• Vitamin D to suppress ____
• Calcimimetics
○ Mimic calcium and can turn off PTH at the level of the ____
○ Calcium-sensing receptors on the PT gland cells > ____ changes in receptors and turn off PTH secretion
• Parathyroidecctoy (sub-total - remove ____ out of 4 parathyroid glands)
○ When the ____ fail
calcium acetate
calcitriol
cinacalcet
resins hypophosphatemic dairy PO4 poor PTH gland conformational 3 medicines
Renal Replacement Therapy
• Initiated at the onset of uremic symptoms- GFR usually ~ \_\_\_\_ cc/min • Options: – Dialysis: \_\_\_\_ or peritoneal dialysis – Transplantation – Palliative/conservative care
• All aggressive management won't help as GFR gets low > \_\_\_\_ syndrome ○ NO longer want to eat ○ Losing weight ○ Vomiting ○ Itching ○ Despite keeping Hb good and BP good and diuretics to keep the fluid out • Time to the RRT ○ Happens when GFR is 10cc/min, but very individual § Some people go down to 5-6 and they still feel \_\_\_\_ □ Need to make sure patient gets \_\_\_\_ □ Have gone for transplant \_\_\_\_ if appropriate and on the list □ Know what kind of \_\_\_\_ they want and we have made preparations □ Or advanced age or poor quality of life > dialysis would not offer the patient much > more \_\_\_\_ care
10 hemodialysis uremic good education evaluation dialysis palliative
Two major types of dialysis
Distinguished by the semipermeable membrane used:
– Peritoneal Dialysis: ____ membrane
– Hemodialysis: ____ (natural) or ____ membranes
• Trying to alter composition of blood by allowing diffusion to occur across the semipermeable membrane • Hemodialysis ○ Synthetic membrane in dialyzer canister; blood pumped through patient thorugh dialyzer (filled with hollow fibers, and blood is inside of fibers which is made of semiperm membranes and outside of fibers is dialysis solution and allowing diffusion of all stuff we want to remove from blood that go into the dialsysi solution and sometimes we allow it to go from solution into blood an dblood pumped back into the patient • Peritoneal ○ Same process of perfusion ○ Dialysis membrane is our own peritoneal membrane § Allowing diffusion to occur across peritoneal \_\_\_\_ into a dialysis solution; have a catheter placed in \_\_\_\_ space and the peritoneal is filled with dialysis and allowing diffusionf rom blood of patient viat periotneal cpailarys to diffuse into the dialysis solution and drained and fresh solution is put back in
peritoneal cellulosic synthetic capillaries peritoneal
RRT OPTIONS FOR END-STAGE-KIDNEY-DISEASE
- IN CENTER DIALYSIS(~89%):
- Daytime Chronic in-center hemodialysis (~88%)
- Typically ____ hours 3 times per week
- In center nocturnal Hemodialysis (~1%)
- Typically ____ hours 3 times/week
- HOME DIALYSIS:(~11%)
- Home ____:(~1%)
- Day time or nocturnal 3-7 times per week
- ____ Dialysis (~10%)
- Palliative care/Conservative measures
• In center ○ Most common in the US ○ Hemodialysis is occurring here ○ Treated 3x a week § 3-4 hours at a time § Unnatural thing we do • More popular > go to center with staff but they sleep in dialysis unit over night ○ 3 nights per week ○ Longer period of time ○ Longer treatment and more \_\_\_\_ and mimicking what their own kidneys used to • Home dialysis ○ More \_\_\_\_ ○ Peritoneal is always a home dialysis ○ Done every day § Go traveling they take it with them ○ Hemodialsysi can be done at home § Stick themselves to access vasculature § Becoming more popular § Takes a lot of \_\_\_\_ § Benefit: patient can dialyze more \_\_\_\_ on their own terms and schedule § Do more days week, \_\_\_\_ treatment and they feel better with more frequent dialsysi
4 8 hemodialysis peritoneal gentle empowering training frequently longer
ARTERIOVENOUS FISTULA
• Vascualr access • Hemodialsysi need two needles ○ Draw blood from patient, and deliver to patient ○ Need very high \_\_\_\_ ○ Cannot be sticking a patient with two needles 3 days a week > need to create a large vascular conduit in order to comfortably with little trauma do hemodialysis in these patients ○ Best access: AV fistula § Surgically created connections bt an \_\_\_\_ and a \_\_\_\_ § Radio-cephalic fistula □ Radial artery to cephalic vein § Doesn't normally \_\_\_\_ § Creates high flow through the vein and the verin arterializes > easie rot sitck □ Can support two large caliber needles □ If someone can get an AV fistula and if it develops > can be the only \_\_\_\_ that this person needs for their entire kidney life □ Push to create these \_\_\_\_; can takes months to mature and develop □ Can be done in upper arm ® Brachial artery to cephilic vein; take months to develop □ When kidney function is \_\_\_\_ (GFR) > evaluate > get fisutal formation early so when time comes they can have this for their dialysis
blood flows artery vein exist access early 20
Dialysis graft
• Second best thing to have is a graft • Synthetic material under the skin that bridges artery to vein • Done in someone without great \_\_\_\_ ○ Common • Sticking the graft under the skin • Only a couple weeks to place and let heal • More c\_\_\_\_and \_\_\_\_ than the fistulas ○ They \_\_\_\_ • Foreign body > scar tissue forms and get \_\_\_\_
veins complications upkeep clot infected
HEMODIALYSIS CATHETER
Advantages of Dialysis Catheters:
May be used ____ following successful placement.
Particularly useful in patients presenting with:
-____ injury
-Newly discovered End-stage-
kidney-diease
-Sudden failure of an existing
____ access
-Sudden failure of Peritoneal Dialysis
vUse until a permanent fistula or graft is ready
Disadvatages:
Infection-____
____ veins
• Don't want to resort to catheters ever! • Temp hemodialysis catheter that's tunnel under skin into IJV • Put in as \_\_\_\_ and used right away when come out of radiology • High risk: ○ Infection ○ Endocarditis ○ Blot \_\_\_\_ ○ High morbidity and mortality • \_\_\_\_ if patient has to use catheter
immediately acute kidney vascular bacteremia damage
emergency
clots
fail
Peritoneal Dialysis Catheter
* Soft silicone catheters that are surgically \_\_\_\_ in belly * Stay there * Removed if unneeded * Patients learn how to \_\_\_\_ * Take a \_\_\_\_ * Can get \_\_\_\_ also
implanted
clearn
shower
infected
Kidney Transplantation
• Do not remove old kidneys > they \_\_\_\_ • Sewn into \_\_\_\_ circulation in the extraperitoneal area ○ Iliac fossa ○ Ureter drains into the patients own \_\_\_\_
stay
iliac
bladder
Goals of Kidney Transplantation
IMPROVE PATIENT QUALITY OF LIFE – sense of \_\_\_\_ – dietary/ fluid restriction – \_\_\_\_ and self-control – employment
INCREASE LONGEVITY IN ESRD PATIENTS
– decreased ____
– reduced mortality
* Way to go if the patient is a good candidate * Better for \_\_\_\_ people; more to gain rather than staying on dialysis * Return of \_\_\_\_
well-being flexibility morbidity young fertility
Life Expectancy for Patients with Stage 5 CKD, Dialysis vs Transplant
• For every age group: \_\_\_\_ offers greater life expectancy than dialysis ○ In \_\_\_\_ and non-diabetics • More life to gain for \_\_\_\_ than older people ○ Still done in older > no age \_\_\_\_ • Healthy kidney failure patient ○ No active \_\_\_\_ ○ No \_\_\_\_disease ○ No active \_\_\_\_, cirrhosis etc.
transplant diabetics young cut-off malignancies VC ischemia
Two Types of Kidney Transplants
- Living Donor
- Deceased Donor• Deceased donor
○ Waiting list
§ Can be placed when GFR hits ____; don’t have uremia yet, but the average wait for a kidney off the WL is ____ years > get patient on WL early, assuming they’ve accumulated time; still unlikely that by time person needs dialysis that they have had name come up for kidney transplant, but there’s still years to wait
• Living donor
○ ____ situation
○ Better quality kidneys
○ Done in light of day preemptively
§ ____ for everyone
○ Best outcomes
• Paired exchange
○ Donor that wants to give; but cross-match is ____, but person still wants to donate > donor can donate to someone else, and maybe that someone else has someone that’s ____ for you
○ Done in a systematic way > all ____ now
§ More and more popular now > get people off the WL and increase the ____ of transplantation
20 4-5 ideal convenient positive right regulated rate
Summary- CKD
• CKD is a ____ problem
• Burden of disease associated with CKD/ESRD is great- multitude of clinical problems that affect overall health status, quality of life and mortality
public health
