6. AKI and CKD Flashcards by J L

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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Ischemic ATN- Pathophysiologic Processes

• Vascular Effects
– \_\_\_\_ alterations 
– \_\_\_\_ cell injury
• \_\_\_\_ Cell Injury 
• \_\_\_\_

hemodynamic
endothelial
epithelial
inflammation

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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

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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

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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

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ATN

• \_\_\_\_ BM
• Cells in \_\_\_\_
• Some tubular epi cells also look \_\_\_\_
	○ \_\_\_\_ phenomenom

naked
lumen
normal
patchy

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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

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Inflammation in Ischemic ATN

* Upregulation of \_\_\_\_ in ischemic ATN
* Damaged epi release proinfl \_\_\_\_ > recruit inflam cells > cause further cell death

inflam

cytokines

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Pathophysiology of Ischemic ATN

CHEKC ME OUT!

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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

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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

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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