18 Chronic Kidney Disease Flashcards
1
Q
Definitions
- Kidney damage
- Chronic kidney disease (CKD)
- End stage renal disease (ESRD) or kidney failure
- Uremia
A
- Kidney damage
- Structural or functional abnormalities of the kidney > 3 months
- Initially: w/o decreaed GFR
- Over time: decreased GFR
- Markers of kidney damage
- Ex. proteinuria, polycystic kidneys, hx of kidney transplant, etc.
- Abnormalities in the composition of the blood or urine
- Abnormalities in imaging tests of the kidney
- Structural or functional abnormalities of the kidney > 3 months
- Chronic kidney disease (CKD)
- Decreased GFR or kidney damage
- End stage renal disease (ESRD) or kidney failure
- Severely decreased renal function (GFR < 15 ml/min/1.73m2)
- Requires renal replacement therapy (i.e. hemodialysis / peritoneal dialysis or transplant)
- Uremia
- Signs & symptoms attributable to advanced reanl failure or ESRD
2
Q
Stages of CKD
- Stage 1
- Stage 2
- Stage 3
- Stage 4
- Stage 5
- CKD
- Very significant independent risk factor for mortality & morbidity
- How we define/stage CKD
A
- Stage 1
- Kidney damage (structural or functional) with normal or ↑ GFR
- GFR > 90
- Stage 2
- Kidney damage (structural or functional) with mild ↓ GFR
- GFR = 60-89
- Stage 3
- Moderate ↓ GFR
- GFR = 30-59
- Stage 4
- Severe ↓ GFR
- GFR = 15-29
- Stage 5
- Kidney failure
- GFR < 15 or dialysis
- CKD
- Stages 3-5
- Very significant independent risk factor for mortality & morbidity
- Proteinuria
- How we define/stage CKD
- Albuminuria
- Reduced eGFR (< 60 ml/min/1.73m2)
3
Q
Measurement & assessment of GFR
- Commonly used indicators of GFR in clinical practice
- Plasma creatinine vs. GFR
- Creatinine production varies with…& is influenced by…
- Take home
A
- Commonly used indicators of GFR in clinical practice
- Serum creatinine and blood urea nitrogen (BUN) concs
- Lab measurement of creatinine and urea is accurate and reliable, but normal values may vary from lab to lab
- Plasma creatinine vs. GFR
- Semi-logarithmic relationship
- Small values (steep part of the curve): a relatively small change in creatinine indicates a large change in GFR
- Large values: a large change in creatinine reflects only a small change in GFR
- Creatinine production varies with…& is influenced by…
- Muscle mass
- Changes in lean body weight over time influence the serum creatinine level
- Age, sex, race influence muscle mass
- Muscle mass
- Take home
- All of these are reasons why an eGFR is preferred in estimating renal function
4
Q
Etiology & natural history of CKD
- Most chronic nephropathies
- Rate of decline
- Electrolyte homeostasis, causes of progressive decline in function, and manifestations of kidney failure
A
- Most chronic nephropathies demonstrate inexorable progression to kidney failure
- The rate of decline ≈ 7-12 ml/min/year in those with untreated chronic nephropathies such as diabetic nephropathy
- Electrolyte homeostasis, causes of progressive decline in function, and manifestations of kidney failure
- Similar enough across the dif pathologies
- –> common underlying routes to progression, symptoms, and (hopefully) amelioration of CKD
5
Q
Prevalence of CKD, risk factors for development, & progression
- Prevalence of CKD
- Risk factors
- CKD is largely a disease of…
- Comorbidities
- Majority of pts with CKD
- Prevalence of ESRD
A
- Prevalence of CKD
- ~14.7% of the US adult population has some form of CKD
- 30x as many pts have CKD than ESRD
- >75 million have an increased risk of developing CKD
- Risk factors
- CKD is largely a disease of older adults
- Higher rates of comorbidities + age related decline in GFR
- GFR decline of ~8ml/min for each decade after 40
- Comorbidities
- DM
- HTN
- Dyslipidemia
- Obesity
- CKD is largely a disease of older adults
- Majority of pts with CKD
- Not aware, even those with an eGFR of 15-30 ml/min/1.73m2
- No clear, early, identifiable signs
- Increae in creatinine is often subtle
- Prevalence of ESRD
- Increasing rapidly
- Will continue for the next few decades
- Mortality
- After ESRD is reached (dialysis), mortality rate is very high
- Cost
- > $20 billion
- Qualtiy of life
- Burden on pt & families comparable to other devastating illnesses
6
Q
Risk factors for CKD
- Non-modifiable
- Modifiable
A
- Non-modifiable
- Older age
- Black race
- Black > native americans > hispanics > asians / pacific islanders
- Genetic predisposition
- Prematurity
- Important for screening purposes & for studying CKD progression
- Modifiable
- HTN
- Diabetes
- Obesity
- Dyslipidemia
- Hyperuricemia
- Smoking
- Heavy consumption of analgesics
- Improtant for understanding the pathophysiology of CKD & possible options for intervention & therapy
7
Q
Pathophysiology of progression of renal disease
- CKD is characterized by…
- Renal adaptation –> maladaptive processes
- 2 major consequences
- Short term –>
- Long term –>
- Remnant kidney animal model
- Glomerular capillary HTN is mediated by…
- RAAS primary mediators
A
- CKD is characterized by…
- Loss of functioning nephrons (not decreased output/function of the same number of nephrons)
- Renal adaptation –> maladaptive processes
- 2 major consequences
- Elevated glomerular pressure –> hyperfiltration by remaining nephrons
- Glomerular / tubular growth –> increased wall stress/inflammation –> hypertrophy
- Short term –> increased single nephron GFR –> hyperfiltration
- Long term –> increased glomerulosclerosis & tubular atrophy
- 2 major consequences
- Remnant kidney animal model
- Remove one kidney & large fraction of other kidney –> decreased nephron mass
- –> increased RPF & GFR in remaining nephrons
- –> glomeruli: increased blood flow, filtration rate, & size
- Glomerular capillary HTN is mediated by AII
- ACE-Is or ARBs –> AII blockade –> prevents glomerular HTN
- Increase renin mRNA synt –> increase DNA synth –> mesangial cells multiply, epithelial cells hypertrophy, epithelial foot processes increase in #, & glomerular capillary length increases
- RAAS primary mediators
- AII, IGF-1, PDGF, prostaglandins, RANTES, endothelin, & AVP
- Modulate renal cell growht in culture &/or circulating blood levels after nephrectomy
8
Q
Glomerulosclerosis
- Most pts have progressiv ekidney disease due to…
- First stage
- Second stage
- Third stage
A
- Most pts have progressiv ekidney disease due to…
- HTN
- Diabetes
- Other chronic glomerulonephropathy
- First stage: e__ndothelial injury & inflammation
- Damaged endothelium loses its anticoagulation, anti-inflammatoyr property
- Endothelium becomes primed for the proliferative stage
- Second stage: proliferation
- Kidney damage is characterized by stretched epithelial cells & proliferated/dedifferentiated mesangial cells
- Third stage: fibrosis
- Hyaline material accumulates int he mesangium & subendothelial regions of the glomerulus
- Hyaline material eventually –> collapse of capillaries (glomerulosclerosis)
9
Q
CKD pathophysiology take home points
- 2 major processes important for CKD progression
- These events eventually lead to…
- RAAS inhibition
A
- 2 major processes important for CKD progression
- GLomerular hyperfiltratoin
- Glomerulra hypertrophy
- These events eventually lead to…
- Fiborsis & sclerosis of glomeruli
- RAAS inhibition
- Prevent development of glomerular HTN & subsequent CKD progression
10
Q
Strategies to slow CKD progression
- Early diagnosis & treatment
- (1) Treat underlying causes
- (2) Control BP
- BP goals
- Urine albumin < 30 mg/ 24 hrs
- Urine albumin > 30 mg / 24 hr
- Risk of progression of CKD is modified by…
- Antihypertensives
- BP goals
- (3) Protein intake
- (4) Smoking cessation
- Nicotine
- Tubuloxic effect
- Vascular effects
- Bottom line
- (5) Nephrotoxins
- Most concerning
- Others
- AKI vs. CKD
A
- Early diagnosis & treatment
- Interventions slow progression of, but don’t reverse, kidney disease
- May help pt avoid dialysis, transplant & kidney failure complications
- Optimal treatment can slow rate of progression from 10 to 2-4 ml/min/year
- Interventions slow progression of, but don’t reverse, kidney disease
- (1) Treat underlying causes
- Identify reversible factors
- Ex. volume depletion, uncontrolled HTN, obstructive uropahty, nephrotoxins
- (2) Control BP
- BP goals
- Urine albumin < 30 mg/ 24 hrs: < 140/80
- Urine albumin > 30 mg / 24 hrs: < 130/80
- Risk of progression of CKD is modified by proteinuria
- Antihypertensives: ACE-Is & ARBs
- Block AII –> decrease glomerular capillary HTN –> decrease proteinuria –> decrease AII fibrosing effects
- Delay progression + cardiovascular benefits
- Don’t ever discontinue
- Side effects: increased creatinine, increased K, angioedema, & cough (ACE-I only)
- BP goals
- (3) Dietary protein restriction
- Decreased protein intake –> decreased hyperfiltration –> slowed progression
- (4) Smoking cessation
- Nicotine
- Increases GFR, urine flow, & Na excretion
- Increases catecholamines, cortisol, & aldo
- Tubuloxic effect
- Increased excretion of NAG & impaired cation transport
- Vascular effects
- Increased platelet aggregation & vasoconstrictor prostaglandins
- Decreased vasodilatory prostaglandins
- Endothelial cel linjury & impaired endothelial cell-dependent vasodilation
- Bottom line
- Tobacco potentiates GFR loss & can cause/worsen proteinuria
- Nicotine
- (5) Avoid nephrotoxins
- Most concerning: NSAIDs & herbal meds
- Others: tacrolimus/prograf/cyclosporine, aminoglycosides, amphotericin, colistin, & IV contrast
- AKI –> CKD & CKD –> AKI
11
Q
Cardiovascular disease (CVD)
- Cause of disparity b/n # of pts receiving renal replacement & # w/ CKD
- CKD vs. CVD
- Traditional risk factors
- Non-traditional risk factors
- Both traditional & non-traditional factors
- Treatment
A
- Cause of disparity b/n # of pts receiving renal replacement & # w/ CKD
- Most pts w/ CKD die from CVD prior to requiring dialysis or transplantation
- Even on dialysis, risk of death from CVD is higher than in general population
- CKD vs. CVD
- Pts w/ CKD are high-risk pts for CVD
- CKD = coronary equivalent
- Pts w/ lower GFRs & microalbuminuria/proteinuria carry a high risk of CVD (equivalent to a prior hx of coronray disease
- Traditional risk factors
- Ex. age, diabetes, lipids, HTN, smoking, etc.
- Account for only a portion of the CVD risk associated w/ CKD
- Non-traditional risk factors
- Ex. anemia, volume overload, hyperparathyroidism, Ca/phosphate disturbances, uremia, & malnutrition/inflammation
- Play a role in increasing CVD risk in CKD
- Both traditional & non-traditional factors
- –> cardiomyopathy & ischemic heart disease
- Treatment
- Optimize management of known CVD risk factors
- Focus on BP, exercise, aspirin, & statins
- High suspicion b/c CKD pts often presnet w/ atypical CVD symptoms
12
Q
Early identification treatment plan / model of care for pts w/ CKD
- Screen
- Diagnose
- Treat
- Prepare
A
- Screen for CKD
- Older pts
- Hx of kidney problems
- Family hx
- African-american
- HTN
- Diabetics
- Diagnose CKD
- Serum creatinine –> eGFR, urine ablumin, or protein
- Treat kidney disease & CVD
- Manage BP
- Reno-protective meds (ACE-Is, ARBs)
- Smoking cessation
- Treat complications
- Prepare for renal replacement therapy
- Dialysis
- Transplant
13
Q
Uremia
- General
- Basic abnormality
- Symptoms vs. GFR
- Uremic symptoms result from…
- Uremia is related to…
- Variability in measuring kidney function
- Usual physical signs can be rapidly assessed by…
- Indication for initiation of dialysis
- Presence of uremic symptoms in a chronic dialysis pt often reflects…
A
- General
- Pathologic manifestation of kidney disease in its most severe untreated form
- Clinical expression of symptoms/signs of decreased GFR (renal failure)
- Basic abnormality
- Presence of waste products that the kidney is no longer removing form the body
- Retained products of metabolism
- Symptoms vs. GFR
- CKD pts may be asymptomatic until GFR < 15-20 ml/min –> uremia
- Uremic symptoms result from…
- Renal excretory failure
- Retention of urea, hormones, polyamines, trace elements, serum proteases (“middle molecules”), pyridine derivatives, beta2-microglobulin, etc.
- Loss of normal metabolic & endocrine functions
- Renal excretory failure
- Uremia is related to protein intake
- Low protein diet –> decreased symptoms
- Multisystem disorder: manifestations include…
- GI: nausea, vomiting, diarrhea, dysguesia, changes in appetitie
- CVS: dyspnea, edema, chest pain
- Neuro: restless legs, twitching, confusion, sleep & memory problems
- Skin: pruritus, bruising, uremic frost
- MSK: bone pain (endocrine), arthritis
- Hematologic
- Variability in measuring kidney function
- CKD pts develop complications s& symptoms at dif thresholds
- Makes it difficult t ouse GFR as the only factor in decision making
- Usual physical signs can be rapidly assessed by…
- BP, pericardial rub, rales, etc.
- Indication for initiation of dialysis
- Development of & failure to alleviate uremic manifestations w/ conservative/pharmacologic therapy
- Presence of uremic symptoms in a chronic dialysis pt often reflects…
- Inadequate treatment
- Need to increase dialysis dose
14
Q
Uremia
- Common signs
- Multisystem disorder: manifestations include…
- Cardiovascular
- Endocrine disorders
- Hematologic
- GI
- Neuropsychiatric
- Immunologic
- Musculoskeletal
- Dermatologic
A
- Common signs
- Sallow pallor, bruising
- Uremic fetor
- Hypertension
- Pericardial rub
- Alteration of consciousness
- Neuropathy
- Malnourished state
- Manifestations
- Cardiovascular
- HTN
- Ischemic cardiac disease
- Pericardial disease (pericarditis)
- CHF
- Dyspnea
- Edema
- Chest pain
- Endocrine disorders
- Secondary hyperparathyroidism
- Glucose intolerance (uremic diabetes)
- Hyperlipidemia
- Sexual dysfunction / infertility
- Hematologic
- Anemia
- Bleeding diathesis
- GI
- Anorexia
- Nausea
- Vomiting
- Gastritis
- Duodenitis
- Dysgeusia
- Changes in appetite
- Neuropsychiatric
- Peripheral neuropathy
- CNS disturbances
- Seizures
- Sleep disorders
- Restless leg
- Twitching
- Confusion
- Memory problems
- Immunologic
- Leukopenia, lymphocytopenia
- Decreased antibody responses
- Decreased cell-mediated immune respones
- Increased susceptibility to infection
- Musculoskeletal
- Mineral & bone disease
- Myopathies
- Carpal tunnel syndrome
- Bone pain
- Arthritis
- Dermatologic
- Pruritus
- Uremic pigmentation
- Uremic frost
- Calciphylaxis
- Nail changes
- Bruising
- Cardiovascular
15
Q
Renal adaptation
- Pt awareness of their kidney disease
- Asymptomatic CKD
- Basis of adaption
A
- Pt awareness of their kidney disease
- >10-12 million adults in the US have CKD w/ GFR < 60 ml/min
- Majority aren’t aware
- Asymptomatic CKD
- CKD is often asymptomatic until late in the disease course
- Renal reserve allows remaining nephrons to hyperfilter/increase their level of function
- Additional compensatory processes maintain adequate homeostasis
- Basis of adaption
- Adaptations in glomerular & tubular function & extra-renal systems maintain electrolyte balance but may contribute to adverse consequences
- Adaptation –> increased solute excretion per remaining functional nephron
- Fractional excretion increases as GFR decreases