Chronic Kidney Disease Flashcards
What are the pathological stages of glomerulosclerosis?
injury
response
repair
maladaptation
What are the clinical phases of glomerulosclerosis
initiation - infection, hypertention, and environmental stimulus
consolidation - inflammation, excessive mediator response, and glomerular hyperfiltration
low progression - low nephron number, “progression” genes, and nephron loss
What are the two stages of progression in chronic kidney disease?
injury and chronic scarring
structural damage that leads to progressive nephron loss and eventually end-stage disease
What functions of the nephron are altered when the kidney is diseased?
sodium and phosphate excretion
potassium secretion
titratable acid excretion
bicarbonate reabsorption
protein metabolism
gluconeogenesis
At what point is dialysis usually required?
at 10% kidney function (10% GFR)
What is unique about oxygen utilization of the kidneys?
the normal O2 content of the medulla is lower than in most tissues and renal extraction of oxygen is relatively high
increased workload drives oxygenation
What happens if oxygen capacity is exceeded?
glycolysis leads to acidosis, generation of reactive oxygen species, and cellular production of hypoxic mediators
What are the endocrinological effects on extra-renal systems in uremia?
parathyroid, PTH, bone resorption
inflammation
puritis
atherosclerosis
What are the endocrinological effects on remaining nephrons in uremia?
hyperfiltration
hypertrophy
intraglomerular hypertension
What are the steps in progressive nephron loss?
nephron loss
remnant hypertrophy
increased filtered load
further scarring and increased tubular transport work
increased oxygen utilization
tissue hypoxia - leads to endothelial dysfunction
acidosis ROS HIF -> nephron loss
characteristics of nephron hypertrophy
rapdi response (24 hrs) to tissue loss
increased SNGFR
critical for maintaining adequate renal function
tubular response to maintain glomerulotubular balance
immediate benefit, long-term problem
What is the major mediator of nephron hypertrophy?
renin-angiotensin-aldosterone system
What are the consequences of nephron loss?
increased SNGFR
increased tubular reabsorption
more energy, more oxygen consumption are required
renal oxygen extraction increases from 7.3% to 13.9% in CKD
loss of peritubular vessels worsens oxygen delivery
What are the causes of disturbed NO-mediated vasodilation?
mediated by increased asymmetric dimethylarginine (ADMA)
dimethylaminoarginine dimethylaminohydrolase (DDAH) is a natural inhibitor of ADMA, which delays the progression of kidney disease in rats
uremia could therefore cause vasoconstriction, decreasing blood flow
How does acidosis affect kidney function?
common in CKD and worsened by ischemia
ammonia generation may activate alternative complement pathway
terminal components (C5-9) play a role in progression
bicarbonate feeding decreases renal tubular peroxide production an damage in CKD mice
bicarbonate supplementation slows CKD progression in humans
How does the generation of ROS in CKD affect renal function?
carbamylated low-density lipoproteins promate oxidative stress in endothelial cells in uremia
hypertension is associated with ROS activity
What are the hypoxic mechanisms of ROS generation in CKD?
superoxide is generated at the mitochondrial inner membrane by complex III enzymes
hypoxia stabilizes these enzymes
What are the non-hypoxic mechanisms of ROS generation in CKD?
TGF-beta activates NAD(P)H oxidase
ferrous iron delivered to the tubulointerstitium may generate free radicals
macrophages may produce H2O2
angiotensin II stimulates ROS production
How do ROS cause disease?
signaling molecule at low concentrations
at moderate concentrations (50-100 microM), off-target effects of oxidizing such as thiol bonds, receptors, and protein structure
in high concentrations, react with lipids and proteins to alter cell membranes and generate more free radicals
What is the role of hypoxia-inducible factor (HIF)?
present in fibrotic kidneys
kockout of HIF decreases kidney fibrosis in mouse models
HIF may play an important role in kidney fibrosis, even in normoxia
What are the factors that can affect per-nephron load?
low birth weight (low nephron number)
prematurity (low nephron number)
obesity (increased metabolism, increased filtration)
hypertension (hyperfiltration, activation of RAAS)
history of acute kidney injury
anemia (poor oxygen delivery)
What are the factors that affect the GFR calculation?
serum creatinine
age
ethnicity
gender
body weight (ideal - amount of muscle mass)
What is the calculation for creatinine clearance?
men - [(140-age)*wt(kg)/(72*SCr)]
women - 0.85*[(140-age)*wt(kg)/(72*SCr)]
Why calculate GFR?
more accurate representation of renal function than serum creatinine, which can be misleading
What is the definition of chronic kidney disease (CKD)?
abnormal kidney function persisting for mroe than 3 months as defined by structural or functional abnormalities of the kidney, with or without decreased GFR
can be due to either a decreased glomerular filtration rate or to anatomic or structural abnormalities or abnormalities in the blodo or urine
can also be defined by a GFR < 60 mL/min/1.73m2 for more than or equal to 3 months, with or without kidney damage
Definition of acute kidney injury (AKI)
increased in serum Cr from baseline by at least 0.3 mg/dL within 48 hours, if the baseline GFR > 60
increase serum Cr by 50% within 7 days, from baseline (any GFR)
baseline defined as lowest creatinine within past 3 months
oliguria of less than 0.5 mL/kg/hr for more than 6 hours
What are the normal ranges for BUN and creatinine?
BUN - 8-27 mg/dL
Cr - 0.57-1.00 mg/dL
azotemia
high BUN level
uremia
high BUN level with symptoms such as confusion/encephalopathy, bleeding, and asterixis (tremor)
What are the common causes of increased BUN:Cr?
prerenal AKI due to renal tubular absorption of urea, as opposed to secretion of creatinine
GI bleed
high protein nutrition
steroids
What are some methods of differentiating AKI from CKD?
best way is to compare to old creatinine values
renal ultrasound - small kidney means chronic
urinalysis - broad casts means chronic
renal bone disease - presence of means chronic
What are the etiologies of CKD?
include all etiologies of AKI
diabetes and hypertension are most common
autoimmune diseases and glomerulonephritis
chronic nephrotoxic medication
anatomical structural changes to the kidneys
stage 1 chronic kidney disease
GFR >= 90 mL/min, proteinuria
kidney damage would be defined by the presence of anatomic or urine finding indicating kidney damage
stage 2 chronic kidney disease
GFR between 60 and 89 mL/min
MDRD equation not accurate at this GFR level
CKD is not present by GFR criteria until the GFR falls below 60
stage 3 chronic kidney disease
GFR between 30 and 59 mL/min
3a = GFR between 45 and 59 mL/min
3b = GFR between 30 and 44 mL/min
the lower the GFR, the more likely for complications to occur
stage 4 chronic kidney disease
GFR between 15 and 29 mL/min
complications likely in this stage
renal replacement options are also discussed
referral to transplant when GFR is less than 20
stage 5 chronic kidney disease
GFR less than 15 mL/min
considered end stage renal disease
patients may have a very low GFR and not be on dialysis
a stage 5 patient on dialysis is sometimes denoted as 5D
What are the classic symptoms of CKD?
dysguesia
anorexia
fluid retention
fatigue
cloudy thinking
non-specific and often not present until more severe CKD has developed
complications of CKD
begin at GFR < 60 cc/min - the lower the GFR, the more likely that there will be complications
anemia - kidneys make erythropoietin
bone disease
fluid and electrolyte abnormalities - usually with lower GFRs
indications for dialysis for acute kidney injury
Acidosis
Electrolytes (hyperkalemia)
Ingestions (lithium, ASA)
Overload (volume, causing hypoxia, decompensated heart failure)
Uremia
indications for dialysis for chronic kidney injury
any acute indication in setting of CKD (GFR < 15 cc/min)
general malaise, failure to thrive, in patient with GFR < 10-15 cc/min
What are some methods to delay progression of CKD?
control blood pressure
control blood sugar if patient has DM
reduce proteinuria
smoking cessation
give sodium bicarb (?)
management of stage 1 and 2 CKD
diagnose, delay progression
reduce CV risk
reduce proteinuria
management of stage 3 CKD
diagnose, delay progression
reduce proteinuria
reduce CV risk
assess for complications
management of stage 4 CKD
diagnose, delay progression
reduce proteinuria
reduce CV risk
assess for complications - more frequently seen
discuss renal replacement therapy (transplant or dialysis)
management of stage 5 CKD
same as stage 4
prepare for transplant or initiate dialysis
