Chronic Kidney Disease

Question 1

What are the pathological stages of glomerulosclerosis?

Answer 1

injury

response

repair

maladaptation

Question 2

What are the clinical phases of glomerulosclerosis

Answer 2

initiation - infection, hypertention, and environmental stimulus

consolidation - inflammation, excessive mediator response, and glomerular hyperfiltration

low progression - low nephron number, “progression” genes, and nephron loss

Question 3

What are the two stages of progression in chronic kidney disease?

Answer 3

injury and chronic scarring

structural damage that leads to progressive nephron loss and eventually end-stage disease

Question 4

What functions of the nephron are altered when the kidney is diseased?

Answer 4

sodium and phosphate excretion

potassium secretion

titratable acid excretion

bicarbonate reabsorption

protein metabolism

gluconeogenesis

Question 5

At what point is dialysis usually required?

Answer 5

at 10% kidney function (10% GFR)

Question 6

What is unique about oxygen utilization of the kidneys?

Answer 6

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

Question 7

What happens if oxygen capacity is exceeded?

Answer 7

glycolysis leads to acidosis, generation of reactive oxygen species, and cellular production of hypoxic mediators

Question 8

What are the endocrinological effects on extra-renal systems in uremia?

Answer 8

parathyroid, PTH, bone resorption

inflammation

puritis

atherosclerosis

Question 9

What are the endocrinological effects on remaining nephrons in uremia?

Answer 9

hyperfiltration

hypertrophy

intraglomerular hypertension

Question 10

What are the steps in progressive nephron loss?

Answer 10

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

Question 11

characteristics of nephron hypertrophy

Answer 11

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

Question 12

What is the major mediator of nephron hypertrophy?

Answer 12

renin-angiotensin-aldosterone system

Question 13

What are the consequences of nephron loss?

Answer 13

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

Question 14

What are the causes of disturbed NO-mediated vasodilation?

Answer 14

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

Question 15

How does acidosis affect kidney function?

Answer 15

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

Question 16

How does the generation of ROS in CKD affect renal function?

Answer 16

carbamylated low-density lipoproteins promate oxidative stress in endothelial cells in uremia

hypertension is associated with ROS activity

Question 17

What are the hypoxic mechanisms of ROS generation in CKD?

Answer 17

superoxide is generated at the mitochondrial inner membrane by complex III enzymes

hypoxia stabilizes these enzymes

Question 18

What are the non-hypoxic mechanisms of ROS generation in CKD?

Answer 18

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

Question 19

How do ROS cause disease?

Answer 19

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

Question 20

What is the role of hypoxia-inducible factor (HIF)?

Answer 20

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

Question 21

What are the factors that can affect per-nephron load?

Answer 21

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)

Question 22

What are the factors that affect the GFR calculation?

Answer 22

serum creatinine

age

ethnicity

gender

body weight (ideal - amount of muscle mass)

Question 23

What is the calculation for creatinine clearance?

Answer 23

men - [(140-age)*wt(kg)/(72*SCr)]

women - 0.85*[(140-age)*wt(kg)/(72*SCr)]

Question 24

Why calculate GFR?

Answer 24

more accurate representation of renal function than serum creatinine, which can be misleading

Question 25

What is the definition of chronic kidney disease (CKD)?

Answer 25

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

Question 26

Definition of acute kidney injury (AKI)

Answer 26

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

Question 27

What are the normal ranges for BUN and creatinine?

Answer 27

BUN - 8-27 mg/dL Cr - 0.57-1.00 mg/dL

Question 28

azotemia

Answer 28

high BUN level

Question 29

uremia

Answer 29

high BUN level with symptoms such as confusion/encephalopathy, bleeding, and asterixis (tremor)

Question 30

What are the common causes of increased BUN:Cr?

Answer 30

prerenal AKI due to renal tubular absorption of urea, as opposed to secretion of creatinine GI bleed high protein nutrition steroids

Question 31

What are some methods of differentiating AKI from CKD?

Answer 31

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

Question 32

What are the etiologies of CKD?

Answer 32

include all etiologies of AKI diabetes and hypertension are most common autoimmune diseases and glomerulonephritis chronic nephrotoxic medication anatomical structural changes to the kidneys

Question 33

stage 1 chronic kidney disease

Answer 33

GFR \>= 90 mL/min, proteinuria kidney damage would be defined by the presence of anatomic or urine finding indicating kidney damage

Question 34

stage 2 chronic kidney disease

Answer 34

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

Question 35

stage 3 chronic kidney disease

Answer 35

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

Question 36

stage 4 chronic kidney disease

Answer 36

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

Question 37

stage 5 chronic kidney disease

Answer 37

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

Question 38

What are the classic symptoms of CKD?

Answer 38

dysguesia anorexia fluid retention fatigue cloudy thinking non-specific and often not present until more severe CKD has developed

Question 39

complications of CKD

Answer 39

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

Question 40

indications for dialysis for acute kidney injury

Answer 40

**A**cidosis **E**lectrolytes (hyperkalemia) **I**ngestions (lithium, ASA) **O**verload (volume, causing hypoxia, decompensated heart failure) **U**remia

Question 41

indications for dialysis for chronic kidney injury

Answer 41

any acute indication in setting of CKD (GFR \< 15 cc/min) general malaise, failure to thrive, in patient with GFR \< 10-15 cc/min

Question 42

What are some methods to delay progression of CKD?

Answer 42

control blood pressure control blood sugar if patient has DM reduce proteinuria smoking cessation give sodium bicarb (?)

Question 43

management of stage 1 and 2 CKD

Answer 43

diagnose, delay progression reduce CV risk reduce proteinuria

Question 44

management of stage 3 CKD

Answer 44

diagnose, delay progression reduce proteinuria reduce CV risk assess for complications

Question 45

management of stage 4 CKD

Answer 45

diagnose, delay progression reduce proteinuria reduce CV risk assess for complications - more frequently seen discuss renal replacement therapy (transplant or dialysis)

Question 46

management of stage 5 CKD

Answer 46

same as stage 4 prepare for transplant or initiate dialysis