CKD Pathophysiology

Question 1

What is the definition of CKD?

Answer 1

A GFR less than 60 ml/min for more than 3 months with or without markers of albuminuria, urine sediment, electrolyte, histologic or structural abnormalitie s

Question 2

define the staging of CKD

Answer 2

defined by GFR if below 60 ml/min or by other abnormalities in structure and function if above GFR cut off

Question 3

Define stage 1 CKD

Answer 3

normal renal function by GFR > 90 but with anatomic abnormality or urinary finding

Question 4

Define Stage 2 CKD

Answer 4

GFR of 60 to 89. If above 60, requires additional structural or functional abnormality

Question 5

Stage 3 CKD definition

Answer 5

GFR of 30 to 59. Subdivided into 3a and 3b

Question 6

Define stage 4 CKD

Answer 6

GFR of 15 to 29. Complications and increased risk of CVD occur here. Pts may have electrolyte abnormalities or fluid retention. begin referral process for transplant

Question 7

Define stage V CKD

Answer 7

GFR less than 15. This is essentially end stage kidney disease. Patients are not automatically on dialysis with GFR < 15 ml/min but often times develop signs and symptoms from kidney failure (i.e nausea, poor appetite, fatigue, dysguesia, fluid retention, hyperkalemia, acidosis) that necessitates renal replacement therapy.

Question 8

When is renal replacement therapy initiated?

Answer 8

usually around stage 5 CKD, Patients are not automatically on dialysis with GFR < 15 ml/min but often times develop signs and symptoms from kidney failure (i.e nausea, poor appetite, fatigue, dysguesia, fluid retention, hyperkalemia, acidosis) that necessitates renal replacement therapy.

Question 9

Why is the estimate of US prevalance for CKD most likely an overestimate?

Answer 9

CKD incidence and prevalence is determined using point in time measurements of serum creatinine

Question 10

In what age group is CKD prevalence and incidence increasing most rapidly?

Answer 10

those over 60

Question 11

Where do the majority of people fall, in terms of CKD staging?

Answer 11

1-3.

4 and 5 CKD are a very small segment of the population

Question 12

When comparing CKD v. matched counterparts with a GFR over 60, what are mortality rates like?

Answer 12

Mortality is increased amongst patients with CKD vs. matched counterparts with GFR > 60
ml/min. A significant proportion of patients with CKD will die of other co-morbidities (usually cardiovascular complications) prior to requiring dialysis or transplant.

Question 13

What is the leading cause of end stage renal disease (as opposed to CKD?)

Answer 13

The leading cause of ESRD in the United States is diabetes followed by hypertension. Together,
these are responsible for almost 65% of cases of kidney failure.

Question 14

In what population is the incident rate of ESRD highest?

Answer 14

The incident rate of ESRD per million population is higher for African Americans and Native
Americans than for Caucasians. In other words, although in absolute numbers there are more
Caucasians on dialysis, these minority populations make up a disproportionate number.

Question 15

What is the 5 year survival rate for ESRD patients who receive a transplant v. those who stay on dialysis?

Answer 15

The 5-year survival rate for
transplant patients is 85.5% compared to 40% for those that remain on dialysis. This 5-year
survival rate is similar to that of some rather aggressive malignancies.

Question 16

What type of renal replacement therapy are the majority of ESRD patients on?

Answer 16

The vast majority of patients with ESRD in this country are on hemodialysis (about 60%),
another 30% receive transplants and the remaining ~10% are on peritoneal dialysis.

Question 17

Which kind of RRT has the highest cost to Medicare for ESRD patients?

Answer 17

hemodialysis, followed by peritoneal and transplant

Question 18

How does hemodialysis work?

Answer 18

The main principle behind hemodialysis is diffusion. Blood and dialysate fluid flow countercurrent through a filter. Excess waste products, urea, potassium etc flow down a concentration gradient from the blood to the dialysate.

Question 19

What is the weekly time commitment for patients on hemodialysis?

Answer 19

Almost all hemodialysis occurs in outpatient dialysis centers. This requires patients to go to a center for treatment 3 days a week for about 4 hours each time.

Question 20

What is an arteriovenous fistula and what is it used for?

Answer 20

it is an artificial spot created by surgeons for insertion of the dialysis catheter in hemodialysis

Question 21

What is the most common kind of RRT world wide?

Answer 21

peritoneal dialysis

Question 22

What is the time commitment for peritoneal dialysis?

Answer 22

Every night, at home

Question 23

How do you convert sodium to the approximate salt equivalent? (for dietary sodium intake)

Answer 23

multiply dietary sodium content by 2.5

Question 24

approximately how many mg of sodium are in 1 gram of salt?

Answer 24

400 mg

Question 25

How do you convert mEq to mg?

Answer 25

mEq x atomic weight

Question 26

What important solute for CKD And ESRD is NOT reported on dietary labels?

Answer 26

phosphorus

Question 27

Bananas, mango, oranges, orange juice, raisins, potatoes, tomatoes, black beans, salmon,
chocolate, milk, peanut butter.

these foods have a high: sodium, calcium, phosphorus, potassium content?

Answer 27

potassium

Question 28

salad dressings, cured meat and fish, cheese, pickles, instant soups, salted nuts, snacks, fast food, canned foods.
do these foods have a high sodium, phosphorus, calcium or potassium content?

Answer 28

sodium

Question 29

Beans, cheese, dairy, milk, fish, whole grains, meats, nuts, peanut butter, chocolate, beer, food preservatives, additives, flavor enhancers, food stabilizers, colas.

these foods have a high sodium, potassium, phosphorus or calcium content?

Answer 29

phosphorus

Question 30

Are organic or inorganic sources of phosphorus more easily absorbed?

Answer 30

inorganic phosphorus is more easily absorbed and should be avoided

Question 31

What are the KDIGO guidelines for sodium intake in CKD?

Answer 31

< 2 grams per day

Question 32

How does limiting sodium intake decrease CKD progression?

Answer 32

Limiting sodium intake may decrease progression of CKD by lowering intraglomerular pressure.

Question 33

What is the potassium intake recommended for CKd?

Answer 33

low potassium (< 40 to 70 mEq day)

Question 34

How much phosphorus is recommended per day in CKD?

Answer 34

We don’t know the exact target, but usually 900 mg/day is recommended because restriction does improve patient outcomes

Question 35

Why is excess dietary protein avoided in CKD?

Answer 35

Leads to accumulation of uremic toxins (although limiting may lead to loss of body mass and malnutrition). In dialysis, protein is already catabolized so a high protein diet is recommended

Question 36

What vitamins are lost or low in patients with dialysis?

Answer 36

Vitamin D, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin b12, vitamin c, biotin, vitamin B5, renal vitamins… all of them

Question 37

In peritoneal dialysis v. hemodialysis what additional dietary restriction is there?

Answer 37

potassium restriction

Question 38

On reviewing monthly labs on a patient on hemodialysis, you notice that his serum potassium value is 6.5 mg/dl (elevated). He tells you that he ate at an all-you-can-eat breakfast. He likely ate all of the following except

a. Fruit bowl with mangos, bananas, and oranges b. Apple Juice
c. Oatmeal with raisins
d. Breakfast potatoes

Answer 38

B - apple juice

Question 39

Which of the following is not required by the FDA to be placed on nutrition labels. a. Serving size

b. Sodium content in mg c. Saturated fat
d. Phosphorus content

Answer 39

d - phosphorus content

Question 40

The 5-year survival rate for patients on either hemodialysis or peritoneal dialysis in the United States is: a. 5%
b. 10% c. 40% d. 70%

Answer 40

c - 40 %

Question 41

What are the 2 stages of chronic nephron loss in CKD?

Answer 41

injury leading to compensation with repair and scarring

compensation of remaining nephrons leading to hypertrophy

Question 42

Why is nephron hypertrophy a problem in CKd?

Answer 42

it leads to increased metabolic demand, which may outstrip thec cellular ability to compensate, leading to hypoxia and further nephron loss

Question 43

At the beginning of the CKD process, how is the GFR?

Answer 43

it is normal at the whole kidney level because remaining nephrons are compensating by expanding tubular function to maintain glomerulotubular balance

Question 44

How is increased single nephron GFR maintained in early CKD?

Answer 44

Increased single-nephron GFR is maintained by increased circulation through the glomerulus and increased intraglomerular blood pressure.

Question 45

Compared to most tissues, how does the medulla extract oxygen? what is the normal O2 content?

Answer 45

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 closer to hypoxic conditions.

Question 46

What effect does decreased nephron perfusion in CKD have on the glomerulus and vascular reactivity?

Answer 46

decreased perfusion leads to less NO, which means already hypoxic nephrons are further vasoconstricted

Question 47

What are the 3 results of exceeding oxygen capacity in a nephron with CKD?

Answer 47

acidosis
ROS
HIF

Question 48

How does CKD lead to acidosis?

Answer 48

Anerobic metabolism of glucose promotes acidosis, and systemic academia increases
with CKD as well. Acidosis enhances complement system activation and renal tubular superoxide production. Studies in experimental models and in patients suggest that bicarbonate supplementation delays the progression of CKD.

Question 49

What effect does bicarb supplementation have in CKD?

Answer 49

it delays progression of CKD by buffering acidosis created by anaerobic glucose metabolism

Question 50

What factors promote the formation of ROS in CKD?

Answer 50

Angiotensin II, acidosis and the activation of mitochondrial responses to hypoxia promote the formation of ROS. These in turn alter signaling mechanisms and my cause direct tissue damage at higher levels.

Question 51

What do HIF’s do in the kidney during CKD?

Answer 51

New findings suggest that hypoxia-inducible factors (HIFs) promote fibrosis in the kidney; such activity is increased in poorly perfused tissues.

Question 52

What effect does increased serum phosphate have on PTH and FGF23 levels in CKD?

Answer 52

they increase

Question 53

What effect does anemia have in CKD?

Answer 53

increases renal tissue hypoxia

Question 54

What happens to vitamin D metabolism in CKd? What are the downstream effects of this?

Answer 54

Vitamin D metabolism is inhibited, promoting bone disease, decreasing exercise and
enhancing insulin resistance.

Question 55

What happens to renin levels in CKD?

Answer 55

they are increased, promoting thirst and furthering edema

Question 56

In response to renal injury, the remaining nephrons increase their function by which of the following? A. Increasing single-nephron GFR.
B. Producing parathyroid hormone. C. Undergoing apoptosis.
D. Producing coagulation factors.
E. Decreasing total renal blood flow.

Answer 56

Answer: A
In response to nephron loss, physical factors and the renin-angiotensin system increase the blood flow to the remaining glomeruli. This increases the amount of filtration that occurs in each glomerulus.

Question 57

The main reason that the renal tubule in progressive chronic kidney disease is rendered susceptible to hypoxic injury is: A. Circulating toxins.
B. Albumin sensitivity.
C. Increased per-nephron transport activity. D. Erythrocytosis.
E. Cigarette smoking

Answer 57

Answer: C
Most of these may affect renal tubular function, but the pathophysiology of CKD progression involves increasing work by remnant nephrons. The renal tubule expends enormous amounts of energy, especially in active sodium reabsorption, in reabsorbing 99% of the glomerular filtrate. This process requires significant amounts of energy substrate (glucose) and oxygen. In order to maintain glomerulotubular balance, with nephron loss, each glomerulus may filter more plasma water and the tubule must reabsorb proportionately more. As a result, oxygen utilization increases to the point that it exceeds supply. Of note, cigarette smoking is a modifiable risk factor for CKD progression.

Question 58

Potential steps to improve renal function or delay progression in CKD include which of the following interventions: A. Blood pressure reduction
B. Smoking cessation
C. A low-sodium diet
D. Restricted protein intake E. Correction of acidosis

Answer 58

Answer:A,B,C,D,E
All of the choices are correct. Reduction of blood pressure delays progression even when it is not directly targeted to glomerular filtration. Smoking is a modifiable risk factor. A low sodium diet, treatment of anemia and bicarbonate supplementation have been shown to delay progression in experimental animals and clinical studies. Protein restriction decreases the rate of progression in animal models, but the severity of restriction in clinical trials has impeded its widespread implementation in clinical practice.