CKD Pathophysiology Flashcards
What is the definition of CKD?
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
define the staging of CKD
defined by GFR if below 60 ml/min or by other abnormalities in structure and function if above GFR cut off
Define stage 1 CKD
normal renal function by GFR > 90 but with anatomic abnormality or urinary finding
Define Stage 2 CKD
GFR of 60 to 89. If above 60, requires additional structural or functional abnormality
Stage 3 CKD definition
GFR of 30 to 59. Subdivided into 3a and 3b
Define stage 4 CKD
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
Define stage V CKD
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.
When is renal replacement therapy initiated?
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.
Why is the estimate of US prevalance for CKD most likely an overestimate?
CKD incidence and prevalence is determined using point in time measurements of serum creatinine
In what age group is CKD prevalence and incidence increasing most rapidly?
those over 60
Where do the majority of people fall, in terms of CKD staging?
1-3.
4 and 5 CKD are a very small segment of the population
When comparing CKD v. matched counterparts with a GFR over 60, what are mortality rates like?
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.
What is the leading cause of end stage renal disease (as opposed to CKD?)
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.
In what population is the incident rate of ESRD highest?
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.
What is the 5 year survival rate for ESRD patients who receive a transplant v. those who stay on dialysis?
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.
What type of renal replacement therapy are the majority of ESRD patients on?
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.
Which kind of RRT has the highest cost to Medicare for ESRD patients?
hemodialysis, followed by peritoneal and transplant
How does hemodialysis work?
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.
What is the weekly time commitment for patients on hemodialysis?
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.
What is an arteriovenous fistula and what is it used for?
it is an artificial spot created by surgeons for insertion of the dialysis catheter in hemodialysis
What is the most common kind of RRT world wide?
peritoneal dialysis
What is the time commitment for peritoneal dialysis?
Every night, at home
How do you convert sodium to the approximate salt equivalent? (for dietary sodium intake)
multiply dietary sodium content by 2.5
approximately how many mg of sodium are in 1 gram of salt?
400 mg
How do you convert mEq to mg?
mEq x atomic weight
What important solute for CKD And ESRD is NOT reported on dietary labels?
phosphorus
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?
potassium
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?
sodium
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?
phosphorus
Are organic or inorganic sources of phosphorus more easily absorbed?
inorganic phosphorus is more easily absorbed and should be avoided
What are the KDIGO guidelines for sodium intake in CKD?
< 2 grams per day
How does limiting sodium intake decrease CKD progression?
Limiting sodium intake may decrease progression of CKD by lowering intraglomerular pressure.
What is the potassium intake recommended for CKd?
low potassium (< 40 to 70 mEq day)
How much phosphorus is recommended per day in CKD?
We don’t know the exact target, but usually 900 mg/day is recommended because restriction does improve patient outcomes
Why is excess dietary protein avoided in CKD?
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
What vitamins are lost or low in patients with dialysis?
Vitamin D, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin b12, vitamin c, biotin, vitamin B5, renal vitamins… all of them
In peritoneal dialysis v. hemodialysis what additional dietary restriction is there?
potassium restriction
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
B - apple juice
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
d - phosphorus content
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%
c - 40 %
What are the 2 stages of chronic nephron loss in CKD?
injury leading to compensation with repair and scarring
compensation of remaining nephrons leading to hypertrophy
Why is nephron hypertrophy a problem in CKd?
it leads to increased metabolic demand, which may outstrip thec cellular ability to compensate, leading to hypoxia and further nephron loss
At the beginning of the CKD process, how is the GFR?
it is normal at the whole kidney level because remaining nephrons are compensating by expanding tubular function to maintain glomerulotubular balance
How is increased single nephron GFR maintained in early CKD?
Increased single-nephron GFR is maintained by increased circulation through the glomerulus and increased intraglomerular blood pressure.
Compared to most tissues, how does the medulla extract oxygen? what is the normal O2 content?
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.
What effect does decreased nephron perfusion in CKD have on the glomerulus and vascular reactivity?
decreased perfusion leads to less NO, which means already hypoxic nephrons are further vasoconstricted
What are the 3 results of exceeding oxygen capacity in a nephron with CKD?
acidosis
ROS
HIF
How does CKD lead to acidosis?
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.
What effect does bicarb supplementation have in CKD?
it delays progression of CKD by buffering acidosis created by anaerobic glucose metabolism
What factors promote the formation of ROS in CKD?
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.
What do HIF’s do in the kidney during CKD?
New findings suggest that hypoxia-inducible factors (HIFs) promote fibrosis in the kidney; such activity is increased in poorly perfused tissues.
What effect does increased serum phosphate have on PTH and FGF23 levels in CKD?
they increase
What effect does anemia have in CKD?
increases renal tissue hypoxia
What happens to vitamin D metabolism in CKd? What are the downstream effects of this?
Vitamin D metabolism is inhibited, promoting bone disease, decreasing exercise and
enhancing insulin resistance.
What happens to renin levels in CKD?
they are increased, promoting thirst and furthering edema
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: 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.
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: 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.
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: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.
