SM 206 CKD Clinical Flashcards
What defines Chronic Kidney Disease?
Abnormalities in structure and function present for at least 3 months
Can you have CKD if overall renal function is normal?
Yes; it’s possible to have vascular abnormalities, electrolyte abnormalities, and renal cysts
What is the GFR cutoff for CKD?
GFR < 60 mL/m
How is CKD classified?
CKD is classified by cause, GFR loss severity, and Albuminuria in the urine
How does GFR relate to CKD Progression?
Lower GFR = Faster CKD Progression
How does Proteinuria relate to CKD Progression?
Higher Proteinuria = Faster CKD Progression
What marker is used to track CKD Progression?
Creatinine is an often used marker for Kidney function, though it is not always accurate
Why is Creatinine not always an accurate marker of kidney function?
As kidney function declines, in theory GFR drops leading to more serum Creatinine
However, Creatinine is secreted in the Kidney and can be excreted in the Gut as well to compensate, so serum Creatinine is not a perfect marker of kidney function
In CKD, is kidney function likely to be overestimated or underestimated by Creatinine secretion?
Kidney function is likely to be overestimated by Creatinine because the kidney has ways to secrete Creatinine, as well as through the gut, lowering serum Creatinine and making kidney function look better than normal
What factors can set a “normal” Creatinine?
“Normal” creatinine values are set by:
Age: young = more muscle = higher Creatinine
Sex: men = more muscle = higher Creatinine
Race
How is GFR calculated?
Direct measurement of 24 hour clearance
Cockcroft-Gault formula
MDRD formula
What are the drawbacks to the Cockcroft-Gault formula for estimating GFR?
Cockcrocft-Gault accounts for Age, Weight, Serum Creatinine and Sex to determine GFR
Less accurate in obese patients due to surface area
What are the drawbacks to the MDRD formula for estimating GFR?
MDRD accounts for Age, race, Serum Creatinine, and Albumin to determine GFR
Less accurate in obese patients and people with normal GFR
What is the best formula for normal or mildly reduced GFR and obese individuals?
CKD-EPI, better epidemiological outcomes
How do drugs toxic to the kidney and CKD form a vicious cycle?
In CKD, Kidney is damaged and GFR is low so excretory capacity of the kidney is impaired
Drugs that are renally excreted like Vancomycin accumulate due to poor excretion
Drugs buildup in the Kidney and damage the kidney more, further lowering excretory capacity
How does sodium effect CKD progression?
Sodium worsens the pro-fibrotic effects of aldosterone and accelerates renal disease progression
What is the role of bicarbonate therapy in CKD treatment?
CKD can result in metabolic acidosis, so bicarbonate therapy can slow CKD progression by normalizing the pH
Describe iron homeostasis?
Iron is taken up by the intestine
Iron is bound to Transferrin in the Serum
Iron is stored in the Liver
Iron is used in RBC’s to form Hemoglobin
Iron is recycled after Macrophages degrade senescent RBC’s in the Spleen
What is the critical membrane transporter that mediates Iron import and export?
Ferroportin
How does CKD effect iron homeostasis?
CKD = inflammatory state = Increase Hepcidin
Hepcidin inhibits Ferroportin and causes Iron deficiency Anemia
What molecule is upregulated in CKD that leads to iron deficiency anemia?
Hepcidin is upregulated by inflammation in CKD and inhibits Ferroportin
What is the treatment for iron deficiency anemia in CKD and how does it work?
Roxadustat treats iron deficiency anemia in CKD
Roxadustat inhibits HIF
How does CKD cause bone disorders?
CKD causes bone disorders by decreasing renal excretion of Phosphate, raising serum Phosphate
Phosphate binds serum Calcium to cause metastatic calcifications and trigger the release of PTH
PTH responds to decreased serum Calcium by resorbing bone to raise Calcium
How does CKD effect cardiovascular health?
CKD causes bone disorders which raise CV risk
How does serum calcium level control PTH?
Negative Feedback Loop:
Lower serum calcium triggers PTH
PTH causes increased renal and bone resorption of Ca
Higher Ca inhibits further release of PTH
What do low Ca and low PTH suggest?
Hypoparathyroidism - PTH should be increasing in response to low Ca
What do high Ca and high PTH suggest?
Hyperparathyroidism - PTH should be low in response to high Ca
What does very high Ca and low PTH suggest?
Cancer - PTHrP can mimic the effects of PTH and raise calcium levels beyond normal
What role does the Kidney play in Vitamin D metabolism?
The kidney can either activate or inactivate 25-Vit D3, with PTH promoting Vit D activation
What effects does PTH have on the Kidney?
PTH promotes Vit D activation and Ca reabsorption
Describe how Vit D is activated?
Provitamin D3 is converted into Pre-D3 by UV light in the skin
Vit D3 is hydroxylated into 25-Vit D3 in the Liver
25-Vit D3 is hydroxylated into active 1,25-Vit D by alpha hydroxylase OR
25 Vit D3 is hydroxylated into inactive 24,25-Vit D by 24 hydroxylase
What the roles of FGF23?
FGF23 stimulates phosphaturia
FGF23 decreases Active Vit D by upregulating 24 Hydroxylase and downregulating 1 Hydroxylase
FGF23 inhibits PTH
How does FGF23 stimulate phosphaturia?
FGF23 inhibits NaPi 2a/c Phosphate channels
What is the trade-off hypothesis for PTH levels in CKD?
In CKD, GFR is low
= Low Phosphate Filtration = High Serum Phosphate
= Phosphate binding Serum Ca
= Low Serum Ca
= PTH release to normalize Ca and lower Phosphate
What is secondary hyperparathyroidism in CKD?
Progressively higher Phosphate which progressively lowers Ca drives higher secretion of PTH to normalize serum Ca, causing hyperparathyroidism secondary to CKD
Which Ca-regulating molecule rises earliest in CKD?
FGF23 rises first due to inflammation and hypoxia in CKD
How does FGF23 mediate bone changes in CKD?
FGF23 rises early in CKD, and inhibits Vitamin D
Lower Vitamin D = Lower Serum Ca
Lower serum Ca = Raise PTH release
PTH drives Ca and Phosphate release from bone
Serum Phosphate rises once CKD diminishes GFR to a low enough level where Phosphate can’t be released
Why does it take time for serum Phosphate levels to rise in CKD, even if PTH is high?
Phosphate levels rise as a result of increased PTH, but the kidneys can filter it out until CKD progresses enough to slow down GFR
Why do serum Phosphate levels drop after a kidney transplant in the setting of CKD?
In CKD, PTH and FGF23 are high
Before transplant, kidney has low excretory capacity so serum phosphate is high despite PTH and FGF23
After transplant, new kidney can excrete phosphate well so serum phosphate drops due to PTH and FGF23
Why is Vitamin D supplementation a treatment for CKD?
Vitamin D is given to increase serum Ca and lower the stimulus for PTH release, saving the bones
Why are phosphate binders given in CKD?
Phosphate binders help clear the elevated serum Phosphate that arises due to low GFR in CKD
How does diabetes change GFR over time?
Diabetes causes an early increase in GFR and a decrease in GFR as the disease progresses
How do ACEi/ARB’s treat diabetic CKD?
ACEi/ARB’s inhibit RAAS and lower GFR to slow the progression of CKD
How does diabetes mellitus lead to glomerular hypertension?
In diabetes, serum Glucose is high
Glucose gets filtered across the Glomerulus
Increased expression of SGLT Na/Glucose transporters in the Glomerulus to reabsorb Glucose
Decreased Na delivery to the Macula Densa causes decreased ATP generation and Adenosine formation
Decreased Adenosine prevents the afferent arteriole from contracting = increase glomerular pressure
How do SGLT2 inhibitors decrease intra-glomerular pressure?
SGLT2 inhibitors decrease Na/Glucose uptake
More Na in the tubule reaches the Macula Densa
More ATP in the MD = More Adenosine
Adenosine constricts the afferent arteriole
= lower glomerular pressure
How do SGLT2i and RAASi differ in their effects on glomerular pressure?
RAASi lower glomerular pressure by blocking Angiotensin II and dilating the efferent arteriole
SGLT2i lower glomerular pressure by increasing sodium delivery to the Macula Densa
Increased Sodium at the MD prevents vasoconstriction of the Glomerulus
What are the benefits of SGLT2i drugs?
SGLT2i protect against cardiovascular events and slow the progression of kidney disease
How should Stages 1 and 2 of CKD be managed?
In Stage 1 and 2 of CKD, focus on CVD risk reduction
How should Stage 3 of CKD be managed?
In Stage 3, treat complications with:
Bicarb therapy
Iron
Vit D
SGLT2i/ACEi
How should Stage 4 and 5 of CKD be managed?
Symptom control as prep for Kidney replacement
What defines rapid progression of CKD?
A sustained decline in GFR more than 5mL/min
What are indications for Acute Dialysis?
AEIOU
Acidosis Electrolytes (Hyperkalemia) Ingestions (Aspirin + Lithium) Overload (Volume overload + repeated CHF exacerbations) Uremia
What would repeated CHF exacerbations suggest?
Acute dialysis due to volume overload
What are the symptoms of Uremia?
Metallic taste in mouth + Nausea + Cardiac rub
What are the indications for chronic dialysis?
Not set in stone and requires a discussion with the patient, but AEIOU (like acute):
Acidosis Electrolytes (Hyperkalemia) Ingestions (Aspirin + Lithium) Overload (Volume overload + repeated CHF exacerbations) Uremia
How do the indications for acute and chronic dialysis differ?
Acute dialysis is simply AEIOU, but Chronic dialysis is not as clear cut and always requires a discussion (though AEIOU still apply)
Acidosis Electrolytes (Hyperkalemia) Ingestions (Aspirin + Lithium) Overload (Volume overload + repeated CHF exacerbations) Uremia
