Chronic Renal Failure: Huch Flashcards
1
Q
What is the definition of chronic kidney disease?
A
- CKD is best thought of as a loss of functioning nephrons -> decreased functioning nephrons leads to decreased GFR
- Best index of overall kidney function is GFR, usually estimated by measurement of creatinine clearance and by changes in serum creatinine concentration
2
Q
How do you dx CKD?
A
- History: voiding complaints (urination complaints), abnormal appearance of urine
- Physical exam: HTN, edema (Na, H2O retention), flank masses (could clue you into polycystic kidney disease or an enlarged bladder)
- Lab data (key to dx): previous urinalysis, serum creatinine (previous and current), BUN
- Imaging studies: ultrasound of kidneys, etc.
3
Q
What are the dx considerations for kidney disease (i.e., differential dichotomies)?
A
- Prerenal, Intrinsic Renal, Post Renal in origin
- Acute or Chronic in nature (can only tell this by serial labs)
- Glomerular or Tubular process
- Inflammatory or Non-inflammatory process
- With or Without a systemic disease
4
Q
What factors favor chronic renal insufficiency as opposed to acute?
A
- Most commonly asymptomatic
- Availability of old records (UA, serum creatinine concentration, BUN)
- Peripheral neuropathy (may suggest chronic condition, i.e., diabetes)
- Bone changes consistent with longstanding hyper-PTH (has to be part of ongoing poor kidney function)
-
Small kidneys (hallmark of CKD), particularly small echogenic kidneys by renal ultrasound
1. You can have CKD without small kidneys, but if you have small kidneys, you have CKD - Waxy casts (renal failure casts): broad, dense, sharp edges
5
Q
What factors suggest tubular etiology?
A
- Absence of heavy proteinuria
- Inability to concentrate or dilute urine, so specific gravity is 1.010, which correlates with urine osmolality of ~300 mOsm/kg
- Presence of hyperkalemia and metabolic acidosis out of proportion to the degree of renal insufficiency (impairment of secretion of H+ and K+)
- Tubular disease: interstitial nephritis
6
Q
What factors suggest glomerular etiology?
A
- Urinalysis is most important element to determine glomerular vs. tubular disease
- Presence of 2+ or greater proteinuria suggests glomerular disease
- Presence of RBC casts is pathognomonic of glomerular disease
- Specific gravity greater than or equal to 1.015 suggests glomerular etiology
- Red cells can come from bladder, ureter, anywhere, but RBC CASTS mean it has to be glomerular disease
7
Q
What factors suggest non-inflammatory glomerular disease?
A
- Proteinuria without signs of inflammation
- Both glomerular and tubular diseases whether inflammatory or non-inflammatory can lead to impaired renal function
8
Q
What factors suggest inflammatory kidney disease?
A
- Glomerulonephritis implies active inflammation with the glomerulus -> urinary fxs of such inflammation incl hematuria and RBC casts and granular casts
- May also be WBC’s in urine without bacteria
- Proteinuria will also be present although it is usually 2+ or less by dipstick
- Tubulointerstitial nephritis implies active inflam surrounding tubules and interstitium
1. Ex: pyelonephritis w/neutrophilic infiltrate 2o to bac infection and allergic interstitial nephritis, usually due to idiosyncratic reactions to drugs
9
Q
What factors imply allergic interstitial nephritis?
A
- Most common cause of eosinophils in the urine (systemic rxn)
- Characterized by presence of sterile pyuria (urine w/WBCs or puss)
1. You may originally think UTI, but the pyuria will be sterile
10
Q
What is uremia?
A
- Term used to describe the constellation of signs & symptoms associated with advanced renal failure
-
100% fatal, unless:
1. Reversible factors identified that can improve GFR -or-
2. Renal replacement therapy (dialysis) instituted - Virtually every organ system affected by presence of chronic renal insufficiency, esp. w/advanced chronic renal insufficiency
11
Q
If you remove the initial injuring stimulus in CKD, what happens?
A
- Probably not going to stop the CKD
- CKD tends to be inexorably progressive, even if the initial injuring stimulus is removed -> there are no relaxing nephrons in CKD
12
Q
What signs and symptoms are associated with ESRD?
A
- Malaise
- Poor appetite
- Weight loss
- Pericardial friction rub
- Chest pain
- Encephalopathic
13
Q
What are the most common etiologies of advanced kidney disease in the US?
A
- Diabetes mellitus
- Hypertensive nephrosclerosis
- Acute and chronic glomerular diseases: glomerular diseases are more progressive than interstitial ones, as a general rule
- Polycystic kidney disease
- Tubulointerstitial diseases
14
Q
What are disease dependent and disease independent mechanisms of nephron injury?
A
- Disease dependent: vascular, glomerular, tubular
- Disease independent: systemic HTN, glomerular HTN (vasodilation of afferent arteriole), glomerular hypertrophy (increased SNGFR per nephron)
15
Q
What are the renal responses to nephron loss?
A
- Compensatory glomerular hypertrophy and hyperfiltration
- Example: 50% DEC in renal mass results in only 20-30% reduction in GFR, so residual nephronsINC SNGFR (single nephron GFR) about 50%
- This is what makes it safe for someone to be a kidney donor
- Losing nephrons is still bad because the ones you have left are still having to work harder
16
Q
What are the effects of the disease independent processes (HTN, hypertrophy)?
A
- Epithelial cell injury promoting proteinuria
- Hyaline accumulation (scarring) in mesangial expansion -> reduced capillary surface area for GFR
- Vascular capillary microaneurysms
- Endothelial cell injury
- Tubulointerstitial fibrosis: ischemic origin, calcium phosphorus deposition, complement activation with inflammatory damage due to local NH3
17
Q
What do these graphs show?
A
- Rats with 5/6 nephrons removed (on bottom) have higher pressure, volume, flow, etc. than those in the healthy rats
- More GFR per nephron
- Ratio of epithelial cells to volume of glomerular capillary damaged (remaining epi cells swelling to try and wrap around the capillaries)
18
Q
What do these graphs show?
A
- More protein excretion by those rats with 5/6 nephrons removed -> whole filtration barrier damaged and leakier, so you have albuminuria, resulting in more scarring (sclerosis)
19
Q
What is the pathogenesis of 2o focal segmental glomerulosclerosis?
A
- Bottom line -> you lose nephrons and have:
1. INC glomerular capillary pressure
2. Mesangial hyperplasia/hypertrophy
3. Collapse of the glomerulus -> feeds back to causing more loss of nephrons
20
Q
What happens with greater than 50% nephron mass loss in humans?
A
-
Dose dependent increase in the risk of:
1. Hypertension (some kidney donors do have this risk)
2. Proteinuria (FSG)
3. Particularly when present >10 years (happens over time)
23
Q
What anti-HTN agents have most effectiveness in proteinuric disease?
A
- ACEi’s and ARB’s have been shown to have a selective advantage over other anti-hypertensive agents
- ACEi and ARBs reduce systemic pressure and reduce glomerular capillary pressure
- This is something very important for TEST-TAKING purposes
-
CHART: really, the only ones that reduce glomerular HTN are the ACEI’s and ARB’s
1. The more proteinuria you have, the more likely you are to progress, so anything you can do to reduce it is going to help
26
Q
What does this graph show?
A
- Enalapril significantly reduces protein excretion (one of the key indicators of progression in CKD)
27
Q
What does this graph show you?
A
- Protein excretion over time (baseline on left and 4 years on the right)
- Those patients on captopril had much less progression of protein excretion in the prescribed period
28
Q
What does all of this mean?
A
- Decreased risk of doubling of creatinine with Losartan (ARB)
- Losartan: helps prevent renal failure and death
31
Q
What are the stages of CKD?
A
- This is important because it helps you get more information to your patients about where they are at
32
Q
Why do we estimate the GFR instead of using the serum creatinine?
A
- She said this is BOUND TO BE A TEST QUESTION
- Serum creatinine affected by MANY factors, incl. age, muscle mass, sex, race, etc.
33
Q
What are the 4 steps in the progression of renal disease? What is the big risk with CKD?
A
- Microalbuminuria
- Proteinuria
- Doubling of serum creatinine levels
- End stage renal disease
- Patients with CKD have highest risk factor for CV events, similar to a diabetic, even if they don’t have diabetes
34
Q
What is the intact nephron hypothesis?
A
- Damaged nephrons generally func appropriately, therefore, loss of renal homeostasis is secondary to a decreased number of nephrons
- Chronic renal insufficiency equals a decreased number of normally functioning nephrons
- GRAPH: shows that normal and diseased kidney can excrete H+ ions at the same rate (this is why we can donate a kidney)
36
Q
What do these graphs show?
A
- Show relationship of salt and water intake to arterial pressure in normal and abnormal kidney (i.e., in a pt with essential hypertension)
- Have to move your curve to a higher BP to maintain homeostasis and get as much salt and water out as you need
- HTN detrimental to whole body and kidney
37
Q
What does this graph show?
A
As you diurese these people (i.e., ppl with essential HTN), getting rid of salt and water, they will get better
39
Q
What does this graph show?
A
- Risk of CV events and dying goes up with worse functioning kidneys (lower GFR)
42
Q
How is anemia related to kidney disease?
A
- Secondary to diminished EPO production
- Occurs at approx 30% normal GFR
- Normocytic, normochromic w/low reticulocyte count
- No significant change in platelet count and white blood cell count
- Burr cells are present
- Responsive to exogenous EPO
