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)
21
Q
How might you prevent progressive nephron loss (CKD)?
A
-
Protein restriction: protein intake normally raises GFR transiently bc have to INC renal flow, so protein restriction may reduce workload of glomeruli
1. Most helpful in proteinuric renal diseases
2. Severe protein restriction -> malnutrition
3. Dietary modification is exceedingly difficult to actually accomplish -> you can also end up with malnutrition and other deficiencies -
HTN accelerates progressive nephron loss in tubular, glomerular, and vascular renal diseases
1. Maintenance of normal BP w/anti-HTN meds + dietary Na restriction can preserve renal func in proteinuric and non-proteinuric renal diseases
22
Q
What % of patients with advanced chronic renal insufficiency have HTN?
A
- 85-90% of patients with advanced CRI have hypertension
- 80% of the hypertension is largely volume driven (i.e., excess volume)
- In contrast, essential hypertension has normal volume status (until GFR becomes depressed)
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
24
Q
What are the adverse effects of activation of RAS?
A
- Vasoconstriction, contributing to systemic HTN
- Sodium retention (aldosterone)
- Glomerular hypertension (efferent arteriole vasoconstriction -> angiotensin II)
- Increased release of TGF-beta (scarring factor for glomerular diseases), promoting fibrosis
25
What are the early changes, clinical effects, and histology associated with diabetic nephropathy?
- Present in 30-40% of type 1 and an undetermined percentage of type 2 diabetics
- _Early changes_: hyperfiltration resulting in glomerular capillary hypertension and glomerular hypertrophy
- _Clinical effects_: first abnormality is microalbuminuria (special test) that over time leads to overt proteinuria, reduced GFR, and hypertension
- _Histology_: increased mesangial matrix, glomerular collapse, and glomerulosclerosis
26
What does this graph show?
- Enalapril significantly reduces protein excretion (one of the key indicators of progression in CKD)
27
What does this graph show you?
- 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
What does all of this mean?
- Decreased risk of doubling of creatinine with Losartan (ARB)
- _Losartan_: helps prevent renal failure and death
29
How do we estimate renal function?
- _GFR is the best index of overall kidney function_
1. Creatinine clearance is best clinical estimate of GFR
- _Renal function can be monitored by_ serial measurements of the _serum creatinine concentration_
1. Serum creatinine concentration is altered by advancing age and by muscle mass (limitations)
30
What are the limitations of serum creatinine as a marker of kidney function?
- INC secretion occurs w/decreased GFR, so serum creatinine will over-estimate true GFR
- INC filtration in remaining nephrons may mask the presence of nephron loss
1. Creatinine can stay stable, but remaining _nephrons could just be doing more work_ -\> may be misleading, but creatinine is best test
- _Net effect_: disease may progress by hemodynamic mediated injury even if original underlying disease is no longer active
- _Patient has to be in steady state_
31
What are the stages of CKD?
- This is important because it helps you get more information to your patients about where they are at
32
Why do we estimate the GFR instead of using the serum creatinine?
- She said this is BOUND TO BE A TEST QUESTION
- Serum creatinine affected by MANY factors, incl. age, muscle mass, sex, race, etc.
33
What are the 4 steps in the progression of renal disease? What is the big risk with CKD?
1. Microalbuminuria
2. Proteinuria
3. Doubling of serum creatinine levels
4. 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
What is the intact nephron hypothesis?
- 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)
35
What is the trade-off hypothesis?
- To maintain homeostasis despite reduced GFR, 2o events occur that help maintain homeostasis at expense of adverse side effects
- _Examples_:
1. Calcium/phosphorus: secondary hyper-PTH
2. Sodium balance: hypertension
3. K+ balance: hyperaldosteronism and HTN
4. Increased filtration by residual nephrons: disease-independent nephron injury
36
What do these graphs show?
- 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
What does this graph show?
As you diurese these people (i.e., ppl with essential HTN), getting rid of salt and water, they will get better
38
What are the cardiac manifestations of chronic renal insufficiency?
- Early chronic renal failure assoc w/HTN, which freq results in _left ventricular hypertrophy_ (LVH)
1. \> 50% of pts reaching ESRD have LVH (makes sense b/c 80% or more have HTN)
- Late renal failure freq assoc w/volume overload, marked anemia, and sxs of _CHF due to fluid overload_
- Late or advanced chronic renal failure can be assoc with _pericarditis_, usually manifested by _chest pain & a pericardial friction rub_
- People who make it to dialysis are the survivors
39
What does this graph show?
- Risk of CV events and dying goes up with worse functioning kidneys (lower GFR)
40
What are the nervous system effects of renal insufficiency?
- Early to moderate renal insufficiency leads to _subtle changes in intellectual function_, particularly in concentrating ability
- More severe renal failure can lead to devo of overt _encephalopathy_ often manifested by presence of _asterixis_ (hand tremor when wrist extended, i.e., hands up -\> resembles bird flapping its wings)
- Advanced renal insufficiency also leads to the development of _distal sensory peripheral neuropathy_
41
What endocrine abnormalities are associated with chronic renal failure?
- **_Fasting hypoglycemia more common_** w/advanced renal failure -\> due to several factors:
1. _DEC insulin degradation_, so endogenous or exogenous insulin has longer 1/2 life
2. _DEC gluconeogenesis_ by kidney
3. Impaired protein/calorie intake, resulting in _decreased glycogenolysis_ by the liver
- Can have hypoglycemia while waiting for a surgery (because they are not allowed to eat)
- Some anorexia as they are approaching dialysis
42
How is anemia related to kidney disease?
- 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
43
How does pressure natriuresis exemplify the trade-off hypothesis?
- INC BP augments Na excretion into urine
- DEC GFR leads to DEC filtered Na and a tendency for Na retention
- HTN INC pressure natriuresis, _promoting ability to maintain Na balance_, but at expense of _HTN, which accelerates progressive nephron loss_
- This is an example of the trade-off hypothesis
44
What is EPO?
- Glycoprotein secreted in response to diminished oxygen delivery to the kidney
- Binds receptors on erythroid precursors -\> tx with erythropoietin often results in increased blood pressure (less anemia induced vasodilatation)
- _Anemia resolves some symptoms of chronic renal failure_
45
What are the GI effects of renal insufficiency?
- With progressive loss of GFR, there tends to be a decreased appetite with a spontaneous reduction in protein intake
- With progressive renal insufficiency, nausea devos largely due to gastroparesis
- More severe renal insufficiency leads to nausea and vomiting
- _Net result of these changes is the development of protein calorie malnutrition_
46
How does renal insufficiency alter drug metabolism?
- Many drugs and drug metabolites renally excreted
- Decreased renal function (decreased GFR) leads to reduced excretion of these drugs and metabolites
- _Unless dose adjustments made, there will be INC drug levels in the serum, with enhanced drug toxicity_
- _Any drug you give -\> always look up the dose_, and always take into account kidney and liver disease
47
How does renal insufficiency affect Ca metabolism?
- Normal conditions: only 10-20% of dietary Ca intake absorbed by the intestine
- Gut Ca absorption strongly influenced by 1,25-di-hydro-VitD3 -\> DEC GFR leads to DEC enzyme 1- α hydroxylase, found almost solely in the kidney
- _DEC 1- α hydroxylase leads to DEC 1,25(OH)2VitD3 and DEC Ca absorption by gut_
- Combo of _hyperphosphatemia INH 1- α hydroxylase_ and DEC GFR leading to DEC 1- α hydroxylase leads to marked impairment of 1,25(OH)2VitD3 production
- _Net result hypocalcemia, leading to PTH secretion_
48
How does renal insufficiency affect phosphate metabolism?
- _Adverse effects of hyperphosphatemia include_:
1. Complexing with calcium, leading to slight reductions in serum calcium concentration
2. Inhibition of 1- α hydroxylase, leading to impaired 1,25(OH)2VitD3 production
3. Direct effect on PTH tissue to enhance PTH secretion
4. Metastatic calcification (vascular calcification): this is a CV risk
- _Tx_: low phosphate diet
- _NOTE_: hyperphosphatemia due to decreased excretion (due to decreased GFR)
49
How does renal insufficiency affect bicarbonate?
- Renal H+ secretion into urine synonymous with addition of new bicarbonate to blood
- With DEC #'s of functioning nephrons, there is a DEC ability to excrete acid into urine (i.e., DEC NH4+ production and DEC new bicarbonate production)
- _Net result is a tendency to metabolic acidosis with a normal plasma anion gap_
- Most often not a big problem, unless they have interstitial disease (same thing with potassium)
50
How does renal insufficiency affect potassium?
- With progressive renal insufficiency, there is a DEC ability to excrete a potassium load
- Under conditions of normal K+ intake, kidney is able to maintain homeostasis until renal failure is far advanced (GFR \<15 ml/min)
- _Potassium is last electrolyte in which homeostasis is lost_ -\> clinically important since severe hyperkalemia is the most life-threatening electrolyte abnormality
