What is CKD (vs. AKD)?
- Not reversible (in contrast to AKD)
- Progressive even after original disease causing kidney damage is treated
- Associated with other illnesses: heart disease, HTN
What are the stages of CKD?
What is the model explaining progressive kidney failure?
Remnant kidney model
Primary renal injury -> loss of nephrons
-> Hyperfiltration of remaining nephrons
-> Increased glomerular pressure
-> Mesangial cell and endothelial cell injury
-> Mesangial cell and matrix expansion
-> Focal sclerosis
-> Loss of nephrons AND REPEAT
Key is to stop the pressure
What is normal GFR?
What is normal Na?
Angiotensin II acts on the ____ (afferent/efferent) arteriole
Angiotensin II acts on the efferent arteriole
- -> constriction
- Also have increased glomerular pressure
What is the pathogenesis of CKD (proteinuria and glomerulosclerosis)?
(Subtotal nephrectomy in rat is good experimental model) Reduction in functioning nephrons increases systemic hypertension and single nephron glomerular filtration rate (SNGFR)
- Systemic hypertension accelerates renal arteriolar damage, contributes to micro aneurysm formation
- Increased glomerular pressure raises SNGFR, but enlarges glom tuft, damages epithelial cells, causing mesangial hyaline deposits, and glomerular thrombi
What is the pathogenesis of CKD (glomerular and tubulointerstitial damage)?
- Glomerular focal sclerosis, and hyalinosis
- Tubules atrophy
- Chronic interstitial inflammation
Tubular-interstitial fibrosis end result
Gross changes seen in CKD?
- Bilateral contracted kidneys
- Thin renal cortex
- Multiple cysts (acquired cystic disease)
What are some interventions to slow progression of CKD?
Control glomerular pressure
- Low protein diet
- BP control
- ACEI and ARBs
(stop Ang II increase in glomerular pressure)
What kind of diet is ideal for slowing progression of CKD? Details?
Low protein diet (0.5 g/kg body mass)
- Loss of renal function limits ability to match intake and output
- Renal diet may conflict with pt's previous dietary practices (e.g. diabetic diets)
- 0.5 g/kg body mass...
- High biological grade protein
- Problems with compliance, food choices, blood sugar control, malnutrition
What are the effects of angiotensin II?
- Aldosterone production
-> Sodium retention
ACEI and ARB may cause what in diabetics?
Bump in creatinine
What are results of kidney failure in terms of:
- Toxin accumulation
- Abnormal electrolyte levels
- Endocrine system
- High BUN and creatinine
Abnormal electrolyte levels
- Fluid retention, CHF...
- Low Vit D -> hypocalcemia (no activation of Vit D 25 to 1,25)
- Anemia (decreased EPO production)
- Hypoglycemia (failure to metabolize insulin)
What are some signs and symptoms of chronic kidney disease (broad categories)?
- Sodium and volume mgmt:
- Phosphorus and bone disease
What are some signs and symptoms of chronic kidney disease in terms of sodium and volume mgmt?
- High Na diet -> volume retention in kidney failure
- Water restriction without sodium -> thirst
- Use a low sodium diet and diuretics to control volume (say no salt rather than more water!)
What are some signs and symptoms of chronic kidney disease in terms of phosphorus and bone disease?
- Hyperphosphatemia: Pi binds to Ca++ and precipitates in vasculature
- PTH elevated, osteodystrophy, vascular calcification
- 1,25 dihydroxyVitD suppresses PTH but increases gut Ca absorption
- Pi found in most foods, restriction limits dietary choices
How to deal with hyperphosphatemia, calcium, vitamin D and PTH in CKD?
Phosphate binders- trap Pi in gut
- Al, Mg, iron, and Ca salts are excellent binders
- Mg is toxic, Al is bone toxic, Ca results in hyper calcemia
- Sevelamer expensive, works poorly
Vitamin D- suppresses PTH
- Works poorly
- Causes hypercalcemia
Cinacalcet- sensitizes PTH gland to Ca, decreasing PTH secretion
- Can cause low turnover in bone disease
How to manage anemia (in CKD)?
Have decreased EPO levels with CRF; long and short acting EPO/ESA available
- Anemia to Hb of 8 g/dL is tolerated
- Excessive epo dosing causes HTN, thrombosis and can accelerate tumor growth!
- Aim for Hb of 10 (not 14!)
Why might EPO not work in anemia due to CKD?
- Chronic blood loss (e.g. GI bleeding)
- Chronic inflammation (e.g. hyper-PTH, chronic infections) suppresses RBC production
- Relative or absolute iron deficiency
What are the main causes of diabetic nephropathy?
3. GN (Other)
What are the stages of diabetic nephropathy Type I diabetics?
- Initially high GFR
- Control of diabetes -> drop in GFR
- After years of mgmt, may have fall in GFR (helped by Anti-HTN treatment)
What are components of the normal glomerulus?
- Bowman's space
- Capillary lumen
- Filtration membrane
What is seen here?
Left: normal glomerulus
Right: glomerulus in diabetes
What are the changes in renal (micro)anatomy due to DM?
- Mesangial expansion and thickening of glomerular basement membrane
- Nodule formation (25 to 30% of patients)
- Thickening of Bowman’s capsule
- Exudative hyaline lesions in Bowman’s capsule, mesangium, dilated capillaries
Why does diabetes damage the kidney?
Renal effects of diabetes:
- Glomerular hypertension (GFR initially elevated)
- Glomerular vascular damage
- Proliferative/fibrotic renal changes
How to manage/treat diabetic damage to the kidney?
Tightly control glucose
Lower glomerular pressure
- Low protein diet if tolerated
- Aggressive hypertension control
- ACEI or ARB
What are some end stage kidney failure symptoms/findings?
- Peripheral nerves
- General: Tired, apathy, itching, copper penny taste - GI: Nausea, vomiting, anorexia, loss of wt
- Cardiac: Pericarditis, uremic myocarditis
- Pulmonary: Edema, pleural effusion
- Peripheral nerves
- Increased conduction times, axonal loss, demyelination
- Paresthesia, restless leg syndrome, cramps
- Apathy, confusion, drowsiness
- Eventually coma, seizures
What are the indications for dialysis?
Renal Clearance: GFR of ~ 10mL/min/1.73m2
Could wait if:
- Stable or increased edema-free weight
- Protein intake > 0.8 g/kg/d
- No clinical signs / symptoms of uremia
Earlier initiation for Diabetics (GFR 15 ml/min) may be beneficial
- However, early initiation of dialysis adds risks and complications for patient
Flow scheme hemodialysis (picture)
T/F: There are methods to do chronic hemodialysis
- Routine access to vasculature is possible
- Complications include bleeding and thrombosis
What is an AV fistula/graft?
- No foreign body (internal)
- Grafts of gortex
What is a hemodialysis catheter?
- Dual lumen
- Provides quick easy access
- Sepsis, endocarditis
- Great vessel thrombosis
- Frequently clot, missed treatments
- Substance abuse
Avoid when possible
How is peritoneal dialysis done?
Fluid put in peritoneal cavity and peritoneal membrane acts as filtration barrier
Where are renal transplants located? What happens to old kidney? Lifetime treatment?
- Can use cadaveric or living donor
- Kidney placed over iliacs!
- Native kidneys not typically removed
- Lifetime immunosuppressive therapy
- CKD is common ( > 7% of the population)
- Pathophysiology of CKD: progressive glomerular sclerosis and kidney fibrosis
- CKD affects many organ systems
- Clinical interventions for CKD reviewed
- Options for renal replacement therapy
- Transplantation (when possible) is best treatment
- Home dialysis, HD, or PD next best Tx
- Essentially all ESKD pts spend some time on dialysis