Term
| What is the National Kidney Foundation's KDOQI guidelines for the 5 stages of CKD? |
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Definition
Basically, if GFR <60, you have CKD (based on population)
- CKD stages 3-5 (GFR 30-59, 15-29, <15- end stage)
**Commonly meant by CKD**
- CKD stages 1-2 (GFR >90, 60-89)
**Proteinuria is an IMPORTANT marker of risk, and should be incorporated** |
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Term
| What is the clinical importance of the semi-logarithmic relationship of Plasma creatinine with GFR? |
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Definition
1) At low values, small changes in plasma creatinine indicate large changes in GFR
2) At large values, large changes in creatinine reflects only small change to GFR |
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Term
| What are the modifiable and non-modifiable risk factors of CKD? |
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Definition
1) Modifiable
- HTN
- DM
- Obesity
- Dyslipidemia
- Hyperuricemia
- Smoking
2) Non-modifiable
- Old age*** big predictor
- Black
- Genetics
- Prematurity |
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Term
True or False:
Most patients with CKD eventually progress to ESRD |
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Definition
False!
However, the prevalence of ESRD is rising! Furthermore, ESRD mortality rates are very high (20%) |
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Term
| What is the "big picture" pathological basis for CKD? |
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Definition
Loss of functioning nephrons arises and leads to
1) Hyperfiltration by remaining nephrons
- RPF and GFR increase 50% (5/6 nephrectomy model)
- Creates capillary HTN via AII signaling (prevent with ACE-i or ARB)
2) Hypertrophy/glomerular growth
- AngII signaling ultimately leads to inflammation, injury and ECM accumulation, producing Glomerular and tubulointerstitial fibrosis |
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Term
| What are the 3 pathological stages of glomerulosclerosis in CKD? |
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Definition
Its like atherosclerosis!
1) Endothelial injury and inflammation
2) Proliferation- with a) stretched epithelial cells and b) proliferated and dedifferentiated mesangial cells
3) Fibrosis- hyaline material accumulates in mesangium and sub-endothelial regions of glomerulus, producing capillary collapse (glomerulosclerosis) |
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Term
| How can you most effectively slow CKD progression? |
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Definition
1) Treat underlying cause and identify reversible factors
- volume depletion
- uncontrolled HTN
- Obstructive uropathy (postrenal AKI)
- Nephrotoxins
2) Control BP with ACE-i and ARB
**taking away ACE-i may show transient improvement, but NOT sustainable**
3) Dietary protein restriction
- Diminish hyper-filtration of remaining nephrons
4) Stop them from smoking
5) Avoid nephrotoxins (NSAID, Tacrolimus/Cyclosporine) |
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Term
| Why do few people with CKD eventually receive dialysis or a transplant? |
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Definition
Most people with CKD die from CVD! So, CKD is a MAJOR risk factor for CVD
Non-traditional risk factors may account for this |
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Term
| What is a useful model of car for patients with CKD (4 steps)? |
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Definition
1) Screen for CKD- older, african americans with diabetes and HTN are at high risk
2) Diagnose with serum creatinine/eGFR
3) Treat CKD and CVD with ACEI/ARB, smoking cessation
4) Prepare for renal replacement therapy (dialysis/transplant) |
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Term
| What happens to patients when GFR decreases to <15-20 generally? |
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Definition
They become UREMIC.
MULTI-SYSTEM Symptoms arise from
1) Waste retention (excretory failure)
2) Metabolic and endocrine dysfunction in the kidney |
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Term
True or False:
Development of and failure to alleviate uremic manifestations with pharmacologic/conservative measures is an indication for dialysis |
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Definition
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Term
| What are the common systems affected by uremia and their common manifestations? |
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Definition
1) CV- HTN, Ischemic disease, Pericardial disease, CHF
2) Endocrine- Parathyroid, Lipids, Sexual
3) Hematologic- Anemia, Bleeding
4) GI- Anorexia, nausea, vomiting
5) Neuropsych- Peripheral neuropathy and seizures
6) Immunologic- Leukopenia, Lymphocytopenia
7) MSK- Mineral and Bone disease and Myopathy
8) Derm- Pruritus, Uremic pigmentation |
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Term
Which symptoms arise at each of these GFR levels?
1) 90
2) 60-80
3) 50-60
4) 30-50
5) 15-30
6) <15 |
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Definition
1) None
2) Edema or none
3) Fatigue, edema, nocturia or none
4) Loss of appetite, pruritis
5) Weight loss, dyspnea, fatigue, CNS
6) Life-threatening complications, Severe HTN, Pulmonary edema, Acidosis, Hyperkalemia, Encephalopathy. |
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Term
What do each of the following concepts explain about adaptation to CKD?
1) Intact nephron hypothesis
2) Functional reserve
3) Hyperfiltration
4) Osomotic diuresis |
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Definition
Remember, adaptation means that there is more solute excretion per remaining functional nephron
1) Abnormalities occur because of overall reaction in renal mass, rather than general loss of glomerular function.
2) The ability of the kidney to increase their function/work
3) Less nephrons filter more
4) Water loss from remaining nephrons and urine cannot be concentrated effectively |
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Term
| Which fluid/electrolyte changes occur most rapidly with decreasing GFR? |
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Definition
1) You see rapid Creatinine and BUN changes
2) Phosphorus, Bicarbonate and pH are partially regulated
3) Na+ and K+ are well regulated, and do not change until GFR is severe |
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Term
True or False:
Severely disease kidneys are lesss able to maintain homeostasis in the face of further physiological stress. |
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Definition
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Term
| What happens to creatinine and nitrogenous compound handling in CKD? |
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Definition
** ONLY creatinine serum increases are proportional to the fall in GFR**
1) As GFR decreases, creatinine and urea are maintained, increasing serum levels
2) Higher serum levels leads to increased filtration and excretion (compensatory to maintain daily production) |
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Term
| What happens to Na+ excretion as GFR decreases in CKD? |
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Definition
1) Fractional excretion is usually 2-10 % in CKD (<1% normal), which is adaptive under conditions of low GFR
-Decreased Na-K-2Cl (loop) and Na-Cl (thiazide sensitive) transporters
- Increase in ANP
- increase in ECV due to mild sodium retention
2) NARROW excretory range (subject to volume depletion or volume overload)
- prevent marked sodium retention by limiting intake to 2g/day |
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Term
| What happens to water excretion in CKD? |
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Definition
Water balanced maintained with normal thirst and free access to water
Changes can result from
- Reduction in GFR might limit H2O clearance
- Structural damage in medulla and tubulointerstitium, creating ADH receptor deficits
1) Decreased Fractional Reabsorption of water per nephron maintains adequate excretion in setting of reduced filtration. BUT, limits concentrating ability and makes patient sensitive to water deprivation.
2) Urine osmolality is isothenuric (sudden water load or deprivation is poorly tolerated) |
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Term
| What happens to K+ excretion in CKD? |
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Definition
Hyperkalemia occurs RARELY
- As filtered load decreases, distal K+ secretion per nephron increases (increased fractional excretion)
- Augmented by a) elevated aldosterone, b) increased extracellular K+ and c) increased distal tubular flow |
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Term
| Why does metabolic acidosis occur in CKD? |
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Definition
Serum HCO3- decreases with decreasing GFR, causing a positive H+ ion balance.
Occurs because:
1) Reduced NH4 excretion occurs (despite increased fractional excretion) due to decrease in # of functional nephrons
2) Proximal bicarbonate wasting occurs (minor) |
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Term
| What are the 2 patterns of acidosis that occur in CKD? |
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Definition
1) Early hypercholoremic, nonanion-gap with mild-moderate CKD
- Due to reduced NH4+ excretion
2) Later anion-gap acidosis with severe CKD
- due to retention of sulfates, phosphates, ect. |
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Term
| What hematological disorders are common complications of CKD? |
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Definition
1) Anemia
- Corresponds to degree of GFR decrease
- Decreased EPO (Bone marrow can't make RBCs) is primary cause
- Can give synthetic form (ESAs), but they can cause iron deficiency (supplement with iron) and HTN (MORE RISK THAN BENEFIT)
2) Platelet Dysfunction
- Bleeding diathesis due to acquired defect (retention of uremic toxin) leads to easy bruising |
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Term
| What mineral/bone disorders are common complications of CKD? |
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Definition
Abnormalities of divalent ions (calcium and phosphorous)
1) Phosphorus
- Initially unchanged with GFR, because of decreased reabsorption
- If GFR<30, phosphate levels increase (Hyperphosphatemia stimulates secretion of PTH and FGF-23, which increase renal phosphate excretion, but NOT ENOUGH).
2) Vitamin D
- KIdney is site of 1-alpha-hydroxylase for Vitamin D activation (to calcitrol), which enhances GI absorption of calcium and phosphorus.
- When GFR falls below 30, low circulatory levels of calcitrol are found (can't inhibit PTH)
3) Calcium
- Hyperphosphatemia causes Ca-Phos deposites, decreasing serum Ca and low Ca state stimulates PTH
4) PTH
- Elevated due to low calcitrol, elevated phosphorus and decreased calcitrol (partially adaptive)
- PTH usually causes K+ excretion, tubular calcium reabsorption and increased calcitrol synthesis, but CKD has skeletal resistance.
- SECONDARY HYPERPARATHYRODISM causes bone disease. |
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Term
| Why does secondary hyperparathyroidism arise in CKD and what are its clinical consequences? |
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Definition
Hyperphosphaturia, Low serum calcium and low activated Vitamine D (Calcitrol), combined with skeletal resistance to PTH leads to an abnormal increase.
1) Partially adaptive for mineral excess/deficiency
2) BONE DISEASE
- Osteitis fibrosa driven by PTH with increased turnover (Joint aches, bony pain, pruritius, fracture risk).
- Rickets in children (Osteomalacia)
- Adynamic bone disease (less turnover/activity leading to extra-skeletal calcification and fracture because the bone can't take up calcium and phosphorus) |
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Term
| What are the general principles of managing bone disease secondary to CKD? |
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Definition
1) Low phosphorus diet
2) Phosphate binders
3) Give Calcitrol to suppress PTH
4) Maintain Ca X Phos, decreasing extra-skeletal calcification
5) Monitor calcium, phosphate and PTH closely |
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