Renal 3 Flashcards
What are the complications of CKD?
Directly related to progressive inability of the kidney to perform its normal functions:
Regulate fluid, electrolyte, and acid-base balance
Remove metabolic waste products from blood
Removal of foreign chemicals from blood
Regulation of blood pressure
Secretion of hormones
When are the complications of CKD evident?
Can be evident as early as Stage G2
eGFRb and complication relationship
Likelihood of CKD complications increases as GFR decreases
When are lifestyle interventions such as….. required? Every pt?
Lifestyle, dietary, and pharmacological interventions required (Stage G3-5 CKD)
Complications might not occur at the same rate or to the same degree in patients within each CKD category
On average when do pts require tx for complications?
Stage 3
Sodium and Water Imbalance Cause, Sx, and Stage?
Progressive loss of ability of the kidneys to excrete excess water and sodium
Leads to weight gain, hypertension (RAAS activation), peripheral and pulmonary edema
Onset of symptoms usually Stage 4 CKD
TX of Na+ and H20 Imbalance
Sodium and water restriction
90mmol sodium (<2g) and 1-2L of fluid per day
Diuretics: Furosemide +/- metolazone
Stage 5: Dialysis
Diuretics for Na+ and H20 Imbalance
Thiazides less effective for diuresis once GFR < 30 ml/min (Can still have effect on blood pressure tho)
Furosemide preferred
40 mg PO daily (variable doses!)
Becomes less effective as kidney function declines – more frequent, high doses may be required (does not reach drug concentrations high enough in the kidney to have its effect)
FeNa Normal, Tzd, Loop
FeNa Normally 1% in healthy individual
Thiazide 3-5%
Loop Diuretic 20-25% (excreted 4-5x more Na+ than thiazides) More effective diuresis
Where does metolazone work?
Distal Convuluted Tubule
Limitation of Loop Diuretic
Patients can develop resistance to loop diuretics
Describe why loops are often combined with tzds?
Furosemide works on hoop of henle to block reabsorption of Na+ –> More Na+ in kidney, more urine production
- There Can be a compensating mechanism in distal convulted tubule –> Increase Na+ uptake in distal tubule
- Use thiazid elike diuretic like metolazone (blocks at distal tubule)
- Effects are synergistic with one another –> Increase Na+ excretion and therefore H2O
- Dietray Na+ restriction also beneficial here
When does furosemide resistance occur?
Will happen if dietary Na+ is high Na+ restriction helps overcome resistance as well
What may be added to furosemide?
May add metolazone (or other thiazide)
Synergistic diuresis with furosemide due to natriuretic action at distal tubule
Monitoring of Diuretics.When?
Electrolytes (all but specifically K+)
Na+, K+, Cl-, HCO3, Mg, Ca
q1-2 weeks initially, every 3-6 months when stable
Clinical signs and symptoms of dehydration (volume depleted) –> Especially during acute illness (SADMANS)
Metabolic Acidosis Definition.Cause?
Characterized by a ↓ in the pH of the blood (acidemia) and a ↓ in serum bicarbonate levels (<22 mmol/L)
May be due to impaired excretion of acids and/or reabsorption of bicarbonate
Metabolic Acidosis in CKD mechanism
In CKD, can usually still acidify the urine (e.g., secrete H+), but the kidneys produce less ammonia to buffer the H+ –> leads to the retention of H+
Ammonia (NH3) + H+ –> Ammonium (NH4+) – excreted in urine
Exacerbated by hyperkalemia – further depresses NH3 production (correcting hyperK+ may helt correct acidosis to an extent)
Result: Reduction of bicarbonate levels in attempt to maintain blood pH –> As progresses, start to see acid being buffered by protein in mucle (muscle wasting), and by phosphates in bone –> brittle bones, fractures, etc.
When is acidosis the most prominent?
Most prominent in Stage 4-5 CKD
Treatment of Metabolic Acidosis
Sodium bicarbonate tablets
325-500mg PO BID-TID (variable dose)
(Baking soda dissolved in water)
Benefits of Sodium Bicarb and Cautions
Benefits: ↓ CKD progression, improved nutritional status
Concern: Possibility of sodium loading (not to same extent as NaCl)
Severe Acidosis Tx
Intravenous sodium bicarbonate
Severe acidosis in hospitalized patient
Dialysis (Stage 5 CKD)
HyperK+ Definition, Stage, and Cause
Inability to maintain a normal serum potassium of 3.5-5.0 mmol/L
Stage 4-5 CKD (v. mild in Stage 3)
Primarily due to decreased potassium excretion
Exacerbating factors of hyperK+
Describe the relationhsip between metabolic acidosis and hyperK+
Metabolic ACidosis –> excess H+ ions
Exchange at cellular level –> exchange K+ for H+ to improve pH of the blood
K+ ions in the blood that results in hyperkalmeia (more of it moved from the tissues into the the blood stream)
Many pt’s with hyperkalemia are…… Why?
Many patients are asymptomatic, especially with chronic hyperkalemia (adapt)
In response to continuously elevated K+ in CKD, the body finds ways to eliminate K+ (often the GI tract) –> Can maintain levels for a while through other mechanisms
Mild-Moderate HyperK+ range and sx
Mild to Moderate: (5.1 -7mmol/L)
Non specific sx such as Weakness, confusion, muscle & respiratory paralysis, ECG changes (6 - 7 mmol/L) such as peaked T-waves
Severe HyperK+ Range and Sx
Severe: (>7 mmol/L)
ECG changes (7-8 mmol/L) widened QRS complex, small amplitude P wave; (8-9 mmol/L) sinus waves; (>9 mmol/L) heart block, ventricular tachycardia, sudden cardiac death
HyperK+ 1st Line Tx
Identify/correct exacerbating factors
Drugs, diet
Most CKD patients with mild hyperkalemia (~5.5 mmol/L) can be managed with dietary potassium restriction
Mild HyperK+ Drug Tx
Mild acute or refractory chronic hyperkalemia potassium binders (remove K+ in GI tract)
Sodium polystyrene sulfonate (Kayexalate®, Solystat®)
Patiromer (Veltassa®)
Sodium zirconium cyclosilicate (Lokelma®)
Kayexylate MOA
Cation exchange resin: Removes K+ ions by exchanging it for Na2+ ions
Not absorbed by the GI tract
Kayxelate A/e
GI: Constipation, NVD
Kayexlate Formulation
Oral powder (15g = 4 level tsp) or liquid suspension
Can be given PO or as rectal enema
15-60g daily-QID
Oral route most common - lowest GI toxicity risk
Kayexylate Monitoring
Monitor for hypokalmeia
Compare K+ binders: MOA, Dose, Onset/Duration, Safety
Severe HyperK+ Tx
Severe hyperkalemia (>7 mmol/L or ECG changes) → Medical Emergency!
Calcium gluconate IV (to stabilize myocardium)
Glucose plus human regular insulin
Sodium bicarbonate IV (*only if metabolic acidosis)
Salbutamol via nebulizer
Kayexalate® 30-60g PO q4h until K+ normalized
Dialysis (Stage 5 CKD or severe acute hyperkalemi
Goal of tx for severe HyperK+
Prevent severe cardiac arrhythmia, death, correct potassium <5.5 mmol/L
CKD-BMD Definition
A systemic disorder of mineral and bone metabolism due to CKD manifested by either one, or a combination of, the following:
Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism (i.e., minerals)
Abnormalities in bone turnover, mineralization, volume, linear growth, or strength (i.e., bone metabolism)
Vascular or other soft tissue calcification
When does CKD-BMD occur? Outcomes?
Changes in bone and mineral metabolism begin in stage 3 CKD (GFR <60 ml/min) and progress
Bone abnormalities present in nearly all dialysis patients
Outcomes: bone pain, fractures, CVD, death
CKD-BMD Mechanism
Increased serum phosphate (PO4) due to decreased kidney excretion
–> Calcium binds to excess phosphate in the blood
Decreased serum calcium (Ca) due to decreased GI absorption due to decreased Vitamin D (also due to binding with phosphate)
–> Why? Because the final synthesis step to active calcitriol occurs in the kidney
Negative feedback between serum Ca2+ and parathyroid galnd/PTH
Negative feedback leads to increased parathyroid hormone (PTH) which ultimately depletes Ca2+ from the bone
Describe the calcium-PTH-phosphorous pathway and CKD-BMD
Because we a reduction in calcitriol production with impaired kidney production, less Ca2+ reabsorbed from the gut –:> Increase activation of PTH and ultimately deplet Ca2+ from the bone (why it is a bone dx in the end)
Diagnosis of CKD-BMD
Biochemical abnormalities
–> Serum calcium, phosphorus, PTH, alkaline phosphatase (ALP)
–> Help predict underlying bone turnover
Bone abnormalities
-Definitive diagnosis requires a bone biopsy (not routinely used)
- Bone Mineral Density (BMD or DXA) (predict fracture risk and osteoporosis)
–> Does not predict the type of renal osteodystrophy (not routinely done in those with CKD)
Vascular calcification (increasingly worried about in regards to mortality of CKD pt’s)
E.g., echocardiogram to identify valvular calcification
Screening for CKD BMD Recommendation Canadian Society of Nephrology
Severe abnormalities in Ca, PO4 and PTH are uncommon in CKD G3
Recommend monitoring these parameters (and consequently initiating treatment) in CKD G4-G5
CKD-BMD Monitoring Summary
CKD-BMD Phosphate Risk
Phosphate (PO4)
Increasing serum concentrations associated with increased risk of all-cause mortality in CKD G3a-G5D
Prevantative Tx of Hyperphosphatemia
No benefit (and possible risk) in treatment to prevent hyperphosphatemia in patients with normal serum concentrations (only tx if high)
Goals of Phosphate in CKD-BMD
Lower levels toward normal range (0.81-1.45 mmol/L) in patients with overt hyperphosphatemia
Goals:
ND-CKD > 1.49 mmol/L
HD/PD-CKD > 1.78 mmol/L (dialysis; all will require tx)
Calcium Level Risks CKD-BMD
Low levels contribute to secondary hyperparathyroidism and renal osteodystrophy, and prolong the QT interval
Elevated serum concentrations associated with higher mortality and risk of CV events in CKD patients
Tx of Hypocalcemia. Sx?
Mild and asymptomatic hypocalcemia may not require treatment
Severe or symptomatic hypocalcemia (e.g., numbness, tingling, myalgia) should be corrected BUT avoid hypercalcemia (risks are acute)
Lab Tests for Calcium
Ionized calcium = “active” calcium
Total calcium = free (ionized) + calcium bound to albumin
Corrected calcium = calcium adjusted for albumin levels
PTH Risks CKD-BMD
Severe hyperparathyroidism (HPT) is associated with calciphylaxis, CVD, neuromuscular disturbances, and death in CKD stages 3-5D
Optimal PTH Levels
Optimal PTH level is unknown in CKD patients not on dialysis
Modest increases may be an appropriate response to worsening kidney function (to overcome PTH resistance and to ↓ PO4)
PTH Treatment and Goals
PTH should be progressively rising or persistently high in order to initiate treatment (specifically in pt’s not on dialysis)
Target in CKD G5D: PTH 2-9x upper limit of normal (in dialysis)
Upper limit of normal is around 8; do not treat until around 50 or higher; significantly higher levels
Hyperparathyroid Bone Dx Mechanism
