Complications of CKD

Question 1

Describe consequences of sodium retention in CKD

Answer 1

• Sodium retention complications:
  
  • Volume expansion
  • Peripheral oedema
  • Hypertension

Question 2

Describe what happens to sodium and water retention in CKD

Answer 2

• Normal GFR (100 ml/min) reabsorbs most of the filtrate in the proximal tubule. Stage 5 CKD (GFR 10 ml/min) significantly reduces this reabsorption
• Sodium intake and urine osmolality considerations: typically 100-300 mmol Na a day = 200-600 mOsm
• Urea= 500 mmol = 500 mOsm
• Urine osmolarity range 100 to 1000 mOsm
• In CKD, ability to concentrate urine is lost, and becomes fixed at 300 mOsm
• Reabsorption in PCT is fairly static at about 60%, only 6 L reaches the loop of Henle, even less reaches distal nephron
• Note: loop diuretics will work to some extent. distal nephron diuretics probably will not
• In severe CKD, urine’s ability to adapt to sodium and water intake changes is limited
• Thirst becomes the primary regulator of serum osmolality
• Higher sodium intake leads to thirst, hypertension, heart failure, and electrolyte imbalances (hyponatraemia more common than hypernatraemia – occurs in cases of dementia and severe delirium)

Question 3

What are the goals of blood pressure control in CKD?

Answer 3

• Hypertension is a real risk with fluid retention, very common presentation in kidney disease
• Goals vary based on renal and cardiovascular risk
• Definition of hypertension remains BP > 140/90 for most risk groups
• Target goal for high-risk groups is often < 130/80

Question 4

How is hypertension treated in CKD?

Answer 4

• Most antihypertensives can be used
• Salt restriction and diuretics are the exception
• Treatment is often necessary
• Limitations of diuretics’ effectiveness in severe CKD

Question 5

What are the consequences of potassium retention?

Answer 5

• Potassium retention consequences:
  
  • Hyperkalemia (depolarises cell membrane, cardiac and muscular effects)
  • bradycardia, conduction delays, cardiac arrest
  • skeletal muscle weakness

Question 6

Which medications lead to potassium retention?

Answer 6

• ACEi
  
  • ARBs
  • Spironolactone
  • Beta blockers
  • Trimethoprim

Question 7

Describe the distribution of potassium in the body

Answer 7

• Distribution between intracellular and extracellular compartments: largely intracellular
• Ratio of extracellular and intracellular potassium key to establishing membrane potential
• Significance of intracellular buffering for short-term potassium regulation: otherwise, chips would kill you

Question 8

Discuss potassium homeostasis

Answer 8

• Largely role of kidney, some excretion by bowels
• Role of aldosterone in potassium regulation
• This is largely independent of its volume/sodium control function

Question 9

Describe how potassium retention is treated

Answer 9

• dietary and medication changes
  
  • very high levels are acutely life threatening and require hospital admissions
  • very high definition is inconsistent: 6 or **6.5

Question 10

Discuss issues of calcium and phosphate retention

Answer 10

CKD is associated with vitamin D deficiency due to decreased 1-alpha hydroxylase activity. By reducing intestinal absorption of calcium, vitamin D deficiency also causes low calcium levels, which in turn stimulates the secretion of PTH, leading to secondary hyperparathyroidism. Although high levels of PTH normally stimulate renal reabsorption of calcium and excretion of phosphate, phosphate excretion is impaired in CKD, resulting instead in hyperphosphatemia. Other laboratory abnormalities in patients with CKD include hyperkalemia and metabolic acidosis.

Question 11

Describe sources of phosphate

Answer 11

• Natural phosphate mainly comes from high-protein foods, often elevated in kidney disease
• Absorption differences between meat phosphate, additive phosphate, and phytate-bound plant phosphate: meat and additive is better
• Lack of definitive evidence supporting specific target levels for these parameters

Question 12

How is high phosphate treated?

Answer 12

• Approaches include dietary changes and medication interventions
• Phosphate binders (calcium-containing, aluminum-containing ^[cheap], lanthanum, sevelamer, iron)
• Minimization of vitamin D
• Correction of hyperparathyroidism

Question 13

Describe how acidemia occurs in CKD and how it is treated

Answer 13

• Inability to excrete acid in CKD leads to chronic acidemia
• Consequences include bone dissolution, malaise, catabolism, accelerated renal function decline

Treatment options to manage acidosis
- reduce animal protein
- consider calcium carbonate: but risk of hypercalcaemia
- sodium bicarbonate: but issues of water retention and oedema

Question 14

Discuss how anaemia emerges in CKD and how it is managed

Answer 14

• Erythropoietin’s role in regulating haemoglobin by sensing kidney hypoxia
  
  • but risk of thrombosis, heart attack, stroke
• Inflammatory state in severe CKD
  
  • inhibits iron transport and use due to hepcidin
  • Intravenous iron often required for erythropoiesis

Question 15

How are calcium stones treated?

Answer 15

• Except perhaps in extreme diets, most oxalate is endogenously produced
• Intake of some high oxalate things (tea, coffee) is actually associated with a lower stone risk
• Citrate chelates calcium and improves solubility
• Urine citrate excretion can be increased by plasma alkalinisation (inhibits reabsorption tubular cells)
• Unfortunately, Calcium phosphate is more soluble at lower pH
  ### Urate Stones:
• Characteristics of urate stones: 15 times more soluble than uric acid
• Influence of urine pH on solubility: pKa is 5.4 in urine. at this pH half is dissociated
• At higher pH solubility improves markedly

Question 16

Discuss kidney stones

Answer 16

• Calcium oxalate and calcium phosphate stones are most common
• Most oxalate is endogenously produced
• Stones are radio opaque
• Citrate chelates calcium and improves solubility
• Urine citrate excretion can be increased by plasma alkalisation (increases net
  secretion by tubular cells) - more urine citrate permits greater concentration of
  calcium before stone occurs
• Calcium phosphate is more soluble at lower pH
• Urate stones around 10% of cases
• Stones radiolucent, rhomboid
• Urate is 15x more soluble than uric acid
• pKa is 5.4 in urine - at this pH, ½ will be dissociated - at higher pH, solubility
  improves markedly as 90% is in rate form
• i.e. easiest way to improve urate stones is to raise pH
• Struvite stones are associated with infection

Question 17

60yo man presents following extraction of 4th
calcium oxalate renal calculi. Obese, BP 150/90. No
medications. Creatinine, electrolytes, PTH normal.
Vitamin D 25mmol (>50). Acidic urine. Hypercalciuria,
hyperoxaluria, hypocitraturia, high Na+ intake. What should be his treatment?

Answer 17

Commence potassium bicarbonate/
citrate. Measure bone density. Commence
chlorthalidone.
Oxalate mostly endogenous ∴ dietary change not
recommended
Lowering calcium intake not recommended
Sodium citrate/bicarbonate not recommended as
more calcium would be excreted (stones)

Question 18

Discuss how sodium becomes deranged in CKD

Answer 18

• ↓ GFR can cause sodium retention
• Normal: GFR 100mL/min = 140L/day → most reabsorbed in proximal tubule
• Stage 4 CKD: GFR 10mL/min = 14L/day
• Normal diet produces ~1000mOsm urine
• 100-300mmol Na+ consumed/day ∴ 200-600mOsm of urine is Na+
• ~500mmol is urea from protein ∴ 500mOsm urea
• Urine osmolality range can be from 100 - 1000mOsm/L
• In patients with CKD, urine osmolality usually remains fixed around 300mOsm/kg
• Only ~2.5L of fluid can be excreted before hyponatraemia occurs
• Patient with kidney failure and low sodium is usually drinking too much fluid
• Assuming a relatively normal diet
• Minimum necessary urine volume is ~1L to excrete electrolytes (osmolality up to 1000mOsm)
• Maximum urine volume is ~10L to excrete water loads (minimum osmolality of 100mOsm)
• This flexibility is lost in CKD
• Ability to concentrate urine is lost in CKD - urine osmolality fixed at ~300mOsm/L
• Urine volume for homeostasis is fairly fixed - cannot adapt to changes in sodium or water intake
• Thirst becomes the main regulator of serum osmolality
• Higher sodium intake leads to thirst → hypertension and heart failure
• Negative thirst does not exist - hypernatraemia is rare (since we fix this by drinking), but hyponatraemia is more common
• Reabsorption in PCT is fairly static (around ⅔) so only about 6L of filtrate reaches LOH and even less reaches Na+/H2O regulating
  areas in distal nephron
• Loop diuretics will still work, but distal nephron diuretics probably will not

Question 19

72yo female with BP 165/80, HR 72bpm. Hx of MI
last year. Taking hydrochlorothiazide 12.5mg daily,
ramipril 5mg daily and amlodipine 5mg daily. EUC
normal, except serum sodium 128 (135-145). Serum K is
5.2 (3.5 - 5.2). What does treatment entail?

Answer 19

Stop hydrochlorothiazide and double
amlodipine (due to low Na+) - thiazide diuretic causes
low sodium and high potassium (in exchange for sodium)
Not recommended to increase ramipril dose since anti-
hypertensive drugs are most effective in first few mg and
K+ may increase if dose increase (already upper end of
normal)

Question 20

Discuss how potassium is deranged in CKD

Answer 20

• Potassium retention (hyperkalaemia) - depolarises cell membranes

Homeostasis:
* Dietary potassium mainly excreted by kidneys (92% usually), however in the short
term, intracellular buffering occurs
* e.g. Insulin pushes K+ intracellularly
* Renal potassium homeostasis is controlled by aldosterone - largely independent of
volume (sodium retention) control function
* Not always independent - in severe volume depletion, body may retain sodium
and so lead to low potassium

Kidney damage impairs this process
In hypovolaemic and hyperkalaemic state, kidney struggles to excrete excess K+ since not enough Na+ delivered to distal
tubule

Question 21

24yo man develops profuse diarrhoea. He
has not passed urine for 12 hours. BP is 105/60, HR
110bpm. ECG normal except for sinus tachycardia.
Plasma creatinine 150μmol/L (<110), bicarbonate 12
(22-32), K+ 2.6 (3.2 - 5.2), adjusted Ca2+ 1.8mmol/L
(2.15 - 2.55)
Hypokalaemia due to high aldosterone causing Na+
retention (to counterbalance hypovolaemia

Answer 21

Treatment: 0.9% saline 1L with 10mmol KCl at 1L/
hour (for hypovolaema) with oral potassium
supplements 30mmol 4hr (for hypokalcaemia)
Low bicarbonate due to diarrhoea ∴ no need for
treatment
Low adj. Ca2+ - adjusted calcium only for albumin
not for pH ∴ probably closer to normal so doesn’t
need treatment
Saline only not indicated as this would further dilute
plasma K+

Question 22

30yo male with non-proteinuria Stage III CKD and hypertension
presents for routine review with BP 160/95 and HR 55min. K+, Na+
and Ca2+ levels all normal. He is taking ramipril 10mg daily

Answer 22

Add chlorthalidone (thiazide-like diuretic) 12.5mg daily
Spironolactone (aldosterone antagonist ∴ effective anti-hypertensive)
not indicated due to severe anti-testosterone effects (↓ libido, erectile
dysfunction, etc.) and raises potassium
Frusemide loop diuretic acceptable in severe kidney failure (>Stage 4),
but thiazides would still work for this patient
Atenolol (selective ß1 blocker) not acceptable given low HR

Question 23

Patient with Stage V chronic kidney disease
and Hx of hypertension presents with potassium of
6.5 (3.2-5.5) and normal calcium. He follows a low
potassium diet. His regular medications are: ramipril,
frusemide, calcium carbonate and amlodipine

Answer 23

Treatment: Stop ramipril (which raises K+) and
advise ultra low potassium diet (though probably less
to gain from this since already on low K+ diet)
In hospital: salbutamol, insulin
(shuttle K inside cells) with dextrose,
resonium and calcium gluconate/chloride. Order ECG

Question 24

Descrine how phosphate becomes deranged in CKD

Answer 24

• 15% in ICF, <0.5% in ECF and 85% in bony matrix
• Phosphate retention (PO43-)
• Secondary hyperparathyroidism (PTH helps to excrete phosphate from kidney)
• Vascular calcification
• Phosphate homeostasis
• Natural phosphate comes from high protein foods and is often too high in kidney
  disease
• Meat phosphate and additive phosphate is better absorbed than phytate-bound
  plant phosphate
• 90% of phosphate that is not protein-bound is filtered by GBM
• 70% of filtered phosphate reabsorbed in PCT by Na+/PO43- cotransporter
• Dietary phosphate → ↑ PTH production → phosphorous mobilised from bone = vicious
  cycle of rising phosphates
• Inhibits Na+-phosphate cotransporter in PCT ∴ ↓ phosphate reabsorption and ↑
  urinary excretion of phosphate
• Kidney failure means phosphorous can’t be excreted - negative feedback loops
  controlling PTH and FGF-23 are lost
• Calcitriol increases phosphorous absorption
• High phosphate treatment
• Dietary (lower meat diet, less cured meats, less coca cola)
• Phosphate binders
• Calcium-containing
• Lanthanum (expensive heavy metal)
• Sevelamer (ion exchange resin that exchanges phosphorous for chloride or
  bicarbonate)
• Iron (expensive)
• Vitamin D minimisation (reduce calcitriol, but this may increase PTH so surgical correction may be required)
• Correct hyperparathyroidism

Question 25

patient with stage IV renal failure presents with
BP 145/60, PTH of 10 (ref 1.5-7.5). Calcium is 2.4
(2.1-2.5), phosphate is 1.6 (0.75 - 1.5). He has meat
with every meal.

Answer 25

Prescribe calcium carbonate with meals
(binds to phosphate in diet and stops absorption - ↑
Ca2+, ↓ Phos, ↓ PTH), prescribe soy based high
protein diet, ask him to reduce intake of cured meats
Calcitriol contraindicated - this would ↑ Ca2+, ↑
Phos, ↓ PTH
Haemodialysis too extreme