Chronic kidney disease

Question 1

Common causes of ESRD

Answer 1

Congenital and inherited - PKD, Alports syndrome
Renovascular disease
Hypertension
Glomerular diseases - IgA nephropathy most common
Interstitial diseases - often drug-induced
Systemic inflammatory diseases - SLE, vasculitis
DM
Unknown - 5-20%

Question 2

Typical presentation of CKD

Answer 2

Routine blood test - raised urea and creatinine
Hypertension
Proteinuria
Anemia
Rate of change in renal function is relatively constant for an individual - useful prognostic information! - Follow GFR

Question 3

General symptoms of CKD

Answer 3

Symptoms are usually not present until GFR is below 30 (stage 4-5) when disease is slowly progressive
Nocturia - early symptom
S&S can affect almost all body systems when GFR is below 15-20

Question 4

Typical symptoms of CKD

Answer 4

Tiredness and breathlessness
Pruritus
Anorexia
Weight loss
Nausea and vomiting
Further deterioration - hiccups, Kussmaul breathing (due to metabilic acidosis), muscular twitching, fits, drowsiness, coma

Question 5

Immune dysfunction in CKD

Answer 5

Cellular and humoral is impaired in advanced disease

Increased susceptibility to infection - the second most common cause of death in dialysis patients after CVD

Question 6

Hematological abnormalities in CKD

Answer 6

Increased bleeding tendency in advanced - cutaneous echymoses and mucosal bleeding. PLT function impaired and BT is prolonged.
Dialysis partially corrects it (due to uremia)
Increased risk of complications from anticoagulants (needed for hemodialysis)
Anemia - common, decreased Epo. Not in PKD (?)

Question 7

Electrolytes in CKD

Answer 7

Fluid retention common in advanced
Episodic pulmonary edema can happen in earlier stages - especially in renal artery stenosis
Tubulo-interstitiall disease - may develop salt-wasting - need high sodium and water intake
Metabolic acidosis - common. Usually asymptomatic. May increase tissue catabolism and decrease protein synthesis, exacerbate bone disease and rate of decline in renal function

Question 8

Endocrine function in CKD

Answer 8

Loss of libido - hypogonadismm due to hyperprolactinemia (both genders)
Half-life of insulin is prolonged (reduced tubular metabolism), but also increased insulin resistance and reduced apetite – leads to unpredictable insulin requirement in diabetic patients in advanced CKD

Question 9

Neurological and muscle function in CKD

Answer 9

Generalized myopathy may occur - poor nutrition, hyperparathyroidism, vitamin D deficiency, disorders of electrolyte metabolism
Muscle cramps are common
Restless leg syndrome - jumpy legs during night
Sensory and motor neuropathy - paresthesia and drop foot - late in the course - unusual due to widespread RRT availability

Question 10

Cardiovascular disease in CKD

Answer 10

Increased R in stage 3 or more (GFR less than 60) and those with proteinuria or microalbuminuria
LV hypertrophy - caused by hypertension - increased risk of sudden death (dysarrythmia)
Pericarditis - ESRD - pericardial tamponade, constrictive pericarditis
Medial vascular calcification - common, high serum phosphate (stage 3b and above)
Hyperphosphatemia also may cause itching
FGF23 - increases in response to serum phosphate - an independent predictor of mortality in CKD

Question 11

Metabolic bone disease in CKD

Answer 11

Disturbance of Ca and Ph - almost universal in advanced CKD
Other types of bone disease that mayt occur - osteitis fibrosa cystica, osteomalacia, osteoporosis
Impaired final vitamin D synthesis (renal tubular cell damage and increased FGF23)
Decreased vit D – impair intestinal absorption of calcium – hypocalcemia – increased PTH
Decreased GFR – rised serum Ph
Increased production of FGF23 from osteocytes – phosphate excretion - eventually fail as renal failure progresses – hyperphosphatemia
Rised serum phosphate + calcium – ectopic calcification in blood vessels and other tissues

Question 12

Hyperparathyroidism in CKD

Answer 12

Often develop parathyroid gland hypertrophy and secondary hyperparathyroidism
Tertiary hyperparathyroidism supervenes in some cases - autonomous production of PTH by enlarged parathyroid glands
Presents with hypercalcemia

Question 13

Different histology of bone disease in CKD

Answer 13

Osteitis fibrosa cystica - increased bone turnover due to high levels of PTH
Overtreated with vit-D metabolites - low bone turnover (adynamic bone disease)
Overtreatment of hyperphosphatemia - osteomalacia

Question 14

Main aim of investigation in CKDF

Answer 14

Find underlying cause - may influence treatment
Identify reversible factors that may worsen renal function - hypertension, UT obstruction, nephrotoxic drugs, salt and water depletion
Screen for complications of CKD - anemia and renal osteodystrophy
Screen for cardiovascular risk factors

Question 15

Referral criteria of CKD to nephrologist

Answer 15

Younger than 40 years old
Stage 4 CKD or worse (less than 30 GFR)
Rapid deterioration in renal function (fall in GFR more than 5-10 over 5 years)
Significant proteinuria - PCR more than 100 mg/mmol
Significant hematuria - after exclusion of UTI, stones, tumors

Question 16

Aims of management in CKD

Answer 16

Prevent or slow further renal damage
Limit adverse physiological effects of renal impairment on skeleton and on hematopoesis
Treat risk factors for CVD
Prepare for RRT, if appropriate

Question 17

Antihypertensive therapy in CKD

Answer 17

Lowering of BP slows progression of CKD, decreases R of hypertensive heart failure, stroke, peripheral vascular disease, reduces proteinuria
Goal - 130/80 in uncomplicated, 125/75 in complicated (proteinuria more than 1g/day
May need multiple drugs

Question 18

Reduction of proteinuria in CKD

Answer 18

Clear relationship btw degree of proteinuria and rate of progression
ACEI and ARB - reduce proteinuria and retard progression of CKD
- Reduce blood pressure as well
- Especially beneficial in CKD with proteinuria or with diabetic nephropathy
- Reduce risk of cardiovascular events and all cause mortality in CKD
- May be an immediate reduction of GFR at initiation (decreases glomerular perfusion pressure). Can be continues as long as reduction in GFR is less than 20% and nonprogressive
- Prescribe to all with proteinuria and diabetic nephropathy (even if no hypertension) as long as hyperkalemia does not occur

Question 19

Dietary and lifestyle interventions in CKD

Answer 19

Stage 4 - 5 - prevent excessive protein consumption, ensure adequate caloric intake, limit potassium and phosphate intake
Severe protein restriction - not recommended
Stop smoking - slows decline in renal function, reduces CV risk
Exercise and weight loss - may reduce proteinuria, beneficial for CVS

Question 20

Lipid-lowering therapy in CKD

Answer 20

Hypercholesterolemia - almost universal in patients with significant proteinuria
Increased TGA levels - common in CKD
Reduce vascular events
Control of dyslipidemia with statins may slow rate of progression of renal disease

Question 21

Treatment of anemia in CKD

Answer 21

Common in GFR less than 30
Recombinant human Epo
Does not influence mortality
Correcting Hg may include extra risk - hypertension, thrombosis
Less effective in presence of iron deficiency, active inflammation, malignancy, aluminium overload (may occur in dialysis)

Question 22

Maintaining fluid and electrolyte balance in CKD

Answer 22

Fluid retention - limit dietary sodium to 100mmol/day
Loop diuretics - often needed to treat fluid overload
Hyperkalemia - review drug therapy - stop potassium-sparing diuretics, ACEIs, ARBs. Correction of acidosis may be helpful. Limiting potassium intake to 70mmol/day may be needed in late CKD. Potassium binding resins - calcium resonium - useful only shortterm.
Plasma bicarbonate - should be maintained above 22 mmol/L by sodium bicarbonate supplements (1g 3x per day, increasing as required). Alternative is calcium carbonate up to 3 g per day (if sodium bicarbonate cause hypertension, edema)

Question 23

Renal bone disease treatment in CKD

Answer 23

Active vit D metabolites in patients with hypocalcemia or increased PTH (more than twice upper limit) - goal to reduce PTH to less than 2-4 times upper limit - avoid oversupression and adynamic bone disease
Avoid hypercalcemia!
Hyperphosphatemia - dietary restriction (milk, cheese, eggs, protein) + phosphate-binding drugs - calcium carbonate, aluminium hydoxide, lanthanum carbonate, polymer-based phosphate binders (sevelamer)
Maintain serum phosphate below 1,8 mmol/L
Parathyroidectomy - tertiary hyperparathyroidism. Alternative - calcimimetic agents such as cinacalce - bind to calcium-sensitive receptor and reduce PTH secretion.

Question 24

Definition of CKD

Answer 24

Irreversible deterioration of renal function
Usually develops over a period of years
Initially only biochemical manifestation
Eventually clinical symptoms and signs of renal failure develops = uremia
ESRD - when death is likely to occur without RRT