Kidney Disease 2

Question 1

What is chronic kidney disease

Answer 1

Long term, often progressive loss of normal kidney function

–Commonly leads to cardiovascular disease and other complications and may result in end-stage kidney failure

–Affects about 10% of the population and is asymptomatic until renal function severely reduced

–As kidney function deteriorates, the incidence of complications eg anaemia, CVD, disordered bone mineral metabolism and calcification of blood vessels, increases.

–It may, (but does not always) result in end-stage kidney failure

Question 2

What is the relationship between age and GFR

Answer 2

There is a well recognised decline in gfr from the age of approximately 30yo

Question 3

End stage renal disease has not improved in recent years. What is the prognosies for the different age categories

Answer 3

5 year survival:
Age 18-34   >90%
Age  45-54   70%
Age 65-74   30%
Age >75     <20%

Dialysis patients are 20x more likely to die a CV death than the general population

A cardiac cause is implicated in >40% of all deaths at ESRD

Question 4

What is the most common cause of death for early ckd patients

Answer 4

Cardiovascular related death (not kidney failure)

Question 5

Howdo we define CKD

Answer 5

Kidney damage for >3/12 (3 months) as evidenced by structural or functional abnormalities with normal or decreased GFR (GFR>60ml/min/1.73m2).

–Diagnosed using blood/Urine tests or Imaging

• GFR <60ml/min/1.73m2 with or without kidney damage for more than 3/12 .
• higher levels of albinaurea and a severly reduced function, thr risk for adverse outcomes in increased

Question 6

How common is ckd

Answer 6

Exact prevalence is unknown – many cases of eary ckd are unrecognised

CKD prevalence rises with age from 78 per million <40yrs to 5900 pmp >80

More common in many ethnic minority groups eg in association with diabetes in south east asians and hypertension in black patients

Question 7

Which stage of ckd is most common

Answer 7

stage 3 - stages beyond that have poorer outcomes (more patients have died)

Question 8

What are ther risk factors for CKD

Answer 8

-Diabetes
–Hypertension
–Acute kidney injury
–Cardiovascular disease
–Structural renal tract disease, recurrent renal calculi, prostatic hypertrophy
–Multisystem disease with potential kidney involvement, eg SLE, lupus
–Family history of end stage kidney disease
–Detection of haematuria

Question 9

What are the non-modifiable factors for ckd

Answer 9

Old age
Male sex#
Race/ ethnicity
Genetic predisposition
Family history
Low birth weight

Question 10

What are the modifiable factors for ckd

Answer 10

Systemic hypertension
Diabetes melilitus
Proteinuria
Dyslipidaemia
Smoking
Obesity
Alcohol consumption
Low socio-economic status
Drugs and herbs/analgesic abuse
Auto-immune disease/obstructive uropathy/ stones

Question 11

Which patient types do we refer to secondary care based on nice guidelines

Answer 11

CKD 4/5

Heavy proteinuria (ACR≥70mg/mmol or proteinuria 1g/d) unless on diabetes treatment

Haematuria and proteinuria (ACR≥30mg/mmol or proteinuria 0.5g/d)

Rapidly declining GFR (>5ml/min in 1 yr or >10ml/min over 5yrs)

Poorly controlled BP on 4 agents

Possible genetic/multi-system cause of CKD

Suspected renal artery stenosis

Question 12

How do we identify progressors

Answer 12

Exclude causes of acute deterioration of GFR eg patients of ace inhibitors

Define as >5ml/min in 1 yr or >10ml/min in 5 yrs

Minimum of 3 GFR estimations required

Focus on those whom continuing decline at observed rate would lead to end stage renal failure within lifetime

Question 13

What are the most common causes for ckd

Answer 13

Diabetes, unknown (as patients may present at end stage), adpkd (inherited condition), glomelular nephritis

Question 14

How do we manage ckd

Answer 14

Fist need a definitive Diagnosis

Treatment/prognosis depends on

Stage of CKD
Complications
Risk of cardiovascular events and death
Risk of end stage renal disease

Question 15

How do we manage each stage of CKD

Answer 15

Increased risk - screen for ckd and introduced ckd risk reduction plans

Stage 1&2 - monitoring of renal function, slow the progression, obtain a diagnosis, control bp, RAAS bikade

Stage 3 - treat complications (anaemia, acidosis, bone disease)

Stage 4 - prepare patient for renal replacement therapuy (give them a choice), consider transplant

Stage 5 - conservative management

Question 16

What is the link between cardiovascular disease and patients on dialysis

Answer 16

Patients who are on dialysis have a similar annual mortality of patients over 85 in the general population

Question 17

In which stage of ckd is cvd most common

Answer 17

Stage 4 as many die of cvd before progressing to renal replacement therapy (NB all stages of ckd see an increased risk of cvd in compariston to the general population)

Question 18

What’s the link between CKD & CVD

Answer 18

Both may be consequences of same diseases eg diabetes, HTN, atherosclerosis

CKD may cause or exacerbate CVD eg anaemia, RAAS activation, oxidative stress, hyperhomocystinaemia, vascular calcification

CVD may cause or exacerbate CKD

Patients with CKD are likely to receive less aggressive therapy for their CVD

Question 19

What are the traditional CV risk factors more common in CKD

Answer 19

hypertension  (almost always present)
Diabetes
Dyslipidaemia
Obesity
Reduced physical activity

Question 20

What are the risk factors more common or unique to advanced CKD

Answer 20

Arteriosclerosis 
Diastolic dysfunction
Vascular calcification
Albuminuria
Volume overload
Anaemia
Oxidant stress
Inflammation
Malnutrition
Vitamin D deficiency
Accumulation of advance glycation end products
LVH
Hyperparathyroidism
RAS activation + more

Question 21

How do we manage the raised bp typical of ckd using ace/arbs

Answer 21

Glomerular filtration pressure and increased proteinuria = increased renal injury

ACE/ARB–Decrease arteriolar tone, decrease intraglomerular pressure and decrease proteinuria
–Decrease A2 activity – A2 induced inflammation = decreased fibrosis and scarring
–ACEi affect both angiotensin type 1 and type 2 receptors but may not completely inhibit A2
–ARBs block A1 but not A2

Question 22

Which diuretics do we use to treat ckd

Answer 22

Frusemide , bumetanide –may require high doses eg 500mg frusemide–may be given by prolonged iv infusion

avoid thiazides if moderate to severe renal impairment as they are ineffective

avoid potassium sparing diuretics eg spironolactone, amiloride as to not excacerbate hyperkalaemia

Question 23

How do we use calcium channel blockers in the treatment of ckd

Answer 23

Often requires maximum doses
Eg: nifedipine LA 90mg daily, amlodipine 10mg daily

side effect of ankle swelling should not be confused with fluid overload

Question 24

How do we use Ace inhibitors & A2R blockers blockers in the treatment of ckd

Answer 24

Expect a creatinine rise of 20% or decline in GFR of 15% on initiation

Potassium–Overall incidence of hyperkalaemia (K+>5.1mmol/l) is ~10%–Pts with no kidney disease or CKD 1-3 should expect a rise of 0.5mmol/l–CKD 4 or 5 more prominent
hyperkalaemia

See ace and arb combination in–Difficult hypertension, gross proteinuria, Diabetics

Question 25

What is the role of SGLT2 inhibitors in CKD

Answer 25

SGLT2 inhibitors offer both cardiovascular and kidney protection in both diabetic and non-diabetic CKD and, additionally, improve glycaemic control in T2DM, making them first-line therapy for CKD independent from diabetic status.

Question 26

Why is anaemia a common side effect of ckd

Answer 26

Causes:
uraemia increases the risk of GI bleeding (more significant cause),
nausea and vomiting decreased appetite

amount of iron absorbed is decreased
leading to low iron stores

Decreased erythropoietin production

Impaired bone marrow response to epo. and the lifespan of rbcs is also reduced

Question 27

Anaemia is also present in those with diabetes. When does it become common in terms of eGFR ratios

Answer 27

Anaemia with an hb <10 becomes common in patients with a GFR of <30

Question 28

Anaemia due to reduced renal function is usually an isolated normacytic anaemia. How do we treat this

Answer 28

Iron - oral or iv
blood transfusions
ESA – erythropoesis stimulating agents (takes 2-3 months to reach steady states)

Question 29

Is the administration of iv iron beneficial for ckd patients on dialysis

Answer 29

Higher dose iv iron given to dialysis patients decreased the risk of death, hospitalisation for heart failure and other major cardiovascular events, decreased dose of epo required and of blood transfusions

Question 30

What is the next steps for the treatment of anaemic ckd patients

Answer 30

Roxadustat, an oral medicine, is the first in a new class of medicines called HIF-PH inhibitors that promotes erythropoiesis, (red blood cell production) , through increased endogenous production of erythropoietin, improved iron absorption and mobilisation, and downregulation of hepcidin. Roxadustat is also in clinical development for anaemia associated with MDS and for chemotherapy-induced anaemia.

Not currently licenced in europe

Question 31

What is another recognised complication of ckd

Answer 31

Mineral bone disorder

Question 32

What is ckd-mbd

Answer 32

Disturbances of calcium and phosphate metabolism are usually seen in patients with CKD stage G4 and G5.

•CKD –MBD is a systemic disorder strongly linked to cardiovascular disease and mortality

Question 33

What are the primary drivers of ckd mbd

Answer 33

The primary drivers are –phosphate retention due to reduced renal clearance,
–disordered vitamin D metabolism –hyperparathyroidism

Question 34

Howdo we treat ckd-mbd

Answer 34

Treatment of CKD-MBD in all stages of CKD should be based on serial measurements of phosphate, calcium and PTH and individualised.

General -keep serum Ca and Phosphate within the normal range, keep bone turnover and strength as near normal as possible, keep serum PTH appropriate to these and prevent the development of parathyroid hyperplasia

Question 35

Why is high phosphate problematic

Answer 35

Calcification of major vessels 
•Also called renal bone disease
•High phosphate symptoms for patients
–Severe Itching
–Painful, gritty eyes

Question 36

Describe the feedback loop seen in patients with secondary hyperparathyroidism and

Answer 36

In renal failure there is a decrease in 1-25 dihydroxycholecalciferol (vitamin d precursor) and and increase in phosphate due to reduced renal clearance. This corresponds with low serum calcium, detected in the hyperparathyroid gland, which is stimulated to produce more pth which has an impact on bones and systemic toxicity

Question 37

What 2 types of arterial narrowing do patients with ckd demonstrate

Answer 37

uraemic arteriopathy and atherosclerosis

Question 38

How does vitamin D play a role in kidney disease

Answer 38

Active vitamin D is essential to maintain normal calcium levels

• Vitamin D is activated by the kidney then liver
• In kidney disease, vitamin D supplements such as alfacalcidol may be prescribed.
• Doses of alfacalcidol/ calcitriol may be daily, alternate days or twice a week.

Question 39

What does a lack of vitamin d result in and how do we treat and monitor it

Answer 39

• Osteomalacia
• Secondary hyperparathyroidism
• Low serum calcium

•Alfacalcidol - treatment •Measure parathyroid hormone levels (PTH) - monitoring

Question 40

Why do patients with ckd experience pruritis and how do we treat it

Answer 40

Caused by high phosphate levels and/or uraemia

• treatment:–dialysis, phosphate binders
• symptom control:–antihistamines & topical preparation

Question 41

Why do patients with ckd experience nausea and how do we treat it

Answer 41

Caused by a build up of toxins

•Treatment: anti-emetics –metoclopramide
–cyclizine
–haloperidol (low dose)
–Ondansetron
–levomepromazine