SAP - CKD

Question 1

Definition of CKD and prevalence.

Answer 1

CKD is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health (KDIGO, 2012)

Kidney damage refers to a range of abnormalities observed during clinical and laboratory assessment.

Question 2

criteria:

Answer 2

DECREASED GFR <60

Markers of kidney damage 
e.g. Albumin in urine
Urine sediments
Structural abnormalities detected by imaging
Abnormalities detected by histology
History of Kidney Transplantation

Question 3

What is GFR?

Answer 3

Glomerular Filtration Rate (GFR) is the best marker of kidney function in health and disease = volume of plasma filtered by kidney per unit time.
We usually estimate the GFR using a prediction equation and serum creatinine.

Question 4

Causes of CKD

Answer 4

1. Pre renal
   Any condition leading to persistently decreased renal perfusion e.g. Heart Failure
2. Renal causes
   a. ) renal vascular disease –> Hypertensive Nephrosclerosis
   - -> Renal Artery Stenosis
   b. ) Glomerular disease –> Primary Glomerular Diseases – many examples –> Secondary Glomerular Diseases e.g. Diabetic Glomerulosclerosis
   c. ) Tubular and interstitial disease
   - -> Repeated Urinary Tract Infections, Reflux Nephropathy –> Drugs and Toxins
3. Post renal
   Chronic Obstruction – any cause e.g. prostatic disease
   UTI / drugs etc

Intrinsic Renal causes of CKD are divided into vascular causes, glomerular causes and problems with the tubular system.

Causes can be divided into primary renal defects (i.e. disease originating in the kidney), or secondary (i.e. kidney disease secondary to a systemic disease affecting multiple organs, such as Diabetes).

Primary Glomerular diseases include diseases such as Focal and Segmental Glomerulosclerosis.

Question 5

According to USA data, what is the commonest cause of Chronic Kidney Disease?
Hypertensive Nephrosclerosis
Diabetic Nephropathy
Primary Glomerular Diseases
Reflux Nephropathy

Answer 5

Diabetic Nephropathy

then

High blood pressure

Question 6

Causes of Chronic Kidney disease: Diabetic Nephropathy

Answer 6

Advanced CKD occurs in as many as 40% of diabetics.
Most common lesions involve the glomeruli and the arterioles.

Thickened GBM (Glomerular Basement Membrane) and increased mesangial matrix

Question 7

There are four major histologic changes in the glomeruli in diabetic nephropathy:

Answer 7

mesangial expansion; glomerular basement membrane thickening; podocyte injury; and glomerular sclerosis

Question 8

Diabetic Nephropathy: Microalbuminuria

Answer 8

The earliest evidence of protein leak is microalbuminuria.

It is the earliest marker of glomerular disease – appears before reduction in GFR

Measured as Albumin Creatinine ratio (ACR)

Clinically important proteinuria = ACR of >3mg/mmol

Question 9

Classifying CKD

Answer 9

CKD should be classified according the Glomerular Filtration Rate and the level of albuminuria (i.e. protein leak) – both NICE and KDIGO recommend this.

G1, G2, G3a, G3b, G4, G5

G1 = >90 = normal, not CKD
G2= 60-89 = normal, not CKD
G3a =45-59
G3b = 30-44
G4 = 15-29
G5 = <15 = kidney failure

Classifying CKD by ACR:
A1, ACR <3
A2, ACR 3-30
A3, ACR >30

Question 10

Causes of Chronic Kidney disease: Hypertensive Nephrosclerosis

Answer 10

In hypertensive patients, there is arteriosclerosis of the major renal arteries and changes in the intra-renal vasculature (Nephrosclerosis).

increased BP –> medial and intimal thickening, hyalanization of arteriolar walls –> Affected vessels have thickened walls, narrowed lumens leading to ischaemia. –> lesser blood reaching the AE, so decreased GFR –> causes increase in renin –> RAAS –> increase fluid retention –> increases HBP again -> repeating cycle

Question 11

glomerular disease presentations

Answer 11

protein in the urine = nephrosis or blood and protein in the urine (nephritic).

Question 12

Cause of CKD: Reflux Nephropathy

Answer 12

It leads to tubulointerstitial nephritis.
It results from a combination of VUR and infections.
Typically, there is papillary damage and cortical scarring as well.

Question 13

Exmination findings of the CKD stage 5

Answer 13

Symptoms common when urea level exceeds 40 mmol/L:
Malaise
Loss of Appetite
Itching
Nausea
Symptoms associated with CKD complications

In uraemia associated with CKD Stage 5, symptoms can be more severe – mental slowing, seizures and myoclonic twitching

Pallor, brown discolouration of the nails, scratch marks due to uraemic pruritus, signs of fluid overload. Pericardial friction rub, flow murmurs

Question 14

COMPLICATIONS OF CKD

Answer 14

Anaemia 
Bone Pain 
Cardiovascular disease
Pericarditis
Volume overload

Question 15

COMPLICATIONS OF CKD Anaemia

Answer 15

Erythropoetin deficiency - CKD kidney cannot produce Epo which is needed to act on bone marrow to produce more RBC

There is also often haematinic deficiencies (B12, Folate, Iron) and Bone Marrow Toxins are retained in CKD.

Anaemia symptoms – Pallor, Lethargy and Shortness of Breath on exertion.

Question 16

COMPLICATIONS OF CKD: mineral bone disorder

Answer 16

Abnormalities in calcium, phosphorous, PTH, Fibroblast Growth Factor 23 and Vitamin D metabolism.

Bone turnover and mineralization affected

Extraskeletal calcification

• **Reduced calcium absorption and vitamin D activity - due to Decreased renal production of 1 alpha hydroxylase - due to phosphate retention due to CKD
• -> leading to increase parathyroid hormone due to low calcium

Question 17

COMPLICATIONS OF CKD: Cardiovascular Disease

Answer 17

Life expectancy is severely reduced in CKD – owing to a 16-fold increased incidence of cardiovascular disease.
Especially MI and Heart Failure.
Likely related to HTN, a frequent complication of CKD, and coronary artery calcification.

Pericarditis can also occur in severe uraemia.

Question 18

Complications of CKD – Volume Overload

Answer 18

reduced perfusion –> RAAS –> vasoconstriciton and Na reabsorption –> Hypertension, p/p oedema

Question 19

Complications of CKD – Patients can develop high K+ and acid base disturbances

Answer 19

increase K+ ====> ECG abnormalities

endogenous acid production increased, less output ====> Acid base disturbances

Question 20

CKD Progression

Answer 20

CKD tends to progress to End Stage Kidney disease, although the rate of progression depends on underlying pathology.

Hypertension and Heavy Proteinuria are bad prognostic indicators.

Question 21

CKD – What can we do about it?

Answer 21

Control HBP - below 140/90. if diabetic, aim <130/80

RAAS antagonists helpful eg Ramipril

Be careful in the elderly or those with neuropathy.

Set patient specific targets.

Need to manage cardiovascular risk.

Need to consider statins to lower cholesterol (i.e. correct abnormal lipid profiles)

Good glycaemic control - target HbA1c of 53mmol/mol

Salt intake reduced to < 2g per day, unless contraindicated.

Lifestyle changes – dietary advice, physical activity compatible with cardiovascular health and tolerance. Stop smoking.

Question 22

CKD – Managing Complications

ANAEMIA

Answer 22

Investigate anaemia in CKD if Hb < 110g/litre or less; or develop symptoms

As due to erythropoietin (EPO) deficiency, can be treated with synthetic (recombinant) human EPO.

Need to investigate also for other causes of anaemia such as Iron Deficiency Anaemia.

Need to regularly monitor blood counts when using synthetic erythropoietin.

Question 23

CKD – Managing Complications

Mineral Bone Disorder

Answer 23

Need to try and reduce phosphate levels – dietary restriction is seldom effective alone.

Can use Gut Phosphate binders to help absorb gut phosphate. Examples include calcium carbonate.

Can consider Vitamin D analogues such as alfacalcidol.