Chemical pathology of renal disease

Question 1

What kidneys are affect early in AKI and late in CKD?

Answer 1

Excretion and homeostasis

• waste products of metabolism
• fluid and electrolyte balance
• acid-base balance
• removal of drugs and toxins

Question 2

What kidneys functions are not normally disturbed by AKI?

Answer 2

endocrine functions but in the later stages of CKD they are disrupted

• renin-angiotensin system
• erythropoietin production
• hydroxylation of vitamin D

Question 3

What is stage 1 AKI?

Answer 3

creatinine rises >26.5 micromol/L in 48 hours OR 1.5-1.9x baseline

urine output - <0.5ml/kg/h for 6-12hours

Question 4

What is stage 2 AKI?

Answer 4

creatinine rises 2-2.9x baseline

urine output - <0.5ml/kg/h for >12hours

Question 5

What is stage 3 AKI?

Answer 5

creatinine rises >353.6 micromol/L OR 3x baseline OR need for renal replacement therapy

urine output - <0.3ml/kg/h for >24 hours or anuria for >12 hours

Question 6

How can the 3 main causes of AKI be divided?

Answer 6

Pre-renal
Renal
Post-renal

Question 7

What is pre-renal damage?

Answer 7

damage due to underperfusion of an otherwise normal kidney
Therefore as the kidney is normal the metabolic consequences are reduced
Over 1 million nephrons in each kidney which are highly sensitive to toxic and hypoxic injury so underperfusion is very damaging

Question 8

What are the causes of pre-renal AKI?

Answer 8

hypovolemia - due to hemorrhage or dehydration

sepsis and vasodilation

renal artery stenosis and atherosclerosis

pump failure

Question 9

What is intrinsic renal damage and what are the causes?

Answer 9

Damage can be of the tubules or the glomerulus

• ischemia
• nephrotoxicity from drugs, poisons, myoglobin, and paraproteins (myeloma)
• pyelonephritis - direct infection of the kidney itself
• trauma
• early stage CKD - glomerulonephritis and interstitial nephritis

Question 10

What are involved in post renal damage?

Answer 10

post-renal obstruction

• kidney stones
• tumour
• prostatic hypertrophy

Question 11

What are the key biochemical findings for an AKI caused by pre-renal damage?

Answer 11

urine volume: low 
urine:plasma osmolality: >2:1
urine [Na]: <15
Plasma Na: high 
Elevation of urea vs creatinine: urea>>creatinine

Question 12

What are the key biochemical findings for an AKI caused by intrinsic renal damage?

Answer 12

urine volume: initially high
urine:plasma osmolality: <1:1
urine [Na]: >40
Plasma Na: low
Elevation of urea vs creatinine: urea=creatinine

Question 13

What is the treatment for pre-renal damage AKI?

Answer 13

Give fluid to increase renal perfusion

whereas if you did this in intrinsic AKI then it would cause fluid overload and can potentially kill the pt

Question 14

In intrinsic AKI what are some of the key clinical features?

Answer 14

acidosis - occurs as 100mmol/day of acidic waste products of metabolism are retained - becomes life threatening when pH <7
hyperkalaemia - occurs as K isn’t excreted - becomes life threatening when it increases >8mmol/L

Question 15

As AKI progresses due to lack of treatment what can happen ?

Answer 15

nitrogenous waste builds up and patients experience nausea, malaise and confusion
also begin to retain electrolytes and water due to the reduction in GFR - leads to hyponatraemia as more water is retained than salt
Fluid overload can follow on from this

Question 16

How is an AKI managed?

Answer 16

first find cause
stop any NSAIDS, ACE inhibitors or angiotensin receptor inhibitors and any other nephrotoxic drugs
correct any life threatening fluid, electrolyte and acid-base abnormalities

pre-renal = renal perfusion needs to be restored
intrinsic = renal function should be supported with dialysis
post-renal=any obstruction should be removed

Question 17

What is CKD and what are the causes?

Answer 17

gradual, irreversible changes in renal function
causes: hypertension, diabetes, polycystic kidneys, recurrent pyelonephritis and reflux nephropathy, glomerulonephritis, interstitial nephritis and drugs

Question 18

How is CKD staged?

Answer 18

determined by serum creatinine and GFR

• early disease - GFR is more sensitive as creatinine levels don’t begin to rise until relatively late in the disease
• creatinine levels are used to monitor disease later on

Question 19

How is eGFR calculated?

Answer 19

using MDRD formula - calculated based on age, sex, plasma creatinine and a correction factor for ethnicity and paeds

Question 20

What is the albumin/creatinine ratio?

Answer 20

this may replace GFR estimate in the future
A1 <3
A2 3-30
A3 >30

Question 21

What are the different stages of CKD?

Answer 21

1 - GFR >90ml/min 
2- 60-90
3a- 45-60
3b- 30-44
4- 15-30
5-<15

Question 22

What are the consequences for stages 3-5?

Answer 22

3a - hypertension due to water retention, increased CVD risk
3b - low calcium due to decreased vitamin D
4- anaemia, anorexia, and hyperphosphataemia
5- salt and water retention, acidosis and hyperkalaemia

Question 23

How are stages 1-3 CKD managed?

Answer 23

monitoring GFR and urinary albumin:creatinine ratio
Also monitoring of bone health and cardiovascular risk
Any causes treated - e.g. diabetic control and anti-hypertensive treatments

Question 24

What are the more severe biochemical changes that occur in stages 3-4 CKD?

Answer 24

Largely due to reduced GFR
- elevated ACR, elevated cholesterol and triglycerides (increasing cardiovascular risk) and impairment of immune function
Several endocrine changes occur too

Question 25

How are patients with stages 3-4 CKD managed?

Answer 25

- need to take 1,25-OH vitamin D due to decreased hydroxylation = leads to low calcium and secondary hyperparathyroidism - increased PTH leads to osteomalacia and osteitis fibrosa due to increased calcium reabsorption - decreased GFR leads to an increased phosphate level, these form precipitous with calcium which can cause metastatic calcification - erythropoietin production also drops causing anaemia

Question 26

What symptoms start to develop in stage 5 CKD?

Answer 26

Uremic symptoms - due to high levels of creatinine and urea | Phosphate and potassium will be high and patient will be acidotic

Question 27

What are the main areas that specialists focus on when treating patients with CKD at stage 3b +?

Answer 27

correcting endocrine and metabolic abnormalities with hormone replacement (alfacalcidol and EPO), phosphate binders are given to prevent metastatic calcification, diet modified to reduce potassium and fluids monitored acid base balance corrected with bicarbonates dialysis (haemo or peritoneal) and kidney transplant are used as renal replacement

Question 28

When do CKD patients become oliguric?

Answer 28

not until the very late stages

Question 29

What is the GFR like in glomerular disease and what is the consequence of this?

Answer 29

very little GFR therefore fluid overload and oliguria

Question 30

What is the water balance like in polycystic kidneys?

Answer 30

in this kidney disease the nephrons remain healthy so there will be an initial osmotic diuresis, causing polyuria

Question 31

What happens to the water balance in tubular damage to the kidneys?

Answer 31

there is ineffective water absorption causing polyuria

Question 32

What are the key characteristics of AKI?

Answer 32

rapid onset hospitalized risk increased but not caused by multi morbidity CKD predisposes to AKI creatinine and urine output used to classify

Question 33

What are the key characteristics of CKD?

Answer 33

``` Gradual onset patient in community often caused by multi morbidity AKI contributes to CKD deterioration eGFR and ACR used to classify ```

Question 34

What are the features of pre-renal AKI in terms of: - urea/creatinine - electrolyte balance and acid base balance - fluid balance - endocrine abnormality ?

Answer 34

- urea/creatinine = urea >> creatinine - electrolyte and acid base = hypernatraemia - fluid balance = hypovolemia - endocrine abnormality = none

Question 35

What are the features of renal AKI in terms of: - urea/creatinine - electrolyte balance and acid base balance - fluid balance - endocrine abnormality ?

Answer 35

- urea/creatinine = urea = creatinine - fluid balance = hypervoleamia - electrolytes . acid base = hyperkalaemia, hyponatriaemia, acidosis - endocrine abnormality = none

Question 36

What are the features of CKD in terms of: - urea/creatinine - electrolyte balance and acid base balance - fluid balance - endocrine abnormality ?

Answer 36

- urea/creatinine = urea= creatinine - electrolyte balance and acid base balance = hyperkalaemia and acidosis - fluid balance = euvolaemia (until late) - endocrine abnormality = persistent

Question 37

What is renal glycosuria?

Answer 37

due to lack of glucose uptake

Question 38

What are examples of generalised and selective kidney disorders that do not constitute renal failure?

Answer 38

``` generalized = faconi syndrome selective = cysteinuria (lack of amino acid uptake) ```

Question 39

What are the 3 main forms of renal tubular acidosis?

Answer 39

causes acid base and electrolyte balance disturbance 1) type 1 = distal - causes hypochloracaemic hypokalemic acidosis and kidney stones - due to failure to secrete H+ causing acidosis and excess K+ being lost in exchange for Na Tx = bicarbonate and K 2) type 2 - proximal = leads to alkalosis - due to bicarbonate leak 3) type 4 is hyperkalaemia due to low aldosterone and renin

Question 40

When can you get high or low urea other than renal problems?

Answer 40

High - protein load and upper GI bleed low - low protein diet and anorexia

Question 41

When can you get high or low creatinine other than renal problems?

Answer 41

high - muscle breakdown low - small muscle mass