Chronic Kidney Disease Flashcards
1
Q
What are the 8 functions of the Kidneys?
A
- Regulation of inorganic ions (Na+, K+, Ca2+, Cl-, Pi, Mg2+)
- Regulation of water balance and osmolality
- Excretion of nitrogenous wastes (urea, creatinine)
- Excretion of foreign chemicals (drugs, pollutants etc.)
- Regulation of pH and HCO3-
- Synthesis of renin
- Synthesis of erythropoietin + activation of Vitamin D3
- Gluconeogenesis (liver much more important for this)
2
Q
What is RRT (Renal Replacement Therapy) and what does it involve?
A
RRT = therapy that replaces blood filtering function of the kidneys
Used in AKI and Chronic Kidney Disease
It involves:
- Hemodialysis
- Peritoneal dialysis
- Renal transplant
3
Q
What is Orthostatic Proteinuria?
A
- It is a benign condition caused by changes in renal hemodynamics
- Present in 2-5% of otherwise normal pts
- Caused by prolonged period of standing
4
Q
Proteinuria can occur in other situtations, which do not indicate CKD, name 6?
A
- After physical exercise
- Fever
- Pregnancy
- UTI
- Abnormally high BP
- Nephrotic / nephritic syndrome
5
Q
What are the 4 main features of Nephrotic Syndrome?
A
- Proteinuria ( >3.5g in 24hrs, ++++ Protein Dipstick, urine looks frothy)
- Hypoalbuminaemia (Albumin lost in urine due to gaps in podocytes of glomerulus)
- Oedema (Albumin lost in urine –> ↓ intravascular oncotic pressure –> fluid moves into into surrounding tissues)
- Hyperlipidemia (Liver compensates for hypoalbuminaemia by ↑ production, but side effect is ↑ lipid production)
6
Q
What are the 4 main features of Nephritic Syndrome?
A
-
Haematuria (+++ Blood dipstick - microscopic or macroscopic)
- Possible ‘red cell casts’ = microscopic cylindrical structure, present in urine, produced in nephrons in diseased states
- Haematuria occurs due to gaps in podocytes of glomerulus
- Proteinuria (++ Protein dipstick = small amount)
- Hypertension (usually mild)
- Low Urine Volume (i.e. oliguria, < 300 ml/day) - due to ↓ renal function
7
Q
Urine dipstick detects proteinuria, in which 2 areas of the Kidney’s can the problem be?
A
- Glomerulus pathology
- Tubulointersitial pathology
8
Q
What 2 things can Pyuria (pus in urine) and/or white cell casts (microscopic cylindrical white cell structures which form in nephrons in pathological states) in urine indicate?
A
- Intersitial Nephritis (most commonly caused by reaction to medication e.g. β-lactam Abx and NSAIDs, but can also be casued by infection)
- UTI
9
Q
What can Spot Urine Collection for total protein : creatinine ratio be used as an estimate of?
A
24hr Urinary Protein Excretion
- Degree of proteinuria correlates with progression of kidney disease
- Degree of proteinuria is most reliable prognostic factor in CKD
10
Q
Which has greater sensitivity for low levels of proteinuria;
Protein:creatinine ratio
OR
Albumin:creatine ratio
A
Albumin:creatinine Ratio
11
Q
Which method of monitoring proteinuria is recommended for diabetics;
Protein:creatinine ratio
OR
Albumin:creatine ratio
A
Albumin:creatine ratio
12
Q
What should a patient with urinalysis indicating non-visible haematuria have done?
A
Urine Culture (to exclude UTI)
- If UTI is excluded –> repeat urinalysis TWICE to confirm PERSISTENT non-visible haematuria –> refer for urological review
13
Q
Which is the most important factor to address to ↓ risk of future cardiovascular disease?
Cholesterol
Blood Pressure
Diabetes
Weight
Smoking
A
Blood Pressure
- Several multi-national trials suggest that although all factors are important, blood pressure control has the MOST impact on CV events in future
14
Q
How can you assess a patients riks of developing Cardiovascular Disease?
A
QRISK
- Estimate the risk of developing cardiovascular disease over the next 10-years
- Influential Factors:
- Age
- Gender
- Ethnicity
- Smoking status
- Comorbidities: Diabetes status, SLE, Migraine, RA, AF
- Medications e.g. BP meds, steroids, antipsychotics
15
Q
What are normal values for:
- PCR (Protein : Creatinine ratio)
- ACR (Albumin : Creatinine ratio)
A
PCR < 15 mg/mmol
ACR < 3 mg/mmol
16
Q
What 2 factors are used to Stage Chronic Kidney Disease?
A
eGFR and ACR (albumin:creatine ratio)
- Patient is classified as G1, G2, G3a, G3b, G4 or G5 based on eGFR
- Patient is classified as A1 - A3 based on ACR
17
Q
What ranges for 24hr urine collection, spot urine albumin, and spot ACR indicated microalbuminuria (moderate ↑ urine albumin)?
A
- 24hr urine collection = 30-300 mg/24hr
- Spot urine albumin = 30-300 mg/L
- ACR = 3.5-35 mg/mmol
18
Q
Which protein is secreted by renal tubules up to 150 mg/day
and forms the boundary for the normal level of protein in urine
(<150 mg/day)?
A
Tamm-Horsfall Glycoprotein (THP) also called Uromodulin
- > 150 mg/day = proteinuria –> suggests ↑ glomerular permeability
- This protein is not tested for by urine dipstick (which usually tests for albumin)
19
Q
What classes of drugs are considered ‘Renoprotective’ and are used to; mangage progression of CKD, lower BP and manage nephropathy in diabetics?
A
ACE-I and ARBs (Angiotensin II receptor blockers)
- Progression of CKD can be slowed using ACE-I or ARBs independent of their effect on BP
- In Type 1 DM:
- ACE-I –> ↓ albuminuria + reduce diabetic nephropathy
- ARBs –> ↓ proteinuria
- In Type 2 DM:
- ACE-I –> ↓ abuminuria + reduce diabetic nephropathy + reduce CDK progression
- ARB –> ↓ abuminuria + reduce CDK progression
20
Q
Via what 3 mechanisms does Diabetes cause Nephropathy?
A
-
↑ Glomerular Pressure
- Hyperglycaemia –> ↑ RAAS system –> ↑ angiotensin II –> vasocontriction of efferent arteriole + ↑ peripheral resistance –> heart responds by ↑ BP
-
Barotrauma of mesangium (Cells surrounded by cappilary lumen - see pic)
- ↑ BP in glomerulus –> mesangial cells secrete cytokines (inflammation) + undergo mesangial expansion - which causes:
- ↑ pressure applied to glomerular cappilaries –> ↓ surface area for filtration
- Podocytes to move apart –> allowing larger molecules to be filtered
- ↑ BP in glomerulus –> mesangial cells secrete cytokines (inflammation) + undergo mesangial expansion - which causes:
-
Nephron Ischaemia
- The vasculature suuplying the nephrons comes off the efferent arteriole - hence vasoconstriction of this vessel ↓ blood supply to nephrons –> atrophy + destruction
21
Q
What clinical finding is indicative of the first stage of Diabetic Nephropathy?
A
↑ eGFR
- This is due to ↑ glomerular BP caused by RASS activation and the heart working against ↑ vasocontriction
22
Q
Are the Kidneys intraperitoneal or retroperitoneal?
A
Retroperitoneal
23
Q
At what Spinal level are the Kidneys?
A
T12 - L3
24
Q
What is included in the definition of Chronic Kidney Disease?
A
- Presence of Kidney damage for ≥ 3 months and/or …
- Kidney damage defined as pathological abnormalities in;
- Blood
- Urine
- Imaging - renal structure or renal tract abnormalities
- Renal biopsy evidence
- Kidney damage defined as pathological abnormalities in;
- eGFR < 60 ml/min/1.73m2 on at least 2 seperate occasions seperated by at least 90 days (with or without markers of kidney damage)
25
Is it common or not for patients with non-advanced CKD to have overt symtpoms?
**Uncommon**
* Overt symptoms from CKD are restricted to those with advanced CKD
26
Is CKD as a whole more common in the eldery or the young?
What are the 3 most common causes of CKD?
**Elderly**
1. Diabetes
2. Hypertension
3. Glomerulonephritis
27
Is advanced CKD more common in the elderly or the young?
**Young**
* In later stages of CKD (4 or 5) there is ↑ prevalence of young patients with glomerulonephritis and genetic causes of CKD
* Elderly patients tend not to have advanced CKD as they often have other co-morbidities which result in death before development of advanced CKD
* There is concern that elderly patients are given a higher CKD classification as a pathology when it may be due to natural decline in kidney function with age
28
Is End-Stage Kidney Disease rare or common?
Rare
* Incidence (2009) was 109 per million population
29
What nitrogenous waste product is used to calculate eGFR?
Creatinine
30
What are common side effects of ACE-I?
* **Dry Cough** (~10% suffer from this) - often requires cessation
* Angioedema (1-2 per 1000 white population) i.e. swelling of lower layer of skin in face, tongue, larynx, abdomen, arms or legs
* Hypotension
* Hyperkalemia
* ↓ eGFR (up to 15% is acceptable, \>15% stop medication and review)
31
How might plasma creatinine change due to ACE-I / ARBs?
**↑ plasma creatinine**
* **25-30%** increase is considered acceptable
* Plasma [Creatinine] must be checked **after starting** ACE-I / ARB and after **every dose change** (same with plasma K+)
* If creatinine does ↑ then blood needs to be checked regularly as a more significant ↑ could indicated --\> renovascular disease / **renal artery stenosis**
32
In which patients are ACE-I contraindicated?
**Pregnant** or mothers desiring pregnancy
* Avoid unless essential
* Affect fetal BP and renal function
* ↑ risk of congenital malformations
33
In what situtations should a patient be referred to Nephrology?
According to eGFR (ml/min/1.73m2):
* **\< 15** (CKD 5) - Immediate referral/discussion
* **15-29** (CKD 4) - Urgent referral/discussion (routine if pt is stable)
* **30-59** (CKD 3) - Routine referral if:
* Sustained **↓ in eGFR of ≥25%** **AND** a change in GFR category within 12 months
* OR
* Sustained **↓ in GFR of ≥15 ml/min/1.73m2** within 12 months
* Unexplained microscopic haematuria
* Proteinuria PCR \> 45 mg/mmol
* Unexplained anaemia (i.e. Hb \<110 g/L), abnormal K+, Ca2+ or phosphate
* Systemic illness e.g. SLE, RA
* Uncontrolled BP (\>150/90 on 4 agents)
* **60+** (CKD 1/2) - referral not required unless other evidence of kidney disease
Referral Irrespective of eGFR:
* Malignant HTN
* Life threatening Hyperkalaemia ( K+ \> 7.0 mmol/L)
* Nephrotic Syndrome
* Macroscopic haematuria + negative urological tests
* Proteinuria + microscopic proteinuria
* Dipstick proteinuria + PCR \> 100 mg/mmol
34
What is the target Ferritin for Renal Anaemia due to CKD?
**\> 200** ug/L
35
What is the mechanism of Renal Anemia in CKD?
CKD causes damage to the Kidney peritubular cells --\> ↓ erythropoietin production
↓ erythropoietin production --\> ↓ RBC / Haemoglobin = Anaemia
36
What are the 4 main effects of CKD on the body?
1. Anaemia (renal)
2. Metabolic Acidosis
3. Secondary Hyperparathyroidism / Hypocalcaemia
4. Hypertension
Analyse this diagram on management of CKD + Complications
37
What is the normal size of a Kidney?
Size of Kidney in the following;
Atrophy
Hypertrophic
Polycystic
* **11 cm** = normal
* 7.5 cm = atrophy
* 13.5 cm = hypertrophy
* 18.4 cm = polycystic
Note - besides the normal size, these are example measurements (not cutoffs)
38
What is Azotemia?
**Raised nitrogenous waste compounds** (urea and creatinine) in the **blood** often due to insufficient filtering of blood by Kidneys
39
What is Uraemia?
Clinical syndrome that results from failing Kidneys and progressive azotaemia - **High** blood **urea** levels
40
What is the normal range of eGFR?
**100-130** ml/min/1.73m2
41
What are 6 indications for dialysis?
1. **pH \< 7.2** (acidaemia due to metabolic acidosis, where sodium bicarb may cause fluid overload)
2. **K+ \> 7** mmol
3. **Fluid overload** (unresponsive to diuretics)
4. **Toxins SLIME** = salicylic acid, lithium, isopropanol (antiseptics, disinfectant and detergent), magnesium and ethylene glycol (antifreeze)
5. **Creatinine \> 400**
6. **Uraemia complications** e.g. encephalopathy or uraemic pericarditis (urea enters pericardial sac and fluid follows)
42
What are the 4 types of Diuretics?
1. **Osmotic** diuretics e.g. mannitol or urea (IV), glycerin or isosorbide (oral)
* Osmotic diuretics limit reabsorbtion of H2O in nephron via increasing osmolality in renal tubule --\> results in ↑ excretion of Na+, K+, Ca2+, Mg2+, Cl-, HCO3-, phosphate and H2O
2. **Loop** diuretics - e.g. furosemide, bumetanide
* NKCC2 antagonists --\> inhibiting Na+, K+ and Cl- reabsorption --\> ↑ H2O loss
3. **Thiazide** diuretics e.g. hydrochlorothiazide and chlorothiazide
* Na+/ Cl- symporter antagonist (distal convoluted tubule) --\> results in ↑ excretion of Na+, K+, Cl-, and Ca2+ but ↓ excretion of Mg2+
4. **K+ sparing** diuretics - 2 types:
* ENaC (epithelial sodium channel) blockers e.g. amiloride or triamterene
* Aldosterone antagonists e.g. Spironolactone or eplerenone
43
Hemodialysis has 1 absolute contraindication and 5 relative contraindications - what are they?
Absolute = Inability to achieve suitable vascular access
Realtive:
1. severe dementia
2. severe HF
3. bleeding disorder
4. low BP
5. severe active psychotic disorder
44
What are the 5 absolute contraindications for peritoneal dialysis?
Peritoneal dialysis has many relative contraindications, list some
Absolute Contraindications:
1. IBD
2. Ichaemic bowel
3. Acute diverticulitis
4. Abdominal abscess
5. Pregnancy 3rd trimester
Relative Contraindications: Stomas, VP shunt, abdo hernias, blind, obesity, severe obstructive airway disease, severe active psychotic disorder
45
Describe Hemodialysis
* Involves filtering your blood via a dialysis machine
* **4 hour** sessions **3 times per week**
* Involves patient going to a clinic or hospital for appointments
* Done via an IV line inserted into neck or a **fistula** (which is created in your arm and can take ~3 months before it's ready for use)
46
Describe Peritoneal Dialysis
* **Catheter** is inserted through abdomen into **peritoneum** (tummy cavity)
* Dialysate solution is inserted into your peritoneum
* Toxins filter into peritoneum from blood
* Requires **emptying every 4-6 hours**, and takes **30 mins**
* Peritoneal dialysis is portable but requires patient training
* **CAPD** (continous ambulatory peritoneal dialysis) - patient does themselves and can move about between 30 min fluid exchange (toxin filled fluid out and new fluid in)
* **APD** (automated peritoneal dialysis) - done by machine over **7-10 hours** every night **whilst you sleep**
47
What is the target BP for a proteinuric CKD patient?
**\< 130/80**
48
Name 9 risk factors for CKD!
* Diabetes
* HTN
* Age \> 50 yrs
* Male
* Black or Hispanic
* FHx
* Smoking
* Obesity
* Autoimmune disorders
49
What are 6 signs/symptoms of CKD?
1. **Fatigue** - CKD is associated with renal anaemia due to ↓ erythropoietin production once GFR \< 50
2. **Pruritis** - due to accumulation of toxic waste products e.g. urea
3. **Hypertension**
4. **Oedema** - periorbital / peripheraly oedema develops due to salt and H2O retention due to low GFR
5. **Nausea** with/without vomiting - accumulation of toxic waste products (urea)
6. **Reduced urine output** - low GFR
50
Which of the following is a contraindication to renal transplant?
Active Malignancy
HIV
Age \> 80
Concurrent or recurrent infections
Diabetes
Active Malignancy
Concurrent or recurrent infections
51
What are the 2 most common causes of ESRD (End Stage Renal Disease) in the UK?
1. Diabetes
2. Hypertension
52
What is the drug Cinacalcet used for and how does it work?
* Cinacalcet = **calcimimetic** (mimics Ca2+)
* It binds to and activates the **calcium-sensing receptors** on the parathyroid glands --\> ↑ negative feedback and inhibiting the gland from further PTH production and section
* **↓ PTH**
53
What is IgA Nephropathy (Berger's Disease)?
How does it present?
How is it Managed?
* IgA nephropathy = **mesangioproliferative glomerulonephritis**
* Commonest cause of glomerulonephritis
* Pathologenesis = mesangial deposition of IgA immune complexes
Presentation:
* **Young** (20-30), **Male** : Female (2:1)
* More common in; asian and caucasian
* Recurrent **haematuria** - often painless, sometimes loin pain
* 50% with visible haematuria post URTI or gastroenteritis
* 33% with asymptomatic micoscopic haematuria
* **Proteinuria** - norm \<2/3 g/day (often less than nephrotic syndrome range i.e. \>3.5g/day)
Management:
* If HTN and/or proteinuria --\> **ACE-I** or **ARBs**
* Steroids/immunosuppressant not shown to be useful
Prognosis:
* 25% develop ESRF
54
How is IgA Nephropathy different to Henoch–Schönlein purpura (HSP)?
1. IgA Nephropathy is more common in **young adults** vs HSP is more common in **children**
2. IgA Nephropathy typically affects only the **kidneys** vs HSP is a **systemic** disease
HSP Summary:
* Henoch-Schonlein purpura = an IgA mediated small vessel vasculitis
* Primarily seen in children
* Features:
* Palpable purpuric rash - buttocks, extensor surfaces of arms and legs
* Abdo pain
* Polyarthritis
* Features of IgA nephropathy can occur: haematuria + renal failure
* HSP is self-limiting with excellent prognosis (especially without renal involvement) - 1/3rd have relapses of symptoms
55
What drugs are commonly used for immunosuppression in Renal Transplant?
1. **Ciclosporin** - inhibits calcineurin (a phosphatase involved in T-cell activation)
2. **Tacrolimus** - inhibits calcineurin (a phosphatase involved in T-cell activation)
* Less HTN or hyperlipidaemia compared to ciclosporin
* Higher incidience of diabetes
3. **Monoclonal antibodies** e.g. Daclizumab or Basilximab - IL-2 receptor inhibitors on T-cells
56
What 3 factors can affect the result of a patient estimate GFR?
1. Pregnancy
2. Muscle mass (e.g. amputees, body-builders)
3. Eating red meat 12 hours prior to sample being taken
