Chronic Kidney Disease Flashcards
What are the 8 functions of the Kidneys?
- 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)
What is RRT (Renal Replacement Therapy) and what does it involve?
RRT = therapy that replaces blood filtering function of the kidneys
Used in AKI and Chronic Kidney Disease
It involves:
- Hemodialysis
- Peritoneal dialysis
- Renal transplant
What is Orthostatic Proteinuria?
- 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
Proteinuria can occur in other situtations, which do not indicate CKD, name 6?
- After physical exercise
- Fever
- Pregnancy
- UTI
- Abnormally high BP
- Nephrotic / nephritic syndrome
What are the 4 main features of Nephrotic Syndrome?
- 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)
What are the 4 main features of Nephritic Syndrome?
-
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
Urine dipstick detects proteinuria, in which 2 areas of the Kidney’s can the problem be?
- Glomerulus pathology
- Tubulointersitial pathology
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?
- Intersitial Nephritis (most commonly caused by reaction to medication e.g. β-lactam Abx and NSAIDs, but can also be casued by infection)
- UTI
What can Spot Urine Collection for total protein : creatinine ratio be used as an estimate of?
24hr Urinary Protein Excretion
- Degree of proteinuria correlates with progression of kidney disease
- Degree of proteinuria is most reliable prognostic factor in CKD
Which has greater sensitivity for low levels of proteinuria;
Protein:creatinine ratio
OR
Albumin:creatine ratio
Albumin:creatinine Ratio
Which method of monitoring proteinuria is recommended for diabetics;
Protein:creatinine ratio
OR
Albumin:creatine ratio
Albumin:creatine ratio
What should a patient with urinalysis indicating non-visible haematuria have done?
Urine Culture (to exclude UTI)
- If UTI is excluded –> repeat urinalysis TWICE to confirm PERSISTENT non-visible haematuria –> refer for urological review
Which is the most important factor to address to ↓ risk of future cardiovascular disease?
Cholesterol
Blood Pressure
Diabetes
Weight
Smoking
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
How can you assess a patients riks of developing Cardiovascular Disease?
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
What are normal values for:
- PCR (Protein : Creatinine ratio)
- ACR (Albumin : Creatinine ratio)
PCR < 15 mg/mmol
ACR < 3 mg/mmol
What 2 factors are used to Stage Chronic Kidney Disease?
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
What ranges for 24hr urine collection, spot urine albumin, and spot ACR indicated microalbuminuria (moderate ↑ urine albumin)?
- 24hr urine collection = 30-300 mg/24hr
- Spot urine albumin = 30-300 mg/L
- ACR = 3.5-35 mg/mmol
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)?
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)
What classes of drugs are considered ‘Renoprotective’ and are used to; mangage progression of CKD, lower BP and manage nephropathy in diabetics?
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
Via what 3 mechanisms does Diabetes cause Nephropathy?
-
↑ 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
What clinical finding is indicative of the first stage of Diabetic Nephropathy?
↑ eGFR
- This is due to ↑ glomerular BP caused by RASS activation and the heart working against ↑ vasocontriction
Are the Kidneys intraperitoneal or retroperitoneal?
Retroperitoneal
At what Spinal level are the Kidneys?
T12 - L3
What is included in the definition of Chronic Kidney Disease?
- 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)
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
Is CKD as a whole more common in the eldery or the young?
What are the 3 most common causes of CKD?
Elderly
- Diabetes
- Hypertension
- Glomerulonephritis
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
Is End-Stage Kidney Disease rare or common?
Rare
- Incidence (2009) was 109 per million population
What nitrogenous waste product is used to calculate eGFR?
Creatinine
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)
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
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
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
What is the target Ferritin for Renal Anaemia due to CKD?
> 200 ug/L
What is the mechanism of Renal Anemia in CKD?
CKD causes damage to the Kidney peritubular cells –> ↓ erythropoietin production
↓ erythropoietin production –> ↓ RBC / Haemoglobin = Anaemia
What are the 4 main effects of CKD on the body?
- Anaemia (renal)
- Metabolic Acidosis
- Secondary Hyperparathyroidism / Hypocalcaemia
- Hypertension
Analyse this diagram on management of CKD + Complications
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)
What is Azotemia?
Raised nitrogenous waste compounds (urea and creatinine) in the blood often due to insufficient filtering of blood by Kidneys
What is Uraemia?
Clinical syndrome that results from failing Kidneys and progressive azotaemia - High blood urea levels
What is the normal range of eGFR?
100-130 ml/min/1.73m2
What are 6 indications for dialysis?
- pH < 7.2 (acidaemia due to metabolic acidosis, where sodium bicarb may cause fluid overload)
- K+ > 7 mmol
- Fluid overload (unresponsive to diuretics)
- Toxins SLIME = salicylic acid, lithium, isopropanol (antiseptics, disinfectant and detergent), magnesium and ethylene glycol (antifreeze)
- Creatinine > 400
- Uraemia complications e.g. encephalopathy or uraemic pericarditis (urea enters pericardial sac and fluid follows)
What are the 4 types of Diuretics?
-
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
-
Loop diuretics - e.g. furosemide, bumetanide
- NKCC2 antagonists –> inhibiting Na+, K+ and Cl- reabsorption –> ↑ H2O loss
-
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+
-
K+ sparing diuretics - 2 types:
- ENaC (epithelial sodium channel) blockers e.g. amiloride or triamterene
- Aldosterone antagonists e.g. Spironolactone or eplerenone
Hemodialysis has 1 absolute contraindication and 5 relative contraindications - what are they?
Absolute = Inability to achieve suitable vascular access
Realtive:
- severe dementia
- severe HF
- bleeding disorder
- low BP
- severe active psychotic disorder
What are the 5 absolute contraindications for peritoneal dialysis?
Peritoneal dialysis has many relative contraindications, list some
Absolute Contraindications:
- IBD
- Ichaemic bowel
- Acute diverticulitis
- Abdominal abscess
- Pregnancy 3rd trimester
Relative Contraindications: Stomas, VP shunt, abdo hernias, blind, obesity, severe obstructive airway disease, severe active psychotic disorder
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)
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
What is the target BP for a proteinuric CKD patient?
< 130/80
Name 9 risk factors for CKD!
- Diabetes
- HTN
- Age > 50 yrs
- Male
- Black or Hispanic
- FHx
- Smoking
- Obesity
- Autoimmune disorders
What are 6 signs/symptoms of CKD?
- Fatigue - CKD is associated with renal anaemia due to ↓ erythropoietin production once GFR < 50
- Pruritis - due to accumulation of toxic waste products e.g. urea
- Hypertension
- Oedema - periorbital / peripheraly oedema develops due to salt and H2O retention due to low GFR
- Nausea with/without vomiting - accumulation of toxic waste products (urea)
- Reduced urine output - low GFR
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
What are the 2 most common causes of ESRD (End Stage Renal Disease) in the UK?
- Diabetes
- Hypertension
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
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
How is IgA Nephropathy different to Henoch–Schönlein purpura (HSP)?
- IgA Nephropathy is more common in young adults vs HSP is more common in children
- 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
What drugs are commonly used for immunosuppression in Renal Transplant?
- Ciclosporin - inhibits calcineurin (a phosphatase involved in T-cell activation)
-
Tacrolimus - inhibits calcineurin (a phosphatase involved in T-cell activation)
- Less HTN or hyperlipidaemia compared to ciclosporin
- Higher incidience of diabetes
- Monoclonal antibodies e.g. Daclizumab or Basilximab - IL-2 receptor inhibitors on T-cells
What 3 factors can affect the result of a patient estimate GFR?
- Pregnancy
- Muscle mass (e.g. amputees, body-builders)
- Eating red meat 12 hours prior to sample being taken
