Lecture 6: Clinical Renal Failure Flashcards
Renal Failure
Reduction in Kidney Function/GFR
GFR normally 100ml/min (90-110) (think of renal failure as a % of kidney function)
Acute Kidney Injury or Chronic Kidney Disesase
When are blood tests needed re kidney failure?
Collection of non-specific symptoms dont hint to kidney failure w/o blood test evidence
Mainly measure Urea and Creatine levels
Plasma Urea
main excretory product from waste nitrogen
Formed in live from aa (urea cycle)
35g (600mmol) formed per day based on average protein intake
Urea is the major solute in urine contributing to urine osmolarity
What is the amount of Plasma urea dependant on?
Dietary protein intake Protein breakdown (catabolism), increased by infections (septic), trauma, immobilisation Bleeding into GIT (equivalent to high protein diet as blood breaks down, increasing protein levels)
Why could a body builder be referred to a GU specialist?
Lots of muscle = high creatine
Lots of protein in diet = high urea
- doctors think have kidney failure
Renal handling of urea
Urea is Freely filtered
Fraction of Urea reabsorbed in tubules (back diffusion)
Urea Back diffusion increases during slow flow rate (dehydrated patient)
Urea excretion rate DEPENDS on GFR but isnt exact (creatine is more accurate)
Plasma urea as a renal function test
Renal failure –> Decreased GFR –> Decreased urea filtered through glomeruli –> Increased Plasma Urea
Reflects rough index of glomerular function but creatine levels more accurate (as is effected by back diffusion (-ve vs filtration))
Plasma Urea levels Affected by factors other than renal function (protein diet, hydration status, intestinal bleeding)
Dehydrated patient
Dehydrated patient –> decreased volume –> decreased flow –> increased back diffusion –> increased urea reabsorption into tubules –> increased urea in blood
- urea levels rise more than creatinine in dehydration
Creatinine
Derived from creatine in muscle –> peoples levels change depending on the body size
Purely waste product (no biological function)
1% of muscle creatine converts spontaneously to creatine daily (irreversible)
- formation rate propn to muscle mass (8-20mmol/day)
Freely filtered
No tubular reabsorption of secretion –> Clearance rate of creatine is propn to GFR
Increase GFR –> increased filtration –> decreased plasma creatinine
Relationship b/w plasma creatinine and GFR
Increase GFR –> increased filtration –> decreased plasma creatinine
INSENSITIVE index of renal function, failing to detect early renal disease
Muscle mass varies widely in population
Serial plasma creatine measurements can be used to monitor the course of renal disease
graph
Effect on meat and fish intake on creatinine and eGFR
normal creatinine 60-80umol/L
creatinine formation occurs in the meat/fish (esp during cooking) –> plasma creatinine rises by 10-30umol/L after meat/fish meal –> FALSE LOW eGFR (looks like lots of creatinine has been filtered into blood)
THEREFORE: blood sample for creatinine should be taken 12 hours after last consumption of meat/fish
Gold standard measurements of GFR
inulin clearance
51Cr-EDTA clearance (nuclear medicine scan, kidney donors)
- impractical for everyday clinical use (therefore use equations and blood tests)
vs
eGFR estimates GFR via plasma creatinine levels
Factors in eGFR
- Weight: 2x people with same large weight and same creatinine, Fat person would be more likely due to kidney failure rather than muscle mass
- Age: Decreased muscle mass and possible reduction in nephron function (GFR 130 –> 80)
- Gender: due to popn norms, woman tend to have less muscle mass than men
Creatinine as a surrogate measure
- Quantity of waste product produced
2. Ability of the kidney to get rid of the waste product
eGFR
normal GFR 100ml/min
Creatine better than urea in 2x ways re eGRF:
1. More accurate representation of kidney function
2. Accounts for muscle mass
Components of eGFR calculators
- age
- gender
- race
- creatinine
CKD-EPI equation requires: plasma creatinine, age, sex
Limitations of eGFR
eGFR is inaccurate if muscle mass is unusually low or high
- e.g. amputees (renal function looks dispropn good), muscle wasting, body builders
eGFR is only valid for patients in a steady state (stable creatinine levels)
- not valid if creatinine is rising (acute renal failure) or falling (Recovery from acute kidney injury) (good for chronic kidney disease?)
Creatinine levels if different body sizes
Small and v skinny: creatinine 80 = GFR 102
Body builder: creatinine 140 = GFR 102
Fat man: creatinine 140= GFR 60 (lower kidney function due to less muscle mass)
Acute Kidney Injury
Sudden rapid reduction in GFR (decreased blood flow due to other causes 70% of time)
days/weeks
reversible usually
70% due to non-renal causes
- something else bad has happened –> decreased blood flow to kidney –> acute kidney injury
Aetiology of AKI
PreRenal: blood supply has problem in body so cant get to kidneys
Renal: Intrinsic nephron problem
PostRenal: Blockage
Prerenal AKI
- Dehydration
- Septic shock (meningicocal infection –> increased cytokine release –> decreased BP –> AKI)
- Haemorrhage (leg cut off)
- Cardiogenic shock ( HF –> decreased CO –> decreased BP)
- Severe Renal Artery Stenosis (Bilateral narrowing)
Causing: Decreased BP –> Not enough blood to kidneys:
Dehydration/sepsis/haemorhage/cardiogenic shock / RA stenosis –> Decreased BP –> brain/gut/heart/lungs receive prioritised blood supply –> Decreased/deficient blood supply to liver and kidneys –> acute as kidneys/liver are able to regenerate/repair themselves
AKI Clinicians response
- History: Reasons for low BP (IG bleeding/vom, dehydration, infection, heart failure, recent surgery)
- Urine Output: Oligouric: unusually low urine output initially (<1 L/day) (Note: “oligo”=less anurea=<100mL/day)
- Blood Tests: High creatinine (defining test) Hyperkalaemia, high phosphate, calcium pot. low
- Treatment: Fix underlying problem respectively (rehydrate, treat bleeding, fix heart, antibiotics for sepsis, ICU treatment for persistent low BP/NE)
Prerenal AKI Outcomes
- Gets better (non-severe insult to kidneys)
2. Acute Tubular Necrosis (hypotensive for too long, necrosis of renal tubules in short time)
Renal AKI
- 80% Acute Tubular Necrosis (ATN)
2. RPGN Rapidly Progressive Glomerulonephritis (10% of acute kidney injury in the renal form)
ATN
Acute Tubular necrosis (80% of Renal AKI)
- Mainly DUE to Prerenal (that hasnt been treated quickly or vigorously enough)
Persistent oliguria (Low urine output) and Renal Failure after correction of underlying pre-renal condition
May take 4-6 weeks to recover (regeneration)
Mainly necrotic changes
High creatinine and low urine output continues –> dialysis
High potassium sometimes too
ATN Treatment
Maintain normal BP
Treat underlying problem
If kidneys keep getting worse –> Dialysis (usually GFR <10ml/min)
ATN Recovery
95% gets better (decreased tubule function –> decreased ability to hold onto salt and water -(cannot concentrate urine) –> very dilute urine –> increased volume of urine –> massive decreased in body water levels)
Polyuric Phase in Recovery
- Tubules cant concentrate. Pee up to 20L of urine/day.
Tubules recover –> concentrate urine –> dont pee out much needed salt and hence water)
Causes of ATN
- unresolved Pre-renal problems
- Drugs (Pharmaceuticals, crack/heroine, angiogram contrast)
- Toxins(severe reactions) (bee stings, snake venom)
RPGN
Rapidly Progressive Glomerulonephritis - Blood and/or protein in urine - consider if exclude e.g. toxin Renal AKI: due to glomerular disease RPGN Diagnosis: Renal Biopsy --> important to diagnose as is a specific treatment
Post Renal AKI Causes
Blockage post kidneys –> back up of urine –> damage to kidneys –> post renal failure
- Kidney Stones
- Tumour
- Prostate Hypertrophy
- Urinary Retention
Post Renal AKI Treatment
Ultra sound: - quick, easy, non-invasice, non-harmful - everyone with AKI should have US normal: white Hydronephrosis: urine cannot get out --> dilated renal pelvis --> black and dilated US
AKI treatment summary
Make a diagnosis –> institute appropriate treatment
CKD
Chronic Kidney Disease
months/year there is a Gradual decline in Renal function
Scarring causes it to be IRreversible –> therefore treatment is now to stop/slow down progression of injury
Elevated Creatinine and Urea
Usually have normal urine output
Quantified in Stages
CKD Stages
1 - normal kidney function –> 90 GFR (intrinsic problem: diabetes –> increased protein leaked into urine or blood)
2 - early (50% of popn over 30) –> 60-89 GFR ml/min –> increased PTH
3 - moderate absorption –> 30-59 GFR ml/min –> decreased Ca
4 - severe (renal clinic) –> 15-29 GFR ml/min –> anaemia (low EPO), Increased CV risk, High phosphate, Acidosis, Potassium may rise, Malnutrition
5 - ESFR –> <15 GFR ml/min –> uraemia
Causes of CKD
- Diabetes
- Glomerulonephritis
- Hypertension
- Loads of others
CKD cellular
Gradual increase in creatinine due to underlying disease
Scarring of glomerular and intersitium (irreversible)
CKD patient symptoms (“feel”)
None in early stages (asymptomatic)
Usually found on blood tests
URINE OUTPUT NORMAL
Uraemia: symptoms of kidney failure (mild –> progressive. variable depending on person)
“signs” vs “symptoms”
signs = examine (e.g. BP) symptoms = feel (e.g. tired)
Uraemia (Kidney Failure) symptoms (“felt”)
anorexia, nausea, vomiting, itchiness (pruritus - toxins/high phosphates affects skin), SOB (due to anaemia/fluid overload) (lungs/breathlessness), COLD INTOLERANCE (commonest symptom), swelling, seizures, coma
CKD signs “examined”
Non consistent signs early on
Most common is Hypertension (vs acute hypo)
3x signs of KF (all assoc. with fluid overload)
1. Oedema
2. Pulmonary Oedema
3. Raised JVP
How is CKD diagnosed?
Routine blood tests
- Urea (increased), creatinine (increased), decreased eGFR
- Hb low
Hemoglobin levels in CKD
RBC>electrolyte measurement
RBC 1/2 life = 90 days
Decreased RBC levels –> must be CHRONIC kidney disease
- unless actively bleeding
Bone disease in relation to Kidney Failure
Preservatives = increased phosphates
Diet/Skin a.k.a Sun –> Vit D3 –> Liver contains storage enzyme (storage form of Vit D) –> Kidney contains 1-hydroxylase enzyme converting Vit D into Active form
Hence in KF –> Kidney not functioning –> no 1-hydroxylase enzyme to convert Vit D from storage form –> Inadequate Vitamin D in active form (regardless of how much sun you get)
High Serum Phosphate of Kidney Failure
Phosphate metabolism:
1/2 absorbed in gut (400mg/day)
2/3 excreted in urine (800mg/day)
Increased GFR –> Hyperphosphaturia –> increase serum phosphate
Hyperparathyroidisim
HypoCa2+ and Hyperphosphatemia –> High PTH –> Hyperparathyroidism –> Excessive Bone Resorption of Ca2+
Stimulation
1. Fractures
2. Extra-osseous calcification
3. Vascular calcification –> increased CVD risk –> increases BP and Dodgy rough BV
PTH
4x parathyroid glands (top and bottom)
Parathyroid hormone
- polypeptide hormone
Cell contains Calcium sensing receptor –> intracellular receptor –> PTH packaged in vesicle –> fusion and release
Stimulation for PTH secretion: low Ca2+ and high phosphate
- decrease Ca2+ in serum via leeching Ca2+ out of bones to correct hyperclacaemia
CKD blood test results
Decreased renal secretion –> High Serum Phosphate (Cannot pee out)
Low 1,25 (OH) Vit D
Low Ca2+
High PTH (due to hypocalcemia and hyperphosphatemia) = Hyperparathyroidism = Excessive Bone Resorption of Ca2+
CKD potassium
often high as dont pee out –> Cardiac arrythmias
CKD concerns
Dialysis = increases mortality = tend to die from Cardiovascular problems
Transplant > dialysis
- but even still CKD with transplant is 10x greater mortality risk than general popn w/o CKD
–> therefore important to prevent worsening of chronic kidney disease
Aims of CKD Therapy
- Prevent Renal failure worsening
2. Control Renal Failure complications
Prevention of Deterioration of Renal Function
BP is the key thing to control to stop kidneys from worsening in both males and females
(high BP - Increased risk of End stage renal failure)
TREAT CKD WITH AGGRESSIVE BP REATMENT
