kidneys Flashcards
Functions of the kidney
- Elimination of waste: carbohydrate; Nitrogenous (urea, creatinine); sulphate and phosphate; water and acid regulation: fluids and electrolytes
- Endocrine: vitamin D deactivation; secretion of erythropoietin
- Blood pressure regulation: renin/ angiotensin and volume control
acute kidney injury- facts
- 100,000 deaths a year in hospital are associated with acute kidney injury
- 30% could be prevented with the right care
- one in five people admitted to hospital as an emergency has acute kidney injury
Acute kidney injury AKI or ARF
- Serious medical emergency that can develop very quickly (usually within 48 hours)
- Definition is varied
- Is not a single state disease with uniform aetiology
- Prognosis is not good if left untreated in a timely manner
- Hypovolaemia (shock) main cause-falling renal perfusion pressure. But also nephrotoxicity and acute glomeruli nephritis
Definition of AKI
- A rising serum creatinine of 26 µmol/litre or greater within 48 hours -50% or greater rise in serum creatinine known or presumed to have occurred within the past seven days
- falling urine output to less than 0.5 mil/kg/hour >6 hrs in adults and >8 hrs in children and young people
- 25% or greater fall in e GFR in children and young people within the past seven days
RIFLE criteria
Risk Injury Failure Loss End stage renal disease
AKIN criteria
See BB slides for an illustration of the AKIN criteria
Symptoms Of acute kidney injury
• Nausea and vomiting • Dehydration •Confusion • High Blood Pressure • Abdominal Pain • Slide Back out • Oedema
Risk of developing acute kidney injury
- aged over 65
- patients with existing kidney problems e.g. CKD
- dehydrated patients who are unable to maintain their fluid intake independently
- urinary tract blockage
- sepsis
- medication : NSAIDs, ACEI, diuretics, antibiotics (gentamicin)
Classification and cause of AKI
Pre-renal: reversible decreased perfusion through hypo-perfusion, via hypovoleamia or decreased CO, altered renal vascular regulation; 40-80%
- Intra renal (including acute tubular necrosis) : renal parachymal injury, tubular necrosis; 10-50%
- Post-renal: Urinary Tract obstruction, malignancies ; >10%
Pre-renal causes acute kidney injury
Occurs before the kidneys blood vessels
Decreased effective extracellular volume
Example: hypovolaemia; decreased cardiac output; systemic dilation Altered renal vascular regulation
intra renal
Cause within the kidney Caused by acute tubular necrosis
post renal
This occurs after the kidneys: bladder, ureter, urethra Caused by obstruction of the urinary tract e.g.prostate hyperplasia, malignancies
causes of acute tubular necrosis
- Hypoperfusion
- Radio contrast media (used to diagnose certain conditions)
- sepsis
- Rhabdomyolysis (breakdown of muscle from within the cell)
- Renal transplantation (immunosuppresants cause kindey toxicity)
- hepatorenal syndrome (End stage liver disease
- Nephrotoxins: NSAIDS, ahminoglycosides, immunosuppressant, chemotherapy, poisons
Causes of AKI
- reduce fluid intake
- increased fluid loss
- urinary tract symptoms (post renal cause)
- recent drug ingestion
- sepsis
Phases of recovery of acute tubular necrosis
- Oliguric phase: 10 to 30 days; glomerular and tubular dysfunction
- Polyuric phase: persisting tubular dysfunction
- Recovery phase: maybe prolonged-six months or sometimes longer
Investigation of AKI
Full history- drug history
Clinical examination, including fluid balance assessment
Urinalysis- if it is conc urine it is pre renal cause; itra-renal or obstructive cause they will have isotonic urine; Obstructive uropathy the patient will have anuria (reduced urine productio) or crystal uria
Blood examination
Ultrasound scan renal tract is mandatory- this is to exclude obstruction and prepare patients for renal biopsy
management of acute kidney injury
- Non-specific remedy
- Early aggressive intervention at the first sign of oliguria may prevent sustained oliguria-
- If due to shock-restoration of CVS function may involve transfusion, osmotic erratics or high dose of loop diuretics (furosemide 3mg/kg/6 hours)
- Otherwise careful management-fluid intake monitoring, may use plasma expanders, use of diuretics depends on a aetiology
Chronic kidney disease
- One in 10 people live in CKD
- 6 million people in England
- Progressive loss of renal function over a period of months or years symptoms of worsening kidney function unspecific may include feeling generally unwell,
- Severity is in five stages: stage I is mildest causing few symptoms so stage V severe illness with poor life expectancy
- Stage 5 it is called established chronic kidney disease
- persistent fall in GFR (< 60 mil/Min/1.73 m²) for three months will be considered CKD
Signs and symptoms of chronic kidney disease
CNS: confusion; seizures; coma
BLOOD: anaemia; platelet abnormalities
RENAL: polyuria; Na+, H2O retention, noturia
HORMONAL: infertility; loss of libido; impotence
BONE: osteomalacia; pain; osteosclerosis; hyperparathyroidism
CVS (RAAS malfunction): hypertension; HF; vascular disease; peripheral oedema
GI TRACT: nausea; vomiting; weight loss
PERIPHERAL NEUROPATHY
Causes of CKD
- Diabetes- 16%
- Chronic Glomerulonephritis- 19%
- Pyelonephritis and obstructive uropathy-11%
- Polycystic Kidneys-10%
- Hypertension-6%
- Renovascular disease-3%
- Other-16%
- Unknown aetiology-16%
- Data not sent-3%
Urine volumes by definition
OLIGURIA (Decreased urine output): in adults <500 ml/day
- may indicate CKD but may also indicate dehydration or urinary obstruction
- Anuria is below 50 ml/day
POLYURIA: in adults >2.5 L/day
- May cause diabetes (osmotic effect), high volume intake, diabetes insipidus
- May occur in early stage CKD
- Loss of urine concentrating capacity
Renal clearance and GFR
- Direct measurements of clearance is difficult
- Clearance is used to measure renal function
- Equals the volume of blood from which a substance completely removed by filtration in one minute
- Clearance x [plasma] = [urine] x urine vol/min -Clearance = (Uc x Uv) / Pc
- If a substance were completely cleared and there is no tubular secretion of absorption then clearance = GFR
Measurement of GFR
- Inulin: ideal but need to infuse and obtain steady plasma concentration: measure plasma conc and urea conc
- Creatinine: natural constituent from muscle
+Freely filterd but some tubular secretion
+Somewhat overestimates GFR
+Need 24 hour urine collection- difficult
-Various methods to estimate creatinine clearance and so GFR from single data point e.g. serum creatinine (oppsed to creatinine in urine)
Cockroft-Gault equation
Derived from average population data 1976
Normal values for GFR fall with age- halve by age 75
-Most medicines that effect renal functions or are predominantly excreated through renal clearance use the cockroft-gault equation to adjust dose dependant on severity of kidney dysfunction (increased half life and so toxicity of drug)
MDRD formula
- Developed for use in CKD. No evidence of applicability in acute renal failure
- Underestimates GFR in healthy (>60 ml/min)
eGFR=186x(serum creatinine (mcmol/L)-1.154x(age)-0.203xK1xK2
- K1= 0.724 if female
- K2= 1.212 if afro-American
chronic kidney disease epidemiology collaborated
- More accurate than MDRD
- Clinical labs should: use the CKD epidemiology collaboration (CKD-EPI) creatinine equation to estimate GFR creatinine, using creatinine assays with calibration traceable to standardized reference material
Plasma creatinine and GFR
- Plasma Cr inversely related to GFR
- Initially, relatively large falls in GFR causes small rises in PCr e.g. GFR 50% normal, PCr doubles to 200 mcg/L
- Serum Cr measurements are not reliable for measuring small changes in GFR
- Progression of disease best followed by reciprocal plot
- Serum Cr increases as renal function deteriorates
Progression of CKD
- Diminished renal reserve: GFR (120-90 ml/min), urine production UP(normal/mild polyuria)
- Renal impairment: GFR (90-60 Ml/min), UP (polyuria)
- early stage renal failure: GFR (60-30), UP (oliguria)
- Pre-end stage failure: GFR (30-15), UP (oliguria)
- End-stage renal failure:GFR <15, UP (oliguria)
Plasma urea
- Normal <8mmol/L. Some symptoms when 20-25 mmol/L and severe symptoms 50-60 mmol/L
- Uraemia is common in CKD but urea only one of the nitrogenous products affected
- Plasma urea still a general index of renal function
- Affected also by diet, liver function, muscle damage etc
Tubular function
- SPECIFIC GRAVITY: (1.01 to 1.02 normal adults)
- OSMOLARITY (normal adult 50-1400 mOsmol/L; random; 500-800 mOsmol/L 24 hours)
- Changes reflect concentration and can be used to indicate concentrating capacity e.g. water deprivation (lost in CKD)
- Also affected by fluid intake and ADH release (diabetes insipidus)
Fluid and electrolyte imbalance
- Maybe very slow onset- patients don’t recognize urinary symptoms. Often mild polyuria early (loss of conc, capacity)
- Later stages inadequate renal function and Na+ and H20 retention. Maybe hypervolemia and oedema- including pulmonary. HF a possibility
- Late stage hyperkalemia and often acidosis- failure of K+ and H+ secretion
Potassium
- Generally Hyperkalaemia
- Levels over 7mmol/L are life-threatening
- Acidosis exacerbates hyperkalaemia because of movent of intracellular K+ out of the cell
- Major ECG changes as a result of hyperkalaemia
- If allowed to continue to rise will result in cardiac arrest
Cardiovascular effect
- Hypertension almost inevitable- number of causes: fluid retention, RA abnormalities
- Cardiomyopathy associated with Ca2+ and phosphate (PO4) imbalance
- Cardiac failure- volume overload, oedema, hypertension, anemia
- Overall CVS events account for over half the deaths in CKD
Anaemia
- Bone marrow hypoplasia (wont produce RBC) due to reduced or no erythropoietin
- Haemoglobin levels fall:<8d/dl Rf 12-18 g/dl
- Fe and or folate deficiencies exacerbates the above- Poor dietary uptake and losses e.g. bleeding from the GI tract
- Aggravates effects on heart and major effect on quality of life
Calcium and phosphate
- Kidney essential for final stage activation of Vit D
- Lack of Vit D causes reduction GI Ca2+ absorption and renal reabsorption
- Hypocalcaemia stimulates PTH release- increased bone resorption. osteomalacia–> renal rickets
- Poor phosphate excretion leads to solubility product for Ca and PO4 to be exceeded. Ectopic calcification
- This can be treated by restricting phosphate in the diet however this is hard because it is in alot of food stuff, phosphate binders can be used to absorb them
- AlOH used to be used as a phosphate binder but patients used to absorb and not eliminate Al so would get neurological side effects including dementia
Management of CKD
- BP control: ARBs, ACEI this is used bevause they reduce protein uria and progression of CKD
- Anaemia management
- Oral bicarbonate supplement for management of metabolic acidosis
- Encourage those with CKD to exercise, achieve a healthy weight and stop smoking
- Offer dietary advice about K+, PO4, calorie and salt intake, but patient needs dietary assessment to prevent malnutrition
- Low protein diets are no longer offered
Drug use in renal impairment
- Avoid drugs that are likely to cause further damage
- Many drugs are excreted by the kidneys
- Some drugs may need to be excreted in order to work
- ADRs are more likely with many drugs
Drug use in renal impairment
PATIENT FACTORS: degree of renal impairment; stable, improving or deteriorating; concomitant medication/disease
DRUG FACTORS: is the drug essential; How quickly is needed; what proportion is renally cleared; is the drug nephrotoxic; does the drug have a narrow therapeutic index; measure safety/efficacy parameter; our ADRs more likely in renal impairment; mechanism of action; half life
Renal replacement therapy
- Towards end-stage CKD-how shall require an organ transplant
- there is a waiting list
- the best option for most CKD patients
- 2929 Kidney Transplants Took Pl; aprox one third were live donors
- major limiting factor is donors-UK one of the worst in Europe for diners
Dialysis
Peritoneal: up to 25 L of sterile fluid into the peritoneal cavity under gravity. The exchange between peritoneal capillaries and fluid. drain out under gravity
Haemodialysis-artificial kidney with large area exchange membrane. Arterial blood pumped by peristaltic pump countercurrent flow of dialysis fluid
continuous venovenous haemofiltration- short-term treatment using ICU patients with acute or chronic renal failure. Blood is passed through hemofilter
-Dialysis fluid is adjusted to the individual- low in ions to be removed and high in those to be added to patient plasma
Erythropoietins
- Recombinant human erythropoietins
- Epoetin alpha, beta, theta and zeta and darbepoetin (hydroxylated derivative with longer half life)
- Can be used in CKD
- MRHA warning on use in cancer- increase in mortality- 2008
- Revised NICE guidelines- erythropoiesis stimulating agents are recommednend, within their MA as options for treating anaemia in people with cancer who are having chemotherapy
Dialysis
- This is taking toxins out of the blood
- The blood passes through a semi permeable membrane that lets low MW compounds through
- This is via difusion which is dependant on conc gradients as well as movement of dialysis pores of membrane so small moleucles are cleared better
- This can be done with pressure changes
- The movement of substances can be done by convection- small molecules move with ultrafilrate
Peritoneal dialysis
- Rarely used but is used when Haemodialysis
- A catheter is then placed into the peritoneal cavity
- 1-2L of dialysis fluidis then placed into the abdomen and left for around 30 minutes then drained into bag
- This can be carried out up to 20 times a day
- This is keep and simple and doesn’t need specialist kidney untis or staff
- However this can take a long time and be tiring for the patient; Cause infection of peritoneum as well as protein loss
Haemodialysis
- A dialysis line is used, this is placed in a vein and an artery
- This can be intermittent of continuous
- This is expensive bevcause it has to be in a renal unit as well as specialist staff (this can be inconvient, travel)
Continuous venvenous haemofiltration
- Blood is passed through a haemofilter
- For each case the dialysis fluid is adjusted dependant on electrolyte and needs for the specific patient
