AKI, CKD, Dialysis Flashcards
Features of rhabdomyolysis
- Syndrome of muscle necrosis and release of intracellular muscle contents into circulation
- Reddish brown urine due to myoglobinuria in half of cases
- High CK, hyperkalaemia, hypocalcaemia, hyperphosphatemia, HAGMA
Post-obstructive polyuria leads to impairment in:
UO > 200ml/hr for 2 hours or >3L/day
Impairment in:
- urine concentrating ability
- sodium reabsorption
- urinary acidification
- potassium secretion
Acute Interstitial Nephritis
- Drug exposure accounts for > 70% of AIN
- Development of drug-induced AIN is not dose dependent and a recurrence/exacerbation of AIN can occur with second exposure to the same or related drug
- Triad of rash, fever, eosinophilia
Can also cause eosinophiluria
How much protein should be eaten in patients with CKD to prevent progression
Reduced to 0.8g/kg/day
Top 3 causes of CKD
Diabetes
Glomerulonephritis
HTN
What is “fixable” and “unfixable” with dialysis
Fixable:
• Salt and water balance - fluid overload
• Clearance of “uraemic toxins” - uraemia
• Potassium homeostasis - hyperkalaemia
• Acid-base balance - metabolic acidosis
Unfixable
• Erythropoietin production - anaemia
• Vitamin D synthesis and phosphate - secondary hyperparathyroidism
Effect of CKD on other organ systems
- Cardiovascular disease
- Hyperparathyroidism
- Uremic pruritus
- Malnutrition
- Uremic neuropathy
- Sexual dysfunction: Reversible factors (testosterone, prolactin, oestrogen), sildenafil, optimise dialysis if needed
Definition of CKD
Stages of CKD
DEFINITION - eGFR < 60 present for 3 MONTHS (with or without other evidence of kidney damage) OR Presence of the following >3 months (irrespective of GFR) - Albuminuria - Glomerular haematuria - Structural abnormality (on imaging) - Pathological abnormality ( on biopsy)
Stage 1: GFR >90 Stage 2: GFR 60-89 Stage 3a: GFR 45-59 Stage 3b: GFR 30-44 Stage 4: GFR 15-29 Stage 5: <15 or dialysis
Stage 3A CKD with macroalbuminuria is normally due to diabetic kidney disease
Normal Urine ACR
- Male < 2.5, Female < 3.5
Microalbuminuria
Male Urine ACR: 2.5-25mg/mol
Female Urine ACR: 3.5-35mg/mmol
Macroalbuminuria
Urine ACR Male > 25mg/mmol
Urine ACR Female > 35mg/mmol
eGFR
- Assumes steady state of creatinine generation and excretion
- Useful for monitoring patients in CKD
- Not appropriate in:
AKD/AKI
Children
Pregnancy
Extremes of body weight
Patients taking extra creatinine
What is used to calculate eGFR
CKD-EPI?
The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) is currently used now
- More accurate at higher eGFR
– Validated across more populations
– Better prediction of adverse clinical outcomes cf. MDRD
What is the most common cause of death in CKD and transplant
- CKD: Withdrawal is the most common cause of death followed by cardiovascular events
- Transplant: cancer and cardiovascular disease is the most common cause of death
CV disease and CKD
Cardiovascular disease
– Principal cause of death at all stages of CKD
– Left ventricular hypertrophy
– Myocardial fibrosis
– Accelerated vascular disease (non-atherosclerotic)
– Widened pulse pressure
Antihypertensive agents (beta-blockers, RAS blockers) effective Lipid lowering agents not proven to be effective
CKD and anaemia
- Common: less with ADPKD
- Proportional to CKD
Multifactorial
- Inflammation
- Higher blood loss
- Hyperparathyroidism
- Dysfunctional iron access
- Reduced EPO
Target Hb 110-120
Needs sufficient iron (T sats >20%, ferritin > 300)
Does not increase length life
Improves QOL
Reduces transfusions
Causes of EPO resistant anaemia
- Iron deficiency (most common cause)
- Intercurrent infection
- Hyperparathyroidism
- Primary bone marrow pathology
- Folate/B12 deficiency
- Pure red cell aplasia
Production of antibodies against EPO related to exogeneous treatment.
Less common with newer diluents.
Side effects of EPO
– Hypertension (commonest) - can be associated with
hypertensive encephalopathy
– Thrombosis of access
– Pure red cell aplasia
Adverse effects of higher Hb targets (death 45 – 48% increased risk, CVA, vascular access thrombosis) well
proven
Causes of iron deficiency in HD patients
Most patients on HD are not physically able to absorb enough orally absorbed iron to prevent iron deficiency
– Loss of blood during dialysis (10-30mL)
– Increased mucosal loss (anticoagulation during dialysis)
– Clotted circuit – 200-500mL blood
– Low haem iron diet
– Increased hepcidin (reduces GI duodenal iron absorption by binding ferroportin and sequestering iron in the macrophages)
Hepcidin is a key regulator of iron homeostasis and plays a role in the pathogenesis of anaemia of chronic disease. Its levels are increased in patients with chronic kidney disease (CKD) due to diminished renal clearance and an inflammatory state.
Iron management in HD
Target levels
– Ferritin > 300ug/mL
– Transferrin saturation > 20%
Intravenous iron required in majority
– Oral iron absorption poor and cannot replace average
daily iron loss
– Typically infused during HD treatment
– Maintenance protocols more effective than ‘reactive’ protocols
– Withhold during active infection
How much renal function is substituted by dialysis?
15-20%
Which patients are excluded from peritoneal dialysis
- Obese patients
- Abdominal surgery
- Poor vision
- Unstable home environment
- Not attentive to hygiene
- Patients without any residual renal function
If anuric or passing urine <500ml/day then they need to be transitioned to dialysis
RESIDUAL RENAL FUNCTION is required for a patient to undergo peritoneal dialysis
PD vs HD
- PD catheter inserted 2-3 weeks before starting PD
Patients need RESIDUAL RENAL FUNCTION for PD - HD: fistula created 2-3 months prior
When to start dialysis
- eGFR 5-10ml/min
- Uraemic symptoms eg: itch, cognitive dysfunction, fatigue, SOB, muscle cramps, N+V
- Fluid overload that cannot be treated with
diuretics/fluid and salt restriction
- Hyperkalaemia that cannot be managed with dietary vigilance and potassium binders
- Pericarditis, uraemic encephalopathy
AEIOU Acidosis Electrolytes Ingestion of toxins Overload Uremia
Haemodialysis access sites
- AV fistula
- AV grafts
- Tunnelled dialysis catheters
Descending in order for greater infection risk and less reliable
Dialysis catheter related bacteremia and tx
• 40-80% gram positive
• S aureus CRB associated with 20-30% mortality
• ‘Around catheter’ contamination more common than ‘inside catheter’
• Higher in
– Patients with diabetes
– Non tunnelled lines
– Femoral>internal jugular>subclavian
• Always assume the catheter is source of infection in a febrile dialysis
patient until proven otherwise
• Cultures from catheter and peripheries
• Mandatory removal (send tip for culture) if
– Non tunnelled line
– Severe sepsis in tunnelled line
• Broad spectrum antibiotics
– Empiric vancomycin or linezolid if MRSA/ VRE colonised
– Include gram negative cover
– 14 days treatment for S aureus
• Evaluate for metastatic infection (endocarditis, osteomyelitis, epidural
abscess) if persistent fevers or bacteraemia
Which of the following statements regarding haemodialysis (HD) and peritoneal dialysis (PD) is correct?
a. Patients on PD suffer greater fluctuations in their fluid state than patients on HD
b. Both HD and PD lose their effectiveness with time
c. Low serum urea levels are a reliable indicator of effective therapy
d. Weight gain in the absence of fluid overload commonly occurs in patients on PD
e. HD has a proven advantage over PD in preservation of residual kidney function.
d. Weight gain in the absence of fluid overload commonly occurs in patients on PD
- Which of the following is true regarding mortality in HD patients?
a. Similar to the general population when high quality HD has been given
b. Commonest cause of fatality is infection
c. Fatality in HD patients is highest after a longer interdialytic break
d. Cardiovascular mortality is explained by traditional CV risk factors
e. Statin therapy for hyperlipidaemia has an established role in high risk patients on HD
c. Fatality in HD patients is highest after a longer interdialytic break
In PD, how do solute and water move across the peritoneal membrane?
3 transport processes occurring at the same time
1. DIFFUSION – where substances of high
concentration move towards areas of low
concentration.
- CONVECTION – the difference in osmolality leads to movement of water and associated solutes across the
membrane. - ABSORPTION – the lymphatics constantly absorbs water and solutes.
Peritoneal Clearance is the net result of diffusion + convection – absorption.
Diffusion in PD
This is critical for removal of uraemic toxins in peritoneal dialysis.
Relies on –
• Concentration gradient
• Effective peritoneal surface area
• Intrinsic peritoneal membrane resistance
• Molecular weight of the solute concerned
(A) How can peritoneal clearance by increased?
(B) How can fluid removal be increased by?
(A) Peritoneal CLEARANCE can be increased by:
1. Maximising time on PD
- Maximising concentration gradient
• Increasing number of exchanges
• Increasing dwell volumes - Maximising effective peritoneal surface area
• Increasing dwell volumes - Maximising peritoneal fluid removal
(B) FLUID REMOVAL can be increased by:
1. Maximising the osmotic gradient
• Higher glucose concentration
• Increase number of exchanges
- Use an osmotic agent that is not absorbed well
- Increase urine output
- Increase in % of bags = increase amount of fluid removed
Different Bags: 1.5%, 2.5%, 4.25%, 7.5% (isodextrin) - Increase in fill volume/number of cycles = increase solute clearance (eg: urea, K+)
What is the peritoneal equilibration test?
- Gives us an idea of the transport characteristics of an individual’s peritoneal membrane
- Assessed by using equilibration ratios between dialysate and plasma for urea (D/P urea), creatinine (D/P creatinine)
- By waiting for equilibration, this test measures the combined effect of diffusion and convection.
- UF volumes are inversely proportional to peritoneal transport characteristics for solutes
- High transporters rapidly absorb the osmotic agent into peritoneal capillaries, diminishing stimulus for ultrafiltration within a few hours of dwell, leading to reabsorption of fluid through rest of the dwell
- Low transporters have good ultrafiltration, because the osmotic gradient is maintained throughout the entire dwell
High Transporters:
- Benefit from APD modalities that use shorter dwell times (so they need more cycles for better solute clearance)
- Excellent solute clearance
- Poor ultrafiltrate
· High Transporters: require more cycles for better solute clearance, normally diabetics are high transporters
Low Transporter
- Benefit from longer dwell modalities such as CAPD
- Inadequate solute clearance
- Excellent ultrafiltration
- Patients with a so-called high transport status of the peritoneal membrane (i.e. a more permeable peritoneal membrane), characterized by a high dialysate to plasma (D/P) ratio of creatinine, have a low UF volume due to rapid dissipation of glucose from the PD fluid to the capillaries.
· Low Transporters: it would be ideal to start as a low transporter as most PD patients progress to being high transporters
○ The ideal would be to be a low transporter and non-diabetic
· Low Transporter –> High Transporter –> Membrane Failure
○ Membrane Failure: when dwell time of 4 hours, 4.25% bags, UF <400mL
When there is membrane failure, the patient will need to be transitioned from PD to HD
What are high transporter states
- Inherent high transporter
- Peritonitis: transient and reversible
- Acquired on long term PD, esp in patients with a greater cumulative dextrose load
Types of PD
2 main Types: APD (automated peritoneal dialysis) vs CAPD (continuous ambulatory peritoneal dialysis)
○ APD (automated): using a cycler, done at night, frees up the morning/afternoon, overnight using machine
○ CAPD (continous ambulatory): manual, done by the patient - 3 manual bags in the morning + afternoon and isodextrin bag at night 4-5 bags/day every day
§ Patients who are on CAPD are normally low transporters
Benefits of 7.5% icodextrin
- Relatively inert high molecular weight polymaltose
glucose polymer - Less permeable than dextrose - ultrafiltration occurs for
a longer period of time. - Equivalent UF volume as a 4.25% dextrose
- Best used in a long dwell
- Reduced carbohydrate load
- Potential advantage of reducing the long term metabolic complications associated with hypertonic dextrose
No impact on – Residual renal function – Urine output – Incidence of peritonitis – Peritoneal creatinine clearance – Technique failure – Patient survival
Icodextrin can lead to:
- Over estimation of Blood Glucose levels
with Glucometers based on glucose
dehydrogenase (Advantage, Acucheck)
- Under estimation of Serum amylase level
(false low)
Using low GDP (glucose degradation products) neutral pH solutions
Low GDP, neutral pH solutions on
other outcomes
• Preserved urine output • Less inflow pain • No effect on: – Ultrafiltration – Peritoneal clearances – Peritonitis episodes – Technique failure – Mortality
Methods to preserve residual renal function with patients on PD
- Use of ACEi/ARBs for treatment of hypertension
- Low GDP, neutral pH PD solutions
Avoid
• Prolonged use of Aminoglycosides
• NSAIDS
• Contrast agents
GDP: glucose degradation products
What conditions favour PD vs HD
Favours PD
- BP control
- Lower EPO dose
- Quality of life as able to do at home
Favours HD
- CCF
- Hypoalbuminaemia
- Survival from critical illness in ICU
Indications for PD catheter removal
Indications for catheter removal include:
- refractory peritonitis (failure to respond to appropriate antibiotics within 5 days)
- relapsing peritonitis
- refractory exit-site and tunnel infection
- fungal peritonitis.
Also consider catheter removal if the patient is not responding to therapy, in infections caused by mycobacteria, or in polymicrobial infection with enteric pathogens.
If removed may require vascath for haemodialysis
Complications of PD
Infective
- Peritonitis
- Exit site infection
- Tunnel Infection
Pressure related: intra-abdominal pressure lowest when supine, greatest while sitting
- Hernias
- Dialysate leaks: pericatheter, abdominal, genitalia, pleural
Non-infective - Access Related: Catheter obstruction Omental entrapment Tip migration can occur due a mass or constipation Cuff extrusion - Ultrafiltration failure - Technique failure
PD Peritonitis Features
- Clinical features consistent with peritonitis: abdominal pain, cloudy dialysate
- Dialysate WCC > 100, >50% polymorphs/neutrophils, positive gram stain
The most common pathogens are:
- Coagulase-negative staphylococci (eg Staphylococcus epidermidis)
- Staphylococcus aureus
- enteric Gram-negative bacilli
- Streptococcus and Enterococcus species.
- Infection with fungi is uncommon
Microbiology:
• 50% Gram positives = SKIN
- coagulase negative staph, staph aureus, enterococcus, streptococcus
• 15% Gram negatives = GUT
• 20% Culture negative = Don’t Know
• 4% Polymicrobial infection = Laparotomy/Remove Tenckhoff
• multiple Gram negatives or Gram positives and Gram negatives
• <2% Fungal infection = Panic and remove Tenckhoff
• 13% exit site infection
• 3% peritoneal fluid leak
• 31% hospitalization i.e. most treated in the community
Tx:
- IP Gentamicin 80mg daily (added to 1 bag of dialysis fluid) if level <0.6 for 2 weeks [dwell time 6 hours]
- IP Cephazolin 1.5g daily (added to 1 bag of dialysis fluid) [dwell time 6 hours]
o Replace cephazolin with vancomycin if history of MRSA, systemic symptoms or immediate hypersensitivity to penicillins - IP Vancomycin 2g daily if level <20 for 2 weeks
- IP Heparin 1000 units to be given with IP antibiotics or IP heparin 500 units/L of PD fluid (ie: 1000 units in a 2L bag of PD fluid)
- Antifungal Cover: PO Nilstat 1mL QID - to cover for fungal infections
- Gram Negative/enterococcus: can add PO ciprofloxacin 250mg BD, enterococcus does not respond to cephalosporins
Gram Positive: can add PO keflex
Recurrent peritonitis can result in sclerosing peritonitis which is fatal
Differential diagnosis of cloudy effluent
- Culture-positive infectious peritonitis
- Infectious peritonitis with sterile cultures
- Chemical peritonitis - Eosinophilia of the effluent
- Hemoperitoneum
- Malignancy (rare)
- Chylous effluent (rare)
- Specimen taken from “dry” abdomen
Risks for renal progression
Proteinuria
Hypertension
Proteinuria most important marker for progressive renal failure
• Reducing proteinuria key goal of renal preservation
• Hypertension reduction vital to delay CKD progression
• Aggressive BP targets i.e. 125/75 (<130/80) in patients with diabetic and nondiabetic
nephropathy with proteinuria.
• ACE-I or ARBs for proteinuric nephropathies, combination no longer
recommended.
• Tight glycaemic control essential in diabetics.
• Salt restriction and bicarbonate therapy appear beneficial
• All other renal protection methods e.g. protein restriction, statins not sufficient
evidence to ask questions about.
How doe proteinuria cause damage?
Damage via: – Hyperfiltration – Tubular toxicity from resorbing certain proteins – Increased tubular work – Mesangial toxicity
Proteinuria thought to be reduced by reducing intraglomerular pressure – hence ACEi
