Acut renal failure and treatment

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Acut renal failure and treatment

• Székely Andrea

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Objectives

• To define acute renal failure
• To discuss causes of acute renal failure
• Diagnosis and Treatment of ARF
• Introduce Chronic renal failure
• Methods using case presentations

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Case 1

• 24 year old student collapsed after running the
  Dublin Marathon
• Had complained of muscle cramps during race and
  these continued
• Admitted to A/E after passing a small amount of
  red urine
• O/E normal BP and Pulse
• Urinalysis 2 Protein, 4 Blood
• Light microscopy renal tubular casts

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Case History continued

• Urea 20 mmol/L
• Creatinine 350 micromol/L
• Sodium 140
• Potassium 6.1
• Calcium 2.01 mmol/l
• Phosphate 2.4 mmol/l
• Urate 500 micromol/l
• Bicarbonate 17 mmol/l
• Creatinine Kinase markedly elevated

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Diagnosis

• Raised muscle enzymes
• Assume urinary myoglobin
• Kidneys normal size and shape on U S
• Acute renal failure
• Acute tubular necrosis due to Rhabdomyolysis

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Acute Renal FailureTreatment

• Establish the cause of acute renal failure
  exclude other causes
• Intrinsic renal disease sepsis obstruction
  Background chronic renal disease
• ATN due to Rhabdomyolysis requires aggressive
  volume expansion (With What ?) with correction of
  acidosis with close monitoring of urine output
  blood pressure, pulse, breathing and blood gases
  and electrolyte and renal function
• Even if late presentation and established ATN
  will recover function to normal

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What does the kidney do?

• Extracellular Environment maintenance
• Excretes by-products of metabolism like urea,
  creatinine, uric acid
• Individual regulation of salt, water and H by
  changes in tubular reabsorbtion and secretion
• Hormonal function Ca PO4 via 1,25 cholecalciferol
• Systemic and Renal haemodynamics Renin
  angiotensin 2, prostaglandins, bradykinin
• Red cell production via erythropoiten
• Potential dysfunction depends on type and extent
  of renal disease

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Assessment of Renal Function

• Blood Urea
• Serum Creatinine
• GFR Used clinically to assess the level of renal
  function no information on cause
• GFR is the sum of filtration rates of all
  nephrons
• Is the GFR changing or Stable Creatinine is used
  if monitoring change
• Creatinine clearance UCr V(mls) / PCr gives
  ml/day
• Chromium EDTA in children
• MAG 3 isotope scanning

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Urea and Creatinine as measures of function

• Urea can be higher in prerenal failure due to
  volume changes Avid tubular reabsorbtion
• Blood loss into GI tract
• Excessive breakdown of Protein Catabolism
• Creatinine lower in small frame, poor muscle mass
• Creatinine higher if muscle breakdown
• Creatinine is freely filtered by the kidney and
  is not reabsorbed or metabolised 15 is secreted
  into proximal tubule How does this affect
  functional assessment???

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3 Categories of Renal Failure

• Pre-Renal
• Condition that causes a decrease in blood flow to
  the kidneys
• Reduced HP at glomeruli results in poor
  filtration
• Post-Renal
• An obstruction in the outflow of urine
• Increase HP in Bowmans capsule results in poor
  filtration
• Intra-Renal
• Direct damage to kidneys, esp. glomeruli
• Less effective surface area results in poor
  filtration

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Post-Renal Ureteral Stone

• The material that makes up the stones often
  consists of calcium deposits, among other things
• These can cause blockage of urine flow
• Urine backs up into the kidneys causing nephrons
  to shut down due to an increase in pressure

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Analogy

• In this analogy the ureter acts as a stream
• Beavers come and build a dam (ureter stones) that
  block the passage of water down the stream
• The dam causes a backflow of water that damages
  the surrounding habitat (kidneys)

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Pre-Renal Myocardial Infarction

• The heart weakens and cannot pump sufficient
  amounts of blood to the kidneys
• Glomerular filtration rate decreases (kidney
  failure ensues)
• The kidneys may compensate by retaining more salt
  and water to increase blood volume

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Analogy

• In this analogy blood is represented by water
• A drought occurs (myocardial infarction)
• Kidneys act as a dam conserving water (blood),
  which supplies the people with enough water to
  survive (i.e. blood supplying tissues)

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Intra-Renal Glomerulonephritis

• A Streptococcus bacterial infection of the throat
  or skin can lead to acute post-streptococcal
  glomerulonephritis
• Strep antigens and antibodies form complexes that
  attach to the glomerulus
• The inflammation impairs the kidneys ability to
  filter and eliminate waste causing low output of
  urine

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Analogy

• In this analogy a river represents the kidneys
• An oil spill represents Acute post-strep
  glomerulonephritis
• The river cannot filter out or diffuse all the
  sticky oil
• Therefore the oil ends up disturbing natural
  habitat around the river and it cannot function
  properly

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What can go wrong (Cause)Acute Hours Days weeks

• Blood from renal artery is delivered to glomeruli
  Perfusion
• Glomeruli form Ultrafiltrate which flows into
  tubules Glomerular Diseases
• Tubules reabsorb and secrete water electrolytes
  from the ultrafiltrate ATN
• Urine leaves the kidney and drains into the renal
  pelvis ureters bladder and urethra Obstruction

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Prerenal Disease

• Prerenal
• Anything which affects the renal perfusion
  through volume loss hypotension or effective
  volume depletion
• What is the hydration status of the patient
• History and Physical Examination
• Background History
• Risk Factors for Acute renal failure
• If impaired perfusion is prolonged severe and
  untreated, prerenal failure manifests as Acute
  Tubular Necrosis

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Post Renal Failure

• Causes of renal impairment due to Obstruction of
  the renal tract
• Tumours
• Fibrosis
• Blood clots
• Stones
• Papillae

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Case 2

• 76 year old man admitted with urinary symptoms
  and incontinence found by GP to have abnormal
  renal function
• Main complaints were urinary frequency nocturia
  double micturition and poor stream
• Past history of MI and TIA
• O/E Hypertension 180/95 with evidence of volume
  expansion Raised JVP and cardiomegaly sacral and
  leg oedema
• Abdominal examination revealed a large mass
  arising from the pelvis which was dull to
  percussion
• PR no rectal masses but prostate enlarged with
  smooth nodularity

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Investigations

• Urea 20
• Creatinine 600
• Sodium 136
• Potassium 6.0mmol/l
• Bicarbonate 18 mmol/l
• Renal Ultrasound Severe bilateral hydronephrosis
  with dome like bladder expansion
• Chest Xray Cardiomegaly with upper lobe diversion
• ECG Twave tenting

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Treatment

• Renal Failure
• Time frame to presentation not clear unwell for
  weeks
• Clinical examination suggests obstruction as
  cause probably due to prostatic hypertrophy
• Catheter inserted and achieved massive diuresis
• As bladder reduced in size developed haematuria
• Urologistsarranged TURP for 4 weeks after
  presentation

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Intrinsic renal disease

• Systemic Disease
• SLE, Amyloidosis, Wegeners Granulomatosis,
  Diabetes mellitus
• Primary renal disease
• Glomerulonephritis, Acute interstitial nephritis,
  Acute tubular nephritis

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Urinalysis and Urinary microscopy

1. Haematuria heavy proteinuria dysmorphic red cells
2. Pyuria with white cell casts no proteinuria
3. Pyuria alone
4. Few cells low grade proteinuria Bland urinary
   sediment
5. Haematuria Alone

1. Glomerular disease or vasculitis
2. Tubular or interstitial disease or Obstruction
3. Renal tract infection or TB
4. Prerenal disease renal ischaemia some cases of
   ATN, tubular interstitial disease
5. IgA or Thin BM will have some proteinuria, Renal
   tract tumours Renal calculi, sloughed papillae

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Case 3

• A 59 year old man presents with weight loss and
  night sweats. He had recurrent sinusitis aching
  joints and a painful left ear. He had shortness
  of breath for 4 days before and had a small
  amount of haemoptysis
• On examinatio . Tender over maxillary sinus and
  left ear drum was inflamed. He appeared pale he
  was hypertensive 190/100 he had bilateral fine
  crepitations in his lungs and his JVP was mildly
  raised. He had moderate leg oedema and all
  peripheral pulses were present with no femoral or
  aortic bruits. He had a purpuric rash on his
  lower limbs with some bullae

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Investigations

• Urinalysis showed 3 Proteinuria and 3 Blood,
  microscopy saw some dysmorphic red cells
• Spot urinary protein 8g/24 hours
• Hb was low 8.8g/dl
• Urea 35 mmol/l, Creatinine 480 micromol/l
• Chest Xray showed interstitial infiltrates
• Auto antibodies were sent
• ANCA ANA dsDNA complement Anti GBM antibodies
• A definitive Test was preformed

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ANCA related disease

• Antibodies to neutrophil cytoplasmic antigen are
  found in 90 of vasculitides
• C-ANCA diffuse cytoplasmic stippling PAN, now
  known as anti myeloperoxidase antibody
• P-ANCA perinuclear staining Wegeners now known as
  anti proteinase 3
• Initially by indirect immunoflourescence now by
  ELIZA gives more accurate quantification

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Multisystem disease Wegeners Granulomatosis

• Active urinary sediment with haematuria and
  proteinuria glomerular
• Biopsy Rapidly progressive GN with focal
  segmental necrotizing GN with crescent formation.
  Immunofluorescence negative findings or traces
  only of IgG and C3 Pauciimmune on renal biopsy
• Systemic disease due to small vessel vasculitis
  with granuloma causes areas of focal necrosis

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Treatment

• Assess organ involvement
• Exclude other causes
• Treat Disease process
• Immunosupression with pulse methylprednisolone
  and cyclophosphamide has revolutionised outcome
  from Wegeners

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RIFLE Global description of ARF

• R-risk of renal impairment Creatinine gt1.5 x
  Normal UO lt0.5 mls/kg/hour for 6 hours
• I-Injury renal injury Creatininegt2 x Normal UO
  lt0.5 mls/kg/hour for 12 hours
• F Failure Creatinine gt 3 x Normal or gt350
  Anuria for 12 hours
• L Loss complete loss of renal function for more
  than 4 weeks (Needing renal replacement)
• E ESRF complete loss of function needing renal
  replacement forgt 12 weeks

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Summary

• Renal Impairment can be acute or chronic
• Rate of change of function and baseline function
  is important
• Prerenal failure is a term to describe reduced
  renal perfusion
• Intrinsic renal disease is important as it may be
  treatable or may be systemic
• Obstruction is an important cause of renal
  failure especially in the elderly
• RIFLE criterion is a new method of describing
  acute renal failure

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Questions

1. Does the patient have ARF?
2. Why does the patient have ARF?
3. What is the immediate management?
4. What is the intermediate management?
5. Does the patient need to be transferred?
6. Does the patient need RRT?

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What is ARF?

• Acute, usually reversible, decline in GFR
• ........over days, occasionally weeks
• ........not necessarily from normal baseline
• ........usually with a rising plasma urea
• ........usually with a rising plasma creatinine
• ........often, but not always with oliguria

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What is not ARF?

• Oliguria due to fluid retention
• .......post-operatively
• .......as initial response to ECF depletion
• .......in cardiac failure and other diseases
• Urinary retention
• ESRF presenting as uraemic emergency

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Consequences of ARF

• Acute metabolic complications
• Acute cardiovascular complications
• Prolonged hospitalisation
• Resource consumption
• Patient Death Common
• Renal Death Uncommon

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ARF in Hospital (Boston Study)
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Incidence of ARF (RA Study)
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Causes of Severe ARF (RA Study)
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Survival to hospital discharge with ARF (RA/ICS)

• ARF alone 90
• SCARRF 40-50
• Severe Combined Acute Renal and Respiratory
  Failure
• SCARRF 1 5-10
• All cases of MODS with ARF
• should have RRT
• if other therapy continues

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Causes of ARF

• Pre-Renal Azotemia ischaemic
• Acute Tubular Necrosis
• ischaemic
• toxic
• Acute Interstitial Nephritis immunological
  toxic
• Acute Glomerulonephritis immunological
• Obstruction / Thrombo-embolic

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Why does ARF occur?

• Insult
• Usually identifiable
• Often predictable
• Sometimes preventable

• Risk Factors
• Usually identifiable
• Sometimes correctable

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W.R.I.S.T.

• W.. kers!
• R isk Factors
• I nsults
• S tatus
• T reatment

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Risk Factors

• Age
• Pre-existing renal disease
• Co-existing cardiac and hepatic disease
• Generalised vascular disease
• Conditions interfering with fluid
  balance (includes dementia broken legs)
• Usual medications

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Insults

• Disturbance of ECF volume status
• Disturbance of cardiovascular functioning
• Disturbance of renal haemodynamics
• Sepsis
• Operative procedures/anaesthesia
• Obstruction
• Prescription of nephrotoxic agents

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Status

• Compromised?
• ECF status Hyperkalaemia Acidosis
  Uraemia
• Likely to improve?

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ECF Volume Status

• Is established on clinical examination
• Corrected and repeatedly re-assessed with
  rational/detailed/appropriate fluid therapy
• Facilitated when appropriate by..... CVP Mon
  itoring PCWP Monitoring

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Treatment

• Resuscitate/review
• Correct other contributors
• Predict outcome
• RRT or other investigations as needed
• Wait..

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Hyperkalaemia

• Calcium carbonate/chloride
• Insulin/Dextrose (1unit5g)
• Nebulised Salbutamol
• 30mins 90mins 6hrs
• Bicarbonate/Calcium resonium

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Magic bullets.

• Loop diuretics
• Mannitol
• Atrial natriuretic peptide
• Dopamine

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Kellum JA, M Decker J. Use of dopamine in acute
renal failure a meta-analysis. Crit Care Med
2001 291526-31.

• 1966-2000
• Prevention/Treatment
• 58 (n2149) studies
• 24 (n1019) outcome
• 17 (n854) RCT

• Mortality 0.44-1.83
• ARF 0.55-1.19
• RRT 0.55-1.24
• Power for gt50 effect on ARF/RRT

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Is it bad for you?

• Skin necrosis
• Tachydysrythmia
• Ventilatory dysfunction
• Gut hypoperfusion
• Ineffective pressor

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Until proven otherwise....

• The patient has not had.....
• Risk Factors identified
• Insults identified
• ECF volume depletion
• Cardiovascular dysfunction
• Drug toxicity
• Obstruction

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Indication of RRT (renal replacement therapy)

• Rescuscitated
• Precipitating event corrected
• Unlikely to recover quickly
• MODS

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Emergent Indications For Initiation of RRT

• K gt 6.5
• Volume overload Refractory to diuretics.
• Severe Acidosis
• Uremic complications Pericarditis
• Drug Overdose

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Principles of CRRT

• Solute removal
• Diffusion
• Convection

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Diffusion
Diffusion The movement of solutes from a higher
to a lower solute concentration area.
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Hemodialysis
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Convection
Convection The movement of solutes with a
water-flow,solvent drag, e.g., the movement of
membrane-permeablesolutes with ultra filtered
water.
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Hemofiltration
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Hemodiafiltration

• Diffusive clearance (hemodialysis)
• Convective clearance (hemofiltration)
• Use of dialysate on fluid side of filter and
  replacement solution on the blood side of the
  filter.

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Hemodiafiltration
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Dialysis Access

• Arterial Venous (AV)
• Needs 2 catheters one in artery and other in vein
• No blood pump required Depends on systemic BP
• Complications embolization, bleeding,
  pseudoaneurysm
• Not used anymore

63
Dialysis Access

• Veno-venous (VV)
• One dialysis catheter in vein
• Less complications
• Blood flow more reliable since external blood
  pump
• Technically more complicated.
• Widely used

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Types of CRRT

• SCUF - Slow Continuous Ultra Filtration
• CVVH - Continuous Veno-Venous Hemofiltration
• CVVHD - Continuous Veno-Venous HemoDialysis
• CVVHDF - Continuous Veno-Venous HemoDiaFiltration

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Types of CRRT

• CAVH - Continuous Arterio-Venous
  Hemofiltration
• CAVHD - Continuous Arterio-Venous HemoDialysis
• CAVHDF Continuous Arterio-Venous
  HemoDiaFiltration

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SCUF

• Primary therapeutic goal
• Safe management of fluid removal
• UF rate ranges up to 2 L/Hr
• No dialysate
• No replacement fluids
• Large fluid removal via ultrafiltration
• Blood Flow rates 10-180 ml/min

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CVVH

• Primary therapeutic goal
• Convective solute removal
• Safe fluid management
• UF rate ranges 12-20 L/24 hours (gt500 ml/hr)
• Requires replacement solution to drive convection
• No dialysate

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CVVHD

• Primary therapeutic goal
• Solute removal by diffusion
• Safe fluid volume management
• Requires dialysate solution
• UF rate ranges 2-7 L/24 hours (300 ml/hr)
• Dialysate Flow rate 15-45 ml/min (1-3 L/hr)
• Blood Flow rate 10-180 ml/min
• No replacement solution
• Solute removal determined by Dialysate Flow

69
CVVHDF

• Primary therapeutic goal
• Solute removal by diffusion and convection
• Safe fluid management
• Combines CVVH and CVVHD therapies
• UF rate ranges 12-20L/24hr
• Uses dialysate solution
• Uses replacement solution
• Blood Flow rate 10-180ml/min
• Dialysate Flow rate 15-45 ml/min

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Summary
SCUF
CVVH
CVVHD
CVVHDF
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Complication Vascular access

• Monitor for complications
• Subclavian or jugular vein
• Respiratory distress
• Hematoma/bleeding at site
• Infection
• Cardiac arrhythmia during placement
• Tubing disconnection
• Hemorrhage/air embolism

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Potential patient problem

• Air embolism
• Hypothermia
• Blood leak
• Ekg interference

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Peritoneal Dialysis (PD)

• Use of the peritoneal membrane for
  ultrafiltration and diffusion
• Acute PD -temporary catheter -2 days
• Chronic PD- permanent catheter
• Continuous ambulatory peritoneal dialysis-CAPD
• 4 exchanges/day
• Ultrafiltration- osmotic pressure 1.5-4.25
  glucose

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Peritoneal dialysis - advantages

• Dependency on medical staff
• Restriction of fluid and food intake
• Continued dialysis-stable hemodynamic and
  metabolic conditions

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Peritoneal dialysis- disadvantages

• Hypoalbuminemia and malnutrition
• Exacerbation of DM
• Exacerbation of respiratory disturbances
• Efficiency -BIGpatients,low residual function
• Less efficient for emergent fluid and K removal
• Peritonitis, sclerosing peritonitis
• Burnout

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COMPLICATIONS OF PERMANENT DIALYSIS

• CARDIOVASCULAR
• Accelerated Atherosclerosis
• Coronary calcification
• Ischemic heart disease
• Peripheral vascular disease
• Left ventricular hypertrophy- HTN, Anemia
• Valvular calcification
• Heart failure

• BONE and JOINTS disease
• secunder hyperparathyroidism
• b 2 microglobuline amyloidosis

77
Renal Transplantation

• Cadaveric renal transplantation (CRT)
• Living related renal transplantation (LRD)
• Living unrelated renal transplantation
• Kidney and pancreas transplantation

78
IMMUNOSUPPRESSION

• Steroids
• Calcineurin Inhibitors- cyclosporine, FK506
• Azothioprine, Mycophenolate mofetil
• ATG, OKT3
• Rapamycin
• Anti IL2 antibodies

79
Renal Transplantation -Common Complications

• Ischemia-ATN
• Rejection
• Infections- Bacterial
• CMV
• Opportunistic infections

80
Renal Transplantation - Late Complications

• Rejection
• Cyclosporine toxicity
• Recurrence of primary disease- FGS
• Renal artery stenosis
• Chronic allograft dysfunction
• Atherosclerosis, osteoporosis

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Advantages of transplantation

• Freedom from dialysis
• Improvement in nutritional state
• Improvement in Fertility and sexual function
• Less restriction of food and fluid intake
• Improved QOL and survival

82
Limitations of transplantation

• Early
• Medication - need for compliance
• Immunosupression and infections
• Exacerbation of diabetes
• Hyperkalemia and volume overload- possible
• Procedures during follow up- biopsies etc

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Limitations of transplantation

• Late
• Chronic allograft dysfunction-T1/27 years
• Atherosclerosis, osteoporosis
• Exacerbation of hepatitis B and C
• Malignancy-frequency and severity