JULIAN WRIGHT Consultant Nephrologist Manchester Royal

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Renal Failure Acute and Chronic

• JULIAN WRIGHT
• Consultant Nephrologist
• Manchester Royal Infirmary

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Acute renal failure hard to define
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Acute renal failure not hard to recognise
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Definition of Acute Renal Failure

• No agreed definitions
• UKRA Guidelines
• Decline of renal excretory function over hours
  or days
• recognized by the rise in serum urea and
  creatinine
• Liano et al, KI 50811(1996) gt177 µmol/L
• Doubling of serum creatinine
• Use of Renal Replacement Therapy

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Acute vs Chronic Renal Failure

• Anaemia
• Renal size
• Tolerance of severe uraemia
• Metabolic bone disease
• hypocalcaemia
• secondary hyperparathyroidism

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Diagnosis of Acute Renal Failure

• History and examination
• Routine bloods
• Extra bloods bicarbonate, CK, CRP blood
  cultures
• ECG
• CXR

• GN screen - immunology, dipstick urine
• Renal USS
• Biopsy

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The renal troponin

• Cystatin C
• endogenous cysteine proteinase inhibitor
• stable and constant rate of production by all
  nucleated cells
• freely filtered by glomerulus not secreted
  by tubules increases 2-3 days prior to
  creatinine

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The renal troponin

• Urinary excretion of
• kidney injury molecule-1 neutrophil
  gelatinase associated lipocalcin
• IL-18

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ARF causesLiano et al, 1996

• Acute tubular necrosis 45
• Prerenal 21
• Acute on chronic renal failure 13
• Obstructive 10
• Glomerulonephritis (primary secondary) 3
• Acute tubulointerstitial nephritis 2
• Vasculitis 1.5
• Vascular 1
• Other 3.5

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Acute renal failure Rasmusan, 1982
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Classification of Acute Renal Failure

• The Undergraduate Classification works fine!
• Pre Renal Circulatory Failure Shock
• Renal The cells of the kidney
• Post Renal Obstruction

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Pre-renal Acute Renal Failure

• Volume depletion
• Decreased effective blood flow
• Renal vasoconstriction
• Altered intra-renal haemodynamics
• Increased renal vein pressure

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Urine electrolytes in Pre-renal ARF
Avid Na H2O reabsorption
Osmolality gt 600 Na lt 20mmol/l
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Urine electrolytes in ATN
Impaired Na H2O reabsorption
Osmolality lt 400 Na gt 20mmol/l
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Intrinsic Acute Renal Failure

• Acute tubular necrosis
• Acute interstitial nephritis
• Acute glomerulonephritis
• Acute vascular syndromes
• Intratubular obstruction

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ARF - management

• Calcium gluconate 10mls 10 (20-30 mins)
• Insulin dextrose 10 units Humulin S in 50ml 50
  glucose over 10 minutes
• Salbutamol nebs 2.5mls 2hrly
• Get the fluid balance right
• Remove causes drugs, sepsis
• Furosemide
• Calcium resonium (4-6 hours to work)
• Laxatives
• Bicarbonate
• Renal replacement therapy

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ARF managementFluids

• Examine the patient fluid status
• Replace deficits
• Balance I O
• Account for insensible losses
• Leave sufficient volume space for Rx and
  nutrition.

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Furosemide

• Loop diuretic decrease oxygen consumption by
  decreasing Na transport less ischaemic injury
• Increases urinary flow reduce intratubular
  obstruction and backleak of filtrate
• Help with fluid management

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Furosemide

• Does not prevent ARF post cardiac surgery
• Increases risk of ARF when given to prevent
  contrast nephropathy
• Mannitol osmotic diuretic
• Decreases cell swelling, scavenge free radicals,
  induce intrarenal prostaglandin renal
  vasodilatation

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Dopamine

• Synthesised in proximal tubular cells from L-Dopa
• DA-1 receptor in vasculature and proximal and
  basolateral proximal tubular membranes cause
  renal vasodilatation and decreased Na tubular
  reabsorption
• DA-2 receptor less sensitive to dopamine
  sympathetic nerve terminals innervating blood
  vessels

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Dialysis in acute renal failure

• Start HD/CVVH
• if established oliguria is present
• if any (serious) complications of uraemia are
  present
• refractory hyperkalaemic
• refractory acidosis
• if (serious) fluid overload is present
• if serum urea gt50 mmol/l (?)

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Advantages of IHD

• Rapid solute removal
• Rapid volume removal
• Effective for some drug intoxications
• Rapid correction of electrolytes disturbances

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Advantages of continuous RRT

• Slower volume removal greater haemodynamic
  stability
• Absence of volume or solute fluctuation over time

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Summary

• Acute Renal Failure
• Common
• Serious
• Work out the causes and consequences
• Treatment is logical in many cases and reduces
  mortality
• Early organ support
• If it could be supplied IHD may be as good in ICU
  setting

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Complications of chronic kidney disease
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Stages of CKD
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Malnutrition Inflammation Atherosclerosis Syndrome
UREMIA
Infection Inflammation
Fluid Overload Hypertension
High CRP
Acute Phase response
CYTOKINES
Congestive Heart failure
High fibrinogen
High Lp(a)
Low albumin
Athero sclerosis
Malnutrition
DEATH
Bergstrom and Lindholm AJKD 1998
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Complications

• Hypertension
• Left ventricular hypertrophy
• Anaemia
• Renal bone disease
• Acidosis
• Cardiovascular co-morbidity and death

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Hypertension and CKD NEOERICA

Stage1
Stage2
Stage3
GFR?60
Stage4
Stage5
GFRlt60
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Blood Pressure and Progression of CKD AIPRD
Study Group
1860 patients with non-diabetic kidney disease
Meta-analysis of 11 RCTs of ACEIs
RR
Systolic BP (mmHg)
Jafar et al, Ann Intern Med 2003139244-252
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Blunting of nocturnal dipping in BPFarmer,
Goldsmith, NDT 1997
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Hypertension

• Causes of hypertension in CKD Salt and water
  overload Activated RAA system
• Life-style management
• Drugs A B C D
• Blockade of renin-angiotensin system

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REIN STUDY
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Proteinuria is strongly associated with renal
progression
R20.06,?-0.25,plt0.001
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Left ventricular hypertrophy

• Causes Concentric LVH hypertension Ecce
  ntric LVH fluid overload, anaemic LV
  dilatation maladaptive

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Left Ventricular Hypertrophy(Prevalence)
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• Chalk

Cheese
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Anaemia

• Targets
• Patients with CRF should achieve Hb gt 10g/dL
  within 6 months of seeing a nephrologist
• Serum ferritin gt 100µg/l (transferrin saturation
  gt20)

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Anaemia

• Causes
• Iron deficiency Erythropoietin
  deficiency GI blood loss Malnutrition
• Hepcidin affects iron metabolism
• Effect on patients quality of life

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Anaemia

• Assessment Haematinics
• Iron / TIBC
• FBC
• Treatment
• IV iron
• Erythropoietin

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HyperparathyroidismCalcium-phosphate balance in
CKD

• Targets
• Serum phosphate lt1.9mmol/l (1.13-1.78 KDOQI)
• Serum calcium 2.2-2.6mmol/l (HD/PD) (2.10-2.37
  KDOQI)
• Parathyroid hormone lt4 x ULN (150-300pg/mL KDOQI)
• Calcium-phosphate balance (lt4.4mmol2/L2 KDOQI)

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HyperparathyroidismCalcium-phosphate balance in
CKD

• Decrease in serum calcium - less active vitamin
  D so less calcium absorbed from food
• Increase in phosphate not excreted by kidney
• Secondary hyperphosphataemia stimulated by low
  calcium and active vitamin D, causes increased
  calcium absorption from food and bones as well as
  increased phosphate
• Acidosis increases the severity of bone disease

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Renal bone disease

• Renal osteodystrophy weakness, pain caused by
  osteoporosis and cystic resorption osteitis
  fibrosa cystica sub-periosteal erosions on the
  radial border of the phalanges characteristic
• Aluminium bone disease
• Osteoporosis defective bone mineralisation
  thin bones, pain and fractures malnourishment
  and steroid use
• Adynamic bone disease decreased reabsorption
  and laying down of bone cant soak up calcium
• Amyloid ß-2 microglobulin weak bones
  especially wrist, hip and neck carpel tunnel
  syndrome
• Osteoarthritis problems with analgesia
• Osteosclerosis component of rugger jersey
  spine on x-ray
• Gout
• Infection especially in dialysis patients
• Tertiary hyperparathyroidism

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High-Turnover Bone DiseaseImpact on Metastatic
Calcification
P
Ca
Phosphorus
Hyperplasia of parathyroid glands
Calcium
PTH
Magnesium
Deposition into tissues
Calcification
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Treatment of renal bone disease

• Low dietary phosphate
• Phosphate binders Calcium containing Non
  -calcium containing
• Active vitamin D (after phosphate corrected)
• Correct acidosis
• Adequate dialysis / Transplantation
• Parathyroidectomy
• Calcimimetic
• Calciphylaxis
• Fetuin-A
• Vascular calcification

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Acidosis

• Target bicarbonate in normal range
• Causes of low bicarbonate Renal impairment
  excess ammonia and organic acids
• Treatment sodium bicarbonate

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Principles of Management of CKD

• CARDIOVASCULAR RISK MANAGEMENT

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Prevalence of Co-morbidity and Level of GFR
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Any Cardiovascular Disease and CKD

Stage 1
Stage 2
Stage 3
GFR?60
Stage 4
Stage 5
GFRlt60
Population
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Patients with CKD are more likely to die than
require dialysis
27,998 CKD patients followed for 5 years
Keith DS, AIM 2004164659-663
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Mortality in Unreferred CKD
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Causes of Death in CKD
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CKD treatment of complications

• CKD 45 management
• Check GFR/Hb/Potass/Cal/Phos/Bicarb/PTH 3/12ly
• Rx anaemia/metabolic abnormalities/CV risk
  factors
• Rx hypertension/proteinuria
• End Stage Renal Failure counselling

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CKD treatment of complications

• CKD 3 Management
• Check GFR/Hb/Potass/Cal/Phos/Bicarb
• 6/12ly
• 12 monthly urine PCR if proteinuria, haematuria,
  glomerulonephritis, diabetes, or reflux
  nephropathy
• Target BP lt130/80mmHg or lt120/75mmHg if
  proteinuria (PCRgt100mg/mmol)
• CVD risk factor management
• Immunization
• Regular review to avoid nephrotoxic drugs

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CKD and CVD

• CKD patients highest CVD risk category
• CVD risk factors accelerate CKD
• CKD exacerbates CVD
• Most CKD patients die of CVD before ESRD
• Majority of new ESRD patients have CVD
• CKD need treatment for CVD risk reduction

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Conclusion

• CKD has a lot of complications
• CKD has a lot of co-morbidity
• CKD has a lot of cardiovascular death
• It is challenging to understand
• It is challenging to treat