Transcript Effects of different doses in continuous veno

Renal
Disease
Dr. George
Mellotte
The Kidneys
Two bean-shaped
organs, each the size
of a fist.
Weighing ~0.5% of
total body weight
20% of Cardiac
output goes to Kidney
Adrenal Glands
Kidneys
Rib
Cage
On Examination
Move with Respiration
Ballotable
Can get above them
Overlying resonance
Bladder
Rib
Cage
Function of the Kidney
Primary balancing organ needed to
keep blood in a stable state
Remove waste products and toxins
• Urea & Creatinine:
• Drugs, toxic substances
Maintain fluid and electrolyte balance
• Total body water and fluid distribution
– 50-70% of body weight is water
• Sodium
Potassium
Maintain normal mineral balance
• Calcium
Phosphate
Regulate acid/base balance
Magnesium
Function of the Kidney
Endocrine Role of the Kidney
Regulates blood pressure:
Renin-angiotension System and aldosterone
Adjusts final concentration of urine
Antidiuretic hormone ADH
Stimulates the production of red blood
cells Erythropoietin
Activates Vitamin D (Calcitriol,
1,25(OH)2D3)
• Response to Parathyroid hormone
Target Organ Damage
 Heart
• Left ventricular hypertrophy
• Angina or prior myocardial infarction
• Prior coronary revascularization
• Heart failure
 Brain
• Stroke or transient ischemic attack
 Chronic kidney disease
 Peripheral arterial disease
 Retinopathy
Estimating Renal Function
Serum creatinine is widely used BUT
Serum creatinine is based on muscle mass
‘Normal’ values are lower for elderly, female or physically
inactive patients
During early nephron loss, adaptive changes
compensate to minimise rise in creatinine
What is normal?
Newer evidence suggests lower thresholds
should be used, especially for women
Creatinine :
Men
Women
50 - 115 umol/l
40 - 95 umol/l
Defining Renal Failure
Cr Clearance = (140 - age) × weight in Kg × SF
serum Cr
SF = 1.2 males / 1.05 females
Normal GFR = 90-120mls/min
Grade
Mild
Moderate
Severe
Endstage
GFR
60 - 90ml/min
30 - 60ml/min
15 - 30ml/min
< 15ml/min
Sr Creatinine
100 - 150umol/l
150 - 250µmol/l
250 - 500µmol/l
> 500µmol/L
Cockcroft & Gault Formula
Classification of Chronic kidney disease (CKD)
1
GFR
(mL/min/1.73 m2)
Kidney damage with normal / GFR  90
2
Kidney damage mild GFR
60–89
3
Kidney damage Moderate  GFR
30–59
4
Kidney damage Severe  GFR
15–29
5
End Stage Kidney failure
< 15 (or dialysis)
Stage Description
eGFR can be thought of as equivalent to % kidney Function
www.kidney.org/professionals/kdoqi
GFR, glomerular filtration rate
Key Concepts
The importance of early identification
Kidney Disease
Cardiovascular Disease
Focus on quality of care before starting
Dialysis
Slowing the progression of Kidney Disease
Slowing the progression of Co - Morbid Disease
Interplay of pathophysiology
Progressive Kidney Disease
Progressive Cardiovascular Disease
JNC 7 Report on Hypertension
 For persons over age 50, SBP is a more
important than DBP as CVD risk factor.
 Starting at 115/75 mmHg, CVD risk
doubles with each increment of 20/10
mmHg throughout the BP range.
 The BP relationship to risk of CVD is
continuous, consistent, and
independent of other risk factors
New Features and Key Messages
 Thiazide-type diuretics should be initial drug therapy for most,
either alone or combined with other drug classes.
 Certain high-risk conditions are compelling indications for other
drug classes.
 Most patients will require two or more antihypertensive drugs to
achieve goal BP.
 If BP is >20/10 mmHg above goal, initiate therapy with two
agents, one usually should be a thiazide-type diuretic.
All Patients with nephropathy – particularly diabetic patients
Target BP = 125/75 mmHg
Re proteinuria - a lower BP is permissible/desirable
in order to maximise ACEI & ARB
– Target Proteinuria
<0.3g/day
Benefits of Lowering BP
Average Percent Reduction
Stroke incidence
35–40%
Myocardial infarction
20–25%
Heart failure
50%
In stage 1 HTN and additional CVD risk factors, achieving
a sustained 12 mmHg reduction in SBP over 10 years will
prevent 1 death for every 11 patients treated.
Ambulatory BP Monitoring
 ABPM is warranted for evaluation of “white-coat” HTN in the
absence of target organ injury.
 Ambulatory BP values are usually lower than clinic readings.
 Awake, individuals with hypertension have an average BP of
>135/85 mmHg and during sleep >120/75 mmHg.
 BP drops by 10 to 20% during the night; if not, signals
possible increased risk for cardiovascular events.
CVD Risk Factors
 Obesity (BMI >30 kg/m2) Physical inactivity
 Cigarette smoking
 Hypertension
Hyperlipidaemia
 Diabetes mellitus
 Microalbuminuria
Proteinuria
 eGFR <60 ml/min
Mild Renal failure Creatinine>125
 Age (older than 55 for men, 65 for women)
 Family history of premature CVD
(men under
age 55syndrome.
or women
*Components
of the metabolic
under age 65)
Identifiable
Causes of Hypertension
 Chronic kidney disease
 Renovascular disease
 Primary aldosteronism
 Sleep apnea
 Drug-induced or related causes
 Chronic steroid therapy and Cushing’s syndrome
 Pheochromocytoma
 Coarctation of the aorta
 Thyroid or parathyroid disease
Laboratory Tests
 Routine Tests
• ECG
• Urinalysis
• Blood glucose, and haemoglobin
• Renal profile (potassium, creatinine, calcium)
• Lipid profile,
Hypokalaemia without diuretics – secondary cause?
 Optional tests
• Microalbuminuria or albumin/creatinine ratio
• Renal Ultrasound if renal impairment
 More extensive testing for identifiable causes is not generally
indicated unless BP control is not achieved
Lifestyle Modification
Modification
Approximate SBP reduction
(range)
Weight reduction
5–20 mmHg/10 kg weight loss
DASH diet
8–14 mmHg
Salt reduction
2–8 mmHg
Physical activity
4–9 mmHg
Moderation of alcohol
consumption
2–4 mmHg
Minority Populations
 In general, treatment similar for all demographic groups.
 Socioeconomic factors and lifestyle important barriers
to BP control.
 Prevalence, severity of HTN increased in African
Americans.
 African Americans demonstrate somewhat reduced BP
responses to monotherapy with BBs, ACEIs, or ARBs
compared to diuretics or CCBs.
 These differences usually eliminated by adding
adequate doses of a diuretic.
Risk Factors for Vascular Disease in
CKD 1
Traditional Risk Factors
Hypertension
Left Ventricular Hypertrophy
Hyperlipidaemia
DOQI Guidelines – Treat similar to Diabetes/Post MI
• Total Cholesterol < 4.0 mmol/l
• LDL Cholesterol < 2.5 mmol/l
• Will require statins –
Beware of the patient with Hypocholesterolaemia
Marker of nutritional deficiency & of increased mortality risk
Risk Factors for Vascular Disease in
Renal Failure 2
Renal Specific Risk Factors
Proteinuria
Anaemia
Hyperhomocysteinaemia
Hyperphosphataemia
Uremia per se?
Main Factors in Progression of
Renal Failure
Genetic / Racial determinants
Age of onset of nephropathy
Sex
Underlying Disease
Co-Morbid Disease
Blood Pressure control
Degree of Urinary Protein
Excretion
Progression in
Renal Failure
Destruction of
Nephrons
Remaining
Nephrons
Destruction of
Nephrons
Focal & Segmental
Glomerulosclerosis
Glomerular
Hyperfiltration

Renal damage induces hypertension via
 Plasma
volume expansion,
 Sodium retention,
 Overactivity of both the sympathetic nervous
system and the renin-angiotensin-aldosterone axis,
 Accumulation of circulating endogenous vasoactive
substances.
“Early CRF typically results in a 10-20 mm Hg increase
in diastolic blood pressure until, and unless, renal
impairment is identified and treated”
Lancet 2000; 356 147-52
Relationship between achieved BP control and
declines in GFR in clinical trials of diabetic &
non-diabetic renal disease
Blockade of the renin angiotension
system is ‘RENOPROTECTIVE’
Evidence based medicine suggests preferred
initial therapy is either an ACE Inhibitor or
Angiotension II Receptor Blocker 3
Most trials note a 24%- 50% risk reduction
of overt nephropathy, independent of BP
reduction
Recent evidence suggests a synergy
between ACE inhibitors and AII Blockers
Acute Renal Failure (ARF)
A clinical condition – defined as an abrupt rise in Urea &
Creatinine
(with or without Oligiouria)
3 - 6 % of all hospital admissions develop ARF
Incidence higher in complicated cases such as seen in Cardiac
surgery
Incidence ARFS (Acute Renal Failure Scotland) Study
• Rise in Creatinine requiring intervention 237.9 pmp/year
• Incidence requiring dialysis 118.7 pmp/year
60% treated in ICU
33% had preexisting renal disease
Development of ARF increases the risk of death
associated with a particular procedure - 5 fold
CASES OF SEVERE ARF (%)
Cause
Developing Developed
Countries
Countries
ATN
Medical Disease
Obstetrics
Surgery
35
14
8
44
<1
39
Primary renal disease
10
10
Post renal failure
20
4
Other
13
2
Classification of ARF
Pre-Renal
Pump Failure Hypovolaemia Glomerular
5%
Renal
Post Renal
Tubular
Interstitial Obstructive
10%
Ischaemic Nephrotoxic
50%
35%
Pathophysiology of ARF
Not simply a renal hypoperfusion problem
Restoration of renal blood flow would correct urine
flow
Altered renal blood flow post ischaemic insult
Changes in renal vasoconstriction/vasodilation
Pooling of blood in Renal medulla
Changes in inflammatory markers
Increased leukocyte adhesion
Increased pro-inflammatory markers (TNF, IL6)
Increased pro-coagulation activation
Tubular Alterations
Effects of cytoskeletal Breakdown – loss of polarity
Avoiding Renal Failure
Prevent Dehydration in High Risk Patients
Patients with S. Creatinine >125umol/l (?lower in females)
Patients with Diabetes, Peripheral Vascular Disease or Myeloma
Controlled trials recommend N. Saline @ 1ml/kg/hr 12 hrs
pre & post procedures –
particularly important pre Major Surgery or where contrast
will be administered
CRF patients have a fixed urinary concentrating deficit
Role for N-Acetyl Cysteine to prevent contrast Nephropathy
Adjust drug dosing where there is renal impairment
Renal tubules more sensitive to the effect of nephrotoxins in
the presence of renal hypoxia
Guidelines for immediate management
of patients with oliguria or anuria
Assess & correct any respiratory or circulatory
impairment
Manage any life threatening consequences of renal
dysfunction (hyperkalaemia, salt and water overload,
extreme acidosis)
Exclude obstruction of the urinary tract - Get
Ultrasound
Establish underlying cause(s) and institute prompt
remedial action
Get a drug history and alter prescriptions appropriately
Get help from senior appropriately trained specialists
Initial Investigations
Blood Tests
SPEP,
Urine
X-ray
FBC, blood film, Coag screen,
U/E, LFT's, Bone profile, ABG,
Immunology if appropriateANA, DsDNA, C3,C4, CRP,
ANCA & Anti GBM ASOT titre
Electrolytes & Osmolarity
Urine Microscopy
Renal Ultrasound
Isotope Perfusion scan
Diagnostic Imaging
Plain films (K.U.B.)
Screening tool for renal stones. renal calcification
Ultrasound
safe, high quality images can be obtained on most patients
Good screening tool – esp in ARF
Used to evaluate renal size, renal masses and obstruction
Intravenous Pyelography (I.V.P.)
assesses the collecting system and urinary tract
Increasingly being replaced by CT-IVP & MRI
Not for patients at risk of contrast nephropathy Renal failure,
Multiple Myeloma,
Diabetics
Volume depleted patients
Nuclear Medicine – Renogram
Used to asses renal function - DTPA or MAG3
MRI
Increasingly being used in general nephrology
MR Angiography
MR Urography
Pre-Renal Vs Established Renal failure
Pre-renal RF
Inadequate renal perfusion
The kidneys concentrating power is normal and the urine
produced is highly concentrated
Established RF
Failure of tubular function
The kidney’s concentrating power is severely damaged
and the urine produced is dilute
Early restoration of effective circulation will avert ATN
(Acute Tubular Necrosis)
Renal Hypoperfusion V Established ARF
Measurement
Pre Renal
ATN
Urinary Na (mmol/l)
<20
>40
Fractional excretion
of Na (%)
<1
>4
Only appropriate if diuretics not given
Management of Pre Renal Failure
Restore Renal
Perfusion
Correct Hypovolaemia
Target CVP = 10 cm
Correct Hypotension
Target MAP > 75mmHg
Use fluids in first instance
Start Inotropic support if
response insufficient
No Diuresis
 Frusemide 100 - 250mg IV
Pt must be euvolaemic

Diuresis
Measure hourly urine
output & replace losses
Lack of response indicates that ATN has developed
Guidelines for fluid management in
ARF
Diuretic therapy
Ineffective once ATN is established
Inappropriate in inadequately treated prerenal
• Will require a higher dose to achieve effect
If overloaded
• Diuresis should not be at the expense of hypotension
• Aim negative balance 0.5 – 1L day unless clinically
indicated
Replacement for even balance is
• Positive 0.5L for insensible losses
• This is true irrespective of urine output!
Drugs that induce renal damage
Damage
Class of drug
Decrease in renal perfusion Diuretics, ACE inhibitors,
Impaired intrarenal
haemodynamics
Tubular toxicity
B-Blockers,
vasodilators
NSAID’s, radiocontrast
Aminoglycosides,
Allergic interstitial nephritis
amphotericin, cisplatin
lactams,(penicillins)
NSAID’s
ECG changes of Hyperkalaemia
Peaked T waves, Flattened P wave
Prolonged PR interval  sinus arrest
Wide QRS complexes & deep S waves Sine Wave V. Fib 
asystole
Management of Hyperkalaemia
Hyperkalaemia is a medical emergency
and must be corrected immediately.
V. Fib likely if K+ > 7.0 mmol/l (in ARF)
Rx
1.
2.
3.
acidotic
10-20 mls of 10% Calcium Gluconate
50 mls of 50% Dextrose with 12 IU
Insulin over 30 mins
followed by infusion @ 10ml/hour
50 - 100 mls of 8.4% NaHCO3 if
Indications for renal replacement
therapy
Uncontrollable hyperkalaemia (K+ > 6.5)
Salt and water overload unresponsive to diuretics
Anuric and/or need to administer fluid/feed
Severe uraemia (Creat >500umol/l ARF)
Acidaemia
Consider if pH <7.2
Multiple indications may trigger earlier
intervention
Chronic
Renal
Failure
Defined as permanent loss of renal function
Prevalence underestimated
In USA - while only 0.1% of population require dialysis
5-10 % have renal dsease
Most patients have no symptoms until CRF is advanced
Advanced CRF often termed End Stage Renal Disease
(ESRD)
Defined as a GFR <15mls/min
Typical symptoms are nausea, anorexia, fatigue, itch and
bruising
Typical signs are hypertension, ankle swelling, breathlessness
and anaemia
Chronic Renal Failure
Clinical features
Symptoms
Nausea
Fatigue
Pruritus
Signs
Vomiting
Obtunded
Bruising
Hypertension
Oedema
CCF
Anaemia
Pericarditis - late
Neuropathy - late
Laboratory features
 Urea & Creatinine
–
–
–
–
–

Hyperkalaemia
Hypocalcaemia
Hyperphosphataemia
Metabolic Acidosis
Normochromic Anaemia
Radiology - Ultrasound
– Small kidneys - often
scarred
Progression of Renal Disease
Progression in CRF due in part
to secondary factors
unrelated to the activity of the
initial disease
focal segmental
glomerulosclerosis Proteinuria
Good evidence to support
strategies to minimise amount of
proteinuria
Chiefly
- ACE inhibitors
- BP control
- Diabetic control
Normal Renal function
Initiating factors
Genetic or Enviromental
Active Nephropathy
Progression of renal disease
Disease Modifiers
Chronic Renal Failure
Treatment Choice
Haemodialysis
C.A.P.D. /A.P.D.
Transplantation
Intermittent
Complex
Hospital Based
Simple
Independent
Patient dependent
Not a cure
Problems
Problems
Peritonitis risk
Poorly tolerated in cardiac
Catheter Malfunction
disease
Protein losses
Vascular access
Most suitable
Most Suitable
Diabetics
Active patients
Elderly
Patients with limited ability
Patients living away from a
to self care
HD unit
Nephrotic Syndrome
Desirable
Scarce resource
Problems
Graft Failure
Infection risk
Cancer Risk
Only medically fit
patients are
Transplanted
When to start Dialysis
Accepted reasons
Patient has symptoms of uraemia
Kidney function approx 15% of predicted
(GFR < 10-15mls/min)
• Can wait until lower if patient remains well
Patient develops high serum potassium levels
The need to start Dialysis can often be delayed using
Erythropoietin (EPO) to minimise symptoms
Controversial - does “early start” benefit patient?
?less malnutrition ?less cardiac damage
http://www.kidneypatientguide.org.uk/site/pdanim.html
Peritoneal dialysis
A silastic catheter in the peritoneal cavity
Sterile dialysis fluid (supplied as 2 - 5L bags)
An area for exchange in the home
A pumping device (APD)
The dialysis fluid is infused into the peritoneal cavity
(which lies around the bowel) and allowed to dwell for
4-6 hours during which time toxic waste products enter
the fluid. The fluid is the drained out and replaced –
“An exchange”.
Each exchange lasts 30 - 40 minutes
For CAPD,
For APD,
done 4 times daily, 7 days a week
done 4-6 times nightly using a machine “Home Choice”
It is a home based system & requires a committed patient
Automated Peritoneal Dialysis (APD)
Automated Peritoneal Dialysis (APD) uses a
machine to perform the fluid exchanges.
Dialysis is done at home, at night while pts
sleeps.
The APD machine controls the timing of exchanges, drains away
the used solution, and fills up the peritoneum with new solution
When patient goes to bed, they connect their catheter to the
APD machine's tubing and switch on.
The APD machine does exchanges for 8 to 10 hours. In the
morning, the patient disconnects from the machine.
Haemodialysis
http://www.kidneypatientguide.org.uk/site/HDanim.html
It is a hospital based system –
original type of dialysis
A vascular access device
Machine to pump blood & dialysis fluid
An Artificial Kidney
A Water treatment unit
The machine pumps blood through one side
of the membrane in the artificial kidney and
dialysis fluid on the other side where toxic
waste products are removed and electrolyte
imbalances corrected.
Each session lasts 4-5 hours and is needed 3
times per week
this is independent of travelling time
Haemodialysis
Dialysis outcomes
Survival is dependent on a number of variables
Age starting dialysis
Duration of Dialysis
Cardiovascular Disease
Diabetes
Country of dialysis
Expected death rate is 8-40 times that of controls (10 -15% pa)
Transplantation
Recipient Evaluation
Cardiovascular risk, Viral screen, Urological
assessment
Only 30% patients on dialysis are fit for transplan
list
Average waiting time is gone up to 24 months
All transplants done in Beaumont
Patients require long term
Immunosuppression
Average 1 year graft survival
92%
Average Graft survival
12-20 yrs
Main cause of graft loss currently
• Death of patient! - mainly due to Cardiac disease
USRDS - Projected half-life of all
transplants 1988 to 1995
The projected half-life for transplants
living donors
12.7 years 1988
21.6 years 1995
Cadaveric donors
7.9 years 1988
13.8 years 1995,
Censoring for patients who died with
functioning grafts,
Living Donors
16.9 years 1988
35.9 years 1995
Cadaveric Donors
11.0 years
1988
19.5 years 1995
NEJM Mar 2000; 342:605-612
Graft Loss
Rejection
Kidney fails due to
“wearing out”
Cancer related
problems
Return to Dialysis
Patient dies from another
disease with a functioning
graft
ZRAP052/0301
Date of Preparation: March 2001
Dipstick Urinalysis – Haematuria
Dipstick urinalysis detects Haem protein (either red
blood cells or haemoglobin)
Highly sensitive but many false positive tests
Confirm with urine microscopy.
Transient haematuria is relatively common in young
subjects and is not indicative of disease.
• Yearly urinalyses in 1000 men between the ages of 18 & 33
haematuria – 39% at least once
– 16% two or more occasions BMJ 1984 288:20
Negative tests reliably excludes abnormal
haematuria
Coexistent dipstick proteinuria is usually significant
and should be investigated further
Dipstick Urinalysis – Protein
Standard dipstick detects albumin >300mg/l
highly specific, but not very sensitive
Measures urinary protein concentration
The categories are only a rough guide
Patients with persistent proteinuria should
undergo a a 24-hour urine measurement of
protein excretion.
Proteinuria > 1g/24 hrs – consider renal
biopsy
may biopsy at lower levels
Microalbuminuria
Protein excretion above normal but below the
threshold of “Standard Dipstick”
Albuminuria normally <20mg/24 hrs (15 µg/min);
Microalbuminuria = 30-300mg/24 hrs (20-200
µg/min)
Albumin-to-creatinine ratio
microalbuminuria = 2.25 - 3.4 mg alb/mmol
creatinine
Risk factor in Diabetic Nephropathy
High incidence of false positives
Microalbuminuria
Early marker of Diabetic Nephropathy
Usually develops within 10 years of onset of DM
Duration of disease before onset of Microalbuminuria
correlates with risk of progression to nephropathy
Microalbuminuria < 10 years - Most progress
Microalbuminuria > 10 years 30 -50 % progress
Outcome much better than original studies –
?effect of active Rx
Dipstick Urinalysis – other
Pyuria - detects White cells in urine
Leukocyte esterase – (75 – 95% sensitivity)
Nitrites - indicates bacterial infection
Enterobacteriaceae convert urinary nitrate to nitrite
False negative at low colony counts UTIs
Touted as simple and inexpensive screen for UTI
May detect pyuria not associated with infection
Nitrite alone insufficient for diagnosis
Abnormalities on dipstick urinalysis seen with UTI should
be shown to resolve with clinical cure
Major Clinical Syndromes of
Glomerular Disease
Nephrotic Syndrome
Nephritic syndrome
Rapidly Progressive Glomerulonephritis
Chronic Glomerulonephritis
Persistent urinary abnormalities with no
symptoms
Proteinuria
Indicative of significant renal disease
Glomerular Proteinura
» predominantly Albumin
» >3.5g/day - classifies as “nephrotic range”
» selectivity index useful
» amount correlates with long term prognosis
Tubular Proteinuria
» usually < 2 g/day
» due to a failure to reabsorb small molecular weight
proteins e.g.. B2 Microglobulin
Light Chain Disease
Glomerular Proteinuria
Primary GN Minimal Change*
IgA Nephritis
FSGS*
Membranous*
Hereditary Alport’s*,
Infectious SBE, HIV*, Hepatitis,
Immunological/Systemic Disease
Vasculitis , SLE, PAN, Wegner’s, Goodpastures
Diabetes*, Pregnancy-associated,
Drugs
Pencillamine, Gold, NSAIDs, Heroin*.
Neoplasm's Solid organ CA*, Lymphoma, Leukaemia
Others
Amyloid*, Renal Tx rejection
*Typically nephrotic range
Nephrotic Syndrome
Hypoalbuminaemia, (<30g/L)
Proteinuria
(>3.5g/day)
Generalised oedema (JVP = N)
hypercholesterolaemia
+/- hypertriglyceridaemia
Associated with
- Increased risk of infection
- Increased clotting tendency
Pt > 10 years of age should have a renal Biopsy
Acute Poststreptococcal Glomerulonephritis
Principally a disease of children (M>F)
Characteristic 10 day latent period between
sore throat and renal disease
Nephrotic Urine - ‘Smoky Brown’ haematuria
- oliguria
Associated with oedema and hypertension
Dx rising ASO titre,
throat culture - streptococcal A,
renal biopsy
Rapidly Progressive Glomerulonephritis
Progression to ESRF within weeks or months of onset
Focal necrotizing GN with crescent formation on renal biopsy
Can form part of a vasculitic process
Anti GBM disease
ANCA positive vasculitis
Churg strauss
SLE
any CT
Can complicate any primary GN
Goodpasture’s disease
Wegners Granulomatosis
microscopic polyarteritis
disease
Outlook for recovery poor unless treated early
Steroids & Cyclophosphamide
Pulse Methyl Prednisolone - plasmapheresis
IgA Nephritis
Commonest form of GN worldwide - 30%
typically young males (M:F = 3:1)
66% - macroscopic haematuria following (1224 hours) onset of sore throat or URTI
may produce ARF
- often recurrent
33% -- persistent proteinuria and haematuria
No serological marker
50% raised circulating IgA levels
Long term risk of CRF = 25 - 50%
Membranous Glomerulonephritis
Clinical Features
80-90% > 30 years of age - m:f = 2:1
80% have nephrotic range proteinuria
(>3.5g/day)
commonest cause in adults
Microscopic haematuria found in 50% of adults
25% hypertensive at diagnosis
4 - 10% have underlying neoplasm
Renal vein thrombosis (10 -20%)
• Increased risk albumin < 20g/L
Minimal Change GN
76% of Nephrotic syndrome in children
accounts for only 25% adults
93% steroid sensitive in children - no need to biopsy
Most relapse off steroids at least once.
recurrent relapsers - cyclophosphamide
excellent long term prognosis
renal biopsy Normal on Light microscopy
Effacement of foot processes on EM
classical association - Hodgkins lymphoma, NSAIDS
Focal Segmental Glomerulosclerosis
Presents with nephrotic syndrome in 75%
secondary FSGS consequent on glomerular
scarring
IgA Nephritis
Post vasculitis
Sickle cell disease Alport’s disease
HIV infection
IV drug abuse (Heroin)
reflux
Histology - focal & segmental sclerosis
Can recur in renal Tx - 23% ~ graft loss 10%
MesangioCapillary GN -MCGN
(Membranoproliferative GN)
Presentation - Nephrotic (50%) - Nephritic (25%)
Histologically
Type 1 - Subendothelial deposits
Type 2 - Dense deposit disease
Associated with low complenent levels
C3 nephritic factor
Partial lipodystrophy
No treatment shown to be effective
50 % ESRF at 10 years
Can recur in renal Tx - 15 -35% ~ graft loss 10%
Autosomal Dominant
Polycystic Kidney Disease
2 Types
PKD 1
PKD 2
Prevalence
(Europe)
1 : 500 - 1 : 1000
patients
Sex
85%
15%
8 - 10% of dialysis
Males = Females
Clinical onset Typically 20’s - 50’s
Pathophysiology
Disease begins in utero
Multiple cysts, lined by tubular-type cells
Cysts contain uriniferous fluid, blood or
pyogenic secretions
Cysts can arise anywhere along the
nephron
only 1 - 5% of nephrons are involved
Intervening areas show nephrosclerosis
and chronic interstitial nephropathy
Renal failure
“70% by age 70”
Progresses to ESRF in about 10yrs once
serum creatinine rises above normal
Rate of progression of CRF usually similar in
families
-
Progression is faster with
PKD1:
Median age of ESRF = 56 years
PKD2:
Median age of ESRF = 68 years
high BP
- gross haematuria
proteinuria
- pregnancy
male sex
- larger kidneys
Age at presentation
Subaracnoid Haemorrhage
Risks & Prevalence overestimated
Berry aneurysms
4% young adults rising to 10% in elderly 10%
65% risk of rupture
Tend to cluster in families
Prevalence in asymptomatic patients is felt to
be lower
Role of screening controversial
Risk of hypertensive stroke or intracerebral haemorrage
is still 10x higher than risk of subarachnoid
GENETICS
2 genes involved
PKD 1
Short arm of
chromosome 16
Encodes polycystin 1
- ? adhesion
PKD 2
Long arm of
chromosome 4
Encodes polycystin 2 ? cation channel
GENETICS
Complete penetrance & variable
expression
Onset of the disease may be earlier if
inherited from the mother
Rate of progression of CRF varies from
family to family & within families
Positive Family history in > 60%
Remainder ? spontaneous mutation
DIAGNOSIS
Ultrasound
Very sensitive and specific
Especially in Patient > 30 years of age
Detects cysts as small as 1 - 1.5 cm
Increased false negatives in young patients
Characteristically multiple cysts in both kidneys which
are large
CT (with contrast )
More sensitive than USS
Detects cysts of 0.5cm
Definitive radiological test
Genetics
Only 1 - 5% of nephrons develop cysts even
though they all carry a copy of the abnormal
gene
2 hit hypothesis
At a cellular level ADPKD seems to be acting
as a recessive trait
A ‘ second hit ‘ or mutation in the normal
copy of the gene seems to have to occur
sporadically before the nephron will produce
cysts
Renal Ostodystrophy
Develops early in course of CRF
First signs at GFR~ 40mls/min
Treatment Goals
PTH =
Phosphate =
Calcium =
Treatment
150 - 300ng/l (2-3x normal) in ESRD
0.8 – 1.4 mmol/l
2.1 – 2.4 mmol/l
Restrict phosphate in diet
Phosphate Binders – Ca & non Ca based
Activated Vitamin D (calcitriol / alfacalcidolol/parcalcitriol)
New agents being developed - calcimimetics
Increasing concern regarding vascular calcification