1. Renal Disease
Dr. George Mellotte

2. The Kidneys On Examination
Two bean-shaped organs, each the size of a fist.
Weighing ~0.5% of total body weight
20% of Cardiac output goes to Kidney
On Examination
Move with Respiration
Ballotable
Can get above them
Overlying resonance
Adrenal Glands
Rib Cage
Kidneys
Rib Cage
Bladder

3. 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 Magnesium
Regulate acid/base balance

4. 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

5. 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

6. 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 umol/l Women umol/l

7. Defining Renal Failure
Cr Clearance = (140 - age) × weight in Kg × SF serum Cr
SF = 1.2 males / 1.05 females
Normal GFR = mls/min
Grade GFR Sr Creatinine Mild ml/min umol/l Moderate ml/min µmol/l Severe ml/min µmol/l Endstage < 15ml/min > 500µmol/L Cockcroft & Gault Formula

8. Classification of Chronic kidney disease (CKD)
Stage
Description
GFR
(mL/min/1.73 m2) 1
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
In the USA, the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) has sought to formalize the clinical definition of renal failure.1
Thus, it has adopted a new standard term for the condition, chronic kidney disease (CKD), and classified the disease into five distinct stages. These stages are defined in the above slide and this standard terminology will be used throughout the slide kit. 1. 5
End Stage Kidney failure
< 15 (or dialysis)
eGFR can be thought of as equivalent to % kidney Function
GFR, glomerular filtration rate

9. 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

10. 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

11. 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.

12. 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

13. 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.

14. 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.

15. 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 55 or women under age 65)
*Components of the metabolic syndrome.

16. 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

17. 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

18. Lifestyle 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

19. 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.

20. 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

21. Risk Factors for Vascular Disease in Renal Failure 2
Renal Specific Risk Factors
Proteinuria
Anaemia
Hyperhomocysteinaemia
Hyperphosphataemia
Uremia per se?

22. 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

23. Progression in Renal Failure
Destruction of
Nephrons
Destruction of
Nephrons
Remaining
Nephrons
Focal & Segmental
Glomerulosclerosis
Glomerular
Hyperfiltration

24. 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 mm Hg increase in diastolic blood pressure until, and unless, renal impairment is identified and treated” Lancet 2000;

25. Highlight whar we can change
Prevention

26. Relationship between achieved BP control and declines in GFR in clinical trials of diabetic & non-diabetic renal disease

27. 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

28. 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 pmp/year
Incidence requiring dialysis 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

29. CASES OF SEVERE ARF (%)

30. Classification of ARF

32. 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

33. 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. 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

34. 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

35. Initial Investigations
Blood Tests FBC, blood film, Coag screen, U/E, LFT's, Bone profile, ABG, Immunology if appropriate ANA, DsDNA, C3,C4, CRP, SPEP, ANCA & Anti GBM ASOT titre
Urine Electrolytes & Osmolarity Urine Microscopy
X-ray Renal Ultrasound Isotope Perfusion scan

36. 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

37. 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)

38. Renal Hypoperfusion V Established ARF
Measurement Pre Renal ATN
Urinary Na (mmol/l) <20 >40
Fractional excretion <1 >4 of Na (%)
Only appropriate if diuretics not given

39. 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 mg IV Pt must be euvolaemic ê
Diuresis
Measure hourly urine output & replace losses
Lack of response indicates that ATN has developed

40. 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!

41. Drugs that induce renal damage
Decrease in renal perfusion
Impaired intrarenal haemodynamics
Tubular toxicity
Allergic interstitial nephritis
Class of drug
Diuretics, ACE inhibitors, B-Blockers, vasodilators
NSAID’s, radiocontrast
Aminoglycosides, amphotericin, cisplatin
lactams,(penicillins) NSAID’s

42. ECG changes of Hyperkalaemia
Peaked T waves, Flattened P wave
Prolonged PR interval è sinus arrest
Wide QRS complexes & deep S waves èSine Wave èV. Fib è asystole

43. 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 mls of 10% Calcium Gluconate
2. 50 mls of 50% Dextrose with 12 IU Insulin over 30 mins followed by 10ml/hour
mls of 8.4% NaHCO3 if acidotic

44. Guidelines for management of acidosis in ARF
Cause of acidosis governs management
Tissue hypoxia/lactic acidosis - Optimise circulation & oxygenation
Salt and water depletion - Normal saline
Established renal failure - NaHCO3, ?dialysis
Poisoning NaHCO3, ?dialysis ( Methanol, Salicylates)
Diabetes mellitus - Insulin, saline

45. 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

46. Chronic Renal Failure Defined as permanent loss of renal function
Prevalence underestimated
In USA - while only 0.1% of population require dialysis % 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

47. Chronic Renal Failure Clinical features Laboratory features Symptoms
Nausea Vomiting
Fatigue Obtunded
Pruritus Bruising
Signs
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

48. 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

49. Treatment Choice Only medically fit patients are Transplanted
Haemodialysis
Intermittent
Complex
Hospital Based
Problems
Poorly tolerated in cardiac disease
Vascular access
Most suitable
Active patients
Patients with limited ability to self care
Nephrotic Syndrome
C.A.P.D. /A.P.D.
Simple
Independent
Patient dependent
Problems
Peritonitis risk
Catheter Malfunction
Protein losses
Most Suitable
Diabetics
Elderly
Patients living away from a HD unit
Transplantation
Desirable
Scarce resource
Not a cure
Problems
Graft Failure
Infection risk
Cancer Risk
Only medically fit patients are Transplanted

50. 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

52. 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 minutes
For CAPD, done 4 times daily, 7 days a week
For APD, done 4-6 times nightly using a machine “Home Choice”
It is a home based system & requires a committed patient

53. 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.

54. Haemodialysis
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

55. Haemodialysis

57. 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)

58. Transplantation Recipient Evaluation
Cardiovascular risk, Viral screen, Urological assessment
Only 30% patients on dialysis are fit for transplant 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 yrs
Main cause of graft loss currently
Death of patient! - mainly due to Cardiac disease

59. USRDS - Projected half-life of all transplants 1988 to 1995
The projected half-life for transplants living donors years years Cadaveric donors 7.9 years years 1995,
Censoring for patients who died with functioning grafts, Living Donors years years Cadaveric Donors 11.0 years years 1995
NEJM Mar 2000; 342:

60. Graft Loss Rejection Kidney fails due to “wearing out” Cancer related12
Graft Loss
Rejection
Cancer related
problems
Kidney fails due to “wearing out”
Patient dies from another disease with a functioning graft
Return to Dialysis
Acute rejection, cardiovascular death with a functioning graft, side effects and chronic renal allograft dysfunction/nephrotoxicity are all interdependent. There is a central role for immunosuppression.
ZRAP052/0301
Date of Preparation: March 2001

61. 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 :20
Negative tests reliably excludes abnormal haematuria
Coexistent dipstick proteinuria is usually significant and should be investigated further

62. 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

63. Microalbuminuria
Protein excretion above normal but below the threshold of “Standard Dipstick”
Albuminuria normally <20mg/24 hrs (15 µg/min);
Microalbuminuria = mg/24 hrs ( µg/min)
Albumin-to-creatinine ratio
microalbuminuria = mg alb/mmol creatinine
Risk factor in Diabetic Nephropathy
High incidence of false positives

64. 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 % progress
Outcome much better than original studies –
?effect of active Rx

65. 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

66. Major Clinical Syndromes of Glomerular Disease
Nephrotic Syndrome
Nephritic syndrome
Rapidly Progressive Glomerulonephritis
Chronic Glomerulonephritis
Persistent urinary abnormalities with no symptoms

67. 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

68. 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

69. 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

70. 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

71. 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 Goodpasture’s disease
ANCA positive vasculitis Wegners Granulomatosis Churg strauss microscopic polyarteritis
SLE any CT disease
Can complicate any primary GN
Outlook for recovery poor unless treated early
Steroids & Cyclophosphamide
Pulse Methyl Prednisolone - plasmapheresis

72. IgA Nephritis Commonest form of GN worldwide - 30%
typically young males (M:F = 3:1)
66% - macroscopic haematuria following ( 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 = %

73. 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

74. 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

75. Focal Segmental Glomerulosclerosis
Presents with nephrotic syndrome in 75%
secondary FSGS consequent on glomerular scarring
IgA Nephritis Post vasculitis reflux
Sickle cell disease Alport’s disease
HIV infection
IV drug abuse (Heroin)
Histology - focal & segmental sclerosis
Can recur in renal Tx - 23% ~ graft loss 10%

76. 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 % ~ graft loss 10%

78. Autosomal Dominant Polycystic Kidney Disease
2 Types PKD 1 85% PKD 2 15%
Prevalence 1 : : 1000 (Europe)
8 - 10% of dialysis patients
Sex Males = Females
Clinical onset Typically 20’s - 50’s

79. 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

80. 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

81. 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

82. 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

83. 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

84. DIAGNOSIS Ultrasound Very sensitive and specific
Especially in Patient > 30 years of age
Detects cysts as small as 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

85. 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

86. Renal Ostodystrophy Develops early in course of CRF Treatment Goals
First signs at GFR~ 40mls/min
Treatment Goals
PTH = ng/l (2-3x normal) in ESRD
Phosphate = 0.8 – 1.4 mmol/l
Calcium = 2.1 – 2.4 mmol/l
Treatment
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