Transcript The Kidney in Systemic Disease

The Kidney in
Systemic Disease
Dr Dana Kidder
Renal Registrar
Objectives
 Diabetes
mellitus
 Vasculitis
 Lupus
nephritis
 Renovascular disease
 Multiple myeloma
Diabetes
 The
prevalence of DM contibues to
rise with an expected 370 million to
be affected in 2030
 Leading
cause of ESRD in Western
countries
Diabetic Renal Disease
Can develop in the course of both Type I & Type II
diabetes
 The proportion of patients who develop proteinuria
and elevated serum Cr is related to duration of
diabetes
 Overt diabetic nephropathy is characterized by
persistent albuminuria 300mg/24h on at least 2
occasions separated by 3- 6 months

Scottish Renal Registry Report 2009
Prevalent counts &
adjusted rates of
ESRD, by primary
diagnosis
Figure 1.15 (Volume 2)
December 31 point prevalent ESRD patients.
Adj: age/gender/race; ref: 2005 ESRD patients.
Pathogenesis of Diabetic
Nephropathy
Haemodynamic changes- increased GFRafferent arteriolar vasodilatation mediated by
range of vasoactive mediators
 Renal hypertrophy- plasma glucose
stimulates several growth factors within the
kidney
 Mesangial expansion & nodule formation
 Proteinuria
 Tubulo-interstitial fibrosis

Normal glomerulus
Kimmelstiel-Wilson
Nodule
Diagnosis
 History
of Diabetes Mellitus
 Proteinuria
 Presence of other diabetic complications
eg retinopathy
 Renal Impairment in later stages
no haematuria – if present may
require renal biopsy
 Note
Albuminuria
 Normoalbuminuria
<30mg/g
creatinine
 Microalbuminuria 30-300 mg/g
creatinine
 Macroalbuminuria >300 mg/g
creatinine
Time Course of Type 2 Diabetic Renal Disease
Microalbuminuria
Proteinuria
ESRD
Cardi ovascular Morbidity and Mortality
Early Stage
Late Stage
Kidney Disease
End Stage
Proteinuria and Diabetic
Complications
The worse the proteinuria, the more likely the patient is to have diabetic
complications
Proteinuria in Diabetics
The greater the proteinuria, the higher the CV risk
Prevention & Treatment



Glycaemic control
 Maintain tight glycaemic control
(HbA1c < 7)
Anti-hypertensive therapy
 Tight BP control
 ACE inhibitors and ARBs
Lipid control
Renal Replacement Therapy
for Diabetic Nephropathy
Haemo and Peritoneal Dialysis
 Treatment of complications:

– Retinopathy/Neuropathy
– Vascular Disease
– Infection
 Simultaneous
(type 1 only)
Kidney Pancreas Transplant
Mortality on Dialysis

Type 1 Survival
1 year
 2 year
 5 year


81%
62%
24%
Non Diabetics 82, 70
and 40%

Type 2 Survival
1 year
 2 year
 5 year

75%
56%
20%
Conclusions 1
 Diabetes
is most common cause of renal
failure in the UK.
 Screening to detect urinary protein
abnormailities and deranged renal function
is part of diabetes care
 Microalbuminuria progesses to proteinuria
and overt nephropathy
Conclusions 2
 In
diabetic nephropathy, reducing
proteinuria slows progression
 Very good evidence for the use of ACE
inhibitors and angiotensin II receptor
blockers to slow progression
 Patients who reach end stage renal
failure require dialysis and or
transplantation
 Diabetic dialysis patients tend to do
badly
Vasculitis
 Kidneys
are targets for a variety of
systemic vasculitides
 Characterized as large vessel, medium
vessel or small vessel
 Nephrologists usually encounter small
vessel vasculitis
Small Vessel – ANCA
associated
 Patients
present with constitutional
symptoms e.g. fever, migratory arthralgia,
weight loss, anorexia and malaise
 Prodromal symptoms may last for weeks
to months before specific organ
involvement
Churg-Strauss
 Small
vessel vasculitis
 Characterised by chronic rhinosinusitis,
asthma, and prominent peripheral blood
eosinophilia
 Lung most commonly involved (asthma
in > 95%)
 2/3 have skin involvement (palpable
purpura to subcutaneous nodules)
MPA/ GPA
ENT involvement
 More
common in GPA 90 vs 35%
 Nasal crusting, sinusitis, persistent
rhinorrhea, otitis media, oral/nasal ulcers,
bloody nasal discharge
 GPA-evidence of bony/cartilage
destruction (saddle nose)
Pulmonary Disease


Cough,
hoarseness,
haemoptysis,
SOB, pleuritic
pain
CXR – highly
variable
Renal
 Common
in GPA & MPA, less
common in Churg-Strauss
 ARF- with proteinuria, red cell
casts
 Renal biopsy- shows segmental
necrotizing glomerulonephritis
Cutaneous Manifestations
About half have cutaneous
manifestations
 Purpura affecting lower extremities

Organ involvement in ANCA associated vasculitis
MPA
GPA
CSS
Renal
90
80
45
Lung
50
90
70
ENT
35
90
50
Neuro
30
50
70
GI
50
50
50
Skin
40
40
60
Diagnosis
 Examination
 Routine
bloods, CRP, ESR, complement,
ANCA, virology
 Urinalysis
 Tissue –kidney, skin, nasal, lung
Treatment
 Immunosuppressive
 Plasma
therapy
Exchange
 May require renal support
SLE
 Chronic
inflammatory disease of unknown
cause affecting skin, joints, kidneys, lungs,
nervous system, serous membranes
 Women in their 20s -30s more commonly
affected
Clinical Manifestations of Lupus
Diagnosis of Lupus
Lupus Nephritis
 Renal
involvement common
 Most frequently observed abnormality
proteinuria
 A number of types of renal disease
differentiated by renal biopsy
 Positive ANA, dsDNA, Sm Ab, low
complement
ISN Classification
 Class
 Class
 Class
 Class
 Class
 Class
I: Minimal mesangial
II: Mesangial Proliferative
III: Focal Proliferative
IV: Diffuse Proliferative
V: Membranous
VI: Advanced sclerosing
Treatment - Proliferative
 Non-immunosuppressive
– ACE/ARB
target BP 130/80
 Immunosuppressive
therapycyclophosphamide/ MMF, prednisolone
Prognosis

Varied clinical course form benign illness
to rapidly progressive disease

Most have relapsing/remitting course

Poor prognostic factors for survival: renal
disease, HBP, male sex, young age, older
age at presentation, poor socioeconomic
status, antiphospholipid syndrome, high
overall disease activity
Renovascular Disease

Pathology
– Ostium in 85% of pts
– Bilateral in 30-80% of pts
Epidemiology
– Older pts >50
– M>F
– Risk factors for generalised atherosclerosis
– Predominantly caucasians
– Prevalence of 4-20% (autopsy)
– Rarely renal alone
Clinical Presentation



AKI after treatment of hypertension, usually
with ACEi.
CKD elderly with diffuse vascular disease
‘Flash’ pulmonary oedema
Microscopic haematuria
Hypertension
Abdominal bruit
Atherosclerotic disease elsewhere
Diagnosis of Ischaemic Renal
Disease

Screening tests
– Renal ultrasound*
– Captopril renography
– Plasma renin
activity/renal vein renin
– Renal doppler studies
– MRA*
* Commonly used
Therapeutic approaches
Angioplasty
 Angioplasty + stenting
 Stenting alone
 Medical therapy


ACE inhibitors are contra indicated in
BILATERAL renal Artery Stenosis
Multiple myeloma
Epidemiology
• Incidence 30-40 per million per year.
• Average age
–
–
–
–
Male 80
Female 70
10% under age of 50
Incidence doubled in Blacks
• Renal Impairment at presentation 50%
• 10% require dialysis at presentation
Multiple myeloma

Renal impairment
– 50% Scr >110
– 20% Scr 170-250
– 10% RRT
 Knudsen
et al, Eur J Haematol 2000;65:175-181
Myeloma Kidney
• Lymphoid malignancy
•
•
•
•
Bone Pain
Weakness and Fatigue
Weight Loss
Symptoms related to
other manifestations
– Hypercalcaemia
– Renal Failure
– Amyloidosis
• Increased risk of
infection
Precursor B Cells
Transform
Malignant Plasma Cells
Bone Marrow
Plasmacytoma
Plasma cell Leukaemia
Monoclonal Protein
(M protein)
Investigations
•
•
•
•
•
Normocytic Anaemia 75%
Raised ESR/PV 30%
Rouleaux formation 50%
Renal Impairment
Monoclonal Band 97%
• IgG 50% IgA 20% LC only 16%
• Kappa: Lambda 2:1
• Increased B2M
• Lytic lesions on skeletal survey
Treatment of the patient with
Myeloma and ARF
• Stop Nephrotoxins
– NSAID’s
– Diuretics in view of risk increasing cast formation
• Treat hypercalcaemia
– IV NaCl to volume resuscitate
– IV Pamidronate if required
• Avoid contrast agents
• Treat infections promptly
• Chemotherapy to reduce tumour load
– High dose dexamethasone may help reduce tumour
load.
– Thalidomide/ bortezomib
• Plasma exchange
– To remove light chains
• Dialysis to support ARF and CRF
Questions?