Inherited and Systemic Diseases of the Kidney Flashcards
what is overt diabetic nephropathy characterised by
persistent albuminuria
i.e. 300mg/24h on at least 2 occasions separated by 3-6 months
how can haemodynamic changes in diabetes cause nephropathy
- afferent arteriolar vasodilatation mediated by range of vasoactive mediators e.g IGF-1
- hyperfiltration
- increased GFR
what cause nephropathy in diabetes
haemodynamic changes Renal hypertrophy Inflammation Proteinuria Tubulo-interstitial fibrosis
how is proteinuria caused in diabetic nephropathy
GBM thickening and podocyte dysfunction
how does renal hypertrophy come about in diabetic nephropathy
plasma glucose stimulates several growth factors within the kidney
Mesangial Expansion
Nodule Formation
what does nodule formation on the kidneys lead to
nodular diabetic glomerulosclerosis ( Kimmelstiel-Wilson lesion) and diffuse glomerulosclerosis
what is the relation ship of proteinuria and diabetic complications
The worse the proteinuria, the more likely the patient is to have diabetic complications
what is diagnostic for diabetic nephropathy
Levels of 24 hour and overnight urinary albumin excretion
what are the normal values of urinary albumin excretion
24-hr = > 30
Overnight = > 20
what are values of microalbuminuria in urinary albumin excretion
24hr = 30-300
Overnight = 20-200
what are values of overt nephropathy in urinary albumin excretion
24hr = > 300
Overnight = > 200
prevention/treatment of diabetic nephropathy
Maintain tight glycaemic control
ACE inhibitors AND ARBs
Lipid control
Diuretic can also be added
what is the blood pressure target in diabetes
130/85mmHg
when is dialysis normally started
when GFR is 10-12 ml/min
what are the possible renal replacement therapy for diabetic nephropathy
Simultaneous Kidney-Pancreas Transplant (Type 1 only)
Kidney transplant
Haemodialysis and Peritoneal Dialysis
what does microalbuminuria progress to
proteinuria and frank nephropathy
how can diabetic nephropathy be slowed down
if we slow down proteinuria
- can be done by ACEi or ARB
what is renovascular hypertension
secondary form of hypertension usually caused by renal artery stenosis
reduction in renal perfusion pressure activates a series of hormonal and neuronal responses that raise systemic arterial BP
what are causes of renovascular disease
Fibromuscular dysplasia
Atherosclerotic Renovascular disease
what is ischaemic nephropathy
Refers to the reduced GFR associated with reduced renal blood flow beyond the level of autoregulatory compensation
Over time can lead to renal atrophy and progressive CKD
what is Fibromuscular Dysplasia
non-atherosclerotic, non-inflammatory disease of the blood vessels that causes abnormal growth within the wall of an artery commonly the renal arteries
Causes renal artery stenosis
what is Fibromuscular dysplasia associated with
Ehlers-Danlos
how commonly gets Fibromuscular dysplasia
Females 15-50 years
what is Atherosclerotic Renovascular disease
combination of renal ischaemia and renal artery stenosis
what are risks of Atherosclerotic Renovascular disease
risk for generalised atherosclerosis - rarely renal alone
what is the clinical presentation of Atherosclerotic Renovascular disease
Renovascular hypertension
AKI after treatment of hypertension (usually with ACEi)
CKD in elderly with diffuse vascular disease
‘Flash’ pulmonary oedema
- sudden onset without LV impairment
Microscopic haematuria
Abdominal bruit
Atherosclerotic disease elsewhere
Ix of ischaemic renal disease
US - renal size asymmetry, affected side is smaller
CT/MRI angiography
Angiography - gold standard booted after CT/MRI as it is invasive
Tx of ischaemic renal disease
Medical therapy
- manage hypertension
Surgical therapy
- Angioplasty
- Angioplasty + stenting
- Stenting alone
when are ACEi contra-indicated
Bilateral Renal Artery Stenosis
what is multiple myeloma
cancer of the plasma cells
what is produced in multiple myelomas that can cause kidney problems
paraprotein
what are Sx of myeloma
Bone Pain
Weakness
Fatigue
Weight Loss
what are signs of myeloma
Anaemia Hypercalcaemia Renal Failure Amyloidosis Recurrent infections
Ix for myeloma
FBC
- normocytic anaemia
- Rouleaux formation
- Raised CRP/PV
- raised calcium
Renal impairment
- raised urea and creatinine
Protein electrophoresis
Bence-Jones protein in urine
Lytic lesions on skeletal survey
e.g. pepper pot skull
what are renal manifestations of multiple myeloma
AKI secondary to hypercalcaemia
Monoclonal Immunoglobulin Deposition Disease
Cast nephropathy
- formation of plugs in the renal tubules from light chains leading to renal failure
Amyloidosis
what is amyloidosis, how is it characterised and classified
Generic name for a family of diseases
Characterised by the deposition in extracellular spaces of a proteinaceous material
Classified by the type of precursor protein that makes up the main component of the fibrils
what are renal amyloidosis
primary (AL) amyloid and secondary (AA) amyloid
how do renal amyloidosis present histologically
Positive Congo red staining showing apple-green birifringence under polarised light
(BUZZWORD)
Tx of 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
Chemotherapy to reduce tumour load
- High dose dexamethasone may help reduce tumour load.
Plasma exchange
- to remove light chains
Dialysis
- to support AKI and CKD
what type of vasculitis more commonly affects the kidneys
small vessel vasculitis
what are examples of small vessel vasculitis
ANCA associated
- Wegener’s, Churg-Strauss, Microscopic polyangitis
Immune complex associated
- HSP, Behcets disease, anti-GBM disease e.g. Good pasture disease
what is Granulomatosis with Polyangiitis
(previously Wegeners)
Necrotising granulomatous inflammation which most commonly affects the respiratory tract
Sx of Gw/P
Nasal crusting, sinusitis, persistent rhinorrhea, otitis media, oral/nasal ulcers, bloody nasal discharge.
Evidence of bony/cartilage destruction (saddle nose)
what is Eosinophilic Granulomatosis with Polyangiitis
(previously Churg-Strauss)
necrotising granulomatous inflammation
Asthma and eosinophilia
Lung most commonly involved (asthma in > 95%)
2/3 have skin involvement (palpable purpura to subcutaneous nodules)
what is microscopic polyangiitis
Small vessel vasculitis, no granulomatous infiltration
what do all 3 ANCA associated vasculitis have
pulmonary haemorrhage as a consequence of alveolar capillary involvement
what is seen in renal involvement of small vessel vasculitis
(more common in GPA and MPA)
Haematuria and proteinuria
AKI
Renal biopsy- shows segmental necrotizing glomerulonephritis
Tx of small vessel vasculitis
Immunosuppressive therapy
Plasma Exchange
May require renal support
what is seen in SLE in relation to the kidneys
Lupus Nephritis
- Proteinuria
- number of other renal diseases
how can the renal disease affecting the kidney in SLE be differentiated
Renal Biopsy
Tx for SLE affecting Kidneys
Non-immunosuppressive:
ACE/ARB target BP 130/80
Immunosuppressive therapy:
1 - Induction;
High dose steroids
Cyclophosphamide/ MMF
Azathioprine, rituximab, tacrolimus
2 - Maintenance
Steroids
MMF/azathioprine
what is the classification of kidney disease in SLE (Class I-VI)
Class I: Minimal mesangial Class II: Mesangial Proliferative Class III: Focal Proliferative Class IV: Diffuse Proliferative Class V: Membranous Class VI: Advanced sclerosing
what drugs can cause pre-renal failure
e.g. hypotension, hyopvoemia
Diuretics > dehydration
ACEi/ARBs > diarrhoea and vomiting
what drugs can renal failure
e.g. Acute Interstitial Nephritis/Tubular necrosis
Gentamicin
Sulphonamides
Aspirin
what drugs can post-renal failure
e.g. Retroperitoneal fibrosis, crystaluria, urinary calculi
Methysergide
Chemotherapy
what can beta blockers cause if on for prolonged therapy
Diabetes
what can NSAIDs cause
hypertension through renal damage
what can abrupt stop of beta blockers cause
angina
what are the two forms of polycystic disease
Autosomal Recessive
Autosomal Dominant - more common
what are the two mutations seen in ADPKD and which is more common
PKD gene1 mutations; more common
- located on chromosome 16
PKD2 mutations; less common
- located on chromosome 4
who develops end stage kidney failure at an earlier stage
PKD1
renal features of ADPKD
Reduced urine concentration ability
Chronic pain
Hypertension-common, early(31 yrs-mean age)
Haematuria- cyst rupture, cystitis, stones
Cyst Infection
Renal Failure
non-renal features of ADPKD
Hepatic Cysts - very common :
Liver function generally preserved. Can result in SOB, Pain, Ankle swelling
Intra Cranial Aneurysms
Cardiac Disease
- Mitral/Aortic value prolapse
Diverticular disease
- Diverticulitis and colonic perforation
Hernias - Abdominal/Inguinal
Ix of ADPKS
Ultrasound-presence of multiple bilateral cysts
Renal enlargement seen.
CT/MRI-when unclear on USS
in children, what suggests that it is ARPKD and not ADPKD
USS suggestion of Congenital Hepatic Fibrosis
if a person has ADPKD how likely is it that there child will have it
50%
Mx of ADPKD
Control Hypertension (target level 130/80 mmHg) e.g. ACEi best choice
Tolvaptan - to reduce cyst volume and progression
how gets ARKD and what is it associated with
children
hepatic lesions
what is the mutation in ARKD
PKDH1 on chromosome 6
what is the renal involvement in ARKD
Renal involvement is bilateral and symmetrical
Urinary tract is generally normal
Histologically cysts are seen appearing from the collecting duct system
what is the clinical presentation of ARPKD
Kidneys always palpable
Hypertension
Recurrent Urinary Tract Infections
Slow Decline in GFR -less than 1/3 reach dialysis
Ix of ARPKD
US
CT scan
MRI
what is Alports Syndrome and what is the genetic role in it
Hereditary Nephritis - Disorder of Type IV collagen matrix
X-linked inheritance
Mutation of COL4A5 leads to deficient collagenous matrix
Alports Syndrome manifestations
Sensorineural deafness
Pyelonephritis
Haematuria
Renal failure
when should Alports be suspected
Haematuria and hearing kiss
Ix of Alports
Renal Biopsy-
Variable thickness GBM- characteristic feature
Tx for Alports
No specific treatment
Will need dialysis/transplantation
what is Anderson Fabrys disease
X linked disease lysosomal storage disease
Leads to a deficiency of alpha-galactosidase A
Affects kidneys, liver, lungs, erythrocytes
Uncommon
Tx of Fabrys disease
Enzyme replacement-Fabryzyme
Management of Complications
what is medullary cystic kidney
autosomal dominant inherited disroder
causes tubular loss and medullary cyst formation
See shrunken kidneys
Tx for medullary cystic kidney
Renal transplantation
what is medullary sponge kidney
Sporadic Inheritance
Dilatation of collecting ducts
Severe cases- medullary area appears like a sponge
Cysts have calculi
Ix of Medullary sponge kidney
Excretion Urography
