Week 8: Renal disease (3) (renal pathology con.) Flashcards
main causes of CKD
diabetic nephropathy
hypertensive nephropathy
polycystic kidney disease
Diabetic nephropathy
Type 1 DM or long duration of Type 2 DM
Also associated with other diabetic microvascular complications such as
- Retinopathy
- Peripheral Neuropathy
diagnosis of diabetic nephropathy
most diabetic patients will undergo screening for diabetic nephropathy
- Raised Urine Albumin: Creatinine Ratio/PCR
- Evidence of long-standing/poorly controlled DM
- Evidence of other microvascular disease
treatment of diabetic nephropathy
- ACEi/ARB to reduce proteinuria
- Anti-hypertensives for BP control
- Cardiovascular risk modification
- Improved glucose control
- Continue other screens for microvascular complications – eye checks and foot checks
hypertensive nephropathy
- Chronic raised BP causing nephrosclerosis
- Often difficult to tell if advanced renal disease at presentation whether HTN caused the renal impairment or renal impairment caused secondary HTN
investigations for hypertensive nephropathy
to identify if primary or secondary HTN (based on clinical findings and index of suspicion):
- 24 hour Urinary metanephrines (Phaeochromocytoma)
- Aldosterone: Renin ratio (Primary aldosteronism)
- Cortisol & Dexamethasone suppression test (Cushing’s syndrome)
- TSH (hyperthyroidism)
- Magnetic resonance angiography (MRA) (Renal artery stenosis)
hypertensive nephropathy treatment
Anti-hypertensives (see ABCD guidelines)
polycystic kidney disease
2 Types (both are autosomal dominant)
- Type 1 (85%; PKD1 mutation on Chromosome 16)
- Type 2 (15%; PKD2 mutation on Chromosome 4)
- Mutation in chromosome 16 (ADPKD1) and chromosome 4 (ADPKD2)
presentation of polycystic kidney disease
Characterised by multiple cysts bilaterally in both kidneys and may be present in other organs, which causes
- Hypertension
- Acute loin pain
- Haematuria
- Bilateral palpable kidney
Symptoms can be related to
- the size of the kidney
- infection of the cysts (flank pain, haematuria, and fever)
- or can be asymptomatic
diagnosis of polycystic kidney disease
- Family history is KEY
- USS
complications of APKD
- Pain
- Infection
- hypertension
- Haematuria
- Kidney failure
treatment of polycystic kidney disease
- Control BP as per CKD management
- Tolvaptan (Vasopressin receptor-2 antagonist) is available for some patients to slow progression of CKD.
- Genetic counselling and testing
prognosis of APKD
- Morbidity and mortality are often the result of hypertension, e.g. MI and cerebrovascular disease
- Berry aneurysms
- Conditions lead to progressive CKD
-
Treatment involves controlling BP
- Medication
- Low salt diet
- Dialysis and renal transplant needed if end-stage renal failure develops
Causes of ESRD
- Diabetes
- Glomerulonephritis
- Hypertension
- Polycystic kidney
- Pyelonephritis
anaemia of chronic kidney disease
- Decreased production of erythropoietin from the kidney
- Absolute iron deficiency (poor absorption and malnutrition)
- Functional iron deficiency (inflammation, infection)
- Blood loss
- Shortened Red Blood Cell survival
- Bone marrow suppression from uraemia
- Medication induced
- Deficiency of Vit B12 and folate
management of anaemia of CKD
ESA = erythropoietin stimulating agents
mineral bone disease and CKD
Can be diagnosed if a patient with CKD has evidence of one or more of:
- Abnormalities of calcium, phosphate, alkaline phosphatase, PTH or vitamin D metabolism
- Vascular and/or soft tissue calcification
- Abnormalities in bone turnover, metabolism, volume, linear growth or strength
- Low turnover states
- Adynamic bone disease Osteomalacia
- High turnover states
- Osteitis Fibrosa
- Low turnover states
As CKD develops, disturbances in the homeostatic pathways lead to…
- hypocalcaemia,
- hyperphosphataemia
- Vitamin D deficiency
- development of secondary hyperparathyroidism
Tertiary Hyperparathyroidism
Occurs when PTH release continues despite raised serum Calcium levels (independently)
- As a result of parathyroid gland nodular hyperplasia
- Consequence of advanced CKD
Extra-renal involvement in APKD
- Liver- doesn’t impact renal function
- Bloating and distension- symptomatic resection
- Berry aneurysm- cerebral aneurysm
Management of CKD-MBD
Focus is to reduce:
(1) The occurrence and/or severity of renal bone disease
(2) Cardiovascular morbidity and mortality caused by elevated serum levels of PTH and high phosphate levels and calcium overload.
causes of glomerulonephritis
- Nephrotic and nephritic syndromes often characterised by glomerulonephritis
- Inflammation of glomeruli
which structures of the glomerulus can be damaged in glomerulonephritis
- Capillary endothelium
- Glomerular basement membrane
- Mesangial cells- support skeleton of capillary network in glomerulus
- Podocytes
glomerulonephritis often involves
the immune system
summary of nephrotic syndrome
- Damage to podocytes large amounts of protein being lost in urine e.g. albumin
- O of nephrotic links to oedema
- Reduction of albumin in the body – lost in urine
- Less oncotic pressure
Active urine sediments with or without renal insufficiency, with nephrotic range proteinuria (>3g in 24hrs)
- Diabetes
- Minimal changes disease
- Membranous
- FSGS (focal segmental glomerular sclerosis)
amyloid
summary of nephritic syndrome
- Inflammation that disturbs basement membrane
- Bigger gaps in basement membrane
- RBC can pass through into the urine
- Haematuria – coke coloured urine
Active urine sediments with or without renal insufficiency, with mild proteinuria – blood in urine
- IgA nephropathy
- Lupus
- Mesangial proliferative glomerulonephritis
- Vasculitis
features of nephrotic syndrome
- A triad of :
- Proteinuria > 3g per 24h
- Pitting oedema
- Hypoalbuminaemia
- Oedema
- Usually accompanied by high cholesterol
- Proteinuria > 3g per 24h
- Other features:
- BP often normal (can be low or high)
• Creatinine may be normal
• Proteinuria > 350 mg/ mmol alone = nephrotic range proteinuria
- BP often normal (can be low or high)
Remember you can have a normal eGFR with glomerulonephritis
clinical presentation of nephrotic syndrome
- Swollen e.g. periorbital and oedema
- Proteinuria >3 g in 24s hours
- Low serum albumin
- Hyperlipidaemia
- Hypercoagulable state
investigations for nephrotic syndrome
- Urine di
- Protein creatinine ration
- Bloods
- UEs
- FBC
- Albumin
- Serum glucose
- Imaging
- Renal biopsy (not usually in children)- USS guided
causes of nephrotic syndrome
In children
- 90% minimal change disease
In adults
- Minimal change
- Membranous nephropathy
- Focal segmental glomerulosclerosis (35%)
- Amyloid
minimal change disease
Pathophysiology of minimal change
Where podocyte become effaced losing the ability to control the amount of protein leaked into the urine
management of neprhotic syndrome
- Oedema
- Diuretics, need large doses and may need to be I.v. if gut oedema
- Salt and fluid retention
- ACE-i
- Anti-proteinuria but caution if intravascularly deplete or if renal function deteriorating acutely
- Hypercholesterolaemia
- Atherogenic if long-term nephrotic
- Life style advice and statins
- Treat underlying condition
- Steroids for Minimal change disorder, underlying cause of disease e.g. amyloid
presenation of nephritic syndrome
-
A triad of:
- Haematuria
- Reduction in GFR (renal impairment / oliguria)
- Hypertension
-
Other features
- Often some proteinuria but less than nephrotic syndrome
- Disruption of the endothelium results in inflammatory response & damage to the glomerulus
- Onset may be acute or rapidly progressive (RPGN)
- Rapidly Progressive / Crescentic GN - a fulminant form of nephritic syndrome
causes of nephritic syndrome
- IgA nephropathy (most common form)
- Lupus
- Mesangial proliferative glomerulonephritis
- Vasculitis
Management of nephritic syndrome
-
Blood pressure control / reduction of proteinuria
- ACE-I or AIIR first line if renal function allows
- Salt restrict
-
Treatment of oedema
- As for nephrotic syndrome if adequate renal function
-
Disease specific treatments
- Generally immunosuppressants
- e.g. RPGN – prednisolone, cyclophosphamide or rituximab +/- plasma exchange
-
Cardiovascular risk management
- Stop smoking, statin etc
- Dialysis (often short-term)
Vasculitis
- Vasculitis involves inflammation of the blood vessels. The inflammation can cause the walls of the blood vessels to thicken, which reduces the width of the passageway through the vessel. If blood flow is restricted, it can result in organ and tissue damage.*
- Large, medium or small blood vessels affected
presentation of vasculitis
- Skin
- Non blanching rash
- Hands and feet
- Joint pain in ankles and wrists
- Eyes
- Eyes look red or burn
- Giant cell arteritis
- Ears
- Dizziness
- Digestive system
- Ulcers and perforations
- Lungs
- Vasculitis of lung tissue
- Kidney
- Nephritic syndrome
- Symptoms
- Fever, headache, fatigue, weight loss
vasculitis Pathophysiology
- Driven by antibodies e.g. ANCA (anti-neutrophil cytoplasmic antibodies)
- ANCA attach neutrophils, activating these to attack basement membrane of the blood vessels
diagnosis of ANCA
- Look for ANCA antibodies
Treatment of vasculitis
- Immunosuppression e.g. plasma exchange
- Take blood from patient, filter , removing circulating antibodies and return to patient
- Drugs
- Prednisolone
- Azathioprine
- Mycophenolate
- Cyclosporin
- Cyclophosphamide
