Nephrology Flashcards
What genetic pattern of inheritance does Polycystic Kidney Disease have? What are the main genetic mutations?
Autosomal Dominant
PKD1/PKD2 - polycystic (ciliopathies)
Which mutations convey a poorer prognosis in PCKD
Truncating mutations
PKD1
Early manifestation of PCKD
Hypertension (with normal eGFR)
Extra-renal manifestation of PCKD
CNS: Cerebral aneurysm CVS: Valvular disease, cardiomyopathy, AF, aortic dissection and aneurysm Hepatic Cysts Pancreatic Cysts (IPMN) Seminal vesicle cysts
Main risk factor for progression/poor prognostic factors for PKCD
Male Early onset of symptoms Kidney size PKD1/Truncating mutations Proteinuria
Diagnostic Criteria for PKCD (with and without family history)?
\+ Family history >/= 3 cysts ( 15-39) >/= 2 cysts in both kidneys (40-59) - Family history >/= 10 cysts each kidney \+ bilateral kidney enlargement
Can use CT/MRI if needed
Can use genetic testing if necessary
Pharmacological management in PCKD
> CVS
> Targeted
RAAS Blocker (Ace inhibitor/ARB)
Tolvaptan (V2 vasopressin antagonist)
> Earlier treatment associated with more benefit
> eGFR <90, + eGFR progressively worsening by 2.5-5ml/min/yr over 5 years.
Main adverse effects of tolvaptan include: Polydipsia, polyuria/nocturia and LFT derangement
Thiazide induce hyponatraemia time frame
Most commonly occurs within 2 weeks of commencing or with intercurrent illness.
Treatment for PCKD
BP control <110/75
Reduce NA
Increase fluid intake
Tolvaptan
IGA nephropathy secondary causes
ETOH
Coeliac Disease
Treatment for IGA nephropathy
ACE to decrease proteinuria - BP target <130/80
Transplant
No benefit to immunosuppression
Acute allograft dysfunction
First 7 days: Ureteric obstruction/HLA mismatch
1-12 weeks: Acute rejection
AIN findings
Raised Cr Eosinophilia Urine sediment: WCC/RCC/WC casts Evidence of tubulointerstital damage Raised fractional sodium
Resistant Hypertension
Not complete
A C D > Not within limits despite triple therapy Add in
Note refractory, not response to 5 drugs.
RTA
Not complete
1: Hypokalaemia. Impaired hydrogen secretion (distal)
2: Hypokalaemia (Proximal). Impaired Bicarb reabsorption. Raised urinary PH.
4: Hypoaldosteronism
Histological finding of Amyloidosis affecting the kidney
Proteinuria only
Nodular Glomerulosclerosis
Congo red staining
Note often stem with cardiac involvement
Rapidly progressive glomerulonephritis causes
Anti-GBM
Small vessel vasculitis (ANCA)
Cryoglobulinaemia
Lupus Nephritis
RPGN is a clinical syndrome characterised by evidence of GN (haematuria/proteinuria/leukocytes in urine) and progression to kidney failure in a short period of time.
Most common causes of Nephrotic Syndrome in adults?
Secondary causes
Diabetes (Also most common overall)
Infection
Autoimmune disease
Primary causes
Minimal change disease
Focal segmental glomerulosclerosis (most common)
Membranous nephropathy (most common)
Membranoproliferative glomerulonephritis:
Nephrotic Syndrome
Nephrotic range proteinuria: 3500mg/24 hr or P:Cr 3000mg/g
Hypoalbuminaemia: <35
Oedema
Hyperlidipidaemia
Treatment for neprhotic syndrome
Treat cause
Statins (Hyperlipidaemia +/- treatment for triglycerides)
Anticoagulant in patients with additional risk factors or low risk with albumin <28 (prothrombotic tendency)
Low salt diet and diuretics (oedema)
Note patients with nephrotic syndrome are also more likely to develop infections ? due to loss of immunoglobulins through the glomerulus.
Nephritic Syndrome
Haematuria (+/- dysmorphic eryhtrocyte casts)
Proteinuria
+/- leukocytes
Clinically
Hypertension
Oedema
Kidney Failure
Reflects proliferation in the glomeruli.
Investigation for nephrotic syndrome?
Usually requires a kidney biopsy to diagnose
●Glycated hemoglobin (HbA1C, to diagnose diabetes)
●Antinuclear antibody and anti-double stranded DNA (dsDNA) antibody
●Anti-PLA2R autoantibody
●In patients older than 50 years – Serum free light chains and serum protein immunofixation
●Tests for hepatitis B and C viruses and HIV
●Serum C3 and C4 complement levels
Which cause of nephrotic syndrome is most likely to cause renal vein thrombosis>?
Membranous nephropathy
Seek secondary causes particularly occult malignancy
Treatment options for Membranous Nephropathy
1/3 spontaneous remission Persistent disease after 6-12 months or thromboembolic event RAS blockade Immunsuppression Rituximab (esp if PLAR2 +)
Secondary causes of minimal change disease
Malignancy - Hodgkins lymphoma - Thymoma Medications - NSAID's - Lithium - Pamidronate - Interferons
Treatment of minimal change disease
Initially: Glucocorticoids
Relapsing: Cyclophosphamide, calcinuerin inhibitors, mycophenolate or rituximab
Risk factors for progression of renal impairment
1) Renal impairment i.e GFR <90
2) Proteinuria (predicts ESRF and reducing it delays ESRF)
3) Diabetes
4) Hypertension
Mainstay of treatment for proteinuria in non-diabetic patients
Ace Inhibitor and salt restriction
Which anti-hypertensives reduce proteinuria and thus progression to renal failure
ACE inhibitor or ARB
- Reduce progression to ESRF
- Reduced cardiovascular death
Target BP in diabetic patients (no-nephropathy and nephropathy?)
No nephropathy: <130/85
Nephropathy: <125/75
Note blood pressure control has the greatest effect on delaying progression to ESRF in diabetics. Microvascular endpoints tight BP control is better than glycemic control.
Target BP in proteinuria?
<125/75
What is the most likely cause of death in a patient commencing dialysis?
Cardiovascular event
Need to monitor and control cardiovascular risk factors
Kidney biopsy findings in RPGN
Crescent formation
Specific diagnosis of cause is made with IF
Treatment of patient’s with non-infectious cause of RPGN
High dose pulse IV steroids then transition to oral steroids
- Pauci-immune GN: Cyclophosphamide/Rituximab
- ANti-GBM: Plasmapharesis in the context of pulmonary haemorrhage or rapid kidney failure to remove circulating antibodies
RPGN + Pulmonary Haemorrhage
Anti-GBM disease (Goodpastures)
Antibody against type IV collagen –> bind –> inflammatory response.
RPGN + Pulmonary Haemorrhage
Anti-GBM disease (Goodpastures). Cause of RPGN in young patients.
Antibody against type IV collagen –> bind –> inflammatory response.
Positive antibody for Anti-GBM 1
Kidney biopsy: crescents with linear deposition of immunoglobulin
Complement level = normal
Treatment: Plasmapharesis (to remove circulating antibodies), steroids and cyclophosphamide.
Pauci-immune glomerulonephritis causes and associations
Caused by microscopic vessel vasculitis affecting the kidney –> necrotising lesions but no immune deposits.
+/- systemic vasculitis
Complement levels normal.
Associated with
Granulomatosis Polyangitis (URT - C-ANCA (Pr3ANCA) +
Granulomatosis Polyangitis with eosinophils (Asthma/eosinophils)
Microscopic Polyangitis (Haematuria - PANCA (MPO ANCA) +
Treatment
Induction: Steroids + Cyclophosphamide +/- plasmapheresis
Rituximab for mild disease
Maintenance with azathioprine/mycophenolate/methotrexate
Pathophysiology of IGA Nephropathy
Abnormal IGA (Galactose deficient) –> Body forming antibodies against same –> immune complex formation –> inflammatory lesions in the glomerulus (or extra-renal sites in the context of HSP).
Classical presentations of IGA Nephropathy (two)
1) Asymptomatic microscopic haematuria
2) Haematuria post URTI (synpharyngitic nephritis)
Finding on microscopy of IGA Nephropthy
Mesangial proliferation and deposition of IGA
Crecent formation may be occasionally seen –> RPGN
Treatment for IgA Nephropathy
If proteinuria then commence on ACE
Can use steroids for six months
Which classes of lupus nephritis do you commence steroids for?
Most of III: Focal, proliferative <50% gloms involved
All IV: Diffuse, proliferagtive >50% gloms involved
V: Membranous LN If neprhotic range proteinuria
Induction: glucocorticoids + cyclophosphamide/mycophenolate
Infection related glomerulonephritis causative organisms
Streptococcus (onset 1-6 weeks post)
Staphylococcus (onset at time of infection)
Rarely gram negative organisms
Infection related glomerulonephritis diagnosis
Strep related: Anti-streptolysin-O antibodies or Anti-DNAase antibodies
Other
- Cultures to identify potential inciting organism
- Depressed complement levels, esp C3
- Kidney biopsy: diffuse endocapillary proliferation and exudative glomerulonephritis and C3 dominant IF staining (forming humps in a subepithelial location)
Membranoproliferative glomerulonephritis causes
Immune complex deposition - Monoclonal gammopathy - Autoimmune disease (SLE) - Hepatitis C Activation of the alternative pathway - Dense deposit disease - C3 glomerulonephritis
Membranoproliferative glomerulonephritis findings on biopsy
Immunoglobulin deposition +/- complement deposition
Mesangial and endocapillary proliferation with thickening of the basement membrane.
Glomerulonephritis with reduced complement levels
Infection related glomerulonephritis
Lupus nephritis
Membrano proliferative nephritis
Glomerulonephritis with normal complement levels
IgA Nephropathy Membranous nephropathy Anti-GBM1 Pauci-immune glomerulonephritis Minimal change disease FSGS
Hallmark of FSGS
Segmental scars in some glomeruli. Podocyte effacement but no immune deposits.
What type of collagen is affected in all port syndrome?
Type IV (similar as that affected in Anti-GBM disease or good pastures syndrome).
Elevation of which parameter carries this highest risk of mortality in dialysis patients?
Phosphate
How to reduce phosphate in dialysis patients?
1) Phosphate binder with food
2) Prevent hyperparathyroidism
- giving vitamin D
- Consider calcimimetics or PTH
Main reason to treat elevated phosphate in dialysis patients?
Reduce the risk of cardiovascular disease
Blood pressure targets
<140/90
<130/80 (diabetics)
Treatment for hypertension
1) ACE/ARB
2) Calcium channel blocker
3) Diuretic
*can individualised based on patient profile i.e for patient with BPH consider using prazosin.
Note: Three drugs at half standard dose will be more effective than one drug at maximal dose
Which anti-hypertensive to consider adding in context of resistant hypertension (hypertensive despite 3 agents)
Spironolactone (Rehot study) best add in if already on 2/3 agents.
Most common presentation of Conn’s
Hypertension and normokalaemia
Note severe = hypertension and hypokalaemia
HB target for patients on dialysis
110-130
When to given iron replacement therapy in CKD patients
HB <110
TSAT <30%
Ferritin <500
Given IV iron rather than oral iron as GIT absorption of iron insufficient to keep up with demand
In dialysis patients aim;
Ferritin >200
TSAT > 20%
What effect does vitamin D have on calcium and phosphate?
Gut absorption:
- Increase absorption of calcium and phosphate
Urinary losses:
- Reduces urinary losses of calcium and phosphate
Vitamin D = interested in building bone
What effect does Parathyroid hormone have on calcium and phosphate?
Urinary losses:
- Reduced urinary losses of calcium
- Increased urinary loss of phosphate
PTH is concerned with maintaining serum calcium homeostasis.
Initial investigation for primary hyperaldosteronism (conn’s syndrome)
Morning blood sample in seated patient
- Plasma aldosterone concentration
- Plasma renin activity
- ensure patient off eplenerone/aldosterone blockade/ amiloride
PAC/PRA >555 pmol/ng/ml = further investigation for primary hyperaldosteronism