15 - AKI, CKD and Glomerulonephritis Flashcards
What is the definition of an AKI?
Decreased renal function over a short period of time defined by a rise in serum creatinine from patients normal baseline, OR drop in urine output
- Rise in serum creatinine >26 umol/L within 48h
- Rise in creatnine >1.5 baseline within 7 days
- Urine output <0.5ml/kg/h for >6 consecutive hours
How is the severity of an AKI graded?
Stage 1: 1.5-1.9x rise in creatinine to baseline OR >26.5umol/L increase
Stage 2: 2-2.9 x rise in creatinine to baseline
Stage 3: >3x rise in creatinine to baseline OR renal replacement therapy initiated OR >353.6 umol/L increase
What are some limitations of the use of serum creatinine to define an AKI?
- Muscle mass dependent
- Dilution
What are some risk factors for AKI?
- Diabetes
- CKD
- IHD/CCF
- Aged>75
- Sepsis
- Medications e.g ACEi, NSAIDs, ARBs, Abx
MEASURE SERUM CREATININE DAILY IN HOSPITAL FOR THESE PATIENTS!!
What are some causes of an AKI? (commonest first)
(N.B look at picture)
Pre-renal: sepsis, cardiogenic shock, hypovolemia, heart failure, myeloma, hepatorenal syndrome, rhabdomyolysis, contrast induced, urate nephropathy
Renal: drugs, contrast, abx,
Post-renal: obstruction e.g stones, BPH
What are some complications of an AKI?
- CKD
- Hyperkalaemia
- Fluid overload
- Metabolic acidosis
What are some investigations you should do if there is an AKI to establish the cause?
- URINE DIPSTICK before catheter to look for proteinuria and haematuria
- US KUB within 48 hours if risk of obstruction to rule out
- LFTs for hepatorenal syndrome
- Check platelets, if low need to look at blood film for haemolysis (HUS/TTP)
- If blood on urine dipstick suspect intrinsic renal disease so check immunoglobulins, paraprotein, complement (C3/C4), autoantibodies
- FBC, U+Es, Bone profile, CRP, CK, Serum bicarbonate
What are some autoantibodies you should look for if you suspect nephritic disease is causing an AKI?
- Anti-GBM
- ANA
- p-ANCA
- c-ANCA
Also do myeloma screen, look at C3/C4 if suspect lupus nephritis and immunoglobulins
If you suspect an AKI is due to post-steptococcal GN, what investigation should you do?
Anti streptolysin O titres
What is involved in a haemolysis screen?
- Blood film
- LDH
- Bilirubin
- Reticulocytes
- Haptoglobin
CALL RENAL SpR URGENTLY
What are some things you should monitor in a patient with AKI?
- Daily creatinine until falls
- Fluid balance with catheter and hourly urine out put
- K+ until creatinine falls
- General observations every 4 hours
- Lactate if signs of sepssi
How is an AKI managed in general?
- Treat underlying cause
- Consider referral to renal/critical care for dialysis
- Send off investigations to find out cause
- Stop any nephrotoxic drugs and change dose of any drugs e.g antibiotics
- Check volume status and correct if too high or low
- Monitor urine output and daily bloods
- Avoid hyperglycaemia
How are the different types of AKI managed in general?
Treat underlying cause. For all types manage fluid balance, hyperkalemia and consider those who may need renal replacement
Pre-renal: correct volume depletion, correct any sepsis, cardiac support
Renal: refer for biopsy and treatment of intrinsic renal disease
Post-renal: catheter, nephrostomy or urological intervention
How should you treat patients with an AKI that have fluid overload?
- IMMEDIATE REFERRAL TO RENAL/CRITICAL CARE FOR RENAL REPLACEMENT THERAPY
- Monitor weight daily
- Oxygen supplementation if required
- Fluid restriction
- Loop diuretics if symptomatic overload
What are dangers of giving sodium bicarbonate to correct a metabolic acidosis caused by an AKI?
- Generates CO2 so need adequate ventilation
- May precipitate fluid overload due to the sodium in it
When should you refer a patient with an AKI to the renal team?
e.g if they developed an AKI on cardiology ward when do you escalate?
- AKI not responding to treatment
- AKI with complications e.g fluid overload, acidosis, rising K
- AKI stage 3
- AKI with difficult fluid balance e.g heart failure
- AKI due to intrinsic renal disease
- AKI with hypertension
What are some indications for renal replacement therapy in an AKI?
- Fluid overload refractory to diuretics
- Metabolic acidosis refractory to treatment
- Hyperkalaemia refractory to treatment
- Uraemic pericarditis
- Uraemic encephalopathy
- Intoxications e.g methanol, salicyclates, lithium
What are some possible complications of using RRT to treat an AKI?
- Risks of catheter insertion e.g pneumthorax, infection
- Procedural hypotension
- Bleeding due to need for anticoagulation
- Altered nutrition
- Drug clearance
What are some causes of a raised serum urea?
- AKI
- Upper GI bleed (not lower)
- Dehydration
How can you distinguish malena due to a upper and lower GI bleed?
Upper GI cause will have raised serum urea
What is the definition of CKD?
Presence of kidney damage (abnormal structure or function) for >3 months.
Measured using eGFR and albuminuria
Need to have markers of kidney damage or decreased function on 2 occasions in 3 months
How is chronic kidney disease classified?
Using eGFR and ACR on KDIGO score
Stage 1: eGFR>90 with proteinuria
Stage 2: eGFR <90 but more than 60 with proteinuria
Stage 3A: eGFR<60
Stage 3B: eGFR<45
Stage 4: <30
Stage 5: <15 kidney failure
What does the KDIGO score calculate?
Risk of adverse outcomes with CKD based on ACR/Albuminuria and eGFR
The G part of the KDIGO score is for eGFR. What does the A score stand for?
ACR or albuminuria
A1
A2
A3
What are the three most common causes of CKD and then some other causes?
- Diabetes
- Glomerulonephritis
- Hypertension
- Renal vascular disease
- Polycystic kidney disease
- Obstructive nephropathy
- Recurrent UTIs
What are some complications with CKD?
- CVD (Number 1 cause of mortality)
- Anaemia of CKD
- Mineral and bone disease
- Secondary hyperparathyroidism
- Malnutrition
- Dyslipidaemia
- AKI
- Late stage: electrolyte disturbance, fluid overload, metabolic acidosis, uraemic pericarditis/encephalopathy
What are some important questions in the history when trying to work out the cause of a patient’s CKD?
- History of DM, HTN, IHD, renal colic?
- Ask about previous UTIs?
- Drug history?
- Family history of renal disease or SAH?
- Check systems review e.g eyes, skin, joints for systemic disorders
What are some important things to check on examination of a patient with CKD?
- Peripheries
- Face
- Neck
- CVS
- Respiratory
- Abdomen
What are some important investigations to do for a newly diagnosed CKD patient?
- Bloods: U+Es, Hb, glucose, HbA1c, decreased Ca, increased PO4, increased PTH, ANA/ANCA/Anti-GBM
- Urine: dipstick for proteinuria, MC+S, ACR, Bence Jones for myeloma
- Imaging: USS for size (may be smal) and symmetry. Look for APKD
- Histology: renal biopsy if progressive disease or nephrotic syndrome
How often should you monitor renal function in CKD paitients?
- Check eGFR and albuminuria
- Drop >25% or >5ml in a year is significant
Low risk: annually
High risk: every 6 months
Very high risk: every 3-4 months
What are some risk factors for CKD progression?
- HTN
- DM
- Volume depletion
- NSAIDs
- Smoking
- AKI
- Untreated urinary outflow obstruction
Who is involved in an MDT for patients with CKD?
- Renal consultants
- Renal specialist nurses
- GP
- Dieticians
- Pharmacists
- Vascular/transplant surgeons
When should you refer someone with CKD to nephrology?
- Stage 4 and 5
- Moderate proteinuria ACR>70 unless diabetic
- Proteinuria with haematuria
- Declining eGFR (SEE IMAGE)
- Poorly controlled BP despite 4 antihypertensives
- Genetic cause of CKD
What are the 5 principles of management for CKD?
1. Treat underlying disease e.g HTN, diabetes, tolvaptan for ADPKD
2. Reduce progression of CKD e.g reduce proteinuria with ACEi/ARBs, control BP
3. Reduce cardiovascular risk e.g statin, bp/DM control, stop smoking
4. Prevent or treat complications of CKD e.g anaemia, oedema, bone-mineral disorders
5. Future planning for RRT
What drugs are patients with CKD started on and why?
- Statin: reduce CVD risk
- Low dose aspirin: reduce CVD risk
- Antihypertensives: BP control to prevent complications and progression of CKD
- ACEi/ARB: reduce proteinuria to prevent progression of CKD
- Diabetic control
What measures are put in place to reduce risk of progression of CKD and reduce the cardiovascular risk?
Reduce progression:
- ACEi or ARB if proteinuria
- Glycaemic control
- Lifestyle advice e.g weight loaa, smoking cessation, sodium restriction
Reduced CVD risk:
- Statin
- Aspirin
- Control BP and diabetes
- Stop smoking, exercise, lose weight
In general, what is given to CKD patients to prevent or treat complications that can arise from CKD?
Diet: low K/low phosphate and phosphate binders
Anaemia: EPO and IV iron/folate/B12
Bone-mineral disorders: Vitamin D supplement, Calcimimmetics for hyperparathyroidism
Oedema: restrict fluids and sodium intake, loop diuretics
Acidosis: sodium bicarbonate with caution in HTN and overload patients due to Na component
When considering referring a CKD patient for renal replacement theray, what things need to be done?
- Put on deceased donor transplant list 6 months before start of RRT. Work up for transplant
- Consider where haemodialysis units are
- Refer for fistula (venous mapping) or PD catheter
What blood tests should you interpret with a pinch of salt when a CKD patient has an eGFR<60?
- Troponins
- BNP
Will naturally be raised
How is diabetic nephropathy diagnosed as CKD and managed?
Dx:
- Early morning ACR is raised (albumin:creatine ratio)
- Evidence of other microvascular disease
- Evidence of long standing poorly controlled diabetes
Mx
- ACEi/ARB* to reduce proteinuria
- Antihypertensives* for BP
- CVD risk factor modification*
- Check for other microvascular complications e.g foot checks, retinopathy
Hypertension can cause CKD, however it is sometimes difficult to tell whether the HTN has caused the renal disease or the other way around.
What are some investigations done to identify if HTN is due to a primary or secondary cause and how is it treated if primary?
Ix
- 24 hour metanephrines rules out phaeochromocytoma
- Aldosterone:Renin ratio rules out primary hyperaldosteronism
- Cortisol and Dexamethasone suppression test rules out Cushings
- TSH to rule out hyperthyroidism
- MRA to rule out renal artery stenosis
Mx
- Lifestyle changes e.g weight loss, stop smoking, reduce stress
- Antihypertensives (ABCD)
Polycystic kidney disease can cause CKD. How is this diagnosed?
- Symptoms: asymptomatic, flank pain/haematuria from cysts
- Family history is key
- USS
What is the inheritance pattern of polycystic kidney disease, and what gene is affect?
Autosomal Dominant
Type 1 (85%): PKD1 mutation on chromosome 16
Type 2 (15%): PKD2 mutation on chromosome 4
How is CKD caused by ADPKD treated?
- Control BP
- Tolvaptan (Vasopressin receptor-2 antagonist) to slow progression of CKD
- Genetic counselling and testing
Why does anaemia develop in CKD?
- Decreased EPO production from kidneys
- Absolute iron deficiency from malnutrition and poor absorption
- Functional iron deficiency due to inflammation and less hepcidin clearance
- Bone marrow suppression from uraemia
- Shortened RBC life span
- Blood loss
- Deficiency of B12/folate
How is anaemia in CKD managed?
- Measure B12, Folate, Ferritin, Iron, Transferrin saturation
- If deficient in any of above replace. Best to do Iron IV
- Consider EPO (ESA)
How do you manage oedema and acidosis that might arise as a complication of CKD?
Oedema: fluid restrict, sodium restrict, loop diuretics
Acidosis: sodium bicarbonate only if not hypertensive or fluid overloaded
Why does secondary hyperparathyroidism occur in CKD?
- Decline in hydroxylation of Vitamin D in kidneys
- Less vitamin D so less Ca reabsorbed from gut
- Low Ca causes parathyroid to release PTH to resorb Ca from bone and increase gut absorption. This also causes phosphate increase
What is tertiary hyperparathyroidism and how does it develop in CKD?
When PTH release continues to be high despite normal/raised Ca levels
Due to parathyroid gland nodular hyperplasia which is due to long standing secondary hyperparathyroidism
Why does CKD-Bone Mineral Disease develop?
Development of secondary hyperparathyroidism
- Vitamin D deficiency due to less hydroxylation in kidneys
- Hypocalcaemia so Ca dragged from bones due to increase PTN
- Hyperphosphataemia
What investigations should you do if you suspect CKD-MBD?
- Serum Ca and PO4
- ALP
- PTH
- Vtamin D
How is CKD-MBD diagnosed?
Evidence of any of the following:
- Abnormalities of Ca, PO4, ALP, PTH or Vitamin D metabolism
- Vascular or soft tissue calcification due to phosphate
- Osteomalacia
How is CKD-MBD managed?
Hyperphosphataemia:
- Restrict phosphate in diet
- Phosphate binders (e.g calcium carbonate or aluminum hydroxide) to prevent vascular calcification. Better with no Ca
Low Vitamin D:
- Ergocalciferol or Colecalciferol to suppress PTH
- If above do not work synthetic Paricalcitol can be used that doesn’t absorb as much Ca but suppresses PTH
General
- Consider oral bisphosphonates
- Consider parathyroidectomy and calcimimmetics if progressed to tertiary hyperparathyroidism
Why is CKD-MBD an issue?
- Risk of CVD due to vascular calcification
- Risk of osteoporosis
What does glomerulonephritis mean?
Umbrella condition for a number of conditions that:
- Are caused by pathology in the glomerulus
- Present with proteinuria, haematuria or both
- Are diagnosed with renal biopsy
- Cause CKD
- Can progress to kidney failure (NOT minimal chanfe disease)
- Can be nephritic or nephrotic
What is the mainstay of management for glomerulonephritis?
Supportive: ACEi/ARB, control BP, salt and water restriction if overloaded, diuretics, VTE prophylaxis if albumin <20, statins for hypercholesterolaemia
Immunosuppressive therapy: IV/Oral corticosteroids, cyclophosphamide, tacrolimus, ciclosporin, azathioprine
Invasive: RRT if AKI/ESRF, plasma exchange if anti-GBM or AAV
What is nephrotic syndrome?
- Oedema
- Hypoalbuminaemia (<30)
- Proteinuria/PCR >350 or >3g/24h
Also hypercholesterolaemia
What is the pathophysiology of nephrotic syndrome?
Filtration barrier of the kidneys (podocytes, basement membrane and endothelial cells) is damaged, usually the podocytes
This allows protein through into the urine causing low albumin. This decreases osmotic pressure in capillaries so less interstitial fluid reabsorbed so oedema
Liver tries to produce more albumin but this causes hypercholesterolaemia
What are some of the complications of nephrotic syndrome?
- VTE
- Progression of CKD
- Hypertension
- Hyperlipidaemia
- Risk of infections
What are some causes of nephrotic syndrome?
- Minimal Change Disease (most common in kids)
- Focal Segmental Glomerulosclerosis (idiopathic, infection, malignancy or drugs)
- Membranous Nephropathy (underlying malignancy or inflammation)
- Membranous Proliferative GN
- Secondary: DM, Myeloma, Lupus nephritis, amyloidosis
How is nephrotic syndrome managed?
- Treat underlying cause: Take renal biopsy and give drugs to induce remission. If child don’t biopsy just give steroids as likely to be minimal change so will respond to this
- Reduce oedema: water and Na restriction, loop diuretics with added thiazides if needed, daily weights
- Proteinuria: use ACEi/ARB
- Reduce complications (next flashcard)
Why do the following complications arise in nephrotic syndrome and how are they managed?
- VTE
- Infections
- Hyperlipidaemia
VTE: Hypercoagulable due to increased clotting factors and less ATIII. If VTE occurs give LMWH. If albumin <20 consider prophylaxis
Infections: Urine losses of immunoglobulins and immune mediators. Ensure pneumovax given
Hyperlipidaemia: Liver tries to compensate for low albumin by making more but produces more lipids as lipids broken down for albumin. Statin
What is nephritic syndrome?
Inflammation of the glomerular capillaries leading to:
- Oliguria
- HTN
- Haematuria
Can sometimes have AKI
What is the pathophysiology of nephritic syndrome?
Inflammation of the glomerular capillary walls leads to leakage and haematuria
Cells in the Bowman’s capsule leads to less filtration so oliguria and HTN
(see image)
What are some causes of nephritic syndrome?
- IgA nephropathy (most common, a.k.a Burger’s disease)
- Post streptococcal GN
- Small Vessel Vascuitis (ANCA associated)
- AntiGBM (a.k.a Goodpasture’s syndrome)
- Alport syndrome
- Lupus nephritis
What is post-streptococcal glomerulonephritis and how is it investigated if suspected?
- Nephritic syndrome after Group A beta haemolytic strep infections (1-2 weeks after throat or 3-4 weeks after impetigo/cellulitis/skin). Due to antibodies depositing and complement activated
- Usually occurs in children 3-12 and can lead to RPGN
- Investigations: Bloods (Antistreptolysin O ASO titre and Low serum C3) and Renal Biopsy (immune complex deposition IgG, IgM, C3)
How is post-streptococcal GN treated?
- Often self-limiting
- Supportive: ACEi/ARBs for proteinuria and hypertension, low sodium diet, antibiotics
- RRT if progresses to renal failure
What is IgA nephropathy and who does it tend to affect?
- Most common nephritic syndrome that is either asymptomatic or episodic haematuria during or just after URTI or GI infection
- Affects men more than women and tends to occur aged 20-30
- 1/4 of patients will develop ESRF within 20 years
What are some investigations you should do for IgA nephropathy?
- Bloods: increased serum IgA, normal C3/C4
- Urine: microhaematuria or intermitten visible haematuria
- Renal Biopsy: IgA immune complex deposition in mesangium
How is IgA nephropathy treated?
- ACEi/ARB for proteinuria and hypertension
- Steroids if persists over 6 months
What are some ANCA associated vasculitis conditions that can cause glomerulonephritis?
- Granulomstosis with polyangitis (GPA)
- Microscopic Polyangitis (MPA)
- Churg-Strauss Syndrome (eosinophillic granulomatosis with polyangitis)
How do you distinguish between the different ANCA associated GN using the symptoms and investigations?
All have segmental necrotising GN on biopsy but different ANCAs
How is ANCA associated vasculitis treated?
- Immunosuppression e.g corticosteroids, cyclophosphamide, ciclosporin
- Plasma exchange for Churg-Strauss Syndrome
What is Anti-GBM (Goodpastures) disease and how does it present?
- Autoantibodies against type IV collagen that is in alveolar and glomerular basement membranes
- Usually nephritic syndrome and pulmonary haemorrage (haemoptysis)
- Occurs in 30s and 60s most
How is anti-GBM diagnosed and managed?
Diagnosis:
- Bloods: anti-GBM antibodies
- CXR: pulmonary infiltrates
- Biopsy: linear deposition of IgG on basement membrane
Management:
- Plasma exchange
- Immunosuppression with corticosteroids and cyclophosphamide
Thin Basement Membrane Disease and Alport syndrome can both cause glomerulonephritis. How can you distinguish between the two?
- Both often have persistent microscopic haematuria and intermittent visible haematuria
- Differences on biopsy! (see image)
How are thin basement membrane disease and Alport syndrome that are causing GN managed?
Thin BM disease: monitor renal function and give supportive treatment
Alport: supportive treatment, RRT, renal transplant but risk of Anti-GBM (Goodpasture’s) developing
How are thin basement membrane disease and Alport syndrome inherited?
Thin BM: autosomal dominant
Alport: X-linked recessive
Lupus nephritis can cause nephritic or nephrotic GN. What is the treatment for this?
- Supportive
- Immunosuppressive depending on type of lupus nephritis
What is rapidly progressive GN and what is it caused by?
Any aggressive GN that progresses to renal failure over days or weeks
- Anti-GBM
- Lupus Nephritis
- ANCA associated vasculitis
- IgA
- Membranous
How is rapidly progressive GN diagnosed and treated?
Dx:
- Biopsy: crescents on biopsy as breaks in the GBM has allowed inflammatory cells in
Mx:
- Corticosteroids
- Cyclophosphamide
- Plasma exchange if ANCA/Anti-GBM
- Biologics if lupus nephritis
How are the following nephrotic glomerulonephritis treated:
- Minimal change disease
- FSGS
- Membranous Nephropathy
- Membranoproliferative GN
Minimal change: prednisolone for 4-16 weeks. If relapse can give cyclophosphamide or calcineurin inhibitors
FSGS: ACEi/ARB and BP control. Can give steroids and calcineurin inhibitors second line
Membranous: ACEi/ARB and BP control. Only immunosuppression if high risk of progression
Membranoproliferative: same as above
