Nephrology Flashcards
What is the GFR of a neonate?
20-30ml/min/1.73m2
Becomes adult GFR at age 2
What are the 5 major functions of the kidney?
Waste handling - urea/creatinine Water handling Salt balance - K/Na/Ca/phosphate Acid base control - bicarbonate Endocrine - RAAS/PTH/activation of vit D/EPO
What are the three layers composing the glomerular filtration barrier?
Endothelial cell layer: fenestrated to allow all components of plasma apart from RCs through
Glomerular basal lamina/basement membrane: blocks large proteins getting through
Podocytes: slits prevent medium sized proteins getting through
What is the GBM composed of?
Type IV collage and laminin
What are podocytes composed of?
Proteins (podocin/nephrin)
What are the mesangial cells?
Glomerular structural support
Embedded within GMB
Regulates blood flow of glomerular capillaries
What signifies glomerular injury?
PROTEINURIA
What symptoms are more down the nephritic end of the spectrum of renal damage?
Increasing haematuria
Intravascular overload
What symptoms are more down the nephrotic end of the spectrum of renal damage?
Increasing proteinuria
Intravascular depletion
What are the congenital glomerulopathies?
Podocyte cytoskeleton integrity disorders - defects in podocin/nephrin proteins (AR)
Basement membrane defects - Alports (XL), thin basement membrane dx (AD)
Endothelial/microvascular integrity - complete regulatory proteins (MPGN)
What occurs in nephrotic syndrome?
Proteinuria
Hypoalbuminaemia
Oedema
Why do you get oedema in hypoalbuminaemia?
Not enough oncotic pressure to balance out hydrostatic forces driving water out of cells
What is the appearance of proteinuria?
Frothy urine
How do you test for proteinuria?
Dipstix - 3+ or more usually abnormal
Protein creatinine ratio - early morning urine best (normal Pr:Cr ratio <20mg/mmol, nephrotic range >250mg/mmol)
24hr urine collection is gold standard but not really practical
Why would someone with nephrotic syndrome have low urine sodium?
They are trying to retain sodium to try and retain IV volume
Most kids with nephrotic syndrome will have what?
Minimal change disease (idiopathic)
What are the typical features of MCD?
2-5yrs Nephrotic syndrome Normal BP Resolving microscopic haematuria Normal renal function Steroid responsive
When should you biopsy in suspected MCD?
Only if suggestion of autoimmune dx, abnormal renal function, steroid resistance
How do you Rx nephrotic syndrome (MCD)?
Prednisolone (8wks)
If MCD should go into remission within 2 weeks
What must you warn parents of when putting kids on prednisolone?
SEs - esp. behavioural problems (irritable, moody), GI distress, may impact growth if long term
Check varicella status and pneumococcal vaccination as is immunosupressive
What is the pathogenesis of MCD?
T cell and cytokine mediated damage of the GBM and podocytes –> albumin can leak through and is excreted
What is the prognosis for MCD?
80% long term remission
If MCD is steroid resistant what can you treat it with?
Probably more FSGS if steroid resistant
Can Rx with cyclosporin, tacrolimus, rituximab etc.
What is the most common cause of steroid resistant nephrotic syndrome?
Focal segmental glomeruloscerosis (FSGS)
Infant presentations may be congenital dx e.g. NPHS1, NPHS2
What occurs in FSGS?
Podocyte loss
Progressive inflammation and sclerosis
When should you investigate haematuria?
Macroscopic or microscopic > trace on 2 occasions
What is haemaglobulinuria?
Stix positive & microscopy negative
What does persistent haematuria and proteinuria indicate?
Glomerular disease
What are the causes of macroscopic haematuria?
Glomerulonephritis (post-infectious GN, IgA/HSP), SLE UTI Trauma Stones HUS etc.
What are the causes of microscopic haematuria?
GN (post-infectious GN, IgA, HSP), SLE, ANCA +ve vasculitis UTI Trauma Stones/hypercalcuria HUS Sickle cell dx etc.
What investigations do you want to do in haematuria?
Dipstix Red cells on microscopy Creatnine & electrolytes FBC Albumin Urine culture
What features are consistent with nephritic syndrome?
Reduced GFR Oliguria Fluid overload (raised JVP, oedema) HTN Haematuria Proteinuria
What are the causes of nephritic GN?
Post-infectious GN HSP/IgA nephropathy Membranoproliferative GN Lupus nephritis ANCA positive vasculitis
How do you investigate nephritic GN further?
Renal USS
Anti-streptolysin O titre
Throat swab for GAS
Complete (C3 low, normal C4 as C3 being used in PIGN)
Immune dx - ANA/ANCA
Biopsy not required if ASOT high, nephritic syndrome and +ve throat swab - you know its post-infectious GN
What is ASO?
Antibody against exotoxin produced by group A (C and G) strep
What tends to cause post-infectious glomerulonephritis?
Usually group A (beta-haemolytic) strep
Infection in throat - 7-10 days or skin - 2-4 days
What is thought to cause post-infectious GN?
Glomerular trapping of circulating immune complexes
Nephrogenic antigens on strep bind specific sites in glomerulus
Either of these set up humeral/cellular immune response and activate alternative complement pathway –> AKI
What is the prognosis of acute post-infectious GN?
Self-limiting
How do you diagnose post-infectious GN?
Bacterial culture
+ve ASOT
Low C3 - ensure this normalises - if it doesn’t MPGN is differential diagnosis
How do you Rx post-infectious GN?
Antibiotics (penicillin for GAS)
Support renal function
Overload/HTN (diuretics)
What is the most common GN?
IgA nephropathy
What are typical features of IgA nephropathy?
1-2 days after URTI
Usually adults/older children
Recurrent macroscopic haematuria +/- chronic microscopic haematuria
Varying degree of proteinuria
What is the pathogenesis of IgA nephropathy?
Defective (galactose deficient) IgA clump together and deposit in the kidney –> glomerulonephritis
How do you diagnose IgA nephropathy?
Clinically - +ve autoimmune workup, normal complement
Confirmation biopsy
How do you Rx IgA nephropathy?
Mild disease - proteinuria with ACEi
Mild-mod: immunosuppression
What is the prognosis of IgA nephropathy?
25% end stage renal failure 10yrs post diagnosis
What is Henoch schonlein purpura IgA related vasculitis?
5-15yo Mandatory palpable purpura + 1 of: Abdominal pain Renal involvement Arthritis/arthralgia Biopsy - IgA deposition
Basically it is IgA vasculitis with nephritis
What tends to cause IgA vasculitis?
1-3 days post-trigger, e.g. viral URTI (strep, drugs)
How long does IgA vasculitis tend to last?
4-6 weeks
In IgA vasculitis what is the nephritis a result of?
Mesangial injury
How do you Rx IgA vasculitis?
Steroids
Immunosupression (if mod-severe renal dx) - cyclophosphamide/prednisolone
Long term - HTN & proteinuria
Define AKI
Abrupt loss of kidney function –> retention of urea & other nitrogenous waste productions & dysregulation of extracellular volume & electrolytes
Serum creatinine >1.5x age specific reference/prev. baseline
UO <0.5ml/kg for 8h
What findings are typical of AKI?
Anuria/oliguria (<0.5l/kg/hr)
HTN with fluid overload
Rapid rise in plasma creatinine
What are the classifications of AKI?
AKI 1 - Cr >1.5-2x reference creatinine/ULRI
AKI 2 - Cr 2-3x reference creatinine/ULRI
AKI 3 - Cr >3x reference creatinine/ULRI
What is involved in the Mx of AKI?
Monitor - UO, PEWs, BP, weight
Maintain - good hydration
Minimise - drugs
What are the pre-renal causes of AKI?
Perfusion problems
E.g. volume depletion, hypotension, drugs, renal artery stenosis
What are the intrinsic renal problem causes of AKI?
Glomerular disease - HUS, GN
Tubular injury - ATN
Interstitial nephritis - NSAIDs, autoimmune
What is ATN?
Acute tubular necrosis
Consequence of hypoperfusion/drugs
What are the post-renal causes of AKI?
Obstructive
What does HUS tend to follow after?
Entero-haemorrhagic E. coli (verocytotoxin/shigella toxin) - E. coli 0157 - tends to be 14 days after onset of diarrhoea
Other causes: pneumococcal infection, drugs
What % of children with E. coli 0157 infection will develop HUS?
15%
What does E. coli 0157 colonise?
Sheep/cattle
What is the triad of HUS?
Microangiopathic haemolytic anaemia
Thrombocytopenia
AKI
How do you Rx HUS?
Monitor 5 kidney functions - HTN, IV saline/fluid, RRT
Don’t use antibiotics
What are the complications of HUS?
Seizures, acute abdomen, diabetes, adrenal crisis
May evolve into CKD
What are the causes for paediatric CKD?
Congenital abnormalities of the kidney & urinary tract (e.g. reflux nephropathy, dysplasia, obstructive uropathy)
Hereditary conditions, e.g. cystinosis, cystic kidney disease
CAKUT may not be isolated. What things may it be related to?
Turner
Trisomy 21
Branchio-oto-renal
Prune belly syndrome (absence of abdominal muscles, bilateral cryptorchidism, urinary tract malformations)
Under what GFR do you start to get signs and symptoms of CKD?
60 (large renal reserve)
CKD 2 is asymptomatic
At CKD 5 think about RRT
What is the presentation of CKD?
Pruritus Encephalitis Polyuric (tubular damage) Salt wasting - low Na, K usually high Bladder dysfunction Anaemia HTN - RAAS raised ETC
Define UTI
Symptomatic + bacteria culture from MSSU or any growth on suprapubic aspiration/catheter
What are the symptoms of UTIs?
Neonates - fever, vomiting, lethargy, irritability, poor feeding
Children - fever, dysuria, frequency, abdominal pain, poor feeding, vomiting, nocturnal enuresis
How can you obtain urine specimens from children?
Clean catch urine/MSSU
Collection pads/urine pags
Catheters/suprapubic aspiration if sick
How can you make a diagnosis of a UTI?
Dipstix - leucocytes & nitrates may indicate UTI (but unreliable under 2y)
Microscopy - pyuria >10 WBC per cubic mm, bacturia
Culture >10^5 colony forming units (E. coli)
How is VUR graded?
1 - ureter only 2 - ureter, pelvis, calyces 3 - dilatation ureter 4 - moderate dilatation of ureter 5 - gross dilatation/tortuosity
When do you Rx UTIs?
<6m
Abnormal anatomy/bladder
Septic presentation
Recurrent UTIs
In which children do you screen in UTIs?
Screen in those at risk of progressive scarring (reflux nephropathy)
Capture those with renal dysplasia
What investigations can you do to look at the kidneys?
USS - structure
DMSA - scarring/function
Micturating cystourethrogram/MAG3 - dynamic
How do you Rx UTIs in children?
Lower tract - oral antibx 3 days (trimethoprim, coamoxiclav, cephalosporin)
Upper tract/pyelonephritis - antibx for 7-10 days PO if systemically well
How do you prevent UTIs?
Good hygiene
Avoid constipation
Keep hydrated
What factors affect progression of CKD?
Late referral HTN Proteinuria High intake protein, phosphate, salt Bone health - PTH, phosphate, Vit D Acidosis Recurrent UTIs
How is CKD classified?
KDIGO 2012
How do you measure BP in a child?
Doppler
Oscillometry
Sphingmanometer
24h ambulatory BP monitoring
What factors affect BP?
Sex, age, height
Define HTN
95th centile over above
Borderline is 90-95th centile
How do you Mx CKD?
Watch protein intake Salt, K restriction EPO for anaemia ACEi for HTN etc.
For bone dx - low phosphate diet, phosphate binders, active vit D
If poor on-going growth - HGH
What heart problems do you get in CKD?
Accelerated atherosclerosis
