High yield Flashcards
What role does dopamine have on AKI
NONE
- 3 systematic reviews - concluded no benefit in treating or preventing AKI
- potential harm - incl MI, arrhythmias and reduced intestinal blood flow
e. g Fenoldopam - BAD
Treatment of severe malaria
- mortality 15-25% - jaundice, severe anaemia, ARDS
- IV artesunate - treatment of choice for severe malaria!!!
- resistance has emerged in SE asia - single point propeller region mutation - chromosome 13
- Severe malaria
- IV artesunate 2.4mg/kg bolus IV then daily (S/e cerebellar ataxia)
- switch to oral artemether-lumefantrine to complete 3 days
- if not available, then do IV quinine instead of atesunate
Prophylaxis of malaria
Mefloquine - effective against both vivax and falciparum - resistance in thailand, cambodia - start 2 wks before travel, 4 weeks after reutrn, SE - GI , cardiac, neuro - psychotic episodes, safe in 2nd and 3rd trimester of pregnancy
Doxycycline - 1 day before and 4 weeks on return - contraindicated in pregnancy - SE - photosensistivity, GIT upset, OCP ineffective
Malarone - expensive, start one 1 day before, continue one week after
insufficient data on pregnancy
what is medullary sponge kidney and cystic kidney
Medullary sponge kidney - common, malformation of terminal collectiing ductos - microscopic and macro medullary cysts - generally bilateral
- benign, but associated with nephrolithiasis and UTIs
- majority causes sporadic then inherited
Medullary cystic kidney - misnomer - majority do not have renal cysts evident on imaging - predom a tubulo-interstitial disorder - progress to ESRD
define acute infective endocarditis and likely organisms
Short history (days) of fevers, rigors, unwell,
hypotension, embolic lesions, heart failure
– Aggressive organism eg Staphylococcus aureus
what is NGAL? - Neutrophil Gelatinase Associated liocalin?
- originally found bound to gelatinase from human neutrophils
- expression upregulated following ischaemia in renal prox epithelial cells
- INCREASE in NGAL in blood probably from other organs
- INCREASE in NGAL in urine from renal tubular cells - predicts development of AKI early and sustained AKI.
Define PUO
- Prolonged illness (2-3 weeks duration)
- Fever (above 38.3C) on several occasions
- No diagnosis after intelligent investigations
What is dengue fever?
- spread
- incubation?
- serotypes?
- flaviviruses - spread by mosquitoes
- 4 serotyes - 1 to 4, incubation 3-10 days
- four clinical syndromes - undifferentiated fever, classic fever, dengue hemorrhagic fever, dengue shock syndrome (DSS severe form)
what is autosomal dominant polycystic kidney disease
- inherited disease
irreversible decline in kidney fn, most common cause of genetic cause of CKD - 5% sporadic, 75% fmhx
accnts for 5% of pts with ESRD on dialysis
PKD1 - chromosome 16 - polycystin 1 - more RAPID deterioration, more cysts and ESRD at age 54
PKD2 - chromosome 4 - protein polycystin 2 - more indolent decline renal fn, median age ESRD 74
What is the duke criteria
Duke Criteria (Durack) 1994
– Pathological criteria
– Clinical criteria
2 major - microbiology - typical bugs in two bottles, persistantly positive BC with unusual organism, endocardial involvement - echo criteria and new murmur or positive serology for C.burnetti
1 major and three minor
- 5 minor, fever over 38, vascular phenomena, immunological (osler, roth, glomnephritis), heart cond or IVDU, suggestiev microbio
Nephrotoxic agents that can contribute to AKI
- radiocontrast
- aminogylcosides
- cisplatin
- ACEI, ARBs
- NSAIDs
- Tacrolimus, cyclosporin
What antibiotics to use when resistance - carbapenems, aminoglycosides, colistinm tigecycline, fosomycin?
- Carbapenems - use only if low level Resistance - double therapy
- aminoglycosides - use only if not Resistance (amikacin> gent)
- colistin - nephrotoxicity - complicated dosing
- tigecycline - inappropriate for bacteraemia - large Vd, increased mortality - does not cover pseudomonas
- fosomycin - strongest data only for UTI/prostate
Haematuric renal disorders - general classification
- proliferation of resident glomerular cells
- mesangial
- epithelial
- endothelial
- influx of systemic inflamm cells
minimal change disease ?
- not associated with progressive renal insufficiency
- based upon histopath
- renal biopsy normal on light micro
- electron micro - reveals effacement flattening of podocyte foot processes
- disruption of integrity of protein barrier - resulting in heavy proteinuria
- 90% of cases of nephrotic syn in child less than 10, 10-15% of adult cases of nephrotic syn
- other causes - malignancy (haem) or drugs (NSAIDs and cox2, bisphosphonates)
Tx for PCKD
- vasopressin receptor antagonist - Tolvaptan
other novel tx
- mTOR - rapamycin - no difference
Mx - HTN, haematuria, UTIs, calculi
extra renal - liver disease, vascular (aneurysms, valvular heart disease
Rhabo summary
- leakage of muscle cell contents into circulation
- myoglobin - filtered by glomerulus, enters tubular epi cells - causes toxicity through vasocons (intra renal , direct tub toxicity thru oxidative damage and tubular obstruction in distal tubules
- precipitation of myoglobin within tubules when interacts with TAMM- HORSFALL protein, favoured by acidic urine
- risk of AKI low when CK less than 15-20k
- hypocal can occur due to calcium entering damaged muscle, rise in potassium
Tx - FLUIDS, some evidence for iv sodium bicarb, minimal evi for mannitol
Most common causes of AKI
- SEPSIS
major surgery, cardiogenic shock, hypovolemia, medications
hepatorenal syndrome, trauma, cardiopul bypass, rhabdo, obstructive uropathy
acquisition of which gene makes staph aureus methicillin resistant
SCC MEC - staph casette chromosome mec
most common is MEC A
what is cystic renal disease?
- acquired cystic disease of kidney
multiple bilateral renal cysts
different from ADPCKD - no fam hx, small to normal sized kidneys and smooth contour
associated with renal cell cancer - no screening in AUS
What is chikungunya
- alphavirus
- spread by aegypti and albopictus mosquitos
- same mosquitos that spread dengue fever
- India, malaysia, carribbean
- incubation 2-4 days - range 1-14 days
- Sx FEVERS, arthralgias, rash and myalgia
- Dx - serology and alphavirus PCR
- 72-97% get symptomatic disease - arthritis can be debilitating - bent posture
Define sub acute endocarditis
– Long history (weeks to months) “PUO”
– Malaise, fever, night sweats, weight loss
– Immunological and embolic phenomena
Tx for uncomplicated malaria
- First line - ARTEMETHER-LUMEFANTRINE (riamet)
- 4 tabs BD for 3 days, take with fatty food, >95% cure in p.falciparum, p.vivax good efficacy
- second-line - atovaquone-proguanil (Malarone)
- 4 tabs daily for 3 days, slower parasite clearance than riamet
- treatment failure reported
- can also be used for prophylaxis
- Third line
- quinine + doxy/clinda for 7 days
- mefloquine to be dropped
- quinine + doxy/clinda for 7 days
What are the common complications of endocarditis?
- CCF from valvular dysfunction
- Embolisation - risk drops after first week of abx therapy - increase if >1cm ant MV vege or S. aureus
- Periannular extension of infection - needs valve replacement, may cause AV block (node)
- Splenic abscess
- Mycotic aneurysms - can occur early or late
What is P.falciparum
- plasmodia that infects humans
- almost all death/severe disease
- no dormant liver stage, no late relapses
- medical emergency - almost always chloroquine resistant
Simple renal cysts significance?
- Generally increase in size over time
- do not impact renal fn
no further follow up required
further f.u with CT contrast IF - septated cyst, calcifciation or cluster of cysts potentially masking solid lesion
What is proteinuri nephrotic disorders ?
nephrotic range proteinuria > 3.5g day
hypoalbuminaemia
peripheral oedema - associated with hyperlipidaemia
thrombotic disease more frequently observed
disturbance of podocyte functn or endothelial/gbm/podocyte interface
What is dengue haemorrhagic fever?
- more common after repeated infections and in children described in first time travellers
- 4 necessary criteria for DHF
- fever or recent hx of acute fever
- hemorrhagic manifestations
- low platelet count - less than 100,000
- objective evidence of leaky capillaries
- elevated hematocrit 20% or more over baseline
- low albumin
- pleural or other effusions
What is cystatin C?
- biomarker of AKI
- endogenous cysteine proteinase inhibitor
- produced at a constant rate by all nucleated cells - released into plasma
- 99% filtered by glomeruli - no tubular secretion or reabosorption into plasma
- after filtration –> completely absorbed in to prox tubular cells
- hence NONE in urine
- SO PLASMA cystatin C is good marker of GFR and Urine cystatin C is a good marker of tubular injury
What are the common organisms for Subacute endocarditis - top being most likely?
- Viridans strep - mutans, mitis, bovis
- Enterococcus
- HACEK group - 5% - haemophilus, acinomycetamcomitans
Others - culture neg - rare 7%, Q fever, Bartonella, coag neg staph
Indications for surgical treatment of IE?
Valve replacement indications
- heart failure
- paravalvular extension
- uncontrolled infection/difficult organism
- recurrent embolic events despite appropriate Ab - mobile vegetations above 10mm
What is the mechanism of action of calcimimetics (Cinacalcet)?
Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion
Treatment for viridans strep SBE ?
2-4 weeks IV benzylpenicillin IV 4hrly + 2 weeks IV gent (low dose)
or
ceftriaxone 2g IV for 4 weeks (outpt course)
or
benzylpenicillin as a single agent for 4 weeks
What is classic dengue fever?
- 1st phase - abrupt onset of fevers 39-40 for 2-3 days, severe back pain, HA, retro-orbital pain, arthralgias, maculopaplular rash, metallic taste
- 2nd phase - D-3-6, A/N/V/D, lymphadenopathy
- 3rd phase - defervescence for 1-2days
- 4th phase - fever recrudescence, morbilliform rash, skin desquamation
- 5th phase: cnvalescence with prolonged lethargy
What is tolvaptan
vasopressin V2 receptor antagonist that inhibit cyst growth and decline of renal function - however only 2-3 % less increase in renal volumes - ? not widely used yet
used in PCKD
- suppression of vasopressin release reduces second messenger systems - cAMP identified as promoters of kidney-cyst cell proliferation and luminal fluid secretion
what is membranous GN
- Deposition of IgG and C3 along the GBM
- IgG4 most commonly associated idiopathic membranous nephropathy
- most commonly idiopathic - commonest cause of nephrotic syn in adults
- malignancy responsible for 5-10percent of cases - solid tumour such as cancer of lung or colon
- SLE - 10-20% of cases of lupus nephritis have a MN picture
- Spontaneous remission of proteinuria occurs in 5 to 20 percent of cases
- Partial remission (
- incidence of end‐stage renal disease ~14 percent at 5 year
HIV
retrovirus of the lentiviridae family
human HIV-1 is genetically similar to chimp isolates
HIV 2 rare in aus, less virulent
cellular target of HIV - CD4 T cells - predominant target in all tissues
What are the non-immunosuppresive therapies for nephrotic syndrome?
used most often in cases of FSGS and membranous nephropathy - response to immuosup tx slow or partial
issues to address - proteinuria, oedema, HTN, dyslipidaemia, thrombotic risk
- proteinuria - target BP 125/75, proteinuria > 1g/day - use ACEI or ARB, aldo antag- spiro
- diuretics - loop, thiazides (greater anti-hypertensive effect than diuretic)
- statins
- pro-thrombotic - decreased levels of anti-thrombin III - urinary losses , anticoag when alb less than 20,
What steps should you take to prevent contrast induced AKI
- pre-hydration - N/Saline (IV)
- minimise contrast volume
- use non-ionic contrast which is low or iso-osmolar
- discontinue nephrotoxins (ACEI or ARB)
- NAC (variable effect, also results in minor lowering of Creatinine) - 1200mg BD shown benefit compared to low dose
- ? Statins - ongoing trials
- periprocedural haemofiltration - no benefit
pathophysiology of AKI
- reduction in kidney perfusion –> ATP depletion in renal tubular epithelial cells - causes cell death (apoptosis / necrosis)
- prox tubular cells are susceptible - high metabolic rate 2* to ion transport, limited capacity for anaerobic glycolysis
- endothelial injury with microvascular congestion, hypoerfusion particularly in the S3 segment of nephron - outer stripe of medulla
- SEPSIS - cytokines and bacterial factors - binds TLR4 on tubular cells and causes cell damage through oxidative stress
- microvascular changes - hypo-perfusion in peritubular capillaries - generation of reactive oxygen and nitrogen species
what is first line for gonorrohea
- Ceftriaxone!!! + azithromycin and doxy to cover for chlyamdia
- established fluoroquinolone resistance
Diagnosis of Malaria - The great imitator!!
- FBE - haemoyltic anaemia, WCC normal/low, no eosinophilia, thrombocytopenia common
- Thick and thin blood smear
- antigen capture tests - rapid dx 15-20mins
- ICT
What is the treatment for uncomplicated TV endocarditis/IVDU?
2 weeks of IV fluclox and gent has been used
What is the anti-relapse therapy for malaria?
- Primaquine
- eliminates liver forms of P vivax and ovale
- need G6PD screen
- total dose of primaquine received is important
- no other alternatives
Clinical approach to ARF
- Pre renal: hypovolemia, hypotension, CCF, aortic dissection
- Renal - ATN, tubular injury - ischaemic, toxic - drugs causing acute tubulo-interstitial nephritis, infetions, acute GN - pauci-immune, anti-gbm
- Post renal - obstruction - staghorn calculi, retroperitoneal fibrosis.
What was the SAFE study? What did it show?
- was an RCT of 7000 patients
compared albumin as resus fluid vs N/Saline
- Showed NO overall benefit in mortality or need for RRT
fluids containing synthetic colloid - HES - found to be associated with increased need for renal replacement therapy - and increased mortality
FSGS
Focal – involving some of the glomeruli
Segmental – involving a portion of the affected glomerulus
Electron microscopic findings same as MCD- Effacement of podocyte foot processes
pathogenesis - injury to the podocyte via an immune mechanism - associated with progressive renal insufficiency in 25-50% of cases
Tx - immunosupp tx for primary FSGS, no role for secondary forms
- glucocorticoids, cyclosporin - in conj for resistant cases,
Glomerulonephritis classes
Proteinuric -nephrotic - minimal change, FSGS and membranous
Haematuric - nephritic - IgA nephropathy, SLE, Pauci-immune GN, anti GBM, post step
Both - membrano-proliferative GN - mesangio capillary GN
What is the treatment for enterococcal IE and side effects?
4-6 weeks of IV benzylpenicillin or amoxil/AMP + Gentamicin (4-6weeks)
combination of AMP with ceftriaxone may be effective
for enterococci resistant to AMP - use Vanc + Gent
SE: ototoxicity and renal failure
if E.faecalis - then replace gent with ceftriaxone - therefore Amp + Cef
What is carbapenem resistance and where?
- frequently due to carbapenemase - hydrolyse all B-lactams incl carbapenems
- esp ppl from india, asia and hospitals in america
MUST know - New Delhi metallo- beta lactamase - does not occur in isolation, co-transmission of other resistance elements
What is the diagnosis of dengue fever?
Lab findings - early neutropenia with subsequent lymphocytosis, mildly raised ALT and AST
severe disease- low platelet count - less than 100,000
elevated transaminases 3-5 of ULN
Dx - serology - 4 fold rise in antibody titre over 2 weeks
flavivirus PCI, NS1 antigen
Mx - symptomatic, supportive
What is MERS CoV
- middle eastern respiratory syndrome coronovirus
- pt presents with pneumonia and ARDS
- human to human transmission possible
- consider in travelllers from middle east in the last 14 days
- mortality rate 55%
Treatment of AKI
- Treat/remove causes/ exacerbating factors
- fluids, renal perfusion- resus
- mx of hyper K and acidosis
- RRT as required - fluid overload, azotemia
- stress ulcer prophylaxis
- modify med dosing
What is the sensitivity and specificity of echo for IE?
TTE - sensitivity less than 60%, specificty 98%
TOE - sens very high, spec very high
- neg predictive value 99-100% in NVE, Pos PV 90%
- PVE 86-94%, 88-100%
What abx would you use for culture negative endocarditis?
Ceftriaxone 3-4 weeks + gent for 2 weeks - active against bartonella/strep/HACEK
for Bartonella endocarditis - switch to IV doxy or azithromycin + ? gent
Q fever endocarditis - doxy + plaquenil (12-18months) + RIF
Cause of host genetic resistance to HIV
delta 32 mutation in CCR5 - found in 10% caucasians - heterozygous
associated with slower HIV disease progression
Biomarkers of AKI - Are they sensitive?
NO - do not become abnormal until GFR reduced by 50%
- begin to change late after injury occurs
confounding - muscle mass, age, sex, nutrition, meds (steroids)
Causes of PUO
- infections - SBE usually viridans, TB, intra-abdominal abscess, HIV related infection
- connective tissue diseases - PMR, Giant cell arteritis, vasculitis (PAN), SLE, thyroiditis
- Malignancy - lymphoma, necrotic mets, Renal cell cancer
- other - drug fever, factitious
Remember role of PET scan
What is the treatment of Staph IE?
4-6 weeks IV fluclox - 2g 4hrly
MRSE or MRSE - vancomycin 4-6 weeks - Rifampicin + Fusidic acid in prosthetic valve endocarditis
**TG - states if vanc resistance or intermediate - then use daptomycin or linezolid***
Hepato renal syndrome
- occurs in severe liver dysfunction - progressive oliguria with very low urinary sodium (
- sepsis, hypovolemia due to diuretics/paracentesis
- splanchnic circulation dilatation, intra-renal arteriolar constrction
- POOR prognosis
Prevention - IV albumin reduces AKI after paracentesis, vasoconstriction with terlipressin (improves short term survival and renal fn)
Who to treat with Membranous GN
- Those with heavy proteinuria- Less likely to spontaneously remit
- Those with renal dysfunction - Disease more likely to progress
Cyclophosphamide and steroid based regimens 1st line immunosppressive therapy
2nd line - cyclosporine - provided preserved GFR, rituximab
What is the nerve supply of the bladder - emptying and filling?
emptying - S2-4 parasympathetic innervation via pelvic nerves mediated by M2 & M3 receptors
filling - sympathetic T11-L2 innervation via hypogastric nerve mediated by B3 receptors
Urethra - closure is via external sphincter S2-4 pudental N - somatic originating in onuf’s nucleus
closure - male bladder neck - alpha1A adrenergic
opening NOS/NO
What stimulates the bladder empyting
- sensory bladder afferents - complex suburothelial sensory network
- myelinated Adelta fibres - 30% - mechanoreceptors mediating sense of fullness via spinobulbospinal pathway via pontine micturition centre - PMC
- unmyelinated C fibres - 70% - normally silent, high mechanical threshold, activated by noxious stimuli eg. infection
after spinal dysfuntion - drive spinal segmental reflex pathway
what causes ARF in terms of acute GN
- pauci immune - anca associated vasculitis
- linear IgG - anti- gbm
- immune complex deposition - SLE, IgAN, PIGN, MPGN
what in polycystic kidney disease genetics is associated with worse disease?
- PKD1 gene on chromosome 16, encodes protein polycystin 1
more rapid deterioration in renal function
increased number of cysts
cysts at an earlier age - cf PKD-2
median age of ESRD at age 54 compared to 74 for PKD-2 on chromosone 4
What are the sonographic criteria for the diagnosis of ADPKD in individuals with a family hx of PCKD
(remember no dx criteria in those with no family hx)
15-29 - 3 or more cysts - unilateral or bilateral
30-39 - 3 or more cysts unilateral or bilateral
40-59 - 2 or more cysts in each kidney
greater than 60 - 4+ cysts in each kidney
What are the extra-renal manifestations of ADPCKD
- polycystic liver disease
- intracranial aneurysms - in 6% of pts with neg fmx, 16% with fmx
- thoracic aortic, cervico-cephalic dissections, coronary artery aneuysms
- valvular heart disease - mitral valve prolapse and aortic incompetence
Prognosis of FSGS is related to ?
• Prognosis dependent upon
- Severity of proteinuria
- Degree of renal dysfunction
- Degree of background renal damage on renal biopsy
- Response to therapy
What is the primary tx for FSGS
Glucocorticoids cornerstone of therapy
• Cyclosporin (in conjunction with glucocorticoids) in
resistant cases
- Provided renal function is preserved
- Other agents – less studied
- Cyclophosphamide
- Tacrolimus
- Mycophenolate
- Sirolimus
- Rituximab
what is the first line treatment for membranous GN
1) cyclophosphamide and steroid based regiments 1st line immunosuppresive therapy
alt immunosuppresive therapies
- cyclosporine 2nd line - provided preserved eGFR
rituximab
what is the auto-antibody found in serum of patients with idiopathic membranous nephropathy?
M-Type Phospholipase A2 receptor as Target antigen in idiopathic membranous nephropathy
- apparently (anti-phospholipase A2 receptor antibodies) correlate with clinical status in idiopathic membranous nephropathy
what calcium channel blockers possess anti-proteinuric properties?
the non-dihydropiridine calcium channel blockers
- verapamil
- diltiazem
needed to reach target blood pressure of 125/75 for nephrotic syndromes
why do u have a pro-thrombotic state in nephrotic syndrome
- decreased levels of anti-thrombin III due to urinary losses
- increased platelet activation
- presence of high molecular weight fibrinogen moieties in the circulation
- additional possiblilty is that immune mediated injury in the glomerulus results in increased procoagulant activity sufficient to have a systemic effect
10-40% of cases have deep vein or renal vein thrombosis
What are the light microscopic findings for Mesangial prolif GN / mesangio-capillary GN
Common to all causes
- Mesangial hypercellularity
- Endocapillary proliferation
- Duplication of the glomerular basement membrane
(producing double contours)
what causes seconday MPGN ?
- usually in association with chronic infections - predominantly hep C
what is the pathophysiology of MPGN
immune complex mediated
- deposition of immune complexes in the glomeruli resulting from persistent antigenaemia
- development of antigen-antibody complexes - chronic infectons (hep c)
Complement mediated MPGN
- commencing and involving regulation of C3 , loss of complement regulation
independent of antigen/antibody stimulation
What is the potential treatment of complement mediated MPGN
poor quality of evidence available
- can use immunosuppressive therapy
plasma infusion
OR
non specific inhibition of complement cascade - Eculizumab - anti C5 monoclonal antibody - inhibition of C5 activation
What suggests chronicity of renal disease?
Evidence suggesting chronicity:
- Normocytic anaemia
- ↑phosphate, ↓calcium, ↑PTH, osteodystrophy
- Small, echogenic kidneys
What are the aims of Hb and iron in CRF
treat if hb less than 100 - aim for 100-120
egfr less than 60 for pbs funding
functional iron deficiency with EPO therapy - aim Tsat 20-50%, ferritin 300-500
need to give enough iron as relative functional iron deficiency
what are the targets for ca, phos, pth in CRF pts
Targets: CARI guidelines
Parameter Target
PO4 0.8–1.60 mmol/L
Ca 2.1–2.4 mmol/L
[Ca x PO4] <4.0 mmol2/L2
iPTH 2–3 times the upper normal limit
what are the agents to help treat renal bone disease?
* Control PO4 with phosphate binders
- Ca Carbonate (Calsup), Sevelamer (Renagel), Lanthanum (Fosrenol)
* Use Calcitriol (Vit D3) to titrate up Ca2+
- Measure PTH 2-3 monthly
- PTHectomy if autonomous
- i.e. High PTH & Ca, whilst off all Ca/Vit D agents.
* Calcimimetics eg. Cinacalcit (Sensipar)
- Parathryroid sensitised to respond to lower ca levels.
- Improve survival surrogotes PTH, Ca, PO4, [CaxPO4]
- BUT – ‘Evolve’ trialno survival benefitPBS de-listing 8/15
what are the classess of lupus nephritis
I Minimal mesangial LN
normal light microscopy
II Mesangial Proliferative LN
III Focal LN
<50% glomeruli involved
IV Diffuse LN
>50% of glomeruli involved
V Pure Membranous LN
VI Advanced Sclerosing LN
≥ 90% of glomeruli
what are some of the features seen on proliferative lupus nephritis histology
• Subendothelial immune deposits
/wire loops
- Hypercellularity
- Leukocyte infiltration
- Fibrinoid necrosis /hyaline thrombi
- IF- deposits of IgG,C1q,C3,IgA,IgM
what are the agents used for induction of lupus nephritis?
- steroids
- IV methylpred x 3 pulses or pred 1mg/kg/day then wean
- cyclophosphamide
- improves renal remission rate, less risk of doubling Cr /ESRF
- either IV cyclo monthly for 3-6 months then MMF or Aza
- IV route less toxic than oral (cumulative dose accumulation - infertility )
- mycophenolate
- 1-3g/day in 2 divided doses
- Rituximab
what is the major SE of cyclophosphamide treatment?
- gonadal toxicity
major infection
herpes zoster
bladder toxicity
malignancy
bone marrow suppression
cumulative dose of 14g - haemorrhagic cystitis
how does mycophenolate work and major toxicities - relating to lupus nephritis
- Inhibitor of inosine monophosphate dehydrogenase
- Inhibits purine synthesis
- Anti-proliferative effects on lymphocytes
- myco is as effective as cyclophos at inducing remission
- less major infection and minimizes gonadal toxicity
- SE
- gastrointestinal upset
- pancyotpaenia
- infection
- malignancy - skin - NEEDS YEARLY SURVEILLANCE
what agents are used for maintenance treatment in lupus nephritis
- myco, aza at least as effective as cyclo with less toxicity
- maintanence treatment for at least 2 yrs
- ? lifelong if relapse
- myco superior in maintaining renal response post induction and preventing relapse
what is rituximab and what role does it have in lupus nephritis?
- murine/human monoclonal antibody
- anti-CD 20, b cell depletion
- no benefit over standard treatment in LUNAR trial
- however possible role in severe refractory or relapsing disease
what is pauci-immune RPGN, ANCA + vasculitis ?
- Autoantibodies reacting with myeloperoxidase(MPO) or proteinase 3 (PR3)
- Characteristic cytoplasmic (c-ANCA) or perinuclear (p-ANCA) IF staining on ethanol fixed neutrophils.
- Three major
- wegner’s granulomatosis - 90% ANCA +, 80-90% PR3
- microscopic polyangitis - 70% ANCA, most have MPO
- renal limited vasculitis - most anca +, 75-80% MPO
what is the induction treatment for pauci immune RPGN
- cyclophos - 3-6 months, oral vs IV as IV smaller cumulative dose
- steroids - iV methylpred pulse than pred in severe disease
- in severe disease ANCA + vasculitis - plasma exchange resulted in higher rate of renal recovery
- esp in severe renal failure, concurrent anti-gbm antibodies and anca pos, pul haemorrhage
what is the maintenance therapy for pauci immune RPGN
- aza verus cyclophos
- aza for 18months shown to be as effective as cyclo to minimise relapse
- aza more effective than mycophenolate at maintaining remission in ANCA associated vasculitis
- rituximab - as alternative to cyclo - no difference in adverse events, as effective
what are the ranges for microalbuminuria?
Urine albumin : Creatinine ratio (UACR)
males 2.5-25mg/mmol
females 3.5-35mg/mmol
Albumin excretion rate (AER)
30-300mg/ 24hrs
20-200μ g/min in timed collection
If positive then further 1-2 checks within 3
months
what is the definition of macroalbuminuria
Urine albumin : Creatinine ratio (UACR)
males >25mg/mmol
females >35mg/mmol
Albumin excretion rate (AER)
>300mg/ 24hrs
>200μ g/min in timed collection
What is atherosclerotic RAS and what part of renal aa does it involve
- ARAS part of generalised atherosclerosis
common in pts with or without HT
- typically involves the proximal 1/3rd of main renal aa
men and women age over 55
ostial/proximal renal aa
radiologically eccentric or concentric lesions - total occlusion and ischaemic atrophy
what is fibromuscular dysplasia?
in women aged 30-40
mid-distal renal artery, bilateral in 60%
radiologically string of beads
can affect carotid, visceral and peripheral arteries
total occlusion and ischaemic atrophy is rare
perimedial fibroplasia can threaten, cause dissection
What happens in the proximal tubule and what drug acts here
60 – 65% sodium reabsorbed
Site of HCO3 - reabsorption
All glucose and amino acids reabsorbed
Site of solute secretion
- anions (urate, ketoacid, penicillins, cephalosporins, radiocontrast media, diuretics)
- cations (cr, cimetidine, Li)
Target carbonic anhydrase inhibitors
• Mild metabolic acidosis
what happens in the thick ascending limb
- 25-30% of sodium reabsorption
- concentration of medulla and counter current system
- mg and ca transport passive
- frusemide decreases mg absorption - less positive lumen
- claudin 16 gene encodes for mg transport paracellular pathway
- mutations in paracellin 1 gene - hypomagnesemia and nephrocalcinosis
What is Bartter’s syndrome
- autosomal recessive
- normotensive
- hypokalaemic, metabolic alkalosis
- hypercalciuria +/- hypomg
- increase in urine prostaglandin E
- increase renin and aldo
- neonatal presentation
Affects NKCC - losing sodium, cannot retain hence high renin and aldo to compensate
What is the distal tubule responsible for and what diuretics ?
- 5% of total NACL absorption
- thiazide action - indapamide
- mg and ca reabsorption
- Mg absorption via TRPM6/M7 - this is inhibited by tacrolimus
- 2-5% of mg absorbed
- Thiazides
- inhibit Na/CL co-transporter
- compete for Cl site
- decrease absorption of Na
- increase calcium reabsorption - prevention of renal calculi
what is gitelman’s syndrome
- Autosomal recessive - disorder of NaCl transporter
- Salt wasting
- Normotensive, metabolic alkalosis, hypokalemia,
- hypomagnesemia, hypocalciuria (similar thiaside)
- Increase renin and aldosterone
- Urine prostaglandin E normal
- Diagnosed late childhood or adulthood
- Musculoskeletal presentation
what is pseudohypoaldosteronism type 2
- •Autosomal dominant
- •Hypertension 2nd /3rd decade
- •Normal anion gap acidosis
- •Hyperkalemia
- •Hypercalciuria
- •High aldosterone levels
- •Treatment thiasides
- •Mirror image to thiaside use
what is the action of potassium sparing diuretics
Amiloride and Triamterene, High dose trimethoprim
- close sodium channels directly
- Amiloride used to inhibit Lithium entry into cells
Spironolactone and Eplerenone
- competitively antagonises aldosterone at receptor level
- Eplerenone more specific less anti‐testosterone side effects
what is liddle syndrome
- Autosomal dominant (chromosome 16)
- Early onset H/T + hypokalemic metabolic alkalosis
- decreased plasma renin and aldosterone levels
- Increased number of Na channels
- Mutation identified in or subunit of Na channel (unable to catabolise Na channel)
- Presentation similar to apparent minerocorticoid excess (Licorice)
- Amiloride and Triamterene, not Spironolactone used for treatment as they close the channels
how does aldosterone and ANP act in the cortical connecting tubule
Fine tuning by renin angiotensin
Electronegative lumen promotes K+ and H+ excretion
Aldosterone increase number of sodium channels
increase Na reabsorption and secretion of K+
ANP binds to basolateral receptor decreases Na
channels
Li enters these cells via Na channels
what is anion gap and causes
- Anion gap Na+ ‐ (Cl‐+ HCO3)
- Anion gap 8‐15
- Measure of unmeasured anions (albumin ,Phosphate and sulphate)
Anion gap increased
- Decrease K+, Ca2+ or Mg2+
- Increase anions – lactate, ethylene ketones
- 2* to increased lactate, methanolol, alcohol, rhabdo, renal failure or ketoacidosis
Anion gap decreased
- Low albumin (correction .25 x albumin g/L)
- Multiple myeloma
what is the urine anion gap and what does it signify?
Urine anion gap = [Na+] + [K+] – [Cl‐]
GI causes: “neGUTive” UAG +
• Infusion ++ amounts Na Cl
Positive anion gap
• Type 1 RTA, Type 4 RTA, renal failure
Impaired renal acid excretion
Urinary anion gap unreliable
pH > 6.5
U Na < 20 mmol/L
Toluene/lactic/ketoacidosis
what is type 1 RTA
- Distal defect —> decreased H+ secretion
- K+ secreted instead of H+ (hypokalemia)
- Urine pH > 5.5
- Hypercalciuria
- Most acidotic of the three types of RTA
- Renal Calculi
- • Hypercalciuria
- • Hypocitraturia
- Confirmatory test –Ammonium Cl acidification
- primary causes
- idiopathic, sporadic, mutation in H+-ATPase and AE1 gene , association nerve deafness
- secondary causes
- autoimmune - sle, sjogrens, RA, drugs - PPI, lithium, chronic hep, renal transplant , thyroid disorders
*
- autoimmune - sle, sjogrens, RA, drugs - PPI, lithium, chronic hep, renal transplant , thyroid disorders
what is type 2 RTA
Failure of proximal tubular reabsorption of HCO3
Acidosis is milder that in type 1 RTA (HCO3 ‐ 12‐20 mmol/L)
Urine pH varies with serum HCO3 ‐ (pH < 5.5)
Threshold distal reabsorption of HCO3
‐Treatment may require high dose HCO3 ‐ (10‐15 mmol/kg/day)
Often associated with generalised proximal tubule dysfunction
(Fanconi syndrome - generalised prox tube dysfunction)
Confirmatory test fractional excretion of Bicarbonate > 25%
What is type 4 RTA
Aldosterone deficiency or distal tubule resistance to Aldosterone
Decrease in Na+ absorption
Decreased H+ and K+ secretion hyperkalemia and acidosis
Urine pH < 5.5
Impaired ammonium production
Acquired causes - dec renin 2* to Diabetic nephro, NSAIDs, interstital nephritis, normal renin dec aldo - ACEI arb, heparin, primary adrenal response
dec response to aldo - meds - spiro, tac, sle, amloid
treatment - dietary restriction of Na and frusemide
What is Wegner’s granulomatosis - GPA
granulomatous polyangitis
eponymous description of disease entity
small vessel vasculitis affecting respiratory tract vessels – nose to lungs and renal vessels
what is goodpastures disease?
- anti GBM antibodies cause this disease
- mainly present with rapidly progressive disease
- areas of necrosis and crescents
- antibody – IgG – deposits on the basement membrane
- always a cresenteric disease
- combination of haemoptysis, renal failure and linear IgG deposits points to a diagnosis of good pasture’s syndrome.
- An antibody to alpha 3 component of type IV collagen
- More common in men
- Bimodal distribution – peaks in 20-30 and 60-70, associated with HLA DR2
- Ix – renal biopsy and raised transfer factor secondary to pul haemorrhage
- Management – plasma exchange, steroids and cyclophosphamide
- ANCA related nephropathies are associated with crescentic glomerulonephritis
What is the main risk factor for IgAN progression? Note - IGAN is the most common cause of GN leading to ESKD in ANZ
PROTEINURIA!!!!!
- degree of proteinuria - esp not responding to tx generally the strongest predictor for renal decline in glomerular diseases
interaction between BP & proteinuria
- reflects glomerular injury
BP control still essential - generally more treatable
- proteinuria and albuminuria is also a predictor of CV events and all cause mortality in CKD
Tx - ACEI, ARB, fish oil, glucocorticoids and cyclophosphamide
what is the treatment of ANCA associated vasculitis than is PR3-ANCA pos, anti-gbm negative
so ideal treatment is cyclo IV to reduce cumulative dose,
can use rituximab as alternative
plasmapheresis is used short term in achieving dialysis independence in ANCA pos vasculitis presenting as dialysis requiring - serum Cr greater than 500
- also in pts with pul haemorrhage or co-existing anti-GBM antibody
but u also need to use cyclophosphamide as induction therapy
what is the first line treatment of membranous nephropathy
- cyclophosphamide and prednisolone alternating monthly for 6 months
- remember PLA2R Ab - present in 70% of idiopathic MN and negative in secondary MN
steroids alone do not work for iMN
can use for 6 or 12 months
another target for idiopathic MN is THSD7A
what are the donor requirements for kidney transplant -
do they need to be ABO compatible
do they have a higher rate of ESKD compared to the popn
So
- transplant donors are generally from a highly selected population - lower risk of ESKD
- higher risk than healthy non donors - but absolute risk is LOW
- cannot transplant melanomas - even past hx - as high death rates
ABOI no longer an absolute contraindication in living donor kidney Tx - generally requires antibody removal pre- TX - antibody remoal for low antibody titres
- kidney exchange program for high titres- to avoid unsuccessful attempt at Ab removal or higher risk of early rejection
what is the main cause of death in dialysis patients
1 CVD!!!!!
- withdrawal from dialysis - however now nearly the same as CVD
- infection
- vascular - stroke, GI bleed, bowel infarction
first few months - high risk of infections
How does calcitriol work and SE
- 1,25 OH vitamin D reduces PTH secretion - directly or indirectly via relative hypercalcaemia
- increases GI absorption of Calcium and phosphate - unwanted SEs
- avoid relative hypercalcaemia, hyperphosphataemia and low PTH - adynamic bone disease - vascular calcification
*
when is egfr most accurate - MDRD
for patients with CRF and egfr 15-45 mls/min
