Renal Flashcards
Horeshoe kidney complications
hydronephrosis
nephrolithiasis
infection
increased renal ca
Difference between CrCl and GFR
CrCl estimates GFR
CrCl slightly overestimates as creatinine is moderately secreted by renal tubules
Where do loop diuretics act
Ascending loop of henle
Blocks Na/K/Cl transporter
Where to thiazide diuretics act
early DCT
blocks Na/Cl transporter
Where is majority of Na and water reabsorped in nephron
early PCT
Aldosterone effect on principal cells vs alpha-intercalated cells
principal cells - promotes Na and water reabsoprtion, K secretion
alpha intercalated cells - promotes K reabsorption and H secretion
Fanconi syndrome mechanism
generlised reabsorption defect in PCT
- increased excretion of AA, glucose, HCO3, PO4
Fanconi syndrome lab findings
metabolic acidosis (type 2 RTA)
low phosphate and K
What can cause Fanconi syndrome?
hereditary -> wilsons, glycogen storage disease
ischaemia
multiple myeloma
drugs (tenofovir, isofosfamide, cisplatin, lead poisening)
What is Bartter syndrome and lab findings
autosomal recessive reabsorption defect in thick ascending loop of henle
Like being on chronic loop diuretics
metabolic alkalosis, low K and high Ca
What is Gitelman syndrome and lab findings
AR defect of NA/CL transporter in DCT
causes metabolic alkalosis, low Mg K and Ca
similar to chronic thiazide use
What is Liddle’s syndrome and lab findings
Gain of function mutation to reduce Na channel degradation -> increased Na reabsorption
Metabolic alkalosism, low K, low aldosterone and HTN
What is SAME (syndrome of apparent mineralocorticoid excess) pathophys
AR 11beta-HSD deficiency leads to higher cortisol (rather than cortisone) which increased mineralocorticoid activity
Caused metabolic alkalosis, low K, low aldosterone and HTN
Actions of angiotensin 2
vasocontricts arterioles -> increase BP
contricts efferent arteriole -> increased GFR when renal blood flow low
Increases Na/H transporter activity in PCT
Secretes aldosterone -> H2O net absorption
Posterior pit to secrete ADH
Inhibitor for RAAS
ANP and BNP -> dilates afferent arteriole increasing renal blood flow and reducing renin
promotes naturesis
Most common cause of GN in developed countries
IgA nephropathy
IgA nephropathy presentation
40-50% macroscopic haematuria, flank pain and fever
30-40% microscopic haematuria plus mold proteinuria
10% rapid progressive GN
Rare to have malignant HTN or AKI
IgA nephropathy clinical associations
Cirrhosis
Coeliac disease in 1/3
Dermatitis hepatiformis
HIV
Minimal change and membranous
GPA when in remission
Small cell carcinoma
Bronchiolitis obliterans
Lymphoma
TB
IBD
Indications for Bx in IgA nephropathy
Protein >1g
Elevated creat
New HTN
Elevation in BP above previous stable baseline
Characteristic IF finding in immune complex GN
granular deposits of polyclonal Ig
Predictors of outcome in IgA nephropathy
reduced GFR worse
HTN worse
degree of proteinuria most important predictor in one study
what is considered remission in IgA nephropathy
protinuria < 1g/day
treatment of IgA nephropathy
aim ACEi, BP control, lifestyle for 6 months
if protein >1g/day or other factors (minimal change disease, AKI, RPGN) consider immunosuppresion with glucocorticoids
Characteristic histo findings in lupus nephritis
“full house” IF pattern
glomerular deposits that stain for IgG, IgA, IgM, C3 and C1q
seen everywhere
therapy immunosuppression for lupus nephritis
Induction: MMF or cyclophosphamide
Maintence: AZA
How to Dx infection related GN
kidney bx in those with preceeding or current infection and low C3
Most common GN in adults >50yo
pauci immune (ANCA associated)
Which ANCA is GPA
PR3
Which ANCA is MPA
MPO
Genes associated with ANCA vasculitis
MHC
PRTN3 gene
SNPs associated with PR3
HLA-DP
SERPINA1
PRTN3
SNP asscoiated with MPO
HLA-DQ
Most likely type of ANAC vasculitis to have replapsing renal disease
GPA and PR3
Better treatment for relapsing ANCA vasculitis renal disease
rituximab is superior to cyclophosphamide
Treatment with rituximab is better in what subgroup of ANCA vasculitis
PR3
Avacopan use in ANCA vasculitis trial findings
ADVOCATE study
avacopan non-inferior but not superior to tapered pred at 26 weeks, but superior at 52 weeks for sustained remission
Bx findings in pauci immune GN best and worse outcomes
focal -> best
sclerotic -> worse
Characterstic IF findigs in anti-GBM
linear deposits of IgG and frequently with C3
Histo findings of anti-GBM
severe necrotising and crescenteric pattern if active
Anti-GM antigen
alpha 3 chain of type 4 collagen
Assocations with anti-GBM
smoking and lung haemorrhage
hydrocarbons
alemtuzumab
HLA-DR2
anti-GBM presentation
rapidly progressive GBM
40% have alveolar haemorrhage
anti-GBM treatment
PLEX
steriods
cytotoxic therapy (cyclophosphamide)
What can occur after transplant for alport syndrome
de novo anti-GBM
How common is relapse of anti-GBM after transplant
uncommon
Proliferative GN with monoclonal Ig deposits most common Ig deposit
IgG
rarely IgA
less common IgM
Most common pattern of pathology in fibrillary GN
mesangial proliferative GN in 70%
IgG in all pt with C3 deposits
cryoglobulinemic GN histo findings
membranoproliferative pattern with infiltrating macrophages and PAS deposits
deposits most often IgM
Can differenciate between C3GN and dense deposit disease based on what
EM findings
Pathophys difference between dense deposit disease and C3GN
Both lead to C3 convertase activity increasing
C3GN -> C3 mutation so is not inhibited by factor H
DDD -> C3 mutation leading to functional factor H deficiency
treatment of membranoproliferative (C3GN)
mild - supportive
moderate >1.5g/day -> steriods, MMF
RPGN -> steriods plus cyclophosphamide or MMF +/- eculizumab +/- PLEX
refractory - eculizumab
Mutations of Bartter syndrome
NA-K-Cl type 1
ROMK T2
CIC kb type 3
barttin T4
upregulation of CaSR t5
frusemide effects on Ca
inhibits all downstream events, reduced Ca reabsorption
thiazide effect on Ca
compensatory increase in NAKCl, increases Ca reabsorption
Familial hypercalcaemia hypocaluria mutation and bloods
mutation in CaSR
slightly high Ca, high or inappropriate normal PTH
urinary Ca/Cr ratio <0.01 or low 24 hr urine Ca
Pathology of lithium and hypercalcaemia
damaged CaSR
same as FHH
15-20% of people on lithium have high Ca
Target Hb in CKD
> 100
New therapies for anaemia in CKD
hypoxia inducible factor inhibitors or stabilisers
Target for acidosis in CKD
aim HCO3 23-29
sodium bicarb
issue with fluid retention
Most common causes of renovascular disease
atheroscelrotic disease 60-80%
fibromuscular disease 10-20%
Difference physiologically between bilateral and unilateral renal artery stenosis
both have HTN
unilateral -> normal volume, high renin
bilateral -> hypervolaemia, normal renin
When is stenting beneficial in renovascular HTN
in FMD
high risk atheroscleosis - recurrent flash APO, advancing renal impairment
Most common cause of KD in dialysis
in decreasing order
diabetic nephropathy
GN
HTN
most common side effects of dialysis catheter
infection
Most common cause of death of dialysis
CVD
Mortality benefit patter in renal transplant
higher early, but lower in longer term
Causes of HLA sensitisation (difficult to match for transplant)
Previous transplant
Pregnancy
blood transfusions in past
Most used induction agent for transplant
Basilixumab (anti CD25 and IL2 receptor)
Most common immunosuppression regime for renal transplant
pred
tacro
MMF
What immunosuppressant to use for induction if high immunological risk group
ATG (rabbit thymoglobulin polyclonal Ab)
Major interactions between renal transplant immunosuppressants
cyclosporin lowers MMF levels but tacrolimus doesnt
Side effects of mTOR inhibitors
wound complications
proteniuria
Most common cause of renal graft loss in early (1st year)
infection 33%
cardiovascular 29%
cancer 7%
Most common cause of renal graft loss in late (beyond 1st year)
cancer 29%
cardiovascular 22%
infection 13%
Most common cause of graft loss (due to graft failure)
early: graft thrombosis (technical)
late: chronic allograft nephropathy
Most common cause of delayed graft function
native kidney ATN (decease donor 30-40%)
Causes of early graft rejection
acute rejection
CNI toxicity
renal artery stenosis
recurrent disease in early: primary FSGS and aHUS (late more IgA)
Underlying physiology behind acute graft rejection
can be T cell mediated or Ab mediated
Treatment for acute graft rejection
t-cell mediated: IV methylpred, ATG (if steriod resistant)
Ab mediated: PLEX, IVIG
Features of BK virus on Bx
intranuclear viral inclusions and SV40 staining (only in medulla)
Rule of thumb for infection post transplant
first 1 month - donor derived and nocicomal
first 6 months - reactivation, oppurtunistic
langer term - sommunity acquired (CMV, PJP)
Most risk profile for CMV in kidney donation
donor +ve recipient -ve
prophylaxis for CMV in renal transplant
D+R- : prophylaxis for 6 months, valgancyclovir
D-R+ or D+R+ : prophylaxis for 3 months
Cancers which are higher risk in renal transplant
NHL
lung
colorectal
Best combo of immunosuppression in renal transplant for lowest skin cancer risk
reduced dose CNI with no MMF
most common inhereted renal disease
polycystic kidney disease
mode of inheretance PCKD
AD
Most common mutation type PCKD
PKD1 (polycystin1) 78%
PKD2 15%
mostly monoalleleic
complete penetrance
Which are the most severe PCKD mutations?
PKD1 worst than PKD2
if non-truncating mutation -> less severe
CNS extrarenal manifestation of PCKD
cerebral aneursyms - most in MCA
5% in younger, 20% in >60yo
only screen high risk pt
hepatic manifestations of PCKD
hepatic cysts with severe PLD in 15%
avoid estrogen replacement in women if liver cysts
Most common valvular disease in PCKD
MVP and AR
DIagnostic criteria for PCKD
if positive Fhx: if 15-39yo need >3 cysts, if 40-59 need 2 cysts in both kidneys
if negative FHx, need bilat renal enlargement and >10 cysts in each kidney
Tolvaptin MoA
vasopressin V2 receptor antagonist
Tolvaptin use in PCKD
for every 4 years on the drug, delay dialysis for 1 year
