Nephrology Flashcards
Aldosterone stimulates which part of the renal tubule to reabsorb Na?
Cortical collecting duct
ANP affects which part of the renal tubule to inhibit Na reabsorption?
Medullary collecting duct
Which part of the tubule is the site for excretion of trimethoprim?
Proximal tubule
Dapagliflozin exerts its effect on which part of the renal tubule?
Proximal tubule
Why is Gaddolinium avoided in CKD?
Nephrogenic systemic fibrosis from gad chelators
Renal Tx, detection of graft rejection risk modalities and when risk is greatest
CDC +ve> Flow cytometry > virtual cross matching
Renal transplant x2 induction agents
Basilixumab (anti-CD25) and ATG (superior in high risk)
Renal Tx Immunosuppression maintenance
Pred + Tac + MMF
CNI pathway affected:
Signal 1: TCR/CD3 -> calcineurin -> NFAT -> IL-2,IL2R
mTORi pathway
Signal 3: IL2 -> CD25/JAK3 -> mTOR -> cell cycling
What is belatacept?
soluble CTLA4-Fc
Tacrolimus side effects
Twitchy and shorn, more diabetes, seizures
Cyclosporin side effects
Cheesy (gums) and neanderthal (hirsuitism)
MMF MOA
Inhibits IMPDH
MMF side effects
myelosuppressive, diarrhoea
Everolimus vs. Sirolimus side effects
Everolimus less cancer and less infection
Most important HLA group re. rejection
HLA-DQ
T cell mediated rejection rx
Methylpred and increase maintenance
Ab mediated rejection Rx
PLEX or IVIg or Rituximab
CMV prophy duration
6/12 if mismatch, 3/12 if R+ irrespective of donor; give if needing ATG
CMV rx
double dose valgan or gan
Rx for resistant CMV
foscarnet, cidofovir, CMV Ig, reduce anti-metabolite immunosuppression
Change of immunosuppression because of skin cancer
cease Aza and use mTORi
pattern of transplant glomerulopathy
MPGN
BK nephropathy specific stain
Simian virus 40 stain
Areas of kidney most susceptible to AKI
outer medulla and proximal tubules
biggest risks for contrast induced nephropathy
CKD and diabetes
Mgmt of Contrast induced nephropathy
isotonic IVH, iso/low osmolar contrast low volume
MOA of rhabdo
Causes vasoconstriction, direct tubular damage and cast nephropathy
Top 3 causes of isolated glomerular haematuria
IgA, Alport’s, Thin BMD
Nephrotic diseases
Kids- MCD; middle age= FSGS; old- membranous
Nephritic diseases
Kids- Post-infectious; young- IgA, SLE; old- AAN
What GN often recurs early post Tx?
FSGS
Secondary MCD is due to
NSAIDs, infection, allergy, cancer
2nd most common Ab in primary membranous
THSD7A (thrombospondin)
Secondary causes of membranous GN
cancer or SLE
main cell damaged in membranous GN
podocyte
Rx for primary membranous GN
Rituximab
Primary FSGS MOA
Elevated suPAR (soluble urokinase-type Plasminogen Activator Receptor) gets trapped in BM -> protease results in foot process effacement
Causes of secondary FSGS
HIV (collapsing), obesity, heroin, cancer, hyperfiltration
What is TINU?
Tubulointerstitial nephritis with uveitis. Occurs in young women, HLA assoc, Rx AIN w. steroids
Where go Ig complexes deposit in IgA GN?
mesangium
Biggest predictor of ESRF in IgA?
proteinuria >1g/day
When to biopsy in SLE?
Any renal involvement unless bland urine with <0.5g/day or creatinine too high to salvage
Mgmt of lupus nephritis
steroids + cyclophosphamide -> MMF maintenance
classic cause of secondary MPGN
chronic infection, Hep C +/- cryo
IN relapsing AAV mgmt
Rituximab better than cyclophosphamide. Argument for Ritux upfront if PR3
To what are antibodies directed in Anti-GBM disease?
against noncollagenous domain of alpha 3 chain of type 4 collagen
HLA/other links w. Anti-GBM
HLA-DR2; lung damage from smoking, hydrocarbons, influenza A, Alemtuzumab
Immunuotactoid GN details
Monoclonal IgG GN. usually IgG1. proliferative. nephritic. forms microtubular structure with HOLLOW tubes on EM. usually assoc. w. lymphoproliferative malignancy
Fibrillary GN details
Monoclonal IgG GN. MPGN. IgG in all. Bad nephritic/ RPGN. <20% have MGUS. Assoc. w. Hep C/Ca/AID. Tubules are thick
Type 1 cryo =
Monoclonal PTN due to haem usu. CLL/Waldenstroms. Often hyperviscous. TMA presentation
Type 2 cryo =
mixed, usually IgM-k mono + polyclonal IgG. Often assoc. infection Hep B/C. present as arthralgia, weakness, rash, neuropathy
Type 3 cryo =
mixed. polyclonal from infection/ AID. complement mediated MPGN.
PCKD % 1 vs. 2
78% 1 vs. 15% 2
PCKD inheritance
AD, complete penetrance
PCKD mutation type
point mutations causing either truncating (66%) or non-truncating in rest (milder).
Risk factors for progression in PCKD
PKD1 truncating > non-truncating > PKD2. Male, early onset sx, FHx. ESRF, proteinuria, HTN, size on MRI
Extra-renal manifestations ADPKD
MCA berry aneurysms/ hepatic cysts/ pancreatic and seminal vesical cysts/ valvular (MVP, AR)/ aorta (Dissection, aneurysm), GI (diverticulae, hernias)
PCKD diagnosis
No Fhx: >10 cysts bilateral with renal enlargement. FHx: 15-40yrs 3 cysts total. 40-60 2 cysts each. >60 4 cysts each
Tolvaptan MOA
Vasopressin-2 receptor antagonist
uOsmol aim of Tolvaptan
<280
Causes of death in PCKD
CVD > ICH
Dialysis Kt/V aim
HD 1.2, PD 1.7
Dialysis adequacy urea reduction ratio
Urea pre-urea post/ urea pre
single factor w. biggest impact on longevity of PD
PD peritonitis
Biggest factor to improve dialysis adequacy
time on dialysis
Best access method of dialysys
AVF
Dialysis disequilibrium mechanism
osmotic gradient -> cerebral oedema
Ways to improve Peritoneal dialysis
higher dextrose, more bags, higher volume
Where are aldosterone receptors located?
cortical collecting duct
Where does ANP work?
medullary collecting duct
Where are V1 receptors?
On vasculature
Where are V2 receptors?
On TAL/DCT/CD
V2 receptor activation ->
aquaporin channels and free water re-absorption
What does CA-inhibition cause e.g. acetazolamide
metabolic acidosis from excess bicarbonate loss from proximal tubule (form of T2 RTA)
Where is Na reabsorbed in kidney
67% PCT, 25% TAL Na-K-Cl. 5% DCT
Where do thiazides work?
DCT Na-Cl channel
Channel on which loop diuretics work
Na-K-Cl
electrolyte changes of Bartters
HypoK, HypoCa,HypoMg, volume depletion, alkalosis; secondary hyperaldosteronism
Rx of Bartter’s
NSAIDs, Electrolyte replacement
Gitelman’s inheritance
AR
What are prostaglandins in Bartter’s
elevated +++ due to poor perfusion
Gitelman’s sx
polyuria, cramps
Liddle’s defect
ENaC in collecting tubule permanently turned on -> excessive Na reabsorption -> HTN (like apparent mineralocorticoid excess)
Liddle rx
Amiloride
Gordon’s defect
defect in thiazide sensitive Na-Cl co-transporter, gain of function; excessive Na reabsorption (opposite of Gitelman)
Findings in Gordon’s
HTN, Acidosis, Hyperkalaemia
Rx of Gordon’s
Thiazide
RTA Type 1 features
NAGMA, hypokalaemia, alkaline urine, nephrolithiasis
T1 RTA causes
AID- SS, RA
T2 RTA features
NAGMA, hypokalaemia, urine pH low
T2 RTA causes
Monoclonal IgG disease, drugs- Tenofovir, Fanconi’s
T4 RTA features
hypoaldosteronism, low BP, NAGMA, hyperkalaemia
T4 RTA causes
adrenal insufficiency, CNIs, NSAIDs, interstitial nephritis, DM nephropathy, acute GN
T4 RTA mgmt
fludrocortisone
Gentamicin type of nephrotoxicity
ATN
Top 4 medications in order of benefit for BP/proteinuria
ACE-i/ARB, diuretics/ CCB/ spiro
FIrst biochemical change in CKD-MBD
lose klotho; FGF23 rises
why is 1,25-vitD reduced in CKD-MBD?
FGF-23 inhibition of 1-OH and destruction of 25-OH-vitD
FGF23 normally suppresses
PO4 and PTH
Most common form of CKD-MBD in dialysis patients
adynamic bone disease
PTH target in dialysis patients
2-9x ULN
Iron target in ESRF
Ferritin >100-200 and TfSat >20%
side effects of EPO
pure red cell aplasia with Abs to EPO; stroke
Target Hb of ESRF
100-110
Diabetic nephropathy biopsy finding
Kimmelstiel-wilson nodules = nodular glomerulosclerosis
Lithium action on tubules
Nephrogenic DI- from impaired responsiveness of distal nephron to ADH/ decreased expression AQP2
Hypercalcaemia- impairs CaSR so doesn’t inhibit Ca reabsorption in the tubule
Response to desmopressin in nephrogenic DI
no/minimal rise in urine osmolality
mgmt lithium DI
thiazides and amiloride when urine vol >4L/day