Nephrology Flashcards
Gaddolinium contrast load in CKD
Causes Nephrogenic Systemic Fibrosis
Symmetrical skin involvement with waxy, thickened and hardening of extremities and torso
Can have fibrosis of deeper structures such as lung, heart, fascia, muscles
CD34 + fibrocytes
HLA sub-typing and risk of rejection
Complement Dependent Cytotoxicity (CDC) - Highest risk if Positive (holds most weight on decision!)
Flow
Virtual - Lowest risk if positive
Most important HLA group is HLA DQ
Induction therapies in Renal transplant
Basilixumab - Bind IL2 recetor to inhibit CD25 on T cells
Anti-Thymboglobulin (ATG) - Rabbit Thymoglobulin Ab - Mechanisms; Antibody dependent cell mediated cytotoxicity & complement dependent cytotoxicity
Most common treatment regime in renal transplant
- Basilixumab
- Prednisolone
- Tacrolimus
- Mycophenolate
MOA Tacrolimus
Calcineurin inhibitor; inhibit activation of NFAT (Nuclear Factor activated T cells) and reduce trascription of cytokines including IL2
MOA mTORi
i.e. Everolimus, Sirolimus
Binds FK receptor to inhibit mTOR (mammalian target of rapamycin) and arrest the T cell cycle to prevent proliferation (arrest of cell cycle at G1) -> which would normally be stimulated by IL2
Tacrolimus side effects
“TACROLIMUS”
Tremor
Alopecia
Cardiovascular - HTN
Renal insufficiency
Oncological risk - skin cancers
Lipid elevation
Insulin dependent diabetes (depletion not resistance)
Magnesium wasting
Uric acid elevation
Seizures
Cyclosporin Side effects
Gum Hypertrophy
Hirsutism
Mycophenolate MOA
Pro-drug of Mycophenolic Acid. Inhibits Inosine-5- Monophosphate dehydrogenase (IMPDH) to reduce purine synthesis (Guanine) and cell replication of T and B cells
Side effects are diarrhoea and BM suppression (within 6 months)
Types of renal transplant rejection
T- Cell (Donar APC: Host T cell)-> treat with pulse methyl pred +/- thymoglobulin and increase maintenance therapy.
Antibody mediated (Host APC: Host T cell) -> requires IVIG or PLEX +/- Rituximab. C4D+
Mixed
CMV prophylaxis indications
D + / R - = 6 months
D - / R + = 3 months
D - / R - = no prophylaxis unless
Oral Valganciclovir
CMV treatment
Double dose of prophylaxis with PO Valganciclovir or IV Ganciclovir, cautiously reduce immunosuppression, switch to mTORi, if resistance - Foscarnet or Cidofivor (but nephrotoxic!)
CMV treatment
Double dose of prophylaxis with PO Valganciclovir or IV Ganciclovir, cautiously reduce immunosuppression, switch to mTORi, if resistance - Foscarnet or Cidofivor (but nephrotoxic!)
Immunosuppressant with low risk skin cancer
mTORi (Everolimus, Sirolimus) - if skin cancer -> change AZA to mTORi
BK Virus
Polyoma virus
Post transplant nephropathy
Risk factors; female, HLA mismatch, Older age, immunosuppression
Ix;
- SV 40 stain shows intracellular inclusions on biopsy
- BK Virus PCR (100% of patients!), should be screened at 12 months
- Viral load
Rx with reduction in immunosuppression, Cidofovir, Ciprofloxacin
RIFLE Criteria
for AKI (injury within 7 days);
Risk - 1.5 x Cr, UO < 0.5ml/hr/kg for 6 hours
Injury - 2 x Cr, UO < 0.5ml/kg/hr for 12 hours
Failure - 3 x Cr, UO < 0.3ml/kg/hr for 24 hours, anuria for 12 hours
Loss - Persistent renal failure for 4 weeks
ESRD
Management AKI; Type fluid, BP target, Dialysis commencement time
- Resuscitation with N.Saline - Albumin had increased mortality
- Aim MAP 65mmHg
- Dialysis - NO benefit with early dialysis < 48 hours
Rx contrast induced nephropathy
IVH, no benefit from other therapies
Rhabdomyolysis in AKI
- Dehydration with renal hypoperfusion
- Increased water resorption with precipitation of tubular casts
- Cast nephropathy
= Tubular ischaemia due to casts and hypoperfusion
Secondary causes of minimal change disease
Presents as acute onset Nephrotic Syndrome, with effacement of foot podocytes on light microscopy
- NSAIDs
- Lithium
- Lymphoma
- Thymoma
- Infection
- Atopy
Membranous Nephropathy
Nephrotic syndrome
“S”
Staining PLA2R
Subepithelial immune deposition
SLE
Screen for malignancy
Rx with observation +/- ACE or ARB for proteinuria. Immunosuppression if not resolved > 12 months
Secondary causes Membranous Nephropathy
Malignancy
SLE
Causes of FSGN
- Genetic predisposition - APOL1 gene in young Africans
- SuPAR (soluble urokinase-dupe plasminogen activator)
- Shear stress - HTN, prematurity, Obesity, single kidney
- Drugs - Lithium, Pomidronate, IFN, heroin
- HIV
Biopsy findings FSGN
Focal segmental sclerosis in < 50% glomerulus
IgA GN pathophysiology
Nephritic disease
Defect in IgA1-secreting cells forming an IgA that creates immune complexes with mesengial cells
Post-infectious
Worse prognosis if > 1g protein/day
Types of Lupus Nephritis
“No Man Faces Diffuse Menstrual Situations”
- Normal - conservative Mngmt + ACE/ARB
- Mesingial - conservative Mngmt + ACE/ARB
- Focal Proliferative - Medical Mngmt
- Diffuse - Medical Mngmt
- membranous - Medical Mngmt
- Sclerosing - requires preparation for dialysis
Indications for renal biopsy in SLE
If proteinuria > 0.5g/day
Management Lupus nephritis
For Class 3-5
Induction - Steroids (Methyl pred or pred) + Mycophenolate or cyclophosphamide
Maintenance - Mycophenolate or Azathioprine
Resistant - consider Rituximab
Pathognomonic features: Minimal Change Disease
- Nephrotic syndrome
- Young
- Podocyte effacement on light microscopy
- Due to; Thymoma, Lymphoma, Atopy, NSAIDs, Lithium
Pathognomonic features: Membranous
Nephrotic syndrome
Old -> middle age
PLA2R serology & staining at subepithelium
Causes: Malignancy & SLE
Pathognomonic features: Focal Segmental GN
Nephrotic syndrome
< 50% sclerosis on biopsy
Associated with APOL1 gene commonly in Africans
Due to:
- Shear stress; Obesity, HTN, Solo Kidney
- SuPAR
- Lithium, HIV, Pamidronate, IFN Heroin
Pathognomonic features: IgA nephropathy
Nephritic Syndrome
2-4 weeks post-URTI
IgA-1 and complement deposits in mesengium
Pathognomonic features: MPGN
Rapid Nephritic/nephrotic syndrome
Associated with Hep C, Chronic infection and Cryoglobulins
Type 1 - Immune complex deposits (IgG and C3)
Type 2 - Complement deposits (C3 only - dense deposit disease)
Tram Tracking with immune deposition on Biopsy
Anti-GBM target
Alpha 3 chain of type 4 collagen
Risk factors Anti-GBM
- Male
- HLADR2
- Alemtuzumab use
- Hydrocarbons
- Influenzae A
- Smoking
Lipid changes with Nephrotic syndrome
- Unchanged HDL
- Increased LDL
- Increased TAGs
- Increased Lipprotein A
Common associations hypercoaguable state of nephrotic syndrome
- Most commonly due to membranous nephropathy
- Renal Vein thrombosis most common site
- Proportional to hypoalbuminaemia
Management of Membranous Nephropathy
DO NOT USE STEROIDS ALONE - no evidence
- Observe for 6 - 12 months
- Immunosuppression w calceinerin inhibitors in combination with prednisolone
- Anticoagulation (given highest risk prothrombotic state with renal vein thrombosis)
Pathognomonic features: Anti- GBM GN
- Anti- GBM +
- Linear IgG staining
- HLA DR2
- Use Alemtuzumab
- Hydrocarbon exposure
- Pulmonary-renal syndrome
Diagnosis Polycystic Kidney Disease
Positive FHx;
On USS
- > 3 cysts/total < 40 years age
- > 2 cysts/kidney 40-60 years
- > 4 cysts/kidney > 60 years
On MRI
> 10 cysts by age 40
If no cysts by 18 years of age, diagnosis unlikely
Negative FHx;
On USS
Enlarged kidneys, with > 10 cysts/kidney
PCKD inheritance
Autosomal Dominant, point mutations, with complete penetrance;
- PKCD type 1 - Polycystin -1 on Chromosome 16 (severe), ESKD by 50’s
- PKCD type 2 - Polycystin-2 on chromosome 4 (less severe), milder - ESKD by 70’s
*Non-truncated genes have milder phenotype (40%)
*Variant of autosomal recessive but often causes fetal death
Worse prognosis in PCKD
- Truncated, PKD1 mutation
- Male (but polycystic liver disease more common in women)
- Obesity
- HTN
- Degree Proteinuria
- Larger kidney size
- FHx ESRD < 55
- Earlier onset symptoms
Extra-renal manifestations of PCKD
- Liver cysts - most severe in women due to oestrogen
- Pancreatic cysts
- Brain Aneurysms
- Aortic Aneurysm
- Valvular pathologies - most often mitral valve prolapse and AR
- Seminal Vesicle cysts
- Diverticular disease
- Hernias
Tolvapton
Vasopressin 2 receptor antagonist
Used in PCKD to reduce cyst size
causes hypotonic urine
Aim Urine Osmo < 280
Dialysis Disequilibrium Syndrome
Aggressive dialysis causing cerebral oedema.
Decrease in Urea in blood post-dialysis but persistent Urea in brain therefore osmotic shift of fluid across BBB
Kt/V
Clearance of Urea in the context of time on Dialysis
ANP
Released from atria with stretch
Atrial Natriuretic peptide - decreases extracellular fluid volume by increasing GFR through dilation afferent arteriole and inhibition of Na resorption at ENAC and Na/K+ channels. inhibits Renin.
Types of Vasopressin receptors
V1 - smooth and cardiac muscle
V2 - thick ascending LOH, DCT, medullary & cortical collecting duct (target for Talvaptan)
V3 - anterior pituitary - releases ACTH, prolactin
Carbonic Anhydrase inhibitors
Act at proximal convoluted tubule - Inhibit HCO3- resorption, leading to decreased activity of Na/H+ exchange and more to more urinary Na having a weak diuretic effect
I.e. Acetazolamide and Topiramate
Will cause a metabolic acidosis (Type 2 renal tubular acidosis)
Sites of Na resorption Kidney
65% PCT
25% Thick ascending LOH
5% DCT
3% Cortical collecting duct
1% Medullary collecting duct
Bartter Syndrome
Autosomal recessive
Ineffective Na/K/Cl transporter at LOH - mimicking loop diuretics
- Young children with growth and mental delays
- Interrupts gradient for Mg, Ca
- Low volume leads to hyperaldosteronism & increased Na uptake with H+ secretion.
- Increased renin with high prostaglandins
Leads to
- Low K
- Low H+ with metabolic alkalosis
- Low Mg
- Low Ca
Treat with NSAIDs to block prostaglandin production. Replace electrolytes
Gitelman Syndrome
Autosomal recessive
Interrupts Na/Cl- transporter at DCT to mimic thiazide diuretics
Presents in adulthood with polyuria and craps
Interrupts the electrochemical gradient of Mg resorption causing hypomagnesium
Type 1 RTA
- Loss of H+ ATPase at collecting duct
- Increased retention H+ with metabolic acidosis
- Decreased Na+/H+ exchange, leading to overactivity of Na+/K+ exchange and hypoklaemia
- Hypercalcaemia as Ca drawn from bones to buffer H+, but consequence of reduced renal reabsorption calcium leading to Nephrocalcinosis
Electrolyte disturbances
- NAGMA
- Hypokalemia, urine pH > 5.5
- Hypercalcaemia
Rx with HCO3- which will increase urine pH and drive H+ excretion, reduces need for Na+/K+ exchange and decreasing hypokalaemia
Causes - Autoimmune conditions - Sjogrens, RA
Type 2 RTA
Decreased capacity to resorb HCO3- at proximal tubule resulting in increased K+ secretion at DCT as compensatory mechanism
Electrolyte disturbance
- Hypokalaemia - made worse with BiCarb Rx given ++ renal wasting
- Serum bicarb 12-20
- Lower urine pH
- Can occur with other defects including impaired resorption of phosphate, glucose, uric acid and amnio acids
Due to Fanconi’s syndrome, monoclonal gammopathies, Tenofovir
Type 3 RTA
Combination of Type 1 and 2
Type 4 RTA
Hyperkalemia NOT hypokalaemia as with other RTA. Can be secondary to Heparin
Due to hypoaldosteronism
Rx Fludrocortisone (has mineralocorticoid activity)
Causes of Type 4 RTA
NSAIDs
Calcineurin inhibitors - i.e Tacrolimus
Chronic interstitial nephritis
DM nephropathy
Acute GN
Heparin -> which has a toxic effect on adrenal glomerulosa cells
Primary adrenal insufficiency/Addisons disease
Ang2 inhibitors
Potassium sparing diuretics
