Renal Flashcards
Key progression factors for kidney disease
Proteinuria
HTN
Hyperglycaemia
Smoking
Aetiology of AKI
Pre-renal: hypovolaemia, CCF, sepsis, ACE-i, NSAIDs, hepatorenal
Nephrotoxins, contrast, atheroembolism
Obstruction: prostatic > others
Classification of AKI
Stage 1: SCr 1.5-2x
Stage 2: SCr 2-3x
Stage 3: > 3x or dialysis
Definition of CKD
> 90 days of AKI
Causes of ATN
Ischaemic
- prolonged pre-renal
- hypotension, shock
- CCF
Sepsis
- COVID
Nephrotoxic
- Drug induced - radiocontrast, aminoglycosides, cisplastinum
- Pigment nephropathy
TLS features
Hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcaemia
Associated with lymphoproliferative and leukaemia malignancies
Management with fluids + rasburicase
Hepatorenal syndrome
3 phases
- Pre-ascitic: compensated Na+ retention
- Ascites: sodium retention, mostly DCT, urinary Na < 10
- HRS: PCT Na+ retention
Diagnosis:
- Urine Na < 10
- falling GFR
- no urine blood/protein
Rx: Stop diuretics, give fluids
Terlipressin
DIalysis then liver transplantation
Features of radiocontrast nephropathy
Acute rise in serum Cr 24-48 hours post contrast, peaks day 5-7, resolves day 14
Non-oliguric
Risk factors: heart failure, dehydration, diuretics, CKD, diabetes, myeloma
Hydration w/ normal saline has best evidence
Athero-embolism features
Livedo reticularis + AKI
Clinical classification of glomerulonephritis
- Asymptomatic urinary abnormalities: subnephrotic range proteinuria and/or microscopic haematuria
- Nephritis syndrome: recent onset of haematuria and proteinuria, renal impairment and salt and water retentio
- Rapidly progressive GN: progression to renal failure over days to weeks, usually in context of nephritic presentation
- Nephrotic syndrome: nephrotic range proteinuria, hypoalbuminaemia, hyperlipidaemia, and oedema
- Chronic glomerulonephritis: Persistent proteinuria with/without haematuria and slowly progressive impairment of renal function
Histological classification of GN
- Glomerular involvement
- Cell involvement
- Changes in non cellular components of glomerulus
Features of minimal change disease
Affects mostly children
Pure nephrotic syndrome
Normal light microscopy on histology, flattened podocytes on EM
Management of minimal change disease
Responds well to steroids in children, slower responses in adulthood
Clinical features of focal & segmental GN
Proteinuria, nephrotic syndrome
Hypertension, decrease GFR +/- haematuria
Histology - focal and segmental glomerulosclerosis and hyalinosis, juxtamedullary nephrons involved firstMana
Management of FSGS
Prednisone (often shows poor response)
If necessary, PLUS other immunosuppressants (e.g., cyclosporine, tacrolimus)
RAAS inhibitors
Usually leads to ESRD if left untreated
Clinical features of primary membranous nephropathy
Proteinuria, usually nephrotic
Histology: thickened GBM
Silver stain - intramembranous Ig deposits, spikes and domes appearance
Interstitial fibrosis at later stages
Causes of primary membranous nephropathy
Primary: anti-PLA2R antibodies
Secondary:
Infections (HBV, HCV, malaria, syphilis)
Autoimmune diseases (e.g., SLE)
Tumors (e.g., lung cancer, prostate cancer)
Medications (e.g., NSAIDs, penicillamine, gold)
Management of primary membranous nephropathy
RAAS inhibitors
Prednisone (often shows poor response)
PLUS other immunosuppressants (e.g., cyclophosphamide) in severe disease
Usually leads to ESRD if left untreated
Role of PLA2R in membranous nephropathy
Differentiates primary and secondary MN
Initiate immunosuppression if high titer or rising titer
Clinical features of IgA nephropathy
Asymptomatic haematuria, often synpharyngitis
Hypertension, proteinuria, decrease GFR
M > F
Histology - mesangial hypercellularity and matrix expansion, IgA +
Interstitial damage and fibrosis, occasionally crescents
Poor prognostic factors of IgA nephropathy
Persistent proteinuria, hypertension, reduce GFR, old age, interstitial fibrosis or crescents on biopsy
IgA nephropathy pathophysiology
Increased number of defective, circulating IgA antibodies are synthesized (often triggered by mucosal infections, i.e., upper respiratory tract and gastrointestinal infections) → IgA antibodies form immune complexes that deposit in the renal mesangium → mesangial cell and complement system activation → glomerulonephritis (type III hypersensitivity reaction)
Management of IgA nephropathy
RAAS inhibition - IgA with proteinuria or HTN
SGLT-2 inhibition
Prednisone
- IgA with superimposed MCD
- IgA with proteinuria >1g/day
Clinical features of membranoproliferative GN
Proteinuria + haematuria
Reduced GFR and HTN, nephrotic
Histology: Reduplication of membrane - “wire loops”
Cellular proliferation, interstitial damage
Most commonly nephritic but can be nephrotic
Classification of MPGN
Immunoglobulin (IG)-mediated membranoproliferative glomerulonephritis (type 1 MPGN)
- Associated with SLE, monoclonal gammopathy
- Can also be idiopathic
Complement-mediated membranoproliferative glomerulonephritis (type 2 MPGN: associated with dense deposit disease (IgG antibodies that stabilize C3 convertase, i.e., C3 nephritic factor, cause a persistent complement activation, leading to a depletion of C3)
- Both associated with HBV, HCV, and cryoglobulinemia
Hereditary diseases (e.g., sickle cell disease, α1-antitrypsin deficiency)
- Drugs (e.g., heroin, α-interferon)
- Tumors (e.g., lymphoma)
- Autoimmune diseases (e.g., SLE)
- May manifest with concomitant nephrotic-range proteinuria (nephritic-nephrotic syndrome)
Histology of MGPN
IG-mediated (type 1)
- IF: subendothelial and mesangial IgG immune complex deposits with granular appearance
- ↓ Serum C3 complement levels
Complement-mediated (type 2)
- Intramembranous C3 deposits (dense deposit disease) on basement membrane
- ↓ Serum C3 complement levels
Both types: LM with H&E or PAS stain shows mesangial ingrowth, which leads to thickening and splitting of the glomerular basement membrane (tram-track appearance)
Management of MGPN
Rule out myeloma
If familial, for supportive care only
Complement mediated - consider anti-C’ Rx i.e. eculizumab
Immunemediated MPGN - consider steroid, plex or rituximab
Features of rapidly progressive GN/crescentic GN
Rapidly decline in renal failure
Haematuria, proteinuria, oliguria, HTN, reduce GFR, haemoptysis, arthralgia/myalgia/weight loss, lupus
Histology of RPGN
Crescents > 50% glomeruli, interstitial inflammation
ANCA associated vasculitis - necrosis, eosinophils, pauci-immune
Anti-GBM - linear IgG
SLE - mixed features, lots of complement and Ab
Management of RPGN
Urgent diagnosis via renal biopsy, SLE, ANCA, anti-GBM
Pulse prednisone
Cyclophosphamide or rituximab, MMG
Plasmapheresis for anti-GBM or AAV
Class of lupus nephritis
Class I - normal/minimal disease
Class II - mesangial disease
Class III - focal proliferative GN
Class IV - diffuse proliferative GN
Class V - membranous FN
ABO compatibility of renal transplantation
O to all
AB to all
Others must be matched
Renal transplant rejection types
Hyperacute
- rare and early. Untreatable.
- vascular thrombosis
- PMNs
- infarction
Acute
- common, early and treatable
- T cell mediated or antibody mediated
Chronic
- common and progressive
Pathogenesis of antibody mediated rejection
- Alloantigen exposure
- Antigen presentation + T cell help
- B cell maturation
- Plasma cell - high affinity DSA
- Antibody mediated rejection
Histology of chronic allograft nephropathy
Tubular atrophy
Interstitial fibrosis
Patchy infiltrate
Arteriolar hyalinosis
Glomerulopathy
Site of action for acetazolamide
PCT
Site of action for furosemide
Thick ascending loop of Henle
Medications acting in DCT
Thiazide, indapamide
Site of action for spironolactone
CD
Site of action for amiloride
DCT, connecting tubules, CD
Features of Bartter’s syndrome
NKCC2, ROMK, CIC-Kb mutation
Low potassium, low calcium
Elevated urine prostaglandin
Features of Gittelman’s
NKCC1 mutation
Low potassium, high calcium
Normal urine prostaglandin
Function of parenchymal cells
Make up nephrons
Function of principal cells
Responsible for sodium reabsorption and potassium secretion in the kidney
Intercalated cell in CD function
Alpha intercalated cell is responsible for secreting excess acid and reabsorbing base (in form of bicarbonates)
Beta intercalated cells is responsible for secreting excess base (bicarbonate) and reabsorbing acid
Function of peritubular cells
Makes erythropoietin
What cells make erythropoietin?
Peritubular cells
Advantages and disadvantages of EPO
Advantages
- improve QOL
- improves exercise tolerance
- improves sexual function
- improves cognitive function in dialysis
- leads to regression of left ventricular hypertrophy
Disadvantages
- expensive
- hypertension
- increase peripheral resistance due to loss of hypoxia vasodilation and increased blood viscosity
- encephalopathy
Risk factors for calciphylaxis
ESKD
Obesity
Diabetes
Female
Dialysis-dependence > 2 years
Repetitive skin trauma from SC injections
Elevated Ca or PO4
Primary/secondary hyperparathyroidism
Oversuppressed PTH levels
Elevated ALP
Vitamin K deficiency
Warfarin
Hepatobiliary disease
Thrombophilia
SLE
Hypoalbuminaemia
Metastatic cancer
Recurrent hypotension
Rapid weight gain
Exposure to UV light
Exposure to albuminum
Elevated FGF-23
What medication is high risk for calciphylaxis
Warfarin –> vitamin K deficiency
How does warfarin cause calciphylaxis
Antagonises vitamin K –> blocks MGP carboxylation –> promotes vascular smooth muscle cell transdifferentation and matrix mineralisation
Most common cause of death in calciphylaxis
Sepsis due to wound infection
Gold standard investigation for diagnosis and classification of renal osteodystrophy
Unexplained fractures
Persistent bone pain
Unexplained hypercalcaemia
Unexplained hypophosphataemia
Possible aluminum toxicity
Mechanism of hyperkalaemia in ACEi/ARBs
Reduces aldosterone biosynthesis by interrupting RAS
Reduces effective glomerular-filtration rate
Mechanism of hyperkalaemia from amiloride
Blocks Na channels of luminal membrane of principal cells
Mechanism of hyperkalaemia from beta blockers
Inhibits renin secretion
Decreases cellular K uptake
Mechanism of hyperkalaemia from cyclosporine
Inhibits adrenal aldosterone biosynthesis
Induces chloride channel shunt
Increases K efflux from cells
Mechanism of hyperkalaemia from digoxin
Inhibits Na+/K+-ATPase
Mechanism of hyperkalaemia from heparin
Inhibits adrenal aldosterone biosynthesis
Decreases number and affinity of angiotensin-II receptors
Mechanism of hyperkalaemia from NSAIDs
Induces hyporeninemia hypoaldosteronism through inhibition of renal prostaglandin synthesis
Mechanism of hyperkalaemia from spironolactone
Mineralocorticoid receptor antagonist (competing with aldosterone)
Inhibits adrenal aldosterone biosynthesis
Mechanism of hyperkalaemia from succinylcholine
Causes potassium leakage out of cells through depolarisation of cell membranes
Mechanism of hyperkalaemia from tacrolimus
Inhibits adrenal aldosterone biosynthesis
Induces chloride channel shunt
Increases K efflux from cells
Mechanism of hyperkalaemia from trimethoprim
Blocks Na channels in luminal membrane of principal cells
Mechanism of patiromer
Used for hyperkalaemia
Sodium-free binding polymer that exchanges calcium for potassium in GIT –> increases faecal K excretion and reduces serum K levels
Can result in low Mg and GI side effects
Mechanism of sodium zirconium cyclosilicate
Used in hyperkalaemia
Potassium-selective cation exchanger
Can result in peripheral oedema and GIT side effects
Mechanism of roxadustat
Reversible hypoxia-inducible factor prolyl hydroxylase inhibitor –> stimulates erythropoiesis
Role of hypoxia-inducible factors
Transcription factors that regulate expression of genes in response to hypoxia
Prolyl hydroxylases (PHDs - hydroxylate HIF-a subunit, resulting in rapid proteasomal degradation) is lessened in hypoxia –> enhanced erythropoiesis
Reduces levels of hepcidin
Decreases level of total cholesterol, LDL and triglycerides
Clinical criteria to commence erythropoiesis stimulating agents
- Requires transfusion
- Hb < 100g/L
- Intrinsic renal disease as assessed by nephrologist
Features of podocyte
Highly differentiated epithelial cell, connects to GBM
Function of podocyte
Structural support of capillary loop
Major component of glomerular filtration barrier
Synthesis and repair of GBM
Production of growth factors - VEGFs, PDGFs
Immunologic function
Most common malignancy post renal transplant
Non-melanotic skin cancer
Malignancies highest risk of occurring post renal transplant
Lung
Colon
Liver
Lymphoma (PTLD)
Melanoma
Non-melanoma skin cancer
Drugs cleared by haemodialysis
BLAST
- Barbiturate
- Lithium
- Alcohol
- Salicylates
- Theophyllines
Risk factors associated with BK nephropathy
- aggressive immunosuppressive treatment
- older recipient age
- female donor
- HLA DR mismatching
Why is gadolinium exposure avoided in significant renal impairment?
Risk of nephrogenic systemic fibrosis
Characterised by symmetrical skin involvement with extensive waxy thickening and hardening of extremities and torso
Treatment of PTLD
Reduction of immunosuppression and monitor respond
Rituximab - induce remission
Indications for renal biopsy
- Glomerular haematuria
- Acute on chronic kidney disease of unclear cause
- Severely increased albuminuria
- Transplant dysfunction or monitoring
Features of AIN
Classic clinical presentation
- Fever
- Rash
- Peripheral eosinophilia
Urinary findings
- Eosinophiluria
- Leukocytes
- Erythrocytes
- Leukocyte casts
Causes of drug-induced AIN
Antibiotics
NSAIDs
PPIs
Fractional excretion percentage of phosphorus in type 2 RTA
> 5%
