Renal Flashcards
For diabetic patients receiving ACEi or ARB, how do they work?
Decreased afferent arteriole tone
Then
Decreased intraglomerular pressure
Then
Decreased GFR followed by stabilisation
Name 4 types of glomerular pathologies that arise from the trapping of circulating immune complexes?
Post-infectious
Membranoproliferative
Glomerulonephritis (chronic infection)
IgA nephropathy
Name 3 types of glomerular pathology that arise from in situ immune deposit formation from exogenous antigens.
Lupus nephritis
Post-infectious glomerulonephritis
Secondary membranous GN
Name two types of glomerular pathology that arise from in situ immune deposit formation from endogenous antigens.
Anti-GBM GN
Membranous
How is post-streptococcal GN treated?
Self-limiting
Clearance of infection = removal of circulating immune complexes
Of note - post-strep GN usually comes on 2 weeks or so after the infection; IgA nephropathy is more likely to be seen earlier on
What is the pathophysiology of post-streptococcal GN?
Activated immune-complexes and/or nephritogenic antigens circulating from strep infection
Attract and activate complement with injury as complexes contact endothelium - neutrophils recruited via chemotaxis
Proteases activated
What features would you see on microscopy for post-strep GN?
Diffuse endocapillary proliferation
“Hump” deposits
Effacement of podocyte foot processes
What is the pathophysiology of membranous GN?
Antibodies and complement inflict cytotoxic injury on the podocyte, resulting in a non-exudative non-proliferative capillary wall lesion
No influx of inflammatory cells or expansion of mesangium, but basement membrane is expanded
What features would you expect to see on microscopy for membranous GN? Name 2 features.
New basement
Which antibodies are implicated in primary membranous GN? Name 2.
Anti-PLA2R antibody - found on podocytes - 80% assoc with primary GN
IgG4 antibody specific for THSD7A (2-5%)
How is primary membranous GN treated?
1st line - steroid + cyclophosphamide based regimen
2nd line - ciclosporin if preserved eGFR, otherwise consider rituximab
In membranous GN, how many patients would be expected to have remission, and how many would progress to ESRD?
Spontaneous remission 5-20%
Partial remission 25-40%
ESRD
- 14% at 5 years
- 35% at 10 years
- 41% at 15 years
Name two features in membranous GN that would suggest progress rather than remission in the future.
Heavy proteinuria
Renal dysfunction
What are the blood pressure and urine protein targets in membranous glomerulonephritis?
BP - 125/75
Urine protein - <1g/day
What drugs should be used in membranous GN to achieve BP/urine protein targets?
ACEi/ARB
Spironolactone
Loop diuretics +/- HCT
Membranous GN can pre-dispose to thrombotic events. Why is this, and how/when is this treated?
Loss of antithrombin III via urine
Warfarin if albumin <20; discontinue if albumin >20, or continue post-event for 3/12
No evidence for DOACs
What is the most common secondary cause of membranous GN, and how is it treated?
Malignancy
Treated by removal of tumour
Consider tumour work-up only if weight loss, +ve FOBT, anaemia etc.
What parameters are required for a diagnosis of nephrotic syndrome?
Proteinuria 3.5g/day
Albumin <30
Peripheral oedema
Assoc with raised protein:creatinine ratio, hyperlipidaemia and thrombotic disease
What are the BP and urine protein targets for IgA nephropathy?
BP - 130/80
Protein <1g/day
Use ACEi/ARB if protein >1g/day
For patients with persistent proteinuria in the context of IgA nephropathy, how should they be treated?
If proteinuria for 3-6 months without improvement - give steroids for 6 months
How should crescenteric rapid IgA nephropathy be treated?
Steroids + cyclophosphamide - however evidence is not great
Which glomerular pathologies are types of nephrotic syndome? Name 3.
Minimal change disease
Focal segmental glomerulosclerosis
Membranous GN
Which glomerular pathologies are types of nephritic syndome? Name 4.
IgA nephropathy
Lupus (most forms)
Pauci-immune
Anti-GBM
Post-strep
Which type of glomerular disease exhibits characteristics of both nephritic and nephrotic syndrome?
Membranoproliferative disorder (also known as mesangio-capillary GN)
What are the 4 different categories of mesangio-proliferative GN?
Immune-complex mediated MPGN
Complement-mediated MPGN/C3 glomerulopathies
Thrombotic microangiopathic MPGN
Idiopathic
Move away from type I and II; the first two are the main two categories, and C3 convertase is involved with both
Name 3 features you would expect to see on light microscopy with mesangio-proliferative GN.
Mesangial hypercellularity - mesangial cells and monocytes
Endocapillary proliferation - interpositioning of mesangial cell cytoplasm between GBM and endothelial cells
Thickened/double GBM due to complement (C3) deposition
Name 3 ways that immune-complex mediated MPGN can develop.
Chronic infection (hepatitis C, bacterial endocarditis)
Autoimmune (SLE, Sjogren’s, RA, mixed connective tissue disease)
Paraproteinaemias
Which gene/protein is implicated in congenital nephrotic syndrome?
NPHS1 - nephrin
No response to steroids
Which genes are implicated in familial FSGS?
NPHS2 - podocin
TRPC6
Name 5 causes of secondary focal segmental glomerulosclerosis.
Obesity
Heroin abuse
HIV
Malignancy
Loss of renal mass
Which receptor is found in elevated levels in patients with focal segmental glomerulosclerosis?
suPAR (serum soluble urokinase-type plasminogen activator receptor)
Found in 2/3s of FSGS patients
Renal disease only occurs when sufficient circulating suPAR activates podocyte B3 interim causing foot process effacement, proteinuria and FSGS-like glomerulopathy
Name 6 secondary causes of IgA nephropathy.
Alcoholic liver disease
Coeliac disease
IBD
Ankylosing spondylitis
Dermatitis heretofore is
Mycosis fungoides
Majority of cases are idiopathic
How many types of IgA are there, and which is typically implicated in IgA nephropathy?
IgA1 and IgA2
Glomerular deposition - polymeric IgA1
Bone marrow, lymph and spleen produce mainly IgA1. Plasma cells produce both.
What did the Stop-IgAN study look at, and what was the outcome?
Looked at immunosuppressive therapy to stop disease progression vs supportive care
No change in progression between groups, with much greater side effects in treatment arm - therefore intensive immunosuppressive regimens can not be recommended over and above maximal supportive care
Which epidemiological factors would predispose a patient towards developing lupus nephritis? Name 4.
Female
“Pigmented races”
Chinese
Polynesian
Name the 6 classifications of lupus nephritis.
I - minimal mesangial lupus nephritis
II - mesangial proliferative
III - <50% glomeruli (focal proliferative)
IV - >50% glomeruli (diffuse proliferative)
V - pure membranous
VI - advanced sclerosing
In lupus nephritis class III or IV (+/- V) disease in white or Asian populations, what are the stages of treatment?
Corticosteroids and MMF or reduced dose cyclophosphamide
If good response - maintenance with low dose steroids + MMF/azathioprine
If poor response - corticosteroids + high dose cyclophosphamide/rituximab/calcineurin inhibitor
In lupus nephritis class III or IV (+/- V) disease in black or Hispanic populations, what are the stages of treatment?
Corticosteroids + MMF
If good response - maintenance with low dose steroids + MMF/azathioprine
If poor response - Corticosteroids with high-dose cyclophosphamide/rituximab
In class V lupus nephritis with non-nephrotic range proteinuria, what is the treatment?
ACEi/ARB
In class V lupus nephritis with nephrotic-range proteinuria, what are the treatment stages?
Corticosteroids and cyclophosphamide/MMF/azathioprine/calcineurin inhibitor
Maintenance immunosuppression with low-dose corticosteroids and MMF/azathioprine/calcineurin inhibitor
ACEi/ARB
What 3 types of medication should be given in lupus nephritis as non-immunosuppressive therapy, and for what reason?
Antihypertensives
Lipid-lowering therapy
Anti-coagulation
Consider the above given increased risk of cardiovascular disease
What are the 3 classifications of cryoglobulinaemia?
Type 1 - single monoclonal - haem malignancies
Type 2 - monoclonal antibody against polyclonal IgG (Hep C)
Type 3 - polyclonal antibodies
How are factor H mutations involved in C3 nephropathies?
Factor H restrains complement activation on host surfaces that do not express other complement regulators, including exposed GBM (which express glycoaminoglycans) - endothelium is fenestrated.
What association does C3 nephritic factor have with regard to adipocytes?
Partial lipodystrophy
Name 6 triggers for atypical HUS?
Toxins
Infection
Pregnancy
Malignancy
Drugs
Malignancy hypertension
Name 3 factors that may predispose towards atypical HUS.
Mutations in factor H, predominantly at C terminal
Autoantibodies binding to C terminal epitomes
C3 mutations prevent factor H binding
What are the treatment options available for HUS? Name 4.
Eculizumab (complement inhibitor)
Plasma exchange
FFP
Transplantation (delay by 6 months following resolution of TMA and extra-renal manifestations)
Name 2 diseases that polyarteritis nodosa is classically associated with.
Hepatitis B
Hepatitis C
Which HLA allele is PR3 ANCA associated with?
HLA-DP
Which genes is PR3 ANCA associated with?
SERPINA1 (a1 antitrypsin)
PRTN3 (proteinase 3)
Which HLA allele is MPO ANCA associated with?
HLA-DQ
PR3-ANCA is associated with which vasculitis?
Granulomatosis with polyangiitis
PR3-ANCA = c-ANCA
MPO-ANCA is associated with which vasculitis?
Microscopic polyangiitis
What immunosuppressive therapy is provided to patients receiving a renal transplant?
Induction - IL-2 monoclonal, polyclonal
Maintenance therapy
- ciclosporin or tacrolimus
- MMF or azathioprine
- prednisolone
What is betalacept, and how does it work?
Costimulation blocker binding to CD 80/86 on the APC
Prevents T cell activation
In which patients is betalacept contraindicated, and why?
Patients who are EBV seronegative
10x increased risk of lymphoma
What is the treatment for acute rejection in renal transplant patients?
Methylprednisolone 500mg-1g daily for 3 doses
Rescue dose MMF
Change ciclosporin to tacrolimus
Antithymocyte globulin
If antibody mediated, rituximab/PEx/IVIG
What is the main factor resulting in patients requiring renal replacement therapy?
Diabetes
Name 5 factors relating to mineral metabolism that can increase CVD risk in CKD patients.
FGF 23 mediated
Increased calcium and phosphate
Hyperparathyroidism
Vitamin D insufficiency
Vascular calcification
What is the main factor resulting in patients requiring renal replacement therapy?
Diabetes
Name 5 factors relating to mineral metabolism that can increase CVD risk in CKD patients.
FGF 23 mediated
Increased calcium and phosphate
Hyperparathyroidism
Vitamin D insufficiency
Vascular calcification
Name 4 mechanisms that contribute towards having HTN in the setting of CKD.
Inability to excrete Na load with Na retention
RAAS activation
Increased sympathetic neural activity
Altered auto regulation of vascular factors
What is the most potent predictor of ESKD and renal death?
Proteinuria
What level of protein has been shown to potentially slow progression on CKD, and what level has been shown to increase mortality?
- 8g/kg/day may slow progression
0. 6g/kg/day increases mortality
Name 5 factors that stimulates osteoblasts and osteocytes to secrete FGF23.
Increased dietary phosphate intake (mechanism unclear)
Increased 1,25 dihydroxyvitamin D
Increased parathyroid hormone
Less in response to high calcium
Possible response to iron deficiency
What does FGF23 do?
Stimulates phosphaturia by down-regulating sodium phosphate co-transporters (proximal tubule)
Reduced 1,25 vit D by directly inhibiting 1a hydroxylase (renal) and stimulating 24 hydroxylase (catabolic)
Directly inhibits PTH secretion
What happens to FGF32 in CKD?
FGF23 is progressively elevated in CKD to compensate for persistent phosphate retention
This is the driver for increased PTH secretion in CKD
Name 5 methods of managing bone disease in ESKD
Optimise dialysis
Phosphate binders - non-calcium assoc with reduced mortality compared to calcium-containing binders
Vitamin D (1,25 vit D analogues effectively control PTH)
Calcimimetics
Bicarbonate (?)
What is the target Hb for CKD?
Hb 110
Hb >125-130 in CKD is associated with increased CV mortality and stroke
How does smoking impact upon overall survival and graft loss post-transplant?
2 x risk of graft loss
Half the overall survival
What is the most common side effect of EPO?
Hypertension
What type of cancer should be screened for more commonly in transplant patients?
Skin cancers, particularly SCC and BCC
Name 2 phosphate binders you may consider using in a dialysis patient with high adjusted Ca and PO4.
Sevelamer
Lanthanum
What accounts for the majority of deaths in haemodialysis patients over the age of 75?
Withdrawal of haemodialysis
Name 7 indications for dialysis that are not considered absolute indications (in otherwise appropriate patients).
Declining nutritional status
Persistent or difficult to treat volume overload
Fatigue with no other reversible contributory pathologies
Mild cognitive impairment
Refractory acidosis
Refractory hyperkalaemia
Refractory hyperphosphataemia
Name 3 absolute indications for dialysis
Uraemic pericarditis
Uraemic pleuritis
Uraemic encephalopathy
Contraindications to living kidney donation include being incapable of making a decision (e.g. minor), coercion, illegal financial exchange and the hospital’s discretion. Name 6 others.
Uncontrolled HTN/history of HTN with end-organ damage
HIV infection
Diabetes mellitus
Active/incompletely treated cancer
Evidence of acute symptomatic infection
Uncontrolled, diagnosable psychiatric conditions
Name 6 opportunistic infections that are most likely to occur after 6 months post-renal transplant.
Aspergillus
Nocardia
BK virus (polyoma)
Herpes zoster
Hepatitis B
Hepatitis C
What histological features would you expect to see with lupus nephritis? Name 6.
Subendothelial immune deposits/wire loops
Hypercellularity
Leukocyte infiltration
Fibrinogen necrosis
Hyaline thrombi
Crescents in severe LN
Name 6 opportunistic infections that are most likely to occur before 6 months post-renal transplant.
PJP
CMV
Legionella
Listeria
Hep B
Hep C
Name 5 (groups of) drugs that can be cleared via dialysis.
“BLAST”
Barbiturates
Lithium
Alcohol
Salicylates
Theophylline
What is the most sensitive and reliable indicator of possible rejection in renal transplant patients?
Rise in serum creatinine
For patients looking to become pregnant who are on MMF for lupus nephritis, how should this be managed?
MMF should be changed to azathioprine 6 weeks prior to conception
A prolonged course of immunosuppression in lupus nephritis helps to reduce relapse rates. How long should this be for?
> 2 years
Which immunoglobulins/complement constituents could you expect to see deposits of in proliferative lupus nephritis?
IgG
C1q
C3
IgA
IgM
“Full house”
Name 3 indications for PLEX in ANCA-positive vasculitis
Pulmonary haemorrhage
Anti-GBM
Haemoptysis
In AKI, in which two areas are cells particularly affected?
Proximal convoluted tubule - high metabolic rate due to ion transport
S3 segment of nephron in outer stripe of medulla
Name 6 potential markers for tubular injury besides Cr in AKI.
Cystatin-C - made by all cells, 90% filtered by glomeruli then reabsorbed PCT; better than Cr for estimations in patients with low muscle mass
NGAL - gives early diagnosis and predicts sustained AKI
IL-18
KIM-1
TIMP-2
IGFBP7
Top 2 are the important ones
What is used for prevention and treatment in hepatorenal syndrome?
Prevention - IV albumin
Treatment - terlipressin
However, definitive management is liver transplantation
What are the chromosomes and proteins associated with autosomal dominant polycystic kidney disease 1 and 2 respectively?
ADPKD1 - chromosome 16, polycystin 1
ADPKD2 - chromosome 4, polycystin 2
ADPKD1 is associated with more rapid decline
As well as the kidneys, in which 4 other organs can polycystin be found?
Liver
Heart
Brain
Lung
If patients have a positive family history for ADPKD, what are the criteria on imaging required in order to make a diagnosis?
Aged 15-40 - 3 or more cysts unilaterally or bilaterally
Aged 40-59 - 2 or more cysts in each kidney
Aged 60 and above - 4 or more cysts in each kidney
What type of antibiotics should be used in patients with ADPKD and UTIs?
Fluoroquinolones - good cystic penetrance
Name 2 cardiac complications associated with ADPKD.
Mitral valve prolapse
Aortic incompetence
When should patients with ADPKD be screened for cerebral aneurysms?
FHx of cerebral aneurysms
High risk professions
Headache
