Kidney fifth yr Flashcards
Summary of renal tubular acidosis?
All associated with hyperchloaraemic metabolic acidosis (normal anion gap) - increased acidity of blood due to renal tubules not getting rid of protons
Type 1 - distal
inability to generate acid urine (secrete H+) in distal tubule, causes hypokalaemia
complications - nephrocalcinosis and renal stones
causes - idiopathic, RA, SLE, Sjogrens, amphotericin B toxicity, analgesic nephropathy
high calcium
pH >5.5
Type 2 - proximal
decreased HCO3- reabsorption in proximal tubule, causes hypokalaemia
complications - osteomalacia
causes - idiopathic, Fanconi syndrome, Wilsons disease, cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors (acetazolamide, topiramate)
normal calcium
pH <5.5
no stones
Type 3 - mixed
extremely rare
caused by carbonic anhydrase II deficiency
causes hypokalaemia
Type 4 - hyperkalaemic
reduction in aldosterone leads in turn to a reduction in proximal tubular ammonium excretion
causes hyperkalaemia
causes include hypoaldosteronism, diabetes
ass w/ SLE, sickle cell
normal calcium
pH <5.5
no stones
Summary of acute interstitial nephritis?
Accounts for 25% of drug-induced AKI
most often eosinophilic nephritis that can be:
drug-induced (e.g. NSAIDs, penicillin, diuretics, rifampicin, allopurinol),
infection-induced (e.g. tuberculosis, legionella, Hanta virus, staphylococci),
immune-mediated (e.g. sarcoidosis, SLE, Sjogrens or IgG-related disease (IgG4-RD))
Thought to be a type 1 or IV hypersensitivity reaction
Histology - : marked interstitial oedema and interstitial infiltrate in the connective tissue between renal tubules
Features - fever, rash, arthralgia, eosinophilia, mild renal impairment, HTN
Ix - sterile pyuria, white cell casts
Summary of glomerular disease?
nephritic and nephrite syndromes
may be primary renal disease (e.g. anti-glomerular basement membrane (anti-GBM), or part of systemic disease with immune complex deposition (e.g. IgA vasculitis) or without immune complex deposition (e.g. granulomatosis with polyangiitis (GPA))
Examples of intra-tubular obstruction?
multiple myeloma with paraprotein, pigment (e.g. rhabdomyolysis)
Summary of acute tubular necrosis?
the most common cause of AKI which occurs due to ischaemic or toxic injury to the cells of the proximal convoluted tubules
Epithelial cells lining the tubule become necrosed. Reversible if cause removed in early stages.
due to:
ischaemia - usually caused by some pre-renal AKI injury that leads to less perfused blood into kidney (shock/sepsis)
nephrotoxins - e.g. Aminoglycosides, heavy metals, myoglobin, ethylene glycol, radiocontrast dye, lead and uric acid
when cells die and enter the tubule, can form a plug. blocks tubule and ends up generating higher pressure tubule, and hence lowering GFR rate and builds up hyperkalaemia
Features - AKI features (raised urea, creatinine, K+), muddy brown casts in urine
Histopathology - tubular epithelium necrosis: loss of nuclei and detachment of tubular cells from the basement membrane
dilatation of the tubules may occur
necrotic cells obstruct the tubule lumen
Patterns of glomerulonephritis?
- Minimal change
o Large amounts of protein are lost in the urine
o Most common cause of nephrotic syndrome - Membranous GN
o Develops when inflammation of your kidney structures causes problems with the functioning of your kidney - Mesangial proliferative
- Focal segmental GN
- Diffuse endothelial proliferative
- Mesangiocapillary
- Crescentic
Summary of minimal change glomerulonephritis?
Nephrotic syndrome
Light microscopy normal
Electron microscopy - foot processes effaced, filtration barrier lost
Most respond to steroids
Summary of focal segmental glomerulosclerosis?
Cause of nephrotic syndrome and CKD
Most common cause of nephrotic syndrome in African Americans and hispanics
Generally affects young adults
Causes - idiopathic, secondary to other renal pathology (e.g. IgA nephropathy, reflux nephropathy), HIV, heroin, Alport’s syndrome, sickle-cell
Can be due to continuation of minimal change disease?
noted for having a high recurrence rate in renal transplants
Ix - renal biopsy - focal and segmental sclerosis and hyalinosis on light microscopy, effacement of foot processes on electron microscopy, immunoflourescence (nonspecific focal deposits of IgM and complement)
Tx - steroids +/- immunosuppressants
Prognosis - untreated FSGS has a < 10% chance of spontaneous remission
Summary of minimal change disease?
nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults. Most common nephrotic syndrome in children
Causes - idiopathic (majority), drugs: NSAIDs, rifampicin
Hodgkin’s lymphoma, thymoma, infectious mononucleosis
Pathophysiology - T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss, the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin
Features - nephrotic syndrome, normotension, highly selective proteinuria (albumin and transferrin)
Ix - renal biopsy - normal glomeruli on light microscopy, electron microscopy shows fusion of podocytes and effacement of foot processes, negative immunofluorescence
Tx - oral corticosteroids, cyclophosphamide is the next step for steroid-resistant cases
Prognosis- 1/3 have just one episode, 1/3 have infrequent relapses, 1/3 have frequent relapses which stop before adulthood
Phases of acute tubular necrosis?
oliguric phase
polyuric phase
recovery phase
7-21 days for full recovery
Urinalysis of acute tubular necrosis?
Muddy brown casts - pathognomonic for ATN
Renal tubular epithelial cells
Management of acute tubular necrosis?
Supportive
IV fluids
Stop nephrotoxic meds
Tx complications
What is tubulointerstitial nephritis with uveitis?
usually occurs in young females.
Symptoms include fever, weight loss and painful, red eyes.
Urinalysis is positive for leukocytes and protein.
Summary of anti-GBM disease? (Goodpastures)
small vessel vasculitis - associated with pulmonary haemorrhage and rapidly progressive glomerulonephritis
rapid onset AKI. Nephritis = proteinuria and haematuria
anti-GBM antibodies against type IV collagen
M>F, peaks 20-30 and 60-70. Associated w/ HLA DR2
Ix - renal biopsy (linear IgG deposits along basement membrane), raised transfer factor secondary to pulmonary haemorrhage
Tx - plasma exchange, steroids, cyclophosphamide
Summary of IgA nephropathy
Bergers disease - commonest cause of glomerulonephritis worldwide
presents - macroscopic haematuria in young people following URTI
Associated conditions - alcoholic cirrhosis, coeliac/dermatitis herpetiformis, Henoch-Schonlein purpura
Pathophysiology - mesangial deposition of IgA immune complexes, histology - mesangial hypercellularity, positive immunofluorescence for IgA and C3
difference between IgA and post-strep? post-step =low complement, post-strep = proteinuria, time interval with post-strep
Tx -
isolated haematuria/minimal proteinuria and normal GFR - no Tx needed, follow up to check renal function
persistent proteinuria, only slight reduction in GFR - initial Tx with ACEi
active disease, falling GFR, failure to respond to ACEi - immunosuppression with corticosteroids
Prognosis - 25% develop ESRF
Prognosis of IgA nephropathy?
25% of patients develop ESRF
markers of good prognosis: frank haematuria
markers of poor prognosis: male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD
Summary of membranoproliferative glomerulonephritis?
also known as mesangiocapillary glomerulonephritis
may present as nephrotic syndrome, haematuria or proteinuria
poor prognosis
Type 1 - 90%, causes (cryoglobulinaemia, hep C), renal biopsy - electron microscopy - subendotheial and mesangium immune deposits - ‘tram-track’ appearance
Type 2 - dense deposit disease - causes (partial lipodystrophy (patients classically have a loss of subcutaneous tissue from their face), factor H deficiency, persistent activation of alternative complement pathway), low C3, biopsy - electron microscopy - intramembranous immune complex deposits with ‘dense deposits’
Type 3 - causes - hep B and C
Tx - steroids
Summary of membranous glomerulonephritis?
commonest type of glomerulonephritis in adults and is the third most common cause of end-stage renal failure (ESRF).
presents with nephrotic syndrome or proteinuria.
biopsy - electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a ‘spike and dome’ appearance
causes - idiopathic, infections (hep B, malaria, syphilis), malignancy (prostate, lung, lymphoma, leukaemia), drugs (gold, penicillamine, NSAIDs), AI (SLE, thyroiditis, rheumatoid)
Tx - ACEi or ARB (reduce proteinuria), immunosuppression (if severe or progressive), anticoagulation for high risk pt
Rule of thirds for prognosis
one-third: spontaneous remission
one-third: remain proteinuric
one-third: develop ESRF
Good prognostic features include female sex, young age at presentation and asymptomatic proteinuria of a modest degree at the time of presentation.
RFs for contrast media nephrotoxicity?
known renal impairment (especially diabetic nephropathy)
age > 70 years
dehydration
cardiac failure
the use of nephrotoxic drugs such as NSAIDs
Summary of contrast media nephrotoxicity?
Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within 3 days of the intravascular administration of contrast media.
Contrast-induced nephropathy occurs 2 -5 days after administration.
Eg., CT w/ contrast, CT angio, PCI
Prevention - intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure.
Withhold metformin for 48 hours and until renal function normal if at high risk
Summary of post-streptococcal glomerulonephritis?
Typically occurs 7-14 days following a group A beta-haemolytic Streptococcus infection (usually Streptococcus pyogenes)
Caused by immune complex (IgG, IgM, C3) deposition in glomeruli
Common in young children
Features - headache, malaise, visible haematuria, proteinuria, HTN, oliguria, bloods (raised anti-streptolysin O titre to confirm diagnosis, low C3)
Renal biopsy - cute, diffuse proliferative glomerulonephritis, endothelial proliferation with neutrophils, microscopy - sub epithelial humps, immunoflourescnece - granular ‘starry sky’ appearance
Causes of rapidly progressive glomerulonephritis?
used to describe a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.
Goodpasture’s
Wegener’s granulomatosis
SLE
Microscopic polyarteritis
Causes of rapidly progressive glomerulonephritis?
Goodpasture’s
Wegener’s granulomatosis
SLE
Microscopic polyarteritis
Summary of rapidly progressive glomerulonephritis?
used to describe a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.
Features - nephritic syndrome - haematuria with RCC, proteinuria, HTN, oliguria
features specific to underlying cause (e.g. haemoptysis with Goodpasture’s, vasculitic rash or sinusitis with Wegener’s)
Renal complications of SLE?
Lupus nephritis > can result in end-stage renal disease
should be monitored by performing urinalysis at regular check-up appointments to rule out proteinuria.
WHO classification - Class I normal kidney, class VI - sclerosis GN
Class IV (diffuse proliferative glomerulonephritis) is more common and severe form
Renal biopsy - glomeruli shows endothelial and mesangial proliferation, ‘wire-loop’ appearance
if severe, the capillary wall may be thickened secondary to immune complex deposition
electron microscopy shows subendothelial immune complex deposits
granular appearance on immunofluorescence
Summary of renal artery stenosis?
Secondary to atherosclerosis accounts for around 90% of renal vascular disease
Fibromuscular dysplasia is most common of remaining 10%
Features - accelerated or difficult to control HTN, CKD, flash pulmonary oedema
worsening kidney function, especially after initiating renin-angiotensin blockade
Ix - creatinine, K+, urinalysis, sediment evaluation, aldosterone:renin ratio
Tx - controlling RFs, lower HTN, surgery (angioplasty and stunting)
Definition of renal failure?
defined as a glomerular filtration rate of less than 15ml/min
management options are renal replacement therapy (RRT), to take over the physiology of the kidneys, or conservative management, which will be palliative.
Types of renal replacement therapy?
haemodialysis - regular filtration of the blood through a dialysis machine in hospital. Need AV fistula
peritoneal dialysis - filtration occurs within the patient’s abdomen. The high dextrose concentration of the solution draws waste products from the blood into the abdominal cavity across the peritoneum. After several hours of dwell time, the dialysis solution is then drained, removing the waste products from the body, and exchanged for new dialysis solution. Continuous ambulatory peritoneal dialysis (CAPD) and Automated peritoneal dialysis (APD)
renal transplant - involves the receipt of a kidney from either a live or deceased donor. The average wait for a kidney in the UK is 3 years. The donor kidney is transplanted into the groin, with the renal vessels connected to the external iliac vessels. patient must take life-long immunosuppressants to prevent rejection of the new kidney.
Complications of haemodialysis?
site infection
endocarditis
stenosis at site
hypotension
cardiac arrhythmia
air embolus
anaphylactic reaction to sterilising agents
disequilibrium syndrome
Complications of peritoneal dialysis?
peritonitis
sclerosing peritonitis
catheter infection
catheter blockage
constipation
fluid retention
hyperglycaemia
hernias
back pain
malnutrition
Complications of kidney transplant?
DVT/PE
opportunistic infection
malignancies (lymphoma, skin cancer)
bone marrow suppression
recurrence of disease
urinary tract obstruction
CVD
graft rejection
ATN of graft
UTI
urine leakage
Summary of hyperacute rejection?
due to pre-existing antibodies against ABO or HLA antigens
an example of a type II hypersensitivity reaction
leads to widespread thrombosis of graft vessels → ischaemia and necrosis of the transplanted organ
no treatment is possible and the graft must be removed
Summary of acute graft failure (<6m)?
usually due to mismatched HLA. Cell-mediated (cytotoxic T cells)
usually asymptomatic and is picked up by a rising creatinine, pyuria and proteinuria
other causes include cytomegalovirus infection
may be reversible with steroids and immunosuppressants
Summary of chronic graft failure (>6m)?
Causes:
both antibody and cell-mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)
recurrence of original renal disease (MCGN > IgA > FSGS)
Immunosuppression for renal transplant?
Example:
Initial: ciclosporin/tacrolimus with a monoclonal antibody
maintenance: ciclosporin/tacrolimus with mycophendlate mofetil (MMF) or sirolimus
add steroids if more than one steroid responsive acute rejection episode
Regular monitoring:
Cardiovascular disease - tacrolimus and ciclosporin can cause hypertension and hyperglycaemia. Tacrolimus can also cause hyperlipidaemia. Patients must be monitored for accelerated cardiovascular disease.
Renal failure - due to nephrotoxic effects of tacrolimus and ciclosporin/graft rejection/recurrence of original disease in transplanted kidney
Malignancy - patients should be educated about minimising sun exposure to reduce the risk of squamous cell carcinomas and basal cell carcinomas
Type of transplants
- Allograft -> tissue graft from donor of same species as recipient but not genetically identical
- Autograft -> graft of tissue from one point to another of the same individual’s body
- Isograft -> graft of tissue between 2 individuals who are genetically identical
- Orthotopic graft -> tissue or an organ that is transplanted into normal place in the body
- Xenograft -> transplant of an organ, tissue to an individual of another species
Summary of transplantation and the immune system?
Major histocompatibility complex
- Genes coding for human leukocyte antigens
- Class I antigens (HLA-A, B, Cw) expressed on all nucleated cells
- Class II antigens (HLA-DR, DQ, DP) expressed on antigen presenting cells, B-lymphocytes and activated T cells
- Inherited – highly variable between individuals
o Each have 2 alleles on each gene, so express 2 copies of each HLA type
o e.g. 2 copies of A, B, Cw
HLA and renal transplantation
- Most interest has been on HLA types A, B and DR
o If donor HLA-type matched to recipient HLA-type then transplant survival is better
