Kidney fifth yr

Question 1

Summary of renal tubular acidosis?

Answer 1

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causes - idiopathic, Fanconi syndrome, Wilsons disease, cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors (acetazolamide, topiramate)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

Question 2

Summary of acute interstitial nephritis?

Answer 2

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

Question 3

Summary of glomerular disease?

Answer 3

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))

Question 4

Examples of intra-tubular obstruction?

Answer 4

multiple myeloma with paraprotein, pigment (e.g. rhabdomyolysis)

Question 5

Summary of acute tubular necrosis?

Answer 5

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

Question 6

Patterns of glomerulonephritis?

Answer 6

• 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

Question 7

Summary of minimal change glomerulonephritis?

Answer 7

Nephrotic syndrome

Light microscopy normal

Electron microscopy - foot processes effaced, filtration barrier lost

Most respond to steroids

Question 8

Summary of focal segmental glomerulosclerosis?

Answer 8

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

Question 9

Summary of minimal change disease?

Answer 9

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

Question 10

Phases of acute tubular necrosis?

Answer 10

oliguric phase
polyuric phase
recovery phase

7-21 days for full recovery

Question 11

Urinalysis of acute tubular necrosis?

Answer 11

Muddy brown casts - pathognomonic for ATN

Renal tubular epithelial cells

Question 12

Management of acute tubular necrosis?

Answer 12

Supportive

IV fluids

Stop nephrotoxic meds

Tx complications

Question 13

What is tubulointerstitial nephritis with uveitis?

Answer 13

usually occurs in young females.

Symptoms include fever, weight loss and painful, red eyes.

Urinalysis is positive for leukocytes and protein.

Question 14

Summary of anti-GBM disease? (Goodpastures)

Answer 14

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

Question 15

Summary of IgA nephropathy

Answer 15

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

Question 16

Prognosis of IgA nephropathy?

Answer 16

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

Question 17

Summary of membranoproliferative glomerulonephritis?

Answer 17

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

Question 18

Summary of membranous glomerulonephritis?

Answer 18

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.

Question 19

RFs for contrast media nephrotoxicity?

Answer 19

known renal impairment (especially diabetic nephropathy)

age > 70 years

dehydration

cardiac failure

the use of nephrotoxic drugs such as NSAIDs

Question 20

Summary of contrast media nephrotoxicity?

Answer 20

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

Question 21

Summary of post-streptococcal glomerulonephritis?

Answer 21

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

Question 22

Causes of rapidly progressive glomerulonephritis?

Answer 22

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

Question 23

Causes of rapidly progressive glomerulonephritis?

Answer 23

Goodpasture’s
Wegener’s granulomatosis
SLE
Microscopic polyarteritis

Question 24

Summary of rapidly progressive glomerulonephritis?

Answer 24

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)

Question 25

Renal complications of SLE?

Answer 25

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

Question 26

Summary of renal artery stenosis?

Answer 26

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)

Question 27

Definition of renal failure?

Answer 27

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.

Question 28

Types of renal replacement therapy?

Answer 28

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.

Question 29

Complications of haemodialysis?

Answer 29

site infection
endocarditis
stenosis at site
hypotension
cardiac arrhythmia
air embolus
anaphylactic reaction to sterilising agents
disequilibrium syndrome

Question 30

Complications of peritoneal dialysis?

Answer 30

peritonitis
sclerosing peritonitis
catheter infection
catheter blockage
constipation
fluid retention
hyperglycaemia
hernias
back pain
malnutrition

Question 31

Complications of kidney transplant?

Answer 31

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

Question 32

Summary of hyperacute rejection?

Answer 32

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

Question 33

Summary of acute graft failure (<6m)?

Answer 33

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

Question 34

Summary of chronic graft failure (>6m)?

Answer 34

Causes:
both antibody and cell-mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)

recurrence of original renal disease (MCGN > IgA > FSGS)

Question 35

Immunosuppression for renal transplant?

Answer 35

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

Question 36

Type of transplants

Answer 36

• 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

Question 37

Summary of transplantation and the immune system?

Answer 37

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