Week 14 - Renal Flashcards
What are some of the functions of the kidney?
Metabolic waste excretion Endocrine functions Drug metabolism/excretion Control of solutes and fluid status Blood pressure control Acid/base balance
What would be a normal amount of protein in the urine?
Less than 150mg of protein / 24h
How would you measure urinary protein excretion?
24 hour urine collection: grams of protein/24hours (this is hard in clinical practice.)
So would normally do:
Protein:creatinine ratio (PCR) on morning spot sample(mg/mmol)
How would you calculate the eGFR?
(urine creatinine concentration x urine volume)/plasma creatine concentration
What GFR would be considered normal unless they had evidence of kidney disease?
≥60 ml/min/1.73m^2
What is glomerulonephritis?
An inflammatory disease involving the glomerulus and the tubules.
What are the three layers of the glomerular filtration barrier?
Endothelial cell Basement membrane Epithelial cells (podocytes)
What are the 4 targets for injury in glomerulonephritis?
Podocytes, glomerular capilliaries, basement membrane, mesangial cells.
How is glomerulonephritis diagnosed?
Kidney cortex biopsy
What are the 3 features of nephrotic syndrome?
- Proteinuria - either 3.5g proteinuria/24 hours or PCR>300
- low serum albumin (<30)
- Oedema
What are the potential complications of nephrotic syndrome?
Risk of venous thromboembolism
Increased risk of infection
What are some secondary causes of glomerulonephritis?
Diabetes Drugs i.e. NSAIDs, bisphosphonates Rheum - RA, lupus, amyloid CV - Subacute bacterial endocarditis Respiratory - bronchiectasis, lung cancer, TB Hepatitis, HIV
Which types of glomerulonephritis would fall under a more nephritic, nephrotic or rapidly progressive glomerulonephritis?
Rapidly progressive - IgA, lupus, vasculitis
Nephritic - IgA, lupus, post-infectious.
Nephrotic - minimal change, FSGS, membranous.
What is the pathology behind IgA nephropathy? How does the clinical picture progress? How is it treated?
IgA depositions in the mesangial cells. 1. haematuria 2. hypertension 3. proteinuria 4. renal failure ACEi, ARBs then corticosteroids if still proteinuria
How does membranous glomerulonephropathy present? What is it often secondary to? What antibodies are present in 70%?
Nephrotic syndrome
Malignancy, CTD, drugs.
Anti-phospholipiase A2 receptor antibody.
How is membranous nephropathy treated?
Treat underlying disease
supportive non-immunological - ACEi, diuretics, statins
Specific immunotherapy i.e steroids, cyclosporin, rituximab, alkylating agents
What age group is minimal change disease most common in? How does it present? What is the pathogenesis? What is it sometimes secondary to?
Children - 90% under 10
Nephrotic syndrome
T cell, cytokine mediated disease targeting the glomerular epithelial cell basement membrane.
URTI, malignancy.
What is the treatment of minimal change disease?
High dose steroids - prednisolone.
What are 3 causes of rapidly progressive glomerulonephritis?
ANCA vasculitis
Goodpasture’s syndrome
Lupus nephritis.
What is the hallmark of diabetic nephropathy? What other diabetic complication is it usually associated with?
Proteinuria
Retinopathy
What is the pathophysiology of diabetic nephropathy?
hyperglycaemia which leads to volume expansion which causes intraglomerular hypertension. This leads to hyperfiltration resulting in protein leaking through into the urine and ultimately, hypertension and renal failure.
How do you prevent people developing diabetic nephropathy?
Tight glycaemic control, control blood pressure well with ACEi, ARBs and SGLT2 inhibitors.
What is the pathogenesis of renovascular disease?
Progressive narrowing of renal arteries with atheroma.
Perfusion is reduced to 20%, GFR falls but tissue oxygenation maintained.
RA stenosis progresses to 70% and cortical hypoxia causes microvascular damage and activation of inflammatory and oxidative processes.
Parenchymal inflammation and fibrosis progress and become irreversible, restoration of blood flow provides no benefit.
How is renal artery stenosis managed?
Blood pressure control (not ACEi/ARB)
Glycaemic control if diabetic.
Smoking cessation, exercise, low sodium diet.
Angioplasty if rapidly deteriorating renal failure.
What is the pathophysiology of lupus nephritis?
Auto-antibodies produced against dsDNA or nucleosomes.
Form intravascular immune complexes or attach to GBM.
Activate complement (low C4)
Renal damage
What is the treatment of lupus nephritis?
Immunosuppression - steroids, MMF, cyclophosphamide, rituximab.
What is the diagnosis of lupus nephritis?
Autoantibodies and renal biopsy.
What is cystitis? What is its presenting features?
Infection of the bladder. Dysuria (pain passing urine) Frequency Urgency Suprapubic pain Haematuria
What is pyelonephritis? What are its presenting features?
All of the features for cystitis...PLUS Fever >38 degrees Chills/rigors Flank pain Costo-vertebral angle tenderness Nausea and vomiting
What are the risk factors for developing UTI?
Infancy - boys and girls under 1 Abnormal urinary tract - congenital or other. Females Bladder dysfunction/incomplete emptying Foreign body i.e. catheters, stones Diabetes mellitus Renal transplant Immunosuppression
How is urinary tract infection diagnosed?
Urinalysis - positive for leucocyte esterase and nitrite.
Microscopy/flow cytometry to detect pus cells and bacteria.
Urine culture
What are the most common bacteria that causes UTI?
E-coli - 90%
Klebsiella
Proteus (kidney stones)
What should be done in ALL children under three when clinical suspicion of a UTI?
Urine culture
What is the management of UTI in children?
Prompt identification - test urine if infant/child presents with urinary symptoms or unexplained fever >38 degrees.
Begin empirical antibiotics while awaiting culture and sensitivities. Oral antibiotic unless severely ill, vomiting or under 6 months.
What IV and oral antibiotics would be used in UTI?
IV - cefriaxone or gentamicin
Oral - co-amoxiclav, nitrofurantoin, trimethoprin, cephalosporin, quinolone.
What imaging modalities are used when investigating UTI?
Ultrasound
MCUG (micturating cystourethrogram)
Nuclear medicine imaging - DMSA, MAG3 indirect cystogram, MAG3 diuesis renogram.
What is vesico-ureteric reflux (VUR)? What does it predispose you to?
Retrograde passage of urine from the bladder into the upper urinary tract.
Recurrent UTIs
What is the management of VUR?
Antibiotic prophylaxis for high grade VUR (grade III-V) until toilet trained by day.
If this failed (i.e. recurrent febrile UTI, new scarring)
STING procedure
Open ureteric re-implantation
Circumcision
What are some of the causes of bladder outlet obstruction?
Posterior urethral valve
Prostatic hypertrophy
Functional neuropathy
Prune belly syndrome
What is the inheritance pattern of adult polycystic kidney disease?
Autosomal dominant
What two genes commonly cause polycystic kidney disease? What is the result of these mutations?
PKD1
PKD2
Overexpression of polycystins in the renal tubular epithelium forming cysts.
What is the natural history of adult polycystic kidney disease?
Cysts gradually enlarge and kidney volume increases. There is some compensation and then eGFR falls, usually 10 years before kidneys fail.
How is APKD diagnosed?
Ultrasound scan
CT or MRI scan more sensitive.
Genetic test
What are the clincial consequences of APKD?
End stage renal disease Cyst accidents - bleeding, infection, rupture Hypertension Intracranial aneurysms Mitral valve prolapse Aortic incompetence Colonic diverticular disease Liver/pancreas cysts Hernias
What is the management of polycystic kidney disease?
Supportive management
Early detection and management of blood pressure
Treat complications
Manage extra-renal associations
Renal replacement therapy i.e. transplant, dialysis
What can be used to treat APKD?
Tolvaptan - vasopressin V2 receptor antagonist to slow cyst formation.
What is the inheritance pattern of Alport’s syndrome? What protein is abnormal? What does alport’s syndrome cause?
X-linked
Collagen 4 - affects glomerular basement membrane
Deafness and renal failure
What are the clinical consequences of alport’s syndrome?
Microscopic haematuria, proteinuria and ESRF
90% on dialysis or transplant by age 40.
Sensorineural hearing loss late childhood
What is the inheritance pattern of fabry’s disease? What enzyme is deficient and what does this lead to? What other issues does it cause?
X linked
Alpha galactosidase A resulting in Gb3 accumulation in glomeruli and podocytes. Progression to ESRF.
Also causes neuropathy, cardiac and skin features.
What is the diagnosis and management of fabry’s disease?
Diagnosis: measure alpha-gal A activity in leukocytes. Renal biopsy.
Management: enzyme replacement therapy.
Give a definition of acute kidney injury.
AKI: decline of renal excretory function over hours or days, recognised by the rise in serum urea or creatinine.
What are the three main classification of causes of AKI?
Pre-renal - circulatory failure
Renal - problem with the cells of the kidney
post renal - obstruction
What are some pre-renal causes of AKI?
Hypotension Hypovolaemia (D&V, burns, haemorrhage) Hypoperfusion Hypoxia Sepsis Drugs, toxins
What are some of the renal causes of AKI?
Glomerulonephritis, drugs i.e. gentamicin.
Tubulo-interstitial nephritis, rhabdomyolysis
What are some of the post renal causes of AKI?
Renal papillary necosis, kidney stones, tumours (can be extrinsic), prostatic hypertrophy, urethral strictures, lymph node compression.
What is the most common cause of intrinsic AKI?
Acute tubular necrosis.
What is the cause of acute tubular necrosis?
ATN is always due to underperfusion of the tubules and/or direct toxicity:
- hypotension
- sepsis
- toxins
- or often, all three
What exogenous and endogenous toxins can cause ATN?
Exogenous - drugs i.e. NSAIDs, gentamicin, ACEi. Contrast, poisins e.g. metals, antifreeze.
Endogenous - myoglobin, haemoglobin, immunoglobulins, calcium, urate.
What is the treatment of AKI?
Airway and breathing
Circulation - shock - restore renal perfusion - treat hyperkalaemia and pulmonary oedema.
Remove causes - drugs, sepsis
Exclude obstruction and consider renal causes - ultrasound.
Ask for help: ICU or renal unit.
How is hyperkalaemia treated?
Calcium resonium to reduce absorption from the gut.
Insulin + dextrose to move K into cells.
Calcium gluconate as cardiac membrane stabiliser.
What are the indications for dialysis?
Refractory potassium ≥6.5 mmol/l Refractory pulmonary Oedema. Acidosis - pH <7.1 Uraemia (esp if urea >40) - pericarditis, encephalopathy Toxins (lithium, ethylene glycol.)
What is the definition of chronic kidney disease?
Kidney damage or GFR<60ml/min per 1.73m^2 for 3 months or more.
What is the aetiology of CKD?
Diabetic nephropathy
Renovascular disease/ischaemic nephropathy
Chronic glomerulonephritis
Reflux nephropathy/chronic pyelonephritis
Adult polycystic kidney disease
Obstructive uropathy
What are the symptoms of advanced CKD?
Pruritis Nausea, anoerxia, weight loss Fatigue Leg swelling Breathlessness Nocturia Joint/bone pain Confusion
What are the signs of advanced CKD?
Peripheral and pulmonary oedema Pericardial rub Rash/excoriation Hypertension Tachypnoea Cachexia Pallor &/or lemon yellow tinge
What are the general principles of managing CKD?
Targeted screening for CKD
Interventions to slow the rate of progression of CKD and reduce cardiovascular risk
Medicines to replace impaired individual functions of the kidney
Advanced planning for future renal replacement therapy
Renal replacement therapy
How do you slow the progression of CKD?
Aggressive BP control Good diabetic control Diet Smoking cessation Lowering cholesterol Treat acidosis
Which would be the drugs of choice to reduce hypertension in CKD?
ACEi or ARB
How do we treat CKD-MBD (mineral and bone disorder)?
Activated vitamin D Occasional Mg supplements Phosphate binders Calcimimetic: cinacalet Occasionally parathyroidectomy
What options are there for renal replacement therapy?
Transplant, conservative care, haemodialysis (home or hospital)
What would be the indications for renal replacement therapy?
Medically resistant hyperkalaemia Medically resistant pulmonary oedema Medically resistant acidosis Uraemic pericarditis Uraemic encephalopathy Specific drug overdoses
What are some of the symptoms of clinical uraemia?
Anorexia, vomiting, itch, restless legs, weight loss, metallic taste.
What GFR level would you start someone renal replacement therapy?
No absolute rule. Generally eGFR between 5-10ml/min/1.73m^2.
Assessed on an individual patient basis.
What are the three options for renal replacement therapy?
Haemodialysis
Peritoneal dialysis
Renal transplant
What are the two aims of haemodialysis?
Removal of solutes i.e. urea, potassium via diffusion.
Removal of fluid via hydrostatic filtration.
What are the different methods of getting haemodialysis access?
Creating an arteriovenous fistula, central venous catheter, arteriovenous graft.
What are the potential complications of haemodialysis?
Crash - acute hypotension Access problems Cramps Fatigue Hypokalaemia Blood loss Dialysis disequilibrium Air embolism
What are the principles of peritoneal dialysis?
Osmotic filtration to remove fluid, diffusion to remove solutes.
What are the benefits of peritoneal dialysis?
Home based therapy.
Simple to do once taught
Can maintain independence.
What are the potential complications of peritoneal dialysis?
Infection - peritonitis
Glucose load can result in developing or worsening diabetes.
Peritoneal membrane failure.
Mechanical - hernia, diaphragmatic leak, dislodged catheter.
Hypoalbuminaemia
Encapsulating peritoneal sclerosis.
What do you need to give patient’s who are on dialysis?
EPO injections
Phosphate binders and vitamin D
What are the pros and cons to renal transplantation?
Pros - no dialysis, better renal function, can live more independently, better life expectancy, fertility better.
Cons - immunosuppressive medication, increased CV risk, increased infection, post transplant diabetes, skin and other malignancies.
In what patients should you treat asymptomatic bacteriuria?
Pre-school children
Pregnancy
Renal transplant
Immunocompromised
What are the common organisms that cause UTI?
Majority gram negative bacilli:
- E Coli
- Klebsiella
- Proteus
- Pseudomonas
What gram positive can cause UTI?
Streptococcus - enterococcus, group B strep
Staphylococcus - aureas (associated with catheter).
What would you do for a first presentation of UTI in non-pregnant women?
Dipstick urine (high false +ve) Check previous culture results, antibiotics for 3-7 days. If no response to treatment: Urine culture Change antibiotic
What would you do for a first presentation of UTI in children and men?
Send urine away for culture, treat appropriately.
What would you do for a presentation of UTI in pregnancy? What antibiotics would you avoid?
Send urine for culture every time.
Treat for 7-10 days
Amoxicillin and cefalexin relatively safe.
Avoid trimethoprin in 1st trimester and nitrofurantoin near term.
What are the treatment options for recurrent UTI?
Self administered single dose/short course therapy.
Single dose post coital abx.
Prophylactic antibiotics
- if all measures fail, ideally 6 months of trimethoprim, nitrofurantoin (PF)
What is the management of acute pyelonephritis?
Check previous/recent microbiology results.
Send urine +/- blood culture +/- imaging
Community: co-amoxiclav/ciprofloxacin/trimethoprim
Hospital: often broad spectrum antibiotics +/- radiological/surgical infection
What is the management of complicated UTI?
FBC, U&Es, CRP Urine sample Blood culture if pyrexia or hypothermic Renal ultrasound CT KUB Antibiotic therapy for two weeks or more.
What could cause pyuria with no bacteria?
Previous/recent antibiotic Tumour Calculi Urethritis (check for chlamydia) TB
What would be the antibiotic therapy used for complicated UTI?
Usually IV therapy - amoxicillin/vancomycin
Gentamicin/aztreonam/temocillin
What are the clinical features of acute bacterial prostatitis?
Fever, perineal/back pain, UTI, urinary retention.
Diffuse oedema, microabscesses.
How would investigate acute bacterial prostatitis?
Urine culture, usually positive
Blood culture
Trans-rectal U/S
CT/MRI
What are the potential complications of acute bacterial peritonitis?
Prostatic abscess Spontaneous rupture - urethra, rectum Epipidymitis Pyelonephritis Systemic sepsis
What antibiotic therapy is commonly used for Acute bacterial prostatitis?
Ciprofloxacin
What is epididymitis? What is the aetiology? What are the symptoms?
Inflammatory reaction of the epididymis Ascending infection from the urethra Urethral instrumentation Pain, fever, swelling, penile discharge Symptoms of UTI/urethritis
What organisms commonly cause epididymitis?
Gram negatives i.e. enterococci, staphylococci
TB
Chlamydia, N.gonorrhoea
What is orchiditis and its symptoms?
Inflammation of one or both testicles.
Testicular pain and swelling, dysuria, fever, penile discharge.
Usually viral - i.e. mumps
What are the potential complications of bacterial orchiditis?
Testicular infarction
Abscess formation
What is fournier’s gangrene? What are the risk factors?
Form of necrotising fasciitis of the genital region due to infection.
Risk factors: UTI, complications of IBU, trauma, recent surgery.
What are the common pathogens that cause fournier’s gangrene? What investigations would you do?
Gram negatives and anaerobes.
Blood cultures, urine, tissue/pus.
Surgical debridement + broad spectrum antibiotics i.e. gentamicin, metronidazole, clindamycin.
What are the three broad causes of stone formation in the urinary tract?
Abnormal urine
Urinary obstruction
Urinary infection
What can cause too much salt in the urine, causing stones?
Hypercalciuria - i.e. through hyperparathyroidism, sarcoid
Too much acid - metabolic syndrome
Renal tubular acidosis
Hyperoxaliuria
What can cause not enough water in the urine, causing stones?
Not drinking enough water
What 4 substances act as stone inhibitors? Which
Citrate, magnesium, pyrophosphate, glycoproteins.
What factors encourage stone formation?
Low volume, low pH, low citrate, low magnesium.
High uric acid, high calcium, high oxalate.
List some congenital and acquired causes of urinary obstruction?
Congenital - medullary sponge kidney, PUJ obstruction, mega ureter, urterocele.
Acquired - ureteric stricture, anastomotic stricture.
What type of urinary infection causes stones to form?
Urease producing organisms i.e. proteus mirablis
Name 3 different types of stones?
Calcium stones i.e. calcium oxalate, calcium phosphate
Infection stones - struvite (proteus)
Uric acid stone
What different ways can stones present?
Incidental finding on imaging.
Pain - colic, radiates from loin to groin, cannot settle, unable to stay still.
Haematuria
UTI or Sepsis
What initial investigations would you do for stones?
History and examination
Bloods FBC, U&E, CRP
Urine examination and dipstick
Imaging - CT KUB gold standard
How are stones managed?
If they are small or asymptomatic - observation
Medical therapy - dissolution therapy
Non-invasive therapy
Invasive therapy
What medical therapies can be used to treat stones that are causing acute pain?
Analgesics - i.e. NSAIDs
Medical expulsive therapy i.e. tamsulosin
What are the surgical options for stones?
ESWL Rigid ureteroscopy and fragmentation/basket extraction FURS - flexible ureteroscopy Percutaneous nephrolithotomy Emergency stent or nephrostomy Laparoscopic or open surgery
