Week 14 Flashcards
What are the functions of the kidney?
- Metabolic waste excretion (urea, creatinine)
- Endocrine functions (vitamin D, EPO, PTH)
- Drug metabolism/excretion
- Control of solutes and fluid status (sodium, potassium, fluid)
- Blood pressure control
- Acid/base
How is kidney function assessed?
Measure what is put out in urine or what’s left in blood
Urinalysis:
- detects proteinuria
- 24hr urine collection (grams/24h)
- PCR ratio (mg/mmol)
- albumin:creatinine ratio (mg/mmol)
- haematuria
- visible or non-visible (only detectable on dipstick)
U&Es: urea, creatinine and eGFR
Describe limitations of kidney function tests:
- Creatinine is affected by muscle mass, so 2 people of same age with different muscle masses will have different creatinine
- 15% of creatinine is secreted by tubule
- Urea is not as sensitive as creatinine
- eGFR assumes stable renal function
- Not suitable in AKI
Describe the aetiology of GN:
Extrinsic causes: antibodies, immune complexes, complement
Intrinsic causes: cytokines, growth factors, proteinuria
Can be primary or secondary
Secondary causes
- CV: subacute bacterial endocarditis
- respiratory: bronchiectasis, lung cancer, TB, pulmonary renal syndromes
- ID: hepatitis, HIV, chronic infections, abx, malaria
- rheumatology: RA, SLE, amyloidosis, CT disease
- drugs: NSAIDs, bisphosphonates, heroin
- GI: ALD, IBD, coeliac disease
- diabetes
- haematological: myeloma, CLL, PRV
Discuss diagnosis of GN:
Approach:
- presentation, history/exam
- kidney biopsy (of cortex) findings
- likely cause and specific management
Describe different clinical presentations of GN:
Rapidly progressive GN:
- rapid rise in serum creatinine
- crescentic damage
- vasculitis/lupus/IgA; often have other clinical features
Nephritic:
- blood and protein in urine, high BP, rising sCr
- proliferative/acute inflammation
- IgA/lupus/post-infectious
Nephrotic:
- > 3.5g/d proteinuria, low sAlb, oedema
- non-proliferative, podocyte damage (scarring)
- minimal change/FSGC/membranous
Overlap:
- blood/heavy proteinuria
- IgA/MCGN/SLE
Other:
- urinary abnormalities alone
- hypertension
Outline treatment and prognosis of GN:
Possible therapeutic strategies:
- Control infection, CTD (cyclophosphamide, dexamethasone, thalidomide)
- Remove Ab/IC or block Ab
- Steroids, cytotoxics and anti-hypertensives
- Dialysis, transplantation
Treat:
IgA; antihypertensives, ACEi
Membranous; treat primary cause, supportive treatment (ACEi, statin, diuretics, salt restriction) or specific immunosuppression
Minimal change with high dose steroids
Describe the pathophysiology, presentation, and management of diabetic nephropathy:
Not diabetic nephropathy if no proteinuria and if not presenting with other microvascular symptoms
Pathology: hyperglycaemia -> volume expansion -> intra-glomerular hypertension -> hyperfiltration -> proteinuria -> hypertension and renal failure
Management:
- good glycaemic control
- good BP control
- ACEi/ARB
- SGLT2 inhibitors
Describe the pathophysiology, presentation, and management of vascular disease affecting the
kidneys:
Presentation: likely other vascular complications, PVD, hypertension, angina
Pathology:
- progressive narrowing of renal arteries with atheroma
- perfusion falls, stenosis progresses
- cortical hypoxia causes microvascular damage and activation of inflammatory pathways
- parenchymal inflammation and fibrosis progresses and becomes irreversible
Management:
- medical: BP control (not ACEo/ARB), statin
- lifestyle: smoking cessation, exercise, low sodium diet
- angioplasty only in rapidly deteriorating renal failure, uncontrolled raised BP and flash oedema
Describe the pathophysiology, presentation and management of other diseases, such as lupus
and amyloidosis and their effect on the kidneys:
SLE:
- multiple autoAbs directed against cells of the GBM
- activation of complement
- presents with nephritic syndrome and abnormal immunology results
- management with immunosuppression
- steroids
- MMF
- cyclophosphamide/rituximab
Amyloidosis:
- depositions insoluble proteinous (beta-pleated sheets) material in extracellular space
- high affinity for constituents of capillary wall
- presents with hypoalbuminaemia, elevated uPCR, nephrotic syndrome
- amyloid evident on biopsy
- treat underling source of inflammation/infection or underlying haematological condition (myeloma)
Describe APKD:
APKD:
- cysts arise from tubules
- cysts gradually enlarge
- kidney volume increases
- some compensation
- eGFR falls, usually 10yr before kidneys fail
- genetic (PKD1 and 2 gene mutations)
- code for polycystin 1 and 2, locate in renal tubular epithelia (liver and pancreas ducts)
Management is supportive
Early detection and management of BP
Treat complications
Renal replacement therapy
What are some other inherited kidney diseases?
Alport’s syndrome: X-linked kidney disease caused by collagen 4 abnormality (affects BM) and presents with deafness and renal failure
Fabry’s disease: X-linked storage disorder caused by alpha galactosidase deficiency resulting in accumulation of Gb3 in glomeruli- causing ESRF
Also has neuropathy, cardiac and skin features
What are presenting features of cystitis and pyelonephritis:
Cystitis - infection of the bladder dysuria frequency urgency suprapubic pain haematuria
Pyelonephritis - infection of the kidney the above PLUS fever (>38ºC) chills/rigors flank pain costo-vertebral angle tenderness nausea/vomiting
What are the clinical consequences of tubulointerstitial abnormalities?
Renal scarring in 10-15% of children with UTI in childhood
20% of children and adults with ESRD have scarring
Congenital abnormalities:
- vesico-uretetic reflux
- retrograde passage of urine from the bladder into the upper urinary tract
- obstruction of urinary drainage tracts
Chronic renal failure, recurrent UTIs, renal scarring
What is glomerulonephritis?
- Inflammation of glomerulus and tubules
- Affects both kidneys but not necessarily all of each
Describe specific aetiologies of GN:
IgA:
- mesangial disease (proliferation caused by mesangial IgA)
- can be precipitated by infection; synpharyngitic presentation
- may be secondary to HSP, cirrhosis, coeliac disease
Membranous:
- presents with nephrotic syndrome
- 10% secondary to malignancy, CTD, drugs
- variable natural history
Minimal change:
- commonest form of GN in children
- podocyte fusion
- idiopathic but may be secondary to malignancy
Crescentic:
- aggressive disease which quickly progresses to ESRF
- commonly caused by ANCA vasculitis, and other immune conditions
What is nephrotic syndrome?
- 3.5g proteinuria per 24h
- Serum albumin <30
- Oedema
- Hyperlipidemia
Must have first 3 for diagnosis
Children get swollen eyes
Risk of VTE and increased risk of infection (loss of anti-thrombotic factors and immunoglobulins)
What are the clinical consequences of APKD:
Renal complications: ESRD Cyst accidents Other: - hypertension - intracranial aneurysms - mitral valve prolapse - aortic incompetence - colonic diverticular disease - liver/pancreas cysts - hernias
What are the risk factors for UTI?
Infancy - boys and girls under 1 year Abnormal urinary tract - congenital or other abnormalities Females - Anatomy - Sexual intercourse - Pregnancy Bladder dysfunction/incomplete emptying - Constipation (‘dysfunctional elimination syndrome’) - Neurogenic bladder - Prostate enlargement in men ‘Foreign' body - catheters - stones Diabetes mellitus - glycosuria promotes bacterial growth Renal transplant Immunosuppression
What factors can contribute to the development of AKI?
Pre-renal: anything that impairs renal perfusion
- hypotension
- hypovolaemia (burns, diarrhoea, haemorrhage)
- hypoperfusion
- hypoxia
- sepsis (vasodilation so effective perfusion decreases)
- drugs, toxins
Renal:
- glomeruli: GNs, drugs (gentamicin)
- tubules: tubule-interstitial nephritis, rhabdomyolysis
Post-renal: obstructive causes
- calculi
- tumours (ureter, bladder, prostate, cervix, ovarian)
- lymph nodes (commpression)
- prostate
What are the outcomes for AKI?
Acute tubular necrosis
- Often polyuric phase for 48-72 hr
- May be up to 6l urine/day
- Often subsequent low K, Ca, Mg
- Tubules can fail to concentration urine
- ~10-15% will never recover renal function, may have chronic renal failure following ATN
Outline the diagnostic process in patient presenting with AKI:
AKI or CKD?
History and exam (e.g. septic, rashes, haemoptysis, rhabomyolysis etc)
Drugs (prescribed, OTC, supplements, radio-contrast and abuse)
Urinalysis
Renal ultrasound- to exclude obstruction
‘GN’ screen – ANCA, ANA, Immunoglobulins + EP, complement, aGBM, Urine Bence Jones protein
Others blood film, lactate (LDH), CK etc
Outline emergency management of the patient with AKI:
Immediate
Airway and Breathing
Circulation – shock - restore renal perfusion
- hyperkalaemia
- pulmonary oedema
Remove causes; drugs or sepsis
Exclude obstruction & consider ‘renal’ causes: are the pre-renal causes sufficient to account for ARF?
Ask for help: ICU or renal unit
K >6.5 is a medical emergency
- treat with calcium gluconate 10ml 10% as cardiac membrane stabiliser
- see CBL for other treatments
How is the severity of CKD classified?
CKD = kidney damage or GFR<60ml/min per 1.73m2 for 3 months or more
With eGFR: Stage 1: >90 Normal or increased eGFR with other evidence of kidney damage Stage 2: 60-89 Slight decrease in eGFR with other evidence of kidney damage Stage 3a: 45-59 Moderate decrease in eGFR Stage 3b: 30-44 Moderate decrease in eGFR Stage 4: 15-29 Severe decrease in eGFR Stage 5: <15 Established renal failure
SEE NICE 2014 GUIDELINES
Describe clinical features of CKD:
Symptoms:
Pruritus Nausea, anorexia, weight loss Fatigue Leg swelling Breathlessness Nocturia Joint/bone pain Confusion
Signs:
Peripheral and pulmonary oedema Pericardial rub Rash/excoriation Hypertension Tachypnoea Cachexia Pallor &/or lemon yellow tinge
Outline clinical consequences of progressive CKD:
Anaemia:
- common, when eGFR <30
- iron absorption and utilisation suboptimal
- replace iron, B12, folate first if low
- then ESA
CKD mineral and bone disorder:
- accumulation of phosphate
- calcium reabsorption decreases
- PTH is activated to compensate
- further increases phosphate causing calcium decrease
- treat with activated via D, phosphate binders, calcimimetic, parathyroidectomy
How are patients with CKD managed?
General principles:
- 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 (RRT)
- renal replacement therapy
Slowing progression: Aggressive BP control Good diabetic control Diet Smoking cessation Lowering cholesterol Treat acidosis
What are the indications for renal replacement therapy?
- Medically resistant hyperkalaemia
- Medically resistant pulmonary oedema
- Medically resistant acidosis
- Uraemic pericarditis
- Uraemic encephalopathy
and specific drug overdoses
Describe haemodialysis:
2 aims:
removal of solutes- e.g. potassium, urea by DIFFUSION
removal of fluid: ultrafiltration- pressure: HYDROSTATIC FILTRATION
Blood in=> blood out => diffusion removes solutes => filtration removes fluid => dialysate discarded
Often requires surgical creation of AV fistula or AV graft for ease of access
Complications: crash, access problems, cramps, fatigue, hypokalaemia, blood loss, dialysis disequilibrium, air embolism
Describe peritoneal dialysis:
Dialysate (high glucose concentration)-filled peritoneal cavity with high osmolality
Blood in peritoneal capillaries with low osmolality
Water, urea, creatinine and electrolytes and macromolecules diffuse to peritoneal cavity where they are removed by catheter
Can be continuous ambulatory or automated
Complications:
Infection - peritonitis
Glucose load – development or worsening control of diabetes
Mechanical – hernia, diaphragmatic leak, dislodged catheter
Peritoneal membrane failure
Hypoalbuminaemia
Encapsulating peritoneal sclerosis
Some patients not suitable:
- grossly obese
- intra-abdominal adhesions
- frail
- home not suitable
Describe renal transplantation:
Pros: No dialysis Better level of renal function Can live much more independently Better life expectancy Fertility better
Cons: Immunosuppressive medication for duration of transplant Increased cardiovascular risk Increased infection Post transplant diabetes Skin malignancies and others
Describe pathophysiology of UTI:
Ascending urethral colonisation female>male multiplication in bladder ureteric involvement Descending/haematogenous blood-borne infections involvement of renal parenchyma
CFs:
- suprapubic discomfort
- dysuria, urgency, frequency
- cloudy, blood stained and smelly urine
- low-grade fever
- sepsis
Describe the pathophysiology of pyelonephritis:
Upper urinary tract infection Moderate to severe infection Ascending infection involving pelvis of kidney Enlarged kidney Abscesses on surface of kidney
Describe the pathophysiology of prostatitis:
Localised infection Usually spontaneous May follow urethral instrumentation Fever, perineal/ back pain, UTI, urinary retention Diffuse oedema, micro abscesses Likely organisms Gram negative bacilli, e.g. E.coli, Proteus sp. S.aureus (MSSA, MRSA) N.gonorrhoea (less common)
What organisms can cause UTI/PYN/PRT?
UTI:
G-ve bacilli: e coli, klebsiella, proteus, pseudomonas
G+ve: strep; enterococcus, gp B strep, S. aureus
Anaerobes
Candida sp
PYN:
PRT:
Describe antimicrobial treatment of UTI:
UTI:
Uncomplicated
- in pregnancy amoxicillin and cefalexin relatively safe, avoid trimethoprim in 1st trimester, avoid nitrofurantoin near term
- recurrent; encourage hydration, short course therapy
- recurrent: if simple measures fail 6 monthly trimethoprim/nitrofurantoin prophylaxis
Complicated
- catheter associated UTI
- colonisation common, treatment not always required
- related UTI treat with empirical abx (gent/ciprofloxacin), remove catheter if not needed
Complicated:
All patients
FBC, U+Es, CRP
- Urine sample
- Urethral, CSU, Suprapubic, Nephrostomy
Blood culture if pyrexia or hypothermic
Renal ultrasound
CT KUB
Antibiotic therapy 14/7 or more
- usually IV
- amoxicillin/vancomycin
- gent/aztreonam/temocillin
What are the complications of pyelonephritis?
Renal abscess:
- similar symptoms to PYN
- usually positive urine and blood culture
- G-ve bacilli likely organisms
- can become life-threatening
- poor response to abx
Perinephric abscess: - uncommon - risk factors - Untreated LUTI, anatomical abnormalities - Renal calculi - Bacteraemia, haematogenous spread Common organisms - Gram negative bacilli, E.coli, Proteus sp. - Gram positive cocci, S.aureus, Streptococci - Candida sp. - treat empirically as complicated UTI - surgical management
Define key pharmacokinetic variables:
Pharmacodynamics: what the drug does to your body
Pharmacokinetics: what your body does to the drug
Bioavailability: fraction of the administered dose of drug that reaches the systemic circulation
Clearance: volume of plasma ‘cleared’ of drug per unit time
Half life: time required for serum plasma concentration to decrease by half
Linear pharmacokinetics: concentration that results from a dose is proportional to the dose ie double the dose, double the concentration
Non-linear pharmacokinetics: concentration that results is not proportional to dose, rate of elimination is constant regardless of amount of drug present
Volume of distribution (VD) is the volume in which the amount of drug would need to be uniformly distributed to produce observed blood concentration
How are these variables altered in renal and hepatic disease?
Renal disease:
- same hepatic metabolism
- same/increase VD and prolonged elimination (half life increased)
- thus, increased dosing interval
Hepatic disease
- same renal elimination
- same/increased VD and slower rate of enzyme metabolism (half life/bioavailability increased)
- decreased dosage and increased dosing interval
Describe prescribing issues to using drugs in the elderly:
The more medications a person is on, the higher the risk of drug-drug interactions or adverse drug reactions
The more medications a person is on, the higher the risk of non-adherence
Drug-disease interactions (PD increased risk of drug induced confusion)
Drug-drug interactions: statins and erythromycin and other abx, ACEi increase hypoglycaemia effect of sulfonylureas
Undertreatment to avoid risk (ie anticoagulation in AF from fear of falls)
Polypharmacy/prescribing cascade:
NSAID => hypertension => antihypertensive therapy
How are commonly prescribed drugs altered in renal and hepatic dysfunction?
Renal important examples: Antibiotics- nephrotoxic, uraemia (reduce dose) LMWH (reduce dose) Metformin (avoid) NSAIDs- fluid retention (avoid) Digoxin- electrolyte disturbances (reduce dose) Phenytoin (reduce dose) ACE Inhibitors (caution)
Hepatic: High extraction - Metabolised at high rate by liver - Rate varies with delivery - Affected by changes in blood flow - Morphine, verapamil, lignocaine Low extraction: - Metabolised at low rate by liver - Independent of blood flow - Sensitive to changes in liver enzyme activity - Chloramphenicol, theophylline
Describe pathophysiology of tumours in the kidney and lower urinary tract:
Prostate:
- majority is adenocarcinoma, usually arising in peripheral zone of prostate
- can metastasise to bone, can cause spinal cord compression or ureteric obstruction
Bladder:
- transitional cell carcinoma most common (superficial and invasive), squamous carcinoma and adenocarcinoma
- strongly associated with inhalation of polycyclic aromatic hydrocarbons and smoking; excretion of chemicals in urine and frequent exposure in bladder
- often pulmonary mets
Renal:
- usually renal cell carcinoma, can be transitional CC, sarcoma or mets
- RFs: smoking, obesity, hypertension, haemodialysis
Testicular:
- conventional or clear cell (80%), papillary (10%), chromophobe (5%), collecting duct or medullary cell rare
- have paraneoplastic syndrome: polycythaemia, hypercalcaemia, hypertension, deranged LFTs, rarely ACTH
Describe the presentation of tumours in the kidney and lower urinary tract:
Prostate:
- local: often asymptomatic, painful or slow micturition, UTI, haematuria, urinary retention, lymphedema
- mets: bone pain, renal failure
- elevated PSA, present on DRE, can do TRUS biopsy
Bladder:
- classically painless frank haematuria
- should have cystoscopy, renal U/S or KUBS
Renal:
- 80% incidental
- <25% systemic symptoms: night sweats, fever, fatigue, weight loss, haemoptysis
- 10% classic triad of mass, pain, haematuria
- varicocele, lower limb oedema, paraneoplastic syndrome
Testicular:
- majority present as painless lump
- may be noticed after incidental trauma
Describe the management of tumours in the kidney and lower urinary tract:
Prostate:
- watchful waiting, active surveillance
- radiotherapy
- radical prostatectomy
- cryotherapy
- TURP if symptomatic
- androgen ablation therapy (medical castration) if advanced
Bladder:
- urgent TURBT
- intravesical mitomycin reduces risk of recurrence
Renal:
- large renal mass: radical nephrectomy, If no absolute indication for NSS
- Small Renal Mass
1. Biopsy
2. Treatment
Nephron sparing surgery
Partial Nephrectomy
Cryotherapy
Radical Nephrectomy
Surveillance
- Radical Nephrectomy: removal of kidney and gerota’s fascia, sparing adrenal gland
- Indications for NSS; single kidney, CKD, CV risk factors, pT1a tumours
Testicular:
- radical orchidectomy, chemotherapy, para-aortic node dissection, retro-peritoneal node dissection
Describe pathophysiology of stones of the urinary tract:
Abnormal urine:
- under-saturated; too much salt, not enough water, lack of inhibitors, abnormal proteins
- abnormal blood: hypercalcaemia, acidosis
- hypercalciuria or hyperoxaluria
Urinary obstruction
- congenital; medullary sponge kidney, PUJ obstruction, mega ureter, uterocele
- acquired; ureteric stricture, anastomotic stricture
Urinary infection
- urease producing organisms
- proteus mirablis, causing STRUVITE
Describe presentation of stones of the urinary tract:
Incidental - Imaging for another reason Pain - Colic, radiates from loin to groin, cannot settle, unable to stay still Haematuria - Visible or non visible UTI or Sepsis - Unknown source until imaged
Describe management of stones of the urinary tract:
Where do stones cause pain?
Renal – asymptomatic
3 points – PUJ,VUJ, crossing iliacs
<4mm – 75% chance of passing
<7mm – 25% proximal, 45% mid, 64% distal ureter
Medical:
Analgesia
NSAIDs or opiates?
- NSAIDs reduce pain due to reduced glomerular filtration, renal pressure and ureteric peristalsis
Medical expulsive therapy- only beneficial in large distal stones
Surgical:
ESWL – extracorporeal shockwave lithotripsy
Rigid ureteroscopy and fragmentation/ basket extraction
FURS – flexible ureteroscopy
PCNL – percutaneous nephrolithotomy
Emergency stent or nephrostomy
What is ATN?
Acute tubular necrosis
Any pre-renal cause of AKI if severe/of sufficient duration
ATN is always due to under perfusion of the tubules and/or direct toxicity: Hypotension Sepsis Toxins Or often, all three
Toxins can be exogenous: drugs, contrast, poisons or endogenous: myoglobin, haemoglobin, immunoglobulins, calcium, urate
Describe management of acute pyelonephritis:
Check previous/recent microbiology results Send urine +/- blood culture+/- imaging Community: Co-amoxiclav/ Ciprofloxacin/ /Trimethoprim (NICE guideline) - Options may be limited - Allergy - Drug interaction - Antimicrobial resistance
Hospital: often broad spectrum abx
May remain symptomatic for few days
No response warrants further investigation
Uncomplicated pyelonephritis, 7-14/7 antibiotic
Complicated pyelonephritis, ≥ 14/7 therapy
+/- radiological/surgical intervention
What are the complication son acute bacterial prostatitis?
Complications Prostatic abscess Spontaneous rupture Urethra, rectum Epididymitis Pyelonephritis Systemic sepsis
Describe the antibiotic management of acute bacterial prostatitis:
Check recent/previous microbiology
Ciprofloxacin/ Ofloxacin (no streptococcus cover)
D/W microbiology in systemic infections
What are the types of renal stones commonly seen?
Calcium stones – 80% ( mixed ) - Calcium oxalate monohydrate or dihydrate - Calcium phosphate Infection stones - 10% - struvite (proteus) Uric acid stone - 5% - not seen on xray Others -1% - cystine, xanthine, silica, drug stones -indinavir (not seen on CT)
