Renal Flashcards
A patient today has a creatinine of 130, when they arrived in hospital it was 62. What stage AKI do they have?
Stage 2:
2x creatine of baseline
Or 0.5mL/kg/hour for 12 hours
If the patient weighed 60kg and had produced < 360mL in the last 12 hours it would also be stage 2
Causes of acute kidney injury:
Pre-renal: hypoperfusion- low BP or renal artery stenosis
Intrinsic:
Tubular- necrosis from contrast, nephrotoxic drugs, myoglobin, stones or myeloma
Glomerular- glomerulonephritidies, autoimmune, infections
Interstitial- infiltration from lymphoma, infection, tumour lysis syndrome
Vascular- vasculitis, hypertension, emboli, HUS/TTP
Post-renal:
Blockage- stones, clots, strictures, malignancy
Compression- malignancy, retroperitoneal fibrosis
Bedside tests to do in an AKI:
Dipstick (blood + protein = glomerulonephritis, or leukocytes)
MC+S (crystals)
Culture
Bence Jones protein
Bloods (including CK-myoglobin, ESR + ANCA, ANA if suspect autoimmune cause)
Renal USS- small kidneys suggest CKD
Patient with an AKI starts getting chest pain, why is an ECG warranted?
They may have hyperkalaemia or uraemia causing pericarditis
Indications for dialysis in AKI
Refractory pulmonary oedema or hyperkalaemia (>7mmol)
Severe metabolic acidosis
Uraemia causing encephalopathy or pericarditis
Drug overdose- BLAST (barbituates, lithium, alcohol, salicylates, theophylline)
Emergency management of hyperkalaemia
10mL of 10% calcium gluconate IV, repeated until ECG improves
IV 10U actrapid + 20% glucose
Ultimately: Rx cause of AKI- catheterise, give fluids, haemodialysis/haemofiltration
Stages of AKI
1: 1.5 x baseline of creatinine
or creatinine rise >26mmol/L in 48 hours
<0.5mL/kg/hr for 6 hours
2: 2 x baseline of creatinine
<0.5mL/kg/hr for 12 hours
3: 3 x baseline of creatinine Or >350 umol rise Or renal replacement therapy commenced <0.3mL/kg/hr for 24 hours Anuria for 12 hours
What are the 3 layers that comprise the glomerular filtration surface in the kidney?
Endothelial cells (prevents red cell + platelet passage) Basement membrane Epithelial cell layer of podocytes
Which hormone is catabolised by the kidney?
Insulin
Histological patterns of nephrotic syndrome:
Primary and Secondary causes will give rise to one of the following patterns:
Minimal change
Membranous (silver membrane spikes)
Membrano-proliferative (Mesangiocapillary, tram line capillary walls)
Focal Segmental Glomeulosclerosis (diabetes, amyloid)
SLE
Hepatitis is associated with which histological patterns of nephrotic syndrome?
Membranous nephropathy- Hep B
Immune complex mediated mesangiocapillary- Hep C
Common secondary causes of nephrotic syndrome and the histological change associated?
NSAIDs + gold + penacillamine
Hepatitis + SLE + paraneoplastic- normally membranous
HIV + amyloid + diabetes- FSGS
Membrane spikes on silver stains and subepithelial dense deposits seen on histology. What type of nephrotic syndrome is it?
Membranous nephropathy
May also see diffuse IgM
Other types: minimal change, focal segmental glomerulosclerosis (also IgM seen), mesangiocapillary
Kimmelstein wilson nodules are associated with which cause of nephropathy?
Diabetes
HIV and heroin causing nephrotic syndrome produce what histological pattern of glomerular damage?
Focal segmental glomerulosclerosis
Focal- some glomeruli, segmental- some parts of the glomerulus
Features of nephrotic syndrome?
HOP
Hypoalbuminaemia, oedema, proteinuria
Adults should undergo renal biopsy
3 Complications of nephrotic syndrome:
Infection susceptibility- loss of Ig and complement
Thromboembolism- increase in clotting factors (stimulated in the liver by a loss of albumin)
Hyperlipidaemia- hepatic response to low oncotic pressure is to produce more cholesterol + triglycerides
Rx of nephrotic syndrome
- Steroids
- Cyclophosphamide or ciclosporin
Loop diuretics, salt + fluid restrict
ACEi to reduce proteinuria
Hepatic response to low oncotic pressure is higher clotting factors + cholesterol so start a statin + anticoagulate
Which cause of glomerulonephritis do you not treat with immunosupression or plasma exchange?
Post-streptococcal GN
Just supportive care, as tends to be self-limiting eventually
Pneumonic for remembering causes of glomerulonephritis?
A Hen SLEeps in the PASTURE as the COCK was MEAN and AGGRESSIVE
IgA Henoch Shonlein + vasculitidies SLE Goodpastures Post-streptococcal Mesangio-capillary GN Rapidly progressive GN
Which glomerulonephritidies demonstrate deposition of the following Ig on immunofluorescence:
- IgG
- IgM
- IgA
- Post-strep and Anti-GBM
- Focal segmental glomerulosclerosis
- IgA nephropathy + Henoch Schonlein vasculitis
What is the definition of CKD?
Impaired renal function for 3 months evidenced by: Abnormal structure (ie <9cm in size) GFR <60mL/min/1.73
Top 5 causes of chronic kidney disease
- Diabetes
- Glomerulonephritis (commonly IgA)
- Unknown- too late to biopsy
- Hypertension or renovascular disease
- Pyelonephritis/reflux nephropathy
Difference in histology on renal biopsy between a patient with post-streptococcal GN and IgA nephropathy GM?
IgA nephropathy: mesangial proliferation (lots of pink)
Post-strep: mesangial + capillary proliferation (lots of nuclei + pink)
Different types of bladder tumour
90% transitional cell Ca
7% squamous cell Ca- associated with chronic irritation (UTIs, schistosoma haematobium, catheters)
2% adenocarcinoma - urachas remnant
4 main different types of primary kidney cancer:
- Renal cell carcinoma
- Transitional cell ca- renal pelvis
- Nephroblastoma (Wilms)
- Epithelial- sarcomas
IHx to rule out suspected bladder cancer
Flexible cystoscopy ± protoporphyrin (to highlight neoplasms) Urine cytology (sterile pyuria)
Staging:
MRI pelvis
CT chest, abdo, pelvis
bone scan
For prostate and bladder cancer TNM staging, what T grade is given if the cancer has extended beyond the bladder or prostate?
T3
Treatment of bladder cancer that has not invaded the muscle of the bladder wall (T1)
For low grade: transurethreal resection of bladder tumour
For higher grade or relapse: resection
+ intravesical BCG or chemo (mitomycin C, doxorubicin, cisplatin)
Treatment of bladder cancer that has invaded the muscular bladder wall (T2-T3 no mets)
Gold standard:
Radical cystectomy
Neoadjuvant chemotherapy improves survival
Conservative:
Transurethral resection + radiotherapy + chemotherapy
Patient presents with haematuria, loin pain and fever (of unknown origin), what tests should be done for suspected renal cell carcinoma?
Urine MC+S- RBCs, cytology
US scan
CT- pre and post contrast will show an enhancing mass
What is unusual about the treatment of renal cell carcinoma?
How is it treated?
It is resistant to chemotherapy and radiotherapy
Localised:
radical nephrectomy ± nephron sparing, robotic or laparoscopic
Advanced:
Immunotherapy- Interleukin 2 or VEGF tyrosine kinase inhibitor (as RCC’s are very vascular)
Child has haematuria and an abdominal mass, what tests are warranted to rule out suspicious cause?
US + CT/MRI to diagnose Wilms tumour
From mesodermal cells
Prognosis 90% long term survival
How does Wilms tumour management differ to renal cell carcinoma Rx?
RCC is radiotherapy and chemo-resistant
Wilms is treated with chemotherapy
Stages of CDK
Stage 1: GFR >90 + renal damage:
Proteinuria, haematuria, abnormal anatomy
Stage 2: 60-89 + renal damage Stage 3a: above 45 Stage 3b: above 30 Stage 4: above 15 Stage 5: <15
Can factor in ACR to determine risk
What rate of fall in eGFR shoudl prompt referral to the nephrologist?
> 5mL/min over a year
Or >10mL/min over 5 years
What is the target BP for a patient with CKD ± diabetes or Albumin Creatinine Ratio >70
CKD 130/80
Diabetes + CKD 125/75
Rx for CKD that limits progression or complications
If diabetic or >130/80: ACEi or ARB (even if BP is normal)
If PTH is high: phosphate binders, Ca+ supplements, vit D analogues
Aspirin- reduces CVS risk
Symptomatic Rx of CKD:
Anaemia: iron, B12, folate, recombinant erythropoietin
Acidosis: failure to reabsorb bicarbonate leads to low pH and serum HCO3 levels > sodium bicarbonate (caution- BP)
Oedema: loop diuretics
Resless legs: benzodiazepines + increase ferritin levels
In what unique circumstance would you consider biopsying a kidney if it was the patient’s only working one?
For kidney transplant
3 categories of rapidly progressive glomerulonephritis
Immune complex: post-strep, SLE, IgA/Henoch Schönlein
Pauci-immune: ANCA+ (Wegners), microscopic polyangiitis, Churg-Strauss (no complement or IgG with immunofluorescence)
Anti-GBM: Goodpasture’s
What symptoms might indicate a patient has a rapidly progressive form of glomerulonephritis?
AKI + systemic features: fever, myalgiaa, weight loss, haemoptysis
Goodpastures and vasculitidies may cause pulmonary haemorrhage
What screening test helps identify those with diabetes mellitus at risk of renal damage?
Annual check for albumin levels in 24 hour urine
Microalbuminaemia (30-300mg/24 hours) gives early warning.
All patients with microalbuminaemia should be given ACEi, irrespective of BP
Renal causes of hypertension
Kidneys produce renin (AT2) and may retain salt and water
Intrinsic renal disease:
glomerulonephritis, polyarteritis nodosa, systemic sclerosis (anti-scl70 and anti-RNA), chronic pyelonephritis, polycystic kidneys
Can do urine dipstick to look for blood, protein, nitrates, leukocytes
Renovascular disease:
Atheromatous artery stenosis
or fibromuscular dysplasia (non-inflammatory, non-atherosclerotic thickening of artery wall)
How is renal artery stenosis investigated?
Renal Doppler ultrasound
CT or MR angiography is more sensitive
RENAL ANGIOGRAPHY IS GOLD STANDARD (more invasive)
How much protein in the urine suggests nephrotic syndrome proteinuria (over a day)?
3g/day
What is the definition of microalbuminuria?
30-300mg in 24 hour urine collection
Indicates those with diabetes at risk of kidney deterioration = need ACEi
A patient has found to have proteinuria on a urine dipstick, they have no symptoms. What would prompt a referral to urology or nephrology?
Urology:
over 40
persistent protein +++
Nephrology:
hypertensive >140/90
EGFR <60
Albuminuria (ACR >30 or PCR >50)
Recommended investigations for a 45 year old patient with haematuria discovered on urine dipstick?
Check if recent UTI, menstruation, vigorous exercise
Serum creatinine, spot ACR BP Bloods- including ESR, clotting Urine MC+S USS + renal referral if also getting proteinuria, GFR decline or casts seen
Drugs that can cause microscopic haematuria?
Cephalosporin + ciprofloxacin (both broad spectrum)
Furosemide + captopril (ACEi)
NSAIDs
What are the pro’s and con’s of PSA testing?
Around 70% of 70 year olds are likely to have prostate ca
Test may not mean you live longer, even if you have prostate ca- likely to die of something else
False +ve leads to more tests- biopsies etc
False -ve unnecessary worry
Patient keeps getting UTIs and has pain around his bladder, on DRE a boggy prostate is felt (swollen). Likely cause and eitiology?
Prostatitis (acute or chronic)
Due to: E Coli, Strep faecalis or chlamydia
What’s the difference between haemodialysis and haemofiltration?
Haemodialysis: semi-permeable membrane, with blood flowing in opposite direction to dialysis fluid.
Problems: large fluid shifts, larger solutes clear less well
Haemofiltration: permeable membrane, with dialysis fluid flowing in same direction.
Problems: very slow, less fluid shifts
Pros and cons of peritoneal dialysis:
Peritoneum = semi-permeable membrane used to filter fluids across it by infusing fluids into the peritoneal cavity.
Pros: can be done more slowly, at home, less fluid shifts
Cons: Peritonitis or infection of the catheter site, blockage or loss of membrane function.
6 long term complications occurring in patients on renal replacement therapy?
CAP BMI
CVS disease: MI + stroke
Amyloidosis: arthralgia, carpel tunnel
Protein calorie malnutrition: reduce intake
Bone disease: osteodystrophy + osteitis fibrosa (fibrosis replaces calcium)
Malignancy: commoner
Infection: sepsis, related to mode of dialysis (ie peritonitis)
Contraindications to renal transplant:
Active infection
Cancer in the last 5 years
Comorbidity
How is immunosuppression induced and maintained in kidney transplants?
Induction: anti-IL 2R antibody or anti-CD52 (on lymphocytes)
Maintenance:
- Calcineurin inhibitor (tacrolimus, ciclosporin)
- Antimetabolite (azathioprine, mycophenolate)
- Prednisolone
Types of graft rejection in kidney transplants
Hyperacute: within 2 days, mediated by pre-existing antibodies
Acute: weeks - months later, cellular-mediated lymphocyte infiltration
High dose IV methylprednisolone + more immunosupression
Chronic allograph nephropathy: vessel walls thicken, tubules atrophy + interstitial fibrosis is seen
What side effects occur in kidney transplant immunosuppression regimes?
Calcineurin inhibitors- tremor, confusion
Ciclosporin- gum hypertrophy, hirsutism
Antimetabolites (azathioprine)- hepatitis, agranulocytosis
Patient has loin pain, what tests can identify if there is urinary tract obstruction and what level it is?
US- hydronephrosis or hydroureter
If +ve
CT- determines the level of obstruction
Radionucleotide imaging- functional assessment
Rx for upper urinary tract obstruction:
Nephrostomy (artificial ureter implanted that drains to skin surface)
Stent ± alpha blocker to reduce ureteric spasms
Patient has been getting progressively reduced kidney function, blood tests show:
Raised urea + creatinine
Raised ESR + CRP
US shows dilated ureters
CT shows periaortic mass
Diagnosis + Rx?
Periaortitis / Retroperitoneal fibrosis
Ureters get embedded in dense fibrous tissue around the aorta, which fibroses in response to vasculitis/SLE, drugs or idiopathically.
Rx: stent to relieve obstruction
±Dissection of the ureters from retroperitoneal tissue + immunosupression
Rx for retroperitoneal fibrosis compressing the ureters bilaterally?
Upper urinary tract obstruction
Rx: stent to relieve obstruction
±Dissection of the ureters from retroperitoneal tissue + immunosupression
In children under 6 months, found to have an atypical or recurrent UTI, what tests should be done to look for renal abnormalities?
Ultrasound (during the acute phase or within 6 weeks if responding to ABx)
DMSA 4 months later (functional test for scarring)
MCUG- injects contrast + xrays to see reflux
DMSA= dimercaptosuccinic acid scintigraphy MCUG= micturating cystourethrogram
In a child aged 6months-3 years, how does investigation of atypical and recurrent UTIs differ to such UTIS in infants under 6 months?
Atypical UTI: any age gets acute USS (or within 6 weeks if quickly resolving)
Under 3 years: DMSA (scarring)
Under 6 months: add MCUG (reflux)
Recurrent UTI:
All get DMSA
Over 6 months: add USS at 6 weeks
Under 6 months: add MCUG
How is a typical UTI resolving in 48 hours investigated differently in children aged under 6 months vs those aged 6 months to 3 years?
No follow up IHx routinely needed for children aged 6 months to 3 years, if under 6 months USS at 6 weeks warranted
In a child aged 6 months to 3 years who has a non E Coli UTI, what features would prompt a micturating cystourethrogram?
PC: poor urine flow
FHx: vesicoureteric reflux
IHx: dilatation on ultrasound
non-E Coli infection (atypical infection)
What is vesicouteric reflux and why is it a problem?
Retrograde backflow of urine to the kidneys, thought to cause pyelonephritis and scarring, leading to hypertension + end stage renal failure ultimately.
What features constitute an atypical UTI in a child/infant?
PC: seriously ill, poor urine flow, bladder mass, septicaemia
HPC: failure to respond to suitable Abx within 48 houra
IHx: non E Coli organism, raised creatinine
How is recurrent UTI defined in children/infants?
1 pyelonephritis + 1 UTI/pyelonephritis
Or
3 UTI
Prevention of renal scarring in children waiting for imaging to exclude or diagnose vesicoureteral reflux?
Trimethoprim prophylaxis to reduce chance of infection being transmitted to kidneys
A hypertensive patient is on some antihypertensive meds, after starting an ACEi, their renal function worsens, what needs to be investigated?
Renal artery stenosis (loss of angiotensin mediated afferent dilatation worsens function)
Can do a doppler USS
CT or MR angiography are more sensitive
Renal angiography is gold standard
7 year old boy has been getting bloody diarrhoea and has not weed much for the last 6 hours.
Bloods: anaemia, low platelets
Blood film shows schistocytes
Diagnosis?
Haemolytic uraemic syndrome:
E Coli 0157 strain produces verotoxin which attacks endothelial cells.
Endothelial damage = thrombosis, platelet consumption + fibrin strand deposition (which mechanically destroys RBCs- schistocytes)
Rx of haemolytic uraemic syndrome?
AKI + bloody diarrhoea + haematuria
Dialysis for AKI may be needed
Plasma exchange to remove venotoxin from E Coli 0157 strain may be needed
Patieent is jaundiced, has reduced consciousness and has stopped seizuring, they have an AKI brewing. What could be the cause?
Thrombotic thrombocytopenic purpura
Lack of ADAM13 protease that normally cleaves von Willebrand factor meaning large vWF multimers form and aggregate platelets.
IHx: dipstick (protein ++ blood++), blood film (schistocytes), low platelets + Hb
Treatment for thrombocytopenic purpura?
Low platelets and Hb > blood film
Rx: Urgent plasma exchange
Steroids
Biologics in development (targeting C5 pathway)
Difference between type 1 and type 2 renal tubular acidoses?
Both have alkaline urine production pH >5.5 despite metabolic acidosis in blood
Type 1: inability to excrete H+ ions at distal convoluted tubule, osteomalacia occurs as Ca+ from bone tries to buffer high H+ levels
Type 2: bicarbonate leak at proximal tubule- defect in reabsorption. Diagnosed by high fractional urinary excretion of NaHCO3 when given IV, get hypokalaemia also
Which type of renal tubular acidosis is associated with a high K+ level?
Type 4- hyporeninaemic hypoaldosteronism
Low aldosterone reduces K+ and therefore H+ excretion
Rx: Mineralocorticoid like Fludrocortisone are used
Patient has recurrent calcium phosphate stone formation, low K+ and osteomalacia. What is the linking diagnosis?
Type 1 renal tubular acidosis
failure to excrete H+ in the distal tubule (despite metabolic acidosis) means more H+ in the blood.
Ca+ leaves bones to buffer high H+ levels- osteomalacia, then the combination of hypercalciuria, low urinary citrate (reabsorbed as H+ buffer) and alkaline urine favours stone formation.
Low pH means more K+ is swapped for Na+ absorption instead
Technically Fanconi syndrome might have similar features (PCT loss of amino acids, glucose, phosphate and bicarbonate)
The inherited Bartter syndrome and Gitelman syndrome mimic which types of diuretics?
Bartter syndrome- low K+, metabolic alkalosis, hypercalciuria
Inherited mutation in NA+/K+/Cl co-transporter
Like LOOP diuretics, presents in infancy
Gitelman syndrome- low K+, metabolic alkalosis, hypocalciuria, low Mg2+
Inherited mutation in Na+/Cl co-transporter
Like THIAZIDE diuretics, presents with muscle cramps, weakness, low BP
How do the metabolic abnormalities differ and compare in Bartter syndrome and Gitelman syndrome?
Both have low K+ and metabolic alkalosis
Gitelman will have hypocalciuria- without Na/Cl symporter on tubular side, less Na gets into tubule cell, so on the other basolateral cell side Na/Ca antiporter is more active and more Ca is reabsorbed
Bartter has hypercalciuria- normally K+ is uptaken via the Na/K/Cl cotransporter and then leaks back into the tubule providing a gradient to allow cations (Ca, Mg) to be absorbed
Where and what is the genetic defect in most cases of polycystic kidney disease?
85%: Autosomal dominant mutations in PKD1 gene on chromosome 16
End stage renal failure in 50s
Other: PKD2 is on chromsosme 4
What heart and gynae complications are associated with polycystic kidney disease?
Heart: mitral valve prolapse
Gynae: ovarian cyst
What is the best test to determine if a patient has polycystic kidney disease?
Ultrasound scan
Genetic testing for PKD1 (chromosome 16- 85% of patients) is difficult due to size of the gene and hundreds of mutations
Clinical definition of polycystic kidney disease?
USS findings
Under 39 years: >3 unilateral or bilateral cysts
40-59 years: >2 cysts in each kidney
>60 years: >4 cysts in each kidney
Which inherited syndrome is associated with a constellation of end stage renal failure- with cyst formation, and retinal degeneration, cerebellar ataxia ad retinitis pigmentosa, liver fibrosis?
Medullary cystic disease- autosomal recessive
Boy is found to have blood +++, protein +++ and rising creatinine on his U+Es. He was born deaf, what is the most likely heritable syndrome?
Alport syndrome
X linked type IV collagen mutation
What is Fabry disease?
X linked lysosomal storage disease (GLA gene abnormalities)
Glycosphingolipids in: Skin - angiokeratoma, hypohidrosis Eyes- lens opacities Heart- angina, MI, syncope, LVH, arrythmias Kidneys- renal failure CNS- stroke Nerves- neuropathies
Why are renal transplant patients with Fabry disease at risk of anti-GBM glomerulonephritis post-transplant?
The gene abnormality affects type IV collagen, which is the immunogenic antigen in anti-GBM glomerulonephritis
