RENAL Flashcards
Triad of HUS?
AKI
Microangiopathic haemolytic anaemia
Thrombocytopenia
What causes HUS?
Most causes are typical HUS which is secondary to shiga toxin producing E.Coli 0157:H7
Can also be secondary to pneumococcal infections, HIV, SLE, drugs and cancer
Primary HUS is rare and is due to complement dysregulation
Investigations necessary for HUS?
FBC to look for anaemia and thrombocytopenia
Coombs test -should be negative
Blood film - shows schistocytes and helmet cells
U&Es for AKI
Stool culture looking for evidence of STEC infection. PCR for shiga toxins
Tx of HUS?
Hospital admission!
Supportive - IV fluids, blood transfusion, dialysis
Self-limiting - most pts fully recover!
Plasma exchange if very severe HUS and not associated with diarrhoea
Eculizumab has some evidence that its greater than plasma exchange alone in treatment of adult atypical HUS
What increases the risk of HUS?
Children <5
Using antibiotics or antimotility meds if STEC is suspected (e.g. loperamide) to try to Tx the gastro
Pathophysiology of HUS?
Formation of blood clots = consumes platelets = thrombocytopenia
Thrombi & damaged RBCs = affect blood flow through kidney = AKI
Haemolysis of RBCs due to thrombi partically obstructing small blood vessels = causes churning of the RBCs and rupture
Management of ascites?
- Reduce dietary sodium or ff sodium is low (<125) = fluid restrict
- Aldosterone antagonist e.g. spironolactone (if they don’t respond add a loop diuretic)
If tense ascites - therapeutic abdominal paracentesis (if large volume >5L then albumin cover is needed
If ascetic protein is <15 = prophylactic ABx to reduce risk of SBP
TIPS can be considered
Outline the management of proteinuria in CKD?
Dietary protein restriction, tight glycaemic control & manage hypertension and hyperlipidaemia
If pt has diabetes and ACR >=3 = SGLTi
If they dont have diabetes…
ACR 30-70 and hypertension = ACEi/ARB
ACR >70 = ACEi/ARB regardless of bp
How do ACEi and ARBs treat proteinuria in CKD?
ACEi inhibits the conversion of angiotensin 1 to angiotensin 2 whilst ARBs block angiotensin 2 from binding to its receptor. This leads to dilation of the efferent arteriole, reducing intraglomerular pressure and the amount of protein leaking into the urine = decreases the hyperfiltration injury
How do SGLT2i treat proteinuria in CKD?
Blocks the sodium-glucose cotransporter in the proximal tubule, leading to increased Na+ delivery to the macula densa = triggers tubuloglomerular feedback causing afferent arteriolar construction and reducing intraglomerular pressure = minimises proteinuria
Pathophysiology of diabetic nephrology?
Causes a nephrotic syndrome!
Diabetes causes non-enzymatic glycation which damages the blood vessels = thickens capillary basement membrane by increased deposition of type 4 collagen and causes atherosclerosis of arterioles = increases permeability of vessels & tublar cells to proteins
Osmotic damage to glomerular capillary epithelium = thickening of capillary basement membrane by deposits of type 4 collagen = diffuse mesangial sclerosis +/- kimmelstiel-Wilson nodule
Affects efferent arteriole before afferent arterioles = increased GFR = hyperfiltration injury = protein loss
Typical causes of focal segmental glomerulosclerosis?
HIV - most important to remember
Drugs e.g. anabolic steroids
Heroin
Alports syndrome
Sickle cell
Secondary to other renal pathology
Idiopathic
Minimal change disease what age does it affect?
75% of cases are in children
25% in adults
Cause of minimal change disease?
90% of cases are idiopathic
Other causes:
Drugs - NSAIDs and rifampicin
Hodgkin lymphoma
Thymoma
Infectious mononucleosis
Management of minimal change disease?
Low salt diet to stop body retaining any more fluid
80% of cases respond to oral corticosteroids
Cyclophosphamide is second line
Prognosis of minimal change disease?
1/3 have just one episode
1/3 have infrequent relapses
1/3 have frequent relapses which stop before adulthood
What is the difference between primary and secondary hyperaldosteronism?
Primary - adrenal glands directly responsible for producing too much aldosteronism so serum renin will be low as hypertension suppresses it
Secondary - there is a disproportionately lower bp in the kidneys = excessive renin stimulates the release of excessive aldosteronism
Causes of primary hyperaldosteronism?
B/L adrenal hyperplasia - most common
Conns syndrome - an adrenal adenoma secreting aldosterone
Rarely can be familial
Causes of secondary hyperaldosteronism?
Renal artery stenosis
HF
Liver cirrhosis and ascites
Investigations for hyperaldosteronism?
BP
Bloods - U&Es look for low K+. Blood gas look for alkalosis
Aldosterone-to-renin ratio (ARR)
CT or MRI to look for adrenal hyperplasia or tumour
If ?RAS - Renal artery Doppler/CT angio or MR angio
Adrenal vein sampling can be done from both adrenal veins to locate which gland is producing more aldosterone
Management of hyperaldosteronism?
Aldosterone antagonists e.g. eplerenone and spironolactone
Treat undelryign cause e.g. surgical removal of adrenal adenoma or a percutaneous renal artery angioplasty for RAS
Most common cause of secondary hypertension?
Hyperaldosteronism
What is anti-GBM disease?
A rare type of small-vessel vasculitis associated with pulmonary haemorrhage and rapidly progressive glomerulonephritis
Caused by anti-GBM antibodies against type 4 collagen
Associated with HLA DR2 and more common in men
Investigations when considering anti-GBM disease?
Bloods - U&Es, measure antiGBM antibody level, ANCA, complement 3&4 levels, ANA, anti-streptomycin O titre to rule out PSGN, clotting screening necessary before renal biopsy
Renal biopsy with immunofluorescence will show linear IgG deposits along the basement membrane
Raised transfer factors secondary to pulmonary haemorrhage
Management of anti-GBM disease?
Oral corticosteroids & Plasma exchange
Consider cyclophosphamide
What is the most impprtant complication of anti-GBm disease?
What makes this more likely to occur?
Pulmonary haemorrhage
Smoking, LRTI, pulmonary oedema, inhalation of hydrocarbons, young males
Pathophysiology of anti-GBM disease?
Auto-antibodies that attack the GBM and alveoli due to the presence of the type 4 collagen in both of these structures = rapidly progressive glomerulonephritis & pulmonary haemorrhage = haemoptysis and haematuria
Risk factors for bladder cancer
Males aged between 50-80
Smokers
Exposed to hydrocarbons
Pelvic radiation
Cyclophosphamide
Chronic bladder inflammation from a schistosomiasis infection, log term catheters or recurrent UTIs
Whats the most common type of bladder cancer?
Transitional cell carcinoma (90%)
Most common cause of squamous cell carcinoma bladder cancer?
Prolonged inflammation within the bladder e.g. schistosomiasis but also occasionally recurrent UTIs/long term catheters
This is why its more commonly seen in Africa and Asia
Referral criteria for ?bladder cancer?
> =45 with either unexplained visible haematuria or visible haematuria that persists/recurs after successful Tx of UTI
=60 with unexplained non-visible haematuria + either dysuria or raised WCC
Investigations for bladder cancer?
Urinalysis ans culture to exclude infection
FBC, U&Es
Urgent flexible cystoscopy
Consider CT or MRI staging scan
For complete diagnosis a transurethral resection of bladder tumour (TURBT) must be done to get a histological analysis
Management of bladder cancer?
If non-muscle invasive - may only need TURBT, may need some intra-vesicle chemotherapy
If muscle-invesive - neoadjuvant chemo & radical surgery e.g. radical cystectomy. More modern approaches now recommend TURBT & chemo & radiotherapy and suggest a similar prognosis to radical cystectomy
How does contrast cause an AKI?
Contrast agents are directly nephrotoxic to renal tubular cells but they can also alter the vasoactive substances such as renin, angiotensin etc -? Reduces glomerular blood flow
Definition of contrast media nephrotoxicity?
25% increase in Cr occurring within 3 days of IV administration of contrast media
How to prevent contrast media nephrotoxicity?
IV 0.9% sodium chloride at a rate of 1ml/kg/hour for 12 hours pre- and post-procedure
Also remember if pt is high risk hold metformin for 48 hours and then until renal function has normalised to prevent lactic acidosis
What is the most common type of glomerulonephritis in adults?
Membranous glomerulonephritis
Renal biopsy findings in membranous glomerulonephritis?
On electron microscope you can see a thickened BM with subepithelial electron dense deposits = spike and dome appearance
Causes of membranous glomerulonephritis?
Malignancy - commonly asked in exam Qs so remmeber M for malignancy
Idiopathic e.g. due to anti-phospholipase A2 antibodies
Infections - malaria, hep B, syphilis
Drugs - gold, penicillamine, NSAIDs
Autoimmune diseases
Management of membranous glomerulonephritis?
ACEi or ARB to reduce proteinuria and improve prognosis
Immunosuppression e.g. corticosteroid & cyclophosphamide
Consider anticoagulant for high risk pt
Prognosis of membranous glomerulonephritis?
Prognosis - rule of thirds
one-third: spontaneous remission
one-third: remain proteinuric
one-third: develop ESRF
Types of renal calculi?
Calcium oxalate - most common ~60%!!
Calcium phosphate uric acid ~20%
Uric acid ~15%
Struvite (magnesium ammonium phosphate) ~1-5%
Cystine ~1%
Drug induced stones ~1%
Where do renal stones usually obstruct?
The vesicoureteric junction
The mid ureter where the ureter crosses the iliac vessels
The pelvic ureteric junction
What are calcium oxalate stones associated with?
Low urine volume
Hypercalciuria
Hyperuricosuria
Hyperoxaluria
Hypocitraturia
What are calcium phosphate stones associated with?
Low urine volume
Hypercalciuria
Hypoctraturia
High urine pH
Primary hyperparathyroidism
RTA
What are uric acid renal stones associated with?
Hyperuricosuria
Low urinary pH (<5.5)
What causes struvite stones?
Bacterial infections which hydrolyze urea to ammonia and raises the urine pH to >7.2
Consist of a mixture of magnesium, ammonium and phosphate
What are cystine stones associated with?
Cystinuria - a genetic condition causing cystine to leak through kidneys (different to homocystinuria)
Risk factors for renal stones?
Males (3:1)
40-60 year olds
White people
Diet intake high in oxalate, urate, sodium and animal protein
Chronic dehydration
Obesity
High ambient temperatures (affect fluid status)
FHx
Anatomical abnormalities of urinary tract
Genetic conditions e.g. cystinuria, RTA, CF
Some GI conditions
Conditions which alter urinary volume, pH or concentrations of certain ions e.g. hyperparathyroidism, diabetes, gout
Some drugs
How common are kidney stones?
It is estimated that 12% of men and 6% of women will have one episode of renal colic at some stage in their life
Complications of renal stones?
Obstruction of urinary flow - can decrease GFR of aefcted kidney. If obstruction >48 hours it may lead to reduced renal blood flow and irreversible kidney damage
Obstructive pyelonephritis or pyonephrosis (build up of high pressure pus behind the obstruction) - very high risk of sepsis!!
Less commonly:
- renal carcinoma
- CKD
- coronary heart disease
- spontaneous rupture of renal calyx -> urinoma
Features of renal stones?
Colic - abrupt onset of severe unilateral abdominal pain originating in the loin or flank and radiating to the labia in women or to the groin or testicle in men. Spasms which last mins-hours
N&V
Haematuria
Dysuria, urinary frequency and straining when the stone reaches the vesicoureteric junction and irritates the detrusor muscle
Investigations for renal stones?
Urine dipstick and culture
U&Es, FBC, CRP, calcium and urate plasma levels, clotting if intervention planend
Stone analysis once stone has passed
Urgent low-dose non-contrast CT KUB within 24 hours of presentation… USS KUB is less preferred but an alternative e.g. in pregnancy or children (but not a negative result does not exclude renal stone)
Which renal stones are opaque on radiograph?
Calcium oxalate
Calcium phosphate stones
Struvite stones
Cystine stones may be semi-opaque with a ground glass appearance
What are stag-horn calculi?
Stones which involve the renal pelvis and extend into at least 2 calyces
Caused by struvite stones
Why does hypocitraturia increase the risk of calcium renal stones?
citrate forms complexes with calcium making it more soluble so when its low we get Hypercalciuria
Why does hyperuricosuria increase the risk of calcium renal stones?
May cause uric acid stones which calcium oxalate can bind to!
Which renal stones have urine pH <5.5?
Uric acid stones
Which renal stones have urine pH >7.2?
Struvite stones
Which drugs can cause calcium-based renal stones?
loop diuretics, steroids, acetazolamide, theophylline
Which drugs can prevent calcium-based renal stones?
Thiazide diuretics as they increase distal tubular calcium reabsorption
Management of renal stones generally?
Analgesia - NSAIDs by any route (IM Diclofenac is the most common)
Antiemetics for N&V
If infection present pt may need ABx
Management of renal stones <5mm and asymptomatic?
Watchful waiting
Management of distal ureteric stones <10mm?
Medical expulsive therapy with an alpha blocker to facilitate spontaneous stone passage
When is surgical treatment considered for renal stones?
If pain is ongoing and stone unlikely to pass i..e >5mm
Surgical options for renal stones?
5-10mm -> shockwave lithotripsy
10-20mm shockwave lithotripsy OR ureteroscopy
>20mm percutaneous nephrolithotomy
Management of ureteric stones that are 10-20mm?
Ureteroscopy
How to prevent calcium renal stones?
High fluids, add lemon to drinking water, avoid carbonated drinks, limit salt intake, potassium citrate (to bind to Ca) or thiazide diuretics
How to prevent oxalate renal stones?
cholestyramine & pyridoxine both reduces urinary oxalate secretion
How to prevent uric acid stones?
Allopurinol
Urinary alkalinization e.g. oral bicarbonate
Why is it common for a pt to get recurrent UTIs after a kidney transplant?
The ureteroneocystostomy can lead to stasis or reflux of urine as its placed lower down than the original kidney so there is less of a gravity effect
Pt is on immunosuppressive Tx
Post-surgery may get strictures/colonisation
Why is the L kidney the preferred kidney to donate for a renal transplant?
As it has a longer renal vein
(R side has a shorter vein and is more often associated with renal vein thrombosis)
Where is the new kidney placed in a renal transplant?
In the iliac fossa & extraperitoneal
Efefcts of missing a dialysis session?
Hyperkalaemia
Hyper or hyponatraemia
Metabolic acidosis
Fluid overload/oedema
Uraemia - fatigue, nausea, confusion, encephalitis at the most extreme
Indications for dialysis?
Acidosis not responding to Tx
Electrolyte imbalances not responding to Tx - most importantly hyperkalaemia
Intoxication i.e. OD of a drug
Oedema not responsive to Tx
Uremia Sx
Most commonly these are caused by ESRF
Investigations for hydronephrosis?
Abdominal USS to identify
IV urogram
CT KUB may be needed if ?stones
Bloods and urine investigations for infections also
Management of acute and chronic hydronephrosis?
Acute - usually a nephrostomy or suprapubic catheter
Chronic - need a ureteric stent or pyeloplasty
If a prostate problem and you can get a catheter around it this may be a temporary fix
All require Tx of underlying cause
How do you manage a pt who presents with blood clots which are blocking the catheter?
Use a 3 way catheter to irrigate the bladder to try to push the blood clots out - will take multiple attempts until the body can undergo haemostasis and stop the bleeding cause
Also used if debris blocking catheter e.,.g after TURP
When do hyper acute, acute and chronic graft failures occur?
Hyper acute - mins/hours
Acute - weeks - <6 months
Chronic - >6months-years
What causes a hyper acute transplant rejection?
It’s a T2 hypersensitivity reaction where pre-existing antibodies exist against ABO or HLA antigens of the graft, activating the complement system
This leads to widespread thrombosis of the graft vessels -> ischaemia and necrosis of transplant
Management of hyperacute organ rejection?
No Tx
Graft must be removed
Pathophysiology of acute organ rejection?
Primarily T4 hypersensitivity reaction but also T2 contributes
Usually due to mismatched HLA - recipient CD4+ T helper cells recognise the donor HLA on graft cells and cause CD8 T cells to destroy the graft cells. They also stimulate a B cell mediated reaction
Other causes e.g. CMV infection!!
This is acute rather than hyperacute as the antibodies are not pre-made like in hyperacute!
Management of acute organ rejection?
May be reversible with steroids and immunosuppressants
Pathophysiology of chronic organ rejection?
T2 and T4 hypersensitivity reaction
Recipient antigen-presenting cells recognise the graft MHCs and present them to T cells which damage the transplant. B cells are also activate and can produce donor-specific antibodies
In a renal transplant this is chronic allograft nephropathy -> progressive vascular narrowing, interstitial fibrosis and tubular atrophy
Management of chronic organ rejection?
No Tx
What is graft versus host disease?
T cells in the graft mount an immune response against the host cells!
This is mostly seen in allogenic bone marrow transplants but it can rarely be seen following solid organ transplantation or transfusion in immunocompromised pts
How can graft versus host disease by prevented?
By using irradiated blood products to eliminate lymphocytes before transplantation
how to confirm a kidney transplant failure
Biopsy!
