Renal Flashcards
Pre-renal causes of renal disease
Decr blood flow to kidneys:
- Shock
- Heart Failure
- Hypotension
- Renal artery stenosis
- Dehydration
Renal Causes of Renal Disease
GN (nephritic/nephrotic)
ATN
Interstitial disease
- Vascular (vasculitis, thrombus/dissection)
- Infiltration (sarcoid, Tb)
- Systemic (SLE, DM)
Post-renal causes of renal disease
Urinary tract obstruction:
- prostate obstruction
- strictures
- stones
- clots
- malignancy
- sloughed papillae occluding lumen (DM)
Causes of glomerular nephritis
Autoimmune (SLE, HSP) Drugs Infection Malignancy Primary GN
Causes of ATN
Pre-renal damage
Nephrotoxins (aminoglycosides)
Contrast medium
Rhabdomyolysis (muscle breakdown) !!
Interstitial disease causes
Drugs (penicillin allergy)
Infiltration (lymphoma, infection-Tb, post-chemo, Sarcoid)
Causes of renal vascular damage to kidneys
Vasculitis
Malignant HTN
Large vessel occlusion (thrombus, dissection)
What does a urine dipstick detect?
Leucocytes
Nitrates
Blood
Protein
RAAS
JGA detects decr in renal perfusion -> activates RAAS:
Renin secreted from kidneys -> converts angiotensinogen to angiotensin 1 -> ACE converts angiotensin 1 to angiotensin 2 -> Ang II does the following to incr BP:
- incr symp activity
- Incr Na/H20 reabsorption; incr K excretion
- Aldosterone secretion from adrenals
- Vasoconstriction to increase BP
- ADH/vasopression secretion from posterior pituitary -> aquaporins inserted into collecting duct increases Na reabsorption
1-5 increase circulating volume and BP leading to reperfusion of JGA
What is the commonest renal cause of kidney disease?
ATN
Nephrotic Syndromes
- Membranous nephropathy most common cause for adults
- Minimal change disease most common cause for kids
- FSGS
- Membranoproliferative GN
- Secondary causes due to hepB/C, SLE, NSAIDs, neoplastic syndrome, diabetic nephropathy, amyloidosis
Nephritic Syndromes
- IgA nephropathy most common cause for adults
- Post-infectious (strep) GN
- Rapidly progressive GN (IgA, vasculitis, anti-GBM/Goodpastures GN)
Ways to evaluate volume status
Capillary refill, Mucus membranes and skin turgur, urine output
Peripheral oedema, JVP
What is the protein deposited in the kidneys in Multiple Myeloma called?
Bence Jones Protein or M protein (light chains) or paraprotein
Blood tests in kidney disease
UE FBC LFT Clotting CRP ABG If systemic cause suspected: Ig and paraprotein electrophoresis, C3/C4, autoantibodies (ANCA, ANA, Anti-GBM), blood culture - low C3 indicates immunological cause - low C4 indicates SLE
Investigations for kidney malfunction
Renal USS shows cysts/small kidneys/masses
CTKUB: obstruction (non-contrast) or IVU (contrast for strictures)
XRKUB: stones
Urine dipstick (proteinuria, haematuria)
Urine spot test (microalbuminuria)
Urine MCS (glomerular in origin, infection?)
Renal biopsy -> immunohistochemistry
Signs of chronic kidney disease
Small kidneys on USS Anaemia Low Ca, high PTH High phosphate High creatinine/low GFR
Complications of AKI
- Electrolyte imbalance: Hyperkalaemia, hypnatraemia
- Acid base: metabolic Academia
- Fluid balance: Pulmonary Oedema from fluid overload (need diuretics or dialysis)
- Uraemia (need dialysis at this stage)
Nephritic syndrome criteria
Haematuria mostly Oedema HTN Mod-severe decr GFR Non-nephrotic range proteinuria
Nephrotic syndrome criteria
Proteinuria mostly
Hypoalbuminaemia -> pitting oedema
Hypercholesterolaemia
Normal-mild decr GFR
Most common cause of childhood nephrotic syndrome and prognosis/treatment
Minimal change disease
- Good prognosis with steroids
Most common cause of adult nephrotic syndrome and prognosis/treatment
Membranous nephropathy (primary/secondary causes)
Prognosis: 1/3 get better on own w supportive care; 1/3 relapse/remit; 1/3 progressive renal failure
Treatment: BP control, supportive measures only
Complications of CKD
CV disease leading cause of death due to poorer prognosis after AMI
Dyslipidaemia
Oedema
Metabolic Acidosis due to increased H retention
Anaemia due to Epo deficiency and decreased RBC survival time
Hyperkalaemia due to reduced K excretion
CKD mineral and bone disorder due to incr PO4 which suppresses Ca which stimulates rise in PTH to stimulate Ca resorption from bone -> SECONDARY HYPERPARATHYROIDISM and calcification of soft tissues and vasculature
Vitamin D deficiency due to inability to add the second OH onto 25 hydroxyvitamin D -> OSTEOMALACIA
What are medications that impair K excretion?
K sparing diuretics
ACE inhibitors
NSAIDs
Treatment of CKD mineral and bone disorder
Phosphate binders (prevent dietary absorption of PO4) + Restrict dietary PO4 (milk, cheese, eggs)
1,25 OH Vit D analogues
Cinacalcet (allosteric activator of Ca-sensing R on body tissues)
+/- subtotal parathyroidectomy
Hyperkalaemic ECG changes
Widened QRS
Tall peaked T waves
Depressed ST segment
Treatment of CKD metabolic acidosis
Sodium bicarbonate
Lifestyle factors to adjust in CKD
SNAP: smoking, nutrition, alcohol, physical activity
Nephrotoxic drugs
ACE inhibitors NSAIDs Amino glycosides (gentamycin) Amphotericin (anti-fungal) Lithium IFNalpha
+ penicillin (allergic interstitial nephritis), flucloxacilin (in pre-existing RF), BActrim
Role of PTH including the organ that produces it
Parathyroid gland produces PTH when serum Ca low -> leads to bone resorption of Ca to incr serum Ca -> inhibits PTH production
What is the active form of vitamin D called?
1,25 hydroxyvitamin D3
How is the active form of vitamin D produced?
Vitamin D is made in the skin as calcitriol and converted to cholecalciferol or vitamin D3 via sunlight -> liver hydroxylates this to 25-hydroxyvitaminD3 and then kidney adds a second OH to form 1,25 hydroxyvitaminD3
Actions of 1,25 hydroxyvitamin D3
Increased intestinal absorption of Ca and Phosphate
Incr Bone mineralisation
Incr bone resorption (remodelling)
Immunity
Muscle and bone health/strength
What happens if you are deficient in vitamin D?
Can result from lack of sunlight exposure.
Leads to bone softening diseases such as
Osteomalacia (Adults)
Ricketts (kids)
Pathology seen in glomerulonephritis
Acute:
- proliferation of mesangial or endothelial cells
- WBC infiltration
- Crescent formation
- Ab deposition, immune complex formation, C’ activation
Chronic:
- Hyalinosis
- Sclerosis
- BM thickening
What is the definition of rapidly progressive GN?
ARF + blood and protein in urine (nephritic)
What is the definition of chronic glomerulonephritis
CRF caused by glomerulonephritis + HTN + proteinuria + SMALL AND SHRUNKEN KIDNEYS
What is the most common cause of macroscopic haematuria?
UTI
What is the most common adult glomerulonephritis? and common symptoms of this
IgA nephropathy (may be asymptomatic/have macroscopic haematuria or nephritic syndrome)
What is the pathophys of IgA nephropathy?
IgA + C3 forms immune complexes and deposits in mesangial cells
Mesangial proliferation
What is the treatment for IgA nephropathy?
Ace inhibitors or ARBs to lower bP and thus amt of protein in urine
Fish oils
Corticosteroids with rapidy progressive RF
What electrolytes are commonly deranged in kidney disease?
Na, K, Ca
Phosphate and Mg
What hormones control sodium?
Aldosterone - Na/K exchange in DCT
Angiotensin
Renin
What hormone controls water content and how?
Vasopressin/ADH
Inserts aquaporins in collecting duct.
Where is ADH made and secreted from?
Made in hypothalamus, stored and secreted in posterior pituitary
Where is aldosterone secreted from?
Adrenal cortex
What determines serum osmolarity?
Na
K
Glucose
Urea
Difference btw AKI and CKD in terms of
- definition
- urine output
- SX
AKI: low urine output with general SX of malaise (nausea, vomiting etc)
- rapid reduction in kidney function over hours to days as measured by increase in serum urea and creatinine (>x1.5 baseline)
CKD: normal to high urine output with NO SX due to adaptation
- Impaired renal function (evidence of renal damage) >3mo
○ Microalbuminuria
○ Proteinuria
○ Glomerular haematuria
○ Pathological abnormalities on renal biopsy
○ Anatomical abnormalities (cysts on ultrasound etc)
- OR GFR <60ml/min/1.73m^2 for >3 mo with or without evidence of kidney damage
Complications of nephrotic syndrome
- susceptible to infection (loss of Ig in urine, and steroid use)
- hyperlipidaemia
- hyper coagulable state -> incr risk of VTE
What do you think of if a patient presents with haematuria a few weeks after infection?
post-strep glomerulonephritis
What do you think of when a patient presents with a purpuric rash and macroscopic haematuria?
Hence Schonlein -> IgA nephropathy
What do you think of when a patient presents with a purpuric rash and macroscopic haematuria?
Henoch Schonlein -> IgA nephropathy
At what stage do patients need dialysis or renal transplant?
Stage 5 CKD (when eGFR<15ml/min) = ESRF
What are the various stages of CKD
at what stage do sx/signs become evident?
1-2: GFR is >60 with evidence of renal damage (proteinuria, haematuria or abnormal anatomy or systemic disease)
3: GFR 30-60 with/without evidence renal damage
4: GFR 15-30 Sx/signs
5: ESRF (GFR<15) sx/signs
SYMPTOMS of CRF
Polyuria, nocturia
+/- Macroscopic haematuria
Uraemia symtoms
- lethargy, malaise
- fluid overload
- pruritus
- seizures and restless legs + peripheral neuropathy
- anorexia, N&V
Broad classes of causes of CRF
- Diabetic nephropathy (2>1)
- Glomerulonephritis
- IgA nephropathy, membranous nephropathy, FSGS - Hereditary disorders (PCOS, familial nephritis, reflux nephropathy)
- Analgesic (drugs) -> interstitial nephritis
- most commonly chronic NSAID overuse (women in 50s and 70s) - Hypertensive nephrosclerosis
What are the histopathological features of diabetic nephropathy
- Arterial hyalinisation
- Thickening of GBM and mesangial matrix
- Nodular Kimmelstiel-Wilson glomerulosclerosis OR diffuse glomerulosclerosis
- Papillary necrosis
Progression of Diabetic nephropathy (4 stages)
- Elevated GFR (transient, early on)
- Glomerular hyperfiltration due to increased mesangial matrix
- Microalbuminuria (GFR normal)
- Macroalbuminuria = overt nephropathy (GFR decr, proteinuria incr)
Pathophysiology of membranous nephropathy
Diffusely thickened GBM
Sub epithelial IgG+C3 deposits
Hereditary disorders of CRD
Adult polycystic kidney disease
Familial nephritis
Reflux nephropathy with vesicoureteric reflux
How does PKD present ?
What does renal US show?
Autosomal dominant:
- abdo pain +/- haematuria (bleeds into cyst), cyst infection, renal calculi, HTN, progressive renal failure
Recessive often presents in infancy with multiple renal cysts and congenital hepatic fibrosis
Renal U/S: kidneys enlarged and full of cysts
What other medical conditions are associated with PKD?
Liver cysts
Diverticular disease
Ovarian cysts
Intracranial aneurysm -> SAH
At what age do people with PKD typically reach ESRF?
mutation in:
- PKD1 (85%): by 50s
- PKD2 (15%): by 70s
Management of CRF
Identify and treat cause!
Control HTN (SBP<130)
- ACEi or ARB (second line is CCB)
BSL control
Fluid balance
- loop diuretics
- salt and fluid restriction
Diet
- low protein diet to reduce nitrogenous wastes (urea, uric acid)
- restrict K and PO4
Adjust meds (avoid nephrotoxic and renally excreted meds)
Manage complications
- Vit D and Ca supplements
- phosphate binders
- Epo +/- Iron
- sodium bicarbonate
- statin
Dialysis when GFR <15ml/min or uraemic SX onset
What are the different types of dialysis and what are the main concepts of each?
Haemodialysis:
- blood circulates at high volume through a dialysed composed of many tubes of semi-permeable membranes
- solutes move by osmosis
- fluid moves by ultrafiltration
Peritoneal dialysis
- dialysis solution infused into peritoneal cavity, left to dwell for equibrilation of solutes and fluids, then the used dialysate is discarded
- semi permeable membrane is the visceral capillary wall lining the peritoneal cavity
- solutes leave blood via diffusion
- fluids leave blood by mix of osmotic and hydrostatic pressure
Complications of renal transplant
- Graft rejection
- surgical complications
- drug toxicity
- infection (opportunistic due to long-term immunosuppression)
- malignancy 5x increased risk
- CV disease
Absolute CI to renal transplant surgery
Cancer
Active infection
Severe comorbidity
What is the leading cause od death amongst CKD patients?
CVD
What is hypertensive nephrosclerosis?
What does it feature?
How can it present?
Damage to kidney resulting from chronic high BP
Features renal hyaline arteriolosclerosis -> narrows arteriole lumina -> ischaemia -> tubular atrophy, interstitial fibrosis and glomerulosclerosis
Presents in hypertensive patient as mild proteinuria OR haematuria and proteinuria
Risk factors for renal stones
White male High protein, salt, Ca intake dehydration Metabolic abnormalities (can be hereditary) Urinary tract abnormalities Medication (loop diuretics)
Clinical presentation of renal stones
Asymptomatic
Acute severe flank pain or waxing and waning severe loin to groin pain
Haematuria (90% microscopic)
Nausea, vomiting
+/- Frequency, urgency (LUTS from bladder stones)
Fever, hypotension, tachycardia and tachypnoea
Types of bladder stones and their treatment.
radio-opaque or lucent on KUB?
Analgesia and fluids for all +/- antiemetics
Calcium (75%) - incr fluid +/- thiazides, Ca channel blockers or alpha blockers to promote stone passage
- radiopaque on KUB
Uric acid (5-10%) - incr fluid intake and alkalinise urine +/- allopurinol - radiolucent on KUB
Struvite (5-10%) - often harbour bacteria, needs removal and ABx
Cysteine (1%) - incr fluid intake and alkalinise urine
What is the order of investigations for suspected renal stones?
- Non-contrast helical CT of abdo/pelvis is first line!
If CT shows stone:
- KUB X-ray (for follow up)
- intervention required if solitary kidney/bilateral stones/ARF/intractible pain OR low likelihood of stone passage.
If recurrent Ca stone formation, investigate for metabolic causes
- 2x 24 hour urine
- PTH
- Cr
- Ca, Na, Ph, Mg
- Oxalate, citrate, cysteine
Risk factors for RCC
Smoking, HTN, obesity
Male and >50
Haemodialysis (15%)
Where does RCC metastasise to?
Lungs first -> cough -> CXR -> cannon ball mets
Bone -> bony pain
Liver
25% at presentation have metastatic disease
Paraneoplastic syndromes (SX of cancer not explained by its anatomical position)
PUO/flu-like illness
Hematopoietic:
- anaemia
- polycythemia
- raised ESR
Endocrinopathies
- hypercalcaemia
- incr epo
- incr renin -> HTN
- incr prolactin, gonadotropins, TSH, insulin, cortisol
Hepatic cell dysfunction w abdominal LFTs and reversible areas of hepatic necrosis
How does RCC present?
- Commonly asymptomatic - detected incidentally by U/S or CT
- Loin pain/ flank pain
gross haematuria
palpable mass - Weight loss, weakness, bone pain, anaemia
Treatment for RCC
Systemic therapy (immunotherapies and chemo) doesn’t work!
Surgery the only curative treatment
-> remove the kidney (or partial nephrectomy if bilateral tumour or only one remaining kidney) and solitary mets
+ targeted therapies (T kinase, MTOR, anti-VEGF inhibitors) for advanced stage disease
+ pal care
Differentials for haematuria
Urothelial malignancy
- TCC (bladder)
- RCC (kidney)
- Prostate
UTI, cystitis, pyelonephritis BPH Stones Trauma (surgery or blunt trauma) PCKD/simple renal cyst GN or IN Systemic disease - SLE, autoimmune
Investigations for haematuria
Dipstick - nitrates, WCC, protein, microscopic haematuria (nephrological)
Urine MCS (cytology for cancer cells)
FBE - anaemia, WCC
UEC
Imaging: U/S first line +/- IVU (CT + contrast)
+ CYTOSCOPY (unless <40)
What is the most common form of carcinoma of the renal pelvis and ureter?
What are clinical features?
Papillary urothelial carcinoma
Gross/microscopic hematuria
Flank pain
LUTS
Flank mass +/- hydronephrosis
Investigate w IVU + cystoscopy and retrograde pyelogram
Risk factors for bladder common
Smoking Aromatic amines Cyclophosphamide Pelvic Radiation Chronic irritation: cystitis, chronic catheterisation, bladder stones
What are the 2 most common forms of bladder cancer?
TCC >90%
SCC 5-7%
Clinical features of bladder cancer
HAEMATURIA!! Painless (50%) or painful (50%)
Cystitis like symptoms with no infection on urine test (storage LUTS)
Advanced disease: bony pain, ureteric obstruction
Treatment for bladder cancer
Depends on stage
Superficial (non-muscle invasive):
- TURBT + adjuvant intravesical therapy (6 week course of BCG or mitomycin C to decrease recurrence)
- cystectomy with high grade disease or non-responders
Invasive disease
- radical cystoprostatectomy + neoadjuvant chemo-radiotherapy
Investigations for RCC
U/A, Urine MCS and urine cytology
U/S bladder
IVP (filling defect)
Cystoscopy with bladder washings GOLD STANDARD
Biopsy - establish diagnosis and determine staging
Bladder tumour markers
CT/MRI, CXR, LFTs etc for invasive disease
Investigations for prostate cancer
DRE and PSA
TRUS-guided needle biopsy
Bone scan if PSA >10
CT scan (mets?)
What scoring system is used to assess mortality risk of prostate cancer?
Gleason score! Scale of 10 - GRADE the 2 most common histological patterns on a scale 1-5 on biopsy and add the scores to get the gleason score <7 low risk 7 moderate risk 8-9: high risk
Treatment options for prostate cancer
Prostatectomy Hormone therapy (androgen deprivation therapy)
Side effects of androgen deprivation thearpy
Hot flushes
loss of libido, impotence
tiredness, loss of muscle, osteoporosis
cognitive dysfunction
Why is prostate cancer screening poor?
We are over diagnosing low grade and under diagnosing aggressive high grade cancers.
Due to lead time and lag time bias.
□ Likelihood of getting aggressive fast growing cacner whilst it is curable and screenable is very low. These men are missed with screening, and these are the people that need treatment most.
Vs much higher likelihood with slow growing cancers because the window of time that it is curable and screenable is much longer. But these are the men that would do well anyway.
Treatment of Prostate cancer
○ Watchful waiting - no treatment or monitoring
§ Wait for symptomatic disease and then paliate
○ Active surveillance - monitor tumour for signs of growth or symptoms to appear
§ Serial PSA, DRE, repeat biopsies
§ Goal is to avoid overtreatment and side-effects
§ Radical prostatectomy (high-risk disease or young patients)
§ Radiation therapy (brachytherapy etc) - for low volume, low grade cancer
§ Chemotherapy
§ Hormonal therapy (anti androgens, GnRH agonists, oestrogens, bilateral orchidectomy removes 90% of testosterone )
When to start screening for prostate cancer?
All men at age 50 + if >10 year life expectancy.
Initial screening involves serum PSA and DRE
High risk individuals at age 40
Clinical presentation of urinary retention
What presentation is a medical emergency?
Poor urinary stream w intermittent flow Strain Sense of incomplete voiding Hesitancy Incontinence, nocturia, frequency
ANURIA and suprapubic, dull constant pain is a medical emergency!
Investigations for suspected urinary retention
U/S bladder
PSA (raised in prostate cancer, BPH and prostatitis)
CT
MRI if cauda equine syndrome suspected
Causes of urinary retention
Bladder
- trauma
- scarring of bladder neck (iatrogenic causes)
- neurogenic bladde (splanchnic nerve damage or cauda equina syndrome)
- detrusor sphincter dyssynergia
Prostate
- BPH
- Prostate cancer
- Prostatitis
Penile urethra
- congenital
- phimosis or pinhole meatus
- circumcision
- obstruction
- Gonorrhoea, chlaymadia
Other
- drugs
- psychogenic
Treatment of urinary retention
URinary catheter to empty bladder OR suprapubic puncture if can’t catheterise
+ Alpha blockers and TOV
Acute surgery - Prostatic stent, TURP, laser, open prostatectomy etc
Treat the underlying cause (BPH etc)
bladder outlet surgery
Complications of urinary retention
Acute
- bladder rupture
- hydronephrosis and pyonephorisis leading to ARF
- Sepsis
Chronic
- bladder damage
- CKF
- bladder stones
- hydronephrosis
- diverticula in bladder wall -> stones, infection
LUTS
Voiding SX
- hesitancy
- slow or intermittent stream
- incomplete emptying
- terminal dribbling
Storage SX
- frequency
- urgency
- nocturia
- incontinence
Aetiology of problems with ‘waterworks’ in males
Obstructive
- BPH or prostate cancer
- stricture
Irritative
- secondary to obstruction
- UTI
- Bladder cancer
- stone
- diabetes
- TB
- medical causes (diuretics, anticholinergics); caffeine and alcohol etc
Treatment of BPH
Alpha blockers (relaxes smooth muscle of urethra)
+/-
5 alpha reductase inhibitors (blocks conversion of testosterone to DHT) reduces prostate volume.
Surgical
- TURP
- open prostatectomy
What type of bladder retention is painful and which is more dangerous?
Which is associated with bed wetting?
Acute retention for both pain and dangerousness.
Chronic assoc w bed wetting due to overflow. Not painful.
Causes of acute bladder retention
BPH, prostate cancer, stricture
Weak detrusor muscle due to old age
Acute precipitants: - UTI (urethritis) - diuresis (alcohol) - drugs (anticholinergic) - post-op - prolapse in women Neurological - DM - Stroke - PD - spinal cord compression
How is obstructive nephropathy defined?
Elevated Creatinine
Bilateral hydronephrosis
Due to significant back pressure from bladder (AUR) causing renal dysfunction
MX: admit, monitor urine output and U&Es regularly and replace urine output with normal saline + electrolytes as needed.
