Week 2 Flashcards
Myeloma - signs and symptoms (including classical presentation)
Classical presentation - back pain and renal failure
Signs
- Anaemia
- Hypercalcaemia
- Renal failure
- Amyloidosis
- Recurrent renal infections
Symptoms
- Bone pain
- Fatigue
- Weight loss
- Weakness
CKD - symptoms
Uraemia
- nausea and vomiting
- anorexia and weight loss
- fatigue
- itch
- altered taste
- restless legs and muscle twitching
- difficulty concentrating and confusion
Anaemia
- fatigue
- muscle weakness
Pain
- bony
- neuropathic
- ischaemic
- visceral
Minimal Change Nephropathy is the most common cause of nephrotic syndrome in children/adults
What is the target in minimal change? What are the investigations and treatment?
Does this condition cause progressive renal failure?
Minimal Change Nephropathy is the most common cause of nephrotic syndrome in children
The podocyte is the target of an unknown antigen and antibody
Investigations - light microscopy and immunofluorescence of renal biopsy will appear normal, but electromicroscopy will show foot process fusion of podocytes
Treatment - 94% have complete remission with oral steroids. Second-line is cyclophosphamide
No, this condition does NOT cause progressive renal failure
Renal Artery Stenosis - diagnosis and treatment
Diagnosis
- Clinical history - e.g. patient will be a little older and likely have signs of general atherosclerosis
- Imaging
- Renal USS
- CT/MR/Conventional angiography
Treatment
- Pharmacological - Statins, antiplatelets, ACE inhibitors
- Surgical intervention - angioplasty +/- stenting
What are some of the life-threatening complications of an AKI?
Hyperkalaemia
Fluid overload (resulting in pulmonary oedema)
Severe acidosis (pH <7.15)
Uraemic pericardial effusion
Severe uraemia (Ur >40)
If dysmorphic red cells were noted on urinoscopy, where would the bleeding likely be coming from?
Bleeding likely coming from the kidneys themselves - dysmorphic appearance is due to the red cells being squeezed through the tubules at the glomerulus
If the blood cells were normal, the bleeding would be likely from a structure further down the renal system e.g. the bladder
GN treatment - what are some of the non-immunosuppressive options?
Anti-hypertensives (target of <130/80, or <120/75 if proteinuria)
ACE inhibitors/ARBs to reduce both BP and proteinuria
Diuretics if the patient is fluid overloaded
Statins if the patient has hypercholesterolaemia
Anticoagulants/Aspirin/Antiplatelets?
Some evidence for Omega 3 fatty acids and fish oil
What % of patients with lupus will have associated renal dysfunction, and what is the most commonly seen sign?
Up to 50% of patients with SLE will present with renal involvement, and up to 60% will develop it over the course of their condition
Most frequently observed abnormality is proteinuria
What type of vasculitides to nephrologists typically deal with?
small-vessel e.g. MPA/GPA/eGPA
What gene and on what chromosome is involved in ARPKD?
What is the classical presentation?
PKDH1 on chromosome 6
Classic presentation is young children and a constant association with hepatic lesions.
Kidneys are always palpable
Again, hypertension is common
Patients also experience recurrent UTIs
What are the two types of reabsorption that can occur?
Transcellular
Paracellular, using the tight junctions
How is Pre-Renal AKI treated?
1) Assess hydration of patient
- Clinical observations (BP, HR and urinary output)
- JVP, cap refill time, oedema
- Pulmonary oedema
2) Fluid challenge for hypovolaemia
- Crystalloid (0.9% NaCl) or Colloid (Gelofusin)
- NB - do not use 5% dextrose
- Give a fluid bolus, then reassess and continue as necessary
- Seek help if over 1,000 mls given and no improvement
When leaving the proximal tubule, what is the osmolarity of the tubular fluid?
300 mosmol/l
The tubular fluid is iso-osmotic with the surrounding interstitial fluid
Give some examples of substances that are a) reabsorbed and b) secreted in the proximal tubule
Reabsorbed in the PT
- sugars
- amino acids
- phosphate
- sulphate
- lactate
Secreted in the PT
- H+
- Hippurates
- Neurotransmitters
- Bile pigments
- Uric acid
- Drugs e.g. atropine, morphine, penicillin etc.
- Toxins
Where is aldosterone secreted from?
When is it secreted?
What effect does it have?
Secreted from the adrenal cortex
Secreted in response to rising K+ or falling Na+ in the blood, or in response to activation of the renin-angiotensin-aldosterone system
Stimulates Na+ reabsorption (= increased blood volume and pressure) and K+ secretion
Diabetic nephropathy - diagnosis (also, what is the earliest clinical sign?)
Long history of diabetes (this is not an acute condition!)
Presence of albuminuria/proteinuria (NB - earliest sign is microalbuminuria)
Presence of other diabetic complications e.g. retinopathy, ulcers etc.
Renal impairment (late finding, not a good sign)
NB - need to regularly screen diabetic patients for microalbuminuria and closely monitor renal function
CKD - signs
Anaemia -> pallor
Weight loss
Advanced uraemia
- jaundice
- twitching
- encephalopathy
- confusion
- flapping tremor
- pericardial rub/haemorrhagic pericardial effusion
- Kussmaul breathing (due to metabolic acidosis)
How is glomerulonephritis classified histologically?
Proliferative or non-proliferative (usually referring to the presence or absence of proliferation of mesangial cells)
Focal/Diffuse - are more or less than 50% of the glomeruli affected?
Global/Segmental - is all or part of the glomerulus affected?
Crescentic - presence of a crescent shape of endothelial cells around the glomerulus e.g. RPGN in vasculitis
What confounding factors are taken into account when calculating the estimated GFR (eGFR)?
Sex
Age
Ethnicity
What are the three categories of renal tubular dysfunction? Give an example of each
Pre-renal (reduced renal perfusion) - blood loss/hypovolaemia
Renal (intrinsic kidney tissue damage) - glomerulonephritis or nephrotoxins
Post-renal (ureteric/urethral obstruction) - stones or malignancy
What is the most common form of glomerulonephritis globally?
How might it present?
What other condition is it associated with?
IgA nephropathy is the most common GN in the world
May have asymptomatic microhaematuria, with or without proteinuria
This may become macroscopic haematuria, especially if the patient has recently suffered from a resp/GI infection (due to excess IgA being deposited in the kidney)
IgA nephropathy is associated with Henoch-Schonlein Purpura (HSP)
What substances do the kidneys (usually) reabsorb?
- fluid (99%)
- salt (99%)
- glucose (100%)
- amino acids (100%)
- urea (50%)
- creatinine (0%)
When determining urine protein, what is the gold standard test?
What tends to be done instead? Why?
What are the cutoffs for grading proteinuria based on this other test?
24 hour urine collection is the gold standard (normally <150mg/24 hours)
Instead, urine protein/creatinine ratio tends to be used (50mg/mmol, ~0.5g/24 hours). This is because it can be done on the spot and is easier on patients, however it only gives an indication and so is not the gold standard
Asymptomatic/low grade proteinuria - urine protein/creatinine ratio of <1 g/day
Heavy proteinuria - urine protein/creatinine ratio of 1-3 g/day
Nephrotic range - urine protein/creatinine ratio of > 3g/day
Clinical scenario - 24 year old man incidentally found to have ++ blood and + protein on dip, BP 148/92
Protein quantified at 0.7g/day, creatinine 72
What glomerular cells are likely to be affected?
Mesangial cells - slow, gradual process and red cells are present
What condition is associated with glomerular crescents on biopsy?
Is this a treatable cause of acute renal failure?
Name some of the conditions that this form of GN is associated with
Rapidly Progressive Glomerulonephritis (RPGN)
This is treatable
Associated with both ANCA-positive and ANCA-negative conditions
ANCA-positive
- Systemic vasculitis
- GPA
- MPA
ANCA-negative
- Goodpasture’s disease
- HSP
- SLE
What are some of the consequences of CKD-MBD?
Secondary/tertiary hyperparathyroidism
Vascular calcification
Bone pain
Fractures
CV events
Reduced QoL
High morbidity and mortality
What hormones are involved in the regulation of ion and water balance? What does each do?
ADH
- increases water reabsorption (and therefore decreases urine output)
Aldosterone
- increases Na+ reabsorption (Na+ rises)
- increases H+ and K+ secretion (H+ and K+ lowers)
Atrial Natriuretic Hormone
- decreases Na+ reabsorption (effectively has the opposite effect to aldosterone on sodium)
Parathyroid hormone
- increases Ca2+ reabsorption
- decreases PO43- reabsorption
How might hyperkalaemia present on an ECG?
With tall, peaked T waves
Renal artery stenosis - aetiology
Tends to appear in older patients (>50yrs)
M > F
Same risk factors as for generalised atherosclerosis
Very common, prevalence of 4-20% on autopsy
Usually unilateral, and rarely only renal - usually there’ll be other appearances of atherosclerosis elsewhere in the body
What are the survival %s of dialysis like in patients with diabetes?
Not good.
5 year survival T1DM - 24%
5 year survival T2DM - 20%
What amount of glucose is usually reabsorbed in the proximal tubule?
Why does reabsorption plateau as the amount of plasma glucose increases?
Usually, 100% of glucose is reabsorbed in the proximal tubule
This rate of reabsorption plateaus because the transport mechanisms driving this reabsorption can become saturated
Excess glucose that isn’t reabsorbed is then excreted in the urine (as is the case in DM)
What marker can be used instead of Inulin and why? What is it’s downside?
Creatinine can be used as an endogenous replacement to inulin, and is also easy to measure
However, creatinine is excreted into the renal tubule
Also, creatinine exhibits a lag phase in which a steep fall in GFR is only represented by a small rise in creatinine. A frankly elevated creatinine would demonstrate obvious kidney disease
What cells release renin?
What cells sense the amount of NaCl in the distal tubule?
What happens to renin secretion if NaCl is reduced, or if afferent arteriole pressure drops?
Renin is released from granular cells
Macula densa cells sense NaCl levels
If NaCl is reduced or if pressure in the afferent arteriole drops then more renin is released, more Na+ is reabsorbed and blood volume and pressure rises
What enzyme is deficient in Anderson Fabrys disease?
How is this condition inherited?
alpha-galactosidase A is deficient
Condition is inherited in an X-linked manner
How common are the various stages of CKD? Why is it important to monitor?
Stage 1 and 2 - ~7%
Stage 3 - 5%
Stage 4 and 5 - 0.1-.02%
CKD increases cardiovascular risk
Patients with proteinuria are more likely to progress to more severe stages of CKD. Higher the proteinuria, the faster the progression
On diagnosis of a patient with Alport’s Syndrome, what is typically seen on renal biopsy?
Variable thickness of the GBM, shows lots of splitting
When performing an examination of a patient, what are some classical clinical signs that could point in the direction of kidney disease?
Retinopathy
Leukonychia (due to loss of protein)
Gouty tophi
Splinter haemorrhages (NB - also associated with bacterial endocarditis)
Vasculitic skin rashes e.g. Henoch-Schonlein Purpura (HSP)
Malar rash in patients with SLE
What other extra-renal clinical features may be seen in a patient with ADPKD?
Cardiac disease
Diverticular disease
Increased incidence of hernias
What does “microalbuminuria” mean (hint: it doesn’t mean a small amount of albumin!)
What is it an early indicator of?
Refers to excretion of albumin at abnormal quantities, but still below the limit of protein detection with a urine dipstick
It is the earliest expression of diabetic nephropathy, and is a standard part of routine diabetic assessment
What drugs would you avoid in a patient with an AKI?
NSAIDs
ACE inhibitors/ARBs
Diuretics
Gentamicin
Contrast
Trimethoprim
Potassium-sparing diuretics
What are some of the predisposing risk factors for developing an AKI?
Increasing age
Diabetes
Previous AKI
CKD
Cardiac failure
Liver disease
How is CKD-MBD managed (via medication and dietary changes)?
Medication
- Alfacalcidol (active Vitamin D)
-
Phosphate binders
- Calcium-based
- Aluminium
- Non-calcium based
- Calcimimetics
Dietary
- Phosphate restriction
- Salt reduction
- Potassium restriction (if persistently elevated)
- Fluid restriction
- Correct metabolic acidosis
Is the likelihood of developing CKD increased with advancing age?
Yes! As age increases, so does the likelihood of developing CKD
What membrane is the Na+/K+ pump exclusively presented on?
The basolateral membrane - essential for reabsorption of Na+
What markers are involved in development of Mineral and Bone Disease (as a consequence of CKD)?
Calcium
Phosphate
PTH
Vitamin D
FGF-23
and they’re all interconnected
What staging criteria is used to grade AKI?
KDIGO staging
A strong acid dissociates partially/completely in solution
A weak acid dissociates partially/completely in solution
Strong - dissociates completely
Weak - dissociates partially
What 4 factors is eGFR based on?
Serum creatinine levels
Age
Sex
Ethnicity
Henoch-Schonlein Purpura (HSP) - what symptoms might it present with? In particular, where might you see rash development?
Abdominal pain
Joint pain
Acute Kidney Injury
Characteristic rash is seen over the buttocks, backs of legs and feet
What traits would an ideal marker for GFR possess?
- Appear at a constant rate
- Be freely filtered at the glomerulus
- Not be reabsorbed from the renal tubule
- Not be secreted by the renal tubule
- Not undergo extra-renal elimination
NephrOTIC syndrome - treatment
General
- fluid restriction
- salt restriction
- diuretics
- ACE inhibitors/ARBs
- Maybe anticoagulation, and IV albumin if the patient is volume depleted
Immunosuppression
The aim of treatment is to induce sustained remission
Describe the reabsorption of NaCl in the thick ascending limb of the Loop of Henle. How many ions are transported out in each passage, and what is the net charge change?
What class of drug interferes with this?
Triple co-transporter (Na+, K+ and Cl-) on the apical membrane allows reabsorption of NaCl.
For each turn, there is 1 Na+, 1 K+ and 2 Cl-, giving a neutral change in charge
(Reminder - H2O cannot be reabsorbed here as the thick ascending limb is impermeable to water)
Loop diuretics target the triple co-transporter and prevent reabsorption of NaCl
What are the blood pressure targets when treating someone with CKD?
How is this affected by diabetes/those with an ACR >70 mg/mmol?
Systolic below 140 mmHg and diastolic below 90 mmHg
If diabetic/high ACR - systolic below 130 mmHg and diastolic below 80 mmHg
What does the appearance of red cell casts in the urine tell us?
Tell us there is an active inflammatory process
How might haematuria present?
How might proteinuria present? What are the classifications?
Haematuria
- asymptomatic, microscopic haematuria
- episodes of painless macroscopic haematuria, usually in the context of an infection
Proteinuria
- microalbuminuria (30-300 mg/day)
- asymptomatic proteinuria (< 1g/day)
- heavy proteinuria (1-3g/day)
- nephrotic syndrome (>3g/day)
Focal Segmental GlomeruloSclerosis (FSGS) is the most common cause of nephrotic syndrome in children/adults
What are the investigations and treatment?
Does this condition cause progressive renal failure?
FSGS is the most common cause of nephrotic syndrome in adults (35% of cases)
Investigations - Renal biopsy shows minimal Ig/Complement deposition on light microscopy and focal scar tissue may be seen
Treatment - remission with prolonged use of steroids in 60% of patients (much more resistant than minimal change)
50% of patients progress to end stage renal failure after 10 years
Damage to what structures results in a proliferative lesion? What is present in the urine?
Damage to what structures results in a non-proliferative lesion? What is present in the urine?
Damage to endothelial or mesangial cells leads to a proliferative lesion, and the presence of red cells in the urine
Damage to podocytes leads to a non-proliferative lesion, and the presence of protein in the urine.
ADPKD is more likely to be symmetrical/asymmetrical
ARPKD is more likely to be symmetrical/asymmetrical
Where do cysts seen to be appearing from in ARPKD?
Autosomal dominant is more likely to be unilateral and asymmetrical
Autosomal recessive is more likely to be bilateral and symmetrical
In autosomal recessive, cysts are seen to appear from the collecting duct system
Describe the reabsoprtion of Na+, Cl- and H2O in a) the Descending limb and b) the Ascending limb of the Loop of Henle
How does this affect osmolarity?
Descending limb
- NaCl is not reabsorbed
- highly permeable to H2O
Ascending limb
- NaCl is reabsorbed
- highly impermeable to H2O
Selective permeabilities enable an osmotic gradient to be established in the medulla
What is the Henderson-Hasselbach equation?
pH = pK + log[A-]/[HA]
A- = base
HA = acid
What is the (expensive) treatment for Anderson Fabrys disease?
enzyme replacement of alpha-galactosidase A, using Fabryzyme
Which of the following drugs does NOT cause hyperkalaemia?
- Spironolactone
- Ramipril
- Amiloride
- Furosemide
- Atenolol
Furosemide
Alport’s Syndrome - treatment
No specific treatment
Standard aggressive management of BP and proteinuria, but ultimately the mainstay of treatment is dialysis/transplantation
Kidney disease - signs on presentation (both systemic and local/renal)
Systemic Signs
- related to disease
- pyrexia, skin rash, heart murmurs, consolidation, ENT signs, retinopathy, neuropathy
- related to loss of kidney function
- pallor, arrythmia, pericardial rub, raised JVP, lung crepitations, oedema, gout
Local/Renal signs
- tenderness in loins or upper abdomen
- arterial bruits
- palpable kidneys
If a patient presented with a vasculitis and also had asthma and eosinophilia, what would be the likely type of vasculitis?
What about if they presented with inflammation within the respiratory tract?
eGPA
If presenting with resp symptoms, more likely GPA
What measurement is widely accepted as the best overall measure of kidney function?
How is it used to stage chronic kidney disease?
GFR - basically anything below 60 mL/min is concerning
Stages of CKD
- Stage 1 - evidence of kindey damage with normal or raised GFR (>90 mL/min/1.73m2)
- Stage 2 - evidence of kidney damage with normal or mildly reduced GFR (60-89 mL/min/1.73m2)
- Stage 3 - moderately reduced GFR (30-59 mL/min/1.73m2)
- Stage 4 - severely reduced GFR (15-29 mL/min/1.73m2)
- Stage 5 - kidney failure (<15 or dialysis
What is the difference between central and nephrogenic diabetes insipidus?
Central - inability to produce/secrete ADH
Nephrogenic - ADH doesn’t have an effect on the tubules in the kidney and
Briefly describe the cycle in cardio-renal syndrome
Reduced cardiac output > decreased bloodflow > decreased perfusion of kidneys > impaired renal function, meaning increased Na+ and water retention > decreased cardiac input
What’s the diagnosis?
Who gets this condition most commonly?
Fibromuscular dysplasia
Prevalence of 4/1000
Most common in women aged 15-50
Familial in 10% of cases and tends to involve both renal arteries. Also has associations with other hereditary conditions
What amount of all salt and water is reabsorbed in the proximal tubule?
The reabsorption of Na+ drives the reabsorption of what anion? By what reabsorption pathway is this done?
67% of all salt and water is reabsorbed in the PT
Na+ reabsorption drives the reabsorption of Cl- via the paracellular pathway
Briefly describe the pathogenesis of diabetic nephropathy
Renal Hypertrophy - Plasma glucose stimulates growth factors within the kidney, which causes expansion of mesangial cells. This results in nodule lesion formation and glomerulosclerosis
This then goes on to cause inflammation, proteinuria (due to GBM thickening and dysfunction of podocytes) and a resulting tubulointerstitial fibrosis
What two processes govern micturation?
Micturation reflex - initiated by stretch receptors in the wall of the bladder. Causes simultaneous bladder contraction and opening of both the internal and external urethral sphincters
Voluntary control - deliberate tightening of the external sphincter and surrounding pelvic diaphragm
What is the definition of AKI?
An abrupt (<48 hours) decline in kidney function defined as…
- an absolute increase in serum creatinine by 26.4 micromol/l
OR
- an increase in creatinine by >50%
OR
- a reduction in urinary output
How is ADPKD managed?
What new treatment has recently been approved by NICE to reduce cyst volume and progression?
Rigorous control of hypertension
Ensuring adequate hydration
Aim to reduce amounts of proteinuria
Monitor closely for cyst haemorrhage/infection
Tolvaptan is the new drug approved by NICE
Can eGFR be used for both CKD and AKI?
No! eGFR is of no use in an acute setting
Stretching of what structure also has an effect on ADH release?
What effects do nicotine and alcohol have on ADH release?
Activation of left atrial stretch receptors affects ADH release
A decrease in atrial pressure results in an increase in ADH release (the body is signalling that there is a need for a large change in plasma volume)
Nicotine - stimulates ADH release
Alcohol - inhibits ADH release
Give a general definition of glomerulonephritis
Immune-mediated disease of the kidneys affecting the glomeruli, with secondary tubulointerstitial damage
Disruption of the glomerular basement membrane between the glomerular capillary and Bowman’s space leads to haematuria and/or proteinuria
There are numerous types of glomerulonephritis! Site and type of injury determines the clinical presentation
How is glomerulonephritis diagnosed?
Clinical presentation
Blood tests
Urine examination
- urinalysis - haematuria, proteinuria
- urine microscopy - RBC (dysmorphic), RBCs and granular casts, lipiduria
- urine protein:creatinine ratio - used to quantify proteinuria
Kidney biopsy - uncomfortable and considerable risk of bleeding, so rarely done
Above what level is considered hyperkalaemia? What can it cause?
Normal K = 3.5-5
Hyperkalaemia = anything above 5 (life-threatening if above 6.5)
Associated with arrhythmias
Need to assess ECG and muscle weakness
What is the normal GFR?
How much of this is absorbed in the proximal tubule?
125 ml/min, or 180 litres/day
80 ml/min is absorbed in the proximal tubule i..e the majority of reabsoprtion occurs at the beginning of the nephron
What hormones does the kidney produce?
What hormones act on the kidney
Produced
- Renin - forms part of the RAAS
- Erythropoetin - stimulates RBC production in the bone marrow
- 1,25-dihydroxycholicalciferol
Acting on
- ADH
- PTH
- Aldosterone
What is the triad of kidney-related symptoms that is seen in NephrOTIC syndrome?
What cells in the glomerulus are affected? Is this proliferative or non-proliferative?
How will patients typically present?
Proteinuria >3g/day (mostly albumin, also globulins)
Hypoalbuminaemia (<30)
Oedema/fluid retention
(also hypercholesterolaemia)
NB - renal function is usually normal!
Podocytes are affected, and indicates a non-proliferative process
Presentation - patients swell up! May also have periorbital oedema
How would the kidneys appear on imaging if a patient had ischaemic nephropathy?
They would appear smaller - compromised blood supply causes atrophy and a reduction in size, eventually resulting in CKD
In the event of overhydration, what happens to the aquaporins present on the luminal membrane?
ADH is turned off in an overhydrated state, resulting in internalisation of aquaporins back into the cytoplasm of the distal tubular cell
Tubular fluid leaving the Ascending Loop of Henle and entering into the Distal tubule is hypo/hyper-osmotic to plasma
Hypo-osmotic (100 mosmol/l), while the surrounding interstitial fluid of the cortex is 300 mosmol/l
What is the pH of the following…
- arterial blood
- venous blood
- average pH of blood
arterial - 7.45
venous - 7.35
average - 7.4
How does osmolarity vary through the Loop of Henle?
Comes from PT as 300 mosmol/l
Water leaves descending limb by osmosis > 400 mosmol/l
NaCl is removed from the ascending limb, increasing the osmolarity of the interstitial fluid and diluting the tubular fluid > 200 mosmol/l
This is process continues and a steady state is reached
Fluid then leaves the Loop of Henle and passes into the DT as hypo osmotic
What clinical features might you see in a patient with Anderson Fabrys disease?
Renal failure
Angiokeratomas e.g. telangiectasia around the umbilicus
Cardiomyopathy/valvular disease
Neurological and psychiatric manifestations as well
What two hormones are in opposition with regards to Na+ levels?
Aldosterone (increases sodium reabsorption) and Atrial Natriuretic Hormone (decreases sodium reabsorption)
How long should patients that have suffered an AKI be monitored for to investigate the possible progression to CKD?
Following AKI, patients need to be monitored for at least 2-3 years, even if serum creatinine has returned to normal
What antibody test can be used to detect Goodpasture’s Syndrome?
Anti-GBM antibody
The distal tubule can be thought of as two segments: “early” and “late”
What ions are reabsorbed/secreted in each segment?
Early segment
- Na+-K+-Cl- triple co-transporter (NaCl reabsoprtion)
Late segment
- Ca2+ reabsorption
- H+ secretion
- Na+ reabsorption
- K+ reabsorption
How can myelomas potentially cause renal dysfunction?
Myeloma = cancer of plasma cells
A collection of abnormal plasma cells aggregate in bone marrow and cause impairment of production of normal red cells
There is also abnormal production of a paraprotein (abnormal antibody), which can result in renal dysfunction
What blood tests must be requested when dealing with a patient with a suspected AKI?
What other easy clinic-based test needs to be performed? What further testing might this lead to?
Haemoglobin
Bicarbonate
Phosphate
Calcium
If suspecting sepsis - CRP, lactate and cultures
Patients also need urine dipstick testing - if evidence of haematuria/proteinuria, then test immunology (ANCA, ANA, immunoglobulins and complement)
How is ADPKD diagnosed?
USS of kidneys - appearance on multiple bilateral cysts
Renal enlargement - may be up to 14/15cm in size
CT/MRI if unclear on USS
Genetic analysis (linkage, mutation analysis)
What is the purpose of “countercurrent multiplication”?
To concentrate the medullary interstitial fluid
This allows the kidneys to produce different volumes and concentrations of urine in accordance to the amount of circulating ADH
The majority of cases of GN are primary/secondary
Give some causes of secondary GN
Majority are primary (idiopathic)
Secondary causes include infections, drugs, malignancies or systemic diseases e.g. systemic vasculitides, lupus, Goodpastures, HSP etc.
What would the following crystals indicate when viewed on urine microscopy?
- Calcium oxalate
- Uric acid
- Phosphate
- Cysteine
Calcium oxalate - kidney stones
Uric acid - gout
Phosphate - UTIs/pseudogout
Cysteine - cystinuria
What are the principles of treatment for glomerulonephritis?
Reduce the degree of proteinuria
Induce remission of nephrotic syndrome
Preservation of long term renal function
CKD progression - risk factors
CVD
Proteinuria
AKI
Hypertension
Diabetes
Smoking
Afro-caribbean/Asian ancestry
Chronic use of NSAIDs
Untreated urinary tract outflow obstruction
What is Renal AKI, and what are some of the causes?
Diseases causing inflammation/damage to kidney cells
Vascular causes - vasculitis, renovascular disease
Glomerular causes - GN
Interstitial nephritis - drugs (most common cause), infection (e.g. TB), systemic (e.g. sarcoid)
Tubular injury - ischaemia, drugs (e.g. gentamicin), contrast, rhabdomyolysis
What are some of the clinical features of ADPKD?
Reduced ability to concentrate urine
Chronic pain
Hypertension in younger patients - most common feature
Haematuria - if the cyst ruptures
Cyst infection
Renal failure
NB - be suspicious of young people with high blood pressure and no family history
Membranous nephropathy is the second commonest cause of nephrotic syndrome in adults, and can have primary or secondary causes. Name some of the common secondary causes
What might be seen on renal biopsy, and what is the treatment?
Secondary causes
- infection
- connective tissue diseases
- malignancies
- drugs
Biopsy shows subepithelial immune complex deposition in the basement membrane
Treatment - Steroids/alkylating agents/B cell monoclonal antibodies
What are the chances of an affected individual having children with ADPKD? How does this affect management?
50% chance that children will also have the disease. This means that genetic counselling is required both pre- and post-testing
How is AKI managed?
If hypovolaemic, prescribe fluids and carefully manage. Recommend a series of 250ml boluses for resusc. and reassess after each
Stop high risk medicines and contrast
Treat the underlying cause
GN treatment - what are some of the immunosuppressive options?
Drugs
- corticosteroids (prednisolone po, MethylPred IV)
- azathioprine
- alkylating agents (cyclophosphamide/chlorambucil)
- calcineurin inhibitors (cyclosporin/tacrolimus)
- mycophenolate mofetil (MMF)
Plasmapharesis (therapeutic plasma exchange, used if e.g the patient has vasculitis and you want to rapidly remove the circulating antibodies
Antibodies
- IV immunoglobulin
- Monolonal T or B cell antibodies
If it was essential to get an accurate assessment of GFR, what measurement would be used?
51Cr-EDTA clearance
eGFR is useful but not entirely accurate, especially at higher GFR (hence reports using “above 60 ml/min”)
In a patient with ADPKD, where else might cysts be seen? How does this affect the organ in question’s function?
Hepatic cysts are the most common extra renal manifestation
Liver function is typically preserved, however cysts can result in SoB, pain, ankle swelling and ascites
Cysts may also present in the brain and lead to intra-cranial aneurysms
How is myeloma with renal dysfunction diagnosed? In particular, what is looked for in bloods and urine?
Have a high index of
Bloods - serum protein electrophoresis and serum free light chains
Urine - Bence Jones protein
Other tests - bone marrow biopsy, skeletal survey, renal biopsy
Reminder - what are the classification of CKD based on eGFR?
Stages 1-5
Anything sub 60 GFR is stage 3-5
Hyperkalaemia - medical treatment
Protect the myocardium
- 10mls 10% calcium gluconate (2-3 mins) - FIRST THING!!!
Move K+ back into cells
- Insulin (10 units of actrapid) with 50mls 50% dextrose
- Salbutamol nebuliser
Prevent absorption from GI tract
- Calcium resonium (NB - this is not done in the acute setting)
Which of the following is NOT an indicator for emergency dialysis?
- Pulmonary oedema (in the context of AKI)
- Life threatening hyperkalaemia
- Uraemic pericarditis
- Elevated creatinine >500
- Severe acidosis
Elevated creatinine >500
Where is atrial natriuretic peptide/hormone (ANP or ANH) produced and stored?
When is it released?
Produced by the heart and stored in atrial muscle cells
ANP is released when these cells are mechanically stretched due to increased circulating plasma volume
Why is blood pressure important in the context of kidney disease? What complications could develop?
Kidney disease could result in hypo OR hypertension
This could result in the development of accelerated hypertension (recent significant increase in BP over baseline, associated with end organ damage). Accelerated hypertension is a medical emergency, features a diastolic BP >120 mmHg, and may cause papilloedema, encephalopathy, fits, cardiac failure and acute renal failure
What is Alport’s Syndrome?
What mutation is involved and how is the disease inherited?
Hereditary nephritis due to a disorder of Type IV collagen matrix
Mutation on the COL4A5 gene leads to a deficient collagenous matrix (nb - COL4A3 and A4 also cause Alport syndrome, but these are on autosomes, whereas A5 is on the X chromosome)
Inheritance pattern for COL4A5 mutation is X-linked
Describe the following in a) dehydration and b) overhydration
- ADH levels
- water permeability
- tonicity of urine
Dehydration
- High ADH
- High water permeability (aquaporins expressed)
- Hypertonic urine (up to 1400 mosmol/l)
Overhydration
- Low ADH
- Low water permeability (aquaporins internalised)
- Hypotonic urine (<50 mosmol/l)
What are some of the causes of Pre-Renal AKI?
What drug needs to be avoided in this context?
What complication may develop if a Pre-Renal AKI isn’t treated?
Hypovolaemia and Hypotension. Also renal hypotension as a result of e.g. NSAIDs/COX-2 inhibitors, ACEi/ARBs or Hepatorenal syndrome.
ACE inhibitors cause a slight reduction in the GFR, if there is a major drop in renal perfusion there will then be a major drop in GFR. (Also the other drugs listed above)
If left untreated, a pre-renal AKI may develop into Acute Tubular Necrosis
What are some of the causes of Post-Renal AKI?
Post-renal is obstructive, leading to hydronephrosis and a resulting loss in concentrating ability
- Stones
- Malignancy
- Strictures
- Extrinsic pressure
As a result of the variance in osmolarity through the loop of Henle, where in the kidney is the osmolarity of the tubular fluid highest?
In the medulla (as this is where the Loop of Henle is found), osmolarity then decreases again as the nephron passes back into the cortex
What are urinary casts? When is their formation pronounced and what can the different types of cast tell us?
Microscopic cylindrical structures that present in the urine in certain disease states. Formation is pronounced in environements favouring protein denaturation and precipitation (e.g. low urine flow, low pH etc.)
Types of Cast
- Hyaline casts - usually benign
- Red cell casts - always pathological, usually associated with nephritic syndrome
- Leucocyte casts - signals infection or inflammation
- Granular casts - indicative of chronic disease
Alport’s syndrome - clinical presentation
Haematuria (also proteinuria at a later stage, but this confers a bad prognosis)
Sensorineural deafness
Ocular defects
Leiomyomatosis of oesophagus/genitalia
Describe the following with regards to increasing ADH levels
- urine osmolarity
- urine volume
- NaCl excretion
As ADH levels increase, osmolarity increases and volume decreases
NaCl excretion is completely unaffected by ADH!!
What is seen on renal biopsy on a patient with IgA nephropathy?
How is this condition treated, and what % will progress on to ESRF?
Renal biopsy shows mesangial cell proliferation and expansion with IgA deposits in the mesangium (mesangial cells prolierate and expand in repsonse to IgA complexes being deposited in the kidneys)
Treatment is with BP control/ACE inhibitors and ARBs/Fish oil
25% progress to end stage renal failure within 10-30 years
What are the two types of proteinuria to be familiar with? How do they differ?
Overflow proteinuria - excessive amounts of protein in the blood is passed into glomerulus, meaning not all protein can be reabsorbed e.g. Bence Jones proteinuria
Glomerular proteinuria (MOST COMMON)- excessive amounts of protein is passed from the glomerulus into the tubule, despite normal amounts of protein in the blood e.g. albuminuria
What is the timescale for
- Acute Kidney Injury
- Chronic Kidney Disease?
Acute - decline in GFR over hours/days/weeks
Chronic - at least 90 days
What are some of the signs and symptoms of Renal AKI?
Non-specific symptoms
- Constitutional - weight loss, anorexia, fatigue etc.
- N and V
- Itch
- Fluid overload - oedema, SoB
Signs
- Fluid overload
- Uraemia > itch and pericarditis
- Oliguria
What simple test can be used to establish whether a patient is presenting with glomerulonephritis vs a non-glomerular disease like interstitial nephritis?
Urine dipstick - non-glomerular conditions will have no protein/red cell leakage
If blood and protein are present in the urine, then the condition is likely GN
What drug is prescribed to patients with CKD to prevent the development of primary and secondary CVD?
Statins e.g. atorvastatin
What effect does the release of ANP have?
Promotes the excretion of Na+ and diuresis, thus decreasing plasma volume
Give some examples of drugs that should be avoided in patients with kidney disease?
- NSAIDs
- ACE inhibitors/ARBs/diuretics
- Antibiotics - gentamicin, trimethoprim, penicillins
- PPIs
- Radiology contrast
When would you alter the dose of ACE inhibitors/ARBs in a patient with CKD?
If the GFR decrease from pre-treatment baseline exceeds 25%
or
The serum creatinine increase from baseline exceeds 30%
What is the main treatment for myeloma with renal dysfunction?
Stem cell transplant and chemotherapy
Also need to stop nephrotoxic drugs and manage hypercalcaemia
Can also perform plasma exchange to remove free light chains
Dialysis can be performed as supportive treatment
What are some of the signs of NephRITIC syndrome?
What cells in the glomerulus are affected? Is this proliferative or non-proliferative?
Acute kidney injury and haematuria
Oliguria (reduced urine output)
Oedema/fluid retention
Hypertension
Active urinary sediment - RBCs, granular casts, proteinuria etc.
Endothelial cells are affected, and is indicative of a proliferative process
What new measurement was incorporated alongside eGFR in 2014?
What are the categories?
Albumin Creatinine Ratio (ACR)
A1 - <3 mg/mmol
A2 - 3-30 mg/mmol
A3 - >30 mg/mmol
Has a big clinical effect on patient’s outcome
What are some of the common causes of chronic kidney disease?
Diabetes and Hypertension - make up 66% of all CKD causes
Glomerularnephritis - primary and secondary
Vascular causes - mainly renal artery stenosis and small vessel vasculitis (GPA, microscopic polyangiitis)
Reflux nephropathy and polysystic kidneys
What are the main two chromosomal mutations associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD)?
Which is more common? Which develop ESRF at an earlier stage?
PKD gene 1, located on chromosome 16 (85% of cases)
PKD gene 2, located on chromosome 4 (15% of cases)
PKD gene 1 is the more common of the two, and PKD1 patients develop End-Stage Renal Failure earlier on
Describe the secretion of ADH from the posterior pituitary
Octapeptide is synthesised by the supraoptic and paraventricular nuclei in the hypothalamus
This is then transported down nerve terminals and stored in granules in the posterior pituitary
Primary stimulus e.g. dehydration > drop in plasma osmolarity resulting in Ca2+-dependent exocytosis > release of ADH
What marker satisfies all of these criteria?
What are its downsides?
Inulin satisfies these criteria. However, it is not endogenous and it is not easy to measure
When diagnosing an ANCA-associated vasculitis, what antibodies might be detected on immunology? Give a condition associated with elevated levels of each
Anti-MPO (more commonly raised in microscopic polyangiitis)
Anti-PR3 (more commonly raised in GPA
Diabetic nephropathy - prevention and management. In particular, doing what slows progression?
Glycaemic control (as per usual with DM)
Anti-hypertensive therapy - keep BP <130/80 and give ACE inhibitors/ARBs
Lipid control
Reducing proteinuria slows progression (done through ACEIs/ARBs)
Renal replacement therapies are also an option - simultaneous kidney-transplant (type I DM only), kidney transplants, haemodialysis and preitondeal dialysis
What is the average age of patients with ADPKD? How early might this condition present?
Mean age of presentation is 31
Early onset may be seen in utero, or first year of life
What antibody is seen in 70% of patients with primary membranous nephropathy?
Anti PLA2r antibody
Which parts of the nephron are found in…
- the cortex
- the medulla?
Cortex
- proximal tubule
- distal tubule
Medulla
- Descening and Ascending limbs of Loop of Henle
Name some of the common causes of primary (idiopathic) glomerulonephritis
Minimal change
Focal Segmental GlomeruloSclerosis (FSGS)
Membranous GN
Membranoproliferative GN
IgA Nephropathy
