Renal Flashcards
Goodpasture’s syndrome overview
Rapidly progressing acute nephritic syndrome leading to renal failure, antibodies against specific type IV collagen types within alveolar basement membrane and glomerular basement membrane
Also known as anti-glomerular basement membrane disease
Goodpasture’s syndrome investigations
LM - crescentic GN
Immunofluoresence - continuous linear deposition of IgG along GBM
Serum anti-GBM Ab, normal C3
IgA nephropathy investigations
(Follows viral infections)
LM - focal proliferation
Immunogluorescence - diffuse mesangial IgA
EM - mesangial deposits
Lupus nephritis overview
Range of presentations, varying from haematuria and/or proteinuria to nephritic/nephrotic syndrome
Involves immune complex deposition
Lupus nephritis investigations
LM and immunofluorescence - varying in severity but related to immune complex deposits (Ig, C3) in mesangium/subendothelial layers
Increased ANCA, anti-dsDNA, decreased C3 and C4
Mesangiocapillary GN overview
Presents with anything from asymptomatic haematuria/proteinuria to acute nephritic/nephrotic syndrome
Type 1: circulating immune complexes trapped in glomerular sub endothelial space
Type 2: derangement of complement regulation
Low serum C3
‘Tram-tracking’ appearance
Post-infectious GN overview
Acute nephritic syndrome (gross haematuria, oedema, HT, renal insufficiency) 1-2 weeks post strep pharyngitis or 3-6 weeks post strep pyoderma
Mediated by immune complexes ?glomerular deposition/complement activation by directly deposited strep antigens
Post-infectious GN investigations
LM - diffuse proliferation, increased neutrophils
Immunofluorescence - granular, “hump-like” sub epithelial IgG and C3
EM - sub epithelial humps
Decreased C3-C9, normal C1 and C4, increased ASOT/antiDNAse B
Alport syndrome overview
Hereditary disease of collagen IV (part of glomerular BM)
Hereditary nephritis - microscopic haematuria (macroscopic 1-2 days after infections), proteinuria frequently
Sensorineural deafness - high frequency initially and progressive
EM - variable thickness of basement membrane with splitting
Benign familial haematuria overview
Refers to isolated haematuria in multiple family members without renal dysfunction
IgA nephropathy follow up?
Ongoing follow up for life indicated due to ESRF in 25% of patients 15-20 years after disease onset
IgA nephropathy poor prognostic factors
Hypertension, proteinuria
As GFR declines, urinary creatinine clearance overestimates GFR due to what mechanism?
As GFR declines, an increasing proportion of creatinine is secreted by the tubules, resulting in an overestimation
Physiological changes associated with HIV associated nephropathy?
Focal segmental glomerulosclerosis seen in 65% of patients
Antiretroviral therapy induces remission in most cases, but rarely HIVAN can occur in patients with well controlled HIV
Most common cause of nephrotic syndrome in children?
Minimal change disease, especially in 1-10 year olds
Membranoproliferative GN overview
Most common in second decade
Can be primary or secondary
Can present with nephrotic syndrome, nephritic syndrome, or persistent microscopic haematuria and proteinuria
Causes of secondary MPGN?
Infections such as Hepatitis B or C, syphilis, or subacute bacterial endocarditis
Treatment for post infectious GN?
Rest, fluid restriction
Loop diuretic e.g. frusemide
- if resistant to frusemide, use hydralazine or nifedipine
ACEi effective but usually not used due to hyperkalaemia risk
Best treatment for moderate hypertension following post-infectious GN?
Frusemide
If resistant, try hydralazine or nifedipine
Most likely teratogenic consequence of ACEi/ARB in pregnancy?
Renal insufficiency is the most common Cx of intrauterine ACEi/ARB exposure
Limb defects are also a complication, in 17% of neonates exposed after 20 weeks
Risk of long term hypertension following UTI is related to?
Presence/degree of renal scarring
Best method of assessing renal scarring?
Renal scintigraphy using DMSA (dimercaptosuccinic acid)
- DMSA is injected IV, and uptake by the kidney is measured 2-4 hours later
- areas of reduced uptake suggest pyelonephritis (acute) or scarring (chronic)
What does DTPA (diethylenetriamine pent-acetic acid) scan show?
Used to assess differential renal function, and when frusemide is given, drainage/obstruction can also be measured
What is IV pyelogram used for?
Looks for evidence of renal tract obstruction
Micturating cysto-urethrogram (MCU) is the best test for?
Test of choice to establish the presence and degree of VUR, but will not detect renal scarring
Distal renal tubular acidosis overview
RTA type 1 = distal renal tubular acidosis
Defective H+ secretion from the distal tubule
Low K+, sometimes low Na+
Hypercalciuria
Positive urinary anion gap (Na + K - Cl)
AR and AD forms
Proximal renal tubular acidosis overview
RTA type 2 = proximal renal tubular acidosis overview
Wasting HCO3-, inability to reabsorb
Low K+, normal Na+
Normal urine calcium
Fanconi’s biochemical findings
Low serum phosphate, uric acid
Increased urine glucose, amino acids, LMW proteins
How is Alport syndrome most commonly inherited?
X linked (mutations in COL4A5 gene)
Can also be AR (15%, mutations in COL34A3 or COL4A4) or AD (up to 5%, mutations in COL4A3 or COL4A4)
What is the mechanism to explain low serum Na in patients with marked hyperglycaemia?
The increase in serum glucose raises the serum osmolality, which pulls water out of cells and lowers the serum sodium concentration (pseudohyponatraemia)
Addison’s disease overview
Autoimmune adrenal insufficiency - deficiency of mineralocorticoids
Causes hyponatraemia, low bicarb and chloride, hyperkalaemia
What is the first step of management in DKA?
Fluid resuscitation to replace losses from polyuria and vomiting, and to avoid shock
Resuscitation fluids are always normal saline
Melnick Fraser syndrome overview
Also known as branchio-oto-renal syndrome
AD disorder with complete penetrance
Occurs in 1 in 40,000, associated with mutations in EYA1 and SIX1 and SIX5 genes
Not all children have renal lesions, may have 1-2 features only
Preauricular pits
Features of rhabdomyolysis
Raised CK (usually >5000mmol/L), mainly CK-MM rather than CK-MB
Raised creatinine and potassium
Muscle pain, dark urine due to myoglobinuria
Also usually associated with hypovolaemia, hyperphosphataemia, hypocalcaemia, raised urea and a metabolic acidosis
Management of rhabdomyolysis
Hydration
Sodium bicarbonate (to prevent renal failure from accumulation of myoglobin and irate crystal in the tubules)
Diuretics to improve urinary flow
ECG monitoring
DIC management
Dialysis if oliguric renal failure
Surgery if required for compartment syndrome
Late complications include cardiac issues from hyperkalaemia, AKI, compartment syndrome and DIC
Rhabdomyolysis overview
Occurs due to muscle necrosis where the intracellular muscle constituent are released into the circulation
What is the gold standard investigation for renal artery stenosis?
Renal arteriography
What is the most common cause of renal artery stenosis in children?
Fibromuscular dysplasia
Best pre-operative imaging for Wilms tumour?
MRU (magnetic resonance urography) - gives a more detailed assessment of renal anatomy
Presentation with acute renal failure and sterile pyuria?
Acute interstitial nephritis
Presentation of acute tubular necrosis?
Muddy brown casts and heme.
Patients are usually oedematous
Diabetes insipidus impact on kidneys
Deficiency of ADH, leads to inappropriately dilute urine leading to dehydration
Recommendations for bilateral renal pelvis dilatation?
Bilateral dilatation of >10mm suggests very high likelihood of underlying pathology (bladder outlet obstruction, severe reflux etc)
Should have ultrasound within first week of life, earlier if there is reduced urinary output
What is the most common cause of hypertension in patients with neurofibromatosis?
Essential hypertension
Renal artery stenosis is more common in children with neurofibromatosis
Treatment for minimal change nephrotic syndrome
High dose daily steroid for 6 weeks, then alternate day for 4 weeks, then tapered over 1-2 months
If ongoing proteinuria on daily steroids = steroid resistant and needs renal biopsy
If relapses whilst on alternate day steroid OR relapses within 28 days of successful steroid course = steroid dependent
If responds well to steroids but relapses >4 times per year = frequent relapsers
If steroid dependent, frequent relapser or steroid resistant, consider alternative therapies
Clinical triad of HUS
Microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure
Link between VUR and hypertension?
Of a study of patients with VUR, children with renal scarring were at risk of hypertension, and those without scarring did not develop hypertension
Liddle syndrome overview
Monogenic AD disorder causing increased expression of epithelial sodium channels in the distal nephron (resulting in increased sodium resorption, therefore features similar to hyperaldosteronism)
Serum aldosterone levels are typically low
Typically presents in second or third decade of life
Microscopic haematuria and proteinuria, hypertension, creatinine 88, EM shows thick and thin “basket weave” pattern of the BM
Alport syndrome - common cause of chronic microscopic haematuria
Can also affect vision and hearing
COL4A3/COL4A4/COL4A5 genes can be affected
Features of nephronophthisis
Reduced urinary concentrating ability with a bland urinary sediment
Chronic tubulointerstitial nephritis and progression to end-stage renal disease (usually by 20 years)
Poor growth may be related to dehydration initially, then due to CKD
Normal BP and normal sized kidneys
Denys-Drash syndrome triad
Infantile nephrotic syndrome due to diffuse mesangial sclerosis, Wilms tumour and 46 XY
46 XX patients have normal external genitalia but may have streak gonads or bicornuate uterus
Disorder due to mutation in WT1 gene at 11p13
Features of WAGR syndrome
Wilms tumour
Aniridia
Genitourinary abnormalities (cryptorchidism and/or hypospadias, could have ambiguous genitalia)
Intellectual Disability (previously retardation)
Chronic renal failure due to FSGS occurs in 60%
Decreased afferent arteriole pressure leads to…
Increased renin = increased angiotensin II = increased aldosterone
Decreased atrial stretch leads to…
Decreased ANP
Increased vasopressin
Overview of ADH (vasopressin)
Produced by hypothalamus, secreted by posterior pituitary
Released in response to decreased atrial pressure (i.e. hypovolaemia)
Kidney causes increased water reabsorption by increasing permeability in collecting duct, producing more concentrated urine
The predominant cause of anaemia in chronic renal failure?
Decreased production of erythropoietin
Causes of anaemia in CRF - decreased EPO production, iron/folate/B12 deficiency, decreased EPO survival
Calculation for fractional excretion of sodium?
(Urine Na / Urine Cr) x (Plasma Cr / Plasma Na) x100
Up and salt (urine first then plasma, salt first)
In a child with suspected multi cystic dysplastic kidneys, which is the most appropriate imaging?
DTPA or Mag3
DTPA is an excretory nuclear medicine scan which assesses obstruction
Following treatment of nephrotic syndrome (presumed post-infective), what pathology result would indicate consideration of renal biopsy?
Hypocomplementaemia
Persistent low C3/C4 raises suspicion for MPGN
Features of infantile nephronophthisis
Rare disorder, most severe form of nephronophthisis (usually results in ESRF by 12 months)
Caused by mutations in NPHP2 and NPHP3
Severe hypertension is common (unlike older forms where hypertension not usually seen)
Renal imaging shows normal kidneys with cysts
Extra-renal findings in 80% of patients
Can be detected antenatally with oligohydramnios/renal abnormalities
Action of aldosterone?
Increases reabsorption of sodium by acting primarily on principal cells in collecting ducts
Responsible for sodium reabsorption and subsequent water conservation
Action of angiotensin II?
Produces arteriolar constriction, increases SBP and DBP
Very potent vasoconstrictor
Also acts on adrenal cortex to increase secretion of aldosterone
Action of anti-diuretic hormone?
Causes retention of water by increasing permeability of collecting ducts
Urine becomes more concentrated and volume decreases
Osmolality of body fluid decreases
Action of prostaglandin I2?
Unstable cyclooxcygenase metabolite found in vascular endothelial cells
Potent vasodilator and inhibitor of platelet aggregation
Action of thromboxane?
Promotes platelet aggregation and vasoconstriction
Activated in acute severe blood loss to constrict bleeding vessels and form clot
During acute hypovolaemia, which mediator produces dilation of the renal afferent arteriole?
Prostaglandin (can dilate or constrict)
Likely would cause dilation of the renal afferent arteriole, whilst angiotensin II constricts the efferent arteriole
What embryological structure develops into the adult kidney?
Metanephros - arises from the nephrogenic cord as a metanephric diverticulum which grows into the nephrogenic cord to form a metanephric blastema
Complications of primary VUR?
Pyelonephritis, reflux nephropathy and ESRD
Rate of spontaneous resolution of low grade VUR diagnosed in infancy?
80%
Definition of grade I VUR
Reflux into the ureter but not into the collecting system
Definition of grade II VUR
Reflux into the ureter and collecting system WITHOUT dilatation
Definition of grade III VUR
Reflux into the ureter and collecting system with mild ureteric and renal pelvis dilatation
Definition of grade IV VUR
Reflux fills and grossly dilates the ureter and collecting system, causing ureteric tortuosity and significant blunting of the calyces
Definition of grade V VUR
Reflux fills and grossly dilates the ureter and collecting system, with blunted calyces and loss of papillary impressions, and intrarenal reflux may be present
Hypokalaemic metabolic alkalosis with hypercalcuria, high urinary chloride, normal BP?
Bartter syndrome
Metabolic alkalosis, hypokalaemia, high urinary chloride, normal BP?
Occult diuretic use
Hypokalaemia, ?hypernatraemia (due to water loss), water depletion, metabolic alkalosis?
Occult laxative use
Urinary loss of potassium, chloride, hypokalaemia, metabolic alkalosis?
Hyperaldosteronism (common cause of secondary hypertension)
Low/normal BP, loss of chloride, metabolic alkalosis, hypokalaemia, hypochloraemia with urinary chloride close to zero, secondary hyperaldosteronism and renal loss of potassium?
Self-induced vomiting
Which of the following is least likely to lead to a progression of chronic renal failure?
Hyperlipidaemia, hypocalcaemia, metabolic acidosis, phosphate retention, proteinuria
Hypocalcaemia
Proteinuria -> renal function decline
Hypertension -> causes arteriolar nephrossclerosis and increases hyperfiltration injury
Phosphate retention -> leads to calcium-phosphate deposition in the renal interstitial and blood vessels
Hyperlipidaemia -> oxidant-mediated injury
Factors that result in progressive renal failure?
Hyperfiltration injury
Persistent proteinuria
Systemic or infrarenal hypertension
Renal calcium-phosphorus deposition
Hyperlipidaemia
What is hyper filtration injury?
Final common pathway of glomerular destruction (independent of the underlying cause of renal injury)
Remaining nephrons undergo structural and functional hypertrophy, with increased blood flow
What cells are produced as a result of exposure to high levels of urea?
Burr cells - short and evenly separated spikes over the surface of the red blood cell
Primary site of action of thiazide diuretics?
Proximal portion of the distal tubule
Mechanism of action of thiazide diuretics?
Sodium reabsorption via the Na-Cl cotransporter is blocked through competition with the Cl site of the cotransporter
Impact of thiazide diuretics on calcium levels?
Can enhance reabsorption of calcium ions through a direct action on the early distal tubule, therefore useful agents to reduce calciuria in patients with kidney stones
Impact of thiazide diuretics on magnesium levels?
Magnesium excretion is increased by thiazides, which may result in hypomagnesemia
What electrolyte imbalances are expected from chronic thiazide diuretic use?
Hyponatraemia
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia (although magnesium can be normal)
Other less common side effects from thiazide diuretic use?
Hypercalcaemia, hyperglycaemia, hyperuricaemia and gout, rash and photosensitivity, altered plasma lipids, pancreatitis, neutropenia and thrombocytopenia, intrahepatic cholestasis, acute renal failure
Primary causes of nephrotic syndrome?
Minimal change disease (most common)
Focal segmental GN
Membranoproliferative GN
Membranous nephropathy
Diffuse mesangial proliferation
Secondary causes of nephrotic syndrome?
SLE
HSP
Malignancy (lymphoma, leukaemia)
Infections (hepatitis, HIV, malaria)
Triad of clinical findings associated with large urinary losses of protein?
Hypoalbuminaemia
Oedema
Hyperlipidaemia
What is AD thin glomerular basement membrane nephropathy?
Diffuse thinning of GBM
One of the most common causes of isolated haematuria
Exact prevalence and prognosis unclear, usually considered a benign cause of haematuria with usually no effect on renal function
Indications for MCUG?
VUR in children (recurrent UTI)
Stress incontinence
Urethral stricture
Bladder dysfunction
Contraindications for MCUG
Current UTIs
Contrast media allergies
Most common cause of severe obstructive uropathy in children?
Posterior urethral valves
Classic triad of renal vein thrombosis?
Thrombocytopenia
Haematuria
Flank mass
(Most patients do not experience all 3 signs)
Pneumococcal can lead to anaemia, thrombocytopenia and renal dysfunction due to what pathological process?
Haemolytic uraemic syndrome
How is a diagnosis of pneumococcal related HUS made?
AKI
Microangiopathic haemolytic anaemia
Thrombocytopenia
Treatment of HUS
IV fluids
Transfusion of WASHED packed red blood cells
Dialysis
Plasmapheresis
Definition of nocturnal enuresis
Involuntary voiding at night after 5 years of age
First line treatment of nocturnal enuresis?
Restrict fluid intake after 6pm
Motivational therapy
Conditioning therapy - enuresis alarm
Medications are second line treatment
Anterior lenticonus is pathognomonic of which syndrome?
Alport syndrome (up to 30% of patients)
Perlman syndrome overview
Overgrowth syndrome caused by mutation of DIS3L2 on 2q37, AR inheritance
60% risk of Wilms tumour if child survives beyond neonatal period
Risk of Wilms tumour in Sotos syndrome?
<5%
Risk of Wilms tumour in Simpson-Golabi-Behmel syndrome?
<10%
Where is the primary site of potassium reabsorption in the nephron?
Proximal convoluted tubule (50%)
Why are steroids indicated in HSP?
Shortens duration of abdominal pain (and likely shortens duration of arthralgia/arthritis)
Low C3 is suggestive of….
Post-strep GN
Overview of post-infectious GN
90% = acute nephritic syndrome characterised by sudden onset of gross haematuria, oedema, hypertension and renal insufficiency
Which enzymes are involved in Vitamin D metabolism in the kidneys?
1-alpha-hydroxylase and 24-alpha-hydroxylase
The former metabolises vitamin D to 1,25 dihydrocholecalciferol (active form of vitamin D)
The most accurate measure of GFR is provided by…
Cr EDTA clearance
- freely filtered, not reabsorbed or secreted by tubules
At what point will serum creatinine rise in response to poor renal function?
Creatinine will not rise until the GFR falls by 30-40%
What drug will most likely lead to an increase in tacrolimus drug levels and nephrotoxicity?
Fluconazole (>80% excreted unchanged in the urine)
Fluconazole mechanism of action
Inhibits fungal CYP450 which is responsible for fungal sterol synthesis, i.e. weakens fungal cell walls
Medullary cystic disease: changes on biopsy?
Renal architecture shows distribution of variably sized cysts in the medulla and corticomedullary junction
Patient with poor growth, intermittent vomiting, normal anion gap metabolic acidosis, hypokalaemia, hypocalcaemia. Differentials of NAGMA?
Diarrhoea
Renal tubular acidosis
Post hypocapnea metabolic acidosis
Pathophysiology of type 1 (distal) RTA
Impairment of the distal tubule’s ability to excrete acid in the form of ammonium, urine pH is thus >5.5
If in infancy, is usually due to AR mutation, can sometimes also cause sensorineural hearing loss
Acquired causes of Type 1 RTA?
Amphotericin B or lithium administration
Sjogren’s disease
SLE
Treatment for Type 1 RTA?
Oral alkali therapy with bicarbonate or citrate
Pathophysiology of type 2 (proximal) RTA?
Impairment in proximal tubule reabsorption of HCO3, urine pH is los (<5.5) once total body bicarbonate depletion occurs
Genetic forms most often manifest as Fanconi syndrome
Type 3 RTA refers to…
Combination of proximal and distal RTA, due to inherited mutation in carbonic anhydrase
Pathophysiology of Type 4 (hyperkalaemic) RTA?
Caused by hypoaldosteronism or aldosterone resistance
Inherited forms may be caused by CAH or aldosterone synthase deficiency
Most commonly due to drugs (NSAIDs, heparin, ACE inhibitors, tacrolimus, cyclosporine and potassium sparing diuretics)
Overview of Fanconi syndrome
Proximal tubule wasting of glucose, phosphate, amino acids, uric acid and potassium
What is the approximate GFR of a term neonate on day 1 of life?
20ml/min/1.73m2
Extremely low due to decreased renal blood flow, GFR improves markedly within the first two weeks
At what age does a child’s GFR reach adult levels?
2 years
Why are premature neonates more at risk of an AKI?
Premature neonates have lower GFRs at birth, which is closely linked to gestation at birth and birth weight. They have rapid improvement in GFR. Incomplete nephrogenesis results in a poorer GFR than their term counterparts, and they are more susceptible to an AKI.
Adverse effects of tacrolimus administration after renal transplantation?
Alopecia, hypertension, nephrotoxicity, high cholesterol (more mild than other immunosuppressants), hyperglycaemia (diabetes), low Mg, tremor, parasthesias, neurotoxicity (seizures), high K+, gingival hyperplasia
Rare - confusion, seizure, coma, psychosis, HUS
Definition of congenital nephrotic syndrome?
Nephrotic syndrome under the age of 3 months
Common causes of congenital nephrotic syndrome?
More than 80% are due to mutations in NPHS1 (encodes nephron), NPHS2 (encodes podocin), NPHS3 (encodes phospholipase C epsilon), WT1 (endorse transcription tumour suppressor) and LAMB2 (encodes laminin beta 2).
Classic triad of acute interstitial nephritis?
Fever, rash, arthralgia
(rarely seen)
Features of AIN
If mediated by renal pathology, urine osmolality is low (<350) and Fractional Excretion of sodium is >2%
Low grade haematuria and pyuria are typical, white cell casts and urinary eosinophils are suggestive but not diagnostic
Common medications causing AIN?
NSAIDs, antimicrobials, anticonvulsants
Treatment of AIN?
Withdrawal of the offending medication
Supportive care
Occasionally corticosteroids are required
Complications of multicystic dysplastic kidney (MCKD)?
The kidney is replaced by cysts and does not function
15% have contralateral VUR
5-10% have contralateral hydronephrosis
0.2-1.2% develop hypertension
0.3% risk of Wilms
Complete cyst regression by age 7 in nearly half of patients
What are the expected insensible water losses (mls/kg/hr) on day 1 of life, for very preterm infants?
2-3ml/kg/hour
Mechanism of hypokalaemia in refeeding syndrome?
Insulin secretion in response to a caloric load, shifting potassium into cells
Overview of nocturnal enuresis treatment
Motivational therapy
Bladder training (alarms)
Fluid management
Treatment of hypovolaemia in nephrotic syndrome?
IV 20% albumin, 1g/kg over 1-2 hours followed by frusemide (give over 4 hours if concerned regarding rapid fluid shifts and pulmonary oedema)
Where is most sodium reabsorbed in the kidney?
65% of filtered sodium and water are reabsorbed by the proximal tubule
40% of sodium/chloride/potassium are reabsorbed in the thick ascending limb of the LoH via the cotransporter
5% in the distal tubule, 2% in the collecting duct
Recommended treatment for steroid-dependent nephrotic syndrome with frequent relapses?
Cyclophosphamide
Long term lithium therapy can lead to what renal complication?
Nephrogenic DI due to ADH resistance
What is the best test to distinguish between central and nephrogenic DI?
Administering desmopressin and assessing the response in urine osmolality
Epithelial sodium channels located in the collecting duct is regulated by which hormone?
Aldosterone
Best initial treatment for stage III-IV lupus nephritis?
Pulse IV methylprednisolone and IV cyclophosphamide
The addition of IV cyclophosphamide has greatly improved mortality and rates of progression to ESRD
Most common renal lesion in tuberous sclerosis?
Angiomyolipomas (80%)
What medications can increase cyclosporin levels?
Ketoconazole, erythromycin, warfarin, verapamil, ethanol, imipenem-ciastatin, metoclopramide, itraconazole and fluconazole
What medications decrease cyclosporin levels?
Phenytoin, phenobarbital, carbamazepine, valproate, nafcillin, octreotide and trimethoprim
What is one of the key known side effects of cyclosporin?
Neurotoxicity - tremors, paraesthesia, headache, confusion, somnolence, seizures, coma
What is the role of magnesium in renal stone formation?
Magnesium is an inhibitor of calcium oxalate stone formation, therefore hypomagnesuria predisposes to stone formation
What is the role of citrate in renal stone formation?
Citrate is an inhibitor of calcium stone formation, therefore low urinary citrate (hypocitraturia) predisposes to stone formation
Clinical features of renal stones
Gross/microscopic haematuria
Abdominal or flank pain (if causing obstruction), radiates anteriorly
If stone in distal ureter - dysuria, frequency, urgency
If in urethra - dysuria and difficulty voiding may occur
Diagnosis of renal stones
90% are radiopaque on plain AXR
CT abdo/pelvis (nonenhanced) often used to delineate number and location of stones, and hydronephrosis if present
Features of calcium oxalate/calcium phosphate stones
30-60% have hypercalciuria without hypercalcaemia
Other predisposing factors include hyperoxaluria, hypocituria, hyperuricosuria, heterozygous cystinuria, hypomagnesuria, hyperparathyroidism, renal tubular acidosis
Features of cystine calculi
Cystinuria accounts for 5% of renal calculi in children
Rare, AR disorder of epithelial cells of the renal tubule (cannot absorb the four dibasic amino acids including cystine)
Features of struvite calculi
UTIs with urea-splitting organisms with alkaline urine and excessive ammonia product - formation of magnesium ammonium phosphate (struvite)
Often seen in patients with neurogenic bladder
Features of uric acid calculi
<5% of cases
Radiolucent stones
Associated with inborn errors of purine metabolism (hyperuricosuria)
Other associations: Lesh-Nyhan syndrome, short bowel syndrome, G6PD
Increased risks with some tumours and myeloproliferative diseases
Indinavir (drug used for HIV treatment) - can lead to calculi
Management of renal stones
Surgical removal/ablation can be considered
Treat underlying metabolic disorder
Hypercalciuria (decrease Na and Ca intake, thiazides, potassium citrate)
Uric acid stones - allopurinol
Cystine calculi - maintain high urinary pH (sodium bicarb or sodium citrate)
RTA - correct metabolic acidosis and replace Na and K
Primary hyperoxaluria - liver transplant
At what vertebral level do the renal arteries branch from the aorta?
T12
Initial investigation for day and night enuresis, with no history of UTI or faecal incontinence and developmentally appropriate?
IV pyelogram - helpful to review anatomy, ensure no ectopic ureter (which is a cause of frequent wetting)
Purpose for urodynamic testing?
To aid in understanding physiologic mechanisms of lower urinary tract dysfunction, thereby improving the accuracy of diagnosis and facilitating targeted management
Examples include cystometry (measures pressure and volume during phases of bladder emptying), uroflowmetry (measures rate of flow), urethral pressure profile (tests urethral function), leak point pressure (determines bladder/abdominal pressure when leakage occurs to assess urethral resistance)
Presenting features of Guillain-Barre syndrome
Ascending paralysis
Loss of reflexes, loss of sensation, and weakness
Presenting features of transverse myelitis
Loss of spinal cord function (in a distinct region) over several hours to weeks
Sudden onset of lower back pain, muscle weakness or abnormal sensations which can then progress to more severe symptoms including paralysis, urinary retention and faecal incontinence
Reflexes will be reduced
Patient presenting with nephritic syndrome, with hepatomegaly, lymphopenia, thrombocytopenia and haemolytic anaemia?
Consider lupus nephritis - milder forms present with haematuria, normal renal function and mild proteinuria. More severe cases can have nephrotic syndrome or acute renal failure
Most common symptoms of catheter-related peritonitis?
Abdominal pain, nausea and vomiting
Fevers are present in a minority of patients, and usually dialysis fluid looks clear
Is AD or AR polycystic kidney disease more commonly seen in children?
ADPKD usually presents in adults
Radiological findings of ARPKD?
Both kidneys would be enlarged and have gross cysts in the cortex/medulla. Usually bilateral flank masses, markedly enlarged and hyperechogenic kidneys with poor corticomedullary distinction on USS
Horseshoe kidney overview
Most common renal fusion anomaly
Fusion occurs between week 5 and week 9 of gestation
Most children will be asymptomatic and don’t require Rx
If diagnosed antenatally, should be confirmed on RTUS
Higher risk of UTIs due to stasis, no prophylactic antibiotics indicated
Horseshoe kidney is associated with which syndromes?
Turner syndrome and Laurence-Moon-Biedl syndrome
Which physiological processes stimulate renin release?
Beta-1 adrenergic activation (via cardiac and arterial baroreceptors)
Decreased distal tubule sodium delivery (detected by macula densa)
Decreased afferent arteriolar pressure (detected by local baroreceptors)
Effect of ANP on renin?
ANP (stimulated by atrial stretch receptors) inhibits renin release
Liddle’s syndrome and RAAS?
Low plasma renin, low aldosterone, low potassium
Fibromuscular dysplasia and RAAS?
Fibromuscular dysplasia causes reduced renal blood flow, therefore RAAS activated causing high renin and aldosterone
Gordon’s syndrome and RAAS?
Gordon’s syndrome is also known as pseudohypoaldosteronism type 2 or familial hyperkalaemia hypertension
Low renin, low aldosterone, high potassium
Pseudohypoaldosteronism type 1 and RAAS?
Aldosterone is raised in pseudohypoaldosteronism type 1, because it is a rare disorder where there is resistance to aldosterone
Relationship between IgA nephropathy and URTI?
Many children with IgA nephropathy are asymptomatic, but symptoms can occur after an URTI, and there is usually a pattern of recurrence
Can be confused with post strep GN, but this usually occurs at least 1 week after infection and recurrence is rare
What is the difference in causes of low C3 between post strep GN and mesangiocapillary/membranoproliferative GN?
PSGN = proliferative GN, consumes C3 (immune activation of alternative pathway), the low C3 should therefore resolve in 6-12 weeks
Mesangiocapillary/membranoproliferative GN (particularly dense deposit disease) is complement mediated GN, therefore will have persistently low C3
Rate of Wilms tumour in Beckwith-Wiedemann syndrome?
5-10%
Renal complications in Denys-Drash syndrome?
Progressive renal disease, male pseudohermaphroditism and 90% of patients will develop Wilms tumour
Rate of Wilm’s tumour in WAGR?
50%
(Wilms, aniridia, genitourinary abnormalities, ID)
Rate of Wilm’s tumour in isolated hemihypertrophy?
<5%
Most common organism in PD patients with localised exit or tunnel tract infections?
Staph aureus (42%)
Gram +: thick cell wall stains purple - bacillus, listeria, staph, strep, clostridium
Gram -: thinner cell wall stains pink - spirochetes, pseudomonas, E. coli, salmonella, enterobacter
Polyuria, microscopic haematuria, proteinuria or kidney stones?
Dent disease - X linked recessive nephrolithiasis
Caused by mutations in CLCN5 gene, which inactivates voltage gated chloride transporter
Some are mutations in OCRL1 gene (associated with Lowe oculocerebrorenal syndrome)
Overview of cystinosis
Lysosomal storage disease
Cysteine accumulates in organs and tissues, leads to severe organ dysfunction
Often have vitamin D resistant rickets at presentation secondary to phosphate wasting
High levels of cysteine in leukocytes or fibroblasts
Autosomal dominant thin glomerular basement membrane nephropathy is among the most common causes of what?
Isolated haematuria (benign)
Renal hypoplasia, ocular abnormality, mutation of CHD7 gene
CHARGE syndrome
= coloboma, heart defects, choanal atresia, restricted growth, GU defects, ear anomalies
CHARGE due to CHD7 mutation
Primary amenorrhoea, normal phenotype, renal agenesis and vaginal agenesis noted on USS
Mayer-Rokitansky-Kuster-Hauser syndrome
- also known as vaginal agenesis or Mullerian agenesis
Unknown cause, up to 50% have associated renal abnormalities
Joint laxity, ocular abnormality and renal hypoplasia, mutation in PAX2 gene
Renal coloboma syndrome
AD disorder with coloboma, renal abnormalities, SNHL, seizures, joint laxity
(c/w Marfan’s which is similar, but NO renal issues)
Cells seen in peripheral blood smear due to exposure to high levels of urea?
Burr cells - short and evenly separated spikes over the surface of the RBC
Hypertension with low renin, low aldosterone, high potassium
Gordon’s syndrome
Also known as pseudohypoaldosteronism type 2 or familial hyperkalaemia hypertension
Anterior lenticonus is associated with?
Alport syndrome
- thinning of lens capsule leading to a regular conical protrusion on the lens
Adrenal hypoplasia overview
Caused by mutation of DAX1 gene, affects boys mainly
Boys with AHC develop hypogonadotrophic hypogonadism
Chronic thiazide diuretic use leads to…
Hyponatraemia
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia (although magnesium can be normal)
Can also cause hypercalcaemia, hyperglycaemia, hyperuricaemia, etc
Renal consequence of long term lithium therapy?
Nephrogenic DI due to ADH resistance
Clinical triad of neonatal renal vein thrombosis?
Haematuria
Palpable flank mass
Thrombocytopenia
Risk factors for neonatal renal vein thrombosis?
Gestational diabetes
Maternal lupus
Umbilical vein catheter insertion
Hypoxia at birth or fetal distress
Major side effect of sirolimus?
Poor wound healing (problematic after transplant surgery), therefore patients may be switched to tacrolimus
Sirolimus vs tacrolimus?
Both good agents for immunosuppression for transplant
Sirolimus associated with poor wound healing
Tacrolimus associated with hypertension and increased risk of diabetes
Risk in patients on tacrolimus who have diarrhoea?
Require increased monitoring in the setting of acute diarrhoea due to the risk of increased trough levels and toxicity
Mechanism of tacrolimus toxicity in patients with acute diarrhoea?
First pass metabolism of tacrolimus occurs in the liver
Absorption in the gut is limited by active transport away from enterocytes, back to the intestinal lumen by P-glycoprotein. During enterocolitis, epithelial cells secreting P-glycoprotein may be damaged and more of the drug is absorbed by enterocytes.
Similar to process seen with cyclosporine
Patients with cystic fibrosis are most vulnerable to which kind of renal stones?
Calcium oxalate
- occurs due to excessive enteral absorption of oxalate, which leads to increased urinary excretion
Classic radiological finding in nephrocalcinosis?
Acoustic shadowing
Calcium phosphate stones are more likely to occur in which condition?
Renal tubular acidosis
Struvite stones usually occur in what setting?
In the setting of infection
Form a ‘Staghorn’ shaped calculus
Cystine stones are more likely to occur in what setting?
If there is an underlying condition causing cystinuria, such as Dent’s disease
Primary defect in Bartter’s syndrome?
Impairment of the sodium/chloride cotransporter located on the thick ascending limb
- i.e. in a crisis can present with vomiting and diarrhoea
Moderate dehydration despite lots of fluid intake, high urinary output, urine osmolality of 280mosm/L?
Diabetes insipidus
Primary defect in the nephron seen in nephrogenic diabetes insidious?
Collecting duct
- nephrogenic diabetes insipidus occurs due to decreased response to vasopressin
- normally, vasopressin facilitates water reabsorption by binding to the V2 receptor in the collecting duct, increasing expression of aquaporin 2 channels
Primary defect seen in Gitelman’s syndrome?
Diminished sodium and chloride transport in the distal convoluted tubule
- history can include fatigue, weakness, muscle cramps
Escalation of treatment in a child with steroid-resistant nephrotic syndrome?
Rituximab - immunotherapy is the most appropriate treatment after trialling calcineurin inhibitors and steroids
Mechanism of immunotherapy in steroid-resistant nephrotic syndrome?
Depletes B cells and therefore suppresses B and T cell interactions
Stepwise management for steroid-responsive nephrotic syndrome (with frequent relapses)?
- Low dose alternate day steroids
- Levamisole
- Oral cyclophosphamide
- Calcineurin inhibitor (ciclosporin or tacrolimus)
- Mycophenolate mofetil
- Rituximab
Definition of frequently relapsing nephrotic syndrome?
> 4 relapses per year
Vomiting and positional headaches in a child with nephrotic syndrome should raise concerns for which complication?
Cerebral sinus venous thrombosis
- multifactorial cause: hypercoagulable state due to increased blood viscosity, hypoalbuminaemia and steroid administration
Grading of renal pelvis dilatation in hydronephrosis?
Normal = <7mm
Mild = 7-10mm
Moderate = 10-15mm
Severe = >15mm
Follow up for hydronephrosis?
Early renal tract ultrasound (<72 hours) if anuria or ballotable kidneys
If mild to moderate hydronephrosis, has passed urine and kidneys are not ballotable: RTUS should be delayed until day 4 or later (as earlier imaging can be falsely reassuring)
Most common GN to occur after a renal transplant?
Focal segmental glomerulosclerosis
Membranoproliferative GN also recurs at a high rate
Hypertension, haematuria and low C3?
Membranoproliferative disease
- more common in girls and children >8 years
Population risk factors for FSGS?
African males who carry the gene APOL1
Onset of proteinuria after renal transplant despite immunosuppression?
Suspicious for initial presentation of FSGS
Why is nifedipine used frequently for hypertension in children but avoided in adults?
Calcium channel blocker with associated risk of decreased coronary artery and cerebral perfusion if there is underlying atherosclerosis
- therefore should consider risk if planning to use in obese adolescents or in children with a metabolic syndrome
Typical history of post-streptococcal GN?
Macroscopic haematuria 7-10 days after infection
Can be associated with features of nephrotic syndrome (proteinuria, oedema, hypertension)
Microscopic haematuria can persist for up to 2 years, not an indication for renal biopsy
Difference in incisions and vessel anastomosis for renal transplant depending on weight?
If <30kg: midline incision with anastomosis to the aorta and IVC
If >30kg: iliac incision with anastomosis to external iliac artery/vein
IgG and C3 deposits along the glomerular basement membrane in a starry sky distribution on immunofluorescence?
Post-infectious GN
Normal appearance on light microscopy, electron microscopy shows effacement of the epithelial cell podocyte foot processes?
Minimal change disease
- effacement of the podocyte foot processes cause the normal barrier to become leaky, leading to proteinuria
Diffuse and global reduction in the capillary lumens and ‘tram-track’ appearance of the glomerular basement membrane on staining under light microscopy. Immunofluorescence shows deposition of IgG, C3 and IgM
Immune complex-mediated membranoproliferative GN
- characteristic duplication of the glomerular basement membrane appears like a ‘tram-track’
Normal anion gap metabolic acidosis with hypercalciuria?
Renal tubular acidosis type 1
- familial types can be associated with sensorineural hearing loss
Findings in RTA type 1?
Hyponatraemia, hypokalaemia, hypercalciuria, low bicarbonate and low C3 - occurs due to sodium wasting in DCT
Hyponatraemia leads to increase in aldosterone which drives excretion of potassium. Hypercalciuria is due to hyperchloraemia metabolic acidosis
Long term complications of RTA type 1?
Hyperparathyroidism
Osteomalacia
Rickets
Alport’s syndrome vs RTA type 1?
Alport’s is an important differential, as both conditions cause sensorineural hearing loss.
Persistent microscopic haematuria is needed to diagnose Alport’s, and C3 would be normal (low in RTA type 1)
Normal calcium and urinary pH <5.5 is which type of RTA?
RTA type 2
Hyperparathyroidism in chronic renal disease occurs due to which mechanism?
Due to reduced calcium reabsorption in the kidney (secondary hyperparathyroidism, as is in response to a low serum calcium)
Mechanisms of anaemia, metabolic acidosis and hyperphosphatemia in chronic renal disease?
Anaemia - multifactorial, due to decreased erythropoietin production in the kidney, reduced RBC half-life and dietary deficiencies
Metabolic acidosis - impaired ammonia excretion, reduced bicarbonate production and reabsorption
Hyperphosphatemia - occurs as a result of hyperparathyroidism as part of the calcium homeostasis mechanism
Triad of haemolytic uraemic syndrome?
AKI
Microangiopathic haemolytic anaemia
Thrombocytopenia
Common causes of HUS?
Shiga toxin from enterohaemorrhagic E. coli is most common
Second most common cause is pneumococcal infection (pleural fluid pH of <7.2), also more common in children <2 years
Risk factors for renal graft thrombosis?
Age of donor (<6 or >60), deceased donor kidney, prolonged cold ischaemia time
Renal tubular acidosis type 4?
Hypoaldosteronism causing hyperkalaemia and high bicarbonate
Renal tubular acidosis type 1?
Primary issue is in the distal convoluted tubule, causing hyponatraemia, hypokalaemia, hypercalciuria, low bicarbonate and low C3
Renal tubular acidosis type 2?
Lower bicarbonate and potassium due to reduced reabsorption in the proximal convoluted tubule
Is a fluid restriction recommended in peritoneal or hemodialysis?
Peritoneal dialysis is less efficient therefore a fluid restriction should be recommended
Temporary remission of nephrotic syndrome is associated with which infection?
Measles - associated with remission for 3-6 months
Should be considered if the child presents with classic features (coryza, conjunctivitis, rash along the hairline, unimmunised)
Teenager with myalgia, fatigue and ‘tea-coloured’ urine after running a marathon in the heat?
= Myoglobinuria
Tea coloured urine is suspicious for myoglobinuria, where the underlying mechanism is likely rhabdomyolysis after running a marathon in the heat
High creatinine after treatment with vancomycin, with granular/broad brown casts in the urine?
= Acute tubular necrosis
- granular/broad brown casts form due to tubular cell breakdown and are excreted in the urine
Bloody diarrhoea, abdominal pain, anuric, large bruises on shins?
= Haemolytic uraemic syndrome
- most common cause is Shiga toxin producing E coli, with 30-50% of children developing oligouria/anuria as a result
Overview of Dent’s disease?
X linked disorder, affects proximal convoluted tubule and causes hypercalciuria, deposition of calcium in the kidney as well as stones
Diagnosis is based on elevated beta 2 microglobulins, and there is also increased urinary low molecular weight protein
Presenting symptoms in ARPKD (when not detected antenatally)?
Usually present before the age of 3:
Hypertension (develops first few months of life)
Recurrent UTIs
Abdominal mass
Worsening symptoms of renal failure develop after 3 years of age
Most useful investigation in haematuria with dysmorphic RBCs?
Serum complement (C3, C4)
- dysmorphic RBCs are glomerular RBCs
Hypocalcaemia and hyperphosphataemia despite elevated PTH?
Pseudohypoparathyroidism
- low calcium and high phosphate despite the elevated PTH
Effect of parathyroid hormone on phosphorus reabsorption?
Parathyroid hormone DECREASES phosphorus reabsorption in the kidneys
Physiology of vitamin D deficient rickets
Less calcium is absorbed from the gut due to less Vit D
Due to slight decrease in serum calcium concentration, PTH is secreted leading to an increase in calcium and phosphorus mobilisation from bone
Therefore calcium is maintained but rickets changes in bone are seen with low phosphorus and increased ALP
Genes associated with congenital nephrotic syndrome?
NPHS1 - encodes nephrin (Finnish type CNS)
NPHS2 - encodes podocin
NPHS3 - encodes phospholipase C epsilon
WT1 - encodes transcription tumour suppressor (Denys Dash)
LAMB2 - encodes laminin beta 2 (Pierson syndrome)
More than 80% of cases are associated with a mutation in one of the above
