Renal Flashcards
What is the nephrotic syndrome triad
Proteinuria 3+ or PCR>200
Hypoalbuminemia <25
Oedema
Can also have microscopic haematuria, mild transient hypertension, or high triglycerides
Presentation nephrotic syndrome
Often initially mistaken for allergies- periorbital oedema
Volume depletion- dizziness, abdo cramps, tachycardia, reduced UO, prolonged cap refill, cold peripheries, hypotension late sign
Oedema- periorbital oedema, up to gross peripheral oedema, pleural effusion and ascites
Anemia- as excreting EPO
Fever- SBP, cellulitis ( high infection risk as urinating immunoglobulins + complement)
Thrombosis - high risk as excreting clotting factors
Hypothyroidsm
Management nephrotic syndrome
Admit for 1st presentation
Treat sepsis if needed
Oedema- no added salt diet, daily weight, fluid restriction
Albumin 20% over 4 hours with frusemide half way if significant overload
Prednisolone 60mg/m2 4 weeks with slow wean over next 4 weeks (alternate daily pred)
Consider penicillin prophylaxis (phenoxymethylpenicillin- if severe oedema and unimmunised) + PPI while on steroids for gastric protection
Delay live vaccines while on high dose steroids
Nephrotic syndrome
Defining disease types
Response to therapy-
Steroid sensitive
Steroid dependant
Steroid resistant
Pattern- frequently relapsing
Histology- MCD, FSGN
Genetics- gene pos or neg
If gene pos, unlikely to respond to immunosuppressive and progress quickly to ESRF, need transplant;but low recurrence risk post transplant
What percentage of nephrotic syndrome is idiopathic?
90%- MCD, FSGS
May be secondary to SLE, HSP etc - usually have atypical features
What percentage of children with nephrotic syndrome are steroid sensitive??
80-90% will respond to initial steroid therapy
Of those with steroid sensitive NS, 80% will have one or more relapses
When would you give prophylactic penicillin V in nephrotic syndrome
If risk of pneumococcal infection- gross or symptomatic oedema, and unimmunised
What do you tell parents post discharge with nephrotic syndrome?
Check urine protein daily for 1-2 years in order to quickly identify relapse (=3 + protein for 3 consecutive days) at which they should contact their Dr and start prednisolone prior to onset of oedema
Daily weights while nephrotic for signs fluid over load
Convey that 80% chance relapse - most commonly triggered by inter current infection
Functions of kidney
a. Excretion of waste products
b. Regulation of water and electrolytes
c. Regulation of fluid osmolality
d. Regulation of BP
e. Regulation of acid base
f. Synthesis/ excretion of hormones - EPO , activation of vitamin D , renin
Level of kidneys
T12-L3
Renin produced by which cells?
Juxtaglomerular cells
Specialised smooth muscle cells located in walls of afferent arteriole
secrete renin in response to a drop in pressure detected by stretch receptors in the vascular walls, or when stimulated by macula densa cells a
renin catalyses conversion of angiotensinogen produced by liver to ang I (then ACE from lungs converts to Ang 2)
Describe production of Ang II
Angiotensinogen produced in liver
Converted to Angiotensin I, catalysed by renin (rate limeting step)
ACE (produced by lungs) catalyses conversion of Ang I to Ang II
Actions of Angiotensin II
Arterioles: Vasoconstriction –>increase BP
Brain: increased thirst
Adrenal cortex: Increased aldosterone production –> increased sodium reabsorbtion, increased potassium excretion –> increased water retention –> increased blood volume –> increased BP
Posterior pituitary: Increased ADH secretion –> increased water reabsortion in the collecting duct –> increased blood volume
Kidney: Efferent arteriole constriction –> increased GFR (at low dose)
Net effect: salt and water retention and increased effective circulating volume, to increase perfusion of the juxtaglomerular apparatus (negative feedback to reduce renin release)
Stimulus for renin release
SNS input (beta adrenergic stimulation) in response to low BP
Hypotension - sensed by baroreceptors in the afferent arterioles
Low renal blood flow- sensed by macula densa (distal tubule) as reduced Na+ concentration
Drugs- ACEI, ARB
Chronic diseases w oedema
Renal artery stenosis (due to hypoperfusion state)
Inhibition of renin release
Ang II
ADH
Hypernatremia
Hyperkalemia
NASAIDs
Aldosterone
secreted by zona glomerulosa of adrenal cortex (outermost layer)
Acts on principal cells of collecting duct - mineralocorticoid receptor
Upregulates ENAC channels in collecting duct to increase permeability to Na+ (and water follows)
Also acts on a intercalated cells to increase hydrogen excretion (increased expression H-ATPase)
Also stimulates Na/K/ATPase pump on basolateral side of membrane –> increased excretion of potassium
ADH
Synthesised in hypothalamus
Release triggered by hyperosmolarity and hypotension (ie dehydration)–> end goal is to reabsorb more water to bring BP and osmolarity back to normal
Binds to V2 receptor at DCT+ CD –> CAMP -> G protein coupled receptor –> insertion of aquaporin 2 at luminal membrane –> water reabsorption
Concentrated urine and lowering of serum sodium
Also binds to V1 receptor on vessels –> peripheral vasoconstriction –> increased BP
ANP
Secreted by R atrium
Triggered by HTN (increased blood volume) in response to atrial stretch Actions to decrease blood volume and increase excretion of sodium
i. Dilates afferent + constricts efferent arterioles = ↑ GFR, ↑ natriuresis
ii. Inhibits aldosterone + renin secretion
iii. Inhibits Na Cl reabsorption in CD
iv. Inhibits ADH action on kidney
PTH
Trigger: low calcium
Acts on distal tubules + LOH to increase calcium reabsorption
Inhibits phosphate reabsorption proximal tubule
Action prostaglandins
Trigger: hypoperfusion of nephron
Action: dilate afferent arteriole –> increase GFR
Action endothelins
Vasoconstriction
reduce renal blood flow and reduce GFR
NSAIDs action on kidney
Inhibit prostaglandin release
–> reduced GFR
Reduced renal blood flow sensed by:
- Baroreceptors (carotid/cardiac/afferent arteriole)–> SNS stimulation
- Juxtaglomerular cells (in walls of afferent arterioles)–> release renin
- Macula densa cells in DCT–> communicates with JG cells and mesangial cells to stimulate renin release
Renal embryology
Metanephric mesenchyme (mesodermal layer)
Bowmans capsule
Prox tubule
LOH
Distal tubule
Ureteric bud (from Wolfian duct):
Collecting duct
Renal pelvis
Ureter
first nephron develops at 8-9 weeks of age
Urine production starts at 10 weeks
Complete by 36 weeks BUT GFR continues to increase for years - doesnt approximate adult values until ~ age 3 (so cant make more nephrons after birth can can compensate somewhat)
Alports disease
Most commonly X linked
Absent/abn collagen 4, replaced by immature glomerular basement membrane
Vasoconstriction of afferent/efferent arteriole leads to …
constriction afferent: reduced GFR (eg due to NSAIDs, noradrenaline, high dose Ang2
constriction efferent: increased GFR (eg ANP, Ang2 (low dose)
Vasodilation of afferent/efferent arteriole leads to..
dilation afferent : increased GFR (eg prostaglandins, ANP)
dilation efferent: reduced GFR (eg ACE-I, ARB)
Triple whammy
· ACE-I = Dilates the efferent arteriole reducing the GFR
· NSAID = Prevents PG mediated vasodilation of the afferent arteriole to maintain GFR; thereby further reducing GFR
Diuretics = reduce plasma volume and GFR
Proximal convoluted tubule
BULK OF REABSORPTION
-65% sodium
- 70% bicarbonate
- 30-50% potassium
-chloride
-100% glucose + amino acids
- 70% H2O
Secretion of:
-H+
-organic ions (urate, citrate, penicillins)
Loop of Henle
Creates concentration differences
i. Thin = squamous epithelium with high water permeability (reabsorbs 20% water)
Thick = cuboidal epithelium –> lots of mitochondria for active transport, no water permeability
iii. 25-30% of sodium absorption (NKCC2 co transporter)
iv. Sodium absorption important in making the countercurrent system with hyperosmotic medulla
Distal convoluted tubule
FINE TUNING SALT AND WATER
Reabsorbs 5% of Na Cl and bicarbonate
Reabsorbs Mg and calcium
Collecting duct
Concentrates urine - ADH mediated
Aquaporins inserted to allow H2O reabsorption when plasma is too concentrated/low blood volume
Major transporter in proximal convoluted tubule
Na/H (antiporter)
Na/glucose (symporter) = SGLT2 (remember SGLT1 is in the intestine)
Paralell transport of Mg etc
Thin loop Henle main tranporters
Trick Q!
i. Permeable to sodium
ii. Water is reabsorbed freely – 20%
Everything transported via simple diffusion
Thick loop of Henle main transporters
Luminal NKCC2 transporter (Na, K, 2 x Cl) co transporter
Back leak of K+ via ROMK
Na/H+ antiporter
IMPERMEABLE to water
Reabsorption of Ca and Mg (paracellular) via electrochemical gradient created by Na+ reabsorption
therefore inhibition of NKCC transporter will lead to reduced Ca and Mg reabsorption
Distal convoluted tubule - main transporters
Impermeable to water and urea
Permeable to Na, also small amount Ca and Mg reabsorbtion
NCC (Na, Cl co trnasporter)
NCC defect= Gitelmans disease
What is the significance of principle cells and intercalated cells in the collecting duct
Principle cells – site of aldosterone action
Intercalated cells – site of acid base balance
Main sodium channel in collecting duct
ENAC channel
- upregulated by aldosterone
- creates gradient to drive K+ and H+ secretion
Mutations:
inactivating ENAC mutation –> pseudohypoaldosteronism type 1 (neonatal salt wasting, hyperkalemia)
Activating mutation ENAC = Liddels disease
Aldosterone secretion is stimulated by…
- angiontensin 2
- increased serum potassium
- acidosis
Aldosterone stimulates reabsorbtion of salt (and water), secretion of K+, as well as H+ via the H+/ATPase in the intercalated cells–> increasing blood volume/pressure, reducing serum potassium and reducing plasma acidosis
Primary hyperaldosteronism
Primary = overproduction of aldosterone by the adrenal glands, when not a result of excessive renin secretion. eg Conns syndrome (aldosterone producing adenoma)
–> HTN + hypokalemia (due to excessive excretion of potassium), usually a diagnostic clue. (same presentation as Liddels)
Secondary hyperaldosteronism is due to overactivity of the renin–angiotensin system.
Rx: surgical (if adenoma), or medical w spironolactone
Only type of diarrhea that causes metabolic alkalosis rather than metabolic acidosis
congenital chloride diarrhoea
chloride responsive vs chloride resistant metabolic alkalosis
Chloride responsive - loss of H+
· Low ECFV
· Low urine chloride (<25 mEQ/L), hyperaldosteronism secondary to dehydration leading to sodium retention and potassium loss, and excretion of bicarbonate
· Alkalosis likely to improve fairly easily with chloride supplementation- fluids with NaCl (ie. non-renal chloride loss)
Examples:
· Vomiting
· Diuretic
· Congenital chloride diarrhoea
· Volume depletion (contraction alkalosis)
· CF
· Non-absorbable anion eg. imipenem
· Stool chloride loss – laxative abuse
· Post-hypercapnoea
Chloride resistant, retention of HCO3/shift of H+ into cells:
· High ECFV
· High urine chloride (>40 mEQ/L)
· Alkalosis likely to persist despite NaCl containing fluids (ie. likely renal chloride/ hydrogen loss)
Examples:
· Hypokalemia - shift of potassium out of cells, leading to H+ shift into cells
· Hyperaldosteronism/Conns syndrome
§ Increased RAAS activity
· Bartter’s/ Gitelman’s syndrome
· Liddle syndrome
Dent disease
Think Fanconi syndrome /(but mostly just protein) with renal stones
X linked recessive
CNL5 gene mutation
Disorder of proximal tubules
Triad: proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis
Fanconi syndrome
Polyuria, microscopic hematuria
Phenotype of Lowe syndrome overlaps with Dent disease - LMW proteinuria + hypercalciuria
Lowe syndrome: + renal tubular acidosis, cataracts, intellectual disability
Lowe Syndrome
X linked recessive
Congenital cataracts
Mental retardation
Fanconi syndrome
- progresses to renal failure
Proximal RTA features
Impaired ability of proximal tubule to reabsorb filtered bicarb
Often occurs as global proximal tubulopathy - Fanconi syndrome
Non anion gap metabolic acidosis
HYPOkalemia - worsens with bicarb therapy
Urinary pH <5.5
No stones
Presentation:
Polyuria, polydypsia, dehydration
Growth failure
Rickets
Distal RTA features (type 1)
Impaired hydrogen secretion in distal tubule
Urine pH >5.5
HYPOkalaemia - improves with therapy
HYPERcalciuria
Hyperammoniaemia
Nephrolithiasis/nephrocalcinosis (think- high urinary calcium)
Type 4 RTA features
Urine pH >5.5
HYPERkalemia
causes:
most common - impaired renal response to aldosterone (pesudohypoaldosteronism)
Hypoaldosteronism
RAAS blockage
Drugs- spironolactone, amiloride, calcinurin inhibitors
pseudohypoaldosteronism: during pyelonephritis, urinary obstruction/obstructive uropathy
polyuria, dehydration due to salt wasting
growth failure
what is the effect of low aldosterone on K+ and H+?
↓ aldosterone action = ↓ sodium reabsorption = ↓ H+ and K + secretion = acidosis and hyperkalemia
Similarities bw Bartter and Gitelman syndromes?
Inherited tubulopathies
Both HYPOkalaemic metabolic ALKALOSIS
w NORMAL renal function
Bartter syndrome
AR mutations in transporters in the TAL Henle
Usually present in prenatal period - childhood
Recurrent episodes polyuria + dehydration
FTT
Growth + mental retardation
*same biochemical anomalies as loop diuretics
HYPOkalemia
HYPOchloremia
Metabolic ALKALOSIS
Magenesium low/NORMAL
Renin and aldosterone ELEVATED but normal BP
Prostaglandins ELEVATED
Urine- hYPERcalciuria –> renal stones
Gitelman syndrome
AR mutations in transporters in DCT (NCC transporter)
Present in adolescence/adulthood
Hx recurrent muscle cramps
Polyuria without dehydration
*same biochemical anomalies as thiazide diuretics
HYPOkalemia
HYPOmagnesemia
Metabolic ALKALOSIS
Renin and aldosterone NORMAL
Prostoglandins NORMAL
HYPOcalciuria (hypercalciuria in Barterrs) + high Mg in urine
When to suspect either Bartter or Gitelman syndrome
The two inherited hypokalemic salt-wasting tubulopathies, BS and GS, are clinically suspected in individuals who present with hypokalemic hypochloremic metabolic alkalosis, high urinary chloride excretion and normal to low blood pressure (BP) despite elevated renin and aldosterone levels.
congenital chloride diarrhea vs Bartter syndrome differentia investigation findings
Both present with hypokalemic metabolic alkalosis
CD can be differentiated from BS as it is associated with low urinary chloride excretion, whereas BS is characterized by high urinary chloride excretion
Pseudohypoaldosteronism vs Bartter syndrome differential investigation findings
Pseudohypoaldosteronism: hyperkalemia and metabolic acidosis
Normal aldosterone but impaired response
BS: hypokalemic metabolic alkalosis.
Elevated aldosterone/renin
Loop diuretics
Act on thick ascending loop of Henle
NaK2Cl transporter- reabsorption of Na down its concentration gradient allows movement of C into the cell
Na/K ATPase drives the concentration gradient (low Na inside cell)
Loop diuretics bind and block the chloride part of NaK2Cl–> excretion of Na, K, and Cl
Calcium and magensium are also excreted as they depend on the concentration gradient for reabsorption
Side effects:
Ototoxicity
Hypomagnesemia
Hypocalcemia
Hypokalemia
Metabolic alkalosis
Thiazide diuretics
Distal convoluted tubule
Blocks Na/Cl symporter
The sodium/calcium exchanger on the basolateral side works overtime to pump more Na into cell (as Na/CL symporter not pumping Na into cell on apical side) thus increasing movement of Ca out of cell into interstitium –> more calcium is reabsorbed from the urine
A/E:
Hypokalemia
Metabolic alkalosis
Hypercalcemia
Hyperuricemia
Hyperglycemia
Hyperlipidemia
Potassium sparing diuretics
Act on distal convoluted tubule and collecting duct
Principal cells: Aldosterone binds on mineralocroticoid receptor in cytoplasm –> increased synthesis of ENacs and Na/K ATPase transporters to increase Na reabsorbption into blood and K secretion into urine
In alpha intercalated cells: aldosterone increases synthesis of H/K transporters to increase H+ secretion
Spironolactone directly inhibits aldosterone receptors
Uses: hyperaldosteronism
Amiloride blocks Enac channals –> reduced synthesis of Na/K ATPase on basolateral membrane
Total effect: increase excretion of sodium, decrease excretion of hydrogen and potassium
A/E-
Hyperkalemia
Acidosis
***Liddle syndrome- increased activity of ENAC channels —>too much sodium retention, too much potassium excretion , HTN
Carbonic anhydrase inhibitors
- End in “zolomide”
- Inhibit carbonic anhydrase in proximal convoluted tubule
- Leads to reduced bicarbonate reabsorption in the proximal tubule –> water follows
- Also causes urine alkalinization - used in cystinuria
- Also used in the treatment of idiopathic cerebral HTN and glaucoma (reduced aqueous humor production)
Cystinuria
AR
High cystine in urine –> cystine kidney stones
- type aminoaciduria
Nephrogenic DI
Inability to concentrate urine in presence of ADH
Inherited- usually X linked recessive, AVPR2 gene (ADH receptor)
Acquired- obstructive uropathies, nephrocalcinosis, intersitital kidney disease, lithium, acute or chronic kidney disease etc
Presentation: polyuria, hypernatremia
Ix: paired serum + urine osmolality, serum osmolality >290 mOsm/kg with urine of <290 mOsm/kg diagnostic (ie concentrated plasma with inappropriately dilute urine)
No/minimal improvement with desmopressin
Acute interstitial nephritis
Classic triad: fever, rash, eosinophilia
AKI + sterile pyuria, white cell casts, eosinphilia
Wide range depending on cause- rash, joint pain, fever, nausea, weight loss , hematuria, HTN
Can be caused by any drugs, but most commonly penicillins or NSAIDs
Acute tubular necrosis
Oedema + muddy brown casts
Can be toxic or ischemic
Toxic- medications such as aminoglycosides, statins, cisplatin, ethylene glycol
Ischaemic- caused when the kidneys are not sufficiently perfused for a long period of time (i.e. renal artery stenosis) or during shock.
if underlying cause address- revovery in 1-2 weeks as cells grow back
fractional excretion of sodium is >2%, used to differentiate from prerenal AKI
Tubulointerstitial nephritis
Inflammatory infiltrate in kidney interstitial, sparing glomeruli and vessels
Usually drug induced - penicillin, cephalosporins, carbemazepine, infections
usually occurs 1-2 weeks post drug exposure
Fever, rash and arthralgia, rising creatinine
May have rash
Haematuria, proteinuria, WBC casts
VCUG/MCUG used for…
Distal obstruction
Vesicoureteric reflux
Posterior urethral valves
MAG3/DTPA used for …
Functional scan - info about uptake (blood flow through kidney) + excretion (obstruction)
Assess tubular function/GFR and proximal obstruction (PUJ)
in a duplex kidney, lower pole is associated with VUR, and upper pole with obstruction–> obstruction needs MAG3 to diagnose
DMSA used for..
STATIC imaging
- structure, scarring, ectopic tissue
transient proteinuria can be caused by…
- Typically, after vigorous exercise, fever, dehydration, seizures and adrenergic agonist therapy. can also be postural/orthostatic (proteinuria when upright)
2. Usually mild, glomerular in origin, and always resolves within a few days
3. Does NOT indicate renal disease
4. ALWAYS follow up with early morning urine when well/rested
What is the cause of idiopathic nephrotic syndrome
Minimal change disease (85%) - usually age 3+ years
Focal segmental glomerulosclerosis (FSGS)- 15%- usually age 6+ years
Overall 90% of nephrotic syndrome in kids is ideopathic
Significance of gene positive nephrotic syndrome
unlikely to be steroid responsive
progress quickly to ESRF
very low risk recurrence post renal transplant
Definition of remission in nephrotic syndrome
urine protein excretion < 4 mg/hr/m2(<30 mg/mmol PCR) 3 consecutive days
Definition relapse nephrotic syndrome
urine protein excretion > 40 mg/hr/m2(>200 mg/mmol PCR), OR dipstick >=3 for 3 consecutive days
Nephrotic syndrome can be secondary to ..
SLE
HSP
MPGN
Hep B membranous nephropathy
Denys Drash ( nephrotic syndrome, ambiguous genitalia, Wilms tumor)
Pierson syndrome (nephrotic syndrome, eye probems)
Nail patella syndrome
Fabry disease (X linked lysosomal storage disorder - angiokeratomas, peripheral burning pain)
Where is the aldosterone receptor located
As with all steroid hormones, aldosterone passes through cell membranes to bind to cytoplasmic receptors which translocate to the nucleus to influence mRNA transcription and subsequently protein synthesis
Located DCT and collecting duct
Differential diagnosis oedema
Heart failure
Liver failure
Renal - nephrotic syndrome
Protein losing enteropathy
Protein malnutrition
Minimal change disease
most common cause nephrotic syndrome
100% of those with MCD present with nephrotic syndrome
Age: 2-3 years
is there likley to be ongoing haematuria in IgA nephropathy?
there is often microscopic haematuria in between episodes of macroscopic haematuria
often triggered by intercurrent illness
features associated with ESKD in IgA nephropathy
Proteinuria >1g/day
HTN
Reduced baseline GFR
Persistent hematuria
Biopsy findings = glomerulosclerosis,
Key features of IgA nephropathy
Usually presents as haematuria(+/- pain/proteinuria), or nephritic syndrome. Nephrotic syndrome rare
Usually occurs 1-2 days post onset URTI symptoms
May have recurrent episodes macroscopic haematuria with illness, with microscopic haematuria in between
NORMAL C’levels
<20% have elevated IgA
Rx: control BP and proteinuria with ACEI/ARB
If severe- imunnosuppress with steroids
20-30% will develop ESKD 20 years after disease onset
RF: proteinuria >1g/day, HTN, reduced GFR, persistant haematuria, biopsy markers
Alport syndrome
X linked (but can be AD and AR less commonly)- Mutations in COL4A5 gene - for type IV collagen (major component of GBM)
Multisystem disorder – includes nephritis, sensorineural deafness and eye abnormalities
Renal:
Micoroscopic haematuria, some episodes of macroscopic (from infancy)
Proteinuria
Hearing:
Bilat SN hearing loss
50% deaf by age 15, 90% end up deaf
HTN by mid teens
Microhaematuria –> gross haematuria with urti –> proteinuria –> renal failure
50% have ESRD by age 25
Eyes:
ANTERIOR LENTICONUS 2nd to 3rd decade
Diagnosis:
Normal C’ levels
Opthal- anterior lenticonus pathognemonic
Genetic testing - COL4A5 x linked (also COL4A3-4 in autosomal)
Skin biopsy
Renal biopsy
FHX and urinalyisis of relatives
Rx: ACE/ARB
Female carriers can be affected, just later in life
Acute Post Streptococcal GN
Post GAS infection
2 weeks post throat infection
3-6 weeks post skin infection
Haematuria (tea/cola), oliguria, HTN, oedema - nephritic syndrome (but can be just isolated hematuria)
Nephrotic syndrome rare (~5%)
Most common kids 2-12 years
Immune complex mediated
Ix:
throat swab, ASOT (3 weeks post infection), ANti-DNAse (6 weeks post infection),
low C3 –> returns to normal in 6-8 weeks
C4 normal
If C3 doesnt normalise at 6 weeks consider MPGN or SLE
Renal biopsy indicated for : RPGN, persistent proteinuria >6 mo, low C3 at 8 weeks
Rx:
Oral penicillin
Fluid restrict to 400ml/m2
HTN- frusemide 1st line (as fluid overloaded)
NOT ACE-I
Persistent haematuria can persist for 2 years, need to follow up to ensure resolution
3-5% have rapidly progressive GN
95% resolve spontaneously
gross haematuria and HTN should resolve by 1 week
SLE Nephritis
GN is the most important cause of morbidity and mortality in SLE
kidney disease is present in up to 80% of kids
Deficiency C1q s strongest genetic factor
Immune complex mediated
Clinical manifestations
a. Mild lupus nephritis (class I-II, some class III) = haematuria, normal renal function, proteinuria <1 g/24 hours
b. Class III (some) and ALL patients with class IV nephritis = haematuria, proteinuria, hypertension, reduced renal function, nephrotic syndrome, or acute renal failure
c. class V nephritis = nephrotic syndrome
Ix: ANA, dsDNA, anti smith
Rx:
Class >3 (reduced renal function, proteinuria, HTN)= prednisolone, mycophenolate, other immunsuppression, depending on subtype
Also need ACE-I
everyone with SLE needs hydroxychloroquine
HSP nephritis
Most common small vessel vasculitis in childhood
PURPURIC RASH, ARTHRITIS, ABDOMINAL PAIN
100% have rash - can be maculopapular initially, later purpuric
GIT- abdo pain, N/V, GI bleed, intussuception
50% have renal manifestations, asymptomatic microscopic haematuria–> severe progressive GN
If renal manifestations will occur, they usually develop by first 3 months
Rx:
Supportive- NSAIDS
Steroids for abdo pain (1 week then slow wean), not for renal
ACEI if HTN/proteinuria
Systemic manifestation of IgA nephropathy
Refer reanl team if nephrotic or nephritc syndrome at presentation, or persistent proteinuria
If untreated, risk renal failure 2-5%
RPGN
- Key points
a. Nephritic syndrome with rapidly deteriorating renal function – commonly dialysis requirement
b. Crescents on biopsy - Etiology
a. Primary
i. IgA nephropathy
ii. MPGN
iii. Anti-GBM
b. Secondary
i. ANCA-mediated
ii. SLE nephritis
iii. Post-streptococcal GN – note rarely proceeds to CGN but as it is the most common cause of GN in childhood accounts for significant percentage of patients with CGN
iv. IgAV/HSP nephritis - Pathology + pathogenesis
Hallmark = crescents in glomeruli - Prognosis + management
a. Children with crescentic post-infectious GN can spontaneously recover
b. Natural course of other forms of RPGN = ESRF in weeks to months
c. Poor prognosis = fibrous crescents (irreversible)
Immunosuppression needed
Goodpastures disease
Pulmunary renal syndrome
Pulumunary haemorrhage + cresenteric GN
Antibodies against type 4 collagen –> GBM
(type 2 hypersensitivity)
Hemoptysis + acute GN–> rapid progress to ESRF
Cresenteric GN on biopsy, C3 normal
Poor prognosis
Needs immunosuppression
ANCA Vasculitis
Chronic, often relapsing, multi organ involvement
Ab directed against neutrophil cytoplasmic Ag
ANCA = PR3 ANCA = granulomatosis with polyangiitis (GPA or Wegners)—> granulmoas of respiratory tract, sinusitis
pANCA = MPO ANCA = microscopic polyangiitis (MPA) –> no granulomas but can have resp involevement with pulm haemorrhage, interstitial nephritis
High mortality if untreated
Treat with immunosuppression
Haemolytic uraemic syndrome
- Microangiopathic haemolytic anemia (DAT-) (due to microvasuclar injury/endothelial damage/platelet aggregation)
- Thrombocytopenia
- Acute renal injury
Presentation:
pallor
irritabiility –> can have more severe CNS involvement with seizures, encephalopathy
lethargy
haematuria
fever
anemia, thrombocytopenia
Often post gastro illness with bloody diarrhoea OR very unwell with a pneumonia
Most often secondary to shiga toxin producting E.coli (shigella dystenteriae)
Strep pneumoniae - usually very unwell with this
Ix:
FBE + film: low Hb, platelets, SHISTIOCYTES on film
Normal coags
Markers of haemolysis
Negative coombs
AKI
Urine- haematuria, proteinuria
Stool MCS
Pneumonocccal PCR
Rx:
Supportive- fluid and electrolytes
Dialysis
No antibiotics for STEC
30% have long term CKD
Renal vein thrombosis
a. Occurs in 2 distinct clinical settings
i. Newborns and infants – associated with asphyxia, dehydration, shock, sepsis, congenital hypercoagulable states, maternal diabetes
ii. Older children – nephrotic syndrome, cyanotic heart disease, inherited hypercoagulable states, sepsis, following kidney transplantation
2. Clinical manifestations
a. Typical = sudden onset gross haematuria and unilateral or bilateral flank masses
b. Other features
i. Hypertension
ii. Microscopic haematuria
iii. Oliguria
USS: renal enlargement
Doppler to confirm
Rx: supportive, anticoagulation, thrombolysis only if bilateral
if unilateral without AKI, can be monitored
Idiopathic hypercalciuria
AD
Cause of haematuria, dysuria, abdo pain
Ix: 24 hr urinary calcium excretion, or calcium/creatinine ratio
Can lead to nephrolithiasis if untreated
Rx: thiazide diuretics, sodium restriction, potassium citrate
Management frequently relapsing nephrotic syndrome
1st line: Cyclosporin (calcinurin inhibitor)
2nd line: rituximab
Microangiopathic haemolytic anemia
Destruction of RBC in small blood vessels
Anemia, evidence of hemolysis (bili, LDH elevated), DAT neg, schistocytes on blood film
eg HUS, DIC
The endothelial layer of small vessels is damaged with resulting fibrin deposition and platelet aggregation. As red blood cells travel through these damaged vessels, they are fragmented resulting in intravascular hemolysis.
Nephritic syndrome
Haematuria
HTN
Oedema
Oliguria/AKI
most common cause in childhood is post strep GN
Simple cysts
Usually asymptomatic
occasionally cause pain, haematuria, obstruction
USS- thin wall, no septations, no calcifications
usually solitary and unilateral
If above features present- increased risk of malignancy
complications: rupture, infection, haemorrhage
Conservative management
Surgery should be restricted to symptomatic large compressive cysts, increase in cyst size on follow-up imaging, and when there is uncertainty about the underlying diagnosis
Laparoscopic marsupialization may be considered for a simple renal cyst in a symptomatic child
Multicystic dysplastic kidney (MCDK)
Most severe form of cystic renal dysplasia - non hereditory
Numerous non communicating cysts separated by dysplastic tissue. No identifiable kidney tissue.
Usually detected antenatally
Usually unilateral
Natural history: involution of affected kidney (60% completely involute by age 5)
Contralateral kidney undergoes compensatory hypertrophy –> monitor with serial USS to ensure this occurs appropriately
No/minimal increased risk of HTN or malignant transformation
Usually no long term complications, but more at risk of ESKD if any insult to remaining kidney
Increased risk of VUR in remaining kidney (30%)
No specific management apart from long term follow up up ensure remaining kidney ok
Autosomal Recessive Polycystic Kidney Disease (ARPCKD)
THINK BILATERAL KIDNEY AND LIVER INVOLVEMENT
Presentation:
Perinatal: oligohydramnios, Potter sequence, pulmunary hypoplasia
Neonatal: bilat flank masses, HTN, USS: enlarged echogenic kidneys, cystic changes develop over time (microscopic –> macroscopic)
50% with early presentation develop ESRF by age 10
Some patients present in adolescence- typically present with hepatomegaly, portal hypertension
Liver disease always present but clinical complications may become obvious at any point in childhood or adulthood
Rx:
Supportive
Treat HTN
Dialysis
Liver-kidney transplant
DDx – other causes of bilateral renal enlargement
a. Multicystic dysplasia
b. Hydronephrosis
c. Wilm’s tumour
d. Bilateral renal vein thrombosis
Autosomal Dominant Polycystic Kidney Disease (ADPCKD)
Most common hereditary form of CKD
Rare in kids, often only presents in adulthood
Most commonly an incidental finding during USS for other causes
THINK- CYSTS EVERYWHERE in adults
Symptoms- very variable
Asymptomatic, haematuria, proteinuria, HTN, polyuria/polydypsia
Adults will develop cysts in liver, pancreas, spleen, intracranial aneurysms, bowel divirtucular disease, abdo wall hernia
Mitral valve prolapse in 12% kids
Diagnosis: enlarged kidneys with bilateral macroscopic cysts in patient with affected 1st degree relative (may need to check parents)
however kids often have normal kidney size and unilateral disease
Rx: supportive, regular review, ACE-I for HTN, avoid NSAIDs, high fluid intake, avoid high protein diet
CKD usually develops in late adulthood
Nephronophthisis
Group of AR cystic kidney diseases which progress to CKD
Characterized by impaired urinary concentrating ability (polyuria, polydypsia), a bland urinalysis (no proteinuria or mild tubular proteinuria, no hematuria or cellular elements), chronic tubulointerstitial disease, and progression to end-stage kidney disease (ESKD) generally by 20 years of age.
Infantile: ESRF by 3 years
Severe HTN
Extra renal: hepatic, cardiac, valve/septal, recurrent lung infections
Juvenile: most common
ESRF by adolescence
Present with polyuria/polydypsia in middle childhood, enuresis (impaired urine concentrating ability)
BP normal
Nephrogenic DI- dilute urine, no improvement with ADH
Sodium wasting, poor growth
Retinitis pigmentosa
Progression to ESRF universal by age 20 yrs
b. Renal USS i. Increased echogenicity of kidneys with loss of corticomedullary differentiation ii. Normal/ slightly reduced size + no dilation of urinary tract Renal cysts NOT typically identified on initial USS – may appear later
Renal anomalies in Tuberous sclerosis
Angiomyolipoma
Simple cysts
Renal cell carcinoma
Joubert Syndrome
Cerebellar- delay motor milestones, ataxia, hypotonia, abnormal eye moebments
Retinitis pigmentosa
Syndromic cause of Nephronopthisis
Bardet-Biedl Syndrome
Syndromic cause of Nephronopthisis
Retinitis pigmentosa
polydactyly
Hypogonadism
Dev delay, low IQ
Ataxia
Craniofacial dyphmorphism
WAGR syndrome
Wilms tumor
Andridia
Genitourinary abnormalities
Retardation (mental)
Denys Drash syndrome
Wilms tumor -90% will develop (compared to 5-10% in BWS, 50% in WAGR)
Ambiguous genitalia (male)
Progressive nephropathy
Calculating Fractional Excretion of Sodium
(urine sodium x serum creatinine) / (serum sodium x urine creatinine)
Kidney largely formed from the
Metanephros
all except the collecting duct, renal pelvis, and ureters
What does the mesonephros become
vas deferens in males
broad ligament in females
Liddle Syndrome
AD
Gain of function mutation of ENAC channel - too much Na and water reabsorbtion
HTN
High sodium, low potassium, metabolic alkalosis
Rx; amiloride, blocks the channel
Most accurate measure of glomerular filtration is by..
51 Cr EDTA clearanace
Freely filtered, not reabsorbed or secreted in tubules
**gold standard= inulin, but only used in research
Causes nephrotic syndrome
Primary/idiopathic (most children)
minimal change disease (most common)
focal segmental glomerulosclerosis
membranoproliferative glomerulonephritis
membranous nephropathy
diffuse mesangial proliferation
Iga nephrotpathy
Post strep GN
Secondary
SLE
HSP
malignancy (lymphoma/leukaemia)
infections (hepatitis, HIV, malaria)
AD thin membrane disease causes isolated hematuria , NOTT nephrotic syndrome
What is the natural history for rapidly progressive/cresenteric glomeruopnephritis
Often recover spontaneously if post strep
Use steroids, cyclophosphamide with SLE, IgA nephropathy, HSP
In other conditions, prognosis is worse
Pseudohypoaldosteronism type 1 presents with
Collecting duct resistance to aldosterone
High aldosterone levels
Low sodium reabsorbtion, low K excretion
–>Low plasma sodium, high potassium
Pseudohypoaldosteronism type 2
AKA Gordons syndrome
Low sodium, high potassium
but low aldosterone/renin (unlike type 1)
+ arthrogyposis
Most common cause HTN in NF1
Essential HTN
Less common- renal artery stenosis
Phaemochromocytoma
most common drug related cause of nephrogenic DI
lithium
Differentiating glomerular bleeding from non glomerular bleeding
Glomerular: tea colourerd or coca cola
No clots
May have proteinuria
Dysmorphic RBC
RBC may be present
Non glomerular: red or pink, may have clots, no proteinuria, normal RBC morphology, no casts
Lower urinary tract and parenchymal causes of haematuria
infection- haemorrhagic cystitis (eg adenovirus), urtethitis, bacterial UTI
injury- urethral trauma, stone
tumor
polyp
malformation
pyelonephritis
interstitial nephritis
cyst rupture
Wilms tumor
obstruction
renal trauma
sickle cell disease
nutcracker syndrome
renal vein thrombosis
hypercalciuria
What if there is red urine but no blood on urine mcs?
Haemaglobinuria from haemolytic anemia (intravscular hemolysis)
Myoglobinuria from rhabdomyolysis
what is thin basement membrane disease
aka benign familal haematuria
usually presents with microscopic haematuria
gross haematuria uncommon
part of nephritic syndromes, never nephrotic
no treatment needed
medications causing haematuria
aspirin
cyclophosphamide
diuretics
anticonvulsants
aminoglycosides
Membranoproliferative disease (MPGN)
HYPOCOMPLEMENTEMIA (deposition of circulating immune complexes, or deranged complement regulation)
c3 low, C4 usually normal (but can also be low)
Presentation- isolated haematuria +/- proteinuria to nephritic/nephrotic syndrome
Diagnosis can be made when child previosly diagnosed with post strep GN and complement fails to rise after 6-8 weeks
Biopsy diagnostic- tram track appearance
Without treatment (immunosuppression), 50% develop ESKD within 10 years
Which diabetic med can be used for non diabetic CKD including IGA nephropathy
SGLT2 inhibitor
eg dapaglifzolin
not yet approved in aus yet for kids
Electron microscopy findings in Alport syndrome
Thickened basement membrane
Basket weave pattern
Nephrotic range proteinuria
> 40mg/m2/hr
Urine PCR >200mg/mmol
Treatment of steroid resistant nephrotic syndrome
Persistant proteinuria after 4 weeks of daily prednisolone 60mg/kg/day
Do genetic testing
Commenced ACE-I
Cyclosporin or tacrolimus for 6 months; 2nd line rituximab
what is the definition of frequently relapsing nephrotic syndrome
2+ relapses in first 6 months
4+ relapses in any 12 month period
if frequent relapses, can trial low dose alternate day steroids, or increased steroids during URTI (dont need to taper)
PUJ obstruction
Most common cause antenatally detected hydronephrosis
Most common obstructive lesion
Presentation: intermittent flank pain, hematuria, renal calculi, UTI –> scarring of kidney if untreated
Rx: pyeloplasty to relieve obstruction
Grades of VUR
- Reflux into the ureter but not into collecting system
- Reflux into ureter without mild ureteric and renal pelvis dilatation
- Reflux into the ureter and collecting system with mild-mod ureteric and renal pelvis dilatation
- Gross dilation of the ureter and collecting system, causing significant blunting of the calyces and ureteric turturosity
5.Gross dilation of the ureter and collecting system, causing significant blunting of the calyces as well as loss of papilllary impressions; intrarenal reflux may be present
Duplex kidney
a. Classification
i. Upper moiety
ii. Lower moiety
VUR – usually into lower
Obstruction – usually of upper
Ectopic ureter
more common in girls
2nd ureter drains outside kidney
if drains distal to sphincter–> continous urinary incontinence “always wet”
What are the differences in renal function between 32 week neonate and 38 week neonate
Prem neonate will have reduced GFR, lower renal excretion of K+ (thus higher serum K+) and lower acid excretion (thus lower plasma pH)
in salt loaded person, the main mechanism by which salt is excreted involves..
Increased ANP
Dilates afferent + constricts efferent arterioles = ↑ GFR, ↑ natriuresis
ii. Inhibits aldosterone + renin secretion
iii. Inhibits Na Cl reabsorption in CD
iv. Inhibits ADH action on kidney
Renal fanconi syndrome - genetic conditions
cystinosis
dent disease
tyrosinemia type 1 (presents very early)
galactosemia
wilsons disease
hereditory fructose intolorence
Drugs associated with development renal fanconi syndrome
aminoglycosides
cisplatin
ifosphamide
tacrolimus
valproate
heavy metals
Signs/symptoms fanconi syndrome
Growth failure
Polyuria (due to salt wasting)
Rickets, osteopenia
Muscle cramps, weakness, constipation
Ix: glucosuria, proteinuria
Metabolic acidosis
hypophosphatemia
hypokalemia
Prune belly syndrome
Cryptorchidism, abdominal wall defects and genitourinary defects
Urinary tract abnormality such as unusually large ureters, distended bladder, vesicoureteral reflux
most common abnormality associated with renal stones
hypercalciuria
associated with:
dent disease
glycogen storage disease type 1
bartter syndrome
wilsons syndrome
most common type of stones in kids
calcium oxolate 60-90%
calcium phosphate 10%
struvite 1-10%
uric acid 1-5%
cystine 1-5%
which bacteria are most associated with stone formation
e.coli
proteus - struvite stones, staghorn calculi
medical management of stones
tamsulosin (alpha blocker)
stones <5mm will usually pass spontaneously
risk factors for stone formation
a. High salt diet= biggest risk factor
b. 50% have underlying metabolic condition
c. 25% due to UTI
d. 20% due to urinary obstruction/stasis
e. Strong genetic factors
Geography = hot climate
management renal stones
a. Dietary
i. High fluid intake - daily intake of 2-2.5L
ii. Low salt intake (to reduce urinary Ca) – high Na increases urinary excretion of Ca
b. Medical
i. Alpha-adrenergic blockers
c. Metabolic defects
i. Potassium supplements – to reduce urinary Ca excretion
ii. Citrate forms soluble complexes with Ca; supplemental potassium citrate - prevents calcium stones
iii. Bicarbonate supplementation increases urinary citrate
iv. Allopurinol – prevents uric acid stones
v. Cystinuria/oxalosis = surveillance USS, urine 3-6/12
vi. Monitor bloods on penicillamine
d. Assess likelihood of spontaneous passage
i. <7mm = wait and repeat USS 3/12
ii. >7mm = surgical referral
e. Surgical
Percutaneous nephrostomy OR stent – if acute obstruction
risk factor for calcium oxolate stones
- genetic
-malabsorptive syndromes- IBD, CF, pancreatic insufficiency if not taking creon - low calcium diets
causes AKI
pre renal - dehydration, haemorrhage, sepsis , hypoalbuminemia/oedema, hypovolemia
renal artery/vein thrombosis, HUS
renal- GN, ATN, tumor lysis syndrome, AIN, pyelonephritis
Postrenal- any kind of obstruction
AKI- determining if acute or chronic
hx antenatal abnormality
previous UTIs
polyuria/polydypsia
family hx
lethargy
short stature
renal osteodystrophy/rickets
Treatment of AKI complications
correction of Na imbalance
When would AKI lead to poluria
tubulointerstitial pathology - impaired reabsorption
Oliguia with glomerular pathology- no filtration
features of ATN
impaired concentrating ability
muddy brown casts
dilute urine with high urinary sodium > 40- cant reabsorb
high fractional excretion of sodium >1-2
to differentiate from pre renal AKI: can still concentrate urine so higher serum osmolality, sodium <20, fractional excretion sodium <1
most common causes non glomerular CKD
CAKUT
hyperplasia/dysplasia
obstructive nephropathy
cystic disease
cystinosis
reflux nephropathy
glomerular causes of CKD
FSGS
congenital nephrotic syndrome
SLE
MPGN
HSP
IGa
Alport
HUS
triple immunosuppression for renal transplant
tacrolimus
mycophenolate
prednisolone
mechanism of HTN in VUR
renal parenchymal scarring
Infections post transplant
post op- bacterial infections related to surgery itself eg UTI, line infections, pneumonia, wound infections
Next 6 months- viral (CMV, BK virus), PJP
Features of self induce vomiting
BP is low normal. Loss of chloride and hydrogen
metabolic alkalosis, mild renal insufficiency.
Hypochloraemia with urinary chloride close to zero. Secondary hyperaldosteronism and renal loss of potassium.
Urinary potassium usually >10mmol/L. Metabolic alkalsosis - renal excretion of sodium bicarbonate, so urinary sodium higher than chloride. So urine will have reasonably elevated sodium, very low chloride, high potassium, and be alkaline
Juvenile nephronophthisis
Presents with
- polyuria, polydypsia, dehydration
- growth failure
- anemia
- chronic renal failure by adolescence
Imaging - small kidneys with cysts
The clinical manifestations are related to tubular injury that leads to a reduction in urinary concentrating capacity, renal sodium loss, and insidious but inevitable progression to renal failure. The tubular defects precede the decline in renal function and may be present in asymptomatic siblings with the disease.
In most patients, the signs associated with decreased urinary concentration capacity are present by age 5 years.
Because of salt wasting, hypertension is rare, even in patients with severe renal insufficiency.
Gold standard for renal artery stenosis
Renal arteriography
Renal Doppler ultrasound first line
Renal artery thrombosis presentation
flank mass + hematuria
Peritoneal dialysis
Solute moves down concentration gradient across peritoneal membrane by diffusion
Water moves across peritoneal membrane by osmosis (ultrafiltration)
Ultrafiltration causes movement of solutes by drag forces even without concentration gradient
Haemodialysis
Removes solutes by diffusion, via dialysate fluid. Solutes passively flow from one fluid compartment to the other down their concentration gradient ie urea, creatinine and potassium move from blood to dialysate; calcium and bicarbonate move from dialysate to blood
Haemofiltration
Solutes removed by convection. Uses hydrostatic pressure to induce filtration of plasma fluid across the filter membrane, so small and mid molecular weight solutes move in same direction as water. No dialysate fluid used.
nephrocalcinosis
calcification of renal tissue
commonly seen in prem neonates receiving frusemide (causing hypercalciuria) or Barters syndrome
children with Medullary sponge kidney
type 1 distal RTA
hyperparathyroidism
what is the main predisposing factor to calcium oxolate stones
IBD
pancreatic insufficiency
biliary disease
–> GI malabsorption of fatty acids, which bind intraluminal calcium and form salts. Oxolates therefore dont have calcium to bind to as they do normally, therefore there is increased gut absorption of unbound oxalate
main inhibitor of calcium stone formation
citrate
citrate forms complexes with calcium –> increasing urinary calcium soluability
inhibitng aggregation of calcium phosphate or calcium oxalate
prevention renal stones
fluids
low sodium diet
potassium citrate
normal calcium
thiazide diuretics - reduce renal Ca excretion
allopurinol if uric acid stones (inhibits xanthine oxidase)
maintain high urinary pH- sodium bicarb or citratw
