Renal Flashcards
Accelerated renal failure
factors increasing progression of renal failure:
1. hyperlipidaemia: CVD and renal dysfunction
2. metabolic acidosis: increased local ammonia
3. phosphate retention: CaPO4 precipitation
4. Proteinuria: likely toxicity
Acid/Base
Henderson-Hasselbach:
pH= 6.1 + log ([HCO3]/(0.235 x [PaCO2]))
pH equation:
pH= -log [H+]
pKa
- pH at which 50% acid molecules are undissociated and 50% associated
Acute Kidney Injury
definition: inability to excrete solute load
diagnosis: GFR< 100ml/min/173m2, increase Cr >1.5X baseline, UO<0.5ml/kg/hr
- increased Cr/urea/K/PO4
- decreased Na/Ca/VitD/HCO3
- AKI: large swollen kidneys versus CKI: small shrunken kidneys
clinical:
- water causing oedema
- Na causing HTN
- K causing arrhythmias
- H causing metabolic acidosis
- urea causing nausea/vomiting/encephalopathy
- phosphate causing decreased calcium
management
- electrolyte mx, fluid management, treat infection, remove nephrotoxins, monitor weight/BP
prognosis: complete loss of function >4weeks, ongoing unlikely to recover after 2-3 months
ADH/vasopressin
synthesised in hypothalamus and released from posterior pituitary
control of secretion:
- increased osmolality: stimulation osmoreceptors in anterior hypothalamus AND
- decrease fluid vol: tension/stretch of volume receptors in vena cavae/great pulm veins/carotid sinus/AA
actions:
- acts on V2 receptors which are G protein coupled
- phosphorylate ATP to cAMP and cause insertion of aquaporin 2 channels in DT/CD
causes excess ADH:
- pituitary ADH excess: hypoadrenalism/stress, drugs (barbiturates/vincristine), lung disease, IC disease, systemic disease (acute int prophyria)
- increased ADH sensitivity: carbamazepine
- ectopic ADH secretion: bronchogenic carcinoma
ADPKD
incidence: 1/1000
genetics: chromosome 16, polycystin 1/2 maintain renal cell tubular differentiation/proliferation
- 10% new mutation
clinical: most paediatric patients asymptomatic until adulthood
- renal: large bilat hyperechoic kidneys due to cysts
- symptoms in adulthood: haematuria, HTN, proteinuria, infection cysts, abdo/back pain, renal insufficiency
- cardiac valve, hepatic, pancreatic, colonic diverticular, splenic cysts, berry aneurysm 10%
diagnosis (Ravine’s criteria):
- postive family history and renal US
- genetic testing if US indeterminant
prognosis: normal renal function until 40’s
Aldosterone
definition: C21 mineralocorticoid hormone secreted by zona glomerulosa of adrenal cortex
actions: Na/Cl reabsorption and K/H excretion in distal tubules/collecting ducts
secretion: via RAAS
- cAMP mediated (indep ACTH) or ACTH stimulation
increased secretion
- 10% decrease plasma Na or 10% increase plasma K
- upright postion
- loss ECF
- surgery/anxiety
- hyperaldosteronism
- RAS
decreased secretion:
- increased Na, adrenalectomy
Alport syndrome
type: diffuse GBM
incidence: AR 15%, AD 5%, X linked 85% mutation of type IV collagen
- associated family history
pathogenesis: GBM/tubular membrane thinning/thickening/splitting with foam cells (lipid containing tubular cells), progressive, may also affect ears/eyes
clinical: microscopic haematuria with episodes of synpharyngitic macrohaematuria +/- proteinuria
- SNHL deafness (NOT congenital)
- anterior lenticonus, corneal erosions, macular flecks
diagnosis: genetic studies, biopsy
Anion Gap
Anion gap= [Na + K] - [Cl + HCO3]
Normal anion gap= 10-16 mmol/l
increased AG: renal failure, diabetic/alcoholic ketoacidosis, lactic acidosis, ingestion salicylate/methanol/ethylene glycol/paraldehyde
decreased anion gap: increased unmeasured cation eg. potassium/Mg/calcium, decreased unmeasure anion eg. hypoalbuminaemia
ANP
ANP: secreted from atrial tissues with fluid overload and causes natriuresis/vasodilation
renal effect:
- dilates afferent/constricts efferent glomerular arteriole
- relaxes mesangial cells
- increased excretion Na/water
- decreased reaborption in DCT/CD
- inhibition of renin secretion
- reduction in aldosterone secretion in zona glomerulus
vascular effect:
- relaxation vascular SM
- inhibition of catecholamines
Antenatal hydronephrosis
outcome:
- hydronephrosis w/o ureteric dilation not concerning: transient, pelvic ureteric obstruction, VUR
- hydronephrosis with ureteric dilation needs Ix
risk factors:
- bilateral hydro APD >10mm, unilateral APD > 15mm
- single kidney, duplex system, ureteric dilation, ureterocoele, oligohydramnios
management: AB at birth, US day 4-7
- if less dilation then repeat in 1 month
- if severe admit
investigations: MAG3 < 6weeks, DTPA > 6 weeks
ARPKD
(aka infantile PKD)
incidence: 1/10,000
genetics: carriers 1:70, chromosome 6, PKHD1 gene for protein fibrocystin/polyductin
pathogenesis: renal cystic disease in utero with dilation of CD
antenatal dx: antenatal scan: large echogenic kidneys with microcysts <3mm
clinical:
- neonatal: enlarged kidneys, oligohydramnios, pulmonary insufficiency
- renal: hyponatraemia, poor [] ability, metabolic acidosis, recurrent UTIs, proteinuria, glycosuria, hyperphosp, magnesiuria, HTN, renal failure
- liver: congenital hep fibrosis, dilation intrahep/main bile ducts, degree varies, develop hepatomegally, portal HTN
- resp: lung dysplasia, Potter syndrome
prognosis: survive 1st month then 80% chance to 15yrs
diagnosis: renal imaging +1 (hep fibrosis/pathology, absence cysts both parents/ARPKD in siblings/consanguinity)
- renal US: large echogenic kidneys with poor corticomed differentiation
- liver: increased echogenicity, dilation of intrahep ducts
management: no disease recurrence in transplant
complications: UTI, bacterial cholangitis, portal HTN
Acetozolamide
mechanism: inhibits carbonic anhydrase
effect: NaCl and NaHCO3 loss but NET diuresis
- LOH then absorbs it
- diuretic action attenuated by met acidosis from loss of HCO3
indication: diuretic for oedematous patients with met alkalosis
Bardet-Biedel
incidence: 1:140,000
genetic: AR digenetic, 12 genes localised to primary cilia/basal bodies
clinical: polydactyly, truncal obesity, retinal dystrophy, hypogonadism, renal involvement 70%, ID, anosmia, situs inversus
Bartter/Gitelman syndrome
-tubular hypomagnesemia/hypokalaemia-
incidence: onset infancy, Gitelman 1/40,000, Bartter 1/1,000,000
genetics: AR
pathophysiology: tubular defect in NaCl transport
Bartter: acts as loop diuretic and prevents NaCl reabsorption in ascending LOH
Gitelman: acts as Thiazide
- unable to concentrate urine
- hypocalciuria
- less severe
clinical: severe, growth/mental retardation, polyuria, polydipsia
diagnosis: hypokalaemic met alkalosis, low serum Na/Mg, high urine Cl
- H+ ions lost to reabsorb K+
- elevated renin/aldosterone
treatment: KCl, NSAIDs, spironolactone, ACEi, fluids
Benign familial haematuria
aka. thin basement membrane disease
type: diffuse
incidence: family hx haematuria, sporadic/AD mutations type IV collagen
pathogenesis: thinning GBM
clinical: microscopic haematuria with episodes of gross haematuria
diagnosis: normal complement
prognosis: benign
Buffers
children make 2-3mEq/kg of acid
buffers:
- HCO3 in ECF
HCO3 + H+ ⇔ H2CO3 ⇔ dissolved CO2 + H2O
- H renally excreted and HCO3 reabsorbed
base excess:
- normal -2 to 2
- reflects the excess or deficit of base
Hypertension
classification:
normal: <90th centile
preHTN: 90-95th centile
stage I: 95-99th centile +5mmHg
stage II: >99th centile +5mmHg
types:
primary
secondary (30%): more common in infants
- renal (60-80%): parenchymal, vascular, obstruction
- cardiac
- endocrine: CAH, cushing’s, phaeo, thyroid
- central
- OSA
- drugs: steroids, OCP, thyroxine
- tumours: neuroblastoma
diagnosis: BMI, 4 limb BPs and pulses
investigations: UEC, LFT, FBC, urine (Pr:Cr), renin, aldosterone, renal dopplers, MAG3, angiography, TTE, CXR, TFTs, cortisol, HbA1c
treatment: nifedipine, ACEi, prazosin
Calcium calculi
hypercalciuria
incidence: commonest cause (60-90%)
increased urine Ca by:
- increased dietary Na
- increased dietary Ca, Vit C, Vit D
- decreased Ca (increases oxalate absorption as usually Ca bound)
- immobilisation
- oliguria
- drugs: lasix, topiramate, steroids
- genetics: Bartters, Bents, Cl channel defect
clinical: calculi, nephrocalcinosis, decreased BMD
treatment: fluids, decreased dietary Na, increase dietary K, calcium chelation, thiazides (reabsorb Ca in tubules
causes of haematuria
‘SHIRT’
Stones
Haematologic abnormalities
- AVM, coagulopathy, sickle cell
Infection/Iatrogenic/Idiopathic/Immunologic
- BFH, haemorrhagic cystitis, collagen vasc disease, epididimytis, exercise, UTI, vasculitis
Renal abnormalities: anatomic, Alport’s, nephritis, renal vein thrombosis
Tumour/Trauma: hypercalcaemia, foreign body, perineal irritation/trauma
Chronic kidney disease
definition: GFR< 60 for >3months or with evidence of structural damage
stages:
stage 1: normal GFR >90,
stage 2: GFR 60-69
stage 3: GFP 30-59
stage 4: GFR 15-39
stage 5: GFR<15
OR <2yrs: 1-2 SD from mean is moderate, >2SD from mean is severe
cause: congenital abnormalities (60%), cystic (ARPKD, ADPKD), GN (17%)
progress: once diagnoses, gradual progression and decline
management: SLOW progression, maintain growth/development, preserve vasculature
treatment: dyslipidaemia (statins >10yrs, exercise), proteinuria (ACEi), hyperphosphataemia (low Ph diet, Ph binders), Na retention (low Na diet), hyperkalaemia (low K diet, frusemide), met acidosis (NaBicarb), osteodystrophy (Ph binders, vit D), anaemia (EPO, Fe)
CMV in immunosuppressed
various clinical syndromes in immunocompromised patients with multiple organ system involvement
clinical:
- most important manifestations: pneumonitis, GI disease, and retinitis
- GI disease: esophagitis, gastritis, gastroenteritis, pyloric obstruction, hepatitis, pancreatitis, colitis, and cholecystitis
- nausea, vomiting, dysphagia, epigastric pain, icterus, and watery diarrhea.
Complement mediated HUS
incidence: rare, 50% non Shiga HUS
pathophysiology: trigger event with gene mutation leads to uninhibited activation of the alternative pathway with formation MAC
- results in renal endothelial damage and activation of coag cascade and thrombotic microangiopathy
clinical: microangiopathic haem anaemia, thrombocytopaenia, AKI
- assoc family hx, HTN, trigger
diagnosis: screening for mutations not widely available, consider in family hx or previous episodes HUS
treatment: supportive
Congenital nephrotic syndrome
onset: at birth or within 3 months
clinical: oedema, FTT, infections, hypothyroidism, thrombosis
- most progress to ESKD
causes:
primary: congenital, diffuse mesangial sclerosis, MCNS, FSGS, membranous
- mutations in 4 genes: NPHS1/2, WT1, LAMB 2 (GBM components)
- Denys-Drash syndrome: WT1 mutation with abnormal podocytes
- Pierson syndrome: LAMB2 gene for B2 laminin
secondary: infection, drugs, SLE, syndromes, HUS
Cystine calculi
incidence: 1-5% stones
onset: in childhood
mechanism: defective reabsorption of dibasic AAs in tubule causing cystine precipitation in hexagonal crystals
diagnosis: urine microscopy, RADIOLUCENT
treatment: fluids, alkalinise urine, decreased Na, penicillamine
Cystinosis
definition: AR lysosomal storage disorder, most common cause of Fanconi’s
clinical: FTT, rickets, cystine deposits (cornea, renal, pancreas, thyroid, cardiac, muscle)
- normal intelligence
treatment: very treatable with cysteamine caps and eye drops
Dent’s disease
definition: XLR of renal tubules due to defect Cl Channel CLC-5
clinical: nephrocalcinosis, hypercalciuria, calculi, renal failure, renal rickets, proteinuria
Denys Drash syndrome
genetics: point mutation WT1 gene chromosome 1
clinical: (triad)
- progressive renal disease (early nephrotic sx then mesangial sclerosis)
- undifferentiated genitals
- Wilm’s tumour (90%)
Diagnosis SIADH
hypo-osmotic overhydration
diagnosis:
- hyponatraemia/low plasma osm
- urine Na output inappropriately high >50mmol/day
- urine osm inappropriately high relative to serum: 350-400mosmol
- no evidence hypovolaemia
- increasing plasma osm in response to restriction of water
Dialysis
indications: acidosis, hyperkalaemia, uraemia >80, fluid overload
effectiveness:
- conventional HD/PD: 15% normal function
- short daily HD: 25% normal function
- home nocturnal HD: 50% normal function
**peritoneal dialysis preferred in children
Differential Glomerular Disease
Diffuse cystic dysplasia
genetics: sporadic or associated syndrome
pathology: small cysts in cortex, sometimes duplex kidney/GUT abnormalities
associations: tuberous sclerosis, Zellweger, trisomy 13
Distal RTA
(type 1)
defect: inability to excrete acid
- failure NH3 concentration in medullary interstitium
- failure of distal H+ secretion
causes: genetic, drugs, carbonic anhydrase def (OP), AI, obstructive uropathy
complications:
- calculi: no citrate in urine and Ca/PO4 insoluble at high pH
- assoc deafness
diagnosis: alkaline urine (low K+, high NH3)
treatment: correct acidosis, K citrate
Distal tubule/collecting duct
reabsorption: 5% Na and 3% bicarb
- variable water reabsorption in collecting ducts depending on ADH
tubular absorption: Na absorbed via channel coupled to K excretion
tubular secretion: ammonium, H+, K+ under influence of aldosterone
DMSA scan
- scarring
Dimercaptosuccinic acid (radio-labelled)
1) Scarring: sticks to PT and outlines cortical mass to detect cortical scarring
2) Differential function of each kidney= time taken to uptake
Electrolyte dysfunction
Endothelins
potent vasocontricting peptides produce various tissues
types: endothelins 1- 2- 3- interactive with 2 G protein receptors type A and B
- increased iCa and stimulate protein kinase C
function: modulate vasomotor tone, cell proliferation, hormone production
endothelin 1:
- produced in endothelial and vascular smooth muscle cells
- most potent vasoconstrictor
- role in heart failure, renal failure
Enuresis
definition: repetitive voiding or urine into clothes/bed
- at least twice/week for 3 months in child >4yrs
epidemiology: 5yrs (7% boys, 3% girls), 18yrs (1% men, 1% girls)
risk factors: low SE, large families, institutionalised children, family hx
subtypes:
diurnal
nocturnal can be:
- monosymptomatic: no assoc daytime sx
- nonmonosymptomatic (more): 1 subtle daytime sx
- primary enuresis (85%): never dry
- secondary enuresis: resumption post dry 6 month
voiding
- bladder vol= (age x 30) + 30
- frequency: 3-8 x
resolution: 15% spontaneous cure rate annually
Enuresis
causes and treatment
causes
diurnal/nocturnal: renal (CKD, UTI), endo (DM, DI), GI (constipation), sleep (OSA), neuro (SC disorder/GDD)
nocturnal: primary rousability, genetic component, nocturnal polyuria (low ADH night), psychological
diurnal: MOST overactive bladder, voiding postponement, bladder dys, giggle incontinence, vaginal voiding
treatment:
1. Conservative: education, charting, void before bed
2. Alarm (best treatment): 75-95% success at 3 months (NOT <7 yrs)
3. Medications: DDAVP (high relapse when ceased), imipramine (<50% respond)
diurnal: + oxybutinin, tolteridone
- refer to urology IF: diurnal, abnormal voiding, UTIs, genitals abnormal
Fanconi’s syndrome
definition: generalised proximal tubular dysfunction
causes:
- genetic: cystinosis, Lowe’s, Dent’s disease, galactossaemia, tyrosinaemia, Wilson’s, heredity fructose intolerance
- acquired: interstitial nephritis, drugs, heavy metals, frusemide, aminoglycosides, cyclo, tacro, amphotericin, ifosfamide
clinical: vomiting, FTT
diagnosis: urine osm <300, glycosuria, phosphaturia, low PO4, amnioaciduria, tubular proteinuria
Functional scans (MAG3 and DTPA)
DTPA: isotope purely excreted like creatinine
MAG 3: 20% isotope secreted at the tubules so always dye even if GFR is 0 (better images)
functional scans show:
- contribution of each kidney to overall function
- obstruction
process:
- baseline image then dye injected
- 2nd image at 2-3 mins to assess uptake/% contribution to function of each kidney
- frusemide given at peak uptake (20-30 mins)
- measure for washout time: if <15 mins then no obstruction, if >20 mins obstruction
Gitelman syndrome
site: distal tubule
age: teens/adults
defect: NaCl in distal collecting duct
- causes thiazide like effect
- hypovolaemia/hypotension, high renin/aldosterone, K/Mg wasting, low urine Ca, high urine Cl
clinical: low growth, salt craving, muscle cramps, tetany, hypotension, fatigue, polyuria
diagnosis: hypokalaemic met alkalosis, high urine Cl, low serum Mg, high serum Ca
- NORMAL urine concentrating capacity
treatment: KCl, Mg, spironolactone, fluid
Glomerular Filtration
GFR= no. nephrons X single nephron GFR
Normal GFR= 100ml/min/m2
Newborn GFR= 15ml/min/m2
renal blood flow (20-30% CO): renal perfusion pressure (BP)/ renal vascular resistance
filtration fraction: GFR/RBF
filtration of plasma: 20X/hour
Glomerular structure
mesangial cells: connective tissue that controls pressure in glomerula
filtration (3 layers): endothelium, GBM, podocytes with foot processes
macula densa: epithelial cells in DCT, sense change in BP
juxtaglomerular apparatus: sits next to afferent arteriole and responds to signals from macular densa to secrete renin
Glomerulocystic kidney disease
incidence: uncommon
clinical: present in neonatal period
- 10% liver fibrosis
pathology: large echogenic kidneys, microscopic glomerular cysts
Glomerulonephritis
pathophysiology: preformed immune complexes or insitu immune complex formation with secondary injury via complement cascade and coagulation
clinical:
- haematuria +/- proteinuria
- AKI with oliguria, hyperkalaemia
- nephrotic syndrome with 2 types: SLE and membranous
diagnosis:
- GN screen: C3/C4, ANA, dsDNA, ANCA, antiGBM, ASOT/DNAse B, urine
- granular and red blood cell casts
- renal biopsy
Glomerulonephritis
definiition: symptoms haematuria, proteinuria, oedema, HTN caused by glomerular injury accompanied by inflammation
pathogenesis: immunologic response to several biological processes
- may be isolated to the kidney or part of a systemic disorder
- primary disease: humoral response to inciting agent with Ig deposition and complement activation
- secondary disease: primary disease activates complement, coagulation and leukocyte systems that cause disease
presentations:
- acute GN: PSGN, HSP, post bacterial endocarditis
- RPGN: anti-GBM, IgA nephropathy, MPGN, SLE, PSGN, HSP, granulomatosis with polyangitis
- recurrent macroscopic haematuria: IgA nephropathy, Alport syndrome
- chronic GN: MPGN, IgA , antiGBM, SLE, granulomatosis
evaluation: light microscopy, immunofluorescence, electron microscopy
Goodpasture’s disease
type: focal
cause: unknown
pathogenesis: anti-GBM to type IV collage of GBM of lung/glomeruli
clinical: rare in childhood, smokers
diagnosis:
- antiGBM, normal C3
- biopsy: linear deposition of anti-GBM IgG Ab
treatment: IV steroid, immunosuppressants, IvIg
- ALL progress to ESKD
Haematuria
definition: >500 RBC/ml
incidence: asymptomatic haematuria in 0.5-2% children
RBC casts/dysmorphic: glomerular pathology
Haemodialysis
advantage: rapid correction of fluid overload/electrolyte abnormalities, removes burden from carer
disadvantage: big central venous access (CVC/AV fistula), blood in fillter at all times
mechanism (counter-current)
- dialysate flows opposite direction to blood through cylinders maintain concentration gradient for exchange of solutes
- fluid removes by hydrostatis pressure of dialysate fluid
complications: hypotension, renal ischaemia, dysequilibrium syndrome (rapid shifts in urea)
contraindications: haem instability, severe coagulopathy
Haemolytic Uraemic Syndrome
definition: simultaneous microangiopathic haemolytic anaemia, thrombocytopaenia and AKI
pathophysiology: post gastroenteritis then thrombotic microangiopathy causing fibrin/clot in glomerulus and secondary poor filtration/acute renal failure
clinical: renal failure, hepatomegally, CNS (30%) with irritability, pancreatitis (<10%), myocarditis
- similar to TTP but more renal/neurological symptoms
diagnosis: anaemia, thrombocytopaenia, Coomb’s negative, fragments/schistocytes on film, raised transaminases
subtypes:
primary causes
- complement gene mutations
- antibodies to complement factor H
secondary causes
- infection: shiga toxin producing ecoli (STEC), strep pneumo, HIV
- inborn error of cobalamin C metabolism
- drug toxicity
HSP Nephritis
type: focal IgA (similar to IgA vasculitis)
pathogenesis: small vessel vasculitis with IgA deposits in glomeruli
clinical:
- purpuric rash, abdo pain, arthritis
- 50% renal often weeks to months post initial symptoms
diagnosis:
- normal C3
treatment:
- no evidence for steroids in HSP to prevent renal injury
- steroids, immunosuppressants
prognosis: worse if acute renal involvement at diagnosis
Hyperkalaemia
7% filtered potassium is excreted with almost all reabsorbed PCT
regulation K excretion: aldosterone, serum [K]
causes:
pseudohyperkalaemia: haemolysis
redistribution: met acidosis, DKA, familial hyperkalaemic periodic paralysis
true hyperkalaemia
- low GFR: poor clearance, increased K load, decreased K excretion
- normal GFR/low aldosterone: low renin (diabetic nephropathy, interstitial nephritis, obstructive uropathy), normal renin (adrenal insuff, drugs ACEi/ARB)
- normal GFR/high aldosterone: pseudohypoaldosteronism, drugs (K sparing), obstructive uropathy/sickle cell nephropathy, post renal transplant
clinical: arrhythmia if >8.5mmol/L
diagnosis:
- ECG: small p waves, prolonged PR, wide QRS, peaked t waves
management:
acute: cardiac monitor, ECG, calcium gluconate, salbutamol, insulin/dextrose, frusemide, resonium, dialysis
chronic: low K diet, loop diuretic
hypoaldosteronism RTA
type 4
mechanism:
- aldosterone deficiency
- eg. CAH, pseudoaldosteronism with UTI - tubular aldosterone resistance
- drugs that impair aldosterone
- eg. heparing, NSAIDs, calcineurin inhibitors, trimethroprim - interstitial nephritis
diagnosis: decreased Na, increased K acidic urine, increased renin, low aldosterone
treatment: mineralocorticoids
IgA Glomerulonephritis
type: focal
incidence: sporadic (family hx uncommon), linked 6q22-23, assoc HSP
pathophysiology: mesangial deposits IgA complexes (glomerulus not involved)
clinical variable presentations:
- synpharingitic episodes of haematuria
- persistent micro haematuria
- acute nephritis
- nephrotic syndrome
diagnosis: biopsy (IgA levels not helpful)
treatment: BP control, +/- steroids, immunosuppressants
prognosis: often benign, 20% CKD
Imaging UTIs
Interstitial renal disease
acute interstitial nephritis
mechanism: inflammatory infiltrate in kidney interstitium with immune mediated inflammation of the tubules
cause:
- drugs: NSAIDs, antibiotics
- infections
- TINU: tubulointerstitial nephritis and uveitis syndrome
- systemic disease: SLE, sarcoidosis
clinical: usually 1-2 weeks post exposure
- nausea, vomiting, abdo pain
diagnosis: non oliguric, no proteinuria, increased Cr
- biopsy if severe or systemic cause suspected
management: removal of offending agent, supportive, ?steroids
Intrinsic Renal AKI
causes:
- vascular disease: HUS, thromboses
- glomerular disease: GN
- CAKUT (congenital): cystic
- tubular disease
- interstitial disease
Joubert syndrome
genetic: AR, 3 mutations, also NHPH gene defect
clinical:
- renal: variable cystic
- cerebellum: vermal aplasia
- eye: coloboma, retinitis pigmentosa
- congenital hypotonia
- ocular-motor apraxia
Kidney anatomy
Liddle syndrome
aka. Pseudohyperaldosteronism
genetics: rare AD
pathogenesis: increased activity luminal membrane sodium channels
diagnosis: low aldosterone/renin
clinical: present at young age with HTN, hypokalaemia, metabolic alkalosis
treatment: amiloride
Loop diuretic
Frusemide
mechanism: acts on thick ascending limb to decrease Na reabsorption via Na/Cl/2K transporter
effect: excretion 25% filtered Na and increases Ca excretion
side effects:
- high glucose/TG/cholesterol
- low uric acid/Ca/Cl/K/Mg/Na
- metabolic acidosis
Loop of Henle Function
Counter current multiplier system establishes osmotic gradient in interstial tissue from cortex to medulla
- descending tubule: impermeable solute, loses water, increasing concentration
- ascending tubule: impermeable to water, loses solutes, more dilute
Na absorption: Na/Cl/2K co transport
- inhibited by frusemide
Lowe syndrome
definition: oculorenal syndrome
genetics: OCRL1 gene defect
clinical: presents like Dent’s disease
- renal: PT failure (type 2 RTA), nephrocalcinosis, renal calculi, renal osteodystrophy
- congenital cataracts
- mental retardation
Mannitol
mechanism: non reabsorbable sugar alcohol
- acts as osmotic diuretic inhibiting sodium and water reabsorption in PT and LOH
MCUG
micturating cystourethrogram
investigation: obstruction, VUR
process: catheterise, fill bladder with radiolabelled material, scan with voiding
diagnosis: shows bladder wall thickening/trabeculation
VUR
grade 1: reflux into ureter
grade 2: into collecting system w/o dilation
grade 3: into collecting system with mild dilation
grade 4: moderate dilation but still impression of calyces
grade 5: severe dilation
- note: prophylactic AB> grade 2
Meckel-Gruber syndrome
incidence: AR, rare
clinical: neurosurgical and renal problems
Medullary cystic disease
aka. Juvenille nephonopthisis
(AD tubulointerstitial kidney disease)
genetic: AD rare
clinical:
- progressive decline in kidney function from adolescence
- polyuria, enuresis, anorexia, pallor
- ESKD in adulthood (or earlier if juvenille form)
pathophysiology: tubulointerstitial kidney disease
biopsy: cortico-medullary cystic changes
US: normal/small kidneys
diagnosis: elevated uric acid/creatinine
Membranoproliferative GN
incidence: adolesence/teens
type of GN with:
- characteristic light microscopy changes: mesangial hypercellularity, endocapillary proliferation and double-contour glomerular capillary walls
- histological changes: thickened GBM, increased mesangial/endocap cellularity
immune-complex mediated:
most common with chronic antigenemia/circulating immune complexes
- associated chronic infections (eg HBV, HCV, fungus, parasites), AI diseases (eg SLE, Sjorgens, RA), monoclonal gammopathies (eg multiple myeloma)
complement-mediated MPGN:
less common from dysregulation and persistence of alternative complement p/w
- deposition of complement along capillaries in mesangium
classification with electron microscopy
MPGN I: immune deposits mesangium/subendo space
MPGN II (worst prognosis): dense deposits along GBM, tubules, bowman’s capsule
MPGN III: type I with subepithelial deposits
diagnosis: low C3, normal C4
treatment: prednisone, immunomodulators, Ig, recurs post transplant
prognosis: ESKD 50% in 10 yrs
Membranous Glomerulonephritis
type: focal non proliferative
pathogenesis: subepithelial immune deposits (not cellular)
- secondary to SLE, HepB, tumours
clinical: nephrotic syndrome
- haematuria common
diagnosis:
- normal C3
- biopsy: thick BM, spikes on silver stain
treatment: steroids if nephrotic, ACEi if non nephrotic
Metabolic acidosis
Increased AG
Increased anion gap‘MUDPILES’
Methanol
Uremia
Diabetic Ketoacidosis
Paracetamol
Iron, Inhalants (CO, cyanide, toluene), Isoniazid, Ibuprofen
Lactic acidosis
Ethylene glycol, ethanol ketoacidosis
Salicylates, starvation ketoacidosis, sympathomimetics
Metabolic acidosis
renal compensation
- HCO3 reabsorption: 85% in PCT
- regeneraton of HCO3 by excretion of NH4 in DCT
- NH3 + H+ and NH4 excreted
Metabolic acidosis
Normal AG
Normal AG acidosis ‘USED CARP’
Ureteric diversion
Small bowel fistula
Excessive Cl
DKA resolving
Carbonic anhydrase inhibitors
Addisons
Renal tubular acidosis (Types 1, 2 & 4)
Pancreatic fistula
Metabolic alkalosis
cause: diuretic use, diarrhoea
mechanism: chloride loss causes alkalosis
- impaired HCO3 secretion
- fall in ECF volume: decreased GFR, decreased filtered HCO3, increased Na reabsorption, increased NaHCO3 reabsorption, increased K excretion, increased NH4 excretion, increase HCO3
chloride responsive: renal cause (Ur Cl>40)
- Barttner’s, Giltelman’s, diuretics
chloride responsive: non renal cause (Ur Cl<25)
- vomiting, diarrhoea, CF
chloride resistant (volume overload/hypertensive)
- mineralocorticoid excess or impaired Cl- excretion
Multicystic dysplastic kidney
incidence: 1:3000, sporadic not inherited
pathogenesis: failure of ureteric bud to fuse metanephros
- renal parenchyma replaced non-communication cysts
- non functioning kidney with atretic/obstructed ureter
clinical:
- 30% abnormal contralateral side, PUJ obstructions 15%, VUR 10%
- usually normal renal function
treatment: nephrectomy if symptoms
prognosis: cysts involute 5 yrs, malignant change possible, RF uncommon
Neonatal electrolyte disturbances
hyponatraemia:
- early: excess TBW and normal Na
- later: renal causes
hypernatraemia:
- almost always hypovolaemic hypernatraemia
- preterm: insensible losses
- term: poor feeding
hypokalaemia:
- excess renal loss K
hyperkalaemia:
- renal failure, haemolysis, tissue destruction
Neonatal renal function
antenatal
- urine from week 10 gestation
- small volume but 60% AF
- oligohydramios: eg. PUV
- polyhydramnios: eg. nephrogenic DI, Bartter’s
- Cr crosses placenta: neonatal Cr= maternal Cr
postnatal:
- relative renal insufficiency: low BP, high SVR, poor tubular reabsorption Na/HCO3
- initially low urine vol, poor urine concentration, GFR 10-15ml/min
Nephritic syndrome
‘Ho Hum’
Haematuria
Oliguria
Hypertension
Uraemia
Mild proteinuria
Nephrocalcinosis
definition: laying down of calcium in the kidney in nondiscrete locations
incidence: common <1 week and disappears with urine production
pathology: lays around renal pyramids first
causes: same as for metabolic calculi
- hyperoxaluria
- hypercalciuria
Nephrogenic diabetes insipidus
definition: partial or complete renal resistance to ADH
cause: hereditary or acquired
pathophysiology: urine output determined by solute intake/excretion
treatment:
- low salt/protein diet
**protein highest renal solute load, best control UO
- diuretics (increase proximal Na/H2O reabsorp and reduce distal water delivery)
- NSAIDs (inhibit renal PG synthesis/afferent vasodilation)
- exogenous ADH (only for non hereditary)
- water q2 hourly day and night
Juvenille nephronophthisis
incidence: most common cause of genetic cystic disease, incidence: 1:50,000
genetics: AR, chromosome 2, NHPH1-6
pathogenesis: ciliary defect causing problem with apotosis causing tubular BM thickening/wrinkling with tubular atrophy/fibrosis and few cysts at CM junction
3 variants:
- infantile: 1yr with ESKD
- juvenille (most): 13yrs ESKD
- adolescent: 19yrs ESKD
clinical:
- renal (due to tubular injury): polyuria/polydipsia, reduced concentrating ability, Na loss, renal failure, anaemia
* normal BP
US: loss of CM differentiation, normal/small size
treatment: nil specific, renal transplant
Nephrotic syndrome
- definition and pathology
4 criteria
1. proteinuria >50mg/kg/day
2. hypoalbuminaemia <25
3. oedema
4. hyperlipidaemia: liver compensation for decreased albumin so increased other protein production
incidence: M>F 2:1, <6 yrs usually MCNS, >6yrs FSGN
clinical:
- usually present with oedema first
- then anorexia, abdo pain, cool peripheries
pathophysiology: effacement of podocyte foot processes
causes:
- steroid sensitive: no known cause
- steroid resistant: associated with genes for proteins podocin, nephrin, WT1
associated:
- infections: encapsulated, urinary loss Ig and C3 precursor
- thrombosis: 2-5% in children due to hypercoagulable state from stasis, haemconcentration, increased factor production, urinary loss anticoagulants
- hyperlipidaemia
Nephrotic syndrome
- causes
primary causes:
minimal change disease (85%):
- EM effacement foot processes
- 90% sensitive to steroids and rarely ESKD
focal segmental glomerulosclerosis (most severe):
- LM mesangial proliferation/segmental scarring
- IF +ve IgM/C3
- EM segmental scarring of glomerular tufts/obliteration capillary lumen
- 20% respond to steroids and most ESKD
mesangial proliferation:
- LM increased mesangial cells/matrix
- IF mesangial IM/IgA staining
- EM increaesd mesangial cells/effaced epithelium
- 50% respond to steroids
secondary causes:
- any of GN: SLE, HSP, membranoproliferative, PSGN
- malignancy (immune complexes with tumour Ag deposit in glomeruli
- drugs: lithium, gold, phenytoin, NSAIDs
- infection: HIV, hepatitis, malaria, syphillis
Nephrotic syndrome
- treatment
treatment
-
high dose steroids tapered 4 months
- 6 weeks 60mg/m2/day then 4 weeks 40mg/m2/day and taper
- high dose and long course prevents relapse
- 40 % relapse, 90% respond to steroids in 3 weeks
2. frusemide
3. fluid restrict
4.albumin
5. antihypertensives
definition of relapse: 3x >3+ protein in urine
treatment of relapse: 60mg/m2/day until remission (urine negative 3/7)
steroid dependent: relapse on alternate days or within 28 days ceasing
steroid resistant: ongoing proteinuria at 8 weeks, 80% FSGN, need biopsy
- consider cyclosphospamide, rituximab
prognosis:
- steroid responsive: most have repeated relapses, decreased frequency with age
- steroid resistant: poorer prognosis, renal insufficiency
Obstructive uropathy
causes: PUJ obstruction, renal calculi, thrombi, tumours
Ureteric stricture
- congenital with extrinsic compression where the right ureter sits behind IVC
Ectopic ureter
- F>M, ureter enters urethra/cervic/uterus
- reimplantation if renal function is preserved otherwise nephrectomy
ureterocele
- cystic dilation at end of ureter
- surgical resection/correction
Osmolarity
calculated plasma osmolarity= 2[Na+Ka] + glucose + urea
plasma osmolarity= 280-295 mosmol/l
osmoles
osmolality= no. of osmoles/kg of solutes (mosmol/kg)
osmolarity= no. of osmoles/L of solution (mosmol/L)
Oxalate calculi
incidence: RARE. genetic
mechanism: overproduction oxalate in liver due to primary or secondary disease
clinical: reccurent nephrolithiasis and progression to ESKD
treatment: pyridoxine, fluids, transplant
Oxybutynin
mechanism: anticholinergic
- prevents muscarinic recepter activation by anticholine on bladder smooth
use: decreases bladder spasm to prevent incontinence
Peritoneal dialysis
dialysate contains: osmotic agent, electrolytes, acid buffer
ultrafiltrate: fluid removed from patient
volumes: 10-50ml/kg each cycle
contraindications: intraabdominal pathology, peritonitis
advantages: gentle, less fluid shift, higher peritoneal SA in children, no central venous access devise
disadvantages: infection (IP ceftazidime/ceftriaxone or if <2yrs IP ceftaxidime/vancomycin with continuous PD), peritoneal fibrosis, career burnout
Pneumococcal HUS
incidence: 5-15% HUS, younger 1-2yrs
pathophysiology: pneumococcus produces neuroaminidase and exposes T antigen on RBC/platelets (cryptantigen considered FB) causing haemolysis
clinical: pneumonia (70%) with empyema/effusion, meningitis (20-30%)
- more severe initial disease
- complications: pancreatitis, purpura fulminans, cholecystitis, cardiac dys, hearing loss
treatment: supportive
Post renal AKI
mechanism: obstruction
pathophysiology:
- collecting tube dysfunction (type 4 renal tubular acidosis)
- water/Na loss, H/K retained - more proximal dysfunction
- RAAS, reduced GFR, ATN - ATN assoc sepsis
- poor outcome
Post strep glomerulonephritis
PSGN
type: diffuse proliferative glomerular injury with inflammation
incidence: 5-12 yrs, 15% post GAS infections, increased with family history
pathophysiology: GAS infection, diffuse mesangial cell proliferation, glomerular inflammation
- usually GAS but also EBV, CMV, HepB, endocarditis
clinical: 1-2 weeks post throat infection/3 weeks post skin infection
- gross haematuria, flank pain, oliguria, HTN, oedema, hyperkalaemia, hypocalcaemia
- MRI can show reversible posterior leukencephalopathy
diagnosis:
- low C3, normal C4, ASOT+ (throat 90%, skin 50%), AntiDNAse B+ (95% spec)
- urinalysis: protein, casts
- biopsy: IgG/C3 deposits, diffuse proliferation
treatment: dialysis, fluid restrict, frusemide
- NO STEROIDS
prognosis: 95% fully recover
- micro haematuria may persist for 1 yr
- 5% relapse or ESKD
Posterior urethral valve
pathophysiology:
- embryological remnant: a valve with leaflets with only a slit like opening at a point along the urethra
clinical: severe obstructive uropathy
- poor urinary stream, trabeculated bladder, ESKD 30%
diagnosis: often diagnoses antenataly with hydronephrosis, oligohydramnios, pulmonary hypoplasia
associations: VUR, dysplastic kidney
treatment: antenatal decompression, IDC/vesicostomy, valve ablation, prophylactic AB, monitor renal function
Potassium sparing diuretics
amiloride/spironolactone/eplerenone
mechanism: act on cortical collecting duct
- amiloride: directly decreases Na channel activity
- spironolactone: inhibits aldosterone receptor and decreases number of Na/Cl cotransporters
effect: weak natriuretic activity with only 2% filtered Na excreted
side effects: hyperkalaemia, gynaecomastia
- amiloride: hyperchloremic met acidosis, hyponatraemia
Predictive Acid/Base
Respiratory compensation 1 CO2: 1 HCO3
- 30 mins-24 hrs
met acidosis: decrease pCO2 1.3 for decrease 1 HCO3
met alkalosis: increase pCO2 0.6 for increase 1 HCO3
Metabolic compensation
- 1 to 5 days
resp acidosis ACUTE: increase HCO3 1 for increase 10 CO2
resp acidosis CHRONIC: increase HCO3 3.5 for increase 10 CO2
resp alkalosis ACUTE: decrease HCO3 2 for decrease 10 CO2
resp alkalosis CHRONIC: decrease HCO3 3 for increase 10 CO2
Prerenal AKI
cause: hypovolaemia, poor perfusion, sepsis, CV failure
pathophysiology to counter hypovolaemia:
- intrarenal PG release: dilation afferent arteriole and improve filtration
- decreased pressure at macula densa, increase renin/ATII, selectrive vasoconstriction efferent arteriole, increased hydrostatic pressure across glomerulus
- further increase renin/ATII, systemic vascoconstriction afferent/efferent arterioles, ATN and oliguric RG
Proteinuria
definition: >4mg/m2/hr
diagnosis: early morning protein to creatinine ratio most reliable
dipsticks: most sensitive for albuminuria and miss other proteinurias
- 1+ 30mg/dl
- 2+ 100mg/dl
- 3+ 300mg/dl
- 4+ 2000mg/dl
non-pathological: exercise, fever, posture
pathological: tubular, glomerular, tumour, drugs, stone, infection
Proximal RTA
type 2
definition: inability to reabsorb HCO3 (and Na)
cause: can be isolated or generalised proximal dysfunction
ie Fanconi’s syndrome: genetic or acquired
- decreased PO4, renal glycosuria, aminoaciduria, tubular proteinuria, T2 RTA
causes of isolated proximal RTA
- idiopathic
- cystinosis
- ifosfamide
diagnosis: acidic urine <5.5, NH4 in urine, NO calculi (citrate present)
treatment: BICARB
Proximal tubule function
iso-osmotic reabsorption of 2/3 glomerular filtrate
active reabsorption: Na, K, glucose, galactose, fructose, AA, Ca, uric acid, Vit C
passive reabsorption: urea and water due to osmotic gradient generated by solute reabsorption
active secretion: organic acids eg. PAH, diuretics, salicylates, penicillin, probenicid
PUJ obstruction
-pelvicoureteric junction-
incidence: most common obstruction, M:F 2:1
pathophysiology: congenital instrinsic stenosis (90%) and less commonly extrinsic compression (10%) causing partial obstruction of the ureter resulting in thin ureter and dilated kidney
- 60% left, 10% bilateral
diagnosis:
US: hydronephrosis
MCUG: detect VUR (10%)
DTPA: diagnose obstruction
management: AB prophylaxis, pyeloplasty (91-98% success)
RAAS
causes of increased renin:
- decreased BV/Na concentration
- catecholamines
- standing
causes of decreased renin release:
- angiotensin II, ADH, hypernatraemia, hypokalaemia
- indomethacin/beta blockers/ACEi
Renal absorption/secretion other molecules
hydrogen: secretion 85% PCT, 10% distal tubules, 5% CD in exchange for Na
- via 3 mechanisms
chloride: moves passively with Na except for active transport in LOH
sugar/AA: completely reaborbed in PT via Na dependent active transport
- glucose is saturable: at 10mmol/l glycosuria occurs
urea: 87% filtered reabsorbed (50% in PT)
water: passively reabsorbed 80% PT, 15% LOH, distal tubule via ADH
Renal acid output
Renal H+ excretion
- minimal H+ excretion but excrete H+ via NH4
Urine anion gap
- urine ammonia can be estimated by the UAG:
UAG= (urine Na + urine K) - urine Cl
- usually Na + K > Cl
Acidosis
- increased excretion of NH4 combines with Cl to make ammonium Cl and increases renal Cl so Cl> Na + K
Urine pH
- if high: bicarb in urine
- if low: H+ present
Renal acid/base
1. Renal bicarb reabsorption
- H+ secretion tubular cells binds HCO3- to form H2CO3 that divides to CO2/H20 with reabsorption of CO2 into tubular cells
2. Ammonium secretion
- NH3 in tubular cells accepts H+ to form NH4+ which is then excreted
3. Dihydrogen phosphate
- exchange H for Na converts monohydrogen phosphate to dihydrogen phosphate (acid)
**Excess H+: 2/3 excreted as annium, 1/3 excreted as dihydrogen phosphate
Renal angiomyolipomata
incidence: most common benign tumour kidneys
- 1/10 in patients with TS
pathogenesis: benign tumour of blood vessels
clinical: retroperitoneal haem with sudden pain, nausea, vomiting, shock
renal US: bilateral multiple echogenic foci
Renal biopsy
differention:
- proliferative vs non proliferative
- diffuse vs focal
- segmental vs global
- crescenteris: cellular vs fibrous types
specific patterns:
- cresenteric= RPGN
- tram tracking= MPGN
- wire loops= SLE
- spikes on special stains= membranous
- starry sky= PSGN
- subepithelial humps (immune complexes on GBM)= PSGN
immunofluorescence: c3, IgA/M/G, C1q
- granular= immune complex
- pauci immune= ANCA assoc
- linear IgG at GBM= antiGBM
- gull house pattern (all present)= SLE
electronmicroscopy: good for the site of immune deposition
Renal calculi
incidence: M>F, 1% children, 60% metabolic risk factor
- variables: diet, geography, race, family history
diet: increased protein/cereal, high or low calcium, high salt
stone composition:
- calcium oxalate 60-90%
- calcium phosphate 10%
- struvite 1-14%
- urate 5-10%
- cystine 1-5%
formation: forms in tubules at site of injury usually in medulla
clinical: flank pain (50%), renal colic (7%), haematuria (10% macro, 90% micro), passage of stone, UTI, CKD
- chance of passing stone <5mm high, 5-7 mm 50%, >7mm review
diagnosis:
- US: detects stone, shows obstruction
- urine/stone analysis
complications: UTI (FTT and intermittent urosepsis), functional impairmonet, decreased bone density
Renal clearance
clearancex= [urinex] x urine volume/[Plasmax]
- if clearance>GFR: secretion of solute
- if clearance<gfr: absorption of solute>
<p><strong>clearance of solute</strong></p>
<p>- ideal solute: freely filtered at glomerulus, no metabolism/secretion/reabsorption ie. inulin</p>
<p><strong>creatinine:</strong> small endogenous product muscle metabolism</p>
<p>- secreted in tubules so can overestimate GFR</p>
<p><strong>urea: </strong></p>
<p>- 40-50% passively reabsorbed in proximal tubule</p>
<p>- can underestimate GFR</p>
<p><strong>cystatin C: </strong>small molecule produced nucleated cells in body</p>
<p>- metabolised in tubules so can't measure clearance</p>
<p>- BUT serum cystatin C may correlate better with GFR</p>
<p> </p>
</gfr:>
Renal cysts
pathogenesis: problem non-motile cilia from tubular epithelial cells facing lumen
- loss of tubule orientation causing dilation and cysts
polycystic: ARPKD, ADPKD, MCDK
CAKUT: renal agenesis, dysplasia, aplasia
tubulointerstitial: renal tubular dysgenesis, nephronopthisis, medullary cystic disease, Bardet-Biedl
neonplasms: cystic nephroma/nephroblastoma/RCC, von Hippel Lindau, lymphangioma, hygroma renalis
other: simple corticol cyst, medullar sponge kidney, localised renal cystic disease
Renal cysts and diabetes syndrome (RCAD)
genetics: AD, HNF1B activates polycystin/uromodulin
clinical: DM (20-40yrs), gout, bicornuate uterus, hypomagnesiua, LFTs
Renal embryology
timing: 5 weeks gestation, glomerulus development at 9 weeks, urine output 10 weeks
phases
1st: Pronephros day 22
2nd: Mesonephros
- mesoderm in thoracolumbar region develops into glomeruli/tubules
3rd: Metanephros week 5
- outpouch of mesonephros forms ureteric bud branches into the ureter and collecting duct system
completion: weeks 32-36 all nephronic units complete
Renal management of sodium
Na reabsorption (99% of filtered)
- 60% PCT: Na/H exchanger (H provided by HCO3 absorption and carbonic anhydrase)
- 25% LOH (thick ascending limb): Na/Cl/2K co transported
- 10% DT: epithelial Na channel coupled to K
- 2% CT
Na regulation by Aldosterone/ANP
- mediate plasma volume NOT Na
Fraction excretion of Na: % of Na filtered by kidney excreted in urine
- (FENa)= 100x (Nau x Crp)/(Nap x Cru)
- <1%: prerenal disease, 1-2%: ATN or prerenal, >2%: ATN
Renal osteodystrophy
mineral bone disease
prevalence: very common early on with CKD
pathogenesis:
- decreased renal mass causes decreased renal 1 alpha-hydroxylase and 1, 25 vitamin D3 production
- decreased GI calcium absorption and hypocalcemia, and increased PTH activity
- excessive PTH secretion corrects hypocalcemia by increased bone resorption
- later mechanisms to enhance phosphate excretion inadequate causing hyperphosphatemia with further hypocalcemia and increased PTH
4 types:
1. Osteitis fibrosa cystica: increased bone turnover due to secondary hyperPTH
- increased PTH due: increased Ph, decreased Ca/VitD
2. Adynamic bone disease: decreased bone turnover
- most common renal bone disease
- decreased osteoblast/osteoclast activity
- over suppression of PTH (vit D tx, Ca based phosphate binder)
3. Osteomalacia: decreased bone turnover and more undermineralised bone
- common when Al would deposit in bone with Al based Ph binders
diagnosis: PTH, ALP, BMD testing, bone biopsy
management: control of PTH and PO4
Renal reabsorption
PCT (65%): site of signficant reabsorption (NaCl, water, HCO3, nutrients) and excretion (H, drugs)
LOH (25%): countercurrent mechanism, descending limb impermeable to solutes and reabsorbs water, ascending limb impermeable to water and Na/Cl/K reabsorbed
DCT (8%): electrolyte reabsorption in smaller shifts
CD (1.5%): site ADH/aldosterone action
- Aldosterone: Na/water retention, K/H secretion, stimulates ADH
- ADH: acts on cortical part of CT
NB. % Reabsorption of solutes
Renal transplant
types: preemptive, living related donor, deceased donor
graft survival: approx 15 years
immunosuppresants: steroids, basiliximab for induction (anti CD25 monocloncal Ab), tacrolimus/cyclosporine (calcineurin inhibitors), azathioprine/MMF (antiproliferative agents), sirolimus/everolimus (mTOR inhibitors)
complications:
rejection: creatinine best indicator of rejection
- hyperacute: preexisting HLA Ab, occurs anytime
- acute: T cell medicated, interstitial inflammation/arteritis, treat with methylprednisone/anti-thymocyte globulin
- chronic: donor specific antibiodies, CD4 staining on biopsy, glomerulitis/vascular thrombosis, optimise immune suppression
infection: EBV, CMV, BK
NODAT (new onset diabetes after transplant): same as DM2, increased BMI/steroids
PTLD (post transplant lymphoproliferative disease): related to infection, treat with reduced immunosuppression, monitor EBV levels
malignancy: most adults, skin (SCC/BCC), increased all types due to immune suppression
Renal tubular acidosis
definition: normal AG acidosis but failure to acidify urine
types:
- distal (type 1) RTA
- proximal (type 2) RTA
- mixed (type 3) RTA
- type 4 RTA
treatment: treat underlying condition, sodium bicarb
complications: lactic acidosis, hypernatraemia, volume overload, hypokalaemia, hypocalcaemia, alkalosis
Shigatoxin HUS
epidemiology: 90% all cases usually <5years, 3/100,000
organism: 6-9% STEC infections
pathophysiology: microangiopathic anaemia by nonimmune RBC destruction due to shearing through platelet microthrombi
- glomerular thrombotic microangiopathy with can extend to afferent arteriole
clinical: preceded 5-10 days before with abdominal pain, vomiting, blood diarrhoea usually post exposure to undercooked beef
- AKI 50%
- neurological symptoms 25% and seizures assoc HTN
- GI haemorrhagic colitis
- also cardiac dysfunciton, pancreatitis, liver dysfunction, haem disorders
prognosis: 30% CKD, 5% mortality
treatment: fluids, dialysis, eculizumab (monoclonal complement Ig), plasma exchange
Single renal cyst
incidence: sporadic, M>F 2:1
cause: unknown
diagnosis: cortical, solitary, unilateral
clinical: pain, haematuria, obstruction, rupture, infection
SLE glomerulonephritis
type: diffuse
epidemiology: 25% SLE in children
pathogenesis: minimal change (mild, haematuria/proteinuria), mesangial (mildest 25%, haematuria/proteinuria), FSGN (20%, + impaired RF), diffuse proliferative (most common/severe 40%, + impaired RF), membranous (15%, nephrotic syndrome), advanced sclerosis
diagnosis: (FULL HOUSE)
- low C3/C4, ANA+ve, ESR, dsDNA+ve
- biopsy: wire loops, all stains positive: IgG, IgA, IgM, C3, C1q
treatment: steroids, immunomodulators, IVIg, ACEi, statin
prognosis: ESKD 20% at 10 yrs
Thiazide diuretic
mechanism: inhibit Na transport in DT via inhibition NaCl cotransported
- also cause increased reabsorption of calcium
effect: smaller proproportion of filtered load, so smaller natriuretic effect
side effects: hyperglycaemia, hypokalaemia, hyperuricaemia, hypercalcemia, hypochloremic alkalosis
Transplant rejection
Tubular renal disease
ATN:
cause: ischaemic 60%, nephrotoxic 40%: aminoglycosides, chemotherapy (cisplatin), IVIG, contrast
pathophysiology: oedema, sloughing of cells, Na/K pump dysfunction
management: hydration, nutrition, time
Contrast nephropathy/dermopathy:
cause: CT contrast, MRI gadolinium (lower toxicity)
pathophysiology: rise Cr after 48 hours
- MRI gadolinium associated nephrogenic systemic fibrosis if GFR<3
management: hydration, ?NAC (free radial scavenger)
Urate calculi
causes: disorders of purine metabolism (5-10%), uric acid overprod, tumour lysis, Lesch-Nyhan, gout, ketogenic diet, salicylates, glycogen storage 1
treatment: alkalinise urine, ?allopurinal, uricase
Urinanalysis
specific gravity: normal 1.010-1.035
osmolality: normal 300mosm (more accurate than SG)
microscopy
urinary casts: cylindrical structures produced by kidney (DCT/CD) and present in urine
- hyaline casts: transparent, most common, solidified Tamm-Horsfall mucoprotein secreted from the tubular epithelial cells of nephrons with dehydration/exercise, not pathological
- granular casts: 2nd most common, breakdown of cellular casts or inclusion of aggregated protein, glomerular/tubular disease
- white cell casts: indicate inflammation/infection ie. acute pyelonephritis, interstitial nephritis
- red cell casts: always pathological, usually glomerulonephritis
- fat globules: hyperlipidaemia
- glycosuria: steroids, FSGS
UTI
incidence: 7% febrile infants
- <12 months M=F, <3 months M>F
risk factors: FHx, abnormal flow, constipation, abdo mass, antenatal dx renal abnormality, HTN
definitions:
- cystitis: bacteruria but no systemic symptoms
- pyelonephritis: bacteriiuria + fever/pain
pathogens: ecoli (>80%), klebsiella, proteus, enterobacter, enterococcus
diagnosis:
- leuks+/nitrites+: AB
- leuks-/nitrites+: AB
- leuks +/nitrites-: AB IF clinical evidence
- leuks-/nitrites-: DONT treat
treatment:
- <6m or unwell: IV AB (benpen, gent)
- >6m and not unwell: PO AB (trimethoprim, bactrim, ceph)
Prune belly syndrome
VUJ obstruction
incidence: 1/40,000, 95% male
triad: lack of abdominal muscles, undescended tests, antenatal urethral obstrution
clinical: oligohydramnios, pulmonary hypoplasia
- often assoc malrotation
prognosis: dependes on pulm/renal dysplasia
Wegener’s
PR3 ANCA
microscopic polyangitis
MPO
incidence: usually adults with sinusitis/renal/skin involvement
pathophysiology: focal segmental GN (may be crescenteric), NO immune deposits (oie. pauci immune)
clinical:
- systemic disease: ENT/pulmonary
- microhaematuria, AKI with haematuria/casts, proteinuria below nephrotic range, RPGN common
diagnosis: ANCA +ve
- biospy: ANCA
- immunofluorescence: pauci immune
treatment: non specific
- dialysis, steroids, immunosuppressants, IVIg
Atypical UTI
CRITERIA:
- seriously ill/septicaemia
- poor urine flow
- abdominal mass
- elevated creatinine
- failure to respond to appropriate AB within 48 hours
- non Ecoli organisms
