Renal Flashcards
3 layers of filtration in Glomerulus
- Endothelium (glomerular capillary)
- Basement membrane
- Epithelium (podocytes that extend into BM)
Haematuria Ddx
Glomerular (red cell casts, dysmorphic RBC, +/- Proteinuria)
- Glomerulonephritis - primary or secondary
PSGN/MPGN/RPGN/HSP/HUS
- Inherited GBM problem (Alports, Goodpastures, thin BM)
- Nephrotic
Non Glomerular
- infective (UTI, Viral - Adeno/BK, TB, schisto)
- Urological (stone/trauma/PUJO - pain)
- tumour/vascular - Wilms
- Sickle cell
- Hypercalciuria (check urine ca/cr)
- Renal V thrombosis
- Cystic disease
- Med (Aspirin, cyclophosphamide)
- Vascular - nutcracker (compression left renal being between aorta and SMA), coagulopathy
Haematuria investigations
FBC, U&E, Complement, Strep serology
ANA, Anti-dsDNA
Urine Protein:Cr ratio, urine calcium/cr ratio
Renal US
Glomerulonephritis
Post infectious GN
IgA / HSP
SLE
RPGN (ANCA +ve, Anti-GBM, HSP - crescents on biopsy)
Inherited collagen disorders
- Alports (80%XLR COL4A5 gene, defect type 4 collagen)
- Thin GBM disease (benign familial haematuria)
HUS (Oliguria / anuria ; MAHA, thrombocytopenia)
Onset PSGN
7-14 days after throat infection
3-6 weeks after skin infection
Timing of symptom resolution PSGN
Gross haematuria - 2 weeks Hypertension - 4 weeks Low C3 - 8 weeks Persistent proteinuria - 6 months Intermittent proteinuria - 12months Microsopic haematuria - 2 years
Hypocomplementaemic GN
Post infectious GN
MPGN
SLE (low c3 and c4)
Shunt nephritis
GN with normal complement
IgA Nephropathy HSP ANCA vasculitis Alports Goodpastures
Post infectious GN
Age 2-12
Onset 1-2 weeks post Strep throat
3-6 weeks post strep skin infection
Low C3 with normal c4 ; complement normalises by 8 weeks
IF - deposit C3 and IgG, granular deposits
HUS (typical / D+ HUS)
most common type >90%
- Caused by shiga toxin producing E.Coli 0157:H7 or shigella ; most frequently <3yrs age
- Rare can be caused by severe invasive pneumococcal disease in patients <18months ; pneumomococcal meningitis or pneumonia with empyema. COOMBS +ve
Triad
AKI
Thrombocytopenia
MAHA (low Hb with red cell fragments (normal Fibrinogen differentiates from DIC), Low Hb, high retics, high LDH, low haptoglobin
Clinical
Diarrhoea by D3
Bloody diarrhoea by D5 (in 80%)
10-15% patients with STEC develop HUS by D7
Poor prognostic factors Haemoconcentration Neutrophilia or leucocytosis CNS disease (10-15% get seizures ; Intracranial haemorrhage) Haemorrhagic colitis
50% require RRT
5-10% ESRD
5-7% mortality
20-60% have long term HTN, Proteinuria, CKD
IVF in first 4 days illness reduce risk severe
Abx and Loperamide increase risk severe HUS
Atypical HUS
Complement mediated HUS - familial or genetic
<10% HUS ; alternative complement pathway overactivaton
Recurrent episodes of haemolysis and renal failure
Rx - plasmapheresis +/- FFP
IgA nephropathy
Abnormally glycosylated IgA1 which forms immune complexes in glomerular mesangium
Recurrent gross haematuria ; occurs within 5 days of URTI (synpharyngitic)
Can progress to ESRD
IgA mesangial deposits on IF
HSP nephritis looks same as IgA on biopsy
Normal complement
<20% have elevated IgA
HSP - small vessel vasculitis
Occurs age 3-15years ; M:F=2:1
Deposition IgA in glomeruli
Skin(100%): Symmetrical purpura lower limbs
Joint(80%) - oligoarthritis
GI (50-75%) Abdo pain ; risk intussusception
Renal (20-60%) - Micro haematuria, gross haematuria, hypertension, nephritic/nephrotic
Orchitis (25%boys)
CNS(2%) - seizures
Renal involvement occurs within 2 months of disease
1/3 <2weeks symptoms
1/3 2-4weeks symptoms
1/3 >4weeks symptoms
2/3 recur (within 4 months)
Urinalysis weekly for 3/12 then monthly for 6/12
2% risk nephritis after 2/12
MPGN
Primary
Secondary - to Hep B/C, shunt nephritis, SBE
Type 1, most common ; IF C3+ve, IgG-ve
Type 2 - dense deposit disease
2nd decade life
4 presentations
- Nephrotic (40-70%)
- Acute Nephritic (20-30%)
- Asymptomatic proteinuria, haematuria (20-30%)
- Recurrent gross haematuria
Low c3 (remains low) Idiopathic MPGN, poor prognosis, 50% ESRD 10 years after diagnosis
RPGN
crescents seen on biopsy
ANCA +ve (GPA/wegners =cANCA PR3 ; granulomas, URTI, sinusitis, saddle nose ; MPA=pANCA MPO ILD; pauci immune GN -no immune deposits)
HSP Goodpastures (antibodies to type 4 collage - pulmonary haemorrhage and GN)
Rx immunosuppression
-Steroids, cyclophosphamide, rituximab
Alports
Mutation type 4 collage
X linked 80% (COL4A5 mutation)
Others AD or AR
Recurrent microscopic haematuria
Kidneys: ESRD in early 20s
Hearing: SNHL males adolescence (50%by 25)
Eyes: Anterior lenticonus pathognomonic, only present 25%
Basket weave appearance GBM (laminated)
ACEi reduces risk ESRD
Indications Dialysis (AEOIU)
Acidosis / Ammonia Electrolyte (High K) Ingestion toxic Overload (pulmonary oedema) Uraemia
Insensible losses neonates
Older kids
<1500g = 30-60ml/kg/day 1500-2500g = 15-35ml/kg/day >2500 = 15-25ml/kg/day
Baby - 40ml/kg/day
Infant - 30ml/kg/day
Preschool 20ml/kg/day
> 5 yrs 15ml/kg day
Older kids 400ml/m2/day
Evaluation Paediatric HTN - MONSTER
Medications - steroids, Tac/ciclosporin, OCP, Ritalin Obesity Neonatal Hx - umbi lines, asphyxia Symptoms/signs Trends in family Endocrine Renal
Lupus nephritis
More common girls 9:1 ; Indian/maori/pi
Lymphopenia
Low C3&C4
Nephritis is commonest presentation
Grades 1-5
RENAL Biopsy needed for confirmation
Proteinuria
Glomerular vs tubular
Glomerular - increased filtrations macromolecules such as albumin. Urine ACR (Urine A:P ratio >0.4)
Rx ACEi
Tubular - LMWP, smaller proteins not getting reabsorbed by tubules
Urine A:P ration<0.4 ; have normal serum, albumin
Causes Proximal tubule dysfunction
- Drugs (Cisplat, aminoglycosides, anticonvulsants)
- Cystinosis (lysosomal storage disorder, renal issues 3-6mo age, Vit D resistant rickets and PO4 wasting
- LOWE
- DENT - XLR nephrolithiasis / stones / hypercalciuria
-Wilsons
- ATN, reflux nephropathy, PCKD, TIN
Dipsticks mostly detect albumin
False +ves - alkaline urine, concentrated, blood/pyuria
False -ves - LMW proteinuria, dilute, polyuria
Nephrotic range proteinuria
Urine protein: creatinine ratio >200mg/mmol
>40mg/m2/hr protein
Normal protein excretion = <4mg/m2/hr (150mg/day)
Normal PCR <23 mg/mmol
Nephrotic syndrome
Nephrotic range proteinuria
Low albumin (<25)
Oedema
Hyperlipidemia
Cause
Primary
- MCD most common 75%, average age 2.5yr ; effacement of podocytes
-FSGS. 7%, average age 6yrs (50% have HTN and gross haematuria)
-MPGN
-Membranous (Hep B)
Systemic - SLE/HSP
Syndrome - Denys drash (assoc DSD), Nail patella , Frasier, Pierson
Biopsy if steroid resistant or red flags at presentation such as <12months or >12 years diagnosis, HTN, gross haematuria, persistent renal insufferable
Nephrotic definitions
Remission= Trace on dipstick for 3 consec. days(PCR<30) Relapse = 3+ on dip for 3 consec days (PCR>200)
Freq relapse = >2 in 6mo or >4 in 12mo
Steroid dep = 2 consec relapses within 2/52 stopping steroid or whilst on steroids
Steroids Resistant = no remission after 4 weeks on 60mg/m2/day
80%respond to steroids
Steroid sensitive nephrotic syndrome
25% no relapse
25% infrequent relapse
50% (FR/SD/SR)
75% relapse so need urine monitoring
Alternative - steroids - > cyclophosphamide -> MMF–> CSA/Tac - > Ritux
FSGS outcome
1/3 improve
1/3 persistent proteinuria
1/3 ESRD by 5 years
1/3 idiopathic have recurrent disease in transplant
Nephrotic syndrome complications
HTN (FSGS + MPGN > MCD)
Hypovolaemia
Thrombosis (DVT)
Infection - low IgG ; encapsulated organisms
Primary peritonitis - strep pneumo 60-75%
Disseminated VZV/measles
Cellulitis
Congenital nephrotic syndrome
present <3months - 90% genetic
present 3-12mo(Infantile) - 50% genetic
NPHS1 or NPHS2 - Finnish type, AR
WT1 - Denys drash (nephrotic, DSD, risk wilms)
Nail patella syndrome
Pierson - LAMB2 gene mutation - bilateral microcoria(fixed narrowing of pupil)
Antenatal may have elevated AFP
Autosomal recessive polycystic kidney disease
AR - 1:10,000-40,000 ; PKHD1 gene
Cystic dilations collecting ducts
Hepatic fibrosis
Antenatal - oligohydramnios, causing pulmonary hypoplasia ; echogenic kidneys
Large palpable renal masses
HTN
Renal impairment (normal in 20%)
Intrahepatic bile duct dilation (Caroli syndr), can cause portal HTN and hepatomegaly, risk varies and cholangitis
Rx supportive
30% die neonatal period due to pulmonary hypoplasia
ADPKD
Mutation PKD1(85%)/PKD2(15%) ; 1:1,000 Variable phenotype -Asymptomatic children, onset 20-30s often -HTN, proteinuria, HTN Renal US: Macroscopic cysts
Assoc with cerebral aneurysms and SAH and cysts in brain/liver/pancreas ; MVP
Nephronophthisis
Autosomal recessive disorder, 1:80,000
Tubular cysts
Polyuria, growth delay, anaemia
Cause ESRD children and adolescents
Associated findings Retinal degeneration (Senior loken synd) Cerebellar ataxia (Joubert) Hepatic fibrosis (Boichis)
Conditions associated with renal cysts
- Tuberous Sclerosis ( AD ; TSC1 OR TSC2 gene ; angiomyolipomas 80%, cystic disease 20%, risk RCC)
- VHL (AD, Cysts, renal cell ca)
- Bardet-Biedl (AR, obesity, syndactyly)
- NF1
Hypertension
normal BP <90th gentile for age or <120/80 for >13yrs
Elevated BP 90-<95th centile fo age or 120-129/80 for >13
Stage 1 HTN 95th-95+12mmHg or 130-139 / 80-90
Stage 2 HTN >95+12mmHg or >140/90
HTN urgency = Stage 1 +30mmHg ( >180/120 >13yr)
HTN emergency = Stage 2 HTN with symptoms/end organ damage
Symptoms - encephalopathy, seizures, headaches, epistaxis, vomiting, hemiplegia, diplopia, lethargy
HTN Treatment
Elevated BP: Lifestyle modification (diet, exercise, sleep) ; repeat 6/12
Stage 1: :lifestyle, recheck 2/52 ; check upper/lower limb ; if still elevated at 3rd visit ABPM monitor
Stage 2 - check upper and lower, Lifestyle, recheck 1 week ; if still high, ABPM, renal referral
Ddx HTN by age
<1month
- Renal artery thrombosis
- CoA
- Congenital renal disease (PUV, Renal hypoplasia or dysplasia, Reflux nephropathy, Cystic disease)
- BPD
1mo-6years
- renal parenchymal disease (GN, PKD, TIN, Renal scarring or dysplasia)
- Renovascular (? umber lines, neonatal asphyxia)
- CoA
> 6years
- Essential HTN
- Renal parenchymal and renovascular
HTN workup
ABPM
Urine - blood/protein/WCC ; metanephrines
Bloods - U&Es, catecholamines, TFTs, Cortisol, Renin/aldosterone
US kidneys +/- doppler
Organ damage
Echo for LVH (ECG not recommended)
Retinopathy - opthal
Microalbuminuria
HTN treatment
ACEi - first line in DM, CKD, proteinuria ;
CI if renal after stenosis
CCB - avoid in PKD
Thiazides
Nephrotic Management
Fluid restrict IV Albumin if hypovolaemia, severe oedema Low salt diet Penicillin prophylaxis Steroids -60mg/m2/day x 4 weeks - 40mg/m2 alt days x 4 weeks - wean over the next 4-6 weeks (3/12 total)
Relapse - 60mg/m2/day until remission and then 40mg/m2 alt days xs28days then stop
second line
Steroid resistant - CSA / tac, then Ritux
Steroid resp - consider cyclophosphamide >mmf>ritux
AKI - failure of kidneys to regulate water and electrolytes
Hyperkalemia / HTN/ Oedema
Pre-renal
- Low FeNa (<1%), Urine Na <20
- True volume depletion (bleeding, GI/Skin loss)
- Effective renal hypo perfusion: Hypotension - CHF, Septic shock, cirrhosis
Intrinsic (FeNa >1%, urine Na>40)
- Vasc - renal V thrombosis
- GN
- Interstitial - pyelo ; Tubulointerstitial nephritis
- Tubular - ATN (Aminoglycosides, tumor lysis,)
Post renal (obstructive)
- to cause AKI needs to be bilateral
- Stones / trauma / clots / tumour
- Bladder outlet obstruction
AKI management
Treat cause
Fluid overload is independent mortality RF
Fluid management - insensible losses + urine output
Nutrition - prevent catabolism, electrolyte control
Causes Paediatric CKD
Glomerular (oliguria, haematuria, proteinuria, HTN)
- Chronic GN
- FSGS
- Congenital nephrotic
- Alports
- HUS
- Cortical necrosis
Non glomerular
- Reflux nephropathy
- Hypoplasia/dysplasia
- Cystic - PKD, nephronopthisis
- Obstructive uropathy (PUV, prune belly, neurogenic bladder - UTIs, Type 4 RTA, pseudohypoaldosteronism - hyperkalemia, hyperchloraemic acidosis)
- Tubular / tubuloinstestital disorders - polyuria
eg cystinosis - fair skin, blue eyes, phosphate wasting
Metabolic bone disease / renal osteodystrophy
Reduced 1 alpha hydroxylase activity caused reduction in active vitamin D
- leads to reduced calcium ; hypocalcemia stimulates PTH production (PTH increases calcium reabsorption and PO4 excretion)
- Excess PTH causes bone resorption
Also GFR falls, reduced PO4 excretion - leads to hyperphosphatemia which further causes hypocalcemia and increased PTH
Weakness, bone pain, fractures ; Rickets in growing children
Rx: Activated Vitamin D (calcitriol) suppresses PTH (monitor for hyeprcalcemia)
Multicystic dysplastic kidneys
1/4000 live births ; M:F= 2:1 Unilateral non functional cystic mass No identifiable parenchyma or renal shape Atretic proximal ureter Often involute if <5cm by 2yrs
Often get VUR in contralateral kidney (25%)
Acute interstitial Nephritis
immune mediated infiltration kidney interstitium by inflammatory cells
Hypersensitivity to Drugs - NSAIDs, penicillins, cephalosporins, sulphonamides
(Occurs 1-2 weeks after exposure)
Autoimmune with uveitis (TINU)
Infection - HIV, Hep B
Polyuria, often have rash/fever
Urine: White cell casts ; eosinophils
Side effects Calcineurin inhibitors
Tac / CSA - inhibit T cell activation
Ciclosporin: Nephrotoxic, HTN, gingival hyperplasia, hirsutism, hyperuricemia, high cholesterol
Tacrolimus: tremors, low magnesium, diarrhoea, alopecia, DM
Peritoneal Dialysis
Indications AEOIU
Increase ultrafiltration
- Increase dwell/fill volume
- increase no cycles
- increase glucose concentration dialyse
Risk PD peritonitis ; fluid >100WCC
CONS>Staph aureus > strep > pseudo
Rx IP Abx x 3 weeks
Paediatric AKI
pRIFLE
Risk: Reduce GFR by 25% ; UO <0.5ml/kg/hr x 8 hours
Injury: Reduce GFR 50% ; UO <0.5ml/kg/hr x 16hours
Failure: Reduce GFR by 75% ; UO <0.3ml/kg/hr 24hours or anuria for 12 hours
Loss : Persistent failure for >4weeks
End stage: Persistent failure >3mo
Stage 1: Cr 1.5x baseline
Stage 2: Cr 2-3x baseline
Stage 3: Cr >3x baseline
Neonatal AKI, serum cr>130
VUR
Diagnosed on MCUG
30% patients who have had febrile UTI
5-15% infants with congenital hydronephrosis
- Reflux into non dilated ureter
- Reflux into upper collecting system with no dilation
- Reflux into dilated ureter +/or blunting of calyces fornices
- Reflux into grossly distended ureters
- Massive VUR with significant ureter dilation and tortuosity, loss of papillary impression
High Pressure = reflux on passing urine Low pressure = reflux on bladder filling Genetic component (AD with variable penetrance)
Renal imaging
US - anatomy and cysts
MCUG - assess VUR and PUV
DTPA - dynamic scan, assess function - use for investigation of obstruction follow up post op for dilated kidneys. Excreted by GFR
MAG3 - assess function. Secreted by tubules
DMSA - static scan, assess cortical scars
Mycophenolate mofetil (Cellcept)
antimetabolite, blocks purine synthesis, inhibits proliferation B/T cells
SE Blood (cytopenias), GI (N+V), dose related SE
Medications that elevate Tacrolimus levels and risk toxicity
Macrolides Fluoroquinolones (Cipro) NSAIDs Antifungals Omeprazole
Medications that lead to reduction Tacrolimus levels and risk rejection
AEDs
Rifampicin
FeNa
urine na x serum cr / urine cr x serum na
FENa <1% suggests pre renal AKI, a FENa above 2% suggests ATN, a FENa between 1 and 2% is non-diagnostic.
ATN urine results
Casts
Low osmolality
<40 urea/cr ratio
High Na
Chloride in urine
High in diuretic abuse, Bartters, Gitelmans
Low with vomiting and laxative abuse
Six causes of allograft dysfuncTION
DehydraTION MedicaTION InfecTION ObstrucTION RejecTION PrefusION problem
Normal anion gap metabolic acidosis (not due to diarrhoea) causes
RTA
Type 1: unable to excrete H+ (urine mor alkaloid making a higher urine pH) low hCO3 level
Type 2: reduced bicarb reabsorption (assoc w Fanconi syndrome), acidic urine (no bicarb buffer)
Type 4: hyperkalaemia major feature, lose sodium in urine and keep potassium from mineralocorticoid def/insensitivity (hx obstructive uropathy or due to adrenal disease)
Bladder capacity child
(Age x 30) + 30
Nephrogenic DI
90% are mutations in the ADH receptor (AVPR2)
gene; X‐linked.
• Over 180 mutations so variable affects.
• Remaining 10% are mutations in the aquaporin 2
(AQP2) channel; autosomal recessive/dominant
What are the causes of an increased AG metabolic acidosis?
MUDPILES Methanol, Uremia, DKA, Paraldehyde, Iron or Isoniazid, Lactate, Ethylene Glycol, Salicylates
What are the renal manifestations of tuberous sclerosis?
- Renal angiomyolipomas 80% (if >4cm tx sirolimus)
- Cystic disease 20%
- Renal cell carcinoma <1%
What is the pRIFLE criteria?
Used for AKI
- Risk - decr GFR by 25%, <0.5ml/kg/hr for 8 hrs
- Injury - decr GFR by 50%, <0.5ml/kg/hr for 12 hrs
- Failure - decr GFR by 75%, anuric 12hrs
- Loss - persistent failure > 4 weeks
- End stage - persistent failure > 3 months
What is the 10-4 rule with albumin?
A 10g/L drop in albumin leads to a 4mmol/L drop in the anion gap
nephrocalcinosis
- USS: diffuse speckled calcification
- Calcification of renal tissue
- Causes of nephrocalcinosis: distal RTA, ex-prems (frusemide, steroids), Vit D treatment for phosphatemic rickets, oxalosis
What are the causes and complications of neurogenic bladder?
- Spina bifida, sacral agenesis (maternal diabetes), tumour, trauma, transverse myelitis
- Can lead to renal damage, incontinence, UTI (incomplete emptying), high pressure VUR, progressive renal scarring, detrusor-sphincter dyssynergia (leading to bladder hypertrophy and trabeculation, hydronephrosis), atonia (large, chronically distended, poor emptying)
- Ix: video urodynamic assessment, kidney function/scarring
- Tx: bladder relaxation with oxybutynin if unstable contractions, and clean intermittent catheterisation, augmentation cystoplasty (larger capacity, low pressure)
What are the dietary considerations in CKD?
- Aggressive nutrition, many need NGT/PEG
- Generous H20 intake, Na+ supps (wasting in polyuria) or restriction (if oedema + water retention)
- No protein restriction
- Phosphate restriction, use of phosphate binders (calcium carbonate) to control secondary hyperparathyroidism
- Restriction of potassium (fresh fruit, potatoes)
- Sodium bicarb supps for acidosis
Lowe syndrome (oculocerebrorenal syndrome of Lowe)
- X-linked
- Congenital cataracts, mental retardation, and Fanconi syndrome
- Mutations in the OCRL1 gene, abnormal transport of vesicles within the Golgi apparatus
- Present in infancy with cataracts, progressive growth failure, hypotonia, and Fanconi syndrome
- Significant proteinuria is common
- Blindness and renal insufficiency often develop
- Characteristic behavioral abnormalities: tantrums, stubbornness, stereotypy (repetitive behaviors), and obsessions
- There is no specific therapy for the renal disease or neurologic deficits
features and causes of Fanconi syndrome
Diffuse proximal tubular dysfunction leading to excess urinary loss of:
- Glucose - glycosuria, normal BSL
- Phosphate - low phos, low TRP, rickets
- Amino acids - no obvious consequence
- Bicarb - proximal RTA
- K+ - hypokalaemia
- Na, Cl, H2O - polyuria, polydipsia, chronic decr ECF volume, faltering growth
- Tubular proteins - LMW e.g. retinol-binding + N-acetylglucosamine
Polyuria, polydipsia, faltering growth, constipation, rickets
- Causes:
- Metabolic - cystinosis, tyrosinemia, Lowe syndrome (oculocerebrorenal syndrome)
- Galactosemia
- Wilson disease
- heavy metal toxicity (lead, mercury, cadmium)
- idiopathic, ifosfamide, cisplatin, azathioprine
- ATN, tubulointerstitial nephritis
- Tx: replacement of fluid, bicarb
Discuss X-linked hypophosphatemic rickets
- Vitamin D resistant rickets
- Mutation in PHEX gene on X-chromosome
- Defect in phosphate resorption, low TRP (<85%), normal PTH and calcitriol level, hypophosphatemia
- Age 3-4m - inc ALP
- Age 6-9m - decr phosphate
- Age 12m - delayed growth, low phos, inc ALP, x-ray signs of rickets, delayed dentition, recurrent dental abscesses
- Tx: phos + calcitriol supps, watch for hypercalcaemia and nephrocalcinosis, may need growth hormone
What molecules act on the kidney to increase renal blood flow?
- ANP and BNP (from heart) - cause afferent dilation and efferent constriction - inc GFR
- Prostaglandin I2 and E2 (from kidney) - cause afferent and efferent dilation - inc GFR
- Dopamine (from brain and kidneys) - cause afferent and efferent dilation - inc GFR
Vit D synthesis
Vit D (cholecalciferol) from UV light - hydroxylated in liver to 25 (OH) vitamin D3 (by 25-hydroxylase)
- Production of 1-25 (OH) Vit D3 (calcitriol) via renal 1-hydroxylase in kidney = most biologically active Vit D metabolite
- 24-alpha hydroxylase in kidney converts Vitamin D to an inactive form
hypocalcaemia
Rickets, seizures, tetany, stridor, cramps, paresthesia
- Treatment: IV 10% calcium gluconate with ECG monitoring, PO calcium supps, Vit D/alfacalcidol
causes:
- Low calcitriol: Vitamin D def, renal failure or liver failure
- Iatrogenic: frusemide
- Hypoparathyroidism - transient neonatal, DiGeorge, PT removal
- Acute pancreatitis
- Acute alkalosis or correction of acidosis in context of normal-low calcium
- Hyperphosphatemia (complexes free calcium): RF, rhabdo, tumour lysis
- Pseudohypoparathyroidism e.g. Albright’s hereditary osteodystrophy
hypercalcemia
Constipation, renal stones, nausea, lethargy, confusion, headaches, muscle weakness, polyuria, dehydration
- IV hydration, loop diuretics, rarely bisphosphonates (stop bone resorption)
- Familial hypocalciuric hypercalcaemia, Williams (rarely persists >1y age)
- Hyperparathyroidism - neonate or MEN1+2
- Iatrogenic: Vit D excess
- Macrophage production of calcitriol (sarcoidosis, subcut fat necrosis)
- Malignancy
influence of pH on calcium
As pH decreases (acidosis), H+ displaces Ca2+ from binding sites and the amount of iCa2+ increases
- Conversely, as the blood pH increases (alkalosis), albumin and the globulins become more negatively charged and bind more calcium, causing the amount of iCa2+ circulating to decrease. Therefore always correct acidosis prior to giving albumin, otherwise will cause hypocalcaemia as albumin will bind to the increased free calcium
hypophosphatemia
- Hyperparathyroidism (increased urinary excretion of phosphate)
- Dietary deficiency. Appropriately high TRP (low urine phosphate)
- Hypophosphatemic rickets, Fanconi syndrome. Inappropriately low TRP (high urine phosphate)
- Tx: PO phosphate, Vit D replacement
hyperphosphatemia
- High urine phosphate, low TRP (appropriate) - rhabdomyolysis, tumour lysis
- Low urine phosphate, high TRP (inappropriate) - CRF, hypoparathyroidism, pseudohypoparathyroidism
- Tx: phosphate binders (ec calcium carbonate), dialysis
X-linked hypophosphatemic rickets
- Vitamin D resistant rickets
- Mutation in PHEX gene on X-chromosome
- Defect in phosphate resorption, low TRP (<85%), normal PTH and calcitriol level, hypophosphatemia
- Age 3-4m - inc ALP
- Age 6-9m - decr phosphate
- Age 12m - delayed growth, low phos, inc ALP, x-ray signs of rickets, delayed dentition, recurrent dental abscesses
- Tx: phos + calcitriol supps, watch for hypercalcaemia and nephrocalcinosis, may need growth hormone
Nocturnal enuresis
Monosymptomatic nocturnal enuresis is defined as urinary incontinence occurring during sleep, without any other lower urinary tract symptoms and without a history of bladder dysfunction, in children > 5 years of age. • It is very common, affects boys more than girls, and resolves spontaneously at 15%/year. • 5 years – 15 % of children affected • 6years–13% • 7years–10% • 8years–7% • 10years–5% • 12to14years–2to3% • ≥15years–1to2%
Prune-belly (Eagle-Barrett) syndrome (PBS)
Incidence 1 in 40,000 to 50,000 births, males > females
congenital disorder w clinical triad of:
Abdominal wall muscle deficiency –complete/partial (thus wrinkled belly)
Severe urinary tract abnormalities
Bilateral cryptorchidism in males
May be a/w CHD (ASD, VSD, TOF), GI anomalies
Consequences of oligohydramnios: pulmonary hypoplasia, hip dislocation/subluxation, talipes
Nephrocalcinosis
• Distal RTA
• Ex-premature neonates:
• Furosemide – hypercalciuria
• Steroids – hypercalciuria
• Vitamin D treatment for hypophosphataemic rickets:
• Enhances tubular reabsorption of Ca2+
• Oxalosis:
- Autosomal recessive disorder
- Primary hyperoxaluria associated with defect in alanine:glyoxylate aminotransferase (AGT) enzyme, which leads to excess oxalate production and urinary oxalate excretion
- Calcium oxalate precipitates, nephrocalcinosis and obstructing stones form, renal failure ensues
- Systemic oxalosis – joints, heart, blood vessels
- Treatment – liver transplantation alone if renal function only moderately reduced; sequential liver then kidney transplantation if renal failure established, with intense dialysis therapy between the two operations to lower the systemic oxalate burden (simultaneous liver–kidney transplantation presents high risk of oxalate deposition in newly transplanted kidney)
Nutcracker syndrome
compression of left renal vein between aorta and proximal SMA, causes microscopic haematuria
Renal Stones
Composition of stones
• radioopaque stones (90%): CaPO4, CaO..
• relatively radiolucent: cystine, struvite…
• radiolucent stones: uric acid, xanthine, indinavir)
Causes
Calcium stones - most common
• hypercalciuria (polygenic, may be autosomal dominant in some families)
o idiopathic
o absorptive - high Ca or Na diet (NB: dietary K is protective), Vit D excess, Vit C (oxalate precursor),
o renal - renal leak, distal RTA type 1, frusemide,
o resorptive - hyperparathyroidism, immobilisation, sarcoid, corticosteroids, Cushing
• hyperoxaluria {progress to ESRF in 20s]
o primary (AR),
o secondary (Vit C, malabsorption, pyridoxine deficiency)
o enteric (IBD, pancreatic insufficiency, biliary disease)
o NB: CF ~5% – pancreatic insufficient, malabsorption and NaCl failure to excrete
• hypocitruria (chronic diarrhoea, malabsorption, idiopathic)
• renal tubular acidosis (RTA) – Type I (alkaline urine, hyperchloraemic hypokalaemic metabolic acidosis,
• hyperuricosuria
• cystinuria (heterozygous)
Cystine stones
• cystinuria
Struvite stones (Magnesum ammonium phosphate)
• UTI (urea splitting organisms such as Proteus, Klebsiella, E coli, Pseudomonas)
• Foreign body
• Urinary stasis
Uric acid stones (RADIOLUCENT)
• Hyperuricosuria
o Inborn errors of metabolism - Lesch-Nyhan syndrome, G-6-PD,
o Rapid purine turnover - myeloproliferative disorders, post-chemotherapy,
o Short bowel, IBD
Indinavir stones – HIV Rx, 4% of patients develop stones
Nephrocalcinosis
• Commonest - prem neonates receiving frusomide
• Other common - medullary sponge kidney, distal RTA, hyperparathyroidism, hypophosphataemic rickets, sarcoid, cortical necrosis, hyperoxaluria, prolonged immobilisation, Cushing syndrome, hyperuricosuria, renal candidiasis.
Inihibitors of stone formation
• Citrate, Magnesium – inhibits crystallization and aggregation.
• Glycosaminoglycans, Tamm-Horsfall protein
• Proximal RTA protective – decreased HCO3 resorption U citrate (vs dRTA –ass stones)
Stones work up
Urinalysis - ?infection
Renal USS ?obstructed system – need urological input
Stone analysis if possible (?Cystine, Uric acid, Struvite, CaO/CaPO4)
-if likely CaO/CaPO4 (most are):
Urine: urinalysis, pH, M/C/S
Ca:Crt ratio (usually <0.2, if fasting should be <0.7), Oxalate:Crt ratio
Citrate, L-gllyceric acid
+/- Urate:Crt, Cystine
24hour: Ca, Oxalate, Uric acid, citrate, crt. ?Na
Plasma: UEC, C/M/P, HCO3, Cl, PTH +/- Urate
-if cystine – microscopy/cyanide-nitropresside/urine aa chromatography as above.
Treatment
• Address specific underlying disorder if possible
o Uric acid stones -> allopurinol (xanthine oxidase inhibitor)
o Cystine stones -> urine alkalinisation, D-penicillamine (chelating agent), NAC?
o RTA I – correct acidosis, replace K and Na.
o Hyperoxaluria primary – pyridoxine, liver transplantation (ideally before renal failure)
• General prevention
o Increase fluid intake (Increase urine volume), night and day
o Reduce Na intake, normal Ca intake (not reduced for growing kids),
o Reduce animal protein intake/vegetarian diet, limit sucrose/fructose, small quantity of wine!
o Thiazide diuretics (reduce renal calcium excretion)
o Potassium citrate (inhibitor of stone formation), or lemonade/lemons
o Urinary alkalisers – sodium bicarbonate/citrate,
• Surgical/endoscopic/lithotripsy removal/stent – consider if large, causing significant obstruction or infection.
• Enhance passage – alpha-adrenergic blockers
A high sodium diet is one of the strongest contributors to stone disease in western society. High sodium diet leads to increased sodium excretion from kidney. Increased sodium excretion is accompanied by increased calcium excretion.
Magnesium is an inhibitor of calcium oxalate stone formation. Hypomagnesuria therefore predisposes to stone formation.
Citrate is an inhibitor of calcium stone formation. Therefore, LOW urinary citrate (hypocitruria) predisposes to stone formation.
Renal stones in pancreatic insufficiency
Oxalate
Uric acid stones
Lesch Nyan, G6PD, post chemo
Juvenile Nephronopthisis
- AR inheritance
- Paediatric disease (clinical similar but genetically distinct from MCD)
• Signs & symptoms
o Polyuria, polydipsia
o Anaemia due to failure of EPO production
o EPO made by cells at corticomedullary junction (this is the site of maximal pathology) => EPO insufficiency occurs early (c/f CKD)
o Growth retardation
Due to salt deficiency (rather than due to renal failure)
o ESRF - major cause of ESRF in kids
o Urinalysis is often normal/minimally abnormal
• Pathology
o Kidneys normal size
o Corticomedullary cysts - Small, not seen distinctly on USS, No extra-renal cysts
• Histopathology o Tubules Basement membrane thickening/attenuation Distal tubular atrophy Cysts o Interstitium Lymphocytes Fibrosis o Glomeruli Periglomerular fibrosis • Genetics o NPH (AR) o NPH1 – juvenile form (common – probably what this kid has) o NPH2 – infantile (uncommon) o NPH3 and NPH4 o Syndromic (many related to cilia dysfunction) Oculomotor apraxia (large NPH1 deletion)
Senior-Loken
• Retinitis pigmentosa by 10y
• Present with blindness/coarse nystagmus by age 2 (not related to NPH1)
• Liver fibrosis
Joubert type B (cerebello-oculo-renal syndrome) • NPH • Coloboma • Retinal degeneration • Aplasia of cerebellar vermis • Polydactyly • Developmental delay
Jeune • Asphyxiating thoracic dysplasia • Neonatal RDS • Limb shortening • Polydactyly, nail abnormalities • Other skeletal abnormalities • Liver disease • Nephronophthisis • With heavy proteinuria • Not linked to NPH1, 2 or 3 genes Ellis-van Creveld • Skeletal abnormalities same as Jeune
Bardet-Biedl • Group of 6 diseases • Polydactyly • Truncal obesity • Renal dysfunction (15% ESRF) • Pigmentary retinopathy • Short stature • Intellectual disability • MCKD (AD – adults) • MCKD1 and MCKD2 • NPH1 (Juvenile Nephronophthisis) • 80% of nephronophthisis • 2q13 – large deletion in 2/3 • NPH1 – codes for nephrocystin – protein that fits into lateral tubular cell wall and basement membrane • Early onset polyuria, polydipsia, dilute urine • Anaemia later • Growth retardation is later • Hypertension is rare • Diagnosis: o Clinical picture fits renal ultrasound presumptive diagnosis o Confirmatory genetic testing, renal biopsy o Normal kidney size on US o Check family history o ?any extra-renal manifestations o NPH2 (infantile) Rare Enlarged kidneys
• Differential diagnosis of nephronophthisis
o Renal dysplasia (USS)
o Hypoplastic kidneys (USS)
o VUR with reflux nephropathy (hypertension, proteinuria)
o Obstructive uropathy (DMSA, US)
Posterior urethral valves
• Most common cause of severe obstructive uropathy in children
o 1:8000 boys
o Valves = tissue leaflets fanning distally from prostatic urethra to external urinary sphincter, with slit-like opening between leaflets
• Severity of obstruction varies
o 30% ESRF/CRF
o 50% VUR
• Renal sequelae vary along spectrum
o Mild hydronephrosis
o Up to severe renal dysplasia
o Severity probably relates to severity of obstruction and time of onset during development
o Oligohydramnios with consequent pulmonary hypoplasia
• Diagnosis
o Antenatal scans – bilateral hydronephrosis, distended bladder, +/- oligohydramnios
o Palpable, distended bladder with weak urinary stream in male neonate
o If unrecognised may present later with FTT (uraemia, sepsis) if severe; if less severe present later in childhood with difficulty toilet-training or UTI
o Confirmatory investigations
Voiding cystourethrogram
Perineal US
o Other investigations
Renal function
Delineate upper tract anatomy
• Management
o Well neonate – insert small feeding tube into bladder
If Cr improves transurethral valve ablation
If urethra too small temporary vesicotomy
If doesn’t improve (Cr or static)
Consider renal dysplasia, irreversible renal damage, secondary urethral obstruction
Vesicodomy
o Sick baby
Manage sepsis, stabilize electrolyte balance, resuscitate
May need temporary percutaneous nephrostomy (to drain upper tract) and dialysis
o Older kid
Primary valve ablation
• Prognosis Favorable Normal 18-24/40 USS Cr <0.08-0.1 after bladder decompression Corticomedullary junction visualized on renal USS Oligohydramnios in utero
Unfavorable Hydronephrosis identified <24/40 Cr >0.1 after bladder decompression Bilateral cortical renal cysts Persistence of diurnal incontinence >5y of age
• In neonates:
o Prognosis relates to degree of pulmonary hypoplasia and potential for recovery of renal function
o In very severe disease – may be stillborn
o If survive neonatal period – 30% have persistent renal insufficiency and may require transplant
• Post-definitive treatment
Sodium regulation
There are 4 main sites of sodium transport proximal tubule (60%) ascending loop of Henle (25%) distal tubule (15%) collecting tubule
Major hormonal mechanisms mediating sodium balance:
Renin-angiotensin-aldosterone axis
angiotensin II increases sodium reabsorption in proximal tubule
aldosterone increases sodium reabsorption in distal tubul, therefore suppression of renin promotes sodium excretion
Atrial natriuretic factor
produced in response to atrial distension, angiotensin II stimulation and sympathetic stimulation
therefore, increased in hypervolaemic states
promotes sodium excretion (increases GFR, decreases renin release)
Noradrenaline
released in response to volume depletion
decreases renal blood flow, therefore decreases the amount of sodium filtered and stimulates renin release (reduction in afferent arteriole pressure causes release of renin from JG cells)
therefore indirectly increases sodium concentration
Na-K ATPase is ATP-dependent pump system essential for maintaining Na and K concentrations across sarcolemmal membranes (e.g. cadiac myocytes)
Tubulo-glomerular feedback
macula densa cells sense Na levels in tubular fluid and alter GFR (i.e. high Na concentration indicates high GFR and vice versa)
detection of high Na levels triggers release of signalling molecules from macula densa which drops GFR, problaby by constriction of afferent arteriole
Juvenile Nephronophtisis
- AR inheritance
- Paediatric disease (clinical similar but genetically distinct from MCD)
• Signs & symptoms
o Polyuria, polydipsia
o Anaemia due to failure of EPO production
o EPO made by cells at corticomedullary junction (this is the site of maximal pathology) => EPO insufficiency occurs early (c/f CKD)
o Growth retardation
Due to salt deficiency (rather than due to renal failure)
o ESRF - major cause of ESRF in kids
o Urinalysis is often normal/minimally abnormal
• Pathology
o Kidneys normal size
o Corticomedullary cysts - Small, not seen distinctly on USS, No extra-renal cysts
• Histopathology o Tubules Basement membrane thickening/attenuation Distal tubular atrophy Cysts o Interstitium Lymphocytes Fibrosis o Glomeruli Periglomerular fibrosis
• Genetics o NPH (AR) o NPH1 – juvenile form (common) o NPH2 – infantile (uncommon) o NPH3 and NPH4 o Syndromic (many related to cilia dysfunction) Oculomotor apraxia (large NPH1 deletion) Senior-Loken • Retinitis pigmentosa by 10y • Present with blindness/coarse nystagmus by age 2 (not related to NPH1) • Liver fibrosis Joubert type B (cerebello-oculo-renal syndrome) • NPH • Coloboma • Retinal degeneration • Aplasia of cerebellar vermis • Polydactyly • Developmental delay Jeune • Asphyxiating thoracic dysplasia • Neonatal RDS • Limb shortening • Polydactyly, nail abnormalities • Other skeletal abnormalities • Liver disease • Nephronophthisis • With heavy proteinuria • Not linked to NPH1, 2 or 3 genes Ellis-van Creveld • Skeletal abnormalities same as Jeune Bardet-Biedl • Group of 6 diseases • Polydactyly • Truncal obesity • Renal dysfunction (15% ESRF) • Pigmentary retinopathy • Short stature • Intellectual disability
- MCKD (AD – adults)
- MCKD1 and MCKD2
- NPH1 (Juvenile Nephronophthisis)
- 80% of nephronophthisis
- 2q13 – large deletion in 2/3
- NPH1 – codes for nephrocystin – protein that fits into lateral tubular cell wall and basement membrane
- Early onset polyuria, polydipsia, dilute urine
- Anaemia later
- Growth retardation is later
- Hypertension is rare
• Diagnosis: o Clinical picture fits, then renal ultrasound and presumptive diagnosis o Confirmatory genetic testing, renal biopsy o Normal kidney size on US o Check family history o ?any extra-renal manifestations o NPH2 (infantile) Rare Enlarged kidneys
• Differential diagnosis of nephronophthisis
o Renal dysplasia (USS)
o Hypoplastic kidneys (USS)
o VUR with reflux nephropathy (hypertension, proteinuria)
o Obstructive uropathy (DMSA, US)
Metanephric mesenchyme gives rise to
Majority of nephron - Bowmans capsule, proximal tubule, Loop of Henle, distal tubule
Ureteric bud gives rise to
Collecting duct, renal pelvis, ureter
Fe NA
(UNa/SNa) / (Ucr/SCr) x 100%
= (UNaXSCr) / (SNaxUcr) x 100%
Pre renal <1% ; post renal >2%
Cant use if on diuretics, use Fe Urea (<35% pre-renal)
