04 Nephrology
Transcript of 04 Nephrology
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4) NEPHROLOGY
General Outline
Urinary Tract Infections
Acute Glomerulonephritides
Nephrotic syndrome
Acute Renal Failure
Chronic Renal Failure Approach to Haematuria
______________________________________________________________
Urinary Tract Infections (UTIs)
Introduction
UTI in infants may be associated with bacteraemia or sepsis
Pyelonephritis and urinary tract malformations form a major cause of chronic renal failure in childhood
Association with vesico-ureteric reflux
Indicator of an underlying congenital abnormality that may require
surgical intervention 50% of these children have a structural abnormality
Symptomatology of UTI in children
Diagnosis of UTI
Urine dipstick for nitrites and leukocyte esterases
Urine microscopy for pyuria
o Boys: >10/µ l uncentrifuged urine
o Girls: >50/µ l uncentrifuged urine
Urine microscopy for bacteria
Urine cultureo Midstream
o Catheter
o Suprapubic aspiration
Criteria for significant bacteriuria
Method of collection Colony count/ml(Pure culture)
Probability of infection
Suprapubic aspiration GNB: any number GPC: >103
> 99%
Transurethralcatheterization
>105
104-105
103-104
<103
95%Infection likelySuspicious, repeatInfection unlikely
Clean voidBoyGirl
>104
3 specimens >105
2 specimens >105
1 specimen > 105
5x104-105
104-5x104
<104
Infection likely95%90%80%Suspicious, repeatSyptomatic: suspicious,repeatAsymptomatic: infection
unlikelyInfection unlikely
Symptoms of UTI
Specific
• Frequency• Urgency
• Dysuria
• Abdominal pain
• Cloudy urine
• Loin pain
• Enuresis
Non-specific
• Fever, fits• Vomiting
• Diarrhea
• FTT
• Jaundice
• Feeding difficulty
• Screaming attacks
If positive
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Predisposing factors
Infecting organisms (usually bowel flora)o E.coli : more often in girls
o Proteus: more often in boys as it is present under prepuce and
predisposes to phosphate stoneso Pseudomonas: indicates structural abnormality affecting
drainage
Incomplete bladder emptying urinary retention and stasiso Infrequent voiding
o Hurried micturition
o Constipation
o Neuropathic bladder
o Bladder neck obstruction
o Posterior urethral valve
Suspect if stone excluded in male infant with bilateralhydronephrosis
Vescio-ureteric reflux (VUR)
Pelvi-ureteric junction obstruction
Clinical classification of UTI
Clinical Upper Tract Lower tract
Age < 2 years > 2 years
Fever + -
Voiding problem - +
Suprapubic pain - +
Loin pain + -
CRP ↑ N
Renal involvement(Cr, US, DMSA scan)
+ -
Initial investigations of confirmed UTI Ultrasound of urinary tract
o Non-invasive procedure which gives information on the renal
size and shape, bladder size and configuration, bladder wallthickness, presence of absence of pelvicalyceal and ureteraldilatation.
DMSA (Dimercaptosuccinic acid) scano Radioisotope scan that picks up focal areas of decreased
uptake.
o Useful for diagnosing acute pyelonephritis in the acute stage
whereas scans performed 3-6 months later may demonstratethe presence of established scars.
o Differential function of the 2 kidneys can be estimated from
this scan.
MCU (Micturiting cysto-urethrogram)o Gives information on bladder and urethral lesions, on
competence of the vesico-ureteric valves and the grade of
VUR if present. MAG-3 renogram
o If the ultrasound scan of the kidney shows significant
pelvicalyceal dilatation, the next investigation would be a99mTc DTPA or MAG3 renograrn to distinguish between atrue mechanical obstruction and nonobstructive pelvicalycealdilatation.
o It also gives the differential function of both kidneys.
o Better than IVU as children cannot concentrate contrast well.
Once ultrasound shows hydronephrosis and hydroureter, differentialdiagnosis include
o Vesico-ureteric reflux
o Obstruction
Bladder outlet obstruction
• Neurogenic bladder
≤ 2 yrs > 2 yrs
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• Posterior urethral valve
Vesico-ureteric junction obstruction
VUR is best diagnosed by MCU.
VUR is significant only in the presence of infection
Summary
o All children will confirmed UTI will go for a DMSA + MCU
EXCEPT
o Those with pelvicalyceal dilatation of more than 1cm who will
go for a MAG-3 renogramAND
o Girls older than 2 years with a first febrile UTI who will go for a
DMSA first and proceed to a MCU only if DMSA if positive
Most likely infection in these children is likely to belower tract. Hence once DMSA has ruled out renalscarring, we can begin treatment as for a lower urinary tract infection.
Treatment of UTI
Principles of anti-microbial therapy
o Organism should be susceptible to the antimicrobial durg,hence the importance of appropriate urine cultures beforestarting.
o The drug should have minimal adverse effects on the major
organ systems.o A high concentration of the drug should be present in the urine
after administration.o The drug should have a convenient route of administration.
Problems of short-course therapy in childhoodo Bacteraemia present in 20-30% of children with UTI
o Case fatality rate with septicaemia is 10%
o Higher incidence of congenital abnormalities including vesico-
ureteric reflux in the young child. Uncomplicated infectionso Oral antibiotics for 5-7 days can be used to initiate treatment.
o Response to chosen antibiotics should be seen after 3 days of
treatment.o If repeat cultures done then are still +ve, one must consider
the possibility of resistant organisms, inadequate drugdosages or drug interactions or an obstructed urinary tract.
Complicated infections
o Parenteral antibiotics should control the symptoms within 48-
72h of instituting therapy.o Once results of the antibiotic sensitivity tests are available,
one single, appropriate drug should be continued.o Use of aminoglycoside may be hazardous in children with
underlying renal abnormalities and renal impairment.
o Once the infection is under control, as confirmed by a repeat
urine culture after 72h of treatment, the child can be continued
on the appropriate oral antibiotics Prophylactic antibiotic therapy (is recommended for)
o Children with obstructive uropathies before surgery and up to
6 months post-surgery if the urinary tract remains grosslydilated.
o Those with VUR on conservative medical therapy.
o Some children with recurrent UTI in the absence of anatomical
defects. Local factors should first be excluded i.e. poor hygiene, constipation with infrequent voiding, preputialcontamination, incorrect cleaning after defaecation, tightclothing with perineal moisture accumulation. Patient andparental education are useful in minimizing the infectiveepisodes. In boys with problems due to preputial colonization,circumcision is recommended. If these factors are correctedbut the infections persist with symptoms, these children maybenefit from 6 to 12 months of antibiotic prophylaxis.
Clinical diagnosis of UTI
Fever No Yes
Lower Tract Infection Upper Tract Infection
Age Age
< 12 yrs ≥ 12 yrs
7-10 daycourse
3 daycourse
1. Trimethoprim-sulfamethoxazole(Bactrim)2. Cephalexin/Cefaclor (G6PD deficient)Review antibiotics onceculture results areavailable.
< 28 days ≥ 28 days
Full sepsiswork-up
Ampicillin and Gentamicinpending culture results for minimum of 48-72 hoursthen oral therapy.
Non-toxicToxic
Admit +/- Admit
Parenteral untilasymptomatic for 24h thenoral to complete 10-14 daycourse1. Gentamicin or Amikacin+/- Ampicillin2. Cefotaxime or Ceftriaxone+/- Ampicillin
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Vesico-ureteric reflux (VUR)
Introduction VUR is a condition in which urine from the bladder is able to flow backup into the ureter and kidney.
It is caused by a problem with the valve mechanism.
Pressure from the urine filling the bladder should close the tunnel of the ureter. It should not allow urine to flow back up into the ureter.
When the ureter enters the bladder at an unusual angle or when thelength of the ureter that tunnels through the bladder wall is too short,reflux can occur.
VUR becomes a problem when the urine in the bladder becomesinfected. The infected urine easily travels backwards to the kidney andcan cause a kidney infection. Kidney infections lead to kidney damage.
May be associated with renal dysplasia
May be familial
Pathophysiology
Incomplete bladder emptying as urine returns to bladder from uretersafter voiding
Pyelonephritis may occur especially if there is intrarenal reflux
Bladder voiding pressure transmitted to renal papillae which results inrenal damage, hydroureter and clubbed calyces.
Infection destroys renal tissue, which results in scarring.o Causes shrunken segment of kidney
o Severe bilateral scarring may lead to chronic renal failure
o Scars produce increased quantities of renin which leads to
hypertension.o Scarring is associated with increased risk of eclampsia in
pregnancy.
International classification of VUR
o Grade I – reflux into non-dilated ureter
o Grade II – reflux into the renal pelvis and calyces without
dilatationo Grade III – mild/moderate dilatation of the ureter, renal pelvis
and calyces with minimal blunting of the forniceso Grade IV – dilation of the renal pelvis and calyces with
moderate ureteral tortuosityo Grade V – gross dilatation of the ureter, pelvis and calyces;
ureteral tortuosity; loss of papillary impressions
Causes of VUR
Primaryo Incompetence of vesico-ureteric (VU) sphincter
Anatomical distortion of VU junction
• Congenital paraureteral diverticulum
• Ectopic ureter
Bladder dysynergia
Secondaryo Infection
o Bladder outlet obstruction
Posterior urethral valves
Neurogenic bladder
Management
Conservative (Medical) Surgical
Grades I-III: spontaneous resolution Grades IV-V: Progression of scarring(recurrent pyelonephritis)
Long-term antibiotic prophylaxis Re-implantation of ureter or endoscopic injection
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For grades I-III there is a good chance that the reflux will disappear asthe child grows and the bladder matures. These children are givenlow-dose antibiotics daily, to suppress bacteria from growing.Occasional blood tests and urine cultures may be ordered.
An option for patients with grades I-IV is a cystoscopy with injection of Deflux. This is a procedure where under general anesthesia, a smalltelescope is inserted into the bladder through the urinary opening. A
gel (Deflux) is injected where the ureters enter the bladder. A littlebulge is formed in the bladder wall, preventing the backflow of urine.This is an outpatient procedure.
Patients with "high grade" reflux, grades IV-V, will take low doseantibiotics and have periodic blood tests, x-ray tests and urine culturesdone. These children will often need ureteral re-implantation surgery tocorrect the reflux and prevent progressive damage of the kidneys.
VUR grades III-V
Monitor urine cultures- covert bacteriuria- febrile episodes
< 3 yrsold
3-6 yrsold
≥ 6 yrs old
Abx prophylaxis for 2yrs or until age 3
Abx prophylaxis for 2yrs or until age 6
NoUTI
1 febrile UTIor
≥ 2 covertbacteriuria
1 febrile UTIAND
≥ 2 covertbacteriuria
OR≥ 2 febrile UTI
Stop Continue till6 yrs
Surgery
Covertbacteriuria
1 febrile UTI
≥ 2 febrileUTI
Treatsymptomatic
UTI
Abx for 2 yrsand then off
Surgery
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Neurogenic bladder
Causes
Spina bifida
Sacral agenesis (IDM)
Autonomic neuropathy
Transverse myelitis
Spinal cord tumour
Spinal cord trauma Non-neurogenic neurogenic bladder (Hinman’s syndrome)
Unknown etiology
Acute glomerulonephritides
Clinical presentation of glomerulonephritides
Nephrotic syndrome
Acute nephritic syndrome
Rapidly progressive glomerulonephritis
Chronic gromerulonephritis
Asymptomatic haematuria and/or proteinuria
Recurrent gross haematuria
Complications of acute glomerulonephritides
Hypertensive encephalopathy
Fluid overloado Acute pulmonary edema
o Congestive cardiac failure
Acute renal failureo Uremia
o Hyperkalemia
Management
Hypertensiono Calcium-channel blockers
o ACE inhibitors
Fluid overloado Salt and fluid restriction
o Loop diuretics
Uremiao Protein restriction
o Dialysis
Hyperkalemia
o Dietary K+ restriction
o Ion-exchange resins
o Emergency drugso Dialysis
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Nephrotic syndrome
History 1. Biodata
2. Presenting complaint
a. Peripheral oedema – what parts of body affected? Limbs? Face?
Perineum (scrotal or vulvar oedema)? Abdominal distension?Breathing difficulty (pleural effusion)?
b. Urine – bubbly? Any blood? Any other lower urinary tract symptoms
(frequency, urgency, dysuria, nocturia etc)?
c. Any abdominal pain - may be due to 1) Shock with mesenteric vessel
vasoconstriction; 2) Renal venous thrombosis; or 3) Spontaneousbacterial peritonitis on top of ascites
d. Other acute complications:
i) Change in mental state (encephalopathy from sagittal sinusthrombosis)
ii) Fits (hyponatraemia)iii) Red warm swollen limb (DVT)iv) Palpitations, dyspnoea, diaphoresis, feeling faint and weak
(hypovolaemic shock)
e. Other systemic symptoms: lethargy, anorexia
f. What was the trigger for this particular episode, if any?
3. History of first presentation and diagnosis
a. Initial presenting symptomsi) Oedema with facial involvement (anasarca), worse in the morning;
oedema involving lower limbs and sacrum, perineum later in theday
ii) Proteinuria – bubbly urine; any blood? (as above)iii) Any acute complications (as mentioned above)
b. Diagnosis
i) What investigations were done? Any renal biopsy?ii) What is the diagnosis?
4. History of course of disease
a. Has disease been well controlled? How frequent are relapses, how
frequent are hospitalisations?
b. How are relapses treated? Does patient require albumin infusion withdiuretics (indicates more severe oedema)?
c. Any triggers for relapses e.g. URTI
d. Chronic complications of disease
i) Frequent infections e.g. cellulitis (esp scrotal, vulvar), peritonitis,UTI
ii) Impaired growthiii) Hypercoagulability – DVT, etciv) Hyperlipidaemia – being controlled?v) Did doctor say that renal function was becoming worse?
5. History of treatment and monitoring
a. What medication is patient on currently?
i) Steroids – what is the dose? Any side effects e.g. obesity,hirsutism, acne, thin skin, easy bruising, short stature,hypertension, diabetes, visual problems
ii) Steroid sparers:
Cyclophosphamide – dose? Side effects: neutropaenia(severe infection requiring isolation in hospital; FBC results onfollow up), haemorrhagic cystitis, hepatitis, GI irritation, oralulcers, alopecia etc
Chlorambucil – dose? Side effects: neutropaenia, seizures, GIsymptoms, rash
Levamisole – dose? Side effects: neutropaenia
Cyclosporin A – dose? Side effects: renal impairment (has
renal biopsy been done to assess nephrotoxicity? Any
relapses after cyclosporin stopped poor response to further treatment with cyclosporin
Mycophenolate mofetil – dose? Side effects: neutropaenia, GI
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symptoms, rash
b. Compliance to medication; if non-compliant, why?
c. Monitoring at home – daily urine dipstick; any diary to record daily
readings? Weight measurement?
d. Adjustment of medication to match dipstick readings (relapse)? If so,
what are the indications for change of medication, and what are thechanges made?
e. Follow-up at hospital – with whom? What investigations are done
(e.g. urine dipstick, urinalysis, serum creatinine level, urineprotein/creatinine ratio etc)?
f. Recent change of medication – increase or decrease in dose? New
medications added?
g. Has doctor advised anything e.g. to stay away from crowded
places? Diet modification?
6. Exclude systemic cause of NS
a. Namely SLE – ask about skin rash (malar, discoid), oral ulcers,
photosensitivity, joint pains
b. Henoch-Schonlein purpura can also cause nephrotic picture (less
common) – ask about palpable purpura on the limbs, abdominal pain, joint pain (in weight-bearing joints e.g. ankles)
c. Drugs – take a drug history
7. Social history
a. Schooli) How is patient doing in school?ii) Does disease affect schoolwork adversely e.g. frequent absence
due to illness/relapses?iii) Able to do P.E.?iv) Do teachers know about the disease, are they supportive?v) Do friends know about the disease, are they supportive?
b. Body image issues – Cushingoid appearance from steroids;
generalised oedema
c. Parents – do they support the patient, remind the patient to takemedications etc and take precautions where necessary e.g. not goingto crowded places
d. Finances – any financial problem due to disease and medical fees?
e. Understanding of disease
f. Any support groups?
8. Other relevant points (as per all paediatrics history-taking)
9. Summary:
My patient is (name), a (age/race/gender) who has nephrotic syndromethat is:
Steroid sensitive with infrequent relapses/Steroid sensitive withfrequent relapses/Steroid dependent/Steroid resistant
Currently admitted for relapse with symptoms of (_______)
Complicated by (_____)
Physical examination
1. General appearance – anasarca, signs of Cushing’s (short, round face,etc)
2. Vitals – stable?
3. Pedal oedema – pitting (up to what level? Scrotum/vulva involved?)
4. Abdomen – ascites5. Lungs – pleural effusion
Definition
Massive proteinuria
o ≥ 3g/1.73m2/24h
o ≥ 50mg/kg/14h
o ≥ 40mg/h/m2
o Urine protein/creatinine ratio ≥ 0.2 g/mmol (N: < 0.02 g/mmol)
Hypoalbuminaemiao < 25 g/l
Hyperlipidaemia
o ↑cholesterol
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o ↑triglycerides
o ↑LDL
o ↑VLDL
Edema
Causes
In children , nephrotic syndrome is usually idiopathic (and not
secondary); most common cause is minimal change disease (80%)
Other less common causes: focal segmental glomerulosclerosis(FSGS – 10%); membranoproliferative glomerulonephritis (MPGN –10%); membranous GN (1.5%)
Think also of secondary causes of nephrotic syndrome: SLE, Henoch-Schonlein purpura, post-streptococcal GN, drugs, etc.
In adults , most common cause is membranous GN (30%) followed by
mesangioproliferative GN (27%) and minimal change disease (23%);secondary causes are also more common
Pathophysiology
Glomerular injury results in increased permeability of the glomerulus to
protein, and proteinuria results With decrease in circulating protein, the oncotic pressure of blood
decreases resulting in third-spacing of fluid (leading to development of oedema, ascites, pleural effusion) and a drop in plasma volume
The fall in circulating volume results in activation of the renin-angiotensin-aldosterone system to reabsorb salt and water
Thus the pathophysiology in nephrotic syndrome in an intravascular hypovolaemia (as opposed to hypervolaemia in nephritic syndrome)
Hypoalbuminaemia results in increased production of lipoproteins bythe liver, resulting in increased serum lipid levels
Clinical features
Peripheral oedema
o Usually in the periorbital region in the morning, progressing to
involve the lower limbs and sacrum, scrotal/vulvar regionslater in the day
Ascites
Pleural effusion with shortness of breatho Not common, usually in severe oedema state
o Pulmonary oedema is unlikely, as compared to in nephritic
syndrome
Lethargy, anorexiao Due to low circulating protein
Normal to low blood pressureo Unlike in nephritic syndrome where there is hypervolaemia
and consequent hypertension, there is normal to low bloodpressure in nephrotic syndrome
o Hypovolaemia is a complication
Complications Increased susceptibility to infection
o Due to loss of immunoglobulins, complement in urine,
impaired T cell function, and also due to steroid therapyo Usually due to encapsulated bacteria and gram negatives e.g.
pneumococcal peritonitis (on ascites)o Other infections: cellulitis of oedematous areas, UTI
Hypovolaemiao Abdominal pain can be a sign of hypovolaemia due to
mesenteric ischaemiao Other signs/symptoms: cool peripheries, postural drop in
blood pressure, increased capillary refill time, decreased urine
outputo Requires albumin infusion and crystalloids (fluid loading)
Thrombotic tendencyo Due to fall in antithrombin III levels with increase in clotting
factors (increased hepatic production)o Tendency increases with other concomitant causes of fluid
depletion e.g. vomiting
o Common sites are in the brain (sagittal vein thrombosis
encephalopathy) and kidney (renal vein thrombosis
abdominal pain)
Hyponatraemiao Due to maldistribution of extracellular fluid volume with
increase in water reabsorptiono Can result in seizures
Impaired growtho Due to low protein levels
Hyperlipidaemiao Can result in other complications e.g. coronary artery disease
in the long run
Renal failureo Rare in nephrotic syndrome due to minimal change disease
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o Higher likelihood in patients with steroid-resistant FSGS – 8-
10% of these will progress to end stage disease
Complications of treatment
o Steroids (Cushing’s): Rounded moon face, truncal obesity
with peripheral wasting, short stature, violaceous striae,supraclavicular fat pad, dorsal fat pad, hirsutism, acne, skinatrophy, telangiectasia, easy bruising, oral thrush, proximalmyopathy, posterior subcapsular cataracts, hypertension,
glucose intolerance, osteoporosiso Other drugs: neutropaenia (almost all), haemorrhagic cystitis,
sterility (cyclophosphamide), nephrotoxicity (cyclosporin A)
Investigations
Urine dipsticko Proteinuria 3+ (>3g) or 4+ (>20g)
o Should not have gross haematuria; slight haematuria is
common
Urine FEME and urine phase contrasto Evaluate haematuria – red cell casts, dysmorphic red cells
o Should not have any cellular casts in minimal change disease,
but may see hyaline or waxy casts
Urine protein-creatinine ratio or 24 hour urine total protein (UTP)o More accurate measure of proteinuria
Full blood counto Haemoglobin should be normal in minimal change dz
Urea, electrolytes, creatinineo Should not have any renal impairment
Serum albumin level
Fasting lipids
Serum complement (C3, 4)o Should not be reduced in minimal change disease; decreased
in SLE
Hepatitis statuso Hep B can result in membranous nephritis, hep C in
mesangiocapillary GN
Renal biopsyo Reserved for those with very atypical features (i.e.
hypertension, low serum C3) and those who do not respond tosteroids; it is not a routine requirement.
Typical features of minimal change nephrotic syndrome
Age of onset 1-10 years
No hypertension
No gross haematuria
Normal renal function
Normal serum complement
Highly selective proteinuria (mostly albumin)
Steroid responsive
Indications for renal biopsy
Atypical featureso Age of onset <1 year or >10 years old
o Systemic hypertension
o Gross haematuria
o Renal failure
o Persistently low serum complement
o Poorly selective haematuria
o Steroid resistance
Family history of glomerulonephritis
Steroid-dependent patient with unacceptable steroid toxicity
Management
I NITIAL TREATMENT
1. If hypotensive, crystalloids with albumin
2. Diuretics with albumin- Problems: worsens hypovolaemia if not given correctly; fluid and
electrolyte abnormalities
- Indications: gross oedema, steroid-resistant disease, use of steroidscontraindicated, unacceptable steroid toxicity
- Intravenous 20% albumin infusion 1g/kg over 4 hours followed byintravenous frusemide 0.5-1mg/kg
3. Salt restriction only if oedema present; no fluid restriction
4. Steroid therapy
- Starting dose: 60mg/m2 /day (up to maximum of 80mg/m2/day) for 4
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weeks
- Watch for clinical remission within 10-14 days of treatment : loss of
oedema (weight decreases) and urine dipstick negative/trace for threeconsecutive days
5. Daily monitoring of urine and serum albumin, weight, electrolytes- Monitoring for remission, as above
6. Activity- No evidence that restriction influences outcome.
7. Immunizations- No live attenuated vaccines
LONG - TERM TREATMENT
1. Steroid therapy
- Follow-up treatment: after 4 weeks initial treatment, tail down to
40mg/m2 EOD for another 4 weeks, then stop
- Relapse (oedema, urine dipstick positive)
Start 60mg/m2 /day for at least 14 days until remission, then40mg/m2 EOD for 4 weeks
- Long-term steroids dependent on frequency of relapses:
(a) Infrequent relapsers : <2 relapses in first 6 months or <4 in any
subsequent 1 year period
No need for long term steroids, just treat relapse
(b) Frequent relapsers : >2 relapses in first 6 months or >4 within any
subsequent 1 year period
0.1-0.5 mg/kg EOD for 3-6 months
(c) Steroid dependent: frequent relapsers with 2 consecutive relapses
while on steroid therapy or within 2 weeks of stopping steroids
0.1-0.5mg/kg EOD (pre-school age) or 0.5-1.0mg/kg EOD(school age) for 6-12 months
2. Patient education (patient + parents)
- Regarding nature of disease and prognosis (good prognosis), outcome,
recurrence (a third will not recur, another third will recur infrequently,and a third will recur frequently)
- Explain mode of action of treatment and emphasise compliance to
treatment
- Explain side effects of treatment
- Self-monitoring at home, recognising symptoms and signs of relapse,
and adjustment of medications for relapse (not all relapses requirehospitalisation)
- Need to avoid crowded places due to susceptibility to infection
- Vaccination for encapsulated bacteria e.g. pneumococcu
3. Use of second line treatment
- Aims: to achieve control of nephrotic syndrome in frequent relapsers or
steroid-dependent patients with a smaller dose of steroids to reduceadverse steroid side effects
- Indications:
Severe growth retardation Clinically significant cataracts
Difficult hypertension
Diabetes mellitus
Disabling emotional disorders related to physical appearance
- Options
(a) Frequent relapsers:
Levamisole 2.5mg/kg EOD for 6-12 months withcyclophosphamide 2-2.5mg/kg EOD for 8 weeks
OR Chlorambucil 0.15mg/kg/day for 8 weeks
(b) Steroid-dependent patients:
Levamisole 2.5mg/kg EOD for 6-12 months withcyclophosphamide 2-2.5mg/kg EOD for 8-12 weeks
OR Chlorambucil 0.15mg/kg/day for 8 weeks with cyclosporin A6mg/kg/day
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- Side effects:
Cyclophosphamide: neutropaenia (monitor FBC),haemorrhagic cystitis (ensure good water intake), hepatotoxicity(monitor LFT), sterility (limit dosing to 12 weeks maximum)
Chlorambucil: neutropaenia, seizures, rash
Cyclosporin A: nephrotoxicity (monitor U/E/Cr, renal biopsy)
Steroid-resistant patients- Definition: Failure to achieve remission despite 6 weeks of high dose
steroids (60mg/m2/day)- Renal biopsy indicated in these patients- Subsequent treatment guided by biopsy results- Treatment options:
Cyclophosphamide 2-2.5mg/kg/day for 12 weeks
Cyclosporin A 6mg/kg/dayAcute renal failure
Clinical approach to a child with renal failure
Suspect azotemia if
Oliguria (urine output <0.5ml/kg/h)o Acute non-oliguric renal failure
o GFR: 5-15 ml/min/1.73m2
Anuria
Acidosis (Kussmaul’s breathing) Haematuria, proteinuria or other urinary abnormalities
Hypertension
S/s of obstructive uropathy
S/s of renal tubular dysfunctiono Polyuria, polydipsia, enuresis (beyond 6 yrs of age), rickets,
growth retardation
Anemia of unknown etiology
Features to suggest chronicity
Historyo Family history of hereditary nephritides
o History of polyuria, polydipsia, enuresis beyond 6 yearso Past history of significant renal disease
Physical examo Short stature
o Sallow appearance
o Anemia
o Chronic hypertensive retinopathy
o Dystrophic fingernails
o Pinguenculae
SUSPECT RENAL FAILURE
↑Plasma urea and creatinine
Look for features of chronicity
NO YES
ACUTE RENALFAILURE
CHRONIC RENALFAILURE
Urinary sedimentUrinary diagnostic indicesTrial of volume expansion
UltrasonographyMCUIsotope renography
ACUTE RENALFAILURE
Pre-renal Renal Post-renal
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o Neuropathy
Investigationso Renal osteodystrophy/rickets
o Small shrunken kidneys
Causes of acute renal failure
Pre-renal Renal Post-renal
• Heart failure (severe)
• Volume contraction- GI losses- Renal losses- Sweat
• 3rd space losses- Hypoalbuminemia- Peritonitis- Crush injury- Burns- Sepsis
• GN
- Acute GN- Post-infectious GN- Lupus nephritis- HSP nephritis- IgA nephropathy
- RP GN
• Vascular - HUS- Renal vein
thrombosis
• Interstitial nephritis- Allergic- Post-infectious- Fulminating PN- Papillary necrosis
• Acute tubular necrosis- Prerenal
(vasomotor)- Nephrotoxins- Pigment injury
• Obstructive uropathy
- PUV- Neurogenic bladder - Ureteric obst of
single kidney
• Crystalluria- Uric acid:- Tumor-lysis- Post-cardiac op for
cyanotic CHD- Dehydration- Hyperuricemia
- High dose MTX- Calcium oxalate
- Hyperoxaluria- Glycol toxicity
Urinary sediment in renal failure
Finding Cause
Isomorphic red cells Renal vein thrombosis
Distorted red cells and red cell casts HUSGN
White cells Pyelonephritis
Eosinophils Acute interstitial nephritisRenal tubular epithelial cells, tubular cell casts and coarse granular casts
Acute tubular necrosis
Crystals- urate, calcium oxalate Crystal luria
Scant findings Pre- or post-renal
Urinary diagnostic indices
Indices Pre-renal ARF Ischaemic Intrinsic ARF
Urine osmolality, Uosm > 500 < 350
Urinary Na+, UNa < 20 > 40Fractional excretion of Na+, FeNa
< 1 > 1
Renal failure index, RFI < 1 > 1
FeNa= U/PNa ÷ U/PCr x 100%RFI = UNa ÷ U/PCr
Therapeutic trial of volume expansion
Child with oliguria, azotemia(NOT in fluid overload)
Infuse 20ml/kg normal saline or plasma (if in shock) over 1-2h
Oliguria persists Gd urine output
IV frusemide 2mg/kg
Oliguria persists
Intrinsic ARF Pre-renal ARF
Response
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Problems in management of acute renal failure
Problems Management
Fluid overload • Fluid restriction- 1st 10kg – 100 cal/kg- Next 10kg – 50 cal/kg- Next 10kg – 20 cal/kg- INS H2O loss – 45ml/100cal- HID H2O metab – 15ml/100cal- Fluiq req = INS H2O loss – HIDH2O metab + U.O. + other loss
Aim at wt loss 0.5-1.0% daily
↑Nitrogenous waste(Hypercatabolism)
• Adequate caloric intake
• Protein intake 2g/kg/day(8% of total calories)
• Essential L-amino acids
Hyponatremia • Dilutional: restrict fluids• True loss: replacement saline
Hyperkalemia • IV 10% Ca2+ gluconate 0.5ml/kg
• Salbutamol IV 4µ g/kg or nebulized2.5mg(BW≤25kg)
• IV NaHCO3 3mmol/kg (?)
• IV 50% glucose 0.5g/kg + InsulinIU/5g glucose
• Resin exchange
• Dialysis
Hypocalcemia • Ca2+ supp 0.5-1.0 mmol/kg/day
Hypertension • Diuretics – frusemide
• Anti-hypertensives
Convulsions/Coma- Hypocalcemia- Hypomagnesemia
- Hypertension- Uremia- ICH- Dialysis- Dysequilibrium syndrome
• Anti-convulsants
• Correct metabolic abnormalities
• Dialysis
Cardiac failure • Dialysis
Pericarditis • Dialysis
Anemia • Exchange transfusion in neonates
• Dialysis and trransfusion
Infection • Antibiotics (dose adjustmentnecessary for nephrotoxic agents
Indications for dialysis Hyperkalaemia K+>7mmol/L unresponsive to conventional treatment
Uncontrolled acidosis HCO3- <10mmol/L
Severe fluid overload with uncontrollable hypertension, pulmonaryedema or cardiac failure
Progressive uremia with deterioration of general condition
Hypercatabolic states with increase in blood urea by > 10mml/day
Problems of fluid restriction
Insufficient calories and protein malnutrition
No space for blood products
Difficulty in drug delivery
Propensity for hypoglycaemia
Chronic renal failure
History 1. Biodata
2. History of presenting complaint
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Change in urine colour
Change in urine volume (oliguria, polyuria)
Voiding symptoms (FUDACLE)
Dysuria Urethral discharge, genital rash
Storage symptoms
Renal/ureteric colic, suprapubic discomfort, aching pain in loin
Fever a/w chills and rigors, URTI
Nausea, vomiting, sweating
3. Signs of renal failure and systemic review
CVS – edema, fatigue, palpitations (anemia)
Respi – pleuritic chest pain, dyspnea
GIT – LOA, LOW, nausea, vomiting, metallic taste in mouth, pruritus, jaundice (HRS), bruising, abdominal distension, abdominal pain,change in bowel habits
Neuro – dizziness, headache, confusion, inability to concentrate,restless leg syndrome, seizures/fits, paraesthesia (peripheralneuropathy)
MSK – bone pain4. History of first presentation and diagnosis
Describe when first diagnosed, presenting complaints, what was doneand investigations, meds given, compliance, follow-up, complications,self-monitoring
5. Past history
Renal stones, UTI, PKD, asthma, DM, HPT, deafness
Past illnesses and hospitalizations, surgeries
Allergies
6. Drug history
Drug allergies
Any long-term medications, recent ingestion of medications
Complications of medications
TCM use?
Compliance
EPO injections?
7. Social history
Smoking, drinking if relevant
Overseas travel
Who does patient live with? Main care-giver? How many siblings?
Parent’s occupation and family income
Character of child, performance in school, amount of school missed?
How disease affects child and family
8. Family history
PKD
Similar problem
Renal malignancies
Renal calculi GM
Deafness (Alport’s syndrome)
9. Birth history
Pregnancy – any problems, fever and rash, DM, long-term meds
Gestational period
Birth weight
Delivery
Condition after birth
Antenatal problems
+/- G6PD status
10. Immunization status
BCG, polio, diphtheria, tetanus, Pertussis, MMR, hepatitis
11. Developmental milestones
Social smile
Head control
Sitting independently
Walking
Talking
Toilet-trained
12. Nutritional history
Breast feeding
Infant feeding
Weaning
Diet
Physical Examination
1. General inspection
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Hyperventilation
Mental state – alert, confused, drowsy
Hydration status
Sallow complexion
Anemia
Growth parameters
Edema – periorbital, peripheral
Cushingoid features
Hearing aid Abdominal – scars, distension, visible masses, CAPD catheter
2. Vitals
PR, RR
3. Peripheral examination
Fingernails – leukonychia, clubbing, Terry’s nails, Beau’s lines,Lindsay’s ½ and ½ nails
Limbs – asterixis, palmar crease pallor, AV fistula, bruising,pigmentation, scratch marks, uremic frost
Eyes – pallor, jaundice, pinguenculae, cataracts, periorbital edema
Mouth – hydration, uremic fetor
Face – malar rash
Neck – cervical, supraclavicular, submental lymph nodes4. Abdominal examination
Organomegaly
Ascites
Percussible bladder
5. Cardiorespiratory examination
CVS – JVP, apex beat, murmurs, pericardial rub
Respi – pulmonary edema, pleural effusion, pleuritis
6. Neurological examination
Tone, reflexes, proximal myopathy, sensation
Gait – foot slapping 2°peripheral neuropathy
7. Request
PR exam
Fundoscopy
BP
Temperature chart
Urinalysis
Acute reversible factors in chronic renal failure i
Dehydration
Electrolyte abnormalitieso Hyponatremia/hypokalemia
o Acidosis
Infection
o UTIo Septicemia
Obstructive uropathy
Uncontrolled hypertension
Cardiac failure
Hypotension
Causes of chronic renal failure in childhood
Small kidneyso Equal
Chronic GN
Hereditary nephritis
Cystinosis Tubulointerstitial nephritis
Juvenile nephronophthiasis
Bilateral renal hypoplasia
o Unequal, irregular
Chronic atrophic pyelonephritis
Bilateral segmental hypoplasia
Large kidneyso Obstructive uropathy
o AR PKD
o Renal dysplasia with associated malformations
Cardiac GI esp imperofrate anus
Spina bifida
Management
Aimso To improve or stabilize renal function and maintain
homeostasiso To permit as much growth as possible
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o Permit the child to continue an active life
Issue in managemento Nutrition
o Growth failure
o Renal anemia
o Renal osteodystrophy
o Hypertension
o Psychosocial development
Issue Management
Nutrition • Water: thirst regulated unlessoliguric and fluid overloaded
• Na+: up to 2gm (80mmol)/dayRestrict only in edema and HPT
• K+: up to 1.5mmol/kg/day unlesspatient is hypokalemic (esp in PDpatients)
• Acidosis: restore HCO3 to 18-20mmol/l
Growth failure
- Acidosis- Reduced caloric intake- Anemia- Hypertension- Renal osteodystrophy- Insulin resistance- Growth hormone resistance
• Treat contributing factors
• If child > 2yrs, ht < 3rd
%, growthvelocity <50th%- Start on rhGH 4U/m2/day- If good response, stop when target& reached (defined by meanparental ht)
- If not, rhGH 8u/m2/day for 6 months
Anemia- Shortened RBC survival- Fe and folate deficiency- Aluminium toxicity- Osteitis fibrosa a/w hyperPTH- ? retained inhibitors of EPOiesis
- ↓EPO production
• Treat with EPO if symptomatic or Hb<10 g/dl (r/o Fe deficiency)
• R/o drugs like Al
• If Fe deficient, correct Fe first thenre-evaluate need for EPO
• Monitor: BP, Hb, retic, Fe sats,
ferritinRenal osteodystrophy • Control of serum phosphat
- Diet- PO4
3- binders: Al, CaCO3 (chewed)Ca acetate (swallowed)
• Ca2+ replacement- 0.5-1.0 mmol/kg/day
• Vitamin D therapy
- 1,25-OHD3: 1-α (children) andcalcitriol (adults)
- Monitor: UCa/UCr < 0.70 mmol/mmol[Ca][PO4
3-] < 6.0 (mmol/L)2
Hypertension • Treat with anti-hypertensives
• Always correct fluid overload
Psychosocial development • Refer to child psychiatrist
• Medical social worker
Management of ESRD in childreno Dialysis
Chronic peritoneal dialysis
• CAPD
• APD
Haemodialysiso Transplantation
Living related
Cadaveric
Common drugs used in renal transplantationo Monoclonal antibodies
o Prednisoloneo Azathioprine/Mycophenolic acid
o Cyclosporine/Tacrolimus
o Anti-hypertensive drugs
* Macrolides inhibit liver enzymes ↑tacrolimus (toxicity)Erythro > Clarithro > Azithro(readjust doses if have to give)
Approach to haematuria
Definition
> 5 rbc/mm3 in fresh uncentrifuged midstream urine
> 3 rbc/hpf in a fresh centrifuged midstream urine Test positive 2 out of 3 occasions
Causes of haematuria
Haematuria
Non-glomerular Glomerular
• UTI
• Hypercalciuria
• Trauma
• Renal calculi
• Exercise-induced
• Coagulopathy
• Malignancy(Wilm’s)
• Factitious
• Familial benignhaematuria
• Non-familialbenign
haematuria
‘Benign’ ‘Malignant’
• GN
- 1°/2°
• HUS
• Alport’s
• Renal veinthrombosis
• Interstitialnephritis
• Cystal renaldisease
OR NOTS:Myoglobinuria } Positive dipstickHaemoglobinuria } Exclude from historyIntravascular haemolysisDrugs/chemicals: quinine
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Approach to haematuria
Thorough history and physical examinationo Persistent microscopic haematuria
o Gross haematuria
o Associated pain, frequency, dysuria, fever, edema,hypertension, rash, joint pain
o Positive family history (i.e. GN, calculi, ADPKD)
Investigationso Confirm haematuria
o Differentiate glomerular vs non-glomerular
Causes of glomerulonephritis
Acuteo IgA nephropathy
o Post-streptococcal
o HSPo SLE
o Vascular
o Wegener’s
o Goodpasture’s
Chronic
o Chronic GN ESRD
Rapidly progressive GN
Confirm haematuria with dipstickUFEME
Urine C/S
Urine phase contrastUrine total protein/creatinine
• Isomorphic rbc, nocast, proteinuria - Urine Ca2+ / creatinine- Coagulationscreen- AXR/US- Cystoscopy
• Dysmorphic rbc,cast, proteinuria
- Urea/ electrolytes- 24h UTP/CCT- Serum C3/C4 • post-infectious GN
• SLE
• MPGN
- Screen relatives- Audiology/US- Renal bx
Non-glomerular Glomerular
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o Same as acute
Management of acute GN See above under ‘Acute glomerulonephritides’