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



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



• 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



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



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



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



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



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



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



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



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



- 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



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



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



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



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



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



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



o Same as acute

Management of acute GN See above under ‘Acute glomerulonephritides’

04 nephrology

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