04 Nephrology

4) NEPHROLOGY General Outline  Urinary Tract Infections  Acute Glomerulonephritides  Nephrotic syndrome  Acute Renal Failure  Chronic Renal Failure  Approach to Haematuria ______________________________________________________________

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

If positive 

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

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Urine culture o Midstream o Catheter o Suprapubic aspiration Criteria for significant bacteriuria

Method of collection Suprapubic aspiration Transurethral catheterization

Symptomatology of UTI in children Clean void Boy Girl

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

Colony count/ml (Pure culture) GNB: any number GPC: >103 >105 104-105 103-104 104 3 specimens >105 2 specimens >105 1 specimen > 105 5x104-105 104-5x104

Infection likely 95% 90% 80% Suspicious, repeat Syptomatic: suspicious, repeat Asymptomatic: infection unlikely Infection unlikely

99% 95% Infection likely Suspicious, repeat Infection unlikely

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 stones o Pseudomonas: indicates structural abnormality affecting drainage  Incomplete bladder emptying  urinary retention and stasis o 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 bilateral hydronephrosis  Vescio-ureteric reflux (VUR)  Pelvi-ureteric junction obstruction

Useful for diagnosing acute pyelonephritis in the acute stage whereas scans performed 3-6 months later may demonstrate the 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 a 99mTc DTPA or MAG3 renograrn to distinguish between a true mechanical obstruction and nonobstructive pelvicalyceal dilatation. o It also gives the differential function of both kidneys. o Better than IVU as children cannot concentrate contrast well. o

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Clinical classification of UTI Clinical Age Fever Voiding problem Suprapubic pain Loin pain CRP Renal involvement (Cr, US, DMSA scan)

Upper Tract < 2 years + + ↑ +

Lower tract > 2 years + + N -

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 wall thickness, presence of absence of pelvicalyceal and ureteral dilatation.  DMSA (Dimercaptosuccinic acid) scan o Radioisotope scan that picks up focal areas of decreased uptake.

≤ 2 yrs

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> 2 yrs

Once ultrasound shows hydronephrosis and hydroureter, differential diagnosis include o Vesico-ureteric reflux o Obstruction  Bladder outlet obstruction • Neurogenic bladder

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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 renogram AND 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 be lower tract. Hence once DMSA has ruled out renal scarring, we can begin treatment as for a lower urinary tract infection.

Treatment of UTI 

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Principles of anti-microbial therapy o Organism should be susceptible to the antimicrobial durg, hence the importance of appropriate urine cultures before starting. 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 childhood o Bacteraemia present in 20-30% of children with UTI o Case fatality rate with septicaemia is 10% o Higher incidence of congenital abnormalities including vesicoureteric reflux in the young child. Uncomplicated infections o 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 drug dosages or drug interactions or an obstructed urinary tract. Complicated infections

Parenteral antibiotics should control the symptoms within 4872h 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 grossly dilated. 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, preputial contamination, incorrect cleaning after defaecation, tight clothing with perineal moisture accumulation. Patient and parental education are useful in minimizing the infective Clinical diagnosis of UTI episodes. In boys with problems due to preputial colonization, circumcision is recommended. If these factors are corrected but the infections persist with symptoms, these children may No benefit from 6 to 12 months Fever of antibiotic prophylaxis. Yes o

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Lower Tract Infection

Upper Tract Infection

Age

Age

< 12 yrs

≥ 12 yrs

7-10 day course

3 day course

1. Trimethoprimsulfamethoxazole (Bactrim) 2. Cephalexin/Cefaclor (G6PD deficient) Review antibiotics once culture results are available.

< 28 days

Full sepsis work-up Ampicillin and Gentamicin pending culture results for minimum of 48-72 hours then oral therapy.

≥ 28 days

Toxic

Non-toxic

Admit

+/- Admit

Parenteral until asymptomatic for 24h then oral to complete 10-14 day course 1. Gentamicin or Amikacin +/- Ampicillin 2. Cefotaxime or Ceftriaxone +/- Ampicillin

Vesico-ureteric reflux (VUR) Introduction  VUR is a condition in which urine from the bladder is able to flow back up 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 the length 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 becomes infected. The infected urine easily travels backwards to the kidney and can 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 ureters after voiding  Pyelonephritis may occur especially if there is intrarenal reflux  Bladder voiding pressure transmitted to renal papillae which results in renal 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 o o o o

Grade I – reflux into non-dilated ureter Grade II – reflux into the renal pelvis and calyces without dilatation Grade III – mild/moderate dilatation of the ureter, renal pelvis and calyces with minimal blunting of the fornices Grade IV – dilation of the renal pelvis and calyces with moderate ureteral tortuosity Grade V – gross dilatation of the ureter, pelvis and calyces; ureteral tortuosity; loss of papillary impressions

Causes of VUR  Primary o Incompetence of vesico-ureteric (VU) sphincter  Anatomical distortion of VU junction • Congenital paraureteral diverticulum • Ectopic ureter  Bladder dysynergia  Secondary o Infection o Bladder outlet obstruction  Posterior urethral valves  Neurogenic bladder Management Conservative (Medical) Grades I-III: spontaneous resolution Long-term antibiotic prophylaxis

Surgical Grades IV-V: Progression of scarring (recurrent pyelonephritis) 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 as the child grows and the bladder matures. These children are given low-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 small telescope is inserted into the bladder through the urinary opening. A gel (Deflux) is injected where the ureters enter the bladder. A little bulge 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 dose antibiotics and have periodic blood tests, x-ray tests and urine cultures done. These children will often need ureteral re-implantation surgery to correct the reflux and prevent progressive damage of the kidneys. VUR grades III-V

Monitor urine cultures - covert bacteriuria - febrile episodes

< 3 yrs old

3-6 yrs old

Abx prophylaxis for 2 yrs or until age 3

No UTI

Stop

1 febrile UTI or ≥ 2 covert bacteriuria

Continue till 6 yrs

≥ 6 yrs old

Abx prophylaxis for 2 yrs or until age 6

1 febrile UTI AND ≥ 2 covert bacteriuria OR ≥ 2 febrile UTI

Surgery

Covert bacteriuria

Treat symptomatic UTI

1 febrile UTI

Abx for 2 yrs and then off

≥ 2 febrile UTI

Surgery

Neurogenic bladder

Acute glomerulonephritides

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

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 overload o Acute pulmonary edema o Congestive cardiac failure  Acute renal failure o Uremia o Hyperkalemia Management  Hypertension o Calcium-channel blockers o ACE inhibitors  Fluid overload o Salt and fluid restriction o Loop diuretics  Uremia o Protein restriction o Dialysis  Hyperkalemia o Dietary K+ restriction o Ion-exchange resins o Emergency drugs o Dialysis

i) ii)

What investigations were done? Any renal biopsy? What is the diagnosis?

Nephrotic syndrome 4. History of course of disease History 1. Biodata

a. Has disease been well controlled? How frequent are relapses, how frequent are hospitalisations?

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) Spontaneous bacterial peritonitis on top of ascites

d. Other acute complications: i)

Change in mental state (encephalopathy from sagittal sinus thrombosis) 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 symptoms i) Oedema with facial involvement (anasarca), worse in the morning; oedema involving lower limbs and sacrum, perineum later in the day ii) Proteinuria – bubbly urine; any blood? (as above) iii) Any acute complications (as mentioned above) b. Diagnosis

b. How are relapses treated? Does patient require albumin infusion with diuretics (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 growth iii) Hypercoagulability – DVT, etc iv) 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 on follow up), haemorrhagic cystitis, hepatitis, GI irritation, oral ulcers, alopecia etc  Chlorambucil – dose? Side effects: neutropaenia, seizures, GI symptoms, 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

generalised oedema c.

b. Compliance to medication; if non-compliant, why? c. Monitoring at home – daily urine dipstick; any diary to record daily readings? Weight measurement?

d. Finances – any financial problem due to disease and medical fees?

d. Adjustment of medication to match dipstick readings (relapse)? If so, what are the indications for change of medication, and what are the changes made?

e. Follow-up at hospital – with whom? What investigations are done (e.g. urine dipstick, urinalysis, protein/creatinine ratio etc)?

Parents – do they support the patient, remind the patient to take medications etc and take precautions where necessary e.g. not going to crowded places

serum

creatinine

level,

urine

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. School i) 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;

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 syndrome that is:  Steroid sensitive with infrequent relapses/Steroid sensitive with frequent 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 – ascites 5. 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)  Hypoalbuminaemia o < 25 g/l

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Hyperlipidaemia o ↑ cholesterol

o ↑ triglycerides o ↑ LDL o ↑ VLDL 

Edema

Causes

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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, HenochSchonlein 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 reninangiotensin-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 by the 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 regions later in the day  Ascites  Pleural effusion with shortness of breath o Not common, usually in severe oedema state o Pulmonary oedema is unlikely, as compared to in nephritic syndrome

 Lethargy, anorexia o Due to low circulating protein  Normal to low blood pressure o Unlike in nephritic syndrome where there is hypervolaemia and consequent hypertension, there is normal to low blood pressure 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 therapy o Usually due to encapsulated bacteria and gram negatives e.g. pneumococcal peritonitis (on ascites) o Other infections: cellulitis of oedematous areas, UTI  Hypovolaemia o Abdominal pain can be a sign of hypovolaemia due to mesenteric ischaemia o Other signs/symptoms: cool peripheries, postural drop in blood pressure, increased capillary refill time, decreased urine output o Requires albumin infusion and crystalloids (fluid loading)  Thrombotic tendency o 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)  Hyponatraemia o Due to maldistribution of extracellular fluid volume with increase in water reabsorption o Can result in seizures  Impaired growth o Due to low protein levels  Hyperlipidaemia o Can result in other complications e.g. coronary artery disease in the long run  Renal failure o Rare in nephrotic syndrome due to minimal change disease

Higher likelihood in patients with steroid-resistant FSGS – 810% 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, skin atrophy, telangiectasia, easy bruising, oral thrush, proximal myopathy, posterior subcapsular cataracts, hypertension, glucose intolerance, osteoporosis o Other drugs: neutropaenia (almost all), haemorrhagic cystitis, sterility (cyclophosphamide), nephrotoxicity (cyclosporin A) o

Investigations  Urine dipstick o Proteinuria 3+ (>3g) or 4+ (>20g) o Should not have gross haematuria; slight haematuria is common  Urine FEME and urine phase contrast o 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 count o Haemoglobin should be normal in minimal change dz  Urea, electrolytes, creatinine o 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 status o Hep B can result in membranous nephritis, hep C in mesangiocapillary GN  Renal biopsy o Reserved for those with very atypical features (i.e. hypertension, low serum C3) and those who do not respond to steroids; it is not a routine requirement. Typical features of minimal change nephrotic syndrome

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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 features o Age of onset 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 INITIAL 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 steroids contraindicated, unacceptable steroid toxicity - Intravenous 20% albumin infusion 1g/kg over 4 hours followed by intravenous 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 three consecutive 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, then 40mg/m2 EOD for 4 weeks - Long-term steroids dependent on frequency of relapses:

(a) Infrequent relapsers: 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 require hospitalisation) - 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 reduce adverse 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 cyclophosphamide 2-2.5mg/kg EOD for 8 weeks

with

 OR Chlorambucil 0.15mg/kg/day for 8 weeks

(b) Steroid-dependent patients:  Levamisole 2.5mg/kg EOD for 6-12 months cyclophosphamide 2-2.5mg/kg EOD for 8-12 weeks

with

 OR Chlorambucil 0.15mg/kg/day for 8 weeks with cyclosporin A 6mg/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/day Acute renal failure Clinical approach to a child with renal failure SUSPECT RENAL FAILURE

↑ Plasma urea and creatinine

Look for features of chronicity

NO

ACUTE RENAL FAILURE

YES

CHRONIC RENAL FAILURE

ACUTE RENAL FAILURE

Pre-renal

Renal

Urinary sediment Urinary diagnostic indices Trial of volume expansion

Post-renal Ultrasonography MCU Isotope renography

Suspect azotemia if  Oliguria (urine output 500 < 350 < 20 with oliguria, azotemia > 40 Child < (NOT 1 >1 in fluid overload) 1

FeNa= U/PNa ÷ U/PCr x 100% RFI = UNa ÷ U/PCr Infuse 20ml/kg normal saline or plasma (if in shock) over 1-2h Therapeutic trial of volume expansion

Oliguria persists

IV frusemide 2mg/kg

Gd urine output

Response

Oliguria persists

Intrinsic ARF

Pre-renal ARF

Hypocalcemia Hypertension Convulsions/Coma - Hypocalcemia - Hypomagnesemia - Hypertension - Uremia - ICH - Dialysis - Dysequilibrium syndrome Cardiac failure Pericarditis Anemia Problems in management of acute renal failure Problems Fluid overload

↑ Nitrogenous waste (Hypercatabolism)

Hyponatremia Hyperkalemia

Management • 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 – HID H2O metab + U.O. + other loss Aim at wt loss 0.5-1.0% daily • Adequate caloric intake • Protein intake 2g/kg/day (8% of total calories) • Essential L-amino acids • Dilutional: restrict fluids • True loss: replacement saline • IV 10% Ca2+ gluconate 0.5ml/kg • Salbutamol IV 4µ g/kg or nebulized 2.5mg(BW≤25kg) • IV NaHCO3 3mmol/kg (?) • IV 50% glucose 0.5g/kg + Insulin IU/5g glucose

Infection

• Resin exchange • Dialysis • Ca2+ supp 0.5-1.0 mmol/kg/day • Diuretics – frusemide • Anti-hypertensives • Anti-convulsants • Correct metabolic abnormalities • Dialysis

• Dialysis • Dialysis • Exchange transfusion in neonates • Dialysis and trransfusion • Antibiotics (dose adjustment necessary for nephrotoxic agents

Indications for dialysis  Hyperkalaemia K+>7mmol/L unresponsive to conventional treatment  Uncontrolled acidosis HCO3- 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 (peripheral neuropathy)  MSK – bone pain 4. History of first presentation and diagnosis  Describe when first diagnosed, presenting complaints, what was done and 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?

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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 nodes 4. 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

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Urinalysis

Acute reversible factors in chronic renal failurei  Dehydration  Electrolyte abnormalities o Hyponatremia/hypokalemia o Acidosis  Infection o UTI o Septicemia  Obstructive uropathy  Uncontrolled hypertension  Cardiac failure  Hypotension Causes of chronic renal failure in childhood  Small kidneys o Equal  Chronic GN  Hereditary nephritis  Cystinosis  Tubulointerstitial nephritis  Juvenile nephronophthiasis  Bilateral renal hypoplasia Unequal, irregular  Chronic atrophic pyelonephritis  Bilateral segmental hypoplasia Large kidneys o Obstructive uropathy o AR PKD o Renal dysplasia with associated malformations  Cardiac  GI esp imperofrate anus  Spina bifida o

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Management  Aims o o

To improve or stabilize renal function and maintain homeostasis To permit as much growth as possible

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o Permit the child to continue an active life Issue in management o Nutrition o Growth failure o Renal anemia o Renal osteodystrophy o Hypertension o Psychosocial development Issue

Nutrition

Growth failure - Acidosis - Reduced caloric intake - Anemia - Hypertension - Renal osteodystrophy - Insulin resistance - Growth hormone resistance Anemia - Shortened RBC survival - Fe and folate deficiency - Aluminium toxicity - Osteitis fibrosa a/w hyperPTH - ? retained inhibitors of EPOiesis - ↓ EPO production Renal osteodystrophy

Management • Water: thirst regulated unless oliguric and fluid overloaded • Na+: up to 2gm (80mmol)/day Restrict only in edema and HPT • K+: up to 1.5mmol/kg/day unless patient is hypokalemic (esp in PD patients) • Acidosis: restore HCO3 to 18-20 mmol/l • Treat contributing factors • If child > 2yrs, ht < 3rd%, growth velocity Azithro • Exercise• GN (readjust doses if have to give) induced - 1°/2° • Coagulopathy • HUS Approach to haematuria • Familial benign • Malignancy • Alport’s haematuria (Wilm’s) • Renal vein Definition • Non-familial • Factitious 3  > 5 rbc/mm in fresh uncentrifuged midstream urine thrombosis benign  > 3 rbc/hpf in a fresh haematuria centrifuged midstream urine • Interstitial nephritis  Test positive 2 out of 3 occasions • Cystal renal disease Causes of haematuria 

OR NOTS: Myoglobinuria } Haemoglobinuria } Intravascular haemolysis Drugs/chemicals: quinine

Positive dipstick Exclude from history

Confirm haematuria with dipstick UFEME Urine C/S

Urine phase contrast Urine total protein/creatinine

Non-glomerular

Glomerular

Approach to haematuria  Thorough history and physical examination o Persistent microscopic haematuria o Gross haematuria • Dysmorphic rbc, edema, o Associated pain, frequency, dysuria, fever, cast, proteinuria hypertension, rash, joint pain • oIsomorphic rbc, no Positive family history (i.e. GN, calculi, ADPKD) - Urea/ electrolytes cast, proteinuria  Investigations - 24h UTP/CCT o Confirm haematuria - Serum C3/C4 2+ - Urine Ca / creatinine o Differentiate glomerular vs non-glomerular • post-infectious GN - Coagulation • SLE • MPGN screen - Screen relatives - AXR/US - Audiology/US - Cystoscopy - Renal bx

Causes of glomerulonephritis  Acute o IgA nephropathy o Post-streptococcal o HSP o SLE o Vascular o Wegener’s o Goodpasture’s  Chronic o Chronic GN  ESRD  Rapidly progressive GN

o

Same as acute

Management of acute GN See above under ‘Acute glomerulonephritides’