Prevention Active immunization exists for both HAV and HBV. Within 24hr after an infectious contact, infection may be prevented by giving pooled serum immunoglobulin for HAV and CMV, or speci \201 c HBV serum immunoglob- ulin for HBV. 10_McClure_10.indd 343 11/14/2012 11:28:50 PM CHAPTER 10 Gastroenterology and nutrition 344 Chronic liver failure Causes \200 \200 \200 A \200 \200 \200 \200 \200 \200 \200 \200 \200 Chronic hepatitis (after viral hepatitis B or C). Biliary tree disease, e.g. biliary atresi a. Toxin-induced, e.g. paracetamol, alcohol. 1-antitrypsin de \201 ciency. Autoimmune hepatitis. Wilson \200\231s disease (age >3yrs). Cystic \201 brosis. Alagille syndrome or non-syndromic paucity of bile ducts. Tyrosinaemia. Primary sclerosing cholangit is. PN-induced. Budd \200\223Chiari syndrome. Presentation \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Jaundice (not always). GI hemorrhage (portal hypertension and variceal bleeding). Pruritis. FTT. Anemia. Enlarged hard liver (though liver often small in cirrhosis). Non-tender splen omegaly. Hepatic stigmata, e.g. spider naevi. Peripheral oedema and/or ascites. Nutritional disorders, e.g. rickets. Developmental delay or deterioration in school performance. Chron ic encephalopathy. Investigations Blood tests \200 LFT ( \200 FBC ( \200 Coagulation (prothrombin time d \200 or n blood glucose. \200 U&E ( rickets). Viral serology or PCR for hepatitis B and C. IgG, d complement (C3, C4), autoimmune antibodies (see b p.343). i or n bilirubin, i AST/ALT (x 2 \200\22310), albumin <35g/L). d Hb if GI bleeding); d WCC and platelets (hypersplenism). i if vitamin K de \201 ciency). d Na+, d Ca2+, i PO4 3 \200\223, i alkaline phosphatase if biochemical i \200 Metabolic studies \200 d \200 i \200 A Serum copper and caeruloplasmin (Wilson \200\231s disease). 24hr urinary copper (Wilson \200\231s disease). 1-antitrypsin level and phenotype. Sweat test (cystic \201 brosis); Abdominal US \200 \200 \200 \200 Hepatomegaly. Echogenic liver. Splenomegaly. Ascites. 10_McClure_10.indd 344 11/14/2012 11:28:50 PM CHRONIC LIVER FAILURE 345 Upper GI endoscopy \200 \200 Oesophageal or gastric varices. Portal hypertension related gastritis. EEG To con \201 rm chronic encephalopathy if suspected. Liver biopsy Histology; enzymes; electron microscopy. Management \200 \200 \200 Treat the underlying cause and give nutritional support. Lower protein, increased energy, h igher carbohydrate diet. Vitamin supplementation, particularly fat soluble vitamins A, D, E , K. Involve a pediatric dietitian. Drug therapy \200 \200 \200 \200 \200 Prednisolone +/ \200\223 azathioprine for autoimmune hepatitis. Interferon- Penicillamine f or Wilson \200\231s disease. Colestyramine may be useful to control severe pruritis. Vitami n K A +/ \200\223 ribavirin for chronic viral hepatitis. 1 and FFP (10mL/kg) if signi \201 cant coagulopathy or bleeding. Oesophageal varices Endoscopy, i.e. sclerotherapy or surgery. Ascites \200 + restriction (2/3 maintenance and 1mmol/kg/day, Fluid and Na respectively). Spironolactone (1 \200\2232mg/kg 12-hourly). Consider IV 20% al bumin if ascites is resistant to above treatment. \200 Encephalopathy Reduce GI ammonia absorption using oral or rectal lactu- lose, neomycin, or soluble \201 bre pectin. Liver transplantation See b p.347. Prognosis There is up to 50% 5yr mortality without liver transplant. Poor prognostic factor s are: \200 \200 \200 \200 \200 \200 bilirubin >50 mol/L; albumin <30g/L; PT >6s; ascites; encephalopathy; malnutrition. 10_McClure_10.indd 345 11/14/2012 11:28:50 PM CHAPTER 10 Gastroenterology and nutrition 346 Alpha1-antitrypsin de \201 ciency Alpha1-antitrypsin is a serum protease inhibitor respons ible for control- ling in \202 ammatory cascades. \200 It is the commonest genetic cause of liver disease in children, with autosomal dominant inh eritance. Prevalence is 1:2000 to 1:7000. Genetic variants are identi \201 ed by enzyme el ectrophoretic mobility as medium (M), slow (S), or very slow (Z). S is associated with 760% Alpha1-antitrypsin level of normal; Z 715%. Normal genotype is designated PiMM. Only PiZZ individuals are at risk of liver disease. Presentation \200 \200 Cholestasis in infancy, may progress to liver failure. Cirrhosis can occur in late childhoo d to adult. Chronic liver disease affects 25% of patients in late adulthood. Pulmonary emph ysema is the commonest presentation in adulthood. Diagnosis \200 1-antitrypsin level d. A Serum \200 Phenotyping by enzyme isoelectric fo cusing (see Alpha de \201 ciency). 1-antitrypsin Treatment \200 \200 \200 Supportive treatment of liver complications. Strongly advise against smoking. Liver transpl ant for end-stage liver failure. Wilson \200\231s disease A rare autosomal recessive disorder leading to toxic accumulation of cop- per in the liver and, subsequently, other tissues especially the brain and eye. See also b p.976. Presentation \200 Kayser \200\223Fleischer rings (copper deposition in Descemet \200\231s membrane of the eye ) often present (45% with hepatic presentation and 90% with neurological) and are pathognom onic. May require slit-lamp examination to visualize. Hepatic problems usually present in c hildhood (hepatitis, cirrhosis, fulminant hepatic failure). Adolescents/young adults usuall y present with neurological disease. Investigations \200 \200 d. Serum copper and caeruloplasmin 24hr urinary copper excretion >100microgram (normal <40micr ogram). Molecular genetic testing \200\224Wilson \200\231s disease gene ( ATP7B) mutation. Treatment \200 Lifelong chelation therapy with penicillamine (reverses pre-cirrhotic liver disease, but no t neurological damage). Liver transplantation if end-stage hepatic failure. 10_McClure_10.indd 346 11/14/2012 11:28:50 PM LIVER TRANSPLANTATION 347 Liver transplantation Indications for liver transplantation The commonest underlying condit ions leading to irreversible liver failure and transplant are: \200 \200 \200 \200 Fulminant hepatic failure: Biliary atresia. Chronic end-stage liver disease: Liver based me tabolic conditions: de \201 ciency, Crigler \200\223Najjar syndrome, tyrosinaemia. Acute l iver failure following a liver transplant: of transplant or hepatic artery thrombosis. Neon atal hepatitis. Autoimmune hepatitis. Unresectable tumor con \201 ned to the liver: e.g. viral, toxic, Wilson \200\231s disease. e.g. post-viral hepatitis with cirrhosis. e.g. Wilson \200\231s disease, 1-antitrypsin e.g. primary non-function \200 \200 e.g. hepatoblastoma. Clinical features requiring consideration for transplantation \200 \200 \200 \200 \200 \200 \200 Bleeding varices due to portal hypertension. Failure of growth or development. Resistant as cites. Hepatic encephalopathy. Poor quality of life: Coagulopathy (PTT >2 Multi-organ failu re: syndrome. e.g. pruritis, lethargy. x normal). e.g. hepatorenal syndrome, hepatopulmonary Preparation for transplant Requires multidisciplinary evaluation to include the following: \200 \200 \200 \200 \200 \200 Nutritional support. Development and psychological assessment of child and family. Educatio n and counseling. Ensure vaccinations are current: e.g. MMR, varicella, hepatitis A and B. Cardiac evaluation (ECG, echocardiogram). Abdominal US (patency of major hepatic blood vess els). Post-transplant complications \200 \200 \200 \200 \200 \200 Primary non-function of the liver (<5%). Hepatic artery thrombosis (10 \200\22315%). Biliar y leaks and strictures (20%). Acute rejection (50%). Chronic rejection (5 \200\22310%). Sep sis (main cause of death). Prognosis Long-term studies indicate normal psychosocial development and quality of life in survivors. Patients require lifelong immunosuppression drug ther- apy, e.g. ciclosporin or tacrolimus. \200 \200 1yr survival is 90%. 5yr survival is 80%. 10_McClure_10.indd 347 11/14/2012 11:28:51 PM This page intentionally left blank 349 Chapter 11 Nephrology Polyuria and frequency 350 Abdominal/renal mass 351 Haematuria 352 Proteinuria 354 Urinary tract infection 356 Vesicoureteric re \202 ux 360 Acute kidney injury 362 Acute kidney inj ury: diagnosis and treatment 364 Chronic kidney disease 366 Chronic kidney disease: treatme nt 368 Congenital urinary tract anomalies 370 Inherited renal disease 372 Glomerulonephriti s 374 Haemolytic \200\223uraemic syndrome 376 Nephrotic syndrome 378 Nephrotic syndrome: co mplications and follow-up 380 Renal tubular disorders 382 Proximal renal tubular acidosis 3 84 Bartter \200\231s syndrome 386 Renal calculi 388 Hypertension: de \201 nition 390 Hyper tension: causes and features 394 Hypertension: management 396 11_McClure_11.indd 349 11/14/2012 3:25:28 PM CHAPTER 11 Nephrology 350 Polyuria and frequency This is often subjective and dif \201 cult to assess, particularly in small children. Frequency can be considered to be the inappropriate and frequent pas- sa ge of small amounts of urine. Polyuria can be quantitatively de \201 ned as the passage of greater than 2000mL/1.73m2 per 24hr period. Assessment of polyuria and frequency requires a detailed history of uri- nary frequency habit. Causes of polyuria \200 Renal disorders: \200 chronic kidney disease (see \200 post-o bstructive uropathy; \200 nephrogenic diabetes insipidus (see \200 Fanconi syndrome (se e Metabolic/endocrine disorders: \200 \200 \200 Excess and inappropriate water intake : psychogenic polydipsia (see b p.450). b p.366); b p.450); b pp.372, 384). diabetes mellitus; cranial diabetes inspidus (see hypoadrenalism. b p.450); Causes of urinary frequency \200 Urinary tract infection (see \200 Bladder irritability and instability. \200 All causes of polyuria. \200 Small bladder capacity. b p.356). Investigations Baseline screening investigations should include the following. Urine \200 \200 \200 Urinalysis by urine dipstick testing. Urine culture. Urine osmolality. Blood \200 \200 \200 Urea and electrolytes. Plasma osmolality. Blood glucose (random or fasting). 11_McClure_11.indd 350 11/14/2012 3:25:28 PM ABDOMINAL/RENAL MASS 351 Abdominal/renal mass A rare presentation of urinary tract problems, which needs to be diffe ren- tiated from other causes of abdominal mass and swelling. Causes Intrarenal \200 \200 \200 \200 \200 b p.668. Wilms \200\231 tumor (young child with rapidly growing mass). See Renal venous thrombosis ( newborn with haematuria). Benign nephroma (rare neonatal problem). Horseshoe kidney. Pyelon ephritis (renal abscess). Other renal Hydronephrosis associated with the following. \200 Pelviureteric junction (PU J) obstruction. \200 Vescioureteric junction (VUJ) obstruction. \200 Large bladder and bladder outlet obstruction: e.g. \200 \200 \200 Urinoma: i.e. an encapsulated extrape lvicalyceal collection of urine that forms from urine leakage through a tear in the collect ing system or the proximal ureter. Single cyst (benign renal cyst). Multicystic dysplastic kidney \200\224usually newborn. Polycystic disease: \200 \200 Haematoma (trauma). posterior urethral valves (PUV); prune belly syndrome; neurogenic bladder. \200 \200 autosomal recessive; autosomal dominant \200\224rare in children. Extrarenal Adrenal mass (e.g. neuroblastoma). See b p.666. Investigation \200 \200 US will distinguish between most of the above. Further investigation, depending on likely c auses and discussion with radiology and urology colleagues, e.g. CT, MRI. 11_McClure_11.indd 351 11/14/2012 3:25:28 PM CHAPTER 11 Nephrology 352 Haematuria Blood in the urine (haematuria) may be visible to the naked eye or it may be mic roscopic and detected only by dipstick testing or by microscopy. The presence on microscopy of 10 or more RBCs per high-power \201 eld is abnormal. Urinary dipsticks are very sensi tive and can be positive at <5 RBCs per high-power \201 eld. Asymptomatic haematuria is f ound in about 0.5 \200\2232% of children. Presentation \200 \200 \200 Episode of macroscopic haematuria (causes alarm to child/family). Incidental \201 nding o f microscopic haematuria. Family screening and routine urinalysis. Other causes of \200\230red urine \200\231 The following can usually be distinguished from haematuria by taking a careful history, and with urine dipstick testing and microscopy: \200 \200 \200 \200 \200 \200 Haemoglobinuria/myoglobinuria. Foods \200\224coloring (e.g. beetroot). Drugs (e.g. rifampic in). Urate crystals (in young infants, usually \200\230pink \200\231 nappies). External so urce (e.g. menstrual blood losses). Fictitious \200\224consider if no cause found. Causes of haematuria \200 Urinary tract infections: \200 \200 \200 \200 Glomerula r: \200 \200 \200 Urinary tract stones: Trauma. Other renal tract pathology: \200 \200 Vascular: \200 \200 Hematological: Drugs: Exercise-induced. bacterial; viral (e.g. adenovirus in outbreaks); schistosomiasis (history of foreign travel ); tuberculosis. post-infectious glomerulonephritis; Henoch \200\223Sch nlein purpura IgA nephropathy, SLE; hereditary \200\224thin basement membrane, Alport \200\231s syndrome. e.g. due to hypercal ciuria. \200 \200 renal tract tumor; polycystic kidney disease. renal vein thrombosis; arteritis. \200 \200 coagulopathy/sickle cell disease. cyclophosphamide. History \200 UTI: \200 Renal stones: fever/frequency/dysuria. colicky abdominal pain. 11_McClure_11.indd 352 11/14/2012 3:25:28 PM HAEMATURIA 353 \200 \200 \200 Glomerular: Coagulopathy: Trauma . Family history: sore throat/rashes. easy bruising. haematuria, deafness (Alport \200\231s), sickle cell disease. Examination \200 \200 \200 \200 BP. Abdomen: Skin: Joints: palpable masses. rashes. pain/swelling. Investigations It is important to identify serious, treatable, and progressive conditions. During an acute illness, exclude UTI by urine culture. Asymptomatic or \200\230benign haem aturia \200\231 in children without growth failure, hypertension, oedema, proteinuria, urin ary casts, or renal impairment is a frequent \201 nd- ing. Many such children require no immediate investigation but need to be checked in the outpatient clinic to see if the probl em persists. \200 Urine: \200 \200 \200 Bloods: \200 \200 \200 \200 US urinary tract. Urinalysi s of parents (hereditary causes). Cystoscopy: microscopy (look for casts \200\224suggestive of nephritis) and culture; protein:creatinine ratio (normal, <20mg/mmol); calcium:creatinine ratio (normal, <0.7mmol/mmol). U&E/creatinine/albumin; FBC/clotting; complement ANA/anti-dsDNA. \200\224C3/C4, ASOT titres; \200 \200 rarely indicated in children. Treatment \200 \200 \200 \200 \200 \200 \200 If obvious cause (e.g. UTI), treat. If complex diagnosis (impaired renal function, proteinu ria, or family history) refer to pediatric nephrology unit. If no cause found and normal re nal function, BP, and no proteinuria, monitor until resolves. If no resolution after 6mths or change in any of above parameters refer to pediatric nephrology unit. 11_McClure_11.indd 353 11/14/2012 3:25:29 PM CHAPTER 11 Nephrology 354 Proteinuria This is de \201 ned as excessive urinary protein excretion. Protein may be fou nd in the urine of healthy children, and does not exceed 0.15g/24hr. Detection of proteinuria Urinalysis Performed by dipstick testing (Table 11.1), this is a c heap, practicable, sen- sitive method that primarily detects albumin in the urine. It is le ss sensitive for other forms of proteinuria. Table 11.1 Urinalysis by dipstick testing Test result Equivalent protein estimate (g/L) + 0.2 ++ 1.0 +++ 3.0 \211 20 ++++ Urinary protein:creatinine ratio (UP:UCr) Collection of an early morning urine (EMU) specim en for measurement of the urinary protein to creatinine ratio. Normal <20mg/mmol 24hr urinary protein excretion This is the gold standard test and requires a 24hr collectio n of urine to estimate urinary protein excretion. \200 \200 \200 Normal: <30mg/24hr. Microalbuminuria: 30 \200\223300mg/24hr. Proteinuria: >300mg/24hr. Causes Proteinuria may be due to benign or pathological causes. Non-pathological proteinuria \200 \200 \200 \200 \200 Transient. Fever. Exercise. Urinary tract infection (UTI). Orthostatic proteinuria (postura l proteinuria). This is a common cause of referral in older children. There is usually no h istory of signi \201 cance and a normal examination. Investigations reveal a normal UP:UCr ratio in early morning urine with elevated level in afternoon specimen (may require two 12 hr collections). This is regarded as a benign \201 nding and requires no treatment. 11_McClure_11.indd 354 11/14/2012 3:25:29 PM PROTEINURIA 355 Pathological (persistent) proteinuria This may be seen in a number of renal disorders inclu ding: \200 \200 \200 \200 b p.378); b p.374); Nephrotic syndrome (see Glomerulonephritis (see Chronic kidney disease (see Tubular interst itial nephritis. b p.366); Investigations Proteinuria detected on dipstick testing should be con \201 rmed using EMU UP:Ucr ratio. If the proteinuria is combined with haematuria, investigations should be dire cted at causes of haematuria and nephritis. \200 \200 A renal US scan should also be performed. Patients with persistent proteinuria detected ove r a period of 6 \200\22312mths should be referred to a pediatric nephrology center for cons ideration for biopsy. 11_McClure_11.indd 355 11/14/2012 3:25:29 PM CHAPTER 11 Nephrology 356 Urinary tract infection Up to 3% of girls and 1% of boys suffer from UTI during childhood. A UTI may be de \201 ned in terms of the presence of symptoms (dysuria, fre- quency, loin pain) plus the detection of a signi \201 cant culture of organisms in the urine: \200 \200 Any growth on culture of suprapubic aspirate. 5 Organisms/mL in pure growth from a carefull y collected urine >10 sample (midstream urine, clean catch urine, or bag urine). Ideally 2 consecutive growths of the same organism with identical sensitivities, but this is not alwa ys practical. Note: Bacteriuria in the absence of symptoms does not necessarily need treatment, but needs to be considered in the clinical context (e.g. previous UTI, predisposing urinary tract ab normalities). Guidance on the investigation, treatment and management of UTIs have been published.1 Clinical features Presentation varies; symptoms in infants may be non-speci \201 c: \200 \200 \200 vomiting/diarrhea; poor feeding/failure to thrive; prolonged neonatal jaundice. Examination \200 \200 \200 \200 \200 Height and weight: plot on growth chart. BP. Examination for abdominal masses. Examine geni talia and spine for congenital abnormalities. Examine lower limbs for evidence of neuropath ic bladder. Diagnosis Try to distinguish between upper (fever, vomiting, loin pain) vs. lower uri- nary tract symptoms (dysuria, frequency, mild abdominal pain, enuresis). Differentiation is oft en not possible in the younger child. \200 \200 UTI is a major cause of sepsis in a young infant. Ask about urinary stream in boys and fami ly history of vesicoureteric re \202 ux (VUR) or other urinary tract abnormality. Dipstick test in the urine. \200\230Leucocytes \200\231 and \200\230nitrites \200\231 strongly su ggests UTI. Urine should be sent for microscopy, culture, and sensitivity. Acute treatment Antibiotics should be started after urine collection (see Table 11.2). 11_McClure_11.indd 356 11/14/2012 3:25:29 PM URINARY TRACT INFECTION 357 Table 11.2 Antibiotic regimes If child is younger than 3mths of age Treat with parenteral antibiotics If child 3mths or older with acute pyelonephritis/upper UTI Treat with oral antibiotics for 7 \200\22310 days or IV antibiotics for 2 \200\2234 days fo llowed by oral antibiotics for a total duration of 10 days If child 3mths or older with cystitis/lower UTI Treat with oral antibiotics for 3 days. If the child is still unwell after 24 \200\22348hr, reassess Chose antibiotic from: \200 \200 \200 \200 \200 \200 \200 Trimethoprim 4mg/kg twice daily. Cefradine 25mg/kg twice daily. Cefalexin 25mg/kg twice dai ly. Co-amoxiclav 125/31 (1 \200\2236yrs), 5mL 3 times a day. Co-amoxiclav 250/62 (7 \200 \22312yrs) 5mL 3 times a day. IV cefuroxime 25mg/kg 8-hourly; or IV gentamicin 2.5mg/kg/dos e 8-hourly. A repeat urine culture should be obtained on completion of antibiotics. Follow-up and investigations All children presenting with UTI should be investigated for an y renal scar- ring and predisposing urinary tract abnormalities. Pyelonephritis or recur- r ent pyrexial UTIs need more comprehensive investigation than those at low risk (single, unc omplicated UTI with lower tract symptoms). Oral an- tibiotic prophylaxis (see b p.358) may need to be started and continued until investigations are complete. Recommended imaging tests (Tables 11.3 \200\22311.5) Table 11.3 Infants aged <6mths Test Responds well to treatment with 48hr Atypical UTI or recurrent UTI US during the acute infection NO YES US within 6wks YES NO DMSA 4 \200\2236mths after acute infection NO YES Micturating cystoure- thrography (MCUG) NO YES 11_McClure_11.indd 357 11/14/2012 3:25:29 PM CHAPTER 11 Nephrology 358 Table 11.4 Children aged >6mths, but <3yrs Test Responds well to treatment with 48hr Atypical UTI Recurrent UTI US during the acute infection NO YES NO US within 6wks NO NO YES DMSA 4 \200\2236mths after acute infection NO YES YES MCUG NO NO YES Table 11.5 Children aged >3yrs Test Responds well to treatment with 48hr Atypical UTI Recurrent UTI US during the acute infection NO YES NO US within 6wks NO NO YES DMSA 4 \200\2236mths after acute infection NO NO YES MCUG NO NO YES UTI prevention Predisposing factors to recurrent UTIs should be avoided: \200 \200 \200 \200 Treat and prevent constipation. Hygiene: Avoid nylon underwear and bubble baths. Encourage \202 uid intake and regular toileting with double micturition. clean perineum front to back. Do not routinely use antibiotic prophylaxis after \201 rst-time UTI, but con- sider it af ter recurrent UTI. Oral antibiotic prophylaxis (trimethoprim 2mg/kg at night or nitrofuran- toin 1mg/kg) is required if: \200 \200 VUR. Recurrent UTIs (more than 2 \200\2233 episodes). Reference 1 NICE (2007). Urinary tract infection in children: diagnosis, treatment and long -term infection, Clinical Guideline CG54. Available at: M www.nice.org.uk/nicemedia/pdf/CG5 4fullguideline.pdf 11_McClure_11.indd 358 11/14/2012 3:25:29 PM URINARY TRACT INFECTION 359 11_McClure_11.indd 359 11/14/2012 3:25:30 PM CHAPTER 11 Nephrology 360 Vesicoureteric re \202 ux This is the retrograde \202 ow of urine from the bladder into the upper uri- nary tract. VUR is usually congenital in origin, but may be acquired (e.g. p ost-surgery). VUR combined with UTI leads to progressive renal scar- ring. Such re \202 ux nephropathy may progress to end-stage renal failure if untreated. Incidence of VUR is 71% in newborn infants. It is observed in 30 \200\22345% of young children (<5yrs) presenting w ith UTI. There is often a strong family history with a 35% incidence rate among siblings of affected children. So called \200\230congenital re \202 ux \200\231 is also now recogniz ed as result of routine antenatal scanning. This can result in small, smooth underdevel- op ed kidneys in otherwise asymptomatic children. Grade of VUR The extent of retrograde re \202 ux from the bladder can be graded according to the International Re \202 ux Study grading system: I: \200 into ureter only. \200 \200 \200 II: III: IV: tortuosity of ureter, obliteration of sharp angle of fornices. V: into ureter, pelvis, and calyces with no dilatation. with mild/moderate dilatation, slight or no blunting of fornices. with moderate dilatation of ureter and/or renal pelvis and/or gross dilatation, tortuosity, no papillary impression visible in calyces. Diagnosis The diagnosis of VUR is established by radiological techniques. Micturating cystourethrogram This technique involves urinary catheterization and the admini stration of radiocontrast medium into the bladder. Re \202 ux is detected on voiding. \200 \200 Advantages: Disadvantages: grade of re \202 ux seen. requires bladder catheterization, radiation dose. Indirect cystogram A radionucleotide method. Includes mercaptoacetyltriglycine (MAG-3) and diethylenetriamine pentaacetic acid (DTPA) scans. \200 \200 Advantages: Disadvantages: needed. no catheterization required; lower radiation dose. false negatives found; co-operation of child to void is Follow-up and treatment The aims are to prevent progressive renal scarring. Prophylactic an tibiotics may be used to prevent this and imaging by indirect cystogram (e.g. MAG-3) and DM SA are sometimes used for follow-up. Randomized controlled trials of medical versus surgica l treatment show surgery can reduce the incidence of pyelonephritis, but there is no differ ence in scarring compared with med- ical treatment. Medical therapy Antibiotic prophylaxis therapy (as for UTI \200\223 see b previous section ). 11_McClure_11.indd 360 11/14/2012 3:25:30 PM VESICOURETERIC REFLUX 361 Surgery Not routinely recommended. Indications for surgery include failed medical therapy, or poor compliance. \200 \200 \200\230STING \200\231 procedure (subureteric Te \202 on injection): Endoscopic injection of materials behind ureter to provide a valve mechanism during bladder \201 lling and em ptying. Longevity and need for repeat treatments not fully known. Open surgery: commonly used. re-implantation of ureters. Prognosis \200 Spontaneous resolution of VUR often occurs, especially with lower grades of re \202 ux. Bi lateral re \202 ux (grades IV and V) and re \202 ux into duplex systems is associated wit h lower probability of resolution. 11_McClure_11.indd 361 11/14/2012 3:25:30 PM CHAPTER 11 Nephrology 362 Acute kidney injury Acute kidney injury (AKI) is a sudden reduction in glomerular \201 lt ration rate resulting in an increase in blood concentration of urea and creatinine and dist urbed \202 uid and electrolyte homeostasis (see also b p.94). Classi \201 cation The causes of AKI (Box 11.1) can be divided into pre-renal, renal, and post-renal. A patient may have more than one cause for their AKI. Box 11.1 Causes of AKI Pre-renal \200 \200 \200 \200 \200 Hypovolaemia, e.g. s to gastroenteritis, hemorrhage, DKA, nephrotic syndrome Peripheral vas odilatation, e.g. sepsis Impaired cardiac output, e.g. congestive cardiac failure Drugs, e. g. ACE inhibitors Renal \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Acute tubular necrosis (usually following pre-renal) Interstitial nephritis (usually drug-i nduced) Glomerulonephritis Haemolytic \200\223uraemic syndrome (HUS; see Cortical necrosis Bilateral pyelonephritis Nephrotoxic drugs, e.g. aminoglycoside, IV contrast, NSAIDs Myoglo binuria, haemoglobinuria Tumor lysis syndrome (see Renal artery/vein thrombosis b p.376) b p.684) Post-renal \200 \200 \200 \200 \200 Obstruction Post-urethral valves (PUV) Neurogenic bladder Calculi Tumors (rhabdomyosarcoma in infancy) History It is important to include the following points: \200 \200 History of sore throat/rash (e.g. streptococcal glomerulonephritis). Urinary symptoms of: \200 haematuria, frequency, dysuria (e.g. pyelonephritis); \200 poor stream (e.g. PUV). Signi \201 cant antenatal history. Drugs. \200 11_McClure_11.indd 362 11/14/2012 3:25:30 PM ACUTE KIDNEY INJURY 363 Examination It is important to assess and document the following. \200 \200 \200 \200 \200 \200 \200 Height and weight (compare with any recent/past measurements). Fever. Hydration status: Hae modynamic status including BP. Presence of any rashes/arthropathy. Abdomen: Neurology: any evidence of oedema/dehydration? tenderness or masses. exclude possible neuropathic bladder. Investigations Urine \200 \200 \200 \200 \200 \200 Urinalysis with microscopy of fresh urine, e.g. evidence of casts. Culture, e.g. pyelonephr itis. Osmolality, Na, creatinine, fractional excretion of sodium ( Protein:creatinine ratio to document proteinuria if dipstick +ve. Myoglobin if evidence of rhabdomyolysis. Urine ca lcium/oxalate to creatinine ratios if renal calculi suspected. b p.364). Blood investigations \200 3 \200\223, albumin, glucose, 2+, PO4 Urea, electrolytes, creatinine, Ca bicarbonate. Plasma osmolality. FBC and \201 lm. Blood cultures, if clinically septic. In suspected nephritis: \200 complement levels; \200 a nti-streptolysin O titre (ASOT), antiDNAaseB; antinuclear antigen (ANA), anti-dsDNA, anti-n eutrophil cytoplasmic \200 antibodies (ANCA). \200 \200 \200 \200 \200 \200 \200 Uric acid if tumor lysis suspected. Creatinine kinase if possible myoglobinuria. Clotting i f septic or potential need for biopsy or dialysis access. Drug levels if relevant (e.g. gen tamicin). Escherichia coli 0157 serology. Cultures \200 \200 Stool culture: Throat swab. E. coli 0157 (HUS). Radiology \200 \200 US(+/ \200\223 Doppler): CXR if evidence of \202 uid overload. kidneys and bladder. 11_McClure_11.indd 363 11/14/2012 3:25:30 PM CHAPTER 11 Nephrology 364 Acute kidney injury: diagnosis and treatment Diagnosis The following urinary indices may be helpful providing no diuretics have been given (Table 11.6). Table 11.6 Urinary indices indicating AKI Test Pre-renal Renal Post-renal Urine osmolality (mosmol/kg) >400 \200\223500 <350 Variable Urine/plasma Cr ratio >40 <20 <20 Urine Na (mmol/L) <20 >40 Variable FENa <1% >2% Variable To accurately interpret fractional excretion of sodium (FENa), patients should not have rec ently received diuretics. FENa is greater than 1% (and usually greater than 3%) with acute tubular necrosis and severe obstruc- tion of the urinary drainage. FENa = [(UNa \227 PCr)/(PNa \227 UCr)] \227 100 where UNa and UCr are urinary Na and creatinine, respectively, and PNa and PCr are plasma N a and creatinine, respectively. Treatment Liaise with a pediatric nephrology center early and treat the following. \200 + >6.5mmol/L; see b p.93). \200 \200 \200 \200 \200 \200 Hyperkalaemia (K Metabolic acidosis (see Hypertension (see b p.56). Shock (see Fluid overlo ad (see Hypocalcaemia (see Hypo/hypernatraemia (see b p.104). b pp.58, 396). b p.375). b p.93). b p.92). Speci \201 c treatment depends on the underlying cause. However, the follow- ing general m anagement principles apply: \200 \200 Observations: Fluids management: and furosemide. Otherwise, restrict to insensible losses ( 400mL/m2) + urine output. Consider adding diuretic therapy. Electrolytes: restricted diet. Consider adding PO4 binder. daily weight, BP, strict \202 uid input and output monitoring. Pre-renal \200\224 \202 uid bolus (10mL/kg of 0.9% saline) monitor at least 12-hourly until stable. K+ and PO4 11_McClure_11.indd 364 11/14/2012 3:25:30 PM ACUTE KIDNEY INJURY: DIAGNOSIS AND TREATMENT 365 \200 treat hypertension (see b p.396). BP: Medications: adjust drug doses according to level of renal impairment. The patient may require transfer to a pediatric nephrology center if dialy- sis looks likel y or there is uncertainty about the diagnosis. Indications for dialysis The following are indications for urgent dialysis in ARF. \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Severe hyperkalaemia. Symptomatic uraemia with vomiting/encephalopathy (usually urea >40mmo l/L). Rapidly rising urea and creatinine. Symptomatic \202 uid overload, especially cardi ac failure or pericardial effusion. Uncontrollable hypertension. Symptomatic electrolyte pr oblems or acidosis. Encephalopathy or seizures. Prolonged oliguria: nutritional failure. Re moval exogenous toxins or metabolite (inborn error). conservative regimen controls ARF, but causes Note: Patients with haemolytic \200\223uraemic syndrome should be referred as soon as the c hild becomes oliguric or if urea is raised as current prac- tice is to dialyse early to red uce neurological complications and to allow transfusion. Acute dialysis \200\224methods \200 \200 \200 Peritoneal dialysis (abdominal catheter). Haemodialysis (femoral or jugular access). Haemo \201 ltration (usually continuous veno-venous haemo \201 ltration). 11_McClure_11.indd 365 11/14/2012 3:25:30 PM CHAPTER 11 Nephrology 366 Chronic kidney disease Most children with CKD are asymptomatic until approaching chronic re nal disease stage 4 (see Table 11.7). CKD should be suspected if: \200 \200 \200 \200 failure to thrive; polyuria and polydipsia; lethargy, lack of energy, poor school concentra tion; other abnormalities such as rickets. See Box 11.2 for summary of causes. Table 11.7 Stages of chronic kidney disease Stage Description GFR* (mL/min/1.73m2) 1 Kidney damage with/without increased GFR >90 2 Kidney damage with mild decrease in GFR 60 \200\22389 3 Moderate decrease in GFR 30 \200\22359 4 evere decrease in GFR 5 \200\22329 5 Kidney failure <15 (or dialysis) GFR, Glomerular \201 ltration rate. CKD: correcting common misconceptions \200 \200 Plasma creatinine can remain normal until GFR reduced to <50%. Urine \202 ow rate may not mean a good GFR as many children with renal dysplasia have polyuria and nocturia. Other ur inary abnormalities such as proteinuria, glycosuria can be an indicator of tubular dysfunct ion. The focus is on GFR and not plasma creatinine \200 GFR can be formally measured by the Iohexol method or alternatively by 51Cr EDTA or inulin methods clearance, In ordinary clinical practice GFR (mL/min/1.73m (note: less accurate in children <2yrs or >14yrs): 2) may be estimated GFR (estimated) = 40 \227 height (cm)/creatinine ( mol/L). 11_McClure_11.indd 366 11/14/2012 3:25:30 PM CHRONIC KIDNEY DISEASE 367 Box 11.2 Causes of CKD Congenital (55%) \200 Renal dysplasia \200 Obstructive uropathies \200 Vesicoureteric re \202 ux nephropathy Hereditary (17%) \200 \200 \200 \200 \200 Polycystic kidney disease Nephronophthisis Hereditary nephritis Cystinosis Oxalosis Glomerulopathies (10%) Focal segmental glomerulosclerosis Multisystem disorders (9%) \200 \200 \200 Systemic lupus erythematosus Henoch \200\223Sch nlein purpura Haemolytic \200\223uraemic s yndrome Others \200 \200 \200 Wilms \200\231 tumor Renal vascular disease Unknown Investigations \200 Urinalysis. \200 Blood: \200 \200 \200 \200 Renal tract US. Left hand and wrist X-ray for bone age and renal osteodystrophy score. ECG/echocardiograph y for signs of left ventricular hypertrophy if hypertensive. FBC + iron studies if anemic; electrolytes/Ca/PO pH/bicarbonate; parathyroid hormone (PTH). 4/ALP/albumin; \200 11_McClure_11.indd 367 11/14/2012 3:25:30 PM CHAPTER 11 Nephrology 368 Chronic kidney disease: treatment There should be early liaison with and referral to a regi onal pediatric nephrology center. Urgent life-threatening abnormalities \200 +. \200 \200 High/low plasma K Low plasma Na High/low BP. 3 \200\223. +/acidosis/low Ca2+/high. PO4 Nutrition Early involvement of the pediatric dietician is needed. \200 Estimated average requirement (EAR) should be worked out. \200 \200 Minimum protein int ake of EAR for age. Vitamin supplements (but not vitamin A). often require supplements to achieve this; NG/gastrostomy feeds. \200 Fluid and electrolyte balance \200 \200 +-containing foods (e.g. banana, chocolate). Avoid high K Many causes of chronic renal failure (CRF) cause polyuria and Na wasting; ther efore, Na+ supplements are needed. If clinical \202 uid overload, Na + + restriction and diuretics. Acid \200\223base balance sodium bicarbonate supplements. Renal osteodystrophy \200 Control of plasma PO \200 Calcitriol (vitamin D) 15ng/kg/day. \200 Monitor PTH. 4. Restrict dietary intake/PO4 binders. Anemia \200 \200 \200 Assess iron status: oral iron supplements. Subcutaneous erythropoietin. b p.396. Hypertensi on, see Preservation of renal function \200 \200 Control hypertension. Reduce proteinuria: angiotensin receptor blocker therapy. \200\230St atin \200\231 therapy: e.g. angiotensin-converting enzyme (ACE) inhibitor/ evidence of bene \201 t from adult CRF trials. 11_McClure_11.indd 368 11/14/2012 3:25:31 PM CHRONIC KIDNEY DISEASE: TREATMENT 369 Growth \200 \200 Optimize nutrition, acid \200\223base balance, electrolyte balance. If failing height veloc ity (HV \200\2232 SD or below) or short stature (Ht \200\2232 SD or below) despite correc tion of above, treatment with recombinant human growth hormone is indicated. Education and preparation for dialysis/transplantation \200 \200 \200 Information provision. Meet team. Meet other families. Dialysis Peritoneal dialysis (PD) \200 \200 \200 \200 Preferred choice is automated peritoneal dialysis (APD) performed in patient \200\231s home (with mobile machines); therefore minimal disruption. Main risks: peritonitis and catheter blockage. Needs family and social support. Haemodialysis (HD) \200 \200 \200 Extracorporeal circuit. Vascular access by jugular venous catheter. Increasingly, long-term vascular access is by AV \201 stula (wrist or elbow). Therefore, avoid non-dominant arm for venepuncture and IV. Usually 4hr session, 3 times/wk in hospital. Home HD possible if t here is a family member to support this. \200 Renal transplantation This is the ultimate goal in CRF. \200 \200 \200 \200 \200 \200 Minimum 10kg (or when immunizations complete). Deceased donor vs. living-related donor (LRD ) source. Pre-emptive transplantation before dialysis required is ideal. LRD by laparoscopi c donor nephrectomy is now standard. Graft survival 85% after 2yrs. Lifelong immunosuppress ion is required. Psychosocial support \200 \200 \200 For patient and family this is crucial as CRF is lifelong treatment. Focus on prevention of cardiovascular disease, which is a major cause of mortality and morbidity in adult life. 11_McClure_11.indd 369 11/14/2012 3:25:31 PM CHAPTER 11 Nephrology 370 Congenital urinary tract anomalies \200 Increasingly, urinary tract anomalies are being detected earlier by the use of routine ante natal ultrasound scans. Renal anomalies account for about 20% of all signi \201 cant abnor malities found on detailed scans at 18 \200\22320wks gestation. Close liaison between obste tricians, pediatrician, and surgeon with regard to counseling the parents and follow-up is vital. Centers should have a postnatal investigation protocol as the majority of infants wi ll be asymptomatic. Amniotic \202 uid volume \200 Oligohydramnios: excretion that may lead to pulmonary hypoplasia. Polyhydramnios: low urine production or obstruction of urine polyuria. Renal size \200 Enlarged: \200 Small: cystic kidneys (any cause); hydronephrosis. dysplasia. Hydronephrosis \200 Unilateral: obstruction; vescioureteric re \202 ux (VUR). Bilateral: syndrome. pelviureteric junction (PUJ) or vescioureteric junction (VUJ)