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) bladder outlet obstruction, e.g. PUV, VUR, prune belly Renal cysts \200 \200 \200 Multicystic dysplastic kidneys (MCDK). Polycystic kidney disease (PCKD). Cystic dysplasia. Abnormal renal parenchyma Echogenic: \200 \200 \200 cystic kidneys (any cause); congenital nephrotic syndrome (may have polyhydramnios, large p lacenta). Investigations If a major problem is suspected (e.g. PUV, bilateral severe hydronephro- sis , palpable kidneys), a renal US should be performed after 24hr of age. Otherwise routine po stnatal investigation with U/S (at 2 \200\2234wks), MCUG (at 4 \200\2238wks), and radionucl ide scan (at 8 \200\22312wks of age). 11_McClure_11.indd 370 11/14/2012 3:25:31 PM CONGENITAL URINARY TRACT ANOMALIES 371 Clinical management In the postnatal period, ensure male infants have voided and that a goo d urinary stream is observed. The initial postnatal US \201 nding guides further manageme nt. \200 MCUG only routine if strong suspicion of VUR (e.g. dilated ureters/ intermittent dilatation of pelvis). Will need cover with antibiotics (e.g. oral trimethoprim) for the procedure. G ive antibiotic prophylaxis (e.g. oral trimethoprim) to all babies with suspicion of VUR. Ra dionuclide scan depends upon lesion: \200 \200 DMSA if function of kidney required (e.g. MCDK, VUR); MAG-3 renogram if \200\230obstructio n \200\231 being evaluated (e.g. PUJ, VUJ). Most infants with hydronephrosis can be conservatively managed if they are asymptomatic. 11_McClure_11.indd 371 11/14/2012 3:25:31 PM CHAPTER 11 Nephrology 372 Inherited renal disease Many renal abnormalities are inherited. Recognition of these is imp ortant, not only in terms of diagnosis and treatment of the patient, but also for screening and genetic counseling for the whole family. \200 \200 New therapies may become available as gene therapy is researched. Ethical considerations ar e very important in this group in terms of family screening and counseling. Databases such as Online Mendelian Inheritance in Man (OMIN) provide comprehensive lists. Below are a few of the more common conditions. Autosomal dominant inheritance Polycystic kidney disease (ADPKD). Commonest inherited renal disease (1/400 to 1/1000), which usually only manifests in adult life, but cysts can be se en on US scan in children. Multi-organ involvement (intracranial aneurysms, liver and pancr eatic cysts, mitral valve prolapse), abdominal mass, haematuria, pain (rare presentation in neonatal period with abdom- inal masses and/or high or low BP, renal impairment). Tuberous sclerosis (see b pp.530, 947) \200 \200 \200 \200 \200 \200\230ash-leaf \200\231 macule; adenoma sebaceum; shagreen patch. Skin: Neurological: Cardiac: Renal: Neuro \201 bromatosis: should be monitored (see b pp.5 61, 986). Branchio-oto-renal syndrome Hearing loss, branchial arch defects, renal anomalies . seizures. rhabdomyoma. cysts; angiomyolipomas; high or low BP; renal impairment. neuro \201 broma, renal artery stenosis; therefore, BP Autosomal recessive inheritance Polycystic kidney disease (ARPKD) \200 Incidence 1:20 000 to 1:40,000. \200 Oligohydramnios and large echogenic kidneys. \200 Fusiform dilatatio n of collecting tubules. \200 Prognosis depends on degree of pulmonary involvement. \200 This usually presents at an earlier age than ADPKD and progresses to renal failure in a s horter time. Liver involvement leads to portal hypertension in later life Bardet \200\223Bi edl syndrome: retinitis pigmentosa, hypogenitalism, renal anomalies commonly found (b p.949 ). Cystinosis (Fanconi \200\231s syndrome): in transportation system of cystine out of cell . Accumulates in various organs (cornea, thyroid, brain, leading to growth failure) \200 \224eventual renal failure. Nephronophthisis: renal failure. Primary hyperoxaluria: Cystinu ria: \200 obesity, polydactyly, mental retardation, excess storage of cystine due to defect polyuria, polydipsia, tubulopathy and childhood onset \200 see b p.389 (renal calculi). recurrent calculi. 11_McClure_11.indd 372 11/14/2012 3:25:31 PM INHERITED RENAL DISEASE 373 X-linked \200 \200 \200 Alport \200\231s syndrome: Nephrogenic diabetes insipidus. Fabry \200\231s disease: (b p.96 8). sensorineural deafness with progressive nephritis. de \201 ciency of alpha-galactosidase A; now treatable Sporadic \200 VATER association: (see b pp.948, 951); renal problems include agenesis, ectopy, or obstruc tion. CHARGE association choanal atresia, retarded growth, genital anomalies, ear abnormali ties (renal anomalies include dysplasia, agenesis, and ectopy). Turner \200\231s (XO): Will iam \200\231s syndrome: Bartter \200\231s: (b p.386). vertebral, anal, tracheo-oesophageal, radial/renal (b pp.846, 950): Coloboma, heart defects, \200 \200 horseshoe or duplex kidneys (see b pp.469, 948). hypertensive, hypercalcaemia (see b pp.237, 941). metabolic alkalosis, low K+, high aldoste rone with normal BP 11_McClure_11.indd 373 11/14/2012 3:25:31 PM CHAPTER 11 Nephrology 374 Glomerulonephritis A combination of haematuria, oliguria, oedema, and hypertension with var iable proteinuria. \200 \200 Majority of cases post-infectious. Usually presents 1 \200\2232wks after a URTI and sore th roat. Causes of acute glomerulonephritis Post-infectious \200 Bacterial: \200 Mycoplasma pneumoniae \200 Virus: \200 Fungi: \200 Parasites: streptococcal commonest, Staphylococcus aureus, , Salmonella herpesviruses (EBV, varicella, CMV) candida, aspergillus toxoplasma, malaria, schistosomiasis Others (less common) \200 \200 \200 \200 \200 MPGN IgA nephropathy Systemic lupus erythematosis Subacute bacterial endocarditis Shunt nep hritis Investigations \200 Urine: \200 \200 Throat swab: Bloods: \200 FBC; \200 U&E, including creatinine, bic arbonate, calcium, phosphate, and \200 albumin; \200 ASOT/antiDNAase B; \200 compleme nt (expect low C3, normal C4); \200 autoantibody screen (include ANA). Renal US (urgent). CXR (if \202 uid overload suspected). urinalysis by dipstick: haematuria +/ \200\223 proteinuria; microscopy \200\224casts (mostl y red cell casts). \200 culture. \200 11_McClure_11.indd 374 11/14/2012 3:25:31 PM GLOMERULONEPHRITIS 375 Management Most require admission because of \202 uid balance, worsening renal function, or hypertension. Treat life-threatening complications \201 rst: \200 \200 \200 \200 \200 b p.93); b pp.58, 396); hyperkalaemia (see hypertension (see acidosis (see seizures (see hypocalcaemia (see b p.104); b p.80); b p.93). Otherwise supportive treatment. \200 Fluid balance: \200 weigh daily; \200 no added/restricted salt diet; \200 if oliguric , \202 uid restrict to insensible losses (400mL/m \200 output; \200 consider furosemi de 1 \200\2232mg/kg bd if \202 uid overloaded. Hypertension: \200 \200 \200 Note: Infection: but limits spread of nephritogenic bacterial strains). 2) + urine treat \202 uid overload; blockers and calcium channel blocker usual \201 rst choice; Do not use ACE inhibitor (may worsen renal function). 10-day course of penicillin (does not affect natural history, When to refer to pediatric nephrology unit \200 \200 Patients with life-threatening complications (see Management). Those with atypical features , including: \200 \200 \200 \200 \200 \200 \200 \200 worsening renal function; nephrotic state; evidence of systemic vasculitis (e.g. rash); nor mal C3 complement levels; increased C4 complement levels; +ve ANA; persisting proteinuria a t 6wks; persisting low C3 at 3mths. Prognosis \200 95% with post-streptococcal glomerular nephritis (GN) show complete recovery. Microscopic h aematuria may persist for 1 \200\2232yrs. Discharge from follow-up once urinalysis, BP, and creatinine are normal. \200 11_McClure_11.indd 375 11/14/2012 3:25:31 PM CHAPTER 11 Nephrology 376 Haemolytic \200\223uraemic syndrome This is the commonest cause of AKI in children in Europ e and the USA. It typically has a seasonal variation with peaks in the summer and autumn mo nths. It presents with a triad of: \200 \200 \200 microangiopathic haemolytic anemia; thrombocytopenia; acute renal failure. Two forms of HUS are recognized. \200 Atypical/sporadic: \200 \200 Epidemic form: \200 \200 \200\223 HUS); not diarrhea-associated (D often familial. + HUS); diarrhea-associated (D commonly associated with verocytotoxic producing H7 type, although o ther pathogens have also been implicated (e.g. Shigella, Streptococcus pneumoniae). E. coli 0157. E. coli are common bacteria, normally found in the gut of warm-blooded animals. There are m any types of E. coli, most of which are harmless. However, the enterohaemorrhagic E. coli ( EHEC) produce toxins (poi- sons) that can cause gastroenteritis with blood in the stool. Th e toxins are called shiga toxins or verotoxins; hence, EHEC is also called STEC or VTEC. VT EC is found in the gut of cattle, and can also be found in the gut of humans without causin g illness. The bacteria can be passed on to humans by: \200 \200 \200 \200 \200 \200 Eating improperly cooked beef, in particular, ground or mince beef. Drinking raw (unpasteur ized) milk. Close contact with a person who has the bacteria in their feces. Drinking conta minated water. Swimming or playing in contaminated water. Contact with farm animals. Clinical features Acute renal failure Gut \200 \200 \200 \200 Prodrome of bloody diarrhea. Rectal prolapse. Haemorrhagic colitis. Bowel wall necrosis and perforation. Pancreas (occurs in <10%) \200 \200 \200 \200 Glucose intolerance/insulin-dependent diabetes mellitus. Pancreatitis. Liver jaundice. Neur ological Irritability to frank encephalopathy. 11_McClure_11.indd 376 11/14/2012 3:25:31 PM HAEMOLYTIC \200\223URAEMIC SYNDROME 377 Cardiac myocarditis (rare) Investigations \200 FBC + \201 lm. \200 Blood cultures. \200 U&E. \200 LFTs. \200 E. coli \200 Stools: polymerase chain reaction (PCR). microscopy and culture. Treatment Early liaison with a pediatric nephrology unit is required, as early dialysis may be needed. Management is mainly supportive and directed at treating the clinical features of HUS. Antibiotics for underlying E. coli infection are not indicated. \200 \200 \200 \200 \200 \200 Monitor electrolyte balance. Monitor \202 uid balance. Nutrition. Blood transfusion (note risks/concerns regarding \202 uid overload and hyperkalaemia). Treat hypertension. Outcome \200 \200 \200 Generally good. Mortality <5%. Long-term: up to 30% may develop mild impairment of GFR. 11_McClure_11.indd 377 11/14/2012 3:25:31 PM CHAPTER 11 Nephrology 378 Nephrotic syndrome This is de \201 ned as a combination of: \200 \200 \200 \200 Heavy proteinuria (urinary protein to creatinine ratio >200mg/mmol). Hypoalbuminaemia (albu min <25g/L). Oedema. Hyperlipidaemia. The incidence is approximately 2/100,000 children with a peak age of onset in children aged <6yrs. Boys are more commonly affected than girls (2:1) and there is an increased frequenc y in certain ethnic groups, e.g. Indian subcontinent. Nephrotic syndrome can be either prim ary or secondary Primary \200 \200 Congenital. Infantile. Secondary \200 \200 \200 \200 Minimal change disease (MCD): Focal segmental glomerulosclerosis (FSGS; 10%). Membranoproli ferative glomerulonephritis (MPGN; 5%). Membranous glomerulonephritis (MGN). commonest (85%). Classi \201 cation Nephrotic syndrome can be clinically classi \201 ed as being either st eroid- sensitive (SS), steroid dependent or steroid-resistant (SR). The majority of MCD is SS. \200 \200 \200 MCD (SS), >95%. FSGS (SS), 20%. MPGN (SS), 55%. Clinical features Most children present with insidious onset of oedema, which is initially perorbital, but becoming generalized with pitting oedema. Perorbital oe- dema is often most noticeable in morning on rising. Ascites and pleural effusions may subsequently develop. Examination This should establish the extent of dependent oedema, e.g. facial, ankle, scrot al, etc. Assessment should also include: \200 \200 \200 Height and weight (compare with previous/recent measurements). BP. Peripheral perfusion. 11_McClure_11.indd 378 11/14/2012 3:25:31 PM NEPHROTIC SYNDROME 379 Investigations Urine \200 \200 \200 Urinalysis: Microscopy: Na received diuretics this is not accurate.) Culture. Protein:creat inine ratio (early morning urine specimen). protein +++. haematuria/casts (suggest causes other than MCD). +: If <10mmol/L suggests hypovolaemia. (N ote: If patient has \200 Bloods \200 \200 Serum albumin (reduced, <25g/L). U&E/creatinine (decreased sodium and total calcium \200 \224with normal ionized calcium). C3/C4 (if decreased suggests not MCD). Consider ANF, ASOT , ANCA, immunoglobulins if mixed nephritic/ nephrotic picture. Lipids: lipoprotein (VLDL). Hemoglobin may be increased or decreased depending on plasma volume. Varicella zoster immun ity status. \200 total cholesterol/low density lipoprotein (LDL)/very low density Management Patients should be admitted, particularly if this is their \201 rst episode or if there are concerns regarding complications. Management is initially aimed at \202 uid restriction and prevention of hypovolaemia. A trial of oral steroid therapy to induce remi ssion is also started. Prophylaxis against bacterial infection (particularly pneumococcal) is also required. Treatment \200 \200 \200 Treat hypovolaemia if present but albumin infusion is not routine. Fluid restriction to 800 \200\2231000mL/24hr. Diuretics if very oedematous and no evidence of hypovolaemia. Furosem ide/spironolactone. Steroid therapy: \200 \200 \200 \200\224slow wean over next 4mth s with slow taper, but need to 2/day for 4wks; oral prednisolone 60mg/m followed by 40mg/m stop consider side-effects of steroids. 2/alternate days for 4wks; then Other measures \200 \200 \200 Diet (no added salt and healthy eating \200\224not high protein). Prophylactic antibiotics (oral penicillin V) until oedema-free. Immunize with pneumococcal vaccine. 11_McClure_11.indd 379 11/14/2012 3:25:32 PM CHAPTER 11 Nephrology 380 Nephrotic syndrome: complications and follow-up Complications Complications are s to the re lative hypovolaemic state and to impaired immunity. Infection Predisposition to infection is s to decreased IgG levels, and to impaired opsoniz ation due to steroid immunosuppression. Bacterial peritonitis (especially Streptococcus pne umoniae) is an important complication and should be considered in any child with nephrotic syndrome who com- plains of abdominal pain. Urgent assessment, cultures, and IV antibiotic therapy are required. Thrombosis Nephrotic syndrome produces a hypercoagulable state and predisposition to both a rterial and venous thrombosis is recognized. Hypovolaemia Suggested by development of oliguria and or presence of low BP. Patients may a lso complain of abdominal pain. If present, administration of an in- fusion of 20% human al bumin solution 1g/kg over 2hr with furosemide (2mg/kg IV) should be given. Acute renal fail ure This is pre-renal and s to hypovolaemia. Indications for renal biopsy The majority of patients will have MCD and will respond to ste roids. Biopsy is therefore reserved for those with atypical features: \200 \200 \200 \200 \200 \200 Age <12mths or >12yrs. Increased BP. Macroscopic haematuria. Impaired renal function. Decre ased C3/C4. Failure to respond after 1mth of daily steroid therapy. Follow-up Prognosis \200 \200 \200 30% single relapse. 30% occasional relapses. 30% steroid dependence. Relapse \200 Many patients with steroid-sensitive nephrotic syndrome will relapse. A relapse is de \201 ned as detection of urine dipstick ++ proteinuria for >3 days. Frequent relapse is de \201 ned as >2 relapses within 6mths of initial response or 4 or more relapses in any 12mth s. 11_McClure_11.indd 380 11/14/2012 3:25:32 PM NEPHROTIC SYNDROME: COMPLICATIONS AND FOLLOW-UP 381 Management of relapses Each relapse is treated with oral steroids in a similar manner to ab ove. Alternative strategies for frequent relapsers include a trial of therapy with other ag ents such as: \200 Cyclophosphamide. \200 Levamisole. \200 Ciclosporin A. \200 Othe r agents including the immunosuppressants tacrolimus, mycophenolate mofetil and anti-CD20 m onoclonal antibody (rituximab) may be considered. 11_McClure_11.indd 381 11/14/2012 3:25:32 PM CHAPTER 11 Nephrology 382 Renal tubular disorders The renal tubules are responsible for the regulation of \202 uid, acid \200\223base, and electrolyte balance. Abnormalities of renal function may occur at a ny point along the length of the renal tubule system and may lead to a distur- bance in the equilibrium of any of the substances handled by it. It is essen- tial to consider these di sorders when there are any of the following: \200 Glycosuria, amino-aciduria, or impaired ability to concentrate or acidify urine shown on ur inalysis. Stones or nephrocalcinosis: causes. Polyhydramnios and failure to thrive in a new born: associated with hypokalaemic alkalosis. Failure to thrive with rickets: syndrome. Maj or rickets with low plasma phosphate levels: hypophosphataemic rickets. Failure to thrive w ith low urine osmolality: distal tubular acidosis and oxalosis are major e.g. Bartter syndrome cystinosis is commonest cause of Fanconi familial nephrogenic diabetes insipidus. Renal tubular acidosis Renal tubular acidosis (RTA) is a state of systemic hyperchloraemia result- ing from impaired urinary acidi \201 cation. Three types of RTA exist: \200 \200 \200 Proximal type. Distal type. Mineralocorticoid de \201 ciency-associated (see b pp.430 \200\223432, 439). 11_McClure_11.indd 382 11/14/2012 3:25:32 PM RENAL TUBULAR DISORDERS 383 11_McClure_11.indd 383 11/14/2012 3:25:32 PM CHAPTER 11 Nephrology 384 Proximal renal tubular acidosis See also b pp.104, 385. This type of RTA results from reduc ed proximal tubular reabsorption of bicarbonate. \200 25% of urinary bicarbonate is lost. \200 Plasma bicarbonate level falls until it reaches a threshold when urinary bicarbonat e wasting ceases (approximately 15 \200\22318mmol/L). Urinary acidi \201 cation to pH valu es <5.5 is not possible. Proximal RTA may occur as an isolated disorder with no other abnor- malities of tubular fun ction. This form may be transient and is occasion- ally inherited. Proximal RTA also occurs as a more generalized defect of proximal tubular transportation characterized by: \200 \200 RTA. Excessive urinary loss of glucose, phosphate, amino acids, sodium, potassium, calcium, and uric acid. This generalized form is known as Fanconi syndrome, which may be p or s to several inherited and acquired disease states (see Box 11.3). Distal RTA See also b p.385. This is due to de \201 ciency in hydrogen ion secretion by th e distal renal tubules and collecting ducts. Urine pH cannot be reduced 5.8. Hyperchloraemi a and hypokalaemia are characteristic, but less severe than that found in proximal RTA. Nep hrocalcinosis may be present. Distal RTA may be isolated or secondary (see Box 11.3). Clinical features of RTA Children with isolated forms of proximal and distal RTA usually pr esent with failure to thrive in infancy. Those with the s forms of RTA may present in a sim ilar way. Diagnosis Other causes of systemic acidosis (e.g. chronic diarrhea, lactic acido- sis, diab etic ketoacidosis) should be excluded. Investigation to establish a diagnosis of RTA should include: \200 \200 Blood: Urine \200\224early morning sample: \200 \200 pH; bicarbonate (low); potassium (low); chloride (high). pH < 5.5 suggests proximal RTA; \211 5.8 suggests distal RTA. pH If proximal RTA is detected, blood and urinalysis to establish other tubular defects should be undertaken. Treatment The main aims are correction of acidosis and maintenance of normal bicar- bonate and potassium. This can be achieved by alkali (citrate or bicarbon- ate)/potassium-containi ng solutions. 11_McClure_11.indd 384 11/14/2012 3:25:32 PM PROXIMAL RENAL TUBULAR ACIDOSIS 385 Box 11.3 Causes of renal tubular acidosis Proximal \200 \200 \200 Isolated: Primary Fanconi syndrome Secondary Fanconi syndrome, inherited: \200 \200 \200 \200 Secondary Fanconi system, acquired: Secondary Fanconi system: sporadic or inherited cystinosis; galactosaemia; Wilson \200\231s disease; Lowes syndrome. \200 vitamin D de \201 cient rickets. hypothyroidism Distal \200 \200 sporadic or inherited. Isolated: Secondary to nephritis: \200 obstructive nephropathy \200 pyelonephritis Seco ndary to toxins: Lithium \200 amphotericin B 11_McClure_11.indd 385 11/14/2012 3:25:32 PM CHAPTER 11 Nephrology 386 Bartter \200\231s syndrome This is a relatively rare form of renal tubular dysfunction. The condition is best described as a defect in chloride reabsorption in the ascending loop of Henl , resulting in: \200 \200 \200 excessive potassium excretion; increased prostaglandin synthesis; stimulation of the renin \200\223angiotensin \200\223aldosterone system. Clinical features Young children present with: \200 \200 \200 \200 failure to thrive; poor growth; muscle weakness; constipation. Polyuria and polydipsia due to excessive salt and water loss may be evident. Diagnosis Characteristic \201 ndings include: \200 \200 \200 \200 hypokalaemia; hypochloraemia; raised plasma renin and aldosterone levels; normal BP. Urine potassium and chloride levels are high. Treatment Goals are to maintain serum potassium levels >3.5mmol/L and to ensure adequate nu trition. Therapy includes a combination of oral potassium sup- plement together with a pota ssium-sparing diuretic (e.g. spironolactone) and indomethacin (prostaglandin inhibitor). 11_McClure_11.indd 386 11/14/2012 3:25:32 PM BARTTER \200\231S SYNDROME 387 11_McClure_11.indd 387 11/14/2012 3:25:32 PM CHAPTER 11 Nephrology 388 Renal calculi The incidence of renal calculi varies according to geography and socio- econo mic conditions around the world. In the UK it affects approximately 1.5/million child popul ation. Etiology Infective \200 \200 \200 Commonest cause in children in UK. Associated with chronic UTI with Proteus \200\224 \200 \230staghorn \200\231 calculi. Pseudomonas, Klebsiella, E. coli. Also UTI with Associated with urinary stasis Congenital malformations, e.g.: \200 \200 pelviureteric junction obstruction; megaureter. Metabolic \200 \200 i.e. 24hr urinary Ca >0.1mmol/kg/day or urinary Hypercalciuria: Ca:creatinine ratio >0.74mmol/mmol: \200 \200 \200 \200 Cystinuria (autosomal recessive condition): typically radiolucent stones. Oxalosis: Uric acid stones: \200 \200 \200 primary hyperparathyrodism; idiopathic infantile hypercalcaemia; hypervitaminosis D; prolon ged immobilization. \200 primary hyperoxaluria type I (PH1). myeloproliferative disorders following medication/chemotherapy for patients with leukemia, lymphoma; Lesch \200\223Nyhan syndrome. Clinical features Most children will present with either gross or microscopic haematuria. T hey may be otherwise asymptomatic. The classic symptoms of renal colic are uncommon, e.g. i ntense pain located in the abdomen or in the loins and back. Symptoms and signs of a UTI ma y also be present. Some child- ren may describe a sensation of \200\230having passed grave l \200\231 on micturition. Investigations Urine \200 \200 \200 \200 \200 Dipstick analysis. Microscopy (pH, cells, crystals). Culture (exclude infection). Calcium:c reatinine ratio; oxalate:creatinine ratio. Amino acid screen. 11_McClure_11.indd 388 11/14/2012 3:25:32 PM RENAL CALCULI 389 Blood \200 \200 \200 \200 U&E, bicarbonate, creatinine. Calcium, phosphate, PTH. Liver function tests. Uric acid. Renal tract ultrasound Other investigations \200 AXR: \200 \200 IV pyleogram or CT scan. Renal stone analysis: composition. radio-opaque stones: calcium/cysteine/infective; radiolucent stones: uric acid/xanthine. \200 Treatment The acute treatment of renal colic secondary to renal stones is based on the prov ision of adequate analgesia and hydration. Treat any under- lying UTI with antibiotics. If severe renal impairment and urinary tract obstruction is evident refer to the pediatric uro logy team for considera- tion for extracorporeal shock-wave lithotripsy. Surgery (e.g. perc utaneous nephrolithotomy or open surgery) is now seldom indicated. Long-term management is aimed at preventing further obstruction and bouts of renal colic. The simplest and most eff ective measures to achieve this are to ensure adequate hydration and diuresis to maintain a good urinary \202 ow and dilute urine. Treatment of any underlying urinary tract infecti on and metabolic disorder is also required. Primary hyperoxaluria type 1 This is an autosomal recessive condition. Three forms are reco gnized. \200 Infantile form: stage renal failure (ESRF/Stage 5 CKD). Child/adolescent form: Adult form: early nephrocalcinosis and progression to CKD and end- \200 recurrent urolithiasis and progression to ESRF. urolithiasis only. 11_McClure_11.indd 389 11/14/2012 3:25:32 PM CHAPTER 11 Nephrology 390 Hypertension: de \201 nition De \201 ned by reference to sex, height centile charts (see Fig. 11.1). \200 \200 \200 \200 Normal: High normal: Hypertension: Severe hypertension: systolic and diastolic <90th centile. systolic or diastolic between 90th and 95th centile. systolic or diastolic >95th centile. systolic or diastolic >99th centile. BP measurement should be part of routine examination. Measurement technique \200 Cuff size. \200 \200 \200 \200 After 5min rest (ideally!). Sitting position with ar m at level of heart (children). Supine position in infants. On auscultation: systolic and d iastolic values, respectively. bladder width mid-arm circumference; bladder length Note: \200\22470% of acromion olecranon distance or 40% \200\224should completely encircle arm. small cuff area is a common cause of false positive high BP! \200 \200 \200 1st and 5th (disappearance) Korotkoff sounds used for Measurement devices \200 \200 \200 \200 Manual oscillometric sphygmomanometer (mercury now withdrawn). Doppler: not all devices sui table. Automatic oscillometry: Ambulatory blood pressure monitoring (ABPM) for 24-hr pro \201 les: \200 \200 Intra-arterial (in intensive therapy unit (ITU) setting). infants (for systolic pressure). little normative data in pediatrics; signi \201 cant hypertension \211 30% readings above 95th centile. 11_McClure_11.indd 390 11/14/2012 3:25:32 PM HYPERTENSION: DEFINITION 391 Fig. 11.1 Blood pressure centile \201 gures for girls and boys. Copyright Lisa Jackson an d Nandu Thalange. 11_McClure_11.indd 391 11/14/2012 3:25:32 PM CHAPTER 11 Nephrology 392 Fig. 11.1 (Contd.) 11_McClure_11.indd 392 11/14/2012 3:25:34 PM HYPERTENSION: DEFINITION 393 11_McClure_11.indd 393 11/14/2012 3:25:35 PM CHAPTER 11 Nephrology 394 Hypertension: causes and features Causes of hypertension Primary (essential) hypertension This is a diagnosis of exclusion. High body mass index, ex cessive salt intake, lack of exercise, and family history may be underlying predispos- ing factors Secondary hypertension \200 Renal (commonest cause in hospital referral practice): \200 \200 \200 \200 \200 V ascular: \200 umbilical arterial/venous catheters \200 renal artery stenosis \200 ren al vein thrombosis \200 coarctation of aorta \200 vasculitis Endocrine: \200 \200 \200 \200 \200 Trauma Neurological: \200 2 to pain \200 raised intracranial hype rtension Tumors: \200 neuroblastoma \200 Wilms Medication: \200 steroids \200 amino phylline/caffeine \200 oral contraceptive pill \200 erythropoietin \200 calcineurin i nhibitors; decongestants \200 amphetamines; cocaine Others: \200 \200 \200 chronic renal parenchymal disease (re \202 ux/scarring) polycystic kidney disease obstruct ive uropathy acute nephritis chronic renal failure congenital adrenal hyperplasia hyperthyroidism increased steroids (iatrogenic or endogenous ) phaeochromocytoma (BP intermittently raised) hyperaldosteronism \200 bronchopulmonary dysplasia ECMO \200\230white-coat \200\231 hypertension 11_McClure_11.indd 394 11/14/2012 3:25:35 PM HYPERTENSION: CAUSES AND FEATURES 395 Clinical features Most are asymptomatic. Infants \200 \200 \200 Vomiting. Failure to thrive (rare). Congestive cardiac failure/respiratory distress (in new borns). Children \200 \200 \200 \200 \200 \200 \200 \200 Headache/nausea and vomiting. Visual symptoms. Irritable/tired. Bell \200\231s palsy. Epist axis. Growth failure. Fits. Altered consciousness. Examination \200 Check fundi. \200 Feel abdomen for abdominal masses. \200 Listen for renal bruits. \200 Feel femoral pulses and compare to radial/brachial pulses (to exclude \200 coarctation) and check BP in all 4 limbs. \200 Examination of the heart. Investigations A s cause is more likely with severe hypertension. Treatment and inves- tiga tions may need to proceed together. \200 Urine: \200 \200 \200 Blood tests: \200 FBC; \200 U&E and creatinine; \200 bica rbonate, calcium, phosphate, albumin; \200 plasma renin and aldosterone. CXR and ECG. ECG . US of urinary tract + Doppler if renal artery stenosis suspected. Further imaging will de pend upon suspected cause and ultrasound \201 ndings, e.g. DMSA, CT scan, arteriogram. Sp ecialized tests, e.g. for phaeochromocytoma (see urinalysis, microscopy, and culture; vanillylmandelic acid (VMA):creatinine ratio; steroid pro \201 le and toxicology. \200 \200 \200 \200 \200 b p.675). 11_McClure_11.indd 395 11/14/2012 3:25:35 PM CHAPTER 11 Nephrology 396 Hypertension: management Hypertensive crises Acute, severe hypertension will require carefu l monitoring in a pediatric ICU and treatment with drugs shown in Table 11.8. Maintenance antihypertensive therapy Dosing schedules of many hypertensive drugs have not b een evaluated in children. The favored combination is a beta-adrenergic blocker with a vaso dilator. A diuretic can be used if BP is still not controlled. ACE inhibi- tors should be a voided if renal artery stenosis is suspected but are useful for renin-mediated hypertension . Phentolamine is used if catecholamine- induced hypertension is suspected, e.g. phaeochrom ocytoma. Table 11.9 gives dosing schedules for various hypertensive drugs. Table 11.8 Emergency treatment of hypertensive crisis (see also b pp.58, 397)* Drug Administration Onset of effect Side-effects Nifedipine Sublingual hourly prn 200 \200\223500micrograms/kg Minutes Headaches, tachycardia Sodium nitroprusside 0.5 \200\22310micrograms/kg/ min as infusion Seconds to minutes Very rapid effect; titrate dose; cyanide accumulates after 48hr of use Labetalol 1 \200\2233mg/kg/hr 10 \200\22330min Postural hypotension Hydralazine Slow IV 100 \200\223500 - micrograms/kg 10 \200\22330min Tachycardia, \202 ushes, headache Phentolamine 10 \200\223100micrograms/kg Minutes Use in catecholamine excess states The aim is to reduce systolic and diastolic BP to <95th centile for age and sex but, if sev erely hypertensive, only one-third of desired BP reduction should occur in the \201 rst 6 hr. Aim for controlled reduction in BP over 72hr. 11_McClure_11.indd 396 11/14/2012 3:25:35 PM HYPERTENSION: MANAGEMENT 397