diabetes; thalassemia; chronic kidney disease; alcoholic liver disease; occupation (rice pa ddy farmers). The commonest \201 ndings in renal biopsy series are: \200 \200 \200 \200 \200 \200 ATN (70 \200\22380%); acute interstitial nephritis; acute cortical necrosis; mesangiolysis; glomerulonephritis; vasculitis. Causative organism Burkholderia pseudomallei (Gram-negative bacteria found in soil and wate r). Clinical presentation Fever, signs and symptoms of pneumonia, multiple cutaneous/ visceral abscesses. The infection exists in acute and chronic forms. AKI occurs in up to 61% in acut e septicemic melioidosis where mortality is >90% if untreated. Epidemiology AKI following snakebites constitutes 1.2% of AKI in Thailand, 3% in India and up to 70% in Myanmar. AKI is usually caused by snakebites from the Viperidae, Colubridae an d Hydrophidae families, i.e. those with hemotoxic or myotoxic venom. Investigations A complete septic screen is required including cultures of blood, urine, spu tum, throat swab, aspirated pus. Serological tests may be of limited value in endemic areas . Clinical presentation Pain, swelling tissue necrosis at the bite site Systemic involveme nt: \200 \200 \200 \200 \200 Treatment Intravenous antibiotics for 10 \200\22314 days: \200 \200 hypotension; disseminated intravascular coagulation; hemorrhage; intravascular hemolysis; r habdomyolysis. drug of choice: ceftazidime; alternatives: carbapenem/amoxycillin-clavulanate. Maintenance treatment with oral cotrimoxazole and doxycycline is required for 12 \200\22320 weeks. Other infections Rarer causes of tropical infection-associated AKI: AKI is usually hypercatabolic and oligoanuric. Apart from AKI, proteinuria and hematuria ar e commonly seen following snakebites. Mucormycosis Renal vascular invasion with renal infarction and necrosis. Treatment Early administration of antivenom, preferably monovalent. Repeated doses may be r equired due to delayed absorption of venom from the bite. Coagulation indices need to be te sted for up to 3 days. Replacement of blood loss with fresh blood. Tetanus immune globulin administration. Aspergillosis Renal abscesses, infarcts, papillary necrosis and obstructive uropathy from f ungal bezoars. Kala-azar Acute interstitial nephritis. S. BAVANANDAN 370 Antibiotics may be required for pyogenic infection at site of bite wound. Early institution of good \202 uid balance with maintenance of good urine \202 ow and urinary alkaliniza tion may reduce risk of AKI. Dialysis should be instituted early if available. Further reading Adu D, Anim-Addo Y, Foli AK, Yeboah ED, Quartey JK, Ribeiro BF. Acute renal failure in tropical Africa. Br Med J 1976; 1: 890. Barsoum RS. Malarial acute renal failur e. J Am Soc Nephrol 2000; 11: 2147 \200\2232154. Barsoum RS. Tropical acute renal failure. In: Ronco C, Bellomo R, Brendolan A (eds): Sepsis , kidney and multiple organ dysfunction. Contrib Nephrol 2004; 144: 44 \200\22352. Prognosis AKI typically lasts 2 \200\2233 weeks. With cortical necrosis there may be no rec overy/delayed recovery with residual renal impairment. Other animal toxins: Scorpion and je lly \201 sh stings, spider and centipede bites lead to AKI in 6 \200\22310% of incidents. Oral ingestion of raw carp bile may be associated with gastrointestinal toxicity and lead t o hematuria (77%), jaundice (62%) and AKI in up to 54% of cases. Chow YW, Lim BB, Hooi LS. Acute renal failure in the same hospital ten years apart. Med J Malaysia 2007; 62: 27 \200\22332. Chugh KS, Sakhuja V, Malhotra HS, Pereira BJ. Changing trends in acute renal failure in thi rd-world countries \200\223 Chandigarh study. Q J Med 1989; 73: 1117 \200\2231123. Chugh KS, Sitprija V, Jha V. Acute renal failure in the tropical coun- tries. In: Davison A M, Cameron JS, Grunfeld J-P, et al. (eds), Oxford Textbook of Clinical Nephrology, 3rd edn. Oxford: Oxford University Press; 2005. Vol. 2, pp. 1614 \200\2231630. Khakurel S, Satyal PR l, Agrawal RK, Chhetri PK, Hada R. Acute re- nal failure in a tertiar y care center in Nepal. J Nepal Med Assoc 2005; 44: 32 \200\22335. Plant toxins and AKI Mushrooms of the genera Amanita, Galerina and Cortinarius may produce gastrointestinal and hepatic toxicity, and AKI. Mortality can be >50% in severe cases. Attr actyloside, an alkaloid from tubers of Callilepsis laure- ola (commonly used in Southern an d Central Africa as a traditional remedy) can cause AKI, hypoglycemia and liver dysfunction . The mortality rate is >50%. Djenkolic acid in the djengkol bean from the Pithecellobium j iringa/lobatum tree in South East Asia can cause dysuria, hematuria, proteinuria, urolithia sis and AKI. The diagnosis can be con \201 rmed by \201 nding characteristic needle-shap ed crystals of djenkolic acid on urine microscopy. Other plant toxins: \200 Ku G, Lim CH, Pwee HS, Khoo OT. Review of acute renal failure in Singapore. Ann Acad Med Si ngapore 1975; 4 (Suppl):115 \200\223120. Sitprija V. Snakebite nephropathy. Nephrology 2006 ; 11: 442 \200\223448. Sitprija V, Kashemsant U, Arthachinta S, Poshyachinda V. Pathogenesi s of renal failure in tropical diseases. Nippon Jinzo Gakkai Shi 1975; 17: 707 \200\223709. Suleiman AB. Clinical review of acute renal failure: a 5-year experience at Kuala Lumpur. Ann Acad Med 1982; 11: 32 \200\22335. Vetter RS, Visscher PK. Bites and Stings of medically important venomous arthropods. Int J Derm 1998; 37: 481 \200\223496. Internet resources WHO Global Malaria Program: http://www.who.int/malaria Melioidosis Research Center: phenolic compounds (via skin exposure) in the sap of the marking-nut tree of India (Semecar pus anacardium); gaultherin in Securidaca longipe dunculata; divicine and isouramil in Vici s favus (broad bean) in G6PD de \201 cient individuals. http://www.melioid.org/ G6PD De \201 ciency Association: \200 http://www.g6pd.org/favism/english/index.mv Snake bites, a useful introduction to the subje ct: For all the plant poisonings described above, treatment is mainly supportive. With djenkol and Vicis favus, increasing \202 uid intake and alkalinizing urine may be helpful. http://www.usyd.edu.au/su/anaes/venom/snake- bite.html See also Clinical approach to acute kidney injury, p. 318 Renal replacement therapies in ac ute kidney injury, p. XXX Dialysis and hemoperfusion treatment of acute poisoning, p. 336 A cute kidney injury in infants and children, p. 372 Acute tubulointerstitial nephritis, p. 3 44 Hemolytic uremic syndrome and thrombotic thrombocyt- penic purpura, p. 348 Pigment-induc ed acute kidney injury, p. 362 Glucose 6-phosphate dehydrogenase (G6PD) de \201 ciency This affects >400 million people w orldwide, mainly in Africa, the Mediterranean, Middle and Far East. It may confer a surviva l advantage in regions with malaria because infected erythrocytes are cleared more rapidly by the spleen. It is associated with intravascular hemolysis on exposure to oxidative stres s from infection, medication and certain foods. AKI may occur after severe hemolysis due to heme pigment nephropathy. Preventive measures include maintenance of a high urine output a nd urinary alkalinization. This page intentionally left blank K. TULLUS 372 Acute kidney injury in infants and children Many children have edema and respiratory symptoms due to pulmonary edema. Fever, rashes and other symptoms of infection or an in \202 am- matory disease are common. It is important to ask about urine output and whether there is hematuria. It is also important to ask about symptoms such as polyuria and polydipsia which can help in distinguishing between an acute disease and a more longstanding cause for the renal failure. Measurement of blood pressure : high blood pressure must be interpreted in conjunction with other clinical \201 ndings; with cool peripheries it suggests intravascular depletion and with warm peripheries it sug gests volume overload. Introduction Acute kidney injury in children is de \201 ned as a rapid increase in blood c oncentrations of creatinine and urea and an ina- bility to regulate \202 uid and electrol yte balances. In a majority there is oliguria (urine output <0.5 mL/kg/h) or anuria but a p roportion of children will experience normal urine output or polyuria. This is most common with tubular and interstitial diseases. When a child presents with severe renal failure it is impor- tant to try to de \201 ne if the child is suffering from AKI or acute on chronic renal failure. Children with CKD can sometimes present acutely with ESRD, in which case AK I can initially be part of the differen- tial diagnosis. Investigations Initial investigations Life-threatening symptoms must be addressed \201 rs t. Urgent analyzes of serum creatinine, electrolytes and albumin should be performed. Oxyge n saturations and CXR should be undertaken in cases of suspected pulmonary edema. Epidemiology In UK studies the incidence of AKI in children ranges between 6.4 and 8 per mi llion population per year. AKI occurs more commonly in neonates and infants than in older c hildren and it is also more common in hospitalized children. Predisposing factors Children with a lower initial nephron mass are more sus- ceptible to i njuries to the remaining nephrons. Pre-existing CKD may have been unrecognized and chil- dr en can present as AKI as a result of chronic disease. Further investigations All children need the work-up outlined below: \200 \200 blood and urine tests: see Tables 10.11.2 and 10.11.3; abdominal USS: looking for urinary o bstruction, kidney size, echogenicity, cysts; CXR. Clinical features Clinical features will depend on the cause of the AKI. The etiology of AK I varies with the age of the child. It is useful to de \201 ne the cause of the AKI as int rinsic, pre- or postrenal. Additional investigations These will depend on the clinical presentation: Hemolytic uremic syndrome \200 \200 \200 \200 Pre-renal AKI A major cause of AKI in children is decreased circulating blood volume (Table 10.11.1). This is mostly caused by dehydration or third spacing of \202 uids, as may occ ur in sep- ticemia or the nephrotic syndrome, for example. Blood loss in major surgery (for example in heart surgery) may also cause acute tubular necrosis with AKI. blood \201 lm (looking for fragmented red blood cells); blood grouping; stool culture; VT EC serology. If nondiarrhea-associated HUS, test for alternative etiology: \200 \200 \200 T-antigen Streptococcus pneumoniae; SLE; factor H de \201 ciency. Acute nephritic syndrome \200 \200 \200 \200 \200 \200 \200 Intrinsic renal AKI The most common causes of intrinsic AKI in children are glomerular and some tubulointerstitial diseases. These have a quite different diagnostic spectrum to that seen in adults. Hemolytic uremic syndrome (HUS) is the commonest cause of intrinsic AKI (se e below). In neonates renal vein thrombosis is an important cause of AKI. ESR; creatine kinase; complement (C3, C4, C3 nephritic factor); immunoglobulins (including IgA); throat swab; ASOT, anti-DNAse B; ANA, dsDNA, anti-GBM, ANCA, ENA, anticardiolipin ant ibodies. Post-renal AKI In boys, posterior urethral valves are an important cause of AKI. Unusually bilateral ureteral stenosis or obstruction in a sin- gle system can cause AKI. Ongoing investigations \200 Serum creatinine, urea, electrolytes and bicarbonate may be required up to every 6 h. Calci um, phosphate, albumin daily. Full blood count daily. Urine analysis daily. \200 \200 Presentation of AKI Presenting symptoms in children depend on the cause. Generalized sympto ms such as malaise, being unwell with sickness and vomiting are common. CHAPTER 10.11 Acute kidney injury in infants and children 373 Table 10.11.1 Causes of AKI in children Table 10.11.3 Urinary \201 ndings evaluating the cause of AKI Prerenal AKI Hypovolemia due to: dehydration, GI losses, renal losses or third-space losses as in sepsis and nephrotic syndrome Urine component Prerenal AKI Intrinsic renal AKI Circulatory failure Bilateral renal artery or vein thrombosis Intrinsic renal AKI Sediment Speci \201 c gravity Sodium Normal High >1.020 Low <10 mmol/L Neonates <20 mmol/L Low <1% Neonates <2.5% High Cells and casts Fixed 1.010 High >40 mmol/L Acute tubular necrosis (ischemic \200\223hypoxic injury, drug-induced or toxin-mediated) FENa High >3% Uric acid nephropathy/tumor lysis syndrome Rhabdomyolysis Glomerulonephritis (GN) Osmolality Low postinfectious GN \200 lupus nephritis \200 membranoproliferative GN \200 Henoch \200 \223Sch nlein nephritis \200 ANCA-positive nephritis \200 nephritis of chronic infecti on \200 GBM-positive GN \200 idiopathic RPGN Adjust \202 uid replacement according to the child \200\231s \202 uid status. full repl acement of insensible losses and urine output if euvolemic and restrict to 50 \200\22375% o f this if over- loaded. Hyperkalemia: Hyperkalemia is a potentially life-threatening situation that needs urgent tr eatment (Table 10.11.5). Potassium >6.5 mmol/L is an indication for treatment until dialysi s or urine output is established. Vascular lesions (HUS, renal venous or artery thromboses) Interstitial nephritis Postrenal AKI Obstruction in a solitary kidney Bilateral ureteral obstruction Urethral obst ruction Hyponatremia Mild hyponatremia is commonly seen and is often dilutional secondary to \202 uid overload. If sodium >120 mmol/L, \202 uid restriction and \202 uid replace- ment w ith 0.9% saline will usually correct it. If sodium <120 mmol/L there is a risk of seizures and treat- ment is required to return the sodium to 125 mmol/L with hypertonic saline (3 % ) according to formula: Na dose (mmol) = (125 \200\223 measured PlNa \227 weight \227 0. 6) and given over 2 h. PlNa: plasma sodium concentration. Severe hyponatremia with oliguria is an indication for dialysis. Table 10.11.2 Baseline blood and urine tests required for the evaluation of AKI Urine examination Urine analysis Urine microscopy Biochemistry Hypernatremia This is much less common than hyponatremia It may be caused by sodium retenti on or water depletion so careful assessment of \202 uid status is mandatory. Mild hyperna tremia: \200 \200 Electrolytes, creatinine, urea, calcium, bicarbonate, phosphate, PTH, liver function tests and CRP Hematology Full blood count and ESR Coagulation screen give IV furosemide 4 mg/kg; replace insensible losses with 0.45% saline. Microbiology Blood culture Urine microscopy and culture Severe hypernatremia with oliguria is an indication for dialysis. Hypocalcemia Correct if severe: <1.9 mmol/L. Give IV 10% calcium gluconate 0.5 mL/kg over 3 0 min. If less severe, treat with oral supplements and focus on treating the related hyperp hosphatemia with calcium carbonate. In acute on chronic renal failure consider starting 1A- calcidol. Acidosis Correct if serum bicarbonate <18 mmol/L. The required dose is calculated as: NaHCO3 dose (mmol) = (18 \200\223 PlHCO3) \227 0.5 \227 weight Administer half the dose over 1 h and re-evaluate. Give the rest if needed. An oral dose is 1 \200\2232 mmol/kg /day in 2 \200\2234 divided doses. The role of renal biopsy A kidney biopsy should be done as soon as possible in all cases where the kidney function i s deteriorating and the diagnosis from the above investigations is not clear. Treatment Supportive management Fluid balance: Determine if the child is dehydrated, euvole mic or over- loaded and treat as outlined in Table 10.11.4. Ongoing fluid management requir es replacement of insensible losses (400 mL/m2/day) and urinary output. Monitor \202 uid balance on an hourly basis and weigh the child twice daily. K. TULLUS 374 Table 10.11.4 Assessment and management of \202 uid balance in the child with AKI Hydration status Clinical features Initial management Dehydrated Tachycardic Cool peripheries: >2 toe-core gap is signi \201 cant prolonged capillary re \201 ll time Dry mucous membranes Sunken eyes UNa <10 mmol/L (<20 mmol/L in neonates) Fluid resuscitation 10 \200\22320 ml/kg 0.9% saline over 1 h Then reassess Euvolemic Fluid challenge: 10 \200\22320 mL/kg normal saline over 1 h Consider furosemide up to 5 mg/ kg if no urine response Overloaded Furosemide 4 mg/kg if \202 uid overload is severe Dialysis if no response to furosemide Tachycardic Gallop rhythm Elevated jugular venous pressure Edema Hypertension Table 10.11.5 Temporary treatment of hyperkalemia Treatment Dose Comment Quick therapy, as it drives K into the cells but short-acting response Salbutamol Nebulized dose 2.5 mg If nebulized administration not possible, give 4 \200\22310 g/kg ov er 10 min 10% solution 0.2 \200\2230.5 mL/kg IV over 30 min 2( \200\2234) g/kg orally or re ctally Calcium gluconate Calcium resonium Use if signs of cardiotoxicity stabilizes cardiac membrane Should be given to provide a mor e sustained hypokalemic effect Give lactulose in addition Use if acidotic (caution if hypoc alcemic) Sodium bicarbonate 1 \200\2232 mmol/kg as 4.2% solution Insulin and dextrose Give insulin 0.1 U/kg with 5 mL/kg of 10% dextrose Can be used if other methods are ineffec tive Monitor for hypoglycemia Hypertension This is very often related to fluid overload. Diuretics (furosemide) should be given. Failure to respond is an indi- cation for dialysis. Oral nifedipine (1 \200\2232 mg /kg/day in 2 \200\2234 divided doses) is a good second-line drug. In hypertensive emergenci es labetalol IV is often effective in children. The starting dose is 500 g/kg/h titrated up to maximum of 3 mg/kg/h. Drug treatment It is important to adjust drug doses to the estimated renal function. In sev ere AKI assume GFR is <20 mL/min/m2 until onset of improvement. Doses of drugs will need to be changed when kidney function improves. Avoid nephrotoxic drugs. Dialysis Indications for dialysis are given in Table 10.11.6. Nutrition AKI is often associated with a catabolic state and this might delay recovery. The aim is to provide suf \201 cient calories. Dietetic advice is very important. If possible use enteral feeding via a nasogastric tube if needed. Parenteral nutrition should be used if enteral feeding is not possible. Frequent dialysis may be required to allow adequate vol umes of the nutrition to be given. Adequate nutrition can help to prevent potassium and pho sphate abnormalities Table 10.11.6 Indications for dialysis in children with AKI Hyperkalemia >6.5 mmol/L Severe \202 uid overload with pulmonary edema unresponsive to di uretics Severe acidosis unresponsive to treatment Severe hyperphosphatemia Uremic symptoms Anticipation of prolonged AKI, e.g. in HUS CHAPTER 10.11 Acute kidney injury in infants and children 375 Clinical features The diagnosis is con \201 rmed by the triad of: \200 \200 \200 The different modalities for dialysis in children are: \200 \200 \200 peritoneal dialysis; hemodialysis; hemo \201 ltration. renal failure; hemolytic anemia; thrombocytopenia. The choice of RRT depends on: \200 Many affected children will also develop symptoms in other organ systems, in particular cer ebral involvement and pan- creatitis. The cerebral symptoms can be severe including epilept ic \201 ts, confusion and frank psychotic symptoms. the hemodynamic stability of the child (children in ITU are mostly managed with CVVH; the s peed with which the abnormalities need to be cor- rected; the local expertise and availabil ity of equipment. Investigations In D+ cases the diagnosis needs to be con \201 rmed by stool culture or by other means of establishing the infection such as detection of the toxin in feces or serolo gy. In cases of atypical HUS there is a strong clinical bene \201 t from estab- lishing, i f possible, the genetic diagnosis as this will inform the future clinical course and treatm ent. Hemodialysis is the preferred option if plasma exchange is also needed. Active intervention This will depend on the cause of AKI (Table 10.11.1) and may include su rgical intervention in cases of postrenal AKI or more speci \201 c medical therapies some of which are discussed below. Treatment Treatment of children with HUS is mostly supportive with management of their \202 uid balance and, if needed, blood and platelet transfusions. More than 50% of the chil dren will need acute dialysis. Hemolytic uremic syndrome (HUS) This is the most important cause of severe AKI in children. HUS presents with the triad of renal failure, microangio- pathic hemolytic anemia and thro mbocytopenia. There are many causes of HUS (Table 10.11.7) and they have traditionally been divided into: \200 \200 Plasma exchange This has been used in the group of children with worst prognostic markers: cerebral symptoms and high leukocyte counts (>17 \227 109/L). Antibiotics Antibiotic treat ment of hemorrhagic colitis has not been shown to be bene \201 cial for children. On the c ontrary there are reports suggesting that antibiotics might make the HUS worse. Innovative treatments trying to bind the toxin within the gut have not been shown to be effective. Pro gnosis and long-term outcome During recent years the mortality from VTEC HUS has improved a nd is now <5% but up to 30% of survivors will be left with some CKD. The other forms of HUS have signi \201 cantly higher mortality and many have a signi \201 cant chance of a rela psing course. Acute glomerulonephritis The spectrum of glomerulonephritides in children is differ- ent from that in adults and it is a relatively less important cause for renal failu re than later in life. Post-streptococcal GN (PSGN) is the most common diag- nosis, which i s made from the combination of a preceding streptococcal infection, mostly throat or skin i nfection, and the later development of clinical symptoms of nephritic syndrome including ed ema, pulmonary edema, high BP and hematuria and proteinuria. Low serum levels of complement C3 and C4 together with raised streptococcal antibodies (ASOT) will support the diagnosis. PSGN is normally a self-limiting disease but it can cause a rapidly progressive GN requiri ng dialysis. Other forms of GN including Henoch \200\223Sch nlein nephritis, IgA nephropat hy, SLE, ANCA-positive vasculitis, membran- oproliferative GN and Goodpasture \200\231s syn drome can occasionally been seen in children. Diarrhea-positive (D+, typical) HUS; Diarrhea-negative (D \200\223, atypical) HUS. Diarrhea-positive HUS This is most commonly caused by enteropathogenic E. coli of different serotypes, most commonly O157:H7, or some- times by shigellosis. These strains produce an enterotoxin called VT (verocyte toxin). Children present with severe, mostly bloody, diarrh ea. After a few days they develop generalized symptoms with hemolytic anemia and renal fail ure. The incidence of VTEC (verocyte toxin E. coli) is variable but peaks during the warm s eason. The natural reservoir of VTEC is the intestinal tract of farm animals. The bacterium is often spread via milk and meat but can also spread via vegetables contaminated from far m animals. Outbreaks have been described and as the infectious dose is very low person-to-p erson spread is also known to occur. HUS is the tip of an iceberg as infections resulting i n asymp- tomatic colonization of the GI tract can occur in some patients; others may just g et bloody diarrhea. Only some 10% will develop the full-blown HUS. Diarrhea-negative HUS This can result from a range of different disorders (Table 10.11.7). Over the last decade pneumococcal-related HUS has in the UK become the second most common c ause of HUS accounting for 10 \200\22315% of all cases. The reason for this recent increase is not known. In the UK atypical HUS from other causes comprises some 5% of all cases. Man y of these cases never receive an etiological diagnosis. They are often familial and have a relapsing/remitting pattern. The most commonly found diagnoses in this group are complemen t de \201 ciencies, particularly mutation in the factor H gene with or without proven fact or H de \201 ciency. Neonatal AKI AKI is most commonly found in this age group. There are many causes related to the immature kidney function of K. TULLUS 376 Table 10.11.7 Causes of hemolytic uremic syndrome (HUS) in children Treatment of renal venous thrombosis is controversial. Some authors advocate an expectant a pproach while oth- ers use heparin or attempt to dissolve the clot with tissue plasminogen activator. Before considering such an aggres- sive approach the risks of an intracranial bl eed need to be formally assessed. The renal prognosis following renal vein thrombosis is hi ghly variable and depends on the extent of venous thrombus formation. Diarrhea-associated HUS E. coli Shigella Diarrhea-negative HUS Pneumococcus-associated HUS T-antigen-associated HUS \200\230Atypica l \200\231 HUS Complement abnormalities Follow-up All children recovering from AKI need follow-up, preferably by a pediatric nephro logist. A formal GFR examination should be undertaken 1 year after the insult to establish the degree of remaining, if any, renal impairment. It is also important to evaluate whether any degree of proteinuria, hematuria or hypertension remain. Most children who at the 1 ye ar follow-up have normal GFR, BP and urine \201 ndings can be discharged from further fol low up if the diagnosed illness has not been known to have a recurrent pattern, as in atypi cal HUS. Nevertheless some authors advocate long-term follow-up of children with no signs o f kidney damage or remaining disease, as there are reports suggesting an increased risk of CKD in this apparently healthy group of children. factor H, factor I, membrane cofactor protein ADAMTS 13 de \201 ciency von Willebrand factor-cleaving protease Secondary HUS Drugs (ciclosporin, cytotoxic drugs, etc.) Bone marrow transplant Autoimmune disorders (SLE ) Malignancy newborn babies and problems related to prematurity and neonatal intensive unit (NICU) care. During the \201 rst few days of life serum creatinine values in neonates re \202 ect th ose of the mother. Levels then decrease over the ensuing weeks but will, particularly in pr emature babies, continue to be higher than later in infancy, re \202 ecting the lower GFR during the \201 rst year of life. In infants, anuria is de \201 ned as a urine output <1 mL/kg/day. Eight percent of NICU babies develop AKI. The dominating causes are pre-renal A KI, often due to asphyxia or compli- cations of NICU care. Hypoplastic or dysplastic kidney s with or without obstructing urinary disorders might mani- fest during infancy. Renal vein thrombosis is also a cause of AKI in neonates. Post-renal AKI is another important cause o f AKI in neonates and will lead to CKD if not adequately treated. The majority of cases are nowadays diagnosed prenatally, although this depends on local prenatal USS screening polic ies. Ultrasound will normally con \201 rm the diagnosis. The most common diagnosis is post erior urethral valves in boys. The urinary tract should be drained immediately the diagnosi s is made. In most cases a per-urethral bladder catheter will suf \201 ce. The child shoul d be sent to a pediatric urologist. Prognosis The outcome in children who develop AKI depends on the cause of the illness. Chil dren with ATN without other underlying disease have a much better long-term progno- sis, wh ereas children developing AKI in the ITU reportedly suffer \211 50% mortality. Further reading Amirlak I, Amirlak B. Haemolytic uraemic syndrome: an overview. Nephrology (Carlton) 2006; 11: 213 \200\223218. Barletta GM, Bunchman TE. Acute renal failure in children and in- fants. Curr Opin Crit Care 2004; 10 499 \200\223504. Marks SM, Massicotte MP, Steele BT, et al. Neonatal renal venous thrombosis: clinical outco mes and prevalence of prothrombotic disorders. J Pediatr 2005; 146: 811 \200\223816. Strazdins V, Watson A, Harvey B, European Pediatric Peritoneal Dialysis working Group. Rena l replacement therapy for acute renal failure in children: European guidelines. Pediatr Nep hrol 2004; 19: 199 \200\223207. Internet resources Patient Fact Sheet on hemolytic \200\223uremic syndrome: Renal vein thrombosis Renal vein thrombosis occurs in neonates, especially in those with a thrombotic tendency, e.g. due to hemocon- centration, hypovolemia or a clotting problem suc h as pro- tein C de \201 ciency. It is more common in neonates of diabetic mothers and mor e often seen after traumatic deliveries. Thrombus normally develops within the kidney in th e arcu- ate or interlobular vessels and then extends to the main renal veins and the vena c ava. The diagnosis should be suspected in infants with hematu- ria, often macroscopic, impa ired kidney function and reduced urinary output. Anemia and thrombocytopenia will develop. The kidney enlarges and may become easily palpable. Ultrasound and DMSA renogram can be use ful in establishing the diagnosis. http://www.ich.ucl.ac.uk/factsheets/families/ F060408/index.html Treatment of adults and ch ildren with renal failure. UK Renal Association Standards and Audit Measures: http://www.renal.org/Standards/RenalStandards_ 2002b.pdf See also Renal function in the newborn infant, p. 16 Hypertensive children, p. 304 Congenit al abnormalities of the urinary tract, p. 658 This page intentionally left blank S.J. CARR 378 Acute kidney injury in pregnancy Hemorrhage and PeT remain the commonest causes of pregnancy-related AKI in developed countr ies whereas septic abortion and acute pyelonephritis are still common causes in developing countries. 60 \200\22390% women will fully recover kidney function following AKI in pregnan cy. Introduction There is no clear de \201 nition of AKI in pregnancy, therefore the reported incidence varies between studies. The sever- ity of reported cases of AKI varies from uremi a requiring immediate dialysis to a doubling of serum creatinine values, making comparisons across studies dif \201 cult. Clinical features Clinical features will depend on the cause of the AKI. Renal physiology in normal pregnancy Early decreases in peripheral vascular resistance lead to lower BP in early pregnancy which then rises gradually to baseline at term. Cardiac out put increases (50% above nonpregnant at baseline). Plasma volume increases (40% above nonpr egnant baseline). Red cell mass increases (proportionately less than increase in plasma vol ume, therefore a mild anemia results). GFR increases by 50% above baseline (Fig. 10.12.1) due to increased renal plasma \202 ow (45% by 9 weeks and 70% in mid-pregnancy). This is due to dilatation of renal afferent and efferent arterioles and leads to a fall in serum cr eati- nine which persists throughout normal pregnancy. There is no associated increase in i ntraglomerular pressure. Plasma osmolality reduces in the 1st trimester and then remains co nstant during pregnancy. Sodium reabsorption increases (increased GFR increases \201 lter ed sodium load). A relative respiratory alkalosis develops (direct stimulus of respiratory center). Glycosuria develops as the increased \201 ltered load exceeds the maximum tubula r transportation capacity for glucose reab- sorption (Tmax). Renal size increases with adva ncing gestation due to dilata- tion of the renal collecting system, especially on right sid e. Pre-renal AKI Volume contraction, hypotension and vasoconstriction can occur in numerous se ttings in pregnancy: \200 \200 persistent vomiting, diarrhea, or diuretic therapy; PeT is associated with profound vasocon striction and volume depletion; ante-partum and postpartum hemorrhage. Blood loss alone may cause hypovolemia but antepartum hemorrhage may also be associated wit h intravascular coagulation which also compromises intrarenal blood \202 ow. In view of t he pre-existing hypovolemic and increased vasoconstrictor response in women with PeT, they are at greater risk from the effects of hemorrhage. Intrinsic renal AKI Any of the possible causes of acute renal dysfunction can be encountere d in pregnancy but the following are some of the more common causes: \200 acute tubular n ecrosis; \200 bilateral cortical necrosis; \200 microangiopathy; \200 acute interstit ial nephritis; \200 de novo glomerulonephritis. Each will be discussed separately below. Post-renal AKI This is an uncommon cause of AKI in pregnancy. The uri- nary tract undergoes physiological dilatation in pregnancy especially on the right side in later pregnancy. How ever, pathological obstruction can occur. Rarely women can develop an exaggeration of the n ormal physiological dilatation in the urinary tract in pregnancy. This is called \200\230t he overdistention syndrome \200\231. Very rarely this syndrome may lead to rupture of the d ilated urinary tract. Urinary tract obstruction is dif \201 cult to assess in pregnancy. I f the dilatation is gross or there are associated symptoms of \202 ank pain, urinary trac t infection or impaired renal func- tion then further investigation and drainage may be req uired. The pregnant uterus can rarely be the cause of obstruc- tion. This may be more commo n in presence of extreme polyhydramnios or with twin pregnancies. In later pregnancy obstru ction is relieved by delivery, in earlier pregnancy stenting and amniotomy (for polyhydram- nios) have been reported to delay delivery by 5 \200\22315 weeks. Epidemiology Over the last 20 years the incidence of AKI has reduced in developed but less so in developing countries. In the 1960s the incidence was reported as 1 in 3000 preg- nanc ies but now the rate is almost ten times lower in Europe and North America. AKI requiring d ialysis now occurs in 1 in 20 000 pregnancies in Europe and North America. In the develope d nations there has been little overall change in mortality which is reported to be 0 \200 \22330%. In developing countries AKI in pregnancy continues to cause 20% of the total cases of AKI and mortality is as high as 50%. Traditionally, early pregnancy AKI cases were main ly due to septic abortion and later cases due to obstetric complica- tions including hemorr hage and pre-eclampsia (PeT). The legalization of abortion and improvements in antenatal ca re with early detection of antenatal complications of pregnancy are the two main factors th at have led to a reduction in AKI in pregnancy. CHAPTER 10.12 Acute kidney injury in pregnancy 379 Acute fatty liver of pregnancy This is part of the spectrum of the maternal systemic PeT di sease process. It is a rare but potentially fatal complication of the third trimester. Inci dence ranges from 1 in 10 000 to 1 in 15 000 deliveries. It usually presents mid \200\223la te pregnancy (27 \200\22340 weeks), or occasionally postpartum. Symptoms are usually of mal aise, nausea, vomiting, neuro- logical symptoms, upper abdominal pain and jaundice. The cli nical picture is similar to PeT and HELLP syndrome with hypertension, and with abnormalitie s in coagulation which are due to liver dysfunction rather than abnormal platelet consumpti on. 40% of patients develop AKI. 100 e s a e r c n ERPF 50 GFR i % 0 Non pregnant 16 26 Weeks of pregnancy 36 Fig. 10.12.1 Effect of pregnancy on glomerular \201 ltration rate (GFR) and effective ren al plasma \202 ow (EFPF). (Redrawn from: Davison, 1987.) Septicemia This is a rare complication of pregnancy in developed countries. It is one of th e \201 ve leading causes of maternal death world- wide. A decline in the number of cases of sepsis in pregnancy has been reported in the USA over last 25 years (from 0.6% to 0.3%). Prevalence of bacteremia in pregnancy is 7.5 per 1000 admissions but most do not develop s epticemia. One in 8500 deliveries is complicated by septic shock. Death from septic shock i s uncommon in developed coun- tries and outcome is good compared with nonobstetric patients . Mortality rates vary widely \200\223 one recent study reported a mortality rate of 12.5% . Mortality in developing (mainly African countries) was reported to be >1000 per 100 000 l ive births compared to < 20 per 100 000 live births in European countries. Septicemia may a rise from any cause in pregnancy, e.g. cholecystitis, ruptured appendix, etc. However, comm on causes in pregnancy are: Renal calculi The incidence of renal stone disease is the same as non- pregnant women. Typi cal symptoms of loin pain, hematuria and urinary infection may occur but the diagnosis can be dif \201 cult in heavily pregnant women. Suspected cases should be referred to urologis ts for investigation and may require a ureteric stent or nephrostomy. Clinical presentation This will depend largely on the precipitating cause of AKI (Table 10. 12.1). It is important to establish the presence of: \200 \200 \200 fever and other systemic symptoms of sepsis; symptoms of bleeding or other obstetric compli cations; speci \201 c disease associated symptoms e.g. rash in SLE, joint pains, vasculiti c rash. BP may be low in prerenal AKI or raised in the presence of glomerulonephritis or PeT. Jugul ar venous pressure/volume status \200\223 may be low due to volume depletion or high when there is established renal impairment indicating hypervolemia and \202 uid over- load, of ten associated with peripheral and pulmonary edema. It is always important to ask the obste trician to assess the fetal viability and growth and exclude antepartum hemor- rhage and ot her intrauterine complications. Septic abortion This remains common in developing countries, but uncom- mon in developed co untries following the introduction of antibiotics, oral contraception and legalized abortio n. It is usually caused by infection with Clostridium spp. Patients present with systemic f eatures of septicemic shock and may have evidence of gas formation in the uterus or abdomen . Acute pyelonephritis Patients may complain of fever, loin pain, lower urinary tract sympt oms including dysuria, etc. In addition, if the infection is severe there may be symptoms a nd signs of systemic infection and septic shock, decline in renal func- tion and multiple o rgan failure. Acute tubular necrosis in pregnancy This occurs most commonly due to prolonged volume deple tion, hypotension and vasoconstriction. ATN can occur secondarily to a number of underlying pathologies in pregnancy: Pre-eclampsia, HELLP syndrome PeT is accompanied by volume contraction and vasocon- stricti on and patients are more at risk of developing estab- lished ATN following any further volu me depletion. PeT is often associated with intravascular coagulation and gener- alized \200\230endothelial activation \200\231, further compromising renal blood \202 ow and lea ding to multiple organ dysfunction. Other causes of ATN in pregnancy Other complications of pregnancy that may result in preren al AKI and established ATN include prolonged intra- uterine death and amniotic \202 uid e mbolism. S.J. CARR 380 \200 Table 10.12.1 Causes of acute kidney injury in pregnancy neurological symptoms; hypertension. Prerenal causes of AKI Volume contraction, hypotension and vasoconstriction due to: Laboratory investigations \200 thrombocytopenia; \200 anemia; \200 schistocytes/fragm ented red blood cells on blood \201 lm; \200 elevated serum lactate dehydrogenase; \200 reduced haptoglobin; \200 impaired renal function. water and electrolyte depletion persistent vomiting, diarrhea, or overdiuresis edema-forming states pre-eclampsia, nephrotic syndrome hemorrhage antepartum and postpartum hemorrhage Pre-eclampsia Renal causes of AKI Acute tubular necrosis