<p> PART 18 URINARY TRACT DISORDERS AND HYPERTENSION 18.1 Urinary tract infections and malformations C. Jones</p><p>Urinary tract infections Urinary tract infection is the second most common bacterial infection affecting children. Urinary tract infection can cause septicaemia or chronic ill health with failure to thrive and is often an indication of an underlying urinary tract malformation.</p><p>Epidemiology Epidemiologic studies have shown that 2% of boys and 8% of girls have had a urinary tract infection by the age of 7 years; 75% of urinary tract infections occur under the age of 1 year in males and 50% under the age of 1 year in females. The prevalence of urinary tract infection in febrile infants under the age of 3 months presenting to emergency departments is 20–30% and boys outnumber girls. After the age of 3 months the prevalence of urinary tract infection in febrile children falls to around 8% in females and 2% in male children. The incidence of urinary tract infection in uncircumcised boys is 4–10 times that in circumcised boys in the first 3 months of life. Common clinical patterns of urinary tract infection are described in Table 18.1.1.</p><p>Diagnosis The frequency of symptoms of urinary tract infection in a recent series of 304 children less than 5 years of age presenting to a Sydney hospital emergency department is listed in Table 18.1.2. The presentation varies with age because of the developmental status of the child. While a wide range of symptoms can occur, an infant will probably have an acute illness with fever and vomiting or a chronic illness with failure to thrive, reflecting the systemic response to infection at this age. The preschool child, who has usually achieved continence, will often show wetting or frequency, complain of generalized abdominal pain and sometimes indicate dysuria. The teenage girl will usually present with symptoms of cystitis (fever, frequency, dysuria, strangury and accurately localized pain) or pyelonephritis (fever, often with rigor, and loin pain and tenderness). At any age, symptoms of fever, vomiting and systemic unwellness occur with pyelonephritis.</p><p>Urinalysis and microscopy The finding of a positive urinary dipstick test for leukocyte esterase is sensitive for urinary infection (approximately 80% of urine infections detected) and urinary nitrite testing is specific (97% of positive tests indicate infection). Taking the prevalence rates for urine infection at different ages (see Epidemiology) into account, a positive testing for both nitrites and leukocyte esterase in a child under 3 months of age predicts a 90% chance of a urine infection, but negative tests are found in 10% of infants with infection. This is not good enough for clinical purposes as the diagnosis of urine infection would be missed in a significant number of ill infants. In a child aged 3 years or more, or in a circumcised male, the prevalence of urine infection is much lower and the finding of negative tests (leukocyte esterase and nitrites) is reassuring as there is then only a 1% chance of urine infection. Thus, negative tests are quite useful in this older age group in excluding urinary infection and at least justifying withholding antibiotic treatment until the results of urine culture are available. Microscopy will usually reveal leukocytes and non-glomerular red cells (red cells that appear normally haemoglobinized and of uniform size and shape under phase-contrast microscopy) in freshly examined urine. The presence or absence of bacteria on microscopy can be unreliable: the presence of bacteria on microscopy of a fresh, well collected specimen (e.g. by suprapubic aspirate of urine (SPA)) can be sensitive and specific for urinary tract infection, particularly if the white cell count is high (10 white cells/l). The finding of epithelial squamous cells indicates a poorly collected sample and the absence of leukocyturia in a sample with mixed growth or low colony count on culture may indicate a contaminated sample. Urinary nitrite tests are frequently used in monitoring the urine of children prone to recurrent urinary tract infection (for example, continent children with vesicoureteric reflux). Nitrite testing of early morning urine on a weekly basis has been reported to detect urinary tract infection in asymptomatic children, enabling treatment to be initiated earlier than would otherwise occur.</p><p>Practical points</p><p>Dipstick testing • Positive leukocyte esterase is a reasonably sensitive test but is not at all specific for urinary tract infection (UTI) • Positive nitrites is less sensitive but quite specific for UTI • Negative testing for leukocyte esterase and nitrites does not exclude UTI, especially in babies. 10% of babies with UTI will have negative dipstick testing • Always send urine for culture if UTI is suspected • Negative dipstick testing may reasonably be used in making the decision to withhold antibiotics from children over 3 years of age while awaiting urine culture results</p><p>Urine culture The urine culture is the gold standard for diagnosis, but management decisions often have to be made before the results are available. The five common forms of urine collection are compared in Table 18.1.3. Microbiology Escherichia coli accounts for 80–90% of pathogens isolated. Proteus species are the cause of infection in 30% of males over 1 year of age. Coagulase-negative Staphylococcus species are common in teenagers and Klebsiella is frequent in the neonatal period. Pseudomonas species are frequently isolated in children with more complicated anatomical malformations and in those children who have had surgical procedures, especially where foreign materials (e.g. urinary stents) have been left in situ. The enterococcus causes around 5% of urinary tract infections and is the most common organism found that is resistant to gentamicin. Approximately 5% of children will have two organisms isolated.</p><p>Initial treatment Once the urine culture has been obtained a decision on acute treatment must be made. Intravenous therapy is required where the child is systemically unwell (dehydrated, signs of septic shock such as hypotension, tachycardia and decreased conscious state), where there is vomiting, so that oral medications will not be retained, and, in general, in the infant under the age of 6 months. In the child in whom an infection is likely on the basis of urinalysis and presentation, and the child is reasonably well (generally older and not vomiting), oral antibiotics may be commenced, with review once the culture is through in 24–48 hours. In the child in whom a urinary infection is a possibility and the child is not unwell then the results of the culture are obtained before starting treatment. The intravenous antibiotics and oral antibiotics used acutely are listed in Table 18.1.4. Intravenous antibiotics are usually ceased within 2–3 days once culture results have been obtained and the child has improved clinically. Acute treatment is completed with oral antibiotics, usually of 5 days duration.</p><p>Prophylactic antibiotics After acute treatment the child may be placed on prophylactic antibiotics given once each night. The antibiotics usually used for prophylaxis are listed in Table 18.1.4. These antibiotics are excreted in the urine, achieve high urinary concentrations and are well tolerated over long periods of time without inducing excessive microbiological changes in the gut (leading to the emergence of resistant organisms or candidiasis). They are usually given until the results of imaging tests are available, and perhaps for prolonged periods with the aim of reducing the risk of further UTI. This is an area of medical controversy and further research into the benefits of prophylactic antibiotics is currently underway.</p><p>Investigations The investigation necessary after a first urinary tract infection is an area of medical controversy. After several decades where the trend was to perform several detailed investigations, many centres are now more conservative and reserve more invasive investigations, and those involving irradiation, for special situations. Investigations are aimed at excluding obstructive urinary tract lesions and determining whether there are significant underlying urinary tract malformations. Nearly all centres perform a renal ultrasound. This enables the presence, site, size and shape of the kidneys to be determined. In the age group under 5 years, only 15% of abnormalities found on DMSA scan (‘scars/dysplasia’) will be seen on ultrasound examination. The ureters are not visualized unless enlarged. The finding of hydronephrosis or hydroureter leads to further nuclear medical imaging (discussed below) to diagnose obstructive lesions of the urinary tract. An idea of bladder function can be determined by measuring the postvoid residual volume (normally 20 ml in children under 7 years). The radiological examination of the urethra and bladder, using a micturating cystourethrogram (MCU), is performed in some centres as a routine on infants (less than 1 year of age) and selectively at older ages where visualization of the bladder surface and urethra is required. This investigation is performed less frequently than in the past because the demonstration of vesicoureteric reflux (VUR, see below) does not alter management at many centres. The patient and parental acceptability of the test is poor and against the ethos of development of ‘pain- and anxiety-free’ paediatric procedures. I generally have MCU tests performed under general anaesthesia. Nuclear medicine investigations with technetium-99m-labelled radioisotopes are useful for a number of purposes. These investigations carry radiation toxicity of less than one-tenth of a routine chest X-ray. The DTPA radionuclide is injected intravenously, is filtered by the glomerulus and then is neither secreted nor absorbed by the tubule of the kidney. Like creatinine or insulin, it can be used to obtain an accurate measure of the glomerular filtration rate. The Mag 3 scan has largely replaced the DTPA scan because, in addition to some glomerular filtration, the isotope is mainly secreted by the proximal tubular cells into the urine so that the signal to background ratio is higher than in the DTPA scan. This is particularly useful in children with renal impairment or infants in the first 3 months of life when the glomerular filtration rate is low. Both of these investigations are useful for diagnosing the presence of obstruction to urinary flow from the kidneys to the bladder, for determining the ‘split’ of kidney function (between the right and left kidneys), and for estimating overall renal function. The DMSA radionuclide is filtered by the glomerulus and taken up by the proximal tubular cells. Scanning takes place when it has been taken up by these cells, which are in the renal cortex. Lack of uptake gives a defect on the scan and this can be due to either transient impairment of the tubular cell function (e.g. following acute inflammation with pyelonephritis for a period of up to 3–4 months) or absence of kidney tissue (renal ‘scarring/dysplasia’). Delayed uptake of any of these three radionuclides may occur in conditions where perfusion to the kidney is abnormal (e.g. renal artery stenosis in a unilateral case or dehydration in a bilateral case). The ongoing management depends on the results of investigations. A flow diagram of possibilities is shown in Figure 18.1.1.</p><p>Urinary tract infection and normal renal ultrasound If the child is afebrile and asymptomatic, I do not perform another urine culture at the end of treatment. In the case of an infant, prophylactic antibiotics are continued for 6–12 months. In the case of an older child with recurrent infections and normal baseline investigations, the ultrasound would be repeated and an examination for precipitating factors (see Table 18.1.1) such as constipation or a functional voiding disorder (daytime wetting) would be undertaken. Sexual activity should be considered in teenagers.</p><p>Clinical example</p><p>Johnnie had a birth weight of 3.3 kg. He was breastfed and weighed 5.1 kg at 2 months of age. For the next month he put on no weight and his mother noted that he was irritable, fed poorly and had the occasional vomit. The family doctor took a bag sample of urine and found more than 108/l colony forming units (cfu) of an organism growing on culture the next day. The doctor arranged for a suprapubic aspirate of urine to be performed at the emergency department. This was done after a bladder scan showed a moderately full bladder. The child was admitted to hospital and received treatment with gentamicin and penicillin given intravenously for 48 hours before an E. coli sensitive to co-trimoxazole was identified. The infant was discharged to complete 3 days of oral co- trimoxazole therapy and then to commence night-time co-trimoxazole prophylactic antibiotic treatment. An MCU and renal ultrasound were performed in the next few days. The ultrasound showed right-sided hydronephrosis and hydroureter with a normal left kidney. The MCU showed a mild trabeculated bladder with right-sided vesicoureteric reflux; the urethra was abnormal in appearance with dilation of the posterior urethra suggesting a diagnosis of posterior urethral valves (Fig. 18.1.2). Prophylactic antibiotic treatment was continued and the child was referred to a paediatric urologist for cystoscopy and evaluation of the urethra.</p><p>Clinical example</p><p>Amy, a 14-year-old girl, presented to her local doctor on three occasions over 6 months with culture-proven urinary tract infections. There was no family history of urine infections, Amy had never had a urinary tract infection before, and there was no evidence of a wetting disorder. Further history revealed the onset of sexual activity at about the same time as the urinary tract infections started. Amy was counselled regarding contraception and sexually transmitted diseases and she and her parents were offered counselling regarding her sexual activity. She was advised to have a 300 ml glass of water with a citravescent sachet immediately prior to or just after sexual intercourse. However, 1 month later Amy re-presented with another urinary tract infection. She was then advised to take nitrofurantoin (100 mg capsule immediately after sexual intercourse). She was seen for review 3 and 6 months after this treatment, reported no further symptoms and remained compliant with the treatment. As she was frequently changing sexual partners she was advised to continue on the treatment.</p><p>Asymptomatic infection Up to 4% of adolescent girls have asymptomatic bacteriuria. A number of these children will have vesicoureteric reflux or reflux-associated nephropathy (see below). There is no evidence that treatment of asymptomatic bacteriuria is beneficial, and colonization frequently recurs after treatment, sometimes precipitating symptomatic infection caused by a more pathogenic organism.</p><p>Practical points</p><p>Management of urinary tract infection in infancy • Suspect in febrile infant with vomiting or failure to thrive • Urine sample: • Acutely unwell: SPA 1st choice (or CSU) • Not unwell: clean catch • Unwell: commence treatment with intravenous gentamicin and intravenous penicillin initially, changing to oral antibiotic to finish course when improved • Prophylactic antibiotic until renal ultrasound evaluated • Long-term follow-up essential unless DMSA scan normal Management of recurrent urinary tract infection in childhood • Characterize symptoms as pyelonephritis or cystitis • Identify precipitating factors: wetting, vulvovaginitis, phimosis or balanitis, constipation • Bladder abnormality • Individualize therapy to minimize development of symptomatic urine infection • Longer term follow-up essential unless DMSA normal</p><p>Abnormalities of the urinary tract Vesicoureteric reflux This is a disorder in which urine passes in a retrograde direction from the bladder through the vesicoureteric junction into the ureter. It is a common disorder, affecting 40% of children under 1 year of age who are investigated for a first urinary tract infection. The diagnosis is made by MCU or by an indirect MCU done without urinary catheterization. Vesicoureteric reflux (VUR) is a familial trait affecting between 30% and 50% of first-degree relatives of index cases. This developmental abnormality is characterized by the distal end of the ureter running less obliquely through the wall of the bladder and having less muscle around it. In some cases, it is associated with renal malformation (variously referred to as renal scarring, dysplasia, reflux-associated nephropathy), excessive dilatation and tortuosity of the ureter, occurrence on the contralateral side and abnormalities of bladder function including premature detrusor contractions (causing urgency symptoms and wetting) and poor bladder emptying. Higher grades of VUR are associated with higher recurrence rates of UTI. The treatment of VUR has been controversial. Controlled trials (Table 18.1.5) have shown no advantage of either anti-reflux surgery or antibiotic prophylaxis in preventing urinary infections, hypertension, renal injury or renal failure. In fact, it is not clear whether these treatments are better than no treatment or episodic treatment of urine infection alone. Much of the renal injury leading to renal failure in a small number of patients with VUR is congenital and the significance of acquired injury is debated. Thus, the aim of treatment of VUR is prevention of symptomatic UTI, not prevention of renal injury. Attention to reducing and treatment precipitating factors for UTI, the use of antibiotic treatment in a prophylactic or episodic manner and the selective use of antireflux surgery for patients with intractable symptoms form the basis of treatment. VUR often resolves spontaneously (of a cohort of children with reflux, 20% will have resolution occurring spontaneously each 3-year period, with less severe degrees of reflux resolving earlier than more severe degrees). Resolution of reflux is often not associated with resolution of urine infection, which can be expected to occur periodically throughout life in affected females, particularly with sexual activity and pregnancy.</p><p>Reflux-associated nephropathy Once thought to be due to the combination of VUR and infection, this abnormality of the kidney is most often congenital in origin. It is found in approximately 10% of children with VUR. The importance of this lesion lies in the possibility of development of hypertension, which is rare in early childhood but occurs in up to 15% of cases by the age of 20 years. Bilateral extensive reflux associated nephropathy is a cause of renal failure occurring from mid childhood.</p><p>Posterior urethral valves This abnormality is also referred to as congenital obstructive posterior urethral membranes (COPUMs). It affects males and causes obstruction to urine flow at the level of the posterior urethra. The bladder is often thick-walled and trabeculated; there may be associated VUR with tortuous and dilated ureters draining grossly hydronephrotic kidneys. Antenatal ultrasound demonstrating hydronephrosis and megacystis is a common presentation, as is urinary infection in early infancy, but some children present later with dribbling and wetting. Diagnosis is made on the urethrogram phase of the MCU (Fig. 18.1.2) and confirmation is obtained by cystoscopy. Treatment involves complex surgical procedures performed in the setting of a team approach to the patient, involving medical staff and continence physiotherapists. Preparation for end stage renal failure treatment is often necessary. Bladder abnormalities Bladder malfunction is strongly associated with urinary tract infections and often overlooked in clinical management. Table 18.1.6 describes common bladder abnormalities and their management.</p><p>Duplication A kidney is said to be duplex if two separate collecting systems are identified. The ureters may join before entry into the bladder or they may have separate openings into the bladder. The upper pole ureter enters the urinary tract more distal to the lower pole ureter and may enter the urethra, giving rise to incontinence, or may be obstructed at its lower end (ureterocele), in which case the upper pole of the kidney will be abnormal. The lower pole ureter often has vesicoureteric reflux.</p><p>Other causes of urinary obstruction Pelviureteric junction obstruction. This is now most commonly diagnosed following the evaluation of hydronephrosis detected on antenatal scanning of the fetus. At least nine out of 10 such cases will resolve spontaneously over the first year of life. Periodic renal ultrasound observation, sometimes supplemented by diuretic renography using DPTA or Mag 3, or magnetic resonance imaging (MRI), is used to follow these infants. Pelviureteric junction obstruction may present in later childhood with renal colic and these cases usually require surgery. Vesicoureteric junction obstruction. This often presents following investigation of urinary tract infection, with the ultrasound showing a dilated ureter and MRI showing delayed passage of urine from the ureter to the bladder with a widened ureteric image. Treatment is reimplantation of the ureter. Renal calculi. These may present following urinary tract infection, in which case the calculus is usually a triple phosphate (magnesium, calcium and ammonium) stone and the infecting organisms often urea-splitting (such as Proteus mirabilis), or renal colic. Other stones occasionally encountered are composed of cystine (autosomal recessive cystinuria), calcium oxalate and uncommonly uric acid.</p><p>Antenatal renal abnormalities The advent of almost routine antenatal scanning at 18 weeks gestation has led to the detection of approximately 1 in 200 infants having an increased renal pelvis diameter (4 mm at 18 weeks). The postnatal diagnoses are shown in Table 18.1.7.</p><p>Management The antenatal ultrasound should be repeated in the third trimester of pregnancy. The presence of bilateral severe hydronephrosis with an enlarged bladder in the male infant suggests the diagnosis of posterior urethral valves. The presence of oligohydramnios suggests reduced urine output and this is associated with the development of pulmonary hypoplasia. After birth, the infant should be placed on prophylactic trimethoprim until the diagnosis is determined. If the child is unwell or if significant severe abnormalities are suspected, imaging of the kidneys and urinary tract should be performed immediately. In contrast, if the baby is well and without severe urinary tract dilatation, a postnatal ultrasound is undertaken towards the end of the first week of life when the baby is well hydrated. Further investigations, usually looking for reflux or obstruction, are performed, depending upon the results of this ultrasound.</p><p>Cystic renal disease Common forms of cystic renal disease and the modes of presentation are listed in Table 18.1.8. 18.2 Glomerular disease, renal failure and hypertension S. J. McTaggart Glomerular disease presents with various clinical manifestations that include: • isolated urinary abnormalities, e.g. recurrent haematuria, proteinuria • acute glomerulonephritis (nephritic syndrome) • nephrotic syndrome • chronic renal failure.</p><p>Isolated urinary abnormalities Benign microscopic haematuria Asymptomatic isolated microscopic haematuria is common, with screening studies in children of all ages showing a prevalence of 0.5–2%. However, persistent microscopic haematuria is less common (0.5%) indicating that investigation of isolated microscopic haematuria should only be instigated once persistence has been established in at least 3 different specimens taken over a period of 2–3 weeks. Persistent microscopic haematuria is usually benign providing there is no infection or proteinuria, renal function is normal and no structural abnormality is present on ultrasonography. Renal biopsy sometimes shows thinning of basement membrane on electron microscopy (thin basement membrane disease). Often, inheritance is in an autosomal dominant fashion.</p><p>IgA nephropathy This glomerulopathy is present in 50% of children who have recurrent episodes of macroscopic haematuria. The episodes of haematuria often occur simultaneously with intercurrent viral infections and may be associated with flank pain. Other presentations include abnormal urinalysis on medical examination and, rarely, an acute glomerulonephritis with renal failure. The histology of focal proliferative glomerulonephritis with IgA in the mesangium is similar to that of Henoch–Schönlein purpura (Fig. 18.2.1). While the prognosis for most children with IgA nephropathy is good, long-term studies show that about 10% progress to chronic renal failure by 15 years after onset of disease.</p><p>Alport syndrome This is a familial disorder in production of type IV collagen and is inherited as an X-linked dominant (85% of cases), autosomal dominant or autosomal recessive condition. In the X-linked form, males are affected more severely than females. In males this disorder presents in the first 10 years of life with haematuria and proteinuria. Renal histology shows a proliferative glomerulonephritis, with typical changes in the basement membrane of splitting of the internal elastic lamina found on electron microscopy. Renal failure develops in the teenage years. High-tone nerve deafness and eye abnormalities are the other features of the syndrome.</p><p>Postural proteinuria Intermittent or orthostatic proteinuria occurs in 10% of children and is more common in adolescents. Testing with Albustix or protein:creatinine ratio shows a normal amount of urinary protein in the early morning and increased protein during the day. The 24-hour protein estimation can sometimes be as high as 500 mg/d. This phenomenon is benign but proteinuria in an overnight urine specimen will usually require biopsy to determine the cause.</p><p>Glomerulonephritis Most forms of glomerulonephritis result from an immunologically mediated injury involving either deposition of circulating immune complexes in the glomerulus or a specific antibody to the glomerular basement membrane. The clinical features of acute glomerulonephritis are: • haematuria • proteinuria • acute fluid overload – oedema, pulmonary oedema, congestive cardiac failure • hypertension • renal impairment – oliguria, elevated plasma creatinine. Acute presentation with these clinical features is seen most commonly in poststreptococcal glomerulonephritis. Other forms of glomerulonephritis (Table 18.2.1) in childhood may have a less severe onset.</p><p>Poststreptococcal glomerulonephritis This disorder follows 7–14 days after group A haemolytic streptococcal throat infection and 3–6 weeks after streptococcal skin infection. It is hypothesized that streptococcal antigens deposit in glomeruli with activation of the complement system. The pathological appearance consists of proliferation of mesangial and endothelial cells with neutrophil infiltration (Fig. 18.2.2). Crescents may be present. Immunofluorescence shows IgG and C3 and electron-dense deposits are demonstrated by electron microscopy. The usual presentation is a child, usually of school age, with macroscopic haematuria, acute fluid overload and hypertension. Lassitude, fever and loin pain also may be present. Physical examination may reveal hypertension, papilloedema, facial and leg oedema. On laboratory investigation urinalysis shows red blood cell casts and dysmorphic red cells. Serum urea, creatinine and potassium concentrations are often elevated. Mild normocytic normochromic anaemia is common and indicates haemodilution due to fluid overload. The antistreptolysin O titre (ASOT) and antistreptococcal DNAase B are elevated in 90% of cases. Activation of the classical complement pathway leads to low serum levels of C3, which generally return to normal within 6– 12 weeks. Complement C4 may be low in the early stages of the disease. Careful management of the acute renal failure, and especially of the hypertension, is the basis of treatment in this condition. Salt and water accumulation, with suppression of plasma renin, is the major cause of hypertension. Mild hypertension is best managed with furosemide 2–4 mg/kg per day and fluid restriction. Moderate to severe hypertension requires management with oral nifedipine or prazosin, while parenteral hydralazine or nitroprusside are rarely required. Beta blockers should be avoided in the presence of pulmonary oedema. Bed rest is necessary only when the blood pressure is elevated. A course of oral penicillin for 10 days eradicates any existing streptococcal infection but does not alter the natural history of this condition. When renal insufficiency is present the diet consists of restricted protein (1 g/kg/d) and low salt and potassium intake. The major complications of acute post-streptococcal glomerulonephritis are hypertensive encephalopathy, left ventricular failure and acute renal failure. Hypertensive convulsions are often associated with papilloedema and a temporary cortical blindness and require emergency treatment to lower blood pressure. Acute heart failure is related to hypertension and fluid overload. Severe fluid restriction, high dose furosemide administration and adequate control of hypertension are then necessary. The period of oliguria lasts up to 10 days and dialysis is indicated in cases where the blood urea rises above 50–60 mmol/l, or when hyperkalaemia or pulmonary oedema are not controlled by intravenous furosemide and fluid restriction. Dialysis should be performed only in a centre with the appropriate expertise. The long-term prognosis is excellent, with only 1% developing chronic renal failure. Microscopic haematuria may continue for 2 years but proteinuria should clear within 6 months. Renal biopsy is not indicated unless there is uncertainty of diagnosis with the initial investigations or the period of oliguria lasts longer than 3 weeks. Other infectious agents including viral and bacterial organisms rarely can produce an illness similar to poststreptococcal nephritis. These organisms include staphylococci and pneumococcus, Echo, Coxsackie and Epstein–Barr viruses.</p><p>Henoch–Schönlein purpura This disease is a vasculitic illness predominantly involving small vessels in the skin, large joints and gastrointestinal tract (Ch. 16.2). The illness is preceded by upper respiratory tract infection in 30–50% of patients. These children present with a petechial or purpuric rash, abdominal pain and arthritis. A mild nephritis is seen in 50–70% of cases, manifest usually by microscopic haematuria and proteinuria. Rarely, blood pressure and serum creatinine are elevated. Renal histology shows a proliferative glomerulonephritis with IgA in the mesangium. The prognosis is good, with fewer than 5% developing chronic renal failure. Lupus erythematosus Systemic lupus erythematosus (SLE) in childhood is seen more in females in the later childhood years. Facial rash, arthritis and fever are common presenting symptoms. Renal biopsy is indicated if haematuria and proteinuria are present. Serum C3 complement is usually low. This disorder is discussed further in Chapter 13.3. The type of glomerular disease in SLE can vary from a mild focal proliferative glomerulonephritis to a diffuse crescentic glomerulonephritis with associated membranous features. The treatment includes prednisolone, azathioprine, cyclophosphamide and mycophenolate. The amount of immunosuppression is dependent on the severity of renal impairment, proteinuria and type of renal histology.</p><p>Nephrotic syndrome Nephrotic syndrome is defined as: • oedema • proteinuria • hypoalbuminaemia and • hyperlipidaemia. The annual incidence in children is approximately 2–4 in 100 000. The major conditions associated with a primary nephrotic syndrome are listed in Table 18.2.2.</p><p>Minimal change nephrotic syndrome Evidence now suggests that the aetiology of minimal change nephrotic syndrome is caused by an alteration in the glomerular anionic status. Sensitized lymphocytes secrete a number of lymphokines that alter the normal, negatively charged sialoproteins on the glomerular basement membrane. Loss of membrane negative charge allows anionic proteins to leak across the basement membrane into Bowman’s space. Light microscopy shows normal glomeruli but in some cases a mild increase in mesangial cells and mesangial matrix may occur. Immunofluorescence is negative and electron microscopy shows fusion of foot processes. Generalized oedema is the usual presenting symptom (Fig. 18.2.3). Minimal change nephrotic syndrome comprises 80% of cases of nephrotic syndrome in childhood and is more frequent in males than females, the majority presenting between the ages of 1 and 4 years. Renal biopsy is not initially indicated if clinical features suggest minimal change (Table 18.2.3). Unless large pleural effusions, gross ascites or severe genital oedema are present, strict bed rest is not necessary and the child should be allowed normal ward activity. A low-salt diet is encouraged. Fluid intake is generally not restricted because of the risk of hypovolaemia but mild fluid restriction may be beneficial in some children with significant oedema. Prednisolone 2 mg/kg per day or 60 mg/m2 per day induces a remission in 90% of cases. The prednisolone dose is then reduced over 6 months, with later doses being given on alternate days to reduce side effects. If remission, as defined by complete loss of proteinuria, has not occurred by 4 weeks, the nephrotic syndrome is steroid-resistant and a renal biopsy is then indicated to exclude other pathology, particularly focal segmental glomerulosclerosis. Approximately 70% of children have relapses, which are more likely to occur in association with viral upper respiratory tract infections. Frequent relapses (4/year) may be prevented by regular prednisolone 5–15 mg given on alternate days. A course of cyclophosphamide is indicated when steroid side effects become significant. Of children given cyclophosphamide, 50% have no further relapses while most of the remainder have substantially fewer episodes of nephrotic relapse. Cyclosporin reduces the frequency of relapses and preliminary studies suggest that mycophenolate may have a similar effect. Neither drug gives long-lasting remission, with relapse common after withdrawal of treatment, The major complications of the nephrotic syndrome are infections, hypovolaemia and thromboembolism. Infections such as peritonitis and septicaemia can be caused by both Gram-positive and Gram-negative organisms. The susceptibility to infections is related to loss of opsonins and immunoglobulins in the urine. If the patient develops a serious infection, the initial antibiotic treatment should cover both Gram-positive and Gram- negative organisms until cultures and sensitivity results are available. Hypovolaemia is due to loss of plasma water into the tissues with a consequent fall in the circulating blood volume. It occurs in 5% of cases and should be suspected if a child develops oliguria (100 ml/day), poor peripheral perfusion, abdominal pain, tachycardia or postural hypotension. This complication is confirmed by a high haematocrit and a low urine sodium (10 mmol/l). The preferred treatment is intravenous 20% albumin (1 g/kg over 3–6 h), which may need to be repeated, according to response. Intravenous furosemide (2 mg/kg) is given in the middle and at the end of the infusion to promote a diuresis. A hypercoagulable state exists for a number of reasons. These include haemoconcentration and loss of antithrombin III in the urine. Renal vein thrombosis and pulmonary embolism are relatively rare occurrences that require prompt treatment with anticoagulants. The avoidance of bed rest and the treatment of hypovolaemia probably account for the decreasing incidence of these complications.</p><p>Clinical example</p><p>Sasha, a girl aged 5 years, presented with nephrotic syndrome at 2 years. At presentation serum albumin was 18 g/l and 24 hour urine protein 1.5 g/l. Microurine showed 30 rbc/mm3. Blood pressure and complement were normal. Prednisolone 60 mg/m2 per day induced remission in 10 days. In the next 2 years Sasha had six relapses with upper respiratory tract infections and was then managed with prophylactic prednisolone. In the last 6 months she had two further relapses while still on maintenance prednisolone. She was now cushingoid and her height percentile had fallen from the 25th to below the 10th percentile. She commenced a 10-week course of cyclophosphamide (2.5 mg/kg/d). Sasha had steroid-dependent nephrotic syndrome with significant steroid side effects requiring a change in therapy.</p><p>Approximately 90% of children with relapsing nephrotic syndrome cease relapsing by 16 years of age. Even those children who continue to relapse into adult life usually remain steroid-sensitive. It is very rare for a child with a steroid-sensitive minimal change lesion nephrotic syndrome to progress to chronic renal failure. The 20- year mortality has now decreased from 60% to less than 5% since the introduction of antibiotics and corticosteroids. The morbidity and mortality should continue to decrease with adequate management of complications and avoidance of excess immunosuppression.</p><p>Focal segmental glomerulosclerosis This glomerulopathy comprises 5–10% of children with nephrotic syndrome. The presentation is often similar to a minimal change lesion but with steroid resistance. Renal biopsy (Fig. 18.2.4) shows segmental sclerosis or hyalinosis with other glomeruli completely sclerosed or normal. Immunofluorescence shows IgM and IgG in the affected segmental lesions. Mutations in podocin, a podocyte structural protein, are found in 10–30% of sporadic cases of steroid-resistant focal segmental glomerulosclerosis. The majority of children with this lesion are resistant to steroids, cyclophosphamide and cyclosporin. Those children who remain nephrotic require treatment with diuretics (furosemide, spironolactone), mild fluid restriction and a low-salt diet. Approximately 60% progress to end-stage renal failure over 10 years. This glomerulopathy has a 30% recurrence risk in a transplanted kidney and in some cases plasmaphaeresis is beneficial.</p><p>Congenital nephrotic syndrome Nephrotic syndrome in the first 3 months of life is most common in Finland, where the pathology is described as microcystic disease. Other types with minimal lesion histology, diffuse mesangial sclerosis or congenital syphilis are seen occasionally. The Finnish types are now seen in descendants of other European communities and the condition is inherited in an autosomal recessive fashion. The gene is localized to chromosome 19q13.1 and encodes a transmembrane protein called nephrin, which is expressed in the slit diaphragm between glomerular podocytes. Oedema is noted in the first weeks of life, with placentomegaly and prematurity being common precursors. There is no specific treatment, but transplantation can be performed. Proteinuria may occasionally recur following transplantation as a result of the formation of antinephrin antibodies.</p><p>Acute and chronic renal failure The causes of acute renal failure are listed in Table 18.2.4.</p><p>Haemolytic–uraemic syndrome Haemolytic–uraemic syndrome (HUS) is the most common cause of acute intrinsic renal failure in childhood and is characterized by the triad of: • microangiopathic haemolytic anaemia • thrombocytopenia • acute renal insufficiency. It has been broadly classified into two groups: the typical or epidemic form, also known as diarrhoea-associated (D) HUS; the atypical or sporadic form, diarrhoea-negative (D) HUS. This disorder is more common under the age of 3 years. Usually it follows a mild gastroenteritis, but the diarrhoea is often blood-stained. Over the next few days, the child becomes pale, oliguric and unwell. Examination of the blood film shows fragmented red blood cells and thrombocytopenia. Urinalysis reveals haematuria and proteinuria. The serum creatinine is usually elevated and hypertension is often severe. Pathogenesis is related to verocytotoxin production by Escherichia coli, usually serotype O157 : H7, although other serotypes are also involved. The toxin crosses the damaged gut mucosa and adheres to endothelial cells in arterioles, with consequent swelling and widening of the subendothelial space with fibrin deposition. Atypical cases may follow pneumococcal pneumonia in which neuraminidase causes T-cell activation. Dialysis is often necessary in the management of acute renal failure. Management is complex and should only be undertaken by an expert in paediatric renal disease; 90% of children make a complete recovery. Bad prognostic signs are oliguria lasting more than 2 weeks, cerebral involvement and age of onset over 5 years.</p><p>Chronic renal failure The incidence of chronic renal failure in children is 2–4 per million total population per year. The commonest causes include: • chronic glomerulonephritis • reflux nephropathy • obstructive uropathy • medullary cystic disease. The principles of management are as follows: • control of hypertension • adequate nutrition. Growth becomes impaired when the glomerular filtration rate is less than 25% of normal/1.73 m2. With this degree of renal impairment, hyperfiltration can produce further sclerosis of the remaining functioning glomeruli. A low protein diet (0.8–1.5 g/kg/d) with low phosphate and adequate calorie intake may delay the progression of renal failure. Salt and fluid intake will vary with the type of renal disease • prevention of renal osteodystrophy. Hyperphosphataemia should be vigorously treated with a low-phosphate diet and dietary phosphate binders (calcium carbonate or aluminium hydroxide) in an attempt to prevent secondary hyperparathyroidism. Vitamin D supplementation with calcitriol (1,25-dihydroxycholecalciferol) is given in early renal failure to prevent rickets • administration of alkali to control acidosis (2–3 mmol/kg/d) • anaemia is corrected by erythropoietin. This is administered subcutaneously once each week. Iron supplementation is necessary • growth retardation is improved by growth hormone. Resistance to growth hormone is caused by low free insulin-like growth factor-1 levels.</p><p>Clinical example</p><p>Thomas, aged 30 months, had chronic renal failure from birth from urethral valves and dysplastic kidneys. He had a poor appetite and required nasogastric feeding from 3 months. X-ray of the wrist at 18 months showed rickets requiring treatment with calcitriol. At 24 months he developed anaemia (Hb 9.5 g/l) and commenced weekly subcutaneous darbepoietin. Thomas had grown 2 cm in the last 12 months. Investigations showed Hb 11.3 g/l, serum sodium 136 mmol/l, potassium 4.5 mmol/l, urea 42 mmol/l, creatinine 0.65 mmol/l, calcium 2.4 mmol/l, phosphate 2.4 mmol/l, alkaline phosphatase 850 U/l. Parathormone was elevated. Thomas had now reached end-stage renal failure and will commence peritoneal dialysis. Growth hormone was indicated for growth failure. He continued calcium carbonate at meal times in addition to calcitriol for renal osteodystrophy and erythropoietin for anaemia.</p><p>Dialysis and transplantation are now standard for young children with end-stage renal failure. Under 1 year of age there are considerable technical, ethical and psychological problems. Young children tolerate peritoneal dialysis better than haemodialysis and the use of automated machines for overnight dialysis facilitates attendance at school. Both cadaver and live related transplants are performed in children, with good results. Approximately 80% of children survive for at least 10–15 years after entering dialysis/transplant programmes. Practical points</p><p>Glomerular disease • Microscopic haematuria without proteinuria is rarely associated with significant renal disease • Non-postural proteinuria is a more important diagnostic and prognostic finding and requires specialist assessment • Children with typical features of nephrotic syndrome that respond to prednisolone treatment do not require a renal biopsy • Children with frequently-relapsing (2 relapses within 6 months of initial episode or 4/year) or steroid-dependent (relapse on prednisolone) nephrotic syndrome require specialist referral • Control of hypertension and fluid overload is the key to management of acute post-streptococcal glomerular nephritis</p><p>Hypertension The recording of blood pressure should be part of the normal examination in children older than 3 years age. The blood pressure cuff bladder length should cover 80–100% of the circumference of the upper arm, as a smaller cuff will often lead to a falsely high reading. The child should be still and not crying. Using sphygmomanometry, the diastolic component is best recorded by the disappearance of Korotkoff sounds but if difficulties arise in obtaining an accurate recording a machine using oscillometric techniques can be used. Normal blood pressure for children varies with gender, age and height (Fig. 18.2.5). A child should not be regarded as being hypertensive unless three recordings give levels above the 95th percentile for age and height. In borderline hypertension oscillometric 24-hour ambulatory blood pressure recordings are useful to distinguish persistent blood pressure elevation from ‘white coat hypertension’. The major causes of hypertension are given in Table 18.2.5. Renal disease accounts for approximately 80% of cases prior to adolescence. The investigation of hypertension should commence with a good history and examination. The history should specifically include enquiries about urinary tract infections, neonatal umbilical artery catheterization, medication use and hypertension or early stroke in any relatives. Symptoms may relate to the underlying cause (polyuria and polydipsia in chronic renal failure) or the hypertension itself (headaches, irritability). Physical examination may assist in making a specific diagnosis (palpable renal mass, neurocutaneous pigmentation, delayed femoral pulses, renal artery bruits) or may suggest essential hypertension (obesity). The initial evaluation of hypertensive children is summarized in Table 18.2.6. Treatment of hypertension depends on the severity, presence of symptoms and underlying cause. Children with a hypertensive emergency usually present with signs and symptoms involving the: • nervous system – encephalopathy, facial palsy, retinopathy • heart – left ventricular hypertrophy or congestive cardiac failure • kidneys – raised serum creatinine, proteinuria. An acute hypertensive emergency requires immediate intervention with intravenous drugs (Table 18.2.7), which can produce a controlled reduction in blood pressure. The aim is to decrease blood pressure by 25% over the first 8 hours, with gradual normalization over the subsequent 24–48 hours. Severe hypertension without imminent serious clinical sequelae is managed as a hypertensive urgency and blood pressure may be gradually reduced over 24–48 hours. In essential hypertension, advice on a low-salt diet, weight reduction and exercise may assist reduction in blood pressure. Intervention techniques such as transluminal angioplasty for renal artery stenosis, resection of coarctation of the aorta and nephrectomy for a small scarred kidney may cure a small percentage of children. The drug treatment of chronic hypertension is similar to that of adult patients; drugs used include: • angiotensin converting enzyme inhibitors (captopril, perindopril) • angiotensin receptor blockers (irbesartan, losartan) • calcium channel inhibitors (nifedipine, amlodipine) • beta-adrenergic blockers (atenolol, metoprolol) • vasodilators (hydralazine, prazosin) • diuretics (hydrochlorothiazide, furosemide).</p><p>Clinical example</p><p>Sally, aged 6 years, had a blood pressure recording of 140/100 mmHg at the time of tonsillectomy. Urine analysis, renal function and renal ultrasound were normal; an echocardiogram showed left ventricular hypertrophy; a Mag 3 scan showed that the left kidney contributed 44% and the right kidney 56% of total function; a renal angiogram showed a midaortic syndrome with bilateral renal artery stenosis from fibromuscular hyperplasia. Sally’s blood pressure was controlled with metoprolol 7.5 mg daily and amlodipine 5 mg daily. Left balloon angioplasty to 3– 4 mm has been performed and she is awaiting a similar procedure on the right renal artery.</p><p>Practical points</p><p>Hypertension • Hypertension is defined as repeated systolic blood pressure and/or diastolic blood pressure measurements  95th percentile for gender, age and height. Some hypertensive children may have a normal blood pressure at presentation if they are in cardiac failure • ‘White coat’ hypertension is common in children and can be excluded by 24-hour ambulatory blood pressure monitoring • All hypertensive children should be evaluated for target organ damage and have investigations to identify secondary causes of hypertension • Intravenous treatment to achieve a slow, controlled reduction of blood pressure is indicated for hypertensive emergencies • The goal for antihypertensive treatment is reduction of blood pressure to 95th percentile</p><p>Fig. 18.1.1 A flow diagram of ongoing management following a proven urinary tract infection. A normal ultrasound does not exclude scarring. This age is chosen for convenience. Boys uncommonly get recurrent infections after 1 year; girls commonly have recurrent infection until about 3 years. Follow-up includes a yearly blood pressure check. The finding of a normal DMSA scan normalizes the risk of developing hypertension. MCU, micturating cystourethrogram; U/S, ultrasound; VUR, vesicoureteric reflux. Fig. 18.1.2 A. The MCU (from the clinical example) showing a dilated posterior urethra, mildly irregular appearance of the edge of the bladder (‘trabeculation’) and bilateral vesicoureteric reflux into dilated tortuous ureters. B. Hydronephrosis with ‘clubbing’ of the calyces. Fig. 18.2.1 Immunofluorescence shows mesangial IgA deposits (600). Fig. 18.2.2 Mesangial proliferation and neutrophil infiltration in post-streptococcal glomerulonephritis (periodic acid–Schiff 800). Fig. 18.2.3 Child with facial oedema due to the nephrotic syndrome. Fig. 18.2.4 Segmental and global sclerosis (periodic acid–Schiff 500). Fig. 18.2.5 95th percentile blood pressure in boys and girls aged 1–17 years, by height percentile (upper line, height  90th percentile; lower line, height  10th percentile).</p><p>Table 18.1.1 Common clinical patterns of urinary tract infection</p><p>Age Infancy Toddler and young child Adolescent</p><p>Presentation Males more common than Common for females, Common for females, rare for females, especially under 3 uncommon for males males months Mild fever, wetting, dysuria Pyelonephritis or cystitis High fever and smelly urine Systemically unwell Frequent recurrences Commonly recurs</p><p>Precipitating Males: High-grade VUR (often Low-grade VUR – ? associated Often history of VUR factors associated with significant with development of acquired Sexual activity congenital renal malformation), renal injury Vulvovaginitis physiological phimosis Dysfunctional elimination Females: Low-grade VUR, usually symptoms associated with no or minor Detrusor dyssynergia renal malformation Infrequent voiding Both: Immature voiding pattern Constipation with high voiding pressure Vulvovaginitis and detrusor hyperactivity</p><p>Prevention of Prophylactic antibiotic Treatment of precipitating Counselling recurrence factors identified Adjustment of sexual habit (void post-intercourse, antibiotic at time of sexual activity)</p><p>VUR, vesicoureteric reflux.</p><p>Table 18.1.2 Frequency of symptoms in children under 5 years with symptomatic urinary tract infections</p><p>Symptom %</p><p>History of fever 79.6 Axillary temperature 37.5°C 59.5</p><p>Irritability 52.3</p><p>Anorexia 48.7</p><p>Malaise/lethargy 44.4</p><p>Vomiting 41.8</p><p>Diarrhoea 20.7</p><p>Dysuria 14.8</p><p>Offensive urine 13.2</p><p>Abdominal pain 13.2</p><p>Family member with past history of UTI* 11.2</p><p>Previous unexplained febrile episodes 10.5</p><p>Frequency 9.5</p><p>Urinary incontinence† 6.6</p><p>Macroscopic haematuria 6.6</p><p>Febrile convulsion 4.6</p><p>* First-degree relative. † Defined as a noticeable increase in the frequency of daytime wetting. Source: from Craig et al, 1998.</p><p>Table 18.1.3 Comparison of methods of urine collection</p><p>Urine collection method Advantages Disadvantages Recommended use</p><p>Paediatric bag Widespread use in primary care paediatrics Contamination with skin flora common so Collection of urine from infant or toddler at low Considered convenient that only results of 108 cfu/l (excluding risk for UTI (not febrile and no known Avoids invasive procedure infection) are useful urological abnormality) for urinalysis: if Should not be used where immediate ve for leukocytes or nitrites, another urine antibiotic treatment is required collection method should be used for culture</p><p>Clean catch Non-invasive Perceived to be difficult to collect (majority Method of choice in infants and toddlers Good correlation with SPA/MSU/CSU can be collected within 1 h) 108 cfu/l indicates infection, although results presence of squamous epithelia and lack</p><p> of pyuria indicates contamination</p><p>Midstream urine Non-invasive Poor technique (failure to withdraw foreskin Method of choice in toilet trained child 108 cfu/l collection (MSU) Widespread patient acceptance or wash labia) results in contamination indicates infection, although presence of Difficult with phimosis or for obese females squamous epithelia and lack of pyuria</p><p> indicates contamination</p><p>Catheter sample (CSU) Usually results in collection of sample of Invasive – poor acceptance by parents and Second choice to SPA in infants and toddlers urine, reasonable for diagnosis especially can establish fear in child of future clinic with high risk of UTI (febrile and proven if 1st drops of urine discarded visits urological abnormalities) where treatment Difficult with phimosis is required before culture available</p><p>106 cfu/l may indicate infection, although</p><p> presence of squamous epithelia</p><p> and lack of pyuria indicates contamination</p><p>Suprapubic aspirate of Gold standard as avoids contamination. Less ‘Dry tap’ relatively common (ultrasound Method of choice in infants and toddler at urine (SPA) invasive than CSU collection confirmation of full bladder can high risk of UTI minimize this) Useful in obese females with recurrent</p><p> contaminated MSUs</p><p>Any growth significant cfu, colony-forming unit on bacterial culture.</p><p>Table 18.1.4 Antibiotic treatment of urinary tract infection</p><p>Antibiotic Dose Organisms sensitive* (%)</p><p>Acute Intravenous (sick, 6 months old, pyelonephritis) 1. Benzyl penicillin 50 mg/kg (max. dose 2 g) 6 h Covers enterococcus and 2. Gentamicin 8 mg/kg day 1, then 6 mg/kg/day for 10 years, 95 7 mg/kg day 1, then 5 mg/kg/day for 10 years (max. dose 360 mg) Monitoring: trough level 1 mg/l taken on 3rd day and serum creatinine 3rd day</p><p>Oral Trimethoprim 4 mg/kg (max. dose 150 mg) 12 h 85 or Co-trimoxazole (40/200 mg/5 ml) 85 0.5 ml/kg (max. dose 20 ml) 12 h or Cephalexin 15 mg/kg (max. dose 500 mg) 8 h 95 or Augmentin† 10–25 mg/kg/8 h 95</p><p>Prophylactic Co-trimoxazole (40/200 mg/5 ml) 85 0.25 ml/kg/night Nitrofurantoin 1–2 mg/kg/night 85 Cefalexin‡ 5 mg/kg/night 95</p><p>* Percentage of bacteria causing urinary tract infection diagnosed in the emergency department of major Australian hospitals that are sensitive to antibiotics. † Amoxicillin alone only covers 60% of organisms encountered, so Augmentin is preferred. ‡ The suspension forms of the cephalosporins and penicillins lose activity after a few weeks.</p><p>Table 18.1.5 Management of vesicoureteric reflux: evidence and controversies</p><p>Evidence-based analysis of surgical versus antibiotic treatment of VUR shows • No difference in overall rate of urinary tract infection (but reduced rate of pyelonephritis with surgery) • No difference in occurrence of ‘new scarring’ or extension of ‘old scarring’ • No difference in incidence of renal failure • No difference in incidence of hypertension</p><p>Continuing controversies: • Whether VUR surgery or antibiotics make any difference to development of acquired renal injury • The frequency of acquired or congenital renal injury as a cause of reflux nephropathy • The effectiveness of prophylactic antibiotic therapy • The significance of smaller renal scars</p><p>Table 18.1.6 Common bladder abnormalities</p><p>Bladder abnormality causes Urodynamic assessment Symptoms Treatment</p><p>Small bladder Low volume Day and night wetting Frequent voiding Primary High pressure UTI Bladder augmentation Posterior urethral valves Hydroureter Bladder extrophy Neurogenic</p><p>Large bladder Large volume Infrequent voiding Frequent voiding Primary Low pressure UTI Drainage by vesicostomy, Neurogenic High residual volume Wetting CIC or catheterizable conduits Vesicoureteric reflux</p><p>Detrusor dyssynergia Premature detrusor Urge symptoms Anticholinergic drugs syndrome contractions Wetting Frequent voiding Primary UTI Usually resolves Vesicoureteric reflux</p><p>Neurogenic All of the above found Wetting with ‘overflow’ Bladder drainage by vesicostomy, Cord injury* UTI CIC or catheterizable conduit ‘Non-neurogenic’† Obstructive nephropathy Bladder augmentation</p><p>* Cord injury may be clinical apparent (spina bifida) or determined by US in a neonate when the cord can be imaged or MRI at later ages. † Non-urogenic neurogenic bladder is a term used for the clinical and investigational features of a neurogenic bladder but do not have demonstrable spinal pathology. CIC, clean intermittent catheterization; UTI, urinary tract infection.</p><p>Table 18.1.7 Antenatal renal abnormalities: postnatal diagnoses</p><p>Diagnosis %</p><p>Non-refluxing non-obstructive hydronephrosis 55</p><p>Vesicoureteric reflux 15</p><p>Pelviureteric junction obstruction 5</p><p>Multicystic kidney 5</p><p>Vesicoureteric junction abnormalities 5</p><p>Duplex 5</p><p>Agenesis 5</p><p>Posterior urethral valves 2 Table 18.1.8 Forms and presentation of cystic renal disease</p><p>Cystic renal disease Incidence Genetics Clinical features</p><p>Autosomal dominant 1–2 in 1000 Three gene defects Usually discovered because of family history polycystic kidney M  F cause it; 50% risk Uncommon cause of hypertension oroin/abdominal disease in subsequent discomfort in childhood children Progresses to renal failure later in life</p><p>Autosomal 1–2 in 10 000 One gene defect Often present in infancy with enlarged kidneys, recessive kidney births identified; 25% risk polycystic and oligohydramnios, which in turn is disease M  F in subsequent associated with pulmonary hypoplasia. pregnancies Later may get hypertension, renal impairment Associated with hepatic fibrosis causing portal hypertension in mid childhood</p><p>Cystic renal dysplasia Common Polygenic; low Often asymptomatic. Associated with vesicoureteric reflux. recurrence risk May be bilateral</p><p>Multicystic dysplastic Relatively Unknown; low Enlarged completely cystic non-functioning kidney kidney uncommon recurrence risk without blood flow. Contralateral kidney usually normal but may be associated with vesicoureteric reflux or pelviureteric junction obstruction</p><p>Table 18.2.1 Causes of acute nephritis</p><p>• Postinfectious glomerulonephritis • Henoch–Schönlein purpura • IgA nephropathy • Lupus erythematosus • Membranoproliferative glomerulonephritis • Vasculitis</p><p>Table 18.2.2 Classification of primary nephrotic syndrome</p><p>• Minimal change disease • Focal segmental glomerulosclerosis • Membranoproliferative glomerulonephritis • Membranous glomerulopathy • Congenital nephrotic syndrome</p><p>Table 18.2.3 Clinical features of minimal change nephrotic syndrome</p><p>• Age 1–10 years • Blood pressure normal • Renal function normal • Microscopic haematuria 30% • Complements normal • Selective index – low-molecular-weight protein urine loss</p><p>Table 18.2.4 Causes of acute renal failure</p><p>Prerenal Renal Post-renal</p><p>Hypovolaemia Kidney disease Posterior urethral valves Gastroenteritis Glomerulonephritis Neurogenic bladder Haemorrhage Haemolytic–uraemic syndrome Ureterocele Hypoalbuminaemia Interstitial nephritis Calculi</p><p>Peripheral vasodilation Myoglobinuria, haemoglobinuria Tumours Sepsis Nephrotoxic drugs Uric acid (tumour lysis syndrome)</p><p>Decreased cardiac output Congestive cardiac failure Table 18.2.5 Causes of hypertension – REDCAT</p><p>R Renal parenchymal disease • Acute glomerulonephritis • Chronic glomerulonephritis • Reflux nephropathy • Obstructive uropathy • Haemolytic uraemic syndrome • Polycystic kidneys</p><p>Renovascular (renal artery stenosis, renal vein thrombosis) E Essential D Drugs (corticosteroids, ciclosporin) C Coarctation of aorta A Adrenogenital syndrome, hyperaldosteronism T Tumours (Wilms, phaeochromocytoma, neuroblastoma)</p><p>Table 18.2.6 Evaluation of hypertension</p><p>Investigations Potential diagnosis</p><p>Initial screening Creatinine and serum biochemistry Acute or chronic renal failure Hyperaldosteronism (hypokalaemia) Urinalysis and urine culture Acute or chronic glomerulonephritis (haematuria, proteinuria), urinary tract infection Renal ultrasound with Doppler Reflux nephropathy, cystic disorders, tumours, renal artery stenosis DMSA/micturating cystourethrogram Reflux nephropathy Mag3 or DTPA renal scan Obstructive nephropathy Echocardiogram Aortic coarctation, assessment of end-organ damage</p><p>Second line Complement, antistreptolysin O titre and Post-streptococcal glomerulonephritis anti-DNAase B Renal angiogram/renal vein renin sampling Renal artery stenosis Plasma renin/aldosterone Adrenal disorders, renal artery stenosis Catecholamines/MIBG scan Phaeochromocytoma Renal biopsy Acute or chronic glomerulonephritis</p><p>Table 18.2.7 Drug therapy of severe hypertension</p><p>Hypertensive emergency Sodium nitroprusside 0.5–10 g/kg/min i.v. infusion Labetalol 0.5–3 mg/kg/h i.v. Hydralazine 0.1–0.5 mg/kg i.v. or i.m. every 4–6 h Diazoxide 1–3 mg/kg stat i.v. then every 6 h</p><p>Hypertensive urgency Nifedipine 0.5–1 mg/kg oral 12 h Minoxidil 0.1–0.5 mg/kg oral 12 h</p>