Assessment of the kidneys and urinary tract

The glomerular filtration rate (GFR) is low in the newborn infant and is especially low in premature infants; the GFR at 28 weeks’ gestation is only 10% of the term infant. In term infants, the corrected GFR (15–20 ml/min per 1.73 m²) rapidly rises to 1–2 years of age when the adult rate of 80 to 120 ml/min per 1.73 m² is achieved (Fig. 18.1). The assessment of renal function in children is listed in Table 18.1 and the radiological investigations of the kidneys and urinary tract in Table 18.2.

Anomalies detectable on antenatal ultrasound screening

Absence of both kidneys (renal agenesis) – as amniotic fluid is mainly derived from fetal urine, there is severe oligohydramnios resulting in Potter syndrome (Fig. 18.2a, 18.2b), which is fatal.

Multicystic dysplastic kidney (MCDK) – results from the failure of union of the ureteric bud (which forms the ureter, pelvis, calyces and collecting ducts) with the nephrogenic mesenchyme. It is a non-functioning structure with large fluid-filled cysts with no renal tissue and no connection with the bladder (Fig. 18.3). Half will have involuted by 2 years of age, and nephrectomy is indicated only if it remains very large or hypertension develops, but this is rare. Since they produce no urine, Potter syndrome will result if the lesion is bilateral. Other causes of large cystic kidneys are autosomal recessive polycystic kidney disease (ARPKD) (Fig. 18.4), autosomal dominant polycystic kidney disease (ADPKD) (Fig. 18.5) and tuberous sclerosis. In contrast to a multicystic dysplastic kidney, in these disorders some or normal renal function is maintained but both kidneys are always affected. Autosomal dominant polycystic kidney disease has an incidence of 1 in 1000; the main symptoms in childhood are hypertension and haematuria and it causes renal failure in late adulthood. It is associated with several extra-renal features including cysts in liver and pancreas, cerebral aneurysms and mitral valve prolapse.

Abnormal caudal migration may result in a pelvic kidney or a horseshoe kidney (Fig. 18.6), when the lower poles are fused in the midline. The abnormal position may predispose to infection or obstruction to urinary drainage.

Premature division of the ureteric bud gives rise to a duplex system, which can vary from simply a bifid renal pelvis to complete division with two ureters. These ureters frequently have an abnormal drainage so that the ureter from the lower pole moiety often refluxes, whereas the upper pole ureter may drain ectopically into the urethra or vagina or may prolapse into the bladder (ureterocele) and urine flow may be obstructed (Fig. 18.7).

Failure of fusion of the infraumbilical midline structures results in exposed bladder mucosa (bladder extrophy). Absence or severe deficiency of the anterior abdominal wall muscles is frequently associated with a large bladder and dilated ureters (megacystis-megaureters) and cryptorchidism, the absent musculature syndrome (prune-belly syndrome) (Fig. 18.8).

Obstruction to urine flow may occur at the pelvi-ureteric or vesicoureteric junction, at the bladder neck (e.g. due to disruption of the nerve supply, neuropathic bladder) or at the posterior urethra in a boy due to mucosal folds or a membrane, known as posterior urethral valves. The consequences of obstruction to urine flow are shown in Figures 18.9a–18.9d. At worst, this results in a dysplastic kidney which is small, poorly functioning and may contain cysts and aberrant embryonic tissue such as cartilage. In the most severe and bilateral cases Potter syndrome is present. Renal dysplasia can also occur in association with severe intrauterine vesicoureteric reflux, in isolation or in certain rare, inherited syndromes affecting multiple systems.

Some congenital abnormalities of the kidneys and urinary tract

Urinary tract obstruction

Antenatal treatment

The male fetus with posterior urethral valves may develop severe urinary outflow obstruction resulting in progressive bilateral hydronephrosis, poor renal growth and declining liquor volume with the potential to lead to pulmonary hypoplasia. Intrauterine bladder drainage procedures to prevent severe renal damage have been attempted but results have been disappointing. Early delivery is rarely indicated.

Postnatal management

An example of a protocol for infants with antenatally diagnosed anomalies is shown in Figure 18.10. Prophylactic antibiotics may be started at birth to try to prevent urinary tract infection, although practice varies between centres. As the newborn kidney has a low GFR, urine flow is low and mild outflow obstruction may not be evident in the first few days of life. The ultrasound scan should therefore be delayed for several weeks. However, bilateral hydronephrosis in a male infant warrants an ultrasound shortly after birth to exclude posterior urethral valves, which always requires urological intervention such as cystoscopic ablation (Case History 18.1).

Case History

18.1 Posterior urethral valves

Bilateral hydronephrosis was noted on antenatal ultrasound at 20 weeks’ gestation in a male fetus. There was poor renal growth, progressive hydronephrosis and decreasing volume of amniotic fluid (Fig. 18.11a) on repeated scans. After birth, prophylactic antibiotics were started. An urgent ultrasound showed bilateral hydronephrosis with small dysplastic kidneys. The bladder and ureters were grossly distended. The plasma creatinine was raised. A micturating cystourethrogram (MCUG) (Fig. 18.11b) showed vesicoureteric reflux, a dilated posterior urethra and posterior urethral valves which was treated endoscopically. Renal function initially improved but then progressed to chronic renal failure. He had a renal transplant at 10 years of age.

Clinical features

Presentation of UTI varies with age (Box 18.1). In infants, symptoms are non-specific; fever is usually but not always present, and septicaemia may develop rapidly. The classical symptoms of dysuria, frequency and loin pain become more common with increasing age. Serious illness from septicaemia is described in the child with a fever in Chapter 14. Dysuria alone is usually due to cystitis, or vulvitis in girls or balanitis in uncircumcised boys. Symptoms suggestive of a UTI may also occur following sexual abuse.

Collection of samples

The commonest error in the management of UTI in children, and especially in infants, is failure to establish the diagnosis properly in the first place. If the diagnosis of a UTI is not made, the opportunity to prevent renal damage may be missed, or, if incorrectly diagnosed, may lead to unnecessary invasive investigations.

For the child in nappies, urine can be collected by:

In the older child, urine can be obtained by collecting a midstream sample. Careful cleaning and collection are necessary, as contamination with both white cells and bacteria can occur from under the foreskin in boys, and from reflux of urine into the vagina during voiding in girls.

Ideally, the urine sample should be microscoped to identify organisms and cultured straight away. This is indicated in all infants and children <3 years old with a suspected UTI. If this is not possible, the urine sample should be refrigerated to prevent the overgrowth of contaminating bacteria. Urinary white cells are not a reliable feature of a UTI, as they may lyse during storage and may be present in febrile children without a UTI and in children with balanitis or vulvovaginitis. Dipsticks can be used as a screening test. Urine culture should still be performed unless both leucocyte esterase and nitrite are negative or if the clinical symptoms and dipstick tests do not correlate (Table 18.3).

Antenatally diagnosed renal or urinary tract abnormality

Increases risk of infection.

Incomplete bladder emptying

Contributing factors in some children are:

Vesicoureteric reflux

Vesicoureteric reflux (VUR) is a developmental anomaly of the vesicoureteric junctions. The ureters are displaced laterally and enter directly into the bladder rather than at an angle, with a shortened or absent intramural course. Severe cases may be associated with renal dysplasia. It is familial, with a 30–50% chance of occurring in first-degree relatives. It may also occur with bladder pathology, e.g. a neuropathic bladder or urethral obstruction, or temporarily after a UTI. Its severity varies from reflux into the lower end of an undilated ureter during micturition to the severest form with reflux during bladder filling and voiding, with a distended ureter, renal pelvis and clubbed calyces (Fig. 18.12). Mild reflux is unlikely to be of significance, but the more severe degrees of VUR may be associated with intrarenal reflux (IRR), the backflow of urine from the renal pelvis into the papillary collecting ducts; intrarenal reflux is associated with a particularly high risk of renal scarring if UTIs occur. The incidence of renal defects increases with increasing severity of reflux. There is considerable controversy as to whether renal scarring is a congenital abnormality already present in children with reflux and which predisposes to infection or if children with reflux have normal kidneys at birth which are damaged by UTIs and that preventing UTIs in these children prevents scars. Reflux tends to resolve with age especially lower grades of VUR.

Reflux with associated ureteric dilatation is important, as:

Infection may destroy renal tissue, leaving a scar, resulting in a shrunken, poorly functioning segment of kidney (reflux nephropathy). If scarring is bilateral and severe, chronic renal failure may develop. The risk for hypertension in childhood or early adult life is variously estimated to be up to 10%.

Daytime enuresis

This is a lack of bladder control during the day in a child old enough to be continent (over the age of 3–5 years). Nocturnal enuresis is also usually present. It may be caused by:

Examination may reveal evidence of a neuropathic bladder, i.e. the bladder may be distended, there may be abnormal perineal sensation and anal tone or abnormal leg reflexes and gait. Sensory loss in the distribution of the S2, 3 and 4 dermatomes should be sought. A spinal lesion may be present. Girls who are dry at night but wet on getting up are likely to have pooling of urine from an ectopic ureter opening into the vagina.

A urine sample should be examined for microscopy, culture and sensitivity. Other investigations are performed if indicated. An ultrasound may show bladder pathology, with incomplete bladder emptying or thickening of the bladder wall. Urodynamic studies may be required. An X-ray of the spine may reveal a vertebral anomaly. An MRI scan may be required to confirm or exclude a non-bony spinal defect such as tethering of the cord.

Affected children in whom a neurological cause has been excluded may benefit from star charts, bladder training and pelvic floor exercises. Constipation should be treated. A small portable alarm with a pad in the pants, which is activated by urine, can be used when there is lack of attention to bladder sensation. Anticholinergic drugs, such as oxybutynin, to damp down bladder contractions, may be helpful if other measures fail.

Secondary (onset) enuresis

The loss of previously achieved urinary continence may be due to:

Investigation should include:

Nephrotic syndrome

In nephrotic syndrome, heavy proteinuria results in a low plasma albumin and oedema. The cause of the condition is unknown, but a few cases are secondary to systemic diseases such as Henoch–Schönlein purpura (HSP) and other vasculitides, e.g. systemic lupus erythematosus (SLE), infections (e.g. malaria) or allergens (e.g. bee sting).

Nephrotic syndrome

Clinical signs of the nephrotic syndrome are:

The initial investigations are listed in Box 18.3.

Steroid-sensitive nephrotic syndrome

In 85–90% of children with nephrotic syndrome, the proteinuria resolves with corticosteroid therapy (steroid-sensitive nephrotic syndrome). These children do not progress to renal failure. It is commoner in boys than in girls, in Asian children than in Caucasians, and there is a weak association with atopy. It is often precipitated by respiratory infections. Features suggesting steroid-sensitive nephrotic syndrome are:

• Age between 1 and 10 years

• No macroscopic haematuria

• Normal blood pressure

• Normal complement levels

• Normal renal function.

Management

The most widely used protocol is to initially give oral corticosteroids (60 mg/m² per day of prednisolone), unless there are atypical features. After 4 weeks, the dose is reduced to 40 mg/m² on alternate days for 4 weeks and then stopped. The median time for the urine to become free of protein is 11 days. However, there is now good evidence that extending the initial course of steroids, by gradually tapering the alternate day part of the course, leads to a marked reduction in the proportion of children who develop a frequently relapsing or steroid-dependent course, and this scheme is increasingly being adopted. Children who do not respond to 4–8 weeks of corticosteroid therapy or have atypical features may have a more complex diagnosis and require a renal biopsy. Renal histology in steroid-sensitive nephrotic syndrome is usually normal on light microscopy but fusion of the specialised epithelial cells that invest the glomerular capillaries (podocytes) is seen on electron microscopy. For this reason, it is called minimal change disease.

The child with nephrotic syndrome is susceptible to several serious complications at presentation or relapse:

• Hypovolaemia. During the initial phase of oedema formation the intravascular compartment may become volume depleted. The child who becomes hypovolaemic characteristically complains of abdominal pain and may feel faint. There is peripheral vasoconstriction and urinary sodium retention. A low urinary sodium (<20 mmol/L) and a high packed cell volume of red blood cells are indications of hypovolaemia, which requires urgent treatment with intravenous albumin as the child is at risk of vascular thrombosis and shock. Increasing peripheral oedema, assessed clinically and by daily weight, may cause discomfort and respiratory compromise. If severe, this may need treatment with intravenous albumin. Care must be taken with the use of colloid, as it may precipitate pulmonary oedema and hypertension from fluid overload, and also with diuretics, which may cause or worsen hypovolaemia.

• Thrombosis. A hypercoagulable state, due to urinary losses of antithrombin, thrombocytosis which may be exacerbated by steroid therapy, increased synthesis of clotting factors and increased blood viscosity from the raised haematocrit, predisposes to thrombosis. This may affect the brain, limbs and splanchnic circulation with potentially catastrophic results.

• Infection. Children in relapse are at risk of infection with capsulated bacteria, especially Pneumococcus. Spontaneous peritonitis may occur. Pneumococcal and seasonal influenza vaccination is widely recommended. Chickenpox and shingles should be treated with aciclovir.

• Hypercholesterolaemia. This correlates inversely with the serum albumin, but the cause of the hyperlipidaemia is not fully understood.

Prognosis

This is summarised in Figure 18.18. Relapses are identified by parents on urine testing. The side-effects of corticosteroid therapy may be reduced by an alternate-day regimen. If relapses are frequent, or if a high maintenance dose is required, involvement of a paediatric nephrologist is advisable as other drug therapy may be considered to enable reduction in steroid use. Possible steroid-sparing agents include the immunomodulator levamisole, alkylating agents (e.g. cyclophosphamide), calcineurin inhibitors such as tacrolimus and ciclosporin A and the immunosuppressant mycophenolate mofetil.

Acute nephritis

The causes of acute nephritis in childhood are listed in Box 18.6. Increased glomerular cellularity restricts glomerular blood flow and therefore filtration is decreased. This leads to:

Management is by attention to both water and electrolyte balance and the use of diuretics when necessary. Rarely, there may be a rapid deterioration in renal function (rapidly progressive glomerulonephritis). This may occur with any cause of acute nephritis, but is uncommon when the cause is post-streptococcal. If left untreated, irreversible renal failure may occur over weeks or months, so renal biopsy and subsequent treatment with immunosuppression and plasma exchange may be necessary.

Henoch–Schönlein purpura

Henoch–Schönlein purpura is the combination of some of the following features:

• Characteristic skin rash

• Arthralgia

• Periarticular oedema

• Abdominal pain

• Glomerulonephritis.

It usually occurs between the ages of 3 and 10 years, is twice as common in boys, peaks during the winter months and is often preceded by an upper respiratory infection. Despite much research, the cause is unknown. It is postulated that genetic predisposition and antigen exposure increase circulating IgA levels and disrupt IgG synthesis. The IgA and IgG interact to produce complexes that activate complement and are deposited in affected organs, precipitating an inflammatory response with vasculitis.

Clinical findings (Fig. 18.19)

At presentation, affected children often have a fever. The rash is the most obvious feature. It is symmetrically distributed over the buttocks, the extensor surfaces of the arms and legs, and the ankles. The trunk is spared unless lesions are induced by trauma. The rash may initially be urticarial, rapidly becoming maculopapular and purpuric, is characteristically palpable and may recur over several weeks. The rash is the first clinical feature in about 50% and is the cornerstone of the diagnosis, which is clinical.

Joint pain occurs in two-thirds of patients, particularly of the knees and ankles. There is periarticular oedema. Long-term damage to the joints does not occur, and symptoms usually resolve before the rash goes.

Colicky abdominal pain occurs in many children and, if severe, can be treated with corticosteroids. Gastrointestinal petechiae can cause haematemesis and melaena. Intussusception can occur and can be particularly difficult to diagnose under these circumstances. Ileus, protein-losing enteropathy, orchitis and occasionally central nervous system involvement are rare complications.

Renal involvement is common, but is rarely the first symptom. Over 80% have microscopic or macroscopic haematuria or mild proteinuria. These children usually make a complete recovery. If proteinuria is more severe, nephrotic syndrome may result. Risk factors for progressive renal disease are heavy proteinuria, oedema, hypertension and deteriorating renal function, when a renal biopsy will determine if treatment is necessary. All children with renal involvement are followed for a year to detect those with persisting urinary abnormalities (5–10%), who require long-term follow-up. This is necessary as hypertension and declining renal function may develop after an interval of several years.

Haemolytic uraemic syndrome

Haemolytic uraemic syndrome (HUS) is a triad of acute renal failure, microangiopathic haemolytic anaemia and thrombocytopenia. Typical HUS is secondary to gastrointestinal infection with verocytotoxin-producing E. coli O157:H7, acquired through contact with farm animals or eating uncooked beef, or, less often, Shigella. It follows a prodrome of bloody diarrhoea. The toxin from these organisms enters the gastrointestinal mucosa and preferentially localises to the endothelial cells of the kidney where it causes intravascular thrombogenesis. Coagulation cascade is activated and clotting is normal (unlike in disseminated intravascular coagulation, DIC). Platelets are consumed in this process and microangiopathic haemolytic anemia results from damage to red blood cells as they circulate through the microcirculation, which is occluded. Other organs such as the brain, pancreas and heart may also be involved.

With early supportive therapy, including dialysis, the typical diarrhoea-associated HUS usually has a good prognosis, although follow-up is necessary as there may be persistent proteinuria and the development of hypertension and declining renal function in subsequent years. In contrast, atypical HUS has no diarrhoeal prodrome, may be familial and frequently relapses. It has a high risk of hypertension and chronic renal failure and has a high mortality. Children with intracerebral involvement or with atypical HUS may be treated with plasma exchange or plasma infusions, but their efficacy is unproven.

Dialysis and transplantation

It is now possible for all children to enter renal replacement therapy programmes when end-stage renal failure is reached. The optimum management is by renal transplantation. Technically, this is difficult in very small children and a minimum weight, e.g. 10 kg, needs to be reached before transplantation to avoid renal vein thrombosis. Kidneys obtained from living related donors have a higher success rate than deceased donor kidneys, which are matched as far as possible to the recipient’s HLA type. Patient survival is high and first-year graft survival is around 97% for living related and 93% for deceased kidneys in the UK. Graft losses from both acute and chronic rejection or recurrent disease mean that the 5-year graft survival is reduced to 91% for living related kidneys and 79% for deceased donor kidney transplants and some children need re-transplantation. Current immunosuppression is mainly with combinations of prednisolone, tacrolimus and azathioprine or mycophenolate mofetil.

Ideally, a child is transplanted before dialysis is required, but if this is not possible, a period of dialysis may be necessary. Peritoneal dialysis, either by cycling overnight using a machine (continuous cycling peritoneal dialysis) or by manual exchanges over 24 h (continuous ambulatory peritoneal dialysis), can be done by the parents at home and is therefore less disruptive to family life and the child’s schooling. Haemodialysis is an alternative and is usually done in hospital 3–4 times a week.