1 Introduction

In many European countries, obstetric ultrasound (US) is performed routinely during normal pregnancies. This leads to the discovery of many fetal anomalies, and, among them, uro-nephropathies represent one of the largest groups amenable to neonatal management. They are now included in the so-called CAKUT [congenital anomalies of the kidney and urinary tract] group (Renkema et al. 2011; Wiesel et al 2005; Ek et al. 2007).

Changes have occurred in the neonatal management since nowadays these uropathies are detected in mostly asymptomatic patients, and the treatment is mainly preventive. Antenatal detection and postnatal follow-up have yielded new data on the natural history of many uropathies and have shown that a majority of antenatally diagnosed renal dilatations will resolve spontaneously (Barbosa et al. 2012; Ek et al. 2007; Kumar et al. 2012; Quirino et al. 2012; Wollenberg et al. 2005).

The aims of the postnatal work-up will be first to confirm the anomaly, to ascertain the diagnosis (and the prognosis), then to adapt the follow-up to the type of anomaly, and finally to decide on the best treatment (see also chapter “Congenital Urinary Tract Dilatation and Obstructive Uropathy”). The rationale of all the imaging is clearly to prevent further complications on an already damaged kidney (Ismaïli et al. 2004, 2005).

2 Postnatal Work-Up

The ideal postnatal work-up is still debated but it has been markedly standardized. At first the antenatal US findings were standardized (Table 1) differentiating minimal and moderate dilatation from marked dilatation in order to define the proper postnatal management. Secondly the postnatal management has been also standardized depending on the antenatal and postnatal findings (Tables 2a and 2b). All proposed managements are based on the US findings (Riccabona et al. 2008, 2009).

Table 1 Sonographic classification of fetal pelvi-calyceal dilatation (Riccabona et al. 2008, updated 2017)
Full size table
Table 2 (a) Mild to moderate) and (b) (severe dilatation). Proposed neonatal work-up of fetal uropathies. (a) Postnatal imaging algorithm in mild or moderate fetal UTD (Riccabona et al. 2008). (b) Postnatal imaging algorithm in severe fetal UTD (Riccabona et al. 2009)
Full size table

An American consensus panel has recently proposed a further classification and standardization: the UTD (urinary tract dilatation) classification system aimed to describe simultaneously both antenatally and postnatally US findings. It is based on six US findings, anterior-posterior (AP) axial renal pelvic dilatation, calyceal dilatation, renal parenchymal thickness, parenchymal appearance, bladder and ureteral anomalies, as well as the amniotic fluid volume. The system distinguishes whether the findings are antenatal (A) or postnatal (P) followed by a number. UTD A1 represents mild antenatal UTD and UTD P3 marked postnatal dilatation (Nguyen et al. 2014). The examination is intended to confirm the anomaly, differentiate between uro- and nephropathies (knowing that both can be associated), and determine the need for further imaging. Voiding cystourethrography (VCUG) looking for vesicoureteric reflux (VUR) and functional studies (scintigraphy, MRI) will be used afterward as required (Ismaili et al. 2006; Riccabona et al. 2008, 2009; Nguyen et al. 2014).

2.1 Clinical Situations and Antenatal Diagnoses Necessitating a Rapid Management

After birth, severe bilateral renal diseases (renal hypoplasia, posterior urethral valves, polycystic kidney diseases, etc.) can be associated with pneumothorax, lung hypoplasia, and life-threatening respiratory distress (Fig. 1). A respiratory assistance is mandatory even before considering any treatment for the urinary tract anomaly. Conversely, whenever a neonate presents massive – seemingly – spontaneous pneumothorax, an US examination should be performed in order to verify the status of the urinary tract.

Fig. 1
figure 1

Right pneumothorax and bilateral lung hypoplasia in a neonate with recessive-type polycystic kidney disease

Full size image

Several other conditions could necessitate early management and workup in the immediate neonatal period. In posterior urethral valves (Fig. 2), the rapid placement of a bladder catheter (suprapubic or urethral) will help to decrease the high bladder pressure, before valve resection. An ectopic ureterocele associated with an obstructed upper pole of a duplex kidney is prone to prolapse into the urethra during micturition and to provoke acute bladder outlet obstruction (Fig. 3). Cystoscopic unroofing the ureterocele is therefore advocated as the first step in managing this type of duplex kidneys (Uphadhyay et al. 2002; Van Savage and Mesrobian 1995; Hagg et al. 2000) (Fig. 4). Markedly dilated urinary tract (giant pelvi-ureteric junction obstruction) may cause uncomfortable enlargement of the baby’s abdomen and interfere with normal bowel transit, and then early nephrostomy or nephrectomy may become indicated (Fig. 5) (Shimada et al. 2007). Once all necessary therapeutic measures are taken, the work-up can restart more classically.

Fig. 2
figure 2

Posterior urethral valves. (a) US of the bladder – sagittal scan of the bladder displaying a marked thickened well. (b) Left kidney – sagittal scan – dilated pyelocalyceal system and perirenal – urinoma (between the crosses). (c) VCU, micturition phase; typical appearance of PUV

Full size image
Fig. 3
figure 3

Ureterocele prolapse

Full size image
Fig. 4
figure 4

Neonatal puncture of ureterocele. (a) Sagittal scan of the right kidney demonstrating dilatation of the upper pole. (b) Transverse scan of the bladder demonstrating a large ureterocele (limited by the crosses). (c)Transverse scan of the bladder after unroofing of the ureterocele. (d) Sagittal scan of the kidney, the dilatation has resolved

Full size image
Fig. 5
figure 5

Giant PUJO. (a) Plain film of the abdomen: the bowel is displaced to the right by the distended kidney. (b) US: marked dilatation of the left kidney; the limits are hard to define; there is no parenchyma visible. (c) US after nephrostomy, the renal parenchyma can now be identified. (d) Opacification of the pyelocalyceal system (it corresponded to the left part of a horseshoe kidney) confirming a UPJ obstruction

Full size image

2.2 Postnatal Work-Up of Uropathies

As mentioned, the aims of postnatal work-up are to ascertain the diagnosis of the uropathy, determine the degree of “obstruction” and/or renal function impairment, as well as the presence of VUR.

For all uropathies, the workup has been markedly standardized. Nowadays, the major workload of an imaging department dealing with neonatal pathology is related to the management of antenatally diagnosed urinary tract dilatation and its significance. Noteworthy, the extensive neonatal workup performed in recent years by many teams has increased mainly the detection of neonatal VUR, with questionable impact on management in quite a few of these infants (Van Eeide et al. 2007; Ismaïli et al. 2006).

Two work-up approaches have been proposed. For some authors, whatever the result of a neonatal US, a VCUG should be performed in case of any antenatal urinary tract dilatation. For them, US is a poor predictor of VUR (Tibballs and De Bruyn 1996; Walsh and Dubbins 1996). For others, a VCUG should not be performed in all neonates; there will be too many unnecessary negative VCUGs. A VCUG should be performed only in those patients in whom the anomaly has been confirmed after birth (Yerkes et al. 1999). We favor the second approach and recommend a decision tree based on the neonatal and follow-up US findings (Riccabona et al. 2008, 2009) (Tables 2a and 2b). Hence, US is performed first in order to confirm the anomaly (Fig. 6) (Marra et al. 1994; Avni et al. 1997; Hulbert et al. 1992). In any urgent situation and in all cases where the dilatation is known to be marked, it can be performed as soon as the clinical condition permits. For all other cases, it should be delayed to the post physiological dehydration period, namely, after the fifth day of life. At that time, the US examination should be as detailed as possible in order to detect every anomaly that would justify continuing the work-up (Table 3). The presence of a urinary tract dilatation is the most important landmark; seven mm is the most widely accepted upper limit of normal (some prefer 5 mm, others 10 mm or even 12 mm) in the second and third trimester, respectively. Higher degrees of dilatation are associated with higher probability of a significant uropathy. Still, dilatation of the renal pelvis is not the only anomaly that should be looked for. Other US features can be associated with VUR or “obstruction” (Table 2b). One should not forget to examine the bladder; a large bladder with a thickened and trabeculated wall could be a sign of VUR (Fig. 7). With a meticulous US examination, one should be able to detect indirect signs for VUR in over 85 % of cases. Those VURs that are missed are non-dilating or grade I–II VURs with less clinical significance (Nguyen et al. 2014; Pates and Dashe 2006; Weinberg and Yeung 1998; Ismaïli et al. 2004; Bouzada et al. 2004). Finally, particularly in baby boys, the comprehensive US study should include a perineal scan of the urethra during voiding – particularly if indirect signs suggest a possible posterior urethral valve.

Fig. 6
figure 6

Ante- and postnatal diagnosis of PUJ obstruction. (a) Transverse scan of a fetal abdomen (third trimester). The left pyelocalyceal system is dilated (20 mm between crosses). (b, c) Postnatal US ((b) transverse scan and (c) sagittal scan) confirming the dilatation

Full size image
Fig. 7
figure 7

Neonatal VUR (antenatal diagnosis of a megabladder). (a) Sagittal scan of the bladder appearing markedly enlarged. (b) Sagittal scan of the right kidney that appears slightly dilated (between crosses). (c) Sagittal scan of the left kidney that appears markedly dilated (between crosses). (d) VCUG demonstrating bilateral grade IV VUR

Full size image
Table 3 US findings that may be associated with VUR
Full size table

If the initial US examination is entirely normal, it seems reasonable to perform follow-up examinations at 1 or 3 months in order to detect cases that would have escaped the neonatal screening (Riccabona et al. 2008, 2009) (Tables 2a and 2b).

In case of an abnormal US, a VCUG (or ce.-VUS) should be performed, preferably during the first weeks of life. The examination may be performed under prophylactic antibiotic therapy. The aim of the examination is to detect VUR and bladder or urethral anomalies.

If high-grade VUR is demonstrated, the patient is followed up clinically hoping that the VUR will resolve spontaneously. During this period of time, renal growth can be monitored every 3–6 months using US. The persistence of VUR should be verified if infections occur or in the absence of renal growth (Kousidis et al. 2008).

If no VUR is present, marked dilatation can be associated with urinary drainage impairment (possibly obstruction) at the level of the pelvi-ureteric junction, the ureterovesical junction, or below the bladder outlet. US will help to determine the level of obstruction. In some centers, the work-up will be completed by functional studies, including a furosemide nephrogram – especially in cases with severe dilatation (Morris et al. 2009) (see below).

2.3 Further Anatomical Assessment

If drainage impairment seems important and surgery may become indicated, the exact anatomy of the urinary tract must be assessed. Intravenous urography is no longer performed and MR urography is the best technique available to evaluate the anatomy of the urinary tract (Fig. 8). It will assess most precisely the anatomy of the dilated urinary tract (Avni et al. 2000; Darge et al. 2013). Furosemide is usually injected in order to increase diuresis and thus to optimize visualization of the entire collecting and draining system. T2 sequences, inversion recovery sequences, and post-gadolinium enhancement 3D-T1 sequences allow a good evaluation of the entire urinary tract (see chapter “MR of the Urogenital Tract in Children”). The only drawback of the method is that it may require sedation and that it is not widely available.

Fig. 8
figure 8

Neonatal MR urography of a left megaureter (T2w sequence)

Full size image

In case of a duplex collecting system, the work-up is similar to that for obstruction, except that the morphological assessment must be more rapid since an early therapeutic maneuver may become necessary. Again US, VCUG/ce-VUS, and MR urography will optimally evaluate the exact morphology (Fig. 9). MR urography demonstrates accurately the extravesical insertion of an ectopic ureter (Avni et al. 2000; Adeb et al. 2013). An isotope study, using preferably Tc99m MAG 3 or Tc99m ECD, is also mandatory in order to evaluate the remaining function of the two moieties (Piepsz and Ham 2006; Adeb et al. 2013) (see below, and chapter “Nuclear Medicine”).

Fig. 9
figure 9

(a, b) MR imaging in complicated duplex kidney. (a)Left duplex with obstructed upper pole and ectopic infravesical insertion of the dilated ureter (arrow). (b) Left duplex with obstructed upper pole and ectopic ureterocele (arrow)

Full size image

2.4 Functional Assessment: Nuclear Medicine Studies

Radionuclide renogram may be performed starting at 4–6 weeks – ideally around 3–6 months – but in cases of severe dilatation, it may be performed as early as 3–4 days of age (Piepsz et al. 2009; Ismaili and Piepsz 2013). In very young infants, in case of impaired overall GFR or in case of important renal pelvic dilatation, the determination of the differential renal function (DRF) has a poor accuracy (Piepsz et al. 2009). In such situations, the aim will essentially be to roughly estimate the function and drainage impairment of the affected kidney (Piepsz et al. 2011) (Fig. 10). Tubular tracers (Tc99m MAG 3 or Tc99m ECD) are currently recommended, especially in young patients, because their high extraction rate allows accurate quantification of the renogram (Ismaili and Piepsz 2013; Piepsz et al. 2009; Gordon et al. 2001, 2011) (Fig. 10). The same radiopharmaceutical should be used for the follow-up studies (Piepsz et al. 2009). The radiation dose delivered is low, between 0.2 and 0.4 mSv (Stabin et al. 1992; Smith and Gordon 1998; Ismaili 2013). Determining DRF in infants is less precise than in older children; DRF are evaluated from the early phase of the renogram. Normal values are between 45 and 55 % (Gordon et al. 2011; Prigent et al. 1999; Eskild-Jensen et al. 2004). Drainage stimulation, using furosemide, is the procedure of choice to obtain information about renal drainage. Furosemide (1 mg/kg body weight, up to 20 mg) is often injected simultaneously with the radiopharmaceutical agent (“F0 protocol”), reducing the duration of the examination and the number of venous punctures (Piepsz et al. 2011); however, it needs sufficient renal maturity and functional capacity to be effective, as well as sufficient/physiological hydration for the study. A full bladder at the end of the renogram may result in a poor drainage; therefore, post-micturition images obtained in an erect position if possible are mandatory (Gordon et al. 2011; Piepsz et al. 2009, 2011; Ismaili and Piepsz 2013). The evaluation of renal drainage is essentially based upon output efficiency (OE) and normalized residual activity (NORA); these quantitative parameters do not depend on the level of the renal function. They are calculated at the end of the dynamic part of the renogram and on the late post-micturition post-erect images. Normal and abnormal values have been determined (Piepsz et al. 2002; Nogarède et al. 2010).

Fig. 10
figure 10

1 “F0” diuretic renogram (Tc99m-MAG3) of a 1-day-old boy. Antenatal diagnosis of bilateral hydronephrosis. (a) Important background activity related to low function (immaturity). Low right kidney DRF; severe impairment of right kidney drainage without emptying after micturition. Delayed cortical transit time. Impaired drainage of the left kidney with partial emptying after micturition. (b)Same child after right pyeloplasty at age 2 weeks: Low background activity (functional maturation). Normal DRF values. Normal drainage and complete renal emptying after micturition

Full size image

Evaluating the prognosis of these patients on the basis of the analysis of the DRF and drainage remains a challenge and is still controversial (Piepsz et al. 2009; Piepsz 2009; Gordon et al. 2011; Ismaili and Piepsz 2013). Normal drainage strongly suggests the absence of risk for functional deterioration (Piepsz 2009), but impaired drainage does not allow predicting the outcome if a conservative approach is chosen. Several recent studies strongly suggest the importance of the visual analysis of the cortical transit time of the tracer as a prognostic factor (Schlotmann et al. 2009; Piepsz 2011; Duong et al. 2013): severely delayed cortical transit time is associated with a high rate of improvement after surgery (Fig. 10). It also predicts functional deterioration in the absence of surgical treatment. However, a normal cortical transit does not exclude the risk of DRF deterioration.

2.5 The Postnatal Work-Up of Nephropathies

The group of nephropathies with antenatal diagnosis encompasses a large spectrum of diseases with variable degree of renal functional impairment. The largest group includes renal cystic diseases (see chapters “Renal Agenesis, Dysplasia, Hypoplasia and Cystic Diseases of the Kidney” and “Imaging in Renal Agenesis, Dysplasia, Hypoplasia and Cystic Diseases of the Kidney”). The renal involvement will be confirmed by postnatal US. The presence of small cysts is sometimes easier to detect after birth than in utero, and this will help to precise the diagnosis (Fig. 11). US will also be helpful to detect associated malformations especially those occurring in the genital tract, the liver, and the pancreas. The rest of the work-up will mainly be focused on clinical, biological, and genetic data that must be evaluated in order to characterize the diseases or syndromes (Avni et al 2006, 2012). US will be used during childhood in order to follow the renal growth and eventually changing US patterns with time (Fig. 12.).

Fig. 11
figure 11

Case of HNF1β mutation (hyperechoic kidneys in utero) sagittal scan of the right kidney. It appears hyperechoic with small subcortical cysts that were not seen in utero

Full size image
Fig. 12
figure 12

Spontaneous involution of a multicystic dysplastic kidney. (a)In utero at 34 weeks, transverse scan of the fetal abdomen. Typical right multicystic kidney (M); Sp, spine. (b) At birth transverse scan of the right kidney: same appearance of the mass (M) as in utero. (c) At the age of 2 years, sagittal scan of the right kidney: only one small cyst remains (between the crosses)

Full size image

For multicystic dysplastic kidney, renal ectopia, or unilateral agenesis, the work-up should also include US and a VCUG, if US is abnormal (see above) in order to detect ipsi- or contralateral VUR. Again, high-grade VURs might require prophylactic antibiotic therapy (Atiyeh et al. 1993; Flack and Bellinger 1993; Selzman and Elder 1995; Ismaïli et al 2005). Also of interest is to search for associated genital anomalies on pelvic US (Tables 2a and 2b).

Take away

The postnatal work-up of urinary tract anomalies has now been standardized, US being the cornerstone. Depending on the result, VCUG (or ce-VUS), MRI, and/or isotopes will be performed in order to clarify the diagnosis and choose the proper treatment.

3 Long-Term Follow-Up and (Potential Treatment) in the Light of the Natural History of Uro-nephropathies

As mentioned above, antenatal diagnosis has led to dramatic changes in the management of uropathies. First, nowadays, most patients are asymptomatic; second, the medical follow-up of many pathologies confirms their potential to resolve spontaneously. Consequently, surgery has been less and less advocated. The main goal of the prophylactic treatment (if applied) is to prevent further renal damage during the period when spontaneous resolution is expected. It should be noted that infection does occur in some cases despite the prophylactic antibiotic therapy; these cases make alternative treatment necessary (Jaswon et al. 1999; Ismaïli et al. 2006; Lee et al. 2006).

3.1 Vesicoureteric Reflux

Many series have shown that two-thirds of neonatal VURs (mainly grades I-III) are likely to resolve or at least to improve during an observation period of 2 years (Fig. 13). Therefore, once the anomaly is detected, the patient is given prophylactic antibiotic therapy (in cases of high-grade VUR) and followed clinically or by imaging as described above. In some circumstances, another therapeutic approach (surgery or endoscopic injection of bulging agents) should be proposed: in the case of breakthrough infection despite therapy, if there is failure to thrive, or if continuing the treatment is problematic for the family (Herndon et al. 1999; Burge et al. 1992; Bouachrine et al. 1996; Assael et al. 1998; Ismaïli et al. 2006; Van Eeide et al. 2007) (see chapters “UTI and VUR” and “Vesicoureteric Reflux”).

Fig. 13
figure 13

Spontaneous resolution of VUR. (a) At birth, bilateral grade IV VUR. (b) At age 10 month, no VUR anymore

Full size image

3.2 Pelvi-ureteric Junction (PUJ) Obstruction

The therapeutic management of PUJ obstruction has been even more controversial than for VUR. Advocates and opponents of neonatal surgery have published large amounts of scientific material that shows opposite or contradictory results. For some, early surgery is safe and improves renal function notably. For others, the PUJ obstruction has been present for a long time, and there is only a faint chance of improving the condition by surgery, especially since the dilatation itself may resolve spontaneously (Fig. 14). Others suggest operating only those patients who would show functional deterioration. Finally, some suggest following renal growth on US and operating when the contralateral kidney displays compensatory growth.

Fig. 14
figure 14

Partial resolution of left UPJ obstruction. Transverse scan of the left kidney. (a) At birth, dilated pyelocalyceal system. Renal pelvis measures 27 mm. (b) At age 6 months, the renal pelvic dilatation has diminished to 7 mm

Full size image

On the basis of all the data accumulated, conservative management seems the most adequate in mild or moderate cases. Clinical status, renal anomalies, and renal function must be monitored closely. Regular US examinations should be performed (every 6 months, during the first 2 years; every year later – possibly with standardized and comparable hydration). In most cases, the dilatation will be stable or even resolve. Surgery must be proposed if clinical symptoms appear or if renal function and/or cortical transit deteriorate. In rare and severe cases, spontaneous resolution is less likely to occur and symptoms related to abdominal discomfort are more frequent. For such patients, surgery may be beneficial even without other signs of deterioration (Docimo and Silver 1997; Duckett 1993; Capolicchio et al. 1999; McAleer and Kaplan 1999; Chertin et al 1999; Salem et al. 1995; Thorup et al. 2003).

3.3 Ureterovesical Junction (UVJ) Obstruction

Like VUR, UVJ obstruction has shown great potential for spontaneous resolution, probably because of the maturation of the UVJ (Fig. 15). Therefore, after completion of the initial work-up, a prophylactic antibiotic therapy should be started and the urinary tract monitored by US (possibly with standardized and comparable hydration and bladder filling) and eventually functional isotope studies (or fMRU). US may underestimate the drainage impairment, especially since the renal pelvis may not be dilated. Therefore, before confirming complete resolution or before surgery particularly in a more complex anatomy, morphological assessment of the urinary tract may be necessary – best achieved by MR urography (Baskin et al. 1994; Liu et al. 1994; Shukla et al. 2005).

Fig. 15
figure 15

Resolution of left megaureter, sagittal scan of the bladder. (a) At birth, the dilated left ureter measures 14 mm diameter. (b) At age 1 year, the ureter measures 7 mm

Full size image

3.4 Multicystic Dysplastic Kidney (MCDK)

Once the diagnosis of a MCDK appears highly probable (on the basis of the neonatal US examination and on the lack of function demonstrated by nuclear medicine studies or MRI), a clinical and imaging (US) follow-up is the most widely accepted approach. In two-thirds of cases, a MCDK diagnosed in utero will involute spontaneously within the first 2 years of life; the involution may already start in utero (Fig. 12). Complications are very unusual. Only very large MCDKs causing abdominal discomfort and without resolution on follow-up examinations will require surgical removal (Hrair-Georges et al. 1993; Rabelo et al. 2006; Aslam and Watson 2006).

3.5 Complicated Duplex Kidneys

In case of complicated duplex collecting systems, one of the aims of imaging will be to differentiate between an ectopic ureteral insertion and an ectopic ureterocele. An extravesical ectopic ureter insertion with a functional upper renal pole will lead to the reimplantation of the ureter (with or without modeling) in the bladder or its anastomosis into the lower renal pole ureter. A nonfunctioning upper pole with an extravesical ectopic ureter will bring us to an upper pole heminephrectomy and ureterectomy by lomboscopy in case of significant renal pelvis dilatation or infection. An extravesical or an obstructive ureterocele will be punctured or unroofed by cystoscopy before the child is discharged from the maternity hospital (Fig. 4). In case of a pyelonephritis, depending of the renal moieties function and/or if there is a VUR, an upper or lower heminephrectomy with ureterectomy will be proposed or the removal of the ureterocele and the reimplantation of both ureters (Uphadhyay et al. 2002; Husman et al. 1999; Blyth et al. 1993).

3.6 Nephropathies

Congenital nephropathies will be managed individually; the work-up and follow-up are tailored case-by-case and will depend upon the clinical presentation. Some patients will have signs of renal failure directly at birth, while for others the renal failure will develop progressively later in childhood or even only during adult life. Some patients will display only renal symptoms; for others, other organs and systems may be involved (the brain, pancreas, liver, etc.). For the latter, complementary examinations will be necessary (MRI, CT, etc.).

In most cases, US will be sufficient for the follow-up (Fig. 16). Still, imaging will have to be adapted to the type and degree of the anomaly (Avni et al. 2006, 2012).

Fig. 16
figure 16

Evolution of ADPKD.US of the right kidney. (a) At birth. (b) At age 5 years, first cysts are visible

Full size image

Take away

US is the main imaging technique that will be used for diagnosis and the follow-up of all uro-nephropathies. Depending on clinical and biological data, the management will be adapted. If necessary, MRI and isotopes will be used to provide anatomical and functional information.

Conclusions

US is the cornerstone of the work-up of congenital uropathies at birth and during follow-up. The use of other techniques will depend on the US findings at birth. MR imaging and isotopes will help to determine the anatomy and the function of the urinary tract. Apart from acute conditions requiring immediate treatment, the therapeutic approach to congenital uropathies is less and less surgical. Prophylactic antibiotic therapy may be initiated at birth in severely dilated cases.