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The Relationships Between Renal Compensatory Hypertrophy Etiologic Factors and Anthropometric Development in the Pediatric Age Group
Pediatric Urology The Relationships Between Renal Compensatory Hypertrophy Etiologic Factors and Anthropometric Development in the Pediatric Age Group €rkmen, Handan C¸akmakcı, and Demet Alaygut, Alper Soylu, Belde Kasap, Mehmet Tu Salih Kavukcu OBJECTIVE METHODS
RESULTS
CONCLUSION
To evaluate the factors associated with compensatory hypertrophy in the functional kidneys of children. The medical files of patients with a solitary functional kidney were reviewed retrospectively. Data regarding anthropometric measurements, functional renal length, functional renal length of standard deviation score (SDS) of functional kidney at diagnosis, and end of follow-up were obtained. Patients were divided into 2 groups, those with a unilateral kidney function of <10% (hypoplasia, dysplasia, and atrophy, group 1) and those with a solitary kidney (agenesis, and multicystic dysplastic kidney, group 2). A total of 126 patients (70 boys) were evaluated. Both the sizes of the functional kidney and functional kidney SDS values at diagnosis were greater in group 1 relative to group 2. At the end of the follow-up period, anthropometric values including functional kidney size were higher in group 2. Functional kidney size of 2 SDS above the normal was mostly predictive at age 17.5 months (odds ratio [OR] 5.06) and at a body height of 82 cm (OR 5.57). The most determining factors for renal length SDS values were age and height. Solitary kidneys complete compensatory hypertrophy by 17.5 months of age, and after that their growth continues in parallel to normal growth. UROLOGY 82: 442e447, 2013. 2013 Elsevier Inc.
I
n childhood, solitary functional kidney can develop secondary to congenital and acquired causes. Under normal conditions, absence of 1 kidney results in adaptive compensatory hypertrophy of the contralateral healthy kidney.1 As reported in the literature, this kind of hypertrophy can be seen in all age groups from intrauterine life to adulthood.2 Among congenital causes of a solitary functional kidney, there are unilateral renal agenesis (URA) and multicystic dysplastic kidney (MCDK); and the unilateral renal dysfunction/nephrectomy secondary to various etiological factors (tumor, trauma, urinary tract infection, and thrombosis) can be included among acquired types.3 Urogenital or other system abnormalities can accompany unilateral renal agenesis and MCDK. Demonstration of
Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Pediatric Nephrology, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey; and Department of Radiology, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey Reprint requests: Demet Alaygut, M.D., Dokuz Eylul University, Department of Pediatric Nephrology, 35340 Inciralti, Izmir, Turkey. E-mail: demetalaygut@yahoo. com Submitted: January 6, 2013, accepted (with revisions): March 12, 2013
442
ª 2013 Elsevier Inc. All Rights Reserved
the nondysplastic nature of the functional kidney is especially important.4 Many studies have evaluated vertical length of the kidney in healthy children using ultrasonographic techniques and compared its relationship with anthropometric measurements. These studies have demonstrated that vertical length of the kidneys increases in direct proportion with increasing age and body surface area (BSA) of the children.5,6 The purpose of this study was to assess the degree of compensatory renal hypertrophy in single functional kidneys and the effect of anthropometric development on compensatory hypertrophy.
MATERIAL AND METHODS Medical files of patients with solitary or unilateral nonfunctional (unilateral renal agenesis, unilateral multicystic dysplastic) kidneys and with hypofunctional (<10%) atrophic kidneys who were followed-up in Dokuz Eylul University Faculty of Medicine, Department of Pediatric Nephrology, were retrospectively examined. Anthropometric data, serum biochemical parameters such as urinalysis, and urinary protein, and imaging techniques such as urinary system ultrasound, voiding cystourethrography, and 99mTc-dimercaptosuccinic acid static renal scintigraphy findings were evaluated. The patients were divided into 2 0090-4295/13/$36.00 http://dx.doi.org/10.1016/j.urology.2013.03.024
groups, those with single atrophic kidneys (group 1) and those with solitary (agenesis/MCDK) kidneys (group 2). The following parameters were recorded: age, gender, diagnosis, followup period, body weight (BW), BW standard deviation score (BW SDS), patient height, height SDS, BSA, body mass index (BMI), BMI SDS, functional renal length, functional renal length SDS, creatinine level, creatinine clearance, anomalies in the functional kidney, vesicoureteral reflux (VUR) involving the functional kidney, scar(s) in the functional kidney, hypertension, and proteinuria at the end of both diagnostic workup and follow-up period. SPSS 15.0 software package was used to conduct statistical analysis. Age at diagnosis, follow-up period, BW at admission, BW SDS, BMI, BMI SDS, BSA, functional renal length, and renal length SDS values were compared between groups 1 and 2. At the end of the follow-up period, both groups were compared in terms of the same anthropometric variables. While performing these comparisons, t test or Mann-Whitney U test was used based on the number of cases. Factors affecting functional kidney length and its SDS value were assessed using the Pearson correlation analysis. In the comparison of categorical variables, the chi-square test was used. Statistical significance was accepted as P <.05.
RESULTS Data of all 141 patients with solitary functional kidneys were accessed. Fifteen patients whose renal dimensions were not evaluated ultrasonographically were excluded from the study. Population of the study (126 patients) was composed of 70 male (55.6%) and 56 female patients (44.4%). Average age at diagnosis was 47.8 58.3 months (range 1-212 months) and mean follow-up period was 28.0 32.4 months (range 1-191 months). Patients were assessed according to their primary diagnoses, which included atrophic kidney (n ¼ 32, 25.7%), MCDK (n ¼ 49, 38.9%), and agenesis (n ¼ 45, 35.7%). In group 1, 32 patients with solitary atrophic kidneys (function loss >90%) had a male/female ratio of 19/13 (59%/41%). Their average age at diagnosis (83.7 61.2, range 1-212 months, median 83.7 months) and mean follow-up period (35.3 43.2, range 1-191, and median 27 months) were calculated. In group 2, 94 patients with solitary kidneys had a male/female ratio of 51/43 (54%/46%) with an average age of 35.5 52.2 months (range 1-204, median 7.5 months) and mean follow-up period of 25.6 27.9 months (range 1-152, median 18 months). Although there was a significant difference between group 1 and group 2 in terms of age at diagnosis (P <.001), their follow-up periods did not show a difference. There was no difference between group 1 and group 2 in terms of male/female ratio (P ¼ .615). Comparison of the anthropometric parameters of both groups indicated that patients in group 1 had higher ages at the time of diagnosis. Accordingly, patients in group 1 had relatively increasing BW, height, BSA, and BMI compared to patients in group 2. However, no difference was found between the 2 groups in terms of BW SDS, height SDS, and BMI SDS. Patients in group 1 had higher functional kidney size and functional kidney size SDS values compared to patients in group 2 (Table 1). UROLOGY 82 (2), 2013
At the end of the follow-up period, no gender predominance was observed between 21 patients in group 1 (M/F: 14/7) and 74 patients in group 2 (M/F: 43/31) whose functional kidney lengths were measured at the end of the follow-up period (P ¼ .480). Comparing anthropometric parameters in the patients of group 1; average age, BW, height, and BSA were relatively higher, however, difference between the groups in terms of mean BMI values was not statistically significant. Nevertheless, BW SDS, height SDS, and BMI SDS values did not show any difference between the groups. Similarly, mean functional kidney length in group 1 was higher compared to group 2, without any intergroup difference in terms of kidney length SDS values (Table 1). Both groups were also compared with respect to serum creatinine levels, creatinine clearance estimates based on Schwartz formula, and spot urine protein/creatinine ratio (mg/mg) as measured at the time of the diagnosis and at the end of the follow-up period, and as a result of this comparison, higher serum creatinine levels were observed in group 1. In none of the cases were the serum creatinine levels within the normal limits according to the variable of age.7 As a result of examining the distribution of anomalies associated with functional kidney, there was no intergroup difference except for VUR. In group 1, VUR was more frequently detected in the functional kidney (P ¼ .020). In both patient groups, 13 patients (10.3%) had VUR. Any difference was not determined in kidney length and kidney length SDS values estimated at the time of diagnosis or at the end of the follow-up period between patients with or without VUR in their functional kidneys. The patients were also evaluated in terms of the presence of scar tissue in the functional kidney, and the number of patients with scar tissue in their functional kidneys was greater in group 1. Functional kidney length and kidney length SDS values in patients with or without scar tissues as estimated at the time of the diagnosis and during the last follow-up visit were also compared. Dimercaptosuccinic acid scanning determined no presence of scar tissue on kidney length. In both groups, changes in functional kidney length and kidney length SDS values detected at the time of diagnosis and at the end of the follow-up period were evaluated in line with anthropometric data (Tables 2 and 3). In both patient groups, linear regression analysis was used to find the most determinative anthropometric variables among those correlated with functional kidney length SDS values estimated at the time of diagnosis. Only age (months) (P ¼ .006) and body height (P <.001) were significant determinative factors. It is thought that compensatory hypertrophy develops when kidney length increases 2 SD (>95. percentile) above its normal length known for age and height. Based on this assertion, we wanted to determine at what age and body height the kidney lengths of the patients increased 2 SD above the normal values (ie, compensatory hypertrophy occurs at which age and body height). The 443
Table 1. Intergroup comparisons of anthropometric data recorded at the time of diagnosis and at the end of the follow-up period At the Time of Diagnosis Parameters
Group 1
BW (kg) BW SDS Height (cm) Height SDS BSA (m2) BMI (kg/m2) BMI SDS Functional kidney length (mm) (mean SD)
27 0.2 117 0.1 0.92 17.5 0.45 91.0
Median
16.8 1.7 34.5 2.0 0.41 2.8 1.2 22.1
13.5 0.24 81.4 0.13 0.53 15.8 0.12 71.5
93.5
Functional kidney length SDS (mean SD)
15.1 1.9 34.8 2.0 0.39 4.06 1.3 22.3
Group 1
<.001 .247 <.001 .574 <.001 .031 .130 <.001
30.6 0.23 127.2 0.19 1.01 17.3 0.36 100.3
65.0
2.6 2.6
Median
At the Last Follow-up Visit P Value
Group 2
16.7 1.73 34.0 1.8 0.4 2.4 1.5 21.3
108
1.6 2.0
2.4
3.2 3.4
.030
1.3
2.1
Group 2 20.1 0.48 101.8 0.44 0.74 17.0 0.07 87.1
P Value
16.3 1.5 31.8 1.8 0.38 3.9 1.9 21.4
.006 .675 .005 .602 .006 .076 .436 .016
85 3.1 3.1
.939
2.8
BMI, body mass index; BSA, body surface area; BW, body weight; SDS, standard deviation score. The figures in boldface are statistically significant (P <.05).
Table 2. Group 1 comparison of functional kidney length, and functional kidney length SDS values with anthropometric data recorded at the time of diagnosis and at the end of the follow-up period Functional Kidney Length At the Time of Diagnosis
Functional Kidney Length SDS Value
At the End of the Follow-up Period
At the Time of Diagnosis
At the End of the Follow-up Period
Parameters
r
P Value
r
P Value
r
P Value
r
P Value
Age BW (kg) BW SDS Height (cm) Height SDS BSA (m2) BMI (kg/m2) BMI SDS
0.703 0.837 0.275 0.840 0.116 0.861 0.635 0.109
<.001 <.001 .141 <.001 .540 <.001 <.001 .638
0.715 0.780 0.063 0.801 0.120 0.800 0.338 0.277
<.001 <.001 .785 <.001 .606 <.001 .134 .281
0.041 0.184 0.415 0.164 0.233 0.204 0.398 0.346
.823 .314 .022 .369 .214 .262 .024 .124
0.101 0.037 0.319 0.005 0.212 0.044 0.196 0.496
.663 .874 .158 .984 .357 .849 .395 .043
Abbreviations as in Table 1. The figures in boldface are statistically significant (P <.05).
Table 3. Group 2 comparison of functional kidney length and functional kidney length SDS values with anthropometric data recorded at the time of diagnosis and at the end of the follow-up period Functional Kidney Length At the Time of Diagnosis
Functional Kidney Length SDS Value
At the End of the Follow-up Period
At the Time of Diagnosis
At the End of the Follow-up Period
Parameters
r
P Value
r
P Value
r
P Value
r
P Value
Age BW (kg) BW SDS Height (cm) Height SDS BSA (m2) BMI (kg/m2) BMI SDS
0.888 0.822 0.072 0.907 0.001 0.874 0.422 0.170
<.001 <.001 .496 <.001 .993 <.001 <.001 .361
0.782 0.768 0.233 0.831 0.158 0.814 0.366 0.006
<.001 <.001 .049 <.001 .186 <.001 .001 .964
0.350 0.345 0.176 0.408 0.061 0.382 0.253 0.044
.001 .001 .095 <.001 .564 <.001 .014 .815
0.107 0.182 0.128 0.211 0.069 0.207 0.157 0.096
.360 .117 .283 .070 .567 .075 .178 .499
Abbreviations as in Table 1. The figures in boldface are statistically significant (P <.05).
patients were divided into 2 groups according to their kidney length SDS values (kidney lengths 2 SD or >2 SD based on normal values). Then a receiver operating characteristic curve analysis was performed for the age 444
and the body height. The most determinative threshold values for the age and the height, which were 2 SD above the specified limits, were investigated. A total of 17.5 months for age (discriminative power 0.74 0.05, UROLOGY 82 (2), 2013
P <.001, 95% confidence interval 0.65-0.83, sensitivity 0.704, specificity, 0.681, positive predictive value 0.623, negative predictive value 0.754, odds ratio (OR) 5.06, and relative risk 2.53) and 82 cm for body height (discriminative power 0.76 0.04, P <.001, 95% confidence interval 0.68-0.85, sensitivity 0.736, specificity 0.667, positive predictive value 0.619, negative predictive value 0.774, OR 5.57, and relative risk 2.74) were determined as threshold values.
DISCUSSION Increasingly in line with advancements in ultrasonographic imaging techniques, higher number of asymptomatic patients with solitary functional kidneys has been determined.8 Under normal conditions, absence/loss of 1 kidney results in hypertrophy of the other healthy contralateral kidney. Despite not being hypertrophic, these kidneys may increase in volume up to 1.8 times of the normal kidney within the first 4 years of life. On the other hand, in solitary kidneys secondary to acquired and/ or iatrogenic causes (nephrectomies with various indications, function loss due to urinary tract infections, or thromboembolic events), few number of nephrons try to fill the gap with hyperfiltration and hypertrophy.8 This study investigated the degree of compensatory renal hypertrophy in single functional kidneys and the effect of anthropometric development on compensatory hypertrophy. Because the mechanism and potential growth of solitary kidneys due to congenital or acquired reasons might differ, the patients were evaluated in 2 groups. Group 1 consisted of patients with severe renal hypofunction (<10%) and those followed up with urinary tract infection (acquired group). On the other hand, group 2 included patients with solitary kidneys secondary to URA and MCDK (congenital group). Among patients in group 1, cases with congenital hypoplasia/dysplasia can be seen. However, because diagnosis age of patients in this group was relatively higher (84 months in average), it was very difficult to discriminate between congenital and acquired reasons. Therefore, all patients in this group were assumed to have acquired solitary kidneys. Group 1 constituted 25% of the population of the study and group 2 was 75% of the population. Group 2 consisted of patients with URA (48%) or MCDK (52%). Association of multiorgan syndromes with especially renal agenesis has been acknowledged.9 However, no concomitant systemic abnormality was determined in patients in the study group. Various concomitant abnormalities have been reported to accompany the healthy kidney in the patients with unilateral renal agenesis and MCDK. In both entities, the most frequent abnormality in functional kidneys is VUR. In patients with MCDK, the incidence of reflux reportedly ranges from 5%-43%, and the reflux is low grade (grade 1-2).10,11 In unilateral renal agenesis, the incidence of reflux was reported as 24%-28%.12,13 In our study, comorbidities of healthy kidneys were seen in UROLOGY 82 (2), 2013
almost equal frequency except for VUR. VUR was the most frequent abnormality in both groups (22% in group 1 and only 6% in group 2). Apart from VUR, ureteropelvic junction stenosis (7% in renal agenesis and 7%-15% in MCDK) and ureterovesical stenosis (11% in renal agenesis and 6% in MCDK) have been frequently reported.10,12 In this study, although frequencies of hydronephrosis, ureteropelvic, and ureterovesical stenosis in group 1 were 13%, 16%, and 0%, respectively, those frequencies in group 2 were 3%, 3%, and 1%, respectively, this situation did not cause any significant difference between groups. Considering all patients in the population, any difference between patients with or without VUR in terms of functional kidney length and height SDS values was not found. In other words, the presence of reflux into the healthy kidney did not affect renal growth. However, some studies in the literature have demonstrated unfavorable effects of VUR on renal growth. A study determined the presence of VUR into functional kidney in 7 of 27 patients with MCDK and the authors of said study reported smaller sized kidneys in newborns at birth and 2-year-old children.14 Another study compared patients with MCDK with or without reflux, and significantly smaller renal dimensions were estimated in the group with reflux. In the reflux group, functional kidney length SDS values did not increase to 1 SD above the upper limit of normal (ULN) in any patient; however, in 54% of patients in the group without reflux, this value increased to 1 SD above ULN and, in 13% of them, increased to 2 SD above ULN.15 However, some studies have argued that the presence of reflux into the functional kidney did not affect annual growth rate of the functional kidney.16 Renal scar was more frequently encountered in the functional kidney in group 1 (group 1 14%, group 2 3%, P ¼ .046). Some studies have indicated that if failure to develop compensatory hypertrophy in MCDK occurs, the presence of marked scar/dysplasia should be taken into consideration.17,18 However, considering all patients in the population as a whole in this study, there was no difference between patients with or without scars in terms of functional kidney length and its SDS values. However, few number of patients (n ¼ 6) should be taken into consideration, and determining an unfavorable effect of scars/dysplasia on renal growth can be anticipated in further studies with larger patient groups with renal scars. Various studies have evaluated ultrasonographically vertical kidney lengths of healthy children and compared their correlations with anthropometric measurements. These studies have demonstrated that kidney lengths increase in direct proportion to the increases in infant’s height and BSA.5,6 Although many studies have investigated the effect of anthropometric data on kidney lengths by now, a limited number of studies have analyzed anthropometric factors affecting compensatory renal hypertrophy in children with solitary functional kidneys. Another study making comparison between kidney lengths of 160 children with congenital normal single 445
kidneys using anthropometric data, demonstrated the strongest correlation only with BMI (r ¼ 0.85).19 Patients with congenital (group 2 agenesis/MCDK) and acquired (group 1 atrophic kidneys) solitary kidneys were assessed in combination in this study. Average diagnosis age of the patients in group 1 were higher (84 months) compared to group 2 (average age of 7.5 months), which correlatively led to determine higher anthropometric values (BW, BSA, and BMI) and functional kidney lengths in the patients of group 1 at the time of diagnosis. Comparative differences between anthropometric values of group 1 (average age of 116 months) and group 2 (average age of 36 months) persisted after a 2-3 year follow-up period. However, functional kidney length SDS value, which was higher in group 1 at the time of diagnosis, was almost identical between groups at the end of the follow-up period. Correlation of functional kidney length SDS values with anthropometric variables was investigated. In group 2, at the time of diagnosis, kidney length was correlated with age, height, BSA, and BMI; on the other hand, this correlation was not seen in group 1. Furthermore, at the last follow-up visit, if the child was 36 months old, then correlation between functional kidney length SDS values, age, BW, BSA, and BMI disappeared. In other words, in the smaller age group, length SDS values of functional kidneys increase in line with age, but as the patients get older, this characteristic feature disappears. This finding reveals that the rate of increase in kidney length remains at a high level for a while, and, after a certain age, it goes parallel with the growth rate. In other words, this condition indicates that the kidney comes to an end in its compensatory hypertrophy at a certain age and then it continues to grow at a normal rate. Data of all patients only at diagnosis were used to represent all age groups. Using these data, this study investigated the changes in a functional kidney vertical length and its SDS values in correlation with age and anthropometric data. Accordingly, this study concluded that vertical length of the kidney correlates with age, BW, height, BSA, and BMI. The strongest determinative factor was height (r ¼ 0.905). In this study, it was also observed that functional renal length SDS values also changed significantly with the same anthropometric variables, and height was also the strongest determinative factor (r ¼ 0.378). Logistic regression analysis of these parameters affecting functional renal length SDS values, demonstrated that the fundamental determinants were height and age. Receiver operating characteristic curve analysis revealed that length of the solitary kidney reached 2 SD above the normal (occurrence of compensatory hypertrophy, OR 5.06, 95% confidence interval 0.65-0.83) at a chronologic age of 17.5 months and at a body height of 82 cm (OR 5.57, 95% confidence interval 0.68-0.85). There have been a number of studies achieving similar data in the literature. In a study by Rottenberg et al,20 446
56 infants born with a solitary functional kidney and diagnosed with MCDK in the antenatal period were assessed. This mentioned study also demonstrated that the renal growth within the first 6 months was faster compared to the next 6 months, and in an 18-month-old baby, the rate of renal development showed parallelism with normal rate of growth. Another study observed 43 children diagnosed with MCDK in the antenatal period for 42 months on average, and compensatory hypertrophy could be seen at the age of nearly 30 months.21
CONCLUSION In conclusion, compensatory hypertrophy develops at a similar level in pediatric patients with a single or hypofunctional kidney (<10%). Even though the effect of the presence of reflux/scar in the functional kidney on compensatory hypertrophy could not be shown, a number of the patients with reflux/scar could not be overlooked. It can be asserted that the most important parameters determining the compensatory hypertrophy are patient’s age and height. Moreover, a functional kidney rapidly grows in the early years of life to complete compensatory hypertrophy and then continues to grow in parallel with normal rate of bodily development. References 1. Sinuani I, Beberashvili I, Averbukh Z, et al. Mesangial cells initiate compensatory tubular cell hypertrophy. Am J Nephrol. 2010;31: 326-331. 2. Glazebrook KN, McGrath FP, Steele BT. Prenatal compensatory renal growth: documentation with US. Radiology. 1993;189: 733-735. 3. Shapiro E, Goldfarb DA, Ritchey ML. The congenital and acquired solitary kidney. Rev Urol. 2003;5:2-8. 4. Maluf NS. On the enlargement of the normal congenitally solitary kidney. Br J Urol. 1997;79:836-841. 5. Currarino G, Williams B. Dana K. Kidney length correlated with age: normal values in children. Radiology. 1984;150:703-704. 6. Han BK, Babcock DS. Sonographic measurements and appearance of normal kidneys in children. AJR Am J Roentgenol. 1985;145: 611-616. 7. Schwartz GJ, Haycock GB, Spitzer A. Plasma creatinine and urea concentration in children: normal values for age and sex. J Pediatr. 1976;88:828-830. 8. Spira EM, Jacobi C, Frankenschmidt A, et al. Sonographic longterm study: paediatric growth charts for single kidneys. Arch Dis Child. 2009;94:693-698. 9. Woolf AS, Hillman KA. Unilateral renal agenesis and the congenital solitary functioning kidney: developmental, genetic and clinical perspectives. BJU Int. 2007;99:17-21. 10. Hains DS, Bates CM, Ingraham S, Schwaderer AL. Management and etiology of the unilateral multicystic dysplastic kidney: a review. Pediatr Nephrol. 2009;24:233-241. 11. Aslam M, Watson AR; Trent & anglia MCDK Study Group. Unilateral multicystic dysplastic kidney: long term outcomes. Arch Dis Child. 2006;91:820-823. 12. Cascio S, Paran S, Puri P. Associated urological anomalies in children with unilateral renal agenesis. J Urol. 1999;162(3 Pt 2): 1081-1083. 13. Guarino N, Casamassima MG, Tadini B, et al. Natural history of vesicoureteral reflux associated with kidney anomalies. Urology. 2005;65:1208-1211.
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14. Fanos V, Sinaguglia G, Vino L, et al. Multicystic dysplastic kidney and contralateral vesicoureteral reflux. Renal growth. Minerva Pediatr. 2001;53:95-98. 15. Zerin JM, Leiser J. The impact of vesicoureteral reflux on contralateral renal length in infants with multicystic dysplastic kidney. Pediatr Radiol. 1998;28:683-686. 16. Miller DC, Rumohr JA, Dunn RL, et al. What is the fate of the refluxing contralateral kidney in children with multicystic dysplastic kidney? J Urol. 2004;172(4 Pt 2):1630-1634. 17. Goodyer P. Renal dysplasia/hypoplasia. In: Avner ED, Harmon WE, Niaduet P, Yoshikowa N, eds. Pediatric nephrology. 6th ed. Berlin, Heidelberg, Germany: Springer-Verlag; 2009:107-120.
UROLOGY 82 (2), 2013
18. Wang Y, Wang Z, Wang W, et al. Analysis of factors associated with renal function in Chinese adults with congenital solitary kidney. Intern Med. 2010;49:2203-2209. 19. Wilson BE, Davies P, Shah K, et al. Renal length and inulin clearance in the radiologically normal single kidney. Pediatr Nephrol. 2003;18:1147-1151. 20. Rottenberg GT, De Bruyn R, Gordon I. Sonographic standards for a single functioning kidney in children. AJR Am J Roentgenol. 1996; 167:1255-1259. 21. Rabelo EA, Oliveira EA, Diniz JS, et al. Natural history of multicystic kidney conservatively managed: a prospective study. Pediatr Nephrol. 2004;19:1102-1107.
447
RESULTS
CONCLUSION
To evaluate the factors associated with compensatory hypertrophy in the functional kidneys of children. The medical files of patients with a solitary functional kidney were reviewed retrospectively. Data regarding anthropometric measurements, functional renal length, functional renal length of standard deviation score (SDS) of functional kidney at diagnosis, and end of follow-up were obtained. Patients were divided into 2 groups, those with a unilateral kidney function of <10% (hypoplasia, dysplasia, and atrophy, group 1) and those with a solitary kidney (agenesis, and multicystic dysplastic kidney, group 2). A total of 126 patients (70 boys) were evaluated. Both the sizes of the functional kidney and functional kidney SDS values at diagnosis were greater in group 1 relative to group 2. At the end of the follow-up period, anthropometric values including functional kidney size were higher in group 2. Functional kidney size of 2 SDS above the normal was mostly predictive at age 17.5 months (odds ratio [OR] 5.06) and at a body height of 82 cm (OR 5.57). The most determining factors for renal length SDS values were age and height. Solitary kidneys complete compensatory hypertrophy by 17.5 months of age, and after that their growth continues in parallel to normal growth. UROLOGY 82: 442e447, 2013. 2013 Elsevier Inc.
I
n childhood, solitary functional kidney can develop secondary to congenital and acquired causes. Under normal conditions, absence of 1 kidney results in adaptive compensatory hypertrophy of the contralateral healthy kidney.1 As reported in the literature, this kind of hypertrophy can be seen in all age groups from intrauterine life to adulthood.2 Among congenital causes of a solitary functional kidney, there are unilateral renal agenesis (URA) and multicystic dysplastic kidney (MCDK); and the unilateral renal dysfunction/nephrectomy secondary to various etiological factors (tumor, trauma, urinary tract infection, and thrombosis) can be included among acquired types.3 Urogenital or other system abnormalities can accompany unilateral renal agenesis and MCDK. Demonstration of
Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Pediatric Nephrology, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey; and Department of Radiology, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey Reprint requests: Demet Alaygut, M.D., Dokuz Eylul University, Department of Pediatric Nephrology, 35340 Inciralti, Izmir, Turkey. E-mail: demetalaygut@yahoo. com Submitted: January 6, 2013, accepted (with revisions): March 12, 2013
442
ª 2013 Elsevier Inc. All Rights Reserved
the nondysplastic nature of the functional kidney is especially important.4 Many studies have evaluated vertical length of the kidney in healthy children using ultrasonographic techniques and compared its relationship with anthropometric measurements. These studies have demonstrated that vertical length of the kidneys increases in direct proportion with increasing age and body surface area (BSA) of the children.5,6 The purpose of this study was to assess the degree of compensatory renal hypertrophy in single functional kidneys and the effect of anthropometric development on compensatory hypertrophy.
MATERIAL AND METHODS Medical files of patients with solitary or unilateral nonfunctional (unilateral renal agenesis, unilateral multicystic dysplastic) kidneys and with hypofunctional (<10%) atrophic kidneys who were followed-up in Dokuz Eylul University Faculty of Medicine, Department of Pediatric Nephrology, were retrospectively examined. Anthropometric data, serum biochemical parameters such as urinalysis, and urinary protein, and imaging techniques such as urinary system ultrasound, voiding cystourethrography, and 99mTc-dimercaptosuccinic acid static renal scintigraphy findings were evaluated. The patients were divided into 2 0090-4295/13/$36.00 http://dx.doi.org/10.1016/j.urology.2013.03.024
groups, those with single atrophic kidneys (group 1) and those with solitary (agenesis/MCDK) kidneys (group 2). The following parameters were recorded: age, gender, diagnosis, followup period, body weight (BW), BW standard deviation score (BW SDS), patient height, height SDS, BSA, body mass index (BMI), BMI SDS, functional renal length, functional renal length SDS, creatinine level, creatinine clearance, anomalies in the functional kidney, vesicoureteral reflux (VUR) involving the functional kidney, scar(s) in the functional kidney, hypertension, and proteinuria at the end of both diagnostic workup and follow-up period. SPSS 15.0 software package was used to conduct statistical analysis. Age at diagnosis, follow-up period, BW at admission, BW SDS, BMI, BMI SDS, BSA, functional renal length, and renal length SDS values were compared between groups 1 and 2. At the end of the follow-up period, both groups were compared in terms of the same anthropometric variables. While performing these comparisons, t test or Mann-Whitney U test was used based on the number of cases. Factors affecting functional kidney length and its SDS value were assessed using the Pearson correlation analysis. In the comparison of categorical variables, the chi-square test was used. Statistical significance was accepted as P <.05.
RESULTS Data of all 141 patients with solitary functional kidneys were accessed. Fifteen patients whose renal dimensions were not evaluated ultrasonographically were excluded from the study. Population of the study (126 patients) was composed of 70 male (55.6%) and 56 female patients (44.4%). Average age at diagnosis was 47.8 58.3 months (range 1-212 months) and mean follow-up period was 28.0 32.4 months (range 1-191 months). Patients were assessed according to their primary diagnoses, which included atrophic kidney (n ¼ 32, 25.7%), MCDK (n ¼ 49, 38.9%), and agenesis (n ¼ 45, 35.7%). In group 1, 32 patients with solitary atrophic kidneys (function loss >90%) had a male/female ratio of 19/13 (59%/41%). Their average age at diagnosis (83.7 61.2, range 1-212 months, median 83.7 months) and mean follow-up period (35.3 43.2, range 1-191, and median 27 months) were calculated. In group 2, 94 patients with solitary kidneys had a male/female ratio of 51/43 (54%/46%) with an average age of 35.5 52.2 months (range 1-204, median 7.5 months) and mean follow-up period of 25.6 27.9 months (range 1-152, median 18 months). Although there was a significant difference between group 1 and group 2 in terms of age at diagnosis (P <.001), their follow-up periods did not show a difference. There was no difference between group 1 and group 2 in terms of male/female ratio (P ¼ .615). Comparison of the anthropometric parameters of both groups indicated that patients in group 1 had higher ages at the time of diagnosis. Accordingly, patients in group 1 had relatively increasing BW, height, BSA, and BMI compared to patients in group 2. However, no difference was found between the 2 groups in terms of BW SDS, height SDS, and BMI SDS. Patients in group 1 had higher functional kidney size and functional kidney size SDS values compared to patients in group 2 (Table 1). UROLOGY 82 (2), 2013
At the end of the follow-up period, no gender predominance was observed between 21 patients in group 1 (M/F: 14/7) and 74 patients in group 2 (M/F: 43/31) whose functional kidney lengths were measured at the end of the follow-up period (P ¼ .480). Comparing anthropometric parameters in the patients of group 1; average age, BW, height, and BSA were relatively higher, however, difference between the groups in terms of mean BMI values was not statistically significant. Nevertheless, BW SDS, height SDS, and BMI SDS values did not show any difference between the groups. Similarly, mean functional kidney length in group 1 was higher compared to group 2, without any intergroup difference in terms of kidney length SDS values (Table 1). Both groups were also compared with respect to serum creatinine levels, creatinine clearance estimates based on Schwartz formula, and spot urine protein/creatinine ratio (mg/mg) as measured at the time of the diagnosis and at the end of the follow-up period, and as a result of this comparison, higher serum creatinine levels were observed in group 1. In none of the cases were the serum creatinine levels within the normal limits according to the variable of age.7 As a result of examining the distribution of anomalies associated with functional kidney, there was no intergroup difference except for VUR. In group 1, VUR was more frequently detected in the functional kidney (P ¼ .020). In both patient groups, 13 patients (10.3%) had VUR. Any difference was not determined in kidney length and kidney length SDS values estimated at the time of diagnosis or at the end of the follow-up period between patients with or without VUR in their functional kidneys. The patients were also evaluated in terms of the presence of scar tissue in the functional kidney, and the number of patients with scar tissue in their functional kidneys was greater in group 1. Functional kidney length and kidney length SDS values in patients with or without scar tissues as estimated at the time of the diagnosis and during the last follow-up visit were also compared. Dimercaptosuccinic acid scanning determined no presence of scar tissue on kidney length. In both groups, changes in functional kidney length and kidney length SDS values detected at the time of diagnosis and at the end of the follow-up period were evaluated in line with anthropometric data (Tables 2 and 3). In both patient groups, linear regression analysis was used to find the most determinative anthropometric variables among those correlated with functional kidney length SDS values estimated at the time of diagnosis. Only age (months) (P ¼ .006) and body height (P <.001) were significant determinative factors. It is thought that compensatory hypertrophy develops when kidney length increases 2 SD (>95. percentile) above its normal length known for age and height. Based on this assertion, we wanted to determine at what age and body height the kidney lengths of the patients increased 2 SD above the normal values (ie, compensatory hypertrophy occurs at which age and body height). The 443
Table 1. Intergroup comparisons of anthropometric data recorded at the time of diagnosis and at the end of the follow-up period At the Time of Diagnosis Parameters
Group 1
BW (kg) BW SDS Height (cm) Height SDS BSA (m2) BMI (kg/m2) BMI SDS Functional kidney length (mm) (mean SD)
27 0.2 117 0.1 0.92 17.5 0.45 91.0
Median
16.8 1.7 34.5 2.0 0.41 2.8 1.2 22.1
13.5 0.24 81.4 0.13 0.53 15.8 0.12 71.5
93.5
Functional kidney length SDS (mean SD)
15.1 1.9 34.8 2.0 0.39 4.06 1.3 22.3
Group 1
<.001 .247 <.001 .574 <.001 .031 .130 <.001
30.6 0.23 127.2 0.19 1.01 17.3 0.36 100.3
65.0
2.6 2.6
Median
At the Last Follow-up Visit P Value
Group 2
16.7 1.73 34.0 1.8 0.4 2.4 1.5 21.3
108
1.6 2.0
2.4
3.2 3.4
.030
1.3
2.1
Group 2 20.1 0.48 101.8 0.44 0.74 17.0 0.07 87.1
P Value
16.3 1.5 31.8 1.8 0.38 3.9 1.9 21.4
.006 .675 .005 .602 .006 .076 .436 .016
85 3.1 3.1
.939
2.8
BMI, body mass index; BSA, body surface area; BW, body weight; SDS, standard deviation score. The figures in boldface are statistically significant (P <.05).
Table 2. Group 1 comparison of functional kidney length, and functional kidney length SDS values with anthropometric data recorded at the time of diagnosis and at the end of the follow-up period Functional Kidney Length At the Time of Diagnosis
Functional Kidney Length SDS Value
At the End of the Follow-up Period
At the Time of Diagnosis
At the End of the Follow-up Period
Parameters
r
P Value
r
P Value
r
P Value
r
P Value
Age BW (kg) BW SDS Height (cm) Height SDS BSA (m2) BMI (kg/m2) BMI SDS
0.703 0.837 0.275 0.840 0.116 0.861 0.635 0.109
<.001 <.001 .141 <.001 .540 <.001 <.001 .638
0.715 0.780 0.063 0.801 0.120 0.800 0.338 0.277
<.001 <.001 .785 <.001 .606 <.001 .134 .281
0.041 0.184 0.415 0.164 0.233 0.204 0.398 0.346
.823 .314 .022 .369 .214 .262 .024 .124
0.101 0.037 0.319 0.005 0.212 0.044 0.196 0.496
.663 .874 .158 .984 .357 .849 .395 .043
Abbreviations as in Table 1. The figures in boldface are statistically significant (P <.05).
Table 3. Group 2 comparison of functional kidney length and functional kidney length SDS values with anthropometric data recorded at the time of diagnosis and at the end of the follow-up period Functional Kidney Length At the Time of Diagnosis
Functional Kidney Length SDS Value
At the End of the Follow-up Period
At the Time of Diagnosis
At the End of the Follow-up Period
Parameters
r
P Value
r
P Value
r
P Value
r
P Value
Age BW (kg) BW SDS Height (cm) Height SDS BSA (m2) BMI (kg/m2) BMI SDS
0.888 0.822 0.072 0.907 0.001 0.874 0.422 0.170
<.001 <.001 .496 <.001 .993 <.001 <.001 .361
0.782 0.768 0.233 0.831 0.158 0.814 0.366 0.006
<.001 <.001 .049 <.001 .186 <.001 .001 .964
0.350 0.345 0.176 0.408 0.061 0.382 0.253 0.044
.001 .001 .095 <.001 .564 <.001 .014 .815
0.107 0.182 0.128 0.211 0.069 0.207 0.157 0.096
.360 .117 .283 .070 .567 .075 .178 .499
Abbreviations as in Table 1. The figures in boldface are statistically significant (P <.05).
patients were divided into 2 groups according to their kidney length SDS values (kidney lengths 2 SD or >2 SD based on normal values). Then a receiver operating characteristic curve analysis was performed for the age 444
and the body height. The most determinative threshold values for the age and the height, which were 2 SD above the specified limits, were investigated. A total of 17.5 months for age (discriminative power 0.74 0.05, UROLOGY 82 (2), 2013
P <.001, 95% confidence interval 0.65-0.83, sensitivity 0.704, specificity, 0.681, positive predictive value 0.623, negative predictive value 0.754, odds ratio (OR) 5.06, and relative risk 2.53) and 82 cm for body height (discriminative power 0.76 0.04, P <.001, 95% confidence interval 0.68-0.85, sensitivity 0.736, specificity 0.667, positive predictive value 0.619, negative predictive value 0.774, OR 5.57, and relative risk 2.74) were determined as threshold values.
DISCUSSION Increasingly in line with advancements in ultrasonographic imaging techniques, higher number of asymptomatic patients with solitary functional kidneys has been determined.8 Under normal conditions, absence/loss of 1 kidney results in hypertrophy of the other healthy contralateral kidney. Despite not being hypertrophic, these kidneys may increase in volume up to 1.8 times of the normal kidney within the first 4 years of life. On the other hand, in solitary kidneys secondary to acquired and/ or iatrogenic causes (nephrectomies with various indications, function loss due to urinary tract infections, or thromboembolic events), few number of nephrons try to fill the gap with hyperfiltration and hypertrophy.8 This study investigated the degree of compensatory renal hypertrophy in single functional kidneys and the effect of anthropometric development on compensatory hypertrophy. Because the mechanism and potential growth of solitary kidneys due to congenital or acquired reasons might differ, the patients were evaluated in 2 groups. Group 1 consisted of patients with severe renal hypofunction (<10%) and those followed up with urinary tract infection (acquired group). On the other hand, group 2 included patients with solitary kidneys secondary to URA and MCDK (congenital group). Among patients in group 1, cases with congenital hypoplasia/dysplasia can be seen. However, because diagnosis age of patients in this group was relatively higher (84 months in average), it was very difficult to discriminate between congenital and acquired reasons. Therefore, all patients in this group were assumed to have acquired solitary kidneys. Group 1 constituted 25% of the population of the study and group 2 was 75% of the population. Group 2 consisted of patients with URA (48%) or MCDK (52%). Association of multiorgan syndromes with especially renal agenesis has been acknowledged.9 However, no concomitant systemic abnormality was determined in patients in the study group. Various concomitant abnormalities have been reported to accompany the healthy kidney in the patients with unilateral renal agenesis and MCDK. In both entities, the most frequent abnormality in functional kidneys is VUR. In patients with MCDK, the incidence of reflux reportedly ranges from 5%-43%, and the reflux is low grade (grade 1-2).10,11 In unilateral renal agenesis, the incidence of reflux was reported as 24%-28%.12,13 In our study, comorbidities of healthy kidneys were seen in UROLOGY 82 (2), 2013
almost equal frequency except for VUR. VUR was the most frequent abnormality in both groups (22% in group 1 and only 6% in group 2). Apart from VUR, ureteropelvic junction stenosis (7% in renal agenesis and 7%-15% in MCDK) and ureterovesical stenosis (11% in renal agenesis and 6% in MCDK) have been frequently reported.10,12 In this study, although frequencies of hydronephrosis, ureteropelvic, and ureterovesical stenosis in group 1 were 13%, 16%, and 0%, respectively, those frequencies in group 2 were 3%, 3%, and 1%, respectively, this situation did not cause any significant difference between groups. Considering all patients in the population, any difference between patients with or without VUR in terms of functional kidney length and height SDS values was not found. In other words, the presence of reflux into the healthy kidney did not affect renal growth. However, some studies in the literature have demonstrated unfavorable effects of VUR on renal growth. A study determined the presence of VUR into functional kidney in 7 of 27 patients with MCDK and the authors of said study reported smaller sized kidneys in newborns at birth and 2-year-old children.14 Another study compared patients with MCDK with or without reflux, and significantly smaller renal dimensions were estimated in the group with reflux. In the reflux group, functional kidney length SDS values did not increase to 1 SD above the upper limit of normal (ULN) in any patient; however, in 54% of patients in the group without reflux, this value increased to 1 SD above ULN and, in 13% of them, increased to 2 SD above ULN.15 However, some studies have argued that the presence of reflux into the functional kidney did not affect annual growth rate of the functional kidney.16 Renal scar was more frequently encountered in the functional kidney in group 1 (group 1 14%, group 2 3%, P ¼ .046). Some studies have indicated that if failure to develop compensatory hypertrophy in MCDK occurs, the presence of marked scar/dysplasia should be taken into consideration.17,18 However, considering all patients in the population as a whole in this study, there was no difference between patients with or without scars in terms of functional kidney length and its SDS values. However, few number of patients (n ¼ 6) should be taken into consideration, and determining an unfavorable effect of scars/dysplasia on renal growth can be anticipated in further studies with larger patient groups with renal scars. Various studies have evaluated ultrasonographically vertical kidney lengths of healthy children and compared their correlations with anthropometric measurements. These studies have demonstrated that kidney lengths increase in direct proportion to the increases in infant’s height and BSA.5,6 Although many studies have investigated the effect of anthropometric data on kidney lengths by now, a limited number of studies have analyzed anthropometric factors affecting compensatory renal hypertrophy in children with solitary functional kidneys. Another study making comparison between kidney lengths of 160 children with congenital normal single 445
kidneys using anthropometric data, demonstrated the strongest correlation only with BMI (r ¼ 0.85).19 Patients with congenital (group 2 agenesis/MCDK) and acquired (group 1 atrophic kidneys) solitary kidneys were assessed in combination in this study. Average diagnosis age of the patients in group 1 were higher (84 months) compared to group 2 (average age of 7.5 months), which correlatively led to determine higher anthropometric values (BW, BSA, and BMI) and functional kidney lengths in the patients of group 1 at the time of diagnosis. Comparative differences between anthropometric values of group 1 (average age of 116 months) and group 2 (average age of 36 months) persisted after a 2-3 year follow-up period. However, functional kidney length SDS value, which was higher in group 1 at the time of diagnosis, was almost identical between groups at the end of the follow-up period. Correlation of functional kidney length SDS values with anthropometric variables was investigated. In group 2, at the time of diagnosis, kidney length was correlated with age, height, BSA, and BMI; on the other hand, this correlation was not seen in group 1. Furthermore, at the last follow-up visit, if the child was 36 months old, then correlation between functional kidney length SDS values, age, BW, BSA, and BMI disappeared. In other words, in the smaller age group, length SDS values of functional kidneys increase in line with age, but as the patients get older, this characteristic feature disappears. This finding reveals that the rate of increase in kidney length remains at a high level for a while, and, after a certain age, it goes parallel with the growth rate. In other words, this condition indicates that the kidney comes to an end in its compensatory hypertrophy at a certain age and then it continues to grow at a normal rate. Data of all patients only at diagnosis were used to represent all age groups. Using these data, this study investigated the changes in a functional kidney vertical length and its SDS values in correlation with age and anthropometric data. Accordingly, this study concluded that vertical length of the kidney correlates with age, BW, height, BSA, and BMI. The strongest determinative factor was height (r ¼ 0.905). In this study, it was also observed that functional renal length SDS values also changed significantly with the same anthropometric variables, and height was also the strongest determinative factor (r ¼ 0.378). Logistic regression analysis of these parameters affecting functional renal length SDS values, demonstrated that the fundamental determinants were height and age. Receiver operating characteristic curve analysis revealed that length of the solitary kidney reached 2 SD above the normal (occurrence of compensatory hypertrophy, OR 5.06, 95% confidence interval 0.65-0.83) at a chronologic age of 17.5 months and at a body height of 82 cm (OR 5.57, 95% confidence interval 0.68-0.85). There have been a number of studies achieving similar data in the literature. In a study by Rottenberg et al,20 446
56 infants born with a solitary functional kidney and diagnosed with MCDK in the antenatal period were assessed. This mentioned study also demonstrated that the renal growth within the first 6 months was faster compared to the next 6 months, and in an 18-month-old baby, the rate of renal development showed parallelism with normal rate of growth. Another study observed 43 children diagnosed with MCDK in the antenatal period for 42 months on average, and compensatory hypertrophy could be seen at the age of nearly 30 months.21
CONCLUSION In conclusion, compensatory hypertrophy develops at a similar level in pediatric patients with a single or hypofunctional kidney (<10%). Even though the effect of the presence of reflux/scar in the functional kidney on compensatory hypertrophy could not be shown, a number of the patients with reflux/scar could not be overlooked. It can be asserted that the most important parameters determining the compensatory hypertrophy are patient’s age and height. Moreover, a functional kidney rapidly grows in the early years of life to complete compensatory hypertrophy and then continues to grow in parallel with normal rate of bodily development. References 1. Sinuani I, Beberashvili I, Averbukh Z, et al. Mesangial cells initiate compensatory tubular cell hypertrophy. Am J Nephrol. 2010;31: 326-331. 2. Glazebrook KN, McGrath FP, Steele BT. Prenatal compensatory renal growth: documentation with US. Radiology. 1993;189: 733-735. 3. Shapiro E, Goldfarb DA, Ritchey ML. The congenital and acquired solitary kidney. Rev Urol. 2003;5:2-8. 4. Maluf NS. On the enlargement of the normal congenitally solitary kidney. Br J Urol. 1997;79:836-841. 5. Currarino G, Williams B. Dana K. Kidney length correlated with age: normal values in children. Radiology. 1984;150:703-704. 6. Han BK, Babcock DS. Sonographic measurements and appearance of normal kidneys in children. AJR Am J Roentgenol. 1985;145: 611-616. 7. Schwartz GJ, Haycock GB, Spitzer A. Plasma creatinine and urea concentration in children: normal values for age and sex. J Pediatr. 1976;88:828-830. 8. Spira EM, Jacobi C, Frankenschmidt A, et al. Sonographic longterm study: paediatric growth charts for single kidneys. Arch Dis Child. 2009;94:693-698. 9. Woolf AS, Hillman KA. Unilateral renal agenesis and the congenital solitary functioning kidney: developmental, genetic and clinical perspectives. BJU Int. 2007;99:17-21. 10. Hains DS, Bates CM, Ingraham S, Schwaderer AL. Management and etiology of the unilateral multicystic dysplastic kidney: a review. Pediatr Nephrol. 2009;24:233-241. 11. Aslam M, Watson AR; Trent & anglia MCDK Study Group. Unilateral multicystic dysplastic kidney: long term outcomes. Arch Dis Child. 2006;91:820-823. 12. Cascio S, Paran S, Puri P. Associated urological anomalies in children with unilateral renal agenesis. J Urol. 1999;162(3 Pt 2): 1081-1083. 13. Guarino N, Casamassima MG, Tadini B, et al. Natural history of vesicoureteral reflux associated with kidney anomalies. Urology. 2005;65:1208-1211.
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14. Fanos V, Sinaguglia G, Vino L, et al. Multicystic dysplastic kidney and contralateral vesicoureteral reflux. Renal growth. Minerva Pediatr. 2001;53:95-98. 15. Zerin JM, Leiser J. The impact of vesicoureteral reflux on contralateral renal length in infants with multicystic dysplastic kidney. Pediatr Radiol. 1998;28:683-686. 16. Miller DC, Rumohr JA, Dunn RL, et al. What is the fate of the refluxing contralateral kidney in children with multicystic dysplastic kidney? J Urol. 2004;172(4 Pt 2):1630-1634. 17. Goodyer P. Renal dysplasia/hypoplasia. In: Avner ED, Harmon WE, Niaduet P, Yoshikowa N, eds. Pediatric nephrology. 6th ed. Berlin, Heidelberg, Germany: Springer-Verlag; 2009:107-120.
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18. Wang Y, Wang Z, Wang W, et al. Analysis of factors associated with renal function in Chinese adults with congenital solitary kidney. Intern Med. 2010;49:2203-2209. 19. Wilson BE, Davies P, Shah K, et al. Renal length and inulin clearance in the radiologically normal single kidney. Pediatr Nephrol. 2003;18:1147-1151. 20. Rottenberg GT, De Bruyn R, Gordon I. Sonographic standards for a single functioning kidney in children. AJR Am J Roentgenol. 1996; 167:1255-1259. 21. Rabelo EA, Oliveira EA, Diniz JS, et al. Natural history of multicystic kidney conservatively managed: a prospective study. Pediatr Nephrol. 2004;19:1102-1107.
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