Renal
Fu nction
in Obstructive
Neph ropathy:
Long-Term
Effect of Reconstructive
Surgery
Georges Mayor, M.D., Noel Genton, M.D., Antonio Torrado, M.D., and Jean-Pierre Guignard, M.D.
From the Departments of Pediatric Surgery and Pediatrics, H#{244}pital cantonal universitaire, Lausanne, Switz-erland
ABSTRACT. Renal function was studied in 24 children
with chronic hydronephrosis and renal insufficiency. The
follow-up period after reconstructive surgery was 1 to 12
years. Glomerular filtration rate (GFR) was assessed by the
clearance of endogenous creatinine or inulin. Effective re-nal plasma flow was assessed by the clearance of PAH.
Re-constructive surgery was performed during the first year of life in 12 out of 24 patients, between one and two years of life in 6 patients, and after two years of life in 6 patients.
Three different patterns of evolution could be observed
af-ter relief of obstruction: (1) An improvement or a normal-ization of renal function only occurred in patients operated upon before one year of life. (2) A stabilization of renal function without normalization was observed in patients operated upon between one and two years of life. (3) A pro-gressive deterioration of renal function towards terminal re-nal failure was observed in five out of six patients operated upon after two years of age. This deterioration could not be explained by recurrence of detectable urinary tract infec-tion or urinary stasis. The changes in GRF in four patients
with a solitary kidney followed the same pattern.
We conclude that it is essential to correct severe chronic hydronephrosis associated with renal insufficiency before one year of age if a lasting improvement of renal function is to be expected. Pediatrics, 56:740-747, 1975, RENAL
FAIL-URE, HYDRONEPHROSIS, OBSTRUCTIVE NEPHROPATHY,
yE-SICOURETERIC REFLUX, PRIMARY MEGAURETER.
long-term effect of corrective surgery on renal
function has been poorly documented.2’4
It was the purpose of this study to define the
conditions in which corrective surgery can
im-prove renal function or prevent progressive loss
of renal function.
Twenty-four patients with severe congenital
obstructive nephropathy have been followed for
1 to 12 years after surgical treatment.
Improve-ment and normalization of renal function was
only seen in patients operated upon during the first year of life.
PATIENTS AND METHODS
Case Selection
Severe obstructive nephropathy was defined as
follows: (1) radiologically evident bilateral
hy-dronephrosis, or unilateral hydronephrosis with a
solitary kidney. (2) Low endogenous creatinine
clearance at the time of or immediately after
sur-gery.
Twenty-four patients with severe obstructive
nephropathy are included in this study. Twenty
out of 24 patients had radiologically evident
bi-Severe hydronephrosis due to congenital
chronic urinary tract obstruction or primary
ye-sicoureteric reflux occurs in infants and children.’
Obstruction to the outflow from the kidney as
well as reflux can produce renal damage and a
progressive silent deterioration of renal
func-tion.24
Obstruction can be relieved and reflux
abol-ished by various surgical procedures, but the
(Received September 10; revision accepted for publication November 26, 1974.)
Supported in part by grant No. 3. 749. 72 from the Fonds National Suisse de Ia Recherche Scientifique.
Read in part before the European Society for Paediatric Nephrology, Lausanne, Switzerland, July 10, 1974, and in part before the 31st international congress of the British As-sociation of Paediatnc Surgeons, Berne, Switzerland,
Au-gust 29, 1974.
TABLE I
DATA IN 12 PATIENTS OPERATED UPON BEFORE 1 YEAR OF AGE
Patient Sex Diagnosis
Age at Definitive Relief of Stasis Clearance Values at Follow-up0 Duration of Follow-up After Definitive Relief
r- At End
At Start .
Ccv GIN Crur
S.G. M Posterior urethral valve; bilateral megaureters; right
vesicoureteric reflux; small right kidney
3 wk 47 95 - - 1 yr 0 mo
E.O. M Posterior urethral valve; bilateral megaureters 13 mo 52 101 125 490 4 yr 6 mo
C.H. M Bladder neck obstruction; bilateral megaureters; right
vesicoureteric reflux; small right kidney
2 mo 47 1 17 1 17 486 5 yr 1 mo
D.S. NI Primary right megaureter; left renal agenesis 8 mo 67 101 116 570 7 yr 6 mo
H.P. M Primary bilateral megaureters; small right kidney 3 mo 47 87 106 415 2 yr 6 mo
S.A. F Primary bilateral megaureters 4 mo 63 101 1 13 588 2 yr 3 mo
E.J. M Hypospadias with urethral meatus stenosis; bilateral vesicoureteric reflux
8 mo 15 63 64 249 7 yr 0 mo
G.T. M Posterior urethral valve; bilateral megaureters; left vesicoureteric reflux
5 wk 37 69 53 389 1 yr 6 mo
G.S. M Prune belly syndrome with bladder neck obstruction 4 wk 30 93 80 405 4 yr 2 mo
R.X. M Primary left megaureter; small right kidney 12 mo 22 64 40 200 6 yr 8 mo
T.J. M Primary right vesicoureteric reflux; right megaureter; left renal agenesis
6 mo 27 81 79 404 5 yr 6 mo
G.x.
M
Primary left vesicoureteric reflux; left megaureter; right renal agenesis#{176}Clearance values are expressed in milliliters per minute per
3 mo
1.73 sq m.
23 52 41 162 3 yr 11 mo
lateral hydronephrosis and four out of 24 had chronic hydronephrosis on a solitary kidney. Diagnosis was based on clinical, radiological, and endoscopic criteria. Congenital malformations responsible for the development of hydronephro-sis in these patients were pelviureteric ob-struction (one case), vesicoureteric obstruction
(
primary megaureter) (four cases), primaryye-sicoureteric reflux (eight cases), functional or an-atomical obstruction of the bladder outlet (six cases), posterior urethral valves (four cases), and
urethral meatus stenosis (one case). Details of
in-dividual diagnosis are listed in Tables I, II, and
III. Neurogenic bladder obstruction has been
excluded from this study.
The purpose of surgical treatment was to
sup-press definitively both renal stasis and vesico-ureteric reflux (Table IV). Persistence of stasis
after initial repair was corrected subsequently.
Recurrence of stasis or reflux was excluded by
regular uroradiologicat investigations.
Most of the patients presented with urinary tract infection at the time of diagnosis.
Prophy-lactic medical treatment of urinary tract
in-fection was given for at least six months after
surgery. Repeat bacteriological cultures were
performed at monthly intervals. Urinary tract
in-fection was definitely eradicated in all cases.
Methods
Assessment of Renal Function-The 24-hour
endogenous creatinine clearance5 was used to
assess glomerular filtration rate (GFR) after sur-gery. In six out of 24 patients creatinine
clear-ance was also determined before surgery.
Deter-mination of creatinine clearance was repeated
regularly at six-month to two-year intervals. In-dwelling catheters were not routinely used for this purpose. Great care was taken to secure
completeness of the 24-hour urine collection.
When in doubt, collection was repeated.
From 1972, determination of inulin and PAH
clearances were added to the protocol. The clearances of inulin and PAH were determined by the constant infusion technique over a period of four hours. Five urine specimens were
ob-tamed from a bladder catheter, and blood
sam-ples were collected at the midpoint of each urine
collection period. Clearances were calculated by
urn-RESULTS
TABLE II
DATA IN SIX PATIENTS OPERATED UPoN BETWEEN 1 AND 2 YEARS OF AGE
Clearance Values
Age at atFollow-up#{176}
Duration of Follow-up
After Definitive
Relief
Definitive At End
Relief of At Start
Patient Sex Diagnosis Stasis Ccr Cc CIN CPA,!
M.M. M Posterior urethral valve; bilateral megaureters; 1 yr 1 mo 51 50 -
-bilateral vesicoureteric reflux
4 yr
S.S. NI Urethral fibroelastosis; bilateral vesicoureteric 1 yr 7 mo 47 50 -
-reflux ; bilateral megaureters
4 yr
P.P. Ni Bladder neck obstruction; bilateral megaureters; 1yr 5 mo 43 52 50 179 l)ilateral vesicoureteric reflux
10 yr
C.G. \I Bladder neck obstruction; bilateral megaureters; 6 mo 50 60 -
-small bilateral kidneys
8 yr
B.L. F Primary bilateral vesicoureteric reflux; bilateral 2 yr 7 mo 47 71 79 339
megaureters ; small bilateral kidneys
3 yr 7 mo
C.L. F Primary left vesicoureteric reflux; left megaureter; 2 yr 3 mo 23 15 16 44
right renal agenesis
12 yr
#{176}Clearaiice values are expressed in milliliters per minute per 1.73 sq rn
TABLE III
DATA IN Six PATIENTS OPERATED UPON AFTER 2 YEARS OF AGE
Clearance Values Age at at Follow-up0
Duration of Follow-up
After Definitive
Relief
Definitive r- At End
Relief of At Start
Patient Sex Diagnosis Stasis Ccv Cr CIN CPA,!
AN. M Bladder neck obstruction; bilateral megaureters; 2 yr 9 mo 60 45 36 97
small left kidney
1 1 yr 4 mo
DY. F Primary bilateral vesicoureteric reflux; bilateral 17 yr 0 rno 40 55 -
-small kidneys
1 yr 0 mo
CD. M Primary bilateral vesicoureteric reflux; bilateral 7 yr 0 mo 73 65 -
-megaureters
10 yr 0 mo
Q.C. M Primary bilateral vesicoureteric reflux; bilateral 3 yr 2 mo 78 80 67 260 megaureters
1 yr 9 mo
FR. NI Primary bilateral vesicoureteric reflux; bilateral 12 yr 2 mo 21 55 -
-megaureters; bilateral small kidneys
4 yr 0 mo
G.E. NI Right pelvic-ureteric obstruction; left renal 3 yr 8 mo 42 10 7.6 30.9
agenesis
7 yr 0 mo
#{176}Clearance values are expressed in milliliters per minute per 1.73 sq m.
nary tract infection (nitrofurantoin, 1 mg/kg/ 24 hr) was given for a week following the
proce-dure, and bacteriological culture repeated
after-wards.
Analytical Methods-Urine and serum
creati-nine were measured by an auto-analyser
adapta-tion of the Jaff#{233}reaction. Inulin was measured in
plasma and urine by the method of Heyrovsky.6
PAH in plasma and urine was measured
accord-ing to Bratton and Marshall’s reaction.7
Patients were divided into three groups,
ac-cording to the age at which diagnosis and
surgi-cal treatment were performed. Group 1 includes
12 patients operated upon before 1 year of age.
Group 2 includes 6 patients operated upon
be-tween 1 and 2 years of age. Group 3 includes 6
patients operated upon after the age of 2 years.
Pertinent data in patients of each group are
diagnosis of the congenital malformation in each
case, age at the time of definitive relief of stasis
or reflux, duration of follow-up, creatinine
clear-ance at the time of surgery and at the end of the
follow-up period, and inulin and PAH clearances
at the end of the follow-up period.
Changes in GFR (Cr) following surgical
treat-ment in patients operated upon before 1 year of age (group 1) are illustrated in Figure 1. In all
patients of this group, a striking improvement in
GFR was observed after surgical treatment. In
eight out of 12 patients, creatinine clearance reached normal values after the surgical relief of obstruction. In four patients with a marked
de-crease in GFR at the time of treatment, creati-nine clearance rose towards nomal values with-out reaching them during the follow-up period.
(‘1
E
I.-a,
C
E
E
C,
C,
TABLE N
STANDARD SURGICAL TECHNIQUES UTILIZED
Pyeloplasty according to Anderson1’ in pelvi-ureteric
obstruction
Ureterocystoneostomy according to Mathisen (cited in Genton’4) up to 1967 and according to Politano’5
from 1967 in vesicoureteric obstruction and primary vesicoureteric rellux
Repair of megaureter according to Hendren’6 in severe megaureter from 1971
Posterior urethral valves and bladder outlet obstruction
with severe detrusor hypertrophy were repaired in
three steps:
(1)
Ureterocutaneostomy,(2) Endoscopic resection of the valves with or with-out anterior Y-V plasty of the bladder neck,
(
3) Repair according to Hendren16 and Politano’5YEARS
FIG. 1. Changes in GFR following surgical treatment of hydronephrosis in 12 children oper-ated upon before 1 year of age. Solid-line curve and cross-hatched area, range of normal
140
120
I
123456781011 13 14 15 16YEARS
FIG. 2. Changes in GFR following surgical treatment of hydronephrosis in six children
oper-ated upon between 1 and 2 years of age. Symbols are the same as in Fig 1.
2 3 4 12 14 16
YEARS
7 8
1 2 3 4 5 10 11 12 13 11. 15 16
. YEARS
FIG. 4. Changes in GFR following surgical treatment of hydronephrosis in four children with solitary kidney. Symbols are the same as in Fig 1.
FF
Si ‘S
100
**
4001
300-
200-
100-
20-**
L
c1
Cr)
r..
4,
a-C
E
E
U C.)
cm
CPAH- nWrrE) per 1.73 m2
-
500-LII GROUP 1
1111
GROUP 2FIG. 5. Glomerular filtration rate (CIN), effective renal plasma flow (C,A,J), and filtration
frac-tion (CIN/CPAH) in children after surgical treatment of hydronephrosis. Data for 11 subjects
operated upon before 1 year of age (white area) are compared with those for 6 subjects
oper-ated upon after 1 year of age (cross-hatched area). Mean values are those observed at the end
The longest follow-up in this group was seven
years.
Changes in GFR observed in patients operated
upon between 1 and 2 years of age (group 2) are
illustrated in Figure 2. In these patients no
improvement of renal function was observed
af-ter corrective surgery. GFR, however, remained
stable in the follow-up period. The longest
obser-vation period was 12 years.
Changes in glomerular filtration rate in
pa-tients operated upon after 2 years of age (group
3) are illustrated in Figure 3. In five out of six
pa-tients, surgical treatment was followed by a slow
and progressive deterioration of GFR. Three
pa-tients (D.Y., C.D., and F.R.) developed systemic
hypertension. Terminal renal failure occurred in
four patients: two have received transplants and
two are now receiving hemodialysis. This
pro-gressive deterioration of renal function occurred
without recurrence of the urinary stasis or
infec-tion. The longest follow-up period in this group
was 11 years. One patient in this group (D.Y.)
presented with primary vesicoureteral reflux.
Diagnosis was made when she was 3 years old.
She had urinary tract infection and bilateral
small kidneys. Because of the parents’ refusal of
surgical treatment, the natural history of the
dis-ease could be followed for 12 years. During this
time, a slow progressive deterioration of renal
function was observed. At 15 she was admitted to
hospital with hypertension and renal
insuffi-ciency. Correction of reflux did not stop the
evo-lution towards terminal renal failure.
Four out of 24 patients presented with a
soli-tary kidney and hydronephrosis (controlateral
re-nal agenesis). Figure 4 shows the changes in GFR
observed in these patients. Evolution of GFR
fol-lowed the same pattern as described for patients
with two kidneys. A significant improvement in
GFR was noted in two patients operated upon
before 1 year of age. A stabilization or a decrease
in GFR was observed in patients operated upon
after the age of 1 year.
Inulin and PAH clearances were measured
during the two last years of the study in 17 out of
24 patients. Values of inulin clearance correlated
well with that of endogenous creatinine. The
re-sults of inulin and PAH clearances observed at
the end of the follow-up period are described in
Tables I, II, and III.
Figure 5 shows the mean values of C1\, CPAH,
and filtration fraction (CIN/CPAH) observed at the
end of the follow-up period. Patients operated
upon before 1 year of age (group 1) have been
compared to patients operated upon after 1 year
of age (groups 2 and 3). A significant decrease in
both GFR and effective renal plasma flow was
observed in patients operated upon after 1 year
of age. The decrease in effective renal plasma
flow tended to be somewhat greater than the
de-crease in GFR. As a result, mean filtration
frac-tion was higher in patients from groups 2 and 3.
COMMENTS
In the present study, surgical relief of chronic
urinary tract obstruction was followed by a last-ing improvement of renal function only in those
patients operated upon before 1 year of age.
When patients were operated upon between 1
and 2 years of age, renal function did not
im-prove but remained stable at a low level. Finally,
when patients were operated upon after 2 years
of age, a slow and progressive deterioration of
re-nal function occurred in the years following
sur-gical treatment.
In this study, the evolution of renal function
was assessed by the clearance of endogenou.s
cre-atinine. Because creatimne clearance often
over-estimates true GFR at low levels of GFR,8 inulin
clearance was also studied in these patients
dur-ing the two last years of the study. Changes in
inulin and creatinine clearances followed the
same pattern, and a significant decrease in inulin clearance was observed at the end of the
follow-up in patients operated upon after 1 year of age.
Effective renal plasma flow, as studied by the
clearance of PAH, was also markedly decreased
in patients operated upon after 1 year of age.
The fall in CIAII tended to be more pronounced
than that of CIN, resulting in a higher filtration
fraction in these patients, as observed in chronic
pyelonephritis.9
A similar permanent decrease in effective
re-nal plasma flow and GFR has been observed in
dogs after transient (one week) ureteral
obstruc-tion,1#{176}thus suggesting that permanent nephron
destruction occurs after seven days of total
ure-teral obstruction. A slower but similar
destruc-tion of nephrons could occur in children with
chronic hydronephrosis.
The striking improvement of GFR observed in
patients operated upon during the first year of
life shows the reversibility of the functional
dam-age in its early stage. This improvement could
reflect the high capacity of the newborn kidney
for compensatory hypertrophy.”12 It should be
pointed out, however, that in four patients with a
marked decrease in GFR at the time of surgery,
renal function improved after treatment but did
not return to normal. The capacity for
com-pensatory hypertrophy thus appears to be related
The failure of children operated upon after 1
year of age to improve GFR after treatment could be due to the presence of irreversible renal lesions at the time of surgery. Lack of improve-ment could also reflect a state of maximal hyper-trophy already present when obstruction is
re-lieved. It is indeed possible that in these children
the renal compensatory response to nephron dam-age is already fully utilized at the time of treat-ment.
Renal function did not improve, but remained
stable at low levels in patients operated upon
be-tween 1 and 2 years of age. The follow-up in the
six patients of this group ranged from 3 to 12
years. The older child (D.L.) is now 14 years old.
The long-term prognosis of these patients is
diffi-cult to predict. A progressive deterioration of
re-nal function in the next years is not excluded.
The progressive irreversible deterioration of
renal function in patients operated upon after 2
years of age is difficult to explain. This deteri-oration appeared without detectable recurrence of urinary stasis or infection. In three patients the rapid decrease of renal function towards terminal renal failure was concomitant with pubertal
de-velopment. In one boy, terminal renal failure
oc-curred when the patient was 10 years of age. A
causal relationship between growth or pubertal
maturation and the progressive deterioration of
renal function remains to be determined.
The lack of any improvement in kidney
func-tion when corrective surgery is performed after 1
year of age indicates the need to intervene early
before an irreversible state has developed. It thus
appears essential to diagnose and to correct
Se-vere chronic hydronephrosis associated with
re-nal insufficiency before 1 year of age if an
im-provement of renal function is to be expected.
REFERENCES
1. Campbell M: Hydronephrosis in infants and children. J
Urol 65:734, 1951.
2. McCrory WW, Sibuya MD, Leumann E, Karp R:
Stud-ies of renal function in children with chronic hy-dronephrosis. Pediatr Clin North Am 18:445, 1971.
3. Salvatierra 0, Kountz SL, Belzer FO: Primary vesico-ureteral reflux and end-stage renal disease. JAMA
226: 1454, 1973.
4. Mayor G, Torrado A, Genton N, Guignard JP: A follow-up study of renal function in post-obstructive nephropathy, abstracted. Pediatr Res, to be pub-lished.
5. Winberg J: The .24-hour true endogenous creatinine clearance in infants and children without renal disease. Acta Paediatr 48:443, 1959.
6. Heyrovsky A: A new method for the determination of inulin in plasma and urine. Clin Chim Acta 1:471,
1956.
7. Bratton AC, Marshall EK: A new coupling component for sulfanilamid determination. J Biol Chem
128:537, 1939.
8. Arant BS, Edelmann CM, Spitzer A: The congruence of creatinine and inulin clearances in children: Use of the Technicon-autoanalyzer. J Pediatr 81:559, 1972.
9. Reubi F: Nephrologie clinique. Paris, Masson & Cie, 1972, p 93.
10. Kerr WS Jr: Effects of complete ureteral obstruction for one week on kidney function. J Appl Physiol
184:521, 1956.
11. Dicker SE, Shirley DG: Compensatory renal growth
af-ter unilateral nephrectomy in the newborn rat. J Physiol 228: 193, 1973.
12. Karp R, Brasel J, Winick M: Compensatory kidney growth after uninephrectomy in adult and in in-fant rats. Am J Dis Child 121:186, 1971.
13. Anderson JC: Modern Trends in Urology. London, But-terworth, 1953.
14. Genton N: Traitement des anomalies de la jonction ur#{233}t#{233}ro-vesicalepar ur#{233}t#{233}ro-n#{233}o-cystostomieselon
Mathisen. Helv Chir Acta 28:617, 1961.
15. Politano VR: An operative technique for the correction
of vesico-ureteral reflux. J Urol 79:932, 1958.
16. Hendren WH: Operative repair of megaureter in chil-dren. J Urol 101:491, 1969.
ACKNOWLEDGMENT
