I. Wikstad

Five-year study of medical or surgical treatment in children with severe reflux: radiological renal findings: The International Reflux Study in Children

The renal findings on intravenous urography (IVU) are reported in 306 children (73 boys, 233 girls) from eight European centres entered into an international study comparing medical and surgical management of children with urinary tract infection and severe vesico-ureteric reflux followed for 5 years. One hundred and fifty-five children were randomly allocated to medical and 151 to surgical treatment. Protocol and investigative techniques were standardised and randomisation, data collection and analysis were performed centrally in Essen, Germany. At entry 149 (49%) has established renal scarring (79 medical, 70 surgical). Children with normal kidneys (105), areas of thinned parenchyma (52) and grade of reflux were also evenly distributed. IVU was repeated at 6, 18 and 54 months and serial urine culture,99mtechnetium-dimercaptosuccinic acid scans and plasma creatinine estimations were performed. Two hundred and seventy-two children (89%) completed this follow-up. In 174 children (57%), (90 medical, 84 surgical) there was renal growth without morphological change. New renal scars developed in 19 children treated medically and 20 surgically; 12 (5 medical, 7 surgical) developed in previously normal kidneys. Six followed post-operative obstruction. No significant difference in outcome was found between medical or surgical management in terms of the development of new renal lesions or the progression of established renal scars.

Kidney function in adults born with unilateral renal agenesis or nephrectomized in childhood

We have evaluated the long-term prognosis in an unselected group of adult patients either uni-nephrectomized in childhood because of hydronephrosis or born with unilateral renal agenesis. Thirty-six patients aged 7–47 years were followed for 7–40 years. In 23 control subjects aged 20–47 years the glomerular filtration rate (GFR) and thep-aminohippuric acid clearance (CPAH) did not change significantly with age. In patients with a single kidney the size of that kidney was larger and GFR and CPAH were higher than single kidney values in control subjects. However, in patients with a single kidney since childhood the GFR and the CPAH declined slowly but significantly during the follow-up period. Significant microalbuminuria occurred in 47% of the patients with a single kidney and was more frequent with a longer follow-up period. No patient had renal insufficiency or a marked increase in arterial blood pressure. We conclude that in patients with a single kidney since childhood the long-term prognosis is good, but the late decrease in GFR and increase in albumin excretion may indicate a moderate risk for premature renal damage.

Urine interleukin-6 and interleukin-8 in children with acute pyelonephritis, in relation to DMSA scintigraphy in the acute phase and at 1-year follow-up

The relationship between urine interleukin-6 (IL-6) and interleukin-8 (IL-8)/creatinine quotients and99mTc-dimercaptosuccinic acid (DMSA) scintigraphy, performed within 10 days of acute first-time pyelonephritis and after 1 year, was studied in 41 children. The urine IL-6 and IL-8/creatinine quotients were also related to the urineN-acetyl-β-D-glucosaminidase (NAG) and albumin/creatinine quotients. Presence of DMSA uptake defects, reflecting local inflammation, in children in the acute phase of pyelonephritis, were associated with elevated urine IL-6/creatinine quotients (median 27 pg/μmol); in children without DMSA changes there was no increase in quotients (median non-detectable) (P<0.05). Persistent DMSA changes at the 1-year follow-up, probably reflecting renal scarring, were only seen in children with increased urine IL-6/creatinine quotients in the acute phase (P<0.01). No correlation was found between urine IL-8 and DMSA uptake defects. Vesicoureteral reflux (VUR) at 6–8 weeks did not correlate with the urine cytokine levels in the acute phase. The urine excretion of NAG and albumin, reflecting renal dysfunction, was associated with values of both urine IL-6 and IL-8/creatinine quotients, but not with DMSA defects or VUR. Thus, the initial urine IL-6/creatinine quotients might be used as an indicator of risk for persistent renal damage in acute pyelonephritis.

RENAL GROWTH AND FUNCTION IN PATIENTS NEPHRECTOMIZED IN CHILDHOOD

Abstract Aperia, A., Broberger, O., Wikstad, I. and Wilton, P. (Department of Paediatrics and Paediatric Radiology, Karolinska Institute, St. Görans Childrens Hospital, Stockholm, Sweden). Renal growth and function in patients nephrectomized in childhood. Acta Paediatr Scand, 66:185, 1977.—Eight patients nephrectomized in childhood were studied with regard to growth and function of the remaining kidney. The age of the patients ranged between 8½ and 31 years and the follow‐up period was from 1 to 20 years. In most of the patients, repeated renal size determinations were made on postoperative urograms. Normal values for kidney size in childhood are also presented. The structural hypertrophy continued for at least three years after nephrectomy and was most pronounced in patients nephrectomized before three years of age. When more than three years had passed after nephrectomy the remaining kidney was 35–65% larger than normal. Healthy young adults and children with a previous history of urinary tract infection served as controls for function studies. The balance between glomerular and tubular function was well preserved in nephrectomized patients. The renal surface area showed the same relation to GFR and to reabsorption of bicarbonate in nephrectomized patients as in controls. It is therefore concluded that the increase in kidney function following unilateral nephrectomy is, at least in early life, primarily due to structural enlargement.

99mTechnetium dimercaptosuccinic acid scintigraphy in the diagnosis of acute pyelonephritis in rats

The use of99mtechnetium dimercaptosuccinic acid (99mTc-DMSA) scintigraphy for the early diagnosis of pyelonephritis has been evaluated in a study performed on adolescent female Sprague-Dawley rats exposed to an ascendingEscherichia coli infection. The rats were studied with DMSA scintigraphy either before and 5 days after the infection or 5 and 28 days after the infection. One group of rats received anti-microbial treatment during days 6–11. After the last DMSA scintigraphy the rats were sacrificed and the kidneys prepared for light microscopy study. Kidney morphology was normal and DMSA uptake was high and homogeneous in all control rats. The majority of the rats exposed toE. coli developed inflammatory changes, on light microscopy which extended to various degrees in the renal parenchyma. Five days after the infection the DMSA uptake was consistently reduced, if the inflammatory lesion on light microscopy involved more than 15% of the renal cortex. Twenty-eight days after infection the inflammatory changes were less extensive than at 5 days. The DMSA uptake had usually improved. At this time, however, areas of decreased DMSA uptake could be detected even if the light microscopy changes involved less than 15% of the parenchyma. Microscopical lesions were less frequent and less extensive in the treated than in the untreated rats. The complete return to normal of previously abnormal DMSA uptake was only observed in treated rats. In a few untreated rats cortical scars had formed by day 28. The scars appeared in areas with decreased DMSA uptake at 5 days. The results imply that DMSA scintigraphy is a valuable method for the early diagnosis and for the localization of pyelonephritis.

A Comparative Study of Size and Function of the Remnant Kidney in Patients Nephrectomized in Childhood for Wilms’Tumor and Hydronephrosis

ABSTRACT. To obtain more information about the natural history of compensatory renal hypertrophy beginning in childhood we traced those who were nephrectomized in childhood for Wilms tumor (W) and hydronephrosis (Hn) between 1950 and 1978 at one department of surgery in Stockholm. AH W patients had received treatment that suppresses cellular division. None of the patients were in renal failure or treated with antihypertensive drugs. All the patients in the follow‐up study (22 W, 15 Hn) had a normal contralateral kidney at nephrectomy. Five healthy adults served as controls. The kidney was enlarged in both Hn (142 %) and W (125 %), but significantly larger in Hn than in W. Renal compensatory growth in W was retarded during the first two years after nephrectomy. The glomerular filtration rate (GFR) was 92 % of control in Hn and 82 % of control in W. The GFR did not seem to decline with a longer follow‐up time in any of the groups. PAH clearance was the same in Hn and W. Albumin excretion was significantly higher in Hn than in W, but not significantly higher in W than in controls. The highest albumin excretion rates were found among the Hn patients with long follow‐up time. The results suggest that the large increases in size and function that follow childhood nephrectomy can be blunted by antimitotic agents.

Renal involvement in the Laurence-Moon-Biedl syndrome. Functional and radiological studies.

ABSTRACT. The renal abnormality of the Laurence‐Moon‐Biedl syndrome (LMBS) was investigated in six patients. The glomerular filtration rate (CIn) and the effective renal plasma flow (CPAH) were evaluated by standard clearance techniques and the single injection method, and the maximal concentration capacity was estimated by the ddAVP test. The kidney surface area and length were related to the body surface area, as well as the lumbar vertebrae L1‐L3, and the relationship with the GFR was studied. All six patients showed renal abnormalities: Five had small kidneys with reduced GFR and concentrating ability, and one had hyperaminoaciduria (but normal kidney size). Two patients developed terminal renal failure (one of them was successfully transplanted), illustrating the progressive character of the renal lesion. Three of the patients had had recurrent urinary tract infections, but the radiological changes of the kidneys were of the same character as in the others (symmetrical and irregular parenchymal reduction, and blunting and clubbing of the calyces). Since renal abnormalities, with considerable risk for progression to terminal renal failure, are common in the LMBS, regular urine cultures and blood pressure measurements are probably of great importance.

Interleukin‐1α and interleukin‐1 receptor antagonist in the urine of children with acute pyelonephritis and relation to renal scarring

Urinary concentrations of interleukin‐lα (IL‐lα) and interleukin‐l receptor antagonist (IL‐Ira) standardized to urinary creatinine concentrations were studied. The median standardized IL‐1α creatinine quotient in children with first‐time acute pyelonephritis was 3.6 pg/μmol, but was non‐detectable in children with recurrent pyelonephritis, children with non‐renal febrile conditions and children convalescent after acute pyelonephritis (p < 0.05–0.01). IL‐lra levels were also significantly higher in children with acute first‐time pyelonephritis (median of 239 pglpmol) compared to these three groups of children (p < 0.01–0.001). The highest urinary 1L‐lra levels, however, were found in the healthy controls (median value 1.019; p < 0.001). Both cytokines were higher among children younger than one year compared to older children. The acute IL‐lα creatinine quotients were lowest in children with uptake defects on 99mTC‐dimercaptosuccinic acid (DMSA) scintigraphy both during the acute infection (reflecting the acute inflammation) (p < 0.001) and 1 year after the acute infection (reflecting permanent kidney scarring) (p < 0.01). In conclusion, persisting high urinary levels of 1L‐lα were associated with less renal inflammation and scarring.

Incidence of microalbuminuria in children with pyelonephritic scarring

Abstract. There is experimental evidence that loss of renal parenchyma results in hyperfiltration in the remnant glomeruli followed by development of glomerulosclerosis. Microalbuminuria, i.e., a urinary albumin excretion rate of 20 – 200 μg/min, is considered to be an early predictor of diabetic glomerulosclerosis. Hypothetically, increased urinary albumin excretion in patients with pyelonephritic scarring may also indicate glomerulosclerosis, with risk for future deterioration of renal function. This study was performed to determine the incidence of increased albumin excretion in children with mild to moderate pyelonephritic scarring, and to relate the information to glomerular filtration rate (GFR; clearance of inulin) and effective renal plasma flow (clearance of para-aminohippuric acid), as well as to the degree of scarring. The functional investigations were performed under water diuresis. Fifty-seven children, aged 1.7 – 17.9 years, with pyelonephritic renal scarring were included in the study. Nine young healthy adults were used as controls. The GFR was significantly lower in the children with pyelonephritic scarring than in the controls (median 93 ml/min per 1.73 m2, range 48 – 133 vs. 111 ml/min per 1.73 m2, range 89 – 121, P<0.05), and the urine albumin excretion was significantly higher (median 20 μg/min per 100 ml GFR, range 0.8 – 170 vs. 9.2 μg/min per 100 ml GFR, range 3.3 – 21, P<0.05). An inverse correlation was found between urine albumin excretion and GFR. Increased urine albumin excretion was found in 70% of the children with a GFR below 90 ml/min per 1.73 m2 compared with 41% of the children with a GFR above this level. Increased urine albumin excretion (>20 μg/min per 100 ml GFR) was found in 51% of the children with pyelonephritic scarring, while only 14% had increased age-adjusted serum creatinine concentrations. The high incidence of microalbuminuria in children with pyelonephritic scarring indicates long-term follow-up until the ultimate outcome has been better defined.

Functional parameters and99mtechnetium-dimercaptosuccinic acid scan in acute pyelonephritis

The diagnostic value of99mtechnetium-dimercaptosuccinic acid (DMSA) scintigraphy, ultrasonography and renal functional parameters [urineN-acetyl-β-d-glucosaminidase (NAG)/creatinine and urine albumin/creatinine quotients] in acute pyelonephritis (APN) were studied in 39 children (28 girls, 11 boys, median age 9 months, range 2 weeks to 9.4 years, 28 patients <1 year, 11 patients >1 year) with first-time urinary tract infection. Ultrasonography of the urinary tract was performed on admission and together with DMSA scintigraphy (<10 days from admission). Urine NAG/creatinine and urine albumin/creatinine quotients were measured daily and after 6–8 weeks. Ultrasonography revealed abnormalities in 12 of 39 (31%) patients [11/32 patients (34%) with positive DMSA scintigraphy], while DMSA uptake defects were present in 32 of 39 (82%) patients [21/28<1 year (75%), 11/11 >1 year (100%),P=0.08]. Urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in children <1 year with APN, as well as in non-renal fever controls, than in older children. However, in both age groups the urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in APN than in non-renal fever. The urine NAG and albumin excretion decreased rapidly after the initiation of antimicrobial therapy and had normalized at 6–8 weeks. The size and grade of the DMSA uptake defect (DMSA score) did not correlate with duration of disease at admission, maximum C-reactive protein or maximum fever. The urine NAG/creatinine quotient in the children <1 year showed, however, a significant correlation with the DMSA score (r=0.58,P<0.05), while no correlation was found in the older children. We conclude that DMSA scintigraphy is a sensitive method to confirm the clinical diagnosis of APN, although a substantial number of infants appear to have normal scans. Early determination of the urine NAG/creatinine and albumin/creatinine quotients may further improve the diagnostics in the infant.