Distribution of renal scars and intrarenal reflux in children with a past history of urinary tract infection.

The distribution of renal scars in children with vesicoureteral reflux (VUR) and a past history of urinary tract infection was studied to see whether a correlation existed between renal scarring and intrarenal reflux. In 37 children with one or more scars in one or both kidneys, scarring was significantly more frequent in the polar areas than in the lateral area. In 7 children with intrarenal reflux (IRR), the distribution of IRR was almost identical with that of renal scarring. When children with marked VUR (grade IV-V) were analyzed separately, a uniform distribution of scars was found. It was concluded that fused papillae, which normally are most frequent in the polar area, are a prerequisite for the development of IRR/renal scars.

Increased fractional excretion of phosphate and beta 2-microglobulin in unilateral renal disease.

UNLABELLED: Following progressive nephron loss tubular reabsorption in the remaining nephrons will fall to preserve solute and electrolyte excretion. We have examined the fractional excretion (FE) of phosphate, sodium, beta 2-microglobulin (beta 2M) and tubular glucose reabsorption (T glucose) in children with unilateral renal disease to find 1) the threshold for this response and 2) whether intrinsic renal mechanisms can elicit this response. Separate renal function studies were performed using unilateral ureteral compression. Total glomerular filtration rate (GFR) was 93.7 +/- 2.99 ml/1.73(m2)-1 X min-1, and 110.25 +/- 5.40 in control children. GFR in the scarred kidney (SK) was 22.4 +/- 2.46 and in the contralateral kidney (CIK) 67.2 +/- 4.60 ml X 1.73 (m2)-1 X min-1. The kidney area was reduced in proportion to GFR in SK. FE phosphate and beta 2M were significantly higher in SK than in CIK (sign test), but absolute values for FE phosphate and beta 2M were not higher in SK than in control kidneys. FE sodium and T glucose were the same in SK and CIK. CONCLUSION: Following moderate unilateral reduction of GFR selective depression of tubular reabsorption can occur without extrarenal impulses.

Renal function in relation to metabolic control in children with diabetes of different duration.

To evaluate the interpretation of different kidney function tests in diabetic children and teenagers we have studied 47 children with a duration of diabetes up to 5 years, 61 children with a duration of 5.1-10 years and 49 children with a duration of greater than 10 years. Glomerular filtration rate (GFR) measured as inulin clearance or creatinine clearance, clearance PAH (CPAH), filtration fraction (FF), 24-hour urinary excretion of beta 2-microglobulin and albumin were examined and correlated with short- and longterm indices of metabolic control. In all groups of duration GFR as measured by inulin clearance was increased compared with reference values from age matched controls. In patients who had had diabetes for 0-5 years a significant positive correlation was found between inulin clearance and blood glucose during the examination. Inulin clearance was also correlated to HBA1c as well as to 24-hour urinary glucose (mean of 4-6 samples during two years). No such correlation was found in the group who had had diabetes for 5-10 years but in patients with a duration of diabetes greater than 10 years a significant inverse relation was found between GFR and HbA1c. The 24-hour urinary excretion of albumin was significantly higher in all groups of diabetics compared with controls. The urinary excretion of beta 2-microglobulin was similar in diabetics and controls. In the total material no significant correlation could be found between inulin clearance and creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Postnatal control of water and electrolyte homeostasis in pre-term and full-term infants.

A review is given of the progress which has been made during the last decade within the field of renal control of water and sodium homeostasis in newborn infants of varying gestational age. Both preterm and full-term infants have a low capacity for rapid excretion of a salt load. The natriuretic response improves gradually up to the age of 15 months. The capacity to excrete a load of sodium bicarbonate is higher than to excrete a load of sodium chloride. Under basal conditions preterm infants of a gestational age below 35 weeks have a higher renal sodium excretion than full-term infants. They also appear to be unable to retain sodium when in negative balance. The capacity to concentrate the urine is low in newborn infants, the maximal osmolality being only slightly above that of plasma. The concentrating capacity increases relatively fast during the first 4-6 postnatal weeks in full-term as well as in pre-term infants but does not reach the adult level until the second year. Water loaded newborn infants are able to excrete a urine with a osmolality as low as 30-50 mOsm per kg. In full-term infants free water clearance per unit filtered water is higher than in adults. Water-loaded pre-term infants with a gestational age of more than 30 weeks also have a supernormal diluting capacity.

Influence of diuresis on the degree of vesicoureteral reflux. An experimental investigation in rats.

The influence of bladder filling volume (BV), bladder pressure (BP) and diuresis (V) on the occurrence of vesicoureteral reflux (VUR) in Sprague-Dawley rats, where spontaneous VUR is common, has been investigated. The BV and BP at which VUR occurred during constant low diuresis (group I), high inconstant diuresis (group II) and moderately high, constant diuresis (group III), was measured. The abdomen was opened for visual observation of the VUR. The bladder was catheterized with a double-lumen metal catheter for infusion of a Lissamine green saline solution and to enable recording of BP. VUR occurred at significantly lower BV in group II than in group I and at significantly lower BV and BP in group I than in group III.

Glomerular tubular balance in preterm and fullterm infants.

The development of glomerular and tubular function was studied in preterm and fullterm infants of varying gestational and postnatal age. The results indicate that glomerular functional development precedes tubular functional development until the 34th postmenstrual week. After the 34th week the tubular transport capacity seems to be more vulnerable than the glomerular filtration rate in states of disease. The release of a postulated renal vasoconstriction could account for the rapid changes in renal function after birth. The purpose of such a vasoconstriction could be to protect the tubules from an overload.

Renal function and biopsy changes during the course of Henoch-Schönlein glomerulonephritis.

Renal function studies were performed in 18 subjects in different stages of Henoch-Schönlein glomerulonephritis (HS GN). Nine children were serially investigated, and nine adolescents or young adults, who were considered to have clinically recovered, were investigated only once, 10.5-14 years after the onset. Inulin and PAH clearance, as well as sodium excretion, were determined during hydropenia (HP) and 3% volume expansion (VE) with isotonic saline. In most patients in the former group a renal biopsy was performed during the first investigation and again one year later. The early disturbances in renal function resembled those we have found in other types of GN. The GFR was normal during HP or after VE in most cases one year after the onset. The natriuretic response to VE was decreased in most patients initially, and this was found to persist in half of the patients 2-3 years after the onset. Pathological urinalyses then indicated disturbances in the renal handling of sodium. A reduced capacity to excrete sodium, however, did not seem to be of prognostic significance since all patients, except one who developed renal insufficiency and hypertension, had normal urinalyses and blood pressure six years after the onset. This study provides no evidence that subjects with previous HS GN will later develop impaired renal function or be predisposed to hypertension.

Course of renal function in IgA glomerulonephritis in children and adolescents.

The pathophysiology of IgA GN was investigated in different stages of the disease. Seventeen patients who were between 3.5 and 16.5 years of age at the onset were included in the study. Clearance studies were performed repeatedly in 6 patients (in 5 of them over a period extending from the onset to 5-9.5 years) and only once in 9 patients (10-23 years after the onset). Two patients (one with uremia) were only evaluated clinically. CIn, CPAH and UNaV were studied during hydropenia (HP) and 3% isotonic saline volume expansion (VE). Shortly after the onset CIn, CPAH and UNaV were depressed. Renal function was essentially normal and 1 and 2 years after the onset in spite of signs of active disease. A supernormal GFR was found in 7 patients after they had had the condition between 5 and 17 years. After a duration of IgA GN for greater than 9 years 3 of 12 patients had developed hypertension and uremia and 2 had hypertension or labile BP. Three of 10 patients had a normal GFR and BP, but had increased natriuresis during VE. Only 2 of 10 patients were normotensive and had normal renal function. Disturbances in the renal function are thus frequent in all stages of IgA GN and the changes seem to be related to the duration of the disease. Exaggerated natriuresis may indicate progressive disease.

Implications of limitation of renal function for the nutrition of low birthweight infants.

Renal function is immature in low-birth-weight infants. The glomerular filtration rate is low during the entire first month of life. It is 20-50% of that observed in older children and adults. This limits the excretory capacity of the kidney and might set an upper limit for the protein intake. The capacity to reabsorb bicarbonate is not fully developed. This predisposes the low-birth-weight infant to metabolic acidosis. The capacities to excrete sodium when in positive sodium balance and to retain sodium when in negative sodium balance are limited. If the daily sodium balance is not well monitored, conditions of negative sodium balance with hyponatremia as well as of positive sodium balance with hypernatremia might occur.

Postnatal development of renal function in pre-term and full-term infants.

This study has been designed to examine the effect of gestational age (GA) on the postnatal development of renal function and has been performed in pre-term (PT) infants (GA=30-34 weeks) and in full-term (FT) infants (GA=39-41 weeks). Postnatal age has ranged from 1-35 days. From 8 hour urine samples collected after spontaneous voiding and a capillary blood sample, determinations have been made of the clearance of creatinine (CCr), the fractional excretion of beta 2-microglobulin (FE beta 2) and the fractional excretion of sodium (FENa). In some infants receiving fluid parenterally, simultaneous determinations were made of the clearance of creatinine and inulin. As judged from this study, CCr is a reliable indicator of the glomerular filtration rate (GFR). GFR was almost the same in newborn PT and FT, but from 0.3--1 week of age GFR increased significantly more rapidly in FT than in PT. From 1--5 weeks of age GFR increased at approximately the same rate in PT and FT infants. The absolute value for GFR in 3--5 weeks old infants was lower in PT than in FT. FE beta 2 was higher in PT than in FT infants during the entire first month of life and FENa was higher in PT than in FT infants during the first week of life, suggesting a glomerular tubular imbalance at least at the level of the proximal tubule in PT infants. It is concluded that different stages of maturation will alter the preconditions for the renal adaptation to extrauterine life during at least the first month of life. Therefore special attention must be paid to the limited renal function in PT during their entire first month of life.

Long-time effect of large vesicoureteral reflux with or without urinary tract infection.

In children more than one year old the growth rate of the renal parenchyma is delayed if the kidney has a large reflux-ureter and is exposed to urinary tract infection. The growth rate of the parenchyma is normal, if the kidney has a large reflux-ureter but no infection. However, since moderate reduction of the renal parenchyma is often observed in patients with large reflux-ureter but without a history of urinary tract infection, it is concluded that a large reflux may cause back pressure injury on the kidney during infancy but, in children more than one year old, will cause renal growth retardation and renal scarring only be predisposing to pyelonephritis.

Renal compensatory hypertrophy in children with unilateral renal disease.

Kidney parenchymal size was estimated on urograms from 22 children with unilateral vesico-ureteral reflux (VUR), 14 children with bilateral VUR and seven children with unilateral heminephrectomy. In the bilateral VUR group, one kidney was roentgenologically normal and the other was growth-retarded. The GFR was estimated in 19 of the children. The age of the children was 3-17 years and all had a history of urinary tract infection. The size of the smaller kidney varied between 33-97% of normal. Children in the unilateral VUR group with a small kidney due to scarring and/or growth retardation showed a varying degree of compensatory hypertrophy in the contralateral kidney, which was proportional to the parenchymal reduction. This compensation was inhibited in the bilateral VUR group. There was a positive correlation between the GFR and kidney size.

Sodium excretion in relation to sodium intake and aldosterone excretion in newborn pre-term and full-term infants.

The importance of aldosterone for the control of salt balance has been examined in pre-term infants (gestational age 28--34 weeks) and in full-term infants. The post-natal age has varied from 2--21 days. Eight-hour urinary specimens have been analysed with regard to sodium, potassium and aldosterone. The daily sodium intake has been recorded following determination of milk intake and analyses of sodium in breast milk. Due to variations of sodium content of breast milk, the daily sodium intake in pre-term infants was lower than in full-term infants during the first 10 days of life. The sodium excretion was significantly higher in pre-term infants than in full-term infants during the first six days of life. During the first week of life the sodium balance is negative in pre-term infants and positive in full-term infants. Aldosterone excretion is high during the first week of life and increases further from the 2nd to the 3rd week of life in both pre-term and full-term infants. The correlation between aldosterone excretion and urinary potassium/sodium quotient is 0.87 in full-term infants, 0.57 in pre-term infants aged 13--20 days and does not exist in pre-term infants aged 2--10 days. It is suggested that the high sodium excretion in newborn pre-term infants can in part be explained by an unresponsiveness to aldosterone at this developmental stage.

Studies of renal urea cycle enzymes. I. Renal concentrating ability and urea cycle enzymes in the rat during protein deprivation.

Activities of renal urea enzymes were studied in normally fed (21% dietary protein) rats and rats deprived of protein (6% dietary protein) for 3 weeks. Protein deprivation resulted in growth retardation and defective urine concentrating ability. Compared to rats on an optimal diet containing 21% of protein, the protein starved animals had decreased concentrations of protein and urea in serum, reduced urinary excretion of urea and decreased levels of all five urea cycle enzyme activities in the liver. In the kidney, however, protein malnutrition resulted in a significant increase in arginase specific activity from 11.5 +/- 1.1 to 16.3 +/- 1.5 (M +/- SD) whereas the other urea cycle enzymes remained unchanged. It is postulated that this increase in renal arginase might be an early compensatory mechanism to preserve a net synthesis of urea in a situation involving arginine deficiency, thereby preserving an intact hypertonic gradient in the renal medulla.

Studies of renal urea cycle enzymes. II. Human renal arginase activity and location of the adaptive changes of renal arginase in the protein deprived rat.

Rats fed 6% protein for 3 weeks with growth retardation and urinary concentration defect had 3 times higher arginase activity in the kidney cortex (10.8 +/- 28, M +/- SD) compared with controls fed 21% protein (3.3 +/- 0.9, M +/- SD). In the outer medulla there was a 50% increase of arginase activity whereas no change was observed in the inner medulla and papilla. Arginase activity in fresh human cortical tissue was of the same magnitude as in the rat. The results are in agreement with the hypothesis that intrarenal urea synthesis contributes to the maintenance of the intrarenal urea gradient in the protein deprived state. The response in the protein deprived rat might thus be an adaptation to a situation with substrate deficiency.

Renal sodium excretory capacity in infants under different dietary conditions.

An evaluation of dietary effects on sodium (Na) homeostasis was performed in 28 healthy infants 7--13 weeks of age. Each infant received during one week an ordinary formula where either the Na and/or the protein content was increased twice. The high Na diets induced a significant elevation of the natriuretic response to an oral Na load. The response was most pronounced in those infants receiving a high Na as well as a high protein diet. The diet that was only high in protein resulted in an increased osmotic load to the kidneys but did not affect the Na excretion. The maturation of renal Na excretion thus seems to be accelerated by a high Na intake and further potentiated by a high protein intake. The Na excretory capacity was, even after the period of a high Na diet, well above the level of Na then given.