Incidence of microalbuminuria in children with pyelonephritic scarring

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. Received January 17, 1995; received in revised form and accepted April 2, 1996     

The uretero-vesical jet as a functional diagnostic tool in childhood hydronephrosis

 Childhood hydronephrosis (HN) is accurately detected by ultrasound (US), but its functional work-up remains a domain of scintigraphy, the Whitaker-test, and clinical follow-up. We utilized color doppler US (CD-Jet) of uretero-vesical jets (UVJ) to visualize the postobstructive ureteral flow in childhood HN. A total of 177 standardized CD-Jet were performed in 132 children aged 1 day to 14.9 years. Sixty-nine investigations in 43 patients with unilateral HN were compared with a standardized technetium 99m-mercaptotriacetylglycine nephrogram; in 10 infants both procedures were performed consecutively on the same day. UVJ were visible in 96% of all investigations. Ureteral obstruction resulted in absence of UVJ in 85% of examinations; in the remaining 15% the jet frequency was less than 10% observed in the contralateral control. Results are highly significant in both uretero-pelvic (P<0.00007) and uretero-vesical lesions (P<0.00005, Wilcoxon test) and are reproducible in sequential investigations. In nonobstructive distal HN the jet frequency averaged 70% of the unaffected side (P<0.05). In proximal lesions it is equal. Jet evaluation in reflux nephropathy did not differ from controls. Compared with scintigraphy, CD-US identifies obstruction with a specificity of 94.2% and sensitivity of 94.8%. CD-US of UVJ therefore may serve as a reliable screening parameter in unilateral childhood HN. Received June 10, 1996; received in revised form October 8, 1996; accepted October 18, 1996     

Limitations to body length/serum creatinine ratio as an estimate of glomerular filtration in children

The ability of the Schwartz formula (C _SCH) to estimate glomerular filtration rate (GFR) accurately was investigated in children with renal disease. ¹²⁵Iodine-iothalamate clearance (C _IO) was used as the reference standard for measuring GFR. Data from 176 C _IO studies performed on 133 children (aged between 1 and 18 years) were compared with the simultaneous estimation of GFR by C _SCH. The overestimation of GFR by C _SCH was inversely proportional to the level of renal function. When C _IO was >90 ml/min per 1.73 m², C _SCH overestimated GFR by only 0.1%±3%, but when C _IO was ≤15 ml/min per 1.73 m², C _SCH overestimated GFR by 164%±42%. When renal function is normal or mildly reduced (GFR >50 ml/min per 1.73 m²), C _SCH overestimated C _IO by only 10.3±3.0%, compared with 90.3±14.5% when renal function was moderately to severely curtailed (GFR ≤50 ml/min per 1.73 m²). We conclude that C _SCH is valid in predicting GFR only in children with normal renal function and mild insufficiency. Received January 30, 1996; received in revised form and accepted May 14, 1996     

The identification of hyperoxaluria in very low-birthweight infants – which urine sampling method?

The present study was performed to determine the best method of urine collection for measurement of oxalate excretion in very low-birthweight (VLBW) infants and to verify the utility of the oxalate/creatinine ratio in VLBW infants. This has not been investigated in this group with developing renal function. In a prospective study of 30 VLBW infants, we compared oxalate excretion in urine collected over 24 h and in a spot urine sample. The urinary oxalate concentration was measured by the oxalate oxidase method. The correlation coefficient between the amount of oxalate per kilogram body weight excreted daily and the oxalate/creatinine ratio in spot urine sample was 0.80 (P<0.0001) and with the oxalate/creatinine ratio in a 24-h urine collection 0.82 (P<0.0001). The two highest levels of oxalate excretion (>100 μmol/kg per day) were detected with both oxalate/creatinine ratios (>1 mmol/mmol). No circadian rhythm of oxalate excretion was found. The measurement of the oxalate/creatinine ratio in spot urine samples is suitable for screening VLBW infants for hyperoxaluria. Received October 23, 1995; received in revised form and accepted July 29, 1996     

Tubular proteinuria in reflux nephropathy: post ureteric re-implantation

We studied urine protein excretion in 55 adults with reflux nephropathy (median age 26.9 years) who had had normal blood pressure, renal function and ureteric re-implantation in childhood. Urine retinol binding protein (RBP), N-acetyl-β-D-glucosaminidase (NAG), albumin, bacteriuria, systolic blood pressure, glomerular filtration rate (GFR), peripheral plasma renin activity (PRA) and the degree of renal scarring were measured in each subject; 20 had bilateral and 35 unilateral renal scarring; 5 were hypertensive and none were in renal failure. Urinary NAG and RBP excretions were significantly greater in the study group than in 34 healthy controls (median age 29.7 years). Within the study group, NAG excretion significantly correlated with PRA (P = 0.02). RBP excretion correlated with PRA, systolic blood pressure and the laterality (bilateral vs. unilateral) of scarring (P<0.01). Urinary albumin excretion correlated with systolic blood pressure (P = 0.03). We conclude that increased urinary protein, especially NAG and RBP excretion, occur late after ureteric re-implantation in reflux nephropathy independent of GFR. Its association with PRA supports the concept of segmental perfusion and filtration as an important mechanism that may explain the above findings. Received June 26, 1995; received in revised form and accepted March 6, 1996     

Urinary transforming growth factor-β in patients with glomerular diseases

We measured the urinary levels of active transforming growth factor-β (TGF-β) by enzyme-linked immunosorbent assay in 12 healthy controls and 42 patients with various glomerular diseases, including mesangial proliferative (IgA nephritis, Henoch-Sch?nlein purpura nephritis, and IgA-negative mesangial proliferative glomerulonephritis) and non-proliferative (minimal change nephrotic syndrome and focal glomerulosclerosis) types. Urinary TGF-β, expressed as a ratio to urinary creatinine (ng/mg creatinine), was elevated in patients with IgA nephritis and focal glomerulosclerosis, and was significantly higher than in patients with other types of glomerular diseases and healthy controls. There was a significant correlation between urinary TGF-β levels and the grade of interstitial fibrosis. Among patients with proliferative-type disease, urinary TGF-β was significantly correlated with the grade of mesangial matrix increase and the magnitude of proteinuria. The relationship between urinary TGF-β levels and the immunostaining intensity of TGF-β in the glomeruli was not significant. These results indicated that urinary TGF-β reflects the grade of interstitial fibrosis in glomerular diseases and also the mesangial matrix increase in proliferative-type glomerulonephritis. Measuring TGF-β levels in the urine might be helpful in monitoring patients with some types of glomerular disease. Received November 20, 1995; received in revised form October 8, 1996; accepted October 18, 1996     

Glycosaminoglycans,proteins, and stone formation: adult themes and child’s play

The relative infrequency of renal stones in children is probably the main reason for the paucity of literature devoted to the study of urolithiasis in pediatric patients. Nonetheless, when pediatricians do address the issue, the contents of their papers reflect those prevalent in the adult literature; with one notable exception. Papers dealing with the potential role of urinary macromolecules in pediatric stone disease are very scarce indeed; to my knowledge, only four have been published in the English literature in the last 15 years. One of these is to be found in this issue and, like the remaining three, it compares the urinary excretion of glycosaminoglycans in healthy children and those with stones. This article briefly reviews the history of the association of urinary macromolecules, particularly glycosaminoglycans and proteins, with calcium oxalate urolithiasis, and discusses in more detail the published experimental evidence for their fulfilling a determinant role in stone formation. Received May 16, 1996; accepted May 28, 1996     

Superior vena cava thrombosis and chylothorax: relationship in pediatric nephrotic syndrome

We report a 40-month-old black male with nephrotic syndrome who developed chylothorax associated with superior vena cava (SVC) thrombosis. To our knowledge, this is the third reported case of spontaneous SVC thrombosis in a nephrotic patient and the first in which chylothorax was also present. Ultrasonography of the pleura and thoracic vasculature was invaluable in making the diagnosis and monitoring the resolution of this condition during treatment. Contrary to previous reports, thoracic chylous effusions complicating uncontrolled nephrotic syndrome do not originate exclusively as a consequence of abdominal pathology, but rather as this case demonstrates, they can occur from lymphatic obstruction caused by thoracic vein thrombosis. Received January 22, 1996; received in revised form June 17, 1996; accepted June 20, 1996     

Retransplantation after post-transplant lymphoproliferative disease

We present a boy who developed post-transplant lymphoproliferative disease (PTLD) 3.5 months after a first kidney transplant. The diagnosis was made after histopathological examination of the renal graft which was removed because of Pseudomonas aeruginosa septicaemia. After 2 years on dialysis, the patient received a second renal transplant. This graft continues to function after 5 years and there has been no evidence of recurrence of PTLD. This suggests that retransplantation can be undertaken in patients who have recovered from PTLD in a previous graft. Received March 25, 1996; received in revised form October 10, 1996; accepted October 18, 1996     

In vitro adherence of Staphylococcus saprophyticus,Staphylococcus epidermidis,Staphylococcus haemolyticus,and Staphylococcus aureus to human ureter

Summary Staphylococcus saprophyticus adhered to human ureteral epithelium in vitro. The levels of adherence, which were determined quantitatively with the scanning electron microscope, correlated well with bacterial hemagglutinating activities with sheep erythrocytes (r=0.9459, P< 0.01). Transmission electron microscopy revealed that the adhering bacteria and the hemagglutinating bacteria possessed similar pili-like structures on their cell surfaces. Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus aureus did not adhere to the epithelium. Only S. aureus adhered markedly to the connective, tissue of the ureter, and adhesion of this organism was direct via its cell wall. This adherence test system clearly showed up differences in the abilities of these staphylococcal species to adhere to the urinary tract.     

Peritonitis in continuous ambulatory peritoneal dialysis in children living in Saudi Arabia

The clinical aspects of peritonitis and catheter infections were reviewed in 64 children on continuous ambulatory peritoneal dialysis living in Saudi Arabia over a period of 6 years. Peritonitis occurred in 41 children (64%). The mean time from starting dialysis to the first episode of peritonitis was 7.2 months. The incidence of peritonitis was 1 episode in 9 treatment months. Gram-negative organisms were responsible for the majority of episodes (42%), followed by Gram-positive organisms (20%), and Candida albicans (6%); 32% were culture negative. Recurrent peritonitis was present in 20 cases. Catheter was replaced in 24 patients: 44% due to recurrent peritonitis. Peritoneal membrane loss occurred in 7 patients, 3 had Candida peritonitis and 3 had recurrent peritonitis due to Pseudomonas. The mortality rate was 4.6% but none of the deaths were related to peritonitis or dialysis. Received August 23, 1995; received in revised form October 2, 1996; accepted October 18, 1996     

Increased urinary catecholamines in a hypertensive child with renal artery stenosis

We report a hypertensive child with renal artery stenosis who exhibited increased urinary excretion of norepinephrine (NE) and normetanephrine (NMN), while vanillylmandelic acid (VMA) excretion was within the normal range. The NMN values prompted us to investigate the patient for pheochromocytoma; for this purpose, NE was determined by plasma catecholamine assays in venous samples obtained by catheterization. The moderately increased NE levels could not be localized to any particular sampling site. Arteriography demonstrated right renal artery abnormalities. Following right nephrectomy with preservation of the right adrenal gland, arterial blood pressure returned to normal. The cause of increased NMN excretion without a concomitant rise in VMA during hypertension is discussed. Received May 23, 1995; received in revised form and accepted February 6, 1996     

Catch-up growth in children with vesico-ureteric reflux

A longitudinal retrospective study of height Z score (HZ score) and weight-for-height index (WHI) was performed on 94 pre-pubertal children with vesico-ureteric reflux (VUR) and normal creatinine clearance followed for 1 – 6.8 years (mean 3.1 years). Thirty patients had bilateral VUR with scintigraphic signs of renal scarring (B+), 17 had bilateral VUR without renal scarring (B – ), 27 had unilateral VUR with (U+) and 20 unilateral VUR without (U – ) renal scarring. Thirty-three patients received only antimicrobial medication and 61 underwent successful antireflux operation. The increase in HZ score and WHI during the 1st year of follow-up was significantly (P = 0.001 and 0.00003, respectively) higher than during the 2nd year. At first visit, B+ subjects had an average WHI and HZ score that were significantly (P = 0.02 and 0.04, respectively) lower than the other groups of patients together. At last visit this difference was not significant. In B+ subjects, the WHI and HZ score at last visit were significantly (P = 0.04 for both) higher than at the first visit. B+ patients fully recover their body growth deficit compared with other groups of VUR subjects after medical and/or surgical therapy. Received February 23, 1996; received in revised form and accepted June 24, 1996     

Management of patients with hemolytic uremic syndrome demonstrating severe azotemia but not anuria

. There are no specific indications for dialysis in a patient with typical hemolytic uremic syndrome (D+HUS) who does not have anuria, hyperkalemia, volume overload, or severe acidemia. We managed five patients with D+HUS, aged 1.5 – 14 years, without dialysis despite marked azotemia, because they were not anuric and because they had none of the acid-base, fluid, or electrolyte perturbations that may have been indications for dialysis. Each had markedly elevated blood urea nitrogen (range 137 – 234 mg/dl) and serum creatinine concentrations (range 5.4 – 15.4 mg/dl). None was anuric and one was oliguric for 4 days. There were no complications and each recovered. We have reviewed the published literature on the use of dialysis in patients with D+HUS and have not found any guidelines that relate to the management of similar cases. It is our view that management of D+HUS patients without dialysis is appropriate when the patient is passing urine and the acid-base, serum electrolyte concentrations and fluid balances can be managed without dialysis. Received January 11, 1996; received in revised form and accepted April 8, 1996     

Influence of enalapril on experimental cyclosporin A nephrotoxicity

. The purpose of this study was to investigate if enalapril could be administered with cyclosporin A (CyA) to reduce its nephrotoxicity. Sixty rats were divided into five groups: group I, Control group; group II, rats treated with oral enalapril; group III, rats treated with CyA; group IV, rats treated with CyA and enalapril; group V, rats treated with enalapril before the CyA therapy. At the end of the therapy mean serum creatinine concentrations were not statistically different between the groups (P>0.05), in groups treated with CyA there were no statistically significant differences between mean CyA levels (P>0.05), and mean blood urea nitrogen levels of the groups treated with CyA were significantly elevated (P<0.05) compared with groups not treated with CyA. Morphologically acute CyA nephrotoxicity was evaluated by the following features: (1) tubular vacuolization, (2) tubular necrosis, (3) tubular microcalcification, and (4) peritubular capillary congestion. These lesions were scored semiquantitatively on a scale from 0 to 4+. The most common tubular pathology was tubular vacuolization, which was more severe in groups III and IV. Tubular necrosis was most severe in group III. In conclusion, enalapril seems to suppress the severest form of CyA nephrotoxicity, namely tubular necrosis, if administered prior to CyA treatment. Received May 2, 1995; received in revised form September 22, 1995; accepted January 5, 1996     

Bilateral renal venous thrombosis in a neonate associated with resistance to activated protein C

Renal venous thrombosis (RVT) is a serious complication of neonates. In most cases the underlying cause of RVT remains unclear. Here we report a neonate with bilateral RVT and adrenal haemorrhage associated with a heterozygous mutation of the gene encoding for clotting factor V, resulting in resistance to activated protein C. Vigorous thrombolytic therapy with urokinase followed by recombinant tissue plasminogen activator dissolved the thrombus in the inferior vena cava and restored perfusion of both kidneys. However, a haemorrhagic rupture of the right kidney occurred, requiring emergency nephrectomy. Despite reperfusion of the left kidney and resumption of urine output, the patient remained dialysis dependent. Due to persistent adrenal insufficiency, long-term substitution of hydrocortisone was necessary. The patient was prophylactically treated with coumarin during the first 6 months of life and is now waiting for renal transplant at the age of 1 year. Received January 19, 1996; received in revised form and accepted May 10, 1996     

Persistent hypercalciuria and elevated 25-hydroxyvitamin D3 in children with infantile hypercalcaemia

The aim of the study was to characterize abnormalities of calcium-phosphate and vitamin D₃ metabolism in children with a past history of “mild” Lightwood-type idiopathic infantile hypercalcaemia. Seventeen seemingly healthy children aged 2 – 12 years, with long-term idiopathic hypercalcaemic syndrome since infancy were studied. Two reference groups were also included (vitamin D₃ intoxication/healthy and Williams groups). Despite a long-term milk-restricted diet and a restricted vitamin D₃ intake, urinary calcium excretion in the study group was 0.117±0.07 mmol/kg per 24 h. Compared with the reference groups (0.047±0.029 and 0.067±0.06 mmol/kg per 24 h, P<0.05), there was significant hypercalciuria in the children with idiopathic hypercalcaemia since infancy. Serum concentrations of 25-hydroxyvitamin D₃ in the study group were also elevated compared with the reference groups (57.4±15.5 vs. 34.6±9.3 and 22.7±10.5 ng/ml). 1,25-Dihydroxyvitamin D₃ levels were at the upper limit of normal (45.9±13.1 vs. 35.0±8.1 and 30.0±13.7 pg/ml). Non-progressive, clinically silent nephrocalcinosis was visible on ultrasound examinations. The disturbances of vitamin D₃ and calcium-phosphate metabolism persistent in the normocalcaemic phase of idiopathic infantile hypercalcaemia may be a primary metabolic defect of the condition. The mechanisms leading to elevation of metabolites of 1,25-dihydroxy- and 25-hydroxyvitamin D₃ and the relationship between this and persistent hypercalciuria and nephrocalcinosis need pathophysiological explanation. Received September 22, 1995; received in revised form May 3, 1996; accepted May 7, 1996     

Calcium acetate versus calcium carbonate as oral phosphate binder in pediatric and adolescent hemodialysis patients

Calcium carbonate is widely used as an oral phosphorus binder to control hyperphosphatemia in children on maintenance hemodialysis. Intestinal calcium absorption may induce hypercalcemia, particularly if calcitriol is given simultaneously. In adults, calcium acetate binds phosphorus more effectively than calcium carbonate, while reducing the frequency of hypercalcemic events. We therefore compared calcium acetate with calcium carbonate in nine pediatric patients on long-term maintenance hemodialysis. Following a 1-week withdrawal of phosphorus binders, calcium carbonate was administered for 7 weeks; after a second withdrawal, calcium acetate was given for another 7 weeks. All patients received calcitriol regularly. Both agents lowered the serum phosphorus concentration significantly (calcium carbonate 5.7±1.4 vs. 7.7±2.1 mg/dl, P<0.005; calcium acetate 5.8±1.4 vs. 7.8±2.0 mg/dl, P<0.005). Significantly less elementary calcium was ingested with calcium acetate than with calcium carbonate: 750 (375 – 1,500) vs. 1,200 (0 – 3,000) mg calcium/day, P<0.0001. With calcium carbonate serum calcium increased significantly. The number of episodes of hyperphosphatemia or hypercalcemia did not differ between treatments. Intact plasma parathyroid hormone (PTH) decreased significantly with both phosphate binders, and serum 25-hydroxyvitamin D₃ increased. There was a close relationship between serum phosphorus and PTH in prepubertal but not in pubertal patients. We conclude that hyperphosphatemia can be controlled effectively by both calcium acetate and calcium carbonate in pediatric hemodialysis patients. The oral load of elementary calcium is reduced significantly by binding phosphorus with calcium acetate instead of calcium carbonate; nevertheless, hypercalcemic episodes remain equally frequent with both phosphate binders. Received May 9, 1995; received in revised form and accepted February 23, 1996     

Acute interstitial nephritis associated with IgA nephropathy in children

IgA nephropathy (IgAN) is a relatively common glomerulopathy in children and adolescents. The etiology of this disease is uncertain. We previously reported a child with IgAN who developed acute interstitial nephritis. We now describe three pediatric patients, including the index case, who had IgAN and who developed concomitant acute interstitial nephritis in association with renal functional impairment. We suggest that this histopathological lesion be considered in any child with IgAN and unexpectedly severe kidney dysfunction. Received January 19, 1996; received in revised form and accepted June 10, 1996     

Effect of hydrochlorothiazide in pseudohypoaldosteronism with hypercalciuria and severe hyperkalemia

Severe hyperkalemia resistant to treatment with sodium chloride (NaCl) supplements plus cation exchange resins can be found in pseudohypoaldosteronism type I. In a patient with the multiple target organ variant of this condition, hyperkalemia persisted at dangerous levels (8.5 mmol/l) despite large doses of NaCl (50 mmol/kg per day) and cation exchange resins (6 g/kg per day). Hypercalciuria was also present. The total volume of fluids and supplements required was not tolerated orally. Indomethacin (2 mg/kg per day) and later hydrochlorothiazide (2 mg/kg per day) were tried to further correct imbalance. Plasma potassium (K) and Na levels, the urinary Na/K ratio, transtubular potassium gradient (TTKG), and urinary calcium/creatinine (Ca/Cr) ratio were used to evaluate the effect of hydrochlorothiazide. Under treatment, plasma Na was stable (137 – 144 mmol/l), K levels decreased from 8.5 to 5 mmol/l, urinary Na/K from 90 to 24, and TTKG increased from 0.3 to 1.8. Ca/Cr decreased from 3.5 to 1.5 mmol/mmol. The dosage of cation exchange resins was decreased, oral fluids were tolerated, and the patient’s general condition improved. Hence: hydroclorothiazide can be useful in the treatment of severe hyperkalemia and hypercalciuria of pseudohypoaldosteronism type I. Received January 5, 1995; received in revised form November 9, 1995; accepted November 27, 1995