Olli Koskimies

Microscopic hematuria in schoolchildren: Epidemiology and clinicopathologic evaluation

An unselected population of 8,954 children, age 8 to 15 years, was screened for hematuria. Four urine specimens from each were examined; microscopic hematuria was found in one or more specimens in 4.1%, and in two or more specimens in 1.1% of the children. The prevalence was not age or sex dependent. Those with two or more positive samples were re-examined twice during a half-year period: 33 had hematuria of 6 or more RBC/0.9 mm3, or more than 100,000 RBC/hour, on both occasions; renal biopsy performed on 28 of them revealed two cases of IgA-IgG nephropathy, one of focal segmental sclerosis, one of extracapillary glomerulonephritis, and one of possible hereditary nephritis. In 12 patients the biopsy was entirely normal; the rest showed equivocal changes. Co-existing proteinuria and the degree of hematuria correlated well with the severity of the morphologic alterations. Pathologic findings in microscopic hematuria seem to be less frequent than in hematuria in general; in most such patients, renal biopsy is probably not indicated. In some children the low-grade hematuria may merely represent the upper end of physiologic variation.

Henoch-Schönlein nephritis: long-term prognosis of unselected patients.

Progressive glomerulonephritis is the most serious feature of Henoch-Schönlein syndrome. In a series of 141 children with Henoch-Schönlein purpura 39 (28%) had abnormal urinary sediment for a duration of more than one month. This subgroup was followed up for 3.0 to 13.8 (mean 7.2) years. One child progressed to renal failure and 2 developed chronic glomerular disease. In this series most of the patients with Henoch-Schönlein syndrome and nephritis had a good prognosis.

THE VALUE OF LEVEL DIAGNOSIS OF CHILDHOOD URINARY TRACT INFECTION IN PREDICTING RENAL INJURY

Abstract. Pylkkänen, J., Vilska, J. and Koskimies, O. (The Childrens Hospital, University of Helsinki, Finland). The value of level diagnosis of childhood urinary tract infection in predicting renal injury. Acta Paediatr Scand, 70: 879, 1981.‐252 infants and children were followed for 2 years after their first urinary tract infection. Each symptomatic infection was determined by simple laboratory examinations as upper pyelonephritic or lower urinary tract infection. I.v. urography was done at the beginning of the follow‐up and 2 years later; micturating cystourethrography was taken after the third infection at the latest. Urological abnormalities were found in 26 patients (10 %), and 12 subjects (5 %) developed renal scars during the study. Patients, who had their first upper urinary tract infection before the age of 12 months, numbered 93, and 19 of them had urological abnormalities and 10 scars. Two renal scars occurred among the 71 subjects with their first pyelonephritic infection after the age of 12 months. No renal injury was detected in the 88 infants and children with lower symptomatic urinary tract infection or asymptomatic bacteriuria. The determination of the level of the infection may be a useful aid in detecting the harmful scar‐forming urinary tract infections. Infants with a pyelonephritic infection are at high risk, and in need of an early urological evaluation.

Long-term outcome of primary nephrotic syndrome.

One hundred and fourteen children with primary nephrotic syndrome were followed up prospectively for periods of between 5 and 14 years. Urine samples from 94 of them became protein-free during the initial 8-week course of prednisone, and the outcome for these children was good: 74 of them have been free of symptoms for at least 3 years, 18 have had relapses during the last 3 years, and only one child still has proteinuria. All these children have normal renal function and blood pressure. One child died accidentally. Twenty children did not respond to the initial prednisone treatment. Thirteen of them had remissions later, of whom 2 have had relapses during the last 3 years. Seven were totally resistant to prednisone 4 of whom died in renal failure, the remaining 3 have persistent proteinuria with normal levels of creatinine; one has high blood pressure too. Remission during the initial treatment indicated a good prognosis, but two-thirds of the initial non-responders also fared well.

Dominant and recessive polycystic kidney disease in children: evaluation of clinical features and laboratory data

The clinical features and laboratory data of 93 children with polycystic kidney disease were analysed. Family studies showed that the disease was dominant (DPKD) in 17 and recessive (RPKD) in 32 of them. Of the remaining 44 sporadic patients, 1 was classified by histological and/or imaging findings as having DPKD, 41 as having RPKD and 2 could not be classified. The symptoms tended to be more severe in RPKD than in DPKD, but there was much overlap. Death in early life was common in RPKD (55/73) and more rare in DPKD (4/18). If a child with DPKD had disease manifest during the neonatal period, then siblings were usually affected in the neonatal period. Survival to adulthood was seen in both disease. In the patients who survived the neonatal period, hypertension was more common in RPKD (11/18) than in DPKD (4/14). Symptoms of portal hypertension were present in 2 patients with RPKD and none with DPKD. None of the laboratory investigations discriminated between the two entities. Glomerular filtration rate was diminished more often in RPKD (9/11) than in DPKD (2/8). Some difference was seen in the maximal urine concentrating ability; it was always reduced, ofter markedly, in RPKD but usually either normal or only moderately disturbed in DPKD. Studies on hepatic function and hepato-cellular damage were usually normal, but bacterial cholangitis was noted in some children with RPKD. The differential diagnosis between DPKD and RPKD needs to be based on the family history, family studies, radiological and/or histological features.

Renal manifestations of Henoch–Schönlein purpura in a 6-month prospective study of 223 children

Objective To assess the risk factors for developing Henoch–Schönlein purpura nephritis (HSN) and to determine the time period when renal involvement is unlikely after the initial disease onset. Design A prospective study of 223 paediatric patients to examine renal manifestations of Henoch–Schönlein purpura (HSP). The patients condition was monitored with five outpatient visits to the research centre and urine dipstick testing at home. Results HSN occurred in 102/223 (46%) patients, consisting of isolated haematuria in 14%, isolated proteinuria in 9%, both haematuria and proteinuria in 56%, nephrotic-range proteinuria in 20% and nephrotic-nephritic syndrome in 1%. The patients who developed HSN were significantly older than those who did not (8.2±3.8 vs 6.2±3.0 years, p<0.001, CI for the difference 1.1 to 2.9). Nephritis occurred a mean of 14 days after HSP diagnosis, and within 1 month in the majority of cases. The risk of developing HSN after 2 months was 2%. Prednisone prophylaxis did not affect the timing of the appearance of nephritis. The risk factors for developing nephritis were age over 8 years at onset (OR 2.7, p=0.002, CI 1.4 to 5.1), abdominal pain (OR 2.1, p=0.017, CI 1.1 to 3.7) and recurrence of HSP disease (OR 3.1, p=0.002, CI 1.5 to 6.3). Patients with two or three risk factors developed nephritis in 63% and 87% of cases, respectively. Laboratory tests or blood pressure measurement at onset did not predict the occurrence of nephritis. Conclusion The authors recommend weekly home urine dipstick analyses for the first 2 months for patients with HSP. Patients with nephritis should be followed up for more than 6 months as well as the patients with HSP recurrence.

Clinical course of extrarenal symptoms in Henoch–Schönlein purpura: a 6-month prospective study

Objective To describe the extrarenal symptoms and clinical course of Henoch–Schönlein purpura (HSP). Design A prospective national multicentre trial with 6-month follow-up. Patients A total of 223 newly diagnosed paediatric HSP patients. Results Purpura was the initial symptom in 73% of the patients and was preceded by joint or gastrointestinal manifestations in the rest by a mean of 4 days. Joint symptoms, abdominal pain, melena, nephritis and recurrences occurred in 90%, 57%, 8%, 46% and 25% of the patients, respectively. Orchitis affected 17/122 (14%) of the boys. Seven patients developed protein-losing enteropathy characterised by abdominal pain, oedema and serum albumin under 30 g/l, and an additional 49 patients had subnormal albumin levels without any proteinuria. Positive fecal occult blood (26/117, 22%) and α1-antitrypsin (7/77, 9%) suggested mucosal injury even in the patients without gastrointestinal symptoms. HSP was often preceded by various bacterial, especially streptococcal (36%) and viral infections. Previous streptococcal infection did not induce changes in the level of complement component C3. Recurrences were more frequent in patients >8 years of age (OR 3.7, CI 2.0 to 7.0, p<0.001) and in patients with nephritis (OR 4.6, CI 2.3 to 8.9, p<0.001). Patients with severe HSP nephritis had more extrarenal symptoms up to 6 months. There was no difference in the clinical course between the prednisone-treated and non-treated patients during the 6-month follow-up. Conclusions Serum albumin is often low in HSP patients without proteinuria, due to protein loss via the intestine. Although corticosteroids alleviate the symptoms, they seem not to alter the clinical course of HSP during 6 months of follow-up.

Pharmacokinetically determined cyclosporine dosage in young children

To account for the individual variability in cyclosporine pharmacokinetics and the non-existence of dosing recommendations in young children, we studied the pharmacokinetics of cyclosporine before renal transplantation in ten children aged 1.1–2.5 years, to determine the appropriate individual dose. Our aim was to reach a steady-state cyclosporine blood level of 200–300 μg/l, 8 h after a dose in the first days after renal transplantation. Cyclosporine was given as a single oral dose (10 mg/kg) or as a 4-h i. v. infusion (3 mg/kg), and the blood concentration was determined for 24 h by a specific monoclonal radioimmunoassay. The mean terminal cyclosporine half-life (t1/2) was 9.3 h (range 2.8–20.4), blood clearance 10.8 ml/min per kilogram (range 6.8–22.7) and volume of distribution 2.8 l/kg (range 1.4–4.7). The bioavailability of oral cyclosporine was low; the mean amount absorbed was 21.8% of the administered dose (range 11–35). The mean calculated dose needed to attain the intended predose blood cyclosporine level of 200–300 μg/l at steady-state was 5 mg/kg per day for i.v. and 21 mg/kg per day for oral administration. In view of the shortt1/2, we used three doses/day. The validity of the predicted doses is shown by the mean cyclosporine doses used during the first 10 days after transplantation, which were 93.5% of the calculated oral and 96.6% of the calculated i.v. doses. The observed mean cyclosporine concentration during the same period was 196 μg/l.

DIAGNOSTIC VALUE OF SYMPTOMS AND CLEAN‐VOIDED URINE SPECIMEN IN CHILDHOOD URINARY TRACT INFECTION

Abstract. In diagnosing urinary tract infection (UTI) the symptoms of 477 infants and children and the findings in their clean‐voided urine specimens were evaluated. 322 patients were considered infected, when a bacterial culture of suprapubic aspirate was used as a diagnostic reference. No diagnosis was attempted on the basis of symptoms only. Numerous bacteria or ≤200 leuc./mm3 in an uncentrifuged clean‐voided urine specimen or ≤105 bact./ml in quantitative bacterial culture were found in 59%, 42% and 81% of the infected symptomatic patients. The diagnostic accuracies of these indices were 88%, 94% and 95%, respectively. In asymptomatic patients the accuracies were considerably lower. Among these infected patients normal or equivocal isolated findings in the clean‐voided urine specimens were frequently seen, and could not markedly be reduced by the various related factors, such as technique of urine collection, urine specific gravity or pH of urine. None of the above mentioned indices of the clean‐voided urine specimens seems to be alone accurate and sensitive enough for diagnosing UTI, and therefore these should be used in combination. The advantage of immediately obtaining results supports the use of urine microscopy as a primary diagnostic method in symptomatic UTI of childhood in particular.

Predictive factors associated with significant urinary tract abnormalities in infants with pyelonephritis.

BACKGROUND Major urinary tract abnormalities are detected in 20 to 40% of infants with acute pyelonephritis (APN). Early detection of structural defects is essential for protecting the kidneys from reinfection and subsequent scarring. The purpose of this study was to investigate whether any factors present during the acute phase of infection could predict the presence of existing significant urinary tract abnormalities in infants. METHODS A prospective study of 180 infants, aged 1 to 24 months, with APN was conducted. Blood and urine samples were collected. Renal ultrasound (US) was performed within 0 to 6 days from admission. Final diagnosis of the urinary tract anatomy was elucidated using the results of two or more radiologic imaging studies. RESULTS Risk factors for the presence of significant urinary tract abnormalities in infants were pathogens other than Escherichia coli in urine [relative risk (RR) 3.4, 95% confidence interval (CI) 2.2 to 5.3; P = 0.001], positive blood culture (RR 2.3, 95% CI 1.3 to 4.0; P = 0.039), young age (1 to 6 months) (RR 2.2, 95% CI 1.3 to 3.9; P = 0.004), lack of papG adhesin genes of E. coli in urine (RR 2.1, 95% CI 1.2 to 3.9; P = 0.016) and abnormal renal US (RR 2.0, 95% CI 1.2 to 3.4; P = 0.008). CONCLUSIONS Infants 1 to 6 months of age with APN caused by bacteria other than E. coli or by papG-negative E. coli strain, positive blood culture and abnormal renal US carry an increased risk for significant urinary tract abnormalities and need enforced follow-up.