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     

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     

Percutaneous angioplasty of arteriovenous (Brescia-Cimino) fistulae in children

 The development of a stenosis in a Brescia-Cimino fistula is a major clinical problem that threatens vascular access for dialysis. We reviewed the case notes of 46 children undergoing hemodialysis via Brescia-Cimino fistulae. Ten children (mean age 12.5 years) developed 14 stenoses located in the venous (10), anastomotic (3), or arterial (1) part of the fistula. Three (1 arterial and 2 anastomotic stenoses) of the 14 stenoses were treated surgically; the remaining 11 (10 venous and 1 anastomotic stenoses) were treated by angioplasty. Seventeen angioplasty procedures were performed by the percutaneous venous route under local anesthesia. Mean follow-up was 24 months. Restenosis within 6 months occurred in 5 patients, predominantly those who had angioplasty with low balloon inflation pressures; 1 was treated surgically; 4 underwent repeat angioplasty using higher balloon inflation pressures (3 patients) or a bigger balloon (1 patient). None subsequently developed restenosis. Angioplasty can be safely used to treat stenosis of arteriovenous fistulae, with a high initial (60% freedom from restenosis at 6 months) success rate. In summary, balloon angioplasty, repeated if necessary, is a safe and effective treatment for the majority of stenoses occurring in Brescia-Cimino fistulae. Restenosis can be safely treated by further angioplasty, which is associated with a high rate of ultimate clinical success. Received July 15, 1996; received in revised form and accepted December 18, 1996     

Impact of age on renal graft survival in children after the first rejection episode

Infants are thought to be more immunoreactive and at a greater risk for developing irreversible rejection compared with older children. We investigated this by analyzing patient and graft survival rates, incidence of acute rejection, reversibility of acute rejection, development of a subsequent acute rejection, and incidence of graft loss due to rejection in 154 children (<18 years of age) after primary renal transplantation. Most patients (n = 139) were treated with quadruple immunosuppression (antibody, azathioprine, prednisone, cyclosporine). Treatment of the first acute rejection episode (ARE) consisted of antibody and increased prednisone (68%) or increased prednisone alone (30%), and was not significantly different between the age groups. Transplants were from living donors (LRD) in 80% of cases. Patients were followed for at least 1 year (mean 58±30 months); 68% (105/154) of recipients experienced 1 or more ARE. The incidence of ARE was significantly lower in patients <2 years of age (45%) compared with patients 2 – 5 (76%, P = 0.01), 6 – 12 (78%, P = 0.005), and 13 – 17 (76%, P = 0.009) years of age. There was no significant difference in the 1-, 2- and 5-year patient or graft survival rates, the development of a subsequent acute rejection, or the incidence of graft loss due to acute rejection when analyzed by age group. These data suggest that the impact of an ARE is similar for younger and older children in our population receiving predominantly LRD transplants and quadruple immunosuppression. Received April 25, 1995; received in revised form and accepted January 30, 1996     

Immunization practices in children with renal disease: a report of the North American Pediatric Renal Transplant Cooperative Study

 To determine the current immunization recommendations of practicing pediatric nephrologists, a questionnaire was sent to the members of the North American Pediatric Renal Transplant Cooperative Society. Sixty-two percent of the centers responded. The results of the survey suggest that although consensus for approaching immunization does exist, recommendations do vary from center to center. Virtually all centers recommend standard vaccines [DTP, oral poliovirus (OPV), hepatitis B (Hep B), and Haemophilus influenzae B (Hib)] for their renal insufficiency and dialysis patients. Despite the fact that they are not infectious, standard killed vaccines (DTP, Hep B, Hib) are recommended less frequently for transplanted patients (86%) than their renal insufficiency (98%) and dialysis (near 100%) counterparts. Additionally, OPV and measles/mumps/rubella (MMR), both live viral vaccines, are rarely recommended post transplant. Almost 90% of centers recommend the use of influenza vaccine, while only 60% of centers recommend pneumococcal vaccine for children with renal disease. Over 70% of centers recommend the newly licenced varicella vaccine for patients on dialysis and those with renal insufficiency. Between 5% and 12% of centers recommend live viral vaccines, including OPV, MMR, and varicella vaccine, for immunosuppressed patients post renal transplant. Received July 11, 1996; received in revised form and accepted November 19, 1996     

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     

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     

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     

Excess prevalence of non diabetic renal disease in native American children in Manitoba

We undertook a 1-year prospective point prevalence study to test the hypothesis that there is an excess of non-diabetic renal disease in native American children; 29.6% (73/247) of the population attending the only regional pediatric nephrology clinic in 1993 were native compared with 8.2% of the Manitoba population in this age group (odds ratio = 4.4, P<0.001). Patients were classified as low risk (normal renal function, no deterioration expected), high risk (normal renal function, deterioration probable), or established chronic renal failure (creatinine clearance chronically low or post renal transplant). Patients were further classified as suffering from congenital renal anomalies, genetic or metabolic disease, or acquired renal disease. Odds ratios were calculated based on data from the Aboriginal Peoples’ Population Survey and Statistics Canada census data. The odds ratios for low-risk renal disease, high-risk renal disease, and chronic renal failure were 3.8, 5.6, and 6.3, respectively (P<0.001 in all categories). The odds ratios for congenital, genetic, or acquired disease were 4.5 (P<0.001), 0.9 (P = ns), and 6.1 (P<0.001), respectively. Native American children in Manitoba demonstrate increased prevalence of serious congenital and acquired renal disease. These children are also more likely to live in medically underserviced communities, long distances from tertiary care centers. This study emphasizes the importance of considering factors other than diabetes mellitus when considering the problem of renal disease in native Americans. Received November 17, 1995; received in revised form and accepted March 19, 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     

Adverse effect of peritonitis on peritoneal membrane function in children on dialysis

 The effect of peritonitis on peritoneal membrane solute transport characteristics was determined as part of a multicenter study in children on continuous ambulatory/cycling peritoneal dialysis. Ninety-three children each underwent a 4-h peritoneal equilibration test (PET) with 1,100 ml/m² 2.5% Dianeal for determination of mass transfer area coefficients (MTAC), dialysate to plasma ratios (D/P) for creatinine and urea at 0, 30, 60, 120, 180, and 240 min and dialysate glucose levels at 0, 30, 60, 120, 180, and 240 min for calculation of D/Do. The mean age of the study cohort was 10.1±5.6 years (range 0.1–19 years). There were 162 historical episodes of peritonitis; at the time of the PET tests, 36 children had never had an episode of peritonitis (group I) while 57 children had a history of one or more episodes of peritonitis (group II). In group II children, the 4-h glucose D/Do was significantly lower and the 4-h D/P creatinine ratio, the creatinine MTAC, and the glucose MTAC were significantly higher (each P<0.05) than in group I. In children with a history of peritonitis caused by Gram-negative organisms, the 4-h glucose D/Do (P<0.05) and the creatinine MTAC (P<0.05) were significantly lower and the glucose MTAC (P=0.07) nearly significantly lower than in children without a history of peritonitis. Linear regression analysis did not demonstrate a correlation between any of the variables and duration of peritoneal dialysis, while the rate of peritonitis was weakly correlated with glucose MTAC (r=0.34, P<0.05) and with 4-h glucose D/Do (r=–0.222, P<0.01). We conclude that children with a history of peritonitis have peritoneal membranes that are more permeable to glucose and creatinine than children without a history of peritonitis, and that the peritoneal membranes of children who have had peritonitis caused by Gram-negative organisms are also more permeable to creatinine and glucose. Such changes are likely to have an adverse effect on membrane function and could eventually contribute to ultrafiltration failure. Received: 29 December 1997 / Revised: 13 April 1998 / Accepted: 14 April 1998     

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     

Chronic anemia as a complication of parvovirus B19 infection in a pediatric kidney transplant patient

. This is a report of unexplained anemia that persisted for 4 months in an adolescent renal transplant patient receiving immunosuppression that included prednisone, tacrolimus, and mycophenolate mofetil. This patient required monthly blood transfusions for fatigue, palpitations, and hematocrit levels between 15% and 17%. In addition, his posttransplant course was notable for the development of insulin-dependent diabetes mellitus. While receiving low-dose prednisone, he was switched from tacrolimus to cyclosporin and tapered off insulin injections over the next 2 months. At 4.5 months post-transplantation, further diagnostic evaluation was suggestive of parvovirus B19 infection as the cause for our patient’s chronic anemia. After testing negative for serum-specific parvovirus B19 IgM and IgG antibodies, parvovirus B19 infection was detected in blood by the polymerase chain reaction. Treatment with intravenous immunoglobulin (1 g/kg per day × 2 days) resulted in normalization of both his reticulocyte count and hematocrit within 6 weeks. At 4 months after receiving the immunoglobulin infusion, he has maintained a normal hematocrit level and stable renal function without requiring further blood transfusions. Received August 23, 1996; received in revised form and accepted November 20, 1996     

Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors

 Autosomal recessive polycystic kidney disease causes renal and hepatic dysfunction in childhood. We describe the clinical outcome of 52 children with this diagnosis born between 1950 and 1993. Currently 23 are alive, 24 dead and 5 have been lost to follow-up; 1 has been dialysed and 7 transplanted. Life-table analysis of the patients surviving the 1st month of life revealed an actuarial renal survival of 86% at 1 year and 67% at 15 years. The probability of requiring anti-hypertensive treatment was 39% at 1 year and 60% at 15 years of age. Bleeding from gastro-oesophageal varices occurred in 8 patients at a mean age of 12.5 years, and was preceded by haematological evidence of hypersplenism in 6 of them. The study indicates a relatively good prognosis for patients with this condition who survive the neonatal period and emphasises the importance of early detection and appropriate management of systemic and portal hypertension. Received May 17, 1996; received in revised form and accepted October 29, 1996     

Intensive pulse therapies for focal glomerulosclerosis in South African children

 Seven children with steroid-resistant focal segmental glomerulosclerosis (SR-FGS) were placed on a therapeutic protocol of methylprednisolone (MP), oral prednisone (pred) and oral cyclophosphamide (CYC) given over 16 months (regimen A). Another 5 children with SR-FGS were treated with a shorter course of intravenous CYC (monthly doses over 6 months), intravenous MP (3 consecutive daily doses) and oral pred 2 mg/kg (alternate days) (regimen B). With regimen A, 1 child had a short remission, and in the others, oedema subsided, the urine protein/creatinine ratio decreased, haematuria disappeared and the estimated glomerular filtration rate (GFR) increased. The observation period was 21 – 42 months and the drugs were well tolerated. With regimen B, 2 patients went into complete remission, 1 had partial remission, 1 failed to respond and another died because of severe concurrent infections. In the responding children, oedema cleared, the urine protein/creatinine ratio decreased, haematuria disappeared and the GFR rose. The follow-up was between 3 and 34 months. Minor side effects were alopecia and transient hypertension. Both regimens improved the quality of life of most children. Compared with regimen A, regimen B is six times less costly with a quarter of the number of hospital visits. These observations may be of value in designing appropriate multicentre controlled trials, which have been advocated recently, for the rational and optimum management of SR-FGS. Received April 16, 1996; received in revised form December 12, 1996; accepted December 19, 1996     

Charge and size selectivity of proteinuria in children with idiopathic nephrotic syndrome

 Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules. Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (modal pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (± SD) delta modal pI was  – 0.05 ± 0.16, and in MCNS  – 0.05 ± 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS (P<0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P<0.01 and for IgG1/albumin P<0.05). For IgG4/transferrin and IgG4/albumin, P was <0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with heavy proteinuria compared with children with MCNS with heavy proteinuria. Received August 7, 1996; received in revised form and accepted December 16, 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     

Low molecular weight protein excretion in glomerular disease: a comparative analysis

We studied 23 children with steroid-sensitive nephrotic syndrome (SSNS), 21 children with steroid-resistant types of nephrotic syndrome and 32 children with other types of nephritis. Our controls were 43 apparently healthy children. We measured the urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and the low molecular weight (LMW) proteins β₂-microglobulin (B2M), retinol-binding protein (RBP), α₁-microglobulin (A1M) and urine protein 1 (UP1). Results for B2M were considered only for a urine pH greater than 6.0. Comparisons were made with urine albumin excretion, glomerular filtration rate (GFR) and tubular abnormalities in selected renal biopsy samples. We found that abnormalities of LMW protein excretion occurred in between 50% (B2M) and 88% (UP1) of all subjects. In children with SSNS, A1M (r = 0.73), UP1 (r = 0.65) and NAG (r = 0.54) excretion were significantly correlated with albumin excretion, but not RBP or B2M excretion. Increased fractional excretion of A1M, B2M and UP1 and increased plasma A1M were demonstrated in 9 children with SSNS, suggesting competition for tubular reabsorption with albumin, most marked for UP1. In the steroid-resistant nephrotic and nephritic syndromes, correlation with albumin was found for all proteins. In these subjects, RBP (r = 0.37), B2M (r = 0.42) and A1M (r = 0.28) were inversely correlated with GFR, but not UP1, NAG or albumin. We found that RBP excretion was significantly greater in the presence of severe tubular abnormalities in 11 children with recent renal biopsies, but not A1M, UP1 or NAG. We conclude that LMW proteinuria is common in children with glomerular disease, and does not necessarily imply a poor prognosis. Factors other than histologically proven tubular abnormality may account for elevated LMW protein excretion. RBP is the LMW protein most closely associated with structural abnormality and least affected by increasing albuminuria. Received January 31, 1996; received in revised form and accepted October 22, 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     

Variation in the diagnosis of vesicoureteric reflux using micturating cystourethrography

  Variability in the interpretation of micturating cystourethrography by paediatric radiologists for the diagnosis of vesicoureteric reflux in children was evaluated. All 265 micturating cystourethrograms (MCUs) that were available from 304 consecutive children aged 0.5 – 61 months  –  who were investigated after their first urine infection between 1993 and 1995 as part of a prospective cohort study  –  were selected for interpretation. Three experienced paediatric radiologists from the same department independently interpreted the MCUs according to the grading system of the International Reflux Study in Children, from grades 0 to V, with the presence of intrarenal reflux also noted. Apart from being informed that urine infection was the indication for the MCU, no other clinical information was given to the radiologists. The indices of variability used were the percentage of agreement and the kappa statistic, expressed as a percentage. Both measures were weighted with integers representing the number of categories from perfect agreement. Disagreement was analysed for children and kidneys. For the diagnosis of vesicoureteric reflux in individual patients, including grade, the percentage of agreement was 96% – 97% (kappa 90% – 91%) and the weighted percentage of agreement was 96% – 98% (weighted kappa 93% – 94%). The same high level of agreement was present for individual kidneys, with a percentage of agreement of 97% – 98% (kappa 89% – 92%) and a weighted percentage of agreement of 98% – 99% (kappa 94% – 95%). There was near perfect agreement in the interpretation of radiological micturating cystourethrography among three experienced paediatric radiologists for the diagnosis and grade of vesicoureteric reflux. Any variations in the medical care of children suspected of having vesicoureteric reflux are not explained by differences in the reporting of this diagnostic test. Received June 19, 1996; received in revised form November 1, 1996; accepted December 6, 1996