Gitelman’s syndrome is genetically distinct from other forms of Bartter’s syndrome

In the past the term Bartter’s syndrome has been used to describe a spectrum of inherited renal tubular disorders with hypokalemic metabolic alkalosis and overlapping and additional clinical and biochemical features. Pathogenesis remained uncertain until recently Gitelman’s syndrome, the hypokalemic-hypomagnesemic variant with hypocalciuria, was linked to the gene encoding the thiazide-sensitive Na-Cl-cotransporter (TSC) located on chromosome 16q. Various mutations in the TSC gene were identified in patients with Gitelman’s syndrome. To clarify whether different forms of hypokalemic tubular disorders (HTD) represent variable phenotypes of a common genetic defect, we performed linkage analyses in 17 families with different symptoms of HTD with four highly polymorphic chromosome 16 DNA markers closely linked to the TSC gene. Linkage of Gitelman’s syndrome to the TSC locus was confirmed in our families with a maximum two-point Lod score Z = 4.70 (θ = 0.001) for marker locus D16S526. Highly negative LOD scores were obtained at this locus in our families with classic Bartter’s syndrome (Z =  – 9.89, θ = 0.001) and hyperprostaglandin E syndrome (Z =  – 11.24, θ = 0.001). Our data prove that Gitelman’s syndrome is genetically distinct from classic Bartter’s syndrome and hyperprostaglandin E syndrome. It remains unknown if classic Bartter’s syndrome and hyperprostaglandin E syndrome are caused by a common genetic defect. Received February 12, 1996; received in revised form and accepted May 7, 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     

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     

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     

Atherosclerosis in youth: are hypertension and other coronary heart disease risk factors already at work?

The purposes of this review were to describe the natural history of atherosclerosis in youth, discuss the role of adult coronary heart disease (CHD) risk factors in the development of atherosclerosis  –  particularly in the young  –  and present the relationship between atherosclerosis and hypertension. Evidence is presented that, by age 15 years, 100% of the youth have aortic atherosclerosis and about one-half have coronary atherosclerosis. Risk factors for adult CHD, including lipoproteins, smoking, glycohemoglobin (a marker for diabetes), obesity, and hypertension, are associated with extent and prevalence of atherosclerosis in young people. Hypertension seems to play its role mainly by converting early atherosclerotic lesions (fatty streaks) to more advanced lesions (raised lesions). Received June 20, 1996; received in revised form July 11, 1996; accepted July 26, 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     

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     

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     

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     

Absence of α6(IV) collagen in kidney and skin of X-linked Alport syndrome patients

Ab stract. To identify the abnormalities of the type IV collagen α6 chain, α6(IV), in Alport syndrome, we examined renal and skin tissue using rat monoclonal antibodies against non-consensus amino acid sequences of α6(IV). Immunofluorescence of normal human kidney and skin tissue revealed linear α6(IV) staining in the basement membrane (BM) of Bowman’s capsule, in some tubules, and also in the epidermal BM. Renal specimens from five male patients of four families with X-linked Alport syndrome showed no reactivity for α6(IV) in Bowman’s capsules and tubules. In these patients, α1(IV) and α2(IV) were normal, whereas α3(IV), α4(IV), and α5(IV) were absent from the BMs of the kidney. In skin tissue of male patients, neither α5(IV) nor α6(IV) were detected. The epidermal BM of female heterozygotes with X-linked Alport syndrome showed a mosaic staining for α5(IV) and α6(IV). These findings indicate that, in addition to a disturbed α3(IV)-α4(IV)-α5(IV) network, patients with X-linked Alport syndrome have abnormalities in α6(IV) of the renal and epidermal BMs at the protein level. Received October 6, 1995; received in revised form April 25, 1996; accepted April 29, 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     

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     

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     

Distribution of α-integrin subunits in fetal polycystic kidney diseases

An alteration in cell/matrix interactions is one of the suggested mechanisms leading to cyst formation in polycystic kidney diseases. Most of these interactions are mediated by β1-integrins, a subfamily of integrin receptors, formed by the association of the β1-chain with different α-subunits. To date, no study on α-integrin subunit distribution during the early stages of cyst development has been reported. Using immunofluorescence, we analyzed the distribution of α-integrin subunits (α1, α2, α3, α5, and α6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD). The distribution was compared with that observed in normal fetal and post-natal kidneys, and in fetal cystic dysplasia and Meckel syndrome. Marked increase in α1-integrin staining was observed in normal and cystic collecting duct cells of both polycystic diseases (PKD), compared with normal and cystic controls. The distribution of integrin subunits α2, α3, and α6 was irregular in cyst epithelial cells of PKD and cystic controls. The increased expression of the α1-subunit specifically observed in PKD collecting duct cells may be an early consequence of the genetic defect in ARPKD. In ADPKD it parallels the reported expression of polycystin, the protein product of PKD1. The irregular expression of α2, α3, and α6 integrin subunits observed in all types of cysts suggests that cell/matrix interactions are altered early and may participate in the development of cysts, perhaps by contributing to the deregulation of cell survival in cystic diseases. Received May 28, 1996; received in revised form October 2, 1996; accepted October 25, 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     

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     

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     

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     

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     

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