Glomerular filtration rate in children following renal transplantation

Most studies evaluating renal function post-renal transplantation in children have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular filtration rate (GFR), especially during cyclosporine therapy. This study measured GFR in 64 children (age range: 4-19 years) with stable renal function who received renal allografts at the Childrens Medical Center of Dallas, 31 from live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate clearance (C(IO)) was used as the reference standard for measuring GFR. Data from 100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO) performed during the first year after renal transplantation in 23 children who received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/-7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05). Beyond the first year post-renal transplantation there was no difference in C(IO) between LRD and CAD allografts. When S(Cr) was compared to C(IO), the relationship was nonlinear. C(IO) was also compared to the simultaneous estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH) was inversely proportional to the level of renal function. When renal function was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely approximated C(IO). When renal function was moderately to severely curtailed (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%. The study concludes that in children with renal transplant: 1) C(IO) is higher in allografts from LRD compared to CAD kidneys only in the first 12 months following renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH) consistently overestimates GFR children following renal transplantation unless renal function is normal or only mildly decreased.     

Glomerular and tubular function following orthotopic liver transplantation in children

Since its advent, cyclosporine nephrotoxicity has been a major concern to pediatricians attending to liver transplant recipients. The aims of this study were to examine glomerular and tubular function after orthotopic liver transplantation (OLT) in children, their correlation to CsA, and how they differed according to the underlying disease. Patients and methods: Glomerular and tubular function was examined in 28 patients aged 7 months to 14 yr at the time of transplantation (mean 4.0 +/- 3.6), retrospectively examining creatinine clearance, tubular phosphate reabsorption (TRP), calcium/creatinine ratio, sodium excretion fraction, and protein/creatinine ratio. The group with metabolic disease and an underlying tubulopathy was compared with the group with liver disease only. The effect of CsA trough levels and cumulated dose on these indices was examined, as was the effect of antihypertensives on creatinine clearance. Both glomerular and tubular functions improved significantly following liver transplantation. In patients on CsA (n = 21), CrCl decreased significantly at 1 month post-OLT (42.6 +/- 26.6 mL/min/1.73 m(2)) when compared with pretransplantation, and 3, 12 and 60 months post-OLT (p < 0.05). It improved between 12 and 60 months post-OLT (p < 0.05). It was correlated with cyclosporine trough levels (p < 0.03), and with total dose of CsA at 12 months. This was not true for patients on tacrolimus (n = 7). Overall pretransplant TRP was below normal (73.7% +/- 19.6), which was significantly lower than the values at years 2, 3, and 5 post-OLT (p < 0.05), owing mainly to the metabolic group which recovered normal proximal tubular function by the end of the second week post-OLT. Calcium/creatinine ratio was significantly worse in the group with liver disease only (p < 0.01). Protein/creatinine ratio normalized rapidly in both groups. Urinary sodium excretion fraction (FENa) was very abnormal in the early postoperative phase, normalizing thereafter in both groups. Kidney function improved after liver transplantation in patients with and without pre-existing kidney dysfunction. Overall, creatinine clearance was correlated to CsA trough levels suggesting CsA did not have an irreversible 'sclerosing' effect in the medium term. Combined antihypertensive therapy using nifedipine and enalapril may be the optimal choice for patients requiring medical management of their hypertension, although the observed effect on creatinine clearance did not reach statistical significance in this study. Tubular dysfunction is frequent in both groups of patients, pre- and post-transplant, and may contribute to bone mineral density as well as to metabolic disturbances in this population.     

Genetics of insulin-dependent diabetes mellitus in children

Insulin-dependent diabetes in children is a heritable disease, although it does not fit into any simple genetic model. Research is not facilitated by the lack of knowledge of the different etiological mechanisms and the inability to classify the disease. Human leucocyte antigens (HLAs) coded for in the major histocompatibility complex on the 6th chromosome have given the most important insights into the genetics of diabetes, and these genes probably provide the majority of genetic susceptibility to type-I diabetes. Several facts indicate that there are at least two loci of importance, one associated with HLA B8, DR3 and another with HLA B15, DR4, which probably are usually included in extended haplotypes in linkage disequilibrium. There seems to be a substantial DNA polymorphism and further studies may detect fragments that are even more strongly associated with diabetes than the DR type. A combination of more detailed immunological, perhaps virological or other environmental investigations on diabetic patients and their families, together with the use of specific DNA probes for the HLA region, might reveal the susceptibility genes.     

Cognitive profiles of children with insulin-dependent diabetes

Intellectual and reading skills were evaluated and related to disease variables in 42 children with Type I (insulin-dependent) diabetes. A significant interaction revealed lower Wechsler Intelligence Scale for Children-Revised (WISC-R) Performance IQ for children with early disease onset (less than 7 years) and long disease duration (greater than or equal to 5 years). IQ scores were nevertheless in the average range. Although there was no specific pattern of visual spatial impairment, functioning on the Performance subtests was uniformly lower for this group. Slower responding to the timed tasks of the Performance scale may account for generally lower scores. Children with early onset-long duration also evidenced higher rates of reading and memory impairment. These results indicate the importance of ascertaining educational skills in diabetic children before planning diabetic treatment regimens, especially for children with disease of early onset and long duration, who may be especially vulnerable to skill deficits.     

Ophthalmologic complications of insulin-dependent diabetes mellitus in children and adolescents

Diabetes mellitus is a major cause of visual impairment and blindness. Cataracts and retinal vascular abnormalities (retinopathy) are the major defects occurring in the eyes. The frequency of these defects increases with the duration of diabetes. Many believe that the occurrence of eye disease in children with diabetes is rare. Blurry vision, an early manifestation of cataractogenesis, occurs in nearly all children with diabetes. Retinopathy, which is extremely rare prior to puberty, occurs in 70-90% of adolescents with diabetes of more than 10 years' duration. Proliferative retinopathy and blindness due to diabetes also occur in adolescents. Regular, careful ophthalmologic examinations by retinal specialists are indicated for the adolescents at risk. Those at risk are adolescent females with HLA DR3 and DR4 as well as those with limited joint mobility. Early recognition is essential to prevent the blindness that follows untreated proliferative retinopathy.     

Calcitonin secretion in children with insulin-dependent diabetes mellitus

To test the hypothesis that calcitonin (CT) deficiency may contribute to bone mineral loss in insulin-dependent diabetes mellitus (IDDM), we studied basal and calcium stimulated (2 mg/kg body wt. in 5 min) CT levels in 15 children with IDDM and osteopenia. Ten age-sex matched healthy children were studied as controls. Since extractable CT (exCT) allows more sensitive and specific measurement of CT monomer, we measured both total serum CT (tCT) and exCT. Diabetic children had slightly but significantly (P<0.05) higher basal levels of both tCT (24.5±7.1 ng/l) and exCT (5.6±1.6 ng/l) than controls (tCT: 18.7±5.4 ng/l; exCT: 4.3±1.2 ng/l). Calcium stimulation test pointed out significant increase (P<0.001) of tCT and exCT in both groups with peak values not significantly different in IDDM in respect to controls. However, diabetic children showed a reduced CT reserve evidenced by a lower peak/basal ratio (diabetics: tCT 1.68, exCT 1.84; controls: tCT 2.49, exCT 2.88) and by a more rapid decrease in CT levels. We conclude that CT deficiency is not a causative factor of diabetic osteopenia. The slightly higher basal CT values suggest that an increased bone reabsorption may be operative in IDDM and it stimulates CT secretion. This chronic C cell stimulation may induce the reduction in CT reserve observed employing the calcium infusion test.     

Determinants of blood glucose variability in adolescents with insulin-dependent diabetes mellitus

Metabolic control and blood glucose variability in children with insulin-dependent diabetes mellitus (IDDM) during and after puberty were studied. Seventy-two children (43M, 29F), aged 10-19 years, with a 2-16-year duration of IDDM participated in the study. Fourteen of the patients were prepubertal (Tanner stage 1), 27 pubertal (Tanner 2-4) and 31 postpubertal (Tanner 5). They performed self-monitoring of blood glucose (SMBG) five times daily, every 2 days for 4 weeks. The SD (SDbg) for all values in each patient was calculated as a measure of blood glucose variability. Weight-length index, linear growth velocity and Tanner stage were recorded. Hemoglobin (Hb)A_Ic, alkaline phosphatase and sex hormone levels in serum were analyzed. Subjectively experienced hypoglycemic episodes were recorded. HbA_Ic levels showed no relation to Tanner stage. SDbg was lower in stage 5 than in stages 2-4 ( p = 0.02). There was no significant correlation between HbA _lc and SDbg, but the variability was significantly lower in individuals with mean blood glucose in the lower quartile compared with those in the upper three quartiles ( p < 0.001). Alkaline phosphatase concentration, as a measure of growth velocity, was the main independent determinant of SDbg ( r = 0.35, p < 0.005). There was an inverse correlation between levels of sex hormones and SDbg. We conclude that blood glucose variability is lower after than during puberty. This variability seems to be related to linear growth velocity or its biochemical marker.     

Anticardiolipin antibodies in children and adolescents with insulin-dependent diabetes mellitus

Anticardiolipin antibodies were determined in 29 diabetic children and adolescents, aged 3.9–26.8 years, with disease duration from 1 month to 19 years. Anti-islet cell antibodies (ICA-IgG and CF-ICA), anti-insulin antibodies (IAA), antithyroid antibodies and non organ-specifc (NOSA) antibodies were also determined. Patients were grouped according to insulin-dependent diabetes mellitus (IDDM) duration: group I (n=11)<6 months, and group II (n=18)>5 years. Eleven of group II patients showed precocious signs of micro-angiopathic complications. Forty-two age- and sex-matched healthy subjects served as controls. IgG and IgM anticardiolipin antibodies were evaluated by ELISA and their results expressed as arbitrary units (AU). IgG anticardiolipin antibodies were found in 7 patients (24%), while IgM anticardiolipin antibodies were absent in all. IgG anticardiolipin antibodies were more frequent in IDDM patients than in controls (P<0.005) and group I (in 6 out of 11 patients; 54.5%) than in group II (in 1 out of 18 patients; 5.5%) (P<0.025). In five out of six group I patients with IgG anticardiolipin antibodies, ICA-IgG and/or CF-ICA were also found. No correlation was observed between anticardiolipin and other auto-antibodies, micro-angiopatic complications, and HLA typing.     

Signal-averaged electrocardiogram in children and adolescents with insulin-dependent diabetes mellitus

We report on the potential usefulness of the signal-averaged electrocardiogram (SA-ECG) in young patients with insulin-dependent diabetes mellitus (IDDM) to predict subclinical cardiovascular complications. Sixteen patients with IDDM and 18 age-matched healthy subjects were studied. The IDDM group included 4 males and 12 females, aged 7 to 20 y (mean 14.2 +/- 3.8 y, +/- SD). The duration from the onset of IDDM to the study ranged from 1.2 to 9.8 y (mean 5.4 +/- 3.8 y), and HbAlc value ranged from 6.6 to 12.4% (mean, 10.0 +/- 1.8%). SA-ECG was recorded and analyzed using the methods described by Simson. Values of filtered QRS duration (f-QRS), root mean square voltage (RMS), the duration of low amplitude signal (LAS) and late duration (LD) were calculated and compared between the groups. These parameters were not significantly different between the IDDM and control groups. However, in patients with poor glycemic control (HbAlc >10%), f-QRS was long and RMS was significantly low (p < 0.05, each) compared with the control group. Three patients with IDDM were positive for ventricular late potentials, although none had ventricular tachyarrhythmia. None of the control subjects showed ventricular late potentials. CONCLUSION: Certain parameters of SA-ECG showed abnormal values in IDDM patients with poor glycemic control. Thus, SA-ECG is a potentially useful and non-invasive method for the assessment of subclinical cardiac impairment in diabetic children and adolescents.