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Loss of living donor renal allograft survival advantage in children with focal segmental glomerulosclerosis.BackgroundBecause of concerns of increased risk of graft loss with recurrent disease, living donor (LD) transplantation in children with focal segmental glomerulosclerosis (FSGS) has been controversial.MethodsThe North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database from January 1987 to January 2000 was examined to determine differences in demographics, treatment, and outcomes in children with FSGS compared with other renal diseases.ResultsData on 6484 children, 752 (11.6%) with FSGS, demonstrated that FSGS patients were more likely to be older and black, and were less likely to receive either pre-emptive or LD transplant (P < 0.001). No differences existed in human lymphocyte antigen (HLA) matching or immunosuppression regimens. Acute tubular necrosis occurred in more FSGS patients following LD (11.8 vs. 4.6%) or cadaveric (CD; 27.9 vs. 16.3%) transplants (P < 0.001). Graft survival was worse for LD FSGS patients (5 years 69%) compared with no FSGS (82%, P < 0.001) and was not significantly different than CD graft survival in the FSGS (60%) and No FSGS groups (67%). The LD to CD ratios of relative risk of graft failure were higher in FSGS patients (test for interaction, P = 0.01). Recurrence of original disease was the only cause of graft failure that differed between groups (P < 0.001). A greater percentage of LD FSGS graft failures was attributed to recurrence (P = 0.06).ConclusionsThe impact of FSGS on graft survival in children is greatest in LD transplants, resulting in loss of expected LD graft survival advantage. The rationale for LD grafts in children with FSGS should be based on factors other than better outcomes typically associated with LD transplantation.

We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.

It is obvious that at least some of the toxic compounds responsible for uremia are metabolic products of protein catabolism. There is also ample evidence that protein metabolism is significantly altered in children with chronic renal insufficiency (Delaporte et al., 1976, 1978; Conley et al., 1980; Holliday et al., 1970; Grupe, 1981b). These studies, coupled with the empiric demonstration that low-protein diets alleviate many of the symptoms of uremia, have led to a precept that has now become axiomatic: stipulating low-protein intake in chronic renal insufficiency. There is, however, the rational goal of reducing the main dietary sources of hydrogen ion, phosphate, potassium, and sulfate to the lowest possible level commensurate with the patient’s renal function.

Extracorporeal enzymatic heparin removal: Use in a sheep dialysis model. Extracorporeal medical devices such as the hemodialyzer rely on systemic heparinization to prevent thrombus formation. Heparin, however, can lead to serious hemorrhagic complications. A blood filter containing immobilized heparinase, a heparin specific enzyme, was used to degrade heparin into small fragments which have significantly less anticoagulant activity than the parent compound. The heparinase filter was tested in the extracorporeal circuit during the hemodialysis of adult sheep. At a blood flow of 200 ml/min, the clearance of heparin varied from 50 to 70 ml/min (N = 16) depending on the amount of immobilized heparinase in the filter. Hemolysis was insignificant as measured by the animals' red cell counts, hematocrit, total hemoglobin and a plasma-free hemoglobin value of 89 ± 33 mg/dl (N = 16) (less than 1% of the total hemoglobin). The white cell counts dropped to 47 ± 7% (N = 16) of the initial value at 20 minutes and rebounded to 72 ± 10% (N = 16) after one hour. The platelet counts decreased to 55 ± 8% (N = 16) of the initial value after one hour. No change in heparin clearance was observed when reactors were used repeatedly in adult sheep over a 10 week period. The red cell counts, white cell counts, platelet counts, total hemoglobin and hematocrit did not change after 10 weeks of exposure to the device. These results suggest that with further study, heparinase may be useful in removing heparin used to anticoagulate blood in extracorporeal circuits.

Renal osteodystrophy is a significant, if not paramount contri¬butor to growth failure in chronic renal insufficiency (1, 2). Repair of bone damage is clearly difficult (3, 4); therefore, prevention by early treatment seems a more physiologic and reasonable goal. Bone histomorphometry has shown, not surprisingly, that bone damage can appear before any development of clinical symptoms, serum biochemical changes, or radiographic abnormalities (5). However, bone biopsy is invasive for the patient and histomorphometry not widely available for the physician. Therefore, there is a need for a non-invasive, sensitive clinical measure of early osteodystrophic activity.

CHILDREN, in increasing numbers , require long-term dialysi s due to the lack of availability of suitable kidneys for tran splantation, the development of high titers of cytotoxic antibodies, the loss of a functioning allograft, and the need in infants for an increase in body size. The availability in the past decade of automatic cyclers and the development of continuous ambulatory peritoneal dialysis (CAPD) followed by continuous cyclic peritoneal dialysis (CCPD) have resulted in peritoneal dialysis being offered to a greater fraction of children with end-stage renal disease. Peritoneal dialysis, with rare exception, is the modality used for chronic dialysis in neonates . Even though most advances in pediatric dialysis during the past 5 years have occurred in the area of peritoneal dialysis, improvements in pediatric hemodialysis continue. Despite significant advances in dialytic care for children with end-stage renal disease , long-term data comparing various forms of dialysis from single centers are sparse. Considered in this report are data comparing CAPD with hemodialysis and intermittent peritoneal dialysis (IPD) with CAPD. A long-term experience with CAPD in neonates and single-center experience with continuous forms of peritoneal dialysis (CPD) also will be reviewed. Finally, the role of urea kinetic modeling in pediatric hemodialysis will be considered .

The clinical and biochemical effects of continuous ambulatory peritoneal dialysis in 20 children and of hemodialysis in 16 children were compared over a 2 1/2-year Period. Statistically significant differences between the treatment groups included higher hematocrit, higher serum carbon dioxide and cholesterol levels, larger intake of calories and protein, and lower systolic blood pressure and rates of transfusion in the patients receiving continuous ambulatory peritoneal dialysis. These patients had more complications than the patients receiving hemodialysis, but hospitalization rates in the two groups were similar. The cost of continuous ambulatory peritoneal dialysis was $19,600 per patient-year; the cost of hemodialysis was $54,300 per patient-year. There were four treatment failures with continuous ambulatory peritoneal dialysis and one with hemodialysis. Patients treated with both forms of dialysis preferred continuous ambulatory peritoneal dialysis. We conclude that continuous ambulatory pe...

CHROMATOGRAPHY of hemolysates of red cells resolves four minor hemoglobin components from the main hemoglobin A (HbA) fraction. These minor components — HbA1a1, HbA1a2, HbAlb, and HbA1c — collectively referred to as the HbA1 fraction, make up approximately 7 per cent of total hemoglobin in normal subjects and result mainly from the post-translational, nonenzymatic glycosylation of HbA.1 In HbAlc, the most abundant of the glycosylated hemoglobins, glucose is attached to the N-terminal amino group of the β chains by a stable ketoamine linkage; HbA1c is present in increased amounts . . .

To determine at which point in chronic renal insufficiency (CRI) the physiologic conditions for altered bone metabolism appear, radiographs, serum chemistries, parathyroid hormone (PTH), and neph cAMP were evaluated in 25 children with CRI compared to 7 children with benign renal disease and normal renal function: Neph cAMP increases linearly with creatinine (Cr) (r=0.81) and PTH (r=0.89) except for patients on chronic hemodialysis, in whom a metabolic steady state did not exist, or for patients with serum Cr > 8.Omg/dl. Serum Cr appropriate for age and height was universally associated with neph cAMP 1.Omg/dl and all patients with Cr > 3.5mg/dl. Both PTH and neph cAMP were elevated in asymptomatic patients with Cr as low as 1.45mg/dl. Neph cAMP > 4.Onmol/100mlGF is a reliable, non-invasive measure of early changes consistent with the development of renal osteodystrophy even before routine changes are evident.

Few reports have linked glucose intolerance to acute renal failure. We therefore evaluated hyperglycemia (hGlu) noted in a 3 yr. old white male with hemolytic uremic syndrome (HUS) after institution of peritoneal dialysis for oliguria and subsequent hemodialysis. Blood glucose (BG) values ≥ 1000 mg/dl and plasma glucagon levels of ≥ 1000 pg/ml were documented during the oliguric stage. Hyperglucagonemia (hGn) persisted but hGlu resolved with improvement in renal function. Insulin therapy was discontinued before discharge at which time blood glucose was normal, creatinine was 0.7, and total glycosylated hemoglobin (Hgb A1) was 7.5% (n1= 5-9). Three days after discharge hGlu was again documented, but subsequent followup demonstrated normal random glucose levels and elevated glucagon values. Two months later a random BG was 302 mg/dl and Hgb A1 was 11.3%. Pasting BG was 109 mg/dl, increased 1 hr p.c. to 240 mg/dl, and remained elevated for 10 hrs (191-385 mg/dl). Simultaneous insulin levels were ≤ 16 μU/ml. Intravenous tolbutamide and arginine each failed to stimulate insulin secretion. Glucagon levels also did not increase after arginine, whereas in diabetics an excess response is observed. While glucose intolerance and hGn have been documented in chronic uremia in adults, this patient clearly differs by showing both hypoinsulinemia, hGn, and persistent hGlu after return of normal renal function. The findings suggest a role for altered islet cell functions in the pathogenesis of hyperqlycemia associated with HUS.

The recognition of the Lupinus montanus complex by morphological traits is discussed. Ecological modification of traits is discussed and the island nature of distribution from mountain peak to mountain peak produces semi-isolated gene pools. Long range dispersal and introgression from other lupines has occurred at the northern end of the distribution in San Luis Potosi, Mexico, developing L. cacuminus. A similar situation occurred in Costa Rica, with L. valerioi the product of introgression from, as yet, an unknown taxon. In Guatemala var. austrovolcanicus represents local introgression from L. kellermanianus, into L. montanus. Both of the Peruvian (L. praestabilis and L. proculaustrinus) taxa are, likewise the result of long range dispersal and introgression. The geographic range of each of the taxa of the complex is plotted and the interrelationship is discussed. The alkaloids have been plotted from random samples of each of the taxa and the data supports the taxonomic treatment and interpretation of their interrelationship. The lupines of Mexico have never been studied monographically. Previous studies have been floristic for states or regions or miscellaneous descriptions, as contributions to the flora of Mexico. To avoid further nomenclatural complications, the earliest named taxa should be identified first. In this sense, the first taxon named for Mexico was Lupinus mexicanus Cerv. ex. Lag. (1816), which has been identified (Dunn, 1972). Lupinus montanus H.B.K. (1823) was the second epithet published for Mexico, concurrently with L. elegans H.B.K. (Humboldt et al., 1823: 478). Both of the types of these taxa are available at Paris, France, with microfiche illustrations now widely distributed. The topotype material was studied and dissections of 50 collections, representing the geographic range of L. montanus were made, and the mean measurements were used to prepare the illustrations of L. montanus and allies presented in this paper. The illustration of L. montanus was sent to Paris and the curator of the herbarium kindly varified that the illustration accurately represents the species by matching it with the type specimen. Since L. elegans H.B.K. is the first epithet in a different complex of lupines, it will be treated, as soon as the rest of the complex is understood. With this approach it is believed, after ten years of study of the Mexican lupines and dissection of over 100 types for Mexico, that the taxonomic treatment of the L. montanus complex for Mexico and Central America can be presented. C. P. Smith (1948: 608) reported two South Ameri