Continuing improvement in cadaver donor graft survival in North American children: the 1998 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) covers the years 1987-1997, and analyses data on 3,133 cadaver donor (CD) transplants performed in 2,736 patients. There has been a steady decline in the number of CD transplants in children since 1996. Kidneys recovered from donors under 10 years of age accounted for 35% of all transplants in 1987, whereas by 1996 they comprised less than 20%. Caucasian children received 54% of CD transplants, whereas African-American children received 21%. Children under 6 years of age received 17% of CD transplants. Approximately half (46%) of the patients were induced with a T-cell antibody, and at 7 years post-transplant triple therapy is used in 70% of those with a functioning graft. Cyclosporin A is the primary immunosuppressant, with 92% of the patients being maintained on it at 5 years post-transplant. Among patients receiving a transplant in 1997, 11% were initiated with another calcineurin inhibitor, tacrolimus. At 15 days post-transplant 20% of the patients have had a rejection episode and by day 45, 46% have had an acute rejection. The probability of developing a rejection within the first year was reduced from 71% in 1987-1988 to 47% in 1995-1996.

Platelet-derived growth factor receptor beta regulates migration and DNA synthesis in metanephric mesenchymal cells.

Platelet-derived growth factor (PDGF) B-chain and PDGF receptor beta (PDGFR beta) are essential for glomerulogenesis. Mice deficient in PDGF B-chain or PDGFR beta exhibit an abnormal glomerular phenotype characterized by total lack of mesangial cells. In this study, we localized PDGFR beta in the developing rat kidney and explored the biological effects of PDGF in metanephric mesenchymal cells in an attempt to determine the mechanism by which PDGF regulates mesangial cell development. Immunohistochemical and in situ hybridization studies of rat embryonic kidneys reveal that PDGFR beta localizes to undifferentiated metanephric mesenchyme and is later expressed in the cleft of the comma-shaped and S-shaped bodies and in more mature glomeruli in a mesangial distribution. We also isolated and characterized cells from rat metanephric mesenchyme. Metanephric mesenchymal cells express vimentin and alpha-smooth muscle actin but not cytokeratin. These cells also express functional PDGFR beta, as demonstrated by autophosphorylation of the receptor as well as activation of phosphatidylinositol 3 kinase in response to PDGF B-chain homodimer. PDGF B-chain also induces migration and proliferation of metanephric mesenchymal cells. Taken together with the fact that PDGF B-chain is expressed in the glomerular epithelium and mesangial area, as demonstrated in the human embryonic kidney, we suggest that PDGF B-chain acts in a paracrine fashion to stimulate the migration and proliferation of mesangial cell precursors from undifferentiated metanephric mesenchyme to the mesangial area. PDGF B-chain also likely stimulates proliferation of mesangial cell precursors in an autocrine fashion once these cells migrate to the glomerular tuft.

Epidermal growth factor inhibits Na-Pi cotransport in weaned and suckling rats.

In the present study, we determined the effect of epidermal growth factor (EGF; 10 microgram/100 g body wt) on sodium gradient-dependent phosphate transport (Na-Pi cotransport) regulation in suckling (12-day-old) and weaned (24-day-old) rats. Weaned rats had higher proximal tubular brush border membrane vesicle (BBMV) Na-Pi cotransport activity (232 +/- 16 in weaned vs. 130 +/- 9 pmol. 10 s-1. mg protein-1 in suckling rats, P < 0.05). Chronic treatment with EGF induced inhibition of BBMV Na-Pi cotransport in both suckling (130 +/- 9 vs. 104 +/- 7 pmol. 10 s-1. mg protein-1, P < 0. 05) and weaned rats (232 +/- 16 vs. 145 +/- 9 pmol. 10 s-1. mg protein-1, P < 0.005). The inhibitory effect was selective for Na-Pi cotransport as there was no inhibition of Na-glucose cotransport. Weaned rats had a higher abundance of BBMV NaPi-2 protein than suckling rats (increase of 54%, P < 0.001) and a twofold increase in NaPi-2 mRNA. The EGF-induced inhibition of Na-Pi transport was paralleled by decreases in NaPi-2 protein abundance in both weaned (decrease of 26%, P < 0.01) and suckling (decrease of 27%, P < 0.01) animals. In contrast, there were no changes in NaPi-2 mRNA abundance. We conclude that proximal tubule BBMV Na-Pi cotransport activity, NaPi-2 protein abundance, and NaPi-2 mRNA abundance are higher in weaned than in suckling rats. EGF inhibits Na-Pi cotransport activity in BBMV isolated from suckling and weaned rats, and this inhibition is mediated via a decrease in NaPi-2 protein abundance, in the absence of a change in NaPi-2 mRNA.

An overview of renal trauma.

The topic of renal trauma has offered many substantial and poignant issues of debate over the years, such as classification schemes, management techniques, imaging and diagnostic preferences, and post-traumatic sequelae. This overview presents the most recent and applicable arguments and data surrounding the treatment of renal trauma. Various classification structures have been proposed and utilized for over a century, yet they do not all focus on the different features of trauma presentation (pathogenesis, morphologic implications, symptoms, predisposing conditions) in an equal manner. The traditional controversy between observation and invasive surgery with trauma patients still exists, yet new methods of treatment protocol have been proposed for patients in traumatic shock. Concerning the state of the patient, it has been recognized that children with pretraumatic renal abnormalities are more prone to serious injury, but it is still undecided whether renal trauma will predispose a child to later pathologies such as arterial hypertension. Modern advances in imaging, and diagnostic procedures have dramatically shifted the reliance on intravenous pyelograms to computed tomography, yet the question remains of how much imaging actually is needed in the average patient presenting with renal trauma. Pertinent issues such as these are presented, with main emphasis on literature published within the past 18 months.

Cytomegalovirus infections following renal transplantation--effects on antiviral prophylaxis: a report of the North American Pediatric Renal Transplant Cooperative Study.

Post-transplant cytomegalovirus (CMV) infections are a source of significant morbidity. However, the extent of the problem and the benefits of various antiviral prophylactic therapies remain incompletely understood. The North American Pediatric Renal Transplant Cooperative Study registry was screened to identify patients hospitalized for CMV infections during the 1st post-renal transplant year between 1987 and 1993. Using a control group of transplant recipients, we performed a retrospective analysis of risk factors for CMV disease among these hospitalized patients and studied the effects of various viral prophylactic strategies on CMV risk, clinical manifestations, and outcome. We identified 142 patients hospitalized with CMV infections, the majority of which included major organ involvement. A CMV-positive kidney donor was the most significant risk factor for hospitalization [odds ratio (OR) = 5.2, P<0.0001] irrespective of recipient age or CMV immune status. As opposed to antiviral agents (acyclovir, ganciclovir) or pooled IgG, prophylaxis with enriched anti-CMV IgG significantly reduced the risk of CMV hospitalization (OR = 0.31, P = 0.03). The prophylactic use of antiviral agents was associated with a decreased risk of major organ involvement during the CMV infection (OR = 0.34, P<0.005). Among the patients with CMV, the 3-year graft survival was significantly better for those who received any form of prophylaxis compared with those who received none (88% vs. 52%, P<0.001). Our findings suggest a role for combined CMV-enriched IgG and antiviral agent prophylaxis for post-transplant CMV disease. Such an approach could diminish the incidence and severity of CMV infection and appears to have an independent favorable effect on graft outcome.

Renal allograft torsion associated with prune-belly syndrome.

We report a 26-month-old child diagnosed with prune-belly syndrome and end-stage renal disease who received intraperitoneal implantation of an adult cadaveric renal graft which functioned very well for approximately 6 weeks. The patient then presented with acute renal failure which was proved to be secondary to torsion of the graft, twisting the artery and vein. The ureter was wrapped 360 degrees around the graft. These conditions resulted in loss of the graft and nephrectomy. Ours is the second report of such an occurrence; the first was from a living-related kidney donor. We believe the lack of abdominal wall tone contributes to graft mobility and risk of torsion of the kidney. We recommend that nephropexy be considered in these patients. In addition, the risk of torsion must be at the forefront of the differential diagnosis in a prune-belly renal transplant patient with acute onset of oliguria. Renal sonography with Doppler should be employed as soon as possible so that the graft can be saved.

Membranous nephropathy in two human leukocyte antigen-identical brothers.

We describe two Hispanic brothers with membranous nephropathy who had nephrotic syndrome in the first 2 years of life. Secondary causes of membranous nephropathy were excluded by clinical history and laboratory data. The occurrence of membranous nephropathy in these two young brothers, as well as in other familial cases reported to date, suggests an X-linked mode of inheritance.