Richard A. Cohn

Posttransplant diabetes mellitus in pediatric renal transplant recipients: A report of The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS)

BACKGROUND The incidence of renal post transplant diabetes mellitus (PTDM) in adults varies from 3-46%. METHODS We did a retrospective analysis of 1365 children in The North American Pediatric Renal Transplant Cooperative Study with renal transplant (Tx) reported between January 92 and July 1997. PTDM, defined as >2 weeks of insulin therapy after Tx, developed in 36 patients. A control group of 153/1329 non-PTDM patients was selected and matched for age at Tx and primary diagnosis. RESULTS African-Americans were overrepresented (36.1 vs. 17.6%, P=0.017) and Hispanics were underrepresented (5.6 vs. 26.1%, P=0.019) among cases. Although prednisone dose 30 days post-Tx was higher among cases (0.89 mg/kg/day) versus controls (0.71 mg/kg/day), P=0.019, cyclosporine dose was similar. No differences in prednisone or cyclosporine doses were observed at 6, 12, or 24 months post-Tx. Tacrolimus use in PTDM group was high (45%). The estimated incidence of first acute rejection at 1, 3, and 12 months was higher among cases, 0.41+/-0.08, 0.52+/-0.08, 0.61+/-0.08, compared to controls, 0.23+/-0.02, 0.37+/-0.02, and 47+/-0.02 (P=0.058). Crude graft failure rates of 13.5% (5/36) and 12.4% (19/153) were similar between the two groups, so was the calculated creatinine clearance at 12 and 24 months and post-Tx hospitalization days. CONCLUSION PTDM occurs in <3% of children. African-Americans are at higher risk and Hispanics at lower risk for PTDM. Tacrolimus is a significant risk factor for PTDM. Children with PTDM had a higher incidence of acute rejection, but graft survival, kidney function, and hospitalization rates were similar to selected controls.

Adolescent Health‐Related Quality of Life Following Liver and Kidney Transplantation

Health perceptions of adolescent transplant patients should be considered in providing appropriate healthcare. Objectives: (i) quantify health‐related quality of life (HRQOL) in adolescent liver and kidney transplant patients, (ii) compare caregiver ratings of their childrens HRQOL to adolescent self‐reports and (iii) examine the relationship between HRQOL and disease‐specific disability (DSD). Adolescent liver (n = 51) and kidney (n = 26) transplant recipients and caregivers were surveyed using the CHQ‐CF87 and CHQ‐PF50. DSD scores were calculated for each patient. The response rate was >70%. Adolescents psychological and physical health was similar to a healthy population, but general health poorer (p = 0.0006). Caretakers reported lower physical functioning and general health (p = 0.0001) but similar psychological health to a normative population. All caregivers expressed negative emotional impact of their childs health on themselves and family activities (p = 0.0001). Positive correlations were found between liver transplant recipients and caregivers: perceptions of behavior (ICC = 0.55, p < 0.001), mental health (ICC = 0.56, p < 0.001), self‐esteem (ICC = 0.68, p ≤0.001). Positive correlations were found for kidney transplant patients and caregivers: physical function (ICC = 0.85, p < 0.001), bodily pain (ICC = 0.70, p < 0.001), behavior (ICC = 0.67, p < 0.01). Kidney transplant recipients showed negative correlations between physical functioning (R =−0.76, p = 0.0003) and general health (R =−0.60, p = 0.008) with overall DSD. Physical and psychological functioning of adolescent liver and kidney transplant patients is high. Caregivers may serve as adequate proxies of psychological but not physical health.

Implications of Immunohistochemical Detection of C4d along Peritubular Capillaries in Late Acute Renal Allograft Rejection

Background. Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. Methods. C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (≥50% PC C4d+), focal (<50% C4d+), and negative (C4d−). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n=13), 1B (n=26), 2A (n=11), 2B (n=3), and 3 (n=2) met inclusion criteria. Results. PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P≤0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d− biopsies (22% and 16%), P=0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d− (33%) groups 1 year after diagnosis, P=0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. Conclusion. Evidence of acute cellular with occult humoral rejection is identified in more than 40% of late AR episodes. Late acute humoral rejection may be associated with interstitial hemorrhage and plasma cells and contributes significantly to graft loss.

ELEVATED BLADDER URINE CONCENTRATION OF TRANSFORMING GROWTH FACTOR-beta 1 CORRELATES WITH UPPER URINARY TRACT OBSTRUCTION IN CHILDREN

PURPOSE We evaluated urinary transforming growth factor-beta1 (TGF-beta1) concentration in children with upper urinary tract obstruction as a potential tool for supporting the diagnosis of clinically significant obstruction. MATERIALS AND METHODS Renal pelvic and bladder urine samples were obtained for analysis from 30 patients a median of 5 months old who underwent surgery for obstruction at the ureteropelvic (29) and ureterovesical (1)junctions. Urinary TGF-beta1 concentration was measured using a quantitative sandwich enzyme-linked immunoassay technique. Bladder urine TGF-beta1 in patients with obstruction was compared with that in controls. In addition, we compared renal pelvic and bladder urine TGF-beta1 in patients with obstruction. RESULTS Mean bladder urine TGF-beta1 plus or minus standard error of mean was 4-fold higher in patients with upper tract obstruction than in controls (195 +/- 29 versus 47 +/- 7 pg./mg. creatinine, p <0.001). In the obstructed group mean TGF-beta1 in the renal pelvic urine was 378 +/-86 pg./mg. creatinine, or twice that of the bladder urine (p = 0.02). CONCLUSIONS Bladder urine TGF-beta1 in patients with upper urinary tract obstruction is significantly elevated compared with that in controls. To our knowledge our study is the first to identify a bladder urinary marker that correlates with upper urinary tract obstruction with greater than 90% sensitivity. Measuring TGF-beta1 in a voided bladder urine sample may provide an objective and noninvasive test for assisting in the diagnosis of upper urinary tract obstruction.

Recurrence of steroid-responsive nephrotic syndrome after renal transplantation.

the present time, whether these babies should have a Blalock-Hanlon operation, a systemic arterial to pulmonary arterial anastamosis, or intracardiac repair during the early newborn period. Indeed, some of these patients may improve spontaneously as pulmonary vascular resistance decreases. The use o f prostaglandin E~ in infants with transposition of the great arteries may be detr imental if a foramen ovale is the only interatrial communication. In this instance, prostaglandin infusion may cause increased puhnonary blood flow and increased left atrial pressure, which may result in functional closure of the foramen ovale and further decreased atrial mixing of systemic and pulmonary venous return. Thus, until more information regarding the effects of prostaglandin El. in infants with transposition is obtained, it is probably not advisable to use prostaglandin E1 until the diagnosis of transposition is proven, and a successful Rashkind balloon atrial septostomy has been done )

IgA Nephropathy in children and adults: comparison of histologic features and clinical outcomes

BACKGROUND While some studies have reported that IgA nephropathy has a relatively benign clinical course in children, others have shown that renal outcomes of paediatric patients with IgA nephropathy followed into adulthood are similar to those of patients diagnosed as adults. Some of this variability may be related to differences in histologic severity of cohorts of patients diagnosed as children versus adults. METHODS We retrospectively examined correlations between renal biopsy findings, clinical features at presentation and renal survival in 99 children and adolescents (<or=17 years old) with IgA nephropathy and compared these findings to those of 125 adults with IgA nephropathy. RESULTS Compared with adults, paediatric patients were more likely to have minimal histologic lesions (24% versus 14%) and less likely to have advanced chronic lesions (3% versus 17%). Similar fractions of paediatric and adult patients showed focal and diffuse glomerulonephritis (GN), respectively. Among these latter two groups, renal survival was significantly better in patients diagnosed as children than as adults by univariate and multivariate analyses. By multivariate analysis, other significant, independent predictors of renal survival were estimated percent interstitial fibrosis and histologic grade (diffuse versus focal GN). CONCLUSIONS In patients with proliferative IgA nephropathy, the clinical course is more likely to be benign when the disease is diagnosed in childhood versus adulthood. This difference can be accounted for only in part by more advanced disease at the time of biopsy in adults.

Favorable outcome of neonatal aortic thrombosis and renovascular hypertension

Fifteen children with renovascular hypertension as a result of aortic thrombosis were followed for a mean of 26 months (range 5 to 58 months) to determine outcome. As neonates, all patients had hypertension and elevated plasma renin activity. Of 11 patients studied with radionuclide renography and scintigraphy, 10 had abnormal renal blood flow; three had complete absence of unilateral perfusion. On follow-up examination all children were normotensive; five children ages 5 to 24 months required antihypertensive medication. Of 15 children, 14 had normal statural growth; all had normal serum creatinine, plasma renin activity, and calculated glomerular filtration rate values. Patients with complete absence of renal perfusion unilaterally remained functionally anephric; children with less severe perfusion deficits had improved perfusion as shown by radionuclide renography and scintigraphy. We believe that many patients with aortic thrombosis and renovascular hypertension who have had aggressive antihypertensive therapy in the neonatal period will have good renal function and increased perfusion to the affected kidney 2 years later.

FAMILY ADJUSTMENT TO PEDIATRIC AMBULATORY DIALYSIS

Continuous ambulatory peritoneal dialysis has recently been a successful medical treatment for children with end-stage renal disease. The psychosocial issues for families and patients are considered within the context of the childs developmental stage (infants and toddlers, school age, and adolescence). The parents conflicting duties as both a provider of medical care and a parent often lead to disturbances in family relationships.

Favorable experience with pre-emptive renal transplantation in children.

We retrospectively examined our experience with live-related donor kidney transplants in 66 children during the 7-year period 1984–1990. We compared the clinical courses of 26 children who did not receive any dialytic therapy prior to transplantation with 40 children who were dialyzed (27 via peritoneal dialysis and 13 via hemodialysis). We did not find any statistically significant differences in patient or graft survival between these three groups with a follow-up period of 6–87 months. Based on our results, we conclude that pre-emptive transplantation is an acceptable treatment for children who will inevitably require renal replacement therapy.

Reversal of severe late left ventricular failure after pediatric heart transplantation and possible role of plasmapheresis

Late acute cardiac graft failure carries a high mortality in adults. Vascular mediators and factors other than classic T-cell-mediated rejection may play a role in this process, and aggressive multimodality therapy may improve survival. We report experience with plasmapheresis in treating late severe acute left ventricular dysfunction in a group of pediatric heart transplant recipients. We retrospectively reviewed clinical records, echocardiograms, hemodynamics, coronary angiograms, biopsy specimens, and treatment regimens for 5 patients with 7 episodes of late-onset severe graft failure who recovered. Plasmapheresis was applied in all cases, in addition to methylprednisolone, cyclophosphamide, lympholytic agents, and aggressive supportive care including mechanical ventilation and hemofiltration. All patients presented with acute severe left ventricular dysfunction 1.4 to 7.9 years (mean 3.6) after orthotopic heart transplantation. Mean shortening fraction at presentation was 13 to 23% (mean 16), initial endomyocardial biopsy specimens were grade 0 to 3B, and immunofluorescence studies were negative. Treatment included plasmapheresis, cyclophosphamide, mechanical ventilation, hemofiltration, and inotropes. Clinical recovery was slow, with 4 to 8 weeks until left ventricular function normalized, and 2.2 to 9.4 (mean 4.6) weeks to hospital discharge. At follow-up (50 to 38 months, mean 24), all are alive. Two patients are well, whereas coronary vasculopathy developed in 3. Thus, survival may improve in patients with late graft failure with low biopsy score and plasmapheresis combined with multimodality therapy.