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Biomedical subjects

A Tejani

Publications and source records attributed to A Tejani.

At least 73 records · Page 4Linked to original sources

Pediatric renal transplantation.

Renal transplantation in children is now a well established mode of optimal therapy for children with end-stage renal disease. The cooperative endeavors of the pediatric renal transplant physicians in the USA and Canada have generated a large volume of data that lends itself to rigorous scientific analysis. With changing practice patterns, the percentage 1- and 2-year graft survivals for cadaveric donor pediatric renal transplants have increased to 83 and 78%, respectively, in 1991 compared with 72 and 65% in 1987. Graft failure from acute irreversible rejection continues to take its toll in children under the age of 6 years. With funding from the National Institutes of Health a major cooperative effort has been organized by the North American Pediatric Renal Transplant Cooperative Study to determine the mechanisms that lead to heightened immune response in young children. Surveillance biopsies done in the early post-transplant days will attempt to identify the molecular mediators of acute rejection. Rehabilitation of children will not be satisfactory without accelerated growth after transplantation. Unfortunately, the longitudinal studies of the natural histories of growth after transplantation demonstrates that catch up growth occurs only in a subset of young children and that for the majority of older children, intervention with recombinant growth hormone is necessary. However, concern regarding the potential of recombinant growth hormone to induce chronic rejection necessitates a controlled trial.

Adolescent↗

Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis.

Short-term cyclosporine (CsA) has been shown to reduce the proteinuria in refractory nephrotic syndrome, but the effect on disease progression has not been evaluated. This study was undertaken to evaluate whether maintenance CsA therapy in steroid-resistant focal segmental glomerulosclerosis (FSGS) will prevent progression to ESRD. Twenty-one black and Hispanic children (mean age, 8.4 +/- 4.5 yr) with biopsy-proven, steroid/cyclophosphamide-resistant FSGS were treated with CsA (initiated at 6 mg/kg per day and titrated to the serum cholesterol level to achieve a response). The mean CsA dose was 7 (4 to 20) mg/kg per day, the duration of CsA therapy was 27.5 (3 to 97) months, and the duration of follow-up was 8.5 +/- 4.7 yr. At the end of CsA therapy, the mean (+/- SE) proteinuria fell from 6.2 +/- 0.2 to 2.0 +/- 0.1 g/24 h (P < 0.001), the mean albumin rose from 1.95 +/- 0.04 to 3.41 +/- 0.04 g/dL (P < 0.001), the mean cholesterol decreased from 472 +/- 12.7 to 257 +/- 5.3 mg/dL (P < 0.005), and the mean creatinine rose from 0.79 +/- 0.02 to 1.16 +/- 0.03 mg/dL (P < 0.005). Seven children continue to receive maintenance CsA therapy, and 14 patients have had CsA stopped: 6 for an increase in serum creatinine and/or continued proteinuria, 5 for sustained remission, 2 for noncompliance, and 1 for pregnancy. Five (24%) of the 21 patients progressed to ESRD.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗

Posttransplant deaths and factors that influence the mortality rate in North American children.

Of 2457 patients in the North American Pediatric Renal Transplant Cooperative Study registry who were followed for 5481 patient-years after the index transplantation, we observed 136 deaths, for an average annual rate of 24.8 deaths per 1000 patient-years. Death resulted primarily from infection (n = 55, 40%), cardiovascular causes (n = 28, 21%), hemorrhage (n = 16, 12%), and malignancies (n = 9, 7%). Cadaver-donor source was associated with greater mortality (6.7%) than a living-donor source (4.0%) (P < 0.005). Recipients aged 0-1, 2-5, 6-12, and 13-17 years old had mortality rates of 17.5, 8.0, 3.6, and 4.5%, respectively (P < .001). Mortality rates increased substantially when examined by recipient and cadaver donor ages (mortality rates of up to 45%), the greater the concordance between young donor and recipient ages. Interestingly, acute tubular necrosis and graft failure less than 30 days after transplantation (GH30) were each associated with markedly elevated mortality rates. (The risk ratio for ATN was 3.1 [P < 0.001] and for GF30 it was 6.4 [P < 0.001].) Mortality after transplantation was also affected by the underlying renal disease, with high mortality rates observed for oxalosis (n = 21, 33.3%), congenital nephrotic syndrome (n = 79, 15.2%), pyelo/interstitial nephritis (n = 54, 11.1%), and Drash syndrome (n = 14, 21.4%). When the joint effect of these risk factors was examined in a Cox proportional hazards model, young recipient age (0-1 years old) and GF30 were significant (P < .001) risk factors of mortality for recipients of living-donor organs. For recipients of cadaver kidneys, young recipient age--0-1 years old (P < .001) and 2-5 years old (P = .002)--ATN (P = .029), and GF30 (P < .001) were all significant risk factors. Recipient age is the major determinant of increased mortality after renal transplantation. Avoidance of acute tubular necrosis by reducing cold time and preventing early graft failure by better matching techniques in this vulnerable population may improve the mortality rate.

Adolescent↗

Analysis of hypertension in children post renal transplantation--a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Hypertension is common in children after renal transplantation and is associated with multiple factors. Data regarding the prevalence of post-transplant hypertension and the relationship between immunosuppressive drugs and the persistence of hypertension in a large population of North American children have not been available. This study was designed by the North American Pediatric Renal Transplant Cooperative Study to evaluate in a large diverse multicenter population of children the prevalence of hypertension post transplantation, the type of antihypertensive medications used to treat this hypertension and to determine the relationship between the blood pressure control and the immunosuppressive therapy. Analysis of 277 patients showed the following: (1) 70% of recipients required antihypertensive medications 1 month post transplant compared with 48% pre transplant; the incidence decreased to 59% at 24 months; (2) the majority of children received multiple drug therapy to control blood pressure; (3) hypertension can be controlled effectively despite inherent etiological factors, such as allograft source, prior hypertension and immunosuppressive therapy.

Adolescent↗

Hypertension after renal transplantation.

Hypertension is a frequent complication after organ transplantation in both children and adults and is a significant risk factor for the development of cardiovascular disease and graft dysfunction. There are multiple mechanisms responsible for the development of posttransplant hypertension. In the precyclosporine era, chronic rejection was the most common cause. The introduction of cyclosporine A has increased the prevalence of hypertension in solid organ transplant recipients. Cyclosporine increases renal vascular resistance by causing vasoconstriction of the afferent arteriole. From a pathophysiologic point of view, a calcium channel blocker should be used as the initial therapy in patients with cyclosporine-associated hypertension. Hypertension needs to be treated aggressively in all transplant recipients in an attempt to minimize allograft and cardiovascular damage.

Adult↗

Pre-emptive renal transplantation in children: report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Of 2213 primary transplants reported to NAPRTCS between 1/1/87 and 10/31/92, 581 (26.3%) were performed without prior dialysis. The rate of pre-emptive transplantation (PET) differed by donor source, 35.7% LD and 16.1% CD (p < 0.001); gender, 29.6% male and 21.1% female (p < 0.001); race, 30.1% white, 16.1% black, 19.5% hispanic, and 20.2% other (p < 0.001); recipient age, 0-1 yr 18.7%, 2-5 yr 27.9%, 6-12 yr 30.5%, and 13-17 yr 22.8% (p < 0.001). The graft survival rate was significantly better for both the LD (p < 0.01) and CD (p = 0.01) grafts in the pre-emptive group; however, the differences were not significant after adjustment for other variables. The major reasons for pre-emptive transplantation were the parents' desire to avoid dialysis and the recommendation of the nephrologist/surgeon. The data indicate that pre-emptive transplantation does not adversely impact on transplant outcome and that the desire to avoid dialysis is the primary motivating factor.

Adolescent↗

Maintenance immunosuppression therapy and outcome of renal transplantation in North American children--a report of the North American Pediatric Renal Transplant Cooperative Study.

The North American Pediatric Renal Transplant Cooperative Study collects extensive data on all transplants entered into its registry. For this study we evaluated 568 cadaver kidney and 492 live-donor recipients with graft function at 30 days post transplant. Utilizing maintenance immunosuppressive therapy at 30 days post transplant, we evaluated patient and graft outcome, mortality and morbidity over the first 6 months post transplant. For cadaver kidney recipients, 36 patients were receiving prednisone and azathioprine (PA), 114 were maintained on prednisone and cyclosporine (PC) and 418 were on prednisone, cyclosporine and azathioprine (PCA). Patients receiving PA had a greater incidence of rejection prior to 30 days, a greater incidence of hospitalization for rejection and for hypertension over the next 6 months and a greater loss of allograft in the first 6 months compared with the other two groups. The only difference noted between PC and PCA was a lower serum creatinine in the PCA group at 6 months. For living-related kidney recipients, there were 78 patients maintained on PA, 97 on PC and 317 on PCA. Again patients receiving PA had a higher rate of hospitalization for rejection and a higher rate of graft loss. When patients receiving PC were compared with those receiving PCA, no differences were noted in the 6-month serum creatinine values, but a greater percentage of PCA patients were receiving antibiotics on day 30. We conclude that PA is poor therapy for both groups, PCA is ideal therapy for cadaver kidney recipients, but no beneficial effects are noted when PCA is used over PC for live-related donor kidney transplants.

Adolescent↗

Renal transplantation in children and adolescents: the 1992 annual report of the North American Pediatric Renal Transplant Cooperative Study.

From January 1987 to January 1992 the North American Pediatric Renal Transplant Cooperative Study registered and followed 2,037 children and adolescents 17 years of age or less who received 2,197 renal transplants at 75 participating centers in the United States and Canada. The cumulative experience over 5 years of data collection demonstrated trends in renal transplantation practice for pediatric patients. The percentage of live donor organ recipients receiving donor-specific blood transfusions decreased from 40% in 1987 to less than 12% in 1991; random blood transfusions also were used less frequently during the most recent 2 years of the study. Immunosuppressive therapy on posttransplant day 0 or 1 with polyclonal and monoclonal antilymphocyte agents was used in over 40% of transplants. There was also a notable preference for the combined use of prednisone, azathioprine and cyclosporine as maintenance immunosuppression. The percentage of live donor source graft recipients receiving cyclosporine increased from 78% in 1987 to 90% in the most recent year, and considered together, nearly 90% of live donor and cadaver organ recipients received cyclosporine. The observed graft survival probabilities for live donor grafts were 88%, 83%, 81% and 76% at years 1-4 post transplantation, respectively. The 1st through 4th year graft survival probabilities for cadaver grafts were 74%, 68%, 63% and 58%, respectively. The five most common causes of pediatric end-stage renal disease have remained as: hypoplastic-dysplastic kidney, obstructive uropathy, focal segmental glomerulosclerosis, reflux nephropathy and systemic immunological diseases throughout the 5 years of this study. There has been a decrease in children 2 years of age or less undergoing transplant surgery. On average, 50% of graft failures were due to the various forms of rejection. Vascular thrombosis (14%) and recurrence of primary renal disease (7%) were the next most frequently encountered causes of graft failure. Poor linear growth was identified as a problem affecting the majority of children both before and after transplantation. Post transplant linear growth was best among recipients less than 6 years of age at transplantation and recipients of all ages who received alternate-day prednisone. A total of 16 malignancies were reported during the 5 years of study. A total of 105 deaths were reported, with infection (41%) the most common primary cause of death. The 2-year patient survival probabilities were 95.5% and 93% for recipients of live donor and cadaver grafts, respectively.

Adolescent↗

Factors predictive of sustained growth in children after renal transplantation. The North American Pediatric Renal Transplant Cooperative Study.

To ascertain growth and rehabilitation of children after transplantation, the North American Pediatric Renal Transplant Cooperative Study collected growth data on renal transplant recipients. From January 1987 through December 1990, a total of 1553 children with one or more transplants were entered into the study by its 75 participating centers. Of these, the first 300 children with a functioning graft and 2 years of linear growth data form the cohort for this study. For the total cohort of 300 patients, the mean (+/- SEM) baseline height z score was -2.41 +/- 0.09, and the change in z score determined after 2 years was 0.18 +/- 0.06 (p < 0.01). Children in the age group from birth to 1 year had the maximal deficit and had the maximal improvement in z score, gaining about 1 SD (p < 0.01). For the 2- to 5-year-old group, the change in z score was about 0.5 SD (p < 0.001). No improvement in z score was noted for children 6 to 17 years of age. Each increase in serum creatinine concentration of 90 mumol/L (1 mg/dl) was associated with -0.17 decrease in the z score (p < 0.001). Gender, donor source, history of previous transplantation, and prior dialysis were not associated with a significant change in the z score; thus the increased rate of growth during the first 2 post-transplantation years occurred mainly in subjects less than 6 years of age.

Adolescent↗

Effect of hemodialysis on left ventricular contractility in pediatric patients with end-stage renal disease.

Assessment of the effect of hemodialysis on myocardial contractility is complicated by variations in loading conditions that can occur during hemodialysis and by the prevalence of coronary artery disease among patients with chronic renal failure. Therefore, we used a load-independent index of left ventricular contractility, derived from analyses of the rate corrected velocity of circumferential fiber shortening (Vcfc)-end systolic wall stress (ESWS) relationship, to study the acute effects of hemodialysis on left ventricular function in the cases of 15 pediatric patients with end-stage renal disease. Prior to dialysis, Vcfc was appropriate for ESWS (102% +/- 16% of predicted) and did not differ significantly from values obtained from a group of nine normal control subjects of similar ages (103% +/- 9% of predicted), indicating that the patients' left ventricles were functioning in a normal inotropic state. After dialysis, Vcfc increased to levels beyond those expected for ESWS (118% +/- 20% of predicted, P < .05 versus control; P < .001 versus predialysis levels), indicating that dialysis was associated with enhancement of the left ventricle's inotropic state. A statistically significant increase in plasma norepinephrine levels was also observed. However, the increase in the percentage of the predicted Vcfc did not correlate with observed changes in this inotropic agent or with dialysis-induced variations in body weight or levels of electrolytes, urea nitrogen, or creatinine, and firm conclusions regarding the identity of the factors responsible for the positive inotropic effect of hemodialysis could not be drawn.

Adolescent↗

The beneficial effects of steroid withdrawal on blood pressure and lipid profile in children posttransplantation in the cyclosporine era.

Steroid therapy posttransplantation has been correlated with hyperlipidemia and hypertension. With improved graft survivals in the cyclosporine (CsA) era, post-tx hyperlipidemia and hypertension may place children at high risk for early atherosclerosis. Presently there are no large studies assessing the metabolic effects of steroid withdrawal in tx children. Thus, we report on the effect of prednisone withdrawal on blood pressure, weight, and serum lipid levels in children post-tx maintained on CsA alone. Pred taper is attempted in patients on CsA (6-7 mg/kg/day) with stable graft function and is extended over a 6-month period. Once a rejection is diagnosed pred is restarted and no future attempts to withdraw are made. BP, weight, and overnight fasting serum cholesterol (Schol) levels were measured 1 month prior to complete withdrawal (A), and after 6 months without pred (B). In patients requiring the restart of pred, subsequent measurements were obtained 6 months later (C). Of 74 tx children, 7 had primary nonfunction. Pred was successfully withdrawn in 49% (33) of the remaining 67. Of these patients, 42% (14/33) are still maintained off pred with stable renal function for a mean duration of 58.5 months (range 8-99 months). Nineteen patients had to be restarted on pred secondary to rejection between 7-36 months after withdrawal. Three of the patients subsequently lost their grafts to further rejection episodes. Univariate and multivariate analysis failed to identify clinical predictors of successful steroid withdrawal. The Schol at B, 171 +/- 5.4 mg/dl (mean +/- SEM) was lower (P < .001) than at A (249 +/- 10 mg/dl) or C (257 +/- 20 mg/dl). The systolic BP at B (108 +/- 2.8 mmHg) and diastolic BP at B (68 +/- 2.6 mmHg) were also lower (P < .001) than at A (122 +/- 3.2, 76 +/- 2.7 mmHg) or C (130 +/- 5, 80 +/- 3.2 mmHg), respectively. No difference in weight was noted. Lipid profile (total chol, triglyceride, HDL, VLDL, LDL) was measured in 10/14 patients off pred (mean age at sample 16.25 years) and was compared with 13 patients on pred (mean 15.5 years). Both the total chol (176 +/- 9.2, 265 +/- 8.3 mg/dl) and LDL (109 +/- 10, 167 +/- 9.2 mg/dl) were higher (P < .001) in the group on pred. Based on our findings of increased LDL and total chol, children on long-term pred therapy post-tx may be at increased risk for atherosclerotic disease.

Adolescent↗

Cadaver renal transplantation in children. Incidence, immunosuppression, outcome, and risk factors.

In North America, about 50% of all renal transplants done in children are from a living-related donor source--a figure two and a half times greater than the comparative figure for Europe. Graft survival in children is lower for cadaveric donor (CD) than for living-related donor (LRD) kidneys. Four of 10 children with a CD kidney lose their graft within four years. Since it is unlikely that the availability of LRD kidneys will increase, attention must be focused on improving outcome of cadaver renal transplants in children. This review analyzes factors that affect graft outcome. Young recipient age, utilization of kidneys from very young donors, and cold ischemia time are detrimental to prolonged graft survival. Additional factors that impact adversely on cadaver graft survival are a history of previous transplantation, absence of a DR match, and black ethnic origin of the recipient. An understanding of risk factors to graft survival should enable physicians to optimize cadaver renal transplantation in children.

Adolescent↗

Maintenance dialysis in North American children and adolescents: a preliminary report. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

During 1992 the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) began to develop a pediatric Dialysis Patient Data Base by collecting data on pediatric patients who had received either hemodialysis (HD) or peritoneal dialysis (PD), or both, at a participating NAPRTCS center. This preliminary report describes study methods and contains detailed, though short-term observations reported by 64 of 87 NAPRTCS centers on 762 patients who were < 21 years of age at enrollment and who received treatment between January 1, 1992 and September 15, 1992. In these 762 patients, a total of 810 independent courses of dialysis therapy were identified (PD = 534 [65.9%]; HD = 276 [34.1%]). Patients age groupings showed a significantly greater proportion of PD patients among younger age groups. Automated peritoneal dialysis was used by about 75% of registered PD patients at one and six months after registration. A total of 196 peritonitis episodes were reported, yielding a peritonitis rate of one episode every 7.1 patient-months. Ten percent of PD catheters were replaced, primarily for mechanical malfunction and leaks. Percutaneous catheters were used for vascular access in about one-half of the HD patients, with the remainder almost equally divided between arteriovenous fistulae and grafts. Vascular access revision was reported in 28% of HD patients, with about one-third of these revisions performed to create a more permanent access. Recombinant human erythropoietin therapy was used in 89% of PD and 94% of HD patients at six months. Recombinant human growth hormone therapy was used in 9% of PD and 5% of HD patients at six months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Steroid withdrawal, rejection and the mixed lymphocyte reaction in children after renal transplantation.

With improved long-term graft survival after renal transplantation, cardiovascular mortality is emerging as the leading cause of death in adults and is also being reported in children. Chronic corticosteroid therapy is thought to be an important cause of post-transplant hyperlipidemia and hypertension. This study describes a steroid withdrawal protocol initiated to reduced cardiovascular risk factors in pediatric renal allograft recipients, reports on the rate of rejection observed and the use of an in vitro method to measure immunoresponsiveness and identify those patients who have not experienced a rejection episode. Thirty-six of 67 patients were able to discontinue prednisone and were maintained on cyclosporine alone. Twenty-two of the 36 patients experienced an acute rejection episode a mean of 14 months (range 1.5 to 36 months) after completion of the steroid taper. Ten of the 22 rejections occurred within 12 months after completion of the taper. Fourteen patients remain rejection free to date for a mean of 70.3 months (range 19 to 111 months) after withdrawal. Using the mixed lymphocyte culture reaction, we tested the hypothesis that steroid dependent recipients (SDR) will express donor antigen specific responsiveness and steroid independent recipients (SIR) will exhibit donor antigen-specific tolerance. Four of seven SDR were tolerant to donor specific antigens but responsive to unrelated controls, while five of six SIR were responsive to donor specific antigens. These unanticipated results highlight the complexity of allograft tolerance.

Child, Preschool↗