Risk factors for hyperlipidemia in long-term pediatric renal transplant recipients.

Hyperlipidemia (HL) is a common problem in adult renal transplant (TP) recipients, contributing to an increased risk of cardiovascular disease and chronic TP nephropathy. There are multiple causes of HL post renal TP in adult patients, including pre TP HL, immunosuppressive agents, renal dysfunction, hypoalbuminemia secondary to nephrotic syndrome, obesity, and conditions that lead to end-stage renal disease (ESRD). We evaluated the incidence and risk factors of HL in 62 pediatric renal TP recipients (15.4+/-4.2 years, range-3.0-22.3 years) with long-term (6.7+/-3.1 years) functioning [glomerular filtration rate (GFR) 66.7+/-23.2 ml/min per 1.73 m(2)] allografts. The mean serum cholesterol (C) level was 205. 5+/-43.6 mg/dl. Thirty-two patients (51.6%) exhibited elevated serum C levels. The mean serum triglyceride (TG) level was 157.3+/-88.4 mg/dl. Serum TG levels were elevated in 32 patients (51.6%). In patients with elevated serum levels of either C or TG, the mean low-density lipoprotein level (LDL) was 138.6+/-44.1 mg/dl (normal <130 mg/dl) and the high-density lipoprotein (HDL) level 54.6+/-15.9 mg/dl (normal>34 mg/dl). Of those patients studied, 45.5% had high LDL levels, whereas 9.1% exhibited low HDL levels. The two risk factors for elevated serum C levels in our patient population were pre-TP HL and increased years since TP. The only risk factor for elevated serum TG levels was reduced GFR. A family history of HL had a significant deleterious impact upon serum levels of C (P=0.01), but did not affect serum TG levels (P=0.7). Years on dialysis prior to TP, history of prior TP, gender, body mass index, and disease leading to ESRD had no influence upon the development of post-TP HL. We conclude that post-renal TP HL is a significant problem in pediatric renal TP recipients.

Use of calcium-channel blockers in pediatric renal transplant recipients.

Hypertension (HTN) is a significant problem in pediatric renal transplant (TP) recipients, predisposing the individuals to the development of cardiovascular disease and graft dysfunction. Calcium channel blockers (CCB) are considered excellent agents to treat post-TP HTN. We compared the efficacy and adverse effects of the two most commonly prescribed CCBs in our pediatric renal TP population: nifedipine (Procardia, or P) and amlodipine (Norvasc, or N). All patients (n = 24) had been started on a CCB for systolic (SBP) and/or diastolic BP (DBP) > 95%. There were no other changes in adjunctive antihypertensive medications or doses during the cross-over period. Post-TP, pretreatment (pretx) SBP was 137.6 +/- 10.9 mmHg. The post-treatment SBP were (in mmHg): 128.5 +/- 11.9 (all patients, n = 24) (p = 0.009 vs. pretx); 126.4 +/- 10.0 (P alone, n = 15) (p = 0.007 vs. pretx); 132.8 +/- 14.4 (P + other antihypertensive(s), n = 9) (p = 0.331, NS vs. pretx). The post-TP, pretreatment DBP was 88.2 +/- 11.1 mmHg. The post-treatment DBP were (in mmHg): 78.5 +/- 6.9 (all patients, n = 24) (p = 0.03 vs. pretx); 77.2 +/- 7.4 (P alone, n = 15) (p = 0.008 vs. pretx); 80.7 +/- 6.1 (P + other antihypertensive(s), n = 9) (p = 0.063, NS vs. pretx). P and N were equally effective in reducing SBP (p = 0.843, NS) and DBP (p = 0.612, NS). Cyclosporin A (CyA) dose (p = 0.81) and trough levels (p = 0.19) were similar in P- and N-treated patients. Calculated GFR was virtually identical in P- and N-treated patients (p = 0.89). Patients (or parents of) reported a higher incidence of various side-effects while receiving P, including headache, flushing, dizziness and leg cramps. Furthermore, 22/24 (91.7%) reported some degree of gingival hyperplasia during treatment with P, and all these patients reported a stabilization or reduction of hypertrophy after the switch from P to N. We conclude that CCBs (N) are efficacious drugs for the purpose of BP control and renal protection in pediatric renal TP recipients.

Superior outcomes in pediatric renal transplantation.

BACKGROUND: Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults. OBJECTIVE: To determine factors important for success in renal transplantation in children. DESIGN: Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry. RESULTS: One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery. CONCLUSIONS: Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.

Kidney and kidney/pancreas transplantation at Stanford University Medical Center.

The disparity between the supply of cadaveric donors and the demand for renal allografts continues to grow. We have taken a multifaceted approach to increase the allograft pool: 1. Spiral computed tomography to evaluate potential living kidney donors is safer, less invasive, less expensive and more time efficient and thus should encourage living organ donation. 2. Use of selected expanded criteria cadaveric donor kidneys (aged 60 or over, hypertensive) in size- and age-matched recipients have short-term function at 3 and 6 months comparable to standard cadaveric renal allografts. 3. Kidneys from expanded criteria donors over age 59 and with an adjusted creatinine clearance less than 90 ml/min should be used as a dual kidney transplant into an appropriate sized- and aged-matched recipient. 4. Kidneys from pediatric donors < 5 years of age should be utilized as en-bloc grafts, when transplanted into adult recipients. Pediatric renal transplantation poses numerous challenges given the different and problematic etiologies of ESRD, the surgical considerations in small children and infants and the enhanced immune response witnessed in children. Nevertheless, renal transplantation is clearly the therapy of choice for children with ESRD and excellent results can be obtained through strict adherence to surgical detail, tight immunosuppressive management, and aggressive fluid management in infants and small children. We feel it is also critically important that transplantation and follow-up care be carried out by an integrated and experienced surgical and medical team. Managed healthcare has had profound effects on the practice and management of transplantation centers. The one area of greatest impact has been the pressure upon programs to reduce their cost of transplantation. We have initiated a number of new outpatient treatment protocols as part of an effort to contain costs. Most patients with acute rejection are evaluated (including transplant kidney biopsy) and treated in an ambulatory setting. Completion of OKT3 therapy in selected patients is also performed at home through visiting nurses or at our ambulatory care center. Additionally, treatment of CMV disease is now performed almost exclusively on an outpatient basis.

Bladder augmentation can be problematic with renal failure and transplantation.

Ten consecutive patients with failure of urinary bladder augmentation (UBA) performed either prior to or after reaching end-stage renal disease (ESRD) were studied. Seven patients developed increased hydroureteronephrosis, infectious complications, and advanced to ESRD after UBA. The mean time to development of ESRD in patients who had UBA performed with moderate chronic renal failure (CRF) was 1.8 years. The UBAs in all seven patients were taken down prior to transplantation. Subsequently, five of these UBA-takedown patients have received kidney grafts and all have stable, good renal function. Three patients had their UBA performed after they reached ESRD, in preparation for renal transplantation. All three of these patients experienced recurrent urosepsis following transplantation, resulting in death in one patient and loss of graft in another. The third patient will undergo takedown of the UBA. This study suggests that UBA may possibly not be the best option for patients with moderate CRF and those awaiting transplantation.

Continuous venovenous hemofiltration with dialysis in combination with total hepatectomy and portocaval shunting. Bridge to liver transplantation.

Children who experience acute liver failure following liver transplantation will have multiple organ failure and a high rate of mortality unless emergency retransplantation can be performed. Transplant hepatectomy with portocaval shunting has been described as a bridge to transplantation in the most severe cases, as well as in patients with fulminant hepatic failure at high risk for mortality who have not undergone liver transplantation. Patients with multiple organ failure who have undergone hepatectomy require renal replacement therapy. Continuous hemofiltration may be used in patients with fulminant hepatic failure to facilitate fluid removal and circulatory and metabolic balance. We used continuous venovenous hemofiltration with dialysis following hepatectomy with portocaval shunting in a patient who remained anhepatic for 66 hr in order to achieve circulatory and metabolic homeostasis as well as stable neurologic function prior to successful retransplantation.

Prevention of rejection and graft loss with an aggressive quadruple immunosuppressive therapy regimen in children and adolescents.

During the two-year period May 1991 to April 1993, 36 kidney transplants were performed in children less than 18 years of age at California Pacific Medical Center using an aggressive quadruple-therapy regimen of immunosuppression. The regimen consisted of induction with an antilymphocyte preparation (MALG in 21, OKT3 in 2, ATGAM in 12, none in 1), initial moderate-dose steroid therapy, early intravenous cyclosporine therapy, and azathioprine. Twenty living-related graft recipients were pretreated with donor-specific transfusions. Long-term cyclosporine was dosed by levels to keep through whole-blood levels (RIA) at 200-300 ng/ml. Twenty-five grafts were from living-related donors, two from living unrelated donors, and nine from cadaveric donors. Eleven (30%) recipients were five years old or under at the time of transplantation. Of these recipients 44% had complex congenital urologic disease and required urologic surgery prior to or at the time of transplantation. Patients have been followed for a mean of one year, with actual patient and graft survivals of 100% and 97%, respectively. Only one graft has been lost, to severe, early recurrent focal segmental glomerulosclerosis. Four of the 36 patients have had one rejection episode each, all reversed completely. Graft function is stable, with serum creatinine proportionate to age--mean serum creatinine in the children under two years old being 0.4 mg/dl, and in the adolescents 1.3 mg/dl, with two adolescent boys having the highest creatinine levels at 1.8 mg/dl. We conclude that an aggressive approach to immunosuppressive therapy in the early posttransplant period with MALG/OKT3/ATGAM induction and rapid achievement of therapeutic cyclosporine levels prevents rejection and results in excellent patient and graft survival with subsequent stable good graft function.

Familial renal adysplasia.

Renal dysplasia and agenesis as isolated findings are usually considered sporadic, noninherited abnormalities. We report three kindreds with familial renal adysplasia. Two or more children were affected in each of the families and at least one member--whether proband, sibling, or parent--had a clinically silent anomaly. Normal kidneys in the parents did not preclude the occurrence of renal adysplasia in more than one child. The empiric risks for offspring and first-degree relatives were 50% and 25%, respectively, suggesting a strong genetic factor such as a major dominant gene with variable expression. Because the disease appears to be genetic in some cases of renal adysplasia, careful screening of the proband's family, subsequent children, and pregnancies is important for the purpose of accurate genetic counseling.

Fungal peritonitis in children treated with peritoneal dialysis and gastrostomy feeding.

Feeding gastrostomies were placed in three children treated with chronic peritoneal dialysis at our center because of persistent, severe malnutrition and inadequate growth. Two had frequent fungal infections of the gastrostomy site and all three developed Candida peritonitis which occurred at 1 month, 2 months and 2 years after insertion of gastrostomy. Complications included multiple intra-abdominal adhesions, abscess formation and loss of peritoneal function necessitating transfer to hemodialysis. The presence of a gastrostomy may predispose to the development of fungal peritonitis with its high morbidity and should be avoided in children on chronic peritoneal dialysis.

Sickle cell glomerulopathy with focal segmental glomerulosclerosis.

Sickle cell disease is known to cause glomerulopathy, including focal segmental glomerulosclerosis (FSGS). Patients who have sickle cell glomerulopathy with FSGS are thought to have a poorer prognosis than patients who have sickle cell glomerulopathy without this lesion. The former patients are more likely to have persistent proteinuria and eventually develop end-stage renal disease. We present a boy with sickle cell glomerulopathy and FSGS who is younger than patients with similar findings reported previously. The histopathology of his renal lesions is remarkable for segmental ultrastructural changes in the glomerular basement membranes and endothelial cells. We speculate that these changes are precursory to the pathogenesis of glomerular sclerosis in patients with sickle cell disease.

Hypernatremia.

Hypernatremia results when the water content of body fluids is deficient compared with sodium content. Hypernatremia can be the result of pure sodium excess but is usually associated with dehydration, secondary to excess losses of water or hypotonic fluids. Hypernatremic dehydration is less common than hyponatremic or isonatremic dehydration, but is associated with the highest morbidity and mortality rate, primarily related to CNS dysfunction. Except when hypernatremia has developed rapidly, the serum sodium concentration should be corrected slowly with frequent monitoring of serum electrolytes. Even then CNS damage can result, either as a consequence of the hypernatremia itself or of rapid lowering of the serum sodium concentration.