A prospective, randomized, multicenter trial of tacrolimus-based therapy with or without basiliximab in pediatric renal transplantation.

In a 6-month, multicenter, randomized, controlled, open-label, parallel-group trial, we investigated the efficacy and safety of adding basiliximab to a standard tacrolimus-based regimen in pediatric renal transplant recipients. Patients < 18 years received tacrolimus/azathioprine/steroids (TAS, n = 93) or tacrolimus/azathioprine/steroids/basiliximab (TAS + B, n = 99). Target tacrolimus levels were 10-20 ng/mL between days 0-21 and 5-15 ng/mL thereafter. Steroid dosing was identical in both groups. Basiliximab was administered at 10 mg (patients < 40 kg) or 20 mg (patients > or = 40 kg) within 4 h of reperfusion; the same dose was repeated on day 4. Biopsy-proven acute rejection rates were 20.4% (TAS) and 19.2% (TAS + B); steroid-resistant acute rejection rates were 3.2% and 3.0%, respectively. Patient survival was 100%; graft survival rates were 95% in both arms. The nature and incidence of adverse events were similar in both arms except toxic nephropathy and abdominal pain, which were significantly higher in the TAS + B arm (14.1% vs. 4.3%; p = 0.03 and 11.1% vs. 2.2%; p = 0.02; respectively). Median serum creatinine concentrations at 6 months were 86 micromol/L in the TAS and 91 micromol/L in the TAS + B arm; glomerular filtration rate was 79.4 and 77.6 (mL/min/1.73 m2), respectively. Adding basiliximab to a tacrolimus-based regimen is safe in pediatric patients, but does not improve clinical efficacy.

Multicystic dysplastic kidney and Kallmann's syndrome: a new association?

BACKGROUND: Kallmann's syndrome is characterized by anosmia and hypogonadotrophic hypogonadism. Radiographic studies of teenagers and older subjects with the X-linked form of the syndrome have shown that up to 40% have an absent kidney unilaterally. Although this has been attributed to renal "agenesis", a condition in which the kidney fails to form, little is known about the appearance of the developing urinary tract either pre- or post-natally in individuals with Kallmann's syndrome. METHODS: We describe two brothers who had features of Kallmann's syndrome, most probably of the X-linked variety, who both had a major urinary-tract malformation detected before birth. RESULTS: The brothers were found to have unilateral multicystic dysplastic kidneys on routine antenatal ultrasound scanning and both underwent surgical nephrectomy of these organs post-natally. Immunohistochemical studies on the younger sibling revealed hyperproliferative dysplastic kidney tubules which overexpressed PAX2, a potentially oncogenic transcription factor, and BCL2, a cell-survival factor, surrounded by metaplastic, alpha smooth-muscle actin-positive stroma: similar patterns have been observed in patients with non-syndromic multicystic dysplastic kidneys. CONCLUSIONS: Our results describe a new type of urinary-tract malformation associated with Kallmann's syndrome. However, since multicystic kidneys tend to involute, only when more Kallmann's syndrome patients are screened in utero or in early childhood using structural renal scans, will it be possible to establish whether multicystic kidney disease is a bona-fide part of the syndrome.

The late histologic findings in diarrhea-associated hemolytic uremic syndrome.

Kidney biopsies were undertaken for persisting proteinuria 3.3 to 7 years (mean 5.4 years) from the onset of diarrhea-associated hemolytic uremic syndrome (D + HUS) in 5 boys and 2 girls (age at presentation mean 3.2 years, range 1.0 to 9.7 years). At 1 year the mean early morning urine protein/creatinine ratio was 100 mg/mmol, and the mean glomerular filtration rate was 65 mL/min/1.73 m2. At 5 years the mean early morning urine protein/creatinine ratio was 81 mg/mmol, and the mean glomerular filtration rate was 73 mL/min/1.73 m2. The biopsy specimens were compared with those of 7 age- and sex-matched children who were investigated for isolated persistent microscopic hematuria but in whom no abnormality was detected. Global glomerulosclerosis was noted in 6 patients with D + HUS, and 2 of these had segmental sclerosing lesions. Tubular atrophy and interstitial scarring were seen in all but 1 patients. The glomeruli in the D + HUS group were significantly larger than in the control group (P < .01). These findings are typically found in kidneys with reduced nephron numbers and are compatible with changes of hyperperfusion and hyperfiltration in surviving nephrons. Long-term follow-up of patients with D + HUS and proteinuria is advisable.

A review of acute renal failure in children: incidence, etiology and outcome.

We reviewed our experience of children with acute renal failure. St James's University Hospital, Leeds, UK is a tertiary referral center that serves a relatively stable regional population (former Yorkshire region). It is a mixed rural and urban population providing a unique profile of the nature of the cases and workload experienced. The data is expressed as a function of age and compared against a previous era of paediatric nephrology and current adult incidence data. Over an 8-year period (1984-1991) 227 children were referred for dialysis management of acute renal failure. The yearly incidence was 0.8 per 100,000 total population. Acute renal failure in the child population was almost a fifth of the adult incidence. Age-related incidence however shows the highest incidence in the neonate/infant population and is comparable to adult data. The intensive care unit was needed for nearly half the children. For all ages hemolytic uremic syndrome was the commonest cause (45%). Surgery for congenital heart disease was predominant (63%) in the neonate group. The overall mortality was 25%. Primary renal disease accounts for only 7% of the etiologies and was the source for the majority that went on to require chronic renal replacement therapy. Acute renal failure is nearly always a secondary event in the face of other organ failure and the majority of the mortality arises from surgery for congenital heart disease. If the underlying condition is treatable, the prognosis for recovery from acute renal failure with appropriate supportive care is excellent.

Neonatal aortic arch thrombosis.

An infant presented shortly after birth with signs suggestive of aortic coarctation. Echocardiography revealed an extensive aortic arch thrombus, not amenable to surgery. Thrombolytic agents reduced thrombus size, enabling survival, but failed to prevent neurological damage secondary to cerebral embolisation.