Measles-associated encephalopathy in children with renal transplants.

Two children, boys of 8 and 13 years, presented with measles-associated encephalopathy several years after kidney transplantation for congenital nephrotic syndrome. In the absence of prior clinical measles, the neurological symptoms initially eluded diagnosis, but retrospective analysis of stored samples facilitated the diagnosis of measles-associated encephalopathy without recourse to biopsy of deep cerebral lesions. Each had received a single dose of measles mumps and rubella vaccine before 12 months of age. Prior vaccination, reduction of immunosuppression and treatment with intravenous immunoglobulin and ribavirin may have contributed to their survival. Persistent measles virus RNA shedding, present in one child, was not controlled by treatment with i.v. ribavirin. Two years later, both patients continue to have functioning allografts with only minimal immunosuppression. These cases illustrate the difficulty in diagnosing measles-associated encephalopathy in the immunocompromised host, even in the era of molecular diagnostics, and highlight the renewed threat of neurological disease in communities with incomplete herd immunity.

Early treatment with allopurinol in familial juvenile hyerpuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease.

BACKGROUND: The efficacy of allopurinol in autosomal dominant familial juvenile hyperuricaemic nephropathy (FJHN) has been disputed. AIM: To address this question, in the absence of controlled trials. DESIGN: Retrospective long-term follow-up study. METHODS: All kindreds were biochemically screened. Measurements included uric acid clearance, creatinine clearance, serum creatinine, and glomerular filtration rate (GFR). We used five siblings who had died or progressed to transplantation, ten other deceased relatives, and two index cases (one untreated, one non-compliant) as controls to assess the effects of allopurinol. RESULTS: Of eight families with FJHN, six had a strong history of renal disease and early parental death (mean age 41 years, n=10). Of 27 patients started immediately on allopurinol and treated uninterruptedly, 21 responded well, including three children born subsequently. Eight siblings (mean age 19 years) with a normal plasma creatinine at start (<120 micromol/l, mean GFR 80 ml/min/1.73 m(2)) retained stable renal function (mean 14.5 years, mean age 34 years, GFR 85 ml/min/1.73 m(2)). Of the 13 other responders, treated for up to 34 years, 10 with a creatinine <200 micromol/l at diagnosis (mean age 28 years, mean creatinine 137 micromol/l at start) now have a mean creatinine of 210 micromol/l. In contrast, five patients (mean age 26 years) with a creatinine >200 micromol/l (GFR <35 ml/min/1.73 m(2)) when allopurinol commenced, plus one untreated index case, all progressed rapidly (mean 6 years) to end-stage renal failure. In two others (one non-compliant, one initially untreated), GFR fell by >50% in 7 years. Introduction of allopurinol in the latter has stabilized GFR. DISCUSSION: Allopurinol reduced the morbidity and mortality from renal failure seen in untreated siblings and previous generations of these families. Early diagnosis of FJHN is important, so that treatment can begin before irreversible renal damage has developed.

Cystic fibrosis and renal disease.

Renal disease is relatively rare in cystic fibrosis even though the cystic fibrosis transmembrane regulator (CFTR) protein is expressed in abundance in the kidney. Aberrant CFTR expression probably explains the subtle abnormalities in renal concentrating and diluting ability described in cystic fibrosis and possibly the increased incidence of nephrocalcinosis. It also provides a hypothesis for the important differences in renal handling of some drugs. As the prognosis improves for patients with cystic fibrosis, secondary renal complications, for example glomerulonephritis and amyloidosis, are likely to become more prevalent. There are also a number of potentially nephrotoxic drugs used in the management of cystic fibrosis.

Growth over 10 years following a 1-year trial of growth hormone therapy.

The growth of short children with chronic renal failure (CRF) and renal transplants was assessed over 10 years following entry into a 1-year trial of recombinant human growth hormone (rhGH) therapy. Patients were divided into three groups: 6 prepubertal patients with CRF (group 1), mean (range) age at start of trial 7.7 (5.0-10.4) years; 6 prepubertal patients with renal transplants (group 2), age 11.9 (9.5-14.6) years; and 6 pubertal patients with renal transplants (group 3), age 15.6 (14.1-18.3) years. In group 1, the mean (range) height standard deviation score (Ht SDS) increased from -2.9 (-3.7 to -2.2) to -1.9 (-2.9 to -0.5) over 4.0 (0.3-9.1) years of rhGH (P=0.04), and was -1.6 (-2.9 to -0.4) after 10 years of follow-up (NS). In group 2 Ht SDS increased from -3.3 (-4.5 to -1.9) to -2.9 (-5.4 to -0.5) over 2.7 (1.0-6.0) years and was -3.0 (-6.3 to -0.1) at final height (NS). In group 3 Ht SDS increased from -3.4 (-4.3 to -2.6) to -3.0 (-3.4 to -2.2) over 1.4 (0.2-2.3) years (NS) and was -2.5 (-3.0 to -1.9) at final height (P=0.03 from stopping rhGH to final height). Final height was attained in 13 patients, in whom Ht SDS increased from -3.2 (-4.3 to -1.9) to -2.6 (-3.9 to -0.5) on rhGH (P=0.004) and to -2.2 (-4.4 to -0.1) after stopping treatment (P=0.04). Four patients died, 2 have chronic hepatitis C, and 1 has had surgery for parathyroid adenomata. In conclusion, the majority of patients had an improvement in Ht SDS while on rhGH, which was maintained after stopping treatment.

Deaths within 90 days from starting renal replacement therapy in the ERA-EDTA Registry between 1990 and 1992.

BACKGROUND: Patients who die within 90 days of commencing renal replacement therapy (RRT) may be recorded by some centres and not others, and hence data on mortality and survival may not be comparable. However, it is essential to compare like with like when analysing differences between modalities, centres and registries. It was decided, therefore, to look at the incidence of deaths within 90 days in the ERA-EDTA Registry, and to try to define the characteristics of this group of patients. METHODS: Between 1 January 1990 and 31 December 1992, 78 534 new patients started RRT in 28 countries affiliated to the ERA-EDTA Registry. Their mean age was 54 years and 31% were over 65 years old. Eighty-two per cent of the patients received haemodialysis (HD), 16% peritoneal dialysis (PD) and 2% had preemptive transplantation as first mode of treatment. RESULTS: From January 1990 to March 1993 the overall incidence of deaths was 19% and 4% of all patients died within 90 days from the start of RRT. Among those dying within 90 days 59% were over 65 years compared to 53% over 65 years in those dying beyond this time (P<0.0001). The modality of RRT did not influence the distribution of deaths before and after 90 days. Vascular causes and malignancy were more common in those dying after 90 days, while there were more cardiac and social causes among the early deaths. Mortality from social causes was twice as common in the elderly, who had a significantly higher chance of dying from social causes within 90 days compared to those aged under 65 years. The overall incidence of deaths within 90 days was 3.9% but there was a wide variation between countries, from 1.8% to 11.4%. Finally, patient survival at 2 years was markedly influenced in different age groups when deaths within 90 days were taken into account. CONCLUSIONS: The incidence of deaths within 90 days from the start of RRT was 3.9%, with a marked variation between countries ranging from 1.8% to 11.4%, which probably reflects mainly differences in reporting these deaths, although variable selection criteria for RRT may contribute. Deaths within 90 days were significantly more frequent in elderly patients with more early deaths resulting from cardiac and social causes, while vascular causes of death and malignancy were more common in those dying after 90 days. Patient survival analyses should take into account deaths within 90 days from the start of RRT, particularly when comparing results between modalities, countries and registries.

Antibody removal and subsequent transplantation of a highly sensitised paediatric renal patient.

We report a successful renal transplant in a highly sensitised paediatric recipient following removal of HLA-specific antibodies by extracorporeal immunoadsorption. The immediate pretransplant cytotoxic titre against the donor was greater than 1:512; this was reduced to negativity by two immunoadsorption sessions prior to transplant surgery. We also describe the presence of unexpected non-HLA-specific antibody activities in this immunoadsorbed patient.

Urinary tract infection: a comparison of four methods of investigation.

The optimal regimen for investigating children with urinary tract infection (UTI) remains uncertain. Ultrasonography, contrast micturating cystourethrography (MCU), intravenous urography (IVU), and technetium-99m dimercaptosuccinic acid (DMSA) studies were performed in 58 children with UTI under 14 years of age attending two teaching hospitals and the results compared. All four investigations were normal in 12 children. In 36 with vesicoureteric reflux (VUR) on MCU, dilatation was reported on ultrasonography in eight children. Radiological renal scarring was seen in 20 children; it was suspected on ultrasonography in nine, with dilatation alone in four, and a normal report in seven. Duplex kidneys identified on IVU were unrecognised on ultrasonography or DMSA studies; ultrasonography showed no change corresponding to presumed acute defects on DMSA studies that later resolved. Disparities were observed at all ages. This study suggests that ultrasonography is unreliable in detecting VUR, renal scarring, or inflammatory change and, alone, is inadequate for investigating UTI in children.

Pitfalls in the investigation of children with urinary tract infection.

The histories and imaging results are presented in 10 children in whom errors had been made in the interpretation of early investigations. Ultrasonography may not detect either vesicoureteric reflux (VUR) or renal scars or inflammation. The reduced nephrogram or renal swelling following a first attack of acute pyelonephritis may not be recognised without renal measurement on an intravenous urogram. Renal scarring may be diagnosed incorrectly on the basis of functional defects of isotope uptake on a technetium 99m-dimercaptosuccinic acid study. In the absence of VUR, the micturating cystogram will not visualise the kidneys.

Excess melanocytic nevi in children with renal allografts.

BACKGROUND: Renal allograft transplantation is associated with an increased incidence of malignant melanoma. The development of excess melanocytic nevi may be an indicator of this risk. OBJECTIVE: This study determines the prevalence of melanocytic nevi in children who have received renal allografts. METHODS: Total and regional melanocytic nevi counts were made in 38 children (27 boys, 11 girls) with a renal allograft and in 38 individually age- and sex-matched healthy controls; counts were related to age, sex, skin type, and duration of immunosuppression. RESULTS: There was a significant increase in the total number of nevi in the renal transplant group compared with the control group (p < 0.05), with most marked increases occurring on the back and at acral sites. A strong positive correlation between nevi count and duration of immunosuppression independent of age was observed (p < 0.005). CONCLUSION: Excess numbers of melanocytic nevi occur in children with renal allografts. These patients constitute a risk group for malignant melanoma and require continued assessment.

The management of renal transplant artery stenosis in children by percutaneous transluminal angioplasty.

Between 1967 and 1989 in this unit 262 children (age at transplantation 9 months to 17 years, mean 9.6 years) had 345 renal transplants performed. Transplant artery stenosis (TAS) was found in 30 (8.7%) as demonstrated by arteriography, performed only when there was unexplained deterioration in transplant function, hypertension that was difficult to control, or in the presence of a vascular bruit. All patients with TAS except one had received a cadaveric allograft. From 1980 onward, percutaneous transluminal angioplasty (PTA) has been available for TAS, and this was attempted on 21 occasions in 16 patients. Nine patients demonstrated angiographic improvement following the procedure, and 7 showed immediate clinical improvement. On one occasion angioplasty precipitated graft loss. Five patients underwent planned corrective surgery, 4 after unsuccessful angioplasties. Our experience suggests that PTA should be the first method of intervention for TAS. Moderate success, both in angiographic and clinical terms, can be achieved, negating the need for surgery, while failure of PTA does not preclude surgical attempts at correction.

Renal disease, epidermal necrosis, and epithelial cell antibodies.

OBJECTIVE: To describe the association between epithelial cell IgM, which has previously been associated with an increased incidence of loss of renal graft in children, with a novel cutaneous eruption and unexplained native renal disease. DESIGN: Observational study on children with epithelial cell antibody presenting with unexplained renal or skin disease. SETTING: General paediatric department and regional paediatric nephrology unit. PATIENTS: Six children (five girls, one boy), who presented to the unit in 1989-90. RESULTS: Three children, two of whom had a history of a hyperpigmented rash, presented with hypertension, proteinuria, and impaired renal function. Renal biopsy specimens from two of these children showed severe arteriolar endothelial cell swelling with arteriolar occlusion. These children fully recovered after treatment with antihypertensive drugs. The third child developed end stage renal failure and required dialysis. Three other children presented with an unusual cutaneous eruption but no evidence of renal disease. Histology of the skin lesions showed acute epidermal necrosis and features consistent with a viral infection. CONCLUSIONS: The aetiology and pathogenesis of the epithelial cell antibody are unknown. These cases indicate that it may have a role in native kidney disease and focal epidermal necrosis. Clinical and histological features suggest that the antibody may be associated with a viral infection.

Chronic renal failure and growth.

Growth was assessed in 38 prepubertal children with chronic renal failure for a mean (range) of 2.3 (1-4) years. At first clinic visit their mean (range) glomerular filtration rate was 17 (7-35) ml/min/1.73 m2, their mean (range) age was 3.4 (0.2-9.1) years, and 23 (61%) were greater than two standard deviations below the mean for height. After intensive medical management of their chronic renal failure, half of the children who presented before 2 years of age showed appreciable catch up growth. Only a slow improvement in growth occurred in most children presenting over 2 years of age. At final assessment, the mean (range) glomerular filtration rate was 15 (6-42) ml/min/1.73(2) and 20 (53%) were greater than two standard deviations below the mean for height. There was no correlation between glomerular filtration rate and growth. There remained a group of children who continued to grow poorly. Many of these were of low birth weight, and had dysplastic kidneys.

Long term outcome of treatment of end stage renal failure.

The most common causes of end stage renal failure in 46 children (mean age 11 years, range 4-14) treated between January 1972 and June 1977 were: reflux nephropathy (n = 12), cystinosis (n = 7), focal and segmental glomerulosclerosis (n = 6), and Schönlein-Henoch disease (n = 5). The quality of life, degree of renal function, and height attainment of the 31 survivors were assessed in June 1985, when their mean age was 22 years (range 14-27), using hospital records and a questionnaire designed to highlight social and psychological problems. Twenty six patients had a functioning transplanted kidney. Average growth during treatment for all survivors was normal, but most were disappointed with their 'final height'. Though five patients had some form of disabling bone disease, all 31 could walk and 27 could run. Sixteen (67%) were in full or part time employment and nine were living independently. A group of 32 patients with juvenile onset diabetes treated at this hospital for at least five years were also asked to complete the questionnaire and of these, 17 responded. On average, their data could usefully be compared with those of cases of end stage renal failure. More of the diabetics had jobs, but most sexually mature patients with renal disease were concerned about their physical appearance and had not achieved any stable long term sexual relationships. We suggest that a poor body image resulting in low self esteem may be responsible for the deficiency and believe that further study in this group is warranted.

The beneficial effect of mannitol on postoperative renal function in children undergoing cardiopulmonary bypass surgery.

A randomized prospective controlled study of prophylactic administration of mannitol 0.5 g/kg body weight in 40 children undergoing cardiopulmonary bypass surgery showed significant lower plasma creatinine concentrations and urinary albumin excretion rates in the treated compared to the control group.

Renal function following cardiopulmonary bypass surgery in children: a randomized comparison of the effects of gentamicin and cloxacillin with cephalothin.

Renal function was studied in 36 children who were randomly allocated to receive either gentamicin and cloxacillin or cephalothin as prophylactic antibiotic cover for complex cardiopulmonary bypass surgery. Both groups of children developed a similar degree of impairment of glomerular function with significant elevations in plasma creatinine concentrations and urine albumin excretion compared to preoperative levels which tended to resolve by the 5th postoperative day. The urine excretion of N-acetyl-glucosaminidase increased in both groups postoperatively but remained significantly elevated only in those children who had received gentamicin. These findings suggest that whilst gentamicin exerts a demonstrable nephrotoxic effect on the proximal renal tubules it does not contribute significantly to either the incidence or severity of postoperative renal glomerular impairment.

Acute renal failure complicating cardiopulmonary bypass surgery.

Acute renal failure developed in 24 (5.3%) of 456 children undergoing cardiopulmonary bypass surgery during a 2-year period. It was more common in younger children, in those with complex cardiac lesions, and in those with long overall bypass times. Fourteen (58%) recovered renal function; renal failure was responsible for death in only two. Early vigorous peritoneal dialysis is advocated after cardiopulmonary bypass surgery if there is oliguria (less than or equal to 1.0 ml urine/kg per hour) resistant to volume repletion, dopamine infusion and diuretics, intractable fluid overload, or hyperkalaemia.