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Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, and copy number variation in complement factors and inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism in the complement inhibitor C4b-binding protein (C4BP) α-chain (c.719G>A; p.Arg240His), which is associated with aHUS. This heterozygous change was found in 6/166 aHUS patients compared with 5/542 normal (χ2 = 6.021; p = 0.014), which was replicated in a second cohort of aHUS patients in which we found 5/170 carriers. The polymorphism does not decrease expression efficiency of C4BP. p.Arg240His is equally efficient as the wild type in binding and supporting degradation of C4BP but its ability to bind C3b and act as cofactor to its degradation both in fluid phase and on surfaces is impaired. This observation supports the hypothesis that dysregulation of the alternative pathway of complement is pivotal for aHUS. Three of the patients carry also mutations in membrane cofactor protein and factor H strengthening the hypothesis that individuals may carry multiple susceptibility factors with an additive effect on the risk of developing aHUS.

We report three infants with severe, early hypertension due to unilateral renovascular disease, whose cardiovascular changes, or polycythaemia, or both, indicated they had been affected as fetuses. All underwent unilateral nephrectomy, and had a similar histology, with patchy areas having relatively normal glomeruli but immature proximal tubules. This pattern may be a marker for renovascular disease in fetal life.

Acute renal failure is common in the neonatal period. It is usually manifest by abnormal biochemistry and decreased urine output (

Our understanding of disorders that present with hypocalcaemia has advanced rapidly in the past decade. The molecular basis of many of these disorders and conditions associated with phosphate wasting has now been established. While many children will need specialist involvement, they often will present to general paediatricians, and appropriate investigations prior to intervention will enable early diagnosis. Not all children with hypocalcaemia and low or low normal parathyroid hormone levels have isolated hypoparathyroidism, and clinicians need to be aware of the potential for misdiagnosis. Outpatient departments and paediatric wards should have a readily accessible and comprehensive list of bloods that need to be taken when a child presents with hypocalcaemia or rickets.

Streptococcus equi subspecies zooepidemicus infection is rare in humans, but a well-known cause of pyogenic disease in cows and horses. S. zooepidemicus uncommonly causes post-strep glomerulonephritis (PSGN) in humans via epidemic outbreaks. We present a sporadic case of post S. zooepidemicus glomerulonephritis in a child most probably contracted from a horse. The 14-year-old girl presented with the typical signs of PSGN, with S. equi zooepidemicus isolated from a blood culture, together with a low C3 and raised anti-DNAse B. This is the first known report of a sporadic case of PSGN in a child caused by this organism.

As outlined in by Wilmshurst,1 black or Asian doctors who have misrepresented their qualifications will be treated differently from their white counterparts. The GMC may well be institutionally racist, but it probably …

Nephrotic syndrome in the first year of life (NSFL) is a heterogeneous group of disorders, the management of which is supportive, as most patients do not respond to immunosuppression. Prognosis is guarded, as the syndrome tends to lead to end-stage renal failure. We describe four cases, all of which went into spontaneous remission. These patients had severe nephrosis that began postnatally at ages 15 days to 7 months and had preceding symptoms of viral infections. One infant had proven pertussis and required ventilation for respiratory failure. Renal biopsies showed varying degrees of mesangial expansion and increased cellularity. Two biopsies showed mild mesangial sclerosis and the other two only scattered globally sclerosed glomeruli. Supportive treatment was started with 20% albumin infusions, diuretics, penicillin, and thyroxine. Angiotensin-converting enzyme (ACE) inhibitors were used to reduce proteinuria in all infants, and one was also treated with indomethacin. The nephrosis gradually resolved, and protein-lowering medications were successfully weaned completely 5–30 months after presentation. The patients were protein free with normal renal function at last follow-up. Investigations including viral studies and autoimmune profiles were negative. Genetic studies for NPHS1, NPHS2, WT1, and LAM-β were negative. We therefore describe a subgroup of NSFL with good prognosis associated with infectious prodromes. This is also the first-described case of pertussis causing nephrotic syndrome.

A total of 192 children and adolescents undergoing renal transplantation were randomly chosen to receive tacrolimus, azathioprine and corticosteroids (TAS, n = 93) or tacrolimus, azathioprine, corticosteroids and two doses of basiliximab (TAS + B, n = 99). Six-month outcome data have previously been reported; this manuscript reports the 2-year data. Complete 2-year data were available on 164 (85.4%) of the original 192 patients. There was a single death in the TAS arm. Kaplan-Meier estimates of survival free of graft loss at 2 years were 94.9% in the TAS + B arm and 89.6% in the TAS arm [hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.17 to 1.54, P = 0.23]. Estimates of survival free from rejection at 2 years were 75.2% in the TAS + B arm and 68.7% in the TAS arm (HR 0.81; 95% CI 0.46 to 1.40, P = 0.44). The mean estimated glomerular filtration rate (GFR) at 2 years, was 65.8 ml/min per 1.73 m(2) body surface area in the TAS arm and 66.7 ml/min per 1.73 m(2) in the TAS + B arm (P = 0.78). Blood pressure and cholesterol levels were similar in the two arms, and there was no evidence of a difference in the incidence of infection or malignancy. These data provide further evidence of a lack of benefit associated with the addition of basiliximab to a TAS regimen for European paediatric renal transplant recipients at low immunological risk.

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. Patients18 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 (patients40 kg) or 20 mg (patientsor = 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.

A 10-yr-old boy who presented with vomiting and abdominal pain 12 days after an uneventful renal transplant had no identifiable transplant-related cause for these symptoms. Four days later a perforated appendix was diagnosed. His case illustrates that common abdominal pathologies may present differently in immunosuppressed, transplanted patients, causing diagnostic delay.

Goodpasture’s syndrome is a rare condition in childhood. We report a case in which a 14-year-old girl with Goodpasture’s syndrome developed seizures due to central nervous system (CNS) vasculitis. At the time of the seizures, anti-neutrophil cytoplasmic antibodies (ANCA) were absent and her anti-glomerular basement membrane (anti-GBM) antibody titre had normalized following 3 weeks of plasma exchange and immunosuppressive therapy. This combination of events has not been reported previously in a child and raises questions as to the aetiology of the vasculitis.

The alleged dominance of diffuse attenuation of the glomerular basement membrane (GBM) in young children and females with Alport's Syndrome (AS) suggests that it might be the initial ultrastructural manifestation of type IV collagen defects. We carried out a 'blind' review of 130 renal biopsies obtained from 100 patients with AS, emphasizing the electron microscopy changes, and related the findings to the clinical presentation and outcome. The intracapillary distribution of (1) thickened, (2) attenuated and (3) normal GBM was assessed individually as: none (grade 0),25% (grade 1), 25-50% (grade 2) and50% (grade 3). Deafness was defined as persistent loss ofor =30 dBs. Proteinuria was measured as protein/creatinine ratios in early morning urine. Heavy proteinuria (or =200 mg/mmol) correlated significantly with the presence of segmental and global glomerulosclerosis and foam cells. Comparing grades 0+1 vs. 3 GBM changes, using a 2x2 chi(2) test, there were significant correlations between grade 3 GBM thickening and male sex (P =0.005), heavy proteinuria (P =0.02) and deafness (P0.001). GBM thickening did not correlate with age at the initial biopsy, but repeat biopsies demonstrated increasing thickening with age. The grades of GBM attenuation did not correlate with either age at biopsy or sex. In 11 biopsies with atypical lamina densa changes in thickened GBM segments, there were no differences in clinicopathological correlations compared with classical biopsies. Our data indicate that diffuse GBM attenuation can be an ultrastructural variant of the Alport nephropathy, but do not support the contention that it is the initial lesion.

An 11 year old girl developed hypertensive encephalopathy and renal failure from reflux nephropathy. Resection of her shrunken left kidney did not control her hypertension. Two selective arterial embolisations of the scarred right lower pole produced only transient benefit, but a heminephrectomy gave good control. Embolisation may delay definitive treatment.

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, α 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.

Background.There is little data on renal function in pediatric heart transplant recipients. Early rejection is a major concern and most units run high cyclosporin A (CyA) levels during the 2 to 3 months after transplantation. We sought to document long-term renal function after transplantation and to assess influence of early CyA levels.Methods.We reviewed all of our pediatric transplants between June 1985 and August 1998 who survived longer than 6 months (n = 54). Glomerular filtration rate (GFR) was estimated at 1, 2, 4, and 8 years posttransplantation using the Schwartz formula:GFR (mL/min/1.73m2) = [Ht(cm)/creatinine(μmol/L)] × XWe also analyzed whether change in renal function correlated with trough CyA levels.Results.Median age at transplant was 4 years and median follow-up was 5 years. Survival rates were 87% at 1 year and 80% at 5 years. Mean GFR pretransplant was 79 ± 19 mL/min/1.73 m2, reflecting prerenal impairment. One year later, mean GFR was 72 mL/min/1.73 m2; after 2 years it was 65 mL/min/1.73 m2, after 4 years (n = 35) it was 60 mL/min/1.73 m2, and after 8 years (n = 14) it was 57 mL/min/1.73 m2. CyA levels during the first 2 months correlated with the change in GFR during the first year (r2 = 0.21).Conclusions.This study demonstrates for the first time that decline in renal function after heart transplantation correlates with early CyA exposure; this dysfunction persists even when CyA doses are subsequently reduced.

The finding of familial haematuria without a history of deafness or renal impairment is often assumed to indicate a benign prognosis. However, we describe three families in whom Alport and thin basement membrane nephropathy were separately identified within the same pedigree. Our findings illustrate the importance of fully investigating families with haematuria, even if thin basement nephropathy has been diagnosed in one member.

EDITOR—In their article on understanding oedema Diskin et al have overlooked an important body of work that challenges the traditional pathophysiological explanation for the development of oedema in the nephrotic syndrome secondary …

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.

We reviewed the clinical and renal biopsy findings in 322 children presenting during the years 1975-1996 with recurrent macro- or continuous microscopic haematuria persisting foror =6 months, in whom non-glomerular causes were excluded. Family involvement was documented for first-degree relatives. All biopsies were examined by light microscopy, 317 by electron microscopy and 315 by immunofluorescence. Biopsies were classified as IgA nephropathy (78), Alport nephropathy (86), thin basement membrane nephropathy (TMN) (50), miscellaneous glomerulonephritis (32), hilar vasculopathy (28) and normal glomeruli (48). Although microscopic haematuria alone was more frequent in Alport nephropathy and TMN, the pattern of haematuria in individual patients did not predict histology. Of patients with familial haematuria, 79% of biopsies showed either Alport nephropathy or TMN. Hilar vasculopathy was observed both in isolation and in all abnormal histological categories.

Standard management of patients with chronic renal impairment includes the avoidance of transfusion of allogeneic red cells where practicable. This encourages erythropoiesis and minimizes exposure to human leukocyte antigen (HLA) molecules present in the transfusion [1]. Where patients become sensitized to HLA following exposure to donor material, this can limit the availability of potential kidney donors from the deceased donor pool. Significantly, there is also potential to be sensitized to living-related donors. We describe a case which led our service to alter our blood transfusion practice. A 7-year-old male with both Leber’s congenital amaurosis (LCA) and infantile pyknodysostosis developed profound marrow failure causing chronic ongoing anaemia which required multiple blood transfusions. His renal function deteriorated from tubulointerstitial nephritis and is now approaching end stage (eGFR 18 mL/min/1.73 m 2 ). The chronic anaemia eventually responded to high doses of recombinant erythropoietin. He has two siblings, one of whom has LCA, and another has pyknodysostosis. There are no suitable living donors, so the child is awaiting a deceased donor. Following repeated transfusions, he has developed antibodies to several HLA molecules with a calculated panel reactivity of 50%, excluding 71% of the UK population as suitable donors. This will likely prolong the waiting time for a suitable deceased donor, impacting on his duration of renal replacement therapy and long-term prognosis. Following recognition that HLA sensitization could devastate the available donor pool, and the fact that leukodepletion has been shown not to reduce sensitization in renal patients awaiting transplant [2] (potentially due to soluble and red-cell-bound HLA) [3], we addressed our transfusion policy. In a limited number of patients, we requested washed red cells, assuming that this would reduce the presence of soluble HLAs in the serum. Further discussion led to more definitive management of the avoidance of allosensitization by using HLA-matched red cells for transfusion as first suggested 25 years ago [4]. A recent study demonstrated matching for HLA-A-, HLA-Band HLA-DR-negated sensitization in 37 patients [5]. Concerns about HLA-matched transfusions include the availability of suitable units and the cost-benefit, given the additional expense in provision. The increased risk of sensitization in paediatric patients, the predictable need for occasional transfusion, the high probability of paediatric recipients needing more then one graft in a lifetime and the subsequent high number of quality-adjusted life years contribute to our justification that matching red cells for HLA-A, HLA-B and HLA-DR is a sensible approach for the paediatric end-stage renal population.

Ibuprofen and paracetamol are equally effective1 and widely used antipyretic agents in paediatric practice. There is no evidence to support the concept that treating a fever with antipyretics, paracetamol, or ibuprofen, will prevent febrile convulsions.2 Ibuprofen is available over the counter and is used in addition to or instead of paracetamol both in hospital and community settings. It is advertised on television. There is an increasing trend to routinely prescribe both drugs for children specifically to manage fever. Although it is considered to be a reasonably safe drug,3 there are reports of nephrotoxicity,4,5 including renal failure when ibuprofen is administered to volume depleted children.6 A previously well, 18 month old, 10.5 kg boy presented with a four week history of intermittent cough and wheeze. In the week prior to admission he developed a fever, increasing lethargy, anorexia, and refusing to drink adequately. His fever was initially treated with paracetamol (5 ml …

THOUGH HYPERTENSION IS A COMMON FEATURE OF HENOCH—Schönlein purpura (HSP) acute nephritis, it is seen only rarely and transiently if renal function is normal and abnormal urinary findings are minimal. We report a 3.4 year old girl who had the typical arthritis and rash of HSP, but also had significant hypertension with only minimal urinary findings. Imaging investigations revealed one normal kidney, and one that was almost destroyed from previous reflux nephropathy; her hypertension resolved after unilateral nephrectomy. Other causes of hypertension should be excluded in children with HSP and minimal urinary findings.

We report the use of granulocyte colony-stimulating factor (G-CSF) in a renal transplant recipient in whom neutropenia developed following a presumed viral infection. G-CSF was successful in producing a rise in neutrophil count which coincided with a resolution of fever; there was no adverse effect on renal function. This is the first use of G-CSF in a paediatric renal transplant recipient, and its use should be considered for the immunosuppressed child with persistent neutropenia.

Sirs, The recent report by Kausman et al. on the effect of vincristine on 12 children with steroid-dependent nephrotic syndrome [1] is the third retrospective publication on this subject in Pediatric Nephrology [2, 3] and brings the number of children reported to 27. As in the previous reports, Kausman’s patients had already been treated with steroids and cyclophosphamide; ten had also received cyclosporin. One of Kausman’s patients achieved longterm remission, bringing the total reported to 5/27. They also record an increase in the mean duration of remissions from 3 months to 8 months. We can add a further 17 patients to this group. Nine had steroid resistance, of whom eight had focal segmental glomerulosclerosis (FSGS), and eight had steroid dependence, of whom three had FSGS, the remainder having minimal lesion. The median (range) age was 5.3 (1.2 to 14.4) years, and 11 were boys. All 17 had received previous treatment with steroids, 12/17 with cyclophosphamide, and 4/17 with levamisole, and all were given weekly intravenous administration of vincristine 1.5 mg/ m for 8 weeks, and followed up for 2 years. Two children with steroid resistance and one child with steroid dependence achieved complete remissions within, respectively, 2 weeks, 5 months and 2 years of treatment, bringing the total to 8/44. Advantages of vincristine include its being inexpensive, its reliable administration in those who are non-compliant with oral medication, and its having few reversible side effects. Eight of our patients had side effects: four with jaw pain (three requiring carbamazepine), two becoming constipated, one with seizures, and one with foot-drop lasting 6 months. Though vincristine does appear to confer benefit on a minority of children with steroid-resistant and steroiddependant nephrotic syndrome, its role is by no means clear. We agree with Goonasekera et al. that it warrants reexamination [3] and believe that a multi-centre trial against other agents is long overdue.

Tissue plasminogen activator was used for a blocked peritoneal dialysis catheter in a child with no vascular access. The catheter was salvaged using tissue plasminogen activator and dialysis could be carried out without any difficulty.

Sirs, The media has periodically highlighted traveller’s thrombosis, particularly where fatalities have arisen [1]. Several studies recognise the risk factors and incidence of deep vein thrombosis (DVT) after a long-haul flight in the adult population [2, 3]. No cases have been described affecting children. In the case we describe here, a child with the additional risk factors of factor V Leiden deficiency and nephrotic syndrome developed a DVT on return from a transatlantic flight. We report the case of a 13-year-old Caucasian girl diagnosed with biopsy-proven focal segmental glomerulosclerosis (FSGS), who responded to steroids and was in remission and steroid free for 2 years subsequently. Routine urine monitoring was not maintained thereafter and only instituted when clinically indicated. She flew across the Atlantic for a vacation and 2 weeks after her return presented with pain in her left groin. Clinical examination revealed a swollen left calf, which on Doppler ultrasound confirmed a DVT. Urinalysis showed 2+ protein (265 mg/mmol, nephrotic range). Blood biochemistry confirmed a low serum albumin of 19 g/l. There was no evidence of peripheral oedema, but the patient was clearly in relapse of her nephrotic syndrome secondary to FSGS. A history of DVT was noted in the maternal grandfather, secondary to immobilisation. A thrombophilia screen revealed factor V Leiden deficiency. Treatment, on confirmation of the DVT, was low molecular weight heparin, elastic stockings and steroids to treat the nephrotic syndrome, with remission achieved within 2 weeks. Following resolution of her clinical symptoms, she was converted to warfarin. Long-haul flights generate a risk for DVT because of the environment. Combining this with an unrecognised thrombosis risk as well as nephrotic syndrome can only have compounded and significantly increased this risk in our patient. Appreciating that factor V Leiden deficiency is seen in 3% of the population [4], it is perhaps not unreasonable to undertake a thrombophilia screen in all patients that present with nephrotic syndrome. This would aid in immediate management as well as in future relapses and allow for targeted advice. We would consider it good practice to advise all patients with a history of nephrotic syndrome to maintain monitoring of their urine for evidence of relapse prior, during and on return from a long-haul journey. This would also apply to those that have apparently been disease-free for a considerable time and are no longer routinely monitoring their urine. Additionally, the advice would also include the wearing of knee-high stockings, adequate mobility and hydration during a flight [5]. Patients would also be made vigilant of symptoms of a DVT on return. Our patient, now well and off warfarin, will in future inject low molecular weight heparin in the departure lounge before all future flights as well as maintain monitoring for proteinuria.