Chronic renal failure after Puumala virus infection

Chronic renal failure has never been described after Puumala hantavirus infection, which usually causes acute renal failure with spontaneous full recovery. We report a 15-year-old boy who presented with Puumala hantavirus infection and initial severe acute renal failure. His renal function gradually improved, but more than 2 years after the acute episode it was still moderately impaired, with a creatinine clearance of about 60 ml/min per 1.73 m² Received: 25 June1998 / Revised: 19 February 1999 / Accepted: 19 February 1999     

Nephrotic syndrome and end-stage renal disease with WT1 mutation detected at 3 years

We report a boy who presented at 3 years with nephrotic syndrome and end-stage renal failure. Although histopathological findings showed end-stage kidney, isolated diffuse mesangial sclerosis (IDMS) was suspected because of his clinical course, and was confirmed by the presence of WT1 (Wilms tumor suppressor gene) mutation. He did not have ambiguous genitalia or Wilms tumor. The karyotype was 46:XY. A constitutional mutation in exon 7 (953G→A, 312Arg→Gin) was detected. A few cases of male IDMS, associated with WT1 mutations, have been reported. We believe that investigation for the WT1 mutation should be performed not only in Denys-Drash syndrome and IDMS, but also in end-stage renal disease with unexplained nephrotic syndrome of early onset. WT1 mutation-associated nephrotic syndrome has an increased risk of Wilms tumor. Careful ultrasound evaluations or bilateral nephrectomies are indicated. Received: 24 November 1998 / Revised: 5 February 1999 / Accepted: 9 February 1999     

Modulation of the immune response by fetal kidney allografts

Fetal kidneys modulate the allogeneic immune response by a synergistic effect: first, fetal kidney tissue tropism is abrogated by the initial relative lack of adhesion molecules. Second, the reduced expression of major histocompatibility complex (MHC) determinants is less effective in inducing the alloantigen-primed T cell response, which in turn induces the downregulation of Th1 cytokines, β chemokines, and Fas ligand, but spares protective Th2 cytokines, and leads to minimal induction of MHC and adhesion molecules on immature renal parenchymal elements. Thus, at the onset and during this altered rejection process, cellular recruitment to the fetal renal site is less prominent than to the adult renal tissue, and effector cells in the fetal graft are less activated. Received: 4 November 1998 / Revised: 15 February 1999 / Accepted: 15 February 1999     

Immediate post-transplant nephrosis in a patient with congenital nephrotic syndrome

A 19-month-old girl with congenital nephrotic syndrome of the Finnish type underwent a living-related renal transplant; 24 h after transplantation she became massively nephrotic. She did not respond to steroids, plasmapheresis, and high-dose cyclosporine. A month later, a renal biopsy showed only glomerular foot process effacement. She was treated with high-dose methylprednisolone pulses and oral cyclophosphamide. She rapidly went into complete remission with no further relapses. Graft function has been stable 2 years after transplantation. Received: 24 June 1999 / Revised: 21 February 2001 / Accepted: 23 February 2001     

The safety of gadolinium in patients with stage 3 and 4 renal failure.

BACKGROUND: Although there is a well-documented risk of acute renal failure (ARF) with the iodinated contrast agents, intravenous gadolinium-based contrast agents are considered non-nephrotoxic and have been widely used for magnetic resonance imaging (MRI). However, debate continues regarding the safety issue of gadolinium, especially in patients with kidney failure. Therefore, we aimed to evaluate the safety of gadolinium in patients with stage 3 and 4 renal failure as well as risk factors for nephrotoxicity. METHOD: We retrospectively analysed 473 patients with chronic renal failure who underwent angiographic MRI procedures in our centre from February 1999 to March 2005 in whom gadolinium was used as the sole contrast agent at a dose of 0.2 ml/kg. Among them, 91 patients with stage 3 or 4 renal failure according to K/DOQI definition, who had available data in their files, were enrolled in the study. The ARF was defined as an increase of at least 0.5 mg/dl in serum creatinine level over baseline after using gadolinium. RESULTS: Eleven of 91 (52 males, 39 females; median age 59 years; median estimated glomerular filtration rate (eGFR) 33 ml/min/1.73 m2) patients developed ARF (12.1%). The median eGFR was lower in patients with ARF than in those who did not develop ARF. The risk factors for ARF were baseline eGFR, older age, diabetic nephropathy and low baseline haemoglobin and albumin levels. Baseline eGFR and diabetic nephropathy were determined as the independent risk factors in regression analysis. CONCLUSIONS: An ARF can occur after gadolinium-based contrast agents in patients with moderate to severe chronic renal failure. Risk factors for ARF after gadolinium toxicity include diabetic nephropathy and low GFR.     

Xenotransplantation of the kidney: a pediatric perspective

The major factor limiting the application of allotransplantation for the treatment of renal failure is a severe shortage of donor organs. One approach to overcoming this limitation is the use of kidneys from animals for clinical transplantation, that is xenotransplantation. Although of interest for many years, the application of xenotransplantation has been prevented because of the devastating immune responses of the recipient against the graft. Research conducted in recent years has elucidated the immune mechanisms underlying the rejection of xenografts and has led to the development of incisive therapeutic strategies, including the genetic engineering of donor animals. Success in dealing with the xenogeneic immune response has encouraged the view that xenotransplantation might be feasible in the near future. It also raises consideration of two additional hurdles, the potential limitations of xenogeneic kidneys as physiological replacement for human kidneys and the possibility that the animal organ might transfer infectious organisms to the recipient and to the wider population. This paper reviews recent progress in the field of xenotransplantation of the kidney and offers a perspective on the hurdles to clinical application that remain. Received: 8 December 1998 / Revised: 4 February 1999 / Accepted: 8 February 1999     

Modulation of endochondral bone formation: roles of growth hormone, 1,25-dihydroxyvitamin D and hyperparathyroidism

Impairment of linear growth occurs invariably in children with chronic renal failure. Recombinant human growth hormone and 1,25-dihydroxyvitamin D (calcitriol) are widely utilized to improve linear growth in children. Large doses of calcitriol, however, have been shown to suppress chondrocyte proliferation and may lead to the development of adynamic bone. Substantial reductions of growth have been shown in children with chronic renal failure treated with intermittent calcitriol therapy. These findings suggest that calcitriol can modify chondrocyte proliferation and/or differentiation in epiphyseal growth plate cartilage and may counteract the effects of growth hormone therapy in increasing linear growth in children with chronic renal failure. Parathyroid hormone related peptide (PTHrP) and its receptor (PTH/PTHrP receptor) play critical roles in regulating chondrocyte differentiation in the growth plate. The expression of PTH/PTHrP receptor mRNA is downregulated in animals with chronic renal failure and advanced secondary hyperparathyroidism; calcitriol and growth hormone therapy may modify the expression of PTH/PTHrP receptor. This article summarizes the separate and combined effects of growth hormone and calcitriol on endochondral bone formation in chronic renal failure and secondary hyperparathyroidism. Received: 10 September 1999 / Revised: 23 December 1999 / Accepted: 30 December 1999     

Steroid responsive nephrotic syndrome associated with bilateral renal dysplasia

Renal dysplasia is characterized by hypoplastic kidneys that contain elements of primitive tubules. Patients may develop end-stage renal failure early in life. Nephrotic syndrome is one of the most common renal diseases in childhood and may occur in association with renal dysplasia. We report a case of a child with bilateral dysplastic kidneys and steroid responsive nephrotic syndrome (SRNS). An association between renal dysplasia with chronic renal failure and SRNS has not previously been reported in the English literature. Received: 15 February 2000 / Revised: 29 January 2001 / Accepted: 29 January 2001     

Hemolytic uremic syndrome associated with Denys-Drash syndrome

The Denys-Drash syndrome is defined by the occurrence of combinations of pseudohermaphroditism, nephrotic syndrome with diffuse mesangial sclerosis, Wilms’ tumor, and constitutional mutations in the WT1 suppressor gene. Most patients develop end-stage renal failure. Atypical hemolytic uremic syndrome (HUS) is defined by onset of acute hemolytic anemia with fragmented erythrocytes, thrombocytopenia, and renal failure in the absence of a gastrointestinal prodromal illness of bloody diarrhea. The purpose of this report is to describe the occurrence of features of atypical HUS and Denys-Drash syndrome in two African-American boys aged 13 and 16 months. Each had nephrotic syndrome, diffuse mesangial sclerosis, and WT1 point mutations. Both had grade III hypospadias and undescended testes. They had normal serum creatinine concentrations and hematology a month before presenting with HUS. Stool cultures for Escherichia coli 0157:H7 were negative. Each patient has been transplanted with cadaver kidneys without recurrence of HUS. Received: 20 July 1999 / Revised: 22 February 2000 / Accepted: 17 March 2000     

Crystals from fat. Acute oxalate nephropathy.

Case A 69-year-old man was admitted with acute renal failure. Pastmedical history included chronic pancreatitis caused by heavyalcohol intake, diagnosed in 1972, with an ensuing requirementfor enzyme replacement therapy and development of non-insulindependent diabetes mellitus. In February 1999 his serum creatinine(SCr) was 80 µmol/l. One month later, he stopped pancreaticenzyme therapy and experienced fatty diarrhoea. At the end     

Improved growth velocity with intensive dialysis. Consequence or coincidence?

Growth failure in children with end-stage renal disease remains a difficult problem. A 2.5-month-old baby in renal failure due to primary hyperoxaluria type I received intensive dialysis aimed at decreasing oxalate tissue accretion. Over 5.5 months, while awaiting transplantation, his growth velocity was 29 cm/year compared with an average 4 cm/year in infants on hemodialysis and 22 cm/year in normal infants of this age. This remarkable growth rate, which could have represented catch-up growth, is hypothesized to be related to the delivered dialysis dose. It is suggested that this relationship be evaluated in a prospective randomized trial. Received: 2 June 1999 / Revised: 14 October 1999 / Accepted: 20 October 1999     

The incidence of end-stage renal failure in 17 years of heart transplantation: a single center experience.

BACKGROUND: Predictions of the incidence of renal failure within a heart transplant population are based on the early experiences of cyclosporine (CsA)-based immunosuppression. We report a single-center experience of end-stage renal failure (ESRF) during a 17-year period encompassing current lower dose CsA regimens. METHOD: Prospectively collected data were analyzed on all patients who underwent first heart transplants between April 1982 and February 1999 (n = 697). We further categorized patients by the date of transplantation into a higher and lower dosage maintenance CsA group. RESULTS: End-stage renal failure developed in 44 patients. The median time to dialysis was 87 months after transplantation and was independent of the initial CsA regimens used (p = 0.798). In the ESRF group, 14 underwent hemodialysis, 28 underwent peritoneal dialysis, and 9 underwent renal transplantation. One- and 5-year survival rates after dialysis were 82% and 62% respectively. The incidence of ESRF at our institution was 5.8%. It increased with post-operative survival and was independent of the initial CsA regimen used. We found no difference in pre-transplant age, sex, diagnosis, immediate post-operative creatinine, or the development of diabetes between the ESRF group and controls. The ESRF group received higher dosages of CsA within the first post-transplant year, although this did not reach significance (CsA dosage, 5.9 microg/kg/day vs 5.1 microg/kg/day, respectively p = 0.075). CONCLUSIONS: Lower dosage CsA regimes have not altered the incidence of ESRF at our institution, suggesting an individual predisposition to nephropathy. Therefore, reduction in the future incidence of ESRF may rely on extremely low-dose or calcineurin-free immunosuppression regimes.     

Spontaneous clinical improvement in dense deposit disease

The clinical course and 3-year follow-up of a female patient aged 11 years who presented with nephrotic syndrome and renal failure is described. The renal biopsy revealed type II membranoproliferative glomerulonephritis or dense deposit disease. She was treated with penicillin prophylaxis, frusemide and captopril, and was not given immunosuppression, anticoagulation or antiplatelet therapy. Despite poor prognostic clinical and pathological features, she had spontaneous resolution of her renal failure and proteinuria, although her proteinuria recurred 17 months post presentation. Her unusual progress, with improvement in her disease activity and normalisation of her glomerular filtration rate, is described. Received: 7 August 1998 / Revised: 13 July 1999 / Accepted: 14 July 1999     

Enterohemorrhagic Escherichia coli infections: following transmission routes

Infections with enterohemorrhagic Escherichia coli (EHEC) are the major cause of hemolytic-uremic syndrome (HUS ), the most-common cause of acute renal failure in childhood. The mortality rate of HUS (0%–5% in most recent series and 10%–30% in individual reports) and residual chronic renal sequelae (in up to 50% of patients in long-term follow-up studies) emphasize the seriousness of HUS for public health. Several studies have described possible sources of EHEC infection. However, in the majority of cases the pathogen cannot be identified in food or animals and the routes of transmission remain unclear. In this review article the hypothesized routes of transmission are summarized. The medical data bases ”Medline” and ”Current contents” were screened for the years January 1966 through November 1998. The difficulties in following the chain of EHEC infection are discussed. A precise evaluation of the environmental aspects of the patient is a precondition for further analysis. Received: 11 September 1997 / Revised: 4 January 1999 / Accepted: 15 February 1999     

Vesicoureteric reflux associated with renal dysplasia in the Wolf-Hirschhorn syndrome

Wolf-Hirschhorn syndrome (WHS) is caused by a partial deletion of the short arm of chromosome 4 (4p16.3) and is characterized by severe pre- and postnatal growth retardation, developmental delay, and multiple congenital anomalies, including malformations of the urogenital system. We describe the renal and urinary tract phenotype in a series of six children with WHS. Vesicoureteric reflux was present in four of our six patients (5 of 10 ureters), an abnormality not previously reported in WHS. Received: 25 February 1999 / Revised: 12 July 1999 / Accepted: 13 July 1999     

Growth hormone and markers of immune function in children with renal transplants

Lymphocyte subsets and T cell activation markers were measured in ten children with renal transplants for up to 1 year before and during their 1st year of recombinant human growth hormone (rhGH) treatment. The number of lymphocytes, helper or cytotoxic T cells or natural killer cells, and the T cell expression of CD25, CD26 and HLA-DR antigens were not altered by rhGH. B cell numbers declined both before and during treatment. There was no difference in lymphocyte subset numbers between children with and without rejection episodes. Received: 5 February 1999 / Revised: 1 February 2000 / Accepted: 10 February 2000     

Autopsy case of miliary tuberculosis with cerebral involvement in renal failure

We encountered an autopsy case of renal failure complicated by cerebral tuberculosis. The patient was hospitalized due to disturbance of consciousness, and dialysis therapy was performed because of end-stage renal failure. Approximately 1 week later, abnormal shadows were observed on chest X-ray, and various examinations were performed until the diagnosis was finally determined as miliary tuberculosis. Disturbance of consciousness was exacerbated, despite the administration of antituberculosis drugs and other treatments, and the patient died on the 105th hospital day. Pathological examinations demonstrated miliary tuberculosis associated with intracranial involvement, in addition to contracted kidneys. In patients with end-stage renal failure, the risk of developing tuberculosis, miliary tuberculosis in particular, is reported to be much higher than in normal subjects. However, the diagnosis of miliary tuberculosis is difficult to establish, because of nonspecific symptoms and the low rate of detection of acid-fast bacteria from the sputum. Comprehensive understanding of the results of frequent culture examinations of sputum and blood, contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), and Polymerase chain reaction (PCR) of cerebrospinal fluid, as well as albumin concentration in the cerebrospinal fluid, are considered useful in diagnosing intracranial tuberculosis. Although cerebral tuberculoma is rare, prolonged disturbance of consciousness may be related to cerebral tuberculosis. Therefore, particular attention should be paid to patients with end-stage renal failure complicated by disturbance of consciousness. Received: October 9, 1998 / Accepted: February 23, 1999     

Acute necrotizing tubulointerstitial nephritis due to systemic adenoviral infection

To date, all the reported cases of acute necrotizing tubulointerstitial nephritis (TIN) secondary to systemic adenovirus infection have occurred in individuals with primary or secondary immunodeficiency, and have resulted in renal failure and death. We present the case of a 12-year-old, immunologically competent girl who developed acute necrotizing TIN with acute renal failure (ARF), hepatitis and meningoencephalitis secondary to a systemic adenoviral infection who completely recovered with supportive care. Received: 11 February 2000 / Revised: 6 July 2000 / Accepted: 18 August 2000     

Towards guidelines for dialysis in children with end-stage renal disease

There are few data describing the current practices of treatment selection for children with end-stage renal disease (ESRD). In an effort to establish a consensus among Spanish pediatric nephrologists for inclusion and exclusion criteria for renal replacement therapy in children with ESRD, in 1995 we surveyed members of the Spanish Pediatric Nephrology Association. Although only 43% of members responded, pediatric nephrologists and bioethicists studied the results and compiled a list of ten guidelines for treatment of children with ESRD. The proposed guidelines are meant to be a starting point for further discussion. An emphasis on flexibility, individual case assessment, and consideration of the best interests of the patient must remain central to any treatment plan. Decision making should ideally be shared by parents, professionals, the child, when appropriate, and ethics committees, as necessary. Received: 9 February 1999 / Revised: 21 June 1999 / Accepted: 28 June 1999     

The ethics of withholding and withdrawing dialysis therapy in infants

Pediatric nephrologists may encounter infants with renal failure who have either unexpectedly survived lung hypoplasia at birth or whose renal failure could be treated but comorbid conditions exist. As a member of the health care team, the pediatric nephrologist may be asked to guide therapeutic intervention with parents, family members, and other care-givers. We present a case study that illustrates some of the difficulties that may arise when conflicting social and economic pressures, as well as public opinion and legal authority, enter the decision-making process. Clinical, theoretical, legal, and economic considerations involved in the ethical decision process are presented. Some tentative guidelines for approaching such dilemmas are offered bearing in mind a goal of consensual decision making. Received: 24 March 1999 / Revised: 28 September 1999 / Accepted: 5 October 1999