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Background Scapholunate interosseous ligament injuries are common but remain a therapeutic challenge. Current treatment modalities prioritize restoration of normal anatomy with reconstruction where appropriate. To date no reconstructive technique has been described that discusses the potential benefit of preservation of the scapholunate ligament remnant. Little is known about the “ligamentization” of grafts within the wrist. However, a growing body of knee literature suggests that remnant sparing may confer some benefit. In the absence of wrist specific studies, this literature must guide areas for potential augmentation of current surgical practices. Objective The purpose of this study was to perform a review of the process of ligamentization and a systematic review of the current literature on the possible role of ligament sparring and its effect on ligamentization. Methods A systematic search of the literature was performed to identify all the studies related to remnant sparing and the ligamentization of reconstructed tendons, regardless of graft type or joint involved from MEDLINE, EMBASE, and PubMed until February 1, 2016 using the following keywords: ligamentization, graft, remodelling, reconstruction, biomechan*, histolo∗, scapholunate ligament. Each selected study was evaluated for methodological quality and risk of bias according to a modified Systematic Review Center for Laboratory Animal Experimentation criteria. Conclusions The available literature suggests that ligament sparring demonstrated a trend toward improvements in vascularity, mechanoreceptors, and biomechanics that lessens in significance over time. Clinical Relevance This review suggests that remnant sparing may be one way to improve outcomes of scapholunate ligament reconstructive surgery. Level of Evidence This is a level I/II, review study.

In 1965, the specialty of paediatric nephrology was in its infancy. Following the development of a landmark collaborative research study, the International Study of Kidney Disease in Childhood in the mid-1960s, the first specialist societies were formed: the European Society of Pediatric Nephrology in 1967 and the American Society of Pediatric Nephrology in 1969. The extraordinary improvements in care delivered to children with kidney disease over the past 50 years are too broad to cover in any one paper. They traverse the spectrum of diagnosis, classification, therapeutics, social well-being and transition to adult care. We have selected four case scenarios to highlight these changes in key areas of paediatric nephrology: post-streptococcal glomerulonephritis, nephrotic syndrome, haemolytic uraemic syndrome and neonatal dialysis and childhood transplantation.

BACKGROUND: The calcium-sensing receptor regulates the secretion of parathyroid hormone in response to changes in extracellular calcium concentrations, and mutations that result in a loss of function of the receptor are associated with familial hypocalciuric hypercalcemia. Mutations involving a gain of function have been associated with hypocalcemia in two kindreds. We examined the possibility that the latter type of mutation may result in a phenotype of familial hypocalcemia with hypercalciuria. METHODS: We studied six kindreds given a diagnosis of autosomal dominant hypoparathyroidism on the basis of their hypocalcemia and normal serum parathyroid hormone concentrations, a combination that suggested a defect of the calcium-sensing receptor. The hypocalcemia was associated with hypercalciuria, and treatment with vitamin D resulted in increased hypercalciuria, nephrocalcinosis, and renal impairment. Mutations in the calcium-sensing-receptor gene were identified by DNA-sequence analysis and expressed in human embryonic kidney cells (HEK-293). RESULTS: Five heterozygous missense mutations (Asn118Lys, Phe128Leu, Thr151Met, Glu191Lys, and Phe612Ser) were detected in the extracellular domain of the calcium-sensing-receptor gene and shown to cosegregate with the disease. Analysis of the functional expression of three of the mutant receptors in HEK-293 cells demonstrated shifts in the dose-response curves so that the extracellular calcium concentrations needed to produce half-maximal increases in total inositol phosphate in the cells were significantly (P=0.02 to P

Objectives: Darbepoetin alfa (Aranesp®) is a novel erythropoiesis stimulating protein that has beenshown in adult trials to have safety and tolerability equivalent to recombinant human erythropoietin.However, to date there is only limited published data on the use of Aranesp inpaediatric patients.The objective of this study was to determine the safety and efficacy of darbepoetin in children withchronic and endstage kidney disease.Methods: From 2003 to 2006, 30 children with either chronic or end stage kidney disease wereenrolled in a prospective observational study. The initialdose of darbepoetin was 0.45 mcg/kgweekly (either IV or SC) and subsequent dose was titrated to achieve haemoglobin (Hb) between110 and 130 g/dl.Results: Data analysis to date includes 22 patients (16 male : 6 female) whose agesranged from 1month to 17 years (mean 9 years). Hb improved significantly with darbepoetin treatment from mean84 g/dl (range 64-107) at start of treatment to 115 g/dl (range 81-147, p

The outcome of transplantation from grandparent donors in comparison with parental donors in paediatric renal transplantation was evaluated in 53 living related donor (LRD) transplantations performed between January 1996 and August 2003. The donor in 13 cases (25%) was a grandparent (Gpar group), and the remaining donors formed the parent group (Par group). The median age of recipients in the Gpar group was 2.75 (1.7-10.6) years and in the Par group was 12.75 (2.4-22) years (P

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.

Immunohistochemistry is a method that can provide complementary diagnostic and prognostic information to morphological observations and soluble assays. Sensitivity, specificity, or requirements for arduous sample preparation or signal amplification procedures often limit the application of this approach to routine clinical specimens. Rolling circle amplification (RCA) generates a localized signal via an isothermal amplification of an oligonucleotide circle. The application of this approach to immunohistochemistry could extend the utility of these methods to include a more complete set of immunological and molecular probes. RCA-mediated signal amplification was successfully applied to the sensitive and specific detection of a variety of cell surface antigens (CD3, CD20, and epithelial membrane antigen) and intracellular molecules (vimentin and prostate-specific antigen) within a variety of routinely fixed specimens, as well as samples prepared for flow cytometry. RCA technology, which has an intrinsically wide dynamic range, is a robust and simple procedure that can provide a universal platform for the localization of a wide variety of molecules as a function of either antigenicity or nucleic acid sequence. The use of RCA in this way could enhance the use of markers of current interest as well as permit the integration of emerging information from genomics and proteomics intocell- and tissue-based analyses.

Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are two related conditions caused by mutations of the Wilms tumor gene, WT1. Both syndromes are characterized by male pseudohermaphroditism, a progressive glomerulopathy, and the development of genitourinary tumors. DDS and FS have previously been distinguished by differences in nephropathy, with DDS patients demonstrating diffuse mesangial sclerosis (DMS) in contrast to focal and segmental glomerulosclerosis (FSGS) in FS patients. The clinicopathological features and genotype analysis of two patients with WT1 mutations are presented in this report. Genotype analysis of the first patient revealed a previously undescribed mutation in exon 8 of the WT1 gene. The second patient presented with a rapidly progressive nephropathy characterized histologically by DMS, but was found to have the genetic mutation seen in FS patients. A summary of all reported patients with the characteristic mutation associated with FS demonstrates the clinical overlap of this syndrome with DDS. This suggests that both these conditions should be considered as part of the spectrum of disease due to WT1 gene mutations rather than as separate diseases. Clinical classification remains important for prognosis, as the underlying renal disease appears to predict the progression of nephropathy independently of the genetic abnormality.

Left ventricular abnormalities in children, adolescents and young adults with renal disease. The cardiac abnormalities that complicate chronic renal failure and renal replacement therapy are not well characterized in young people. These abnormalities are becoming more important because successful renal transplantation has resulted in children with end-stage renal failure living longer. Echocardiographic abnormalities of cardiac function and structure were studied in children and young adults (< 27 years old) with chronic renal failure (CRF, N = 32), end-stage renal failure treated with chronic peritoneal dialysis (CPD, N = 10) or renal transplantation (N = 30) or controls (N = 60). Left ventricular mass indexed for height (LVM/Ht and LVM/Ht2.7) and body surface area (LVM/SA), fractional shortening, measurement of left ventricular diastolic function (peak E and A wave velocities and the E/A ratio) and structural (such as valvular) abnormalities were determined by echocardiography. The median (and range) of LVM/Ht in the groups were control 51.8 (23.1 to 119.8), CRF 60.2 (22.2 to 135.8), CPD 80.2 (44.5 to 100.9) and transplant group 97.8 (51.2 to 182.1) g/m. The increases in LVM/Ht, LVM/Ht2.7 and LVM/SA in the transplant group were significant (P < 0.01). The CRF group had significantly increased LVM/Ht2.7 and LVM/SA (P < 0.01). Systolic function was not significantly different between the groups. A significant correlation between creatinine and LVM indexed for height was found in the CRF group. Systolic or diastolic blood pressure could not be correlated with LVM indices in the transplant group. Changes in diastolic function were found (increased peak A wave velocity and decreased E/A ratios in the CRF and CPD groups, and increased peak E wave velocity in the transplant group). The study demonstrated that left ventricular hypertrophy is a frequent and often severe finding in children with chronic renal failure and those treated with renal replacement therapy. Factors other than hypertension and anaemia are important, and evidence was found for a link between serum creatinine and increased left ventricular mass prior to end-stage renal failure.

Results of renal transplantation in very young children with end-stage chronic renal failure have been poor compared with those in older children and adults. Consequently small children either may not be treated or may be placed on chronic dialysis programmes. Between 1988 and 1992, six children under the age of 5 years received seven renal transplants at the Royal Children's Hospital, Parkville, Victoria, Australia; five from live donors and two from cadaver donors. All children were treated with peritoneal dialysis before transplantation, and immunosuppressed with a standardized regimen of cyclosporine, azathioprine and prednisolone. An extraperitoneal incision was used, and the donor renal vessels were anastomosed to the lower abdominal aorta and inferior vena cava or the common iliac vein. All children received intensive monitoring and fluid replacement during the peri-operative period. Patient survival was 100%. One cadaver graft failed 1 week after transplantation because of irreversible acute rejection. This child subsequently received a successful second transplant. Two children developed postoperative urinary fistulae which were treated successfully by further operation. Current renal function in all children is excellent. The success of this programme has led us to review our attitude towards renal transplantation in this age group and to advocate live donor renal transplantation as the treatment of choice in very young children with end-stage chronic renal failure whenever possible.

Defects seen on early cortical scintigrams of the renal cortex in children with urinary tract infection may represent acute inflammatory change or established scar. The purpose of this study was to determine the relationship between these defects and age, sex, the presence and grade of vesicoureteral reflux, and infective organism in a cohort of children examined after their first proved urinary tract infection.We prospectively examined 193 consecutive patients less than 5 years old who were seen at the ambulatory pediatric department during a 3-year period and had a first proved urinary tract infection. Children with obstructed or solitary kidneys were excluded. All patients were imaged with scintigraphy of the renal cortex and radiographic voiding cystourethrography within 15 days of diagnosis. The association of age, sex, the presence and grade of vesicoureteral reflux, and infective organism with a defect (acute pyelonephritis or a renal scar) seen on a cortical renal scan was studied.The prevalence of cortical defects was greater in the kidneys of patients less than 2 years old (96/290, 33%) than in older children (16/96, 17%) and greater in those with vesicoureteral reflux (41/92, 45%) than in those without it (71/294, 24%). Vesicoureteral reflux was absent in 63% (71/112) of kidneys with a cortical defect. No association with sex or infective organism was established. As well as having a greater prevalence of cortical defects, 145 (75%) of the 193 urinary tract infections included in the study were in children less than 2 years old. The kidneys of these younger patients also had a greater severity and prevalence of vesicoureteral reflux (74/290, 26%) than did those of older children (18/96, 19%).Early cortical defects are associated with an age less than 2 years and vesicoureteral reflux. However, the association of early defects with the presence and grade of vesicoureteral reflux is confounded by the declining prevalence and severity of reflux with age. A significant proportion of cortical defects occur in the absence of vesicoureteral reflux, and the contribution of reflux to scar formation might be less than previously considered.

It has been claimed that low protein diets slow deterioration of chronic renal failure (CRF) by reducing renal solute load. The anabolic effect of recombinant human growth hormone (rhGH) also has potential to reduce renal solute load and thereby slow progression of renal failure. The aim of this study was to determine the effect of rhGH on growth, renal solute load and renal function in children with CRF. Seven prepubertal children, aged 2-14 years, with moderately severe CRF (creatinine clearance 7.7-23.4 mL/min per 1.73m2) were treated with daily subcutaneous rhGH, 1 U/kg per week for 10-12 months. As expected, mean height velocity standard deviation scores (SDS) increased, from -2.87 before treatment to +3.39 on rhGH, and mean height increased from -3.1 to -2.4 SDS. Serum urea concentrations decreased in most patients during the first month of growth hormone treatment from a mean of 20.0 +/- 7.7 mmol/L to 14.8 +/- 5.8 mmol/L (P = 0.006). The serum urea then returned to pretreatment levels over the next few months. In the 12 months before treatment with growth hormone, mean creatinine clearance decreased from 19.3 mL/min per 1.73 m2 to 16.7 mL/min per 1.73 m2. In the next 12 months on rhGH mean creatinine clearance decreased further to 13.5 mL/min per 1.73 m2. Therefore the rate of deterioration of renal function was unaffected during treatment with growth hormone. Initial treatment with rhGH is associated with decrease in serum urea concentrations in children with CRF, probably mediated by stimulation of anabolic incorporation of dietary nitrogen into body protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Rolling circle amplification (RCA) generates a localized signal via isothermal amplification of an oligonucleotide circle reporter sequence. The application of this approach to flow cytometry could extend the utility of existing methods by enhancing the sensitivities and specificities for various applications, including early diagnosis of cancer and of hematologic and other abnormalities. RCA technology is applicable to a variety of platforms for the simultaneous detection of molecules as a function of either antigenicity or nucleic acid sequence (1)(2)(3)(4). In flow cytometry, cells of interest are characterized based on population gating. Efficient gating strategies are crucial for accurate immunophenotyping, more so in a heterogeneous cell suspension such as peripheral blood mononuclear cells (PBMCs). Usually a combination of light scatter (forward and side) and immunophenotypic markers is critical in identifying the specific cells of interest. A panel of antibodies is usually used to characterize a subset of cells based on their surface markers. However, cells can be best characterized only when the staining for each of these markers is bright enough to clearly differentiate them from unstained cells. This requires specific antibodies and intense detection signals. Abundantly expressed cell surface markers are not difficult to stain and identify compared with rare surface antigens, which are currently gaining importance in diagnostics and clinical studies. Therefore, the common challenge in clinical or diagnostic flow analysis is insufficient signal (low-intensity signals) leading to inefficient use of the existing antibody library. RCA technology can help overcome these problems. The RCA technology (RCATTM) also allows for multiplexing or multiparametric analysis of various markers simultaneously, supporting the expanding use of complex marker panels for disease diagnosis and prognosis. RCA-mediated signal amplification has been successfully applied to the detection of cell surface antigens (e.g., …

Collagen studies in newborn rat kidneys with incomplete ureteric obstruction. Collagen studies in newborn rats with incomplete ureteric obstruction were performed to describe and quantify changes in collagen deposition resulting from urinary tract obstruction at an early developmental age. Incomplete ureteric obstruction was created in three-day-old rats by placing the left ureter in a tunnel formed by the psoas muscle, and sham-operated controls underwent a laparotomy. The rats were sacrificed at 10, 17, 24 or 31 days. Collagen types I, III, IV, and V were localized by indirect immunofluorescence microscopy, the total collagen content of the kidney was quantitated using hydroxyproline analysis, and collagen types I and III were quantitated using cyanogen bromide (CNBr) peptide analysis. Increased immunofluorescent staining for all of the collagens was found in the diffusely widened medullary interstitium of the obstructed kidney, and more focally in the cortical interstitium. Collagen types I, III and V, but not collagen type IV, were also found in bands in the interstitium at the junction of the cortex with the medulla. Increased staining for collagen type IV was found in thickened and tortuous tubular basement membranes (TBM) of the obstructed kidneys. The total collagen content of the obstructed kidney was significantly increased compared to the amounts in both the contralateral kidneys and in the kidneys from sham-operated controls at 24 and 31 days of age (P < 0.01 in each case, Wilcoxon matched pairs rank sum test and Mann Whitney U-test, respectively). The amount of collagen in the kidneys correlated with the degree of hydronephrosis (Spearman correlation test, r = 0.78, P < 0.02). CNBr peptide analysis demonstrated that over 50% of the collagen in the normal neonatal rat kidney was collagen type I and approximately 25% was collagen type III. In the obstructed kidneys most of the collagen was also collagen type I and collagen type III, although the proportion of total collagen comprised by these collagen types was decreased compared with the controls. The amount of collagen type III in the contralateral kidneys was reduced compared to that in the controls. Thus, the neonatal renal response to obstruction resulted in increased amounts of a range of collagens in the interstitium and TBM, and the extent of this response was partially related to the degree of hydronephrosis.

Two cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis are reported. A 12-year-old girl and a 10-year-old boy presented with polyarthritis, anaemia, haematuria, proteinuria, impaired renal function, anorexia, nausea, marked loss of weight and lethargy. The boy also had a vasculitic rash and anterior uveitis. Both children had diffuse cytoplasmic ANCA identified by indirect immunofluorescence and confirmed by specific enzyme-linked immunosorbent assay. Renal biopsies showed severe focal and segmental necrotizing glomerulonephritis with 100% crescents. They were treated with plasma exchange, prednisolone, cyclophosphamide and heparin. Within 1 month of commencing treatment, both had normal serum creatinine concentrations and ANCA was not detectable. Renal biopsies 6 weeks following commencement of treatment revealed quiescent disease, although up to 40% of glomeruli were sclerosed or had fibrous crescents. Following cessation of cyclophosphamide and heparin after 7 months and reduction in steroid dose, a biopsy at 10 months in the boy revealed quiescent disease, but the girl had recurrent disease associated with reappearance of a low titre of ANCA and small cellular crescents in 20% of the glomeruli. These cases reflect the potential usefulness of ANCA determination for categorizing paediatric patients, helping in the selection of therapy and as a possible marker of disease activity, similar to the experience in adults.

OBJECTIVE To determine the outcome of patients with end-stage chronic renal failure treated by live donor renal transplantation at the Royal Melbourne Hospital and Royal Children's Hospital between 1973 and 1991, during which time two distinct immunosuppressive regimens were used. DESIGN Data about live donor renal transplant recipients were retrieved from the Australian and New Zealand Dialysis and Transplantation Association Registry, to which we have submitted data on all transplant recipients at six monthly intervals since the commencement of our dialysis and transplant programs. PATIENTS Seventy-two patients with chronic renal failure who received live donor renal transplants during the 19 years from February 1973 to February 1992 were included. MAIN OUTCOME MEASURES Patient survival, transplant survival, transplant function, change in prednisolone requirements, and duration of hospital stay. RESULTS The first 32 patients were treated with immunosuppressive regimens based on combinations of prednisolone and azathioprine ("dual therapy"), while the next 40 patients were treated with combinations of cyclosporin, prednisolone and azathioprine ("triple therapy"). Survival of patients in each group five years after transplantation was 97%. Actuarial graft survival at 5, 10 and 15 years in the dual therapy group was 58%, 52% and 47%, compared with a 5-year actuarial graft survival in the triple therapy group of 96%. There was no statistically significant difference in renal transplant function between the two groups within the first 6 years after transplantation. Twelve of 26 patients (46%) treated initially with triple therapy were able to stop treatment with prednisolone within 12 months of transplantation. Median hospital stay was 12 (range, 6-35) days during the period 1973-1985 and 8 (range, 5-20) days for the 1985-1992 period. CONCLUSION Live donor renal transplantation has provided a highly satisfactory means of treating patients with end-stage chronic renal failure in the short and long term. Our recent experience indicates that excellent patient and graft survival and adequate renal function can be achieved by treating live donor renal transplant recipients with a triple immunosuppressive regimen of low dose cyclosporin, prednisolone and azathioprine.

Sirolimus is an immunosuppressive agent that offers potentially significant benefits for young transplant patients facing life-long treatment. Its action of reducing cell proliferation may reduce the risk of chronic allograft nephropathy and posttransplant neoplasia. Twenty-nine children were converted from calcineurin inhibitors to sirolimus after renal transplantation and followed for a minimum of 12 months. Glomerular filtration increased transiently in those converted before 12 months after transplantation but not in those converted later, when chronic histological changes had developed. Mild acute rejection occurred after conversion in 10%, and side effects led to cessation of sirolimus in 31%. Anemia occurred in 55% of patients and responded well to darbepoetin. Most side effects (anemia, hypercholesterolemia, mouth ulcers, and myalgias) became less severe with time. The number of antihypertensive drugs required decreased significantly on sirolimus. Although side effects are frequent on sirolimus, in the majority of children, they are mild enough to allow the patient to continue taking the drug, and for these children the long-term benefits are potentially valuable.

This study examined how often children with persistent familial hematuria were from families where hematuria segregated with the known genetic locus for the condition known as benign familial hematuria or thin basement membrane nephropathy (TBMN) at COL4A3/COL4A4. Twenty-one unrelated children with persistent familial hematuria as well as their families were studied for segregation of hematuria with haplotypes at the COL4A3/COL4A4 locus for benign familial hematuria and at the COL4A5 locus for X-linked Alport syndrome. Eight families (38%) had hematuria that segregated with COL4A3/COL4A4, and four (19%) had hematuria that segregated with COL4A5. At most, eight of the other nine families could be explained by disease at the COL4A3/COL4A4 locus if de novo mutations, non-penetrant hematuria or coincidental hematuria in unaffected family members was present individually or in combination. This study confirms that persistent familial hematuria is not always linked to COL4A3/COL4A4 (or COL4A5) and suggests the possibility of a further genetic locus for benign familial hematuria. This study also highlights the risk of excluding X-linked Alport syndrome on the basis of the absence of a family history or of kidney failure.

Treatment of children with steroid-dependent nephrotic syndrome (SDNS) continues to be a challenge when relapses recur after treatment with cyclophosphamide and side effects or non-compliance make steroids and cyclosporin unsatisfactory. We treated 12 patients with intravenous vincristine for SDNS in a regime of 1-1.5 mg/m2 weekly for 4 weeks then monthly for 4 months. Four of the 5 patients in relapse when commencing vincristine remitted within 2 doses. Comparing relapse frequency in the 12 months before and after vincristine, there was a reduction from 4 to 1.5 (p=0.004) relapses per year. Median sustained remission was 5 months, but 1 frequently relapsing patient remains in remission 4 years after vincristine. Vincristine was also successfully used in 1 or 2 doses at weekly intervals for subsequent relapses in 5 patients. Side effects were minimal in most cases. Abdominal pain occurred in 2 patients who commenced vincristine at 1.5 mg/m2, but resolved when continued at 1 mg/m2. We felt vincristine had a role in a subset of children with challenging SDNS administered as 1 mg/m2 weekly for 4 weeks then 1.5 mg/m2 monthly for 4 months. Vincristine allowed steroid- and cyclosporin-sparing, contributed to long-term remission in some patients, and was especially valuable in children with poor compliance with oral medication. Many patients expressed a preference for a few doses of vincristine rather than a standard course of oral prednisolone or cyclosporin.

Kimura disease is a rare inflammatory condition of unknown aetiology. It typically presents in young Asian males with the triad of non-tender subcutaneous swellings in the head and neck region, peripheral eosinophilia and raised serum IgE. About 16% of cases have associated renal disease. We present the case of a 10-year-old boy with a past history of steroid responsive, frequently relapsing nephrotic syndrome who developed a right submandibular swelling and eosinophilia. Kimura disease was diagnosed on the basis of clinical and histological findings. The condition recurred during relapses of nephrotic syndrome. Because of poor adherence with oral medication, our patient was treated with intravenous vincristine with synchronous remissions of his nephrotic syndrome and Kimura swellings on each occasion.

Several disorders of hypomagnesaemia of hetary renal origin are now recognised. The cases of two sisters from a consanguineous marriage with the syndrome of renal magnesium wasting, hypercalciuria and nephrocalcinosis are presented. Pathological examination of the heterozygous parental kidneys revealed mild focal interstitial fibrosis. This condition is a previously unreported cause of end-stage renal failure in chilhhood, and this report suggests that transplantation from heterozygous parental donors can be successfully undertaken without recurrence currence of the syndrome.

PURPOSE: To determine the association between vesicoureteral reflux (VUR) and the presence of acute pyelonephritis in children with urinary tract infections. MATERIALS AND METHODS: The authors studied 150 consecutive patients less than 5 years of age with their first proved urinary tract infection. All patients underwent renal cortical scintigraphy (with technetium-99m dimercaptosuccinic acid or Tc-99m gluconate) and voiding cystourethrography (VCUG) to identify the presence of cortical defects and VUR, respectively. RESULTS: Of 300 kidneys, 88 (29.3%) had a cortical defect at scintigraphy. Fifty-four of the 88 patients (61%) did not have VUR demonstrated at VCUG. Conversely, 72 of the 300 kidneys (24%) had VUR; of these, 38 (53%) had no cortical defect. The sensitivity of VCUG in helping predict a defect was 38.6%, and the specificity was 82.1%. CONCLUSION: VUR (as shown by VCUG) and renal cortical scintigraphic defects frequently occur independently of each other. Renal cortical scintigraphy may be a mo...

Recent studies have demonstrated that both congenital hypoplasia and acquired scarring are involved in the parenchymal lesions associated with reflux nephropathy. Medical therapy can prevent symptomatic infection. While there is no proof that either medical or antireflux surgery prevents acquired scarring, paradoxically there is evidence that surgery adds no benefit to medical therapy, and that the results of medical therapy and surgical therapy are similar in children with isolated severe reflux. The group at most severe risk of renal scarring is infants and the effects of medical and surgical therapy in preventing acquired renal injury in this group have not been sufficiently investigated. On the basis of this information it has been our practice to maintain urine sterility using continuous antibiotic prophylaxis throughout infancy and early childhood. Following the development of reliable urine toilet habit and the ability to collect midstream urine specimens, antibiotics are given according to the frequency of urine infection, and weekly testing of morning urine with nitrite strips at home is used for early detection of infection and prevention of symptomatic infection. Antireflux surgery is mandatory for those children with complicated VUR (such as urinary tract obstruction) and should otherwise be reserved for those having persistent breakthrough infections in infancy and early childhood.

Background. Acute pyelonephritis is distinguished from renal scarring using repeat cortical scintigraphy. The defects of acute pyelonephritis resolve, while those of scars persist. Objective. To determine the duration of reversible cortical defects following acute pyelonephritis and the time interval required to differentiate infection from scars. Materials and methods. An observational prospective study of 193 children (386 kidneys) aged less than 5 years following their first proven urinary tract infection (UTI). Renal cortical scintigraphic defects were detected in 112 (29%) kidneys within 15 days of diagnosis. Of these, 95 underwent repeat renal cortical scans 2 years after the UTI, including 50 with additional scans performed within 2–6 months of infection. Results. Of the 50 kidneys undergoing a second renal cortical scan within 2–6 months of the first UTI, 22 (44%) had persistent defects. A third scan was performed on 17 (77%) kidneys after 2 years, by which time defects had resolved in another 8 (47%) kidneys. The predictive value of defects detected within 2–6 months of UTI representing scars is 53% (95% CI 28, 77). Overall, nine (18%) kidneys with initial renal cortical abnormalities had permanent defects. In the 45 kidneys undergoing a second cortical scan more than 6 months after the UTI, 11 (24%) had persistent defects. None of the 95 kidneys undergoing serial scans developed new or larger defects. Conclusions. Renal scars may not be reliably diagnosed by cortical scintigraphy performed within 6 months of UTI because the inflammatory lesions may not have fully resolved.

A male infant is described who had polyuria over the 4 months of his life with urine volumes exceeding 1,000 ml/kg per day, severe serum electrolyte losses, metabolic alkalosis and increased plasma renin activity (56 ng/ml per hour). He had a normal blood pressure and glomerular filtration rate when fluid replete. The urine flow rate was about 25% of the glomerular filtration rate. Renal histology showed hyperplasia of the juxtaglomerular apparatus and abnormalities of the proximal tubules. The features of this case suggest an extreme form of Bartter’s syndrome presenting from the first days of life.

Aims: To review the outcome of renal transplantation in small children treated with triple immunosuppression at a single Australian centre. Methods: The medical records of all children under the age of five years undergoing renal transplantation from 1988 were reviewed. The duration of follow-up was 30 months (range 18–36). Results: Six children received seven renal allografts (five living-related [LR] and two cadaveric [CD]). They had a median age of 3.75 years (range 1.5–4.9) and weight of 11.6 kg (9.1–14.5) at the time of transplantation. All patients received an immunosuppressive regime involving cyclosporin A, azathioprine and prednisolone. There were no deaths. The only graft lost was a CD graft (severe acute rejection within one week of transplantation). Hypertension occurred in all recipients and usually required more than one antihypertensive drug for treatment. Renal function measured by serum median creatinine concentration (range) was 0.05 mmol/L (0.03–0.11) at three months (n= 6) and 0.10 mmol/L (0.07–0.22) at 30 months (n= 4). Growth estimated from median (range) height standard deviation scores was - 1.97 (-1.36- - 4.04) at three months (n= 6) and - 1.90 (- 1.74–2.50) at 30 months (n= 4). No patient was entirely weaned from prednisolone. Cyclosporin A side effects included hirsutism (five patients), gingival hyperplasia (six patients) and nephrotoxicity (three patients). Conclusions: Satisfactory patient and graft survival can be accomplished in this recipient age group. The results compare with other international experience and accumulating Australian experience. Hypertension and poor skeletal growth were consistent observations. The long-term outcome of renal function using triple immunosuppression remains to be determined.

Tamm-Horsfall protein (THP) has been found in the renal interstitium in patients with obstructive uropathy. The aim of this study was to investigate whether serum concentrations of THP could serve as a screening test for urinary tract obstruction. The presence of THP in normal human serum was confirmed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blotting. A specific enzyme immunoassay was then used to measure the serum concentration of THP. Serum THP concentrations were estimated in a cross-sectional study of a group of 23 patients who had technetium-99m-diethylene-triaminepenta-acetic acid (DTPA) nuclear urinary excretion studies to define urinary tract obstruction, and in longitudinal studies in 2 patients who developed acute bilateral ureteric obstruction following operations for ureteric reimplantation. The subjects with DTPA-proven urinary tract obstruction had higher concentrations of serum THP (n = 10, median = 43.9 ng/ml, range 10.4-152.1 ng/ml) than those who did not have obstruction (n = 13, median = 9.6 ng/ml, range 1.26-61.9 ng/ml). While this difference was significant (P0.01, Mann-Whitney U test), 6 of the 10 patients with obstruction had serum THP concentrations within the range of those patients without obstruction. The patients who developed acute bilateral ureteric obstruction both had increases in serum THP concentrations with obstruction and decreases in serum THP concentrations following relief of obstruction. These changes paralleled those in serum creatinine. The studies indicate that urinary tract obstruction results in increases in serum THP concentrations but these changes are not sufficient in magnitude to allow screening of children for urinary tract obstruction.

Thirty-four children (≤15 years of age) with end-stage renal failure received 39 renal allografts between 1985 and 1991 and were treated with cyclosporin A (CyA), azathioprine and low-dose prednisolone (PNL). We aimed to withdraw PNL by 6 months after transplantation. Median duration of follow-up was 2 years 4 months (range 0.1 month to 6 years, 4 months). There were no deaths. Crude graft survival for living-related grafts (n=9) was 100%, although only 1 patient has been followed for >2 years. For cadaveric grafts (n=30), 1- and 5-year actuarial graft survivals were 90% and 79% respectively. At 12 months posttransplant, the median (range) glomerular filtration rate for all patients was 63 (19–109) ml/min per 1.73 m2 (n=25) and at 5 years was 48 (17–64) ml/min per 1.73 m2 (n=9). Complications observed included rejection episodes which occurred after discontinuation of PNL. Long-term (after 12 months), 28% of patients remain on PNL. Hypertension was present in more than 50% of patients. Severe CyA nephrotoxicity was not seen. Catch-up growth as determined by the change (Δ) in mean height standard deviation score (Ht-SDS) was noted at 1 year [ΔSDS/year=+0.60;P

Recurrence of haemolytic-uraemic syndrome (HUS) after renal transplantation may occur in both cyclosporin A (CyA) and non-CyA-treated patients, and in patients receiving anti-lymphocyte globulin. We report a case of recurrent HUS in an 8-year-old boy who received Orthoclone (OKT3) combined with prednisolone and azathioprine therapy on receipt of his first cadaveric renal allograft. Despite avoidance of CyA therapy irreversible HUS occurred.

Eight children with the hemolytic-uremic syndrome were treated with heparin, streptokinase, aspirin, and dipyridamole. Two children died and six survived. Normal renal function at follow-up was demonstrated in all of the surviving children. A retrospective analysis of the results of treatment of this disease over a 10 year period suggested that treatment with heparin reduced the mortality rate in the acute phase of the illness. Heparin alone did not prevent the late occurrence of chronic renal disease, but treatment with heparin, streptokinase, and the anti-platelet agents did appear to prevent this complication of the disease. Bleeding during streptokinase therapy was frequent and was severe in two patients.

Since June 1985 ten consecutive paediatric cadaveric renal transplant recipients (aged from 7 to 15 years) have been studied prospectively to evaluate a triple immunosuppressive regime of low-dose cyclosporin A (CyA), azathioprine (AZA) and prednisolone (PNL) with the aim of eliminating PNL from the regime within 6 months. Follow-up has been over 6-18 months. Patient and graft survival are both 100%. Median (range) serum creatinine values at 6 months were 0.09 (0.05-0.14) mmol/l (n = 10) and 0.09 (0.06-0.16) mmol/l (n = 5) at 12 months. Readily reversible acute rejection episodes occurred in five patients (50%); two of these episodes occurred soon after cessation of PNL. Six months post-transplantation, PNL had been discontinued in six patients (60%). After 12 months, three of five patients were still not receiving PNL. Complications included hypertension (seven patients), cytomegaloviral infections (three patients), labial herpes simplex (one patient), leucopenia (two patients), marked hirsutism (four patients) and transient CyA nephrotoxicity (one patient). Following transplantation, all children had growth velocities greater than 5 cm/year and seven have growth patterns which suggest that "catch-up growth" may be occurring. This preliminary study shows that a triple immunosuppressive regime of low-dose CyA, AZA and PNL allows excellent patient survival, graft survival and graft function and has been associated with few complications, including a low incidence of CyA nephrotoxicity. Growth rates are very encouraging and in a high proportion of children it has been possible to discontinue PNL completely.

The concentrations of serum IgG and IgM antibodies to polyclonal IgA (IgAp), IgA1, and IgA2 were determined by enzyme immunoassay in 31 patients with IgA nephropathy and 30 healthy controls. Patients with IgA nephropathy had significantly raised concentrations of serum IgA compared to controls (Mann-Whitney U test, P = 0.001) and increased concentrations of conglutinin-binding IgA immune complexes (P = 0.024). No differences in the median concentrations of IgG and IgM anti-IgA antibodies were found between the patients and the controls. In serum samples from healthy controls there was a significant positive correlation between IgM anti-IgAp and IgA immune complex concentrations (P = 0.05), which contrasted with the finding of an inverse correlation between IgM anti-IgAp and IgA immune complex concentrations in patients with IgA nephropathy (P less than 0.05). In addition, the concentrations of conglutinin binding IgM immune complexes in serum were found to correlate with the concentration of IgM anti-IgAp (0.010 less than P less than 0.025), IgM anti-IgA1, and IgM anti-IgA2 (P much less than 0.005 for both) in patients with IgA nephropathy but not in controls. IgM anti-IgA antibodies may be important in augmenting the clearance of IgA immune complexes from the serum of patients with IgA nephropathy.

Polymeric IgA and immune complex concentrations in IgA-related renal disease. Polymeric IgA (PIgA) and immune complex concentrations in IgA-related renal disease were measured in cross sectional and longitudinal studies to establish the relationship between these parameters and both mucosal infection and renal dysfunction. These studies were performed in 50 patients with IgA nephropathy (IgAN), 17 patients with Henoch Schonlein purpura nephritis (HSPN), 11 control patients with IgA negative, diffuse mesangial proliferative glomerulonephritis (DMPGN) and 50 healthy controls. Total PIgA (PIgA T ) and PIgA subclass concentrations were measured using a secretory component binding enzyme immunoassay and isotype specific immune complex concentrations were measured using conglutinin (K) binding immunoassays. In cross sectional studies patients with IgAN were found to have increased concentrations of PIgA T , PIgA 1 , K-IgA 1 and K-IgA 2 compared to controls. In the longitudinal studies controls and patients had significant increases in PIgA T and PIgA 1 concentrations during infection. However, in patients with IgAN, the increases were greater, persisted for longer, and PIgA 2 concentrations were also increased. K-IgA 1 and K-IgA 2 concentrations increased significantly during episodes of infection in IgAN patients in contrast to controls. Patients with HSPN had results similar to those of IgAN patients. No significant correlation was found between PIgA or K-IgA concentrations, and either serum creatinine concentrations or the degree of hematuria. The results indicate that patients with IgA-related renal disease have abnormal regulation of PIgA and immune complexed IgA, and that these abnormalities are exaggerated during mucosal infection.

The inhibiting effect of diphosphonates on calcification in tissues has led to their successful use i n conditions associated with abnormal calcification, such as niyositis ossificans (Bassett et al., 1969; Cram et al., 1971; Weiss, Fisher and Phang, 1971; Russell of et al., 1972) and Paget's disease of bone (Smith, Russell and Bishop, 1971; Altman et al., 1973; Russell et al., 1974). In vitroexperiments have shown that diphosphonates inhibit the crystallisation of calcium phosphate and calcium oxalate from solutions of these salts (Francis, 1969; Fraser et al., 1972) and the discdium salt of ethane I-hydroxy-1.1-diphosphonate (EHDP) inhibited the formation of calcium stones in rats with experimental nephrolithiasis (Fraser et al., 1972). Few clinical studies have been reported on the use of diphosphonates in human stone-formers or patients with nephrccalcinosis, but it appears that inhibition of crystal growth may be obtained (Ohata and Pak, 1973; Baumann et al., 1974; Robertson et al., 1974). Whilst Uttley et al., (1975) have recently reported the use of diphosphonates in 3 children with ectopic calcification in skin and subcutaneous tissues, their use in children with renal calcification has not been reported to our knowledge. This paper presents results obtained with the use of EHDP in 4 children with nephrocalcinosis over a 13-month period. Preliminary results of these studies have been previously presented (McCredie, Powell and Rotenberg, 1974).

Synthetic N-terminal 34 amino acid peptide of bovine parathyroid hormone (PTH) produced a consistent rise in plasma renin activity in saline-loaded dogs when given iv either as a single bolus dose of 400 U or infused steadily in lower dosage over a number of hours. Infusion of as little as I U/min produced a significant rise in plasma renin activity, but a greater effect was obtained with 2 U/min. Infusion of 4 U/min had no more effect than 2 U/min. In contrast to transient hypotension after rapid injection of a single large dose, blood pressure did not change significantly during the steady infusion of lower doses of PTH. These findings are compatible with the thesis that an increased distal tubular load of sodium stimulates renin release and suggest that the increased distal sodium absorption after the proximal effects of PTH may be regulated by the renin-angiotensin-aldosterone system.

Renal and hepatic sonography were performed in 2 neonates with glomerulocystic renal disease. One neonate had ultrasound findings of normal hypoechoic medullary pyramids, enabling differentiation from infantile polycystic renal disease. Previous case reports have highlighted the similarity of renal ultrasound findings in these two conditions.

Previous series that described phenotypes in carriers of Alport's syndrome did not distinguish genetically between carriers of X-linked and autosomal recessive disease. In this study, modes of inheritance in unselected families with Alport's syndrome associated with two city and two provincial hospitals were determined using microsatellite markers, and carriers of disease haplotypes were identified within these families. All 47 carriers (100%) from 18 families with X-linked Alport's syndrome had dysmorphic hematuria on phase-contrast microscopy, but few developed renal failure (3 of 40 carriers; 8%), clinical hearing loss (2 of 45 carriers; 4%), retinopathy (1 of 30 carriers; 3%), or lenticonus (0 of 30 carriers; 0%). Eleven of the 14 carriers (79%) from 2 families with autosomal recessive disease had dysmorphic hematuria, but none had renal failure, clinical hearing loss, retinopathy, or lenticonus. Urinary red blood cell counts in carriers of X-linked Alport's syndrome were greater than those in carriers of autosomal recessive disease (P < 0.0001), but the frequency of proteinuria and hypertension and levels of protelnuria were not different. There was more tubulointerstitial damage in carriers of X-linked disease (P = 0.012); however, carriers of autosomal recessive disease had more widespread and more uniform thinning of the glomerular basement membrane (P < 0.0001) and less lamellation (P < 0.04).

Failure of a kidney to grow satisfactorily in childhood is evidence of renal disease. Because kidneys may enlarge during an episode of acute pyelonephritis, concomitant renal length measurements cannot be used as baselines for growth assessment. This study was designed to determine the degree of renal enlargement in children with acute pyelonephritis and the time the enlargement takes to resolve after treatment is started to find the optimum time for obtaining baseline measurements.In a cohort study, 180 children younger than 5 years old with their first proven acute urinary tract infection, with or without pyelonephritis, had renal scintigraphy and sonography within 15 days of starting treatment. The presence of cortical defects on scintigrams indicated pyelonephritis. The lengths of kidneys with and without scintigraphic defects (i.e., with and without pyelonephritis) were compared, adjusting for age and sex, and the length of kidneys with defects was related to time elapsed between the start of treatment and sonography.Ninety-nine kidneys (28%) in 77 children (43%) had scintigraphic defects. Kidneys with defects were an average of 3.2 mm longer than kidneys without defects. Length and time interval between treatment and sonography in kidneys with defects correlated negatively, with mean length approaching that of kidneys without defects by 10-11 days.Kidneys with acute pyelonephritis initially increase in length but return to normal on average by the 11th day of treatment. If poor renal growth is used as an indication of renal disease, sonography should be delayed or repeated at least 2 weeks after the start of treatment to determine the length of the uninflamed kidney.

This paper describes the clinical features of six children who developed the haemolytic-uraemic syndrome after treatment with metronidazole. These children were older and were more likely to have undergone recent bowel surgery than are other children with this condition. While the involvement of metronidazole in the aetiology of the haemolytic-uraemic syndrome is not established firmly, the action of this drug in sensitizing tissues to oxidation injury and the reported evidence of oxidation changes in the haemolytic-uraemic syndrome suggest a possible link between metronidazole treatment and some cases of the haemolytic-uraemic syndrome.