[Acute Kidney Failure Due to Urachal Cyst?] / Akutes Nierenversagen bei Urachuszyste?

A 34-year-old para V woman was referred to our centre at 35+1 weeks of gestation for an assumed fetal malformation with prenatal renal impairment and anhydramnios. Prenatal ultrasound demonstrated unilateral renal agenesis; the bladder was not detectable. The baby was born by caesarian section at 36+2 weeks of gestation because of placental insufficiency. Postnatal adaptation was uneventful, but the newborn presented external stigmas of trisomy 21 and progressive renal impairment with anuria. Nevertheless, the postnatal ultrasound showed two enlarged kidneys in loco typico with impaired perfusion but without signs of malformations. In the lower abdomen, a rosette-shaped structure of unknown origin was noted. Its origin could not be cleared by imaging including voiding cystourethrography and colon contrast radiography. Explorative laparotomy identified the structure as a persistent urachal cyst with secondary obstruction of the upper urinary tract. After removal of the urachus with reconstruction of the bladder dome, renal function recovered completely while urine was drained continuously via suprapubic catheter. A voiding cystourethrogram 3 weeks later showed a posterior urethral valve as an additional unexpected diagnosis. The valve was slit at the age of 6 months without complications, the renal function remained stable in the further course. In retrospect, the main cause for the renal failure remains unclear. It appears to be the obstruction due to the space-consuming character of the urachal cyst, especially because the megacystis typically associated with urethral valve was not viewable. Alternatively, the additional proximal stenosis may have only masked the typical findings of PUV.

Favorable long-term outcome of nephrotic syndrome after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The development of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (HS-CT) is a rare complication with few long-term outcome data. PATIENTS: Clinical course and long-term outcome of three adult patients and one child with NS after HSCT (total number of transplants n = 533) are presented. RESULTS: The median age at onset of NS was 35 years (range 15 - 56), occurring at a median of 17 months (range 11 - 21) after HSCT. Discontinuation of cyclosporine A (CSA) prior to onset of NS was a consistent feature and occurred a median of 6 months (range 2 - 10 months) prior to the development of NS. The histopathological lesion was membranous nephropathy (n = 3) and membranoproliferative glomerulonephritis Type 1 (n = 1). History of acute or concomitant clinically apparent chronic graft versus host disease (GVHD) was present in all cases except the pediatric patient who had abundant DR-activated cytotoxic T cells without evidence of viral reactivation. Long-term immunosuppression for 11 - 36 months with steroids (n = 1), combined steroids and CSA (n = 2) or CSA alone in steroid-refractory NS (n = 1) resulted in sustained remission of the NS in all patients (12 months - 8 years off immunosuppression). CONCLUSION: NS after HSCT seems to be etiologically related to subclinical or overt chronic GVHD, which flares up after discontinuation of CSA. However, resumption of immunosuppression can reverse NS as well as GVHD and induce favorable sustained long-term remission.

Th2 cytokine profile in infants predisposes to improved graft acceptance after liver transplantation.

BACKGROUND: The T helper cell type 1 (Th1) cytokines interleukin (IL)-2 and interferon (IFN)-gamma are mediators of acute graft rejection after liver transplantation and Th2 cytokines, such as IL-4 and IL-10, may have a protective role and correlate with graft acceptance. To test the hypothesis that infants aged <1 year have an immunological advantage with regard to graft acceptance because of a partially immature immune system with a physiological balance toward a Th2 cytokine profile, we conducted the present study. METHODS: We compared the T helper serum cytokine profiles in 105 infants and children after liver transplantation with or without acute graft rejection and analyzed the normal age-distributed concentrations of T helper cytokines in 51 healthy controls. RESULTS: The incidence of acute graft rejection was as follows: 0 to 12 months, 26.8%; 1 to 3 years, 40.0%; and >3 years, 71.8%. There was a significantly lower incidence of acute rejection in infants 0 to 12 months of age compared with children >1 year (11/41 vs. 38/64; P=0.001). In healthy infants, significant increasing Th1 cytokine concentrations and decreasing Th2 cytokine concentrations were found with increasing age. Patients with acute rejection had significantly higher values of Th1 cytokines compared with nonrejecting subjects, who had significantly higher concentrations of Th2 cytokines. A longitudinal analysis of serum cytokines from patients showed that changes of the cytokine patterns in the follow-up did not differ significantly from preoperative values, except in the 4 weeks posttransplant. CONCLUSIONS: We conclude from the data that the physiological balance toward a Th2 cytokine profile of infants in the first months of life predisposes to improved graft acceptance. Transplantation of children with biliary atresia as early as possible, avoiding Th1 stimulation by recurrent infections and vaccinations, may have a positive impact on overall tolerance.

Disseminated islands of gastric mucosa in jejunum and ileum detected by technetium-99m-pertechnetate scintigraphy.

Disseminated islands of gastric mucosa are very rare in the small intestine. The secretion of hydrochloric acid can lead to ulceration which results in gastrointestinal bleeding. It is often difficult to localize the focus in case of gastrointestinal blood loss especially in the small bowel. Technetium-99m-pertechnetate scintigraphy may be a helpful tool in detecting ectopic gastric mucosa. We report a case of a 21-mo-old boy with recurrent gastrointestinal bleeding. By using pertechnetate scintigraphy, extensive tracer accumulation in the jejunum and proximal ileum was detected. Histologically, multiple islands of ectopic gastric mucosa were found in about 50 excited mucosal and transmural biopsies. The unusual finding of disseminated accumulation of 99mTc-pertechnetate in the small intestine was the diagnostic clue for such a rare disease.

Preemptive liver transplantation in primary hyperoxaluria type 1: timing and preliminary results.

Preemptive isolated liver transplantation (PLTX) can cure the metabolic defect in primary hyperoxaluria type 1 (PH1) but there are no uniformally accepted recommendations concerning the timing of this transplantation procedure. We have performed PLTX successfully in 4 children (age 3-9 years) with PH1 with no mortality or morbidity due to the transplantation procedure. Plasma and urinary oxalate levels normalised rapidly and renal function remained stable including one patient with advanced chronic renal failure who showed a stable course for more than 24 months. Although treatment must be individualised in this severe metabolic disorder and PLTX has to be viewed as invasive procedure, we feel PLTX should be offered and discussed not too late in the treatment of PH1 to prevent or at least delay the progression to end stage renal disease and systemic oxalosis.

Adam Politzer, otology and the Centennial Exhibition of 1876.

The Centennial Exhibition of 1876 was held in Philadelphia. Among the exhibits was a collection of temporal bone dissections produced by Adam Politzer of Vienna. This exhibit included both normal and pathological temporal bones, and emphasized the relationship of the tympanic membrane to the middle ear, external canal and bony labyrinth. At the close of the Centennial Exhibition the collection was purchased by the College of Physicians of Philadelphia. This collection and the congress associated with the Centennial had a tangible effect on the otology in this country.

Hyperkalemia: therapeutic options in acute and chronic renal failure.

Hyperkalemia is a life threatening emergency and warrants immediate treatment because of its deleterious cardiac consequences. Initial measures in mild cases include restriction and binding of dietary potassium, correction of metabolic acidosis and increasing urinary excretion by furosemide. In moderate and severe hyperkalemia infusion of glucose with insulin has been regarded as the standard medical treatment so far. However, recently also the beta 2 stimulatory drug salbutamol has been shown to be an effective agent to treat hyperkalemia by inducing a shift of potassium into the intracellular compartment. We treated 15 pediatric patients of different age groups (mean age 5.16, range 0.1-16 years) suffering from acute hyperkalemia (mean level 6.6, range 5.9-7.7 mmol/l) by means of a single infusion of salbutamol (5 micrograms/kg over 15 minutes). Serum potassium concentrations decreased significantly to 5.74 +/- 0.53 after 30 minutes and furthermore to 5.19 +/- 0.48 and to 4.92 +/- 0.53 mmol/l after 60 and 120 minutes, respectively (p < 0.001 at all stages compared to pre-treatment). Since no side effects occurred besides a slight increase of heart rate in 3 patients, we conclude that short-term intravenous salbutamol infusion is an effective, rapid, safe and predictable way to treat children of any age suffering from acute hyperkalemia and therefore has become the first line treatment in our center.

Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome.

BACKGROUND: Growing evidence shows that steroid-sensitive nephrotic syndrome (SSNS) is the result of a primary T-cell disturbance and leads to secondary anatomical and functional, however, not to immunological glomerular changes. In addition, immunoglobulin abnormalities in SSNS indicate a role of B-cell involvement. PATIENTS AND METHODS: We therefore analyzed T- and B-cell activation markers in children with SSNS at different stages of the disease including different treatment regimens by measuring the soluble IL-2 receptor (sCD25) and the soluble low-affinity IgE receptor (sCD23), respectively. Seventy-five patients with SSNS (median age 8.0, range 2.5 - 18 years) were studied, 33 in relapse (RL) including 21 patients relapsing during alternate-day steroids (RL-SD). Forty-two patients were studied in remission (RM; 14 off treatment and 28 on alternate-day steroids (RM-AD)) and 22 age-matched children served as controls. RESULTS: Serum concentrations of sCD25 were increased in RL (113.6 +/- 19.5 micromol/l) compared to RM (79.8 +/- 8 micromol/l, p < 0.02) and controls (74.8 +/- 0.9 micromol/l, p < 0.02). Patients with RL-SD did not have elevated sCD25. In relapse, sCD25 was inversely correlated with age (R = -0.36, p < 0.04) and positively correlated with total IgG (R = 0.37, p < 0.04). Urinary excretion of sCD25 was also significantly elevated in RL of SSNS compared to RM and controls (71.2 +/- 11.9 micromol/g creatinine vs. 39.1 +/- 4.8 and 32.0 +/- 4.2 micromol/g, p < 0.05). Serum levels of sCD 23 were significantly elevated in RL (6.22 +/- 0.65 microg/l) compared to RM (3.1 +/- 0.83 microg/l, p < 0.02) and to controls (3.4 +/- 0.93 microg/l). The highest values, however, were found in RL-SD (7.8 +/- 1.7 microg/l) vs. untreated RL (p < 0.007) and RM-AD (p < 0.002). In untreated RL there was a significant correlation of sCD23 and total IgE (R = 0.67, p < 0.02) and in RL-SD with total IgG (R = 0.45, p < 0.05). sCD23 and sCD25 were not correlated with each other. CONCLUSION: These data document parallel abnormalities of both CD23-mediated B as well as CD25-mediated T-cell activation and suggest that SSNS is not solely a disorder of T-cell dysfunction.

Iron homeostasis in relapsing steroid-sensitive nephrotic syndrome of childhood.

AIM: Urinary transferrin loss is a typical feature in relapse of the idiopathic nephrotic syndrome, however, the impact on serum iron homeostasis and hematological parameters has not been studied systematically so far. PATIENTS AND METHODS: Therefore, we investigated serum iron (Fe), erythropoietin (EPO), ferritin (FN), transferrin (TF), total iron-binding capacity (TEBK), transferrin saturation and the soluble transferrin receptor (sTFR) combined with hematological parameters (hemoglobin, MCV, MCH) in 42 children with relapsing, steroid-sensitive nephrotic syndrome (NS) in remission (RM, n = 26) and relapse (RL, n = 16), including 13 patients who were studied in both states. Thirty-three age-matched healthy children served as controls. RESULTS: Fe, TEBK and TF were significantly reduced in RL compared to RM in cross-sectional as well as in paired studies while ferritin, hematological parameters and EPO levels remained unchanged. A significant increase, however, of the soluble transferrin-receptor could be demonstrated in cross-sectional analysis comparing RL to RM and healthy controls (3568+/-713 mg/ml vs 2625+/-576 vs 2646+/-697; p < 0.001 respectively) as well as in paired analysis of 13 patients in RL and RM (p < 0.001). CONCLUSION: We conclude that transient transferrin and iron deficiency occurs in RL of INS but this seems to be counterbalanced by upregulation of the sTFR, a mechanism that might be important in preventing the development of iron deficiency anemia during the active nephrotic state.

Antenatal oligohydramnios of renal origin: postnatal therapeutic and prognostic challenges.

Urinary tract anomalies (UTA) including polycystic kidney disease nowadays can be detected antenatally by ultrasound. The concomitant presence of oligohydramnios has been regarded as a severe risk factor for renal dysfunction and pulmonary hypoplasia, although clinical data after birth are scarce. We report the postnatal course and long-term follow-up of 10 infants with oligohydramnios due to congenital UTA from two pediatric nephrology centers. The underlying final diagnoses were autosomal-recessive polycystic kidney disease (ARPKD, n = 2), familial tubular dysgenesis (n = 2) and bilateral renal hypoplasia (n = 6) including 3 children with posterior urethral valves. Two children died in the neonatal period while 8 children are currently alive at a median age of 2.5 (range 1.1-10) years. In the postnatal period, respiratory failure necessitating mechanical ventilation occurred in 7 infants (including the 2 non-survivors). All surviving children had chronic renal failure, which could be managed conservatively in 6 children (median GFR 45 (range 15-53) ml/min/1.73 m2) while 2 reached end-stage renal disease; one undergoing preemptive kidney transplantation and one peritoneal dialysis. Seven of 8 children reached normal developmental milestones. In conclusion, the presence of antenatal oligohydramnios in infants with UTA does not always carry a poor prognosis. The high incidence of perinatal complications, the complexity of underlying causes and the prevalence of postnatal chronic renal dysfunction calls for a multidisciplinary approach in the management of these children.

Minimal change (steroid sensitive) nephrotic syndrome in children: new aspects on pathogenesis and treatment.

Steroid sensitive (minimal change) nephrotic syndrome (MCNS) has been regarded as immunological disorder because of clinical and experimental evidence as well as the response to immunosuppressive treatment. Recent work increased dramatically the understanding of podocyte biology which may be the key structure involved in MCNS, Interestingly many treatment options which were thought to work via an immunosuppressive pathway are now known to have a direct -non immunological- impact on the glomerular filtration barrier, i.e. the podocyte. Aim of this review is the presentation of recent research regarding the podocyte biology but also concerning the treatment of this disorder.

Desperately seeking diarrhoea: outbreak of haemolytic uraemic syndrome caused by emerging sorbitol-fermenting shiga toxin-producing Escherichia coli O157:H-, Germany, 2009.

Infection with sorbitol-fermenting Shiga toxin-producing Escherichia coli O157:H- (sf STEC O157:H-) is rare, but emerging in Europe. The pathogen is typically isolated from paediatric patients with life-threatening haemolytic uraemic syndrome (HUS). It is unclear whether this observation primarily reflects the pathogen's virulence or its complex laboratory diagnosis, not routinely conducted in diarrhoeal patients. In summer 2009, four boys living in the same suburb in Germany developed diarrhoea-associated HUS: three were infected by sf STEC O157:H- and one died. We conducted two analytical epidemiological studies, an extensive search for diarrhoeal cases in potentially exposed groups, and an environmental investigation. Outbreak cases were residents of the suburb diagnosed with HUS, sf STEC O157:H- infection, or both between 24 July 2009 and 25 August 2009. Overall, we ascertained eight cases with a median age of 4 years (range: from 8 months to 9 years). Stool screening of 220 persons led to the identification of only four additional cases: two asymptomatic carriers and two diarrhoeal cases. HUS was strongly associated with visiting a local playground in July, particularly on 16th July (odds ratio = 42.7, P = 0.002). No other commonality, including food, was identified, and all environmental samples (n = 24) were negative. In this localized non-foodborne outbreak, the place of likely infection was a local playground. Sf STEC O157:H- infection apparently limits itself rarely to diarrhoeal illness and progresses frequently to HUS. Therefore, detection of and response to this hypervirulent pathogen primarily relies on HUS surveillance.

Primary hyperoxaluria type 2.

UNLABELLED: Primary hyperoxaluria type 2 (PH2) is a rare disease with only 24 patients reported in the literature so far. It should be considered in any patient presenting with urolithiasis or nephrocalcinosis due to hyperoxaluria. The metabolic defect is deficiency of D-glycerate dehydrogenase/glyoxylate reductase leading to characteristic hyperoxaluria and excretion of L-glycerate, the cornerstone of diagnosis of PH 2. Although development of terminal renal failure seems to be less prevalent than in PH 1, recent reports indicate that chronic as well as terminal renal insufficiency may occur. Therefore specific therapeutic measures should aim at reduction of urinary calcium oxalate saturation by potassium citrate or pyrophosphate to reduce the incidence of nephrolithiasis and nephrocalcinosis and thus improve renal survival. Secondary complications (obstruction, urinary tract infections and pyelonephritis) must be avoided. In patients with terminal renal failure isolated renal transplantation seems to carry a high risk of disease recurrence. CONCLUSION: PH 2 is a rare but important cause of urolithiasis and nephrocalcinosis; long-term follow up is necessary, since the renal prognosis may be worse than previously anticipated.

Renal function in congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidneys and urinary tract are a major cause of chronic and end-stage renal failure in children. The molecular mechanisms having been elaborated, there is now growing evidence that kidney function is to a large extent determined genetically at an early stage. Assessment of kidney function is an important tool in clinical medicine and is feasible in utero. Postnatally, determination of absolute glomerular filtration rate and also of split and excretory renal function play an important role in the determination of treatment and prognosis. This is supplemented by other biochemical, molecular and interventional prognostic factors, which are of help in preservation of kidney survival by minimizing modulating factors. If chronic or terminal renal failure ensues in childhood or even in early infancy, however, improved medical care has led to encouraging results, ultimately influencing the motivation in the care of children with congenital anomalies of the kidney and urinary tract.

Nephrocalcinosis in a patient with primary hyperoxaluria type 2.

Although nephrocalcinosis is a classical finding in primary hyperoxaluria type 1 (PH 1) associated with a poor renal survival it is exceptional in patients with PH type 2 (PH 2), characterized by a more favorable outcome. We describe an 8-month-old girl who suffered from recurrent urinary tract infections. Imaging studies revealed a profound corticomedullary nephrocalcinosis with no evidence of calculi. Urinary oxalate and D-glycerate excretion were massively elevated, while urinary glycolate or glyoxylate could not be detected, confirming the diagnosis of PH 2. Although the nephrocalcinosis progressed radiologically, renal function remained stable for over 2 years. Only further follow-up will show whether the associated nephrocalcinosis worsens the prognosis of our patient and of PH 2 in general.

B-cell dysfunction and depletion using mycophenolate mofetil in a pediatric combined liver and kidney graft recipient.

The use of mycophenolate mofetil (MMF) in combination with cyclosporin A (CsA) and steroids is well established after kidney transplantation (Tx) in children. A 9-yr-old girl with primary hyperoxaluria type 1 and systemic oxalosis underwent a combined kidney and liver Tx at our institution. The post-operative immunosuppression consisted of CsA, prednisolone, and MMF. Four weeks post-transplant the girl suffered from a severe urinary tract infection caused by Pseudomonas aeruginosa, when the serum immunoglobulin G (IgG) concentration was found to be critically low (<1.53 g/L). Additionally, there was an isolated B-cell depletion (240/microL) at that time. In the following course, the B-cell count was significantly diminished until the MMF was stopped 13 weeks post-transplant. As a result of the very low serum IgG concentration, intravenous immunoglobulin (IVIG) substitution was necessary. There was no significant loss of immunoglobulins in the ascites and urine and no other medication with possible side-effects on B cells was given. We suggest that MMF can lead to suppressed IgG production by B cells and can cause a defective differentiation into mature B cells. In vitro studies demonstrated these effects of MMF on B cells, but no in vivo cases of this phenomenon have been reported. B-cell counts and serum IgG concentrations returned to normal values after discontinuing the MMF. As we can assume that the observed B-cell dysfunction and depletion were MMF related, we suggest that serum IgG concentrations should be monitored when MMF is used after solid-organ Tx.

IgG2 deficiency in uremic children is not restricted to peritoneal dialysis treatment.

To date there are no data concerning IgG subclasses in children with preterminal chronic renal failure (CRF), although a reduction of total serum IgG, including its major subclasses IgG1 and IgG2, has been demonstrated in patients on peritoneal dialysis (PD). Therefore we studied total IgG, IgA, IgM, and IgG subclasses in preterminal CRF (n = 25), PD (n = 22) patients, and 13 age-matched healthy children and also compared results with age-related normal values previously established in 226 healthy children. While total IgG, IgA, IgM, and IgG 1 were comparable, there was a significant deficiency of IgG2 in children both with preterminal CRF and on PD compared with controls. Moreover, the prevalence of IgG2 deficiency compared with age-related normal values was significantly increased not only in PD but also in preterminal CRF patients. We conclude that there are alterations in serum IgG subclasses in children with CRF, with IgG2 deficiency not restricted to PD, but being present in the preterminal state as well.

[Bilharziasis as the etiology in hematuria and proteinuria in childhood]. / Bilharziose als Ursache von Hämaturie und Proteinurie im Kindesalter.

Haematuria and proteinuria are important symptoms of primary and secondary nephropathies. We report three african children presenting to our center in whom infection with S. haematobium resulted in haematuria and proteinuria. The third patient concomitantly suffered from steroid-sensitive relapsing nephrotic syndrome with the histological features of focal and segmental glomerulo-sclerosis. The diagnosis was in all cases established by light microscopy and urinary symptoms improved after treatment with praziquantel. In the third patients long term remission of the nephrotic syndrome could be maintained after 4 doses of praziquantel for recurrent bladder symptoms. We conclude that bilharziosis must be considered in the differential diagnosis of children with haeamturia and proteinuria even in Europe. The diagnosis can be established easily by light microscopy and an effective and low-risk treatment (with Praziquantel) can be offered.

Simultaneous determination of oxalate, citrate and sulfate in children's plasma with ion chromatography.

To improve our understanding of both diagnosis and treatment of diseases of oxalate metabolism, we first set out to establish a new ion-chromatographic method to determine normal plasma levels of oxalate, citrate and sulfate from single plasma samples. In 50 infants and children (23 girls, 27 boys, aged 0.2 to 17 years) with normal renal function, blood was drawn in Li-heparin tubes, placed on ice and preserved immediately with 40 microliters M HCl/ml plasma in two ultracentrifugation steps. For measurement, plasma was injected onto an ion chromatography system with NaOH as the mobile phase, and then run as a linear gradient from 5 mM to 52.5 mM over 21 minutes. Analysis yielded measurable and reproducible oxalate (6.43 +/- 1.06 microM/liter), citrate (79.3 +/- 27.4 microM/liter) and sulfate (235.0 +/- 85.3 microM/liter) levels, without any age and gender specific differences. The least detectable plasma oxalate level was < 0.3 microM with a high reliability and reproducibility (coefficient of variance 1.95 to 4.75%). In conclusion, we established a reproducible, precise method to determine the relevant plasma anions involved in mineral metabolism, which heretofore have not been easily measurable. Studies of diseases of oxalate and citrate metabolism are ongoing on the basis of the normal plasma values achieved in this study.