Henoch-Schönlein nephritis: a nationwide study.

BACKGROUND/AIM: The aim of this retrospective study was to evaluate the presentation, clinical and pathological manifestations and outcome of the Henoch-Schönlein purpura (HSP) nephritis in children. METHODS: Clinical and laboratory data of 443 children with HSP nephritis aged between 3 and 16 years from 16 pediatric nephrology reference centers were analyzed retrospectively. The biopsy findings were graded according to the classification developed by the International Study of Kidney Disease in Children (ISKDC). RESULTS: Renal biopsy was performed in 179 of the patients with HSP nephritis. The most common presenting clinical finding in patients who were biopsied was nephrotic range proteinuria (25%) which was followed by nephritic-nephrotic syndrome (23.5%). The biopsy findings according to the ISKDC were as follows: class I: 8.3%; II: 44.1%; III: 36.3%; IV: 6.7%; V: 3.3%; VI: 1.1%. All of the patients who developed end-stage renal disease had nephritic-nephrotic syndrome at presentation. Of 443 patients, 87.2% had a favorable outcome and 12.8% had an unfavorable outcome. The overall percentage of children who developed end-stage renal disease at follow-up was 1.1%. Logistic regression analysis did not show any association of initial symptoms and histology with outcome. CONCLUSION: In the presented cohort, the presence of crescents in the first biopsy or presenting clinical findings did not seem to predict the outcome of HSP nephritis in children. We conclude that children with HSP nephritis even with isolated microscopic hematuria and/or mild proteinuria should be followed closely.

BK virus-associated nephropathy in two pediatric kidney recipients.

Posttransplant renal dysfunction episodes can result from a variety of causes, including polyomavirus (BK virus)-associated nephropathy (PVAN). It is a well-recognized entity with a high incidence of graft failure. The delicate balance of viral infection and immune regulation in the transplant population would allow development of successful long-term strategies. In this presentation, we have described two PVAN cases of our institution and reviewed the literature.

Successful solid organ transplantation from septicemic cadaveric donors: case report.

Systemic donor infections especially with gram-negative organisms are regarded as an absolute contraindication to cadaveric organ donation for transplantation. This is largely due to fear of transmitting the pathogenic organisms to the immunosuppressed recipient. However, due to the current shortage of organs available for transplantation, clinicians are faced with the option to use organs from infected donors. Between 1996 to January 2006, we collected 44 solid organs. Two out of nine donors had microorganisms from blood cultured. Case 1 was of 23-year old woman whose cause of brain death was intracerebral bleeding due to a traffic accident. The donor had stayed 9 days in the intensive care unit prior to brain death. Two kidneys, two livers (split), and or heart were used. Klebsiella was the organism on blood culture. Case 2 was of 35-year-old man; cause of brain death was cerebral hematoma due to traffic accident. The donor had stayed 6 days prior to brain death onset. The liver and two kidneys were used. Acinetobacter baumannii was yielded upon blood culture. All donors were treated with appropriate antibiotics for at least 48 hours prior to organ procurement with consequent negative blood cultures, while the recipients received the same culture-specific antibiotics for 10 days following transplantation. One donor (case 1) heart and both donor corneas were not used due to infection. All patients are alive with excellent graft function at a median of 90 days following transplantation. In conclusion, our results suggested that bacteremic donors with severe sepsis under proper treatment can be considered for transplantation.

Osteoprotegerin and RANKL serum levels and their relationship with serum ghrelin in children with chronic renal failure and on dialysis.

BACKGROUND: Osteoprotegerin (OPG) and receptor activator of the nuclear factor kappaB ligand (RANKL) constitute a complex system of mediators involved in the regulation of bone resorption process. Ghrelin, a growth hormone secretagogue, has been shown to modulate proliferation and differentiation of osteoblasts. The present study was carried out to evaluate the serum concentrations of OPG and sRANKL in children with chronic renal impairment (CRI) and on dialysis, and to establish a possible relationship between their serum levels and that of ghrelin. METHODS: 33 patients including 10 patients with CRI, 12 peritoneal dialysis (PD) and 11 hemodialysis (HD) patients and 22 healthy controls were enrolled into the study. OPG, sRANKL and ghrelin levels were studied with radioimmunoassay. RESULTS: Serum OPG levels in CRI, PD and HD groups were significantly higher than the healthy controls (p = 0.002, p < 0.001, p < 0.001, respectively) whereas sRANKL levels were significantly lower than the healthy controls (p = 0.03, p = 0.01, p = 0.001, respectively). Ghrelin levels were significantly higher in CRI, PD and HD groups compared to healthy controls (p = 0.001, p < 0.001, p < 0.001, respectively). We observed a negative correlation between the sRANKL and OPG levels (r = -0.27, p = 0.04) as well as between sRANKL and ghrelin levels (r = -0.31, p = 0.02). OPG levels showed a positive correlation with ghrelin levels (r = 0.63, p < 0.001). CONCLUSION: We found a lower RANKL bioactivity index in children with CRI and on dialysis. The mechanism and the role of elevated OPG and low sRANKL in uremia are unclear, but they might partly represent a compensatory mechanism to the negative balance of bone remodeling in renal bone disease in children. Additionally, we demonstrated for the first time that ghrelin and the RANKL/OPG system have a close relationship in CRF. Therefore, ghrelin may be of importance in mediating the effects of the RANKL/OPG system in renal bone disease.

Renal fibrosis: insights into pathogenesis and treatment.

The progression of chronic renal failure is characterised histologically by glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis. Recent research has identified common mechanisms underlying these fibrotic processes. In particular, the scarring process within the glomeruli and the tubulointerstitium involves the infiltration by inflammatory cells including monocytes, the activation of intrinsic renal cells as well as interactions between infiltrating and resident cells. These interactions depend, to a large extent, on the release by these cells of chemokines, cytokines and growth factors. These factors are in turn involved in the induction of cellular proliferation within the kidney and the stimulation of the synthesis and deposition of extracellular collagenous matrix. Fibrosis is believed to result from excessive synthesis of extracellular matrix and a concommitant decrease in its breakdown. This fibrotic process resulting in end stage renal insufficiency bears strong similarities to that taking place within cirrhotic livers or fibrotic lungs. The new insights in our understanding of renal fibrosis have opened the way to new interventions aimed at its prevention. This may ultimately slow the progression of chronic renal insufficiency and decrease the number of patients requiring dialysis replacement therapy.

Desmopressin versus indomethacin treatment in primary nocturnal enuresis and the role of prostaglandins.

OBJECTIVES: To compare the efficacy of desmopressin and indomethacin and also determine the prostaglandin E2 (PGE2) concentrations in the patient and control groups. METHODS: Eighty-five children with primary nocturnal enuresis were followed up for a baseline period of 4 weeks, during which they recorded wet and dry nights. After this period, the patients were divided into three groups that used desmopressin, indomethacin, or placebo for 4 weeks. The dosage of desmopressin (group A, n = 31 ) was 20 microg/day and the dosage of indomethacin (group B, n = 29) was 100 mg/day. The placebo group (group C) consisted of 25 patients. We determined the serum PGE2 and urine PGE2 concentrations before and after treatment in the three groups and in a control group. RESULTS: Treatment with desmopressin and indomethacin resulted in significantly more dry nights during the 4 weeks of observation than did placebo (P <0.005). The number of dry nights was also significantly different in the desmopressin group than in the indomethacin group (P <0.01). In the total patient group, the mean serum and urine PGE2 concentrations were significantly different from the control group's serum and urine PGE2 concentrations (P <0.001). There was a significant decrease in the serum and urine PGE2 concentrations in group A and group B after the treatment period (P <0.01). CONCLUSIONS: Desmopressin and indomethacin were found to be more effective than placebo. We conclude that prostaglandins have an important role in the pathophysiology of primary nocturnal enuresis.

Comparison of ceftriaxone versus cefotaxime for childhood upper urinary tract infections.

It is very important to treat patients with upper urinary tract infections (UTIs) promptly and effectively because of the potential sequelae. In the present study we compare the efficacy of the two cephalosporins, ceftriaxone and cefotaxime, in childhood pyelonephritis. The study protocal included 10 days of drug therapy. Both in patients receiving ceftriaxone and cefotaxime, successful eradication was achieved at the second day of therapy. The overall cure rate was significantly better in the ceftriaxone group than the cefotaxime group in terms of recurrence and reinfections (p < 0.05). Furthermore, in the complicated group, ceftriaxone was slightly superior to cefotaxime, approaching significance in terms of preventing recurrent infections. No serious adverse effects were observed in either of the groups. The present study has shown that ceftriaxone exhibits favorable clinical and bacteriologic efficacy in patients with complicated and uncomplicated upper UTI. Once-daily injection of ceftriaxone in children is also an attractive advantage of the drug when compared to twice-daily cefotaxime.

Triple immunosuppression with or without basiliximab in pediatric renal transplantation: acute rejection rates at one year.

Acute rejection (AR) is a major determinant of chronic allograft dysfunction and graft survival. This study evaluated the effect of basiliximab on AR in pediatric renal transplantation on triple immunosuppression. Forty-three transplantations (25 males and 18 females; mean age 14.9 +/- 3.6 years) were performed between 1996 and 2002. Thirteen of the grafts came from cadaveric donors and 30 from living-related donors. All patients were placed on immunosuppression with prednisolone + (azathioprine or mycophenolate mofetil) + (cyclosporine [CYA] or tacrolimus). Basiliximab was also administered in 20 cases. The respective rates of biopsy-proven AR in the basiliximab group (BG) and the standard-regimen group (N-BG) were 0% vs 17.4% (P >.05) at 1 month posttransplantation; 0% vs 26.1% (P <.05) at 3 months; 0% vs 26.1% (P <.05) at 6 months, and 7.1% vs 26.1% (P >.05) at 12 months. In the N-BG group the 1- and 3-year graft survival rates were 91.3% (21/23) and 83.3% (15/18), respectively. The mean glomerular filtration rate (GFR) in the first year after the transplantation was 75 +/- 33 mL/min/1.73 m(2) in the N-BG and 98 +/- 21 mL/min/1.73 m(2) in the BG patients (P <.05). Basiliximab significantly reduced the rates of acute rejection at 3 and 6 months after pediatric renal transplantation. The GFR in the first year was significantly higher among the patients treated with basiliximab, which was well tolerated by all patients and caused no significant adverse effects. The effect of basiliximab on long-term graft survival and chronic allograft dysfunction deserves further investigation.

Membranoproliferative glomerulonephritis in sibs.

Idiopathic membranoproliferative glomerulonephritis (MPGN) is a chronic renal disease with variable clinical expression and several distinct morphological subtypes. Two sibs, aged 10 and 13, presented with clinical and laboratory findings of MPGN at the time of admission. After an interval of one year, the diagnosis of MPGN was established by renal biopsies. The complement pathway was unremarkable. HLA typing in the unrelated parents and the two male sibs revealed common HLA A2,A11,Bw60, DR2,DQw1 antigens in the brothers. Of these antigens, A2 has been reported previously in cases of MPGN. The other antigens regarding this disease need to be evaluated from the standpoint of genetic importance.

Diabetes mellitus, diabetes insipidus, optic atrophy and deafness (DIDMOAD syndrome).

Two patients with diabetes mellitus (DM), diabetes insipidus (DI), optic atrophy (OA), deafness (D) and dilatation of the urinary tract-the so-called DIDMOAD syndrome are presented. In one of the patients, the presenting components were DI and OA. In the second case, DM was the first manifestation to be diagnosed, and in this patient the course of the syndrome was complicated by associated epileptical activity disorders, and later septicemia. The admission of these patients led us to review the literature describing this syndrome.

Effects of secondary hyperparathyroidism on cardiac function in pediatric patients on hemodialysis.

Cardiovascular complications are an important cause of morbidity and mortality in chronic hemodialysis patients. In order to examine the effect of parathyroid hormone (PTH) and vitamin D on left ventricular functions, 11 patients between the ages of 13 and 18 years on regular hemodialysis were investigated using M-mode echocardiography and systolic time intervals. The ratio of the pre-ejection period to the left ventricular ejection time was found to be 0.38 +/- 0.02 (range (0.25 +/- )>50) and was elevated above normal in five of the 11 patients examined. Four of these patients has hypertension and one had severe anemia. The left ventricular ejection fraction was 55 +/- 2.54% and fractional fiber shortening was 31.55 +/- 2.26%, both of which were within normal limits for age. Although the velocity of circumferential fiber shortening was within normal limits in the majority of cases, the mean value was 1.437 +/- 0.11 circ/s, which is above normal for this age period. PTH levels were between one and 4.70 ng/ml. All of the hemodialysis patients had been receiving 1 alpha hydroxy-cholecalciferol and had normal calcium levels. Although they had high PTH levels, most of these patients displayed normal myocardial contractility. No significant correlation was obtained between increment in PTH levels and myocardial function indices. These results imply that PTH is not the only factor affecting myocardial functions. Since all of these patients have received vitamin D therapy for long periods, we suggest that vitamin D may have prevented the deleterious effect of PTH on myocardial function.

Acute renal failure due to acute pyelonephritis.

We report a case of acute renal failure due to acute pyelonephritis with microabscess formation. Despite antibiotic therapy renal function deteriorated, necessitating peritoneal dialysis. Although rare, acute pyelonephritis is an important consideration in the differential diagnosis of acute renal failure, and prompt antibiotic therapy is crucial to insure a favourable outcome.

Haemodialysis treatment in phenobarbital intoxication in infancy.

Haemodialysis treatment was performed in a comatose infant who was 9 months old. At the beginning of haemodialysis plasma phenobarbital concentration was found to be 120 micrograms/ml. The constant low flux haemodialysis lowered the plasma phenobarbital concentration to 64.2 micrograms/ml and haemodialysis was terminated at the end of six hours. The patient recovered fully after haemodialysis session. This case indicates that haemodialysis is an effective and successful treatment method in phenobarbital intoxication also in infancy.

Effects of recombinant human erythropoietin on sodium balance in nondialysed children with chronic renal failure.

In this study rhEPO, 70 U/kg, was subcutaneously administered two times a week for eight weeks to twelve nondialysed patients with renal anaemia and chronic renal failure. Renal function tests, blood pressure, Hb, Hct, FENa and Na-K-ATPase enzyme activity before and after administration of rhEPO have been studied. We have searched for correlations, if any, between these parameters. After the treatment period mean Hb concentration and mean Hct values increased from 7.5 +/- 0.3 to 8.6 +/- 0.5 g/dl and from 22.5 +/- 1.2 to 26.7 +/- 1.6%, respectively (p < 0.05), whereas no significant differences between pretreatment and posttreatment Cr and CrCl values were found (p > 0.05). No changes in blood pressure were found throughout the study. While mean FENa decreased from 10.2 +/- 1.6 to 6.15 +/- 1.05% (p < 0.05), mean Na-K-ATPase enzyme activities decreased from 0.120 +/- 0.016 to 0.095 +/- 0.025 mumol Pi/h/mg protein (p > 0.05) after treatment. In conclusion, subcutaneous administration of rhEPO, at doses of 70 U/kg twice a week in nondialysed patients increased Hb and Hct values. A significant decrease of FENa was observed after rhEPO treatment and there was no correlation between Na-K-ATPase enzyme activity and FENa.

A stormy transplant case with happy ending.

A 12-year-old female patient with end-stage renal failure whose primary disease was reflux nephropathy, was first admitted for augmentation cystoplasty by using an ileum segment because of contracted urinary bladder. Four months later, she had a renal transplantation from her father on March 28th 1997. The first three days after the operation were uneventful. On the fourth day, she presented a severe rejection episode and was treated with steroid and ATG. A urinary fistula developed and she underwent surgery again on the 14th postoperative day. At surgery, apical resection + omentoplasty + nephrostomy + DJ replacement were performed. The postoperative period after the second operation was full of problems for both the patient and the transplantation team. She was discharged from hospital on the 40th postoperative day with excellent renal function (a serum creatinine level of 1 mg/dl) and with full recovery.

How often do we face side effects of sirolimus in pediatric renal transplantation?

We analyzed 25 pediatric renal transplantation patients on sirolimus (SRL) therapy to assess changes in serum creatinine, glomerular filtration rate, electrolytes, triglycerides, cholesterol, and side effects. Mean time to initiate SRL therapy was 3.2 years. The serum creatinine levels of patients on SRL treatment at 1, 6, 12, and 24 months were 1.67 ± 1.15 mg/dL, 1.18 ± 0.52 mg/dL, 1.24 ± 0.32 mg/dL, 1.15 ± 0.31 mg/dL, and 1.17 ± 0.12 mg/dL, respectively. We observed proteinuria in 3, hyperlipidemia in 5, and anemia in 2 patients, but none had the treatment discontinued. We diagnosed interstitial pneumonia in (n = 1), nasal acneiform lesions (n = 1), and lower extremity edema (n = 1). Hypokalemia developed in 1 subject with high blood SRL levels. In the follow-up period there was no case of acute rejection episode during SRL therapy.

The CERTAIN Registry: a novel, web-based registry and research platform for pediatric renal transplantation in Europe.

BACKGROUND: The results of pediatric renal transplantation have improved markedly in the last decade. However, a number of relevant clinical problems remain, such as organ damage caused by chronic rejection, long-term toxicity of immunosuppressive therapy, difficulty in developing tolerance-inducing protocols, secondary cardiovascular comorbidity, post-transplantation lymphoproliferative disease, suboptimal longitudinal growth, quality of life, adherence to immunosuppressive medication, and structured transition programs to adult care. These unmet clinical needs require intense collaborative and interdisciplinary clinical research. We recently founded the Cooperative European Paediatric Renal TransplAnt INitiative (CERTAIN; www.certain-registry.eu) as a research network and platform built on a novel, web-based registry. RESULTS: The registry's dataset provides essential information on generic kidney transplantation-related topics and also captures pediatric-specific topics, such as growth, physical and psychosocial development, and adherence. Due to its flexibility the system can be used as follows: (1) as a registry capturing a minimal or an extended dataset; (2) as a center and/or country-specific transplantation database; or (3) as a patient-specific electronic transplantation chart. The data can be exported directly from the CERTAIN web application into statistical software packages for scientific analyses. The rights regarding data ownership, evaluation, and publications are regulated in the registry's rules of procedure. Data quality is ensured by automatic software validation and a manual data review process. To avoid redundant data entry, CERTAIN has established interfaces for data change with Eurotransplant, the Collaborative Transplant Study (CTS), and the registry of the European Society of Pediatric Nephrology (ESPN) and European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) (ESPN/ERA-EDTA registry). CERTAIN fulfils all regulatory and ethical requirements of the European Union and Germany, in particular, regarding patients' data privacy and security. CONCLUSION: Using modern information technology, the recently established multinational CERTAIN Registry fills a gap in Europe for collaborative 5 research and quality assurance in the field of pediatric renal transplantation.

Dilated cardiomyopathy in juvenile chronic arthritis.

A seven year old boy with seronegative systemic onset juvenile chronic arthritis who developed dilated cardiomyopathy, is presented. Treatment with methotrexate, prednisone, and digitalis has been successful in controlling the acute phase of the disease and congestive heart failure.

von Willebrand factor antigen compared with other factors in vasculitic syndromes.

In order to analyse their role as a specific marker of vascular damage and their value in monitoring disease activity the plasma concentrations of von Willebrand factor antigen (vWFAg) and the ristocetin cofactor (RiCoF) activities were determined in 43 children with vasculitis and 20 controls. These patients were sub-divided into three groups according to diagnosis: Henoch-Schönlein purpura (n = 18), polyarteritis nodosa (n = 16), and systemic lupus erythematosus (n = 9). High concentrations of vWFAg and activities of RiCoF were found in all the patient groups. vWFAg and RiCoF returned to normal as the patients became symptom free and remained above normal in those with continuing symptoms. The amount of vWFAg did not correlate with the acute phase reactants. vWFAg acted as a specific marker of vascular damage and was useful for the monitoring of disease activity both in small vessel vasculitis and systemic necrotising arteritis.