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.

Successful Treatment of Renal Infiltration Complicated by Atypical Hemolytic Uremic Syndrome in a Leukemic Child.

Renal infiltration in children with acute leukemia has been reported previously; however, it has rarely been described in association with atypical hemolytic uremic syndrome (aHUS). We present a case of 9-year-old boy who developed life-threatening aHUS in the 1st week of Burkitt leukemia/lymphoma diagnosis with renal infiltration. Complete resolution of aHUS was achieved after therapeutic plasma exchange. This is an uncommon complication of Burkitt leukemia/lymphoma in a pediatric case.

Strategies for optimizing growth in children with kidney transplants.

Children with a well-functioning graft continue to show growth retardation even with low-dose prednisone. We have attempted to utilize the steroid-sparing effect of cyclosporine by discontinuing prednisone after graft stabilization. Since 1983, 53 children have received cyclosporine as primary immunosuppressant for renal graft maintenance. The children, aged 6 months to 18 years, received 60 transplants. One-year and four-year patient survival for cadaveric transplants was 91% and 91%, compared with 96% and 96% for living related transplants. One-year and four-year graft survivals were 82% and 65% for cadaveric transplants (n = 25), compared with 91% and 63% for living related transplants (n = 35). Of 53 patients, 23 were able to discontinue prednisone and be maintained on monodrug cyclosporine therapy, and 21 of the 53 patients had growth hormone measured using L-dopa stimulation. In patients receiving more than 5 mg of prednisone daily, growth hormone levels were lower than normal (less than 10 ng/ml). Of 15 patients who had discontinued prednisone for more than 6 months, 13 showed accelerated growth by improvement in their standard deviation scores. In 4 pubescent children with growth retardation and need for maintenance prednisone, accelerated growth occurred following growth hormone administration for 3-6 months. Based on these data we suggest that (1) discontinuation of even very small doses of prednisone may be essential for normalizing growth hormone response to L-dopa and (2) further studies are needed to exploit the growth stimulation effect of recombinant growth hormone in transplanted children.

The role of plasma arachidonic acid metabolites in the pathogenesis and the prognosis of Henoch-Schönlein purpura.

Henoch-Schönlein Purpura (HSP) involve small vessel inflammation. Arachidonate biochemical pathways play an important role in the pathogenesis of vascular inflammation. The aim of this study was to investigate the change in the ratio of plasma arachidonic acid metabolites in the patients with HSP and evaluate the association between clinical activity and prostanoid activity in the acute phase of HSP. Plasma prostaglandin E2 (PGE2)-like activities were found to be 7.2 +/- 0.8 ng/ml in control group (n = 12) while it was 5.3 +/- 0.6 ng/ml in the patients with HSP (n = 12). Plasma leukotriene C4 (LTC4)-like activities were found to be 16.0 +/- 1.1 ng/ml in control while it was 30.9 +/- 4.3 ng/ml in the patients. The differences of LTC4-like activities and the LTC4/PGE2 ratios between the HSP patients and the controls were significant (p < 0.01, p < 0.001 respectively), but no significant difference was found in PGE2-like activities. Plasma LTC4-like activity and LTC4/PGE2 ratio were also significantly increased in the patients with high clinical score (p < 0.05, p < 0.02 respectively). These results suggested that not only cyclooxygenase products but also LTs may play an important role in vascular inflammation. Therefore LTC4/PGE2 ratio must be taken into consideration in the pathogenesis and the prognosis of HSP.

The role of prostanoids in the complications of extracorporeal shock wave lithotripsy (ESWL) in children.

ESWL is a safe and effective first-line treatment for urinary tract stone disease (UTSD) in children. The major complications arising from this procedure were upper urinary tract obstruction and ureteral colic. It was shown that prostaglandin synthetase inhibitors were effective in the treatment of urethral colic. The aim of this study was to measure urinary and plasma prostaglandin E2 (PGE2)- and leukotriene C4 (LTC4)-like activity in the patients who underwent ESWL before and after the treatment and investigate the role of cyclooxygenase (CO) and lipoxygenase (LO) products in early and late complications of ESWL. Urinary PGE2-like activity were increased 1 h after ESWL. (1.19 +/- 0.12 vs 1.59 +/- 0.15 g/ml, p < 0.02). The plasma values were decreased significantly after the treatment (16.7 +/- 1.7 vs 11.6 +/- 1.2 g/ml, p < 0.005). Urinary and plasma LTC4-like activities were found to be significantly decreased in the post-ESWL samples (0.58 +/- 0.006 vs 0.39 +/- 0.04, p < 0.002; 8.6 +/- 0.9 vs 4.2 +/- 0.6, p < 0.001, respectively). In conclusion, ESWL may stimulate the release of PG from the urinary tract resulting in increased peristaltism and the passage of stone fragments into the bladder. As this group of drugs has also nephrotoxic effects, they can be given prophylactically only to selected patients.

Parathormone, 1,25 dihydroxyvitamin D and prostaglandin E2 correlation in children with idiopathic hypercalciuria.

As urinary prostaglandin excretion might be involved in idiopathic hypercalciuria, we studied the excretion of prostaglandin E2 and calcium together with serum prostaglandin E2, parathormone and 1,25 dihydroxyvitamin D in 20 patients and 11 controls Idiopathic hypercalciuric patients showed increased levels of urinary prostaglandin E2-like activity, which is correlated with calcium excretion. Although no change was observed in serum parathormone level in control and hypercalciuric patients, there was a positive correlation between serum 1,25 dihydroxyvitamin D and prostaglandin E2-like activity. These findings suggest that prostaglandin E2 could play a role in the hypercalciuria syndrome, possibly by increasing 1,25 dihydroxyvitamin D synthesis.

Role of free oxygen radicals and prostanoids in the pathogenesis of Henoch-Schönlein Purpura.

The pathogenesis of Henoch-Schonlein Purpura (HSP) is still controversial. The aim of our study was to investigate the role of oxidative stress and cyclooxygenase (CO) pathway products in the pathogenesis of HSP. In order to investigate this, malondialdehyde (MDA) levels, indicating lipid peroxidation, prostaglandin E (PGE)-like activity as inflammatory mediator and vitamin E (vit-E) levels indicating anti-oxidant status were studied in a group of 10 children with HSP (five girls and five boys, aged 6-21 years, mean 10.7 years), both in the acute and recovery phase of the disease and in five age and sex-matched healthy children as a control group. The patients were also grouped into low and high clinical score groups. Plasma levels of MDA and PGE-like activity were significantly elevated in the active phase of HSP compared to the recovery phase. Vit-E levels were significantly reduced in the active phase compared to the recovery phase. The plasma levels of PGE-like activity of the patients obtained in the active phase were significantly higher than the levels of the control group, whereas the levels of the recovery phase were significantly lower than in the control group. No such difference between the controls and MDA and vit-E levels in the patient group was shown. No correlation between the clinical scores and the parameters studied could be found. Our findings indicate that oxidant stress and CO pathway products may play a role in the pathogenesis of HSP.

Sonographic demonstration of intestinal involvement in Henoch-Schönlein syndrome.

We evaluated the efficacy of intestinal sonography in the diagnosis of gastrointestinal involvement of Henoch-Schönlein syndrome (HSS). Intestinal sonography was performed in 20 children who were clinically diagnosed as HSS and sonographic findings of the intestinal system were reviewed. Out of 20 patients, 10 who suffered from abdominal pain demonstrated sonographic findings consistent with small intestinal involvement (dilatation of intestinal segments, hypomotility, and eccentric thickening of the intestinal wall). Our results reveal that sonography of the intestine may be useful in the evaluation of the involvement of HSS.

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.

Gastric emptying time in renal transplant recipients treated with cyclosporine.

Gastric emptying time (GET) appears to be a rate-limiting factor in the absorption of cyclosporine-A (CsA) and may be responsible for intra- and interpatient variability of CsA bioavailability. Few studies have assessed gastric motility after renal transplantation. The purpose of this study was to evaluate gastric emptying of semi-solid material in stable renal transplant patients with reference to blood CsA levels. The GET of semi-solids (GET t(1/2), half emptying time) was measured in 16 transplant recipients who were taking CsA (Neoral), prednisolone and azathioprine (or mycophenolate mofetil). The GET (t(1/2)) measured by radionuclide methods, was analyzed with reference to the daily CsA doses, levels of CsA (C(0)), and serum creatinine concentrations. The mean GET (t(1/2)) was 89.1 +/- 26.4 minutes. Twelve patients exhibited delayed gastric emptying with a mean CsA level of 171.8 +/- 56 ng/mL and a mean dose of 4.1 +/- 1.1 mg/kg/d. The GET (t(1/2)) was not significantly correlated with the serum creatinine levels, the time since transplantation, or the CsA concentration. In addition, the correlation between the mean daily CsA dose and the GET (t(1/2)) was only weakly positive, (r =.33, P =.2) and therefore, statistically insignificant. In conclusion, it could not be ascertained whether a higher dose of CsA delays gastric emptying or whether patients with delayed emptying require higher doses of CsA. However, it is believed that determining the GET after transplantation helps in the adjustment of immunosuppressant doses.

Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in children with insulin-dependent diabetes mellitus.

Pubertal development has recently been evaluated from the standpoint of changes in insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels in healthy children. We studied puberty related changes in serum IGF-I and IGFBP-3 levels in 24 patients (11 prepubertal) with insulin dependent diabetes mellitus (IDDM) and 26 healthy subjects (14 prepubertal). Serum IGF-I and IGFBP-3 levels were assayed using immunoradiometric assays and radioimmunoassays, respectively. Serum IGF-I and IGFBP-3 levels in diabetics did not increase during puberty, as opposed to those in healthy children. Serum IGF-I and IGFBP-3 levels of diabetic patients were found to be lower than those of control subjects during puberty (p < 0.0001 and p < 0.05, respectively). Proteolysis is believed to be a general mechanism to increase IGF bioavailability in the presence of IGFBPs. Increased IGFBP-3 protease activity has been shown in sera of children with IDDM as well as a decrease in this activity in response to insulin therapy. Our data displaying low IGFBP-3 levels in diabetic children may be due to increased proteolysis, which also causes a shift in IGF-I to its lower molecular weight forms. Higher rate of clearance of the latter may be the reason for the low IGF-I levels we observed in children with IDDM. The moderate correlation between insulin dose and IGFBP-3 levels (r = 0.5, p < 0.01) may suggest insulin to be a contributing factor in the regulation of IGFBP-3 levels. We conclude that regulation of IGF-I and IGFBP-3 concentrations is disturbed in children with IDDM, in particular during adolescence.

The association of nephrotic syndrome and renal vein thrombosis: a clinicopathological analysis of eight pediatric patients.

Cases with a pathological diagnosis of renal venous thrombosis (RVT) associated with nephrotic syndrome (NS) were studied retrospectively for clinicopathological evaluation. The material consisted of 21 RVT cases which were diagnosed in 2000 consecutive pediatric necropsies, with an overall incidence of about one percent. Eight of the 21 RVT cases were associated with nephrotic syndrome (34%), and this group formed 0.4 percent of the total necropsies in our pediatric center. The glomerulopathies of these nephrotic patients consisted of three cases of Finnish-type congenital NS (FCNS), three cases of renal amyloidosis secondary to familial Mediterranean fever, and two cases of membranoproliferative glomerulonephritis (MPGN). The presence of sepsis associated with disseminated intravascular coagulation, and the morphological age of the thrombi suggested that the RVT was secondary to sepsis in the FCNS cases. In the MPGN and secondary renal amyloidosis cases, the long duration of both the nephrotic state and the administration of diuretics along with glucocorticoid treatment and also the newly formed thrombi without infarction are strong evidences, although not definite, that the RVT developed as a complication of the glomerulopathy. Even though there were no definite clinical criteria for the diagnosis of most of the RVT cases, we would like to emphasize the importance of flank pain, the rapid deterioration of renal functions in a stable nephrotic patient, as well as the hypercoagulable state in the consideration of the development of RVT which indicate the need for appropriate radiological studies for confirmation of this condition during life.

The effects of contrast media on renal function in children: comparison of ionic and non-ionic agents.

Nephrotoxicity is a common side effect of intravascular contrast media (CM). Although nephrotoxicity of ionic CM has been widely demonstrated, recent studies suggest that newer and more costly non-ionic agents are not less nephrotoxic. We studied the hemodynamic, hematologic and nephrotoxic effects of CM prospectively in 38 patients (ages six months-16 years) with or without risk factors predisposing to nephropathy and compared ionic and non-ionic CM. We performed intravenous urography (IU) with a ionic CM, sodium meglumine diatrizoate (n = 18) and a non-ionic CM, iohexol (n = 20). The patients were divided into three groups according to glomerular filtration rate (GFR) [GFR < or = 50 (n = 9), 50-80 (n = 13), > or = 80 ml/min/1.732 (n = 26)]. Eleven patients had risk factors for nephropathy. Blood pressure, heart rate, ECG, urine and blood samples were obtained 24 hours and one hour before as well as one, 24, and 48 hours after CM infusion. Although a significant increase was found in urine specific gravity, protein/creatinine ratios and serum Na and creatinine levels, the increased levels were within normal limits. We observed a significant reduction in Hb and Htc and urinary prostaglandin E1 levels. Many of the changes observed in the urine and serum values after the use of CM were minor, insignificant and transient, later returning to their initial values. The GFR levels, the presence of risk factors and the use of ionic vs. non-ionic CM had no effect on the results. The elevated urinary basal beta-2-microglobulin levels further increased after CM in patients with low GFRs. It was concluded that non-ionic CM was not superior to ionic CM in patients with GFRs greater than 50 ml/min regardless of predisposing risk factors. One of the non-invasive radiological methods is advised instead of IU in patients with low GFRs.

Radiologic evaluation of urinary tract infection.

This prospective study was designed to investigate the most relevant radiological approach for the evaluation of urinary tract infections (UTI) in childhood. In the first 48 hours following the diagnosis of UTI, all patients underwent 99mTc dimercaptosuccinic acid (DMSA) scanning, ultrasonography (US) and intravenous urography (IVU). For the imaging of renal parenchymal infection the sensitivity of IVU and US as compared to DMSA scanning were found to be 9.09% and 25%, respectively. It was concluded that 99mTc DMSA, where available, should be the first step for the accurate diagnosis and follow-up of patients with UTI.

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.

The importance of 99mTc DMSA scanning in the localization of childhood urinary tract infections.

The use of 99mTechnetium dimercaptosuccinic acid (99mTc DMSA) scanning for the early diagnosis of upper urinary tract infections has been preferred for a few years. In this research we investigated the use of 99mTc DMSA scanning in the localization of renal parenchymal involvement in urinary tract infection. Twenty-four children presenting with first acute urinary tract infection were studied. Investigations included physical examination, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antibody-coated bacteria (ACB) and early 99mTc DMSA scanning. 99mTc DMSA scanning was taken as the gold standard method in determining renal parenchymal inflammation. According to the 99mTc DMSA scanning the sensitivity of clinical findings was 57.14%, WBC 23.80%, ESR 33.33%, CRP 14.28% and ACB 71.42% in the localization of urinary tract infection. We propose early 99mTc DMSA scanning performed around the time of infection as a good technique for localization of the level of infection in the urinary tract.