Managing recurrent parvovirus B19-associated anemia after a pediatric kidney transplant.

A 13-year-old girl who had a kidney transplant four weeks prior presented with a 10-day history of fatigue, paleness, and headache. On physical examination, tachycardia and paleness were noted. Laboratory testing was notable for severe anemia and mild leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) test for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were negative and for parvovirus B19 (PVB19) was positive. Despite lower immunosuppression and administration of intravenous immunoglobulin (IVIG) it persisted for 15 months, and frequent red blood cell transfusions were needed. PVB19 is a less common but significant complication. The patient's clinical course demonstrates the importance of this complication and the challenges in its management. A notable void exists in the literature regarding standardized treatment protocols for PVB19-induced recurrent anemia after kidney transplant. This case indicates the need for further research and consensus to guide effective clinical interventions in similar cases.

MIS-C Treatment: Is glucocorticoid monotherapy enough for mild cases?

BACKGROUND: The effectiveness of using only glucocorticoids (GCs) in mild multisystem inflammatory syndrome (MIS-C) cases was compared with combined treatment [GCs + Intravenous immune globulin (IVIG)]. METHODS: This retrospective cohort study was conducted between June 1, 2020, and June 1, 2022, in a tertiary care center in Istanbul, Turkey. Clinical and investigational data of the MIS-C patients were analyzed. The patients were divided into two groups: those who received only GCs and those who received the GCs + IVIG combination. The primary outcome focused on assessing the deterioration of the patient's clinical condition, the occurrence of shock, admission to the pediatric intensive care unit (PICU), and the need for additional immunosuppressive medication. Secondary outcomes included evaluating the course of cardiovascular and infection-related complications observed at the one-year follow-up. RESULTS: Ninety-seven MIS-C patients with a median age of 41 (3- 214) months were enrolled. Fifty-six (57.7%) patients were male. All the patients had fever at admission with a temperature of 39 °C (37.5 °C-40.1 °C). Thirty-two patients (33%) had cardiac findings on echocardiography [left ventricular dysfunction (n= 13, 13.5%), coronary artery involvement (n= 11, 11.3%), and dilation of cardiac cavities and/or increased cardiac muscle thickness (n= 8, 8.2%)]. Thirteen patients (13.5%) required intensive care. All patients received GCs [only GCs (group I; n= 65, 67%)], and 32 patients (33%) with severe manifestations and/or cardiac involvement received GCs + IVIG (group II). No mortality was observed. None of the patients had any complaints at the one-year follow-up, and all echocardiography findings were normal. CONCLUSION: This study provides preliminary evidence that GC monotherapy is a safe treatment alternative for mild MIS-C cases without cardiac involvement.

Evaluation of the risk factors for BK virus-associated hemorrhagic cystitis in pediatric bone marrow transplantation patients: Does post-transplantation cyclophosphamide increase the frequency?

BACKGROUND: BKV-HC is one of the most significant complications of HSCT. This retrospective study aimed to determine the frequency of BKV-HC in pediatric patients undergoing HSCT, detect the associated risk factors for the development of BKV-HC, and explore the effects of post-transplantation Cy use. METHODS: Three hundred twenty-seven patients (girls: 121, boys: 206) were analyzed according to sex, conditioning regimen, transplantation type, donor relatedness, stem cell source, the presence and grade of aGVHD, CMV co-existence, and Cy use. RESULTS: Multivariate analysis confirmed the prognostic importance of age (OR: 4.865), TBI use, the presence of aGVHD (OR: 2.794), CMV coinfection (OR: 2.261), and Cy use (OR: 27.353). A statistically significant difference was found between the mean BKV-HC follow-up times compared with post-transplantation Cy intake (p < .001). The BKV-HC rate increased as the number of risk factors of the patient increased. CONCLUSION: BKV-HC is an essential complication of HSCT primarily associated with Cy use, the presence of aGVHD, and donor relatedness. The present study shows that the use of Cy in the post-transplantation period further increases BKV-HC risk in pediatric patients, regardless of dose.

Cardiac functions in children with steroid-sensitive nephrotic syndrome.

BACKGROUND: The aim of the present study was to evaluate the presence of cardiac systolic and diastolic dysfunction in pediatric patients with steroid-sensitive nephrotic syndrome (NS). METHODS: The study population consisted of 19 patients with debut-relapse of NS aged 1-18 years and 30 sex and age-matched healthy controls. Blood and urine samples, two M-mode conventional echocardiograms and tissue Doppler velocity imaging were evaluated in both attack and remission periods. RESULTS: With regard to conventional pulse wave Doppler (cPWD), steroid-sensitive NS patients (both in debut / relapse and in remission periods) had a higher peak of late diastolic flow velocities (A peak), and patients in debut / relapse had a lower E/A ratio than the control group, indicating diastolic dysfunction (overall P = 0.003 and P = 0.006, respectively). Based on tissue Doppler velocity imaging echocardiography results, patients in debut/relapse had a higher A' and a lower E'/A' ratio (overall P < 0.001 and P = 0.001, respectively). There was also a significant difference in the cPWD E/TDI E' ratio between the patients showing an increased cPWD E/TDI E' ratio in remission periods compared to in debut/relapse periods (P = 0.09). The albumin levels were positively correlated with E'/A' and E/ E' ratio (r = 0.609; P = 0.007, r = 0.472; P = 0.041 respectively). CONCLUSIONS: Systolic cardiac functions are preserved but diastolic functions are affected in steroid-sensitive NS patients both in debut/relapse and in remission periods in a relatively short time. The persistence of left ventricular (LV) dysfunction during the remission period requires special attention during the follow up for early detection of cardiac abnormalities.

Correction to: Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study.

The second affiliation of the corresponding author Eda Tahir Turanli was incorrectly published as Istanbul Medeniyet University instead of Istanbul Technical University.

Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study.

Systemic autoinflammatory diseases (sAIDs) are a heterogeneous group of disorders, having monogenic inherited forms with overlapping clinical manifestations. More than half of patients do not carry any pathogenic variant in formerly associated disease genes. Here, we report a cross-sectional study on targeted Next-Generation Sequencing (NGS) screening in patients with suspected sAIDs to determine the diagnostic utility of genetic screening. Fifteen autoinflammation/immune-related genes (ADA2-CARD14-IL10RA-LPIN2-MEFV-MVK-NLRC4-NLRP12-NLRP3-NOD2-PLCG2-PSTPIP1-SLC29A3-TMEM173-TNFRSF1A) were used to screen 196 subjects from adult/pediatric clinics, each with an initial clinical suspicion of one or more sAID diagnosis with the exclusion of typical familial Mediterranean fever (FMF) patients. Following the genetic screening, 140 patients (71.4%) were clinically followed-up and re-evaluated. Fifty rare variants in 41 patients (20.9%) were classified as pathogenic or likely pathogenic and 32 of those variants were located on the MEFV gene. We detected pathogenic or likely pathogenic variants compatible with the final diagnoses and inheritance patterns in 14/140 (10%) of patients for the following sAIDs: familial Mediterranean fever (n = 7), deficiency of adenosine deaminase 2 (n = 2), mevalonate kinase deficiency (n = 2), Muckle-Wells syndrome (n = 1), Majeed syndrome (n = 1), and STING-associated vasculopathy with onset in infancy (n = 1). Targeted NGS panels have impact on diagnosing rare monogenic sAIDs for a group of patients. We suggest that MEFV gene screening should be first-tier genetic testing especially in regions with high carrier rates. Clinical utility of multi-gene testing in sAIDs was as low as expected, but extensive genome-wide familial analyses in combination with exome screening would enlighten additional genetic factors causing disease.

Disseminated fungal infection by Aureobasidium pullulans in a renal transplant recipient.

Renal transplant recipients are on long-term potent immunosuppressive therapy, which makes them highly vulnerable to opportunistic fungal infections. Dematiaceous, or dark-pigmented saprophytic fungi, are being increasingly seen as opportunistic pathogens of mycoses in immunosuppressed patients. One of these is Aureobasidium pullulans, which is a black yeast-like dematiaceous fungus found ubiquitously in the environment that can cause various opportunistic human infections. Most infections occur by traumatic inoculation, such as keratitis and cutaneous lesions; disseminated mycoses are very rare and occur only in severely immunocompromised patients. We report a case of disseminated fungal infection due to A. pullulans in a pediatric patient who underwent renal transplant. The use of voriconazole and vacuum-assisted closure along with surgical drainage most likely contributed to the patient's positive outcome.

Bilateral Idiopathic Carpal Tunnel Syndrome in a 4-Year-Old Girl.

Carpal tunnel syndrome (CTS), the most common entrapment neuropathy in adulthood, is rare in childhood. The symptoms may differ to those in adults, or may be misinterpreted owing to children's difficulties in expressing themselves. Cases of idiopathic, bilateral CTS under the age of 5 are rare. A 4-year-old girl presented with pain in both hands and difficulty opening them in the morning. Bilateral severe CTS was determined at electroneuromyography (ENMG). Bilateral wrist splints were advised for both hands. Improvement in ENMG was seen at 2 weeks following conservative treatment.

Single port laparoscopic and open surgical accesses of chronic peritoneal dialysis in children: A single center experience over 12 years.

INTRODUCTION: The aim of this study was to evaluate patients with end stage renal failure (ESRD) who underwent chronic peritoneal dialysis (CPD). The clinical outcomes of laparoscopic and open placements of catheters were compared. MATERIALS AND METHODS: We reviewed 49 (18 male and 31 female) children with CPD according to age, sex, cause of ESRD, catheter insertion method, kt/V rate, complications, presence of peritonitis, catheter survival rate between January 2002 and February 2014. RESULTS: Thirty-three patients were with open placement and 16 patients were with laparoscopic placement. The rate of the peritonitis is significantly less in patients with laparoscopic access than open access (n = 4 vs n = 25) (P <0.01). Patients with peritonitis were younger than those who had no attack of peritonitis (10.95 ± 0.8 years vs 13.4 ± 0.85 years). According to the development of complications, significant difference has not been found between the open (n = 9) and laparoscopic (n = 3) approaches except the peritonitis. Catheter survival rate for the first year was 95%, and for five years was 87.5%. There was no difference between open and laparoscopic group according to catheter survival rate. The mean kt/V which indicates the effectiveness of peritoneal dialysis was mean 2.26 ± 0.08. No difference was found between laparoscopic and open methods according to kt/V. CONCLUSION: Laparoscopic placement of CPD results in lower peritonitis rate. Catheter survival rate was excellent in both groups. Single port laparoscopic access for CPD catheter insertion is an effective and safe method.

Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort.

OBJECTIVES: Presence of common MEFV gene mutations strengthened the diagnosis of FMF in addition to the typical clinical characteristics of FMF. However, there are also rare mutations. P369S, A744S, R761H, K695R, F479L are the main rare mutations in Turkish population. We aimed to evaluate FMF patients with a single allele MEFV mutation and to compare patients with common and rare mutations. METHODS: We retrospectively reviewed the medical records of FMF patients with a single allele mutation who were followed up between 2008 and 2013 in six centres. We compared the patients with rare and common mutations for disease severity score, frequent exacerbations ( >1 attack per month), long attack period (>3 day), symptoms, age at the onset of symptoms, gender, consanguinity, and family history. RESULTS: Two hundred and seventeen patients (M/F=101/116) with the diagnosis of FMF and single mutation were included. Heterozygote mutations were defined as common (M694V, V726A, M68OI) and rare mutations (A744S, P369S, K695R, R761H, F479L). Sixty-seven patients (27 males, 40 females) had one single rare mutation and 150 (74 males, 76 females) had one single common mutation. No difference was found between the rare and common mutations with respect to the disease severity score. There was no significant difference between common and rare heterozygote form of mutations in terms of disease severity. CONCLUSIONS: Patients with typical characteristics of FMF, with some rare mutations (A744S, P369S) should be treated in the same manner as patients with a common mutation.

Success of eculizumab in the treatment of atypical hemolytic uremic syndrome.

BACKGROUND: Disorders of complement regulation are the most important etiology of atypical hemolytic uremic syndrome (aHUS). Recent studies demonstrate that eculizumab is beneficial in long-term aHUS treatment. We present a series of children with aHUS resistant to/dependent on plasma exchange (PE) who were treated with eculizumab. METHODS: This was a retrospective study in which data were retrieved from the medical files of children who had received PE as treatment for aHUS. The data retrieved included age, sex, presenting symptoms, presence of diarrhea/vomiting, hospitalization duration, laboratory data on admission and follow-up, need for transfusion or dialysis, response to PE, response to eculizumab and outcome. RESULTS: Of the 15 children diagnosed with aHUS in 2011 and 2012 in our departments, ten were resistant to, or dependent on, plasma therapy and treated with eculizumab; these children were enrolled in the study. Three patients had relapses, and seven had a new diagnosis. Nine children had oliguria or anuria, and eight required dialysis. Hypertension was observed in six patients. Neurologic involvement developed in six patients, with the symptoms including seizures, loss of balance, vision loss and severe confusion. Five and five patients were resistant to and dependent on plasma therapy, respectively. Following the start of eculizumab treatment, all patients achieved full recovery of renal function and hematologic parameters. CONCLUSIONS: In our ten pediatric patients with aHUS who did not respond to PE, eculizumab was a lifesaving therapy and improved their quality of life. Early eculizumab use was a rescue therapy for renal function. Our results show that eculizumab is an effective treatment for aHUS. However, more studies are needed on the long-term efficacy and safety of eculizumab in children with aHUS and to determine the optimal duration of treatment.

Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency.

Heterozygous mutations in the NLRP12 gene have been found in patients with systemic auto-inflammatory diseases. However, the NLRP12-associated periodic fever syndromes show a wide clinical spectrum, including patients without classical diagnostic symptoms. Here, we report on a 20-year-old female patient diagnosed with common variable immunodeficiency (CVID), who developed intestinal amyloidosis and carried novel compound heterozygous mutations in NLRP12, identified by whole exome and transcriptome sequencing. CVID is a primary immunodeficiency characterized by low serum immunoglobulins, recurrent bacterial infections and development of malignancy, but it also presents with a magnitude of autoimmune features. Because of the unspecific heterogeneous clinical features of the disease, a delay in diagnosis is common. Secondary, inflammatory (AA type) amyloidosis has infrequently been observed in CVID patients. Based on our case observation and a critical review of the literature, we suggest that NLRP12 mutations might account for a small fraction of CVID patients with severe auto-inflammatory complications.

Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy.

BACKGROUND: Dense deposit disease (DDD) (also known as membranoproliferative glomerulonephritis type II) in childhood is a rare glomerulonephritis with frequent progression to end-stage renal disease (ESRD) and a high recurrence after kidney transplantation. The pathophysiologic basis of DDD is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. CASE-DIAGNOSIS/TREATMENT: A 14-year-old girl presented with edema and nephrotic range proteinuria. Blood tests showed hypoalbuminemia, nephrotic range proteinuria, normal renal function, and a low C3 level. Renal biopsy confirmed the diagnosis of crescentic DDD. Complement analysis revealed strong AP activation (low C3), positive C3 nephritic factor (C3NeF), and a decreased complement factor H (CFH) levels with CFH polymorphisms. Therapy with eculizumab was considered after the failure of corticosteroid and plasmapheresis to modulate the ongoing massive proteinuria and persistence of low serum C3 levels. There was a marked clinical and biochemical response following the administration of eculizumab. CONCLUSIONS: Our case emphasizes the efficacy of eculizumab in the management of crescentic DDD in a patient with a normal renal function, in a short follow-up period. Considering previously reported cases, it appears that eculizumab represents a promising new approach which may prevent progression to ESRD in a subset of patients with DDD.

Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity.

Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M × 10(-5) at 24th hour and 3.93 M × 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61 M × 10(-3) at 24th hour and 2.85 M × 10(-4) at 48th hour. Although cells were treated the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.

The effect of simvastatin and erythropoietin on renal fibrosis in rats with unilateral ureteral obstruction.

Prevention of fibrosis is a very important therapeutic strategy in the treatment of obstructive nephropathy (ON). The aim of this study is to show and compare the actions of Simvastatin (Simv) and Erythropoietin (Epo) in renal expression of nuclear factor kappa B (NFκB), transforming growth factor-ß (TGF-ß), basic fibroblast growth factor (bFGF), platelet-derived growth factor B (PDGF-B), fibronectin and development of interstitial fibrosis in rats with unilateral ureteral obstruction (UUO). A total of 48 Sprague-Dawley rats were allocated to 4 groups of sham, Epo, Simv and control. Unilateral ureteral ligation was performed on all rats except the Sham group. For interstitial fibrosis Masson's trichrome stain and for the expression of TGF-ß, PDGF-B, bFGF, NFκB and fibronectin, immunohistochemical methods were used. In the Epo and Simv groups, expression of TGF-ß and fibronectin and staining with Masson's trichrome were less compared to the control group. In addition, fibronectin expression in the Epo group was less than the Simv group. Unlike the Simv group, NFκB and bFGF expression in the Epo group were less when compared to the control group. Consequently, it was seen that both Epo and Simv prevented fibrosis in ON. Epo was superior in this effect by suppressing the expressions of NFκB and bFGF more effectively than Simv. Based on this finding, Epo might be a better agent than Simv in the prevention of fibrosis in ON.

Effect of free creatine therapy on cisplatin-induced renal damage.

Abstract Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague-Dawley rats were divided into three groups: Group I: Cisplatin (n=20) (7 mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin+creatine monohydrate (n=20) (7 mg/kg cisplatin i.p. single dose and 300 mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n=20) (Serum physiologic, 2.5 mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p<0.05). In group II, there was a slight decrease in body weight at same days (p=0.931 and 0.084, respectively). Kidney function tests, histopathological scores, and mtDNA common deletion ratios were statistically better in group II than group I at 7th and 30th day (p<0.05). Although creatine significantly reversed kidney functions and pathological findings, this improvement was not sufficient to reach normal control group's results at days 7 and 30. In conclusion, the present study demonstrates that creatine administration is a promising adjuvant protective drug for reducing nephrotoxic effect of cisplatin.

Functional capacity, strength, and quality of life in children and youth with familial Mediterranean fever.

PURPOSE: To examine functional capacity and muscle strength in children and youth with familial Mediterranean fever (FMF) as compared with controls, and to assess whether these factors influence quality of life (QOL) in FMF. METHODS: A total of 100 subjects with FMF and 55 control subjects (8-18 years old) without known health issues were enrolled in the study. The 6-Minute Walk Test (6MWT) was used to evaluate functional capacity. Quadriceps strength was measured with a hand-held dynamometer. Quality of life was evaluated with the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0). RESULTS: Significant differences were found between subjects with FMF and controls in the 6MWT and strength test. PedsQL scores of subjects with FMF were significantly lower than the scores of the controls. The 6MWT and quadriceps strength were weakly correlated with the PedsQL. CONCLUSION: Subjects with FMF displayed lower functional capacity and QOL than peers who are healthy. Decreased functional capacity was correlated with decreased QOL in those with FMF.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.