Search

Background The phenotypic and genotypic spectrum and kidney outcome of PLC[epsilon]1-related kidney disease are not well known. We attempted to study 25 genetically confirmed cases of PLC[epsilon]1-related kidney disease from 11 centers to expand the clinical spectrum and to determine the relationship between phenotypic and genotypic features, kidney outcome, and the impact of treatment on outcome. Methods Data regarding demographics, clinical and laboratory characteristics, histopathological and genetic test results, and treatments were evaluated retrospectively. Results Of 25 patients, 36% presented with isolated proteinuria, 28% with nephrotic syndrome, and 36% with chronic kidney disease stage 5. Twenty patients underwent kidney biopsy, 13 (65%) showed focal segmental glomerulosclerosis (FSGS), and 7 (35%) showed diffuse mesangial sclerosis (DMS). Of the mutations identified, 80% had non-missense, and 20% had missense; ten were novel. No clear genotype-phenotype correlation was observed; however, significant intrafamilial variations were observed in three families. Patients with isolated proteinuria had significantly better kidney survival than patients with nephrotic syndrome at onset (p = 0.0004). Patients with FSGS had significantly better kidney survival than patients with DMS (p = 0.007). Patients who presented with nephrotic syndrome did not respond to any immunosuppressive therapy; however, 4/9 children who presented with isolated proteinuria showed a decrease in proteinuria with steroids and/or calcineurin inhibitors. Conclusion PLC[epsilon]1-related kidney disease may occur in a wide clinical spectrum, and genetic variations are not associated with clinical presentation or disease course. However, clinical presentation and histopathology appear to be important determinants for prognosis. Immunosuppressive medications in addition to angiotensin-converting enzyme inhibitors may be beneficial for selected patients. Graphical abstract 'A higher resolution version of the Graphical abstract is available as Supplementary information'., Author(s): Esra Karabag Yilmaz [sup.1] , Seha Saygili [sup.1] , Bora Gulhan [sup.2] , Nur Canpolat [sup.1] , Aysun Karabay Bayazit [sup.3] , Beltinge Demircioglu Kilic [sup.4] , Nurver Akinci [...]

Background: Short bowel syndrome (SBS) is a malabsorptive condition that develops as a result of massive resection of the small intestine and causes morbidities such as chronic diarrhea, dehydration attacks, parenteral nutrition (PN) dependence, and recurrent infections. Kidney transplantation in this patient group may be complicated by aforementioned morbidities, as well as the absorption problems of immunosuppressive drugs. Methods: We report the first pediatric patient (18‐month‐old male) with SBS secondary to volvulus who underwent a successful living related kidney transplantation with a primary diagnosis of autosomal recessive polycystic kidney disease and had a successful 4‐year follow‐up without intestinal transplantation. Results: Tacrolimus, mycophenolate mofetil (MMF), and prednisolone were administered for maintenance of immunosuppression after transplantation. The patient reached therapeutic trough levels of tacrolimus with usual doses. The 4‐year renal survival was excellent without a clinical evidence of rejection, despite long‐term necessity of PN and intravenous fluids. Conclusions: Kidney transplantation should not be avoided in patients with SBS solely because of concerns about the effectiveness of immunosuppressive therapy. Prednisolone, tacrolimus, and MMF combination was effective in our case, and these drugs can be considered as first‐line agents in these patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Eculizumab is a first-line treatment for atypical hemolytic uremic syndrome (aHUS), and patients undergoing eculizumab therapy may become more susceptible to infection caused by Neisseria meningitidis (Nm). While meningococcal vaccination is required for patients undergoing eculizumab therapy, there is limited knowledge about meningococcal carriage in children with aHUS. We aimed to evaluate (1) the prevalence of Nm carriage, (2) serogroup distribution, and (3) the immunization status of children undergoing eculizumab treatment for aHUS. Methods: The Meningo-aHUS study is a prospective, multi-center study evaluating meningococcal carriage in children and adolescents in Türkiye receiving eculizumab for aHUS. We noted the age, gender, daycare, school, or university attendance, passive smoking status, previous infection and antibiotic use, and previous immunization history, including meningococcal vaccines, from the medical records of those children with aHUS. We collected nasopharyngeal samples, tested them for Nm using real-time polymerase chain reaction, and performed a serogroup analysis on the positive samples. Results: We collected nasopharyngeal samples from 62 children with aHUS. Out of 62 children, 61 (98.4%) had received at least one dose of the meningococcal vaccine. The median time since the last meningococcal vaccine dose was 15 months (1–59 months). We detected meningococcal carriage in three (4.8%, 95% CI 1.0–13.5) children, and all three strains were non-groupable (NG). No other serogroups were detected. Conclusions: Almost all the children received their risk-group meningococcal immunization, including booster doses. A 4.8% of children with aHUS carried NG meningococci and, no vaccine serogroups were detected. Patients treated with eculizumab remain profoundly susceptible to IMD due to these NG meningococcal strains. The occurrence of breakthrough cases and carriage of Nm, especially NG strains, highlights the significance of maintaining a state of constant alertness, promptly seeking medical attention, and swiftly treating any symptoms that align with IMD, regardless of their vaccination status or antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Background Alport syndrome (AS) is an inherited glomerular disease caused by mutations in COL4A3, COL4A4, or COL4A5. Associations between clinical manifestations and genotype are not yet well defined. Our study aimed to define clinical and genetic characteristics, establish genotype-phenotype correlations, and determine prognosis of AS in children. Methods A total of 87 children with AS from 10 pediatric nephrology centers, whom had genetic analyses performed at the Hacettepe University Nephrogenetics Laboratory between February 2017 and February 2019, were included. Data regarding demographics, family history, clinical and laboratory characteristics, histopathological and genetic test results, treatments, and yearly follow-up results were retrospectively analyzed. Results Of 87 patients, 16% presented with nephrotic syndrome. In patients with nephrotic syndrome, kidney biopsy findings showed focal segmental glomerulosclerosis (FSGS) in 79%, and COL4A3 mutations were the leading genetic abnormality (50%). Twenty-four percent of all patients progressed to chronic kidney disease (CKD). The rate of progression to CKD and the decline in the glomerular filtration rate of the patients with COL4A3 mutation were higher than other mutation groups (p < 0.001 and p = 0.04, respectively). In kidney survival analysis, nephrotic syndrome presentation, histopathology of FSGS, COL4A3 mutations, and autosomal recessive inheritance were found as independent risk factors for earlier progression to CKD. Cyclosporin A treatment did not improve kidney survival. Conclusions We emphasize that genetic testing is important for patients suspected as having AS. Furthermore, COL4A mutations should be considered in patients with FSGS and steroid-resistant nephrotic syndrome. This approach will shed light on the prognosis of patients and help with definitive diagnosis, preventing unnecessary and potentially harmful medications., Author(s): Gulsah Ozdemir [sup.1] , Bora Gulhan [sup.1] , Emine Atayar [sup.2] , Seha Saygili [sup.3] , Oguz Soylemezoglu [sup.4] , Zeynep Birsin Ozcakar [sup.5] , Fehime Kara Eroglu [sup.6] [...]

Introduction: Calcineurin inhibitors (CNIs) are widely used in transplantation. Although CNI‐related hyperkalemia is common (10%–60.6%), the underlying pathogenetic mechanism is not well‐elucidated and may lead to dose adjustment or treatment withdrawal. Objective: The aim of this study is to describe CNI‐related hyperkalemia due to hyporeninemic hypoaldosteronism in pediatric transplant recipients who were successfully treated with fludrocortisone. Method: In a total of 55 hematopoietic stem cell (HSCT) and 35 kidney transplant recipients followed according to institutional immunosuppression protocols, recipients diagnosed with CNI‐related hyperkalemia were reviewed. Recipients who were receiving intravenous fluid, potassium, or were diagnosed with hemolysis, acute graft rejection, or had an eGFR < 30 mL/min/1.73m2, were excluded. A detailed analysis of clinical history as well as biochemical studies was carried out to reveal possible pathophysiology. Results: Three pediatric transplant recipients (one HSCT, two kidney transplantation) with findings of hyperkalemia, hyponatremia, and a mild elevation in blood urea nitrogen while on CNIs were recruited. Urinary potassium excretion was diminished while sodium excretion was increased. Plasma aldosterone levels were low, and renin was not increased in response. Primary adrenal insufficiency was ruled out, and hyporeninemic hypoaldosteronism was diagnosed. CNI‐related hyperkalemia was detected earlier in case 1, who had HSCT (22 days), than in the second and third cases, who had kidney transplantation (24 and 30 months post‐transplantation, respectively). The discrepancy was hypothesized to be explained by higher overall CNI dose due to higher serum target CNI used in HSCT than kidney transplantation. Electrolyte imbalance was reversed upon administration of physiologic dose fludrocortisone (0.05 mg, daily), while fludrocortisone was ceased after CNI withdrawal in case 1, which is additional evidence for the etiological association of CNIs and hyporeninemic hypoaldosteronism. Conclusion: Our three cases strengthen the premise that CNI‐related hyperkalemia may be due to hyporeninemic hypoaldosteronism, and the timing and severity may be related to CNI dose. Fludrocortisone is a safe and effective treatment in CNI‐related hyperkalemia, providing maintenance of CNIs, which are one of the essential therapeutic agents for pediatric transplantation. [ABSTRACT FROM AUTHOR]

Abstract Objective: The aim of this study was to assess the influence of plasminogen activator inhibitor-1 (PAI-1) 4G/5G or tissue plasminogen activator (tPA) I/D polymorphisms in chronic obstructive pulmonary disease (COPD) cases in a sample of Turkish population. Methods: PAI-1 4G/5G and tPA Alu-repeat I/D genetic polymorphisms in 153 COPD subjects and 160 controls were investigated using PCR-RFLP and PCR methods, respectively. Results: 4G allele frequency was 0.62 and 0.39 for COPD and control groups, respectively. 4G allele had an estimated 2.56-fold [95% CI = 1.85–3.53] increased risk of COPD. tPA I allele frequency was 0.55 and 0.50, for COPD and control groups, respectively. I allele had an estimated 1.19-fold [95% CI = 0.87–1.62] increased risk of COPD Conclusions: PAI-1 4G/4G and 4G/5G genotypes seemed to play a key role in the pathophysiology of COPD in Turkish individuals. Keywords: COPD; Genetic susceptibility; Polymorphisms; Tissue-type plasminogen activator (tPA); Plasminogen activator inhibitor-1 (PAI-1)

Background ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin. We screened adolescent patients to determine the frequency of ADCK4 mutation and the efficacy of early CoQ10 administration. Methods A total of 146 index patients aged 10-18 years, with newly diagnosed non-nephrotic proteinuria, nephrotic syndrome, or chronic renal failure and end-stage kidney disease (ESKD) of unknown etiology were screened for ADCK4 mutation. Results Twenty-eight individuals with bi-allelic mutation from 11 families were identified. Median age at diagnosis was 12.4 (interquartile range [IQR] 8.04-19.7) years. Upon first admission, all patients had albuminuria and 18 had CKD (6 ESKD). Eight were diagnosed either through the screening of family members following index case identification or during genetic investigation of proteinuria in an individual with a history of a transplanted sibling. Median age of these 8 patients was 21.5 (range 4.4-39) years. CoQ10 supplementation was administered following genetic diagnosis. Median estimated glomerular filtration rate (eGFR) just before CoQ10 administration was 140 (IQR 117-155) ml/min/1.73m.sup.2, proteinuria was 1,008 (IQR 281-1,567) mg/m.sup.2/day. After a median follow-up of 11.5 (range 4-21) months following CoQ10 administration, proteinuria was significantly decreased (median 363 [IQR 175-561] mg/m.sup.2/day, P=0.025), whereas eGFR was preserved (median 137 [IQR 113-158] ml/min/1.73m.sup.2, P=0.61). Conclusions ADCK4 mutations are one of the most common causes of adolescent-onset albuminuria and/or CKD of unknown etiology in Turkey. CoQ10 supplementation appears efficacious at reducing proteinuria, and may thereby be renoprotective., Author(s): Mustafa Atmaca [sup.1] , Bora Gulhan [sup.2] , Emine Korkmaz [sup.3] , Mihriban Inozu [sup.2] , Oguz Soylemezoglu [sup.4] , Cengiz Candan [sup.5] , Aysun Karabay Bayazit [sup.6] , [...]

Background: CafeÂ'-au-lait skin macules, Cushing syndrome (CS), hyperthyroidism, and liver and cardiac dysfunction are presenting features of neonatal McCune- Albright syndrome (MAS), CS being the rarest endocrine feature. Although spontaneous resolution of hypercortisolism has been reported, outcome is usually unfavorable. While a unified approach to diagnosis, treatment, and follow-up is lacking, herein successful treatment and long-term follow-up of a rare case is presented. Clinical case: An 11-day-old girl born small for gestational age presented with deterioration of well-being and weight loss. Large hyperpigmented macules on the trunk, hypertension, hyponatremia, hyperglycemia, and elevated liver enzymes were noted. ACTH-independent CS due to MAS was diagnosed. Although metyrapone (300 mg/m2/day) was started on the 25th day, complete remission could not be achieved despite increasing the dose up to 1,850 mg/m2/day. At 9 months, right total and left three-quarters adrenalectomy was performed. Cortisol decreased substantially, ACTH remained suppressed, rapid tapering of hydrocortisone to physiological dose was not tolerated, and supraphysiological doses were required for 2 months. GNAS analysis from the adrenal tissue showed a pathogenic heterozygous mutation. During 34 months of follow-up, in addition to CS due to MAS, fibrous dysplasia, hypophosphatemic rickets, and peripheral precocious puberty were detected. She is still regularly screened for other endocrinopathies. Conclusion: Neonatal CS due to MAS is extremely rare. Although there is no specific guideline for diagnosis, treatment, or follow-up, addressing side effects and identifying treatment outcomes will improve quality of life and survival. [ABSTRACT FROM AUTHOR]

Background The aim of the study was to investigate the prevalence of post-transplant hypertension (HT) and to assess the blood pressure (BP) of transplanted children with possible risk factors. Methods Office and ambulatory blood pressure measurements were performed for each patient. Results Twenty-nine patients were included in the study, including 13 patients with newly diagnosed untreated HT according to the results of ambulatory blood pressure monitoring (ABPM). Fourteen patients were on antihypertensive medication, but only in five of these patients was the HT under control; nine patients receiving antihypertensive drugs had uncontrolled HT. Of the 29 patients, two had normotension without any antihypertensive drug(s). Standard deviation scores (SDS) of the nocturnal diastolic BP of the ABPM were positively correlated with the prednisolone dosage per kilogram (p = 0.013, r = 0.45) and negatively correlated with the time period after transplantation (p = 0.024, r = -0.41). Similarly, the SDS of the 24-h diastolic BP was positively correlated with the prednisolone dosage per kilogram (p = 0.006, r = 0.50) and negatively correlated with the time period after transplantation (p = 0.016, r = -0.44). Patients with alternate-day steroid treatment had lower nocturnal systolic (p = 0.016), nocturnal diastolic (p = 0.001) and 24-h diastolic (p = 0.008) SDS when compared to those receiving daily steroid medication. Conclusion The prevalence of HT among children after renal transplantation was high among our patient cohort, and steroids had direct impact on nocturnal and diastolic BP. Keywords Renal transplant * Children * Hypertension * Ambulatory blood pressure monitoring * Steroid, Introduction Recent studies have shown that pediatric patients with end stage renal disease (ESRD) suffer from significant cardiovascular morbidity and mortality [1]. The United States Renal Data System study demonstrated [...]

Background Atypical hemolytic uremic syndrome (aHUS) is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Neonatal cases are extremely uncommon. Plasma therapy is the first choice therapy in patients with aHUS based on the belief of an underlying complement dysregulation. Alternatively, eculizumab, which targets complement 5, is used to block complement activation. Case-diagnosis/treatment Sudden onset macroscopic hematuria, hypertension, and bruises over the entire body were noted in a 5 day-old newborn. Investigations revealed hemolytic anemia, thrombocytopenia, renal impairment, and a low serum C3, leading to the diagnosis of aHUS. Fresh frozen plasma (FFP) infusions and peritoneal dialysis for acute kidney injury were initiated. This approach yielded full renal and hematological remission. The patient was discharged with FFP infusions, but subsequently developed three life-threatening disease recurrences at 1, 3, and 6 months of age. The last relapse presented with uncontrolled hypertension and impaired renal function while the patient was receiving FFP infusions. After the first dose of eculizumab, his renal and hematological parameters returned to normal and his blood pressure normalized. Genetic screening of the CFH gene revealed a novel homozygous p. Tyr1177Cys mutation. Conclusion Eculizumab can be considered as an alternative to plasma therapy in the treatment of specific patients with aHUS, even in infants. Keywords Atypical hemolytic uremic syndrome * Complement factor H mutation * Eculizumab * Newborn, Introduction Atypical hemolytic uremic syndrome (HUS) is a rare disease and is characterized by the triad of microangiopathic hemolytic anemia [hemoglobin (Hb) upper limit of normal age) [1, 2]. Atypical [...]