Evaluation of endothelial dysfunction in hypertensive children and adolescents.

BACKGROUND: Atherosclerotic changes can be attributed to early endothelial damage in individuals with hypertension. We aimed to explore the relationship between endothelial dysfunction and hypertension in newly diagnosed children without end-organ damage, considering carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), and functional capillaroscopy parameters. We also analyzed the differences between dipper and non-dipper patients. METHODS: In this cross-sectional study, 20 patients diagnosed with essential hypertension with no target organ damage, and 20 age and sex-matched healthy volunteers were enrolled. The patient group comprised newly diagnosed individuals not receiving antihypertensive treatment. Hypertensive patients were divided into two groups (dipper and non-dipper patients). The measurements of CIMT, brachial FMD, and functional capillaroscopy were performed before starting treatment. RESULTS: Among the patients, 11 were boys, and 9 were girls, with a median age of 16.0 (2.13) years. Of 20 hypertensive patients, 10 were dipper and 10 were non-dipper. Significant differences were observed between the hypertensive patients and controls in terms of CIMT (p = 0.04), brachial artery FMD (p = 0.02), and functional capillary density (p < 0.001). Hypertensive patients exhibited increased CIMT, reduced brachial artery FMD, and lower capillary density. However, there were no differences between dippers and non-dippers regarding age, sex, height SDS, weight SDS, CIMT SDS, brachial artery FMD, and capillary density. CONCLUSIONS: Understanding the vascular consequences associated with essential hypertension emphasizes the importance of early detection and management of hypertension. Herein, we have effectively highlighted significant endothelial changes through the analysis of three parameters in newly diagnosed children without apparent target organ damage.

Respiratory function in children with nephrotic syndrome: Comparative evaluation of impulse oscillometry and spirometry.

AIM: To evaluate the respiratory functions of children with nephrotic syndrome (NS) by impulse oscillometry (IOS) and its correlation with spirometry. METHODS: Fifty-five NS patients aged 3-18 years were included as the study group and 40 healthy children of the same age formed the control group. Patients were divided into nephrotic phase (first attack and relapse) and remission. Demographic, anthropometric, and laboratory data of the children were recorded. Respiratory functions were evaluated by IOS and spirometry. Children over 6-years old performed both IOS and spirometry while children under 6 years performed only IOS. RESULTS: The R (R5%, R10%, R5-20), AX and Z5% values of IOS in patients with nephrotic phase were higher than remission patients and control group while spirometry indices of PEF% and MEF25-75% were lower. Z scores of MEF25-75 were significantly negatively correlated with z scores of R5, R10, Z5, and Fres while they were significantly positively correlated with z scores of X values (5, 10, 15, and 20 Hz). Z scores of forced expiratory volume in 1 /forced vital capacity significantly negatively correlated with z scores of R values (R5, R10), Z5 and AX and positively correlated with z scores of X values (X5, X10, X15 Hz). CONCLUSION: Our study demonstrated that respiratory functions measured by IOS and spirometry were affected at the time of nephrotic phase in NS patients. IOS, a novel method easily applicable even in small children, is a potentially valuable tool to detect this condition; given its good correlation with spirometry.

CFH and CFB mutations in Shiga toxin-associated haemolytic uraemic syndrome in a 6-year-old boy.

Haemolytic uraemic syndrome (HUS) is most commonly associated with Shiga toxin-producing Escherichia coli (STEC) while the recurrent hereditary atypical (aHUS) form secondary to complement system control protein mutations is relatively rare. A 6-year-old boy with complement factor H (CFH) and factor B (CFB) mutations and a history of bloody diarrhoea and PCR positivity for Shiga toxin was initially diagnosed as STEC+HUS. Acute kidney injury resolved with Eculizumab but he remains with chronic renal failure. Although the exact role of STEC in the pathogenesis of aHUS in this patient is not certain, there seems to be a relationship. However, several issues remain to be explained including the effect of genetic and environmental factors in modifying susceptibility to develop aHUS in some patients following STEC infection.Abbreviations: aHUS: atypical haemolytic uraemic syndrome; ANA: anti-nuclear antibody; ANCA: anti-neutrophil cytoplasmic antibody; ASO: anti-streptolysin O; BUN: blood urea nitrogen; CFB: complement factor B; CFH: complement factor H; EHEC: enterohaemorrhagic Escherichia coli; MCP: membrane co-factor protein; PD: peritoneal dialysis; STEC: Shiga toxin-producing Escherichia coli; STX 1-2: Shiga toxins 1-2.

Anca-associated crescentic glomerulonephritis in a child with isolated renal involvement / Glomerulonefrite rapidamente progressiva associada a ANCA em uma criança com acometimento renal isolado

ABSTRACT Pauci-immune glomerulonephritis (GN) is more common in elderly people compared to children and the etiology is not completely understood yet. Antineutrophil cytoplasmic antibody (ANCA) positivity occurs in 80% of the patients. We report a case of a 7-year-old girl who presented with malaise and mildly elevated creatinine diagnosed as ANCA-associated pauci-immune crescentic glomerulonephritis with crescents in 20 of 25 glomeruli (80%). Of these 20 crescents, 12 were cellular, 4 fibrocellular, and 4 globally sclerotic. She did not have purpura, arthritis, or systemic symptoms and she responded well to initial immunosuppressive treatment despite relatively severe histopathology. The patient was given three pulses of intravenous methylprednisolone (30 mg/kg on alternate days) initially and continued with cyclophosphamide (CYC; 2 mg/kg per day) orally for 3 months with prednisone (1 mg/kg per day). In one month, remission was achieved with normal serum creatinine and prednisone was gradually tapered. The case of this child with a relatively rare pediatric disease emphasizes the importance of early and aggressive immunosuppressive treatment in patients with renal-limited ANCA-associated pauci-immune crescentic GN even if with a mild clinical presentation. As in our patient, clinical and laboratory findings might not always exactly reflect the severity of renal histopathology and thus kidney biopsy is mandatory in such children to guide the clinical management and predict prognosis.

RESUMO A glomerulonefrite (GN) pauci-imune é mais comum em idosos em comparação com crianças, e a etiologia ainda não é completamente compreendida. A positividade do anticorpo citoplasmático antineutrófilo (ANCA) ocorre em 80% dos pacientes. Relatamos o caso de uma menina de 7 anos de idade que apresentou mal-estar e creatinina discretamente elevada, diagnosticada como glomerulonefrite rapidamente progressiva pauci-imune associada a ANCA com crescentes em 20 dos 25 glomérulos (80%). Destes 20 crescentes, 12 eram celulares, 4 fibrocelulares e 4 globalmente escleróticos. Ela não apresentava púrpura, artrite ou sintomas sistêmicos e respondeu bem ao tratamento imunossupressor inicial, apesar da histopatologia relativamente grave. A paciente recebeu três pulsos de metilprednisolona intravenosa (30 mg/kg em dias alternados) inicialmente e continuou com ciclofosfamida (2 mg/kg por dia) por via oral durante 3 meses com prednisona (1 mg/kg por dia). Em um mês, a remissão foi alcançada com creatinina sérica normal e a prednisona foi gradualmente reduzida. O caso desta criança com uma doença pediátrica relativamente rara enfatiza a importância do tratamento imunossupressor precoce e agressivo em pacientes com GN rapidamente progressiva renal associada à ANCA, mesmo com uma apresentação clínica leve. Como em nossa paciente, os achados clínicos e laboratoriais podem nem sempre refletir exatamente a gravidade da histopatologia renal e, assim, a biópsia renal é obrigatória nessas crianças para orientar a conduta clínica e auxiliar no prognóstico.

Outcome of posterior urethral valve in 64 children: a single center's 22-year experience.

BACKGROUND: Posterior urethral valve (PUV) is the most serious form of congenital anomalies of kidney and urinary tract (CAKUT) in boys with significant risk of progression to chronic kidney disease (CKD). We present our long-term results in children with PUV. METHODS: Retrospective chart review of 113 children with PUV followed within the years of 1996-2018 was performed. Clinical, laboratory and epidemiologic parameters were analyzed for their impact on renal outcome. RESULTS: The median age of diagnosis was 1.00 month (1.00-132.00) and the median follow-up period was 70 months (60.00-216.00). Antenatal diagnosis was present in 33 patients (51.5%) mainly with bilateral hydronephrosis and oligohydramnios. The most common postnatal presentation was recurrent urinary tract infection (UTI) in 14 cases (21.9%) and incontinence in three cases (4.7%). Vesicoureteral-reflux (VUR) was present in 31 cases (48.4%). All patients had surgery and urinary diversion was needed in 18 (28.2%). Varying stages of chronic kidney disease (CKD) developed in 23 cases (35.9%) and rise in serum creatinine was especially prominent after the 4th year of follow-up. Of 23 CKD patients, seven (10.9%) were in ESRD and on dialysis. Mortality occurred in one (1.5%) patient. Hypertension, proteinuria and high initial serum creatinine (>1.28 mg/dL) were statistically significant risk factors for CKD, as expected. Surprisingly VUR and UTI did not show such a significant impact on CKD development. Antenatal detection was with significantly less risk for CKD. CONCLUSIONS: Our results confirm that PUV has a considerable risk for CKD development. Antenatal diagnosis, management of proteinuria and hypertension may modify this progression. But already injured kidneys still have a potential risk. The need for further research to evaluate the impact of any intervention on long term renal outcome is obvious.

Anca-associated crescentic glomerulonephritis in a child with isolated renal involvement.

Pauci-immune glomerulonephritis (GN) is more common in elderly people compared to children and the etiology is not completely understood yet. Antineutrophil cytoplasmic antibody (ANCA) positivity occurs in 80% of the patients. We report a case of a 7-year-old girl who presented with malaise and mildly elevated creatinine diagnosed as ANCA-associated pauci-immune crescentic glomerulonephritis with crescents in 20 of 25 glomeruli (80%). Of these 20 crescents, 12 were cellular, 4 fibrocellular, and 4 globally sclerotic. She did not have purpura, arthritis, or systemic symptoms and she responded well to initial immunosuppressive treatment despite relatively severe histopathology. The patient was given three pulses of intravenous methylprednisolone (30 mg/kg on alternate days) initially and continued with cyclophosphamide (CYC; 2 mg/kg per day) orally for 3 months with prednisone (1 mg/kg per day). In one month, remission was achieved with normal serum creatinine and prednisone was gradually tapered. The case of this child with a relatively rare pediatric disease emphasizes the importance of early and aggressive immunosuppressive treatment in patients with renal-limited ANCA-associated pauci-immune crescentic GN even if with a mild clinical presentation. As in our patient, clinical and laboratory findings might not always exactly reflect the severity of renal histopathology and thus kidney biopsy is mandatory in such children to guide the clinical management and predict prognosis.

Effect of cholecalciferol on local arterial stiffness and endothelial dysfunction in children with chronic kidney disease.

BACKGROUND: As cardiovascular factors are the leading cause of mortality in chronic kidney disease (CKD) and as vitamin D deficiency is prevalent in this population, we aimed to examine the effect of oral cholecalciferol on cardiac parameters and biomarkers for endothelial cell activation in children with CKD. METHODS: Forty-one children with CKD and 24 healthy subjects free of any underlying cardiac or renal disease with low 25-hydroxyvitamin D3 (25OHD) levels were evaluated using echocardiography basally and following Stoss vitamin D supplementation. The local vascular stiffness and endothelial dysfunction markers were compared among the groups. RESULTS: Initial flow-mediated dilatation (FMD) measurements were lower and local arterial stiffness was significantly higher in patients. After vitamin D supplementation, these improved significantly in patients, while no significant change was observed for the healthy group. Homocysteine showed inverse correlation with baseline vitamin D level in CKD children and von Willebrand factor emerged as an independent risk factor for FMD impairment. CONCLUSIONS: Our interventional study revealed the favorable effects of high-dose cholecalciferol on cardiovascular and endothelial parameters, implying the importance of vitamin D supplementation in children with CKD.

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.

Hemolytic uremic syndrome outbreak in Turkey in 2011.

The aim of this retrospective multicenter study was to define the epidemiological and clinical features and prognostic factors of the first diarrhea-related hemolytic uremic syndrome (D+HUS) outbreak in Turkey in 2011. All pediatric nephrology centers in Turkey were asked about D+HUS patients via e-mail. Seventy D+HUS patients (median age: 5.7 years) participated. The seasonal peak was around the 7th, 8th and 9th months with 44 cases, centered in the east Marmara region. No causative agent could be identified. The rate of neurological complications and mortality was 21.4% and 4.2%, respectively. Eculizumab was used in four cases. Two of them had severe neurological complications despite plasma exchange. Elevated polymorphonuclear leukocyte count during hospital admission was the predictor of both severe disease and poor outcome. Duration of prodrome was the predictor of poor outcome (p<0.05). In conclusion, the median age of the affected children was greater than in the previous reports, while clinical features and outcome were similar.

A huge intracardiac thrombus developed in the presence of antithrombin III deficiency in a patient with end-stage renal failure.

In this study, we report a 15-year-old female with end-stage renal disease undergoing hemodialysis, who admitted with acute respiratory failure and generalized edema. Abdominal tomography detected thrombi in the right renal vein, in the hepatic segment of the inferior vena cava and in iliac veins. Levels of proteins C and S, antinuclear antigen, anti-dsDNA, C3, and C4 were in normal limits. The thrombi persisted despite treatment with nadroparin, heparin with fresh frozen plasma and warfarin. Due to heparin resistance, antithrombin III levels were measured and were found abnormally low. The first echocardiographic examination was in normal limits but the second echocardiography revealed a huge thrombus occluding the tricuspid valve. Urgent thrombectomy was planned but the patient died in the intensive care unit due to severe pulmonary edema.

Cryptosporidiosis: a rare and severe infection in a pediatric renal transplant recipient.

Cryptosporidium is an intracellular protozoan parasite that causes gastroenteritis in human. In immunocompromised individuals, cryptosporidium causes far more serious disease. There is no effective specific therapy for cryptosporidiosis, and spontaneous recovery is the rule in healthy individuals. However, immunocompromised patients need effective and prolonged therapy. Here, we present our clinical experience in a six-yr-old boy who underwent living-related donor renal transplantation and who was infected with Cryptosporidium spp. Our patient was successfully treated with antimicrobial agents consisting of spiramycin, nitazoxanide, and paromomycin. At the end of second week of therapy, his stool became negative for Cryptosporidium spp. antigen and spiramycin was discontinued. Nitazoxanide and paromomycin treatment was extended to four wk. With this case, we want to emphasize that cryptosporidiosis should be considered in the differential diagnosis of severe or persistent diarrhea in solid organ transplant recipients where rigorous antimicrobial therapy is needed.

A case of acetaminophen (paracetamol) causing renal failure without liver damage in a child and review of literature.

Acetaminophen (paracetamol) is a widely used drug and known as a safety antipyretic and analgesic drug in childhood. Acetaminophen-associated liver damage is more recognized than kidney damage. Nephrotoxicity and hepatotoxicity can be seen together after acetaminophen overdose, but renal damage without liver damage is a rarely seen entity in all age groups being reported more rarely in childhood. We present here a 16-year-old girl with renal failure without liver damage because of acetaminophen toxicity and a review of literature for pathophysiological mechanisms, clinical course, treatment, and outcome.

Acute pancreatitis as a presenting feature of Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common small vessel vasculitis of childhood. It is characterized by nonthrombocytopenic palpable purpura, abdominal pain, arthritis, and glomerulonephritis. Although HSP is typically known to be self-limited, serious complications can occur. Acute pancreatitis rarely presents as a complication of HSP. It is even rarer as an initial presenting feature of HSP, before the occurrence of characteristic palpable purpura. Herein, we report a 12-year-old girl with HSP who atypically presented with acute pancreatitis.

Acute renal failure with acyclovir treatment in a child with leukemia.

Acyclovir is an effective, frequently used antiviral agent. Adverse effects of this drug are well known and are especially seen with high doses and/or dehydration. In this article, we report a 6-year-old boy with leukemia with nonoliguric acute renal failure in normal hydration status after using acyclovir treatment. He had no preexisting renal impairment, and there were no additional symptoms. Dimercaptosuccinic acid radionucleid scyntigraphy and other laboratory findings revealed impairment of proximal tubule function, in addition to distal tubule. We emphasize that renal functions should be monitored carefully during treatment with acyclovir, and asymptomatic nephrotoxicity must be kept in mind.

A rare cause of recurrent hematuria in children: Nutcracker syndrome.

Nutcracker syndrome (NCS), the left renal vein hypertension due to compression between aorta and superior mesenteric artery, may present with hematuria, flank pain and proteinuria. We report a 6-year-old girl with episodic macroscopic hematuria who was diagnosed as NCS with Doppler ultrasound and 3D computerized tomography angiography. She was managed conservatively with spontaneous resolution of macroscopic hematuria. With this case we would like to emphasize that in children with hematuria and orthostatic proteinuria without an apparent cause, a great index of suspicion and appropriate imaging is necessary for the diagnosis of NCS.

A one-center experience with pediatric percutaneous renal biopsy and histopathology in Ankara, Turkey.

In this study we evaluated the indications, complications, and the spectrum of histopathological results of percutaneous renal needle biopsy (PRNB) performed in our clinic. Between June 1990 and December 2006, 679 PRNBs were performed on native kidneys of 614 children (304 boys, 310 girls) with a mean age of 10.4 years. Most frequent indications for PRNB were nephrotic syndrome (47%), hematuria, and/or proteinuria (15.9%), acute renal failure (14.6%) and complex renal manifestations (18.9%). The overall complication rate was 15.2%. The most common complications were perirenal hematoma (12.4%) and macroscopic hematuria (2.6%). The most frequent histopathological group of diseases were glomerulopathies; these were diagnosed in 376 patients (61.2%) and included membranoproliferative glomerulonephritis (11.1%), mesangial proliferation (10.7%), diffuse proliferative glomerulonephritis (7.7%), and focal segmental glomerulosclerosis (7.3%) as the most frequent. The second most frequent group of histopathology was manifestations secondary to systemic diseases; these were shown in 195 patients (31.8%). Amyloidosis (11.4%) and Henoch-Schönlein nephritis (9.9%) made the majority of this group. In conclusion, our study demonstrated that PRNB is a safe procedure with usually transient complications showing the most frequent renal diseases that cause diagnostic and therapeutic difficulties for pediatric nephrologists.

Chronic kidney disease in children in Turkey.

To determine the incidence, etiology and treatment patterns of chronic kidney disease (CKD) in children a questionnaire was sent to pediatric nephrology centers in Turkey, asking them to report patients under the age of 19 years who had estimated glomerular filtration rates (GFRs) of

Long-term efficacy and safety of quadruple therapy in childhood diffuse proliferative lupus nephritis.

In this study, we evaluated the frequency, clinical presentation, treatment protocols, prognostic factors, and outcome in children with diffuse proliferative lupus nephritis (DPLN). Between June 1990 and December 2004, 46 patients were diagnosed to have systemic lupus erythematosus (SLE), and 26 of them (56.5%) were found to have DPLN. Renal manifestations were present in 25 patients, and the majority of them presented with severe renal findings, such as nephrotic syndrome and renal failure. All patients were given a quadruple therapy protocol including 6-12 monthly courses of methyl prednisolone pulse therapy combined with oral prednisolone, oral cyclophosphamide, azathioprine, and dipyridamole. Nineteen of these patients were regularly followed up with a mean follow-up period of 5.9 years. Complete remission was achieved in 15 of 19 patients, and chronic renal failure developed in four patients. Renal survival rate was calculated to be 78.9% at the end of 5, 10, and 14 years. Although nephrotic range proteinuria, hypoalbuminemia, renal failure, and activity index above 12/24 at presentation seemed to be associated with poor prognosis, no significant difference could be found. Hypertension and chronicity index greater than 6/12 were found to be bad prognostic predictors. We concluded that satisfactory results were achieved with our quadruple therapy protocol; thus, more aggressive and expensive therapies can be avoided and preserved for more serious and persistent diseases.

Characteristics of pruritus in children on peritoneal dialysis.

BACKGROUND/AIMS: The aim of this study was to evaluate the characteristics of pruritus in pediatric patients undergoing peritoneal dialysis. PATIENTS AND METHODS: Twenty-seven patients (16 females, 11 males), aged between 5 and 18 years, were evaluated for the presence, intensity, onset, activation time, duration, characteristics, localization and increasing factors for pruritus. The intensity of pruritus was scored using a visual analog scale. Patients were grouped according to the existence of pruritus and other clinical and laboratory parameters (dialysis duration, dialysis adequacy, hemoglobin, blood urea nitrogen, creatinine, Ca, P, albumin, bicarbonate, parathyroid hormone (PTH), C-reactive protein (CRP)) were compared between the 2 groups. RESULTS: The mean age of patients was 11.85 +/- 4.4 years. There were 21 patients (77.7%) without pruritus and 6 patients with pruritus (22.2%). Serum P, PTH, CRP levels and CaxP product were significantly higher in patients with pruritus compared to patients without pruritus (p = 0.027, p = 0.03, p < 0.026, p = 0.031, respectively). In a stepwise logistic regression model, P (p = 0.01), CaxP product (p = 0.09), PTH (p = 0.03) and CRP (p = 0.02) were independently associated with pruritus. CONCLUSION: Our study indicates that pruritus remains a common but not troublesome symptom in children on peritoneal dialysis. Higher serum P, CaxP product, PTH and CRP concentrations appear to be important factors associated with uremic pruritus in this group.

Takayasu arteritis in children.

OBJECTIVE: To retrospectively evaluate the clinical features, angiographic findings, and outcomes of children with Takayasu arteritis (TA) in Turkey. METHODS: Clinical, laboratory, and angiographic findings and outcomes of 19 children with TA were evaluated with a retrospective chart review. The criteria for inclusion were those proposed by the American College of Rheumatology. RESULTS: Mean followup period was 35.89 +/- 40.75 months (range 1-168, median 30). There were 14 girls and 5 boys. The mean age at diagnosis was 12.84 +/- 2.69 years (range 8-17, median 13). The most common complaints on admission were headache (84%), abdominal pain (37%), claudication of extremities (32%), fever (26%), and weight loss (10%). One patient presented with visual loss. Examination on admission revealed hypertension (89%), absent pulses (58%), and bruits (42%). Angiography revealed type I in 13 patients (aortic arch, descending thoracic, and abdominal aorta), type II in 4 (descending thoracic aorta and abdominal aorta), and type IV in 2 (diffuse aortic and pulmonary artery). The most commonly involved vessels were the renal, subclavian, and carotid arteries. All patients received corticosteroid therapy, and further immunosuppressive therapy was added in 15 patients. Fourteen of the 17 hypertensive patients had renal artery stenosis and 9 underwent surgery or interventional therapy. Thoraco-abdominal bypass graft was performed in 2 patients who had abdominal aortic stenosis. CONCLUSION: Hypertension is the most common clinical feature at presentation. Corticosteroid and immunosuppressive therapy was effective in the control of disease activity. Angioplasty or bypass grafting was successfully performed when needed.