First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults.

This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.

Successful treatment of plasmapheresis followed by interferon beta-1a in a child with severe COVID-19.

COVID-19 outbreak has become a global health concern due to challenges in treatment and high mortality rate; therefore, its therapeutic approaches play an important role in reducing the mortality rate and resolving this concern. Different therapies have been introduced, including interferon beta-1a and purification methods, for instance, plasmapheresis. In this article, we reported a child with severe COVID-19 who fully recovered after receiving plasmapheresis and interferon beta-1a.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.

How may Doppler indices help in the differentiation of obstructive from nonobstructive hydronephrosis?

BACKGROUND: We assess the potency of different Doppler indices in the differentiation of obstructive and nonobstructive hydronephrosis. MATERIALS AND METHODS: In this study, infants and children who were referred for the evaluation of unilateral hydronephrosis were enrolled. Ultrasonography for the assessment of the degree of hydronephrosis and a voiding cystourethrogram for the exclusion of vesicoureteral reflux was performed. Then, Doppler ultrasonography was done for both kidneys of each patient using four classic Doppler indices as well as the difference (delta) of each index between to kidneys. Diuretic renography with 99 mTc-ethylene dicysteine (99 mTc-EC) was performed for each patient. RESULTS: Thirty-nine patients met the inclusion criteria. After diuretic renography, 29 (74.35%) patients had shown a nonobstructive pattern, and ten (25.65%) patients had a partial (intermediate) or complete obstruction. Using receiver operating characteristic (ROC) curve, none of the classic indices of Doppler duplex (i.e., resistive index [RI], resistance index, end diastolic velocity, and peak systolic velocity) had the ability to make a difference between obstructive and nonobstructive hydronephrosis. However, by calculating the difference (delta) of these indices between two kidneys of each patient, delta RI could differentiate the nonobstructive condition, significantly (P = 0.006). A cutoff value of 0.055 has 60% sensitivity and 82.8% specificity. The area under the ROC curve for delta RI is 0.795 (standard error: 0.086, 95% confidence interval [CI]: 0.626, 0.964). Furthermore, RI ratio between two kidneys of each patient could differentiate the nonobstructive condition, significantly (P = 0.012). A cutoff point of 1.075 has 70% sensitivity and 82.8% specificity. The area under the ROC curve for RI ratio was 0.769 (standard error: 0.104, 95% CI: 0.565, 0.973). CONCLUSION: This study shows that RI ratio and delta RI with a high specificity could differentiate nonobstructive hydronephrosis and therefore it is a promising way to use especially in the follow-up of children with hydronephrosis.

Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. RESULTS: Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis. CONCLUSIONS: The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.

Salt intake and the association with blood pressure in young Iranian children: first report from the middle East and north Africa.

BACKGROUND: This study aimed to assess the salt intake of Iranian children, and to assess the correlation of urinary electrolytes excretion with blood pressure. METHODS: This cross-sectional study was conducted in 2011-2012 among 3-10-year-old children, selected by multi-stage cluster sampling from urban and rural areas of Isfahan, Iran. The sodium (Na), potassium (K), and creatinine (Cr) were measured in a random sample of the children's first morning fasting urine. Three-day averages of dietary intakes were analyzed by the Nutritionist-4 software. RESULTS: The mean (SD) of urinary Na was 177.17 (28.68) mEq/day without significant difference according to gender and living area. The mean (SD) dietary intakes of Na and K were 2017.76 (117.94) and 1119.06 (76.03) mg/day, respectively. Children of urban and rural areas consumed similar sources of salty foods (bread, cheese, and snacks) and had low intake of vegetables. No significant association was documented between urinary electrolytes excretions and blood pressure. CONCLUSIONS: This study, which to the best of our knowledge is the first of its kind in the Middle East and North Africa region, revealed that Iranian young children consume a large amount of sodium and small amount of potassium. The non-significant associations of electrolyte excretions with blood pressure may be because of the very young age group of participants. Given the development of preference to salt taste from early childhood, and the tracking of risk factors of chronic diseases from this age, reducing salt intake of young children should be emphasized.

Prevalence and severity of anemia in pediatric hemodialysis patients.

OBJECTIVE: To determine the prevalence and severity of anemia, and to identify independent predictors for anemia in children on hemodialysis. METHODS: We conducted this cross sectional study on 25 children aged 7-20 years receiving hemodialysis from September 2005 to January 2006 in Isfahan University of Medical Sciences, Isfahan, Iran. RESULTS: A total of 22 (82%) patients had hemoglobin (Hb) level of <11 g/dL (anemia) and 12 (48%) patients had Hb values <8 g/dL (severe anemia). The mean age was 15.5 +/- 3.7 years. Mean time on hemodialysis was 20.44 +/- 15.25 months. Anemia was more common and severe among children who were on dialysis <6 months. There was an inverse relation between severity of anemia and duration of hemodialysis (r=-0.465, p=0.019). Nearly all patients were treated with recombinant human erythropoietin (rHuEPO). Children with severe anemia received a slightly higher dose of erythropoietin (r=0.202 p=0.09). There was a correlation between serum albumin and Hb level (r=0.511, p=0.01). Intact parathyroid hormone (iPTH) levels were >200 pg/mL in 16 patients (66%) and >400 pg/mL in 9 patients (37.5%). There was a reverse correlation between iPTH level >200 pg/mL and Hb level (r=-0.505, p=0.046). CONCLUSION: The prevalence of anemia in our study appears to be higher than that reported in the other studies in spite of extensive use of rHuEPO and iron supplementation. We found this to be especially true for patients who were on dialysis <6 months and with low albumin and severe hyperparathyroidism.

Diagnostic value of Doppler ultrasound in differentiating prerenal azotemia from acute tubular necrosis in children.

Differentiating acute tubular necrosis (ATN) from prerenal azotemia is critical for selecting the appropriate treatment. This study was conducted to evaluate the diagnostic value of Doppler ultrasonography in differentiating ATN from prerenal azotemia in children. A total of 50 oliguric or anuric children with previous normal renal laboratory data were included. Doppler examination and calculation of resistive index (RI) was performed within 24 hours of admission and in the recovery phase of ARF. The sensitivity and specificity of RI in differentiating ATN from prerenal azotemia were assessed. At the cut-off point of RI = 0.75, the sensitivity and specificity of RI in differentiating prerenal failure and ATN was 91.3% and 85.2%, respectively. We conclude that Doppler ultrasonography is helpful in differentiating ATN from prerenal azotemia in children. The cut-off value of 0.75 has the highest accuracy for this purpose.