Razi Journal of Medical Sciences

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 According to studies which have been perormed in the following hospitals (Hazrat-e- Aliasghar and Labafi-Nejad 245 children who were affected by end stage renal failure have been taken under studiees in terms of etiology and clinical finding. The principal aim of this study was to find etiologies of CRF of these patients and teaching the families to prevent its complications.

  The methods which have been used, are retrospective and in the from of the study of patients records. All patients had GFR less than 10cc/min/1/73m². The cause of Renal failure were studied in all patients and the epidemic etiology of CRF in different age range has been determined.

  On the basis of these studies, in the ages under 5 years, diseases were congenital and inherited, and in the ages over 5 years the cause of diseases were the reflux nephropathy, and the congential and inherited diseases were the most cause of renal failure.

  Regarding high rate reflux in our studies which have been performed in other countries, the conclusion in that: the absence of regular planing in diagnosis and treatment of children who were affected by UTI and reflux, made the above disease as the most cause of ESRD in age range of 5-9 years and 10-17 years. Also, the late diagnosis of the congential-inherited disease (Specially congential obstrustive diseases) made them as the probable cause of ESRD in the patients over 5 years groups.

  The conclusion of this study was that the average age of final process of CRF in patients of this study was less than other studies in the same category. The lower level of health and awareness in families, and lack of early diagnosis and attention of physician to the patients can be reason of this difference.

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Nephrotic syndrome is an important disease in children and the diagnosis and treatment of its complications is important. Edema is one of these complications which is more common and severe in children and has different treatment in comparison with adults. Treatment of edema in children contains protocols that increase intravascular volume and decrease sodium reabsorption in all parts of nephron especially proximal tubule and aldostrone inhibitors, whereas sodium channel blockers in distal nephron(like amiloride) are used in adults. Albumin is an appropriate drug for the treatment of edema in children, although it has a few side effects such as expensiveness, intensifying interestitium nephritis and reducing furosmide effect. Therefore, nowadays, it has been tried to use drugs that have albumin advantages but no side effects(like manitol) for the treatment of edema. Thus, it was decided to use manitol and compare its effects with albumin on weight loss and reducing edema. The patients of the present study took albumin and manitol patient by patient. Weight loss(first and last weight) which was important for us was remarkable in both groups(Pv<0.001). There was no significant difference between these two groups of patients on manitol or albumin protocol regarding weight loss(Pv>0.005). Also, this weight difference did not have any relation with the amount of serum albumin in these two groups. Complications did not show any remarkable difference in both groups. Complications were evident in 16% of patients with manitol and 17% of other patients with albumin protocol. Complications in manitol protocol were hypokalemia and hypertension whereas they were hypertension and dehydration in albumin protocol. 15.8% of patients treated with manitol did not respond to this drug. This absence of response was seen in 30% of patients with albumin protocol. All the patients who were under manitol treatment and did not respond to it had MCD.

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Hearing loss is an important complication in chronic renal failure. The etiology of hearing loss is various in these patients, but uremia is the most important cause(uremic neuropathy). Other etiologies include electrolyte disorders (hyperkalemia-hyponatremia), vascular disorders, susceptibility to infections, antibiotics (e.g. aminoglycosides) and antihypertensive drugs. Studies on the effects of renal replacement therapy on hearing disorders are various and occasionally contradictory. Most studies have demonstrated that hemodialysis reduces uremia, but it is an ineffective or even intensifying treatment for hearing loss. On the contrary, renal transplantation is more remarkable in treatment of hearing disorders especially in early phase in most assessments However, it was also seen that hearing loss rebounds in later phases ( as much as previous degree or even more). Although hearing is an important sense in pediatric group, a few number of studies have been conducted on it in this group and the assessments in adults have also had various results. Therefore, it was decided to assess and compare hearing loss and its treatment in children with chronic renal failure undergoing dialysis or transplantation in order to be able to recognize the proper treatment for hearing loss in these children. 35 patients with chronic renal failure and hearing disorder who were treated by conservative hemodialysis or transplantation were assessed from 2002 to 2003 in Ali Asghar Hospital. Audiometry was performed in low, moderate and high frequency by an experienced person. The mean age was 12 years old. 20% of patients were treated by conservative therapy, 34% by hemodialysis and 46% of patients by transplantation. Hearing loss was prominent with high frequency and no significant difference was found between these groups regarding hearing disorder.

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  Background & Aim: Cyclosporine-A (CsA) is an immunosuppressant with a narrow therapeutic window. Inter-and-intrapatient variability in cyclosporine pharmacokinetics necessitates frequent blood level monitoring in transplant patients and total blood cyclosporine concentration used to allow dosage adjustment in transplant patients. The purpose of the present study was, first of all, to develop a precise and suitable method for therapeutic drug monitoring (TDM) of cyclosporine in children with renal transplant and to evaluate CsA blood concentrations in patients in order to find out the best time for sampling Iranian children with kidney transplant for TDM of cyclosporine. This can also help us achieve the best immunosuppressant with the least side effects for renal transplant patients.

  Patients and Method: In this experimental study, 29 pediatric transplant recipients (16 boys and 13 girls) who had received renal transplant at least six months prior to the study participated. The mean age of the patients was 14. 5 ±2. 3 years (ranging from 8 to 20 years),and they all showed stable renal function. The patients were also receiving other drugs such as prednisolone, mycophenolate mofetil, iron and folic acid. The clinical status of the patients was recorded. The CsA blood levels were determined using radioimmunoassay (RIA) 0, 0. 5, 1, 1. 5 and 2 hours after drug administration. The data analysis was performed using Pearson correlation coefficient.

  Results: Our results are indicative of good precision and�reproducibility of the method. Minimum detection limit of cyclosporine-A was 5 ng/ml and percentage yield was 86-109%. Inter-and-intraday variability for three cyclosporine-A blood concentrations were 8% and 5. 8% respectively. The mean blood concentrations 0. 5 and 1 hour after drug administration were 100 ± 3. 0 and 515± 19. 2 μ g/dl respectively. The mean serum creatinine level was 0. 9 (0. 1-1. 9) mg/dl. There was a high correlation between CsA dose, serum creatinin and C_{1. 5}, while there was no correlation between age, serum creatinine and C_{1. 5} level. Also, there was no correlation between C₀ and any of the above-mentioned parameters. These results show that C_{1. 5} level is the best indicator for TDM of cyclosporine-A in Iranian children and has the best correlation with dose and creatinin level.

  Conclusion: The developed method is precise,sensitive and suitable for therapeutic drug monitoring of cyclosporine-A. Using single point monitoring can help to improve the cooperation of patients during TDM procedure, and for this purpose C_{1. 5} level seems more accurate than C₀ level in pediatric transplant patients.

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    Background & Aim: Pyelonephritis is one of the most serious and common infectious diseases in children. Its renal infection and scarring is the leading cause of end stage renal disease (ESRD) in some parts of the world including

Iran. Serum and urinary levels of interleukin-6 (IL-6) have been reported to be high in acute pyelonephritis by some of the previous studies. This study was conducted to examine whether serum and urinary IL-6 is high and can be used as a screening test for acute pyelonephritis.

Patients and Method: This prospective, analytical, cross-sectional study was conducted on 40 children with fever, clinical signs and symptoms of urinary tract infection and positive urinary culture who were referred to

Ali

Asghar Children's

Hospital in 2008. Regarding the results of DMSA scan in these children, urinary and serum concentrations of IL-6 were compared in two groups of cystitis (n=20) and pyelonephritis (n=20). For data analysis, independent t-test, Mann-Whitney U-test, Wilcoxon rank, correlation and Receiver Operating Characteristics Curve (ROC) analysis were used.

Results: The mean of baseline urinary concentration of IL-6 was significantly higher in children with pyelonephritis [11.53 (SD=9.51) pg/dl] than the ones with cystitis [4.00 (SD=2.18) pg/dl] (P=0.002). Also, the mean of serum concentration of IL-6 in acute phase of the disease was significantly higher in children with pyelonephritis [15.59 (SD=8.40) pg/dl] than the ones with cystitis [3.21 (SD=4.58) pg/dl] (P<0.001). The optimal cut-point of 6.60 pg/dl for urinary concentration of IL-6 has the sensitivity and specificity of 70% and 95% to differentiate acute pyelonephritis patients from acute cystitis respectively. In addition, serum concentration of 9.25 pg/dl has the sensitivity and specificity of 80% and 95% to differentiate  these two groups of children.

Conclusion: It seems that urinary and serum concentrations of IL-6 possess a high diagnostic value to differentiate  pyelonephritis from cystitis and could be used as an important index to diagnose upper urinary tract infection from the lower one in the acute phase of the disease among children.

 

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PURPOSE: In our study, we evaluated retrospectively the efficacy of extracorporeal shock wave lithotripsy (ESWL) in the treatment of ureteral stones in children. MATERIALS AND METHODS: Between the dates of 2005-2010, 200 children who were applied ESWL due to the ureteral stone in our Clinic and consisted of 103 boys and 97 girls whose mean age was 7.9 ± 3.9 were evaluated. The sizes of the stones were 4 to 27 mm. ESWL was performed in the supine position for upper ureteral stones, in the supine/prone position for middle and lower ureteral stones. RESULTS: Stone-free rate was determined as 85% in three-month follow-up of the patients. Re-treatment was done at 15% of the patients. There was not any serious complication at any of the patients. CONCLUSIONS: According to these findings ESWL with its high stone-free rates and negligible complications is the first method to be refered in the treatment of ureteral stones in children.

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Background & Aims: Idiopathic nephrotic syndrome (INS) is one of the most common kidney diseases in children.INS is classically defined by severe protein excretion (≥40 mg/m2/h or 1000 mg/m2/24h) that subsequently results in hypoalbuminemia (<25 g/L), hyperlipidemia and edema.Two histological subtypes of INS in children, are minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS).
Approximately 80–90% of children with INS achieve remission after four weeks of daily prednisone therapy at a dose of 60 mg/m2 per day and therefore, given the diagnosis of steroid sensitive nephrotic syndrome (SSNS). When biopsied, these patients are more likely to have MCD. Patients with SSNS tend to have an excellent overall prognosis, with <5% progressing to chronic kidney disease (CKD). The remaining 10–20% of patients have primary steroid resistant nephrotic syndrome (SRNS), are more likely to have FSGS on biopsy, and have up to a 50% risk of developing end stage renal disease (ESRD) within 5 years of diagnosis. Therefore response to corticosteroids correlate with the prognosis of the disease. Patients with nephrotic syndrome experience remission and relapse course. Remission is defined proteinuria <4 mg/m2/h or urinary protein/creatinine (mg/mg) ratio of <0.2 for children above age of 2 years or ratio less than 0.5 for children under the age of 2 years. Relapse is defined proteinuria ≥ 40 mg/m2/h or > 50mg/kg/day or urinary protein/creatinine (mg/mg) ratio of ≥2.0 after having been remission.
In some cases of this disease specially steroid-resistant cases, to achieve a reliable diagnosis and determine the prognosis and select the most appropriate treatment, kidney biopsy is necessary. But this method is invasive and on the other hand, because the biopsy obtains only a small portion of the kidney that in some cases it may not accurately portray the disease if the affected portion of the kidney is not sampled. In other cases, the disease may be so far advanced that diagnostic features are obscured.
Given that one of the major challenges that modern nephrology should face is the identification of biomarkers that are associated with the above. Advancements in the understanding of the pathogenesis of nephrotic syndrome have facilitated the identification of a growing numbers of molecules that might be useful for these objectives.
Urine sample for evaluating urinary proteomes seem to be a valuable tool for biomarker discovery and can be collected easily and non-invasively.
Some of urinary biomarkers that have been found after podocyte damage include: proteins (podocalyxin, nephrin, podocin, CR1, CD80, synaptopodin, GLEPP-1, mindin, alpha 3 integrin, CD59, and Wilms tumor protein1-WT1), podocyte specific messenger ribonucleic acid (mRNA) (nephrin, podocin, synaptopodin, podocalyxin, CD2-associated protein-CD2AP, ACTN4-encodes for α-actinin 4, PTPRO-encodes for GLEPP-1, WT1, and B7-1-encodes for CD80), an exosomal transcription factor (WT1), and podocalyxin positive granular structures (PPGS). These biomarkers may be used to identify specific histopathological types of nephrotic syndrome, as well as patients' response to steroids and steroid-resistant or dependent cases.
One of these biomarkers is the CD80 molecule, which is a circulating molecule in nephrotic syndrome and can be found in kidney tissue or excreted in the urine. Viral Infections, Bacterial infections, Allergens and T-cell cytokines such as interleukin-13 directly stimulate the podocytes and increase CD80 expression on them which eventually cause podocyte injury.
By immunofluorescence studies and CD80 staining in glomerulus of patients with INS or measuring urinary level of CD80, it is possible to diagnose a specific type of nephrotic syndrome. In this article we reviewed different studies have been conducted on the role of CD80 in nephrotic syndrome.
Methods: In this study more than 70 articles were reviewed. Papers on nephrotic syndrome of childhood, application of urinary biomarkers in determining the specific histopathological type of INS and prognosis of the patients as well as CD80:CD28 costimulatory pathway have been reviewed. Articles on congenital/infantile nephrotic syndrome, review articles and case reports as well as secondary cases of INS were excluded. The selected articles were from 2002 to 2020.This review has been done by searching in Cochrane, Scholar Google, web of science and PubMed search engines.
Results: CD80 is normally expressed on antigen-presenting cells (APC) or natural killer cells. It functions as a ligand for CD28 and CTLA4 and depending on which ligand it binds to, can regulate immune responses, positively or negatively. CD28 and CTLA4 have opposing effects on T cell stimulation. Activating of CD80-CTLA4 pathway results in down- regulation of the responding T cells. But binding CD80-CD28 on T-cells is an important step for T-cell activation. Recent studies have indicated that podocyte cells in certain circumstances can acquire the phenotype of APC and can be induced to express the CD80 (B7.1) molecule. It has been shown that the expression of CD80 in podocytes is associated with the reorganization of actin molecules in them and can increase their permeability to protein resulting proteinuria.
Indeed one of the hypotheses in pathogenesis of MCD is two-hit theory. The initial hit is the induction of CD80 on the podocyte, resulting in actin disruption and increased glomerular permeability and the second hit is sustained podocyte injury due to T cell dysfunction or impaired autoregulation in these patients.Most studies support the role of CD80 as a permeability factor in minimal change nephrotic syndrome (MCD), that was significantly elevated in the active phase of MCD but remained to be normal in the active and remission phases of other types of nephrotic syndrome and in the remission phase of MCD. A recent study has reported that high urinary CD80 excretion might be a biomarker for steroid responsiveness and a predictor for good prognosis in INS.
Conclusion: CD80 molecule can be used as a valuable and non-invasive biomarker to differentiate MCD-relapse from MCD-remission and other glomerulopathies and also predicts steroid responsiveness and good prognosis in patients with nephrotic syndrome and may facilitate discovering of high-risk patients at an early stage and may lead to better treatment selection. Novel therapeutic agents such as Abatacept and Belatacept which are selective T-cell costimulation blocker and directe against CD80, may assist in the stabilization and reconstruction of podocytes in MCD.