Conceptual Approach to Body Fluids and Edema, Education Determines Clinical Outcomes in Heart Failure.

In this brief communication, we reemphasize the importance of critical thinking in clinical practice using the example of edema. The common practice of thinking and inquiry by practicing clinicians has beneficial implications for healthcare by improving outcomes and patient care while alleviating the burden of misconceptions in practice. We provide an in-depth and interactive investigation of physiological concepts as a foundation for understanding body fluid dynamics. Finally, we offer a new classification of symptoms of heart failure. DOI: 10.52547/ijkd.8171.

Arterial Versus Venous Blood Gas Analysis Comparisons, Appropriateness, and Alternatives in Different Acid/Base Clinical Settings: A Systematic Review.

Arterial blood gases (ABGs) are routinely done in critical clinical settings to ascertain acid-base status. Due to difficulties and the potential side effects following arterial blood sampling, much research has been done to find the possibility of using venous samples as an alternative. However, this comparison needs to be evaluated in various contexts. Hence, this systematic review aims to explore the differences, appropriateness, and alternatives of arterial versus venous blood gas (VBG) analysis in different acid-base states. A comprehensive literature search was conducted through electronic databases using the terms "ABG," "VBG," "Arterial Blood Gas," "Venous Blood Gas," and "Gas analysis." Studies' qualities were assessed by using Newcastle - Ottawa Quality Assessment Scale. Of 531 articles, 22 were included in the study after title, abstract, and full-text screening. Based on the Newcastle - Ottawa Quality Assessment Scale, 23% of the studies had good quality (score ≥ 7), 77% fair quality (score 2-6), and none of the studies had poor quality (score ≤ 1). Moreover, 22.5% of the included articles found a strong correlation between ABG and VBG. 73% compared arterial and VBG parameters among patients with any clinical contexts, 22.5% in respiratory diseases, and 4.5% in metabolic conditions, and their results had a significant disparity. There was a considerable discrepancy among authors about the appropriateness and utilization of VBG as an alternative to ABG. Our findings suggest that those studies did not consider physiological differences between venous and arterial blood values and obviated the significance of sampling procedures.

Targeted Next Generation Sequencing Revealed Novel Variants in the PKD1 and PKD2 Genes of Iranian Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), one of the common inherited disorders in humans, is characterized by the development and enlargement of renal cysts, often leading to end-stage renal disease (ESRD). In this study, Iranian ADPKD families were subjected to high-throughput DNA sequencing to find potential causative variants facilitating the way toward risk assessment and targeted therapy. METHODS: Our protocol was based on the targeted next generation sequencing (NGS) panel previously developed in our center comprising 12 genes involved in PKD. This panel has been applied to investigate the genetic causes of 32 patients with a clinical suspicion of ADPKD. RESULTS: We identified a total of 31 variants for 32 individuals, two of which were each detected in two individuals. Twenty-seven out of 31 detected variants were interpreted as pathogenic/likely pathogenic and the remaining 4 of uncertain significance with a molecular diagnostic success rate of 87.5%. Among these variants, 25 PKD1/2 pathogenic/likely pathogenic variants were detected in 32 index patients (78.1%), and variants of uncertain significance in four individuals (12.5% in PKD1/2). The majority of variants was identified in PKD1 (74.2%). Autosomal recessive PKD was identified in one patient, indicating the similarities between recessive and dominant PKD. In concordance with earlier studies, this biallelic PKD1 variant, p.Arg3277Cys, leads to rapidly progressive and severe disease with very early-onset ADPKD. CONCLUSION: Our findings suggest that targeted gene panel sequencing is expected to be the method of choice to improve diagnostic and prognostic accuracy in PKD patients with heterogeneity in genetic background.

The effect of the Iranian family approach-specific course (IrFASC) on obtaining consent from deceased organ donors' families.

Background: A family approach and obtaining consent from the families of potential brain-dead donors is the most important step of organ procurement in countries where an opt-in policy applies to organ donation. Health care staff's communication skills and ability to have conversations about donation under circumstances of grief and emotion play a crucial role in families' decision-making process and, consequently, the consent rate. Methods: A new training course, called the Iranian family approach-specific course (IrFASC), was designed with the aim of improving interviewers' skills and knowledge, sharing experiences, and increasing coordinators' confidence. The IrFASC was administered to three groups of coordinators. The family consent rate of participants in the same intervals (12 months for group 1, 6 months for group 2, and 3 months for group 3) was measured before and after the training course. The Wilcoxon signed-rank test was used to make comparisons. Results: The family consent rate was significantly different for all participants before and after the training, increasing from 50.0% to 62.5% (P=0.037). Furthermore, sex (P=0.005), previous training (P=0.090), education (P=0.068), and duration of work as a coordinator (P=0.008) had significant effects on the difference in families' consent rates before and after IrFASC. Conclusions: This study showed that the IrFASC training method could improve the success of coordinators in obtaining family consent.

Recurrence of a neuroendocrine tumor of adrenal origin: a case report with more than a decade follow-up.

BACKGROUND: Neuroendocrine tumor (NET) with adrenocorticotropic hormone (ACTH) secretion are very rare. To our knowledge, no follow-up study is published for ACTH-secreting NET, regardless of the primary site, to show second occurrence of tumor after a long follow-up, following resection of primary tumor. CASE PRESENTATION: Here, we describe a 49-year-old-man with cushingoid feature, drowsiness and quadriparesis came to emergency department at December 2005. Laboratory tests revealed hyperglycemia, metabolic alkalosis, severe hypokalemia, and chemical evidence of an ACTH-dependent hypercortisolism as morning serum cortisol of 57 µg /dL without suppression after 8 mg dexamethasone suppression test, serum ACTH level of 256 pg/mL, and urine free cortisol of > 1000 µg /24 h. Imaging showed only bilateral adrenal hyperplasia, without evidence of pituitary adenoma or ectopic ACTH producing tumors. Importantly, other diagnostic tests for differentiating Cushing disease (CD) from ectopic ACTH producing tumor, such as inferior petrosal sinus sampling (IPSS), corticotropin releasing hormone (CRH) stimulation test, octreotide scan or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan were not available in our country at that time. Therefore, bilateral adrenalectomy was performed that led to clinical and biochemical remission of hypercortisolism and decreased ACTH level to < 50 pg/mL, findings suggestive of a primary focus of NET in adrenal glands. After 11 years uncomplicated follow up, the ACTH level elevated up to 341 pg/mL and re-evaluation showed a 2 cm nodule in the middle lobe of the right lung. Surgical excision of the pulmonary nodule yielded a carcinoid tumor with positive immunostaining for ACTH; leading to decrease in serum ACTH level to 98 pg/mL. Subsequently after 7 months, serum ACHT levels rose again. More investigation showed multiple lung nodules with metastatic bone lesions accompanied by high serum chromogranin level (2062 ng/mL), and the patient managed as a metastatic NET, with bisphosphonate and somatostatin receptor analogues. CONCLUSION: This case of surgically-treated NET showing a secondary focus of carcinoid tumor after one decade of disease-free follow-up emphasizes on the importance of long-term follow-up of ACTH-secreting adrenal NET.

Conceptual Approach to Body Fluids and Edema, Education Determines Clinical Outcomes in Nephrotic Syndrome Management.

The objective of our paper is to reemphasize the importance of critical thinking in clinical practice and education in the field of internal medicine using the example of edema. We provide an in-depth and interactive investigation of physiological concepts as a foundation for the understanding of body fluid dynamics. Four fundamental concepts described are the hydrostatic and oncotic pressure gradients, capillary permeability, and lymphatic drainage. Furthermore, we visit the causes of edema in nephrotic syndrome. Traditional teaching considers hypoalbuminemia as a primary cause of edema formation in nephrotic syndrome. It has been proven that other etiologies causing edema include salt and water retention by the kidneys and a possible increase in capillary permeability are more important causes in the development of edema in nephrotic syndrome.

Metabolic risk factors and risk of Covid-19: A systematic review and meta-analysis.

OBJECTIVE: Based on the epidemiologic findings of Covid-19 incidence; illness and mortality seem to be associated with metabolic risk factors. This systematic review and meta-analysis aimed to assess the association of metabolic risk factors and risk of Covid-19. METHODS: This study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Cochrane Library, and Scopus. The search terms developed focusing on two main roots of "Covid-19" and "metabolic risk factors". All relevant observational, analytical studies, review articles, and a meta-analysis on the adult population were included in this meta-analysis. Meta-analysis was performed using the random effect model for pooling proportions to address heterogeneity among studies. Data were analyzed using STATA package version 11.2, (StataCorp, USA). RESULTS: Through a comprehensive systematic search in the targeted databases we found 1124 papers, after running the proses of refining, 13 studies were included in the present meta-analysis. The pooled prevalence of obesity in Covid-19 patients was 29% (95% CI: 14-47%). For Diabetes and Hypertension, these were 22% (95% CI: 12% 33%) and 32% (95% CI: 12% 56%), respectively. There was significant heterogeneity in the estimates of the three pooled prevalence without any significant small-study effects. Such warning points, to some extent, guide physicians and clinicians to better understand the importance of controlling co-morbid risk factors in prioritizing resource allocation and interventions. CONCLUSION: The meta-analysis showed that hypertension is more prevalent than obesity and diabetes in patients with Covid-19 disease. The prevalence of co-morbid metabolic risk factors must be adopted for better management and priority settings of public health vaccination and other required interventions. The results may help to improve services delivery in COVID-19 patients, while helping to develop better policies for prevention and response to COVID-19 and its critical outcomes.

Current Challenges of Kidney Transplantation in Iran: Moving Beyond The "Iranian Model".

Organ Transplantation in Iran has come a long way with many different policies and approaches addressing demand and supply. The first successfully kidney transplantation was performed at Namazi Hospital in Shiraz from a living donor in 1967. However, there had been only limited transplant activities in Iran until mid-1970. Previously, patients compensated the lack of organ transplants in Iran by travelling outside the country including the United Kingdom for living related transplants or to India, taking advantage of commercially available organs, usually with poor outcomes. There have also been attempts in the past to import allografts from Europe and the United States. After 1979 revolution, kidney transplantation was activated in Iran by using living donors which was know as Iranian model. Recently, there has been emphasis to expand deceased donor kidney transplantation. However, there are several challenges to expand transplant care in Iran.

The Impact of Hemodialysis Frequency and Duration on Blood Pressure Management and Quality of Life in End-Stage Renal Disease Patients.

Cardiovascular complications are the most prominent causes of morbidity and mortality among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients undergoing standard hemodialysis (HD) therapy. Cardiovascular disease risk is increased significantly through persistent hypertension and blood pressure (BP) fluctuation, which are the most common complications of CKD. It was hypothesized that an extended approach with lengthier and more frequent dialysis sessions, referred to in this paper as "extended hemodialysis" (EHD), can potentially lower and stabilize blood pressure, and consequently reduce the rate of morbidity and mortality. A greater reduction of volume (salt and water) with higher frequency can improve patient quality of life (QOL). Eleven papers, including clinical trials and systematic reviews were chosen and analyzed. The extracted data was used to evaluate the change in blood pressure levels between standard HD and EHD. Overall, the studies showed that EHD resulted in improved blood pressure management; therefore, we concluded that there will be a decrease in cardiovascular disease risk, stroke, and morbidity and mortality rate. There will be also an improvement in patient QOL due to beneficial effects of the EHD.

Prevalence and determinants of chronic kidney disease in northeast of Iran: Results of the Golestan cohort study.

BACKGROUND: The burden of chronic kidney disease (CKD) is increasing globally in particular in fast emerging economies such as Iran. Population-based studies on prevalence of CKD in Iran are scarce. The objective of the current study was to explore the prevalence and determinants of CKD in the setting of Golestan Cohort Study (GCS), the largest prospective cohort in the Middle East. METHODS: In this observational study, 11,409 participants enrolled in the second phase of GCS were included. Sex, age, literacy, residence, anthropometric measurements, smoking, opium use, self-reported history of cardiovascular diseases (heart disease and/or stroke), hypertension, diabetes, and lipid profile were the predictors of interest. The outcomes of interest were eGFR and CKD defined as eGFR< 60 ml/min/1.73m2. RESULTS: Mean (SD) of GFR was 70.0 ± 14.7 ml/min/1.73m2 among all participants, 68.2 ± 14.2 among women, and 72.0 ± 15.0 among men. Prevalence of CKD was 23.7% (26.6% in women, 20.6% in men). The prevalence of CKD stages 3a, 3b, 4, and 5 were 20.0%, 3.3%, 0.4% and 0.1%, respectively. Female sex, older age, urban residence, history of CVD, hypertension or diabetes, larger body mass and surrogates of body fat and opium use were all associated with CKD. Opium had a significant positive association with CKD in adjusted model. All anthropometric measurements had positive linear association with CKD. Being literate had inverse association. Sex had significant interaction with anthropometric indices, with higher odds ratios among men compared with women. A significantly high association was observed between the rate of change in waist circumference and systolic blood pressure with risk of CKD. CONCLUSION: One in four people in this cohort had low eGFR. Obesity and overweight, diabetes, hypertension, and dyslipidemia are major risk factors for CKD. Halting the increase in waist circumference and blood pressure may be as important as reducing the current levels.

Association between urinary adiponectin level and renal involvement in systemic lupus erythematous.

AIM: To assess association between urinary levels of adiponectin and severity of renal involvement in SLE patients. Also, this study aims to determine the value of urinary adiponectin levels to discriminate renal involvement in these patients. METHODS: In a multi-center cross-sectional survey, 50 consecutive patients diagnosed as having systemic lupus erythematosus (SLE) according to American College of Rheumatology criteria were classified into two groups with or without renal involvement (microscopic hematuria, reduced glomerular filtration rate < 25% of normal value, and proteinuria > 500 mg/24 h) which was confirmed by renal biopsy. Urinary adiponectin was measured by enzyme-linked immunosorbent assay. SLE disease activity levels were assessed by SLE Disease Activity Index (SLEDAI) score. RESULTS: Comparing urinary levels of adiponectin between the two groups indicated considerable discrepancy in this index between the groups with and without renal involvement (146.33 ± 258.83 ng/mL vs. 22.96 ± 44.33 ng/mL, P = 0.023). Also, urinary adiponectin/creatinine ratio was significantly higher in the former group (221.72 ± 414.58 vs. 19.99 ± 41.19, P = 0.019). Our study showed a higher mean SLEDAI score in those with renal involvement than others (23.60 ± 2.53 vs. 9.12 ± 3.03, P < 0.001). Multivariable linear regression analysis with the presence of potential confounders showed that the level of urinary adiponectin was significantly higher in those with renal involvement than other patients (ß = 0.470, P = 0.023). The optimal cut-off point for urinary adiponectin levels to discriminate renal involvement from normal renal state was 7.5 ng/mL, yielding a sensitivity of 80% and specificity of 52%. CONCLUSION: Urinary levels of adiponectin are significantly elevated in SLE patients with renal involvement. The measurement of this biomarker can be helpful to discriminate impaired from normal renal function in SLE patients.

A 4-year follow-up of living unrelated donors of kidney allograft in Iran.

INTRODUCTION: Shortage of deceased donor kidneys has resulted in an increased rate of kidney transplantation from living unrelated donors (LURDs). However, there are concerns about short-term and long-term morbidity of the donors. This study reports the clinical and biochemical factors in a follow-up program of Iranian LURDs, one of the largest reported series of kidney donors. MATERIALS AND METHODS: Of 7500 individuals who underwent living donor nephrectomies between 2005 and 2008, a total of 1549 participated in this study. They were followed for 18 to 48 months after the kidney donation. The average time for the first study visit was 316.72 days after donation. RESULTS: The mean age of donors was 30.43 ± 6.16 years old. Men consisted 82.5% of the group. Systolic hypertension was detected in 0.2% and diastolic hypertension in 1% of the LURDs; however, anemia prevalence was as high as 47.2%. Hyperuricemia was found in 21.2% of the LURDs, while proteinuria was seen in 13.7%. Glomerular filtration rate was greater than 90 mL/min in 38.2% of the donors, 60 mL/min to 90 mL/min in 54.5%, and less than 60 mL/min in 7.3%. A GFR less than 45 mL/min was seen in 0.1% of the donors. CONCLUSIONS: Data suggested that the LURDs in Iran have an appropriate health condition comparable to other donors in other parts of the world. Considering the high prevalence of hyperuricemia in our population and its importance as a risk factor for kidney failure, monitoring serum uric acid in follow-up programs is suggested.

The global registry: hope for the future.

In 2014, there is unanimous agreement that kidney transplant is the optimal treatment for most patients who have end-stage renal failure. Increasing organ shortage is the main obstacle that delays transplant and might even cause death while the patient is on the waiting list for kidney transplant. Many innovations have been proposed to increase the number of organs for transplant in different countries such as increasing awareness about organ donation, based on different cultures and religions. Support of religious and faith leaders exists for procurement of organs for transplant from patients with brain death or circulatory death. In the past decade, use of marginal and expandedcriteria deceased-donor transplant has been very helpful to expand the kidney donor pool. Dual kidney transplant is another procedure that may minimize the waiting list. The 1977 transport of kidneys from Minneapolis to Tehran helped change the life of a 15-year-old girl. At that time, we had the potential to change a life across 2 continents, even though our techniques were new. This should have provided the impetus to develop such a program. Presently, with progress in science, techniques, and organ shipment, it is our responsibility to reach across the globe to change the lives of many more young and adult patients waiting for kidney transplant. There are many countries in which kidneys from patients with brain or cardiac death are being discarded because of the unavailability of a transplant program in these countries, or because these countries have young transplant programs and very limited resources. If a global registry could be organized under the observation of the International Society of Nephrology and The Transplantation Society Sister Transplant Center Program, transplant teams would be able to use kidneys from patients with brain or cardiac death, with strict regulation of organ donation in accordance with World Health Organization guidelines.

Travel for transplantation in iran: pros and cons regarding Iranian model.

Transplant tourism is one of the main unacceptable aspects of medical tourism, implicating travel to another country to receive an allograft. Organ shortages in wealthier countries have persuaded patients to preclude organ waiting lists and travel to other countries for getting organs especially kidneys. On the other hand, in many countries, there is no transplant program, and hemodialysis is expensive. Hence, patients with end-stage kidney disease may have to travel to get a kidney allograft for the sake of their lives. In Iran, a legal compensated and regulated living unrelated donor kidney transplant program has been adopted since 1988, in which recipients are matched with liveunrelated donors through the Iran Kidney Foundation and the recipients are compensated dually by the government and the recipient. In this model regulations were adopted to prevent transplant tourism: foreigners were not allowed to receive a kidney from Iranian donors or donate a kidney to Iranian patients; however, they could be transplanted from donors of their own nationality, after full medical workup, with the authorization of the Ministry of Health. This was first considered as a humanitarian assistance to patients of the countries with no transplant program and limited and low quality dialysis. However, the policy of "foreign nationality transplant" gradually established a spot where residents of many countries, where living-unrelated donor transplant was illegal, could bring their donors and be transplanted mainly in private hospitals, with high incentives for the transplant teams. By June 2014, six hundred eight foreign nationality kidney transplants were authorized by Ministry of Health for citizens for 17 countries. In this review, we examine the negative aspects of transplant for foreign citizens in Iran and the reasons that changed "travel for transplant" to "transplant tourism " in our country and finally led us to stop the program after more than 10 years.

Prevalence of chronic kidney disease and its associated risk factors: the first report from Iran using both microalbuminuria and urine sediment.

BACKGROUND: The incidence of major risk factors of chronic kidney disease (CKD) in the world is on the rise, and it is expected that this incidence and prevalence, particularly in developing countries, will continue to increase. Using data on urinary sediment and microalbuminuria, we aimed to estimate the prevalence of CKD in northeast Iran. METHODS: In a cross-sectional study, the prevalence of CKD in a sample of 1557 regionally representative people, aged ≥ 18 years, was analyzed. CKD was determined based on glomerular filtration rate (GFR) and microalbuminuria. Life style data, urine and blood samples were collected. Urine samples without any proteinuria in the initial dipstick test were checked for qualitative microalbuminuria. If the latter was positive, quantitative microalbuminuria was evaluated. RESULTS: 1557 subjects with a mean age of 56.76 ± 12.04 years were enrolled in this study. Based on the modification of diet in renal disease (MDRD) equation, 137 subjects (8.89%) were categorized as CKD stages III-V. Based on urine abnormalities, the prevalence of combined CKD stages I and II was 10.63%, and based on macro- and microalbuminuria it was 14.53%. The prevalence of CKD was significantly associated with sex, age, marital status, education, diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD), waist to hip ratio, myocardial infarction (MI), and cerebrovascular accident (CVA). CONCLUSION: CKD and its main risk factors are common and represent a definite health threat in this region of Iran. Using and standardizing less expensive screening tests in low resource countries could be a good alternative that may improve the outcome through early detection of CKD.

Renal function and risk factors of moderate to severe chronic kidney disease in Golestan Province, northeast of Iran.

INTRODUCTION: The incidence of end-stage renal disease is increasing worldwide. Earlier studies reported high prevalence rates of obesity and hypertension, two major risk factors of chronic kidney disease (CKD), in Golestan Province, Iran. We aimed to investigate prevalence of moderate to severe CKD and its risk factors in the region. METHODS: Questionnaire data and blood samples were collected from 3591 participants (≥18 years old) from the general population. Based on serum creatinine levels, glomerular filtration rate (GFR) was estimated. RESULTS: High body mass index (BMI) was common: 35.0% of participants were overweight (BMI 25-29.9) and 24.5% were obese (BMI ≥30). Prevalence of CKD stages 3 to 5 (CKD-S3-5), i.e., GFR <60 mL/min/1.73 m(2), was 4.6%. The odds ratio (OR) and 95% confidence interval (95% CI) for the risk of CKD-S3-5 associated with every year increase in age was 1.13 (1.11-1.15). Men were at lower risk of CKD-S3-5 than women (OR = 0.28; 95% CI 0.18-0.45). Obesity (OR = 1.78; 95% CI 1.04-3.05) and self-reported diabetes (OR = 1.70; 95% CI 1.00-2.86), hypertension (OR = 3.16; 95% CI 2.02-4.95), ischemic heart disease (OR = 2.73; 95% CI 1.55-4.81), and myocardial infarction (OR = 2.69; 95% CI 1.14-6.32) were associated with increased risk of CKD-S3-5 in the models adjusted for age and sex. The association persisted for self-reported hypertension even after adjustments for BMI and history of diabetes (OR = 2.85; 95% CI 1.77-4.59). CONCLUSION: A considerable proportion of inhabitants in Golestan have CKD-S3-5. Screening of individuals with major risk factors of CKD, in order to early detection and treatment of impaired renal function, may be plausible. Further studies on optimal risk prediction of future end-stage renal disease and effectiveness of any screening program are warranted.

Common MEFV mutation analysis in 36 Iranian patients with familial Mediterranean fever: clinical and demographic significance.

The aim of our study was to determine the spectrum of the 12 most common familial Mediterranean fever gene (MEFV) mutations in Iranian patients with heterogeneous ethnicity, using the familial Mediterranean fever (FMF) strip assay test. A total of 36 patients were diagnosed according to established clinical criteria. Genomic DNA from all patients was tested for 12 common mutations located in exon 2 (E148Q), 3 (P369S), 5 (F479L), 10 [M680I (G>C), M680I (G>A), I692del, M694V, M694I, K695R, V726A, A744S, R761H], respectively, using the FMF strip assay test. Of the 35 patients with mutations, ten were homozygote, 20 were compound heterozygote, and five were heterozygote. The most frequent genotype was M680I/M680I (6 patients, 16.7%). The most frequent mutation was M680I, followed by M694V, and V726A. The FMF strip assay test for common these 12 mutations was positive in 90.6% of alleles in this study, indicating that it appears to be an effective method for FMF mutation screening in Iranian patients.