The amount of evidence indicates that hyperphosphataemia (HP) can induce endothelial damage and significantly impair endothelial nitric oxide synthase (eNOS) expression. There are no clinical studies that have assessed HP and its correlation with circulating eNOS concentration in patients with end-stage renal disease (ESRD). Our preliminary study aimed to evaluate the relationship between plasma inorganic phosphorus (P) levels and circulating plasma eNOS concentration in patients on haemodialysis (HD). A total of 50 patients on HD were enrolled to the study. They were divided into groups according to the tertiles of P. The examined HD group was also analysed and compared with controls as a whole group; then, the group was divided into patients with and without dyslipidaemia (D) as well as into those with and without type 2 diabetes mellitus (type 2 DM). A total of 26 age-matched healthy volunteers were included in the study as the control group. The plasma levels of eNOS in HD patients are reduced in comparison to those in healthy subjects. There was no difference in plasma eNOS concentrations between HD patients with type 2 DM and those without DM as well as between those with D and without D. In the entire group of HD patients, there were positive correlations between circulating levels of eNOS and plasma P concentrations. In HD patients with D, higher systolic and diastolic blood pressure were accompanied by decreased plasma eNOS concentrations. In conclusion, HP and high blood pressure appear to decrease the circulating eNOS levels. These findings demonstrate an additional negative impact of HP on eNOS activity.

Malignant Hyperthermia (MH), is a rare emergency that happened during General Anesthesia. In Albania, during five last years have three cases diagnosed with Malignant Hyperthermia (MH), and two of them have been fatal finishing with death of two patients. Only one is saved. Malignant hyperthermia (MH), is disease passed down through families that causes a fast rise in body temperature (fever) and severe muscle contractions when the affected person gets general Anesthesia. Malignant hyperthermia’s inheritance is Autosomal dominant. The defect is typically located on the long arm of chromosome 19 (19q13.1) involving the ryanodine receptor. More than 25 different mutations in this gene are linked with malignant hyperthermia. In this article I shall represents problems happened when during General Anesthesia, unexpected has e Malignant Hyperthermia. Malignant hyperthermia (MH), occurs in 1 in 5,000 to 50,000 instances (mainly in young people), in which people are given anesthetic gases. The most common triggering agents are volatile anesthetic gases, such as: Halothane, Sevoflurane, Desflurane, Isoflurane, Enflurane, Cyclopropane, Methoxyflurane; The depolarizing muscle relaxants suxamethonium and decamethonium, used primarily in general anesthesia. Other drugs that have been suspected of causing MH include catecholamines, phenothiazines, and monoamine oxidase inhibitors, caffeine. More frequent after ENT (ORL), squint or dental operation due to related with short anaesthetic procedures. -Researchers have described at least six forms of malignant hyperthermia susceptibility, which are caused by mutations in different genes. Variations of the CACNA1S and RYR1 genes increase the risk of developing malignant hyperthermia. Tests about discovering of MH are North American Protocol: Suspicous clinical history for MH, or The standard procedure is the “caffeine-halothane contracture test”, CHCT. Is an invasive test. The fresh biopsy (under local anesthesia), is bathed in solutions containing caffeine or halothane and observed for contraction; under good conditions, the sensitivity is 97%, and the specificity 78%; the use of the “calcium-induced calcium release” test -in addition to the CHCT to make the test more specific. Genetic testing is being performed in a limited fashion to determine susceptibility to MH. In people with a family history of MH, analysis for RYR1 mutations may be useful. Signs and symptoms are:Tachycardia : one of the earliest but a non specific sign,Tachypnea : in spontaneously ventilating patients. Increased sweating, During fulminant acute MH, body temperature may increase at a rate of 1.8–3.6°F (1–2°C) every 5 minutes, Cyanosis, flushing or blanching of skin, Cola coloured urine• masseter spasm or generalised muscle rigidity or both, Capnogram – Gradually increasing EtCO2 not related to other possible causes.. Biochemical parameters: Respiratory with or without metabolic acidosis, Hypercarbia, Hyperkalemia, Hyper calcemia, Hyper phosphatemia, Lacticacidemia, Myoglobinuria, Increase in creatinine kinase: neither a constant feature nor signifies increase muscle metabolism in intra operative period, Abnormal coagulation tests. Diagnostic Criteria are: Muscle rigidity (generalized rigidity including severe masseter muscle rigidity); Muscle breakdown (CK >20,000/L units, cola colored urine or excess myoglobin in urine or serum, potassium above 6 mmol/l); Temperature increase (rapidly increasing temperature, T >38.8°C); Other (rapid reversal of MH signs with dantrolene, elevated resting serum CK levels); Family history (autosomal dominant pattern). Differential Diagnosis ccan be made with: Pheochromocytoma,, Thyrotoxicosis (thyroid storm), Sepsis, Transfusion reactions (acute haemolytic and non haemolytic), Allergic reactions, Central nervous system dysfunction (pontine hge, hypoxic ischemic encephalopathy etc.), Neuroleptic malignant syndrome, Alcohol withdrawal,Drug interactions (MAOI and meperidine), some sort of cronic myopathy. For susceptible patients to MH, must be an special anesthetic procedures and must be ready with use of Dandrolene. Some anesthetic drugs are considered safe.These include local anesthetics (lidocaine, bupivacaine, mepivacaine), opiates (morphine, fentanyl), ketamine, barbiturates, propofol , etomidate, benzodiazepines. The nondepolarizing muscle relaxants pancuronium, cisatracurium, atracurium, mivacurium, vecuronium and rocuronium also do not cause MH. There is mounting evidence that some individuals with malignant hyperthermia susceptibility may develop MH with exercise and/or on exposure to hot environments, Local anaesthetics, Droperidol . Acute Management of MH crisis include:Stop exposure of triggering agents and give 100% O2, notify surgical team to abort intervention, administer 2.5mg/kg Dandrolene ( or Azumolene) in repeated doses and 3 gr Mannitol, place the catheter Foley, monitor core temperatre, O2, CO2, urine output, Astrupograme, correct HperKalemi or other biochimic abnormality, correct cardiac problems. Conplications are plenty after Therapy as: Kidney failure,rhabdomyolisis, KID, Respiratory failure, muscular dystrophy. Mortality was greater than 80% when do not put the right diagnosis, but with correct and fast diagnosis and the current management, however, mortality is now less than 5%.

Effects of triangle grass decoction on bone metabolism in rats with chronic kidney disease complicated with mineral and bone abnormalities

Determining the Value of Pharmaceutical Treatment of Hyperp hosphatemia with Phosphate Binders: A Systematic Review

Introduction Serum phosphate is a known risk factor for cardiovascular events and mortality in people with chronic kidney disease (CKD), however data on the association of these outcomes with serum phosphate are scarce. We investigate this relationship in people with CKD admitted to Dept of Nephrology and organ transplantation , Sharda superspecialtly hospital, Delhi ncr. Material & Methods Observational data suggest that an elevated serum phosphate increases the risk of cardiovascular events and mortality in patients with chronic kidney disease (CKD). Furthermore, hypophosphatemia is associated with reduced cardiovascular events in people with CKD.. A 55 patients with Chronic Kidney Disease admitted in Nephrology Unit were studied. All patients were subjected to all routine investigations including Complete Blood Count ,Blood Sugar, RFT & electrolytes and other relevant tests. Results Mean Age of the patients was 49.5 + 8.5 years. • 69.3% patients were males and 30.7% patients were females. Stage wise distribution of patients in stage I, II, IIIa,111b, IV, and V was nil, 3.6%, 3.6%, 1.8%, 9.09%& 81.1% respectively 30.9% of the studied patients were having ckd due to diabetic kidney disease. 81.8% of the patients were on maintenance hemodialysis in our study. Number of patients with raised serum po4(more than 4.5mg/ dl) is 67.27% and low serum po4 were 5.4%( less than 2.5mg/ dl). Total number of Patients with raised serum p04 with cardiac abnormalities were seen 27.27% • 5.4% Patients of ckd with low serum p04 had no cardiac abnormalities. Patients with raised serum p04 with cardiac abnormalities were seen from Ckd stage stage 4 i.e 5.4% , and ckd stage 5 patients were 35.13% . Patients with dkd/ckd 29.4% of patient had positive coorelation with raised po4 level and cardiac abnormality. Conclusions Other study confirms these findings. It also is in agreement with previous findings that hyperphosphatemia is associated with increased cardiovascular risk in people with CKD. In people with CKD, phosphate below the normal range has been associated with both improved and worsened cardiovascular outcomes. We found no effect of low phosphate on cardiovascular outcomes in the CKD population . Further research is required to determine the mechanisms Further research is required to determine the mechanisms underlying these associations

Amac: Nutrisyonel rikets, buyume cagindaki cocuklarda D vitamini ve kalsiyum eksikligine bagli olarak gelisen epifizyal kikirdagin defektif mineralizasyonudur. Nutrisyonel riketsin onlenmesi icin D vitamini profilaksisi ulkemizde sut cocuklugu doneminde rutin olarak uygulanmaktadir. Ancak halen semptomatik hipokalsemi ve D vitamini eksikligi nedeniyle hastane basvurularinin olmasi dikkat cekicidir. Calismamizda bu olgularin ozelliklerinin ortaya konulmasi amaclanmistir. Gerec ve Yontem: Ocak 2018-Mayis 2018 tarihleri arasinda nutrisyonel rikets tanisi ile yatirilarak izlenmis olan 28 hastanin (9 kiz, 19 erkek) verisi retrospektif olarak incelendi. Olgularin basvuru anindaki antropometrik ve laboratuvar ozellikleri kaydedildi. Bulgular: Olgularin ortanca basvuru yasi 8,8 (1-35) ay idi. Olgularin %67,9’u Suriye gocmeni idi. Hastalarin %57,1’i hic D vitamini profilaksisi almamis, %42,9’u ise duzensiz almisti. Basvuru yakinmasi olgularin %50’sinde konvulsiyon gecirme, %28,6’sinda rikets bulgulari iken %21,4’unde ise ates, enfeksiyon vb. nedenlerden dolayi hastaneye basvuran hastalarda rastlantisal olarak hipokalsemi tespit edilmis olmasi idi. Ilk basvuruda ortanca kalsiyum 6,6 mg/dL; iyonize kalsiyum 0,85 mmol/L; fosfor 3,5 mg/dL; alkalen fosfataz 787 U/L; parathormon 241 pg/mL ve 25-hidroksi vitamin D 3,4 ng/mL saptanmisti. Olgularin %60,7’sinde hipofosfatemi, %3,6’sinda hiperfosfatemi mevcuttu. Tum olgular hastanede yatirilarak tedavi edilmis ve D vitamini eksikligine bagli nutrisyonel rikets tanisi almisti. Sonuc: Ulkemizde D vitamini profilaksisine ragmen halen nutrisyonel rikets gorulebilmekte ve kis-ilkbahar aylarinda hipokalsemik konvulsiyon nedeniyle hastane basvurularina yol acabilmektedir. Ozellikle gocmen Suriyeli sut cocuklarinda D vitamini destek programina uyumun artirilmasi nutrisyonel riketsin onlenmesi acisindan onemlidir.

Роль приверженности пациентов в лечении гиперфосфатемии при хронической болезни почек

An 8-month-old infant with hypercalcemia and hyperphosphatemia—Answers

An 8-month-old infant with hypercalcemia and hyperphosphatemia: Questions.

Objective To identify and analyze the variants of the KCNJ1 gene in five Chinese patients with Bartter syndrome type 2 (BS2), and to describe their clinical features as well as treatment results. Methods Data and blood samples of five BS2 patients and their relatives confirmed by Qingdao Municipal Hospital from June 2012 to January 2019 were collected. Whole-exome-sequencing (WES) based on the second generation high throughput sequencing was performed to detect variants. The 2015 American College of Medical Genetics and Genomics Standards and Guidelines were applied to analyze the pathogenicity of the variants. The clinical features and laboratory results were retrospectively studied. The response to treatment and follow-up data were reviewed. Results Ten variants including six novel ones of KCNJ1 gene were identified through WES and verified by Sanger dideoxy sequencing. Missense variants accounted for the highest proportion. The common symptoms and signs of five BS2 patients from high to low incidence were polydipsia and polyuria (5/5), one of them (1/5) presented with diabetes insipidus; maternal polyhydramnios and premature delivery (4/5); growth retardation (3/5). Initially, two patients presented with hypochloremic metabolic alkalosis and hypokalemia, whereas the acid-base disturbance was absent in the others. One patient experienced hyperkalemia. In terms of calcium-phosphorus metabolism, one patient had evident parathyroid hormone (PTH) resistance (hypocalcemia, hyperphosphatemia and markedly elevated serum intact PTH levels), three presented with PTH overacting (hypercalcemia, hypophosphatemia and mild elevated serum intact PTH levels), and one showed normal blood calcium and phosphorus concentrations with high-normal serum intact PTH levels. All patients had nephrocalcinosis or hypercalciuria, and one of them complicated with nephrolithiasis. Indomethacin helped to correct the growth retardation, halt polydipsia polyuria, decrease the elevated urinary calcium excretion, and normalize electrolyte disturbance as well as PTH parameters in some patients. Conclusions This investigation identifies ten variants of KCNJ1 gene, including six ones that have not been previously reported, which will enrich the human gene mutation database (HGMD). These patients in our study have atypical BS phenotype, so that careful differentiation from other parathyroid diseases will be required for clinicians. Key words: Bartter syndrome; Genotype; Phenotype; KCNJ1 gene

高磷血症是慢性肾脏病（chronic kidney disease，CKD）患者的重要并发症之一。血磷水平长期过高可导致甲状旁腺功能亢进、肾性骨营养不良、血管钙化等多种并发症，而且与病死率增加密切相关。控制血磷水平达标可有效改善CKD患者的预后。本文将结合最新研究成果进一步探讨高磷血症的发生机制、疾病危害，以及非透析高磷血症患者的临床监测路径和治疗方法，为临床工作提供参考。

Objective To explore the effect of visits by WeChat on the compliance of patients with hyperphosphatemia undergoing peritoneal dialysis. Methods 40 patients undergoing continuous ambulatory peritoneal dialysis and regularly followed up at Second Clinical Medical College, Guangzhou University of Traditional Chinese Medicine from May, 2018 to February, 2019 were selected. The patients were followed up for more than 4 months through a WeChat group. Before and after the intervention, Morisky Drug Compliance Scale was used to evaluate the patients' drug compliance. The subjective satisfaction, general satisfaction, and dissatisfaction were used to evaluate the patients' satisfaction with nursing services. The data before the patients joining the WeChat group and at the last follow-up were retrospectively analyzed. The compliance, blood phosphorus, blood calcium, and nursing satisfaction of the patients were recorded. Results The patients' compliance, blood phosphorus, and nursing satisfaction were (7.14±0.73), (1.92±0.34) mmol/L, and 97.5% after the intervention, which were significantly better than those before the intervention [(5.11 ± 1.36), (2.11 ± 0.32) mmol/L, and 80.0%; all P 0.05]. Conclusion Visits by WeChat can improve the compliance of patients with hyperphosphatemia undergoing peritoneal dialysis and the satisfaction of nursing service, and reduce blood phosphorus. Key words: Visits by WeChat; Peritoneal dialysis; Hyperphosphatemia; Medication compliance

Background Anemia is a common feature of chronic kidney disease and is associated with poor outcomes. Renal anemia has a multifactorial etiology, and the major cause is decreased production of erythropoietin (EPO). The standard of care for the treatment of the renal anemia is EPO for achieving target of hemoglobin levels (11gm /dl), but some causes lead to inadequate response to EPO. Aim The study aimed to determine the frequency and various factors contributing to the etiology of renal anemia refractory to EPO in patients with end-stage renal disease (ESRD) on hemodialysis (HD). A descriptive longitudinal study was performed. The study was carried out on 30 patients with ESRD on HD selected randomly and received EPO drug at the Nephrology Unit and Outpatient Clinic at the Department of Internal Medicine of Assiut University Hospital. The data were obtained from full medical history and clinical examination, such as general data concerning patients (age, sex, comorbidities, and used medications), which were recorded directly from the patients or from their hospital files, laboratory investigations, and follow-up of patients for 4 months, with complete blood count examination every month. Patients and methods The study found that of 30 studied patients, 23 (76.7%) had partial response to reach the targeted hemoglobin level and seven (23.3%) had complete response to reach the targeted hemoglobin level of 11 g/dl. The 23 patients who had partial response had poor nutrition, iron-deficiency anemia (IDA), inadequate dialysis, arteriovenous fistula and chest infections, drugs containing aluminum, acute blood loss, hypocalcemia, hyperphosphatemia, and hyperparathyroidism. These may be possible risk factors of renal anemia refractory to EPO. Results Anemia is a common complication of uremia and a major contributor to morbidity and mortality in HD patients. The availability of recombinant human EPO has led to almost complete disappearance of severe anemia in HD patients; however, despite an increase in its use and average dose, a substantial percentage of patients still fail to achieve the Hb targets recommended by the international guidelines. Anemia refractory to EPO is common in HD patients (76.6%), which may be owing to several factors such as bad nutrition, IDA, inadequate dialysis, arteriovenous fistula and chest infection, aluminum-containing drugs, hypocalcemia, hyperphosphatemia, and hyperparathyroidism. Conclusions The study recommends to monitor serum levels of iron, calcium, phosphate, and parathyroid hormone at the start, with follow-up by complete blood count monthly, as well as treatment of the possible causes, that is, iron for IDA, antibiotic for infections, calcium therapy for hypocalcemia, and management of hyperphosphatemia and secondary hyperparathyroidism, during treatment of renal anemia by erythropoietin (EPO) drug to responded to it. Moreover, the study recommends performing more studies on a larger number of patients with ESRD having renal anemia for more demonstration of the possible causes of this condition.

Objective To explore the management effects of health knowledge-attitude-practice education on phosphorous control in peritoneal dialysis patients with hyperphosphatemia. Methods A total of 64 peritoneal dialysis patients with hyperphosphatemia with long-term stable follow-up in the People’s Hospital of Quzhou from 2016 to 2018 were selected, and randomly divided into control and intervention groups. The groups received regular health education and health knowledge-attitude-practice education for 3 months, respectively. T-test and paired t-test were used to analyze the difference in the two groups, before and after intervention, in the score of knowledge-attitude-practice, serum phosphorus level, daily dietary phosphorous, and dosage of phosphate binder. Results Before the health education intervention,there was no significant difference between the two groups’ questionnaire score of knowledge-attitude-practice of hyperphosphatemia, serum phosphorus, intact parathyroid hormone (iPTH), daily dietary phosphorous, dosage of phosphorus binder, and weekly urea clearance index in gender, age, and other general information. After 3 months of health education, the total score, knowledge, and behavior scores were higher in both groups than before intervention, and the scores of the intervention group were significantly higher than the control group. The scores increased by 16.64, 6.15, and 9.52 points respectively in the control group, and by 26.26, 11.67, and 13.56 points respectively in the intervention group. There was no significant difference in attitudes and beliefs between the groups before and after the intervention. After the intervention, the serum phosphorus level decreased, dosage of phosphate binder increased in both groups, the daily dietary phosphorous and iPTH decreased in the intervention group. These differences were statistically significant. The serum phosphorus level of the intervention group (1.86±0.42) mmol/L was lower than the control group (1.97±0.33) mmol/L, and the daily dietary phosphorous of the intervention group (831.22±187.85) mg/d was lower than the control group (928.23±192.81) mg/d. The difference in dosage of phosphate binder and iPTH of the groups was not statistically significant. Conclusions Health knowledge-attitude-practice education in peritoneal dialysis patients with hyperphosphatemia can improve their level of knowledge-attitude-practice, and promote the reduction of serum phosphorus. Key words: Hyperphosphatemia; Peritoneal dialysis; Health knowledge-attitudes-practice

Childhood is a critical time for the development of healthy skeleton.With the development of chronic kidney disease (CKD), there are disorders of mineral and bone metabolism, such as bone transformation, bone mineralization, volume bone and bone strength disorders.The manifestations are bone pain, fracture, growth and development disorders, vascular and soft tissue calcification, which may increase the incidence and mortality of cardiovascular diseases.The decrease of renal 1α-hydroxylase activity leads to the decrease of intestinal calcium absorption, the increase of serum parathyroid hormone (PTH) level and the high transport renal osteopathy.Phosphorus retention aggravates secondary hyperparathyroidism, and high phosphorus can lead to cardiovascular disease.Treatment of hyperphosphatemia and secondary hyperparathyroidism is helpful to improve growth disorders and high transport osteopathy, and to maintain serum calcium, phosphorus and PTH levels within the target normal range of different stages of CKD.Overtreatment can also lead to progression of nonmotile osteopathy, growth failure, hypercalcemia and cardiovascular calcification.Some new drugs, such as calcium-free phosphorus binders and new vitamin D analogues, can effectively inhibit serum PTH levels, providing a choice for the treatment of CKD in children. Key words: Chronic kidney disease; Mineral and bone disorder; Child

Гиперфосфатемия – значение и методы коррекции

315 Hyperphosphatemia in Dialysis: Rampant and Problematic

Phosphate Binder-combination Study of KHK7791 in Hyperphosphatemia Patients

Objective The purpose of the study was to evaluate the association between serum magnesium and mortality and cardiovascular mortality in peritoneal dialysis patients and search for risk factors influencing serum magnesium. Methods This was a single center retrospective study, this study included peritoneal dialysis patients from January 1st, 2010 to June 30th, 2017 and followed to December 31th, 2017 in our hospital. Demographic, clinical and laboratory indicators of the patients were collected. Risk factors influencing serum magnesium and evaluated the association between serum magnesium and mortality and cardiovascular mortality in peritoneal dialysis patients were searched for. The primary end point was all cause mortality and cardiovascular mortality of peritoneal dialysis patients. Hypermagnesemia was defined as serum magnesium greater than 1.02 mmol/L. Results 204 peritoneal dialysis patients were included in our study, 53.4% of them were male, 46.6% were female and 27.4% of them were diagnosed with diabetic nephropathy. The average age of patients starting peritoneal dialysis was (49.4±15.3) years old and the median duration of peritoneal dialysis was 32 months. Among them, 65 patients (31.8%) had hypermagnesemia, 135 patients (66.2%) had normal serum magnesium, only 4 patients (2%) had hypomagnesemia. Serum magnesium levels had a negative association with age (r=-0.158, P=0.024), and had a positive association with serum albumin (r=0.258, P<0.001), serum phosphorus (r=0.251, P<0.001), serum creatinine (r= 0.223, P=0.001). According to Logistics regression analysis, serum albumin level (P=0.018) was the independent influencing factor affecting serum magnesium level in patients with peritoneal dialysis. There was no significant difference in all cause mortality (P=0.251) and cardiovascular mortality (P=0.693) between serum magnesium normal group and hypermagnesemia group. In the multivariate Cox regression analysis, hyperphosphatemia (HR=0.350, P=0.021), high parathyroid hormone level (HR=2.822, P=0.001), the history of diabetes (HR=7.651, P<0.001) were predictors of all cause mortality in peritoneal dialysis patients. The history of diabetes (HR=16.595, P<0.001) was a major predictor of cardiovascular mortality in peritoneal dialysis patients. Conclusion (1)Serum albumin level was the independent influencing factor affecting serum magnesium level in patients with peritoneal dialysis. (2)Serum magnesium had no effect on mortality of peritoneal dialysis patients. (3)Hyperphosphatemia, high parathyroid hormone level, the history of diabetes had association with all cause mortality and the history of diabetes had association with cardiovascular mortality in peritoneal dialysis patients independently. Key words: Serum magnesium level; Hypermagnesemia; Peritoneal dialysis; Influencing factor; Mortality

Hypoparathyroidism is a rare endocrine disease with abnormal calcium and phosphorus metabolism.It is mainly characterized by hypocalcemia, hyperphosphatemia, and with or without decreasing of the parathyroid hormone (PTH). The current standard treatment for hypoparathyroidism includes calcium and vitamin D. Calcium and vitamin D can correct hypocalcemia, but it is not easy to maintain the balance of calcium and phosphorus.PTH hormone replacement therapy has made adequate progress and may become a treatment option for patients with hypoparathyroidism.This review is trying to introduce the progress in PTH hormone replacement therapy. Key words: Hypoparathyroidism; Parathyroid (1-34); Parathyroid (1-84); Replacement Therapy