Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem / Riscos ocupacionais associados à doença renal crônica de origem não tradicional (DRCnt) no Brasil: é hora de nos aprofundarmos em um problema negligenciado

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.

Natural angiotensin converting enzyme inhibitors: A safeguard against hypertension, respiratory distress syndrome, and chronic kidney diseases.

Hypertension is a serious concern as it is one of the causes of kideny failure and pulmonary fibrosis. An important therapeutic strategy for treating chronic hypertension is to inhibit the angiotensin converting enzyme (ACE). ACE inhibition reduces kidney damage, pulmonary artery pressure, and high blood pressure. Due to their high efficacy and low risk of side effects, natural renin-angiotensin system inhibitors have drawn increasing attention over the past decades. Alkaloids, amino acids, anthocyanidins, flavonoids, glucosinolates, isoflavonoids, phenolic acids, polyphenolics, and triterpenoids are among the bioactive metabolites pocessing an impressive ACE inhibitory activity. Many herbs including Rosmarinus officinalis, Hibiscus sabdariffa, Curcuma longa, Rauwolfia serpentina, Emblica officinalis, Cynara scolymus, Punica granatum, Mucuna pruriens, Capsicum annuum, and Moringa olifera were found having ACE inhibitory activities comparable to captopril and enalpril. These enticing natural ACE inhibitors deserve to be a safeguard medicine against hypertension, respiratory distress syndrome, and chronic kidney diseases. More clinical trials are required before new natural compounds and herbs can be used to treat chronic hypertension and its ramifications, such as respiratory distress syndrome and kidney failure.

Complications after radiofrequency ablation of hyperparathyroidism secondary to chronic kidney disease.

OBJECTIVE: To study the complications of ultrasound-guided radiofrequency ablation (RFA) in chronic kidney disease (CKD) patients undergoing renal replacement therapy with secondary hyperparathyroidism (SHPT). METHODS: This retrospective study reviewed the clinical data, including general information, examination results, treatment times, time interval, and postoperative complications, of 103 SHPT patients who received ultrasound-guided RFA treatment from July 2017 to January 2021. RESULTS: Of 103 patients, 52 required two sessions of RFA within a month. The incidence of recurrent laryngeal nerve injury at the second treatment was significantly higher than that at the first treatment (first session vs. second session, 5.77% vs. 21.15%; p = .021). Of all the enrolled 103 patients, 27 suffered complications after the first session of RFA. When we separated patients into complications group and non-complication group, we detected more ablated nodules in the complications group (Z = -2.222; p = .0026). Subgroup analysis further showed that the patients in the severe hypocalcemia group were younger (p = .005), had more ablated nodules (p = .003) and higher blood phosphorus (p = .012) and alkaline phosphatase (ALP) levels (p = .002). Univariate analysis showed that age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA. CONCLUSIONS: An interval of more than 1 month between two treatments may help to avoid recurrent laryngeal nerve injury. Age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA.

Effects of turmeric extract supplementation on the lipid and lipoprotein subfraction profile in hemodialysis patients: A randomised, double-blind, crossover and controlled trial.

Dyslipidemia is common in patients with chronic kidney disease. Curcumin, a bioactive polyphenol from Curcuma longa, can improve lipid profile. This study aims to analyze the effects of Curcuma Longa extract supplementation on lipid profile and lipoprotein subfractions in hemodialysis (HD) patients. This is a longitudinal, double-blind, washout-period randomized clinical trial. The patients were randomized into two groups: the curcumin group (n = 10) (orange and carrot juice with 2.5 g of Curcuma Longa extract) and the control group (n = 11) (juice without curcumin) 3x/w during HD sessions for 3 months. After the washout period, patients continued the supplementation as a crossover for the same period. The lipid profile was measured using enzymatic assays. The high-density lipoprotein and low-density lipoprotein subfractions analyses were performed using LipoprintTM. In the curcumin group, the triglyceride values tended to decrease with a different triglyceride variation between the pre and post-intervention for the control and curcumin groups of 38.5 (19.8) mg/dL (p = 0.06). There was no statistical difference in the others parameters. In conclusion, Curcuma longa extract may be a good nutritional strategy to reduce triglyceride plasma levels in hemodialysis patients, but it seems ineffective for the other parameter.

Tetrahydrocurcumin Add-On therapy to losartan in a rat model of diabetic nephropathy decreases blood pressure and markers of kidney injury.

Tetrahydrocurcumin (THC), a principal metabolite of curcumin, was tested in a rat model of type 2 diabetes mellitus. THC was administered via daily oral gavage with the lipid carrier polyenylphosphatidylcholine (PPC) as add-on therapy to losartan (angiotensin receptor blocker) to examine effects on kidney oxidative stress and fibrosis. A combination of unilateral nephrectomy, high-fat diet and low-dose streptozotocin was used to induce diabetic nephropathy in male Sprague-Dawley rats. Animals with fasting blood glucose >200 mg/dL were randomized to PPC, losartan, THC + PPC or THC + PPC + losartan. Untreated chronic kidney disease (CKD) animals had proteinuria, decreased creatinine clearance, and evidence of kidney fibrosis on histology. THC + PPC + losartan treatment significantly lowered blood pressure concurrent with increased messenger RNA levels of antioxidant copper-zinc-superoxide dismutase and decreased protein kinase C-α, kidney injury molecule-1 and type I collagen in the kidneys; there was decreased albuminuria and a trend for increased creatinine clearance compared to untreated CKD rats. There was decreased fibrosis on kidney histology in PPC-only and THC-treated CKD rats. Plasma levels of kidney injury molecule-1 were decreased in THC + PPC + losartan animals. In summary, add-on THC to losartan therapy improved antioxidant levels and decreased fibrosis in the kidneys, and lowered blood pressure in diabetic CKD rats.

Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway.

CONTEXT: Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity. OBJECTIVE: Our study aimed to clarify the potential mechanism of SZP in improving chronic DN. MATERIALS AND METHODS: Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing. RESULTS: SZP significantly reduced 24 h urine albumin (p < 0.05) of DN mice. Compared to DN group, SZP significantly decreased the homeostasis model assessment of insulin resistance index, serum creatinine and blood urea nitrogen levels (20.27 ± 3.50 vs. 33.64 ± 4.85, 19.22 ± 3.77 vs. 32.52 ± 3.05 µmol/L, 13.23 ± 1.42 vs. 16.27 ± 0.77 mmol/L, respectively), and mitigated renal damage. SZP also regulated gut microbiota and decreased the abundance of Gram-negative bacteria (Proteobacteria, Klebsiella and Escherichia-Shigella). Subsequently, SZP reduced lipopolysaccharides levels (1.06- to 1.93-fold) of DN mice. Furthermore, SZP inhibited the expression levels of TLR4, phospho-NF-κB p65, NLRP3 proteins and interleukin (IL)-18 and IL-1ß. CONCLUSIONS: These results demonstrated that SZP improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN.

Exploring the clinical efficacy and mechanism of high-position colon dialysis combined with Traditional Chinese Medicine retention enema in real-world patients with stage 3-5 chronic kidney disease (non-dialysis) based on the theory of the Gut-Kidney axis.

Background: With societal and economic development, the annual incidence of chronic kidney disease (CKD) is increasing. Current treatments for CKD are limited, and once patients progress to the uraemic stage, it places a significant economic burden on families and society. Based on the "gut-kidney axis" theory and real-world research, this study aims to evaluate the clinical efficacy, safety, and potential mechanism of high-position colon dialysis combined with traditional Chinese medicine (TCM) retention enema in treating stage 3-5 chronic kidney disease (non-dialysis). Additionally, it seeks to identify new therapeutic targets and approaches for CKD treatment. Methods: The TCM decoction was analyzed using Ultra-Performance Liquid Chromatography-Quadrupole-Orbitrap-High Resolution Mass Spectrometry (UPLC-Q-Orbitrap-HRMS). Participants meeting the inclusion criteria were divided into a control group (n = 153) and a treatment group (n = 159) based on their preferences and physicians' recommendations. Both groups adhered to a high-quality low-protein, low-salt, low-phosphorus, and low-fat diet supplemented with essential amino acids, and were monitored for blood pressure, blood glucose, and blood lipids. The treatment group received high-position colon dialysis combined with TCM retention enemas (administered at least 12 times every other day). Results: Thirteen compounds were identified from the herbs by UPLC-Q-Orbitrap-HRMS. The CKD3-5 treatment group exhibited improvements in blood biochemistry and other laboratory indices, with significant enhancements in renal function-related indices for CKD4 and CKD5 stages (p < 0.05). Following treatment, indoxyl sulfate (IS), endotoxin, and D-lactic acid levels decreased to a certain extent in both groups, with a statistically significant difference observed within the treatment group (p < 0.05). The treatment group displayed a significant reduction in aerobic bacterial colonies, an increase in anaerobic bacterial colonies, a decrease in Escherichia coli colonies, and an increase in Bifidobacterium and Lactobacillus colonies (p < 0.05). No significant changes in colony numbers were observed in the control group. Conclusion: High-position colon dialysis combined with TCM retention enema may serve as an adjuvant treatment for CKD4-5 (non-dialysis), and its mechanism may be related to the reduction of uraemic toxins, improvement of intestinal mucosal barrier function, and regulation of intestinal microecology. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2200062852.

Medical Nutrition Therapy for Chronic Kidney Disease: Low Access and Utilization.

CKD affects approximately half of US adults aged 65 years and older and accounts for almost 1 out of every 4 dollars of total Medicare fee-for-service spending. Efforts to prevent or slow CKD progression are urgently needed to reduce the incidence of kidney failure and reduce health care expenditures. Current CKD care guidelines recommend medical nutrition therapy (MNT), a personalized, evidence-based application of the Nutrition Care Process (assessment, intervention, diagnosis, and monitoring and evaluation) provided by registered dietitian nutritionists (RDNs) to help slow CKD progression, improve quality of life, and delay kidney failure. MNT is covered by Medicare Part B and most private insurances with no cost sharing. Despite recommendations that patients with CKD receive MNT and insurance coverage for MNT, utilization remains low. This article demonstrates low utilization of MNT and inadequate numbers of RDNs and RDNs who are board certified in renal nutrition relative to the estimated number of Medicare eligible adults with self-reported diagnosed CKD by state, with noted disparities across states. We discuss interventions to increase MNT utilization, such as improving MNT reimbursement, augmenting accessibility of RDNs via telenutrition services and increasing health care provider promotion of MNT and referral to MNT to optimize CKD outcomes.

Distal renal tubular acidosis presenting with an acute hypokalemic paralysis in an older child with severe vesicoureteral reflux and syringomyelia: a case report.

BACKGROUND: Distal renal tubular acidosis (dRTA) is the most common type of renal tubular acidosis (RTA) in children. Pediatric dRTA is usually genetic and rarely occurs due to acquired issues such as obstructive uropathies, recurrent urinary tract infections (UTIs), and chronic kidney disease (CKD). Although persistent hypokalemia frequently occurs with dRTA, acute hypokalemic paralysis is not frequently reported, especially in older children. CASE PRESENTATION: An eight-year-old girl presented with an acute first episode of paralysis. A physical examination revealed normal vital signs, short stature consistent with her genetic potential, and decreased muscle strength of her upper and lower extremities. Preexisting conditions included stage 4 CKD due to recurrent UTIs, severe vesicoureteral reflux and bilateral hydronephrosis, neurogenic bladder, and multisegment thoracic syringomyelia. Her laboratory work-up revealed hypokalemic, hyperchloremic metabolic acidosis with a normal anion gap. She also had a urine osmolal gap of 1.9 mOsmol/kg with a high urine pH. Intravenous potassium replacement resulted in a complete resolution of her paralysis. She was diagnosed with dRTA and discharged with oral bicarbonate and slow-release potassium supplementation. CONCLUSIONS: This case report highlights the importance of considering dRTA in the differential diagnosis of hypokalemic acute paralysis in children. Additionally, in children with neurogenic lower urinary tract dysfunction and recurrent UTIs, early diagnosis of spinal cord etiology is crucial to treat promptly, slow the progression of CKD, and prevent long-term complications such as RTA.

The effects of curcumin-containing supplementations on inflammatory markers and lipid profiles in patients with chronic kidney diseases: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: An evaluation the effects of curcumin on inflammatory markers and lipid profiles among patients with chronic kidney diseases (CKD). METHODS: The electronic databases such as PubMed, and Scopus were searched systematically up until 12 December 2021. To evaluate the quality of the included studies, the Cochrane risk-of-bias tool for randomized trials was utilized. Likewise, data pooling was performed using a random effects model, also called a variance components model. Also, the findings were calculated as weighted mean difference (WMD) with a 95% confidence interval (CI). RESULTS: In the end, this meta-analysis comprised a total number of nine studies. Curcumin intake significantly reduced total cholesterol (TC) (WMD=-13.77 mg/dL; 95% CI, -26.77, -0.77; p=0.04) and tumor necrosis factor alpha (TNF-α) (WMD=-18.87 pg/mL; 95% CI, -28.36, -9.38; p<0.001) compared with controls. The results did not confirm the significant effect of curcumin intake on triglyceride (TG) (WMD=-6.37 mg/dL; 95% CI, -26.59, 13.85; p=0.54), low-density lipoproteins (LDL-C) (WMD=-5.65 mg/dL; 95% CI, -20.81, 9.50; p=0.46), high-density lipoprotein (HDL-C) (WMD=0.16 mg/dL; 95% CI, -2.55, 2.88; p=0.91), and C-reactive protein (CRP) (WMD=-0.13 mg/L; 95% CI, -3.25, 3.30; p=0.93). CONCLUSIONS: Our study showed that curcumin significantly impacts TC and TNF levels in CKD patients.

Resveratrol ameliorates muscle atrophy in chronic kidney disease via the axis of SIRT1/FoxO1.

Chronic kidney disease (CKD) is often associated with muscle atrophy. However, the underlying molecular mechanisms are still not well understood. Here, we treated 5/6-nephrectomized (5/6Nx) rats with resveratrol and found that this treatment greatly improves renal function as evidenced by reduced proteinuria and cystatin C. Moreover, resveratrol ameliorates renal fibrosis by reducing transforming growth factor ß (TGF-ß) and connective tissue growth factor (CTGF). Meanwhile, muscle atrophy in these 5/6Nx rats was largely attenuated by resveratrol. Immunoprecipitation revealed that SIRT1 physically interacts with FoxO1 in muscle, and this interaction was weakened in 5/6Nx rats. As a consequence, acetylated FoxO1 was increased in muscle of 5/6Nx rats. The application of resveratrol markedly reverses this trend. These data point out that SIRT1 is a key factor for linking renal disease and muscle atrophy. Indeed, both renal dysfunction and muscle atrophy were further aggravated by 5/6Nx in Sirt1+/- mice. Taken together, our data indicate that SIRT1 plays a pivotal role in muscle atrophy in CKD, and FoxO1 might be a substrate of SIRT1 in this process. Furthermore, resveratrol, together with other agonists of SIRT1, may hold great therapeutic potentials for treating CKD and its related muscle atrophy.

A challenging case of an adolescent and young adult patient with high-risk acute lymphoblastic leukemia: the need for a multidisciplinary approach: a case report.

BACKGROUND: Adolescents and young adults diagnosed with acute lymphoblastic leukemia are treated according to pediatric-based regimens to achieve better results. However, implementation of intensive chemotherapy protocols in this age group is associated with increased treatment-related toxicities, affecting almost every organ and system. In this case, the focus of our interest was on rather rare entities: steroid-induced psychosis that seldom develops in children and adolescents, and choroid plexus hemosiderosis, infrequently identified as a first sign of iron overload. CASE PRESENTATION: The aim of this paper is to present a challenging case of a 15-year-old Caucasian male patient treated for high-risk acute lymphoblastic leukemia and who experienced various adverse incidents during intensive chemotherapy, thus necessitating a high-quality multidisciplinary approach. Slow minimal residual disease clearance was an additional concerning issue. Induction and re-induction were complicated by steroid-induced hyperglycemia that required multiple-week insulin. During consolidation, acute kidney injury on the basis of chronic kidney disease was verified, demanding subsequent drug dose modifications. By the end of re-induction, after dexamethasone cessation, infrequent steroid-induced psychosis, presented as incoherent speech, aggressive behavior, and mood swings, required intensive psychiatric support. Neurological evaluation of seizures revealed uncommon choroid plexus hemosiderosis by brain magnetic resonance imaging, warranting appropriate selection of iron chelation therapy in the context of preexisting nephropathy. Ultimately, iron deposits of moderate intensity were verified by liver magnetic resonance imaging, while heart tissue remained intact. The early diagnosis and adequate treatment of aforementioned difficult toxicities resulted in complete recovery of the patient. CONCLUSIONS: Treating adolescents with high-risk acute leukemia and multiple therapy-related morbidities remains a challenge, even in the era of extensive and effective supportive therapy. Superior survival rates might be achieved by prompt recognition of both frequent and rarely encountered adverse episodes, as well as well-timed and appropriate management by a well-coordinated multidisciplinary team.

Role of Alternative Medical Systems in Adult Chronic Kidney Disease Patients: A Systematic Review of Literature.

There is a growing interest in the use of alternative medical systems (AMS), such as traditional Chinese medicine (TCM), ayurveda, homeopathy, and naturopathy, among chronic kidney disease patients. This review summarizes the efficacy and safety of AMS interventions in chronic kidney disease (CKD) patients. A systematic review was conducted in MEDLINE, Embase, Scopus, CINAHL, CENTRAL, and PsycINFO in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Synthesis without meta-analysis (SWiM) guidelines. Randomized controlled trials (RCTs) which evaluated the use of AMS among adult CKD patients were included. The efficacy of each AMS was assessed based on improvement in biochemical markers or reduction in symptom severity scores. All adverse reactions were recorded. Of the 14,583 articles retrieved, 33 RCTs were included. TCM (n=20) and ayurveda (n=6) were the most well-studied. Majority of studies (66.7%) had a sample size <100. Common indications evaluated included improvement in renal function (n=12), proteinuria (n=5), and uremic pruritus (n=5). Among TCM, acupuncture and syndromes-based TCM granules formulation were shown to improve estimated glomerular filtration rate (eGFR) by 5.1-15.5% and 7.07-8.12% respectively. Acupuncture reduced uremic pruritus symptoms by 54.7-60.2% while Huangkui, Shenqi granules, and Tripterygium wilfordii Hook F reduced proteinuria by 18.6-50.7%, 61.8%, and 32.1% respectively. For Ayurveda, camel milk and Nigella sativa oil improved eGFR by 16.9% and 86.8%, respectively, while capsaicin reduced pruritus scores by 84.3%. Homeopathic verum medication reduced pruritus scores by 29.2-41.5%. Nausea was the most common adverse effect reported with alpha-keto amino acids (0.07%), Nigella sativa oil (7.04%), and silymarin (10%). TCM and ayurveda were more well-studied AMS therapies that demonstrated efficacy in CKD patients. RCTs with larger sample sizes are needed to ascertain the efficacy and safety of promising AMS.

Habitual Fish Oil Supplementation and Incident Chronic Kidney Disease in the UK Biobank.

BACKGROUND: To explore the relation of habitual fish oil use with the risk of chronic kidney diseases (CKD). METHODS: 408,023 participants (54.2% female) without prior CKD and with completed information regarding their consumption of major food groups and fish oil in the UK Biobank were enrolled. Fish oil use and dietary intakes were assessed by touch screen questionnaire and food frequency questionnaire, respectively. Incident CKD was recorded from hospital inpatient records. RESULTS: At baseline, 128,843 (31.6%) participants reported taking fish oil supplements. During a median follow-up period of 12.0 years, a total of 10,782 (2.6%) participants developed CKD. With adjustments for important confounders, habitual fish oil use was associated with a significantly lower hazard of incident CKD (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.95), compared with non-use. Consistently, participants reporting ≥2 servings/week of oily fish (HR, 0.86; 95% CI, 0.79-0.94) and nonoily fish (HR, 0.86; 95% CI, 0.77-0.97) consumption had a lower hazard of incident CKD compared to those reporting no consumption ever. Additionally, among the 97,914 participants with data on plasma fatty acid, there were significant inverse relationships of plasma omega-3 polyunsaturated fatty acid (PUFA) (per SD increment, HR, 0.89, 95% CI, 0.84-0.94) and eicosatetraenoic acid (per SD increment, HR, 0.91, 95% CI, 0.87-0.96) with incident CKD. CONCLUSIONS: Habitual fish oil use was associated with a lower hazard of CKD, which was further confirmed by the consistent inverse relations between fish consumption and circulating omega-3 PUFA concentration with incident CKD.

Perspectives in systems nephrology.

Chronic kidney diseases (CKD) are a major health problem affecting approximately 10% of the world's population and posing increasing challenges to the healthcare system. While CKD encompasses a broad spectrum of pathological processes and diverse etiologies, the classification of kidney disease is currently based on clinical findings or histopathological categorizations. This descriptive classification is agnostic towards the underlying disease mechanisms and has limited progress towards the ability to predict disease prognosis and treatment responses. To gain better insight into the complex and heterogeneous disease pathophysiology of CKD, a systems biology approach can be transformative. Rather than examining one factor or pathway at a time, as in the reductionist approach, with this strategy a broad spectrum of information is integrated, including comprehensive multi-omics data, clinical phenotypic information, and clinicopathological parameters. In recent years, rapid advances in mathematical, statistical, computational, and artificial intelligence methods enable the mapping of diverse big data sets. This holistic approach aims to identify the molecular basis of CKD subtypes as well as individual determinants of disease manifestation in a given patient. The emerging mechanism-based patient stratification and disease classification will lead to improved prognostic and predictive diagnostics and the discovery of novel molecular disease-specific therapies.

Long-term efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in anaemia of chronic kidney disease: A meta-analysis including 13,146 patients.

WHAT IS KNOWN AND OBJECTIVE: Previous studies based on small-sample clinical data proved that short-term use of hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitors increased haemoglobin levels in anaemic patients with chronic kidney disease (CKD). However, these studies reached conflicting conclusions on iron parameters and adverse event profiles. Our meta-analysis aimed to evaluate the long-term efficacy and safety of HIF-PHD inhibitors in renal anaemia. METHODS: Randomized controlled trials comparing treatment with HIF-PHD inhibitors versus placebo or erythropoiesis-stimulating agents (ESAs) were thoroughly searched in the PubMed, Embase, Cochrane Library and international clinical trial registries. Meta-analysis was performed on main outcomes with random effects models. RESULTS AND DISCUSSION: A total of 30 studies comprising 13,146 patients were included. The HIF-PHD inhibitors used included roxadustat, daprodustat, vadadustat, molidustat, desidustat and enarodustat. HIF-PHD inhibitors significantly increased haemoglobin levels in comparison with placebo [weighted mean difference (WMD) 1.53, 95% confidence interval (CI) 1.39 to 1.67] or ESAs (WMD 0.13, 95% CI 0.03 to 0.22). Hepcidin, ferritin and serum iron levels were decreased, while total iron binding capacity and transferrin levels were increased in the HIF-PHD inhibitor group versus those in placebo or ESAs group. Additionally, HIF-PHD inhibitors medication was associated with cholesterol-lowering effects. As for safety, the risk of serious adverse events in the HIF-PHD inhibitor group was increased in comparison with placebo group [risk ratio (RR) 1.07, 95% CI 1.01 to 1.13], but comparable to the ESAs group (RR 1.02, 95% CI 0.94 to 1.10). Compared with placebo, the agents increased the risk of diarrhoea (1.21, 1.00 to 1.47), nausea (1.46, 1.09 to 1.97), oedema peripheral (1.32, 1.01 to 1.59), hyperkalemia (1.27, 1.05 to 1.54) and hypertension (1.34, 1.02 to 1.76). Compared with ESAs, the drugs increased the risk of vomiting (1.30, 1.02 to 1.65), headache (1.27, 1.05 to 1.53) and thrombosis events (1.31, 1.05 to 1.63). WHAT IS NEW AND CONCLUSION: HIF-PHD inhibitors treatment effectively increased haemoglobin levels and promoted iron utilization in anaemic patients with CKD, and they were well tolerated for long-term use. In order to avoid unfavourable effects of excessive iron consumption, it was appropriate to administer HIF-PHD inhibitors in combination with iron supplements for long-term treatment.

Forecasting disability-adjusted life years for chronic diseases: reference and alternative scenarios of salt intake for 2017-2040 in Japan.

BACKGROUND: In Japan, a high-sodium diet is the most important dietary risk factor and is known to cause a range of health problems. This study aimed to forecast Japan's disability-adjusted life year (DALYs) for chronic diseases that would be associated with high-sodium diet in different future scenarios of salt intake. We modelled DALY forecast and alternative future scenarios of salt intake for cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and stomach cancer (SC) from 2017 to 2040. METHODS: We developed a three-component model of disease-specific DALYs: a component on the changes in major behavioural and metabolic risk predictors including salt intake; a component on the income per person, educational attainment, and total fertility rate under 25 years; and an autoregressive integrated moving average model to capture the unexplained component correlated over time. Data on risk predictors were obtained from Japan's National Health and Nutrition Surveys and from the Global Burden of Disease Study 2017. To generate a reference forecast of disease-specific DALY rates for 2017-2040, we modelled the three diseases using the data for 1990-2016. Additionally, we generated better, moderate, and worse scenarios to evaluate the impact of change in salt intake on the DALY rate for the diseases. RESULTS: In our reference forecast, the DALY rates across all ages were predicted to be stable for CVDs, continuously increasing for CKDs, and continuously decreasing for SC. Meanwhile, the age group-specific DALY rates for these three diseases were forecasted to decrease, with some exceptions. Except for the ≥70 age group, there were remarkable differences in DALY rates between scenarios, with the best scenario having the lowest DALY rates in 2040 for SC. This represents a wide scope of future trajectories by 2040 with a potential for tremendous decrease in SC burden. CONCLUSIONS: The gap between scenarios provides some quantification of the range of policy impacts on future trajectories of salt intake. Even though we do not yet know the policy mix used to achieve these scenarios, the result that there can be differences between scenarios means that policies today can have a significant impact on the future DALYs.

Observations on the effect of thunder-fire moxibustion with meridian point on deficiency of kidney and spleen, and blood stasis in chronic kidney diseases stage three / 中国实用护理杂志

Objective@#To observe clinical effect of thunder-fire moxibustion with meridian point, including lumbar spinal cordacupoints of bladder meridian and abdominal acupoints of Ren channel, which treating on deficiency of kidney and spleen and blood stasis in chronic kidney diseases (CKD) stage 3.@*Methods@#Totally 60 patients were randomly divided into treatment and control group. 30 patients in control were treated with blood pressure and lipid adjustment, Chinese medicine and nutritional therapy. 30 patients in treatment group were treated with thunder-fire moxibustion with meridian point based on control. A moxibustion-treated course has 2 weeks, patients were treated every other day. Observe blood urea nitrogen (Bun) , creatinine (Scr) , glomerular filtration rate (eGFR) , Chinese medicine syndrome and quantitative score, as well as clinical efficacy.@*Results@#After 4 weeks of intervention, the TCM syndrome score [8 (4,10)] in the treatment group was significantly lower than that in the control group [12 (10,14)], with a statistically significant difference (Z=-3.706, P = 0.000); in the quantitative score of symptom classification, the patients in the treatment group were significantly lower than those in the control group [2 (0,2)], chills [2 (2,2)], fatigue [2 (2,4)], the difference was statistically significant (Z=-2.625, -3.593, -4.609, P < 0.01). The frequency of nocturia in the treatment group was significantly higher than that in the control group (Z=-1.989, P < 0.05), while that in the treatment group was not significantly better than that in the control group (P > 0.05). In terms of clinical efficacy, the total effective rate of the treatment group was 93.3% (28/30), which was better than73.3% (22/30) of the control group (χ2= 38.19, P = 0.000).@*Conclusion@#Thunder-fire moxibustion with meridian point improve deficiency of kidney and spleen and blood stasis of patients in CKD stage3, such as weak waist, cold chills, poor appetite, weakness and nocturia, as well as ameliorate renal function.

The effect of massage and topical violet oil on the severity of pruritus and dry skin in hemodialysis patients: A randomized controlled trial.

BACKGROUND: Pruritus is one of the common problems in hemodialysis patients that involves more than 45% of Iranian patients. Its exact pathogenesis is unclear. Meanwhile, violet is an old plant with anti-scratching effects, which is extensively used to treat diseases in the Persian medicine. This study aimed to evaluate the effect of massaging the body with and without violet oil in the treatment of uremic pruritus. METHODS: In this study 57 hemodialysis patients who had uremic pruritus were categorized randomly into two groups. The treatment involved massage with and without topical 5 ml violet oil for 7 min during six sessions (two weeks) on the healthy hand which did not have fistula pruritus score questionnaire were completed before and after the intervention. RESULTS: There was no difference between the two groups before the intervention; however, after the intervention, a significant difference was observed within each group and between the groups in terms of skin dryness score, severity, location, and frequency of pruritus, which were recovered significantly in both groups. CONCLUSION: The results of this study indicated that massage with violet oil is more effective than massage alone and is recommended as a complementary treatment for patients with uremic pruritis.

Pilates exercises and quality of life of patients with chronic kidney disease.

BACKGROUND AND PURPOSE: There is a need to investigate the effects of pilates exercises on the quality of life (QOL) of patients with chronic kidney diseases (CKD). The purpose of this study was to determine the effect of pilates exercises on the QOL of CKD patients. MATERIALS AND METHODS: For this randomized controlled clinical trial, we enrolled 50 CKD patients. The participants were randomly assigned to experimental (n = 25) and control (n = 25) groups. Modified classical pilates exercises were performed by the experimental group three times a week over a 12-week period. The Quality of Life Short Form (KDQOL-SF) questionnaire was completed by all participants at the beginning of the trial and two months after completion of the intervention. Data analysis was conducted using Chi-square, independent t-test, and paired t-test. RESULTS: There were significant increases in the scores of QOL dimensions in the experimental group after the intervention (p ≤ 0.05). Comparison of the mean differences at the beginning and two months after the study in the two groups showed that the scores related to QOL dimensions in the experimental group were significantly greater than the control group (p ≤ 0.05). CONCLUSION: The findings indicated the pilates exercises can be valuable for improvement of CKD patients' QOL.