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Martus G, Siddhuraj P, Erjefält JS, Kádár A, Lindström M, Bergling K, Öberg CM. Transcellular transport of 18F-deoxyglucose via facilitative glucose channels in experimental peritoneal dialysis. Perit Dial Int 2024:8968608241299928. [PMID: 39636030 DOI: 10.1177/08968608241299928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Local and systemic side effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transferred via facilitative glucose channels (GLUTs). Whether such transport mainly occurs into (absorption), or across (trans-cellular) peritoneal cells is as yet unresolved. METHODS Here we sought to elucidate whether diffusion of radiolabeled 18F-deoxyglucose ([18F]-DG) in the opposite direction (plasma → dialysate) is also affected by GLUT inhibition. During GLUT inhibition, such transport may either be increased or unaltered (favors absorption hypothesis) or decreased (favors transcellular hypothesis). Effects on the transport of solutes other than [18F]-DG (or glucose) during GLUT inhibition indicate effects on paracellular transport (between cells) rather than via GLUTs. RESULTS GLUT inhibition using phloretin markedly reduced [18F]-DG diffusion capacity, improved ultrafiltration (UF) rates and enhanced the sodium dip. No other solutes were significantly affected with the exception of urea and bicarbonate. CONCLUSION The present results indicate that part of glucose is transported via the transcellular route across cells in the peritoneal membrane. Regardless of the channel(s) involved, inhibitors of facilitative GLUTs may be promising agents to improve UF efficacy in patients treated with PD.
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Affiliation(s)
- Giedre Martus
- Nephrology Division, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden
| | - Premkumar Siddhuraj
- Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, Lund, Sweden
| | - Jonas S Erjefält
- Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, Lund, Sweden
- Department of Allergology and Respiratory Medicine, Skåne University Hospital, Lund University, Lund, Sweden
| | - András Kádár
- Nephrology Division, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden
| | - Martin Lindström
- Department of Laboratory Medicine, Lund University, Malmö, Sweden
- Centre for Molecular Pathology, Skåne University Hospital, Malmö, Sweden
| | - Karin Bergling
- Nephrology Division, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden
| | - Carl M Öberg
- Nephrology Division, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden
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2
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Flythe JE, Watnick S. Dialysis for Chronic Kidney Failure: A Review. JAMA 2024; 332:1559-1573. [PMID: 39356511 DOI: 10.1001/jama.2024.16338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/03/2024]
Abstract
Importance More than 3.5 million people worldwide and 540 000 individuals in the US receive maintenance hemodialysis or peritoneal dialysis for the treatment of chronic kidney failure. The 5-year survival rate is approximately 40% after initiation of maintenance dialysis. Observations Hemodialysis and peritoneal dialysis remove metabolic waste and excess body water and rebalance electrolytes to sustain life. There is no recommended estimated glomerular filtration rate (eGFR) threshold for initiating dialysis, and patient-clinician shared decision-making should help determine when to initiate dialysis. Persistent signs and symptoms of uremia (eg, nausea, fatigue) and volume overload (eg, dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia inform the timing of therapy initiation. A randomized clinical trial reported no mortality benefit to starting dialysis at higher eGFR (10-14 mL/min/1.73 m2) vs lower eGFR (5-7 mL/min/1.73 m2) levels. Observational data suggested no differences in 5-year mortality with use of hemodialysis vs peritoneal dialysis. Cardiovascular (eg, arrhythmias, cardiac arrest) and infection-related complications of maintenance dialysis are common. In the US, hemodialysis catheter-related bloodstream infections occur at a rate of 1.1 to 5.5 episodes per 1000 catheter-days and affect approximately 50% of patients within 6 months of catheter placement. Peritonitis occurs at a rate of 0.26 episodes per patient-year and affects about 30% of individuals in the first year of peritoneal dialysis therapy. Chronic kidney failure-related systemic complications, such as anemia, hyperphosphatemia, hypocalcemia, and hypertension, often require pharmacologic treatment. Hypotension during dialysis, refractory symptoms (eg, muscle cramps, itching), and malfunction of dialysis access can interfere with delivery of dialysis. Conclusions and Relevance In 2021, more than 540 000 patients in the US received maintenance hemodialysis or peritoneal dialysis for treatment of chronic kidney failure. Five-year survival rate after initiation of maintenance dialysis is approximately 40%, and the mortality rate is similar with hemodialysis and peritoneal dialysis. Decisions about dialysis initiation timing and modality are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability and should include shared decision-making.
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Affiliation(s)
- Jennifer E Flythe
- University of North Carolina Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, Chapel Hill
- Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill
| | - Suzanne Watnick
- Division of Nephrology, University of Washington School of Medicine, Seattle
- Section of Nephrology, Seattle VA Medical Center, Seattle, Washington
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3
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Hu YH, Liu YL, Meng LF, Zhang YX, Cui WP. Selection of dialysis methods for end-stage kidney disease patients with diabetes. World J Diabetes 2024; 15:1862-1873. [PMID: 39280188 PMCID: PMC11372645 DOI: 10.4239/wjd.v15.i9.1862] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 07/03/2024] [Accepted: 07/29/2024] [Indexed: 08/27/2024] Open
Abstract
The increasing prevalence of diabetes has led to a growing population of end-stage kidney disease (ESKD) patients with diabetes. Currently, kidney transplantation is the best treatment option for ESKD patients; however, it is limited by the lack of donors. Therefore, dialysis has become the standard treatment for ESKD patients. However, the optimal dialysis method for diabetic ESKD patients remains controversial. ESKD patients with diabetes often present with complex conditions and numerous complications. Furthermore, these patients face a high risk of infection and technical failure, are more susceptible to malnutrition, have difficulty establishing vascular access, and experience more frequent blood sugar fluctuations than the general population. Therefore, this article reviews nine critical aspects: Survival rate, glucose metabolism disorder, infectious complications, cardiovascular events, residual renal function, quality of life, economic benefits, malnutrition, and volume load. This study aims to assist clinicians in selecting individualized treatment methods by comparing the advantages and disadvantages of hemodialysis and peritoneal dialysis, thereby improving patients' quality of life and survival rates.
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Affiliation(s)
- Yao-Hua Hu
- Department of Nephrology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Ya-Li Liu
- Department of Nephrology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Ling-Fei Meng
- Department of Nephrology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Yi-Xian Zhang
- Department of Nephrology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Wen-Peng Cui
- Department of Nephrology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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Wang S, Zhao J, Liu C. Association between prediabetes and the incidence of gastric cancer: A meta-analysis. Medicine (Baltimore) 2024; 103:e39411. [PMID: 39183409 PMCID: PMC11346863 DOI: 10.1097/md.0000000000039411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 04/10/2024] [Accepted: 08/02/2024] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND Prediabetes has been found to be associated with an elevated overall risk of cancer, which may be site-specific. we performed a protocol for systematic review and meta-analysis to investigate the correlation between prediabetes and the incidence of gastric cancer (GC). METHODS A thorough review of the literature was conducted in the PubMed, Embase, and Web of Science databases to identify pertinent observational studies with longitudinal follow-up. The random-effects model was employed to consolidate the data, taking into account the potential impact of heterogeneity. RESULTS A total of 13 datasets from 8 prospective cohort studies were included. The prevalence of prediabetes was 9.6%. During the mean follow-up duration of 7.1 to 12.2 years, 33,135 patients were diagnosed with GC. According to the results of the pooled analysis, prediabetes was associated with a mildly higher incidence of GC over time (risk ratio: 1.07, 95% confidence interval: 1.01-1.13, P = .03; I2 = 44%). Subsequent subgroup analyses indicated that the relationship between prediabetes and the heightened risk of GC may not be substantially influenced by factors such as the country in which the study was conducted, the average age of participants, their gender, the definition of prediabetes used, the prevalence of prediabetes at the beginning of the study, the incidence of GC within the studied population, or the adjustment made for body mass index (P for subgroup difference all >.05). CONCLUSION The presence of prediabetes may increase the risk of GC by a mild amount when compared with people with normoglycemia in community-derived adult populations.
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Affiliation(s)
- Shenggang Wang
- Department of Gastrointestinal Surgery, Weifang People’s Hospital, Weifang, China
| | - Jiamin Zhao
- Department of Urology Surgery, Weifang People’s Hospital, Weifang, China
| | - Chong Liu
- Department of Gastrointestinal Surgery, Weifang People’s Hospital, Weifang, China
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5
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Cheng XBJ, Bargman J. Complications of Peritoneal Dialysis Part II: Nonmechanical Complications. Clin J Am Soc Nephrol 2024; 19:791-799. [PMID: 38190143 PMCID: PMC11168822 DOI: 10.2215/cjn.0000000000000418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Accepted: 12/21/2023] [Indexed: 01/09/2024]
Abstract
Peritoneal dialysis (PD) is a form of KRT that offers flexibility and autonomy to patients with ESKD. It is associated with lower costs compared with hemodialysis in many countries. Unlike mechanical complications that typical arise early in the course of treatment, noninfectious, nonmechanical complications often present late in patients who are established on PD. In this review, we first discuss abnormal-appearing drained dialysate, including hemoperitoneum, chyloperitoneum, and noninfectious cloudy dialysate. The underlying cause is frequently unrelated to PD. We then discuss encapsulating peritoneal sclerosis, a rare complication of PD. Finally, we review metabolic changes associated with PD and methods to mitigate its effects.
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Affiliation(s)
- Xin Bo Justin Cheng
- University Health Network, Toronto, Ontario, Canada
- Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Joanne Bargman
- University Health Network, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
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6
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Li X, Fan C, Wang C, Zhang Y, Niu L. Non-linear relationship between baseline fasting blood glucose and mortality in peritoneal dialysis patients, a retrospective cohort study. Front Med (Lausanne) 2024; 11:1325914. [PMID: 38435391 PMCID: PMC10904652 DOI: 10.3389/fmed.2024.1325914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Accepted: 01/31/2024] [Indexed: 03/05/2024] Open
Abstract
Background The relationship between baseline fasting blood glucose (bFBG) and mortality in peritoneal dialysis (PD) patients has been the subject of debate, with limited exploration of the non-linear relationship between bFBG and death in these patients. Methods This retrospective study categorized patients into four groups based on their bFBG using quartiles. Baseline clinical data at the initiation of dialysis were compared. Survival curves were plotted, and subgroup analyses were stratified by relevant covariates. To address the non-linear relationship, curve fitting and a threshold effect analysis were performed. Results The study included 379 PD patients with a median follow-up of 41.8 (22.6, 60.1) months. The COX proportional hazards model showed an association between bFBG and the risk of death after adjusting for confounding factors [hazard ratio (HR): 1.22, 95% CI: 1.05-1.41, P = 0.009]. Stratified analyses indicated a stable correlation between bFBG and mortality. The Kaplan-Meier curve analysis revealed significant differences in survival rates among different groups based on bFBG levels (P < 0.01). The curve fitting analysis revealed a U-shaped relationship between bFBG and mortality, with an inflection point at approximately 5.1 mmol/L. Conclusion Our study has demonstrated a non-linear relationship between bFBG and mortality in PD patients. Additionally, we have found that the optimal bFBG value associated with the lowest risk of mortality is approximately 5.1 mmol/L.
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Affiliation(s)
- Xiang Li
- Department of Nephrology, Affiliated Hospital of Jining Medical University, Jining, China
| | - Chengjuan Fan
- Department of Nephrology, Affiliated Hospital of Jining Medical University, Jining, China
| | - Chen Wang
- Department of Nephrology, Affiliated Hospital of Jining Medical University, Jining, China
| | - Yiming Zhang
- Department of Nephrology, Affiliated Hospital of Jining Medical University, Jining, China
| | - Lingling Niu
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining, China
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Tang CC, Tsai JP, Chen YH, Hung SC, Lin YL, Hsu BG. Associations of Glucometabolic Indices with Aortic Stiffness in Patients Undergoing Peritoneal Dialysis with and without Diabetes Mellitus. Int J Mol Sci 2023; 24:17094. [PMID: 38069423 PMCID: PMC10707165 DOI: 10.3390/ijms242317094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 11/28/2023] [Accepted: 12/02/2023] [Indexed: 12/18/2023] Open
Abstract
Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (β = 0.52, 95% confidence interval [CI] = 0.01-1.03, p = 0.046), high HOMA-IR (β = 0.60, 95% CI = 0.12-1.08, p = 0.015), and a high PD glucose load (β = 0.58, 95% CI = 0.08-1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness.
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Affiliation(s)
- Chi-Chong Tang
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan;
- Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan
| | - Jen-Pi Tsai
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; (J.-P.T.); (S.-C.H.)
- Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan
| | - Yi-Hsin Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan;
| | - Szu-Chun Hung
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; (J.-P.T.); (S.-C.H.)
- Division of Nephrology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan
| | - Yu-Li Lin
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan;
- Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; (J.-P.T.); (S.-C.H.)
| | - Bang-Gee Hsu
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan;
- Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; (J.-P.T.); (S.-C.H.)
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8
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Zanchi A, Jehle AW, Lamine F, Vogt B, Czerlau C, Bilz S, Seeger H, de Seigneux S. Diabetic kidney disease in type 2 diabetes: a consensus statement from the Swiss Societies of Diabetes and Nephrology. Swiss Med Wkly 2023; 153:40004. [PMID: 36652726 DOI: 10.57187/smw.2023.40004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Diabetic kidney disease is highly prevalent in patients with type 2 diabetes and is a major cause of end-stage renal disease in Switzerland. Patients with diabetic kidney disease are among the most complex patients in diabetes care. They require a multifactorial and multidisciplinary approach with the goal to slow the decline in glomerular filtration rate (GFR) and cardiovascular morbidity. With this consensus we propose an evidence-based guidance to health care providers involved in the care of type 2 diabetic patients with diabetic kidney disease.First, there is a need to increase physician awareness and improve screening for diabetic kidney disease as early intervention may improve clinical outcomes and the financial burden. Evaluation of estimated GFR (eGFR) and spot urine albumin/creatinine ratio is recommended at least annually. Once it is diagnosed, glucose control and optimisation of blood pressure control with renin-angiotensin system blockers have been recommended as mainstay management of diabetic kidney disease for more than 20 years. Recent, high quality randomised controlled trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibition slows eGFR decline and cardiovascular events beyond glucose control. Likewise, mineralocorticoid receptor antagonism with finerenone has cardiorenal protective effects in diabetic kidney disease. Glucagon-like peptide-1 (GLP1) receptor agonists improve weight loss if needed, and decrease albuminuria and cardiovascular morbidity. Lipid control is also important to decrease cardiovascular events. All these therapies are included in the treatment algorithms proposed in this consensus. With advancing kidney failure, other challenges may rise, such as hyperkalaemia, anaemia and metabolic acidosis, as well as chronic kidney disease-mineral and bone disorder. These different topics and treatment strategies are discussed in this consensus. Finally, an update on diabetes management in renal replacement therapy such as haemodialysis, peritoneal dialysis and renal transplantation is provided. With the recent developments of efficient therapies for diabetic kidney disease, it has become evident that a consensus document is necessary. We are optimistic that it will significantly contribute to a high-quality care for patients with diabetic kidney disease in Switzerland in the future.
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Affiliation(s)
- Anne Zanchi
- Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.,Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland
| | - Andreas W Jehle
- Department of Internal Medicine, Hirslanden Klinik St. Anna, Lucerne, Switzerland.,Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Faiza Lamine
- Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.,Unit of Diabetes and Endocrinology, Department of Internal Medicine, Riviera-Chablais Hospital (HRC), Rennaz, Switzerland
| | - Bruno Vogt
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Cecilia Czerlau
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Stefan Bilz
- Internal Medicine and Endocrinology, Kantonsspital St Gallen, Switzerland
| | - Harald Seeger
- Division of Nephrology, University Hospital Zurich, Switzerland
| | - Sophie de Seigneux
- Service of Nephrology and Hypertension, Department of Medicine, Geneva University Hospital, Switzerland
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9
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Bergling K, Martus G, Öberg CM. Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats. J Am Soc Nephrol 2022; 33:1857-1863. [PMID: 35985816 PMCID: PMC9528341 DOI: 10.1681/asn.2022040474] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 07/14/2022] [Accepted: 07/24/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis (PD). We previously showed that inhibition of sodium glucose cotransporter 2 did not affect glucose transport during PD in rats. However, more recently, we found that phlorizin, a dual blocker of sodium glucose cotransporters 1 and 2, reduces glucose diffusion in PD. Therefore, either inhibiting sodium glucose cotransporter 1 or blocking facilitative glucose channels by phlorizin metabolite phloretin would reduce glucose transport in PD. METHODS We tested a selective blocker of sodium glucose cotransporter 1, mizagliflozin, as well as phloretin, a nonselective blocker of facilitative glucose channels, in an anesthetized Sprague-Dawley rat model of PD. RESULTS Intraperitoneal phloretin treatment reduced glucose absorption by >30% and resulted in a >50% higher ultrafiltration rate compared with control animals. Sodium removal and sodium clearances were similarly improved, whereas the amount of ultrafiltration per millimole of sodium removed did not differ. Mizagliflozin did not influence glucose transport or osmotic water transport. CONCLUSIONS Taken together, our results and previous results indicate that blockers of facilitative glucose channels may be a promising target for reducing glucose absorption and improving ultrafiltration efficiency in PD.
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Affiliation(s)
- Karin Bergling
- Division of Nephrology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
| | - Giedre Martus
- Division of Nephrology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
| | - Carl M. Öberg
- Division of Nephrology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
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10
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Zhao YY. Recent advances of gut microbiota in chronic kidney disease patients. EXPLORATION OF MEDICINE 2022:260-274. [DOI: 10.37349/emed.2022.00090] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/21/2022] [Indexed: 01/23/2025] Open
Abstract
Chronic kidney disease (CKD) is a worldwide public health issue and has ultimately progressed to an end-stage renal disease that requires life-long dialysis or renal transplantation. However, the underlying molecular mechanism of these pathological development and progression remains to be fully understood. The human gut microbiota is made up of approximately 100 trillion microbial cells including anaerobic and aerobic species. In recent years, more and more evidence has indicated a clear association between dysbiosis of gut microbiota and CKD including immunoglobulin A (IgA) nephropathy, diabetic kidney disease, membranous nephropathy, chronic renal failure and end-stage renal disease. The current review describes gut microbial dysbiosis and metabolites in patients with CKD thus helping to understand human disease. Treatment with prebiotics, probiotics and natural products can attenuate CKD through improving dysbiosis of gut microbiota, indicating a novel intervention strategy in patients with CKD. This review also discusses therapeutic options, such as prebiotics, probiotics and natural products, for targeting dysbiosis of gut microbiota in patients to provide more specific concept-driven therapy strategy for CKD treatment.
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Affiliation(s)
- Ying-Yong Zhao
- Faculty of Life Science & Medicine, Northwest University, Xi’an 710069, Shaanxi, China
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11
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Bergling K, de Arteaga J, Ledesma F, Öberg CM. Optimised versus standard automated peritoneal dialysis regimens pilot study (OptiStAR): A randomised controlled crossover trial. ARCH ESP UROL 2022; 42:615-621. [PMID: 35034532 DOI: 10.1177/08968608211069232] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND The continuous global rise of end-stage kidney disease creates a growing demand of economically beneficial home-based kidney replacement therapies such as peritoneal dialysis (PD). However, undesirable absorption and exposure of peritoneal tissues to glucose remain major limitations of PD. METHODS We compared a reference (standard) automated PD regimen 6 × 2 L 1.36% glucose (76 mmol/L) over 9 h with a novel, theoretically glucose sparing (optimised) prescription consisting of 'ultrafiltration cycles' with high glucose strength (126 mmol/L) and 'clearance cycles' with ultra-low, physiological glucose (5 mmol/L) for approximately 40% of the treatment time. Twenty-one prevalent PD patients underwent the optimised regimen (7 × 2 L 2.27% glucose + 5 × 2 L 0.1% glucose over 8 h) and the standard regimen in a crossover fashion. Six patients were excluded from data analysis. RESULTS Median glucose absorption was 43 g (IQR 41-54) and 44 g (40-55) for the standard and optimised intervention, respectively (p = 1). Ultrafiltration volume, weekly Kt/V creatinine and urea were significantly improved during optimised interventions, while no difference in sodium removal was detected. Post hoc analysis showed significantly improved ultrafiltration efficiency (ml ultrafiltration per gram absorbed glucose) during optimised regimens. No adverse events were observed except one incidence of drain pain. CONCLUSION Optimised treatments were feasible and well tolerated in this small pilot study. Despite no difference in absorbed glucose, results indicate possible improvements of ultrafiltration efficiency and small solute clearances by optimised regimens. Use of optimised prescriptions as glucose sparing strategy should be evaluated in larger study populations.
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Affiliation(s)
- Karin Bergling
- Department of Nephrology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Sweden
| | - Javier de Arteaga
- Servicio de Nefrología, Hospital Privado Universitario IUCBC, Fundacion Nefrologica de Córdoba, Argentina
| | - Fabián Ledesma
- Servicio de Nefrología, Hospital Privado Universitario IUCBC, Fundacion Nefrologica de Córdoba, Argentina
| | - Carl M Öberg
- Department of Nephrology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Sweden
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12
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Lambie M, Bonomini M, Davies SJ, Accili D, Arduini A, Zammit V. Insulin resistance in cardiovascular disease, uremia, and peritoneal dialysis. Trends Endocrinol Metab 2021; 32:721-730. [PMID: 34266706 PMCID: PMC8893168 DOI: 10.1016/j.tem.2021.06.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/03/2021] [Accepted: 06/15/2021] [Indexed: 02/09/2023]
Abstract
Diabetic nephropathy is highly correlated with the occurrence of other complications of type 1 diabetes (T1D) and type 2 diabetes (T2D) mellitus; for example, hypertension with cardiovascular disease (CVD) being the most frequent cause of death in patients with end-stage renal disease and undergoing renal dialysis. Hyperglycemia and insulin resistance (IR) are responsible for the micro- and macrovascular complications of diabetes through different mechanisms. In particular, IR plays a key role in the etiology of atherosclerosis in both diabetic and non-diabetic patients. IR - exacerbated by organ-level selectivity - is more important than glycemic control per se in determining cardiovascular outcomes. This may be exacerbated by the fact that IR is organ and pathway specific due to the only selective loss of sensitivity to insulin action of specific pathways/processes. Therefore, it is counterintuitive that the use of peritoneal dialysis (PD) in (frequently) diabetic renal disease patients should involve their exposure to high daily doses of glucose peritoneally. In view of the controversy about the causal association between glucose load and CVD in PD patients, we discuss the role that selective IR may play in the progression of CVD in diabetic renal end-stage patients. In discussing these associations, we propose that reducing glucose exposure in PD solutions may be beneficial especially if coupled with strategies that address IR directly, and the avoidance of excessive use of insulin treatment in T2D.
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Affiliation(s)
- Mark Lambie
- Faculty of Medicine and Health Sciences, Keele University, Keele ST5 5BG, UK
| | - Mario Bonomini
- Department of Medicine, G. d'Annunzio University, Chieti 66100, Italy
| | - Simon J Davies
- Faculty of Medicine and Health Sciences, Keele University, Keele ST5 5BG, UK
| | - Domenico Accili
- Columbia University College of Physicians and Surgeons, Department of Medicine, New York, NY 10032, USA
| | | | - Victor Zammit
- Translational & Experimental Medicine, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
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Martus G, Bergling K, de Arteaga J, Öberg CM. SGLT2 inhibition does not reduce glucose absorption during experimental peritoneal dialysis. Perit Dial Int 2021; 41:373-380. [PMID: 33845652 DOI: 10.1177/08968608211008095] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients. Recent experimental data indicated that inhibitors of the sodium and glucose co-transporter (SGLT)-2 could act to reduce glucose uptake during PD, which raises the question of whether glucose absorption may also occur via intracellular or trans-cellular pathways. METHODS We performed PD in anesthetized Sprague-Dawley rats using a fill volume of 20 mL with either 1.5% glucose fluid or 4.25% glucose fluid for 120 min dwell time to evaluate the effects of SGLT2 inhibition by empagliflozin on peritoneal water and solute transport. To assess the diffusion capacity of glucose, we developed a modified equation to measure small solute diffusion capacity, taking convective- and free water transport into account. RESULTS SGLT2 inhibition markedly increased the urinary excretion of glucose and lowered plasma glucose after PD compared to sham groups. Glucose absorption for 1.5% glucose was 165 mg 95% CI (145-178) in sham animals and 157 mg 95% CI (137-172) for empagliflozin-treated animals. For 4.25% glucose, absorption of glucose was 474 mg 95% CI (425-494) and 472 mg 95% CI (420-506) for sham and empagliflozin groups, respectively. No significant changes in the transport of sodium or water across the peritoneal barrier could be detected. CONCLUSION We could not confirm recent findings that SGLT2 inhibition reduced glucose absorption and increased osmotic water transport during experimental PD.
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Affiliation(s)
- Giedre Martus
- Department of Nephrology, Clinical Sciences Lund, Skåne University Hospital, 5193Lund University, Sweden
| | - Karin Bergling
- Department of Nephrology, Clinical Sciences Lund, Skåne University Hospital, 5193Lund University, Sweden
| | - Javier de Arteaga
- Servicio de Nefrología, Hospital Privado de Córdoba, 28187Universidad Católica de Córdoba, Argentina
| | - Carl M Öberg
- Department of Nephrology, Clinical Sciences Lund, Skåne University Hospital, 5193Lund University, Sweden
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Shi Y, Cai J, Shi C, Liu C, Li Z. Incidence and mortality of new-onset glucose disorders in peritoneal dialysis patients in China: a meta-analysis. BMC Nephrol 2020; 21:152. [PMID: 32349684 PMCID: PMC7191695 DOI: 10.1186/s12882-020-01820-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 04/19/2020] [Indexed: 11/10/2022] Open
Abstract
Background Dialysis patients are at high risk of developing glucose metabolism disturbances (GMDs), such as diabetes mellitus (DM), impaired fast glucose (IFG), and impaired glucose tolerance (IGT). However, it is unclear about the incidence of GMDs in Chinese patients with peritoneal dialysis (PD), as well as the influence of new-onset DM (NODM) on the prognosis of PD patients. Therefore, we conducted this meta-analysis to address these issues. Methods A comprehensive literature search was conducted using PubMed, Embase, Web of Science, SinoMed, and CNKI database for studies that evaluated the incidence of GMDs and mortality in patients with PD. Results were expressed as hazard ratio (HR), risk ratio (RR), or estimate (ES) with 95% confidence intervals (95%CIs).Meta-analysis was performed using a fixed-effects or random-effects model to pool the estimate. Results Fifteen studies met the inclusion criteria and were included in this meta-analysis. Pooled results showed that, the incidences of NODM, NOIGT, and NOIFG were 12% (95%CI: 9, 15%; P < 0.001), 17% (95%CI: 4, 10%; P < 0.001) and 32% (95%CI: 3, 30%, P < 0.001), respectively. Compared with patients without NODM, PD patients with NODM had an increased risk of mortality (HR = 1.59, 95%CI: 1.28, 1.98; P < 0.001). There was no significant difference in the incidence of NODM between PD and hemodialysis (HD) patients (RR = 1.23, 95%CI: 0.61, 2.51; P = 0.562). Conclusion Dialysis patients in China had an increased risk of developing GMDs, however, the dialysis modality did not have any significant impact on the incidence of NODM. NODM increased the mortality risk in patients undergoing PD. Thus, physicians should pay attention to the plasma glucose level in patients undergoing dialysis.
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Bergling K, de Arteaga J, Ledesma F, Öberg CM. Optimized vs. Standard Automated Peritoneal Dialysis Regimens (OptiStAR): study protocol for a randomized controlled crossover trial. Pilot Feasibility Stud 2020; 6:81. [PMID: 32528722 PMCID: PMC7285558 DOI: 10.1186/s40814-020-00620-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 05/24/2020] [Indexed: 12/12/2022] Open
Abstract
Background It has been estimated that automated peritoneal dialysis (APD) is currently the fastest growing renal replacement therapy in the world. However, in light of the growing number of diabetic patients on peritoneal dialysis (PD), the unwanted glucose absorption during APD remains problematic. Recent results, using an extended 3-pore model of APD, indicated that large reductions in glucose absorption are possible by using optimized bi-modal treatment regimens, having “UF cycles” using a higher glucose concentration, and “Clearance cycles” using a low concentration or, preferentially, no glucose. The present study is designed to test the theoretical prediction of a lower glucose absorption using these novel regimes. Methods This study is a randomized single-center, open-label, prospective study. Prevalent PD patients between 18 and 75 years old without known catheter problems or recent peritonitis are eligible for inclusion. Patients are allocated to a first treatment session of either standard APD (6 × 2 L 1.36% over 9 h) or optimized APD (7 × 2 L 2.27% + 5 × 2 L 0.1% over 8 h). A second treatment session using the other treatment will be performed in a crossover fashion. Samples of the dialysis fluid will be taken before and after the treatment, and the volume of the dialysate before and after the treatment will be carefully assessed. The primary endpoint is difference in glucose absorption between the optimized and standard treatment. Secondary endpoints are ultrafiltration, sodium removal, Kt/V urea, and Kt/V Creatinine. The study will be closed when a total of 20 patients have successfully completed the interventions or terminated according to interim analysis. A Monte Carlo power analysis shows that the study has 80% power to detect a difference of 10 g (in line with that of theoretical results) in glucose absorption between the two treatments in 10 patients. Discussion The present study is the first clinical investigation of optimized bi-modal treatments proposed by recent theoretical studies. Trial registration ClinicalTrials.gov identifier: NCT04017572. Registration date: July 12, 2019, retrospectively registered.
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Affiliation(s)
- Karin Bergling
- Division of Nephrology, Department of Clinical Sciences Lund, Lund University, Alwall House, Skåne University Hospital, Barngatan 2, 22185 Lund, Sweden
| | - Javier de Arteaga
- Servicio de Nefrología, Hospital Privado Universitario de Córdoba, Universidad Católica de Córdoba, Naciones Unidas 346, 5016 Córdoba, Argentina
| | - Fabián Ledesma
- Servicio de Nefrología, Hospital Privado Universitario de Córdoba, Universidad Católica de Córdoba, Naciones Unidas 346, 5016 Córdoba, Argentina
| | - Carl Mikael Öberg
- Division of Nephrology, Department of Clinical Sciences Lund, Lund University, Alwall House, Skåne University Hospital, Barngatan 2, 22185 Lund, Sweden
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Huang L, Xue C, Kuai J, Ruan M, Yang B, Chen X, Zhang Y, Qian Y, Wu J, Zhao X, Mei C, Xu J, Mao Z. Clinical Characteristics and Outcomes of Community-Acquired versus Hospital-Acquired Acute Kidney Injury: A Meta-Analysis. Kidney Blood Press Res 2019; 44:879-896. [PMID: 31553972 DOI: 10.1159/000502546] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 08/06/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The different clinical characteristics of community-acquired acute kidney injury (CA-AKI) versus hospital-acquired AKI (HA-AKI) have remained inconclusive, and thus, a meta-analysis was conducted to summarize and quantify the clinical significance distinguishing the 2 types of AKI. METHODS We identified observational studies reporting the clinical characteristics and prognosis of HA-AKI and CA-AKI. ORs and mean differences (MDs) were extracted for each outcome and the results aggregated. The primary outcome was defined as the mortality rate; renal recovery, oliguria incidence, dialysis, intensive care unit (ICU) requirement, and length of hospital stay were secondary outcomes. RESULTS Fifteen eligible studies involving 46,157 patients (22,791 CA-AKI patients and 23,366 HA-AKI patients) were included. Mortality was significantly lower in CA-AKI than in HA-AKI patients, with an OR of 0.43 (95% CI 0.35-0.53). The incidence of oliguria and need for ICU were also lower in CA-AKI patients (OR 0.58, 95% CI 0.38-0.88; OR 0.24, 95% CI 0.14-0.40, respectively). CA-AKI patients had a shorter hospital stay (MD -9.42, 95% CI -13.73 to -5.12). The renal recovery rate and dialysis need between CA- and HA-AKI were similar (OR 1.27, 95% CI 0.53-3.02; OR 1.05, 95% CI 0.82-1.34, respectively). CONCLUSIONS CA-AKI showed better clinical manifestations with a lower incidence of oliguria, reduced risk of ICU treatment, and shorter hospital stay. Mortality associated with CA-AKI was lower compared with HA-AKI, indicating a better prognosis. The rate of renal recovery and need for dialysis showed no significant difference between the 2 groups.
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Affiliation(s)
- Linxi Huang
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Cheng Xue
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jianke Kuai
- Third Hospital of Xi'an, Department of Anesthesiology, Xi'an, China
| | - Mengna Ruan
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Bo Yang
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xujiao Chen
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yu Zhang
- Medical team of 32120 troop of PLA, Dalian, China
| | - Yixin Qian
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jun Wu
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xuezhi Zhao
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Changlin Mei
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jing Xu
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Zhiguo Mao
- Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China,
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