scholarly journals Sodium-glucose cotransporter 2 inhibitors for diabetic kidney disease: a primer for deprescribing

2019 ◽  
Vol 12 (5) ◽  
pp. 620-628 ◽  
Author(s):  
Jiahua Li ◽  
Christopher O Fagbote ◽  
Min Zhuo ◽  
Chelsea E Hawley ◽  
Julie M Paik

Abstract Chronic kidney disease (CKD) is a critical global public health problem associated with high morbidity and mortality, poorer quality of life and increased health care expenditures. CKD and its associated comorbidities are one of the most complex clinical constellations to manage. Treatments for CKD and its comorbidities lead to polypharmacy, which exponentiates the morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown remarkable benefits in cardiovascular and renal protection in patients with type 2 diabetes mellitus (T2DM). The pleiotropic effects of SGLT2is beyond glycosuria suggest a promising role in reducing polypharmacy in diabetic CKD, but the potential adverse effects of SGLT2is should also be considered. In this review, we present a typical case of a patient with multiple comorbidities seen in a CKD clinic, highlighting the polypharmacy and complexity in the management of proteinuria, hyperkalemia, volume overload, hyperuricemia, hypoglycemia and obesity. We review the cardiovascular and renal protection effects of SGLT2is in the context of clinical trials and current guidelines. We then discuss the roles of SGLT2is in the management of associated comorbidities and review the adverse effects and controversies of SGLT2is. We conclude with a proposal for deprescribing principles when initiating SGLT2is in patients with diabetic CKD.

2021 ◽  
Vol 22 (9) ◽  
pp. 4480
Author(s):  
Maria Tziastoudi ◽  
Georgios Pissas ◽  
Georgios Raptis ◽  
Christos Cholevas ◽  
Theodoros Eleftheriadis ◽  
...  

Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. In an effort to elucidate the contribution of genetic variants located in several genes in the response to treatment of patients with CKD, we performed a systematic review and meta-analysis of all available pharmacogenetics studies. The association between genotype distribution and response to medication was examined using the dominant, recessive, and additive inheritance models. Subgroup analysis based on ethnicity was also performed. In total, 29 studies were included in the meta-analysis, which examined the association of 11 genes (16 polymorphisms) with the response to treatment regarding CKD. Among the 29 studies, 18 studies included patients with renal transplantation, 8 involved patients with nephrotic syndrome, and 3 studies included patients with lupus nephritis. The present meta-analysis provides strong evidence for the contribution of variants harbored in the ABCB1, IL-10, ITPA, MIF, and TNF genes that creates some genetic predisposition that reduces effectiveness or is associated with adverse events of medications used in CKD.


Author(s):  
Khalikul Razi ◽  
Yopie Afriandi Habibie ◽  
Zulfan Zulfan ◽  
Rovy Pratama

In recent decades, kidney disease has been documented as a global public health problem. The current challenge is about improving the treatment of chronic kidney disease (CKD) patients in order to provide a longer life expectancy for them. In hemodialysis, there has been a considerable development in finding access to the vascular system, one of which developments was the creation of arteriovenous access by Cimino and Brescia (called an AV shunt). Research on the AV shunt is still limited, so the researchers are interested in conducting this descriptive epidemiological survey study on the profile of patients undergoing AV shunt procedures at Dr. Zainoel Abidin General Hospital in Banda Aceh in 2017. Data were obtained retrospectively from the medical records of the Central Surgery Installation Department of Dr.Zainoel Abidin General Hospital in Banda Aceh, and there were 105 patients have undergone AV shunt, 72 men (68.6%) and 33 women (31.4%). The frequency based on the age was the risking age about 45-54 years as many as 30 people (28.6%). Based on the outcomes obtained 95 people (90.48%) who have used the AV shunt for hemodialysis access, consisting of 66 men (62.86%) and 29 women (27.62). Based on the duration of use, AV Shunt is mostly used for 1 year with the number of 48 patients (50.52%) in the proportion of men and women were 38.95% and 11.57%. With an average duration of use of AV Shunt 2,6 years. From the results of this study, we conclude that the result was obtained that the highest cases in patients who have undergone AV Shunt is man as much as 68.6%. Furthermore, Pertaining to this study, it was obtained that the majority of age who undergo Av shunt is 45-54 years. In addition, the result of this study showed that the success rate of surgery AV shunt in Dr. Zainoel Abidin General Hospital in Banda Aceh was high. It is about 90, 48% with an average duration use of Av shunt is 2.6 years.


2019 ◽  
Vol 48 (1) ◽  
pp. 32-39
Author(s):  
Deidra C. Crews ◽  
Aminu K. Bello ◽  
Gamal Saadi ◽  

Kidney disease is a global public health problem, affecting over 750 million persons worldwide. The burden of kidney disease varies substantially across the world. In many settings, rates of kidney disease and the provision of its care are defined by socioeconomic, cultural, and political factors leading to significant disparities. World Kidney Day 2019 offers an opportunity to raise awareness of kidney disease and highlight disparities in its burden and current state of global capacity for prevention and management. Here, we highlight the need for strengthening basic infrastructure for kidney care services for early detection and management of acute kidney injury and chronic kidney disease across all countries and advocate for more pragmatic approaches to providing renal replacement therapies. Achieving universal health coverage worldwide by 2030 is a World Health Organization Sustainable Development Goal. While universal health coverage may not include all elements of kidney care in all countries, understanding what is locally feasible and important with a focus on reducing the burden and consequences of kidney disease would be an important step towards achieving kidney health equity.


2018 ◽  
Vol 34 (11) ◽  
pp. 1853-1863 ◽  
Author(s):  
Ruifeng Wang ◽  
Titi Chen ◽  
Chengshi Wang ◽  
Zhiqiang Zhang ◽  
Xin Maggie Wang ◽  
...  

Abstract Background Chronic kidney disease (CKD) is a global public health problem, which lacks effective treatment. Previously, we have shown that CD103+ dendritic cells (DCs) are pathogenic in adriamycin nephropathy (AN), a model of human focal segmental glomerulosclerosis (FSGS). Fms-like tyrosine kinase 3 (Flt3) is a receptor that is expressed with high specificity on tissue resident CD103+ DCs. Methods To test the effect on CD103+ DCs and kidney injury of inhibition of Flt3, we used a selective Flt3 inhibitor (AC220) to treat mice with AN. Results Human CD141+ DCs, homologous to murine CD103+ DCs, were significantly increased in patients with FSGS. The number of kidney CD103+ DCs, but not CD103− DCs or plasmacytoid DCs, was significantly decreased in AN mice after AC220 administration. Treatment with AC220 significantly improved kidney function and reduced kidney injury and fibrosis in AN mice. AC220-treated AN mice had decreased levels of inflammatory cytokines and chemokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, CCL2 and CCL5 and reduced kidney infiltration of CD4 T cells and CD8 T cells. The protective effect of AC220 was associated with its suppression of CD103+ DCs-mediated CD8 T cell proliferation and activation in AN mice. Conclusion Flt3 inhibitor AC220 effectively reduced kidney injury in AN mice, suggesting that this inhibitor might be a useful pharmaceutical agent to treat CKD.


2013 ◽  
Vol 154 (2) ◽  
pp. 43-51 ◽  
Author(s):  
Judit Nagy

Chronic kidney disease is a general term for heterogenous disorders with >3 months duration affecting kidney structure and function. Nowadays, involving 10–16% of the adult population worldwide, chronic kidney disease is recognised as a major global public health problem. The number of cases is continuously increasing. In this review, epidemiology, definition, new classification and a conceptual model for development, progression and complications of chronic kidney disease as well as strategies to improve outcome are summarized. Orv. Hetil., 2013, 154, 43–51.


2021 ◽  
Vol 10 (11) ◽  
pp. 2255
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom

Chronic kidney disease (CKD), a damaged condition of the kidneys, is a global public health problem that can be caused by diabetes, hypertension, and other disorders. Recently, the MANBA gene was identified in CKD by integrating CKD-related variants and kidney expression quantitative trait loci (eQTL) data. This study evaluated the effects of MANBA gene variants on CKD and kidney function-related traits using a Korean cohort. We also analyzed the association of MANBA gene variants with kidney-related traits such as the estimated glomerular filtration rate (eGFR), and blood urea nitrogen (BUN), creatinine, and uric acid levels using linear regression analysis. As a result, 14 single nucleotide polymorphisms (SNPs) were replicated in CKD (p < 0.05), consistent with previous studies. Among them, rs4496586, which was the most significant for CKD and kidney function-related traits, was associated with a decreased CKD risk in participants with the homozygous minor allele (CC), increased eGFR, and decreased creatinine and uric acid concentrations. Furthermore, the association analysis between the rs4496586 genotype and MANBA gene expression in human tubules and glomeruli showed high MANBA gene expression in the minor allele carriers. In conclusion, this study demonstrated that MANBA gene variants were associated with CKD and kidney function-related traits in a Korean cohort.


2016 ◽  
Vol 130 (23) ◽  
pp. 2209-2216 ◽  
Author(s):  
Sophie Liabeuf ◽  
Cédric Villain ◽  
Ziad A. Massy

Chronic kidney disease (CKD) has emerged as a global public health problem. Although the incidence and prevalence of CKD vary from one country to another, the estimated worldwide prevalence is 8–16%. The complications associated with CKD include progression to end-stage renal disease (ESRD), mineral and bone disorders, anaemia, cognitive decline and elevated all-cause and cardiovascular (CV) mortality. As a result of progressive nephron loss, patients with late-stage CKD are permanently exposed to uraemic toxins. These toxins have been classified into three groups as a function of the molecular mass: small water-soluble molecules, middle molecules and protein-bound uraemic toxins. The compounds can also be classified according to their origin (i.e. microbial or not) or their protein-binding ability. The present review will focus on the best-characterized protein-bound uraemic toxins, namely indoxylsulfate (IS), indole acetic acid (IAA) and p-cresylsulfate (PCS, a cresol metabolite). Recent research suggests that these toxins accelerate the progression of CV disease, kidney disease, bone disorders and neurological complications. Lastly, we review therapeutic approaches that can be used to decrease toxin levels.


2016 ◽  
Vol 311 (4) ◽  
pp. F671-F681 ◽  
Author(s):  
Kunyu Shen ◽  
David W. Johnson ◽  
Glenda C. Gobe

Cyclic nucleotide signal transduction pathways are an emerging research field in kidney disease. Activated cell surface receptors transduce their signals via intracellular second messengers such as cAMP and cGMP. There is increasing evidence that regulation of the cGMP-cGMP-dependent protein kinase 1-phosphodiesterase (cGMP-cGK1-PDE) signaling pathway may be renoprotective. Selective PDE5 inhibitors have shown potential in treating kidney fibrosis in patients with chronic kidney disease (CKD), via their downstream signaling, and these inhibitors also have known activity as antithrombotic and anticancer agents. This review gives an outline of the cGMP-cGK1-PDE signaling pathways and details the downstream signaling and regulatory functions that are modulated by cGK1 and PDE inhibitors with regard to antifibrotic, antithrombotic, and antitumor activity. Current evidence that supports the renoprotective effects of regulating cGMP-cGK1-PDE signaling is also summarized. Finally, the effects of icariin, a natural plant extract with PDE5 inhibitory function, are discussed. We conclude that regulation of cGMP-cGK1-PDE signaling might provide novel, therapeutic strategies for the worsening global public health problem of CKD.


Author(s):  
I. Dudar ◽  
I. Mykhaloiko

Chronic kidney disease (CKD) has become a global public health problem because of its high prevalence and the accompanying increase in the risk of end-stage renal disease, cardiovascular disease, and premature death. At present there is a number of experimental and clinical data that show that one of the important mechanisms of the pathogenesis of CKD is a violation of the blood coagulation system (hemostasis) both locally in the kidneys and with the capture of the microcirculatory channel of other organs, therefore an important task for specialists in the  nephrology, as well as doctors of other specialties is  understanding  the functioning of the system of hemostasis in normal and in various kidney diseases and the correction of this pathology with drugs. There are several types of haemostasis disorders that may occur in CKD: disseminated intravascular coagulation syndrome (DIC), arterial and venous thrombosis and bleeding. In this review, we tried to determine the place of the DIC in the development and progress of the CKD and to assess the prospects for further research.


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