Cause Of Chronic Kidney Disease Research Articles

Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis.

Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD). This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease. A comprehensive systematic review provides a clear conclusion and high-level evidence for the association between ELMO1 gene and DKD for future application in personalized medicine. A comprehensive search of electronic databases, per PRISMA instructions, was conducted in Scopus, EMBASE, Web of Science, and PubMed databases from 1980 to January 2023. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using appropriate models. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and assess the robustness of the findings. A total of 5794 diabetes patients with DKD, 4886 diabetes patients without DKD, and 2023 healthy controls were included in the 17 studies that made up this systematic review. In the investigation of DM (Diabetes Mellitus) with DKD vs. DM without DKD, the susceptibility for DKD for the EMLO1 rs741301 polymorphism indicated a significant difference under the dominant, homozygote, and recessive genetic models. The susceptibility for DKD for the EMLO1 rs1345365, rs10255208, and rs7782979 polymorphisms demonstrated a significant difference under the allele genetic models in the analysis of DM with DKD vs. DM without DKD groups. There was a considerable increase in DKD risk in the Middle East when the population was stratified by the region. The findings of the meta-analysis show that there are a significant connection between the EMLO1 rs741301 polymorphism and DKD susceptibility in overall analyses; as well as rs1345365, rs10255208, and rs7782979 polymorphisms; especially in the Middle East region.

Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity.

Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.

A synthetic agent ameliorates polycystic kidney disease by promoting apoptosis of cystic cells through increased oxidative stress

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of chronic kidney disease and the fourth leading cause of end-stage kidney disease, accounting for over 50% of prevalent cases requiring renal replacement therapy. There is a pressing need for improved therapy for ADPKD. Recent insights into the pathophysiology of ADPKD revealed that cyst cells undergo metabolic changes that up-regulate aerobic glycolysis in lieu of mitochondrial respiration for energy production, a process that ostensibly fuels their increased proliferation. The present work leverages this metabolic disruption as a way to selectively target cyst cells for apoptosis. This small-molecule therapeutic strategy utilizes 11beta-dichloro, a repurposed DNA-damaging anti-tumor agent that induces apoptosis by exacerbating mitochondrial oxidative stress. Here, we demonstrate that 11beta-dichloro is effective in delaying cyst growth and its associated inflammatory and fibrotic events, thus preserving kidney function in perinatal and adult mouse models of ADPKD. In both models, the cyst cells with homozygous inactivation of Pkd1 show enhanced oxidative stress following treatment with 11beta-dichloro and undergo apoptosis. Co-administration of the antioxidant vitamin E negated the therapeutic benefit of 11beta-dichloro in vivo, supporting the conclusion that oxidative stress is a key component of the mechanism of action. As a preclinical development primer, we also synthesized and tested an 11beta-dichloro derivative that cannot directly alkylate DNA, while retaining pro-oxidant features. This derivative nonetheless maintains excellent anti-cystic properties in vivo and emerges as the lead candidate for development.

Factores de riesgo asociados con la tasa de filtración glomerular en adultos mexicanos con diabetes mellitus tipo 2

IntroductionType 2 diabetes mellitus (T2DM) is related to glomerular filtration rate (GFR) impairment, which is one of the main causes of chronic kidney disease. The objective of this study was to identify the risk factors related to GFR in Mexican adults with T2DM, using a validated multiple linear regression model (MLRM), with emphasis in body adiposity, glycemic control, duration of the diabetes and other relevant risk factors. Materials and methodsA cross-sectional, analytical, and observational study was carried out in 252 adults with a previous diagnosis of T2DM. Body mass index (BMI) and waist circumference (WC) were determined and a fasting blood sample was collected for glucose, creatinine and HbA1c determinations. GFR was calculated with the Cockcroft-Gault equation adjusted for body surface area. Four MLRM were performed to determine the factors related to the GFR; it was evaluated whether these models complied with the statistical assumptionsof the linear regression model. ResultsThe average age of the participants was 60±12 years, 62.3% of them were women. GFR correlated with BMI and WC; age and duration of the diabetes were associated inversely. Model 4 of the MLRM reported a coefficient of determination of 53.5% where the variables BMI (β=1.31), male sex (β=-6.01), duration of T2DM (β=-0.57), arterial hypertension (β=-6.53) and age (β=-1.45) were simultaneously and significantly related to the GFR. ConclusionsOlder age, male sex, longer duration of T2DM and the presence of arterial hypertension were associated with a decrease in the GFR; BMI and WC were directly associated. No effect of glucose and HbA1c on GFR was observed.

Development and validation of a diagnostic nomogram to evaluate tubular atrophy/interstitial fibrosis of IgA nephropathy.

Background: IgA nephropathy (IgAN) is a cause of chronic kidney disease (CKD). Tubular atrophy/interstitial fibrosis is associated with IgAN prognosis. However, simple tools for predicting pathological lesions of IgAN remain limited. Our objective was to develop a tool for evaluating tubular atrophy/interstitial fibrosis in patients with IgAN. Methods: In this cross-sectional study, 410 biopsy-verified IgAN patients were included. The factors associated with the incident interstitial fibrosis or tubular atrophy in IgAN were confirmed by using logistic regression analysis. A nomogram was developed using logistic regression coefficients to evaluate tubular atrophy or interstitial fibrosis. Receiver operating characteristic curves (ROC) and calibration curves were used to determine the discriminative ability and predictive accuracy of the nomogram. Results: In this study, the IgAN patients with tubular atrophy or interstitial fibrosis were older and had a higher percentage of males, hypertension and urinary protein excretion (UPE), with high levels of serum cystatin C, serum creatinine, high-sensitivity C-reactive protein and serum C4. The eGFRcr-cys equation calculated using serum creatinine, cystatin C and UPE were considered independent influencing factors of tubular atrophy or interstitial fibrosis in patients with IgAN. Furthermore, the nomogram demonstrated good discrimination (AUC: 0.87, 95% CI 0.81 to 0.93) and calibration in the validation cohort. Conclusion: The eGFRcr-cys and UPE are associated with tubular atrophy or interstitial fibrosis in patients with IgAN. Diagnostic nomogram can predict tubular atrophy or interstitial fibrosis in IgAN.

Chronic kidney disease associated with hypertension

Background: Globally, chronic kidney disease (CKD) is acknowledged as a major public health issue. Both the incidence and prevalence of chronic kidney disease (CKD) are rising with immense pace worldwide. Hypertension and diabetes mellitus is the main risk factor of chronic kidney disease. Objective: To determine chronic Kidney disease associated with hypertension Methods: A cross-sectional study was conducted at district headquarter hospital, Mianwali, Pakistan, which was performed between June 2020 and February 2022, the total number of patients in our study were 120. The number of Male patients were 49 and female were 71. In 120 consecutive patients who underwent for blood tests and Blood pressure monitoring. We also took stages of chronic kidney disease (CKD stage 1,2,3A,3B,4 and 5). We did renal function test for all patients (serum creatinine and serum urea). Data was tabulated and analyzed by SPSS. Results: In a current study total 120 patients were enrolled. The minimum age of patients were30 and the maximum age of the patients were 84. The mean age were 50.60±10.9 years. The minimum systolic blood pressure were 130 and maximum systolic blood pressure were 200. The mean systolic blood pressure were 149.55±13.5. The minimum diastolic blood pressure were 80 and the maximum diastolic blood pressure were 100. The mean diastolic blood pressure were 89.57±3.76 The frequency of male patients were 49 and its percentage were 40.8. The frequency of female patients were 71 and its percentage were 59.2. The frequency of age group 30-50 years were 61 and its percentage were 50.8. The frequency of age group 51-70 years were 52 and its percentage were 43.3. The frequency of age group >70 years were 7 and its percentage were 5.8. The mean of renal functional test Serum creatinine were 7.82 mg/dl and its SD value were 3.59 mg/dl. The mean of renal functional test Serum urea were 109.90 mg/dl and its SD value were 24.30 mg/dl. · The mean glomerular filtration rate were 20.36 ml/min and its SD value were 13.2 ml/min. · The mean weight of patients were 56.61 kg and its SD value were 10.19 kg. · The P-value of stages of Chronic kidney disease (CKD) were 0.133. The P-value of hypertension were 0.074. Conclusion: Hypertension and diabetes mellitus is the main cause of Chronic kidney disease (CKD). Stage 5 Chronic kidney disease (CKD) patients were more in our study as compare to other stages of CKD. We concluded in our study that after age of 30, patients have higher risk of Chronic kidney disease (CKD).

Diabetic Nephropathy: Pathogenesis and Drug Delivery System

Diabetic nephropathy is the leading cause of chronic kidney disease. The pathogenesis of diabetic nephropathy consists of four main pathways that indicate intracellular metabolic abnormalities identified in diabetic nephropathy, namely the activation of polyol and protein kinase C pathways, formation of advanced glycation end products, increased oxidative stress, and intraglomerular hypertension. Conventional treatment approaches for diabetic nephropathy that have been through clinical trials are, among others, the use of glucose-lowering agents, reduction of blood pressure, reduction of capillary permeability, and antioxidants. Although such treatments have been proven to slow the severity of diabetic nephropathy which leads to chronic kidney failure, their effectiveness does not cure diabetic nephropathy in patients. Thus, the modification of drug delivery systems and the widely-performed gene therapy need to be reviewed for their effectiveness with the previous treatments of diabetic nephropathy. This review article discusses the perspective of implementing the most effective diabetic nephropathy treatment system in order to achieve the therapeutic goals of diabetic nephropathy. The modification of drug delivery system and the gene therapies are expected to be able to increase the effectiveness of the drugs and guarantee their safety. The characteristics of the therapeutic targets in each kidney cell need to be understood more deeply so that the therapeutic goals can be achieved. It is hoped that the testing in the clinical phase of diabetic nephropathy by modifications of the drug delivery system and gene-based therapies will be widely carried out in the future.

State-of-the-art trends in the treatment of immune-mediated inflammatory kidney diseases: Translation of the fundamental science into clinical practice. A review

Immune-mediated kidney diseases like glomerulonephritis and tubulointerstitial nephritis are not the most common cause of chronic kidney disease in the population, however the difficulties in their management, as well as a more rapid deterioration of kidney function, compared to diabetes mellitus and hypertension, justify the importance of this problem for internal medicine. Due to the fundamental discoveries in pathology and to the introduction of various methods of laboratory and instrumental investigation in the second half of the XX century substantial progress was made in the diagnostic approaches and treatment of these conditions. State-of-the-art diagnostic approach requires complex evaluation of the clinical, laboratory and morphological data to identify the nosological form of the disease. The accumulation of knowledge in the field of diseases' pathogenesis led to the revision of the current classification of glomerulonephritis that should be based on the immunopathogenesis of these conditions. The following phenotypes were suggested: autoimmunity-related, autoinflammation-related, alloimmunity-related, infections-related, and monoclonal gammopathy-related. The assessment of disease activity and chronicity in the kidney tissue should be mandatory. Personalized selection of the optimal treatment modality on the basis of the diagnosis, severity, and individual features of the patient is currently possible. The leading trends include rational prescription of glucocorticoids (steroid-sparing regimens) and cytotoxic agents, e.g. cyclophosphamide, as well as the introduction of multitarget regimens that include biologic agents or small molecules selectively suppressing B-cells or various complement pathways. Another mandatory component of treatment on par with immune suppression is nephroprotective therapy, which currently comprises not only traditional renin-angiotensin-aldosterone antagonists, but also endothelin receptor antagonists and sodium-glucose cotransporter-2 inhibitors. Current guidelines emphasize the importance of the non-pharmacological interventions for the implementation of the nephroprotective strategy. Rational combination of the aforementioned approaches allows for the optimization of the management of patients with immune-mediated kidney diseases, although it requires high competencies and strict adherence to the principles of the evidence-based medicine from the healthcare providers.

A review on the classification and current treatment of Chronic Kidney Disease

Introduction:
 Chronic Kidney Disease (CKD) is a chronic condition which is characterized by the gradual loss of kidney function over time leading to End-Stage Renal Disease (ESRD). Role of kidneys is very vital to maintain homeostasis of the system. CKD is classified into five stages based on the estimated Glomerular Filtration Rate (eGFR). CKD is a long-term condition which cannot be completely cured. Treatment focuses on managing underlying conditions , slowing disease progression and addressing complications. 
 Aim of the study: 
 Purpose of this study is to encapsulate available knowledge about classification and therapeutic options for patients with Chronic Kidney Disease and End-Stage Kidney Disease. Both old and new treatment methods have been summarized in the following publication.
 Material and methods: 
 Literature available in the PubMed database was reviewed using the following keywords:
 “Chronic kidney disease”, “ACE inhibitors” , “Angiotensin II Type 1 Receptor Blockers", “Diabetic Kidney Disease” ,”End-Stage Kidney Disease”, “Dapagliflozin”, 
 Conclusions:
 Chronic Kidney Disease is a condition which is progressive and affects more than 10% of the general population worldwide totaling over 800 million people. There are many causes of chronic kidney disease; therefore, it is important to focus on slowing the progression of the disease, minimizing complications and modifying risk factors.

The Terminalia chebula retz extract treats hyperuricemic nephropathy by inhibiting TLR4/myd88/NF-κb axis

Ethnopharmacological relevanceHyperuricemic nephropathy (HN) is a renal injury caused by hyperuricemia and is the main cause of chronic kidney disease and end-stage renal disease. ShiWeiHeZiSan, which is composed mainly of components of Terminalia chebula Retz. And is recorded in the Four Medical Tantras, is a typical traditional Tibetan medicinal formula for renal diseases. Although T. chebula has been reported to improve renal dysfunction and reduce renal cell apoptosis, the specific mechanism of the nephroprotective effects of T. chebula on HN is still unclear. Aim of the studyThis study was conducted to evaluate the effects and specific mechanism of T. chebula extract on HN through network pharmacology and in vivo and in vitro experiments. Materials and methodsPotassium oxalate (1.5 g/kg) and adenine (50 mg/kg) were combined for oral administration to establish the HN rat model, and the effects of T. chebula extract on rats in the HN model were evaluated by renal function indices and histopathological examinations. UPLC-Q-Exactive Orbitrap/MS analysis was also conducted to investigate the chemical components of T. chebula extract, and the potential therapeutic targets of T. chebula in HN were predicted by network pharmacology analysis. Moreover, the activation of potential pathways and the expression of related mRNAs and proteins were further observed in HN model rats and uric acid-treated HK-2 cells. ResultsT. chebula treatment significantly decreased the serum uric acid (SUA), blood urea nitrogen (BUN) and serum creatinine (SCr) levels in HN rats and ameliorated renal pathological injury and fibrosis. A total of 25 chemical components in T. chebula extract were identified by UPLC-Q-Exactive Orbitrap/MS analysis, and network pharmacology analysis indicated that the NF-κB pathway was the potential pathway associated with the therapeutic effects of T. chebula extract on HN. RT‒PCR analysis, immunofluorescence staining and ELISA demonstrated that the mRNA and protein levels of TLR4 and MyD88 were significantly decreased in the renal tissue of HN rats after treatment with T. chebula extract at different concentrations, while the phosphorylation of P65 and the secretion of TNF-α and IL-6 were significantly inhibited. The results of in vitro experiments showed that T. chebula extract significantly decreased the protein levels of TLR4, MyD88, p-IκBα and p-P65 in uric acid-treated HK-2 cells and inhibited the nuclear translocation of p65 in these cells. In addition, the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) and fibrotic genes (α-SMA and fibronectin) was significantly downregulated by T. chebula extract treatment, while E-cadherin expression was significantly upregulated. ConclusionT. chebula extract exerts nephroprotective effects on HN, such as anti-inflammatory effects and fibrosis improvement, by regulating the TLR4/MyD88/NF-κB axis, which supports the general use of T. chebula in the management of HN and other chronic kidney diseases.

Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT)

Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below age 30 years. Many monogenic forms have been discovered due to comprehensive genetic testing like exome sequencing. However, disease-causing variants in known disease-associated genes only explain a proportion of cases. Here, we aim to unravel underlying molecular mechanisms of syndromic CAKUT in three unrelated multiplex families with presumed autosomal recessive inheritance. Exome sequencing in the index individuals revealed three different rare homozygous variants in FOXD2, encoding a transcription factor not previously implicated in CAKUT in humans: a frameshift in the Arabic and a missense variant each in the Turkish and the Israeli family with segregation patterns consistent with autosomal recessive inheritance. CRISPR/Cas9-derived Foxd2 knock-out mice presented with a bilateral dilated kidney pelvis accompanied by atrophy of the kidney papilla and mandibular, ophthalmologic, and behavioral anomalies, recapitulating the human phenotype. In a complementary approach to study pathomechanisms of FOXD2-dysfunction-mediated developmental kidney defects, we generated CRISPR/Cas9-mediated knock-out of Foxd2 in ureteric-bud-induced mouse metanephric mesenchyme cells. Transcriptomic analyses revealed enrichment of numerous differentially expressed genes important for kidney/urogenital development, including Pax2 and Wnt4 as well as gene expression changes indicating a shift towards a stromal cell identity. Histology of Foxd2 knock-out mouse kidneys confirmed increased fibrosis. Further, genome-wide association studies suggest that FOXD2 could play a role for maintenance of podocyte integrity during adulthood. Thus, our studies help in genetic diagnostics of monogenic CAKUT and in understanding of monogenic and multifactorial kidney diseases.

Sex-dependent differences in patients treated with regular hemodialysis

<p><strong>Introduction.</strong> The aims of the study were to find out sex differences among patients starting regular hemodialysis (HD) in 2014 and to check whether these differences change over a five-year period.</p> <p><strong>Methods.</strong> The retrospective five-year study included 35 patients (24 men; 11 women) starting HD in HD centers in Leskovac and Pirot in 2014. Demographic data, clinical data, laboratory findings, and medication used for examined patients were taken from medical records.</p> <p><strong>Results.</strong> A comparison of patients of different sexes at the beginning of the study showed that women were significantly older (70.55 ± 13.27 vs. 58.88 ± 15.27 years), but diabetes and hypertension were more frequent causes of chronic kidney disease in men. Women had significantly lower body mass index and serum creatinine level than men in the first year of the study. During all five years, the HD adequacy index spKt/V was higher in women than in men, but the difference reached statistical significance only in the third year (1.4 ± 0.2 vs. 1.2 ± 0.2). Serum iPTH level was higher in women than in men in almost the entire study period. There was no significant sex difference in blood pressure, type of vascular access, number of HD hours per week, in the percentage of patients who used erythropoiesis-stimulating agents or phosphate binders. During the study period 10 (42.7%) men and five (45.5%) women died and the most frequent causes of death were cerebrovascular and cardiovascular diseases.</p> <p><strong>Conclusion. </strong>The study revealed several differences between men and women on regular HD, but no treatment inequality was found. </p>

Kidney damage in hypertension disease

Essential hypertension (EH) is the most common cardiovascular disease and the leading cause of chronic kidney disease (CKD) worldwide. The aim of the study was to investigate the frequency and nature of kidney damage in hypertension. 189 patients (69 men and 120 women) with hypertension (stages I, II, and III) aged 43 years and older were examined. The average age of the patients was 61.2 ± 8.7 years. Clinical and biochemical tests were conducted on all patients, including red blood cell indices, C-reactive protein (CRP), lipid profile, fibrinogen, electrolytes, glucose, uric acid, creatinine, and cystatin C. The duration of hypertension was also recorded for each patient. Kidney function was assessed using serum creatinine (CKD-EPI) and cystatin C (F. Houcke). Patients were categorized according to the degree of decrease in glomerular filtration rate (GFR) based on the recommendations of the Russian Nephrology Society. Patients with kidney damage were divided into two groups: Group 1 consisted of patients with hypertension without signs of CKD (GFR calculated by cystatin C ≥ 60 ml/min), while Group 2 consisted of patients with hypertension complicated by CKD. The results showed that hypertension was accompanied by target organ damage in 70.8% of cases. The prevalence of CKD among patients with hypertension was 28.5%. Proteinuria was mainly detected in patients with renal insufficiency. The frequency of GFR categories according to CKD-EPI and F. Houcke formulas was as follows: G1 — 54.4% and 13.7% (p < 0.05); G2 — 35.9% and 57.6% (p < 0.05); G3a — 5.2% and 19.5% (p < 0.05); G3b — 3.1% and 5.2% (p < 0.05); G4 — 0.5% and 3.1% (p < 0.05) and G5 — 0.5% and 0.5%, respectively. There was a strong correlation between GFR and serum creatinine (r = –0.439; p < 0.05) and cystatin C (r = –0.866; p < 0.0001). Patients in Group 2 (hypertension with kidney damage) had significantly higher levels of CRP, low-density lipoprotein cholesterol, cystatin C, and longer duration of hypertension, but lower levels of total calcium than patients in Group 1. In conclusion, CKD was present in 28.5% of patients with hypertension, and proteinuria was mainly detected in patients with renal insufficiency. Serum cystatin C levels most accurately reflect kidney filtration function.

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62-0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council.

Correlation of Urinary Neutrophil Gelatinase with the Histopathological Extent of Kidney Damage in Patients with Diabetic Nephropathy.

Diabetic nephropathy (DN), a leading cause of chronic kidney disease, is known to develop in around 40% of patients with diabetes. NGAL, a biomarker expressed by the tubular epithelium, has been evaluated in both acute and chronic kidney injury. However, kidney damage revealed by the histology of renal tissue core biopsies has not been quantified by morphometry and its correlation with urinary NGAL (uNGAL) has not been studied. Our objective was to compare levels of uNGAL with the extent of kidney damage in the histopathological results of morphometry in patients with DN. This prospective analytical study was conducted in a tertiary hospital. Urine samples of 42 patients were collected and freeze-dried. uNGAL was estimated through a chemiluminescent microparticle immunoassay. Pearson's correlation coefficients between kidney damage quantified by morphometry and NGAL values were examined. The correlation of uNGAL with the percentage of acute tubular injury assessed by morphometry in the renal core was 7.35% (P = 0.64). uNGAL had the highest correlation with inflammation (r = 54.2%; P = 0.002). Another parameter with a significant correlation was glomerular sclerosis with r = 35.6% (95% confidence interval: 10%-60%) and an associated P = 0.02. UNGAL was strongly correlated with inflammatory kidney damage in patients with DN.

Kidney Disease and Diabetic Patients

The number of people with diabetes mellitus has grown dramatically around the world. This is mostly due to a rise in type 2 diabetes mellitus (T2DM). 537 million people around the world, or 11% of the population, had diabetes in 2021. By 2045, that number is expected to rise to 783 million, or 12% of the population. The rising number of people with T2DM is a result of the obesity epidemic, which is caused by eating more prepared foods, being less active, and spending more time sitting down. This so-called "Western lifestyle" is linked to more people living in cities and better technology. Chronic kidney disease in a person with diabetes is known as diabetic kidney disease (DKD). It is one of the most common and serious long-term effects of diabetes. Twenty to fifty percent of people with T2DM will eventually develop DKD. DKD is the main cause of chronic kidney disease and end-stage kidney disease around the world, making up half of all cases. In addition, DKD causes a lot of heart disease and death and lowers the quality of life for people who have it. This study gives you the most recent information on how to diagnose DKD, how common it is, and what causes it.

An audit of a general practices compliance with national recommendations for the avoidance of complications for type 2 diabetic patients

Abstract Introduction Each week, diabetes leads to more than 700 strokes, almost 600 heart attacks and more than 2000 instances of heart failure, in addition to being the single most common cause of chronic kidney disease in the UK.1 The NHS spends 10% of its annual budget on diabetes with 80% of that treating the complications of diabetes.2 Pharmacists have a crucial role to optimise the medication of diabetic patients and prevent future problems. Aim To assess a general practices (GP) compliance with national recommendations and the Quality and Outcomes Framework for the avoidance of complications for Type 2 Diabetes Mellitus (T2DM) patients. Methods This single-centre, retrospective audit was conducted at a GP in the London Borough of Southwark. Six standards were measured focusing on the prevention of the complications of diabetes. Each standard incorporated an exclusion and inclusion criteria. Standard 1 and 2 reviewed the appropriate management of nephropathy and hypertension respectively. Standard 3 and 4 relate to statin use for primary and secondary prevention. The final standards assess how many patients have documented QRISK2 scores and initiated on a Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitor as per the new NICE guidelines.3 Ethical approval was not deemed necessary for this clinical audit in agreement with the Hurley Group and King’s College Hospital NHS Foundation Trust guidelines. Results Half (50%, n=153/304) of all included T2DM patients at the practice have a blood pressure reading defined as hypertensive. Out of all diabetic patients, 25 of them had clinical proteinuria, micro-albuminuria, or a diagnosis of nephropathy. Of these 25 patients, 19 (76%) were prescribed an angiotensin-converting enzyme inhibitor or angiotensin-receptor blockers. A small portion (7%, n=28/374) of the diagnosed T2DM patients have a documented QRISK2 score. Subsequently, only 32 diabetic patients (9%, n=32/374) are prescribed an SGLT2 inhibitor. For standards 3 and 4, there were 122 patients (73%) who were prescribed a statin for primary prevention and 89 patients (87%) who were prescribed a statin for secondary prevention. Discussion/Conclusion The microvascular and macrovascular complications of diabetes are well documented. The incidence of these complications can be reduced by pharmacological management. Although none of the standards were met, the results are similar to other practices across the country. However, in comparison to the local average, the audited GP underperformed with no standards being better than the average of GPs in the area. Sub-analysis emphasises the disparities in health between various racial and ethnic groups. The results of the two largest demographic groups audited, Caucasian and Caribbean patients, show that the former is more likely to meet the standards. These findings indicate that the processes of the practice require change to meet the needs of our diabetic patients. In particular, work is required to understand the disparities in care for our patients categorised as ethnic minorities. The recommendations fall under 5 main categories – feedback, learn, templates, analyse, and review.

Causes of kidney failure among patients undergoing maintenance hemodialysis in Somalia: a multi-center study

BackgroundKidney failure is one of the leading causes of morbidity and mortality worldwide. The incidence of kidney failure in Somalia has been increasing in recent years. There is no data available on the causes of chronic kidney disease (CKD) leading to kidney failure in Somalia.MethodsThis is a multicentre, descriptive cross-sectional study designed to determine the aetiology of kidney failure among patients receiving haemodialysis in four major demographic areas of Somalia. The study was conducted over a one-year period, from June 2021 to June 2022. Participants were eligible for inclusion if they had been diagnosed with kidney failure, were on regular haemodialysis, and were over 18 years of age.ResultsA total of 127 patients were evaluated, 84 (66.1%) were males and 43 (33.9%) were female. The mean age of kidney failure patients was 49.3 ± 12.2 years. They originated from various regions, 5.6% from the south, 29.9% from the north-eastern, and 64.5% from the northwest. The mean duration of haemodialysis was 4.4 ± 2.2 years. The most common cause of kidney failure in our study was hypertension (33.1%), followed by diabetes mellitus (27.6%), uncertain aetiology (24.4%), glomerulonephritis (7.1%), obstructive uropathy (3.8%), renovascular hypertension (1.6%), neurogenic bladder, polycystic kidney disease, congenital and hereditary diseases (0.8%).ConclusionsOur study showed the leading cause of kidney failure among maintenance haemodialysis patients was hypertension, followed by diabetes mellitus. To reduce the burden of kidney failure in Somalia, primary prevention of hypertension and diabetes and early detection and prompt management of chronic kidney disease (CKD) in high-risk populations should be a fundamental focus.

SGLT2 inhibitor improves kidney function and morphology by regulating renal metabolism in mice with diabetic kidney disease

BackgroundDiabetic kidney disease (DKD) is a secondary complication of diabetes mellitus and a leading cause of chronic kidney disease. AimTo investigate the impact of long-term canagliflozin treatment on DKD and elucidate its underlying mechanism. MethodsDKD model was established using high-fat diet and streptozotocin in male C57BL/6J mice (n = 30). Mice were divided into five groups and treated for 12 weeks. 1) normal control mice, 2) DKD model, 3) mice treated low-dose of canagliflozin, 4) high-dose of canagliflozin and 5) β-hydroxybutyrate. Mice kidney morphology and function were evaluated, and a metabolomics analysis was performed. ResultsCanagliflozin treatment reduced blood creatinine and urine nitrogen levels and improved systemic insulin sensitivity and glucose tolerance in diabetic mice. Additionally, a decrease in histological lesions including collagen and lipid deposition in the kidneys was observed. β-hydroxybutyrate treatment did not yield a comparable outcome. The metabolomics analysis revealed that canagliflozin induced alterations in amino acid metabolism profiles in the renal tissue of diabetic mice. ConclusionCanagliflozin protects the kidneys of diabetic mice by increasing the levels of essential amino acids, promoting mitochondrial homeostasis, mitigating oxidative stress, and stimulating the amino acid-dependent tricarboxylic acid cycle.

Optimization of guideline-directed medical therapies in patients with diabetes and chronic kidney disease.

Diabetes is the leading cause of chronic kidney disease (CKD) and kidney failure worldwide. CKD frequently coexists with heart failure and atherosclerotic cardiovascular disease in the broader context of cardio-kidney-metabolic syndrome. Diabetes and CKD are associated with increased risk of all-cause and cardiovascular death as well as decreased quality of life. The role of metabolic and hemodynamic abnormalities has long been recognized as an important contributor to the pathogenesis and progression of CKD in diabetes, while a more recent and growing body of evidence supports activation of both systemic and local inflammation as important contributors. Current guidelines recommend therapies targeting pathomechanisms of CKD in addition to management of traditional risk factors such as hyperglycemia and hypertension. Sodium-glucose cotransporter-2 inhibitors are recommended for treatment of patients with CKD and type 2 diabetes (T2D) if eGFR is ≥20ml/min/173m2 on a background of renin-angiotensin system inhibition. For patients with T2D, CKD, and atherosclerotic cardiovascular disease, a glucagon-like peptide-1 receptor agonist is recommended as additional risk-based therapy. A non-steroidal mineralocorticoid receptor antagonist is also recommended as additional risk-based therapy for persistent albuminuria in patients with T2D already treated with renin-angiotensin system inhibition. Implementation of guideline-directed medical therapies is challenging in the face of rapidly accumulating knowledge, high cost of medications, and lack of infrastructure for optimal healthcare delivery. Furthermore, studies of new therapies have focused on T2D and CKD. Clinical trials are now planned to inform the role of these therapies in people with type 1 diabetes (T1D) and CKD.