Established Chronic Kidney Disease Research Articles

Uric acid level in Chronic Kidney Disease patients and its association with other established CKD risk factors

Introduction: Chronic Kidney Disease (CKD) is a rising global health concern with increased cardiovascular risks. Hyperuricemia, linked to CKD and related conditions, warrants investigation. Objectives: This study examines the uric acid in different stages of CKD and the association between uric acid levels and established CKD risk factors. Methodology: A hospital-based prospective cross-sectional study was conducted at Birat Medical College Teaching Hospital from 10 June 2023 to 30 August 2023. We enrolled 90 patients with non-dialytic chronic kidney disease (CKD) by complete enumeration sampling method. Ethical approval was obtained from the institutional review committee of the college. Written informed consent was obtained from each participant. Data was collected by means of a self developed questionnaire. Blood samples were obtained for estimation of serum creatinine and uric acid level and recorded in Microsoft excel sheet and analyzed by using SPSS software version 23. Results: Hyperuricemia was seen in 33(36.7%) ranging from 3.5-12 mg/dl with an average uric acid level of 6.38 mg/dl and a standard deviation of 1.43 mg/dl of total 90 patients. The mean serum uric acid level was highest in stage 2 CKD which includes 6.88±2.10 ranging from 4.3-12 mg/dl. CKD patients with a history of alcohol intake had increased risk of hyperuricemia and it was statistically significant (p value 0.005). Different stages of CKD (p value: 0.70), age groups, (p value 0.17), gender(P value 0.082), diabetes(p value 0.954), hypertension(p value 0.364), other CVDs(p value 0.649)and anemia(p value 0.0602)had no statistical significant association with hyperuricemia. Conclusion: In conclusion, hyperuricemia prevalence was observed in CKD patients, with the highest levels in stage 2 CKD. Notably, alcohol intake significantly correlated with hyperuricemia, while other studied factors did not show significant associations.

Cardiovascular Disease in Diabetes and Chronic Kidney Disease.

Chronic kidney disease (CKD) is a common occurrence in patients with diabetes mellitus (DM), occurring in approximately 40% of cases. DM is also an important risk factor for cardiovascular disease (CVD), but CKD is an important mediator of this risk. Multiple CVD outcomes trials have revealed a greater risk for CVD events in patients with diabetes with CKD versus those without. Thus, reducing the risk of CKD in diabetes should result in improved CVD outcomes. To date, of blood pressure (BP) control, glycemic control, and inhibition of the renin-angiotensin system (RASI), glycemic control appears to have the best evidence for preventing CKD development. In established CKD, especially with albuminuria, RASI slows the progression of CKD. More recently, sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1RA) have revolutionized the care of patients with diabetes with and without CKD. SGLT2i and GLP1RA have proven to reduce mortality, heart failure (HF) hospitalizations, and worsening CKD in patients with diabetes with and without existing CKD. The future of limiting CVD in diabetes and CKD is promising, and more evidence is forthcoming regarding combinations of evidence-based therapies to further minimize CVD events.

Short- and long-term survival of patients hospitalized for COVID-19 in relation to cardiovascular risk factors and established cardiovascular disease: the Cor-Cardio study.

The clinical presentation of COVID‑19 may range from asymptomatic infection to severe disease. Previous studies reported a relationship between the course of COVID‑19 and a history of cardiovascular (CV) disease (CVD). We aimed to analyze the influence of CV risk factors, established CVD, and treatment with CV drugs on short- and long‑term survival in patients hospitalized for COVID‑19. We retrospectively analyzed data of patients hospitalized in 13 COVID‑19 hospitals in Poland (between March and October 2020). Individual deaths during the follow‑up were recorded until March 2021. Overall, 2346 patients with COVID‑19 were included (mean age, 61 years; 50.2% women). A total of 341 patients (14.5%) died during the hospitalization, and 95 (4.7%) died during the follow‑up. Independent predictors of in‑hospital death were older age, a history of established CVD, heart failure, and chronic kidney disease (CKD), while treatment with renin‑angiotensin‑aldosterone system blockers or statins was associated with a lower risk of death during hospitalization. Factors that independently predicted death during the follow‑up were older age, a history of established CVD, CKD, and a history of cancer. The presence of CV risk factors did not increase the odds of death either in the hospital or during the follow‑up. Of note, higher systolic blood pressure and oxygen blood saturation on admission were associated with better short- and long‑term prognosis. Established CVD and CKD were the main predictors of mortality during both the hospitalization and the follow‑up in the patients hospitalized for COVID‑19, while the use of CV drugs during the hospitalization was associated with better prognosis. The presence of CV risk factors did not increase the odds of in‑hospital and postdischarge death.

Sodium-Glucose Co-Transporter 2 Inhibitors as a Powerful Cardioprotective and Renoprotective Tool: Overview of Clinical Trials and Mechanisms

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been linked to beneficial effects on cardiovascular risk factors, blood pressure, body weight, and lipid profile, according to a substantial body of literature. Significant cardiac and renal benefits with the use of SGLT2 inhibitors have been shown in patients with type 2 diabetes, as well as in those with heart failure and/or chronic kidney disease (CKD), regardless of diabetes status, in subsequent large cardiovascular outcome trials. Thus, SGLT2 inhibitors have become a mainstay of therapy for type 2 diabetes in patients with established cardiovascular disease and CKD due to their benefits for the heart and kidneys. Based on data from randomized controlled trials and meta-analyses, this article attempts to present a thorough review of the mechanism of action, as well as the benefits of SGLT2 inhibitors for cardiac and renal protection. On the basis of a growing body of literature on diabetes and other conditions, clinical practice guidelines have been updated to suggest the use of SGLT2 inhibitors in specific patient populations. These modifications will also be concisely described, based on evidence-based medicine principles.

Predicting outcomes of acute kidney injury in critically ill patients using machine learning

Acute Kidney Injury (AKI) is a sudden episode of kidney failure that is frequently seen in critically ill patients. AKI has been linked to chronic kidney disease (CKD) and mortality. We developed machine learning-based prediction models to predict outcomes following AKI stage 3 events in the intensive care unit. We conducted a prospective observational study that used the medical records of ICU patients diagnosed with AKI stage 3. A random forest algorithm was used to develop two models that can predict patients who will progress to CKD after three and six months of experiencing AKI stage 3. To predict mortality, two survival prediction models have been presented using random survival forests and survival XGBoost. We evaluated established CKD prediction models using AUCROC, and AUPR curves and compared them with the baseline logistic regression models. The mortality prediction models were evaluated with an external test set, and the C-indices were compared to baseline COXPH. We included 101 critically ill patients who experienced AKI stage 3. To increase the training set for the mortality prediction task, an unlabeled dataset has been added. The RF (AUPR: 0.895 and 0.848) and XGBoost (c-index: 0.8248) models have a better performance than the baseline models in predicting CKD and mortality, respectively Machine learning-based models can assist clinicians in making clinical decisions regarding critically ill patients with severe AKI who are likely to develop CKD following discharge. Additionally, we have shown better performance when unlabeled data are incorporated into the survival analysis task.

THE HIGH-ENERGY DIET/STREPTOZOTOCIN TREATED MUNICH WISTAR FRÖMTER RATS: A NEW EXPERIMENTAL MODEL OF DIABETES INDUCTION IN ESTABLISHED KIDNEY DISEASE

Objective: Chronic kidney disease (CKD) is especially prevalent in patients with diabetes mellitus (DM). We aim to induce diabetes in the Munich Wistar Frömter (MWF) rat, a genetic model of established CKD. Design and method: 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF) or a high fat/high-sucrose diet for 6 weeks together with streptozotocin administration (STZ; 15mg/Kg i.p.) at the start of dietary exposure (MWF-D). Results: Water intake, urine excretion, GTT and HOMA-IR index evidenced the development of diabetes in MWF-D rats. Albuminuria was higher in MWF with no further effect of diabetes. However, renal expression of Kim-1 and Ngal, markers of renal damage, AT1R, AT2R and Collagen 1A1 were significantly higher in MWF-D rats. Perirenal adipose tissue (PRAT) amount was significantly higher in MWF-D rats and exhibited an upregulation of TNF-alpha and profibrotic factors (TGF-beta and Collagen 1A1), together with a downregulation of IL-10. Although blood pressure was not further increased by the induction of diabetes, heart weight and left ventricular wall thickness were higher in MWF-D, coincident with a reduction in systolic volume, but without a change in the ejection fraction. Conclusions: We propose the MWF-D rat as an experimental model of NDKD and suggest a strong relation between alterations in PRAT and increased renal damage.

Risk Factors for Incident CKD in Black and White Americans: The REGARDS Study

Little information exists on the incidence of and risk factors for chronic kidney disease (CKD) in contemporary US cohorts and whether risk factors differ by race, sex, or region in the United States. Observational cohort study. 4,198 Black and 7,799White participants aged at least 45years, recruited from 2003 through 2007across the continental United States,with baseline estimated glomerular filtration rate (eGFR)>60mL/min/1.73m2 and eGFRassessed again approximately 9 years later. Age, sex, race (Black or White), region ("stroke belt" or other), education, income, systolic blood pressure, body mass index, diabetes, coronary heart disease, hyperlipidemia, smoking, and albuminuria. (1) eGFR change and (2) incident CKD defined as eGFR<60mL/min/1.73m2 and≥40% decrease from baseline or kidney failure. Linear regression and modified Poisson regression were used to determine the association of risk factors with eGFR change and incident CKD overall and stratified by race, sex, and region. Mean age of participants was 63±8 (SD) years, 54% were female, and 35% were Black. After 9.4±1.0 years of follow-up, CKD developed in 9%. In an age-, sex-, and race-adjusted model, Black race (β=-0.13; P<0.001) was associated with higher risk of eGFR change, but this was attenuated in the fully adjusted model (β=0.02; P=0.5). Stroke belt residence was independently associated with eGFR change (β=-0.10; P<0.001) and incident CKD (relative risk, 1.14 [95% CI, 1.01-1.30]). Albuminuria was more strongly associated with eGFR change (β of-0.26 vs-0.17; P=0.01 for interaction) in Black compared with White participants. Results were similar for incident CKD. Persons of Hispanic ethnicity were excluded; unknown duration and/or severity of risk factors. Established CKD risk factors accounted for higher risk of incident CKD in Black versus White individuals. Albuminuria was a stronger risk factor for eGFR decrease and incident CKD in Black compared with White individuals. Living in the US stroke belt is a novel risk factor for CKD.

Hepatic and proximal tubule angiotensinogen play distinct roles in kidney dysfunction, glomerular and tubular injury, and fibrosis progression.

Components of the renin-angiotensin system, including angiotensinogen (AGT), are critical contributors to chronic kidney disease (CKD) development and progression. However, the specific role of tissue-derived AGTs in CKD has not been fully understood. To define the contribution of liver versus kidney AGT in the CKD development, we performed 5/6 nephrectomy (Nx), an established CKD model, in wild-type (WT), proximal tubule (PT)- or liver-specific AGT knockout (KO) mice. Nx significantly elevated intrarenal AGT expression and elevated blood pressure (BP) in WT mice. The increase of intrarenal AGT protein was completely blocked in liver-specific AGT KO mice with BP reduction, suggesting a crucial role for liver AGT in BP regulation during CKD. Nx-induced glomerular and kidney injury and dysfunction, as well as fibrosis, were all attenuated to a greater extent in liver-specific AGT KO mice compared with PT-specific AGT KO and WT mice. However, the suppression of interstitial fibrosis in PT- and liver-specific AGT KO mouse kidneys was comparable. Our findings demonstrate that liver AGT acts as a critical contributor in driving glomerular and tubular injury, renal dysfunction, and fibrosis progression, whereas the role of PT AGT was limited to interstitial fibrosis progression in chronic renal insufficiency. Our results provide new insights for the development of tissue-targeted renin-angiotensin system intervention in the treatment of CKD.NEW & NOTEWORTHY Chronic kidney disease (CKD) is a major unmet medical need with no effective treatment. Current findings demonstrate that hepatic and proximal tubule angiotensinogen have distinct roles in tubular and glomerular injury, fibrogenesis, and renal dysfunction during CKD development. As renin-angiotensin system components, including angiotensinogen, are important targets for treating CKD in the clinic, the results from our study may be applied to developing better tissue-targeted treatment strategies for CKD and other fibroproliferative diseases.

Comparing prevalence of chronic kidney disease and its risk factors between population-based surveys in Russia and Norway

BackgroundLittle data exists on the prevalence of chronic kidney disease (CKD) in the Russian population. We aimed to estimate the prevalence of CKD in a population-based study in Russia, compare with a similar study in Norway, and investigate whether differences in risk factors explained between-study differences in CKD.MethodsWe compared age- and sex-standardised prevalence of reduced eGFR (< 60 ml/min/1.73m2 CKD-EPI creatinine equation), albuminuria and or a composite indicator of CKD (one measure of either reduced eGFR or albuminuria) between participants aged 40–69 in the population-based Know Your Heart (KYH) study, Russia (2015–2018 N = 4607) and the seventh Tromsø Study (Tromsø7), Norway (2015–2016 N = 17,646). We assessed the contribution of established CKD risk factors (low education, diabetes, hypertension, antihypertensive use, smoking, obesity) to between-study differences using logistic regression.ResultsPrevalence of reduced eGFR or albuminuria was 6.5% (95% Confidence Interval (CI) 5.4, 7.7) in KYH and 4.6% (95% CI 4.0, 5.2) in Tromsø7 standardised for sex and age. Odds of both clinical outcomes were higher in KYH than Tromsø7 (reduced eGFR OR 2.06 95% CI 1.67, 2.54; albuminuria OR 1.54 95% CI 1.16, 2.03) adjusted for sex and age. Risk factor adjustment explained the observed between-study difference in albuminuria (OR 0.92 95% CI 0.68, 1.25) but only partially reduced eGFR (OR 1.42 95% CI 1.11, 1.82). The strongest explanatory factors for the between-study difference was higher use of antihypertensives (Russian sample) for reduced eGFR and mean diastolic blood pressure for albuminuria.ConclusionsWe found evidence of a higher burden of CKD within the sample from the population in Arkhangelsk and Novosibirsk compared to Tromsø, partly explained by between-study population differences in established risk factors. In particular hypertension defined by medication use was an important factor associated with the higher CKD prevalence in the Russian sample.

Synergic Renoprotective Effects of Combined ASC Therapy with RAAS Blockade in Experimental Advanced CKD.

Global prevalence of chronic kidney disease (CKD) has increased considerably in the recent decades. Overactivity of the renin-angiotensin-aldosterone system (RAAS), associated to renal inflammation and fibrosis, contributes to its evolution. The treatments currently employed to control CKD progression are limited and mainly based on the pharmacological inhibition of RAAS, associated with diuretics and immunosuppressive drugs. However, this conservative management promotes only partial deceleration of CKD evolution and does not completely avoid the progression of the disease and the loss of renal function, which motivates the medical and scientific community to investigate new therapeutic approaches to detain renal inflammation/fibrosis and CKD progression. Recent studies have shown the application of mesenchymal stem cells (mSC) to exert beneficial effects on the renal tissue of animals submitted to experimental models of CKD. In this context, the aim of the present study was to evaluate the effects of subcapsular application of adipose tissue-derived mSC (ASC) in rats submitted to the 5/6 renal ablation model, 15 days after the establishment of CKD, when the nephropathy was already severe. We also verify whether ASC associated to Losartan would promote greater renoprotection when compared to the respective monotherapies. Animals were followed until 30 days of CKD, when body weight, systolic blood pressure, biochemical, histological, immunohistochemical, and gene expression analysis were performed. The combination of ASC and Losartan was more effective than Losartan monotherapy in reducing systolic blood pressure and glomerulosclerosis and also promoted the complete normalization of proteinuria and albuminuria, a significant reduction in renal interstitial macrophage infiltration and downregulation of renal IL-6 gene expression. The beneficial effects of ACS are possibly due to the immunomodulatory and anti-inflammatory role of factors secreted by these cells, modulating the local immune response. Although studies are still required, our results demonstrated that a subcapsular inoculation of ASC, associated with the administration of Losartan, exerted additional renoprotective effect in rats submitted to a severe model of established CKD, when compared to Losartan monotherapy, thus suggesting ASC may be a potential adjuvant to RAAS-blockade therapy currently employed in the conservative management of CKD.

Progression of established non-diabetic chronic kidney disease is halted by metformin treatment in rats

Current treatment strategies for chronic kidney disease (CKD) mainly focus on controlling risk factors. Metformin, a first-line drug for type 2 diabetes, exerts beneficial pleiotropic actions beyond its prescribed use and incipient data have revealed protective effects against the development of kidney impairment. This study evaluated the therapeutic efficacy of metformin and canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor recently approved by the United States Food and Drug Administration to treat diabetic nephropathy, in slowing the progression of established non-diabetic CKD. Rats with adenine-induced CKD were assigned to different treatment groups to receive either 200 mg/kg metformin, four or five weeks after the start of the adenine diet (established mild-moderate CKD), or 25 mg/kg canagliflozin four weeks after the start of the diet, by daily oral gavage administered during four weeks. Each treatment group was compared to a vehicle group. Chronic adenine dosing resulted in severe CKD in vehicle-treated rats as indicated by a marked rise in serum creatinine levels, a marked decrease in creatinine clearance, and a disturbed mineral metabolism. Metformin, but not canagliflozin, halted functional kidney decline. Additionally, kidneys of metformin-treated animals showed less interstitial area and inflammation as compared to the vehicle group. Proteomic analyses revealed that metformin's kidney-protective effect was associated with the activation of the Hippo signaling pathway, a highly conserved multiprotein kinase cascade that controls tissue development, organ size, cell proliferation, and apoptosis. Thus, metformin demonstrated therapeutic efficacy by halting the progression of established CKD in a rat model.

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression

BackgroundThe relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy.MethodsUsing our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR < 60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk.Results25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P = 0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P = 0.71).ConclusionsUse of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy.

Correlation of Kidney Size on Computed Tomography with GFR, Creatinine and HbA1C for an Accurate Diagnosis of Patients with Diabetes and/or Chronic Kidney Disease.

Diabetes is considered one of the major causes of chronic kidney disease (CKD), affecting renal blood vessels and nerves. Diagnosis of CKD by traditional biochemical serum and blood analyses is insufficient and insensitive, thus requiring the development of a more robust technique. This novel study aims to propose a new method for the accurate diagnosis of CKD, quantification of kidney damage, and its prognosis by physicians by measuring the kidney volume on computed tomography (CT). In total, 251 patients were enrolled in this retrospective study. They were divided into four groups: control, patients having diabetes, patients having CKD, and patients having both diabetes and CKD. Results showed that kidney volume correlated negatively with both GFR and HbA1C on CT images, in addition to decreasing faster in males than females. Moreover, HbA1C was shown to correlate positively with creatinine and negatively with GFR. Finally, GFR was more robust than creatinine when correlated with age. The association between kidney volume with GFR and HbA1c can be used to accurately anticipate kidney volume in established CKD on CT scan, especially in resource-poor settings. Furthermore, HbA1C can serve as a powerful biomarker for studying renal function in diabetic CKD patients as it correlates with creatinine and GFR.

Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study.

A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis assessments of NAFLD such as Fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) have been developed to substitute liver biopsy. Little is known about the association between FIB-4 index or NFS and the components of CKD. In the present cross-sectional study, we assessed of 3640 Japanese CKD patients. We examined the association between FIB-4index or NFS and the odds of having low estimated glomerular filtration rate (eGFR) defined as eGFR < 60mL/min/1.73 m2 or albuminuria defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30mg/g. Patients were divided into quartiles according to their baseline FIB-4 index and NFS levels. Linear and logistic regression analysis were conducted, with adjustment for potential confounding factors. FIB-4 index and NFS were negatively associated with eGFR, but not UACR, after adjustment for potential confounding factors. Both FIB-4 index and NFS were significantly associated with low eGFR after adjustment for potential confounding factors. Meanwhile, in the multivariable-adjusted model, no associations were found between FIB-4 index or NFS and albuminuria. The addition of FIB-4 index or NFS to the established clinical CKD risk factors improved diagnostic accuracy of prevalence of low eGFR. We also found that there was a significant trend of higher FIB-4 index and NFS with more advanced renal fibrosis using the kidney biopsy data. Higher non-invasive fibrosis assessments of NAFLD were associated with higher odds of decreased eGFR.

INFLAMMATORY MARKERS AND CHRONIC KIDNEY DISEASE

Objective: Background: Resistant hypertension (RHT) defined as an uncontrolled blood pressure (BP) despite the use of 3 or more antihypertensives presents a high cardiovascular (CV) morbidity and mortality and high prevalence of chronic kidney disease (CKD). High BP levels and kidney injury appear to be strongly associated with inflammatory biomarkers. Objective: To evaluate the relationship between inflammatory markers and subclinical and established CKD in a large cohort of patients with RHT Design and method: Cross-sectional study that evaluated 423 resistant hypertensives (30.5% male, mean age 64.0 ± 10.8 years) submitted to renal function assessment (albuminuria dosage and evaluation of glomerular filtration rate calculated from the CKD-EPI formula) and dosage of inflammatory markers: TNF-alpha, MCP-1, E-selectin and PAI-1. Socio-demographic characteristics, anthropometric measurements and CV risk factors were recorded. We considered subclinical CKD those patients with moderately high albuminuria (30–300 mg/g) and/or GFR between 30 and 60 ml/min/1.73m2 and established CKD those who presented albuminuria &gt; 300 mg/g and/or TFG &lt; 30 ml/min/1.73m2. Variance analysis compared serum levels of the 4 inflammatory markers and bivariate analysis compared patients with and without subclinical and established chronic kidney disease. Results: The prevalence of established CKD was 7.3% (31 patients) and subclinical CKD was 47% (187 patients). Patients with subclinical CKD were older and with higher arterial stiffness (higher pulse wave velocity). TNF-alpha (7.1 [4.4–8.6] vs 51, [3.2–7.5]) and MCP-1(284 [220–379] vs 260 [185–359] were significant higher in this group of patients. When we analyzed patients with established CKD, we observed that they have higher BP levels and that TNF-alpha values (7.8 [5.6–14.0] vs 5.6 [3.5–8.3]) and E-selectin (54.4[41.2–61.3] vs. 47.8 [32.0–65.3]) were significantly higher in this group. Conclusions: Among the inflammatory markers evaluated, which was most strongly correlated with subclinical CKD were TNF-alpha and MCP-1, while those with established CKD have higher TNF-alpha and E-selectin levels, possibly pointing out that the MCP-1 is an earlier marker of kidney injury.

Tobacco Use and the Kidney: A Review of Public Policies and Studies on Kidney Disease Progression.

Clinical Background: Cigarette smoking is one of the leading causes of preventable deaths, including cardiovascular diseases and cancer. However, the effects of tobacco use on chronic kidney disease (CKD) are less widespread. Epidemiology: Smoking tobacco is associated with proteinuria and attenuation of glomerular filtration rate in the general population of different ethnicities. Smoking also accelerates the progression of established CKD and aggravates proteinuria along the wide spectrum of causes determining kidney disease. Furthermore, smoking worsens the survival of kidney transplant recipients and shortens graft survival. Most of the effects of tobacco exposure are dose and time dependent and could be ameliorated with smoking cessation. Challenges: In the last decades, tobacco use policies and regulations were implemented around the world obtaining a global 6% reduction in smoking prevalence. However, the reduction was not proportionally equal in all the geographical areas around the world. The region of Americas experimented the most positive result in reducing smoking prevalence. Smoking trends in South East Asian and Eastern Mediterranean regions show minor decrease or increased rates. The World Health Organization projected reaching a global target prevalence of 15% by 2025. Prevention and Treatment: The results showing smoking cessation slows the progression of kidney disease in smokers should drive our effort to help our patients quit smoking. Smoking prevention at the population level, and particularly in those at risk of CKD or with established CKD should be part of health policies and regulations all around the world.

Acute kidney injury in children with chronic kidney disease is associated with faster decline in kidney function

BackgroundThis study aimed to investigate the association of acute kidney injury (AKI) with change in estimated glomerular filtration rate (eGFR) in children with advanced chronic kidney disease (CKD).MethodsSingle centre, retrospective longitudinal study including all prevalent children aged 1–18 years with nondialysis CKD stages 3–5. Variables associated with CKD were analysed for their potential effect on annualised eGFR change (ΔGFR/year) following multiple regression analysis. Composite end-point including 25% reduction in eGFR or progression to kidney replacement therapy was evaluated.ResultsOf 147 children, 116 had at least 1-year follow-up in a dedicated CKD clinic with mean age 7.3 ± 4.9 years with 91 (78.4%) and 77 (66.4%) with 2- and 3-year follow-up respectively. Mean eGFR at baseline was 29.8 ± 11.9 ml/min/1.73 m2 with 79 (68%) boys and 82 (71%) with congenital abnormalities of kidneys and urinary tract (CAKUT). Thirty-nine (33.6%) had at least one episode of AKI. Mean ΔGFR/year for all patients was − 1.08 ± 5.64 ml/min/1.73 m2 but reduced significantly from 2.03 ± 5.82 to − 3.99 ± 5.78 ml/min/1.73 m2 from youngest to oldest age tertiles (P < 0.001). There was a significant difference in primary kidney disease (PKD) (77% versus 59%, with CAKUT, P = 0.048) but no difference in AKI incidence (37% versus 31%, P = 0.85) between age tertiles. Multiple regression analysis identified age (β = − 0.53, P < 0.001) and AKI (β = − 3.2, P = 0.001) as independent predictors of ΔGFR/year. 48.7% versus 22.1% with and without AKI reached composite end-point (P = 0.01).ConclusionsWe report AKI in established CKD as a predictor of accelerated kidney disease progression and highlight this as an additional modifiable risk factor to reduce progression of kidney dysfunction.Graphical abstract

The The Circulating Visfatin Level Relation to the Severity of Chronic Kidney Disease

BACKGROUND: Adipokines have been associated with atherosclerotic heart disease, which has plenty of common risk factors with chronic kidney disease (CKD), but their association with CKD has not been well characterized. &#x0D; AIM: We investigated the association between the serum visfatin level and CKD.&#x0D; METHODS: The serum visfatin levels in 101 CKD patients and 101 controls were compared. CKD was defined as estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73 m2 or presence of albuminuria (≥30 mg/24 h).&#x0D; RESULTS: After adjustment for established CKD risk factors, the median (interquartile range) of the serum visfatin was 3.65 ng/ml (2.31–4.59) in patients with CKD and 1.66 ng/ml (0.90–2.45) in controls without CKD (p &lt; 0.0001 for group difference). Serum visfatin was significantly and inversely correlated with eGFR (r = –0.79, p &lt; 0.0001) and positively correlated with urine albumin (r = 0.71, p &lt; 0.0001) in the study participants. There was a strong dose-response and the significant relationship between serum visfatin level and CKD severity, assessed by GFR and albuminuria, regardless of established risk factors for CKD, including hypertension, diabetes, and cardiovascular disease.&#x0D; CONCLUSION: Our results show that circulating visfatin is associated with the risk and severity of CKD. These results suggest that longitudinal studies and clinical trials should be conducted to investigate if adipocytokines play a role in the development and progression of CKD independent of body mass index or waist circumference. These important findings may advance our further understanding of CKD risk factors.

Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study.

BackgroundFibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population.MethodsWe included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort. Multi-variable Cox regression was used to study the association of plasma C-terminal FGF23 with new-onset CKD, defined as a combined endpoint of estimated glomerular filtration rate (eGFR) <60 mL/min/ 1.73 m2, urinary 24-h albumin excretion (UAE) >30 mg/24 h or both, or with all-cause mortality.ResultsThe median baseline FGF23 was 68 [interquartile range (IQR) 56–85] RU/mL, eGFR was 95 ± 13 mL/min/1.73 m2 and UAE was 7.8 (IQR 5.8–11.5) mg/24 h. After follow-up of 7.5 (IQR 7.2–8.0) years, 586 participants developed CKD and 214 participants died. A higher FGF23 level was associated with new-onset CKD, independent of risk factors for kidney disease and parameters of bone and mineral homoeostasis {fully adjusted hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.10–1.44] per doubling of FGF23; P = 0.001}. In secondary analyses, FGF23 was independently associated with new-onset eGFR <60 mL/min/1.73 m2 [adjusted HR 1.28 (95% CI 1.00–1.62); P = 0.048] or with UAE >30 mg/24 h [adjusted HR 1.24 (95% CI 1.06–1.45); P = 0.01] individually. A higher FGF23 level was also associated with an increased risk of all-cause mortality [fully adjusted HR 1.30 (95% CI 1.03–1.63); P = 0.03].ConclusionsHigh FGF23 levels are associated with an increased risk of new-onset CKD and all-cause mortality in this prospective population-based cohort, independent of established CKD risk factors.

Impact of chronic kidney dysfunction on serum Sulfatides and its metabolic pathway in mice.

Serum sulfatides are critical glycosphingolipids that are present in lipoproteins and exert anticoagulant effects. A previous study reported decreased levels of serum sulfatides in hemodialysis patients and suggested an association with cardiovascular disease. However, the mechanism of changes in serum sulfatides in chronic kidney dysfunction has not been well investigated. The current study examined whether a chronic kidney disease (CKD) state could decrease serum sulfatide levels using 5/6 nephrectomy (5/6NCKD) mice, an established CKD murine model, and studied the mechanisms contributing to diminished sulfatides. 5/6NCKD mice and sham operation control mice were sacrificed at the 4th or 12th postoperative week (POW) for measurement of serum sulfatide levels. Hepatic sulfatide content, which is the origin of serum sulfatides, and the expression of sulfatide metabolic enzymes in liver tissue were assessed as well. The 5/6NCKD mice developed CKD and showed increased serum creatinine and indoxyl sulfate. The serum levels and hepatic amounts of sulfatides were significantly decreased in 5/6NCKD mice at both 4 and 12 POW, while the degradative enzymes of sulfatides arylsulfatase A and galactosylceramidase were significantly increased. In a Hepa1-6 murine liver cell line, indoxyl sulfate addition caused intracellular levels of sulfatides to decrease and degradative enzymes of sulfatides to increase in a manner comparable to the changes in 5/6NCKD mice liver tissue. In conclusion, chronic kidney dysfunction causes degradation of sulfatides in the liver to decrease serum sulfatide levels. One explanation of these results is that indoxyl sulfate, a uremic toxin, accelerates the degradation of sulfatides in liver tissue.