Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Utilising continuous glucose monitoring for glycemic control in diabetic kidney disease

In this editorial,we comment on the article by Zhang et al.Chronic kidney disease(CKD)presents a significant challenge in managing glycemic control,especially in diabetic patients with diabetic kidney disease undergoing dialysis or kidney transplantation.Conventional markers like glycated haemoglobin(HbA1c)may not accurately reflect glycemic fluctuations in these populations due to factors such as anaemia and kidney dysfunction.This comprehensive review discusses the limitations of HbA1c and explores alternative methods,such as continuous glucose monitoring(CGM)in CKD patients.CGM emerges as a promising technology offering real-time or retrospective glucose concentration measure-ments and overcoming the limitations of HbA1c.Key studies demonstrate the utility of CGM in different CKD settings,including hemodialysis and peritoneal dialysis patients,as well as kidney transplant recipients.Despite challenges like sensor accuracy fluctuation,CGM proves valuable in monitoring glycemic trends and mitigating the risk of hypo-and hyperglycemia,to which CKD patients are prone.The review also addresses the limitations of CGM in CKD patients,emphasizing the need for further research to optimize its utilization in clinical practice.Altogether,this review advocates for integrating CGM into managing glycemia in CKD patients,highlighting its superiority over traditional markers and urging clinicians to consider CGM a valuable tool in their armamentarium.

Reference gene panel for urinary exosome-based molecular diagnostics in patients with kidney disease

BACKGROUND Kidney disease is a severe complication of diabetes that often leads to end-stage renal disease.Early diagnosis is crucial for prevention or delay.However,the current diagnostic methods,with their limitations in detecting the disease in its early stages,underscore the urgency and importance of finding new solutions.miRNAs encapsulated inside urinary exosomes(UEs)have potential as early biomarkers for kidney diseases.The need for reference miRNAs for accurate interpretation currently limits their translational potential.AIM To identify consistently expressing reference miRNAs from UEs of controls and patients with type 2 diabetesmellitus(T2DM)and biopsy-confirmed kidney diseases.METHODS miRNA profiling was performed on UEs from 31 human urine samples using a rigorous and unbiased method.The UEs were isolated from urine samples collected from healthy individuals(n=6),patients with T2DM(n=13),and T2DM patients who also had kidney diseases(including diabetic nephropathy,n=5;membranous nephropathy,n=5;and IgA nephropathy,n=2)through differential ultracentrifugation.After characterizing the UEs,miRNA expression profiling using microarray technology was conducted.RESULTS Microarray data analysis identified 14 miRNAs that were consistently expressed in UEs from 31 human samples,representing various kidney conditions:diabetic controls,diabetic nephropathy,membrane nephropathy,IgA nephropathy,and healthy controls.Through in silico analysis,we determined that 10 of these miRNAs had significant potential to serve as reference genes in UEs.CONCLUSION We identified uniformly expressing UE miRNAs that could serve as reference genes kidney disease biomarkers.

Prevalence, Risk Factors, and Awareness of Chronic Kidney Disease among Diabetes Mellitus and Hypertensive Individuals at the Buea Regional Hospital, Cameroon

Background: Kidney failure, cardiovascular disease, and early mortality are just a few of the major negative effects of chronic renal disease, a serious global health issue. The considerable financial and public health burden associated with chronic kidney disease can be lessened by raising awareness and adopting better practices for its impact, prevention, and early identification. Objective: In this study, individuals with hypertension and diabetes were evaluated for their knowledge of chronic kidney disease, its prevalence, and its risk factors. Method: It was a hospital-based cross-sectional study conducted on adult (>18 years) patients with diabetes mellitus and hypertension. Each participant provided written informed consent before having their data collected through interviews, medical information, and blood samples for CKD screening. The CKD epidemiology collaboration (CKD-EPI) equation was used to calculate the glomerular filtration rate (GFR) from serum creatinine, and CKD was determined using the estimated GFR (e-GFR). To find independent CKD factors, multivariate logistic regression was employed, with a p-value of 0.05 being regarded as statistically significant. This was accomplished using SPSS (Statistical Program for Social Sciences) version 22.0, IBM Corp., Armonk, NY. Result: A total of 156 participants took part in the study among which 95 (60.9%) were male, most of the participants 82 (52.6%) were aged between 51 - 70 years (mean 59.42 ± 11.007), 76 (48.7%) were unemployed and 97 (62.2%) were single. Overall, the knowledge score of participants on CKD was 65.4% for good knowledge and 34.6% for poor or inadequate knowledge of CKD. More than half of the participants (60%) had chronic kidney disease. Among these, the greatest proportion of CKD patients were those who were hypertensive (88.2%) followed by those who were both hypertensive and diabetic (70.7%). Conclusion: There is poor management of CKD in the South West Region of Cameroon which has contributed greatly to the progression of CKD and increases in the mortality rate.

Contribution to the Study of Diabetic Kidney Disease in a Sub-Saharan Environment: An Example of the Aristide Le Dantec University Hospital in Dakar

Introduction: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and dialysis admission. Few studies are available in Sub-Saharan Africa. The objective of this work was to study the epidemiological, clinical, diagnostic and therapeutic characteristics of DKD in our context. Patients and Methods: We conducted an observational, exhaustive and retrospective study focusing on diabetic patients seen in consultation or hospitalized in the Nephrology Department of at the Aristide Le Dantec University Hospital in Dakar during a period of 5 years from January 1, 2017 to December 31, 2021. Results: Of 4735 patients seen during the study period, 491 had DKD, i.e. a hospital prevalence of 10.36%. The average age was 59.1 ± 11.4 years with a sex ratio of 0.95. Type 2 diabetes predominated with 93.4%. The average duration of diabetes was 11.5 ± 7.6 years. Diabetes was associated with high blood pressure in 78.81% of cases, dyslipidemia in 23.2% of cases, active smoking in 6.7% of cases and obesity in 1.6% of cases. Renal failure was the main reason for referral 72.3%. One hundred and forty-eight patients (30.1%) had uncontrolled diabetes. Macroalbuminuria was found in 64.8% and microalbuminuria in 18.7% of cases. One hundred and eighty-five patients (37.7%) were in Stage V of kidney disease and 137 patients were in Stage III (18.1% in Stage IIIb and 9.8% in Stage IIIa). Diabetic nephropathy was the main etiology at 61.30%. Nephropathy was mixed (diabetic and hypertensive) in 18.12 cases. Renin-angiotensin-aldosterone system (RAAS) blockers were prescribed in 83.5% of patients. Conclusion: The different etiologies encountered during the study show the diversity of diabetic kidney disease. Diabetic nephropathy is not the only kidney damage that can occur in diabetics in our context.

Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease:A nested case-control study

AIM: To compare anemia prevalence between matched chronic kidney disease(CKD) patients with and without diabetes mellitus(DM) and to assess factors associated with anemia development.METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate(eG FR). Prevalence of anemia(hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia.RESULTS: The total prevalence of anemia was higher in diabetics(47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3(53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a(60.4% vs 26.4%, P < 0.001), whereas it was nonsignificantly higher in Stage 4(61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM(OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4(Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron(OR = 0.976, 95%CI: 0.968-0.985 per mg/d L increase) were independently associated with anemia.CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts.

Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease

BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease(CKD).Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD,but few have evaluated their mutual connection.Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches;however,with the availability of hypoxia-inducible factor(HIF)stabilizers such as roxadustat,more therapeutic choices for renal anemia are expected in the future.However,the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.AIM To summarize the relationship between renal anemia and abnormal bone metabolism,and to discuss the influence of hypoxia on bone metabolism.METHODS CNKI and PubMed searches were performed using the key words“chronic kidney disease,”“abnormal bone metabolism,”“anemia,”“hypoxia,”and“HIF”to identify relevant articles published in multiple languages and fields.Reference lists from identified articles were reviewed to extract additional pertinent articles.Then we retrieved the Abstract and Introduction and searched the results from the literature,classified the extracted information,and summarized important information.Finally,we made our own conclusions.RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism,blood cell production,and survival rates through multiple pathways.Anemia will further attenuate the normal bone growth.The hypoxic environment regulates bone morphogenetic protein,vascular endothelial growth factor,and neuropilin-1,and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes.Hypoxia preconditioning of mesenchymal stem cells(MSCs)can enhance their paracrine effects and promote fracture healing.Concurrently,hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23.Hypoxia potentially improves bone metabolism,but it still carries potential risks.The optimal concentration and duration of hypoxia remain unclear.CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Endothelial injury and inflammation in patients with hyperuricemic nephropathy at chronic kidney disease stages 1-2 and 3-4

BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease(CKD)stages 3-4 and CKD 1-2.METHODS This study enrolled 80 patients(49 and 31 with HN at CKD stage 1-2 and 3-4,respectively)from the Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022.Plasma levels of heparan sulfate,endocan,oxidized low-density lipoprotein(Ox-LDL),E-selectin,soluble intercellular adhesion molecule-1(slCAM1),interleukin(IL)-1β,and IL-6 and urine levels of lipocalin-type prostaglandin D synthase(L-PGDS),IL-1β,and IL-6 were measured using enzyme-linked immunosorbnent assay.RESULTS Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors(P<0.001 and P<0.010,respectively).There were no statistical differences in sex,heart rate,body mass index,and systolic and diastolic blood pressures.The incidence of hypertension was also significant(P=0.03).Plasma levels of heparin sulfate(P<0.001),endocan(P=0.034),E-selectin(P<0.001),slCAM1(P<0.001),IL-1β(P=0.006),and IL-6(P=0.004)and the urine levels of L-PGDS(P<0.001),IL-1β(P=0.003),and IL-6(P<0.001)were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2.The difference in plasma Ox-LDL levels was not significant(P=0.078).CONCLUSION Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2.Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.

Diabetic patients with chronic kidney disease: Non-invasive assessment of cardiovascular risk

The prevalence and burden of diabetes mellitus and chronic kidney disease on global health and socioeconomic development is already heavy and still rising.Diabetes mellitus by itself is linked to adverse cardiovascular events,and the presence of concomitant chronic kidney disease further amplifies cardiovascular risk.The culmination of traditional(male gender,smoking,advanced age,obesity,arterial hypertension and dyslipidemia)and non-traditional risk factors(anemia,inflammation,proteinuria,volume overload,mineral metabolism abnormalities,oxidative stress,etc.)contributes to advanced atherosclerosis and increased cardiovascular risk.To decrease the morbidity and mortality of these patients due to cardiovascular causes,timely and efficient cardiovascular risk assessment is of huge importance.Cardiovascular risk assessment can be based on laboratory parameters,imaging techniques,arterial stiffness parameters,ankle-brachial index and 24 h blood pressure measurements.Newer methods include epigenetic markers,soluble adhesion molecules,cytokines and markers of oxidative stress.In this review,the authors present several non-invasive methods of cardiovascular risk assessment in patients with diabetes mellitus and chronic kidney disease.

Anemia treatment and left ventricular hypertrophy in non-dialysis chronic kidney disease

To this day, the target hemoglobin level that minimizes cardiovascular risk in chronic kidney disease (CKD) patients remains unclear. When one examines the many randomized trials of epoetin therapy in aggregate, enhanced quality of life provides the most cogent argument for hemoglobin levels above 110 g/L. It remains unclear whether treatment of anemia improves longevity, or even a surrogate marker (such as left ventricular [LV] mass index), especially when applied at earlier phases of CKD.

Percutaneous Angioplasty in Diabetic Patients with Critical Limb Ischemia and Chronic Kidney Disease

Introduction: Diabetes and Chronic Kidney Disease (CKD) are two strong risk factors for peripheral arterial disease (PAD) and Critical Limb Ischemia (CLI). Further renal insufficiency increases the risk of non healing wounds and major amputation. Primary amputation rates of 22% to 44% have been reported for ischaemic foot lesion in End-Stage Renal Disease (ESRD) patients. In our study we evaluated the outcomes after Percutaneus Transluminal Angioplasty (PTA) in diabetic patient in relation to different CKD classes. Materials and Methods: We studied a group of 456 diabetic patients with PAD complicated by foot lesion who underwent PTA because of a CLI. According to the estimated Glomerular Filtration Rate (eGFR mL/min/1.73 m2) we divided the patients into five CKD groups: group 1 eGFR > 90, group 2 eGFR 90 - 60 (n = 160), group 3 eGFR 60 - 30 (n = 152), group 4 eGFR 30 -15 (n = 34) and group 5 < 15 or in ESRD) (n = 60). The following outcomes were recorded: alive without major amputation, alive with major amputation and death. The follow-up was 16.7 ± 14.3 months. Results: Alive without major amputation, alive with major amputation and death were respectively: for group 1 (77.8%, 11.1%, 11.1%), for group 2 (74.4%, 12.5%, 13.1%), for group 3 (80.3%, 11.2%, 8.5%), for group 4 (82.3%, 8.8%, 8.8%). They were 60%, 18.3%, 21.7% for group 5 significantly different from the other CKD groups (χ2 = 0.0175). Our analysis did not highlight any relationship between eGFR and outcomes and eGFR did not show any significant difference according to the different outcomes, and were respectively 60.2 ± 1.3, 61.8 ± 3.4, 63.8 ± 3.5 (P = ns). Conclusion: The outcomes were similar for groups 1-4 and therefore, according to our data, they seemed not to be influenced by the decline of GFR. Outcomes worse significantly in group 5, but this group included only patients with ESRD in dialysis treatment. Although the outcomes after PTA in group 5 was significantly worse than the other groups, still a 60% limb salvage rate was obtained with PTA also in these very fragile patients. PTA was much less aggressive than by-pass and PTA was the only method used to treat CLI in our patients. This could explain why we recorded similar outcomes in all groups despite the decline of GFR that, generally speaking, mirrors a worsening of the general clinical conditions. Worse outcomes were recorded only in group 5 and in this group dialysis by itself might be responsible of the different outcomes.

Sickle Cell Trait, Hemoglobin Levels and Anemia among Black Patients with Predialysis Chronic Kidney Disease: A Post Hoc Analysis

Objective: To assess the relationship between SCT, hemoglobin levels and anemia in CKD black patients. Method: A post-hoc analysis of data from 188 patients, enrolled in a cross-sectional study of sickle cell trait (SCT) and chronic kidney disease (CKD), was performed to assess the relationship between SCT, hemoglobin (Hb) levels and anemia defined as Hb < 12 g/dl in men and <11 g/dl in women. Student t test, Mann Whitney and Chi square test were used as appropriate for different comparisons. P < 0.05 defined the level of statistical significance. Results: SCT (HbAS) and normal hemoglobin (HbAA) were present in 39 (21%) and 149 (79%) CKD patients, respectively. Despite similar estimated GFR (eGFR) and age, HbAS patients had significantly lower Hb levels (8.8 ± 1.8 vs 10 ± 2.2 g/dl;p = 0.001) and a higher proportion of anemia (95% vs 72%, p = 0.001). In multiple linear regression analysis, eGFR, BMI, SBP and SCT emerged as independent determinants of Hb levels. The presence of SCT was associated with 1.185 g/dl decrease in Hb levels. Conclusion: In the present case series, SCT was associated with lower Hb levels suggesting its potential contribution to the pathogenesis of CKD-associated anemia.

Assessment of Patient Perceptions about Use of Wepox Pen^TM(Recombinant Erythropoietin Delivery Device with 30,000 IU Cartridge) in the Management of Anemia in Chronic Kidney Disease Patients

Objective: To assess perceptions about ease of use and other benefits of Wepox PenTM (loaded with 30,000 IU cartridge of recombinant erythropoietin) in the management of anemia in adult chronic kidney disease (CKD) patients. Material and methods: In this prospective, observational, multicentric post marketing surveillance, adult CKD patients treated with erythropoietin were enrolled from November 2015 to December 2016 to understand their opinions about Wepox PenTM. Ease of use of pen, ease of administering accurate dose, confidence in administration and ease of storage and disposal of cartridge were assessed on five points Likert scale: 1. very easy;2. somewhat easy;3. neither easy nor difficult;4. somewhat difficult;5. very difficult. Global assessment was performed on five points scale: 1. excellent;2. very good;3. good;4. average;5. not good. Safety was recorded by checking pain and discomfort and adverse events. Results: A total of 263 patients (mean age 32.87 years;66% male;34% female) were enrolled. Number of patients reporting ease of use as “very easy” from 209 (80.7%) at baseline increased to 245 (94.6%) and 249 (96.1%) at visit 2 (p = 0.001) and visit 3 (p = 0.001) respectively. Number of “very easy” response for accurate dose increased from 236 (91.1%) at visit 1 to 246 (95%) at visit 2 (p = 0.84) and 249 (96.1%) at visit 3 (p = 0.001). Number of the patients with “no pain” at injection site increased from 177 (68.3%) at visit 1 to 205 (79.2%) and 212 (81.9%) at visit 2 (p = 0.001) and visit 3 (p = 0.001) respectively. Improvement in number of patients with “no hurt” at visit 2 (p = 0.538) and visit 3 (p = 0.286) was not statistically significant. Number of patients reporting “somewhat easy” to “very easy” confidence in self injection increased from 251 (96.9%) at visit 2 to 255 (98.5%) at visit 3. Number of patients reporting ease of storage and disposal of cartridge as “somewhat easy” to “very easy” increased from 254 (98.1%) at visit 2 to 256 (98.9%) at visit 3. According to the global assessment, 144 (56.3%) cases reported “excellent” response. “Very good” and “Good” responses were reported by 106 (41.4%) and 6 (2.3%) patients respectively. A total of 230 (98.7%) patients said that they would prefer to use erythropoietin pen device for further treatment too. Conclusion: Wepox PenTM(recombinant erythropoietin) is easy to use and does not cause significant pain or discomfort. Ability to self-administer recombinant erythropoietin with Wepox PenTM is a great advantage which can make a significant difference for both CKD patients and doctors. Storage and disposal of cartridge is also easy.

Diabetic nephropathy:Is it time yet for routine kidney biopsy?

Diabetic nephropathy(DN)is one of the most important long-term complications of diabetes.Patients with diabetes and chronic kidney disease have an increased risk of all-cause mortality,cardiovascular mortality,and kidney failure.The clinical diagnosis of DN depends on the detection of microalbuminuria.This usually occurs after the first five years from the onset of diabetes,and predictors of DN development and progression are being studied but are not yet implemented into clinical practice.Diagnostic tests are useful tools to recognize onset,progression and response to therapeutic interventions.Microalbuminuria is an indicator of DN,and it is considered the only noninvasive marker of early onset.However,up to now there is no diagnostic tool that can predict which patients will develop DN before any damage is present.Pathological renal injury is hard to predict only with clinical and laboratory findings.An accurate estimate of damage in DN can only be achieved by the histological analysis of tissue samples.At the present time,renal biopsy is indicated on patients with diabetes under the suspicion of the presence of nephropathies other than DN.Results from renal biopsies in patients with diabetes had made possible the classification of renal biopsies in three major groups associated with different prognostic features:diabetic nephropathy,non-diabetic renal disease(NDRD),and a superimposed non-diabetic condition on underlying diabetic nephropathy.In patients with type 2 diabetes with a higher degree of suspicion for NDRD,it is granted the need of a renal biopsy.It is important to identify and differentiate these pathologies at an early stage in order to prevent progression and potential complications.Therefore,a more extensive use of biopsy is advisable.

WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Inflammation in diabetic kidney disease

Diabetes mellitus entails significant health problems worldwide.The pathogenesis of diabetes is multifactorial,resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events,with metabolic and hemodynamic alterations.In this context,inflammation has emerged as a key pathophysiology mechanism.New pathogenic pathways will provide targets for prevention or future treatments.This review will focus on the implications of inflammation in diabetes mellitus,with special attention to inflammatory cytokines.

Role of vitamin D in diabetes mellitus and chronic kidney disease

Approximately 30%-50% of people are recognized to have low levels of vitamin D,and insufficiency and deficiency of vitamin D are recognized as global health problems worldwide.Although the presence of hypovitamin D increases the risk of rickets and fractures,low vitamin D levels are also associated with hypertension,cancer,and cardiovascular disease.In addition,diabetes mellitus(DM) and chronic kidney disease(CKD) are also related to vitamin D levels.Vitamin D deficiency has been linked to onset and progression of DM.Although in patients with DM the relationship between vitamin D and insulin secretion,insulin resistance,and β-cell dysfunction are pointed out,evidence regarding vitamin D levels and DM is contradictory,and well controlled studies are needed.In addition,vitamin D influences the renin-angiotensin system,inflammation,and mineral bone disease,which may be associated with the cause and progression CKD.There is increasing evidence that vitamin D deficiency may be a risk factor for DM and CKD;however,it remains uncertain whether vitamin D deficiency also predisposes to death from DM and CKD.Although at this time,supplementation with vitamin D has not been shown to improve glycemic control or prevent incident DM,clinical trials with sufficient sample size,study periods,and optimal doses of vitamin D supplementation are still needed.This review focuses on the mechanism of vitamin D insufficiency and deficiency in DM or CKD,and discusses the current evidence regarding supplementation with vitamin D in patients with these diseases.

Effects of glycaemic management on diabetic kidney disease

Hyperglycaemia contributes to the onset and progression of diabetic kidney disease(DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Tight glucose control has clearly been shown to reduce the incidence of micro-or macroalbuminuria. However, evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Achieving tight glucose control needs to be balanced against the increasing appreciation that glucose targets for the prevention of diabetes related complications need be individualised for each patient. Recently, empagliflozin which is an oral glucose lowering agent of the sodium glucose cotransporter-2 inhibitor class has been shown to have renal protective effects. However, the magnitude of empagliflozin's reno-protective properties are over and above that expected from its glucose lowering effects and most likely largely result from mechanisms involving alterations in intra-renal haemodynamics. Liraglutide and semaglutide, both injectable glucose lowering agents which are analogues of human glucagon like peptide-1 have also been shown to reduce progression to macroalbuminuria through mechanisms that remain to be fully elucidated. Here we review the evidence from observational and interventional studies that link good glucose control with improved renal outcomes. We also briefly review the potential reno-protective effects ofnewer glucose lowering agents.

Patient selection and preparation strategies for the use of contrast material in patients with chronic kidney disease

The prevalence of chronic kidney disease and peripheral arterial disease is increasing.Thus,it is increasingly problematic to image these patients as the number of patients needing a vascular examination is increasing accordingly.In high-risk patients with impaired kidney function,intravascular administration of iodinated contrast media can result in contrast-induced acute kidney injury and Gadolinium can induce nephrogenic systemic fibrosis(NSF).It is important to identify these highrisk patients by means of se-creatinine/e glomerular filtration rate.The indication for contrast examination should counterbalance the increased risk.One or more alternative examination methods without contrast media,such as CO 2 angiography,Ultrasound/Doppler examination or magnetic resonance angiography without contrast should be considered,but at the same time,allow for a meaningful outcome of the examination.If contrast is deemed essential,the patient should be well hydrated,the amount of contrast should be restricted,the examination should be focused,metformin and diuretics stopped,and renal function monitored.Sodium bicarbonate and N-acetylcysteine are popular but their efficiency is not evidence-based.There is no evidence that dialysis protects patients with impaired renal function from contrast-induced nephropathy or NSF.

Stop chronic kidney disease progression: Time is approaching

Progression of chronic kidney disease （CKD） is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointer-stitial disease. The chronic systemic inflammatory status and increased oxidative stress were also inve-stigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of infam-mation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression.

Uric acid and chronic kidney disease: A time to act?

A role for uric acid in the pathogenesis and progression of renal disease had been proposed almost a century ago, but, too hastily dismissed in the early eighties. A body of evidence, mostly accumulated during the last decade, has led to a reappraisal of the infuence of uric acid on hypertension, cardiovascular, and renal disease. The focus of this review will be solely on the relationship between serum uric acid and renal function and disease. We will review experimental evidence derived from ani-mal and human studies, evidence gathered from a num-ber of epidemiological studies, and from the few （up to now） studies of uric-acid-lowering therapy. Some space will be also devoted to the effects of uric acid in special populations, such as diabetics and recipients of kidney allografts. Finally we will briefy discuss the challenges of a trial of uric-acid-lowering treatment, and the recent suggestions on how to conduct such a trial.