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Objective: This meta-analysis was designed to investigate cardio-renal outcomes and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a therapeutic option among chronic kidney disease(CKD) patients with GFR < 60 mL/min/1.73 m2, regardless of their diabetic status. Method: We conducted a full-scale search from MEDLINE, EMBASE and the Cochrane Library database to identify eligible studies up to Jun 2024. All randomized controlled trials (RCTs) comparing cardio-renal outcomes and/or safety of SGLT2i in CKD patients with eGFR < 60 mL/min/1.73 m2 were involved. The relative risk (RR) and 95% confidence interval (CI) for primary outcomes and adverse events were computed by random-effects mode. We used I2 statistic to analyze heterogeneity. Publication bias was assessed by Egger's test. Results: Our study incorporated 17 RCTS, including 27,928 patients. In CKD patients with eGFR < 60 mL/min/1.73 m2, SGLT2i decreased risks of cardiovascular events (seven studies, 17,355 participants, RR 0.77, 95% CI 0.70–0.84), hospitalization for heart failure (HHF) (seven studies, 17,869 participants, RR 0.73, 95% CI 0.65–0.82), cardiovascular death (eight studies, 23,079 participants, RR 0.81, 95% CI 0.74 to 0.88) and renal composite outcomes (eight studies, 22,525 participants, RR 0.70, 95% CI 0.61–0.80) with lower risks of any serious adverse effects(fourteen studies, 19,654 participants, RR 0.91, 95% CI 0.87–0.95), hypoglycemia (nine studies, 16,412 participants, RR 0.91, 95% CI 0.84–0.98), hyperkalemia (four studies, 2693 participants, RR 0.68, 95% CI 0.51–0.93) and acute renal injury (five studies, 5424 participants, RR 0.79, 95% CI 0.65–0.95) compared to placebo. SGLT2i also slowed eGFR decline (total slopes: five studies, 10,370 participants, mean difference 1.17, 95%CI 0.86–1.49; chronic slopes: four studies, 8459 participants, mean difference 2.12, 95%CI 1.64–2.61). Further subgroup analyses revealed that SGLT2i decreased relative risks of cardiovascular outcomes(three studies, 1075 participants, RR 0.76, 95% CI 0.54–0.82), HHF(four studies, 1280 participants, RR 0.74, 95% CI 0.55–1.00) and renal composite outcomes (six studies,4375 participants, RR 0.78, 95% CI 0.68–0.88) with no increased adverse events in the CKD 4 patients. Conclusions: SGLT2i significantly improved cardio-renal outcomes and were generally safe in CKD patients with eGFR < 60 mL/min/1.73 m2 and with eGFR < 30 mL/min/1.73 m2. Future large-scale RCTs are needed to confirm the robustness of these results. [ABSTRACT FROM AUTHOR]

Background Metabolic surgery is recognized for its effectiveness in weight loss and improving outcomes for individuals with type 2 diabetes mellitus (T2DM). However, its impact on renal function, especially in multi-ethnic Asian populations, remains underexplored. This study investigates mid- and long-term renal outcomes following metabolic surgery in Asian patients with T2DM. Methods This retrospective cohort study utilized data from the Asian Diabetes Surgery Study (ADSS), involving T2DM patients aged 20–79 who underwent metabolic surgery from 2008 to 2015. The primary outcome was the change in estimated glomerular filtration rate (eGFR) at 1, 3, and 5 years post-surgery, with adjustments for confounders. Secondary outcomes included changes in chronic kidney disease (CKD) stages and the relationship between weight loss and eGFR changes. Data were analyzed using univariate and multivariable regression analyses, along with the McNemar test. Results The study included 1513 patients with a mean age of 42.7 years. The results revealed that a significant improvement in eGFR was observed at 1-year post-surgery (112.4 ± 32.0 ml/min/1.73 m², P < .001), with a shift toward less severe CKD stages. However, this improvement was not sustained at 3 and 5 years. No significant correlation was found between weight loss and eGFR changes at 1-year follow-up. Conclusion Metabolic surgery significantly improves renal function at 1 year postoperatively in Asian individuals with T2DM, highlighting its potential benefits beyond glycemic control and weight loss. The long-term effects on renal function require further investigation. [ABSTRACT FROM AUTHOR]

Background: Current treatment for chronic kidney disease (CKD) focuses on improving manifestations and delaying progression. Nutritional approaches play a crucial role in CKD management, and various supplements have become available. Ketoanalogues of amino acids (KAs), calcium citrate, and inulin have been proposed as suitable supplements, yet their widespread use has been limited due to insufficient evidence. This study aimed to generate general guidance statements on the appropriateness of these supplements through a RAND/UCLA consensus process. Methods: A RAND/UCLA consensus panel was convened to evaluate the appropriateness of these supplements in different clinical scenarios. In this study, we present a subgroup analysis focusing on a panel of eleven clinical nephrologists from among the experts. Results: Supplementation of low-protein diets (LPDs) and very low-protein diets (VLPDs) with KA was considered appropriate to reduce manifestations and delay CKD outcomes, supplementation with calcium citrate is considered appropriate to reduce CKD manifestations, and supplementation with inulin is considered appropriate to delay CKD outcomes and manage comorbidities. Conclusions: Based on a combination of clinical experience and scientific evidence, the panel reached a consensus that KA supplementation of LPD and VLPD, calcium citrate, and inulin are appropriate in patients with CKD across various scenarios. [ABSTRACT FROM AUTHOR]

Abstract Given the limited head-to-head comparison of cardiovascular and renal outcomes between liraglutide and dulaglutide, our study aimed to investigate the clinical outcomes between dulaglutide and liraglutide in a real-world setting. In this new-user design, comparative and retrospective cohort study, patients with type 2 diabetes mellitus with prescription for GLP-1RAs from January 1, 2016 to December 31, 2022 (n = 8,278) were included. Primary outcome was composite cardiovascular outcomes which was composed of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke. The composite renal outcome was also interested, including new macroalbuminuria, doubling of serum creatinine, worsening of estimated glomerular filtration rate (eGFR), and progression to dialysis. A total of 3,210 subjects receiving liraglutide and 5,068 subjects receiving dulaglutide were identified. In the adjusted cohort by applying inverse probability of treatment weighting, the incidence of composite cardiovascular outcomes was 18.4 and 18.7 events per 1000 person-years in the liraglutide and dulaglutide groups, respectively. The risk of cardiovascular outcomes did not significantly differ between groups (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.85–1.15). Moreover, the risk of composite renal outcomes was also comparable between groups (subdistribution HR 1.07, 95% CI 0.995–1.16). Liraglutide and dulaglutide demonstrated comparable cardiovascular and renal outcomes in a real-world setting.

Abstract Objective This meta-analysis was designed to investigate cardio-renal outcomes and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a therapeutic option among chronic kidney disease(CKD) patients with GFR

Abstract The association of physical activity with renal outcome and mortality in advanced chronic kidney disease (CKD; i.e., estimated glomerular filtration rate [eGFR]

Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111–0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081–0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD. [ABSTRACT FROM AUTHOR]

Background: In patients with transthyretin cardiac amyloidosis (ATTR‐CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR‐CA patients. Objectives: This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR‐CA. Methods: We included patients with ATTR‐CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF. Results: Within a follow‐up period of 326 ± 118 days, the median GFR% change measured −6% [−18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6–9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1–0.7]), and not receiving SGLT‐2i (OR: 0.1, 95% CI: [0.02–0.5]) were significant predictors of wRF. Conclusion: Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR‐CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT‐2i therapy appeared to be protective in this population. [ABSTRACT FROM AUTHOR]

AimsTo investigate whether metabolic syndrome (MetS) could predict renal outcome in patients with established chronic kidney disease (CKD).Materials and methodsWe enroled 2500 patients with CKD stage 1-4 from the Integrated CKD care programme, Kaohsiung for delaying Dialysis (ICKD) prospective observational study. 66.9% and 49.2% patients had MetS and diabetes (DM), respectively. We accessed three clinical outcomes, including all-cause mortality, RRT, and 50% decline in estimated glomerular filtration rate events.ResultsThe MetS score was positively associated with proteinuria, inflammation, and nutrition markers. In fully adjusted Cox regression, the hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome (renal replacement therapy, and 50% decline of renal function) in the DM and non-DM subgroups was 1.56 (1.15-2.12) and 1.31 (1.02-1.70), respectively, while that for all-cause mortality was 1.00 (0.71-1.40) and 1.27 (0.92-1.74). Blood pressure is the most important component of MetS for renal outcomes. In the 2 by 2 matrix, compared with the non-DM/non-MetS group, the DM/MetS group (HR: 1.62 (1.31-2.02)) and the non-DM/MetS group (HR: 1.33 (1.05-1.69)) had higher risks for composite renal outcome, whereas the DM/MetS group had higher risk for all-cause mortality (HR: 1.43 (1.09-1.88)).ConclusionsMetS could predict renal outcome in patients with CKD stage 1-4 independent of DM.

Aim Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD.Methods Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes.Results By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111–0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081–0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018).Conclusion In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

INTRODUCTION: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. METHODS: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. RESULTS: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR

Aim: To evaluate whether sodium‐glucose cotransporter 2 inhibitor (SGLT2i) therapy is associated with a reduction of renal events compared with other glucose‐lowering drugs (oGLDs) among Japanese people with type 2 diabetes (T2D) and grade 3 (G3) chronic kidney disease (CKD) in a real‐world clinical practice setting. Materials and Methods: People with T2D who were newly prescribed an SGLT2i or an oGLD from April 2014 to November 2021 (without prior use of index drugs for ≥ 1 year prior to index date) and G3 CKD (estimated glomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73 m2) were selected from the Medical Data Vision database (MDV‐DB) and the Real‐World Data database (RWD‐DB). SGLT2i and oGLD users were matched (1:1) using propensity score on patient background characteristics. The primary endpoint was a composite of the development of end‐stage kidney disease or a sustained decline in eGFR of 50% or more. Hazard ratios (HRs) were estimated using the Cox proportional hazards model. Results: Overall, 3190 (1595 per group) patients in the MDV‐DB and 2572 (1286 per group) patients in the RWD‐DB were included in the analyses. The composite outcome was significantly lower in the SGLT2i group than in the oGLD group in the MDV‐DB (HR 0.49, 95% confidence interval [CI] 0.33 to 0.74, P < 0.001) and in the RWD‐DB (HR 0.57, 95% CI 0.37 to 0.88, P = 0.011). Conclusions: Japanese people with T2D and G3 CKD initiating an SGLT2i had a lower risk of renal events than people initiating an oGLD. [ABSTRACT FROM AUTHOR]

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits. [ABSTRACT FROM AUTHOR]

Background: Multiple cardiovascular outcomes trials (CVOTs) have shown the efficacy of GLP-1RAs in reducing major adverse cardiovascular events (MACEs) for high-risk patients. However, some CVOTs failed to demonstrate cardiovascular benefits. Objectives: We analyzed the impact of GLP-1RA on cardiovascular and renal outcomes in patients with or without T2DM, with subgroup analysis based on sex, estimated glomerular filtration rate (eGFR), body mass index (BMI), and history of cardiovascular disease (CVD). Methods: A comprehensive database search for placebo-controlled RCTs on GLP-1RA treatment was conducted until April 2024. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with log odds ratios and 95 % confidence intervals (CIs). Results: A total of 13 CVOTs comprising 83,258 patients were included. GLP-1RAs significantly reduced MACE (OR 0.86, 95 % CI: 0.80 to 0.94, p < 0.01) all-cause mortality OR 0.87, 95 % CI: 0.82 to 0.93, p < 0.001, CV mortality (OR 0.87, 95 % CI: 0.81 to 0.94, p < 0.001), stroke (fatal: OR 0.74, 95 % CI: 0.56 to 0.96, p = 0.03; non-fatal: OR 0.87, 95 % CI: 0.79 to 0.96, p = 0.005), coronary revascularization (OR 0.86, 95 % CI: 0.74 to 0.99, p = 0.023), and composite kidney outcome (OR 0.76, 95 % CI: 0.67 to 0.85, p < 0.001. GLP-1RA significantly reduced MACE in both sexes. Furthermore, GLP-1RA reduced MACE regardless of CVD history, BMI, and eGFR level. Conclusion: Significant reductions in MACE, overall and CV mortality, stroke, coronary revascularization, and composite kidney outcome with GLP-1RA treatment were noted across all subgroups.

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits.

Importance: Some medications have effects that depend on the time of day they are given. Current knowledge of the time-of-day effects of specific medications in hospitalized patients with cardiovascular disease is very limited. In hospitalized patients, increased medication efficiency might reduce dose (and associated side effects) and/or the length of time in the Intensive Care Unit (ICU) or hospital–potentially improving patient outcomes and patient and family quality of life and reducing financial costs. We studied whether the time of day or night patients in Cardiac or Intensive Care Units receive a diuretic affects urine volume. Methods: In this observational study, data were collected from 7,685 patients (63% male, 18 to 98 years old) admitted to one hospital’s Acute Care Cardiac units, Cardiac ICUs, Cardiac Surgery ICUs, and/or Non-cardiac ICUs who received intravenous furosemide (a diuretic), had measurements of urine volume, were hospitalized for ≥3 days between January 2016 to July 2021 and were older than 18 years. The outcomes of interest were urine volume normalized by the most recent (not older than 24 h) weight or body mass index (BMI), (i) in the hour after the time of diuretic administration, and (ii) when no diuretics were administered for the previous 3 h. Results: We identified diuretic medication administration time 23:00–04:59 as a predictor of higher urine volume response. For patients without recent diuretic medication, higher urine volume was predicted 11:00–16:59 and 17:00–22:59. Other factors that affected urine volume response to the diuretic were sex, age, medication dose, creatinine concentration, diagnoses, and hospital unit. Discussion: Time-of-day of medication administration may be a factor associated with increased medication efficiency. Randomized controlled trials should be conducted to quantify the relative effect of modifiable factors, such as time of medication administration, that may affect short- and longerterm outcomes. [ABSTRACT FROM AUTHOR]

Aims: To investigate the renal, cardiovascular, and safety outcomes when sodium–glucose cotransporter-2 inhibitors (SGLT2is) were added to insulin therapy in patients with type-2 diabetes mellitus (T2DM). Materials and methods: We searched Embase, PubMed, and Cochrane libraries for reports published up to Feb 2023. Randomized controlled trials (RCTs) comparing SGLT2is and insulin combination therapy (SGLT2is + INS group) with insulin therapy alone (INS group) in T2DM were included. Results: Fourteen RCTs involving six thousand one hundred twenty subjects with durations of 12–104 weeks were included. Compared with the insulin group, the SGLT2is + INS group showed decreased glycosylated hemoglobin values and insulin dosages (P < 0.00001). Meanwhile, the SGLT2is + INS group had a reduced urinary albumin/creatinine ratio (UACR) by 25.42 mg/g and uric acid concentration (P = 0.030; P = 0.001, respectively) but the estimated glomerular filtration rate (eGFR) and renal-related adverse events were unaffected (P = 0.070; P = 0.880, respectively). Blood pressure and body weight were lower in the SGLT2is + INS group (P < 0.01). However, the risk of genital infection was bigger when SGLT2is were added to insulin therapy (P < 0.00001), but the risks of severe hypoglycemia or urinary tract infection were equal between the two groups (P > 0.05). Conclusion: Adding SGLT2is to insulin therapy in T2DM patients showed better glucose control and decreased albuminuria, uric acid, blood pressure, and body weight without a reduction in the eGFR. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21) is deemed to play an important role in kidney outcomes, while the association between FGF21 and various kidney diseases remains largely unclear and inconsistent. Therefore, we conducted this meta-analysis to find out the role of FGF21 in various renal diseases. The outcome indicator of our study was assessed by the pooled standard mean difference (SMD) with 95% confidence intervals (CIs) which were calculated by random-effect model analysis. The risk of bias was assessed by Non-Randomized Studies of Interventions (ROBINS-I) tool. Funnel plot combined with Egger's and Begg's tests was performed to estimate the publication bias that existed in the study. A total of 28 eligible studies with 19348 participants were included in our research. The agreement between authors reached a kappa-value of 0.88. Overall, the serum FGF21 level was strongly higher in CKD patients (SMD = 0.97 (ng/L); 95% CI, 0.70—1.24 (ng/L)) and the renal outcomes in T2DM patients (SMD = 0.54 (ng/L); 95% CI, 0.39–0.70 (ng/L)) compared with the control group. Consistent with this, the incidence of CKD (OR = 2.56; 95% CI, 1.72–3.81) and the incidence of renal outcomes (OR = 1.63; 95% CI, 1.31–2.01) in T2DM patients was significantly higher in the patients with high FGF21 concentration, indicating that high serum FGF21 level may predict the incidence of CKD and the renal outcomes in T2DM patients. Serum FGF21 may be one of the strong predictors for various kidney diseases including the progression of CKD and the hard renal outcomes in type 2 diabetes patients, but more large-scale clinical research are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Aim: An important characteristic of glucose‐lowering therapies (GLTs) is their ability to prevent cardiovascular complications. We aimed to investigate the cardiorenal efficacy and general safety of GLTs. Materials and Methods: Multicentre, randomized, clinical trials that included over 100 participants comparing antidiabetic agents with a placebo or a different antidiabetic agent and reporting major adverse cardiovascular events (MACEs), or primarily reporting heart failure, were searched in the PubMed, Embase and Cochrane databases. Data were extracted independently for random‐effects network meta‐analyses to calculate the hazard ratio estimates. Results: Forty‐three trials that compared nine types of GLTs were included in the present analysis. The risk of three‐point MACE was reduced in the presence of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is) and thiazolidinedione therapy compared with the placebo, dipeptidyl peptidase‐4 inhibitors, or insulin therapy. GLP‐1 RAs were favourable for cardiovascular and renal outcomes. SGLT‐2is reduced renal outcomes by ~40%, which was superior to other GLTs. Thiazolidinedione therapy increased the risks of hospitalization for heart failure and had no benefits on mortality. Adverse events leading to drug discontinuation were higher with GLP‐1 RAs and thiazolidinediones than placebo. Conclusions: GLP‐1 RAs, SGLT‐2is and thiazolidinediones reduced three‐point MACE compared with other GLTs. Each drug class had unique advantages and disadvantages. [ABSTRACT FROM AUTHOR]

Background: This prespecified subgroup analysis of the FIDELIO-DKD trial aimed to evaluate the efficacy and safety of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in China. Methods: 372 participants were recruited from 67 centers in China and randomized 1:1 to oral finerenone or placebo with standard therapy for T2DM. The primary composite outcome included kidney failure, sustained decrease of estimated glomerular filtration rate ≥40% from baseline over at least 4 weeks, or renal death. The key secondary composite outcome included death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results: After a median follow-up of 30 months, the finerenone group showed a relative risk reduction (RRR) of 41% (hazard ratio [HR] = 0.59, 95% confidence interval [CI], 0.39–0.88; p = 0.009) for the primary composite outcome compared with placebo, consistent across its components with treatment benefits with finerenone. Based on an absolute between-group difference of 12.2% after 30 months, the number of patients who needed to be treated with finerenone to prevent one primary outcome event was eight (95% CI: 4–84). For the key secondary composite outcome, the finerenone group showed a RRR of 25% (HR = 0.75, 95% CI, 0.38–1.48; p = 0.408). Adverse events were similar between the two groups. The effects of finerenone on blood pressure were modest. No gynecomastia events were reported in the study. Hyperkalemia leading to discontinuation occurred in eight (4.3%) and two (1.1%) participants in the finerenone and control groups, respectively. The incidence of acute kidney injury was comparable between the two groups (1.6% vs. 1.6%). Conclusions: Finerenone resulted in lower risks of CKD progression than placebo and a balanced safety profile in Chinese patients with CKD and T2DM.

Importance: Some medications have effects that depend on the time of day they are given. Current knowledge of the time-of-day effects of specific medications in hospitalized patients with cardiovascular disease is very limited. In hospitalized patients, increased medication efficiency might reduce dose (and associated side effects) and/or the length of time in the Intensive Care Unit (ICU) or hospital–potentially improving patient outcomes and patient and family quality of life and reducing financial costs. We studied whether the time of day or night patients in Cardiac or Intensive Care Units receive a diuretic affects urine volume.Methods: In this observational study, data were collected from 7,685 patients (63% male, 18 to 98 years old) admitted to one hospital’s Acute Care Cardiac units, Cardiac ICUs, Cardiac Surgery ICUs, and/or Non-cardiac ICUs who received intravenous furosemide (a diuretic), had measurements of urine volume, were hospitalized for ≥3 days between January 2016 to July 2021 and were older than 18 years. The outcomes of interest were urine volume normalized by the most recent (not older than 24 h) weight or body mass index (BMI), (i) in the hour after the time of diuretic administration, and (ii) when no diuretics were administered for the previous 3 h.Results: We identified diuretic medication administration time 23:00–04:59 as a predictor of higher urine volume response. For patients without recent diuretic medication, higher urine volume was predicted 11:00–16:59 and 17:00–22:59. Other factors that affected urine volume response to the diuretic were sex, age, medication dose, creatinine concentration, diagnoses, and hospital unit.Discussion: Time-of-day of medication administration may be a factor associated with increased medication efficiency. Randomized controlled trials should be conducted to quantify the relative effect of modifiable factors, such as time of medication administration, that may affect short- and longer-term outcomes.

AbstractBackground Fibroblast growth factor 21 (FGF21) is deemed to play an important role in kidney outcomes, while the association between FGF21 and various kidney diseases remains largely unclear and inconsistent. Therefore, we conducted this meta-analysis to find out the role of FGF21 in various renal diseases.Methods The outcome indicator of our study was assessed by the pooled standard mean difference (SMD) with 95% confidence intervals (CIs) which were calculated by random-effect model analysis. The risk of bias was assessed by Non-Randomized Studies of Interventions (ROBINS-I) tool. Funnel plot combined with Egger’s and Begg’s tests was performed to estimate the publication bias that existed in the study.Results A total of 28 eligible studies with 19348 participants were included in our research. The agreement between authors reached a kappa-value of 0.88. Overall, the serum FGF21 level was strongly higher in CKD patients (SMD = 0.97 (ng/L); 95% CI, 0.70—1.24 (ng/L)) and the renal outcomes in T2DM patients (SMD = 0.54 (ng/L); 95% CI, 0.39–0.70 (ng/L)) compared with the control group. Consistent with this, the incidence of CKD (OR = 2.56; 95% CI, 1.72–3.81) and the incidence of renal outcomes (OR = 1.63; 95% CI, 1.31–2.01) in T2DM patients was significantly higher in the patients with high FGF21 concentration, indicating that high serum FGF21 level may predict the incidence of CKD and the renal outcomes in T2DM patients.Conclusion Serum FGF21 may be one of the strong predictors for various kidney diseases including the progression of CKD and the hard renal outcomes in type 2 diabetes patients, but more large-scale clinical research are needed to confirm this finding.

Background: Despite progress in the diagnosis and treatment of proliferative lupus nephritis (PLN), the prognosis remains unfavorable. Previous investigations have suggested that the deficiency of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). But the prognostic value of Tregs in PLN remains controversial. This study aimed to investigate the association of Tregs with renal outcomes in patients with PLN. Methods: The baseline and follow-up data of patients with biopsy-proven PLN were collected in this study. All patients were divided into two groups according to whether the renal endpoint event occurred. Clinicopathologic features and therapeutic responses were compared between the two groups. Cox regression analyses curve fitting and threshold effect analysis were implemented to investigate the relationship between Tregs level and the long-term renal outcomes. The renal endpoint was defined as end-stage kidney disease (ESKD) or doubling the SCr value. Results: A total of 405 PLN patients were included. After a follow-up of 71.53 (53.13–97.47) months, 42 (10.4%) patients reached the renal endpoint. The Treg cell counts (16/μL) in the renal endpoint group were significantly decreased than that in the non-renal endpoint group (p < 0.001). Univariate and multivariate Cox regression analyses showed that the high level of Tregs was an independent protective factor for the long-term renal prognosis of PLN. Smooth curve fitting of the generalized additive mixed model analysis indicated that the risk of renal endpoint first decreased with Tregs and then slightly increased along with Treg cell levels. The segmented linear model revealed that when Treg cell counts <46/μL, the risk of renal endpoint decreased by 6.8% for every 1 μL increase in Treg levels (p = 0.0029). Conclusion: Treg cell counts are closely related to the long-term renal outcomes of patients with PLN, and increasing Treg cell levels may play an important role in improving the prognosis of the kidney, but there may be a turning point (i.e., threshold effect) at the Treg cell counts that leads to directional changes in the renal outcomes. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication following endovascular aortic repair (EVAR). An association of AKI with patient survival after fenestrated EVAR (FEVAR) is currently under investigation. Patients undergoing FEVAR between April 2013 and June 2020 were included in the study. AKI was defined according to acute kidney injury network criteria. Demographic and perioperative data, complications, and survival are reported for the study cohort. The data were analyzed to identify possible predictors of AKI. Two hundred and seventeen patients underwent FEVAR during the study period. Survival at last follow-up (20.4 ± 20.1 mo) was 75.1%. Thirty patients experienced AKI (13.8%). Six of 30 patients with AKI (20%) died within 30 days or in-hospital and 1 (3.3%) progressed to hemodialysis. Within 1 y, renal function had recovered in 23 patients (76.7%). In-hospital mortality was higher in patients with AKI (20% versus 4.3%, P = 0.006). A higher rate of AKI was seen in patients in whom an intraoperative technical complication had been documented (38.5% versus 8.4%, P = 0.001). Patients undergoing FEVAR are at risk of developing AKI, especially if they experience technical intraoperative complications. Most patients see recovery of renal function within the first 30 days to 1 y, but AKI remains associated with significantly increased in-hospital mortality. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is the most frequent serious manifestation of patients with systemic lupus erythematosus (SLE). Up to 60% of SLE patients develop LN, which has a significant impact on their quality of life and prognosis. Recent advances have improved the diagnostic approach to LN, and new drugs that block specific pathways and kidney damage progression have been developed. Several randomized and well-powered clinical trials have confirmed the efficacy of these agents in terms of proteinuria remission and preservation of kidney function in the medium and long term, with an acceptable safety profile and good tolerance. The combination of different therapies allows for reduction of the dose and duration of corticosteroids and other potentially toxic therapies and leads to an increase in the number of patients achieving complete remission of the disease. This consensus document carried out by the Spanish Group for the Study of Glomerular Diseases (GLOSEN) provides practical and updated recommendations, based on the best available evidence and clinical expertise of participating nephrologists. [ABSTRACT FROM AUTHOR]

Introduction: Older patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) commonly experience renal impairment and poor prognoses. This study aimed to establish a risk-scoring system for predicting composite renal outcomes in older patients with AAV. Methods: This retrospective observational study included all patients with AAV hospitalized in a single-center tertiary hospital in China between January 2013 and April 2022. Patients aged ≥65 years were defined as older adults and short-term composite renal outcomes included a ≥25% reduction in estimated glomerular filtration rate (eGFR) (for AKI), renal replacement therapy, provision of renal replacement therapy (long-term dialysis, kidney transplant, or sustained eGFR <15 mL/min/1.73 m), or all-cause mortality. Patients were randomly divided into development and validation cohorts (2:1). Logistic regression analysis was performed in the development cohort to analyze risk factors. The scoring system was established accordingly and further validated in the validation cohort. Results: 1,203 patients were enrolled in the study, among whom the older adult group accounted for 36% with a mean age of 71. The older adult group had a worse prognosis, a higher mortality rate, a higher rate of end-stage renal disease, and worsening renal function. Logistic regression showed that age >75 years, chronic heart disease, and elevated serum creatinine and D-dimer values were risk factors for poor prognosis in patients with AAV. The development and validation cohorts in patients with AAV produced area under the curve values of 0.82 (0.78–0.86) and 0.83 (0.77–0.89), respectively. Conclusion: We established a risk-scoring system based on baseline clinical characteristics to predict composite renal outcomes in patients with AAV. Our results suggest that more attention should be paid to older patients with severe renal impairment and active inflammation. [ABSTRACT FROM AUTHOR]

Abstract Background To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR)

Aims: The aim of our meta‐analyses was to compare the effects of glucose‐lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. Methods: Meta‐analyses comparing drugs within the classes of GLP‐1RAs and SGLT‐2 inhibitors were performed and compared to sulphonylureas and DPP‐4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose‐lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. Results: SGLT‐2 inhibitors and GLP‐1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP‐4 inhibitors and sulphonylureas. SGLT‐2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT‐2 inhibitors and GLP‐1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low‐risk subgroup. Conclusions: The findings from our analyses substantiate the relevance of treatment with SGLT‐2 inhibitors or GLP‐1RAs as an add‐on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT‐2 inhibitor treatment in patients with T2D and heart failure or established kidney disease. [ABSTRACT FROM AUTHOR]

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Abstract Background Chronic kidney disease (CKD) is age-related disease, and decreased renal function is associated with the premature aging of T cells and increased incidence of other age-related diseases. However, the relationship between T cell senescence and CKD progression remains unclear. Here, we investigated the relationship between T cell senescence, as indicated by decreased thymic output and increased proportion of highly differentiated CD28− T cells, and CKD progression. Results A total of 175 patients with non-dialysis-dependent CKD were enrolled in this study. Thymic output was assessed based on the CD45RA+CD31+CD4+ cell (recent thymic emigrant [RTE]) counts (RTEs) (/mm3) and the proportion of RTE among CD4+ T cells (RTE%). Highly differentiated T cells were assessed based on the proportion of CD28− cells among CD4+ T cells (CD28−/CD4+) and CD28− cells among CD8+ T cells (CD28−/CD8+). The primary outcome was estimated glomerular filtration rate (eGFR) decline of ≥40% or initiation of renal replacement therapy. The association between T cell senescence and renal outcomes was examined using Cox proportional hazards models and restricted cubic splines. The median age was 73 years, 33% were women, and the median eGFR was 26 mL/min/1.73 m2. The median RTEs, RTE%, CD28−/CD4+, and CD28−/CD8+ were 97.5/mm3, 16.2, 5.3, and 49.7%, respectively. After a median follow-up of 1.78 years, renal outcomes were observed in 71 patients. After adjusting for age, sex, eGFR, proteinuria, diabetes, and cytomegalovirus seropositivity, decreased RTEs, which corresponded to decreased thymic output, significantly and monotonically increased the risk of poor renal outcome (p = 0.04), and decreased RTE% and increased highly differentiated CD28−/CD4+ T cells also tended to monotonically increase the risk (p = 0.074 and p = 0.056, respectively), but not CD28−/CD8+ T cells. Conclusions Decreased thymic output in CKD patients, as well as increased highly differentiated CD4+ T cells, predicted renal outcomes. Thus, the identification of patients prone to CKD progression using T cell senescence, particularly decreased RTE as a biomarker, may help to prevent progression to end-stage kidney disease.

A significant number of patients with systemic lupus erythematosus (between 20% and 60% according to different reported series) develop lupus nephritis in the course of its evolution, which directly influences their quality of life and vital prognosis. In recent years, the greater knowledge about the pathogenesis of systemic lupus and lupus nephritis has allowed relevant advances in the diagnostic approach and treatment of these patients, achieving the development of drugs specifically aimed at blocking key pathogenic pathways of the disease. Encouragingly, these immunomodulatory agents have shown in well-powered, randomized clinical trials good clinical efficacy in the medium-term, defined as proteinuria remission and preservation of kidney function, with an acceptable safety profile and good patient tolerability. All this has made it possible to reduce the use of corticosteroids and other potentially more toxic therapies, as well as to increase the use of combined therapies. The present consensus document carried out by the Glomerular Diseases Working Group of the Spanish Society of Nephrology (GLOSEN), collects in a practical and summarized, but rigorous way, the best currently available evidence about the diagnosis, treatment, and follow-up of lupus nephritis patients, including cases of special situations, with the main objective of providing updated information and well-founded clinical recommendations to treating physicians, to improve the diagnostic and therapeutic approach to our patients. Resumen: Un número importante de pacientes con lupus eritematoso sistémico (entre un 20% a 60%, según diferentes series), desarrolla nefritis lúpica en el curso de su evolución, lo que influye directamente en su calidad de vida y pronóstico vital. En años recientes, el mayor conocimiento sobre la patogénesis del lupus sistémico y de la nefritis lúpica, ha permitido avances relevantes en el abordaje diagnóstico y en el tratamiento de estos pacientes, lográndose desarrollar fármacos dirigidos específicamente a bloquear vías patogénicas claves de la enfermedad. Alentadoramente, estos agentes inmunomoduladores han demostrado en ensayos clínicos aleatorizados y bien ponderados, buena eficacia clínica a mediano plazo, definida como remisión de proteinuria y preservación de la función renal, con un aceptable perfil de seguridad y buena tolerabilidad del paciente. Todo esto ha permitido reducir el uso de corticoides y de otras terapias potencialmente más tóxicas, así como incrementar el uso de terapias combinadas. El presento documento de consenso realizado por el Grupo de Trabajo de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN), recoge de manera práctica y resumida, pero rigurosa, la mejor evidencia actual disponible acerca del diagnóstico, tratamiento y seguimiento del paciente con nefritis lúpica, incluyendo casos de situaciones especiales, con el objetivo principal de brindar información actualizada y recomendaciones clínicas bien fundamentadas a los médicos tratantes, para mejorar el enfoque diagnóstico y terapéutico a nuestro pacientes.

Resumen: Un número importante de pacientes con lupus eritematoso sistémico (entre 20 a 60%, según diferentes series) desarrolla nefritis lúpica en el curso de su evolución, lo que influye directamente en su calidad de vida y pronóstico vital. En años recientes, el mayor conocimiento sobre la patogénesis del lupus sistémico y de la nefritis lúpica ha permitido avances relevantes en el abordaje diagnóstico y en el tratamiento de estos pacientes, lográndose desarrollar fármacos dirigidos específicamente a bloquear vías patogénicas claves de la enfermedad. Alentadoramente estos agentes inmunomoduladores han demostrado en ensayos clínicos aleatorizados, y bien ponderados, buena eficacia clínica a mediano plazo, definida como remisión de proteinuria y preservación de la función renal, con un aceptable perfil de seguridad y buena tolerabilidad del paciente. Todo esto ha permitido reducir el uso de corticoides y de otras terapias potencialmente más tóxicas, así como incrementar el uso de terapias combinadas. El presento documento de consenso realizado por el Grupo de Trabajo de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN) recoge de manera práctica y resumida, pero rigurosa, la mejor evidencia actual disponible acerca del diagnóstico, tratamiento y seguimiento del paciente con nefritis lúpica, incluyendo casos de situaciones especiales, con el objetivo principal de brindar información actualizada y recomendaciones clínicas bien fundamentadas a los médicos tratantes, para mejorar el enfoque diagnóstico y terapéutico a nuestro pacientes. Summary: A significant number of patients with systemic lupus erythematosus (between 20% to 60% according to different reported series) develop lupus nephritis in the course of its evolution, which directly influences their quality of life and vital prognosis. In recent years, the greater knowledge about the pathogenesis of systemic lupus and lupus nephritis has allowed relevant advances in the diagnostic approach and treatment of these patients, achieving the development of drugs specifically aimed at blocking key pathogenic pathways of the disease. Encouragingly, these immunomodulatory agents have shown in well-powered, randomized clinical trials good clinical efficacy in the medium-term, defined as proteinuria remission and preservation of kidney function, with an acceptable safety profile and good patient tolerability. All this has made it possible to reduce the use of corticosteroids and other potentially more toxic therapies, as well as to increase the use of combined therapies. The present consensus document carried out by the Glomerular Diseases Working Group of the Spanish Society of Nephrology (GLOSEN), collects in a practical and summarized, but rigorous way, the best currently available evidence about the diagnosis, treatment, and follow-up of lupus nephritis patients, including cases of special situations, with the main objective of providing updated information and well-founded clinical recommendations to treating physicians, to improve the diagnostic and therapeutic approach to our patients.

Background The relationship between arteriolar hyalinosis and renal progression in immunoglobulin A nephropathy (IgAN) is not fully understood. We aimed to investigate the clinicopathological features and outcomes of IgAN with or without arteriolar hyalinosis.Methods A total of 762 diagnosed with IgAN patients were retrospectively analyzed. We classified IgAN patients into two groups with or without arteriolar hyalinosis. Then, the clinicopathological characteristics of the two groups were compared. We used Kaplan–Meier survival analysis to compare the composite kidney outcome of the two groups and applied multivariate Cox regression analyses to test the association between arteriolar hyalinosis and composite kidney outcome.Results Overall, 412 (54.1%) patients had arteriolar hyalinosis, including 173 patients diagnosed with hypertension. IgAN patients with arteriolar hyalinosis were older and had higher proteinuria, urea, uric acid, and blood pressure, while lower eGFR than those without arteriolar hyalinosis. Subgroup analysis showed similar results in IgAN patients with hypertension. Kaplan–Meier survival analysis showed that IgAN patients with arteriolar hyalinosis had worse composite kidney outcome than those without arteriolar hyalinosis. In addition, subgroup analysis revealed that patients with hypertension have worse composite kidney outcome than those without hypertension. Multivariate Cox regression analyses confirm that arteriolar hyalinosis (HR 2.57; 95% CI 1.41–4.69; p = 0.002) is an independent risk factor for renal prognosis in IgAN patients.Conclusions Our study demonstrated that arteriolar hyalinosis is a common vascular lesion in IgAN patients. Arteriolar hyalinosis connects closely with hypertension, and arteriolar hyalinosis is an independent risk factor for renal prognosis in patients with IgAN.

Background Metabolic acidosis accelerates the progression of chronic kidney disease (CKD) and increases the mortality rate. Whether oral alkali drug therapy benefits pre-dialysis CKD patients is controversial. We performed a meta-analysis of the effects of oral alkali drug therapy on major clinical outcomes in pre-dialysis CKD patients. Methods We systematically searched MEDLINE using the Ovid, EMBASE, and Cochrane Library databases without language restriction. We included all eligible clinical studies that involved pre-dialysis CKD adults and compared those who received oral alkali drug therapy with controls. Results A total of 18 eligible studies, including 14 randomized controlled trials and 4 cohort studies reported in 19 publications with 3695 participants, were included. Oral alkali drug therapy led to a 55% reduction in renal failure events (relative risk [RR]: 0.45; 95% confidence interval [CI]: 0.25–0.82), a rate of decline in the estimated glomerular filtration rate (eGFR) of 2.59 mL/min/1.73 m2 per year (95% CI, 0.88–4.31). There was no significant effect on decline in eGFR events (RR: 0.34; 95% CI: 0.09–1.23), proteinuria (standardized mean difference: −0.32; 95% CI: −1.08 to 0.43), all-cause mortality events (RR: 0.90; 95% CI: 0.40–2.02) and cardiovascular (CV) events (RR: 1.03; 95% CI: 0.32–3.37) compared with the control groups. Conclusion Based on the available and low-to-moderate certainty evidence, oral alkali drug therapy might potentially reduce the risk of kidney failure events, but no benefit in reducing all-cause mortality events, CV events, decline in eGFR and porteninuria.

Background: Systemic lupus erythematosus (SLE) disproportionately affects individuals of African ancestry (AA) compared to European ancestry (EA). In the general population, high risk (HR) variants in the apolipoprotein L1 (APOL1) gene increase the risk of renal and hypertensive disorders in individuals of AA. Since SLE is characterized by an interferon signature and APOL1 expression is driven by interferon, we examined the hypothesis that APOL1 HR genotypes predominantly drive higher rates of renal and hypertensive-related comorbidities observed in SLE patients of AA versus those of EA. Methods: We performed a retrospective cohort study in patients with SLE of EA and AA using a genetic biobank linked to de-identified electronic health records. APOL1 HR genotypes were defined as G1/G1, G2/G2, or G1/G2 and low risk (LR) genotypes as 1 or 0 copies of the G1 and G2 alleles. To identify renal and hypertensive-related disorders that differed in prevalence by ancestry, we used a phenome-wide association approach. We then used logistic regression to compare the prevalence of renal and hypertensive-related disorders in EA and AA patients, both including and excluding patients with the APOL1 HR genotype. In a sensitivity analysis, we examined the association of end stage renal disease secondary to lupus nephritis (LN-related ESRD) with ancestry and the APOL1 genotype. Results: We studied 784 patients with SLE; 195 (24.9%) were of AA, of whom 27 (13.8%) had APOL1 HR genotypes. Eighteen renal and hypertensive-related phenotypes were more common in AA than EA patients (p-value ≤ 1.4E-4). All phenotypes remained significantly different after exclusion of patients with APOL1 HR genotypes, and most point odds ratios (ORs) decreased only slightly. Even among ORs with the greatest decrease, risk for AA patients without the APOL1 HR genotype remained significantly elevated compared to EA patients. In the sensitivity analysis, LN-related ESRD was more prevalent in SLE patients of AA versus EA and AA patients with the APOL1 HR genotype versus LR (p-value <.05 for both). Conclusion: The higher prevalence of renal and hypertensive disorders in SLE patients of AA compared to those of EA is not fully explained by the presence of APOL1 high risk variants. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular and renal outcomes in patients with established cardiovascular disease, chronic kidney disease (CKD), and heart failure (HF) with reduced or preserved ejection fraction. Clinical benefit has been substantiated in patients with and without type 2 diabetes (T2D). Consequently, SGLT2is have an increasingly important role in HF and CKD management that extends beyond T2D treatment. Their pleiotropic pharmacological effects underlying their cardiovascular and renal benefits are not completely understood but include significant effects beyond blood glucose reduction. SGLT2is inhibit the reabsorption of glucose and sodium in the proximal tubule which, in addition to lowering blood glucose, activates tubuloglomerular feedback, leading to reduced glomerular hydrostatic pressure and the mitigation of glomerular filtration rate loss. SGLT2is have diuretic and natriuretic effects, leading to decreased blood pressure, preload, and left ventricular (LV) filling pressure, and improvements in other surrogates of afterload. In HF, SGLT2is mitigate the risks of hyperkalemia and ventricular arrhythmia and improve LV dysfunction. SGLT2is also reduce sympathetic tone and uric acid levels, increase hemoglobin levels, and are postulated to have anti-inflammatory properties. This narrative review discusses the multifactorial and interrelated pharmacological mechanisms underlying the cardiovascular and renal benefits of SGLT2is. [ABSTRACT FROM AUTHOR]

Background: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2. Methods: In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups. Results: A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68–1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56–0.93). Conclusions: GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is. [ABSTRACT FROM AUTHOR]

Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1–4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes (HR 0.715; 95% CI 0.568 to 0.898), but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1–4. [ABSTRACT FROM AUTHOR]

Abstract Background Patient registries provide long-term, real-world evidence that aids the understanding of the natural history and progression of disease, and the effects of treatment on large patient populations with rare diseases. The year 2021 marks the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The primary aims of FOS are to broaden the understanding of Fabry disease (FD), an X-linked lysosomal storage disorder, and to improve the clinical management of affected patients. Here, we review the history of FOS and the analyses and publications disseminated from the registry, and we discuss the contributions FOS studies have made in understanding FD. Results FOS was initiated in April 2001 and, as of January 2021, 4484 patients with a confirmed diagnosis and patient informed consent have been enrolled from 144 centers across 26 countries. Data from FOS have been published in nearly 60 manuscripts on a wide variety of topics relevant to FD. Analyses of FOS data have investigated the long-term effectiveness and safety of enzyme replacement therapy (ERT) with agalsidase alfa and its effects on morbidity and mortality, as well as the benefits of prompt and early treatment with agalsidase alfa on the progression of cardiomyopathy and the decline in renal function associated with FD. Based on analyses of FOS data, ERT with agalsidase alfa has also been shown to improve additional signs and symptoms of FD experienced by patients. FOS data analyses have provided a better understanding of the natural history of FD and the specific populations of women, children, and the elderly, and have provided practical tools for the study of FD. FOS has also provided methodology and criteria for assessing disease severity which contributed to the continuous development of medical practice in FD and has largely improved our understanding of the challenges and needs of long-term data collection in rare diseases, aiding in future rare disease real-world evidence studies. Conclusion FOS over the last 20 years has substantially increased the scientific knowledge around improved patient management of FD and continues to expand our understanding of this rare disease.

Background: Chronic kidney disease (CKD) is a prevalent and progressive condition worldwide, and diabetes is a leading risk factor of this renal disorder. People with diabetes and CKD are at high risk of complications such as cardiovascular events and death. CKD is often unrecognized and undiagnosed amongst people with diabetes. To manage CKD, multiple existing and newer agents have been studied in trials and recommended in clinical practice guidelines. Methods: A narrative review of primary and/or secondary renal outcomes from randomized, controlled trials is summarized in this article. The main objective was to provide the most up-to-date information regarding existing and new pharmacotherapy for the management of CKD amongst people with diabetes, specifically type 2 diabetes (T2D). Discussion: Traditional agents, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have been used for 20 years to preserve kidney function. Other existing agents have received approval by the FDA for the management of CKD such as dapagliflozin, with a role in reducing intraglomerular pressure. Evidence with sodium–glucose cotransporter 2 inhibitors show a potential class effect on improving renal outcomes, independent on their effect on glycaemic parameters. Recently, finerenone was approved for people with T2D and CKD based on clinical evidence as a non-steroidal mineralocorticoid receptor antagonist. Overall, primary and secondary prevention trials have influenced changes in clinical practice guidelines regarding the use of existing and new pharmacotherapy for CKD. Additional considerations include lifestyle modifications, blood pressure management and achievement of glycaemic targets for people with diabetes and CKD, following adequate screening of glomerular filtration rate and/or severity of albuminuria. Conclusion: Due to more robust evidence, clinical practice guidelines have been modified to reflect high-level recommendations for the management of CKD in people with diabetes, specifically T2D. Additional evidence is needed amongst people with lower glomerular filtration rates and in comparison with the standard of care.

Background Hispanic populations are more likely to develop diabetes and its related diseases than non‐Hispanic White populations. Little evidence exists to support whether the cardiovascular and renal benefits of sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide‐1 receptor agonists are generalizable to the Hispanic populations. Methods and Results We included the cardiovascular and renal outcome trials (up to March 2021) that reported the major adverse cardiovascular events (MACEs), cardiovascular death/hospitalization for heart failure, and composite renal outcomes by ethnicity in individuals with type 2 diabetes (T2D), calculated pooled hazard ratios (HRs) with 95% CIs using fixed‐effects models, and tested the differences between Hispanic and non‐Hispanic populations (P for interaction [Pinteraction]). In 3 sodium‐glucose cotransporter 2 inhibitor trials, there was a statistically significant difference between Hispanic (HR, 0.70 [95% CI, 0.54–0.91]) and non‐Hispanic (HR, 0.96 [95% CI, 0.86–1.07]) groups in treatment effects on MACE risk (Pinteraction=0.03), except for risks of cardiovascular death/hospitalization for heart failure (Pinteraction=0.46) and composite renal outcome (Pinteraction=0.31). In 5 glucagon‐like peptide‐1 receptor agonist trials, there was no statistically significant difference in treatment effect on MACE risk between Hispanic (HR, 0.82 [95% CI, 0.70–0.96]) and non‐Hispanic (HR, 0.92 [95% CI, 0.84–1.00]) populations (Pinteraction=0.22). In 3 dipeptidyl peptidase‐4 inhibitor trials, the HR for MACE risk appeared greater in Hispanic (HR, 1.15 [95% CI, 0.98–1.35]) than non‐Hispanic (HR, 0.96 [95% CI, 0.88–1.04]) populations (Pinteraction=0.045). Conclusions Compared with non‐Hispanic individuals, Hispanic individuals with T2D appeared to obtain a greater benefit of lowered MACE risk with sodium‐glucose cotransporter 2 inhibitors.

Background: Chronic kidney disease (CKD) is age-related disease, and decreased renal function is associated with the premature aging of T cells and increased incidence of other age-related diseases. However, the relationship between T cell senescence and CKD progression remains unclear. Here, we investigated the relationship between T cell senescence, as indicated by decreased thymic output and increased proportion of highly differentiated CD28− T cells, and CKD progression. Results: A total of 175 patients with non-dialysis-dependent CKD were enrolled in this study. Thymic output was assessed based on the CD45RA+CD31+CD4+ cell (recent thymic emigrant [RTE]) counts (RTEs) (/mm3) and the proportion of RTE among CD4+ T cells (RTE%). Highly differentiated T cells were assessed based on the proportion of CD28− cells among CD4+ T cells (CD28−/CD4+) and CD28− cells among CD8+ T cells (CD28−/CD8+). The primary outcome was estimated glomerular filtration rate (eGFR) decline of ≥40% or initiation of renal replacement therapy. The association between T cell senescence and renal outcomes was examined using Cox proportional hazards models and restricted cubic splines. The median age was 73 years, 33% were women, and the median eGFR was 26 mL/min/1.73 m2. The median RTEs, RTE%, CD28−/CD4+, and CD28−/CD8+ were 97.5/mm3, 16.2, 5.3, and 49.7%, respectively. After a median follow-up of 1.78 years, renal outcomes were observed in 71 patients. After adjusting for age, sex, eGFR, proteinuria, diabetes, and cytomegalovirus seropositivity, decreased RTEs, which corresponded to decreased thymic output, significantly and monotonically increased the risk of poor renal outcome (p = 0.04), and decreased RTE% and increased highly differentiated CD28−/CD4+ T cells also tended to monotonically increase the risk (p = 0.074 and p = 0.056, respectively), but not CD28−/CD8+ T cells. Conclusions: Decreased thymic output in CKD patients, as well as increased highly differentiated CD4+ T cells, predicted renal outcomes. Thus, the identification of patients prone to CKD progression using T cell senescence, particularly decreased RTE as a biomarker, may help to prevent progression to end-stage kidney disease. [ABSTRACT FROM AUTHOR]

Background: The nonsteroidal mineralocorticoid antagonist finerenone is a new addition to the list of agents (angiotensin converting enzyme inhibitors and sodium glucose cotransporter 2 inhibitors) conferring renal protection to patients with diabetic kidney disease. Two recent meta-analyses using the fixed effect model in patients with chronic kidney disease (both diabetic and nondiabetic populations) came to a conflicting conclusion on the effect of finerenone on eGFR decline. This meta-analysis was undertaken exclusively in the type 2 diabetes (T2D) population to explore the robustness and heterogeneity of the effect size by conducting a random effects model meta-analysis along with draft plots and prediction intervals. Materials and methods: A database search was conducted using the Cochrane library, PubMed, and Embase to identify relevant citations. Analysis was conducted on the 14th of September 2022, using RevMan 5.4.1 and RStudio (2022.07.1, Build 554). The hazard ratio was used as the effect size for the renal composite, while the standardized mean difference (SMD) was used to estimate the effect size of eGFR decline and reduction in the urine albumin creatinine ratio (UACR). The Cochrane risk-of-bias was used to assess the quality of the studies. The primary outcome assessed was the renal composite defined as kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. Results: A pooled population of 13,943 patients from four citations was included for analysis. The Cochrane risk of bias was used to assess the quality of the studies. There was a significant 16% reduction in the renal composite (kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes) [HR: 0.84, 95% CI 0.77-0.92, ² : 0, I2 : 0%). Finerenone was also associated with reduction in UACR (SMD: -0.49, 95% CI -0.53 to -0.46, t ² : < 0.0001, I² : 0%, prediction interval: -0.57 to -0.41) and prevention of decline in eGFR (SMD: -0.32, 95% CI -0.37 to -0.27, t ² : < 0.0001, I2 : 0%, prediction interval: -0.43 to -0.21) without any evidence for significant heterogeneity. Except for an increase in hyperkalaemia (RR: 2.22, 95% CI 1.93-2.24), adverse events were observed with fineronone compared to placebo (RR: 1.00, 95% CI 0.98-1.01). Conclusion: There are significant benefits in renal outcomes associated with finerenone treatment in T2D patients with established chronic kidney disease with a side effect profile comparable to placebo. [ABSTRACT FROM AUTHOR]

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The relationship between arteriolar hyalinosis and renal progression in immunoglobulin A nephropathy (IgAN) is not fully understood. We aimed to investigate the clinicopathological features and outcomes of IgAN with or without arteriolar hyalinosis. A total of 762 diagnosed with IgAN patients were retrospectively analyzed. We classified IgAN patients into two groups with or without arteriolar hyalinosis. Then, the clinicopathological characteristics of the two groups were compared. We used Kaplan–Meier survival analysis to compare the composite kidney outcome of the two groups and applied multivariate Cox regression analyses to test the association between arteriolar hyalinosis and composite kidney outcome. Overall, 412 (54.1%) patients had arteriolar hyalinosis, including 173 patients diagnosed with hypertension. IgAN patients with arteriolar hyalinosis were older and had higher proteinuria, urea, uric acid, and blood pressure, while lower eGFR than those without arteriolar hyalinosis. Subgroup analysis showed similar results in IgAN patients with hypertension. Kaplan–Meier survival analysis showed that IgAN patients with arteriolar hyalinosis had worse composite kidney outcome than those without arteriolar hyalinosis. In addition, subgroup analysis revealed that patients with hypertension have worse composite kidney outcome than those without hypertension. Multivariate Cox regression analyses confirm that arteriolar hyalinosis (HR 2.57; 95% CI 1.41–4.69; p = 0.002) is an independent risk factor for renal prognosis in IgAN patients. Our study demonstrated that arteriolar hyalinosis is a common vascular lesion in IgAN patients. Arteriolar hyalinosis connects closely with hypertension, and arteriolar hyalinosis is an independent risk factor for renal prognosis in patients with IgAN. [ABSTRACT FROM AUTHOR]

Metabolic acidosis accelerates the progression of chronic kidney disease (CKD) and increases the mortality rate. Whether oral alkali drug therapy benefits pre-dialysis CKD patients is controversial. We performed a meta-analysis of the effects of oral alkali drug therapy on major clinical outcomes in pre-dialysis CKD patients. We systematically searched MEDLINE using the Ovid, EMBASE, and Cochrane Library databases without language restriction. We included all eligible clinical studies that involved pre-dialysis CKD adults and compared those who received oral alkali drug therapy with controls. A total of 18 eligible studies, including 14 randomized controlled trials and 4 cohort studies reported in 19 publications with 3695 participants, were included. Oral alkali drug therapy led to a 55% reduction in renal failure events (relative risk [RR]: 0.45; 95% confidence interval [CI]: 0.25–0.82), a rate of decline in the estimated glomerular filtration rate (eGFR) of 2.59 mL/min/1.73 m2 per year (95% CI, 0.88–4.31). There was no significant effect on decline in eGFR events (RR: 0.34; 95% CI: 0.09–1.23), proteinuria (standardized mean difference: −0.32; 95% CI: −1.08 to 0.43), all-cause mortality events (RR: 0.90; 95% CI: 0.40–2.02) and cardiovascular (CV) events (RR: 1.03; 95% CI: 0.32–3.37) compared with the control groups. Based on the available and low-to-moderate certainty evidence, oral alkali drug therapy might potentially reduce the risk of kidney failure events, but no benefit in reducing all-cause mortality events, CV events, decline in eGFR and porteninuria. [ABSTRACT FROM AUTHOR]

Abstract The association of heart rate (HR) dipping pattern with renal outcomes in chronic kidney disease (CKD) patients with hypertension has never been investigated. In order to demonstrate if HR dipping pattern is a risk factor for renal outcomes, cardiovascular (CV) diseases, and mortality in hypertensive patients with CKD, we conducted the prospective longitudinal observational study. Patients were divided into three groups according to their nocturnal HR: HR dippers (night–day HR ratio ≤ 0.9), HR non‐dippers (0.9 1.0). The primary outcome was renal endpoint, a composite outcome of progression to end‐stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50%; the secondary outcomes included poor renal outcomes, CV events, and death. A total of 34 (11.3%) patients reached renal endpoint after a follow‐up of 34 ± 17 months. Both HR non‐dippers and HR risers were predictive to renal endpoint (hazard ratio 2.58, 95% confidence interval (CI) 1.04‐ 6.4, P = .04; hazard ratio 3.95, 95% CI 1.33‐ 11.79, P = .01, respectively), while only HR risers was shown to be correlated with a decline in eGFR≥ 50% (hazard ratio 5.28, 95% CI 1.45–19.16, P