Risk Of Chronic Kidney Disease Progression Research Articles

Association of iron deficiency with kidney outcome and all-cause mortality in chronic kidney disease patients without anemia

BackgroundIron deficiency is prevalent in patients with chronic kidney disease (CKD), even in those without anemia. However, the effects of iron deficiency on CKD progression and all-cause mortality in non-dialysis-dependent CKD (NDD-CKD) patients without anemia remain incompletely understood.MethodsThis multicenter retrospective nationwide cohort study included adult patients with non-anemia NDD-CKD from 24 hospitals across China. The study investigated the associations between serum ferritin or transferrin saturation (TSAT) levels and the risks of CKD progression and all-cause mortality.ResultsAmong 18,878 patients with NDD-CKD, 9,989 patients were included in the kidney outcome analysis, and 18,481 patients in the all-cause mortality analysis. Of the patients with the measurement, 2,450 (27.2%) had ferritin levels ≤ 100ng/mL and 2,440 (13.1%) had a TSAT level ≤ 20%. Compared with patients with TSAT level of > 20%, those with TSAT level of ≤ 20% had significantly higher risks of CKD progression (adjusted hazard ratio [aHR]: 1.66, 95% confidence intervals [CI]: 1.16–2.37; P = 0.005) and all-cause mortality (aHR: 2.21, 95% CI: 1.36–3.57; P = 0.001). The robustness of results was supported by subgroup analyses. However, there was no significant association found between ferritin levels and the risk of CKD progression or all-cause mortality (P > 0.05).ConclusionIron deficiency was prevalent in NDD-CKD patients without anemia, and TSAT could be a modifiable risk factor of CKD progression and all-cause mortality. The screening of iron biomarkers, especially TSAT, in the early stage of NDD-CKD is important to assess and improve prognosis.

Association of peripheral eosinophil count with chronic kidney disease progression risk: a retrospective cohort study in Chinese population

Background The role of peripheral eosinophils in chronic kidney disease (CKD) requires further evaluation. We aimed to determine whether an eosinophil count increase is related to the occurrence of end-stage renal disease (ESRD). Methods This single-center, observational, retrospective cohort study was conducted between January 2016 and December 2018 in Hangzhou, China, and included 3163 patients, categorized into four groups according to peripheral eosinophil count (PEC) quartile values. The main outcome was ESRD development during follow-up. We evaluated the relationship between the serum eosinophil count, demographic and clinical information, and ESRD incidence. Cox proportional hazards models and Kaplan–Meier survival curves were used. Results A total of 3163 patients with CKD were included in this cohort, of whom 1254 (39.6%) were females. The median (interquartile range [IQR]) age was 75 [64, 85] years, and the median (IQR) estimated glomerular filtration rate was 55.16 [45.19, 61.19] mL/min/1.73 m2. The median PEC was 0.1224 × 109/L (IQR, 0.0625–0.212). Among the 3163 patients with CKD, 273 (8.6%) developed ESRD during a median follow-up time of 443.8 [238.8, 764.9] days. Individuals in the highest PEC quartile had a 66.2% higher ESRD risk than those in the lowest quartile (hazard ratio, 1.662; 95% confidence interval, 1.165–2.372). The results from the Kaplan–Meier survival curves confirmed the conclusion. Conclusions Alongside traditional risk factors, patients with CKD and an elevated PEC are more likely to develop ESRD. Therefore, more attention should be paid to those patients with CKD who have a high PEC.

Fasting substrates predict chronic kidney disease progression in CREDENCE trial patients with type 2 diabetes.

BACKGROUNDSodium-glucose cotransporter 2 inhibitors slow down progression of chronic kidney disease (CKD). We tested whether the circulating substrate mix is related to CKD progression and cardiovascular outcomes in patients with type 2 diabetes (T2D) and albuminuric CKD in the CREDENCE trial.METHODSWe measured fasting substrates in 2,543 plasma samples at baseline and 1 year after randomization to either 100 mg canagliflozin or placebo and used multivariate Cox models to explore their association with CKD progression, heart failure hospitalization/cardiovascular death (hHF/CVD), and mortality.RESULTSHigher baseline lactate and free fatty acids (FFAs) were independently associated with a lower risk of CKD progression (HR = 0.73 [95% CI: 0.54-0.98] and HR = 0.67 [95% CI: 0.48-0.95], respectively) and hHF/CVD HR = 0.70 [95% CI: 0.50-0.99] and HR = 0.63 [95% CI: 0.42-0.94]). Canagliflozin led to a rise in plasma FFAs, glycerol, β-hydroxybutyrate, and acetoacetate. Changes in substrate between baseline and year 1 predicted an approximately 30% reduction in relative risk of both CKD progression and hHF/CVD independently of treatment. More patients who did not respond to canagliflozin treatment in terms of CKD progression belonged to the bottom lactate and FFA distribution tertiles.CONCLUSIONIn T2D patients with albuminuric CKD, basic energy substrates selectively influenced major long-term endpoints; canagliflozin treatment amplified their effects by chronically raising their circulating levels.

Cost-Effectiveness Analysis of Finerenone for Treatment of Chronic Kidney Disease in Patients with Type2 Diabetes from Japanese Payer Perspective.

Type2 diabetes (T2D) is a major cause of chronic kidney disease (CKD) in Japan, and there is an increasing treatment need for first- and second-line care in these patients. The addition of finerenone to current treatment modalities lowers the risk of CKD progression and cardiovascular events in patients with CKD and T2D from the Japanese payer perspective. This study investigated the cost-effectiveness analysis of adding finerenone to standard of care (SoC) versus SoC alone for the treatment of CKD in patients with T2D. The FINE-CKD model validated to estimate the cost-effectiveness of finerenone uses the Markov model to simulate the disease pathway of patients over a lifetime horizon. The model was adapted to reflect the Japanese payer perspective and estimated incremental costs, utilities, and incremental cost-effectiveness ratios(ICERs). Sensitivity and scenario analyses were performed to evaluate the effect of the uncertainty of each parameter using a robust model. The quality-adjusted life years (QALYs) for finerenone and SoC were estimated at 9.39 and 9.25, respectively, with an incremental QALY for finerenone for SoC of 0.14. The total cost of finerenone was estimated at ¥8,912,601, at an incremental cost of ¥274,052, leading to an ICER of ¥1,959,516 per QALY gained compared with SoC alone. Finerenone in conjunction with SoC is a more cost-effective treatment alternative to SoC alone for adult patients with CKD and T2D from a Japanese healthcare payer perspective.

Cost effectiveness of empagliflozin in adult patients with chronic kidney disease in the Netherlands.

The recent EMPA-KIDNEY trial showed evidence for preventing disease progression in adult patients with chronic kidney disease (CKD) treated with empagliflozin. It is however yet unknown if use of empagliflozin is cost effective in the Netherlands. We aimed to evaluate the cost effectiveness of empagliflozin in adult patients with CKD in the Netherlands. A cost-effectiveness analysis was conducted using a Markov state microsimulation model, simulating kidney progression of CKD patients with eGFR <90 ml/min per 1.73 m2 comparing empagliflozin plus standard of care (SoC) and SoC alone. KDIGO classification was used to describe the risk of CKD progression. The input data were taken from the EMPA-KIDNEY trial (baseline characteristics, treatment effect, and utilities), and published data and national sources were used for general population mortality, treatment and event costs. The analyses were performed from a societal perspective with applying a lifetime horizon. Discounting was done according to the Dutch pharmacoeconomic guidelines. The incremental cost-effectiveness ratio (ICER) was compared to a willingness-to-pay threshold of €50,000/QALY. Deterministic and probabilistic sensitivity analyses were performed to explore the impact of uncertainty around the input parameters. The base-case results showed total discounted costs for empagliflozin plus SoC and SoC alone of €200,193 and €234,574 respectively, indicating total savings of €34,380. Empagliflozin plus SoC was associated with higher total discounted health benefits of 11.06 life years (LYs) and 9.01 quality-adjusted life years (QALYs), compared with 9.74 LYs and 7.79 QALYs for SoC alone, resulting in an additional 1.31 LYs and 1.22 QALYs for empagliflozin plus SoC. Empagliflozin plus SoC is a dominant alternative compared to SoC alone. Sensitivity analyses confirmed the robustness of the findings and conclusion. Using empagliflozin in addition to SoC in adult patients with CKD is likely to be cost saving compared to the current SoC in the Netherlands, irrespective of diabetes status and albuminuria.

Impact of anemia on renal outcomes in elderly patients with chronic kidney disease: a cohort study

BackgroundWe aimed to examine the impact of anemia on the risk of further deterioration in renal function among elderly and nonelderly patients with chronic kidney disease (CKD).MethodsIn this retrospective cohort study, we included 1098 predialysis patients with CKD hospitalized for an educational program on CKD between January 2010 and December 2018. Patients aged < 75 years (657) were considered nonelderly, and those aged ≥ 75 years (441) were considered elderly; each category was stratified by hemoglobin level to evaluate the incidence of CKD progression: < 9.0 g/dL, 9.0–10.9 g/dL, 11.0–12.9 g/dL, and ≥ 13.0 g/dL. The study was terminated after 3 years of observation.ResultsCKD progression occurred in 550 and 304 patients in the nonelderly and elderly group, respectively. In the nonelderly group, multivariate Cox models revealed that an increased risk of CKD progression was observed in patients with low hemoglobin levels compared with those with hemoglobin levels of 11.0–12.9 g/dL. However, in the elderly group, adverse renal outcomes occurred at rates that did not differ significantly according to the hemoglobin level. Furthermore, we isolated patients with hemoglobin levels of 9.0–10.9 g/dL and 11.0–12.9 g/dL and analyzed the risk of renal outcomes in both nonelderly and elderly people among them. Examination of renal outcomes in 1:1 the propensity-score-matched cohort of patients with hemoglobin levels of 9.0–10.9 g/dL versus patients with levels of 11.0–12.9 g/dL yielded consistent results.ConclusionsMild anemia may be poorly associated with renal prognosis in elderly patients with CKD.

Kidney outcomes associated with SGLT2 inhibitors compared to other glucose-lowering drugs: a real-world study from China.

This study aimed to investigate the association between the utilization of Sodium-dependent glucose cotransporters inhibitors (SGLT2i) in real-world settings and kidney outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) in mainland China. In a retrospective analysis of electronic medical records from West China Hospital of Sichuan University, patients with T2D and CKD were included. Patients were divided into two groups, those initiating treatment with SGLT2i and those receiving other glucose-lowering drugs (oGLDs). The primary focus lies in examining the impact of SGLT2i on the decline slope of eGFR and major kidney events in these patients. We enrolled 944 patients diagnosed with both T2D and CKD. Out of these, 605 patients were prescribed SGLT2i, while the remaining 339 patients received oGLDs. The median follow-up duration were 16.8 months and 20.6 months, respectively. Throughout the follow-up period, we observed a significant decrease in the rate of eGFR decline in patients using SGLT2i (4.94mL/min/1.73m2 per year reduction compared to oGLDs, 95% CI: 4.73-5.15). A total of 101 kidney composite endpoint events occurred, with 31 events in the SGLT2i group and 70 events in the oGLDs group. The use of SGLT2i was associated with a 65% decrease in the risk of kidney composite endpoint events (hazard ratio 0.35, 95% CI 0.19-0.63). In clinical practice, SGLT2i have shown favorable effects on kidney prognosis in patients with T2D and CKD in mainland China. These effects remain consistent across patients with varying risks of CKD progression. ChiCTR2300068497.

CKD Progression following Acute Kidney Injury: A Secondary Analysis of the STARRT-AKI Trial.

Chronic kidney disease (CKD) is a common complication after acute kidney injury (AKI). We aimed to evaluate whether RRT initiation strategy had an effect on CKD progression. Secondarily, we aimed to identify factors that influenced the development or progression of CKD following severe AKI. This secondary analysis of the STARRT-AKI trial included participants with outpatient serum creatinine values available in the year prior to hospitalization and who were alive at 90 days following randomization. Our main analysis focused on patients who had definitive assessment of kidney function at 90 days following randomization. Predictor markers included patient demographics, co-morbidities, markers of acute illness, laboratory values, receipt of renal replacement therapy (RRT), and RRT treatment strategy (accelerated versus standard). The primary outcome was CKD progression, a composite of de novo CKD, defined as new eGFR < 60 ml/min/1.73 m2 if baseline eGFR was ≥ 60 ml/min; a decline in eGFR ≥ 25% if baseline eGFR was < 60 ml/min, or RRT dependence at day 90. The association of RRT treatment strategy with CKD progression was assessed in an unadjusted mixed-effect logistic regression model. Of the 401 surviving patients with a baseline serum creatinine, 39% experienced CKD progression. RRT initiation strategy had no effect on CKD progression (accelerated arm (41%), vs. the standard arm (38%), Odds ratio 1.13, (95% confidence interval 0.75 to 1.72)). Receipt of RRT and aortic surgery were the most potent risks of CKD progression. These findings suggest that CKD progression is common after severe AKI. Risk factors for CKD progression included receipt of RRT and aortic surgery, suggested that these individuals should be prioritized for dedicated kidney follow up after hospital discharge.

Coexisting Tubulointerstitial Inflammation and Damage Is a Risk Factor for Chronic Kidney Disease in Patients With Lupus Nephritis.

This study aims to determine whether the concurrent presence of tubulointerstitial inflammation (TII) and tubulointerstitial damage (TID) predicts the progression of chronic kidney disease (CKD) in patients with lupus nephritis (LN). Data from 175 LN patients, collected at the time of renal biopsy, were analyzed. Patients were stratified into two groups based on the presence or absence of coexisting TII/TID. Uni- and multivariable Cox proportional hazard regression models were utilized to identify independent risk factors for CKD in LN patients. Of 175 patients, 110 (62.9%) exhibited coexisting TII/TID, whereas 65 (37.1%) did not. Patients with coexisting TII/TID tended to be older and presented with higher levels of ESR and 24-h proteinuria, as well as lower levels of eGFR and hemoglobin compared to those without coexisting TII/TID. Over a mean follow-up period of 89.9 months, CKD and end-stage renal disease occurred more frequently in patients with coexisting TII/TID. Notably, the presence of coexisting TII/TID was associated with a higher risk of CKD progression, with adjusted hazard ratios of 2.667 (95% CI: 1.333, 5.335, p = 0.006) for all LN patients, 3.265 (95% CI: 1.451, 7.345, p = 0.004) for those with class III, IV, and V LN, and 3.045 (95% CI: 1.289, 7.195, p = 0.011) for those with class III, IV, V LN, and eGFR ≥ 30 mL/min/1.73 m2. LN patients with coexisting TII/TID are at a heightened risk of kidney function deterioration at LN onset and subsequent development of CKD over the long term.

Estimated potassium intake and the progression of chronic kidney disease.

Lower potassium intake is associated with a higher risk of chronic kidney disease (CKD) in the general population. However, there are no stated recommendations on potassium intake in the CKD population owing to limited evidence of benefits from potassium intake and concerns about the risk of hyperkalaemia. This study aimed to investigate the relationship between potassium intake and CKD progression. A total of 4314 patients aged 18 years or older in Japan were prospectively followed for 5 years using data from the Fukuoka Kidney Disease Registry study. The patients were divided into quartiles according to estimated potassium intake levels assessed by the Tanaka formula from spot urine samples. The primary outcome was CKD progression, which was defined as a composite of a 1.5-fold increase in creatinine concentrations from baseline and development of end-stage kidney disease. We evaluated the relationship between estimated potassium intake and CKD progression using Cox proportional hazards models. A total of 1490 patients showed CKD progression during the follow-up with an incidence rate of 90.1/1000 person-years. Patients in the lowest estimated potassium intake quartile had higher hazard ratios for CKD progression than those in the highest quartiles in the multivariable-adjusted Cox models (hazard ratio [95% confidence interval], 1.24 [1.03-1.48]). Similarly, each 1-standard deviation decrease in estimated potassium intake as a continuous variable was associated with a higher risk of CKD progression (hazard ratio [95% confidence interval], 1.10 [1.03-1.19]). Lower estimated potassium intake is associated with CKD progression in patients with CKD. Therefore, we recommend adequate potassium intake, taking care not to cause serious adverse events.

Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study.

Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes. In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD). We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29mL/min/1.73m2, uACR 88mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25mL/min/1.73m2, uACR 23mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline. Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.

The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a rationale for the EASi-KIDNEY trial.

Patients with chronic kidney disease (CKD) are at risk of progressive loss of kidney function, heart failure, and cardiovascular death despite current proven therapies, including renin-angiotensin system inhibitors (RASi), sodium glucose co-transporter-2 inhibitors (SGLT2i), and statin-based regimens. RASi and SGLT2i reduce risk of CKD progression irrespective of primary cause of kidney disease, suggesting they target final common pathways. Targeting aldosterone overactivity with a nonsteroidal mineralocorticoid receptor antagonist (MRA) also reduces cardiorenal risk in patients with albuminuric diabetic kidney disease already treated with RASi. Together, these observations provide the rationale for trials to assess effects of inhibiting the aldosterone pathway in a broader range of patients with CKD, including those with non-diabetic causes of CKD or low albuminuria. Aldosterone synthase inhibitors (ASi) have emerged as an alternative to MRAs for aldosterone pathway inhibition. Phase II data from 586 patients with albuminuric CKD have shown that 10 mg of an ASi, vicadrostat (BI 690517), reduced urine albumin-to-creatinine ratio by ∼40% compared to placebo with or without concurrent empagliflozin treatment. MRA and ASi increase risk of hyperkalaemia. Combining their use with an SGLT2i may mitigate some of this risk, improving tolerability, and allowing a wider range of patients to be treated (including those with higher levels of blood potassium than in previous trials). The EASi-KIDNEY (NCT06531824) double-blind placebo-controlled trial will test this approach by assessing the safety and cardiorenal efficacy of vicadrostat in combination with empagliflozin in ∼11,000 patients with CKD. It will be sufficiently large to assess effects in patients with and without diabetes separately.

Associations between the Serum Triglyceride Level and Kidney Outcome in Patients with Chronic Kidney Disease: The Fukuoka Kidney disease Registry Study.

Hypertriglyceridemia is a risk factor for chronic kidney disease (CKD). However, whether or not it predicts the risk of CKD progression is unknown. This study evaluated the association between serum triglyceride (TG) levels and kidney disease progression in patients with non-dialysis-dependent CKD. The Fukuoka Kidney disease Registry (FKR) study was a multicenter, prospective longitudinal cohort study. In total, 4,100 patients with CKD were followed up for 5 years. The primary outcome was the incidence of CKD progression, defined as a ≥ 1.5-fold increase in serum creatinine level or the development of end-stage kidney disease. The patients were divided into quartiles according to baseline serum TG levels under non-fasting conditions: Q1 ＜87 mg/dL; Q2, 87-120 mg/dL; Q3, 121-170 mg/dL, and Q4 ＞170 mg/dL. During the 5-year observation period, 1,410 patients met the criteria for CKD progression. The multivariable-adjusted Cox proportional hazards model showed a significant association between high serum TG level and the risk of CKD progression in the model without macroalbuminuria as a covariate (multivariable hazard ratio[HR] for Q4 versus Q1, 1.20; 95% CI, 1.03-1.41; P=0.022), but the significance disappeared after adjusting for macroalbuminuria (HR for Q4 versus Q1, 1.06; 95% CI, 0.90-1.24; P=0.507). The present findings suggest that individuals with high serum TG levels are more likely to develop CKD progression than those without; however, whether or not higher serum TG levels reflect elevated macroalbuminuria or lead to CKD progression via elevated macroalbuminuria is unclear.

Post-hoc analysis of the CARES trial suggests delayed progression of chronic kidney disease in patients with gout during urate-lowering therapy

Based on the hypothesis that hyperuricemia is a modifiable risk factor for chronic kidney disease (CKD) progression, there is an expectation that urate-lowering therapy (ULT) could delay the progression of CKD. Here, we investigated changes in kidney function and the association of the serum uric acid (sUA) level and kidney function during ULT in patients with gout. To do this we conducted post-hoc analysis on patients who received ULT with either febuxostat or allopurinol for more than six months in the CARES trial. The estimated glomerular filtration rate (eGFR) slope (annual rate of change in eGFR) was calculated using the CKD- EPI creatinine equation and linear mixed modeling. Among the 5,002 patients with gout, 3,264 (65.3%) demonstrated an increased eGFR while receiving ULT over a median follow-up of 2.5 years. Increased average sUA levels were significantly associated with declines in eGFR slope (per 1 mg/dL increase, (adjusted beta of -0.1912). Propensity score matched analysis demonstrated a significant association between low average sUA levels below 6 mg/dL during ULT and a reduced risk of eGFR decline (adjusted odds ratio: 0.66, 95% confidence interval 0.57–0.77). Despite the well-documented natural decline of eGFR over time in the general population, more than half of the patients enrolled in the CARES trial did not experience declines in eGFR while receiving ULT. Thus, our study shows maintaining low sUA levels with ULT was significantly associated with a decreased risk of CKD progression in patients with gout.

Population Health Management and Guideline-Concordant Care in CKD: A Secondary Analysis of Kidney Coordinated HeAlth Management Partnership.

Gaps in guideline-concordant care for chronic kidney disease (CKD) lead to poor outcomes. The Kidney Coordinated HeAlth Management Partnership (K-CHAMP) cluster randomized trial tested the effect of a population health management intervention versus usual care on CKD progression and evidence-based care delivery in the primary care setting. K-CHAMP included adults aged 18-85 years with eGFR <60 mL/min/1.73m2 and moderate-high risk of CKD progression who were not seeing a nephrologist. The multi-faceted intervention included nephrology e-consult, pharmacist-led medication management, and patient education. In this post-hoc analysis, we evaluate the effectiveness of K-CHAMP on guideline-concordant care processes (blood pressure and glycemic control, annual albuminuria testing), and medication exposure days (ACEi/ARB, moderate-high intensity statin, SGLT-2i, GLP-1RA). Given multiplicity of outcomes, Benjamini-Hochberg method was used to control false discovery rate (FDR). All 1,596 (754 intervention, 842 usual care) enrolled patients (mean age 74±9 years, eGFR 37±8 mL/min/1.73m2, 928 (58%) female, 127 (8%) Black) were analyzed. After a median 17-month follow-up, intervention arm patients had significantly higher exposure days per year to SGLT-2i (56 vs 32 days, relative benefit 1.72, 95% CI 1.14-2.30) and GLP-1RA (78 vs 29 days, relative benefit 2.65, 95% CI 1.59-3.71) compared to usual care in adjusted analysis. At study initiation in 2019, similar proportion of patients were prescribed SGLT-2i and/or GLP-1RA in intervention and control arm (8% vs 6% respectively, rate ratio 1.23, 95% CI 0-2.99), but by 2022, prescription of these medications was significantly higher in intervention arm (44% vs 27% respectively, rate ratio 1.63, 95% CI 1.32-1.94). There was no significant difference in any process measures or exposure days to ACEi/ARB in patients with albuminuria or moderate-high intensity statin. K-CHAMP was effective in accelerating implementation of SGLT-2i and GLP-1RA but did not increase ACEi/ARB in patients with albuminuria or moderate-high intensity statin use, or improve blood pressure control, glycemic control, or albuminuria testing in individuals with CKD in the primary care setting.

Development and internal and external validation of a nomogram model for predicting the risk of chronic kidney disease progression in IgA nephropathy patients.

IgA nephropathy (IgAN) is the most common primary glomerular disease in chronic kidney disease (CKD), exhibiting significant heterogeneity in both clinical and pathological presentations. We aimed to explore the risk factors influencing short-term prognosis (≥90 days) and to construct a nomogram model for evaluating the risk of CKD progression in IgAN patients. Clinical and pathological data of patients diagnosed with IgAN through biopsy at two centers were retrospectively collected. Logistic regression was employed to analyze the training cohort dataset and identify the independent predictors to construct a nomogram model based on the final variables. The predictive model was validated both internally and externally, with its performance assessed using the area under the curve (AUC), calibration curves, and decision curve analysis. Out of the patients in the modeling group, 129 individuals (41.6%) did not achieve remission following 3 months of treatment, indicating a high risk of CKD progression. A multivariate logistic regression analysis demonstrated that body mass index, urinary protein excretion, and tubular atrophy/interstitial fibrosis were identified as independent predictors for risk stratification. A nomogram model was formulated utilizing the final variables. The AUCs for the training set, internal validation set, and external validation set were 0.746 (95% confidence intervals (CI) [0.691-0.8]), 0.764 (95% CI [0.68-0.85]), and 0.749 (95% CI [0.65-0.85]), respectively. The validation of the subgroup analysis also demonstrated a satisfactory AUC. This study developed and validated a practical nomogram that can individually predict short-term treatment outcomes (≥90 days) and the risk of CKD progression in IgAN patients. It provides reliable guidance for timely and personalized intervention and treatment strategies.

Bidirectional relationship between kidney disease progression and cardiovascular events in type 2 diabetes: new Insights from the CANVAS Program and CREDENCE trial

Abstract Background The extent to which chronic kidney disease (CKD) progression increases cardiovascular risk, and whether different types of cardiovascular events affect risk of CKD progression, is incompletely understood. Purpose We sought to explore risk of cardiovascular events before and after CKD progression, and CKD progression before and after different cardiovascular events in patients with type 2 diabetes. Methods We conducted a pooled individual participant data analysis of the CANVAS Program and CREDENCE trial. Using Poisson regression, we assessed the incidence of major adverse cardiovascular events ([MACE] stroke, myocardial infarction, or cardiovascular death) and hospitalised heart failure (HHF) or cardiovascular death before and after CKD progression (defined as 40% decline in estimated glomerular filtration rate [eGFR] or kidney failure), and CKD progression before and after nonfatal cardiovascular events, with no adjustment for confounding related to subgroups defined by post-randomization variables. We estimated the cumulative incidence of all-cause mortality after different nonfatal cardiovascular and kidney outcomes, including different thresholds of CKD progression (kidney failure, 40% or 50% decline in eGFR or doubling of serum creatine) using Cox regression models. Results Among 14,464 participants (mean age 63.7 years, 35.3% female, mean eGFR 55mL/min/1.73m2 and median urinary albumin:creatinine ratio 34mg/g) over a median follow-up of 2.5 years, 1,482, 1,076 and 1,020 experienced MACE, HHF or cardiovascular death, and CKD progression, respectively. After (vs. before) CKD progression, there was an approximate 3-fold increase in incidence of MACE (30.2 vs. 93.8 per 1000-patient-years) and 4-fold increase in HHF or cardiovascular death (21.0 vs. 79.3 per 1000-patient-years). Conversely, the incidence of CKD progression was approximately 1.5-fold higher after (vs. before) nonfatal myocardial infarction or stroke (21.7 vs. 34.1 per 1000-patient-years) and 5-fold higher after HHF (21.2 vs. 108.2 per 1000-patient-years). These patterns were consistent in both treatment arms, with unadjusted incidence rates for clinical events appearing numerically lower in canagliflozin compared to placebo-treated participants (Figure 1). Of all non-fatal cardio-kidney outcomes, HHF and doubling of serum creatine or kidney failure conferred the highest risk of death (Figure 2). Conclusion Atherosclerotic and heart failure risk increases substantially after CKD progression. CKD progression was accelerated after cardiovascular events, particularly HHF. Treatment with canagliflozin was associated with lower event rates before and after a serious cardio-kidney outcome, suggesting continued use of canagliflozin may be beneficial even after cardiovascular events and CKD progression.Figure 1.Figure 2.

Chronic kidney disease in patients with heart failure in German primary care practices: the InspeCKD study

Abstract Background Chronic kidney disease (CKD) is, alongside type 2 diabetes mellitus, the most common comorbidity in patients with heart failure (HF), with a prevalence of 40-50%. HF patients should therefore be screened, monitored, and treated according to international Kidney Disease Improving Global Outcomes (KDIGO) conclusions for early identification and intervention of CKD, with annual determination of eGFR to monitor kidney function and annual urine albumin-to-creatinine ratio (UACR) testing as appropriate. Early diagnosis is important as therapeutic options can be offered to slow the progression of CKD and reduce the risk of cardiovascular complications and mortality. Purpose Currently, there are only limited data available regarding screening, diagnosis and treatment of CKD for HF patients in German primary care physician (PCP) practices. Therefore, this analysis of the InspeCKD study was designed to examine the frequency of use of CKD-specific laboratory diagnostics in HF patients in routine PCP care. Methods In the current data analysis, fully anonymized patient data from German PCP practices were evaluated. In accordance with the screening recommendation of the KDIGO guideline, adult patients with diabetes, hypertension and/or cardiovascular disease, including HF, with at least one year of observation period were included in the analysis. Results The overall patient cohort comprised 448.837 patients from 1.244 German PCP practices. Of the 7.9% HF patients, 6.1% participated in a disease management program (DMP) for coronary heart disease. The average age of HF patients was 74 years. The prevalence of diagnosed CKD in HF patients during the observational period (mean: 1.7 years) was 26.8%. Within the subgroup of patients with HF, serum creatinine to estimate GFR was measured at least once in 48.5% of patients. Urine dipstick testing for albuminuria was performed in 7.4% of patients and UACR was measured at least once in 0.3% of patients. In patients with at least one documented measurement, eGFR and UACR were checked 2.2 and 0.9 times, respectively, per patient and year. Of the HF patients with laboratory-confirmed CKD according to KDIGO criteria, 81.8% were not diagnosed with CKD. Conclusion The analysis shows that, given the high prevalence of CKD in HF patients and the current KDIGO recommendations for early identification and intervention of CKD, a substantial proportion of HF patients in German PCP practices did not receive adequate laboratory diagnostics for early diagnosis of CKD. In addition, the majority of patients with laboratory-confirmed CKD were not diagnosed. Early detection of CKD and the use of evidence-based therapeutic options can significantly reduce the risk of CKD progression. In conclusion, there is an urgent need to raise awareness among PCPs about secondary and tertiary prevention of CKD in patients with HF and to include coordinated CKD screening recommendations in HF guidelines.

Increased Body Mass Index is Independently Associated with Chronic Kidney Disease among People with Type 2 Diabetes

Background The alarming increase in the prevalence of obesity has implications for chronic kidney disease (CKD) progression in type 2 diabetes (T2D). This study aimed to assess if increased body mass index (BMI) can be an independent risk factor for CKD and T2D in the Indian context. Materials and Methods In this cross-sectional study, 602 (M:F = 378:224) participants were screened using Kidney Disease Improving Global Outcomes (KDIGO) from January to October 2023 in Chennai. Demographic, anthropometric, biochemical, clinical details, and comorbidities were recorded. T2D with CKD low risk was taken as control group, and CKD moderate and high risks were the study groups. BMI was classified based on the Asian criteria into normal (18.5–22.9), overweight (23–24.9), and obese (≥25 kg/m2). Results Majority of participants in moderate and high risk categories were obese compared to the low risk category (60.5% and 66.4% vs. 39.1%; p &lt; 0.001). A higher proportion of participants was on antihypertensive drugs in the high risk group and in the obese category (p &lt; 0.001). Comorbidities and diabetic complications were higher in the high risk group (p &lt; 0.001). Multivariate logistic regression revealed that age of ≥ 60 years [OR(95% CI); 6.3(2.2–18); p = 0.009]; increased BMI as overweight [3.6(2.1–6.3); p &lt; 0.001] and obese [5.2(3.3–8.3); p &lt; 0.001]; smoking [4.2(1.7–10.2); p = 0.002]; increased duration of diabetes of 5–15 years [2.3(1.2–4.5); p = 0.013], 16–25 years [4.8(2.2–10.4); p &lt; 0.001], and &gt;25 years [4.2(1.4–13); p = 0.011]; systolic blood pressure [1.01(1.0–1.03); p = 0.02]; and hemoglobin A1c [1.2(1.1–1.3); p &lt; 0.001] were independent risk factors for the progression of CKD. Conclusion Increased BMI was independently associated with CKD in T2D. Overweight and obese individuals are four to five times at risk for CKD progression. Early identification, lifestyle intervention, and weight-lowering drugs may reduce the complications of obesity in T2D and CKD.

Development and validation of a chronic kidney disease progression model using patient-level simulations

Chronic disease progression models are available for several highly prevalent conditions. For chronic kidney disease (CKD), the scope of existing progression models is limited to the risk of kidney failure and major cardiovascular (CV) events. The aim of this project was to develop a comprehensive CKD progression model (CKD-PM) that simulates the risk of CKD progression and a broad range of complications in patients with CKD. A series of literature reviews informed the selection of risk factors and identified existing risk equations/algorithms for kidney replacement therapy (KRT), CV events, other CKD-related complications, and mortality. Risk equations and transition probabilities were primarily sourced from publications produced by large US and international CKD registries. A patient-level, state-transition model was developed with health states defined by the Kidney Disease Improving Global Outcomes categories. Model validation was performed by comparing predicted outcomes with observed outcomes in the source cohorts used in model development (internal validation) and other cohorts (external validation). The CKD-PM demonstrated satisfactory modeling properties. Accurate prediction of all-cause and CV mortality was achieved without calibration, while prediction of CV events through CKD-specific equations required implementation of a calibration factor to balance time-dependent versus baseline risk. Predicted annual changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio were acceptable in comparison to external values. A flexible eGFR threshold for KRT equations enabled accurate prediction of these events. This CKD-PM demonstrated reliable modeling properties. Both internal and external validation revealed robust outcomes.