Risk Of Chronic Kidney Disease Progression Research Articles

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.

Long-Term Kidney Outcome of Lupus Nephritis by Renal Response Status

IntroductionLimited evidence exists that clinical trial treatment response criteria predict long-term outcomes in Asian patients with lupus nephritis (LN). MethodsThis retrospective analysis of prospectively collected data from the Hong Kong Queen Mary Hospital Cohort categorized adults with biopsy-proven LN (Class III, IV, V, or mixed [III±V, IV±V]) after standard treatment for 2 years (2Y) post biopsy and immunosuppression induction according to modified primary efficacy renal response (mPERR: estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m2 or ≤20% below biopsy value AND urine protein:creatinine ratio [uPCR] ≤0.7) and modified complete renal response (mCRR; eGFR ≥90 ml/min/1.73 m2 or ≤10% below biopsy value AND uPCR ≤0.5). Associations between 2Y mPERR/mCRR status and long-term kidney survival and mild chronic kidney disease (CKD) or worse (Stage ≥3) were assessed. ResultsOf the 176 Chinese patients, 64.2% achieved mPERR and 43.8% achieved mCRR at 2Y post biopsy. After mean follow-up of 15.3 years, significantly higher proportions of mPERR and mCRR responders versus non-responders achieved long-term kidney survival (mPERR: 85.8% vs 71.4%; p=0.029; mCRR: 92.2% vs 71.7%; p<0.001). mPERR and mCRR achievement was associated with adjusted risk reductions for kidney non-survival of 60% (p=0.034) and 86% (p<0.001), respectively. Adjusted risk for mild CKD or worse (Stage ≥3) was 82% (p=0.013) and 87% (p=0.012) lower for mPERR and mCRR responders, respectively, versus non-responders. ConclusionsIn Chinese patients with LN, mPERR and mCRR at 2Y post biopsy predict superior long-term kidney outcomes and lower CKD progression risk.

N-terminal pro-B-type natriuretic peptide, eGFR, and progression of kidney disease in chronic kidney disease patients without heart failure.

Cardiorenal syndrome highlights the bidirectional relationship between kidney and heart dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is the gold standard biomarker in heart failure (HF), may be an important biomarker for chronic kidney disease (CKD) progression. However, NT-proBNP is negatively related with estimated glomerular filtration rate (eGFR). In this study, we investigated the association of NT-proBNP, eGFR, and progression of kidney disease in CKD patients without HF. This multicentric retrospective cohort study recruited 23 860 CKD patients without HF, who had at least one NT-proBNP record from China Renal Data System database. Linear regression model evaluated the relationship between eGFR and NT-proBNP. Cox regression analysis assessed the association between NT-proBNP and CKD progression. Sensitivity analysis examined the robustness of the main findings. This study involved 23 860 CKD patients without HF, distributed across different CKD stages: 10 526 in stages G1-2, 4665 in G3a, 3702 in G3b, 2704 in G4, and 2263 in G5. NT-proBNP was negatively correlated with eGFR, particularly in stages 4-5 CKD. A 15-unit decrease in eGFR was associated with increases in log (NT-proBNP) levels by 1.04-fold, 1.27-fold, 1.29-fold, 1.80-fold, and 3.50-fold for stages 1-2, 3a, 3b, 4, and 5, respectively. After excluding patients who developed CKD progression within 1 year, the Cox regression analysis revealed that the relationship between NT-proBNP and CKD progression was not significant in stages 4 and 5. However, for stages 1-3, each standard deviation increase in log (NT-proBNP) was associated with a 26%, 36%, and 28% higher risk of CKD progression, with P interaction ≤.001. The hazard ratios were 1.26 (95% confidence intervals (CI), 1.18 to 1.35), 1.36 (95% CI, 1.22 to 1.51), and 1.28 (95% CI, 1.14 to 1.43) for stages 1-2, stage 3a, and stage 3b, respectively. Despite its strong inverse association with eGFR, NT-proBNP was positively associated with the risk of progression of kidney disease in CKD patients with stages 1-3 without HF. Future studies should investigate the effectiveness of NT-proBNP as a predictive biomarker for the progression of kidney disease across diverse racial groups and healthcare settings.

Hyperhomocysteinemia in Chronic Kidney Disease: A Meta-Analysis

Background: Hyperhomocysteinemia, an elevated level of homocysteine in the blood, has been implicated in the progression of chronic kidney disease (CKD). This meta-analysis aims to comprehensively evaluate the association between hyperhomocysteinemia and CKD and its potential impact on clinical outcomes. Methods: This study systematically searched electronic databases (PubMed, Embase, Cochrane Library) for studies published between 2018 and 2024 investigating the relationship between hyperhomocysteinemia and CKD. Studies reporting data on the association between hyperhomocysteinemia and CKD progression, cardiovascular events, or mortality were included. We extracted relevant data and performed a meta-analysis using random-effects models. Results: The meta-analysis included 25 studies comprising 5,672 patients with CKD. Hyperhomocysteinemia was significantly associated with an increased risk of CKD progression (pooled odds ratio [OR] 1.85, 95% confidence interval [CI] 1.52-2.24), cardiovascular events (pooled OR 1.63, 95% CI 1.31-2.02), and all-cause mortality (pooled OR 1.48, 95% CI 1.17-1.87) in CKD patients. Subgroup analyses revealed a consistent association across different CKD stages and etiologies. Conclusion: Hyperhomocysteinemia is an independent risk factor for CKD progression, cardiovascular events, and mortality. Monitoring and managing hyperhomocysteinemia may represent a potential therapeutic target to improve outcomes in CKD patients.

Prevalence and characteristics of people with a high body mass index across the kidney disease spectrum: a population-based cohort study

The prevalence of obesity is growing globally and has major health implications, particularly for those with chronic kidney disease (CKD). People with obesity have a higher risk of CKD progression and face barriers to transplantation. Studies on the epidemiology and outcomes of obesity in the Canadian CKD population are lacking. This population-based cohort study included adults aged 18 and over with a hospital encounter in London, Ontario, Canada from 2010 to 2019 where height and weight were recorded. They were stratified into CKD stages 1-5 (by estimated glomerular filtration rate (eGFR)), dialysis or renal transplant status and by body mass index (BMI) using Canada Obesity Guidelines. Outcomes included prevalence of BMIs by CKD stage, and CKD progression and transplant outcomes across BMI classes. Our cohort included 198,151 patients. The prevalence of BMI ≥30 kg/m2 grew as eGFR declined (i.e., 37% in stage 1, 41.5% in stage 3b, 40.9% in stage 4) but fell in end-stages (i.e., 37.4% in Stage 5, 38.8% in dialysis, 38.5% in transplant recipients). CKD progression and kidney failure appeared more frequent in those with a BMI ≥30 kg/m2. In a smaller sample, we noted that end-stage patients with a BMI ≥30 kg/m2 were less frequently transplanted, but experienced post-transplant complications less often. This study revealed that high BMI is a prevalent issue in the Canadian CKD population and may influence kidney outcomes and transplant candidacy. This data will help inform clinical trials to create and study weight loss interventions for those with CKD and obesity.

Unraveling the Mechanisms of Magnesium Supplementation in Alleviating Chronic Kidney Disease Complications and Progression: Balancing Risks and Benefits.

Chronic kidney disease (CKD) is a major cause of death and disability worldwide. It is usually diagnosed at early levels because of its slow progression. Treatment should consider CKD complications (such as electrolyte level imbalance, vascular calcification, and bone mineral disorders), as well as the development of CKD itself. Large-scale studies have shown that current treatment guidelines are nearly ineffective and fail to achieve treatment goals. Guidelines have not paid as much attention to magnesium (Mg) as the other electrolytes, while Mg has a significant role in the treatment goals of CKD. Hypomagnesemia is the only electrolyte imbalance that is equally prevalent in all stages of CKD. A lower plasma Mg level in each stage of CKD is associated with a higher risk of CKD progression and cardiac events. Magnesium exerts its effects both directly and via other ions. Mg supplementation increases insulin sensitivity while reducing proteinuria and inflammation. It lowers blood pressure and inhibits vascular calcification primarily because of its effects on calcium and phosphate, respectively. Vitamin D supplementation for low-active vitamin D in CKD patients increases vascular calcification and cardiac events, but magnesium supplementation enhances vitamin D levels and activity without increasing the risk of cardiac events. However, careful attention is required due to the potential threats of hypermagnesemia, particularly in advanced CKD stages. Starting magnesium supplementation early in patients' treatment plans will result in fewer side effects and more advantages. More original research is needed to determine its optimal dose and serum levels.