Chronic Kidney Disease Stage G4 Research Articles

Determinants of early chronic kidney disease in patients with recently diagnosed type 2 diabetes mellitus: a retrospective study from the Taiwan Diabetes Registry

BackgroundWe tried to identify the risk factor associate with early chronic kidney disease (CKD) in recently diagnosed type 2 diabetes mellitus patients by utilizing real-world data from Taiwan Diabetes Registry.Materials and methodsPatients with type 2 diabetes mellitus recently diagnosed within 1 year. We divided the study participants into control group and early CKD group. Early CKD was defined as either CKD stage G1 with albuminuria, CKD stage G2 with albuminuria, or CKD stage G3a regardless of albuminuria (Urine-albumin to creatinine ratio (UACR) ≥ 3 mg/mmol). Control group was defined as CKD G1 or CKD G2 without albuminuria. Logistic regression analyses were used to compare differences in clinical characteristics between the subgroups. Linear regression models were employed to examine the factors predicting estimated glomerular filtration rate (eGFR) and UACR.ResultsTotal 2217 patients with recently diagnosed type 2 diabetes mellitus were included. 1545 patients were assigned to control group and 618 patients were assigned to the early CKD group. Age (odds ratio (OR) 1.215, 95% confidence interval [CI] 1.122–1.316), systolic blood pressure (OR 1.203, 95% CI 1.117–1.296), glycated hemoglobin (OR 1.074, 95% CI 1.023–1.129) and triglyceride (OR 2.18, 95% CI 1.485–3.199) were found to be significant risk factors. Further, presence of bidirectional association between UACR and eGFR was found.ConclusionsWe reported factors associated with early CKD in recently diagnosed type 2 diabetes mellitus patients. Variables that associated with eGFR and UACR were identified respectively, included a mutual influence between UACR and eGFR.

Plasma Concentrations of Trimethylamine-N-Oxide, Choline, and Betaine in Patients With Moderate to Advanced Chronic Kidney Disease and Their Relation to Cardiovascular and Renal Outcomes

Trimethylamine N-oxide (TMAO) is a gut bacteria mediated liver metabolite of dietary betaine, choline, and carnitine which is excreted by glomerular filtration. We studied whether TMAO is associated with cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Among 478 patients with CKD stage G2 (n = 104), G3a (n = 163), G3b (n = 123), and G4 (n = 88), we studied the association between fasting plasma concentrations of TMAO, choline or betaine at baseline and kidney function, prevalent CVD and future renal outcomes during a mean follow-up of 5.1 years. Decreased glomerular filtration rate was associated with higher plasma concentrations of TMAO, choline and betaine. Baseline concentrations of TMAO were higher in participants with preexisting CVD compared to those without CVD (8.4 [10.1] vs. 7.8 [8.0] μmol/L; p = 0.047), but the difference was not significant after adjusting for confounders. During the follow up, 147 participants experienced CVD or died and 144 reached the predefined renal endpoint. In the adjusted regression analyses, TMAO or choline concentrations in the upper three quartiles (versus the lowest quartile) were not associated with any of the study clinical endpoints. In contrast, the adjusted hazard ratio of plasma betaine in the highest quartile versus the lowest quartile was 2.14 (1.32, 3.47) for the CVD endpoint and 1.64 (1.00, 2.67) for the renal endpoint. Elevated plasma TMAO concentrations were explained by impaired kidney function. Elevated plasma concentrations of betaine, but not that of TMAO or choline predicted adverse outcomes. TMAO might not be an appropriate target to reduce CVD or renal outcomes in patients with preexisting CKD.

Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease.

Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. This is an analysis of the Japan Chronic Kidney Disease Database Ex　(J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7mg/dl), normal (1.7-2.6mg/dl), or high (>2.6mg/dl). The primary outcomes were the composite of an eGFR<15ml/min/1.73m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

The New Creatinine-Based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 Equation: Potential Impact on Screening for Chronic Kidney Disease in an Asymptomatic Black African Population.

In 2021, a new Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation was introduced that excluded race correction. We set out to compare estimated glomerular filtration rate (eGFR) determined using the creatinine-based CKD-EPI 2009 and 2021 equations and the reclassification of chronic kidney disease (CKD) eGFR staging to explore the potential ramifications of adopting the 2021 equation on reported eGFR and CKD staging. We analyzed secondary data previously utilized to determine reference intervals among Black African individuals residing in urban towns in Kenya. Serum creatinine was measured using a standardized modified Jaffé kinetic method on a Beckman AU5800 analyzer. Glomerular filtration rate (GFR) was estimated using both the 2009 and 2021 CKD-EPI creatinine equations. Classification of CKD based on eGFR was performed using the Kidney Disease: Improving Global Outcomes (KDIGO) practice guidelines. Using 533 study samples, the median eGFR was highest when determined using the race-corrected CKD-EPI 2009 equation. The CKD-EPI 2021 equation yielded a median eGFR that was similar to the non-race-corrected CKD-EPI 2009 equation. The race-corrected CKD-EPI 2009 equation classified 93.6% of participants into CKD stage G1 compared with 85.6% by the CKD-EPI 2021 equation. The CKD-EPI 2021 equation classified 14.3% of participants into CKD stage G2 compared to 6.4% by the race-corrected CKD-EPI 2009 equation. The CKD-EPI 2021 equation gave a comparable eGFR to the non-race-corrected CKD-EPI 2009 equation and its implementation in laboratories reporting eGFR in Kenya will help in identifying patients with an appropriate decrease in renal function.

Slope of the estimated glomerular filtration rate and its associated factors among individuals with chronic kidney disease in the general Japanese population

Abstract Background To suppress the incidence of end-stage kidney disease, we need to identify chronic kidney disease (CKD) patients with a high risk of rapid decline in the estimated glomerular filtration rate (eGFR). However, the current status of eGFR slope and its associated factors in the Japanese population have not been fully elucidated. Methods Among examinees aged 40–70 years in the 2014 Specific Health Checkup conducted by the National Health Insurance in Kobe, Japan (n = 61,985), we prospectively observed 7291 examinees with CKD stage G3 from 2014 to 2018. Results Until 2018, 4221 examinees continued to undergo annual SHCs for a total of five checkups per subject and had available records of all necessary data. The median eGFR change was −0.22 ml/min/1.73 m2/year. Only 9.2% of those subjects showed rapid eGFR decline (faster than −2.0 ml/min/1.73 m2/year). Logistic regression analysis identified diabetes, smoking habits, high urinary protein levels, older age, high systolic blood pressure, and low serum low-density lipoprotein cholesterol levels as independent predictors for rapid eGFR decline. Hemoglobin A1c levels did not contribute to the eGFR slope in CKD stage-G3 subjects with diabetes and proteinuria. Conclusion Most Japanese CKD stage-G3 subjects had a very slow decline in eGFR. A small proportion of CKD individuals who have a predictive factor of rapid eGFR decline should receive considerable attention from a nephrologist.

Determinants of the serum phosphate concentration in chronic kidney disease.

If Ccr is creatinine clearance and EP and TRP are rates of phosphate excretion and reabsorption, the serum phosphate concentration (Ps) is the sum of EP/Ccr and TRP/Ccr, i.e., the amounts of phosphate excreted and reabsorbed per volume of filtrate. At equilibrium, influx of phosphate into plasma determines EP, and EP/Ccr quantifies the contribution of phosphate influx to Ps. We used data obtained at 688 clinic visits of 387 patients to analyze the evolution of Ps in chronic kidney disease (CKD) stages G1 - 5 (dialysis excluded). EP/Ccr was calculated as (Pu×crs)/cru and TRP/Ccr as Ps-EP/Ccr (where u is urine, s is serum, and cr is creatinine). Means of these parameters were plotted against CKD stages, and correlations among variables were determined with regression analyses. In comparison to values in CKD stages G1 - 2, EP/Ccr rose and TRP/Ccr fell by the same amount in CKD G3a and G3b, and Ps did not change. In stages G4 and G5, EP/Ccr increased sharply, TRP/Ccr fell minimally, and Ps rose significantly. At estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73m2, TRP/Ccr was the principal determinant of Ps at eGFR < 45 mL/min/1.73m2, contributions of EP/Ccr and TRP/Ccr to Ps were comparable. Taken together, our results show that in CKD stages G4 and G5, the effect of phosphate reabsorption on Ps changes negligibly while that of phosphate influx increases dramatically. Because the tubular response to rising EP/Ccr is limited, maintenance of stable Ps in advanced CKD requires extreme reduction of phosphate influx into plasma. TRP/Ccr may define the lowest attainable Ps.

Risk factor analysis for a rapid progression of chronic kidney disease.

Chronic kidney disease (CKD) is a growing global health concern. Identifying individuals in routine clinical care with new onset CKD at high risk of rapid progression of the disease is imperative to guide allocation of prophylactic interventions, but community-based data are limited. We aimed to examine the risk of rapid progression, kidney failure, hospitalisation and death among adults with incident CKD stage G3 and to clarify the association between predefined risk markers and rapid CKD progression. Using plasma creatinine measurements for the entire Danish population from both hospitals and primary care, we conducted a nationwide, population-based cohort study, including adults in Denmark with incident CKD stage G3 in 2017-2020. We estimated 3-year risks of rapid progression (defined by a confirmed decline in estimated glomerular filtration rate of ≥5ml/min/1.73 m2/year), kidney failure, all-cause hospitalisation and death. To examine risk markers, we constructed a heat map showing the risk of rapid progression based on predefined markers: albuminuria, sex, diabetes and hypertension/cardiovascular disease. Among 133443 individuals with incident CKD stage G3, the 3-year risk of rapid progression was 14.6% (95% confidence interval (CI): 14.4-14.8). The 3-year risks of kidney failure, hospitalisation and death were 0.3% (95% CI: 0.3-0.4), 53.3% (95% CI: 53.0-53.6) and 18.1% (95% CI: 17.9-18.4), respectively. In the heat map, the 3-year risk of rapid progression ranged from 7% in females without albuminuria, hypertension/cardiovascular disease or diabetes, to 46-47% in males and females with severe albuminuria, hypertension/cardiovascular disease and diabetes. This population-based study shows that CKD stage G3 is associated with considerable morbidity in a community-based setting and underscores the need for optimised prophylactic interventions among such patients. Moreover, our data highlight the potential of using easily accessible markers in routine clinical care to identify individuals who are at high risk of rapid progression.

Epidemiology and referral patterns of patients living with chronic kidney disease in Johannesburg, South Africa: A single centre experience.

Chronic kidney disease (CKD) is a significant contributor to the global burden of non-communicable disease. Early intervention may facilitate slowing down of progression of CKD; recognition of at-risk patient groups may improve detection through screening. We retrospectively reviewed the clinical records of 960 patients attending a specialist nephrology outpatient clinic during the period 1 January 2011-31 December 2021. A significant proportion (47.8%) of patients were referred with established CKD stage G4 or G5. Non-national immigration status, previous diagnosis with diabetes, and advancing age were associated with late referral; antecedent diagnosis with HIV reduced the odds of late referral. Black African patients comprised most of the sample cohort and were younger at referral and more frequently female than other ethnicities; non-nationals were younger at referral than South Africans. Hypertension-associated kidney disease was the leading ascribed aetiological factor for CKD (40.7% of cases), followed by diabetic kidney disease (DKD) (19%), glomerular disease (12.5%), and HIV-associated kidney disease (11.8%). Hypertension-related (25.9%) and diabetic (10.7%) kidney diseases were not uncommon in people living with HIV. Advancing age and male sex increased the likelihood of diagnosis with hypertensive nephropathy, DKD and obstructive uropathy; males were additionally at increased risk of HIV-associated kidney disease and nephrotoxin exposure, as were patients of Black African ethnicity. In summary, this data shows that hypertension, diabetes, and HIV remain important aetiological factors in CKD in the South African context. Despite the well-described risk of CKD in these disorders, referral to nephrology services occurs late. Interventions and policy actions targeting at-risk populations are required to improve referral practices.

Effect of dietary protein intake on cognitive function in the elderly with chronic kidney disease: analysis of the National Health and Nutrition Examination Survey 2011–2014

Background Cognitive dysfunction is prevalent among the elderly diagnosed with chronic kidney disease (CKD). Low protein diets are used for retarding the progression of CKD in clinical practice. Nonetheless, the impact of dietary protein consumption on cognitive function in this population remains uncertain. Methods We recruited 2306 participants (≥60 years) from 2011 to 2014 National Health and Nutrition Examination Survey (NHANES). 24-h dietary recall questionnaire was utilized to evaluate protein intake. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Participants’ characteristics were analyzed, and the interaction between protein consumption and CKD on cognitive impairment were analyzed using a logistic regression model. Results We divided participants into three groups based on CKD stages: no CKD, CKD stage G1 to G2 (19%), and CKD stage G3 to G5 (18%). The average protein intake was 0.97 g/(kg·d). In the higher protein intake group, CKD stages G1 to G2 elevated the risk of immediate memory impairment (OR: 2.441, 95% Cl: 1.161–5.132 for protein consumption in 1.0-1.2g/(kg·d); OR: 2.225, 95% Cl: 1.015–4.876 for protein consumption in >1.2 g/(kg·d)). However, no similar resuts were observed in the lower protein intake group. In addition, the interaction between CKD status and protein intake on immediate memory was statistically significant (p = .041). Conclusion A higher probability of cognitive impairment in the elderly with early-stage CKD may be linked to higher protein intake. Low protein diets may be a potential strategy to release cognitive impairment in the elderly with early-stage CKD.

A CKD Clinical Decision Support System: A Cluster Randomized Clinical Trial in Primary Care Clinics

Rationale & ObjectiveThe study aimed to develop, implement, and evaluate a clinical decision support (CDS) system for chronic kidney disease (CKD) in a primary care setting, with the goal of improving of CKD care in adults. Study DesignCluster randomized trial. Setting & Participants32 midwestern primary care clinics were randomly assigned to either receive usual care or CKD-CDS intervention. Between April 2019 and March 2020, we enrolled 6,420 patients aged 18-75 years with laboratory-defined GFR categories of CKD Stage G3 and G4, as well as one or more of six CKD care gaps: absence of a CKD diagnosis, suboptimal blood pressure (BP) or glycated hemoglobin (A1C) levels, indication for angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) but not prescribed, a nonsteroidal anti-inflammatory agent (NSAID) on the active medication list, or an indicated nephrology referral. InterventionThe CKD-CDS provided personalized suggestions for CKD care improvement opportunities directed to both patients and clinicians at primary care encounters. OutcomesWe assessed the proportion of patients meeting each of 6 CKD-CDS quality metrics representing care gap resolution after18 months. ResultsThe adjusted proportions of patients meeting quality metrics in CKD-CDS versus usual care were as follows: CKD diagnosis documented (26.6% vs. 21.8%; RR 1.17, CI 0.91-1.51); ACEi/ARB prescribed (15.9% vs.16.1%;RR 0.95, CI 0.76-1.18); BP control (20.4% vs. 20.2%;RR 0.98, CI 0.84-1.15); A1C control (21.4% vs. 22.1%;RR 1.00, CI 0.80-1.24); NSAID not on the active medication list (51.5% vs. 50.4%;RR 1.03, CI 0.90-1.17); referral or visit to a nephrologist (38.7% vs. 36.1%;RR 1.02, CI 0.79-1.32). LimitationsWe encountered an overall reduction in expected primary care encounters and obstacles to point-of-care CKD-CDS utilization due to the COVID-19 pandemic. ConclusionThe CKD-CDS intervention did not lead to a significant improvement in CKD quality metrics. The challenges to CDS use during the COVID-19 pandemic likely influenced these results.

EGFR slope as a surrogate endpoint for clinical study in early stage of chronic kidney disease: from The Japan Chronic Kidney Disease Database

BackgroundIn clinical trials targeting early chronic kidney disease (CKD), eGFR slope has been proposed as a surrogate endpoint for predicting end-stage kidney disease (ESKD). However, it is unclear whether the eGFR slope serves as a surrogate endpoint for predicting long-term prognosis in Japanese early CKD populations.MethodsThe data source was the J-CKD-Database, which contains real-world data on patients with CKD in Japan. eGFR slope was calculated from the eGFR of each period, 1-year (1-year slope), 2-year (2-year slope), and 3-year (3-year slope), for participants with a baseline eGFR ≥ 30 ml/min/1.73 m2. The outcome was ESKD (defined as dialysis initiation or incidence of CKD stage G5). The relationship between eGFR slope and the sub-distribution hazard ratio (SHR) of ESKD with death as a competing event was investigated using a Fine-Gray proportional hazard regression model.ResultsThe number of participants and mean observation periods were 7768/877 ± 491 days for 1-year slope, 6778/706 ± 346 days for 2-year slope, and 5219/495 ± 215 days for 3-year slope. As the eGFR slope decreased, a tendency toward a lower risk of ESKD was observed. Compared with the 1-year slope, there was a smaller variation in the slope values for the 2-year or 3-year slope and a greater decrease in the SHR; therefore, a calculation period of 2 or 3 years for the eGFR slope was considered appropriate.ConclusionEven in Japanese patients with early stage CKD, a slower eGFR slope calculated from eGFR values over 2–3 years was associated with a decreased risk of ESKD.

Tolvaptan’s Association with Low Risk of Acute Kidney Injury in Patients with Advanced Chronic Kidney Disease and Acute Decompensated Heart Failure

Introduction: Furosemide, a loop diuretic, is often empirically used to treat acute decompensated heart failure (ADHF) initially. Conversely, decongestion using tolvaptan, an aquaretic, is thought to maintain renal function compared to furosemide. However, it has not been investigated in patients with advanced chronic kidney disease (CKD) at high risk of developing acute kidney injury (AKI). This study aimed to investigate AKI incidence using tolvaptan add-on treatment, compared to increased furosemide treatment for patients with ADHF complicated by advanced CKD. Methods: We retrospectively studied patients with advanced CKD (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m²) who developed ADHF under outpatient furosemide treatment. The exposure was set to tolvaptan add-on treatment, and the control was set to increased furosemide treatment. Results: Of the 163 patients enrolled, 79 were in the tolvaptan group and 84 in the furosemide group. The mean age was 71.6 years, the percentage of males was 63.8%, the mean eGFR was 15.7 mL/min/1.73 m², and patients with CKD stage G5 were 61.9%. AKI incidence was 17.7% in the tolvaptan group and 42.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.13–0.86], p = 0.023 in multivariate logistic regression analysis). Persistent AKI incidence was 11.8% in the tolvaptan group and 32.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.10–1.06], p = 0.066 in the multinomial logit analysis). Conclusion: This study suggests that tolvaptan may be better than furosemide in patients with ADHF experiencing complicated advanced CKD.

#3901 PROGRESSION OF INCIDENT CHRONIC KIDNEY DISEASE: A DANISH NATIONWIDE POPULATION-BASED COHORT STUDY

Abstract Background and Aims The increasing global burden of kidney failure calls for targeted interventions to slow progression of chronic kidney disease (CKD). However, the understanding of progression from CKD stage G3 is limited. We aimed to characterise individuals with incident CKD stage G3 in Denmark and to examine CKD progression defined by three different measures. Method We conducted a nationwide, population-based cohort study using routinely collected individual-level data from national health and administrative databases in Denmark (population ∼5.9 million). Using creatinine tests performed in general practice and the outpatient hospital setting from 1 January 2017 to 31 December 2020, we included all adults in Denmark with incident CKD stage G3, based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria (≥2 creatinine measurements corresponding to an estimated glomerular filtration rate (eGFR) between 30-59 ml/min/1.73 m2 separated by ≥90 days). We used the 2009 CKD Epidemiology Collaboration Creatinine Equation for calculating eGFR. The three years leading up to the study period comprised a washout period to minimise inclusion of individuals with prevalent CKD. We explored CKD progression based on three outcome measures of different sensitivity, including 1) rapid CKD progression (decline in eGFR of ≥5 ml/min/1.73 m2/year, that is, for each eGFR measurement taken during follow-up, we considered this and the measurements taken in the prior year (requiring ≥3 eGFR measurements separated by ≥90 days)); 2) drop in GFR category (drop between GFR categories, 45–59 [G3a], 30–44 [G3b], 15–29 [G4], &amp;lt;15 [G5] ml/min/1.73 m2, accompanied by ≥25% drop in eGFR from baseline); and 3) kidney failure (≥2 eGFR measurements &amp;lt;15 ml/min/1.73 m2 separated by ≥90 days and/or kidney replacement therapy). The 1- and 3-year risks of CKD progression according to the three definitions and all-cause mortality were examined as cumulative incidences using the Aalen-Johansen method. Results We included 133,443 individuals with incident CKD stage G3. The median age at inclusion was 75 years (interquartile range (IQR): 69-82) and 55% were females with 59% having hypertension, 18% having diabetes and 10% having heart failure. The median eGFR at inclusion was 56 ml/min/1.73 m2 (IQR: 51-58) and the median number of eGFR measurements was 3 (IQR: 2-5) in the prior year. Among the 133,443 individuals with incident CKD stage G3, 48,997 (37%) fulfilled the criteria for rapid CKD progression at inclusion. Among the 84,446 individuals without rapid progression on the day of inclusion, the 1- and 3-year risks of rapid CKD progression were 25.0% (95% confidence interval (CI): 24.7-25.3) and 46.0% (95% CI: 45.6-46.4), respectively. The risk of a drop in GFR category was 6.9% (95% CI: 6.8-7.1) after 1 year and 16.6% (95% CI: 16.4-16.8) after 3 years. The risks of kidney failure/renal replacement therapy were 0.1% (95% CI: 0.1-0.1) and 0.3% (95% CI: 0.3-0.4) after 1 and 3 years, respectively. All-cause mortality was 6.8% (95% CI: 6.7-6.9) in the first year and the 3-year mortality was 18.1% (95% CI: 17.9-18.4) (Table 1). Conclusion This nationwide, population-based cohort study showed that a substantial proportion of individuals experienced rapid CKD progression in the 3 years following incident CKD stage G3, whereas the risk of drop in GFR category was considerably lower. Kidney failure within 3 years was rare, while all-cause mortality was relatively modest, taking the high average age into account. This highlights the potential for preventive interventions in patients at risk of rapidly deteriorating kidney function, who might benefit from regular monitoring and targeted treatment.

Risk factor for progression to kidney failure with replacement therapy in elderly patients with chronic kidney disease: A retrospective single‐centre cohort study

Although the number of elderly patients with chronic kidney disease (CKD) has increased, few studies have examined their prognosis. The study design was a retrospective cohort study at a single centre. We evaluated 301 patients aged ≥75 years old with CKD stage G3a to G5. The primary endpoint was kidney failure with replacement therapy (KFRT) and secondary endpoints were all-cause mortality and annual decline rates of estimated glomerular filtration rate (eGFR). The incidence of KFRT was estimated using the cumulative incidence method considering the competing risk of death. To identify the independent risk factors related to KFRT, multivariate Fine-Gray regression model analysis were performed. The median age of the patients was 79 years and the median eGFR was 24.0 mL/min/1.73 m2 at baseline. Urinary protein was positive in 70% of patients. With a median follow-up of 24.5 months, 35% of the patients developed KFRT and 9% died. Kidney survival significantly decreased according to the CKD stage at baseline. In patients without proteinuria, the cumulative incidence of KFRT increased in CKD stage G5 patients, while in patients with proteinuria, the incidence of KFRT increased from patients with CKD stage G3b. Multivariate Fine-Gray regression model revealed that less aged, CKD stage G5, baseline data such as proteinuria, hypoalbuminemia, hyperphosphatemia, and hyperuricemia were independent risk factors for KFRT. Elderly CKD patients with proteinuria need to be carefully monitored even at an early CKD stage because of the risk of developing KFRT.

Intraoperative hemodialysis during open-heart surgery in patients with severe chronic kidney disease: a retrospective cohort study

BackgroundAcute kidney injury and chronic kidney disease (CKD) after cardiac surgery are associated with poor renal prognosis and increased mortality. The impact of intraoperative hemodialysis (IHD) on postoperative renal function remains unknown. We aimed to evaluate the utility of IHD during open-heart surgery in patients with severe non-dialysis-dependent chronic kidney disease (CKD-NDD) and its association with clinical outcomes.MethodsThis was a single-center retrospective cohort study that employed IHD during non-emergency open-heart surgery in patients with CKD stage G4 or G5. Patients who underwent emergent surgery, chronic dialysis, and/or kidney transplantation were excluded. We retrospectively compared the clinical characteristics and outcomes between patients from the IHD and non-IHD groups. The primary outcomes were 90-day mortality and postoperative initiation of renal replacement therapy (RRT).ResultsTwenty-eight patients were categorized into the IHD group and 33 into the non-IHD group. When comparing the IHD and non-IHD groups, men accounted for 60.7 vs. 50.3% of patients, the mean patient age was 74.5 (standard deviation [SD] 7.0) vs. 72.9 (SD 9.4) years (p = 0.744), and the proportion of patients with CKD G4 was 67.9 vs. 84.9% (p = 0.138). Regarding clinical outcomes, no significant differences were observed in the 90-day mortality (7.1 vs. 3.0%; p = 0.482) and 30-day RRT (17.9 vs. 30.3%; p = 0.373) rates between the groups. Among the patients with CKD G4, the IHD group had significantly lower 30-day RRT rates than the non-IHD group (0 vs. 25.0%; p = 0.032). RRT initiation was less likely for patients with CKD G4 (odds ratio 0.07, 95% confidence interval [CI] 0.01–0.37; p = 0.002); however, IHD did not significantly decrease the incidence of poor clinical outcomes (odds ratio 0.20, 95% CI 0.04–1.07; p = 0.061).ConclusionsIHD during open-heart surgery in patients with CKD-NDD did not improve their clinical outcomes with regards to postoperative dialysis. However, for patients with CKD G4, IHD may be useful for postoperative cardiac management.

Association of the Kidney Failure Risk Equation With High Health Care Costs

The Kidney Failure Risk Equations (KFRE) are accurate and validated to predict the risk of kidney failure in individuals with chronic kidney disease (CKD), but their potential to predict health care costs in the US health care system is unknown. We assessed the association of kidney failure risk from the 4-variable and 8-variable 2-year KFRE models with monthly health care costs in US patients with CKD stages G3 and G4. This was an ancillary study to a larger observational, retrospective cohort study examining the association between serum bicarbonate and adverse kidney outcomes. Monthly medical costs were calculated from individual health care insurance claims. Generalized linear regression models were used to examine the association of KFRE score with health care costs. A total of 1721 patients qualified for the study (1475 and 246 with CKD stages G3 and G4, respectively). For 8-variable KFRE, each 1% (absolute) increase in risk was associated with 13.5% (P< 0.001) and 4.1% (P< 0.001) higher monthly costs for patients with CKD stage G3 and G4, respectively. For 4-variable KFRE, a 1% increase in risk was associated with 6.7% (P= 0.016) and 2.9% (P= 0.014) increase in monthly costs for patients with CKD stage G3 and G4, respectively. Higher risks of kidney failure as predicted by the 4-variable or 8-variable KFRE were associated with higher 2-year medical costs for patients with CKD stages G3 and G4. The KFRE may be a useful tool to anticipate medical costs and target cost-reducing interventions for patients at risk of kidney failure.

PS-C18-7: EFFECT OF TOLVAPTAN IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE G5 AND IMPACT OF CONCOMITANT USE OF THIAZIDE DIURETICS

Objective: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat congestive heart failure (CHF). Its diuretic effect in patients with severe renal dysfunction remains poorly characterized. Thiazide diuretics decrease urinary volume (UV) in patients with nephrogenic diabetes insipidus, in which V2 receptor function is absent. Likewise, thiazide diuretics may decrease UV in patients receiving tolvaptan. Design and method: This retrospective cohort study included inpatients with chronic kidney disease stage G5, in whom tolvaptan was administered for CHF. UVs at 24-h pre- and post-tolvaptan administration as well as 30-day dialysis initiation were compared between patients with and without thiazide diuretics. Results: Thiazide diuretics were used in 26 of 106 recruited patients (73.4 ± 13.0 years, estimated glomerular filtration rate: 8.07 ± 3.13 mL/min/1.73 m2). In contrast to those who received thiazide diuretics (1177.3 ± 686.5 vs. 1173.1 ± 629.1 mL/day, p = 0.93), patients without thiazide diuretics had significantly higher 24-h UV pre- and post-tolvaptan administration (1043.4 ± 645.6 vs. 1422.2 ± 774.0 mL/day, p &lt; 0.001). In a multivariate regression model, the use of thiazide diuretics was significantly associated with decreased 24-h UV (beta coefficient, -486.7 [95% confidence interval (CI), -674.5 to -298.8]) and increased urine osmolality (beta coefficient, 37.7 [95% CI, 17.1–58.4]), bodyweight (beta coefficient, 0.62 [95% CI, 0.31–0.92]) and 30-day dialysis initiation (odds ratio 3.40 [95% CI, 1.18–9.82]) after tolvaptan administration. Conclusions: Tolvaptan had significant diuretic effects on patients with CHF, even in those with severe renal dysfunction. Concomitant use of thiazide diuretics diminished these effects.

Machine Learning-Based Urine Peptidome Analysis to Predict and Understand Mechanisms of Progression to Kidney Failure

The identification of patients with chronic kidney disease (CKD) at risk of progressing to kidney failure (KF) is important for clinical decision-making. In this study we assesed whether urinary peptidome (UP) analysis may help classify patients with CKD and improve KF risk prediction. The UP was analyzed using capillary electrophoresis coupled to mass spectrometry in a case-cohort sample of 1000 patients with CKD stage G3 to G5 from the French CKD-Renal Epidemiology and Information Network (REIN) cohort. We used unsupervised and supervised machine learning to classify patients into homogenous UP clusters and to predict 3-year KF risk with UP, respectively. The predictive performance of UP was compared with the KF risk equation (KFRE), and evaluated in an external cohort of 326 patients. More than 1000 peptides classified patients into 3 clusters with different CKD severities and etiologies at baseline. Peptides with the highest discriminative power for clustering were fragments of proteins involved in inflammation and fibrosis, highlighting those derived from α-1-antitrypsin, a major acute phase protein with anti-inflammatory and antiapoptotic properties, as the most significant. We then identified a set of 90 urinary peptides that predicted KF with a c-index of 0.83 (95% confidence interval [CI]: 0.81-0.85) in the case-cohort and 0.89 (0.83-0.94) in the external cohort, which were close to that estimated with the KFRE (0.85 [0.83-0.87]). Combination of UP with KFRE variables did not further improve prediction. This study shows the potential of UP analysis to uncover new pathophysiological CKD progression pathways and to predict KF risk with a performance equal to that of the KFRE.

A Systematic Review of Direct-Acting Antivirals for Hepatitis C in Advanced CKD

Direct-acting antivirals (DAAs) have improved treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD). To facilitate the 2022 update of the Kidney Disease: Improving Global Outcomes (KDIGO) guideline for CKD patients with HCV, we systematically reviewed DAA regimens in patients with CKD stages G4 and G5 nondialysis (G4-G5ND), CKD stage G5 on dialysis (G5D), and kidney transplant recipients (KTRs). We conducted a systematic review by searching PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, and conferences from 2019 to 2021. Studies of HCV-infected patients with CKD G4-G5ND, G5D, and KTRs treated with specified DAA regimens were included. Outcomes included death at 6 months or later, sustained virologic response at 12 weeks (SVR12), serious adverse events (SAEs) attributed to DAA, and treatment discontinuation because of adverse events. Maximum likelihood meta-analyses were determined; certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development, and Evaluation). We identified 106 eligible studies (22 reported on CKD G4-G5ND, 69 on CKD G5D, and 29 on KTRs). In each population, the majority of DAA regimens achieved SVR12≥ 93%. We found generally low quality of evidence of low risk of SAEs (mostly 0%, up to 2.9%) and low risk of discontinuation because of adverse events (mostly 0%-5%). Across 3 unadjusted observational studies in KTRs, the risk of death after DAA treatment was substantially lower than without treatment (summary odds ratio, 0.16; 95% CI, 0.04-0.61). Combination DAA regimens are safe and highly effective in patients with advanced CKD, on dialysis, and with kidney transplants.

Rate and Risk Factors of Acute Myocardial Infarction after Debut of Chronic Kidney Disease-Results from the KidDiCo.

Chronic kidney disease (CKD) is a known risk factor for cardiovascular disease, including acute myocardial infarction. However, whether this risk is only associated with severe kidney disease or is also related to mildly impaired kidney function is still under debate. The incidence rate and risk factors of incident acute myocardial infarction (AMI) in patients with CKD are sparse. Potential differences in risk factor profiles between CKD patients with incident AMI and CKD patients with a prior AMI have not been sufficiently investigated. Furthermore, important factors such as albuminuria and socio-economic factors are often not included. The primary aim of this study was to establish the incidence rate of AMI after CKD debut. Secondly, to evaluate the importance of different CKD stages and the risk of having an AMI. Finally, to identify individuals at risk for AMI after CKD debut adjusted for prevalent AMI. Based on data from the kidney disease cohort of Southern Denmark (KidDiCo), including 66,486 CKD patients, we established incidence rates and characteristics of incident AMI among patients within a 5-year follow-up period after CKD debut. A Cox regression was performed to compute the cause-specific hazard ratios for the different risk factors. The incidence rate for CKD stage G3-5 patients suffering acute myocardial infarction is 2.5 cases/1000 people/year. In patients without a previous myocardial infarction, the risk of suffering a myocardial infarction after CKD debut was only significant in CKD stage G4 (HR = 1.402; (95% CI: 1.08-1.81); p-value = 0.010) and stage G5 (HR = 1.491; (95% CI: 1.01-2.19); p-value = 0.042). This was not the case in patients who had suffered an acute myocardial infarction prior to their CKD debut. In this group, a previous myocardial infarction was the most critical risk factor for an additional myocardial infarction after CKD debut (HR = 2.615; (95% CI: 2.241-3.05); p-value &lt; 0.001). Irrespective of a previous myocardial infarction, age, male sex, hypertension, and a low educational level were significant risk factors associated with an acute myocardial infarction after CKD debut. The incidence rate of AMI in patients with CKD stage G3-5 was 2.5 cases/1000 people/year. Risk factors associated with incident AMI in CKD stage G3-5 patients were CKD stage, age, and hypertension. Female sex and higher educational levels were associated with a lower risk for AMI. Prior AMI was the most significant risk factor in patients with and without previous AMI before fulfilling CKD stage G3-5 criteria. Only age, sex, and a medium-long educational level were significant risk factors in this group.