Risk Of Chronic Kidney Disease Progression Research Articles

Decreased chronic kidney disease in rheumatoid arthritis in the era of biologic disease-modifying anti-rheumatic drugs.

ABSTRACTBackgroundWe investigated the incidence of chronic kidney disease (CKD) progression and its factors relevant to patients with stable rheumatoid arthritis (RA).MethodsWe enrolled consecutive patients with RA who had initiated treatment with a biologic disease-modifying anti-rheumatic drug (bDMARD) at our institution and continued the same drug for >5 years between 2001 and 2016. Patients with CKD at bDMARD initiation were excluded. C-reactive protein (CRP) level, Clinical Disease Activity Index (CDAI) score and estimated glomerular filtration rate were measured every 6 months.ResultsWe included 423 patients, with 196 on tumour necrosis factor inhibitors, 190 on tocilizumab and 37 on abatacept. Among these patients, 34 (8.0%) progressed to CKD within 5 years. The mean CRP level and CDAI score over 5 years were significantly lower in patients without CKD progression than in those with CKD progression (P < .001 and P = .008, respectively). Multivariable analysis revealed that age at bDMARD initiation [odds ratio (OR) 1.05, P = .002], non-steroidal anti-inflammatory drug use (OR 3.47, P = .004) and mean CRP >0.14 mg/dL (OR 5.89, P = .015) were independently associated with CKD progression, while tocilizumab use was associated with a decreased risk of CKD progression (OR 0.31, P = .027).ConclusionsControlling inflammation contributes to the inhibition of CKD progression in RA patients.

The Relationship Between Neighborhood Disadvantage and Kidney Disease Progression in the Chronic Kidney Disease in Children (CKiD) Cohort

To examine the relationship between neighborhood poverty and deprivation, chronic kidney disease (CKD) comorbidities, and disease progression in children with CKD. Observational cohort study. Children with mild to moderate CKD enrolled in the CKiD (Chronic Kidney Disease in Children) study with available US Census data. Neighborhood poverty and neighborhood disadvantage. Binary outcomes of short stature, obesity, hypertension, and health care utilization for cross-sectional analysis; a CKD progression end point (incident kidney replacement therapy [KRT] or 50% loss in estimated glomerular filtration rate), and mode of first KRT for time-to-event analysis. Cross-sectional analysis of health characteristics at time of first Census data collection using logistic regression to estimate odds ratios. Risk for CKD progression was analyzed using a Cox proportional hazard model. Multivariable models were adjusted for race, ethnicity, sex, and family income. There was strong agreement between family and neighborhood socioeconomic characteristics. Risk for short stature, hospitalization, and emergency department (ED) use were significantly associated with lower neighborhood income. After controlling for race, ethnicity, sex, and family income, the odds of hospitalization (OR, 1.71 [95% CI, 1.08-2.71]) and ED use (OR, 1.56 [95% CI, 1.02-2.40]) remained higher for those with lower neighborhood income. The hazard ratio of reaching the CKD progression outcome for participants living in lower income neighborhoods was significantly increased in the unadjusted model only (1.38 [95% CI, 1.02-1.87]). Likelihood of undergoing a preemptive transplant was decreased with lower neighborhood income (OR, 0.47 [95% CI, 0.24-0.96]) and higher neighborhood deprivation (OR, 0.31 [95% CI, 0.10-0.97]), but these associations did not persist after controlling for participant characteristics. Limited generalizability, as only those with consistent longitudinal nephrology care were studied. Neighborhood-level socioeconomic status (SES) was associated with poorer health characteristics and CKD progression in univariable analysis. However, the relationships were attenuated after accounting for participant-level factors including race. A persistent association of neighborhood poverty with hospitalizations and ED suggests an independent effect of SES on health care utilization, the causes for which deserve additional study.

Interaction of Serum Alkaline Phosphatase and Folic Acid Treatment on Chronic Kidney Disease Progression in Treated Hypertensive Adults.

The relation of alkaline phosphatase (ALP) with chronic kidney disease (CKD) is still uncertain. We aimed to examine the prospective association between serum ALP and CKD progression, and the modifying effect of serum ALP on folic acid in preventing CKD progression in treated hypertensive patients. This is a post-hoc analysis of 12,734 hypertensive adults with relevant measurements and without liver disease at baseline from the renal sub-study of the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid, or 10 mg enalapril alone. The primary outcome was CKD progression, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of <60 ml/min/1.73 m2 if baseline eGFR was ≥60 ml/min/1.73 m2; or a decrease in eGFR of ≥50% if baseline eGFR was <60 ml/min/1.73 m2; or end-stage renal disease. Over a median of 4.4 years, in the enalapril only group, participants with baseline serum ALP≥110IU/L (quartile 4) had a significantly higher risk of CKD progression (3.4% vs 2.3%; adjusted OR,1.61; 95%CI:1.11, 2.32), compared with those with ALP<110IU/L. For those with enalapril and folic acid treatment, compared with the enalapril only treatment, the risk of CKD progression was reduced from 3.4 to 2.1% (adjusted OR, 0.53; 95%CI:0.34, 0.83) among participants with baseline ALP≥110IU/L, whereas there was no significant effect among those with ALP<110IU/L. In hypertensive patients, higher serum ALP was associated with increased risk of CKD progression, and this risk was reduced by 47% with folic acid treatment.

Impacting Management of Chronic Kidney Disease Through Primary Care Practice Audits: A Quality Improvement Study

Risk prediction tools are important in chronic disease management, but their implementation into clinical workflow is often limited by lack of electronic health record (EHR)-linked solutions. To implement the Khure Health (KH) clinical decision support platform with an artificial intelligence (AI)-enabled algorithm for chronic kidney disease (CKD) risk detection in 201 primary care provider practices across Ontario. Multi-practice quality improvement study. The study was conducted in Ontario, Canada. 201 primary care practices. Per-practice CKD risk stratification and clinician action. Data for estimated glomerular filtration rate (eGFR), albuminuria, demographics, and comorbid conditions were extracted from the EHR using KH's natural language processing (NLP) algorithms. Patients already on dialysis, visiting a nephrologist, older than 85, or already on a sodium-glucose cotransporter 2 inhibitor (SGLT2i) were excluded. The remaining individuals were risk stratified using the kidney failure risk equation, presence or absence of cardiovascular disease (CVD), or other comorbid conditions. A dashboard with disease-specific educational information and links to the EHRs of the identified patients was created. We screened 361 299 individuals and identified 8194 patients with CKD Stage 3 at risk for progression or cardiovascular events. A total of 620 individuals were at high risk for CKD progression or CVD, and 2592 were at intermediate risk. A total of 2010 individuals (10 patients per practice) at high or moderate risk were selected for a chart audit, and appropriate additional testing (repeat eGFR or albuminuria) or prescription of disease-modifying therapy occurred in 24.32% of these patients. Data on comorbidities, medications, or demographic variables are not available for presentation or statistical analysis due to privacy legislation and primary care provider (PCP) custodianship over EHR data. An AI-enabled EHR clinical decision support application that can detect and risk stratify patients with CKD can enable improved laboratory testing and management. Larger trials of clinical decision support and practice audit applications will be needed to impact CKD management nationally.

Loop and thiazide diuretic use and risk of chronic kidney disease progression: a multicentre observational cohort study

ObjectivesTo evaluate the association between diuretic use by class with chronic kidney disease (CKD) progression and onset of end-stage renal disease (ESRD).DesignRetrospective cohort study.SettingLarge integrated healthcare delivery system in Northern...

Interactive effect of obesity and cognitive function decline on the risk of chronic kidney disease progression in patients with type 2 diabetes mellitus: a 9.1-year cohort study.

Background: Obesity and cognitive function decline are independent risk factors for chronic kidney disease (CKD). However, few studies have examined the combined effects of obesity status and cognitive function on change in CKD risk. We aimed to evaluate the association between obesity status, cognitive function and CKD risk change in patients with type 2 diabetes mellitus (T2DM).Methods: Data on 3399 T2DM patients were extracted from a diabetes disease management program between 2006 and 2018. Univariate and multivariate analyses were used to assess the association between obesity, cognitive decline, and CKD risk change. Three indexes, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze interactions. CKD risk was classified according to the KDIGO 2012 CKD definition.Results: In multivariate analysis, the hazard ratio (HR, 95%Cis) for CKD risk progression was 1.34 (1.12-1.61) times higher in the moderate and severely obese patients compared with the normal weight patients, and 1.34 (1.06-1.67) times higher in the patients with a Mini-Mental State Examination (MMSE) score ≤18 compared to those with an MMSE score ≥24. There was a synergistic interaction between moderate and severe obesity and MMSE score ≤18 on CKD risk progression (SI=4.461; 95% CI: 1.998-9.962), and the proportion of CKD risk progression caused by this interaction was 52.7% (API=0.527; 95% CI: 0.295-0.759). However, normal weight and MMSE score ≥24 were not beneficial on CKD risk improvement in the patients with a moderate risk and very high-risk stage of CKD.Conclusion: There may be a synergistic interaction between obesity and cognitive function decline, and the synergistic interaction may increase the risk of CKD progression.

Chronic Kidney Disease and SGLT2 Inhibitors: A Review of the Evolving Treatment Landscape.

There is currently an unmet need for effective treatment of chronic kidney disease (CKD) that slows disease progression, prevents development of end-stage kidney disease and cardiovascular disease, and prolongs survival of patients with CKD. In the last 20 years, the only agents to show a reduction in the risk of CKD progression in patients with and without type 2 diabetes (T2D) were angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, but neither drug class has provided a decreased risk of all-cause mortality in patients with CKD and evidence for their use in patients with CKD without T2D is relatively limited. This review discusses the mechanisms underlying the progression of CKD, its associated risk factors, and summarizes the potential therapeutic approaches for managing CKD. There is increasing evidence to support the role of sodium–glucose cotransporter 2 (SGLT2) inhibitor therapy in patients with CKD, including data from the designated kidney outcome trials in patients with T2D (CREDENCE) and in patients with or without T2D (DAPA-CKD). These studies showed a significant reduction in the risk of CKD progression with canagliflozin (in patients with T2D) or dapagliflozin (in patients with or without T2D), respectively, with DAPA-CKD being the first trial to show a reduced risk of all-cause mortality. On the basis of these data, individualized treatment with SGLT2 inhibitors represents a promising therapeutic option for patients with diabetic and nondiabetic CKD to slow disease progression.

Abstract 11761: Association of Mitochondrial DNA Copy Number With Risk of Progression of Kidney Disease in the Chronic Renal Insufficiency Cohort (CRIC) Study

Introduction: Mitochondrial DNA copy number (mtDNA-CN) is a biomarker of mitochondrial function that has been associated with chronic kidney disease (CKD) and all-cause mortality in several community-based studies. However, there has been little research on mtDNA-CN and progression of CKD. Hypothesis: We hypothesized that higher mtDNA-CN will be associated with lower risk for CKD progression in a cohort of CKD patients. Methods: A total of 2,943 Chronic Renal Insufficiency Cohort (CRIC) study participants had mtDNA-CN calculated from probe intensities of mitochondrial single nucleotide polymorphisms (SNP) genotyped on the Illumina HumanOmni 1-Quad Array. To correct for batch effects, DNA quality, DNA quantity, and latent confounding factors, mtDNA-CN was regressed on 15 principal components generated from autosomal SNP probe intensity signals. mtDNA-CN residuals were then standardized to a mean of 0 and standard deviation of 1 and used in this analysis. CKD progression was defined as incident end-stage renal disease (ESRD) or halving of eGFR from baseline. Cox proportional hazards models were used to calculate hazard ratios for mtDNA-CN and risk of CKD progression. Results and Conclusions: Compared to patients in the lowest mtDNA-CN tertile, those in the middle tertile [HR=0.78, 95% CI: (0.68, 0.91)] and highest tertile [HR=0.78, 95% CI: (0.67, 0.91)] had a statistically significantly lower risk for CKD progression after adjustment for established risk factors (Table). Similar results were seen in race- and sex-stratified analyses (Table). These findings suggest that mtDNA-CN may have potential clinical utility in improving CKD risk classification. Furthermore, mitochondrial dysfunction has been hypothesized to contribute to renal disease through podocyte injury, tubular epithelial cell damage, and endothelial dysfunction. Future research on the mechanisms underlying mtDNA-CN and CKD progression may lead to novel strategies for CKD management.

Finerenone Dose-Exposure-Response for the Primary Kidney Outcome in FIDELIO-DKD Phase III: Population Pharmacokinetic and Time-to-Event Analysis.

BackgroundFinerenone is a nonsteroidal selective mineralocorticoid receptor antagonist that recently demonstrated efficacy in delaying chronic kidney disease progression and reducing cardiovascular events in patients with chronic kidney disease and type 2 diabetes in FIDELIO-DKD, where 5734 patients were randomized 1:1 to receive either titrated finerenone doses of 10 or 20 mg once daily or placebo, with a median follow-up of 2.6 years.MethodsNonlinear mixed-effects population pharmacokinetic models were used to analyze the pharmacokinetics in FIDELIO-DKD, sparsely sampled in all subjects receiving finerenone. Post-hoc model parameter estimates together with dosing histories allowed the computation of individual exposures used in subsequent parametric time-to-event analyses of the primary kidney outcome.ResultsThe population pharmacokinetic model adequately captured the typical pharmacokinetics of finerenone and its variability. Either covariate effects or multivariate forward-simulations in subgroups of interest were contained within the equivalence range of 80–125% around typical exposure. The exposure-response relationship was characterized by a maximum effect model estimating a low half-maximal effect concentration at 0.166 µg/L and a maximal hazard decrease at 36.1%. Prognostic factors for the treatment-independent chronic kidney disease progression risk included a low estimated glomerular filtration rate and a high urine-to-creatinine ratio increasing the risk, while concomitant sodium-glucose transport protein 2 inhibitor use decreased the risk. Importantly, no sodium-glucose transport protein 2 inhibitor co-medication-related modification of the finerenone treatment effect per se could be identified.ConclusionsNone of the tested pharmacokinetic covariates had clinical relevance in FIDELIO-DKD. Finerenone effects on kidney outcomes approached saturation towards 20 mg once daily and sodium-glucose transport protein 2 inhibitor use provided additive benefits.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01082-2.

Serum Magnesium, Blood Pressure, and Risk of Hypertension and Chronic Kidney Disease Progression in the CRIC Study.

[Figure: see text].

Association Between Obesity and Microvascular Diseases in Patients With Type 2 Diabetes Mellitus.

This study aimed to evaluate the association between obesity, evaluated by fat mass index (FMI) with the risk of microvascular diseases in patients with type 2 diabetes mellitus (T2DM) and compare the magnitude of associations of FMI, body mass index (BMI), and waist circumference (WC) with the risk of microvascular diseases. We performed a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes study. The primary microvascular outcomes of the present study included chronic kidney disease (CKD) progression, retinopathy, and neuropathy. Cox proportional-hazards models were performed to evaluate the association of FMI with microvascular diseases. A discordant analysis was performed to compare the magnitude of associations of FMI, BMI, and WC with the risk of microvascular diseases. Our study included 10,251 T2DM participants with a median of 5 years (interquartile range, 4.2–5.7) of follow-up. A total of 6,184 participants developed CKD progression, 896 participants had retinopathy, and 3,213 participants developed neuropathy (Michigan Neuropathy Screening Instrument, >2.0). After the confounding factors were adjusted for, patients in the highest FMI quartile had a higher risk of CKD progression (HR: 1.26, 95%CI: 1.16–1.36) and neuropathy (HR: 1.93, 95% CI: 1.74–2.15), except for retinopathy (HR: 1.17, 95% CI: 0.96–1.43), than those in the lowest quartile. Discordant analyses found that FMI and WC are better in identifying individuals with obesity-related risk of neuropathy, compared with BMI; neither is better in identifying individuals with obesity-related risk of CKD progression and retinopathy. Obesity is associated with CKD progression and neuropathy in T2DM participants. Further randomized trials are needed to test whether obesity control can improve the outcomes of T2DM participants with CKD or neuropathy. FMI and WC are more useful in identifying obesity-related risk of neuropathy compared with BMI in T2DM patients.Clinical Trial Registration http://www.clinicaltrials.gov, NCT00000620.

Mineralocorticoid receptor antagonists in diabetic kidney disease - mechanistic and therapeutic effects.

Chronic kidney disease (CKD) is the leading complication in type 2 diabetes (T2D) and current therapies that limit CKD progression and the development of cardiovascular disease (CVD) include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and sodium-glucose co-transporter 2 (SGLT2) inhibitors. Despite the introduction of these therapeutics, an important residual risk of CKD progression and cardiovascular death remains in patients with T2D. Mineralocorticoid receptor antagonists (MRAs) are a promising therapeutic option in diabetic kidney disease (DKD) owing to the reported effects of mineralocorticoid receptor activation in inflammatory cells, podocytes, fibroblasts, mesangial cells and vascular cells. In preclinical studies, MRAs consistently reduce albuminuria, CKD progression, and activation of fibrotic and inflammatory pathways. DKD clinical studies have similarly demonstrated that steroidal MRAs lead to albuminuria reduction compared with placebo, although hyperkalaemia is a major secondary effect. Non-steroidal MRAs carry a lower risk of hyperkalaemia than steroidal MRAs, and the large FIDELIO-DKD clinical trial showed that the non-steroidal MRA finerenone also slowed CKD progression and reduced the risk of adverse cardiovascular outcomes compared with placebo in patients with T2D. Encouragingly, other non-steroidal MRAs have anti-albuminuric properties in DKD. Whether or not combining MRAs with other renoprotective drugs such as SGLT2 inhibitors might provide additive protective effects warrants further investigation.

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD

Background and aimsThe optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of “the lower, the better” strategy for statin intake. Methods and resultsA total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70–99, 100–129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression.During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70–99, 100–129, and ≥130 mg/dL were 2.06 (1.14–3.73), 2.79 (1.18–6.58), and 4.10 (1.17–14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. ConclusionsThis study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

A Cross-Sectional Study for Prevalence and Association of Risk Factors of Chronic Kidney Disease Among People With Type 2 Diabetes in the Indian Setting.

Introduction: Current evidence demonstrates that people with type 2 diabetes (T2D) are at a higher risk of developing chronic kidney disease (CKD) with greater morbidity and mortality. We, therefore, aimed to document and categorize demographic, anthropometric, and physiological risk factors of CKD in people with T2D in India. Additionally, we also attempted to evaluate the magnitude of each risk factor, namely age, duration of diabetes, HbA1c, and body mass index (BMI) in its etiology.Methods: This observational, single-center, and cross-sectional study was performed at a diabetes care center in Lucknow, India. Out of a total of 504 eligible patients, we could get the required data from 435 patients. The following data were collected: demographic data, estimated glomerular filtration rate (eGFR), serum creatinine, urinary albumin creatinine ratio (UACR), and HbA1c levels. Appropriate statistical tests were applied.Result: The 435 eligible people with diabetes had a mean age (SD) of 51 (±10.52) years; female 48.02%, duration of diabetes 7 (±5.4) years; HbA1c 8.6 (±2.3)% and eGFR values 80.2 (±26.6) mL/min/1.73m2 at the time of presentation. The eGFR values correlated negatively with age and duration of diabetes, and positively with increasing BMI. The Spearman correlation coefficient showed that clinical parameters such as age, duration of diabetes, and BMI have a weak, but statistically significant correlation with eGFR while eGFR did not correlate with HbA1c level in the study. Further, we did not find a correlation between eGFR and UACR.Conclusion: In people with T2D, age and duration of diabetes are important risk factors for the development of CKD based on the eGFR. Hence, even in the absence of high UACR values, a low eGFR should prompt periodic monitoring to reduce the risk of progression of CKD, especially, in older people with long-standing T2D. Our study did not find HbA1c as a suitable tool to assess the CKD progression risk, but historical glycaemic control over longer periods revealed by sequential values of HbA1c over the duration of disease may correlate with the progression of CKD.

MP42-14 UPSTAGING OF CHRONIC KIDNEY DISEASE AFTER PARTIAL AND RADICAL NEPHRECTOMY

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy III (MP42)1 Sep 2021MP42-14 UPSTAGING OF CHRONIC KIDNEY DISEASE AFTER PARTIAL AND RADICAL NEPHRECTOMY Cameron Britton, Christine Lohse, Abhinav Khanna, Vidit Sharma, John Cheville, Stephen Boorjian, Bradley Leibovich, H. Robert Thompson, and Aaron Potretzke Cameron BrittonCameron Britton More articles by this author , Christine LohseChristine Lohse More articles by this author , Abhinav KhannaAbhinav Khanna More articles by this author , Vidit SharmaVidit Sharma More articles by this author , John ChevilleJohn Cheville More articles by this author , Stephen BoorjianStephen Boorjian More articles by this author , Bradley LeibovichBradley Leibovich More articles by this author , H. Robert ThompsonH. Robert Thompson More articles by this author , and Aaron PotretzkeAaron Potretzke More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002063.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Partial nephrectomy (PN) is generally preferred over radical nephrectomy (RN) when technically feasible. Nephron-sparing surgery may be particularly important for patients with chronic kidney disease (CKD). There is sparse literature comparing the outcomes of PN and RN in patients with CKD. We aim to illustrate the degree of renal functional change between PN and RN based on baseline renal function. METHODS: Adults treated with PN or RN for unilateral, sporadic, solid renal masses between 1980 and 2018 were identified. Patients who underwent PN or RN for a solitary kidney, were on dialysis at the time of surgery, or had stage 5 CKD at the time of surgery were excluded. Outcomes included positive margins, 30-day complications, and postoperative renal function assessed by CKD upstaging and percent change in eGFR at 3 months and 1 year following surgery compared to preoperative eGFR. Comparisons of outcomes were evaluated using chi-square, Fisher exact, and Wilcoxon rank sum tests. RESULTS: Amongst a total of 6,912 patients, 2,751 (40%) underwent PN and 4,161 (60%) underwent RN; 70 (2.5%) PNs and 99 (2.4%) RNs resulted in positive surgical margins (p=0.7); 164 (6%) PNs and 209 (5%) RNs resulted in Clavien grade 3 or higher complications. There were 3,471 and 3,256 patients with a 3-month and 1-year postoperative eGFR available for analysis. The interactions between type of surgery and CKD stage in models to predict CKD upstaging and percent change in eGFR were statistically significant (p <0.001 for all), indicating that the association of type of surgery with these outcomes differed by baseline CKD stage; as such, associations of type of surgery with 3-month and 1-year CKD upstaging and percent change in eGFR were stratified by CKD stage (Table). CONCLUSIONS: Patients with preoperative CKD stages 1-3 who underwent PN had significantly less renal functional decline at 3-months and 1-year as assessed by CKD upstaging and percent change in eGFR when compared to patients who underwent RN. There was no significant difference in renal functional outcomes in patients with baseline CKD stage 4, possibly reflecting a selection bias. Patients with stage 3 CKD, in particular, should be counseled regarding the reduced risk of CKD progression with PN. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e777-e777 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cameron Britton More articles by this author Christine Lohse More articles by this author Abhinav Khanna More articles by this author Vidit Sharma More articles by this author John Cheville More articles by this author Stephen Boorjian More articles by this author Bradley Leibovich More articles by this author H. Robert Thompson More articles by this author Aaron Potretzke More articles by this author Expand All Advertisement PDF DownloadLoading ...

A Role for SGLT-2 Inhibitors in Treating Non-diabetic Chronic Kidney Disease.

In recent years, inhibitors of the sodium-glucose co-transporter 2 (SGLT2 inhibitors) have been shown to have significant protective effects on the kidney and the cardiovascular system in patients with diabetes. This effect is also manifested in chronic kidney disease (CKD) patients and is minimally due to improved glycaemic control. Starting from these positive findings, SGLT2 inhibitors have also been tested in patients with non-diabetic CKD or heart failure with reduced ejection fraction. Recently, the DAPA-CKD trial showed a significantly lower risk of CKD progression or death from renal or cardiovascular causes in a mixed population of patients with diabetic and non-diabetic CKD receiving dapagliflozin in comparison with placebo. In patients with heart failure and reduced ejection fraction, two trials (EMPEROR-Reduced and DAPA-HF) also found a significantly lower risk of reaching the secondary renal endpoint in those treated with an SGLT2 inhibitor in comparison with placebo. This also applied to patients with CKD. Apart from their direct mechanism of action, SGLT2 inhibitors have additional effects that could be of particular interest for patients with non-diabetic CKD. Among these, SGLT2 inhibitors reduce blood pressure and serum acid uric levels and can increase hemoglobin levels. Some safety issues should be further explored in the CKD population. SGLT2 inhibitors can minimally increase potassium levels, but this has not been shown by the CREDENCE trial. They also increase magnesium and phosphate reabsorption. These effects could become more significant in patients with advanced CKD and will need monitoring when these agents are used more extensively in the CKD population. Conversely, they do not seem to increase the risk of acute kidney injury.

Association of urinary calcium and phosphorus excretion with renal disease progression in type 2 diabetes

ObjectivesDiabetes is associated with a high incidence of microvascular disease, including nephropathy. The current study aimed to investigate the association of urinary calcium and phosphorus excretion with chronic kidney disease (CKD) progression in type 2 diabetes mellitus. MethodsA total of 159 T2DM patients with chronic kidney disease (CKD stage G1-G4) were retrospectively included. Patients were categorized into three groups according to the tertiles of 24-h urinary calcium and phosphorus excretion, respectively. Clinical parameters and laboratory findings were compared among the three groups. Cox proportional hazards models were used to estimate the associations of urinary calcium and phosphorus excretion with CKD progression and adjusted for baseline eGFR, urinary protein excretion, mean arterial pressure, and use of RAAS inhibitor. A cubic spline curve was used to explore the association between urinary calcium excretion and CKD progression, as well as urinary phosphorus excretion and CKD progression. Moreover, the subgroup effects of urinary calcium and phosphorus excretion on CKD progression were estimated using Cox regression. CKD progression was defined as double of baseline serum creatinine or occurrence of ESRD. ResultsDuring a median of 18.23 months of follow-up, the composite renal outcomes were noted in 27%. Cumulative renal outcomes were significantly lower in the highest tertile of urinary calcium excretion and phosphorus excretion in Kaplan-Meier analyses. The multivariate Cox proportional hazards regression analyses indicated that both the highest tertile of urinary calcium and phosphorus excretion was associated with a lower risk for CKD progression compared with the lowest tertile. Restricted cubic spline analyses of the association between urinary calcium excretion and CKD progression indicated a linear association. Additionally, there was also a linear association between urinary phosphorus excretion and CKD progression. Subgroup analyses showed that higher urinary phosphorus excretion was particularly associated with a lower risk of CKD progression in non-diabetic kidney disease (NDKD) patients. ConclusionHigher urinary calcium and phosphorus excretion were associated with decreased risk of CKD progression in T2DM patients.

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression

BackgroundThe relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy.MethodsUsing our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR < 60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk.Results25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P = 0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P = 0.71).ConclusionsUse of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy.

Effects of veverimer on serum bicarbonate and physical function in diabetic patients with chronic kidney disease and metabolic acidosis: subgroup analysis from a randomized, controlled trial

BackgroundMetabolic acidosis is a complication of chronic kidney disease (CKD) that increases risk of CKD progression, and causes bone demineralization and muscle protein catabolism. Patients with diabetes are prone to metabolic acidosis and functional limitations that decrease quality of life. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis. This post hoc subgroup analysis evaluated effects of veverimer on metabolic acidosis and physical function among patients with diabetes.MethodsThis was a Phase 3, multicenter, randomized, blinded, placebo-controlled trial in 196 patients with CKD (estimated glomerular filtration rate 20–40 mL/min/1.73 m2) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo.ResultsAt Week 52, veverimer-treated patients with diabetes (n = 70), had a significantly greater increase in mean serum bicarbonate than the placebo group (n = 57) (4.4 versus 2.9 mmol/L, P < 0.05). Patient-reported limitations of physical function on the Kidney Disease and Quality of Life-Physical Function Domain (e.g. walking several blocks and climbing a flight of stairs) improved significantly in the veverimer versus placebo group (+12.5 versus +0.3, respectively, P < 0.001) as did objective physical performance on the repeated chair stand test (P < 0.0001).ConclusionsFew interventions for patients with diabetes and CKD have successfully improved quality of life or physical functioning. Our study demonstrated that veverimer effectively treated metabolic acidosis in patients with diabetes and CKD, and significantly improved how these patients felt and functioned.

Urinary Dickkopf-3: a new biomarker for CKD progression and mortality.

Kidney fibrosis has been reported to be a prognostic factor in chronic kidney disease (CKD) progression. Previous studies have shown that the assessment of urinary Dickkopf-3 (uDKK3), a stress-induced tubular epithelial-derived profibrotic glycoprotein, might be a potential tubulointerstitial fibrosis biomarker and might identify patients at short-term risk of glomerular filtration rate loss. We aim to evaluate uDKK3 as a potential biomarker for progression of CKD in a cohort with various aetiologies of CKD and subsequently in an overt diabetic nephropathy cohort. We prospectively studied two independent cohorts comprising a total of 351 patients with Stages 2 and 3 CKD. Combined primary outcome consisted of a 50% increase in serum creatinine, end-stage kidney disease or death. The Progreser cohort included patients with heterogeneous aetiologies and the Pronedi cohort (101 patients) with overt diabetic nephropathy. The median follow-up time was 36 months [interquartile range (IQR) 30-39] and 36 (16-48), respectively. At baseline, median uDKK3 was 2200 pg/mg (IQR 671-7617) in the Progreser cohort and 3042 pg/mg (IQR 661-9747) in the Pronedi cohort. There were no statistically significant differences in the uDKK3 ratio between both cohorts nor between CKD aetiologies. Baseline uDKK3 was significantly higher in patients who reached the primary outcome. In the Cox proportional hazards model, the highest levels of uDKK3 were found to be an independent factor for renal progression in the Progreser cohort {hazard ratio [HR] 1.91 [95% confidence interval (CI) 1.04-3.52]} and in the Pronedi cohort [HR 3.03 (95% CI 1.03-8.92)]. uDKK3 gradually increased in the following months, especially in patients with higher proteinuria. Treatment with renin-angiotensin-aldosterone system blockers did not modify uDKK3 after 4 or 12 months of treatment. uDKK3 identifies patients at high risk of CKD progression regardless of the cause of kidney injury. uDKK3 might serve as a useful biomarker for kidney disease progression and therefore could be used by clinicians to optimize staging for renal progression and monitor the response to potential treatments.