Risk Of CKD Progression Research Articles

MO157: Evaluating the Effect of SGLT2 Inhibitors on Proteinuria and Glomerular Filtration Rate in Non-Diabetic Patients with Proteinuria

Abstract BACKGROUND AND AIMS Proteinuria is strongly associated with the risk of CKD progression in non-diabetic and diabetic patients. SGLT2 inhibitors, as a promising new class, may provide protective effects for the kidney. Even though various studies have been conducted in this area, especially in diabetic patients, little information is available about how SGLT2 inhibitors affect proteinuria, kidney function or blood pressure in non-diabetic patients. Due to the lack of adequate information in previous studies, in this study, we investigated the effect of SGLT2 inhibitors on protein excretion and glomerular filtration rate (GFR) in patients with proteinuria. METHOD The present study was conducted as a single-group clinical trial (before and after). Thirty patients with proteinuria were enrolled. In addition to conventional treatment, empagliflozin 10 mg daily was administered. Height, weight, body mass index (BMI), GFR content, systolic and diastolic blood pressure, proteinuria and side effects in patients at the study's beginning and end were evaluated and recorded. In the end, the data were collected and analysed statistically. RESULTS In the present study, 30 patients with proteinuria were followed for 13.26 ± 5.90 weeks. The mean proteinuria of patients decreased significantly during the follow-up period (from an average of 1007.9 mg at the beginning of the study to 672.33 mg at the end (P < .05)). There was no significant difference in serum creatinine levels and glomerular filtration levels (P > .05). However, there was a significant decrease in blood pressure (systolic and diastolic) (P < .05). BMI and patients' weight were decreased compared to the beginning of the study, but this difference was not statistically significant (P > .05). Hypoglycaemia or hypokalemia did not occur in any of the patients. In 10% of patients, temporary dysuria was seen. Also, urinary tract infection was recorded in one patient (3.3%). In 3.3% of patients, the drug was discontinued due to intolerance. CONCLUSION The results of this study demonstrated that administration of empagliflozin significantly decreases proteinuria in non-diabetic patients with chronic kidney disease. However, further studies are recommended in this area.

FC 123: Baseline Characteristics of the Flow Trial Population: Kidney Outcomes Trial With Once-Weekly Semaglutide in People With Type 2 Diabetes and Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) in type 2 diabetes (T2D) is the most common cause of kidney failure. Despite treatment advances, there is still a large unmet need to prevent CKD progression, which can increase the risk for cardiovascular (CV) disease and kidney failure. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on glycaemic control and body weight. Some agents have also shown CV benefit and can be used in people with T2D regardless of CKD status (except in end-stage renal disease). CV outcomes trials have suggested that GLP-1RAs may have kidney-protective effects, reducing albuminuria and preserving estimated glomerular filtration rate (eGFR). FLOW (NCT03819153) is a dedicated kidney outcomes trial designed to evaluate the effect of the once-weekly (OW) GLP-1RA semaglutide on major kidney outcomes in subjects with T2D and CKD; we report the blinded baseline characteristics of the FLOW trial population. METHOD FLOW is an ongoing randomized, double-blinded, multinational, phase 3b trial in which 3535 subjects with T2D with an eGFR ≥25–≤75 mL/min/1.73 m², and urine albumin-to-creatinine ratio (UACR) >100 to <5000 mg/g were randomly assigned 1:1 to OW semaglutide 1.0 mg or placebo, as add-on to standard-of-care (including maximum labelled/tolerated renin–angiotensin–aldosterone system inhibitors). The primary endpoint is the time to first occurrence of kidney failure (as measured by persistent eGFR <15 mL/min/1.73 m² or initiation of chronic dialysis or kidney transplantation); ≥50% persistent eGFR reduction compared with baseline; and kidney or CV death. RESULTS Baseline characteristics from FLOW are shown in the Table 1. Overall, mean eGFR at baseline was 47.0 mL/min/1.73 m2 with 79.6% of subjects having an eGFR of <60 mL/min/1.73 m2. Median UACR at baseline was 567 mg/g, and 68.5% of subjects had macroalbuminuria (≥300 mg/g). According to Kidney Disease: Improving Global Outcomes categories, 24.8% of subjects were classified as high risk and 68.2% of subjects were classified as very high risk for CKD progression (Figure 1). CONCLUSION The FLOW trial will evaluate the efficacy and safety of semaglutide on kidney outcomes in subjects with T2D and high risk of kidney disease progression, a group for which additional therapies are urgently required.

FC081: Cholinesterase Inhibitors and Kidney Function Decline in Patients with Alzheimer's Dementia

Abstract BACKGROUND AND AIMS Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. This study explores a plausible effect of ChEIs on slowing kidney function decline. METHOD Observational study with a landmark design of patients with incident AD from the Swedish Dementia Registry (SveDem) 2007–2018 with complete extraction of routine serum creatinine tests from the Stockholm CREAtinine Measurements (SCREAM) registry to evaluate estimated glomerular filtration rate (eGFR) over time. Patients starting on ChEI within 90 days of an AD diagnosis were compared to patients with AD not receiving ChEI. The primary study outcome was CKD progression, defined as the composite of a sustained eGFR decline of >30% from baseline, initiation of kidney replacement therapy or death attributed to kidney disease. Secondary outcome was death. Inverse probability of treatment weighting Cox models were used to estimate hazard ratios, balancing 45 confounders. RESULTS We included 11 898 incident patients, of whom 6803 started on ChEI and 5095 did not. Mean age was 80 years, 64% were women and mean baseline eGFR was 68 mL/min/1.73 m2. After weighting, and during median follow-up time of 3.0 (IQR 1.3–4.5) years, 1231 events of CKD progression occurred, along with 5691 deaths. Compared to noninitiators, ChEI use was associated with a 18% lower risk of CKD progression [adjusted hazards ratio (aHR) 0.82; 95% confidence interval (95% CI) 0.70–0.96] and a 21% lower risk of death (aHR 0.79; 0.72–0.86). Results were consistent across subgroups of age, sex, and across ChEI subclasses and after accounting for competing risks. CONCLUSION In routinely cared patients with incident AD diagnosis, use of ChEI (versus no-use) was associated with lower risk of CKD progression and death, lending support to the role of CAP activation on preservation of kidney function.

MO514: Cardiorenal Outcomes Associated With Oral Anticoagulant Use in Patients With Atrial Fibrillation

Abstract BACKGROUND AND AIMS Novel oral anticoagulants (NOAC) are currently the first-line choice for stroke prevention in patients with atrial fibrillation (AF), as they have a better risk/benefit profile compared with vitamin K antagonists (VKA). Secondary analyses of trials suggest that NOAC also reduces kidney outcomes, but this has been less explored. METHOD Observational study from the SCREAM project comparing clinical outcomes of all persons with AF and eGFR ≥15 mL/min/1.73 m2 that initiated NOAC or VKA in Stockholm, Sweden, during 2011–18. The primary outcomes were acute kidney injury (AKI, by diagnosis or sudden creatinine elevation) and the composite of kidney failure and >30% eGFR decline. Secondary outcomes were major bleeding and the composite of hospital admission with stroke or systemic embolism. Inverse probability of treatment weighting (IPTW) was used to balance 51 baseline confounders. Sensitivity analyses included falsification endpoints (pneumonia and cataract surgery), subgroups and evaluation of per-protocol effects. RESULTS A total of 32 699 patients initiated oral anticoagulants (median age, 75 years, 45% women, median eGFR 73 mL/min/1.73 m2), of which 18 323 (56%) used NOAC. Compared with VKA, initiation of NOAC was associated with a 13% lower relative risk of experiencing the composite kidney outcome (HR: 0.87; 95% CI 0.78–0.98) and a 12% relative risk reduction on AKI occurrence (HR: 0.88; 95% CI 0.80–0.97). Compared with VKA, NOAC use was associated with a lower risk of major bleeding (HR 0.77; 95% CI 0.67–0.89), but a similar risk of stroke/systemic embolism (HR: 0.93; 95% CI 0.78–1.11). Results were similar across subgroups, including patients with chronic kidney disease (eGFR <60 mL/min/1.73 m2) and when censoring patients at treatment discontinuation or switch. CONCLUSION Compared with VKA, and regardless of baseline kidney function, initiation of NOAC was associated with a lower risk of CKD progression, AKI and major bleeding, but a similar risk of the composite of stroke and systemic embolism.

Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney Injury.

The mechanisms underlying long-term sequelae after AKI remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for CKD and heart failure. To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure and the secondary outcome of all-cause mortality 3 months after discharge or later. Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression. A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.

Association between Serum Inorganic Phosphorus Levels and Adverse Outcomes in Chronic Kidney Disease: The Fukushima CKD Cohort Study.

Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.

Risk of chronic kidney disease in patients with obstructive sleep apnea.

Chronic kidney disease (CKD) is a global health concern and a major risk factor for cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) may exacerbate this risk by contributing to the development of CKD. This study investigated the prevalence and patient awareness of the risk of CKD progression in individuals with OSA. Adults referred to five Canadian academic sleep centers for suspected OSA completed a questionnaire, a home sleep apnea test or in-lab polysomnography and provided blood and urine samples for measurement of estimated glomerular filtration rate (eGFR) and the albumin:creatinine ratio (ACR), respectively. The risk of CKD progression was estimated from a heat map incorporating both eGFR and ACR. 1295 adults (42% female, 54 ± 13 years) were categorized based on the oxygen desaturation index (4% desaturation): <15 (no/mild OSA, n = 552), 15-30 (moderate OSA, n = 322), and >30 (severe OSA, n = 421). After stratification, 13.6% of the no/mild OSA group, 28.9% of the moderate OSA group, and 30.9% of the severe OSA group had a moderate-to-very high risk of CKD progression (p < .001), which was defined as an eGFR <60 mL/min/1.73 m2, an ACR ≥3 mg/mmol, or both. Compared to those with no/mild OSA, the odds ratio for moderate-to-very high risk of CKD progression was 2.63 (95% CI: 1.79-3.85) for moderate OSA and 2.96 (2.04-4.30) for severe OSA after adjustment for CKD risk factors. Among patients at increased risk of CKD progression, 73% were unaware they had abnormal kidney function. Patients with moderate and severe OSA have an increased risk of CKD progression independent of other CKD risk factors; most patients are unaware of this increased risk.

Finerenone in Patients with CKD and T2D by SGLT-2i Treatment: An Analysis of the FIDELIO-DKD Study

IntroductionThe selective, nonsteroidal mineralocorticoid receptor antagonist finerenone was investigated in FIDELIO-DKD in patients with CKD and T2D (NCT02540993). Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are recommended for CKD in T2D to reduce risk of CKD progression. We report a predefined exploratory analysis of patients by SGLT-2i use. MethodsPatients (N=5674) with T2D, urine albumin-to-creatinine ratio (UACR) 30–5000 mg/g and estimated glomerular filtration rate (eGFR) 25–<75 mL/min/1.73 m2 receiving optimized RAS blockade were randomized to finerenone (10 mg daily increasing to 20 mg daily) or placebo. ResultsOf 5674 patients, 259 (4.6%) received SGLT-2i at baseline. Overall, finerenone significantly reduced the primary (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) vs placebo (p=0.001 and p=0.03, respectively) with no effect on A1C. Results were consistent irrespective of SGLT-2i use at baseline for the primary and key secondary CV outcomes (interaction p-value 0.21 and 0.46, respectively). Reduction in UACR with finerenone was seen without SGLT-2i use (ratio of LS-means 0.68, 0.65–0.71; p<0.0001) and on top of SGLT-2is at baseline (ratio of LS-means 0.75, 0.62–0.90; p=0.0024). Treatment-emergent hyperkalemia events were fewer with SGLT-2i vs no SGLT-2i (post hoc analysis). ConclusionThe benefits of finerenone on kidney and CV outcomes in patients with CKD and T2D appear consistent in the absence or presence of SGLT2i, with UACR improvement observed in patients already receiving SGLT-2i at baseline.

Longitudinal Ankle Brachial Index and Risk of CKD Progression

Longitudinal Ankle Brachial Index and Risk of CKD Progression

Urinary Peptidome Analysis to Predict the Risk of CKD Progression to Kidney Failure

Urinary Peptidome Analysis to Predict the Risk of CKD Progression to Kidney Failure

Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children.

Novel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression. We investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30-90ml/min per 1.73m2. Urine biomarkers were assayed a median of 5 months [IQR: 4-7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period. Overall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression. After multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children.

Organ-Specific Monitoring of Solitary Kidney after Living Donation by Using Markers of Glomerular Filtration Rate and Urinary Proteins

Background: Effective follow-up after living kidney donation is important for maintaining the renal function of the donor. We investigated whether the estimated glomerular filtration rate (eGFR) and urinary protein and enzyme levels can provide important information regarding the state of the remaining kidney after donor nephrectomy. Methods: Seventy-five living donations were included (prospective/retrospective) in the study. The following parameters were measured up to 1 year after donor nephrectomy: serum creatinine and cystatin C as markers of the GFR; the high-molecular-weight urinary proteins as markers of glomerular injury; and the low-molecular-weight urinary proteins and urinary enzymes as markers of tubular function. Results: One year after kidney donation, the creatinine and cystatin C values were 1.38-fold increased than their initial values, while the eGFR was 32% lower. At that time, 38% of donors had a moderate or high risk of CKD progression. The biochemical urinary glomerular and tubular kidney markers examined showed different behaviors. After a transient increase, the glomerular proteins normalized. Conversely, the detection of low-molecular-weight urinary proteins and enzymes reflected mild tubular damage at the end of the study period. Conclusions: Our findings suggest that for the evaluation of mild tubular damage, low-molecular-weight marker proteins should be included in the urine diagnostic of a personalized living kidney donor follow-up.

14-LB: Finerenone in Patients with CKD and T2D by SGLT2i Treatment: An Analysis of the FIDELIO-DKD Study

Introduction: The selective, nonsteroidal mineralocorticoid receptor antagonist finerenone was investigated in FIDELIO-DKD in patients with CKD and T2D (NCT02540993). Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are recommended for CKD in T2D to reduce risk of CKD progression. We report a predefined exploratory analysis of patients by SGLT-2i use. Methods: Patients (N=5674) with T2D, urine albumin-to-creatinine ratio (UACR) 30-5000 mg/g and estimated glomerular filtration rate (eGFR) 25-&amp;lt;75 mL/min/1.73 m2 receiving optimized RAS blockade were randomized to finerenone (10 mg daily increasing to 20 mg daily) or placebo. Results: Of 5674 patients, 259 (4.6%) received SGLT-2i at baseline. Overall, finerenone significantly reduced the primary (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) vs. placebo (p=0.001 and p=0.03, respectively) with no effect on A1C. Results were consistent irrespective of SGLT-2i use at baseline for the primary and key secondary CV outcomes (interaction p-value 0.21 and 0.46, respectively). Reduction in UACR with finerenone was seen without SGLT-2i use (ratio of LS-means 0.68, 0.65-0.71; p&amp;lt;0.0001) and on top of SGLT-2is at baseline (ratio of LS-means 0.75, 0.62-0.90; p=0.0024). Treatment-emergent hyperkalemia events were fewer with SGLT-2i vs. no SGLT-2i (post hoc analysis). Conclusion: The benefits of finerenone on kidney and CV outcomes in patients with CKD and T2D appear consistent in the absence or presence of SGLT2i, with UACR improvement observed in patients already receiving SGLT-2i at baseline. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. G. Schernthaner: None. C. Wanner: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Speaker’s Bureau; Self; Eli Lilly and Company. A. Joseph: Employee; Self; Bayer AG. M. F. Scheerer: Employee; Self; AstraZeneca, Bayer AG, Stock/Shareholder; Self; Bayer AG, Eli Lilly and Company, Novo Nordisk A/S. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck &amp; Co., Inc., Vascular Dynamics Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. A. Kooy: Research Support; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sanofi-Aventis. K. Mccafferty: Advisory Panel; Self; AstraZeneca, Bayer AG, Napp Pharmaceuticals, Pharmacosmos, Vifor Pharma Management Ltd., Research Support; Self; AstraZeneca.

MO458URINARY GROWTH DIFFERENTIATION FACTOR-15 (GDF15) LEVELS AS BIOMARKER OF ADVERSE OUTCOMES AND BIOPSY FINDINGS IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims Growth differentiation factor-15 (GDF15) is a member of the TGF-β superfamily. Increased serum GDF15 has been associated with increased risk of CKD progression. However, no prior study had addressed the significance of urinary GDF15 in adult CKD. Method We have now assessed serum and urinary GDF15 in a prospective cohort of 84 patients who underwent kidney biopsy and then were followed for 29±17 months. Results There was a statistically significant correlation between serum and urine GDF15 values. However, while serum GDF15 values increased with decreasing glomerular filtration rate, urinary GDF15 did not. Immunohistochemistry located kidney GDF15 expression mainly to tubular cells and kidney GDF15 staining correlated with urinary GDF15 values. Urine GDF15 was significantly higher in patients with a histological diagnosis of diabetic nephropathy than in diabetic patients without diabetic nephropathy. This was not the case for serum GDF15. Both serum and urine GDF15 were associated with patient survival in multivariate models. However, when both urine and serum GDF15 were present in the model, lower urine GDF15 predicted patient survival [B coefficient (SEM) -0.395 (0.182) p 0.03], and higher urine GDF15 predicted a composite of mortality or renal replacement therapy [0.191 (0.06) p 0.002] while serum GDF15 was not predictive. Decision tree analysis yielded similar results. The AUC of the ROC for urine GDF15 as a predictor of mortality was 0.95 (95% CI 0.89-1.00, p &amp;lt;0.001). Conclusion In conclusion, urine GDF15 is associated with kidney histology patterns, mortality and need for renal replacement therapy in biopsied CKD patients.

Low muscle mass is associated with progression of chronic kidney disease and albuminuria – An 8-year longitudinal study in Asians with Type 2 Diabetes

AimsWe examined the longitudinal relationship between baseline skeletal muscle mass and its change over time with eGFR decline and albuminuria progression among Asians with type 2 diabetes(T2D). MethodsThis was a prospective cohort study of 1272 T2D patients. Skeletal muscle mass was estimated using tetra-polar multi-frequency bio-impedance analysis and Skeletal Muscle Mass Index(SMI) was defined as skeletal muscle mass/weight * 100. ResultsAfter up to 8 years of follow-up, 33.3% of participants had CKD progression and 28.3% albuminuria progression. Every 1-SD above baseline SMI was associated with 18% lower risk of CKD progression[Hazards Ratio(HR)0.82; 95%CI 0.70–0.97; p = 0.018] and 17% lower risk of albuminuria progression [HR 0.83 (95%CI 0.71–0.97; p = 0.017)]. The largest decrease in SMI over time was associated with 67% higher risk of CKD progression, compared to those with the smallest change from baseline SMI tertile 2[HR 1.67 (95%CI 1.10–2.55); p = 0.016]. Pigment epithelium-derived factor(PEDF) and plasma leucine-rich α-2-glycoprotein (LRG1) accounted for 40.1% of the association between SMI and CKD progression. ConclusionsLow baseline skeletal muscle mass and its reduction over time is associated with increased risk of progression of CKD among Asians with T2D. PEDF and LRG1 mediated the inverse relationship between SMI and CKD progression.

The role of pulse pressure in navigating the paradigm of chronic kidney disease progression in type 2 diabetes mellitus.

Arterial stiffness is a risk factor for chronic kidney disease progression (CKD). Pulse pressure is a surrogate marker of arterial stiffness. It is unclear if pulse pressure predicts CKD progression in type 2 diabetes mellitus. This was prospective study involving 1494 patients with estimated glomerular filtration rate (eGFR) ≥ 15ml/min/1.73 m2. Carotid-femoral pulse wave velocity was measured using applanation tonometry. Pulse pressure was calculated as difference between systolic and diastolic blood pressures. CKD progression was defined as worsening of eGFR categories (stage 1, ≥ 90ml/min/1.73m2; stage 2, 60-89ml/min/1.73m2; stage 3a, 45-59ml/min/1.73m2; stage 3b, 30-44ml/min/1.73m2; stage 4; 15-29ml/min/1.73m2; and stage 5, < 15ml/min/1.73m2) with ≥ 25% decrease in eGFR from baseline. After follow-up of up to 6years, CKD progression occurred in 33.5% of subjects. Subjects in 2nd, 3rd and 4th quartiles of peripheral pulse pressure experienced higher risk of CKD progression with unadjusted hazard ratios (HRs) 1.55 [95% confidence interval (CI) 1.13-2.11; p = 0.006], 2.58 (1.93-3.45; p < 0.001) and 3.41 (2.58-4.52; p < 0.001). In the fully adjusted model, the association for 2nd, 3rd and 4th quartiles remained with HRs 1.40 (1.02-1.93; p = 0.038), 1.87 (1.37-2.56; p < 0.001) and 1.75 (1.25-2.44; p = 0.001) respectively. Similarly, 2nd, 3rd and 4th quartiles of aortic pulse pressure were associated with higher hazards of CKD progression with HRs 1.73 (1.25-2.40; p = 0.001), 1.65 (1.18-2.29; p = 0.003) and 1.81 (1.26-2.60; p = 0.001). Increasing urinary albumin-to-creatinine ratio accounted for 44.0% of the association between peripheral pulse pressure and CKD progression. Individuals with high pulse pressure were more susceptible to deterioration of renal function. Pulse pressure could potentially be incorporated in clinical practice as an inexpensive and readily available biomarker of renal decline in type 2 diabetes mellitus. Graphic abstract.

Kidney damage in patients with chronic heart failure and obesity: the role of leptin and adiponectin

Objectives: to assess the functional state of the kidneys and cardiovascular risk in relation to the level of leptin and adiponectin in patients with chronic heart failure (CHF) and obesity.Materials and methods: a total of 116 patients with CHF of I-III functional class (FC) 45-65 years old were examined, which were divided into three comparable groups depending on body mass index (BMI).Results: a statistically significant decrease in glomerular filtration rate (GFR), a significant increase in the level of albuminuria (AC) and β2-microglobulins (β2-MG) among patients with chronic heart failure and obesity were revealed. The leptin level significantly increased from the 1st to the 3rd group, the adiponectin concentration decreased from the 1st to the 3rd group. Significant correlations were established between the concentrations of adipokines, HOMA-IR and GFR, AC, β2-MG in the group of individuals with heart failure and obesity.Conclusions: reliable deterioration of renal functional parameters in patients with CHF, statistically significant relationships between GFR, AC, β2-MG and adipokines, HOMA-IR with increasing body weight, as well as an increase in the combined risk of CKD progression and the development of cardiovascular complications with comparable FC were established.

Association of Anion Gap with the Risk of CKD Progression

Association of Anion Gap with the Risk of CKD Progression

Baseline Serum Magnesium and Risk of CKD Progression in the Chronic Renal Insufficiency Cohort (CRIC) Study

Baseline Serum Magnesium and Risk of CKD Progression in the Chronic Renal Insufficiency Cohort (CRIC) Study

Biomarker Panels for Discriminating Risk of CKD Progression in Children

Biomarker Panels for Discriminating Risk of CKD Progression in Children