Reduction In eGFR Research Articles

#2817 Preliminary results of dapagliflozin in inactive lupus nephritis cross-over randomized trial

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD). Lupus nephritis (LN) patients in remission may continue with residual proteinuria due to scars and hyperfiltration. However, LN patients were excluded from the main trials with SGLT2 inhibitors. This trial aims to assess the effect and safety of dapagliflozin in inactive LN patients with residual proteinuria. Method For this cross-over randomized trial, we include adult patients with LN class III, IV (±V) without active nephritis but with proteinuria >500 mg/24 h or UPC > 200 mg/g and eGFR ≥ 20 ml/min, in the maintenance treatment with a RAAS and mycophenolate mofetil (<2g/day) in stable a dose for at least four weeks before the randomization. We excluded patients with other etiologies of CKD, those with active LN lesions on the recent biopsy (AI>2), use of induction therapy in the last 12 months (cyclophosphamide, mycophenolate mofetil >2g/day and calcineurin inhibitors) and prednisone dose ≥ 20 mg/day. Due to safety issues, we excluded patients with recurrent urinary infections (>3 times/year). Those included were randomized to receive dapagliflozin 10 mg on top of standard of care therapy (SoC) or not. After 24 weeks the groups were switched and those without dapagliflozin received it for the next 24 weeks. Primary endpoint is reduction of proteinuria compared to baseline at 6 and 12 months. Secondary endpoints are sustained reduction of eGFR>30%; occurrence of hypotension symptoms; and number of infections on dapagliflozin treatment versus exclusive SoC therapy. The sample size was calculated for 28 patients enrolled providing 80% power to detect a 25% relative risk reduction in proteinuria (α level of 0.05). Results From 97 screened class III, IV (± V) LN patients under maintenance therapy, we excluded 67 due to active nephritis, low proteinuria or low eGFR. We included 30 patients that were randomized 14 to start the treatment with dapagliflozin on top of SoC and 16 to remain with the usual therapy for 24 weeks. Six patients were excluded from the analysis due to new LN flare or lost to follow-up. We analyzed the data of 12 patients in the initial Dapa + SoC and 12 patients in the initial SoC group after 3 (n = 21), 6 (n = 18), 9 (n = 14) and 12 (n = 12) months. Patients in initial Dapa group had a significant decrease in proteinuria after 6 months (1159 to 882 mg/day; p = 0.017) but increased to 1105 mg/day 6 months after the drug withdrawal (Fig. 1A). This preliminary analysis shows a significant reduction in the proteinuria of –35.8% in patients after 6 mo of dapagliflozin as opposed to an increase in 7.2% for those in the SoC therapy at the end of a 6 mo period, p = 0.02 (Fig. 1C). The drug was well tolerated, but 4 (33.3%) of the patients reported hypotension symptoms during the first days of dapagliflozin. There was one case of urinary infection in each group, but in the same patient. Conclusion Preliminary results show a significant reduction in residual proteinuria in patients with inactive LN with dapagliflozin without an increase in infections.

#851 Effects of gliflozins on endothelial cells: in vitro and clinical evidence

Abstract Background and Aims Gliflozins are a class drugs widely used in diabetes as they act as sodium-glucose co-transporter type 2 inhibitors (SGLT2i). Irrespective from glycaemic control, SGLT2i are known to possess kidney and heart protective effects. The kidney- and heart-protective effects of gliflozins (SGLT2i) have received different explanations because of their efficacy in non-diabetic patients. Indeed, the non-glycemic effects of SGLT2i are puzzling because SGLT2, the molecular target of gliflozins, is mainly expressed in proximal tubule cells, with very low expression levels in other cell types. Though SGLT2 inhibitors might be nephroprotective because of a reduction of eGFR, this mechanism seems insufficient to explain heart protection. Emerging evidence suggests that SGLT2i have off-target effects in endothelial cells. In this study, we analyze this assumption by testing the effects of gliflozins on endothelial cells in vitro and verifying a differential effect of gliflozins on glomerular diseases involving primarily the endothelial compartment vs those involving podocytes or both. Methods In vitro studies have been conducted on EA.hy926 cells. A dose-response curve of gliflozins on mitochondrial activity and cell viability has been obtained using MTT staining. Morphological parameters were obtained using phase contrast microscopy, and the details of the plasma membranes were studied using Atomic Force microscopy. Patients with IgA nephropathy, minimal change disease or Focal Segmental Glomerulo Sclerosis FSGS, and with diabetic nephropathy (n = 12 per group). were studied for the percent change in albuminuria and creatinine four months after gliflozin treatment (empagliflozin or dapagliflozin). Three additional control groups (IgA, podocytopathies, diabetes) without gliflozin treatment (n = 12 per group) were also included. Results Gliflozin treatment induced a dose-response improvement in EA.hy926 cells' survival and restoration of cell-cell borders in AFM images. In patients, the albuminuria was reduced by a similar extent (−38 ± 6%) in all groups when treated with gliflozins. However, in diabetic patients and podocytopathies, this was associated with decreased eGFR (−6% and −8%), whereas in IgA nephropathy, the eGFR levels were increased after treatment (+3.8%). Conclusion In vitro, gliflozins show a direct endothelial protection effect. In vivo, part of the effects on proteinuria may be explained by a hemodynamic effect on the glomerular filtration rate in diseases affecting podocytes (diabetes, MCD, FSGS), as shown by the increase in creatinine. However, for diseases involving the endothelium (IgA nephropathy), the endothelial protection effect of gliflozins is demonstrated by the reduction in proteinuria and the protective effect on creatinine levels.

#2071 The metabolic syndrome impact in the onco-nephrological scenario of renal cancer: when comorbidities beat surgery

Abstract Background and Aims Metabolic syndrome (MS) represents a pathological state in which many risk factors for CKD including obesity, hyperglycemia, hypertension and dyslipidemia co-occur within individuals. In the past decade different lines of evidence underlined the relationship between MS and CKD, two increasing worldwide serious threat to life. With the rise of onco-nephrology, there is a strong need to define the role of MS in the nephrological management of oncological patients. Our study aimed to assess the impact of metabolic syndrome on renal function in patients undergoing partial nephrectomy (PN) for renal cancer (RC). Method We retrospectively analyzed data from 1,112 patients undergoing PN at a tertiary referral center between 2000 and 2023. Patients with metastatic disease, hereditary cancer or a solitary kidney were excluded. Renal function was evaluated with eGFR values using CKD-EPI 2021 formula. AKI and CKD onset were defined using K-DIGO 2012 criteria. MS was defined as at least 3 of the following conditions: obesity, insulin resistance, dyslipidemia and hypertension. Multivariable analyses (MA) were used to determine the impact of MS on preoperative eGFR impairment and post-operative AKI. Covariates were intraoperative blood loss, surgical experience, pT stage, type of surgery (open vs minimally invasive), pre-existing CKD, age, and comorbidities (defined as Charlson Comorbidity Index>3). Results Overall, the rate of MS was 9% (n = 100). The median follow-up was 60 months (IQR 28-68). Patients with MS had lower preoperative eGFR (78 ml/min vs. 87 ml/min), higher estimated blood loss (500 ml vs. 300 ml) and higher rate of complications (38% vs. 29%) relative to non-MS counterparts (all p < 0.001). Additionally, the rate of AKI was 25% (n = 25) vs 18% (n = 182) for metabolic vs non-MS patients (p = 0.01), respectively. At MVA, MS was an independent predictor for both lower preoperative eGFR (OR 1.07, 95% CI 1.01-1.14, p = 0.01) and higher risk of AKI (OR 2.1, 95% CI 1.3-4.1, p = 0.01). MS patients had a worse kidney function at baseline, had higher risk of AKI immediately after surgery and a higher risk of CKD onset over time, with a steep reduction of eGFR even at long term follow-up (Fig. 1). Conclusion Renal cancer patients diagnosed with MS harbored an increased risk of both AKI and CKD even with a partial nephrectomy. Therefore, the role of onco-nephrologists and nutritionists remains a cornerstone in the management of such cohort of patients, before and after surgery.

USE OF SGLT2-i IN ELDERLY PATIENTS WITH HFrEF- REAL WORD DATA

Abstract Introduction SGLT2-i have been shown to improve prognosis in patients with reduced ejection fraction heart failure (HFrEF) in randomized clinical trials (RCTs). However, we have little data on the use of these drugs in clinical practice, both in terms of safety and efficacy profile, especially in elderly patients. Objectives To describe the characteristics of HFrEF outpatients who started SGLT2-I and evaluate tolerability and effect of therapy. Results We evaluated 42 patients, 32 M and 10 F, with a mean age of 78±8.2 years (62.1% over 75). At baseline, the mean EF was 34.5%± 6.0 and the patients' renal function calculated with CKD-EPI was 56.3±18.6 ml/min/m2. We followed at 6 months 36 patients. After 6 months of SGLT2i therapy, there was a significant reduction in NYHA class (NYHA I 30.6% vs 9.8%, NYHA III 13.9% vs 31.7%), a slight recovery in EF (38% vs 33% p-value = 0.039) and a decrease in diuretic dose (34 mg/day vs 64 mg/day, p-value 0.033). Despite a slight initial reduction in eGFR, like RCTs, there was recovery of renal function at 6 months. At 6 months, only 2 patients discontinued SGLT2i therapy due to urinary infection. Conclusions In our analysis after 6 months of SGLT2-i therapy in elderly patients, there was clinical improvement as evidenced by improvement in NYHA class and reduction in diuretic therapy. SGLT2-i have been shown to be relatively safe, with no adverse effects occurring and no significant worsening of renal function.

Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1

Introduction: The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remain uncertain, warranting further research. Methods: A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS + immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups. Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS + immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-h proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 mL/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable. Conclusion: Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.

Risk Prediction Models for Renal Function Decline After Cardiac Surgery Within Different Preoperative Glomerular Filtration Rate Strata.

Our goal was to create a simple risk-prediction model for renal function decline after cardiac surgery to help focus renal follow-up efforts on patients most likely to benefit. This single-center retrospective cohort study enrolled 24 904 patients who underwent cardiac surgery from 2012 to 2019 at Fuwai Hospital, Beijing, China. An estimated glomerular filtration rate (eGFR) reduction of ≥30% 3 months after surgery was considered evidence of renal function decline. Relative to patients with eGFR 60 to 89 mL/min per 1.73 m2 (4.5% [531/11733]), those with eGFR ≥90 mL/min per 1.73 m2 (10.9% [1200/11042]) had a higher risk of renal function decline, whereas those with eGFR ≤59 mL/min per 1.73 m2 (5.8% [124/2129]) did not. Each eGFR stratum had a different strongest contributor to renal function decline: increased baseline eGFR levels for patients with eGFR ≥90 mL/min per 1.73 m2, transfusion of any blood type for patients with eGFR 60 to 89 mL/min per 1.73 m2, and no recovery of renal function at discharge for patients with eGFR ≤59 mL/min per 1.73 m2. Different nomograms were established for the different eGFR strata, which yielded a corrected C-index value of 0.752 for eGFR ≥90 mL/min per 1.73 m2, 0.725 for eGFR 60-89 mL/min per 1.73 m2 and 0.791 for eGFR ≤59 mL/min per 1.73 m2. Predictors of renal function decline over the follow-up showed marked differences across the eGFR strata. The nomograms incorporated a small number of variables that are readily available in the routine cardiac surgical setting and can be used to predict renal function decline in patients stratified by baseline eGFR.

Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome.

The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the "Victor Babes" Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study's findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.

Electronic Health Record Population Health Management for Chronic Kidney Disease Care

Large gaps in clinical care in patients with chronic kidney disease (CKD) lead to poor outcomes. To compare the effectiveness of an electronic health record-based population health management intervention vs usual care for reducing CKD progression and improving evidence-based care in high-risk CKD. The Kidney Coordinated Health Management Partnership (Kidney CHAMP) was a pragmatic cluster randomized clinical trial conducted between May 2019 and July 2022 in 101 primary care practices in Western Pennsylvania. It included patients aged 18 to 85 years with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 with high risk of CKD progression and no outpatient nephrology encounter within the previous 12 months. Multifaceted intervention for CKD comanagement with primary care clinicians included a nephrology electronic consultation, pharmacist-led medication management, and CKD education for patients. The usual care group received CKD care from primary care clinicians as usual. The primary outcome was time to 40% or greater reduction in eGFR or end-stage kidney disease. Among 1596 patients (754 intervention [47.2%]; 842 control [52.8%]) with a mean (SD) age of 74 (9) years, 928 (58%) were female, 127 (8%) were Black, 9 (0.6%) were Hispanic, and the mean (SD) estimated glomerular filtration rate was 36.8 (7.9) mL/min/1.73m2. Over a median follow-up of 17.0 months, there was no significant difference in rate of primary outcome between the 2 arms (adjusted hazard ratio, 0.96; 95% CI, 0.67-1.38; P = .82). Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker exposure was more frequent in intervention arm compared with the control group (rate ratio, 1.21; 95% CI, 1.02-1.43). There was no difference in the secondary outcomes of hypertension control and exposure to unsafe medications or adverse events between the arms. Several COVID-19-related issues contributed to null findings in the study. In this study, among patients with moderate-risk to high-risk CKD, a multifaceted electronic health record-based population health management intervention resulted in more exposure days to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers but did not reduce risk of CKD progression or hypertension control vs usual care. ClinicalTrials.gov Identifier: NCT03832595.

Whole-body water mass and kidney function: a Mendelian randomization study.

The morbidity and mortality of chronic kidney disease (CKD) are increasing worldwide, making it a serious public health problem. Although a potential correlation between body water content and CKD progression has been suggested, the presence of a causal association remains uncertain. This study aimed to determine the causal effect of body water content on kidney function. Genome-wide association study summary data sourced from UK Biobank were used to evaluate single-nucleotide polymorphisms (SNPs) associated with whole-body water mass (BWM). The summary statistics pertaining to kidney function were extracted from the CKDGen consortium. The primary kidney function outcome measures included estimated glomerular filtration rate (eGFR), albuminuria, CKD stages 3-5, and rapid progression to CKD (CKDi25). Two-sample Mendelian randomization (MR) analysis estimated a potential causal relationship between the BWM and kidney function. The inverse variance weighted MR method was used as the primary analysis, accompanied by several sensitive MR analyses. The increase of BWM exhibited a correlation with a reduction in eGFR (β = -0.02; P = 6.95 × 10-16). Excluding 13 SNPs responsible for pleiotropy (P = 0.05), the increase of BWM was also associated with the decrease of the ratio of urinary albumin to creatinine (β = -0.16; P = 5.91 × 10-36). For each standard deviation increase in BWM, the risk of CKD stages 3-5 increases by 32% (OR, 1.32; 95% CI, 1.19-1.47; P = 1.43 × 10-7), and the risk of CKDi25 increases by 22% (OR, 1.22; 95% CI, 1.07-1.38; P = 0.002). The increase of BWM is associated with impaired kidney function. Proactively managing body water content is of great significance in preventing the progression of CKD.

Association between an Antioxidant-Rich Japanese Diet and Chronic Kidney Disease: The Ohasama Study.

Although physiological effects of hydrophilic- (H-) and lipophilic- (L-) antioxidant capacities (AOCs) are suggested to differ, the association of an antioxidant-rich diet and chronic kidney disease (CKD) incidence has not been examined. We therefore explored the association between the H- or L-AOC of a whole Japanese diet and CKD risk in a general population. A total of 922 individuals without CKD (69.2% women; mean age, 59.5 years old) from Ohasama Town, Japan, were examined. CKD incidence was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) of ＜60 ml/min/1.73 m2. Consumption of H-/L-AOC was determined based on the oxygen radical absorbance capacity in a specially developed Japanese food AOC database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for new-onset CKD using a Cox proportional hazards model. During the median follow-up of 9.7 years, 137 CKD incidents were recorded. After adjusting for potential confounding variables, the highest quartile of L-AOC was significantly associated with a 51% reduced CKD risk among only women. An increased L-AOC intake was more effective in preventing eGFR reduction than in preventing proteinuria in women. These associations were not seen for H-AOC intake in both sexes and L-AOC intake in men. A high intake of lipophilic antioxidants may be associated with a reduced CKD risk. The balance between dietary antioxidant intake and pro-oxidants induced by unhealthy lifestyles may be crucial for preventing future kidney deterioration.

Effects of Novel Insulin Resistance Indices on Early Renal Functions in Donors.

To investigate the relationship between quickly calculable new insulin resistance (IR) indices used to evaluate IR in early kidney functions after donor nephrectomy. Descriptive design. Place and Duration of the Study: Department of Urology, Ufuk University Faculty of Medicine, Ankara, Turkiye, between January 2016 and August 2021. The preoperative biochemical analyses of patients undergoing open donor nephrectomies and estimated glomerular filtration rates (eGFR) were recorded in the preoperative and first postoperative month. The IR indices (triglyceride glucose [TyG] index, TyG-body mass index [TyG-BMI], triglyceride/HDL cholesterol ratio [TG/HDL-C], and metabolic score for IR [METS-IR]) were computed. Additionally, the patients were separated into two categories. Group 1 had a less than 30% decrease in eGFR values in the postoperative first-month period, and group 2 had a more than 30% decrease. The relationship between variables was analysed using the Spearman correlation, and comparisons between groups were analysed using the independent t-test or Mann-Whitney U-test. A total of 107 patients were included in the study. The mean eGFR reduction rate was 31.81 ± 8.87 %. In the correlation analyses, an increase in the rate of decrease in postoperative GFR was associated with higher IR indices, specifically TyG (r = 0.19, p = 0.04), TG/HDL-C (r = 0.21, p = 0.02), and METS-IR (r = 0.21, p = 0.02). No statistically significant difference was found between the groups regarding all the calculated IR indices (p < 0.05). The results suggest a possible link between increased IR and postoperative renal function decline. Insulin resistance, Glomerular filtration rate, Donor nephrectomy, Triglyceride-Glucose index, METS-IR.

Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Cadmium (Cd) is a metal with no nutritional value or physiological role. However, it is found in the body of most people because it is a contaminant of nearly all food types and is readily absorbed. The body burden of Cd is determined principally by its intestinal absorption rate as there is no mechanism for its elimination. Most acquired Cd accumulates within the kidney tubular cells, where its levels increase through to the age of 50 years but decline thereafter due to its release into the urine as the injured tubular cells die. This is associated with progressive kidney disease, which is signified by a sustained decline in the estimated glomerular filtration rate (eGFR) and albuminuria. Generally, reductions in eGFR after Cd exposure are irreversible, and are likely to decline further towards kidney failure if exposure persists. There is no evidence that the elimination of current environmental exposure can reverse these effects and no theoretical reason to believe that such a reversal is possible. This review aims to provide an update on urinary and blood Cd levels that were found to be associated with GFR loss and albuminuria in the general populations. A special emphasis is placed on the mechanisms underlying albumin excretion in Cd-exposed persons, and for an accurate measure of the doses-response relationships between Cd exposure and eGFR, its excretion rate must be normalised to creatinine clearance. The difficult challenge of establishing realistic Cd exposure guidelines such that human health is protected, is discussed.

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.

Long-Term Blood Pressure Reductions Following Catheter-Based Renal Denervation: A Systematic Review and Meta-Analysis.

Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies. A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically. In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of -12.7±4.5 mm Hg from baseline was observed (P=0.05). Likewise, a -14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5-9.4 years; P=0.0051). The observed reduction in estimated glomerular filtration rate across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up. Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function.

Evaluation of Kidney Function in Bipolar Patients: A Cross-Sectional Study

Bipolar disorder is a chronic disease that represents a significant problem to the affected individual. To date, the mainstay treatment for bipolar disorder consists in mood stabilizers, mainly lithium, which have been linked to acute and chronic kidney injury. To investigate the association between Estimated Glomerular Filtration Rate (eGFR) and sociodemographic and clinical characteristics in a group of patients with bipolar disorder (BD) undergoing lithium treatment, with or without concomitant use of other psychopharmaceuticals. In this cross-sectional study data was collected using the instruments: 1 – Clinical and sociodemographic data questionnaire, developed by the Brazilian Consortium for Bipolar Disorder Research; 2 – Structured Clinical Interview for the DSM-IV Axis I Disorders; 3 – Hamilton’s Rating Scale for Depression, to evaluate depressive symptoms and 4 – Young’s Rating Scale for Mania to evaluate mania symptoms. Renal function was calculated through the CKD/EPI formula for eGFR. 95 patients were included in the final analysis. 26 (27.4%) patients presented reduction in eGFR, 21 (22,1%) with eGFR between 60 to 89 and 5 (5,2%) below 60. Higher serum lithium levels and age were associated with such reduction (β = -18.06 [95% CI: -34.70 to -1.42]); (β = -0.72 (95% CI: -1.10 to -0.33)), respectively. Although lithium is considered the “gold standard” in the treatment of BD, its toxicity and tolerability profile in relation to renal function still needs to be better understood. The results of this study reinforce the idea that periodic control of lithium levels is essential for preserving renal function. Long-term longitudinal studies are needed to assess the relationship between renal function and lithium therapy in BD patients. Keywords Lithium, Bipolar Disorder, Kidney, Renal Insufficiency

Factores de progresión en pacientes con ERC-3 KDOQI (estudio PROGRESER)

IntroductionThe PROGRESER study is a multicentre, prospective, observational, 3-year follow-up study of a cohort of patients with stage3 chronic kidney disease (CKD) from different nephrology departments of hospitals in the Spanish healthcare system. The primary study objective was to analyse risk factors for CKD progression, identifying possible differences between patients with and without diabetes mellitus (DM). The secondary objective was to analyse the factors associated with hospitalizations and mortality. Patients and methodsA total of 462 patients (342 men and 120 women; mean age 66.5±11.5 years) were recruited from 25 participating sites in Spain. Clinical, epidemiological and analytical data were recorder in an electronic register each six months. Biological samples were obtained and frozen for a biobank record at baseline and at 18 and 36 months. ResultsThe initial mean glomerular filtration rate estimated by MDRD and after that reestimated by CKD-EPI was 43.9±7.9mL/min/1.73m2; and 29±6,8mL/min/1,73m2 at 3years. 27.3% of patients had microalbuminuria and 22.5% had macroalbuminuria. Two-thirds of the patients (66.2%) presented renal damage progression according to the study criteria (decrease of more than 15% in eGFR over the baseline value). 38.7% presented a reduction in eGFR ≥30%; 20.3% had a reduction in eGFR ≥40%; 10.4% had a reduction ≥50% and 6.9% had a reduction ≥57%. Of the 199 diabetics, 134 (67.3%) suffered renal damage progression. Of the 263 non-diabetics, 172 (65.3%) presented progression (P=.456). 27.3% of patients had microalbuminuria and 22.5% proteinuria. The study found that CKD progression to a higher stage was not greater in diabetic compared to non-diabetic patients. Multivariate analysis revealed that the presence of arterial hypertension bordered on significance as a progression factor in non-diabetic patients (P=.07), and that, in diabetic patients, lower calcium levels and elevated intact parathyroid hormone levels at baseline were associated with progression. ConclusionIn our study we have not found new factors for progression of renal damage, different from the yet well known traditional factors. DM per se was not a differential factor for progression in relation with non DM patients. Progression of renal damage in patients with CKD-3 KDOQI may be interpreted in a multifactorial context. The search for new biomarkers, different from traditional ones, is necessary to establish new therapeutic strategies to prevent the progression of CKD.

Clinical Significance of the Cystic Phenotype in Alport Syndrome

Alport Syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect Type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS. Retrospective cohort study. & Participants: One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA Nephropathy (IgAN). Clinical, genetic, and imaging data were collected from medical records. Cystic kidney phenotype evaluated by ultrasonography and defined as the presence of ≥3 cysts in each kidney. Demographic characteristics and eGFR at disease onset. Cystic kidney phenotype in the AS and IgAN cohorts. Time to CKD stage 3b and longitudinal changes in eGFR in the AS cohort. Logistic regression analysis to test independent strengths of associations of clinical/demographic features with the binary outcome of cystic phenotype. Survival analysis for the outcome of reaching CKD stage 3b and linear mixed models for changes in eGFR over time in the AS cohort. We studied 108 patients with AS; 76 (70%) had genetic diagnosis. Autosomal dominant AS was prevalent, accounting for 68% of patients with genetic diagnosis. Cystic kidney phenotype was observed in 38% of patients with AS and was associated with normal sized kidneys in all but 3 patients, who showed increased total kidney volume, mimicking autosomal dominant polycystic kidney disease (ADPKD). The prevalence of cystic kidney phenotype was significantly higher in patients with AS when compared to comparison group of patients with IgAN (42% vs 19%; p=0.002). Patients with cystic kidney phenotype were older and had more marked reductions in eGFR than patients without cystic changes. Among patients with AS, the cystic phenotype was associated with older age and a faster decline eGFR. Retrospective, single-center study. Cystic kidney phenotype is a common finding in AS. The cystic kidney phenotype is a common finding in AS suggesting a possible role in cystogenesis for the genetic variants that cause this disease.

Combined Serologic and Genetic Risk Score and Prognostication of Phospholipase A2 receptor-Associated Membranous Nephropathy.

The aim of this study was to test whether a combined risk score on the basis of genetic risk and serology can improve the prediction of kidney failure in phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy. We performed a retrospective analysis of 519 biopsy-proven PLA2R-associated primary membranous nephropathy patients with baseline eGFR ≥25 ml/min per 1.73 m 2 . The combined risk score was calculated by combining the genetic risk score with PLA2R ELISA antibody titers. The primary end point was kidney disease progression defined as a 50% reduction in eGFR or kidney failure. Cox proportional hazard regression analysis and C-statistics were applied to compare the performance of PLA2R antibody, genetic risk score, and combined risk score, as compared with clinical factors alone, in predicting primary outcomes. The median age was 56 years (range, 15-82 years); the male-to-female ratio was 1:0.6, the median eGFR at biopsy was 99 ml/min per 1.73 m 2 (range: 26-167 ml/min per 1.73 m 2 ), and the median proteinuria was 5.3 g/24 hours (range: 1.5-25.8 g/24 hours). During a median follow-up of 67 (5-200) months, 66 (13%) had kidney disease progression. In Cox proportional hazard regression models, PLA2R antibody titers, genetic risk score, and combined risk score were all individually associated with kidney disease progression with and without adjustments for age, sex, proteinuria, eGFR, and tubulointerstitial lesions. The best-performing clinical model to predict kidney disease progression included age, eGFR, proteinuria, serum albumin, diabetes, and tubulointerstitial lesions (C-statistic 0.76 [0.69-0.82], adjusted R 2 0.51). Although the addition of PLA2R antibody titer improved the performance of this model (C-statistic: 0.78 [0.72-0.84], adjusted R 2 0.61), replacing PLA2R antibody with the combined risk score improved the model further (C-statistic: 0.82 [0.77-0.87], adjusted R 2 0.69, difference of C-statistics with clinical model=0.06 [0.03-0.10], P < 0.001; difference of C-statistics with clinical-serologic model=0.04 [0.01-0.06], P < 0.001). In patients with PLA2R-associated membranous nephropathy, the combined risk score incorporating inherited risk alleles and PLA2R antibody enhanced the prediction of kidney disease progression compared with PLA2R serology and clinical factors alone.

Effect of Intravitreal Anti-Endothelial Growth Factor Agents on Renal Function in Patients With Diabetes Mellitus

BackgroundIntravitreal administration of vascular endothelial growth factor inhibitors (anti-VEGF) is the treatment of choice in retinal pathology associated with type 2 diabetes mellitus (DM2). We aimed to analyze the effect on renal function in patients with DM2 after intravitreal anti-VEGF administration. MethodsSingle-center retrospective and observational study of patients with DM2 with and without chronic kidney disease (CKD). We analyzed the evolution of renal function after anti-VEGF onset, compared with a control group. ResultsWe included 45 patients (55.6% male) who received anti-VEGF therapy. Mean age was 74.4±11.5 (50-91) years. These were compared with 45 patients with similar characteristics. After 12-months, 76.3% had CKD with a mean reduction in estimate glomerular filtration rate (eGFR) of 19.4%. Nine patients (20%) had a >25% reduction in eGFR, and three patients (6.7%) had a >50% reduction in GFR. At 24-months, 80% of patients had CKD with a mean eGFR drop of 28%. The mean eGRF slope of patients who had received anti-VEGF treatment was 10 ml/min/year compared to 1,5 ml/min/year in the control group (p<0.05). After the first administration, five patients (17.2%) in the CKD group required renal replacement therapy during follow-up (mean time 22±12 months). Main risk factors for need of dialysis were age, presence of previous CKD, and baseline proteinuria. ConclusionIntravitreal anti-VEGF administration is a risk factor for CKD and rapid progression to end-stage kidney disease in patients with previous CKD. Knowing these drugs' implications is crucial to avoid CKD progression and opportunely limit their use in certain patients.

Exposome and Metabolome Analysis of Sugarcane Workers Reveals Predictors of Kidney Injury

IntroductionSugarcane workers are exposed to potentially hazardous agrochemicals including pesticides, heavy metals, and silica. Such occupational exposures present health risks and have been implicated in a high rate of kidney disease seen in these workers. MethodsTo investigate potential biomarkers and mechanisms that could explain chronic kidney disease (CKD) among this worker population, paired urine samples were collected from sugarcane cutters at the beginning and end of a harvest season in Guatemala. Workers were then separated into two groups: those with or without kidney function decline (KFD) across the harvest season. Urine samples from these two groups underwent elemental analysis and untargeted metabolomics. ResultsUrine profiles demonstrated increases in silicon, certain pesticides, and phosphorus levels in all workers while heavy metals remained low. While the KFD group had a reduction in eGFR across the harvest season, kidney injury marker 1 (KIM-1) did not significantly change. Cross-harvest metabolomic analysis found trends of fatty acid accumulation, perturbed amino acid metabolism, presence of pesticides and other known signs of impaired kidney function. ConclusionSilica and certain pesticides were significantly elevated in the urine of sugarcane workers with or without KFD. Future work should determine whether long-term occupational exposure to silica and pesticides across multiple seasons contributes CKD in these workers. Overall, these results confirmed multiple exposures are occurring in sugarcane workers and may provide insight into early warning signs of kidney injury and may help explain the increased incidence of CKD among agricultural workers.