Progression Of Kidney Disease In Patients Research Articles

Soluble Urokinase-Type Plasminogen Activator Receptor, Changes of 24-Hour Blood Pressure, and Progression of Chronic Kidney Disease.

BackgroundSoluble urokinase‐type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24‐hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear.Methods and ResultsA total of 751 patients with CKD stage 1 to 5 were recruited from CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center–High Risk) cohort study (2013–2018). The relationship of serum suPAR levels to 24‐hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2–2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m2 at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24‐hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27–6.76; P=0.01). During a follow‐up of 43.2 (interquartile range, 27.0–55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37–3.21; P=0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02–2.01; P=0.03) with every 1‐unit increase in serum suPAR levels.ConclusionsElevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.

Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial

SGLT2 inhibition decreases albuminuria and reduces the risk of kidney disease progression in patients with type 2 diabetes. These benefits are unlikely to be mediated by improvements in glycaemic control alone. Therefore, we aimed to examine the kidney effects of the SGLT2 inhibitor dapagliflozin in patients with proteinuric kidney disease without diabetes. DIAMOND was a randomised, double-blind, placebo-controlled crossover trial done at six hospitals in Canada, Malaysia, and the Netherlands. Eligible participants were adult patients (aged 18-75 years) with chronic kidney disease, without a diagnosis of diabetes, with a 24-h urinary protein excretion greater than 500 mg and less than or equal to 3500 mg and an estimated glomerular filtration rate (eGFR) of at least 25 mL/min per 1·73 m2, and who were on stable renin-angiotensin system blockade. Participants were randomly assigned (1:1) to receive placebo and then dapagliflozin 10 mg per day or vice versa. Each treatment period lasted 6 weeks with a 6-week washout period in between. Participants, investigators, and study personnel were masked to assignment throughout the trial and analysis. The primary outcome was percentage change from baseline in 24-h proteinuria during dapagliflozin treatment relative to placebo. Secondary outcomes were changes in measured GFR (mGFR; via iohexol clearance), bodyweight, blood pressure, and concentrations of neurohormonal biomarkers. Analyses were done in accordance with the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT03190694. Between Nov 22, 2017, and April 5, 2019, 58 patients were screened, of whom 53 (mean age 51 years [SD 13]; 32% women) were randomly assigned (27 received dapagliflozin then placebo and 26 received placebo then dapagliflozin). One patient discontinued during the first treatment period. All patients were included in the analysis. Mean baseline mGFR was 58·3 mL/min per 1·73 m2 (SD 23), median proteinuria was 1110 mg per 24 h (IQR 730-1560), and mean HbA1c was 5·6% (SD 0·4). The difference in mean proteinuria change from baseline between dapagliflozin and placebo was 0·9% (95% CI -16·6 to 22·1; p=0·93). Compared with placebo, mGFR was changed with dapagliflozin treatment by -6·6 mL/min per 1·73 m2 (-9·0 to -4·2; p<0·0001) at week 6. This reduction was fully reversible within 6 weeks after dapagliflozin discontinuation. Compared with placebo, bodyweight was reduced by 1·5 kg (0·03-3·0; p=0·046) with dapagliflozin; changes in systolic and diastolic blood pressure and concentrations of neurohormonal biomarkers did not differ significantly between dapagliflozin and placebo treatment. The numbers of patients who had one or more adverse events during dapagliflozin treatment (17 [32%] of 53) and during placebo treatment (13 [25%] of 52) were similar. No hypoglycaemic events were reported and no deaths occurred. 6-week treatment with dapagliflozin did not affect proteinuria in patients with chronic kidney disease without diabetes, but did induce an acute and reversible decline in mGFR and a reduction in bodyweight. Long-term clinical trials are underway to determine whether SGLT2 inhibitors can safely reduce the rate of major clinical kidney outcomes in patients with chronic kidney disease with and without diabetes. AstraZeneca.

Ambulatory blood pressure variability and risk of cardiovascular events, all-cause mortality, and progression of kidney disease.

Association between blood pressure (BP) variability and cardiovascular outcome remains unclear in patients with chronic kidney disease (CKD). We evaluated this association between ambulatory BP variability and cardiovascular events, mortality, and kidney disease progression in patients with CKD. From the Cardiovascular and Metabolic Disease Etiology Research Center-HIgh Risk study (2013-2018), a total of 470 patients with CKD were analyzed. Ambulatory BP variability was assessed using average real variability (ARV). Primary outcome was composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. The secondary outcome was rapid kidney function decline [estimated glomerular filtration rate (eGFR), >3 ml/min per 1.73m per year]. During a median follow-up of 51.8 (40.5-56.2) months, the incidences of all-cause death and composite outcomes were higher in the high SBP-ARV group than in the low SBP-ARV group. The Kaplan-Meier analysis showed that a high SBP-ARV, but not a high DBP-ARV and heart rate-ARV, was associated with higher composite outcome risks. In multivariable Cox analysis, a high SBP-ARV correlated with increased composite outcome risks (hazard ratio, 4.53; 95% confidence interval, 1.41-14.58). When subgroup analysis was performed (low vs. high 24-h SBP), this association was only significant in the high 24-h SBP group. The risk stratification for composite outcomes by adding SBP-ARV into the basic model and 24-h SBP, improved by 1.3%. Furthermore, the mean eGFR decline rate was faster, and the rapid eGFR decline risk was 1.68-fold higher in the high SBP-ARV group. Greater ambulatory SBP variabilities were associated with increased risks for nonfatal cardiovascular diseases, all-cause mortality, and rapid kidney function decline in patients with CKD.

Short-Term Systolic Blood Pressure Variability and Kidney Disease Progression in Patients With Chronic Kidney Disease: Results From C-STRIDE.

BackgroundIt is unclear whether short‐term blood pressure variability is associated with renal outcomes in patients with chronic kidney disease.Methods and ResultsThis study analyzed data from participants in the C‐STRIDE (Chinese Cohort Study of Chronic Kidney Disease) who had chronic kidney disease stages 1 to 4. Short‐term blood pressure variability was measured by calculating the weighted SD (w‐SD) of systolic blood pressure (SBP). Renal outcomes were defined as dialysis initiation and/or transplantation. Risk factors associated with w‐SD of SBP were evaluated by linear regression. Associations of short‐term SBP variability with renal outcomes were evaluated by Cox regression. In total, 1421 patients with chronic kidney disease were included in this study (mean age, 49.4±13.6 years; 56.2% men; estimated glomerular filtration rate, 50.5±29.3 mL/min per 1.73 m2; proteinuria, 0.9 [0.3–2.0] g/d). Mean w‐SD of SBP was 12.6±4.4 mm Hg. w‐SD of SBP was independently associated with older age, 24‐hour SBP, blood pressure circadian pattern, and angiotensin II receptor blocker treatment. During a median follow‐up of 4.9 years, 237 patients developed renal outcomes (37.01 per 1000 patient‐years). The incidence rate increased across the quartiles of w‐SD (log‐rank P=0.005). w‐SD of SBP was associated with an increased risk of renal outcomes, both as a continuous variable (hazard ratio [HR], 1.47; 95% CI, 1.09–1.99) and as a categorical variable (quartile 4 versus quartile 1: HR, 1.60; 95% CI, 1.08–2.36), independent of 24‐hour SBP, daytime SBP, and nighttime SBP.ConclusionsShort‐term SBP was independently associated with the risk of dialysis initiation and/or transplantation in patients with chronic kidney disease.

P0416BODY MASS INDEX IS NOT ASSOCIATED WITH ADVERSE RENAL EVENTS IN BIOPSY-PROVEN PRIMARY GLOMERULONEPHRITIDES

Abstract Background and Aims Obesity is a strong risk factor for the development of chronic kidney disease (CKD) through its close association with hypertension and diabetes. As metabolic demands increase with higher body mass indices, a compensatory glomerular hyperfiltration occurs to meet the increasing burden, consequently increasing intraglomerular pressure that can lead to the development of CKD and may influence the progression of already established kidney damage. The aim of our study was to determine whether there was an association between body mass index (BMI) and kidney disease progression in patients with primary glomerulonephritides (GN). Method We performed a single-centre retrospective cohort study in patients with biopsy-proven primary glomerular disease [minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and IgA nephropathy (IgAN)] diagnosed between July 1998 and December 2018. We excluded patients with no available data on weight at presentation or height, and those lost to follow-up. Patients were stratified into three groups according to BMI to &amp;lt;25 kg/m2, between 25-30 kg/m2 and &amp;gt;30 kg/m2. Baseline characteristics were compared between the groups, serum creatinine, proteinuria and microscopic hematuria were recorded at presentation, and yearly afterwards until the end of follow-up. We compared among BMI groups the mean yearly change in eGFR, and yearly increase in proteinuria. Renal adverse outcomes were: time to doubling serum creatinine and initiation of renal replacement therapy (RRT). We performed a multivariate survival analysis to evaluate the risk factors associated with a renal composite outcome that included doubling serum creatinine and initiation of RRT. Results We included 178 patients that presented with a biopsy-proven primary glomerular disease (18 patients with MCD, 38 had FSGS, 38 MN and 84 IgAN), with a mean age of 50.6±18.0 years, 71.3% were males, mean BMI of 28.2±5.4 kg/m2. There were no differences in age at presentation, sex or BMI between the four groups of GN. 24.2% of patients had BMI &amp;lt;25 kg/m2 (Non-obese group), 43.8% had a BMI between 25-30 kg/m2 (Overweight group) and 32% had BMI &amp;gt;30 kg/m2 (obese group). Non-obese group had lower baseline systolic and diastolic blood pressure than the overweight group (p=0.021 and p=0.015) and the obese group (p=0.001 and p&amp;lt;0.001), but there were no differences in blood pressure between the latter two groups. Patients in the non-obese group were younger (p=0.001) than in the other two groups. There were no differences in baseline serum creatinine (p=0.60), proteinuria (p=0.98) or microscopic hematuria (p=0.46) across the three BMI groups. Survival analysis revealed no relation between BMI and the renal composite outcome (log-rank=2.18, p=0.337) or death (log-rank=0.117, p=0.943). Multivariate survival analysis revealed that the risk factors associated with the renal composite outcome were baseline creatinine (χ2=6.61, p=0.010) and urine albumin-creatinine ratio (χ2=6.48, p=0.011), but there was no association with BMI (p=0.427). Conclusion BMI at presentation was associated with higher blood pressure, but not with baseline serum creatinine or proteinuria, and was not associated with an increased risk of progression of kidney disease in primary glomerular diseases.

1120-P: Association between the Inflammatory Marker GDF-15 and Kidney Disease Progression: Results from the CANVAS Trial

Introduction: Growth differentiation factor 15 (GDF-15) is a marker of inflammation and cellular injury. Small clinical studies have suggested that SGLT2 inhibitors exert anti-inflammatory effects. We examined the association of baseline GDF-15 with kidney outcomes in patients with type 2 diabetes mellitus (T2DM) participating in the CANagliflozin cardioVascular Assessment Study (CANVAS) study. We also assessed the effect of the SGLT2 inhibitor canagliflozin (CANA) on GDF-15. Methods: The CANVAS trial randomized 4330 people with T2DM at high cardiovascular risk to CANA or placebo. Plasma GDF-15 concentration was measured with GDF-15 Roche Elecsys assay at baseline and follow-up. The association between GDF-15 and the primary kidney outcome (40% eGFR decline, end-stage kidney disease, or renal death) was assessed using multivariable adjusted Cox regression. Linear mixed effects models were used to assess the effect of CANA versus placebo on GDF-15 levels. Results: We included 3557 CANVAS participants with available plasma samples (mean age 62.8 years, 33.1% female, mean eGFR 76.9 ml/min/1.73 m2, median uACR 11.6 mg/g, median GDF-15 1776.0 pg/ml). During a mean follow-up of 5.7 years, 137 kidney outcomes occurred. Higher GDF-15 levels were independently associated with higher risk of kidney events (HR 1.98 [95% CI 1.40 to 2.81] per log increment GDF-15). Treatment with CANA modestly lowered GDF-15 compared to placebo (-2% [95% CI -5 to 0; p=0.046]). The effect of CANA on the kidney outcome (HR 0.56, 95% CI 0.40-0.79) was consistent regardless of baseline GDF-15 levels (p-interaction=0.75). GDF-15 did however not mediate the renal protective effect of CANA (percent mediation 3.9% [95% CI -3.6 to 14.0]). Conclusion: CANA modestly lowers GDF-15, which is independently associated with a higher risk of kidney disease progression in patients with T2DM at high cardiovascular risk. The modest reduction in GDF-15 with CANA did not mediate the renal protective effect of CANA. Disclosure J. Li: Employee; Self; George Institute. T. Sen: None. B. Neal: Research Support; Self; Janssen Research &amp; Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. B.L. Neuen: Research Support; Self; Australian National Health and Medical Research Council Postgraduate Scholarship, Oxford Australia Clarendon Scholarship from the University of Oxford, University Postgraduate Award from UNSW Sydney. Other Relationship; Self; Janssen Research &amp; Development, LLC. V. Perkovic: Other Relationship; Self; See Other Relationship field. D. de Zeeuw: Advisory Panel; Self; AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson &amp; Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. Y. Yavin: Employee; Self; Janssen Research &amp; Development, LLC. N. Rosenthal: None. M.K. Hansen: Employee; Self; Janssen Research &amp; Development, LLC. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. Funding Janssen Research &amp; Development, LLC

Multi-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and initial patient results.

Background:Autosomal recessive polycystic kidney disease (ARPKD) is a rare but potentially lethal genetic disorder typically characterized by diffuse renal microcysts. Clinical trials for patients with ARPKD are not currently possible due to the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy.Methods:In this study, animal and human MRI scanners were used to obtain quantitative kidney T1 and T2 relaxation time maps for both excised kidneys from bpk and wild type (WT) mice as well as for a pediatric patient with ARPKD and a healthy adult volunteer.Results:Mean kidney T1 and T2 relaxation times showed significant increases with age (p<0.05) as well as significant increases in comparison to WT mice (p<2 × 10−10). Significant or nearly significant linear correlations were observed for mean kidney T1 (p=0.030) and T2 (p=0.054) as a function of total kidney volume, respectively. Initial MRF assessments in a patient with ARPKD showed visible increases in both kidney T1 and T2 in comparison to the healthy volunteer.Conclusions:These preclinical and initial clinical MRI studies suggest that renal T1 and T2 relaxometry may provide an additional outcome measure to assess cystic kidney disease progression in patients with ARPKD.

Association between anemia and renal prognosis in autosomal dominant polycystic kidney disease: a retrospective study.

Though anemia is a sign of poor renal prognosis in chronic kidney disease (CKD), hemoglobin (Hb) levels are typically higher in autosomal dominant polycystic kidney disease (ADPKD) than in other kidney diseases, and anemia has not been examined as a potential prognosticator. Thus, we investigated anemia as a factor for renal prognosis in ADPKD. In total, 115 non-dialysis patients, 48 men and 67 women, with ADPKD were evaluated. The renal outcome of a 50% reduction in the estimated glomerular filtration rate or renal replacement therapy was examined using the Cox regression analysis and Kaplan-Meier analysis. Patients were followed for a median of 5.5years and 50 patients had reached the end point. The mean age of the patients at the first visit was 45.9 ± 13.3years. The overall mean Hb was 12.90 ± 1.85g/dL, and the mean Hb in men and women was 13.82 ± 1.72g/dL and 12.25 ± 1.65g/dL, respectively. Hb levels and uric protein content were statistically significant factors for poor renal prognosis, while hypertension and genetic mutations failed to reach significance. Furthermore, statistical significance was found in men with Hb < 12g/dL and in women with Hb < 11g/dL. Anemia had significant association with kidney disease progression in patients with ADPKD. We found that anemia might be a factor for poor renal prognosis in ADPKD. Furthermore, a sex difference was found, wherein men with Hb < 12g/dL and women with Hb < 11g/dL were at risk of renal disease progression.

Chronic kidney disease progression in patients with resistant hypertension subject to 2 therapeutic strategies: Intensification with loop diuretics vs aldosterone antagonists

IntroductionActually, there are few data about glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how different therapies can modify chronic kidney disease progression (CKD). ObjectiveTo evaluate CKD progression in patients with resistant hypertension undergoing two different therapies: treatment with spironolactone or furosemide. MethodsWe included 30 patients (21M, 9W) with a mean age of 66.3±9.1 years, eGFR 55.8±16.5ml/min/1.73m², SBP 162.8±8.2 and DBP 90.2±6.2mmHg: 15 patients received spironolactone and 15 furosemide and we followed up them a median of 32 months (28–41). ResultsThe mean annual eGFR decrease was −2.8±5.4ml / min / 1.73m². In spironolactone group was −2.1±4.8ml / min / 1.73m² and in furosemide group was −3.2±5.6ml / min / 1.73m², p<0.01. In patients received spironolactone, SBP decreased 23±9mmHg and in furosemide group decreased 16±3mmHg, p<0, 01. DBP decreased 10±8mmHg and 6±2mmHg, respectively (p<0.01). Treatment with spironolactone reduced albuminuria from a serum albumin/creatine ratio of 210 (121–385) mg / g to 65 (45–120) mg/ g at the end of follow-up, p<0.01. There were no significant changes in the albumin / creatinine ratio in the furosemide group. The slower drop in kidney function was associated with lower SBP (p=0.04), higher GFR (p=0.01), lower albuminuria (p=0.01), not diabetes mellitus (p=0, 01) and treatment with spironolactone (p=0.02). Treatment with spironolactone (OR 2.13 IC 1.89–2.29) and lower albuminuria (OR 0.98 CI 0.97–0.99) maintain their independent predictive power in a multivariate model. ConclusionTreatment with spironolactone is more effective reducing BP and albuminuria in patients with resistant hypertension compared with furosemide and it is associated with a slower progression of CKD in the long term follow up.

Ultrastructural changes of platelets in patients with diabetes mellitus type 1 and 2 depending on the state of renal function at different stages of chronic renal failure

The aim of our study was to study the ultrastructural changes of platelets in patients with diabetes mellitus type 1 (T1DM) and type 2 (T2DM) depending on estimated glomerular filtration rate (eGFR) and to assess the possibility of their use as an early marker of diabetic kidney disease progression.Materials and methods. The study included 37 people: 15 patients with T1DM, 15 with T2DM, 7 healthy volunteers. Patients were divided into three groups depending on eGFR: group 1 – eGFR ≥90 ml/min/1.73 m²; group 2 – eGFR 89–60 ml/min/1.73 m²; group 3 – eGFR 59–45 ml/min/1.73 m². Transmission electron microscope PEM-100-01 “SELMI” (Ukraine) was used to determine the ultrastructural changes of platelets.Results. We studied ultrastructural changes of platelets in patients with T1DM and T2DM depending on eGFR and determined the changes in platelet hemostasis in patients with eGFR ≥90 ml/min/1.73 m². We proved that the higher damage degree of kidneys filtration function leads to the worse platelets membrane structures damage, increased number of platelet hyperactivation signs, higher proportion of irreversibly transformed cells.Conclusion. Morphological substrate of platelet hemostasis damage in patients with T1DM and T2DM is increased destabilization of the platelet membranes, massive agglutination with a predominance of various sizes condensed aggregates, the involvement of irreversibly deformed erythrocytes and activated leukocytes in their composition, imbalance of density packing of alpha-, delta-, and lambda- granules. This ultrastructural complex can be considered as an early marker of diabetic kidney disease progression in patients with T1DM and T2DM.

Prevention of chronic kidney disease progression in patients with acute decompensation of chronic heart failure

Aim.To assess the efficiency of the program of prevention of chronic kidney disease (CKD) progression in patients with acute decompensation of chronic heart failure (CHF). The program included the use of nitrendipine, a calcium channel antagonist, and the replacement of single intravenous bolus dosing of furosemide with a prolonged intravenous infusion in the early stage of the disease.Material and methods.One hundred twenty five patients with decompensation of CHF were examined and divided into 2 groups. Group 1 received standard therapy. In the group 2, an additional prevention program was carried out. The criterion of CKD progression was the change in glomerular filtration rate (GFR) in accordance with the KDIGO guidelines (2012). GFR was calculated by two methods: serum creatinine and cystatin C levels. The parameters were monitored and compared with baseline levels at admission to the hospital and on the 10th day of therapy. For the initial level was taken the patient’s GFR, calculated by the serum creatinine level prior to the present hospitalization on the background of a satisfactory condition.Results.At admission to the hospital, in group 1 CKD progression was established in 33,3% of patients, in group 2 — in 29,3%. On the 10th day, CKD progression was noted in 47,4% of patients in group 1, in group 2 — in 23,4%.Conclusion.The prevention program allows to reduce the number of cases of CKD progression in patients with decompensation of CHF by 2 times.

Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3\u20135 chronic kidney disease: a prospective observational study

BackgroundBlood urea nitrogen (BUN) is one of the substances that affects the calculated serum osmolality (cSosm). A previous study demonstrated that BUN and cSosm were independently associated with the development of chronic kidney disease (CKD) in patients with preserved kidney function. In advanced CKD stages, there is a concomitant increase in cSosm and BUN levels. However, it remains unclear whether BUN or cSosm levels are related to renal outcomes in patients with moderate to severe kidney dysfunction. The aim of this study was to clarify whether the BUN or cSosm level is associated with kidney disease progression in patients with advanced CKD.MethodsIn this prospective study, we enrolled 459 patients with CKD (stages 3–5). The composite renal endpoint was end-stage renal disease (ESRD) or death, and ESRD alone was added as an alternative outcome. A Cox proportional hazards model was utilized to determine the risk factors for a poor renal outcome. We adjusted for covariates including estimated glomerular filtration rate (eGFR). The cSosm (mOsm/kg) was calculated using the following formula: (2 × sodium) + (BUN/2.8) + (glucose/18).ResultsDuring a median follow-up of 25.8 months, the renal endpoint was observed in 210 patients. Multivariable Cox analysis determined the hazard ratio (HR) [95% confidence interval (CI)] for the composite renal outcome in the second, third, and fourth BUN quartiles were 1.36 (0.72–2.58), 1.87 (0.95–3.66), and 2.66 (1.23–5.76) (P for trend < 0.01), respectively compared with the first BUN quartile. Conversely, by multivariable Cox analysis, the HRs (95% CIs) for poor outcomes in the second, third, and fourth cSosm quartiles, compared with the first cSosm quartile, were 1.13 (0.69–1.87), 0.95 (0.58–1.55), and 1.26 (0.78–2.03), respectively (P for trend = 0.39). In addition, with regard to the renal outcome of ESRD alone, higher BUN quartiles had a significantly increased risk for the outcome, but cSosm levels were not associated with the outcome.ConclusionsHigher BUN levels, but not cSosm levels, were associated with adverse renal outcomes independent of the eGFR, suggesting that BUN may be a useful marker for predicting kidney disease progression.

Sodium-glucose cotransporter inhibitors: beyond glycaemic control.

Diabetes increases the risk of adverse cardiovascular and renal events. Recently, sodium–glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated to reduce cardiovascular complications and slow diabetic kidney disease progression in patients with type 2 diabetes. The glycaemic control exerted by these drugs is not greater than the one achieved with other classical glucose-lowering medications such as sulphonylureas. For that reason, plausible renoprotective mechanisms independent from glycaemic control have been proposed such as blood pressure control, body weight loss, intraglomerular pressure reduction and a decrease in urinary proximal tubular injury biomarkers. Interestingly, the hypothesis that SGLT2 inhibitors have a direct renoprotective effect has been addressed in diabetic and non-diabetic models. In this editorial, we update the different postulated mechanisms involved in the cardiorenal protection afforded by SGLT2 inhibition in chronic kidney disease.

High neutrophil/lymphocyte ratio is associated with poor renal outcomes in Japanese patients with chronic kidney disease

Background: Several studies have shown that the neutrophil/lymphocyte ratio (NLR) is a marker that reflects the state of systemic inflammation. A high NLR was reported to be associated with cardiovascular events and mortality. However, little is known about the association between NLR and kidney disease progression in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to determine whether NLR is associated with renal outcomes in CKD patients.Methods: This prospective observational study included 350 consecutive patients with stage 1–4 CKD treated between June 2009 and November 2016. Data were collected until June 2017. The endpoint was the composite of end-stage renal disease requiring dialysis or death. Subjects were divided into two groups according to high and low NLR levels. A Cox proportional hazards model was used to determine the risk factors for composite outcomes.Results: The composite endpoint was observed in 83 patients during the median follow-up period of 31.8 months: 29 in the low NLR group and 54 in the high NLR group. Multivariable analysis showed that the high NLR group had a significant increase in the hazard ratio (HR) for composite outcomes (HR 1.67, 95% confidence interval 1.02–2.77) compared with the low NLR group.Conclusion: The present study demonstrated that a high NLR was associated with poor renal outcomes, suggesting that NLR may be a useful marker for prognostic prediction in patients with CKD.

Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment.

In clinical trials involving patients with preserved renal function, tenofovir disoproxil fumarate (TDF) use was associated with mild renal impairment in 1% of patients. To compare serial renal function of entecavir (ETV)-treated, TDF-treated, and untreated patients with chronic hepatitis B. We studied the risk of chronic kidney disease (CKD) progression in a territory-wide cohort of patients with chronic hepatitis B without treatment and of those on ETV or TDF treatment. Estimated glomerular filtration rate (eGFR) was determined by the CKD Epidemiology Collaboration equationand was classified into five CKD stages. CKD progression, defined as an increase of at least one CKD stage, was compared among treated and untreated patients. After propensity score matching, 2254 ETV-treated, 2254 TDF-treated, and 2254 untreated patients were included in the analysis. Their mean baseline eGFR was 90.3±19.6, 91.3±20.6, and 92.2±20.0mL/min/1.73m2 , respectively. During a mean follow-up of 2.4±1.5years, 639 ETV-treated, 706 TDF-treated, and 564 untreated patients exhibited CKD progression ≥1 stage. The 5-year cumulative incidence (95% confidence interval) of CKD progression was 43% (40%-46%) in ETV-treated, 48% (45%-51%) in TDF-treated, and 43% (39%-47%) in untreated patients (reference group), respectively (P=0.267 and <0.001, respectively). The number of patients who exhibited CKD progression ≥2 stages was 92 (4.1%) in the untreated cohort, 95 (4.2%) in the ETV-treated cohort, and 51 (2.3%) in the TDF-treated cohort. The use of TDF was associated with mild renal impairment in a minority of patients; those treated with ETV had a similar risk compared to untreated patients.

The pregnancy outcomes in patients with stage 3\u20134 chronic kidney disease and the effects of pregnancy in the long-term kidney function

ObjectiveTo investigate the pregnancy outcomes for patients with stage 3–4 chronic kidney disease (CKD) and the effects of pregnancy on kidney function.MethodsClinical data of pregnant women with CKD in the Peking University First Hospital between January 1st 2005 and October 1st 2016 were retrospectively analysed. The pregnancy outcomes of patients with different stages of CKD were compared. Patients with stage 3–4 CKD were followed up by telephone interview, and non-pregnant patients with stage 3–4 CKD were selected using the propensity score method to analyse the effects of pregnancy on kidney function.ResultsA total of 293 women with 300 pregnancies met the study criteria. There were 30 cases of stage 3–4 CKD. The incidence of adverse pregnancy outcomes of patients with stage 3–4 CKD was significantly higher than that with stage 1 CKD. The mean postpartum follow-up time of pregnant patients with CKD was 49.0 ± 33.1 months. A total of 26 cases of stage 3–4 CKD were followed up. During the follow-up period, 8 patients progressed to ESRD. A total of 28 non-pregnant patients with stage 3–4 CKD were selected as the control group. The results of multivariate analysis revealed that pregnancy did not increase the risk of deterioration of kidney function.ConclusionPatients with stage 3–4 CKD in early pregnancy had a significantly increased risk of adverse pregnancy outcomes. Pregnancy itself did not seem to accelerate kidney disease progression in patients with stage 3–4 CKD.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery

ObjectiveThe study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. MethodsRisks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. ResultsAcute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. ConclusionsThe degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease.

Different Relevance of Peripheral, Central or Nighttime Blood Pressure Measurements in the Prediction of Chronic Kidney Disease Progression in Patients with Mild or No-Proteinuria

Background/Aims: Arterial hypertension is one of the leading factors aggravating the course of chronic kidney disease (CKD). It seems that the novel parameters used in the assessment of the blood pressure (BP) load (i.e. central blood pressure, nighttime blood pressure) may be more precise in predicting the cardiovascular risk and the progression of CKD in comparison with the traditional peripheral blood pressure measurements in the office conditions. The aim of the study was to assess the impact of the central, or nighttime blood pressure on the progression of CKD in patients with mild or no-proteinuria (autosomal, dominant polycystic kidney disease or IgA nephropathy). Methods: In each of the enrolled 46 patients with CKD stage 3 or 4, serum creatinine concentration was assessed, eGFR (MDRD) was calculated, also central blood pressure and pulse wave velocity (PWV) was assessed and the 24-hour ambulatory blood pressure monitoring (ABPM) was conducted at the beginning of the study and then repeated after one-year observation period. Results: During the observation period mean eGFR decreased from 44.1 (33.2-50.6) mL/min to 36.7 (29.7-46.3) mL/min. No significant differences were observed in the peripheral blood pressure or central blood pressure parameters. After one-year observation period the values of diastolic blood pressure dipping during the night significantly decreased from 16 (13-19) mmHg to 12 (10-15) mmHg; p< 0.05. The values of systolic dipping during the night or the mean BP values recorded in ABPM did not change significantly. Additionally, no significant differences in the PWV values were found. In the multivariate regression model the change of serum creatinine concentration was explained by the initial diastolic dipping values. Conclusion: 1. In patients with CKD stages 3 or 4 and mild or no- proteinuria, peripheral and central blood pressure did not change significantly during a one-year observation period despite the significant decline of eGFR and seems not to participate in the CKD progression. 2. Reduced magnitude of the diastolic dipping, which reflects the increase of diastolic blood pressure load during the nighttime, may play an important role in the pathogenesis of deterioration of kidney function in these patients.

Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass

Background and objectivesHyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass. Design, setting, participants, & measurementsRetrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36–98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed. ResultsOne hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall −1.6ml/min/1.73m2/year (−3.0, −0.7)). Male gender, albuminuria>100mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p=0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06–2.63), p=0.023; 1.02 (1.01–1.03), p=0.001 and HR: 2.14 (1.26–3.64), p=0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p=0.006). ConclusionsHyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass.

Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass

Background and objectivesHyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass. Design, setting, participants, & measurementsRetrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36–98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed. ResultsOne hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall −1.6ml/min/1.73m2/year (−3.0, −0.7)). Male gender, albuminuria>100mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p=0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06–2.63), p=0.023; 1.02 (1.01–1.03), p=0.001 and HR: 2.14 (1.26–3.64), p=0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p=0.006). ConclusionsHyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass.