Identification of Periostin as a Critical Marker of Progression/Reversal of Hypertensive Nephropathy

Progression of chronic kidney disease (CKD) is a major health issue due to persistent accumulation of extracellular matrix in the injured kidney. However, our current understanding of fibrosis is limited, therapeutic options are lacking, and progressive degradation of renal function prevails in CKD patients. Uncovering novel therapeutic targets is therefore necessary

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Selective cyclooxygenase-2 inhibitor use and progression of renal function in patients with chronic kidney disease: a single-center retrospective cohort study

Wisit Kaewput,1,2 Preedee Disorn,2 Bancha Satirapoj2 1Department of Military and Community Medicine, Phramongkutklao College of Medicine, 2Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Background: The use of selective COX-2 (sCOX-2) inhibitors with acute kidney injury, salt water retention, and cardiovascular events have been correlated in subjects with normal kidney function, but sCOX-2 inhibitor use concerning the progression of chronic kidney disease (CKD) remains uncertain. Objectives: To determine the progression of renal function and electrolyte abnormalities among CKD patients after using sCOX-2 inhibitors during short- and long-term periods. Methods: The study employed a retrospective cohort design comprising all types of CKD patients with and without sCOX-2 inhibitors (celecoxib and etoricoxib). Data collected included medical data, estimated glomerular filtration rate (eGFR), and serum electrolytes at 3 and 6 months between January 2009 and January 2014. Subjects attended the outpatient clinic and were then followed up until discontinuation of the drugs at years 1 and 2 until May 2016. Results: Ninety-two CKD patients on sCOX-2 inhibitors and 92 CKD patients without sCOX-2 inhibitors were included. The sCOX-2 inhibitor group showed more decline in eGFR than the control group at 3 and 6 months of follow-up (&ndash;8.27&plusmn;9.75 vs &ndash;1.64&plusmn;6.05 mL/min/1.73 m2, P&lt;0.001 and &ndash;12.36&plusmn;6.48 vs &ndash;4.31&plusmn;5.11 mL/min/1.73 m2, P=0.001, respectively) and at 1 and 2 years of follow-up after subjects discontinued sCOX-2 (&ndash;6.84&plusmn;10.34 vs &ndash;1.61&plusmn;8.93 mL/min/1.73 m2, P=0.004 and &ndash;10.26&plusmn;10.19 vs &ndash;5.12&plusmn;8.61 mL/min/1.73 m2, P=0.005, respectively). In addition, the sCOX-2 inhibitor group had significantly more increased serum potassium during the study follow-up than the control group. Conclusion: The sCOX-2 inhibitors are associated with an increased risk for rapid eGFR decline and hyperkalemia in both the short term and in the long term after sCOX-2 inhibitors were terminated in the setting of a community-based CKD population. For CKD patients, these results suggest that sCOX-2 inhibitors should be closely monitored and chronic exposure to any sCOX-2 inhibitors should be avoided. Keywords: selective cyclooxygenase-2 inhibitor, long-term renal progression, chronic kidney diseas

Efficacy and safety of subcutaneous administration of lyophilized powder of alfa-erythropoietin to maintain hemoglobin concentrations among hemodialysis patients

Bancha Satirapoj, Rattanawan Dispan, Ouppatham Supasyndh Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Background: Anemia associated with chronic kidney disease (CKD) often requires treatment with recombinant human erythropoietin (EPO). This study investigated the therapeutic equivalence between lyophilized powder and standard liquid EPO alfa by subcutaneous (SC) administration in hemoglobin maintenance among patients on hemodialysis.Methods: This was a single-blinded, randomized, controlled, single-center, parallel-group study regarding the treatment of anemia among CKD patients on hemodialysis and being treated with stable doses of EPO alfa at least for 12 weeks. Anemic hemodialysis patients (n=63) received standard liquid or lyophilized powder EPO alfa for 24 weeks by SC administration. Achievement of the target hemoglobin concentration and safety and tolerability end points were documented.Results: Baseline mean hemoglobin level was 11.1&plusmn;0.7 g/dL using lyophilized powder EPO alfa and 11.2&plusmn;0.9 g/dL using standard liquid EPO alfa. The baseline median dose of EPO alfa was 126.4 (interquartile range [IQR] 81.6&ndash;163.6) U/kg/week in the lyophilized powder EPO alfa group and 116.9 (IQR 76.5&ndash;144.1) U/kg/week in the standard liquid EPO alfa group. Treatment with SC lyophilized powder EPO alfa maintained mean hemoglobin and hematocrit concentrations after switching from standard liquid EPO alfa. No statistical significance between groups was reported for hemoglobin concentrations and weekly dose of EPO alfa during the study. No safety concerns were raised, including positive anti-EPO antibodies.Conclusion: In this study of anemia therapy among patients with end-stage renal disease on hemodialysis therapy, the SC injection of lyophilized powder EPO alfa was well tolerated and effectively maintained hemoglobin levels. Future studies of larger size and longer duration will be required to assess safety profiles. Keywords: anemia, hemodialysis, lyophilized powder, erythropoietin, subcutaneous injectio

Performance of the estimated glomerular filtration rate creatinine and cystatin C based equations in Thai patients with chronic glomerulonephritis

Bancha Satirapoj, Ketkan Jirawatsiwaporn, Theerasak Tangwonglert, Panbubpa ChoovichianDivision of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, ThailandBackground: Glomerular filtration rate (GFR) is considered the indicator of overall kidney function, and therefore, its assessment has become an important clinical tool in the daily care of chronic glomerulonephritis (CGN) patients. Currently, practical guidelines recommend using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to assess GFR in CKD patients.Methods: A cross-sectional study was performed in CGN patients. Standard GFR was measured using 24-hour urine creatinine clearance. GFR was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease, CKD-EPI equation based creatinine, cystatin C, and combined creatinine and cystatin C. The performance of GFR estimation equations were examined using bias, precision and accuracy and agreement between standard GFR and estimated GFR by calculating Cohen&rsquo;s k.Results: A total of 125 patients (74 male, 59.2%) with mean age 56.1&plusmn;18.1 years were included. Mean standard GFR was 51.6&plusmn;32.2 mL/min per 1.73 m2. A significant correlation was found between standard GFR and all estimated GFRs (r=0.573 to 0.660, P&lt;0.001). CKD-EPI-creatinine-cystatin C equation had the smallest absolute bias and the significantly highest accuracy, although it was not significantly different from CKD-EPI-cystatin C equation (P=0.523). CKD-EPI-creatinine-cystatin C equation had the highest accuracy to classify CKD staging (Cohen&rsquo;s k=0.345), but it underestimated GFR in 32% and overestimated GFR in 18% of the CGN patients.Conclusion: CKD-EPI-creatinine-cystatin C equation estimated GFR with little bias, and the highest accuracy among CGN patients. This equation gave a better estimate of GFR than the equation based on serum creatinine.Keywords: serum cystatin C, CKD-EPI cystatin C, glomerulonephriti