Taipei, Taoyuan, and Taichung, Taiwan

Beneficial Effect of Amiloride on Progression of Chronic Kidney Disease

Please refer to the protocol

A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants With Chronic Kidney Disease and High Proteinuria

This is a Phase II, multicentre, randomised, double-blind, active-controlled, 2-arm parallel group study to evaluate the efficacy, safety, and tolerability of zibotentan and dapagliflozin in FDC compared to dapagliflozin alone, given QD on top of SoC, in adult participants with CKD and high proteinuria, with or without T2DM. Participants who are not already on SGLT2i at screening will receive a 28 day run in intervention with SGLT2i (dapagliflozin) QD. All participants will undergo a 12-week double-blind period. At the end of the treatment visit, participants will discontinue the blinded study intervention and begin open-label dapagliflozin monotherapy until the conclusion of the 4-week safety follow-up period. The results of this study will provide clinical data on efficacy and safety of an innovation treatment in the new region (the Russian Federation), which will be an important additional data source for Zibotentan/Dapagliflozin FDC approval process in the Eurasian Economic Union.

Proteinuria and Renal Perfusion in Renal Transplant Recipients

Renal transplantation is the treatment of choice for patients with end-stage kidney disease. Although renal transplantation is associated with reduced morbidity and mortality compared to chronic dialysis, cardiovascular disease remains one of the major cause of mortality in this population, with the rate of cardiac death 10-times higher than that of the general population. Proteinuria is not only considered as a diagnostic marker of renal disease in both native as well as the transplanted kidney, but also is widely described as an independent risk factor for cardiovascular morbidity and mortality in general population. Analogous to its impact in the general population, an independent association between post-transplant proteinuria and cardiovascular risk has been previously reported. The prevalence of proteinuria in renal transplant recipients is reported between 10% and 45%. Fernandez-Fresnedo et al. demonstrated that persistent proteinuria doubles the risk of cardiovascular disease and all-cause mortality in renal transplant recipients. Diseased native kidneys with residual urine output or the transplanted kidney could be the source of proteinuria following renal transplantation. A clear differentiation of the source of proteinuria (native kidneys versus allograft) is important for appropriate management. Proteinuria from native kidneys falls rapidly after renal transplantation, and persistent or worsening proteinuria is usually indicative of allograft pathology. The mechanisms behind the resolution of proteinuria of native kidney origin in the early post-transplant period are not well described. CNI-induced renal vasoconstriction causing reduction in urine output from the native kidneys may be an explanation for the early resolution of native kidney proteinuria. However, the resolution of proteinuria of native kidney origin post-transplant have been reported in the pre-cyclosporine era. An association between vascular parameters of the macrocirculation and post-transplant proteinuria has been described. High-grade post-transplant proteinuria has been found to be associated with higher pulse wave velocity, which is a marker of arterial stiffness of large arteries. Up to our knowledge no data is available describing a link between post-transplant proteinuria and vascular parameters of the microcirculation. In this study our goal is to analyze in a clinical trial in patients with end stage renal disease and residual urine output the relationship between proteinuria and renal perfusion of native kidneys before and after renal transplantation. In addition the investigators analyse if pre- or post-transplant proteinuria is associated with vascular and circulatory changes in the retinal circulation. This study is a single-centre clinical study with 25 pre-kidney transplant patients of our living donor kidney transplantation program. This is an exploratory and non-confirmatory study, in which the investigators analyse renal perfusion of native kidneys in patients with end stage renal disease before and after kidney transplantation. Our hypothesis is that renal perfusion of native kidneys correlates with early post-transplant proteinuria. Moreover the investigators hypothesize that post-transplant proteinuria is associated with vascular remodeling processes of the microcirculation 2 and 4-12 months after transplantation.

Proteinuria in Renal Transplant Patients Treated with Dapagliflozin

Recent years have seen the emergence of sodium-glucose co-transporter type 2 (SGLT2) inhibitors, also known as gliflozins, which represent a real therapeutic innovation in the management of type 2 diabetes, heart failure and chronic kidney disease. The prevalence of chronic kidney disease is rising steadily and represents a major public health challenge. Hypertension and proteinuria are two factors strongly associated with the progression of chronic kidney disease (CKD) and the high risk of cardiovascular complications. Achieving blood pressure control and reducing proteinuria is therefore a major objective in the management of chronic renal failure. Until recently, inhibitors of the renin-angiotensin-aldosterone system were the only therapeutic class known to have both anti-proteinuric and anti-hypertensive action, reducing the risk of progression to end-stage renal disease. Several large international studies, initially investigating the efficacy of SGLT2 inhibitors as anti-diabetic therapy, reported that this new therapeutic class reduced the risk of cardiovascular complications and end-stage renal disease. This nephroprotective and cardioprotective effect was independent of the anti-diabetic effect of the drug. The nephroprotective effect is explained in particular by a decrease in proteinuria via a reduction in glomerular hyperfiltration, and a reduction in intraglomerular pressure via vasoconstriction of the afferent artery in response to the blockade of glucose and sodium reabsorption in the proximal convoluted tubule. An international study (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease study) was specifically designed to investigate the nephroprotective effect of dapagliflozin in both diabetic and non-diabetic proteinuric CKD patients. This study, which included 4,300 patients with glomerular filtration rate (GFR) between 25 and 75ml/min/1.73m2 and an albuminuria/creatinuria ratio between 200 and 5,000mg/g, confirmed a significant reduction in proteinuria, a lower risk of progression to end-stage CKD and a lower mortality rate in patients treated with dapagliflozin compared with those who received placebo. Following this study, Dapagliflozin was granted marketing authorization in France in October 2021 for any patient with chronic kidney disease, in patients with a GFR between 25 and 75ml/min/1.73m2 and an albuminuria/creatinuria ratio between 200 and 5000mg/g despite treatment with converting enzyme inhibitor/Angiotensin II receptor antagonists for at least 4 weeks. Renal transplantation is not a contraindication to the use of dapagliflozin, so renal transplant patients meeting these same criteria may receive dapagliflozin as nephroprotective therapy. However, few data are currently available on the evolution of proteinuria and GFR in this population. After renal transplantation, proteinuria is also a major factor associated with impaired graft function and cardiovascular risk. However, transplant patients have specific characteristics compared with non-transplant CKD patients: by definition, they have a single functional kidney and receive immunosuppressive treatments that modify renal hemodynamics, including calcineurin inhibitors, drugs that also have a vasoconstrictive effect. In addition, a moderate increase in the risk of urinary tract infection and genital mycotic infection has been reported with the use of gliflozins, necessitating careful monitoring of the incidence of these side effects in this population. The investigators have been progressively introducing the use of dapagliflozin as a nephroprotective treatment in transplant patients meeting marketing authorisation criteria (chronic renal failure with GFR between 25-75ml/min/1.73m2, albuminuria/creatinuria ratio 200-5000mg/g despite treatment with converting enzyme inhibitors and Angiotensin II receptor antagonists for at least 4 weeks) within the nephrology department of Montpellier University Hospital for several months. To date, more than 30 transplant patients have been treated with dapagliflozin (of whom 12 treated patients have usable data and may be included retrospectively in this study). In this recent experience, a very good safety profile was observed and no drug interactions were identified. Although a reduction in early proteinuria was observed, the follow-up of these patients is not yet long enough to carry out a preliminary analysis. The investigators intend to conduct an observational study with the primary objective of studying the evolution of proteinuria in kidney transplant patients treated with dapagliflozin according to marketing authorization criteria. The secondary objectives of the study are to investigate other expected benefits, including effects on renal function and metabolic effects, as well as potential side-effects of this treatment in this population.

Phase IIb Clinical Trial for the Efficacy and Safety by CU01-1001 for 24 Weeks in Type 2 DM Patients With Albuminuria

The Effect of Blood on the PC Ratio During Pregnancy

The Purpose of the Research: The purpose of this study is to examine the effect of blood on the protein to creatine (PC) ratio in pregnant patients. The Scientific or Scholarly Rationale: The PC ratio is used to diagnosis proteinuria in pregnancy. It is thought that blood in the urine will cause the PC ratio to be elevated but there are no current studies to prove this hypothesis. The Procedures to be Performed: Upon presentation to the Labor and Delivery Triage or the Antepartum Unit, patients will be enrolled in the study. Urine collection that is not needed for medical workup will be collected and saved, and an extra 8 mLs of blood will be drawn during routine lab collection by phlebotomy team. Additional lab costs will be covered by Marshall Obstetrics & Gynecology. Lab protocol: Divide urine into 4 different specimen cups with 20 mLs of urine each to measure urinalysis (UA) and PC ratio: 1. UA and PC ratio on original sample 2. UA and PC ratio with 1 mL of whole blood added 3. UA and PC ratio with 2 mL of whole blood added 4. UA and PC ratio with 5 mL of whole blood added Subjects medical records will be reviewed for past obstetrical history after consent to be in the study. The Risks and Potential Benefits of the Research: Risks: 8 mLs of additional maternal blood will be drawn for study purposes. Possible risks could include pain, bleeding, fainting, bruising, infection, or hematoma (blood clot under the skin) at the injection site. Please note that routine blood would be drawn regardless of study enrollment. Benefits: Our hypothesis is that the PC ratio will be elevated by contamination with blood. It is unknown if this hypothesis is correct. Complete Inclusion/Exclusion Criteria (may be submitted separately if extensive): Inclusion criteria includes patients presenting to Labor and Delivery Triage or Antepartum Unit at Cabell Huntington Hospital between the ages of 18 and approximately 45 years and gestational age of >20 weeks. Exclusion criteria includes pre-existing proteinuria (excess protein in the urine) or hematuria (blood in the urine).

Effect of Sodium Glucose co Transporter 2 Inhibitor ( SGLT2) on Proteinuria in Diabetic Patients

Diabetic nephropathy involves progressive stages including glomerular hyperfilteration , microalbuminuria , overt proteinuria and a decline in glomerular filteration rate leading to end stage renal disease. Despite all the available interventions available for diabetic patients including tight glycemic control , and blood pressure control , using angiotensin converting enzyme inhibitors, angiotensin II receptor antagonist renal disease remains prevalent and progress in these patients. The newer therapy of diabetes is the use of sodium glucose cotransporter 2 inhibitor as it has the potential of renoprotection in patients with diabetic nephropathy just as ACEI and ARBS to reduce glomerular hyperfilteration .This action may reduce albuminuria.

A Crossover Pilot Study of the Effect of Amiloride on Proteinuria

Patients with proteinuric kidney disease will be enrolled and receive either amiloride or triamterene first, a similar diuretic acting on epithelial sodium channel (ENaC) as amiloride, but not inhibiting urokinase plasminogen activator receptor (uPAR), will be used as a control. Then patients will cross over to receive another medication. We postulate that amiloride could be beneficial in the patients with proteinuric kidney diseases and could be used as an adjunct therapy to reduce proteinuria and to delay renal disease progression in this patient population. Specific Aim 1: To examine the effects of amiloride on 24 hour urine protein excretion in patients with proteinuric kidney diseases. Specific Aim 2: To study if the effect of amiloride on proteinuria reduction is mediated by suppressing soluble urokinase plasminogen activator receptor (suPAR) expression. Study Design: The study includes 3 phases. 30 patients will be recruited to this study. All patients need to be on an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) daily at least two month prior to the study. Phase 1: Patients will be randomized to receive either amiloride 5mg twice daily or triamterene 50mg twice daily for 8 weeks. Serum potassium will be monitored one week before and one week after starting phase 1. If serum potassium remains equal to or less than 5.0mmol/L, amiloride or triamterene will be continued at same dose until the end of phase 1. If serum potassium is equal to or above 5.5 mmol/L, the patient will exit the study, and an adverse event will be reported. If serum potassium is between 5.1-5.4 mmol/L, it will be monitored again in one week. If serum potassium is above 5.5 mmol/L, the patient will exit the study, and an adverse event will be reported. If serum potassium remains in the same range, the patient will continue amiloride or triamterene at the same dose to complete phase 1. Phase 2: the patients will discontinue amiloride or triamterene for a washout for 4 weeks, but continue with the ACE inhibitor or ARB. Phase 3: the patients will cross over to triamterene or amiloride for 8 weeks. Use the protocol as described in phase 1.

Proteinuria in Pre and Post Transplant

This study will retrospectively review patient's medical records for protein in the urine, blood creatinine and kidney biopsy results. Also character of the fluid used to flush the kidney before transplant will be analyzed.

Effect of Montelukast on Kidney and Vascular Function in Type 1 Diabetes