Common Antidepressant Sertraline Does Not Improve Depression in Chronic Kidney Disease Patients

MedicalResearch.com Interview with:

Dr. Susan Hedayati MD University of Texas Southwestern Dallas, Texas

Dr. Hedayati

Dr. Susan Hedayati MD
Yin Quan-Yuen Distinguished Professorship in Nephrology
University of Texas Southwestern
Dallas, Texas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We previously showed that Major Depression is associated with a significantly higher risk of death, dialysis initiation, and hospitalization among patients with Chronic Kidney Disease (CKD). Now we show that a common antidepressant medication, a selective serotonin reuptake inhibitors (SSRI), sertraline, does not improve depression in this patient population, a chronically ill group that is not only at significantly increased risk for developing depression but also its serious complications.

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SPRINT Trial: Greater Mean Blood Pressure Reductions Linked To Increased Risk of Kidney Function Decline

MedicalResearch.com Interview with:
Rita Magriço MD

Hospital Garcia de Orta
Almada, Portugal 
 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The SPRINT trial showed that in non-diabetic patients with high cardiovascular risk, intensive systolic blood pressure treatment (<120 mmHg) was associated with lower rates of major cardiovascular events and mortality. However, intensive treatment was unexpectedly associated with increased kidney function decline.

We thought that lowering blood pressure could compromise kidney perfusion, evaluated by mean arterial pressure (MAP). If so, the magnitude of MAP reduction was expected to be associated with kidney function decline. We hypothesized that a greater difference between the baseline MAP and the lowest achieved MAP may be associated with a higher risk of kidney function decline.

Our analysis supports this hypothesis. We discovered that MAP reduction >20 mmHg in patients with a target systolic BP <120 mmHg was associated with higher incidence of kidney function decline. The benefit-risk balance of intensive treatment seemed to be less favourable with greater MAP reduction. Prospective studies evaluating the effect of MAP reduction in addition to hypertension treatment target on kidney function decline and cardiovascular events are warranted.

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Vasopressin-Inhibitor Tolvaptan Reduces Kidney Function Decline in Polycystic Kidney Disease

MedicalResearch.com Interview with:
Dr. TorresVicente E. Torres, M.D., Ph.D.

Director of the Mayo Clinic Translational Polycystic Kidney Disease (PKD) Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Experimental work pioneered by Dr. Jared Grantham showed that cyclic AMP, an intracellular signaling molecule, promotes the development and growth of cysts. Vasopressin, a hormone produced by the pituitary gland, stimulates the production of cyclic AMP in the collecting ducts, from which most cysts derive in autosomal dominant polycystic kidney disease (ADPKD). While this effect of vasopressin is necessary for the kidneys to concentrate and reduce the volume of urine, it promotes the development and growth of cysts in patients with ADPKD. Dr. Vincent Gattone realized that inhibiting the action of vasopressin could be protective in polycystic kidney disease. Work in our and other laboratories confirmed that suppression of vasopressin production, release or action reduces cyst burden, protects kidney function, and prolongs survival in rodent models of the disease.

This experimental work provided a strong rationale for clinical trials of tolvaptan, a vasopressin V2 receptor antagonist. Tolvaptan reduced the rate of kidney growth in the TEMPO 3:4 trial, in patients with early ADPKD. It also reduced the rate of decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), from 10.1 to 6.8 mL/min/1.73 m2 over three years. The eGFR benefit was maintained during two additional years when all the patients were treated with tolvaptan in an open label extension of the TEMPO 3:4 trial (TEMPO 4:4). Safety laboratory tests performed every four months showed elevations of liver transaminases in blood in 4.4% of tolvaptan and 1% of placebo-treated patients. Three of 1,271 tolvaptan-treated patients during TEMPO 3:4 and TEMPO 4:4 had evidence of potentially serious drug-induced liver injury. These abnormalities occurred all within the first 18 months of exposure to tolvaptan.

Based on the TEMPO 3:4 results, tolvaptan was approved for the treatment of rapidly progressive ADPKD in Japan, Canada, European Union, Switzerland and South Korea. In the United States, the Food and Drug Administration requested additional data to further evaluate the efficacy and safety of this drug. The REPRISE trial was performed to determine the efficacy and safety of tolvaptan in patients with later stage ADPKD.

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Non-Medical Factors Affect Racial Disparities in Kidney Transplant Wait Lists

MedicalResearch.com Interview with:
Yue-Harn Ng,
MD
University of New Mexico

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ​African Americans (AA) have a higher incidence of end-stage renal disease but lower rates of kidney transplantation (KT) compared to whites (WH).  Disparities persist after adjusting for medical factors.  We assessed the relationship of non-medical (eg. cultural, psychosocial, knowledge) factors with kidney transplantation wait-listing (WL) within the context of racial differences.

​In this longitudinal cohort study, we found that African American patients were less likely to be wait-listed compared to White patients.  This difference was influenced by factors including age, comorbidities, socio-economic status, being on dialysis, having a living donor, transplant knowledge and social support.

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Poor Functional Status Predicts Increased Mortality After Dialysis Initiation

MedicalResearch.com Interview with:

Silvi Shah, MD, FACP, FASN Assistant Professor, Division of Nephrology University of Cincinnati Cincinnati, OH

Dr. Shah

Silvi Shah, MD, FACP, FASN|
Assistant Professor
Division of Nephrology
University of Cincinnati
Cincinnati, OH

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Elderly represent the fastest growing segment of incident dialysis patients in Unites States. The annual mortality in end stage renal disease (ESRD) patients is very high ~ 20%.

Since most of the deaths occur in the first year of dialysis, it is possible that health conditions present prior to initiation of dialysis may impact long-term outcomes. In this study, we determined the impact of poor functional status at the time of dialysis initiation and pre-dialysis health status on type of dialysis modality, type of hemodialysis access and one-year mortality in elderly dialysis patients. We evaluated 49,645 adult incident dialysis patients (1/1/2008 to 12/31/2008) from the United Data Renal Data System (USRDS) with linked Medicare data for at least 2 years prior to dialysis initiation. Mean age of our study population was 72 years. At dialysis initiation, 18.7% reported poor functional status, 88.9% has pre-dialysis hospitalization, and 27.8% did not receive pre-dialysis nephrology care. Patients with poor functional status had higher odds of being initiated on hemodialysis than peritoneal dialysis, lower odds of using arteriovenous access as compared to central venous catheter for dialysis and higher risk of one-year mortality.

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PPIs for Reflux Linked To Increased Risk of Chronic Kidney Disease

MedicalResearch.com Interview with:
Charat Thongprayoon, MD

Bassett Medical Center
Cooperstown, NY 13326

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We conducted a meta-analysis including 5 observational studies with 536,902 patients to assess the risks of chronic kidney disease (CKD) and/or end-stage kidney disease (ESRD) in patients who are taking proton pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs).

We found a statistically significant association between the use of PPI and 1.3-fold increased risk of CKD or ESRD development. Compared with H2Ras, the use of proton pump inhibitors was significantly associated with 1.3-fold higher risk for CKD development.

Conversely, there was no significant association between the use of H2RAs and chronic kidney disease.

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Elderly Frail Patients At Higher Risk Of Mortality After Dialysis Initiation

MedicalResearch.com Interview with:

Silvi Shah, MD, FACP, FASN Assistant Professor, Division of Nephrology University of Cincinnati Cincinnati, OH

Dr. Shah

Silvi Shah, MD, FACP, FASN
Assistant Professor, Division of Nephrology
University of Cincinnati
Cincinnati, OH

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Elderly represent the fastest growing segment of incident dialysis patients in Unites States. The annual mortality in end stage renal disease (ESRD) patients is very high ~ 20%. Since most of the deaths occur in the first year of dialysis, it is possible that health conditions present prior to initiation of dialysis may impact long-term outcomes.

In this study, we determined the impact of poor functional status at the time of dialysis initiation and pre-dialysis health status on type of dialysis modality, type of hemodialysis access and one-year mortality in elderly dialysis patients. We evaluated 49,645 adult incident dialysis patients (1/1/2008 to 12/31/2008) from the United Data Renal Data System (USRDS) with linked Medicare data for at least 2 years prior to dialysis initiation. Mean age of our study population was 72 years. At dialysis initiation, 18.7% reported poor functional status, 88.9% has pre-dialysis hospitalization, and 27.8% did not receive pre-dialysis nephrology care. Patients with poor functional status had higher odds of being initiated on hemodialysis than peritoneal dialysis, lower odds of using arteriovenous access as compared to central venous catheter for dialysis and higher risk of one-year mortality.

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Acute Care Hospitalizations Prior To Initiation of Dialysis Signal Greater Mortality Risk

MedicalResearch.com Interview with:
Charuhas Thakar, MD Professor

Director of the Division of Nephrology Kidney CARE program
University of Cincinnati

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Based on the plausibility that pre-dialysis health status can impact outcomes after initiation of chronic dialysis, we examined large national USRDS dataset with linked Medicare claims prior to dialysis. We found that 88% of patients who initiate dialysis experience at least one acute care hospitalization in two years preceding their dialysis start.

If they do, that is associated with a significant increase in the risk of mortality at one year. We also examined effect of different types of hospitalizations in the pre-dialysis period – Cardiovascular, Infections, both, and neither of the two. There were statistical differences in the effect of type of hospitalization and post dialysis mortality.

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Chronic Insomnia Associated With Higher Risk of End Stage Kidney Disease and Mortality

MedicalResearch.com Interview with:
Dr. Jun Ling (Lucy) Lu, MD, CCRP
Senior Clinical Research Coordinator in the Department of Medicine

Csaba P Kovesdy MD FASN
Fred Hatch Professor of Medicine
Director, Clinical Outcomes and Clinical Trials Program

Division of Nephrology, University of Tennessee Health Science Center
Nephrology Section Chief, Memphis VA Medical Center
Memphis TN, 38163 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Around one third of the world’s population suffers from insomnia. Previous studies showed that sleep disorders affect the hypothalamic–pituitary–adrenal axis and the sympatho-adrenal system, which may cause abnormalities in several organ systems and pathways causing metabolic or cardiovascular abnormalities. However, there is inadequate evidence of an association between chronic insomnia and adverse renal outcomes.

After examining 938,473 US veterans (4.4% of them had chronic insomnia) with baseline estimated eGFR >60 ml/min/1.73m2, we found that chronic insomnia is associated with a 43% higher risk of all-cause mortality, a 2.5-fold higher incidence of eGFR ≤45ml/min/1.73m2, a 2.3-fold higher ESRD risk, and with rapid loss of kidney function.

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Coffee – Caffeine Linked To Decreased All-Cause Mortality in Kidney Disease Patients

MedicalResearch.com Interview with:
Coffee Wikipedia imageMedicalResearch.com Interview with:
Miguel Bigotte Vieira, MD

Centro Hospitalar Lisboa Norte
Lisboa, Portugal

Response: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains unclear. We examined the association between varying levels of caffeine consumption and mortality among 2328 patients with CKD in a prospective nationwide cohort, using the continuous National Health and Nutrition Examination Survey (NHANES) 1999-2010.

A dose-dependent inverse association between caffeine and all-cause mortality was observed in patients with CKD. This association was independent of influential factors including age, gender, race, annual family income, education level, estimated GFR, albumin/creatinine ratio, hypertension, smoking status, dyslipidemia, body mass index, previous cardiovascular events and diet: consumption of alcohol, carbohydrates, polyunsaturated fatty acids and fibers.

Comparing with 1st quartile of caffeine consumption, adjusted HR for death was 0.88 (95% CI, 0.68-1.44) for 2nd quartile, 0.78 (95% CI, 0.60-1.01) for 3rd quartile and 0.76 (95% CI, 0.59-0.97) for 4th quartile (p=0.027 for trend across quartiles)

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Caffeine Linked To Decrease in All-Cause Mortality in Chronic Kidney Disease Patients

MedicalResearch.com Interview with:

Miguel Bigotte Vieira MD Centro Hospitalar Lisboa Norte Lisbon, Portugal

Dr. Bigotte Vieira

Miguel Bigotte Vieira MD
Centro Hospitalar Lisboa Norte
Lisbon, Portugal 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains unclear. We examined the association between varying levels of caffeine consumption and mortality among 2328 patients with CKD in a prospective nationwide cohort, using the continuous National Health and Nutrition Examination Survey (NHANES) 1999-2010.

A dose-dependent inverse association between caffeine and all-cause mortality was observed in patients with CKD. This association was independent of influential factors including age, gender, race, annual family income, education level, estimated GFR, albumin/creatinine ratio, hypertension, smoking status, dyslipidemia, body mass index, previous cardiovascular events and diet: consumption of alcohol, carbohydrates, polyunsaturated fatty acids and fibers.

Comparing with 1st quartile of caffeine consumption, adjusted HR for death was 0.88 (95% CI, 0.68-1.44) for 2nd quartile, 0.78 (95% CI, 0.60-1.01) for 3rd quartile and 0.76 (95% CI, 0.59-0.97) for 4th quartile (p=0.027 for trend across quartiles)

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