Treatment Of CKD Research Articles

Angiotensin II- and Salt-Induced Kidney Injury through Rac1-Mediated Mineralocorticoid Receptor Activation

Experiments with hyperaldosteronemic animals suggest that, despite lowering plasma aldosterone, salt worsens renal injury by paradoxical activation of the mineralocorticoid receptor (MR). Salt and aldosterone synergistically contribute to renal impairment through Rac1-mediated activation of the MR, but whether angiotensin II also promotes renal injury through this mechanism is unknown. Here, we placed angiotensin II-overproducing double transgenic Tsukuba hypertensive mice on a low- or high-salt intake for 6 weeks and treated some animals with adrenalectomy, the MR antagonist eplerenone, the Rac inhibitor EHT1864, or hydralazine. High-salt intake, but not low-salt intake, led to hypertension and prominent kidney injury. Adrenalectomy prevented angiotensin II/salt-induced nephropathy in mice receiving high-salt intake, which was recapitulated by aldosterone supplementation, suggesting the involvement of aldosterone/MR signaling. Plasma aldosterone levels, however, were lower in high- than low-salt conditions. Instead, angiotensin II/salt-evoked MR activation associated with Rac1 activation and was not dependent on plasma aldosterone level. Both EHT1864 and eplerenone repressed the augmented MR signaling and mitigated kidney injury with partial but significant reduction in BP with high-salt intake. Hydralazine similarly reduced BP, but it neither suppressed the Rac1-MR pathway nor ameliorated the nephropathy. Taken together, these results show that angiotensin II and salt accelerate kidney injury through Rac1-mediated MR activation. Rac inhibition may be a promising strategy for the treatment of CKD.

CKD診療ガイド2012の改訂点とそのポイント

CKD診療ガイド2012の改訂点とそのポイント

93 Improving Chronic Kidney Disease Care in Primary Care Practices

IMPROVING CHRONIC KIDNEY DISEASE CARE IN PRIMARY CARE PRACTICES Chester Fox, Renee Cadzow, Brittany Cooper, Samantha Sessamen, Meredith Snyder, Primary Care Research Institute, Buffalo, New York. The purpose of this study is to improve treatment of CKD in primary care practices by increasing diagnosis of CKD, diagnosing and treating anemia, improving proteinuria with use of ACE/ARB medications, checking for bone disease, treating vitamin D deficiency, and avoiding medicines such as NSAIDS which are harmful to the kidney. Twelve practices have been recruited – 6 were randomly assigned to a basic intervention; 6 to receive an enhanced intervention. All practices received a quick reference guide summarizing the Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease care guidelines. The 6 enhanced intervention sites were assigned a Practice Enhancement Assistant (PEA) to promote implementation of the guidelines. Six practices also received CINA, a computer point of care decision support protocol engine, which integrates with the practices’ existing electronic health record. Data is collected through manual chart review by a research assistant or PEA at the 6 sites without computer decision support. Data is extracted by CINA at the remaining 6 sites. At sites with support of a PEA, data is reported regularly to the practices throughout the 2 year study as part of the quality improvement cycle. This paper will present baseline, 3 month, and 6 month data for each arm of the study with results of chisquare and t-test analyses demonstrating whether differences exist between participating practices.

KDOQI US Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD–Mineral and Bone Disorder (CKD-MBD)

This commentary provides a US perspective on the 2009 KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). KDIGO is an independent international organization with the primary mission of the promotion, coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines for the care of patients with kidney disease. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI), recognizing that international guidelines need to be adapted for each country, convened a group of experts to comment on the application and implementation of the KDIGO guideline for patients with CKD in the United States. This commentary puts the KDIGO guideline into the context of the supporting evidence and the setting of care delivered in the United States and summarizes important differences between prior KDOQI guidelines and the newer KDIGO guideline. It also considers the potential impact of a new bundled payment system for dialysis clinics. The KDIGO guideline addresses the evaluation and treatment of abnormalities of CKD-MBD in adults and children with CKD stages 3-5 on long-term dialysis therapy or with a kidney transplant. Tests considered are those that relate to laboratory, bone, and cardiovascular abnormality detection and monitoring. Treatments considered are interventions to treat hyperphosphatemia, hyperparathyroidism, and bone disease in patients with CKD stages 3-5D and 1-5T. Limitations of the evidence are discussed. The lack of definitive clinical outcome trials explains why most recommendations are not of level 1 but of level 2 strength, which means weak or discretionary recommendations. Suggestions for future research highlight priority areas.

Evidence-based Practice Guideline for the Treatment of CKD

Evidence-based Practice Guideline for the Treatment of CKD

Chapter 4.1: Treatment of CKD–MBD targeted at lowering high serum phosphorus and maintaining serum calcium

Chapter 4.1: Treatment of CKD–MBD targeted at lowering high serum phosphorus and maintaining serum calcium

New decade, new options

It was March 1999, and I'd had my transplant for 18 years. I was very grateful for those 18 years. Besides graduating from California University of Pennsylvania (in California, Pa.) and receiving a degree in computer science, I had married, had a son, and lived a productive life. I felt that God had blessed me and answered my prayers of having a “normal life.” However, at the end of those 18 years, I was hospitalized for pneumonia. The treatment was taking a long time, and I suspected that my transplant wasn't going to survive it. And it didn't. I felt myself going downhill fast. My body weight decreased and I found it difficult to walk. I knew it was inevitable: I would have to start treatment for renal failure. My nephrologist explained the available options for dialysis and, compared with 18 years prior, treatments had definitely changed. She told me to think about them. When she came in the next day, I was in tears. She hugged me and reassured me that I would be put on the transplant list as soon as possible. “No, that's not what I am crying about,” I told her. “I just don't know what treatment to choose.” I didn't have these options when I first underwent dialysis in 1978. The years since have been challenging, yet productive. As it turned out, I only qualified for one treatment: hemodialysis. After leaving the hospital, I went to in-center HD three days a week for four-hour treatments. The renal diet was different from what I went through in the late 1970s. Instead of the “low-protein” diets my healthcare providers had put me on years ago during my first period of dialysis treatments, it was a high-protein diet now. In reality, I liked this, but I didn't have the appetite for it. I couldn't eat what was required to keep my albumin levels up. Life has not ended for me; it has just begun. It's wonderful to be living in a time when we have an opportunity to choose from several options for the treatment of CKD. After that first year, my social worker and staff members approached me about a new treatment option they were trying: home HD. With this treatment, I would train in-center for eight weeks on the dialysis machine. The treatments would be done at home every other night and would be monitored online by patient-care technicians. The goal was to have a gentler and safer treatment for my body. I decided to go for it; it was a chance to take control and have a normal life. My appetite returned and I gained 15 kg. I felt that sense of normalcy, but found that the rigorous setting up and taking down of the machine, inventories, and testing got to me. I was doing this all alone and found that although the treatment was working for me, all the work that went along with it wasn't. Six months into the home modality I found out that they offered the same sort of program in-center. I returned to the dialysis center three nights a week, and this has been the best modality for me to this day. Eight years have gone by, and my treatments are going very well. I have been given that chance for normalcy again. For this I am thankful. I have returned to the workplace during these 8 years, and I appreciate every day that is given to me. Through my work with the Renal Support Network I am able to share my story with others who may need that extra bit of help getting through their challenges with CKD. The Renal Support Network says “an illness is too demanding if you don't have hope.” Life has not ended for me; it has just begun. I still have the option of going back on the transplant list, which I am holding for the future. It's wonderful to be living in a time when we have an opportunity to choose from several options for the treatment of CKD.

Role of Remission Clinics in the Longitudinal Treatment of CKD

Heavy proteinuria is a major determinant of progression to ESRD for patients with chronic nephropathies and reducing proteinuria should be a key target for renoprotective therapy. In the Remission Clinic, we applied a multimodal intervention to target urinary proteins in 56 consecutive patients who had >3 g proteinuria/d despite angiotensin-converting enzyme inhibitor therapy. We compared the rate of GFR decline and incidence of ESRD in this cohort with 56 matched historical reference subjects who had received conventional therapy titrated to a target BP. During a median follow-up of 4 yr, the monthly rate of GFR decline was significantly lower in the Remission Clinic cohort (median -0.17 versus -0.56 ml/min per 1.73 m2; P < 0.0001), and ESRD events were significantly reduced (3.6 versus 30.4% reached ESRD). Follow-up BP, cholesterol, and proteinuria were lower in Remission Clinic patients than in reference subjects, such that disease remission or regression was achieved in up to 50% of patients who would have been otherwise expected to progress rapidly to ESRD on conventional therapy. Proteinuria reduction independently predicted a slower rate of GFR decline and ESRD incidence, but response to treatment differed depending on the underlying disease. Regarding safety, no patient was with drawn because of hyperkalemia. In summary, multidrug treatment titrated to urinary protein level can be safely and effectively applied to normalize proteinuria and to slow the loss of renal function significantly,especially among patients without type 2 diabetes and with otherwise rapidly progressing chronic nephropathies.

Putting "Evidence-based Medicine Practice Guideline for the Treatment of CKD" to Practical Use

Putting "Evidence-based Medicine Practice Guideline for the Treatment of CKD" to Practical Use

Treatment of CKD

Treatment of CKD