WASHINGTON, Feb. 27, 2015 /PRNewswire-USNewswire/ -- Kidney Care Partners (KCP) today praised the bicameral introduction of "The Chronic Kidney Disease Improvement in Research and Treatment Act" (H.R. 1130, S. 598), a bipartisan bill that elevates care, expands access, and promotes research to benefit more than 636,000 Americans living with kidney failure, which is known as end-stage renal disease (ESRD). KCP is a broad-based coalition of patient advocates, clinicians, care professionals, dialysis providers, researchers and manufacturers working together to improve quality of care for individuals with chronic kidney disease (CKD) and ESRD.

Currently, 31 million Americans have some form of kidney disease and are at risk of developing kidney failure absent some form of disease management education or preventive care. Each year, more than 100,000 Americans are diagnosed with ESRD – the final stage of CKD – and therefore require a kidney transplant or dialysis. Due to the limited number of kidneys available for transplantation, 430,000 Americans now rely on life-sustaining dialysis care to survive. In general, patients must undergo dialysis three times a week for several hours per treatment. Under current law, dialysis treatments are covered by the Medicare program, regardless of the individual's age.

Advocates have long stressed that federal policies are needed to provide patient choice and to ensure access to life-sustaining dialysis, to increase research into CKD, and to create stability in Medicare's crucial ESRD program. Ultimately, the legislation introduced by Representatives Tom Marino (R-PA), John Lewis (D-GA) and Peter Roskam (R-IL) in the House and Senators Ben Cardin (D-MD), Mike Crapo (R-ID) and Bill Nelson (D-FL) in the Senate would improve patient outcomes through care coordination, expand access to traditionally underserved patient populations, and set the U.S. on the path towards a cure through efficiently managed and coordinated biomedical research.

"This bill is absolutely vital as it provides a clear blueprint for the future of the ESRD program" said Dr. Ed Jones, Chairman of Kidney Care Partners and a practicing nephrologist. "By supporting care coordination, greater patient choice, coordinated research programs, and economic stability, this legislation would strengthen the delivery of care for millions of Americans living with kidney disease."

Specifically, The Chronic Kidney Disease Improvement in Research and Treatment Act would:

(1) Improve the coordination of care: The legislation would expand care options for patients by, among other things, allowing individuals diagnosed with kidney failure to enroll in the Medicare Advantage program. Under current law, individuals who develop kidney failure are not permitted to enroll in Medicare Advantage (MA) plans despite the Medicare Payment Advisory Commission's recommendation to eliminate the restriction in order to provide ESRD beneficiaries with the same freedom of choice and access to improved coordinated services as other Medicare-enrolled individuals. Therefore, the legislation would allow ESRD patients to enroll in – and reap the benefits of – MA plans. The bill also would reauthorize on a permanent basis the Special Needs Plan (SNP) for patients with kidney failure who need additional care attention, as well as extend the length of time beneficiaries may choose to maintain their existing insurance coverage. Importantly, the legislation looks to the future by establishing a voluntary coordinated care program. The coordinated care program would allow physicians and dialysis facilities to work together to improve the coordination of care and reduce costly hospitalizations and rehospitalizations.

(2) Promote patient access and choice:The legislation would expand patient access to kidney disease education programs and home dialysis treatment options through telemedicine, as well as create incentives for nephrologists and other dialysis health care professionals to work in underserved rural or urban areas. The bills also would establish renal dialysis facilities as a cost-effective alternative to hospital outpatient departments for individuals diagnosed with acute kidney injury.

(3) Expand research and enhance coordination:The legislation would identify gaps in research and improve the coordination of federal research efforts. Specifically, the bills would require the GAO to assess the adequacy of federal funding for CKD research relative to the expenditures for CKD care and identify gaps in research. Additionally, the bills would require improved coordination among the various federal agencies conducting CKD research by requiring the development of a strategic plan. Third, the bills would require the Secretary to conduct a study to better understand the progression of kidney disease and treatment of kidney failure in minority populations.

"The kidney community applauds Representatives Marino, Lewis and Roskam as well as Senators Cardin, Crapo and Nelson for their long-time leadership and ongoing efforts to protect this important and vulnerable patient population, and we look forward to working with lawmakers to advance legislation that will improve patient choice and outcomes," added Dr. Jones. "The Chronic Kidney Disease Improvement in Research and Treatment Act ensures that individuals with kidney disease, have the tools, resources, and care they need to live their lives to the fullest today and into the future."

About Kidney Care Partners
KCP is an alliance of patient advocates, nephrologists, healthcare professionals, dialysis providers and manufacturers dedicated to working together to improve quality of care for individuals with chronic kidney disease (CKD) and end-stage renal disease (ESRD). To learn more about Kidney Care Partners, visitkidneycarepartners.org.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/kidney-community-lauds-bi-partisan-bicameral-legislation-to-improve-care-coordination-expand-choice-and-enhance-research-for-millions-with-kidney-disease-kidney-failure-300042867.html

SOURCE Kidney Care Partners

...

In a recent study entitled “Scleroderma renal crisis,” the authors summarize the most recent findings related to scleroderma renal crisis, a serious but treatable complication of systemic sclerosis. The study was published in the journal Seminars in Arthritis and Rheumatism.

Scleroderma (or systemic sclerosis) is an autoimmune disease characterized by skin thickening, a process known as fibrosis. Several complications associated with scleroderma are due to the fibrosis process that is actually not restricted to the skin, reaching in severe cases, internal organs such as kidneys. As a consequence, a serious complication and a medical emergency emerges, known as scleroderma renal crisis (SRC), which occurs in 5–10% of scleroderma patients. The prognosis of affected patients was significantly improved with the introduction of aggressive treatment with angiotensin-converting enzyme inhibitors, with numbers showing a 65% patient survival rate (before treatment it was less than 10%).

Here, the authors discussed and summarized a literature review on pathophysiology, risk factors and outcomes of SRC. The team reviewed published studies until 2013, accessible in the PubMed database, related to scleroderma and SRC. The authors were able to conclude from the meta-analyses that SRC still affects approximately 10% of all scleroderma patients and is currently described as the result of endothelial injury in the kidneys, accompanied by narrowing of kidneys arterioles (small diameter blood vessels that extend from arteries). This leads to decreased blood flow and accelerated hypertension, the latter a characteristic of SRC, together with progressive renal failure. Additionally, SRC leads to kidney hyperplasia, i.e., an increase in the number of normal cells and hyperreninemia (abnormally high concentration of renin in the blood).

In this study, the research team highlights as risk factors rapid skin thickening as well as anemia and thrombocytopenia (low blood platelet count); certain types of medications, including corticosteroids or cyclosporine and cardiac complications, such as congestive heart failure and arrhythmias are risk factors for SRC. Other factors noted in the literature also included large joint contractions and anti-RNA Polymerase III antibody — this is a specific marker for systemic sclerosis and usually associated with severe states of disease where internal organs are affected.

In terms of mortality, the authors acknowledge that with the introduction of angiotensin converting enzyme (ACE) inhibitors, mortality decreased from 76% to less than 10%. The advent of renal transplantation was also noted as a significant measure for the decrease in mortality; however, SRC can still relapse in transplanted kidneys.

The authors highlight that, despite a significant improvement obtained in recent years, SRC is still affecting a meaningful population of patients with systemic sclerosis and so a vigilant diagnosis and therapy is needed to prevent adverse outcomes and enhance survival.

• Tags
• angiotensin converting enzyme (ACE) inhibitors
• scleroderma renal crisis

Share this article

Patricia Inacio, PhD

...

ATLANTA — Three days a week Chardae Sanders, a senior at Kennesaw State University, has excess fluid, waste and toxins filtered from her blood at a for-profit dialysis clinic downtown. She doesn’t flinch when a clinician pokes a needle the size of a coffee straw into her leg; the only part that still seems unnatural is when the clean blood is reintroduced into her body at the end of the treatment. “It’s like when you drink a glass of ice-cold water really fast,” she says. “It feels like a part of you is in the machine, and then you get her back.” 

Sanders found out that her kidneys had failed the same week as her 21st birthday, in November of 2007. They had been ravaged by the autoimmune disorder lupus, which she has been suffering from since high school. She’s been on dialysis ever since. 

The procedure keeps Sanders alive — there’s no comparable remedy for people whose livers fail, for example. But it’s brutal: Chronic pain afflicts close to two-thirds of dialysis patients, who often complain of fatigue, cramping and nausea, according to a 2011 article by Teri Browne, who studies kidney-transplant disparity at the University of South Carolina. To prevent health complications, doctors recommend a strict diet that regulates patients’ water, potassium and sodium intake. The treatment also restricts movement; most patients on dialysis need to be tethered to a machine four hours a day, three days a week.

Sanders follows her doctor’s orders: She eats well, stays active and is on top of her medication. But she knows that she can’t stay on dialysis forever. While some people spend decades hooked up to a mechanical kidney, the average life expectancy on dialysis is five to six years. Like most patients, Sanders views it as an interim treatment while waiting for a kidney transplant, which is considerably cheaper, adds an average of 10 years to people’s lives and allows patients to resume a relatively normal life.

Whether or when Sanders will receive a transplant, though, is particularly uncertain because she lives in Georgia, which has the lowest transplant rate in the nation. In 2013, less than three percent of Georgians with end-stage renal disease received a new kidney, according to data from the United Network for Organ Sharing. And Emory University researchers found that between 2005 and 2011, people living in some northeastern states were four times more likely to get a transplant than Georgians. As a result, many patients in the southern state spend a disproportionate amount of time on dialysis; they live and die hooked up to the machine. 

...

As discussed on this blog previously, developing histological screening techniques for renal cell carcinomas (RCCs) associated with BHD is important for early diagnosis. Individuals with folliculin (FLCN) mutations are more likely to develop multiple bilateral renal tumours (Zbar et al., 2002, Pavlovich et al., 2002). A misdiagnosis of sporadic RCC may compromise future treatment and wellbeing of the patient and other affected family members. Currently there are no known histological markers to distinguish between all subtypes of sporadic and FLCN-associated tumours.

A new report by Furuya et al., (2015) addressed this by analysed expression of FLCN and one of its downstream targets GlycoProtein Non-Metatastic B (GPNMB) in normal and neoplastic tissue to determine if they could be used to aid differential diagnosis in RCC samples. FLCN is expressed in normal kidney tissue, including in those who carry heterozygous FLCN mutations, but is not detectable in BHD tumours (Warren et al., 2004). In comparison GPNMB is not typically expressed in kidney tissue but is expressed in a range of neoplastic tissues (Hong et al. 2010).

Furuya et al. analysed 27 tumours from 18 unrelated, except for a parent and child pair, Japanese BHD patients: 12 chromophobe RCCs; six hybrid oncocytoma/chromophobe tumours (HOCTs); three papillary RCCs; and two clear cell RCCs (ccRCC). For seven of these tumours sections of non-neoplastic kidney were also frozen for comparison. Expression of FLCN and GPNMB in the BHD-associated tumours was compared to 62 sporadic renal tumours from an unreported number of patients. All patients were medically examined for the classical BHD symptoms – pulmonary cysts, pneumothorax, fibrofolliculomas and multifocal/hybrid RCC – and a family history obtained. One of the sporadic group also had pulmonary cysts so a diagnosis of BHD was ruled out by genetic testing. The rest of this group did not show any BHD manifestations or have any family history so were assumed to not carry FLCN mutations.

FLCN expression in the tumour samples was assessed by western blot and immunohistochemistry using a monoclonal (D14G9) and previously unpublished polyclonal (ab93196) antibody respectively. The western blot results showed a clear loss of FLCN in BHD-associated but not sporadic tumours or non-neoplastic BHD tissue. In addition the typical strong nuclear staining for FLCN was seen in the majority of sporadic tumours whereas the majority of BHD-associated tumours showed only cytoplasmic or no staining. It is suggested that the presence of cytoplasmic staining should be considered a potential BHD indicator.

The presence of GPNMB protein was confirmed by western blot and immunohistochemistry, but mRNA levels were also quantified by quantitative RT-PCR. The markedly higher expression (up to 23-fold) detected in BHD tumours by qRT-PCR correlated with the intensity of the western band seen. GPNMB was barely detectable in the sporadic tumour samples and non-neoplastic BHD renal tissue. Immunostaining showed positive staining in BHD-associated tumours excluding the ccRCC samples and one papillary sample. The majority of sporadic samples were in contrast negative with the exception of 50% of sporadic chromophobe RCC samples which showed weak GPNMB staining.

It was also possible to detect low expression of GPNMB in small nodules of “non-neoplastic” BHD kidney tissue which could indicate the sites of future tumour development. As the formation of multiple small tumours is characteristic of BHD this could also help in differential diagnosis.

The germline FLCN mutations for each patient was determined from a peripheral blood sample; the most common (50%) mutation was duplication in the hypermutable cytosine tract in exon 11 and four patients had the same GATG deletion in exon 13. In addition Furuya et al., attempted to detect secondary somatic mutations in a number of the tumour samples. A second mutation was found in six individual tumours and a loss of heterozygosity in a further two. Only one of these secondary mutations has so far been reported as a germline mutation in a BHD patient. The other mutations may therefore not be pathogenic but as all would result in a frameshift it is more likely they are new unique mutations.

The results from this work suggest that staining for both a lack of FLCN and a gain of GPNMB could help to distinguish sporadic oncocytomas, chromophobe and papillary RCC from BHD-associated HOCTS, chromophobe and papillary RCCs. It would not be sufficient however to definitively classify a ccRCC as FLCN-related, but a lack of nuclear FLCN staining could identify cases appropriate for genetic testing.

• Furuya M, Hong SB, Tanaka R, Kuroda N, Nagashima Y, Nagahama K, Suyama T, Yao M, & Nakatani Y (2015). Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome. Cancer science PMID: 25594584
• Hong SB, Oh H, Valera VA, Baba M, Schmidt LS, Linehan WM. Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization. PLoS One. 2010 Dec 29;5(12):e15793. doi:10.1371/journal.pone.0015793. PMID: 21209915.
• Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, Merino MJ. Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol. 2002 Dec;26(12):1542-52. PubMed PMID: 12459621.
• Warren MB, Torres-Cabala CA, Turner ML, Merino MJ, Matrosova VY, Nickerson ML, Ma W, Linehan WM, Zbar B, Schmidt LS. Expression of Birt-Hogg-Dubé gene mRNA in normal and neoplastic human tissues. Mod Pathol. 2004 Aug;17(8):998-1011. PMID: 15143337.
• Zbar B, Alvord WG, Glenn G, Turner M, Pavlovich CP, Schmidt L, Walther M, Choyke P, Weirich G, Hewitt SM, Duray P, Gabril F, Greenberg C, Merino MJ, Toro J, Linehan WM. Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dubé syndrome. Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):393-400. PubMed PMID: 11927500.

...