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Tight Glucose Control No Help to Kidneys - MedPage Today
By Crystal Phend, Senior Staff Writer, MedPage Today

Published: May 29, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

Action Points

Intensive glucose control for type 2 diabetes may help control some markers of kidney health, but doesn't clearly prevent clinical kidney problems, a meta-analysis determined.

Tighter control in clinical trials with hemoglobin A1c (HbA1c) targets ranging from 7.1% to less than 6% significantly cut down on micro- and macroalbuminuria compared with conventional glucose control, Steven G. Coca, DO, MS, of Yale and the VA Medical Center in West Haven, Conn., and colleagues found.

However, the intensive strategy had no impact on doubling of serum creatinine level, risk of end-stage renal disease, or death from renal disease, they reported in the May 28 issue of the Archives of Internal Medicine.

Given the risks of severe hypoglycemia, minimal cardiovascular benefit, and potential increased risk of death seen with tight glucose control, the renal findings don't do much to justify it, Coca's group argued.

Because of the low rates of end-stage renal disease with conventional treatment, "there is little compelling reason to initiate intensive glycemic control in midstage of the disease with the aim of preventing renal failure," they wrote.

However, that message drew criticism in an accompanying editorial by David M. Nathan, MD, of Massachusetts General Hospital in Boston, who argued that it ignores the benefit of intensive intervention early in the course of diabetes.

He pointed to more than 20-year follow-up results from the UKPDS in type 2 and DCCT study in type 1 diabetes showing a reduction in more advanced clinical outcomes, including cardiovascular events.

That is proof that "early intensive therapy, combined with assiduous attention to control of other recognized risk factors, is necessary to improve long-term prospects of patients with diabetes," he wrote.

The meta-analysis largely included studies with follow up "far too brief to address the effects of intensive therapy on end-stage renal disease," he explained.

When combined with the low absolute rates of severe renal outcomes, it couldn't have hoped to do anything but rule out harm, Nathan argued.

"We should be cautious not to abandon the goal HbA1c level of less than 7% for most patients," he concluded.

The guidelines recommend a target of less than 7% but also allow for personalizing treatment goals to anywhere from less than 8% to less than 6.5% based on factors such as age, comorbidity, complications, and hypoglycemia risk.

But there's little trial evidence supporting a goal less than 7%, argued a second editorial.

The UKPDS tested treatment with metformin, a sulfonylurea, or insulin soon after diagnosis but not any specific glycemic target, wrote Karen L. Margolis, MD, MPH, and Patrick J. O'Connor, MD, MPH, both of HealthPartners Research Foundation in Minneapolis, Minn.

"It is clear that using these drugs has benefit and that they may often lower HbA1c to well below 7%, but the UKPDS did not demonstrate the benefit of sustained multidrug therapy to maintain HbA1c less than 7%," they wrote.

ACCORD and ADVANCE were the first trials to achieve and maintain HbA1c less than 7%. Both showed some reductions in early manifestations of microvascular complications with intensive treatment needed for tight glucose control, but neither reduced more advanced microvascular complications or showed benefits for cardiovascular or mortality outcomes.

Those studies were included, along with the two UKPDS cohorts and three other randomized trials, in the current meta-analysis, for a total of 28,065 adults followed over 2 to 15 years.

Compared with conventional glucose control, intensive glucose control was associated with:

  • 14% reduced risk of microalbuminuria (RR, 0.86, 95% CI 0.76 to 0.96)
  • 24% reduced risk of macroalbuminuria (RR 0.74, 95% CI 0.65 to 0.85)
  • No difference in risk of serum creatinine doubling (RR 1.06, 95% CI 0.92 to 1.22)
  • No significant impact on end-stage renal disease (RR 0.69, 95% CI 0.46 to 1.05)
  • No impact on risk of death from renal disease (RR 0.99, 95% CI 0.55 to 1.79)

The greater the difference in HbA1c among the intensive and conventional therapy arms in any particular study, the greater the benefit in terms of microalbuminuria and macroalbuminuria (P=0.01 and P=0.008, respectively).

But the actual median HbA1c in the intensive group didn't correlate with the magnitude of the relative risk for any of the endpoints.

The average diabetes duration prior to study enrollment ranged from 6.5 to 12 years, but that appeared to be a factor only in risk of serum creatinine doubling.

The researchers cautioned about the low cumulative incidence of the clinically important endpoints across the trials (4% doubling of the serum creatinine level, 1.5% end-stage renal disease, and 0.5% death from renal disease), which may have left the meta-analysis underpowered to detect significant differences.

"Regardless, with a baseline rate of end-stage renal disease so low in the standard therapy group and the overall lack of benefit for cardiovascular or all-cause mortality, it does not seem prudent to expose patients to this therapy to achieve an absolute risk reduction for end-stage renal disease that will be less than 1% in a best-case scenario," Coca's group concluded.

Krumholz reported a grant from the National Heart, Lung, and Blood Institute and receiving a research grant from Medtronic through Yale University.

He also reported chairing a scientific advisory board for United Healthcare.

Margolis, O'Connor, and Nathan reported no conflicts of interest.

Primary source:Archives of Internal Medicine
Source reference:
Coca SG, et al "Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: systematic review and meta-analysis" Arch Intern Med 2012; 172: 761-769.

Additional source: Archives of Internal Medicine
Source reference:
Nathan DM "Understanding the long-term benefits and dangers of intensive therapy of diabetes" Arch Intern Med 2012; 172: 769-770.

Additional source: Archives of Internal Medicine
Source reference:
Margolis KL, O'Connor PJ "Prioritizing treatments in type 2 diabetes mellitus" Arch Intern Med 2012; 172: 770-772.

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Crystal Phend

Staff Writer

Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor’s Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.

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Delta govt subsidises dialysis treatment - Nigerian Tribune

Delta govt subsidises dialysis treatment

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Patients with kidney problems in Delta State can now heave a sigh of relief as the state government has decided to subsidise dialysis treatment.

The action, according to the state governor, Dr Emmanuel Uduaghan, was to enable the patients to have treatment twice a week at the State Central Hospital, Warri, where the state of the arts dialysis equipment were installed.

Briefing newsmen in Asaba, on Monday, Dr Uduaghan noted that the patients ought to have treatment twice or thrice a week to stay alive but could not afford the cost.

According to him, 30 million Nigerians were suffering from the disease and hoped that with the facilities in the state, the number would be reduced drastically.

On security challenges, the governor noted the new dimension of crime where banks in rural areas had become targets of robbery attacks.

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Protest to save dialysis service planned for Tuesday - The Guardian Charlottetown

MONTAGUE — Relocating dialysis service to major centres is just another step by the province to close rural hospitals for good, says a Souris businessman and advocate.

Allen MacPhee was guest speaker at a recent Montague Rotary Club meeting and said closing dialysis units in Souris and Alberton is all part of the “centrist” vision being exhibited by the Liberal government at the expense of rural Prince Edward Island.

“We’ve lost the local hospital boards where the local region had a voice and now we’re facing another move towards closing rural hospitals,’’ said MacPhee, who also encouraged Rotarians to join the protest planned at Province House Tuesday evening.

The Souris businessman said government has provided no rationalization on the dialysis closures – which would force sick people to drive hours to be assisted – and has ignored public consultation on the issue.  He also said there is no indication the move would even save money.

“Right now these patients are served by excellent nurses in their home region, but send them all to Charlottetown or Summerside, and you clog the system and require he services of the nephrologist who drops by and says hello and another $3,000 in fees are chalked up that taxpayers don’t pay now.”

MacPhee said specialized nurses in the Souris region have been guaranteed to be paid travel time and mileage if they travel to Charlottetown to work for a one-year period.

“There is a great sucking of rural tax dollars happening right now for the benefit of the centre,” he said. “We’re in the last throes of Charlottetown trying to make the budget work; otherwise we’re headed for bankruptcy.”

MacPhee invited Rotarians to be part of the protest planned to support rural health options by gathering at 6:45 p.m. at Peakes Quay on May 29 and march to Province House.

“It’s not just about rural life,’’ he said. “It’s for ethics and values that we cherish. You don’t bully the most vulnerable….you do not tax the sick you help them.”

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Chloramines in water June 3 - Brooks Bulletin
JAN BEECHER
Brooks Bulletin

At a council meeting last week, general manager for Newell Regional Services Corporation Ralph Havinga was on hand to discuss the use of chloramines as a disinfectant for the water supply.
Beginning June 3 NRSC will switch from chlorine as a disinfectant to chloramines.
Chloramines are produced through the addition of ammonia to the water stream leaving the water treatment plant.
The process will involve flushing of various distribution systems to accelerate chloraminated water being introduced to the distribution systems. Monitoring, sampling and testing will occur as the change is put into effect.
“Residents may notice an increase in taste and odour of chlorine for a short time as the water is being exchanged in the distribution system,” said Havinga.
Chloramines have been in use in Edmonton, Red Deer and Lethbridge for a number of years, Canadian Drinking Water Standards, Alberta Environment and Alberta Health Services have approved them for use. Havinga noted that Alberta Environment and Alberta Health were part of the discussions when the plans to make the switch were put in place.
“Due to the distance of communities from the water treatment plant and Brooks chloramines provide an effective and stable disinfection of water,” Havinga told council.
The change in treatment has been advertised in the media recently to ensure consumers are informed.
Advertisements have included a warning to owners of fish tanks.
Chloraminated water cannot be introduced into a fish tank without first removing the ammonia. Fish take in oxygen by washing water over their gills - oxygen from the water moves into the blood through a very thin membrane. Chloramines enter the bloodstream through the same process and cause damage to blood cells.
Local pet stores have been informed about the upcoming change.
Councillor Barry Morishita said that residents have expressed concern that chloramines will interfere with dialysis machines.
“Ammonia will interfere with the uptake of oxygen. Red blood cells are very important in exchanging oxygen, so home dialysis patients or dialysis patients should have chloramines and the ammonia taken out of the water,” confirmed Havinga.
According to Alberta Health Services there are no dialysis patients or home dialysis patients within the whole County of Newell. Brooks Hospital does not treat for dialysis.
Cities that do have chloraminated water employ a process to remove ammonia and chloramines from water before it is used in dialysis. It is equally important to remove chlorine and other contaminants from water used in dialysis.
Mayor Martin Shields clarified that the choice to use the chloramine disinfection process was decided on a number of years ago.
“The decision was made. Enquiries were made as to how it worked with the other municipalities. Now it’s come to the surface again because we’re actually doing it - the people are re-asking the questions because it’s been some time since the decision was made.”
Havinga estimated it would have been around 2007-2008 that the chloramine disinfection was designed into the treatment process.
He said Chloramines were chosen over chlorine because chlorine is not stable for a long period and would not be effective over the vast area that the water plant is servicing.
“With the long, long distances that this water travels from, say the city of Brooks to Rolling Hills or Bassano, chloramines is really the treatment of choice. Otherwise each one of the stations would require the addition of chlorine to meet the same objective.”
Many concerns expressed by residents are based on articles found on the internet.
“I’m cautioning people is to review the source of the information.”
He used the example of one article suggested that chloramines advance the breakdown of rubber gaskets. It is written by a company that makes ‘chloramine resistant’ gaskets.
“There’s a sentence in the article that talks a little bit about temperature but it skips by that right away. In warmer climates, southern States, Mexico - there could be an issue but in the cooler climates I don’t believe there is an issue.”
No reports have come out of Red Deer, Lethbridge or Edmonton saying they had to replace all their rubber gaskets because of breakdown.
Another case that appears on a Google search for the dangers of chloramines is that in 2004 lead levels in the Washington, DC water system were discovered to be close to six times the acceptable amount for drinking water.
The city had started using a chloramine disinfection process in 2001. The cause seems to have been a unique combination of the city’s water composition and the extensive network of lead pipes in the old city’s infrastructure.
On the surface this story sounds terrible, but accounting for the uniqueness of the situation, it is more understandable.
“We’re very, very carefully monitoring the levels and Alberta Environment sets levels that we have to meet for our approval to operate. We cannot exceed those levels. We have all sorts of monitoring devices to monitor this change,” said Havinga.
“We take the safety of our residents very seriously.”
There is also a situation that has come up in Orange County, California where a developer is suing water districts over copper pipe leaks claiming that chloramine treatment is responsible for pinholes in the pipe.
According to the American Water Works Association these pinhole leaks have been reported nationwide, particularly in Maryland, California and Texas. The cause of the corrosion is yet to be determined.
Copper corrosion experts in the U.S. have issued reports that conclude that high temperatures and low pH can create corrosive conditions.
A report by American Water Works Association Research Foundation noted that the switch to chloramines seems to have caused problems in some municipalities but the report cautioned that all factors should be considered.
“We need to integrate all the information we have and look at corrosion control comprehensively to figure out the mechanisms that cause corrosion problems. Contributing factors can include lead, copper, iron, cement, pH, alkalinity and corrosion inhibitors. If we oversimplify, we get into trouble.”
Pipe corrosion is always an issue that needs to be addressed in water distribution systems or any other pipeline based distribution system.
“Water chemistry is not rocket science but it is chemistry - pH and temperature are just two of the thousands of things that interact,” explained Havinga.
“It appears to me that temperature seems to be a factor in other places - we’re in Alberta. We vary between two degrees in the winter to around 18 degrees Celcius in the summer. What I’ve seen is water has to be much warmer than that before we start seeing the corrosive effect of the chloramines.”
Water temperature effects pH (acidity) and a lower pH - which translates to higher acidity - can create a more corrosive atmosphere.
“We have pH control here at the water treatment plant and monitoring.”
More information is available on the NRSC website at www.nrsc.ca. Havinga also recommends the following resources: Health Canada, American Water Works Association, The U.S. Environmental Protection Agency and the Canadian Water Works Association.

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Meta-analysis examines intensive glycemic control, renal disease in patients ... - Science Codex

CHICAGO – A review of data from seven clinical trials suggests that intensive glucose control is associated with reduced risk of microalbuminuria and macroalbuminuria (conditions characterized by excessive levels of protein in the urine usually resulting from damage to the filtering units of the kidneys), according to a report published in the May 28 issue of Archives of Internal Medicine, a JAMA Network publication.

The meta-analysis also suggests the data "were inconclusive" that intensive glycemic control was related to reduced risk of significant clinical renal outcomes, such as doubling of the serum creatinine level, end-stage renal disease (ESRD) or death from renal disease during the trials' follow-up years.

Aggressive glycemic control has been hypothesized to prevent renal disease in patients with type 2 diabetes mellitus (T2DM), according to the study background.

"Our analysis demonstrates that, after 163,828 patient-years of follow-up in the seven studies examined, intensive glycemic control lessens albuminuria, but data are lacking for evidence of a benefit for clinically important renal end points," the authors note.

Steven G. Coca, D.O., M.S., of Yale University, New Haven, Conn., and colleagues searched the available medical literature and evaluated seven randomized trials involving 28,065 adult patients.

Compared with conventional control, intensive glucose control was associated with reduced risk of microalbuminuria (risk ratio, 0.86) and macroalbuminuria (0.74), but not doubling of the serum creatinine level (1.06), ESRD (0.69) or death from renal disease (0.99), according to study results.

"Acknowledging the low incidence of clinical renal outcomes coupled with the apparent lack of convincing benefit of intensive glycemic control to prevent CKD (chronic kidney disease) and ESRD in patients with newly diagnosed or existing T2DM, there is little compelling reason to initiate intensive glycemic control in midstage of the disease with the aim of preventing renal failure," the authors conclude.

(Arch Intern Med. 2012;172[10]:761-769. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor's Note: One author chairs a scientific advisory board for United Healthcare and is supported by a grant from the National Heart, Lung and Blood Institute and is the recipient of a research grant from Medtronic, Inc., through Yale University. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Invited Commentary: Understanding Intensive Diabetes Therapy

In an invited commentary, David M. Nathan, M.D., of Massachusetts General Hospital, Harvard Medical School, Boston, writes: "The studies included in the meta-analysis by Coca et al, with the possible exception of the UKPDS [UK Prospective Diabetes Study Group] long-term follow-up, were far too brief to address the effects of intensive therapy on end-stage renal disease. Their short duration and low absolute rates of severe renal outcomes, acknowledged by the authors, preclude such an analysis."

"Although implementing intensive therapy is difficult and imposes burden and expense, all of the primary data continue to support its long-term benefit," Nathan concludes.

(Arch Intern Med. 2012:172[10]:769-770. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Invited Commentary: Prioritizing Type 2 Diabetes Treatments

In an invited commentary, Karen L. Margolis, M.D., M.P.H., and Patrick J. O'Connor, M.D., M.A., M.P.H., of HealthPartners Research Foundation, Minneapolis, Minn., write: "The analyses presented by Coca et al demonstrate the lack of evidence that intensive glycemic control reduces the kinds of advanced complications of major concern to patients, such as renal failure."

"We conclude that for many patients with T2DM, the potential benefits of multidrug intensive glucose control regimens, which are only marginally supported by current evidence, must be weighed against the potential risks of such therapy (including hypoglycemia and possible increased mortality risks) as well as the potentially larger benefits of focusing clinical attention on other domains, such as blood pressure lowering, lipid control and smoking cessation," they conclude.

(Arch Intern Med. 2012:172[10]:770-772. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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