HemoDoc, From Doctor to Patient

Altruistic Donor Leads 60 Person Transplant Chain

By Peter Laird, MD

Altruistic renal donation is the underlying ethical framework for our current donor system in America. Many have prematurely declared altruism dead, but the news highlighted in the New York Times speaks loudly that we have yet to see the full power of a complete stranger willing to offer himself as a gift of life. In this case, it started a chain that will now benefit over thirty renal transplant recipients. His story is worth sharing and extolling the benefits of altruistic donation.

60 Lives, 30 Kidneys, All Linked

What made the domino chain of 60 operations possible was the willingness of a Good Samaritan, Mr. Ruzzamenti, to give the initial kidney, expecting nothing in return. Its momentum was then fueled by a mix of selflessness and self- interest among donors who gave a kidney to a stranger after learning they could not donate to a loved one because of incompatible blood types or antibodies. Their loved ones, in turn, were offered compatible kidneys as part of the exchange. . . 

Dr. Robert A. Montgomery, a pioneering transplant surgeon at Johns Hopkins Hospital, which was not involved in the chain, called it a “momentous feat” that demonstrated the potential for kidney exchanges to transform the field. “We are realizing the dream of extending the miracle of transplantation to thousands of additional patients each year,” he said.

Dr. Montgomery is correct that kidney chains have the potential of transforming the field, but they all begin with a complete stranger willing to give of himself for nothing in return but a scar. The miracle of altruistic donation should never become too frequent to celebrate each and every sacrifice instance. Thank you Mr. Ruzzamenti, you have done well.

Expanding the Renal Transplant Donor Pool: How Far is too Far?

By Peter Laird, MD

The renal transplant waiting list in the United States continues to increase exponentially while the available living and deceased donors stagnates behind this growing demand as seen in this graph from the US Department of Health and Human Services HRSA. News accounts of fathers and mothers giving kidneys to their children make headlines on a routine basis. The news of the so called "gift of life" from renal transplant supersedes any like acknowledgement of nocturnal home hemodialysis which has outcomes equal to cadaveric transplant. Yet, the march to procure even more kidneys is leading America down the path of ethical quagmires as the demand continues to expand the donor pools by ever loosening criteria. A little over a decade ago, the solution for many was the new expanded donor criteria (ECD) where donors previously excluded as "marginal" for HTN, age, diabetes, risk of infectious disease transmission and or malignancy as well as other criteria are now grouped into the ECD category. Most transplant centers now offer shorter waiting times for patients who will agree to the ECD criteria by an informed consent agreement.

Patients waiting for renal transplants faced with nearly ten years on the list now opt more frequently for expanded criteria donors making this the fastest growing segment of available renal donors. Another method of expanding the donor pool is a new criteria of death aside from the standard brain death criteria ushered in during the 1960's. In the 1990's, transplant centers began using donation by cardiac death (DCD) either by controlled DCD by withdrawing life sustaining care, or from uncontrolled emergency room cardiac deaths. Many ethicist have spoken out against this type of donation since the controlled donation by cardiac death occurs before brain death in some instances. Both ECD and DCD cadaveric transplants are increasing dramatically.

Expanded donor criteria may in the end prove more costly for several reasons. First, ECD grafts must undergo extensive testing to assure that they are free of infectious agents easily transmitted by transplant and other tests that add to the direct costs of each transplant. In addition, because ECD and DCD grafts fail to last as long as standard criteria donors (SCD), transplant patients can expect more complications and difficulties with a new organ adding not only to the burden of care, but also the burden of further pain and suffering that these failures bring about.

In my opinion, the most troublesome aspect of the expanded donor criteria is the inclusion of donors at high risk of transmissible agents including HIV and Hepatitis. Today, our testing cannot exclude all new cases of these viruses prior to the donor mounting an immune response to these agents which can take weeks in some cases. The feared transmission of HIV with this new criteria happened in 2007 leading many transplant surgeons to restrict the use of high infectious risk donors in their programs:

High Infectious risk donors: what are the risks and when are they too high?

RECENT FINDINGS: HRD organs are discarded at a higher rate than non-HRDs, and many surgeons have decreased the use of HRDs in response to a recent widely publicized case of HIV and hepatitis C virus (HCV) transmission. Special informed consent use can mitigate legal risk and might increase provider comfort with HRD utilization. Nucleic acid testing (NAT) mitigates infectious risk by decreasing the window period, particularly for HCV in which the risk of undetected window period infection decreases by an order of magnitude. Estimated risk of undetected window period HIV infection varies by HRD behavior category (range 0.035-4.9 per 10,000 donors when NAT is used), HCV risk is higher (range 0.027-32.4 per 10.000).

SUMMARY: Given long waiting times and high wait list mortality, organs from HRDs can be used to expand the organ supply. Estimates of HRD infectious risk can be used to guide patient and provider decision making.

Patients need to know and understand well all of the terms used in transplant programs today what the meaning of ECD and high risk donors (HRD) who include IV drug users, hemophiliacs, prostitution history, high risk sexual activity, exposure to HIV and jail sentencing.  The CDC considers all of these donors high risk and following testing in transplant recipients for HIV and Hepatitis is now standard transplant follow up. The tragedy of four patients hoping for the gift of life in 2007 to only find out a new fatal disease is part of their medical fight should make us stop and consider how far is too far to expand donor criteria. The even more tragic sense of this epic story is that few patients are counseled that nocturnal home hemodialysis has the same survival benefit as cadaveric transplant.

When seeking renal replacement treatment (RRT) options, the patient must realize that all treatment options are not equal especially when evaluating the use of extended donor criteria. The hope of "the gift of life" should not end tragically with a new disease added to their burden. For those that are willing to take these risks, then they must fully realize all of the criteria and all of the terms used. The "gift of life" may not be what it seems as time passes.

I believe that America needs to return to a more sensible realization that the supply of available kidneys will not keep up with the exponential increase in demand for kidneys.  I believe that the real hope for the majority of ESRD patients in America will be an expansion of home dialysis options. So far, the dialysis industry has done little to expand the pool of available home dialysis patients or reduce costs. It is time for a paradigm shift and return to optimal standards for all RRT options including renal transplant lest history record that we have expanded the criteria too far.

Troubling Trends with Blood Transfusions in Renal Transplant Candidates

By Peter Laird, MD

Renal transplant is considered the gold standard renal replacement treatment for American ESRD patients. The longest living survivors of renal transplant such as Nancy Spaeth and Dr. Robin Eady defy the odds stacked against any person in with severe renal failure. The median survival once on dialysis is only 36-38 months depending on whether patients choose conventional in-center hemodialysis or peritoneal dialysis. (here) For those such as Nancy Spaeth and Dr. Eady, their survival since the original days of Dr. Scribner's Seattle program through today came about by a combination of hemodialysis, PD and renal transplantation. For long term survivors, multiple modalities and often successive transplants is common.

Renal transplantation is complicated in patients with high levels of antibodies most often accumulated from multiple blood transfusions. The USRDS notes troubling trends in blood transfusions even in candidates for renal transplant where the transfusions can delay the hoped for transplant. 

Blood transfusions in kidney transplant candidates are common and associated with adverse outcomes

Surprisingly, there are no data regarding transfusion frequency, factors associated with transfusion administration in patients on the kidney transplant waiting list, or transfusion impact on graft and recipient outcomes. We used United States Renal Data System data to identify 43,025 patients added to the waiting list in 1999-2004 and followed through 2006 to assess the relative risk of post-listing transfusions. In 69,991 patients who underwent transplants during the same time period, we assessed the association between pre-transplant transfusions and level of panel-reactive antibody (PRA) at the time of transplant, and associations between PRA and patient outcomes. The three-yr cumulative incidence of transfusions was 26% for patients added to the waiting list in 1999, rising to 30% in 2004. Post-listing transfusions were associated with a 28% decreased likelihood of undergoing transplant, and a more than fourfold increased risk of death. There was a graded association between percent PRA at the time of transplant and adjusted risk of death-censored graft failure, death with function, and the combined event of graft failure and death. These data demonstrate that transfusions remain common and confirm the adverse association between transfusions and PRA, and high PRA and inferior graft and patient outcomes.

Delays while on the renal transplant list can be deadly, especially for those on conventional in-center hemodialysis or PD and not on daily home hemodialysis or nocturnal home hemodialysis which offers survival rivalling cadaveric transplant. (here and here) The issues of blood transfusions in dialysis patients is likely to become more prominent now that Hb parameters of dialysis patients has no minimum level. While the debate over the level of Hb needed for optimal quality of life remains unsettled except of course by patients themselves who know how they feel at each level, those with lower levels subject themselves to increased risks of transfusion under emergency blood loss. Dialysis patients have a high risk of bleeding from the stomach and intestines. The troubling trends that USRDS documents will continue.

Patients as in most matters medical must become their own best advocates. Dr. Scribner believed that dialysis patients should know more about their disease than their doctors.  The risks and benefits of EPO are well documented. Cardiovascular events and increased risk of cancer top the list. However, for someone contemplating renal transplant, the added burden of blood transfusions pushes the risk benefit analysis back into the direction of continued EPO use for those that need this support. I would hope that nephrologist would take these issues into consideration not only for those that have expressed interest in renal transplant, but also for those that may be a candidate in the future.

Renal Transplant Patients have poor Immune Response to Flu Vaccine

By Peter Laird, MD

Influenza is a serious illness especially in  patients with chronic illnesses such as CKD and ESRD. Influenza causes patients to have an increased susceptibility to pneumonia which is the most common cause of death in patients who have had influenza. The chief reason for giving the influenza vaccine is not so much to prevent the flu itself, but to prevent the subsequent pneumonia and its dire consequences. A recent study compared the immune response to the flu vaccine in dialysis patients and those post renal transplant. Not surprisingly, the renal transplant patients on anti-rejection medications had a poorer response than dialysis patients:

Influenza A/H1N1 vaccine in Patients Treated by Kidney Transplant or Dialysis: A Cohort Study

Results The GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P < 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P < 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P = 1, 1, and 0.39).

Conclusions The influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplantedversus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.

Despite the suboptimal immune response in the renal transplant population,  renal transplant patients should still  get vaccinated since they are at such high risk of all cause infections. Dialysis patients likewise should not decline influenza vaccination since the vaccine does elicit an adequate if not completely robust response to justify its continued use.  Although patients may develop fever, chills and muscle aches, with inactivated vaccine there is no risk of actually developing the flu itself. Some that develop these symptoms with the flu vaccine may actually mount a more vigorous immune response.

Single dose vials have no mercury preservatives but the multidose vials have small amounts of mercury. The data on whether this poses a long term health risk are conflicting, but anyone with concerns about this can simply ask for the single dose vial. When you examine all of the evidence, getting your flu shot each makes the most sense.

Is Peritoneal Dialysis the Optimal Choice for America?

By Peter Laird

In the last several weeks, there have been several medical journal reports on the benefits of peritoneal dialysis (PD) for patients and for the American ESRD program. Patients on PD have similar outcomes to patients treated with standard in-center hemodialysis at a much reduced cost to the tax payers funding the ESRD program.  Many are advocating that PD become the default dialysis modality of choice.

The Path Not Taken On Dialysis

If half the new dialysis patients in the U.S. chose PD over HD, Medicare could save more than $5 billion a year. The additional counseling needed to get to those rates might even jump-start the long overdue conversation about why so many people do so poorly once they’re on dialysis; why so many have failing kidneys in the first place; and what preventive measures can be taken to deal with this burgeoning public health fiasco.

The "news" that PD has similar outcomes to HD is not really a new report at all.  Similar outcomes have been documented for more than two decades. What is new according to the latest study is that the 5 year survival remained equal instead of dropping off after two years in prior reports. While this is good news for those that choose PD as their primary dialysis modality, the grim news is that the median survival for PD patients on average is only three years.

Similar Outcomes With Hemodialysis and Peritoneal Dialysis in Patients with End-Stage Renal Disease

Results  There was progressive attenuation in the higher risk fo death seen patients treated with PD in earlier cohorts; for the 2002-2004 cohort, there was no significant difference in the risk of death for HD and PD patients through 5 years of follow-up. THe median life expectancy of HD and PD patients was 38.4 and 36.6 months, respectively. Analysis in 8 subgroups based on age (<65 and  65 years), diabetic status and baselinecomorbidity (none and  1) showed greater improvement in surval among patients treated with PD relative to HD at all follow-up periods.

Once again, while this is good news, it is not the same level of improved survival that we see with the recent short daily hemodialysis report in the FHN, nor is it at the level of cadaveric transplant survival that we have seen with nocturnal hemodialysis on a daily basis that Pauly reported on in 2009 where median survival is greater than 10 years.

Survival among nocturnal home haemodialysis patients compared to kidney transplant recipients

Results. The total study population consisted of 177 NHD patients matched to 1062 DTX and LTX recipients (total 1239 patients) followed for a maximum of 12.4 years. During the follow-up period, the proportion of deaths among NHD, DTX and LTX patients was 14.7%, 14.3% and 8.5%, respectively (P = 0.006). We found no difference in the adjusted survival between NHD and DTX (HR 0.87, 95% CI 0.50–1.51; NHD reference group), while LTX survival was better (HR 0.51, 95% CI 0.28–0.91).

Conclusions. These results indicate that NHD and DTX survival is comparable, and suggest that this intensive dialysis modality may be a bridge to transplantation or even a suitable alternative in the absence of LTX in the current era of growing transplant waiting lists and organ shortage.

In addition, home hemodialysis compares very favorably with home PD for cost savings benefits when the direct and indirect costs of care such as preventable hospitalizations is utilized in the analysis.

Cost savings of home nocturnal versus conventional in-center hemodialysis

HNHD provides about three times as many treatment hours at nearly a one-fifth lower cost, with savings evident even when only program and funding-specific costs are considered.

Dr. Victoria Kumar, et al, at Kaiser Permanente in Southern California reported a direct comparison of observational results of their home PD and home SDHD patients showing a significant benefit to the home hemodialysis cohort in reduced hospitalizations and over all complication rates.

Costs of Home Hemodialysis Offset by Better Health, Fewer Hospitalizations

Daily hemodialysis administered in patients’ homes is associated with better health outcomes compared with peritoneal dialysis, according to an article in the October issue of the American Journal of Kidney Diseases, the official journal of the National Kidney Foundation. . .

Dr. Kumar’s group treated the 22 patients in the daily hemodialysis group and the 64 in the peritoneal dialysis group for at least 6 months between 2003 and 2007. The groups were comparable in age, the number of patients with diabetes, and causes of kidney failure..

Despite these similarities, patients treated by peritoneal dialysis spent nearly twice as many days each year in the hospital compared with patients treated with home hemodialysis (average 5.6 days/patient-year versus 3.3 days/patient-year).

Those treated by daily home hemodialysis were also able to reduce the number of medications required to keep their blood pressure under control, and had better nutritional status than they did prior to starting treatment, as shown by higher serum albumin levels.

In addition, there are certain patient groups who do substantially worse on PD than on HD.  These include morbidly obese patients and patients with CHF, which is the number one complication noted in hospitalized ESRD patients.

Impact of dialysis modality on survival of new ESRD patients with congestive heart failure in the United States

Results The overall prevalence of CHF was 33% at ESRD initiation. There were 27,149 deaths (25.2%), 5423 transplants (5%), and 3753 (3.5%) patients lost to follow-up over 2 years. Adjusted mortality risks were significantly higher for patients with CHF treated with peritoneal dialysis than hemodialysis [diabetics, relative risk (RR) = 1.30, 95% confidence interval (CI) 1.20 to 1.41; nondiabetics, RR = 1.24, 95% CI 1.14 to 1.35]. Among patients without CHF, adjusted mortality risk were higher only for diabetic patients treated with peritoneal dialysis compared with hemodialysis (RR = 1.11, 95% CI 1.02 to 1.21) while nondiabetics had similar survival on peritoneal dialysis or hemodialysis (RR = 0.97, 95% CI 0.91 to 1.04).

Conclusion New ESRD patients with a clinical history of CHF experienced poorer survival when treated with peritoneal dialysis compared with hemodialysis. These data suggest that peritoneal dialysis may not be the optimal choice for new ESRD patients with CHF perhaps through impaired volume regulation and worsening cardiomyopathy.

When cost savings and survival benefits are fitted into the same discussion, home nocturnal hemodialysis is very comparable to PD for overall costs at the same time it is also very comparable to cadaveric renal transplant survival. Looking at the issue of what should be America's default dialysis treatment modality when patients are not able to do a preemptive transplant, in my opinion, that default standard of care should be first line home nocturnal hemodialysis.

Home nocturnal hemodialysis is not the treatment of choice for all patients due to underlying factors including the ability to self cannulate and having supportive family resources available, but as many as 30% of patients starting dialysis could utilize this life saving technology by many estimates. New Zealand has over 25% of its ESRD population on home hemodialysis as proof that high numbers of people can be helped in this manner.

When comparing all aspects of renal replacement therapy, although PD is an excellent and right choice for many, using it as the default standard of care in America is not going to correct our high mortality rate that home nocturnal dialysis does address at a significant cost savings to the system and significant health benefits to the patient. In my opinion, home, nocturnal hemodialysis is the firstline treatment that should be the gold standard of care offered to all eligible patients at the onset of renal replacement therapy for ESRD when transplant is not an immediate option.

Transplant Surgeons Changed Practice after HIV/HCV Transmission Case

By Peter Laird, MD

In 2007, the news that four patients received HIV/HCV contaminated tissues from a high risk organ donor rocked the transplant medical community which still affects decisions on donors today.  One of the patients who received a kidney transplant sued because she was not informed that the donor was a high risk patient.  Unfortunately, even though the donors tests were negative for HIV/HCV at the time of donation, his high risk behaviour as a 38 year old gay man led to an undetected infection which he passed on to the recipients of his organs. The publicity surrounding this case still governs transplant practices among many of the nations transplant surgeons.

Transplant Docs Change Practice After HIV/HCV Case

In 2007, transplants from a single high-risk donor transmitted both HIV and hepatitis C to four organ recipients, despite negative antibody tests before the procedures. The case made national headlines, Segev and colleagues noted, and sparked a debate about informed consent and testing for HIV. . .

To see what effect the case had, Segev and colleagues surveyed transplant surgeons across the U.S. between Jan. 17, 2008, and April 15, 2008, getting responses from 422 surgeons in current practice.

Of those, they found, 297 reported using high-risk donors, but 31.6% changed practice after the 2007 event. Specifically:

• 41.7% of those who changed decreased use of high-risk donors.
• 34.5% increased the emphasis on informed consent.
• 16.7% increased use of nucleic acid testing.
• 6% implemented a formal policy.

In this specific case, CDC guidelines on high risk donors were over looked when the patients were not informed of the donors high risk status.  The patient that sued after her renal transplant had previously turned down an earlier transplant because the donor was likewise high risk.  In this case, the transplant surgeons were all aware of the donor's status but did not pass that information on to the patients.  All four recipients later turned positive for both Hep C and HIV, the first such documented transmission in 20 years.

Transplant Patient a 'Mess" after HIV Diagnosis

CHICAGO — A woman in her 30s who is one of the four organ transplant patients infected with HIV and hepatitis was not told that the infected donor was high risk, and had previously rejected another donor "because of his lifestyle," her attorney said.

Attorney Thomas Demetrio filed a petition Thursday in Cook County Circuit Court on behalf of the woman, asking officials to keep a hospital and an organ procurement center from destroying or altering any records involving the donation.

"She's really a mess right now," Demetrio said of the Chicago-area woman. "She's still in shock."

In the rush to increase organ donations, taking shortcuts on any aspect of this care is paid in the end analysis by the unfortunate patients who learned that their life saving transplant gave them two deadly viruses at the same time.   The current caution on the part of transplant surgeons who have changed their practice standards because of this case is prudent and should be encouraged. Throwing caution to the wind is a losing strategy in any situation, this one turned out to be tragic.

Learning by Osmosis in Renal Dialysis Centers - Where is the Informed Consent?

By Peter Laird, MD

Renal replacement options include transplant but many patients who suffer from anemia while on dialysis have had blood transfusions that produce antibodies that reduce the possibility of ever having a successful transplant. However, a serendipitous insight by a Cedar Sinai doctor led to the current treatment protocol with IVIG. I came across an interesting video detailing one patient's story of how IVIG has helped her and the laymen account of IVIG that is actually quite informative by her mother even if she does get a few details not quite right.  It is also quite informative about in-center dialysis and what happens to an other wise healthy young woman who only recieved 3 hours, thrice weekly dialysis.  No wonder people have such a negative view of dialysis:

 

The story of saving the government billions of dollars and the fact that they only pay for meds for three years after a transplant I am sure are part of the reason for such a push towards renal transplant by the government.  Thankfully, IVIG now offers patients with high PRA the chance to go forward with "the gift of life" for a transplant.  Medscape had a recent review on how IVIG works in this situation.

Intravenous Gammaglobulin (IVIG): Clinical Use of IVIG in Kidney Transplantation

Data from our group and others suggest that IVIG therapy given to highly sensitized patients results in reduced allosensitization, reduced ischemia-reperfusion injuries, fewer acute rejection episodes and higher successful long-term allograft outcomes for cardiac and renal allograft recipients. We and others have confirmed that pre-treatment with IVIG results in reductions of anti-HLA antibodies, and is effective in treatment of allograft rejection episodes.

Unfortunately, the manner in which the patient in the video above heard about plasmapharesis was from a concerned nurse and she then did an internet search finally finding a doctor who stated, I have something better than plasmapharesis, I have IVIG. It is not simply optimal dialysis that patients do not hear about in dialysis units as apparently neither the mother or the patient were ever aware in this video, but also the different transplant options as well.  This patient had only 3 hours thrice weekly dialysis which by many studies does place her at high risk of complications and death as was rightly stated. The issue of informed consent for dialysis patients is well documented for the lack thereof as this case all to well demonstrates.

Learning by "osmosis" about the type of treatment that ultimately gave this patient hope is an all too common story in the dialysis industry. (InformedConsentRLockridge.pdf) IVIG is one of the true wonder drugs of medicine used for many autoimmune diseases that is now one reason more patients are now candidates for this renal replacement option, but it is a quite sad commentary that patients have to luck upon information of this type on their own in many cases.  Sadly, the patient in this video has an undo impression of dialysis from her individual undertreatment.  I would hope patients in the future will not go through her poor treatment, but sadly we have not yet addressed optimal dialysis issues in-center in this country.  We still have much work ahead of us.