Biomarkers for Cancer of the Kidney

Medscape is reporting new research points to several biomarkers (molecules that can be tested for in relationship to a disease) have been found which may predict the odds of survival in renal cell cancer.

The data reviewed is derived from the TARGET study Treatment Approaches in Renal Cancer Global Evaluation Trial.

"Carol Peña, PhD, associate director for clinical cancer biomarkers at Bayer HealthCare Pharmaceuticals, and colleagues conducted an analysis on a subset of the patients enrolled in TARGET to evaluate the relation between biomarker levels and outcomes.

Sleep apnea and Transplantation

Health day has reported that patients with sleep apnoea are at increased risk of high blood pressure, heart disease and stroke. Excerpt below

Timt775

"Kidney transplant patients with sleep apnea are at increased risk for high blood pressure, heart disease and stroke, Hungarian researchers say.

Sirolimus for Polycystic Kidney Disease

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New treatment options for polycystic kidney disease do not come along very often. The nature of the disease is such that treatment is inherently difficult as the pathophysiology is incompletely understood.

Despite that various methods are currently being investigated. One such is the drug sirolimus, which  has been mentioned before. More recently however a pilot study performed in adult polycystic kidney disease patients has added further hope that sirolimus may one day be used routinely in this disease.

Preventing Repeat Hospitalization in Dialysis

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Dialysis patients are known to have greater rates of hospitalization as compared to other patients. The cause for this is believed to be multifactorial. The present study by Chan et. al. looks at possible factors which may reduces the rate of hospitalization of dialysis patients after an initial admission.

The population studied was quite large with over 126,000 dialysis patients involved. The premise of the study was that the management strategy at the time of first discharge was a significant contributor to the time to readmission of the patient.  The Primary outcome of the investigation was therefore readmission of the patient within 30 days.

What is Intradialytic hypertension?

Peng

High blood pressure after dialysis or towards the end of dialysis is a nuisance problem that just seems to keep coming up in every dialysis unit. Frequently patients are kept for observation or admitted which increases the cost of giving care. It can also be quite frustrating to treat. This phenomenon is known as intradialytic hypertension and may require more than loading more and more medication onto the patients chart.

Beneficial Effect of Coffee in Dialysis Patients

Julius Schorzman

Coffee is arguably the most popular beverage worldwide yet its impact on renal disease is largely unknown and its effect on dialysis patients is even more obscure.

There have been many claims of medicinal or health benefits for drinking coffee. Studies have shown apparent reductions in the risks of:

• Alzheimer's disease


• Parkinson's disease


• Heart disease


• Diabetes mellitus type 2


• Cirrhosis of the liver


• Gout.

Recently a small study has reported that dialysis patients who drink coffee were more likely to have lower cholesterol. Of the 30 patients studied 26 were on peritoneal dialysis and only 4 were on hemodialysis.

The patients were divided into two groups. Group I patients drank 1-3 cups of coffee per day for 2 years prior to the study. The second group consisted of patients who self reported no intake of caffeinated coffee over the same period.

The investigators reported that serum lipid profile, anthropometric and bioimpedance measurements, and laboratory indices of nutrition and inflammation status were examined for both groups.

Patients in Group I had higher levels of HDL and lower LDL when compared to group II. Patients in group I were also found to have lower waist and hip circumferences, a lower waist/height ratio, a lower fat body mass, and a higher lean body mass as a percentage of total body mass.

These finding when taken together suggest that dialysis patients who drink coffee may be more likely to have a more favorable lipid profile as well as higher lean body mass and a lower body mass index.

ABSTRACT BELOW:

We checked whether dialysis patients who drink coffee might have a serum lipid profile different from that of nondrinkers of coffee. The study was performed in 30 patients (26 on peritoneal dialysis, 4 on hemodialysis). Group I included patients who drank 1 - 3 cups of coffee daily (140 - 420 mg caffeine) for at least 2 years before the study [n = 11; dialysis vintage: 29.1 months (range: 8.7 - 59.6 months); age: 56.0 +/- 14.6 years]. Group II consisted of patients who said that they were nondrinkers of caffeinated coffee [n = 19; dialysis vintage: 15.2 months (range: 6.3 - 45.4 months); age: 56.3 +/- 19.8 years). Serum lipid profile, anthropometric and bioimpedance measurements, and laboratory indices of nutrition and inflammation status were examined. Compared with group II, group I showed higher serum high-density lipoprotein (HDL) cholesterol (45.1 +/- 12.8 mg/dL vs. 37.7 +/- 6.6 mg/dL, p = 0.045) and lower low-density lipoprotein (LDL) cholesterol (104.7 +/- 15.7 mg/dL vs. 139.0 +/- 41.8 mg/dL, p = 0.007). Other examined parameters did not differ significantly between the groups, with the exception of serum albumin [4.0 g/dL (range: 3.1 - 4.3 g/dL) in group I vs. 3.3 g/dL (range: 2.9 - 4.4 g/dL) in group II, p = 0.020]. Adjustment for age and sex additionally showed differences in bioimpedance and anthropometric measurements. Compared with group II, group I showed lower waist and hip circumferences, a lower waist/height ratio, a lower fat body mass, and a higher lean body mass as a percentage of total body mass. When adjustments were made for age, sex, and fat body mass, differences in lipid profile were nonsignificant. In the overall group, a correlation was seen between lean body mass and total cholesterol (r = -0.487, p = 0.006). Lower LDL and higher HDL serum cholesterol may occur in dialyzed patients who drink coffee not only because of the direct influence of coffee ingredients on serum lipid profile, but mainly because of a more favorable body composition and better protein nutrition in coffee drinkers.

New Dialysis Modality Daily OL-HDF

CVVHD A DIAGRAM AUTHOR UNKNOWN.

A study published in the november issue of Nephrology Dialysis and Transplantation has reported that growth retardation in pediatric dialysis patients (the propensity for children to not achieve normal height) can be improved by a type of dialysis known as daily on line hemodiafiltration (DOLHDF).

OLDHDF is a treatment modality that combines two types of treatment into one. Standard dialysis which utilizes diffusion of solutes from within the blood stream across a dialysis membrane and into the dialysate is combined with toxin removal via a process call ultrafiltration. Many dialysis patients will already by familiar with the process of ultrafiltration, sometimes painfully so as lots of ultrafiltration is associated with cramping on dialysis.

Ultrafiltration is the process of filtering water from the patients blood stream via creation of a negative pressure gradient down which water will naturally flow. The process of ultrafiltration is not purely removal of water however as whatever is dissolved in the water is dragged along with it across the dialysis membrane and out of the blood. The size of the pores in the dialyser determines what stays behind and what is lost. This type of ultrafiltration present in the daily treatment of many patients on dialysis is not particularly effective at clearing toxins from the blood and is primarily used for volume control in the treatment of fluid overload.

By improving the efficiency of the process by adding an additional solution into the dialyser along with the blood more toxins are forced across the dialyser membrane and pure dialysis with ultrafiltration becomes hemodiafiltration. The additional solution added to the dialyser has to be as sterile as IV fluid which has traditionally kept this modality confined to the ICU. But new methods have recently become available that allows for the generation of the replacement solution as needed in a sterile manner. This process has served to reduce the cost of the modality and has allowed studies such as the one outlined hear to be possible.

The efficiencies of dialysis via this modality is superb and when combined with daily dosing may be responsible for the good outcomes outlined in the abstract below.



BACKGROUND:

In children, growth can be used as a measurable parameter of adequate nutrition and dialysis dose. Despite daily administration of recombinant human growth hormone (rhGH), growth retardation remains a frequent problem in children on chronic dialysis. Therefore, we performed an observational prospective non-randomized study of children on in-centre daily on line haemodiafiltration (D-OL-HDF) dialysis with the aim of promoting growth. Patients and methods. Mean age at the start of the study was 8 years and 3 months, and all children had been receiving rhGH treatment for >12 months before enrolment. Mean follow-up time on D-OL-HDF was 20.5 +/- 8 months (range, 11-39 months). Renal residual function was either <3 mL/min/1.73 m(2) or anuric. Vascular access was a fistula (13/15) or a central venous catheter (2/15). Dialysis was delivered daily, six days a week in 3 hourly sessions (18 h/week), in a predilution OL-HDF mode, allowing a high convective volume (18 to 27 L/m(2) body surface area per session), Kt/V(urea) on line measured at least 1.4 per session. RESULTS: Mean growth velocity increased from 3.8 +/- 1.1 cm/year at inclusion to 14.3 +/- 3.8 cm/year during the first year of D-OL-HDF, resulting in a change in height standard deviation score (SDS) over the follow-up period from -1.5 +/- 0.3 SDS to +0.2 +/- 1.1 SDS. Increase in body mass was also noted without impaired control of blood pressure. Time-average deviation for urea (TAD(urea)) was low at 2.5 +/- 0.4 as was TAD(bicarbonate) due to the normal pre and post dialysis bicarbonate levels, respectively, 23.6 +/- 0.5 mmol/L and 26.6 +/- 0.5 mmol/L. The absence of any dietary restrictions permitted a mean protein diet intake (PDI) of 2.5 +/- 0.2 g/kg/day (PDI measured from a 3-day diet survey), contrasting with a mean normalized protein nitrogen appearance (nPNA) of 1.53 +/- 0.12 g/kg/day (nPNA calculated from urea dialytic kinetic). A low C-reactive protein was noted in 13/15 children, and mean beta(2) microglobulin was low, 15.3 +/- 0.3.3 mg/L.

CONCLUSIONS:

Daily OL-HDF promotes catch-up growth in children despite being on chronic dialysis. This catch-up growth if continued, should allow the children to reach their mid-parental target height in the future. It could be speculated that the improved response to rhGH is the result of several combined factors conducting to less malnutrition and to less cachexia.

Latest Kidney News: Post ASN Round Up.

 Some rights reserved by Michael in San Diego, California

Medwire is reporting improved survival among Finnish patients with Type 2 diabetes mellitus on dialysis. This report is based on a study done 314 dialysis patients in Finland published online in the journal nephrology dialysis and transplantation.

The reason for improved survival is believed to be due to improvement in diabetes care over the years studied, which were 1995 to 2005. Elements of improved care which have been cited include better blood pressure control with newer drugs as well as adherence to modern protocols concerning the control of blood glucose in diabetes.

Medpage is reporting that the use of EPO has been trending upwards for the last few years, supporting data has been recently published in abstract and presented at the ASN this year. However the data captured did not include years after the outcome of several negative trials for the use of EPO in the treatment of anemia in CKD. Trials such as CHOIR and CREATE or more recently TREAT. The importance of this abstract lies in the insight that it may give into the prescribing patterns of doctors at baseline. Not surprisingly it seems that the general perception of doctors had been more EPO is better to maintain Hb in as normal away as possible. Given the current evidence that suggests that this may increase stroke related morbidity and mortality a huge amount of effort will have to be invested in education to alter the thought processes in this counter intuitive area of medicine.

It is however good news that in one large nephrology practice in Delaware physicians altered their practice post CREATE and CHOIR sufficiently to see a considerable decline in the use of EPO and the reduction of mean Hemoglobin levels among patients. It is not yet certain if these changes will lead to any increase in survival or decrease in cardiovascular events.

The idea that higher doses of EPO are associated with poorer outcomes has yet to be rigorously tested although potential mechanisms may exist to explain this. Recently as published in Medpage today the dose of EPO required to meet target hemoglobin has been found to be lower in patients on nocturnal hemodialysis. This is a further benefit of a dialysis modality that can be considered the next best thing to transplantation.

Darbepoetin alfa is unsafe as well?

Redbloodcells.jpg: hematologist

Darbepoetin alfa is a an erythropoesis stimulating agent marketed under the name Aranesp by AMGEN. It is used for the treatment of anemia ( a lower than normal blood count) as a consequence of renal failure or cancer.

The use of other similar agents has been questioned over the last 2 to 3 years due to studies in both patients with cancer as well as patients with CKD and on dialysis, which demonstrated an increased risk of mortality, which was due in large part to cardiovascular disease particularly stroke.

The debates that occurred due to the outcome of these studies were legendary, due to the counterintuitive findings that suggested treatment to a target normal Hb was dangerous. Yet some learned individuals maintained that the issue was less the target Hb and more the dose of EPO and time required to achieve the target. With higher doses and more steep rises in Hb associated with increased mortality as suggested by secondary analysis of some rather large studies.

The latest study to tackle this prickly topic hails from the New England Journal of Medicine and the conclusion of the investigators of the TREAT study are as follows:

"The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits."

This is quite a blow for proponents of EPO which I must admit includes the vast majority of nephrologists. Deep down at the gut level it just makes sense that replacing a missing hormone such as erythropoetin and returning the blood count to normal should be a good thing. We can identify very specific negative things that occur when the blood count is low we know by observation that quality of life suffers as well as the function of all organs.

Previous studies have demonstrated the use of Aranesp was..

1. More costly than other similar agents.
2. Safe...? infact Amgen the company developing Aranesp released preliminary results of the TREAT study. One of the Headlines went like this "Amgen Announces Top-Line Results Of Trial To Reduce Cardiovascular Events With Aranesp(R) Therapy (TREAT) In CKD Patients With Type-2 Diabetes" Evidently these top line results were that there was no reduction or increased risk of cardiovascular events at that time. Hardly what I would consider a top of the line result.

Despite logic and gut feelings, the writing on the wall is getting very hard to ignore. We should therefore be very cautious and inform our patients that this is still an area under investigation.