The results of the ACCOMPLISH trial as reported in the LANCET may change the above approach. From the available abstract of the trial;

“ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12·5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1·73 m2or need for dialysis). Analysis was by intention to treat (ITT).”

Of note this is a relatively large trial with a mean follow up of 2.9 years which is adequate. The trial was sponsored by Novartis a large company that manufactures Lotrel a brand of amlodipine. Novartis is one of the largest pharmaceutical companies in the world with annual sales of 42.6 billion USD. The three biggest selling drugs from its pharmaceutical division are DIOVAN, LOTREL and GLEEVEC.

Although a certain degree of bias is suggested by this I would also like to point out that the drug DIOVAN which is one of the major products of the company would also be negatively impacted by the results of this trial. The findings of the study will have to be debated in the scientific literature, however as it stands this interesting finding should give many food for thought when contemplating first line therapy for hypertension.

In my personal experience amlodipine has been a very effective drug at lowering blood pressure however in the past I have tried to avoid using it as first line in those with kidney disease due a theoretical possibility of reducing renal survival and the recommendations of the JNC.

However this study has gone a long way in putting any fears I may have had at rest because at the very least it is not inferior to the diuretic used.

The question does remain though is HCTZ as good an antihypertensive as chlorthalidone and why wasn’t chlorthalidone used in this study. This would have allowed the results to be more directly compared with the ALLHAT study one of the most significant studies in hypertension.

Diuretic or Calcium Channel Blocker for CKD is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.

A study published in the Journal of the American Society of Nephrology has suggested a link between kidney disease and long term steroid use. Body builders who utilize steroid for the purposes of increased training performance seem to be the population at risk. The body builders were confirmed to develop a type of kidney disease known as focal and segmental glomerulosclerosis also known as FSGS. Although categorized as scarring of the kidney and known to occur as a final pathway of injury in numerous

(image from wikipedia.org)

other glomerular diseases FSGS can also be its own unique disease in which case it can be very difficult to treat. Requiring in most cases high doses of …..steroids, although of a different variety than those used in the body builders.

FSGS has also been implicated in obesity related kidney disease and the metabolic syndrome. In these cases the natural increase in size of the filtration apparatus of the kidney that occurs because of increased body mass goes awry and leads eventually to scarring of the filter known as the glomerulus.

If anabolic steroid use is truly associated with FSGS  then we would expect to see patients who are larger having the worst cases, which seems to be the case in this study.

Steroids and Kidney Disease is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.

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.

“We looked at biomarkers for prognosis of RCC in the absence of treatment and also looked at biomarkers that predict response to sorafenib,” said Dr. Peña.

The bio markers studied include

VEGF

soluble VEGF receptor (VEGFR)-2

CAIX

TIMP-1

p21 Ras

The above bio markers are all products of genes that may be turned on or inappropriately regulated to cause cancer or promote its growth.

The study although small is worth mentioning to highlight that the promise of molecular medicince is indeed bearing fruit that will impact the day to day management of patients.

Image from the national library of medicine showing microscopic detail of clear cell carcinoma a variant of renal cell carcinoma.

Biomarkers for Cancer of the Kidney is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.

Break the cycle of sleep apnoea http://en.wikipedia.org/wiki/File:Osa_cycle.gif

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

The study of 100 kidney transplant recipients found that 25 percent had moderate to severe sleep apnea, a rate similar to that seen in kidney disease patients on dialysis awaiting a transplant. This means that both types of patients who have the breathing-related sleep disorder should be considered at high risk for serious heart-related complications, the study authors noted.

Transplant recipients with sleep apnea were more than twice as likely as those without the syndrome to be taking three or more anti-hypertensive drugs, but still had higher blood pressure than those without the sleep disorder. Obesity increased a transplant patient’s risk of developing sleep apnea.

When the researchers calculated risk scores, they found that kidney disease patients with sleep apnea were twice as likely to suffer heart disease or stroke than those without sleep apnea.”

Sleep apnea is a common disease which occurs particularly in obese patients where the windpipe closes during sleep producing periods of no respiration or apnea and subsequent hypoxia ( low blood oxygen levels) this occurs numerous times during the night, the patient usually snores as well. Patients have periodic movements of the feet as if they are trying to move during episodes. Numerous episodes disturb the normal sleep pattern and leads to day time somnolence. This has also been associated with changes in mood and hypertension. The present study has shown an association between sleep apnea and hypertension that is already known. It is however interesting that it occurs in both transplant patients and patients awaiting kidney transplantation in the numbers quoted. That indicates a prevalence that I have never suspected. There may be significant gains to be had by screening these populations for sleep apnea. The treatment of sleep apnea may result in much easier to control blood pressure and improvement in outcome of chronic kidney disease and heart failure.

Sleep apnea and Transplantation is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.

The effect of the drug sirolimus on development and growth of cysts was investigated over 6 consecutive months in 8 patients. Patients also received angiotensin receptor blockers which are considered standard therapy in kidney disease. A control group that consisted of another 8 patients were assigned to angiotensin receptor blocker alone.

Unfortunatley sirolimus is not an innocuous drug its use results in suppression of the native immune system resulting increased risk of infection and negative metabolic effects. There is however a good history of safety in transplantation where it is used primarily.

The use of sirolimus will require close monitoring for possible infectious complications if it is to provide an overall benefit. Patients with adult polycystic kidney disease already have an increased risk of infection and these may include infection of cysts and pyelonephritis which can cause sepsis. An increase in the rate of these infections would have a negative effect on survival of the kidney. The drug may therefore prove to have what is called a narrow therapeutic index for treatment of patients with ADPKD.

The overall result of this small study showed a beneficial effect of sirolimus in patients with ADPKD however please note there was a significant rate of infectious complication. A larger study would have been able to tell us whether the benefits of sirolimus administration truly outweigh the risks for LONG term treatment of patients with polycystic kidney disease.

ABSTRACT below.

A pilot study was performed on adult polycystic kidney disease (PCKD) patients to examine the effects of the anti-proliferative mammalian target of rapamycin inhibitor sirolimus on the growth of renal cysts. Eight consecutive PCKD patients were given sirolimus (1 mg/d PO) for 6 consecutive months, in addition to an angiotensin receptor blocker (ARB), namely telmisartan. Another 8 PCKD patients served as a control group given only telmisartan. All PCKD patients had a serum creatinine value <2 mg/dL with a negative urine culture before enrollment. All patients were diagnosed by renal magnetic resonance imaging (MRI) to measure renal volumes. After a 6-month follow-up, patients were rescanned to remeasure the MRI volumes. Renal function was stable in 5/8 subjects in the sirolimus group, improved in 2 cases, and worsened in 1 with an increase of serum creatinine to >2 mg/dL resulting in his withdrawal after 5 months of follow-up. In contrast, the serum creatinine value was stable in 3 control group subjects, worsen in 3, and improved in 2. Four patients in the sirolimus group experienced infectious complications, namely, urinary tract infections (UTI) in 2 which were treated with antibiotics, and monilial pharyngitis in 2, who were treated and cured with a topical antifungal. In the control group, only 2 developed and were treated for UTIs. Hematologic tests were normal in all patients. There was an insignificant rise in kidney volume as measured by MRI in the sirolimus group (2845 vs 3221 mL after 6 months; P = NS) compared with a significant increase in the control group (2667 vs 3590 mL after 6 months; P < .05). We concluded that sirolimus, in addition to an ARB, might be beneficial for PCKD patients who present early in their illness.

Sirolimus for Polycystic Kidney Disease is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.

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.

Based on the abstract the study can be summarized as follows:

Compared to pre-hospitalization values, the levels of hemoglobin, albumin, phosphorus, calcium, and parathyroid hormone and weight were significantly decreased after hospitalization.

Using statistical models, those patients whose hemoglobin was monitored within the first 7 days after discharge, followed by modification of their erythropoietin dose had a significantly reduced risk for repeat-hospitalization when compared to the patients whose hemoglobin was not checked, nor was the dose of erythropoietin changed.

Similarly, administration of vitamin D within  7 days following discharge was significantly associated with reduced repeat hospitalization when compared to patients on no vitamin D.

Therefore, it appears that immediate re-evaluation of anemia management orders and resumption of vitamin D soon after discharge may be an effective way to reduce repeat hospitalization.

What can we take home from this study?

Hospitalization results in alteration of levels of important electrolytes and molecules important to the pathophysiology of renal disease. The diagnosis or reason for admission may have a significant impact in this respect and hence the specific management of the patient post admission should vary greatly.

It is interesting that by simply focusing on management of anemia and vitamin D metabolism one is capable of reducing re-hospitalization in patients across the board regardless of diagnosis or reason for admission.

image:

Preventing Repeat Hospitalization in Dialysis is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.

blood pressure

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.

Intradialytic hypertension can be defined as an average pre to post hemodialysis Systolic Blood Pressure elevation of >10 mmhg for more than 4/6 of the last dialysis treatment sessions according to investigators currently delving into the possible causative mechanism of this difficult area of patient care. Many patients with this problem are overhydrated and are usually above their dry weight, in my experience these are the easiest to be managed. The problem patients are those who appear to be at their dry weight and are resistant to further ultrafiltration despite still fulfilling the criteria for the diagnosis as outline above.

The cause of intradialytic hypertension in such patients may be due to excessive sympathetic nerve discharge, the body believes that there is a relative lack of fluid within the vascular compartment hence increased sympathetic discharge. This presumably results in increased stiffness of blood vessels. The result of which is decreased compliance and higher blood pressure. This theory s currently the subject of an ongoing study. Other possible causes of this condition include high blood calcium or high calcium in the dialysate being used, decreased blood potassium, subclinical fluid overload, increased dietary salt intake, inadequate salt removal on dialysis, recurrent administration of saline during dialysis.

Intradialytic hypertension is important because it is.

1. Common affecting up to 15% of hemodialysis patients.
2. Is associated with higher rates of hospitalization.
3. Is associated with decreased survival on dialysis.
4. Is commonly ignored.

Prevention & treatment.

Careful attention to dry weight is all well and good but sometimes it can be difficult to know if the patient is truly at the dry weight. This study suggests that use of a body composition monitor to determine percentage fat muscle and water may be able to assist in titrating a patient to the correct dry weight. Such a tool may be very useful in the treatment of patients with intradialytic hypertension.

What is Intradialytic hypertension? is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.

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

From http://en.wikipedia.org/wiki/File:Main_side_effects_of_Caffeine.png

• 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.

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http://crrtinfo.googlepages.com/Hemodialysis_schematic.gif/Hemodialysis_schematic-large.jpg

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.

New Dialysis Modality Daily OL-HDF is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.

Latest Kidney News

image:

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.

Latest Kidney News: Post ASN Round Up. is a post from: All Kidney News Click to subscribe to our RSS Feed and keep up-to-date on the latest Kidney News.