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by Meguid El Nahas - Wednesday, 30 May 2012, 10:38 AM
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Survival in Daily Home Hemodialysis and Matched Thrice-Weekly In-Center Hemodialysis Patients

Eric D. Weinhandl,* Jiannong Liu,* David T. Gilbertson,* Thomas J. Arneson,* and Allan J. Collins*†

*Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota; and †Department of Medicine, University of Minnesota, Minneapolis, Minnesota

ABSTRACT

Frequent hemodialysis improves cardiovascular surrogates and quality-of-life indicators, but its effect on survival remains unclear. We used a matched-cohort design to assess relative mortality in daily home hemodialysis and thrice-weekly in-center hemodialysis patients between 2005 and 2008. We matched 1873 home hemodialysis patients with 9365 in-center patients (i.e., 1:5 ratio) selected from the prevalent population in the US Renal Data System database. Matching variables included first date of follow-up, demographic characteristics, and measures of disease severity. The cumulative incidence of death was 19.2% and 21.7% in the home hemodialysis and in-center patients, respectively. In the intention-to-treat analysis, home hemodialysis associated with a 13% lower risk for all-cause mortality than in-center hemo- dialysis (hazard ratio [HR], 0.87; 95% confidence interval [95% CI], 0.78–0.97). Cause-specific mortality HRs were 0.92 (95% CI, 0.78–1.09) for cardiovascular disease, 1.13 (95% CI, 0.84–1.53) for infection, 0.63 (95% CI, 0.41–0.95) for cachexia/dialysis withdrawal, 1.06 (95% CI, 0.81–1.37) for other specified cause, and 0.59 (95% CI, 0.44–0.79) for unknown cause. Findings were similar using as-treated analyses. We did not detect statistically significant evidence of heterogeneity of treatment effects in subgroup analyses. In summary, these data suggest that relative to thrice-weekly in-center hemodialysis, daily home hemodialysis asso- ciates with modest improvements in survival. Continued surveillance should strengthen inference about causes of mortality and determine whether treatment effects are homogeneous throughout the dialysis population.

J Am Soc Nephrol 23: 895–904, 2012. doi: 10.1681/ASN.2011080761 

 

Once more, these authors, like those before them reporting on the Frequent HD Network, fail to consider the fact that perhaps the Frequent HD group had more HD (in terms of duration/hours per week and in terms of higher weekly KT/V).

Once more, the authors do not seem to distinguishe between Frequent HD and Longer HD.

The Tassin group implied 20 years ago that longer hours on HD per week was good for HD patients, now the whole bandwagon of Frequent HD is rolling without considering that the adequate control group should be:

Group A: Frequent HD

Group B: Thrice weekly HD, BUT with same duration of HD per week copmpared to group A.

That is the propensity analysis that these studies should undertake; comparing hours on HD not how frequent people get on the machine...

Then the modest difference will be even more modest...non-existent!

Even the editorial by David Wheeler doesnt seem to get the point of longer hours versus More Frequent; the FHN study was all about longer hours and better KT/V not too mention better ultrafiltration.

What do we expect the average reader to conclude if even the editorial board doesnt get it!

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Tuesday, 29 May 2012, 10:51 AM
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Rituximab, a chimeric monoclonal anti-CD20 antibody, has now been extensively used in the management of autoimmune diseases including SLE and lupus nephritis as well as AASV (ANCA associated systemic vasculitis).

Concern has been expressed about the association of immunosuppressants, including Rituximab, and the increased risk of Progressive multifocal leukoencephalopathy (PML). The signal and association with Rituximab is of concern and warrants vigilance.

http://www.ncbi.nlm.nih.gov/pubmed/22422012

Whilst rare, such an association may be overlooked when considering teh RISK:BENEFIT of rituximab in autoimmune renal disease. However, the devastating nature of PML warrants careful follow-up and vigilance. This, all the more, since the benefit of Rituximab in conditions such as LN (LUNAR study) and ANCA associated vasculitis (RAVE INT & RITUXIVAS studies) is not superior to current therapies!

A recent article in the NEJM, this month, also shows an increased risk of PML with another monoclonal antibody Natalizumab (anti-integrin a4), with increased risk in those who have a positive status in respect to anti-JC virus antibodies, prior use of immunosuppression and duration of treatment.

http://www.ncbi.nlm.nih.gov/pubmed/22591293

Perhaps, we should screen the patients we treat willi nilly with Rituximab.. for anti-JC (John Cunningham) antibodies?!

Perhaps, we should use  Rituximab less often when evidence supports its indication!?

 

 

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by Arif Khwaja - Monday, 28 May 2012, 7:45 PM
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Once I have had a chance to digest the KDIGO guidelines I will post some thoughts. I note there has been much interest on the KDIGO guidelines on this site. A few things caught my eye - like the suggestion for fish oils in IgA nephropathy. This is based on data by Donadio and colleagues showing a beneficial effect. This has never been reproduced anywhere else and the control group in that study did extraordinarily badly - around 40% ended up on  RRT. KDIGO not unreasonably suggest that fish oils are relatively safe and therefore make a 2D recommendation about their use.

In fact 36% of all the statements in the glomerulonephritis guidelines are 2D. And to remind ourselves what does 2D mean? Well '2' is a suggestion and '1' is a recommendation. D means that the quality of evidence that the suggestion is made is ' very low - the estimate of the effect is very uncertain and often will be far from the truth'  - to me 2D sounds a lot like opinion and theres nothing wrong with opinion but we need to recognise it as opinion and not fact. If we are going to get the most out of guidelines we need to learn how to read them or perhaps just have guidelines about things for which there is good evidence.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Anyone in the world

ERA-EDTA Congress update: 
New discovery!
Searching for molecular mediators
N-acetyl-D-mannosamine could represent a new non immunosuppressive therapeutic agent in the treatment of minimal change nephropathy.
 

Minimal Change Disease (MCD), Despite being nearly a century old disease, the first molecular mediator behind the structural and functional changes in MCD was only recently discovered. Angiopoietin- like-4 (Angptl4), a glycoprotein secreted from podocytes in large amounts, is now shown to mediate most of the above mentioned characteristic features of MCD. This upregulation in podocytes is glucocorticoid sensitive, and declines with glucocortcoid treatment. it was shown that Angptl4 secreted from podocytes binds to the GBM and induces albuminuria even before the development of foot process effacement.
 

A precursor of sialic acid, N-acetyl-D-mannosamine (Man- NAc), leads to improved sialylation of podocyte-secreted Angptl4 and significantly reduced proteinuria. ManNAc is relatively non-toxic, and could represent a new non-immunosuppressive therapeutic agent in the treatment of MCD, if shown to be effective in future clinical trials. It is the first potential drug for MCD that primarily affects protein structure, and could be used alone or synergistically with glucocorticoids, that work at least partly by reducing Angptl4 gene upregulation in podocytes.

Treatment with ManNAc improves other parameters of nephrotic syndrome in PAN rats and also reduces proteinuria in Zucker diabetic fatty rats. One important characteristic of the podocyte that favors the further development of ManNAc as a novel therapeutic agent for nephrotic syndrome is its inability to divide. Since ManNAc crosses cell membranes easily and is also rapidly excreted in the urine after an oral or parenteral dose, it is most likely to accumulate in a non-dividing cell like the podocyte even at small doses without significant systemic effects in other organs composed primarily of dividing cells. 


In summary, the discovery of Angptl4 may lead the way to future therapeutic approaches for MCD.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Anyone in the world

Adam from Paris for GKA 2010
 

The Theme of this 1st Episode: 
 

Back to Old drugs: Aza, MTx, Hydroxychlorquene.
Individualization.
Less Corticosteroids still do the same action with less S/Es.
Cr Nadir is earlier than Albumin one.

Date: Thursday May 24th 2012
*********
08:30 - 12:30 CME Courses
Rheumatology for nephrologists 46
Peritoneal Dialysis Workshop 47

Title: Rheumatology for nephrologists
Speaker: 
Chair: Hans-Joachim Anders, Munich, Germany
David Jayne, Cambridge, UK
i. Welcome and introduction
Hans-Joachim Anders, Munich, Germany
David Jayne, Cambridge, UK

ii. Joint pain in CKD patients: When do we need a joint aspirate?
Hendrik Schulze-Koops, Munich, Germany
1) Sodiumaurate Crystals in Gout is different that those of CPPD crystals in Pseudo gout which may occur in the dialysis population.
2) The Take Home message in unclear monoarthrits; Do Not Wait; and do Aspirate; however;
3) Synovial fluid aspirate is a sterile procedure; however; the risk of complication by sepsis is 1/10,000; which cost a famous German athelet his career by causing septic arthritis for a procedure which is considered in his case may not be justified.

iii. Proteinuria in the patient with arthritis
Volker Vielhauer, Munich, Germany

4) Proteinuria in patients with arthritis include these following 5 main Topics: either Association, Complication, Manifestation, Toxicity and the fifth and the Last but not the least is Co-morbidity. 


5) This need Reply: A 34 yrs old male diagnosed as Behcet and was on CsA and CS. Developed proteinuria 2.8 g/24hrs, Cr 88um/L, with Dysmorphic RBCs, Hence referred to the Nephrologist; with a Bx showed IgA in A Behcet Disease with eGFR 60 ml, with no Cresents and no Fibrosis. How to manage? Opinions so to tell you what happen and what they did?
 

6) Assoicated Renal Disease in Behcet include mainly Amyloidosis 69/156, and GN in 51/152 cases. IgA deposition was found in 22% of GN with Behcet.
 

7) Associated Renal Disease in RA include: Mesangial GN 40/110, Renal Amyloidosis 33/110 and MN 19/110 cases.

8) The 2012 “standard of care” in lupus nephritis – referral,
drugs and monitoring
Frédéric A. Houssiau, Brussels, Belgium

8) LN is a very heterogenous disease which varies from single shot, or relapsing 1/3 or refractory 1/5 of the cases.
9) Poor prognostic factors include many; but on the top of the lists are Race (AA), non-observance to Rx, Absence of primary response to IS.

10) Poor prognostic factors in the pathology; beyond Roman numerals include fibrinoid necrosis, partial cresents and circumferential cresents.
11) Renal Bx is not a routine procedure in all SLE patients. However; Low C3, High Anti-DNA, or renal involvements include Pr > 0.5 g/24hrs and/or Active sediment are red flagged.
12) You may need Renal Bx so as not to miss APL-related Disease.
13) Which LN patients should be immunosuppressed? Class I, II NO ---, III & IV (both have Endo/extra capillary cellularity and sub-endo ID: YES ---, V in Selected Cases. However; wait for

my 2nd Episode from the EDTA concerning ISN/RPS 2003 Classification for more Info and critic by Ian Roberts.
14) LN: Towards no Steroid regimen? By Imperial College of Kidney and Tx Institute in London UK; by Liz Lighstone et al. Giving on Day 1 and 15th : 500 mg MPS + 1g RTx. Then only use MMF with no steroids. Claiming optimal renal protection.
15) Euro Lupus Nephritis Trial showed LD is equivalent to HD of CYP for induction in LN.
16) The cost of MMF is more than 10 times that of CYP for induction of Rx in LN.
17) Both AZA and MMF have similar effect as maintenance Rx for LN as proved by two trials ALMS (David Wafsy; especially if the two arms were induction with IV CYP) and MAINTAIN.
18) Never forget Plaquanil (Hydrochlorequene) in LN not only in SLE. Nephrologists are reluctant to consider it.
19) This need Reply: A Pregnant Lady with Acute flare of SLE; which IS Rx you recommend? Either with or without LN? and Do you recommend Abortion to save the mother from being ESRD or more complication?

v. Non-renal flares in lupus nephritis patients – new options
Falk Hiepe, Berlin, Germany

20) Bortezomib can cause clinical improvement in severe and refractoy SLE. This proteasome inhibition markedly reduced plasmablasts and plasma cells from the peripheral blood and bone marrow.



vii. B cell targeted therapy in nephritis, all hype and no substance?

David Jayne, Cambridge, UK

viii. ANCA-associated vasculitis - an update on therapeutic
strategies
Alan Salama, London, UK

Wait for my 2nd Episode of the Pathology.
The Theme is:
New Pathological Dx with still invalid clinical Significance.
Recent pathological classification of LN 2003 are more confusing than older one and may be wrong.
Criteriae necessary for Dx may not be necessary anymore. (ABMR with C4d –ve).

Wait for my 3rd Episode of the Opening Cermony and Pioneers in European Nephrology .
The Theme is:
There are two "REFRAINS" in the opening Cermony: Continuity and Memory.
Modesty and The Patient is what Kept the Pioneers so Pioneers.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Anyone in the world

Prof Bassam Saeed wrote:

 

ERA-EDTA congress update:
New uraemic toxins: For chronic cardiovascular problems, protein-bound solutes and middle molecules play an essential role.

The new tools made available by the advent of genomic, proteomic, and metabolomic research techniques e.g. mass spectrometry (MS) will result in the identification of several additional uraemic retention solutes. We often focus on the important role of small water-soluble compounds for acute mortality, but that for the chronic Cardiovascular problems of the uraemic syndrome, protein-bound solutes and middle molecules seem to play a more essential role. guanidino compounds, indoxylsulfate... It has been shown that dialytic Removal of middle molecules can be increased by the use of high-flux membranes and further enhanced by adding convection, although data for protein-bound solutes remain less convincing, with post dilution HDF being the most efficient of the available convective strategies. Only a few studies suggest that outcome improves with dialysis on high-flux membranes. Complementary, alternative removal methods (e.g. adsorption) and pharmaceutical strategies blocking responsible pathways could contribute to the aim of improving outcome of CKD patients and might even have implications for a much larger population, perhaps as early as CKD stage 3 (GFR < 60 ml⁄min).
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Soccoh Kabia
by Soccoh Kabia - Friday, 25 May 2012, 9:38 PM
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Just as we thought the ONTARGET trial ended all speculation about dual blockade with ACEI and ARB being beneficial, another study reported by a Spanish group showed once again that there is no benefit from dual blockade.

My first impression was why another trial, that is even smaller in numbers than ONTRGET is trying to prove that dual blokade retards the progression of CKD. 
One could accept the rationale that this trial (PRONEDI) is specifically targeting patients with diabetic nephropathy, and that it was probably designed before ONTARGET reported. 
However, notwithstanding the fact that a negative trial is probably driven  by a high prevalence of atherosclerotic renovascular disease on which RAAS inhibition has a deleterious effect, there were a couple of surprising findings.
The first was that there was no difference in BP with single or dual blockade and secondly, there was no difference in proteinuria. Neither the single or the dual blockade group achieved the internationally recommended BP target for DN and the mean BP for both groups was ~140 systolic.  
It is difficult to know what to make out of these data, but I hope that the nephrology community are now convinced that dual blockade is not the holy grail of delaying progression of CKD, and that no more money and effort is spent trying to prove it.
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Friday, 25 May 2012, 7:06 PM
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Dr Pierre Delanaye Posted from EDTA Paris on OLA French and translated:

First "summary" of EDTA for those who do not have the opportunityto attend.
Study of the session "Late Clinical Trial"
The study was conducted in OkinawaIt is named OCTOPUS and is presented by Dr. Iseki.
The study concerns the interest of olmesartan in patientsundergoing hemodialysisThe defintion used for the HTA is a voltage higher than 140/90Subjects are randomized and followed for 3.6 yearsAre included hemodialysis patients from 20 to 79 yearsExcluded are patients receiving ACE inhibitors or ARBsthesevere hypertension (200/100), hypotension in dialysis frequentdialysis vintage within a month.
235 subjects in the olmesartan group and 234 in the control group.
Patients are randomized with the following characteristics("rounded"): 60 years88 months of dialysis (!), 32% had diabetes,BMI 24KT / V 1.15systolic BP 160 mmHgdiastolic BP to 80 mm Hg
BP was controlled identically in both groups but overall systolic BPremains above 140 mmHg.
The authors observed no difference in mortality nor in theircombined primary endpoint (cardiovascular endpointsInfarstroke,unstable anginaheart failure requiring hospitalization). Side effects are also identical (including hyperkalemia).
Limitations of the studyno data on the water status which is arelatively important limitationselection of patients likely the "best"patients, particularly given the number of years already spent indialysisvery low number of events (even for Japan), for examplemortality of 4.7per year and combined endpoint of 9.1per year.
Another negative study dialysed patients ...
 
 
 
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Soccoh Kabia
by Soccoh Kabia - Friday, 25 May 2012, 1:05 PM
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Results from the COSMOS study were reported today.  This is an observational, non interventional study comparing the outcomes of patients treated with phosphate binders compared to those not received any binders.  It is a nulti-centre study that compared the outcomes of some 4500 patients from 220 centres who received binders to 2000 patients who didn't.  Those treated with binders had a better survival.

Clearly a lot of money has been invested to show that if you have low phosphate not needing binders you are probably elderly, frail and malnourished with likely poor outcome.  In fact the authors admit that the non-binder group were older. 

I am sure we will have many drug reps knocking on our doors telling us how phosphate binders save lives!

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Friday, 25 May 2012, 6:43 AM
Anyone in the world

Dr Alaas Sabry blogged:

ERA/EDTA precongress CME course - Renal Pathology- an interesting course, the following topics were presented:

1-New insight in C3 glomerulopathy ( Terry cook- Imerial college London) THE PATHOPHYSIOLOGY AND CLASSIFICATION OF THIS TYPE OF NEPHROPATHY , RENAL PATHOLOGY AND FUTURE TREATMENT OPTIONS- CASE REPORTS FOR THE VALUE OF ECULIZUMAB IN TREATMENT OF C3 NEPHROPATHY

2-Critical review of the ISN/RPS LN Classification  (IAN ROBERTS , OXFORD ,UK) :

Excellent comparative presentation with WHO classification and the reperoducability of ISN/RPS classification

3- Update in renal Tx biobsy ; stress on C4d negative , microvascular injury ( capilaritis) positive AMR and the future value of Endothelial Cell Associated Transcripts (ENDATA ) was elaborated.

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]