User blog: Meguid El Nahas

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by Meguid El Nahas - Monday, 26 September 2011, 9:23 AM
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Kidney Int. 2011 Jul 20. doi: 10.1038/ki.2011.213. [Epub ahead of print]

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.


The original publication by the Frequent Hemodialysis Network (FHN) implied positive impact of Frequent Daily Dialysis on the coprimary outcomes:

Left ventricular mass index (LVMI)  + Death and LVMI + Quality of Life

This, in spite of the fact that the study was underpowered with an inadequate sample size to estimate impact on death over such a short observation time (12 months)!  The results of the Daily trial were comparable to those in the literature describing improvements by salt restriction and volume control. 

Now the same group publishes that if you do frequent  HD at night, there is no benefit on any of the Primary endpoint: LVMI, Death or Quality of Life!

In fact, The FHN Daily and the Nocturnal trial differ in some respect: Time of dialysis, location and length of treatment but laso in the degree of residual renal function.

So, is Frequent HF, 6 times/week, only beneficial if it is done in Daytime not Nightime...???
Are all these trials and sub-trials un-interpretable because they are badly designed and underpowered?!

So don't rush to switch all your patients at a huge cost and inconvenience to frequent HD. Make sure they are not fluidoverloaded with careful ultrafiltration/volume control and dietary salt restriction.

Wait until Nephrologists know how to conduct and interpret clinical trials....

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Wednesday, 21 September 2011, 3:32 PM
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Warfarin in Atrial Fibrillation Patients with Moderate Chronic Kidney Disease
Hart RG, Pearce LA, Asinger RW, Herzog CA
Clinical Journal of the American Society Nephrology: CJASN (Sep 2011)
Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.
This recent publication supports the benefical effect of warfarin in the prevention of stroke in patients with CKD and atrial fibrillation.
Recently, a number of publications have raised concerns over the use of warfarin in CKD:
Warfarin Nephropathy and worsening renal function in CKD patients treated with warfarin.
Warfarin associated morbidity and mortality in ESRD patients on RRT including increased CVD risk, vascular calcifications and calciphylaxis.
Ultimately, like with all forms of treatment in CKD risk:benefit assessment will determine who may benefit from such treatment, the optimal INR level and the overall risk profile.
CHADS2 scoring may be a key determinant?!
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Saturday, 17 September 2011, 2:09 PM
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Numerous publications suggest that the lower the BP the slower the progression of CKD. A number of guidelines have stipulated target values around 130/80mmHg and even lower in patients with diabetes and those with proteinuria. The evidence upon which these guidelines are based relied primarily on observational data as well as secondary or posthoc analyses of clinical trials and systematic and meta-analyses of heterogeneous data.
So often in Nephrology, evidence is gathered from observational studies that remain unsubstantiated by subsequent attempts at confirmation by RCTs.
So often in Nephrology, evidence is sought from secondary and posthoc analyses not intended or powered to answer the question raised...?!
So often in Nephrology, dogma prevails enforced by unsubstantiated guidelines...?!
Most RCTs that attempted to answer whether intensive BP control is beneficial in slowing the progression of CKD failed to show a significant difference in renal functional outcomes; ABCD, REIN2 and AASK trials. Furthermore, concern about harm has been raised in those submitted to intensive treatment with increased morbidity and mortality (ACCORD). 
Finally, the assumption that one size fits all with targets systolic levels of <130 or 120mmHg is preposterous. Age, race and comorbidities may dictate different target levels. This is becoming apparent in patients on hemodialysis were older and diabetic individuals had higher mortality rates at lower (<140/70mmHg) blood pressure levels. More remarkably was the observation in this cohort analysis that survival did not seem to be harmed by higher systolic and diastolic values: 140-160 and 70-100mmHg (1).
In conclusion,
It is high time that BP related guidelines in CKD are reviewed, this is currently underway by KDIGO.
It is  high time nephrologists base their practice on substantiated guidelines...
It is also high time that nephrologists critically appraise the data submitted to them by "experts"    and refute assertions based on secondary and posthoc analyses as weak at best.
We have a long way to go!"

1. Myers OB, Adams C, Rohrscheib MR, Servilla KS, Miskulin D, Bedrick EJ, Zager PG.Age, race, diabetes, blood pressure, and mortality among hemodialysis patients.  J Am Soc Nephrol. 2010 Nov;21(11):1970-8.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Wednesday, 14 September 2011, 8:20 AM
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An article in the August issue of cJASN by Schinstock and colleagues from the Mayo clinic describe the experience with AVF. They report a large primary and secondary failure rate and identify diabetes mellitus and the size of the arteries as major determinants of reduced primary patency. Larger arteries are associated with better AVF outcomes thus advocating doppler testing and sizing of arteries and veins prior to AVF fashioning. They also raise the important issue of morbidity, complications and subsequent hospitalisations associated with AVF failure.

This leads them to questions whether in elderly patients with comorbidities and reduce life expectancy on HD, the Fistual First approach still holds as failure rate with the associated hospitalisations should be taken into consideration.

In my experience, older age and the associated atherosclerotic arteries specially in those with DM has been a major cause of raised primary and secondary AVF failure. This is indeed associated with frequent hospitalisations, imaging and re-interventions. The question should be raised if AVF in those with low life expectancy and small arteries on doppler should follow the Fistula First Stategy or whether a judicious and careful treatment plan with a permanent internal jugular dialysis catheter is a viable alternative. Some (Allon et al. 2010) have advocated a RCT to address some of these issues.

In the meanwhile, we should not forget the high morbidity and mortality associated with dialysis catheters and should make every asttempt at timely insertion of native AVF.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Monday, 15 August 2011, 2:56 PM
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An interesting controversy and debate is taking place in the Lancet relating to the impact of dietary salt diction on cardiovascular disease (CVD) outcomes. A recent Cochrane review by Taylor and colleagues based on a meta-analysis of 7 trials with 6250 individual implied that dietary salt reduction did not reduce CVD or impact on mortality. This publication led to headlines implying that salt reduction is unnecessary and unjustified. A rebuttal of this publication appears this month in the Lancet by He and MacGregor who criticize the first analysis and reanalyses the data by including all the patients and combining normotensive as well as hypertensive individuals in the new analysis. This draw different conclusions; they show that a dietary salt reduction leads to a significant reduction in CVD events by 20% but no significant reduction in all causes mortality. I would side on He and McGregor side and remind readers that there a large body of evidence in favour of salt reduction for the prevention and treatment of hypertension; hypertension is one of the major causes of CVD morbidity and mortality. The WHO recommends salt reduction as one of the top priorities along with smoking cessation and fighting obesity to reduce the rising tide of non-communicable disease. This debate in the Lancet highlights once more that different results and conclusions can be obtained from the analysis of a single dataset; it all depends on the investigators bias as well as the statistical methods applied. Beware, of the manipulation of statistics to prove a point. Investigators arvall too often i cloned to call statistics as an ally to prove their Pints. Truth is often hostage to statistical analyses...!?


Taylor et al. Reduced dietary salt for the prevention of cardiovascular disease. Cochrane Database Syst Rev 2011;7:CD 009217 
He and MacGregor. Salt reduction lowers cardiovascular risk: meta-analysis of outcome trials. Lancet 2011:378:380-82.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Wednesday, 10 August 2011, 8:50 AM
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Circulating urokinase receptor as a cause of focal segmental



Nature Medicine
952–960, 2

For Review read: McCarthy ET, Sharma M, Savin VJ.Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2010 Nov;5(11):2115-21.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Tuesday, 2 August 2011, 10:54 AM
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Dr Arif Khwaja wrote:

Results from the ORION study are published in this months AJT. This study involved 469 de-novo standard risk allografts who were randomised to either

1) Sirolimus and Tacrolimus aiming for Tacrolimus withdrawal at 3 months.

2) Sirolimus +MMF

3) Standard therapy with Tacrolimus and MMF.

All groups got Daclizumab induction and steroids. Due to higher rate of rejection the MMF+Sirolimus arm was terminated early in the study. The primary endpoint was Nankivell GFR at 12 months and there was no difference between standard therapy (group 3) and CNI withdrawal in group 1. The CNI-withdrawal group did not have any advantage over standard therapy with tacrolimus and MMF: patient (97.0% vs. 94.4%) and graft survival (95.4% vs. 88.5%), renal function (62.0% vs. 59.1 mL/min), rejection prophylaxis (12.3% vs. 17.4% biopsy-proven rejections), discontinuations (35.2% vs. 65.1%) representing overall tolerability and adverse events such as oedema (36.7% vs. 51.3%), anaemia (36.0% vs. 40.8%), hyperlipidaemia (20.1% vs. 36.8%), proteinuria (6.5% vs. 11.2%) and wound healing disorders including lymphoceles (14.4% vs.32.8%). Dyslipidaemia and thrombocytopenia and acne were significantly worse in the CNI withdrawal group whilst other secondary outcomes such as proteinuria whilst worse in the CNI withdrawal group did not reach significance.

Overall the study is consistent with the prevailing belief that Tacrolimus and MMF should be the standard therapy in renal transplantation at the moment both in terms of outcomes and tolerability. whether there is a role for switching from CNI to Sirolimus at a later date is not clear and is an issue that is being explored by the 3C Study in the UK which is evaluating the role of Alemtuzumab and steroid avoidance followed by switching from Tacrolimus to Sirolimus at 6 months. For the time being the role of Sirolimus in transplant immunosuppression remains unclear. (see Flechner SM et al. American Journal of Transplantation. Volume 11, Issue 8, pages 1633–1644, August 2011)

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Sunday, 31 July 2011, 4:15 PM
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Posted by Dr Mostapha HabibAllah
CDC recommendations for prevention and screening of HIV infection in prospective living organ donors:
• All prospective living organ donors should have their initial serologic tests for HIV supplemented with repeat testing with a combination
of an HIV serologic test and HIV NAT as close to the time of organ donation as feasible logistically, but no longer than 7 days preceding
organ donation.
• All living donors should be advised of their obligation to avoid behaviors that would place them at risk for acquiring HIV infection before
transplant surgery.
• For living donors with a history of high-risk behaviors (e.g., high-risk sexual activity or injection drug use) identifi ed during evaluation, individualized
counseling and a detailed discussion of specifi c strategies to avoid high-risk behaviors should be provided.
• Consistent with current policy, documents and counseling information used in the recipient consent process should explain that organ
transplantation carries a risk for transmission of HIV and other pathogens because no available testing can completely eliminate the risk
for transmission of all pathogens.
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Sunday, 31 July 2011, 1:15 PM
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[ Modified: Thursday, 1 January 1970, 1:00 AM ]
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by Meguid El Nahas - Tuesday, 26 July 2011, 2:19 PM
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A recently published article on IgG4-TIN was published (Raissian Y, Nasr SH, et al. Diagnosis of IgG4-Related Tubulointerstitial Nephritis. J Am Soc Nephrol 2011 Jul 22(7):1343 -52. The authors proposed diagnostic criteria that are divided into 4, namely: histological features (plasma cell rich-TIN with > 10 IgG4 + plasma cells/ hpf, TBM immune complex deposits on IF, Immunohistochemistry, and/or EM), radiological features (small peripheral low-arttenuation cortical nodules, round or wedge-shaped lesions, or diffuse patchy involvement), serological findings (elevated serum IgG4 or total IgG level or hypergammaglobulinemia), and other organ involvement (autoimmune pancreatitis, sclerosing cholangitis, inflammatory masses in any organ, sialadenitis, inflammatory aortic aneurysm, lung involvement, retroperitoneal fibrosis). Several important differential diagnoses included: "idiopathic hypocomplementemic TIN with extensive tubulointerstitial deposits," Sjogren's syndrome, and lupus nephritis. Similar to the previously recommended article (Saeki T, Nishi S, Imai N, Ito T, et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int.2010 Nov; 78:1016-23), the authors of this one also observed a decrease in serum creatinine in most patients treated with corticosteroids at one month follow up. Interestingly, some patients responded favorably (decreasing serum creatinine) to a treatment regimen combining prednisone anmd mycophenolate. Such steroid-responsiveness was observed even in those with fibrotic lesions, probably because of the 'patchy' distribution. It is important to be aware that such a disease entity exists, especially since it is quite responsive to corticosteroids. Dr Edgar Lerma
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