User blog: Meguid El Nahas

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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 ]
 
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by Meguid El Nahas - Friday, 25 May 2012, 6:43 AM
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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 ]
 
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35% of transplanted adolescent transferred to adult nephrology unit reject their kidneys within 36 months....non compliance, non-adherence, non-concordance....Transition from pediatric to adult units is a major issue with regard to transplanted adolescent...transition multi-disciplinary approach and transition clinics are key components of a smooth transition.

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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by Meguid El Nahas - Wednesday, 9 May 2012, 8:58 AM
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DAY2 MASTER CLASS IN KHARTOUM:

CRITICAL APPRAISAL SESSION 

MAJOR HIGHLIGHT:

DO NOT EQUATE eGFR with mGFR!!!!!!

eGFR is subject to all the confounders of changes in serum creatinine:
Diet, metabolism, GFR and Tubular secretion

MEASURED GFR IS THE ONLY MARKER OF CHANGES IN GFR AND SHOULD BE USED IN CLINICAL TRIALS TO ASSESS CKD PROGRESSION!!!!

The question is:

WHY ARE NEPHROLOGISTS RELUCTANT TO MEASURE TRUE GFR IN CLINICAL TRIALS OF CKD PROGRESSION????

Is it convenience?

Is it pressure from Sponsors to fudge the real result?

Is it just ignorance that eGFR is an inadequate marker of true GFR?

I am bewildered....!!!!!

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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by Meguid El Nahas - Wednesday, 9 May 2012, 4:12 AM
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Proposed KDIGO staging of AKI

 

Stage

Serum Creatinine

Urine Output

1

1.5-1.9 times baseline

OR

³0.3mg/dl (³26.5mmol/l) increase

<0.5ml/kg/hour for 6-12 hours

2

2.0-2.9 times baseline

<0.5ml/kg/hour for ³12 hours

3

3 times baseline

OR

4.0 mg/dl (353.6mmol/l) increase

OR initiation of renal replacement therapy

OR in patients less than 18 years a decrease in eGFR <35mls/minute/1.73m2

<0.3ml/kg/hour for ³24 hours OR

Anuria 12 hours

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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by Meguid El Nahas - Wednesday, 9 May 2012, 3:47 AM
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The American College of Rheumatology (ACR) has issued the first-ever guidelines for the screening, treatment, and management of lupus nephritis (LN). 
The guidelines are published in the June issue of Arthritis Care & Research
They were initially presented at ACR 2011.

Clinical conclusions
1- the 2012 guidelines are a significant advance because they address total therapy of LN, not just short-term treatment.

2- At this time, more than half of patients with systemic lupus erythematosus develop LN within 10 years and up to 30% of those cases progress to end-stage renal disease within 15 years of diagnosis.

3- The ACR panel, which developed the guidelines, recommends renal biopsy for all patients with clinical evidence of active, previously untreated LN. 

4- They do not recommend immunosuppressive treatment for patients with class 1 (minimal mesangial immune deposits on immunofluorescence with normal light microscopy) or class 2 (mesangial hypercellularity or matrix expansion on light microscopy with immune deposits confined to mesangium) renal damage. However, they do recommend aggressive treatment for patients with class 3 or higher renal pathology.

5- Mycophenolate and cyclophosphamide plus glucocorticoids are the mainstay of treatments for induction of improvement in [LN] of serious histologic classes (except if patient is pregnant), and azathioprine [AZA] and mycophenolate are both acceptable for maintenance of improvement (except in pregnancy). Recommending pulse steroids in treatment of class 3 and 4 active proliferative disease. Rituximab or calcineurin inhibitors should be considered if standard treatments fail."

6- An algorithm for management of pregnant woman with active [LN] is included in the guidelines.The guidelines note that women should be off MMF or CYC for at least 6 weeks prior to conception.

7- Renal failure may not come quite as quickly in pure membraneous nephritis, but the long-term prognosis is not great."

8- Studies have shown that MMF is more effective than CYC in African-American woman, and this is highlighted in these guidelines."

9- Consensus on the use of calcineurin inhibitors: The agents have potential renal toxicity, but have been shown to be effective in membranous lupus during the short term.

10- The role of rituximab in LN also remains somewhat uncertain. Rituximab is listed as a relatively late intervention.

11- Recommendation to perform renal biopsies whenever the therapeutic decisions would be altered by knowing 1) histologic classification and 2) level of activity and of chronicity on the biopsy.

12- There needs to be more use of remission-inducing agents at proper doses for proper duration, transition from induction to maintenance therapies without a gap if possible, prevention of adverse effects when possible.

13- The guidelines do not address the questions of how long to treat during maintenance therapy and when begin to taper MMF because there are few data on the topic.

14- With regard to the increasing incidence of end-stage renal disease associated with LN, there are fibrotic processes plus other reasons such as hypertension that contribute to atherosclerosis. Many patients progress to renal failure not due to active nephritis, but due to the combined effects of irreversible damage accrued over many years.

Arthritis Care Res. 2012;64:797-808.
 
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by Meguid El Nahas - Thursday, 3 May 2012, 9:09 AM
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Annals of Internal Medicine

Screening for, Monitoring, and Treatment of Chronic Kidney Disease Stages 1 to 3: A Systematic Review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline

Howard A. Fink, MD, MPH; Areef Ishani, MD, MS; Brent C. Taylor, PhD, MPH; Nancy L. Greer, PhD; Roderick MacDonald, MS; Dominic Rossini, MD; Sameea Sadiq, MD; Srilakshmi Lankireddy, MD; Robert L. Kane, MD; and Timothy J. Wilt, MD, MPH 

This is a balanced systematic review of the literature relating to the impact of treatment including ACE inhibitors and ARBs on outcomes in CKD; ESRD and Mortality. The authors conclude that the evidence is in general fair but seldom strong and therefore current recommendations for screening and early treatment to prevent hard endpoints such as death or ESRD are weak.

They also reported that the evidence for strict BP control is weak.

They conclude that the role of screening or monitoring in improving outcomes is uncertain as hardly any study reviewed addressed that point. And that the evidence for benefit is strongest for ACE inhibitors and ARBs, and more specifically in patients with albuminuria combined with diabetes and cardiovascular disease. 

This manuscript should be read by all those interested in the management of CKD as it shows the limitations of available data and highlights the value of careful and systematic analysis.

Read the full article on OLA:

https://www.gkaonlineacademy.com/resources/library/cat_view/6-ckd

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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This meeting organised by Professor Neveen Soliman, Cairo University is proving a great success.The meeting is well attended and intends to introduce young nephrologists and older ones...to the complexity of inherited diseases and challenges of genetics, diagnostics and management in these patients. 

A number of excellent talks by Profs Soliman, Sayers and Levtchencko.

Also comprehensive review on hyperoxaluira by Dr Hafez Bazaara followed by discussion of management by Prof Khaled Eweda and Alaa Fayez on the complexities of dual liver and kidney transplantation for patients with type1 hyperoxaluria. Surigcal challenges were highlighted by Dr Fayez who explained difficulties of intraoperative fluid balance between keeping the renal allograft overhydrated and the liver underhydrated...fantastic achievements for Egypt pediatric nephrology and surgery. 

I gave a talk on the genetics of kidney disease which highlighted the relevance of genetics of albuminuria, hematuria as well as decreased GFR and its decline in CKD. Key genes appear to be the complex MYH9/APOL1 on chromosome 22 and the increasingly recognised role of the UMOD gene, coding for uromodulin (Tamm-Horsfall protein), in hypertension, hyperuricemia as well as the progression of chronic interstitial disease. Elevated uromodulin urine levels have been associated with increased risk of CKD progression over a 10 year period in a proof of concept study (1).

The latter may explain the uric acid and its "nephrotoxocity" story; those with UMOD mutations may have progressive CKD with elevated uric acid and even gout as main features. Those with raised uric acid in the absence of UMOD mutations may be harmless?

Genotyping of UMOD may highlight those at risk of progression and raise issues related to allopurinol therapy of hyperuricemia to prevent CKD progression. Pilot studies in children with juvenile hyperuricemic nephropathy have proved of limited impact so far (2). Also, of not eallopurinol is capable of reducing BP.

The observations related to UMOD gene mutations illustrate an interesting and emerging concept that common variants in gene regions known to be associated with monogenic diseases may be associated with milder disease-related phenotypes in the general population (3).

References:

1. Kottgen et al.JASN 2010; 21;337-344.

2. Bleyer et al. QJM 2003;96:867-8.

3.O'Seaghadha and Fox. Nephron 2011;118:c55-63

Follow the IKDW meeting on Facebook Global Kidney Community 

Lectures will be posted on the new Pediatric Nephrology section of OLA

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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READ BLOG AFTER ABSTRACT:

Article by Peraza et al published in the April 2012 issue of AJKD.

 
BACKGROUNd; An epidemic of chronic kidney disease of unknown cause has emerged along the Pacific coast of Central America, particularly in relatively young male sugarcane workers. In El Salvador, we examined residence and occupations at different altitudes as surrogate risk factors for heat stress.
STUDY DESIGN: Cross-sectional population-based survey.
SETTING & PARTICIPANTS:
Populations aged 20-60 years of 5 communities in El Salvador, 256 men and 408 women (participation, 73%): 2 coastal communities with current sugarcane and past cotton production and 3 communities above 500 m with sugarcane, coffee, and service-oriented economies.
PREDICTOR:
Participant sex, age, residence, occupation, agricultural history by crop and altitude, and traditional risk factors for CKD.
OUTCOMES:
Serum creatinine (SCr) level greater than the normal laboratory range for sex, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), and proteinuria categorized as low (protein excretion ≥30-<300 mg/dL) and high grade (≥300 mg/dL).
RESULTS:
Of the men in the coastal communities, 30% had elevated SCr levels and 18% had eGFR <60 mL/min/1.73 m(2) compared with 4% and 1%, respectively, in the communities above 500 m. For agricultural workers, prevalences of elevated SCr levels and eGFR <60 mL/min/1.73 m(2) were highest for coastal sugarcane and cotton plantation workers, but were not increased in sugarcane workers at 500 m or subsistence farmers. Women followed a weaker but similar pattern. Proteinuria was infrequent, of low grade, and not different among communities, occupations, or sexes. The adjusted ORs of decreased kidney function for 10-year increments of coastal sugarcane or cotton plantation work were 3.1 (95% CI, 2.0-5.0) in men and 2.3 (95% CI, 1.4-3.7) in women.
LIMITATIONS:
The cross-sectional nature of the study limits etiologic interpretations.
CONCLUSION:
Agricultural work on lowland sugarcane and cotton plantations was associated with decreased kidney function in men and women, possibly related to strenuous work in hot environments with repeated volume depletion.

 

ANOTHER INTERPRETATION OF THIS STUDY COULD BE:

Dehydration in Agricultural workers working in extreme heat. Whilst the naive cover of the April issue of AJKD falls for it and suggests and "EPIDEMIC"of kidney disease in Central America...the critical reader would notice:

1. Cross sectional analysis with a SINGLE serum creatinine measurement does NOT identify an "EPIDEMIC" of kidney disease!!!!

2. CKD takes more than a single measurement of serum creatinine.

3. Raised serum creatinine in heat exposed manual workers is more likely to reflect dehydration under extremely strenuous conditions.

4. The control group working in the same agricultural fields, sugarcane and cotton plantation, but in the cooler altitude areas of El salvador dont seem to suffer as much...Heat and dehydration being less prevalent in cooler higher altitude!

5. Women in hot coastal areas dont seem to share the men heat induced raised creatinine risk because they have a smaller muscle mass and their serum creatinine is lower; MDRD calcuklated GFR does not fully correct for difference in body mass. I also suspect that women are assigned less strenuous agricultural role with less exposure to heat.

Once more nephrologists have forgotten:

1. That serum creatinine can be raised for many reasons including:

High meat diet, high muscle mass and dehydration; all potential confounders in hard working male agricultural workers.

2. That raised serum creatinine in a cross sectional study doesnt make for CKD!

3. That raised serum creatinine measured once does not make for an EPIDEMIC...!!!

WHEN WILL NEPHROLOGISTS LEARN???

 

 

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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The BalANZ study (David Johnson and Colleagues J Am Soc Nephrol 23: ccc–ccc, 2012. doi: 10.1681/ASN.2011121201)

More than 15 years ago Wieslander and co-workers working in Lund, Sweden, identified a number of components of peritoneal dialysis solutions that are potentially damaging both in mesothelial cells in culture as well as in vivo. Among these are the glucose degradation products (GDP) that occur when glucose containing solutions are sterilised at high temperature. In order to reduce the formation of these agents a new generation of peritoneal dialysis solutions based on 2 separate compartments were developed where the glucose component was sterilised at a very low pH (2-3) in order to reduce GDP formation and then combined with a buffer to neutralise the pH just prior to infusion into the patient. There have been several clinical studies that have explored the clinical benefit of these new solutions but the benefits have not been clearly demonstrated. Against this background the eagerly awaited BalANZ study has just been published in JASN and is important since it is the largest randomised controlled trial of biocompatible peritoneal dialysate vs standard dialysate to date. The investigators are to be congratulated for persisting despite recruitment difficulties, and successfully recruiting 185 incident peritoneal dialysis patients to this 2 year study. Patients were randomized 1:1 to receive either a neutral pH, lactate buffered, low GDP Balance solution (Fresenius Medical Care, Bad Homburg, Germany) or a conventional, standard, lactate-buffered PD solution (stay.safe).

The primary outcome measure was the difference in the slope of the decline in residual renal function and this was not met. However there was a significant difference between the groups both in time to anuria (p=0.009) and time to first peritonitis episode (p=0.01) in favour of the more biocompatible solution. Indeed the peritonitis rate in the biocompatible group was 0.30 vs 0.49 (p=0.01) episodes per year. In addition there was a significant reduction in over all infection in the biocompatible group (4 non PD infections out of 91 patients vs 20 out of 91 in the control group). Thus the biocompatible group demonstrated meaningful benefits in terms of infection and time to anuria compared with the control solution.

As usual with studies of this kind there are several caveats – for example few patients were on automated peritoneal dialysis and the use of icodextrin was relatively low. There was also a difference in ultrafiltration between the groups with lower 24 hour ultrafiltration in the Balance group at 3 and 6 months, although there was no significant difference in dialysate glucose concentrations used. Unfortunately, this study did not report information on membrane function. Furthermore it is not clear that the results would be apply to other types of more biocompatible solutions since the concentrations of glucose degradation products vary between the types – for example Physioneal (Baxter) is reported to contain higher concentrations of 3-deoxyglucosone than the Balance solution. Clearly this study has to be considered in light of those that have gone before where the value for biocompatible solutions has not been clearly demonstrated. However it gives an important signal of a significant benefit for the more biocompatible solution for two important outcome measures in patients on peritoneal dialysis – time to anuria and peritonitis rates. Progress in medicine is incremental, and although this study has not answered all the outstanding questions on the impact of solution design on patient outcomes in PD, it has provided important information relevant to patients and their clinical teams.
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