User blog: Meguid El Nahas
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.
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.
DAY2 MASTER CLASS IN KHARTOUM:
CRITICAL APPRAISAL SESSION
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....!!!!!
Proposed KDIGO staging of AKI
1.5-1.9 times baseline
³0.3mg/dl (³26.5mmol/l) increase
<0.5ml/kg/hour for 6-12 hours
2.0-2.9 times baseline
<0.5ml/kg/hour for ³12 hours
3 times baseline
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
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:
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).
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
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.
Participant sex, age, residence, occupation, agricultural history by crop and altitude, and traditional risk factors for CKD.
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).
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.
The cross-sectional nature of the study limits etiologic interpretations.
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???
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.