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Clin J Am Soc Nephrol. 2016 Aug 8;11(8):1472-83. doi: 10.2215/CJN.13841215. Epub 2016 May 5.

Climate Change and the Emergent Epidemic of CKD from Heat Stress in Rural Communities: The Case for Heat Stress Nephropathy.

Abstract

Climate change has led to significant rise of 0.8°C-0.9°C in global mean temperature over the last century and has been linked with significant increases in the frequency and severity of heat waves (extreme heat events). Climate change has also been increasingly connected to detrimental human health. One of the consequences of climate-related extreme heat exposure is dehydration and volume loss, leading to acute mortality from exacerbations of pre-existing chronic disease, as well as from outright heat exhaustion and heat stroke. Recent studies have also shown that recurrent heat exposure with physical exertion and inadequate hydration can lead to CKD that is distinct from that caused by diabetes, hypertension, or GN. Epidemics of CKD consistent with heat stress nephropathy are now occurring across the world. Here, we describe this disease, discuss the locations where it appears to be manifesting, link it with increasing temperatures, and discuss ongoing attempts to prevent the disease. Heat stress nephropathy may represent one of the first epidemics due to global warming. Government, industry, and health policy makers in the impacted regions should place greater emphasis on occupational and community interventions.

 Comments

This review published in the August issue of cJASN argues for a Heat Stress Nephropathy (HSN) associated with Global warming...

It would involve a variety of incidences of renal impairment in countries such as El Salvador/Central America (Mesoamerican nephropathy, Sugar cane Nephropathy), Sri Lanka and India.

The review implicates global warming, dehydration, nephrotoxins as well as heavy metal contamination of drinking water, not to mention the ever present hyperuricemia and also hypokalemia as well as fructose toxicity...

The reality is that agriculture workers working unprotected for very long long hours in extreme heat are simply prone to dehydration...

Longterm dehydration leads to longterm activation of the renin angiotensin aldosterone system (RAAS) that leads to renal ischemia and chronic hypokalemia; severe dehydration along with chronic hypokalemia (observed in many of these workers) is enough to cause impaired renal function in anybody...

So rather than calling these conditions fancy names, it suffices that we acknowledge that dehydration is not good for the kidneys...and that adequate hydration is essential for workers of any type in any country working under extreme heat conditions!

Nephrologists love to come up with new "Nephropathies", it gives them a claim to have "discovered" and labelled an entity, even when it is as mundane as dehydration...!

Some recent examples of labelling...

Warfarin nephropathy: Basically raised serum creatinine in sick and multi-comorbidities, over anticoagulated, patients with CVD...causal link with warfarin unproven!

Smoking Nephropathy: Basically CKD in heavy smokers...with multiple comorbidities and underlying CVD...causal link with heavy smoking unproven!

Mesoamerican nephropathy: Dehydration in agricultural workers...link with anything else unproven!

Sugar Cane nephropathy: Dehydration in agricultural workers...(not just sugar cane), affecting those working a low altitude and extreme heat and not the cooler higher altitude farmers...

Fructose nephropathy, Uric Acid Nephropathy, etc...

In the case of "Heat Stess Nephropathy"...it would better be called Dehydration induce kidney failure...its prevention in adequate hydration and better working conditions of those exposed to hot climate...it treatment is re-hydration before long term damage takes place!

Lets keep the simple, simple and make its prevention and management equally simple.

As to Climate Change and Global Warming...thats better left to geographers and politicians...as we, as nephrologists, have no data to compare the incidence of impaired kidney function...before and after global warming...!?

Fianlly, another CKD "Epidemic"... another term to make the problem sound more important, urgent, and global...Dehydration on the other hand, would not have the same linguistic impact, but would be much nearer the truth...as the evidence of a HSN induced epidemic is as shaky as that of the CKD "epidemic" that has been branded around the last 20 years...

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

Comments

     
    Picture of Meguid El Nahas
    by Meguid El Nahas - Thursday, 1 September 2016, 11:10 AM
    Anyone in the world

    http://www.ncbi.nlm.nih.gov/pubmed/?term=glaser%2C+lemer%2C+johnson

    A review published in the August issue of cJASN argues for a Heat Stress Nephropathy (HSN) associated with Global warming...

    It would involve a variety of incidences of renal impairment in countries such as El Salvador/Central America (Mesoamerican nephropathy, Sugar cane Nephropathy), Sri Lanka and India.

    The review implicates global warming, dehydration, nephrotoxins as well as heavy metal contamination of drinking water, not to mention the ever present hyperuricemia and also hypokalemia as well as fructose toxicity...

    Comments

    The reality is that agriculture workers working unprotected for extremely long hours in extreme heat are simply prone to dehydration...

    Longterm dehydration leads to longterm activation of the renin angiotensin aldosterone system (RAAS) that leades to chronic hypokalemia; severe dehydration along with chronic hypokalemia (observed in many of these workers) is enough to cause impaired renal function in anybody...

    So rather than calling these conditions fancy names, it suffices that we acknowledge that dehydration is not good for the kidneys...and that adequate hydration is essential for workers of any type in any country working under extreme heat conditions!

    Nephrologists love to come up with new "Nephropathies", it gives them a claim to have "discovered" and labelled an entity, even when it is as mundane as dehydration...and hypokalemia!

    Some recent examples of labelling...

    Warfarin nephropathy: Basically raised serum creatinine in sick and multi-comorbidities, over anticoagulated, patients with CVD...causal link with warfarin unproven!

    Smoking Nephropathy: Basically CKD in heavy smokers...with multiple comorbidities and underlying CVD...

    Mesoamerican nephropathy: Dehydration in agricultural workers...

    Sugar Cane nephropathy: Dehydration in agricultural workers...(not just sugar cane), affecting those working a low altitude and not the cooler higher altitude farmers...

    Fructose nephropathy, Uric Acid Nephropathy, etc...

    In the case of "Heat Stess Nephropathy"...it would better be called Dehydration induce kidney failure...its prevention in adequate hydration and better working conditions of those exposed to hot climate...it treatment is re-hydration before long term damage takes place!

    Lets keep the simple, simple and make its prevention and management equally simple.

    As to Global Warming...thats better left to geographers and politicians...

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

    Comments

       
      Anyone in the world

      Ever wondered what is renal graft outcome (patient and renal graft survival, incidence of acute rejection and long-term renal allograft function) in combined liver & kidney transplantation (CLKT) as compared to isolated kideny transplantation (KT)?


      Read the below to find out what the nephrology and hepatology teams at Birmingham Children’s Hospital found when they carried out this case–control study.

      Key findings:

      The kidney graft survival for CLKT patients (primary diagnosis fibro-polycystic liver & kidney disease- FPLKD in 65% of them) was 87.4, 82, and 82 % at 1, 5, and 10 years .

      Allograft survival rates in KT recipients were 97.2, 93, and 93 % at 1, 5, and 10 year follow-up and this was not significantly different (p > 0.05) from CLKT recipients. That being said, higher initial rate of graft loss was noted in CLKT patients given the higher morbidity and mortality associated with the operation.

      CLKT recipients had fewer acute rejection episodes and better long-term renal graft survival when compared to isolated KT. Only 5 % of CLKT recipients had acute rejection compared to 12.5 % of KT recipients. If this could be attributable to a hepatic immunomodulatory effect leading to a degree of tolerance remains unclear.

      Plasma creatinine at 1 and 5 years following transplantation was significantly lower in children undergoing CLKT for FPLKD compared to those with Primary hyperoxaluria- PH and a significantly higher 1-year e-GFR in patients with FPLKD than in those who had PH. This is presumably due to the risk of oxalate deposition in the transplanted kidney given oxalate mobilization from bones and tissues post-transplantation.

      The decline in mean eGFR between 5 and 10 years from transplantation was greater (−19.14 ml/min/1.73 m2 in 5 years) in KT recipients compared to CLKT (−7.6 ml/min/1.73 m2 in 5 years) (p = 0.043). 

      - Could the noticed trend in favor of better renal graft function in CLKT recipients in comparison to KT recipients in this study  be significantly documented in future studies? This remains remains to be answered.

      READ THE ORIGINAL ARTICLE AND COMMENT!

      Ranawaka R, Lloyd C, McKiernan PJ, Hulton SA, Sharif K, Milford DV. Combined liver and kidney transplantation in children: analysis of renal graft outcome. Pediatr Nephrol 2016;31(9):1539-43

      http://link.springer.com/article/10.1007%2Fs00467-016-3396-3

       

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

      Comments

         
        Anyone in the world

        In this month KI, Eriksen and colleagues reports on a Norwegian longitudinal study of the general population examining the links between age related decline in GFR and Blood Pressure (at baseline) (BP).

        http://www.ncbi.nlm.nih.gov/pubmed/27188503

        The study did NOT show any association between baseline BP parameters and the rate of decline of measured GFR (mGFR) in an older general population with exclusion of those known to have cardiovascular disease or DM.

        Comments:

        The study has a number of advantages and strengths:

        1. It is a general population cohort study where over a period of 5.6 years of follow up the GFR was measured by iohexol clearance.

        2. Measured GFR (mGFR) showed a decline of aroun 098-0.9ml/min/year consistent with previous observations that GFR is lost at a rate ~1ml/min/year after the age of 50.

        3. The study Renal Iohexol Clearance Survey in Tromso 6 (RENIS-T6) also compared mGFR with eGFRCr and eGFRCys and find thme wanting as their values, compared to mGFR, in the general population with near normal renal function were confounded by non-renal variables such as inflammation:

        http://www.ncbi.nlm.nih.gov/pubmed/26668020

        4. mGFR was repeated over the 5.6 years observation period.

        5. BP was measured in day and night time as well as ambulatory (ABPM) in this study: http://www.ncbi.nlm.nih.gov/pubmed/22278141

        The study failed to show an association between baseline BP values and the subsequent rate of mGFR decline with time.

        This observation agrees with older ones showing the impact of BP on the decline in GFR was primarily linked to bouts of accelerated hypertension jeopardising GFR in a stepwise fashion, whilst a steadily elevated BP was not associated with a faster rate of GFR decline. In fact, a meta-analysis of 10 RCTs back in 2002 failed to show a strong association between BP and incident CKD: http://www.ncbi.nlm.nih.gov/pubmed/11981255

        This was supported by observations that non-accelerated, mild to moderate, hypertension was not associated with nephrosclerosis in the general population: http://www.ncbi.nlm.nih.gov/pubmed/?term=freedman+appel%2C+1995

        A limitation of the current study is the emphasis on Baseline BP and subsequent mGFR decline.

        More emphasis on changes in BP control with time would have been more informative; in fact, their unadjusted data suggest that those whose BP (MAP) increased with time had slower mGFR decline...

        whilst those treated for hypertension had faster rate of decline (raising the possibility that antihyeprtensive agents, including RAAS inhibitors may have detrimental effects on GFR decline with time)...

        In spite of its limitations this observation, with accurate GFR measurements and thorough BP recordings, draw attention to the fact that the links between mild to moderate BP elevation and age-related decline in GFR do not show a linear association.

        Confounders, may impact on that association including genetic factors (APOL1 genotype), obesity and environmental factors such as smoking as well as susceptibility to hypertension induced atherosclerosis and its impact on renal perfusion and function.

        The conclusion of this observation has to be:

        There is more to the link between hypertension and CKD decline than elevated Blood Pressure; other confounders and comorbid factors have to be taken into consideration. This notion may lead to a more targeted and individualised approach to the management of hypertension in older people based on the presence or absence of other comorbid confounders. This has been emphasised by the JNC8 recommendations:

        http://www.aafp.org/afp/2014/1001/p503.html

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

        Comments

           
          Picture of Meguid El Nahas
          by Meguid El Nahas - Tuesday, 14 June 2016, 11:06 AM
          Anyone in the world

          FGF23: A novel role in systemic immunosuppression:

          FGF23 an osteoblast produced key stimulator of renal phosphate excretion has previously been known to be associated with CKD-MBD, hypertension, CVD

          http://www.ncbi.nlm.nih.gov/pubmed/24677555

          and now with an immunosuppressive effect through an inhibition of neutrophil recruitment and anti-bacterial activities.

          http://www.ncbi.nlm.nih.gov/pubmed/26878171

          New therapies aimed at neutralising FGF23 may prove to be effective at many levels.

          Comments:

          However, like with all Cytokines, the story is never that simple as experimental data based on neutralisation of FGF23 and/or its receptor Klotho have not proved universally successful. 

          http://www.ncbi.nlm.nih.gov/pubmed/22396168

          Nephropathic cystinosis: Conclusions from a KDIGO Controversies Conference

          This conference held in 2015 involving Prof Neveen Soliman reviewed diagnostic and management approaches to nephropathic cystinosis. Amongst other issues it highlight the discrepancy between access to care in developed and devloping countries. Research questions were discussed including WBC and gene testing for the disease, access to treatment but also issues related to children and adolescent non-compliance. The conference also put a lot of emphasis on the recognition of the systemic nature of cystinosis thus stressing the importance of early diagnosis and initiation of therapy  with cysteamine. Beside the kidneys, bones, eyes, the neurological system, the endocrine system (diabetes, hypothyroidism, GH deficiency) and fertility can all be affected.

          Comments:

          A major challenge resides in how the medical community can address the issue of limited access to healthcare for cystinosis sufferers in non-western world countries and disadvantaged population. Cost of treatment is often unaffordable in these communities. It is high time the Pharmaceutical Industry show more social and global responsibility towards those millions denied care!

          Mining the human urine proteome for monitoring renal transplant injury. Sidgel et al.

          This study shows the result on searching for urine proteins that could enhance teh diagnosis, prognosis and management of renal allograft recipients.

          Out of over 900 proteins identified in the urine of those tested, 11 showed interest in relation to acute rejection, 12 for chronic allograft nephropathy and 12 for BK virus nephropathy.

          Comments:

          This obssession with urinary proteomic in renal transplantation goes back over 20 years and so far has yielded no clinical useful results. One is entitled to ask, whether any of the putative proteins identified in this study are superior in predictive value to; raised serum creatinine (for acute rejection), proteinuria and declining function as well as renal biopsy (for CAN) and to urinary and serum PCR for BKV nephropathy specially when associated with a rising serum creatinine. Also cost-effectiveness of these techniques and the time lag between sampling and obtaining results are likely to be of little value in acute rejection when a prompt diagnosis and treatment is required, as to the other conditions...well there is usually plenty of time to confirm their diagnosis by conventional means without requiring the sophistication and unreliability of urine proteomic analysis. I guess it keeps some scientists interested and giving lectures...many such tests have been validated more than 10-15 years ago and never made it to the bedside...?!

          http://www.ncbi.nlm.nih.gov/pubmed/11750404

          http://www.ncbi.nlm.nih.gov/pubmed/12777869

          http://www.ncbi.nlm.nih.gov/pubmed/20526237

          Endostatin and Transglutaminase 2 are involved in fibrosis ageing. Lin et al.

          Endostatin (EST) a pletropic anti-angiogenic factor and transglutaminase 2 (TG2) its molecular partner may be implicated in renal fibrosis; through the dual mechanism of vascular rarefication and the association interstitlal fibrosis that underly renal fibrosis and scarring. In this study, the injection of EST and/or TG2 to young mice led to an accelerated renal ageing process.

          Comments:

          We, Tim Johnson and myself, were the first to draw attention in the 90s to the putative role of TG2 in experimental renal fibrosis through the observation of an increased levels in scarred SNx rat kidney sassociated with renal fibrosis

          and subsequently through the design of specific TG2 inhibitors that attenuated experimental renal fibrosis.

          http://www.ncbi.nlm.nih.gov/pubmed/10505691

          http://www.ncbi.nlm.nih.gov/pubmed/12874459

          http://www.ncbi.nlm.nih.gov/pubmed/18003782

          The authors of this paper chose to overlook the bulk of our pioneer experiments as it is often the case with medical publications. They should be informed that clinical experimentation is already under discussion aimed at manipulating TG2 in human nephropathies. 

          It is a sad fact of medical research publications for authors to wish to appear to have discovered facts and mechanisms that are already well established and validated by others, years before, that they chose to ignore. It does them little credit...

          Association of short sleep duration and rapid decline in renal function. McMullan et al.

          This paper follows a prospective cohort of 4238 middle aged women participants of the Nurse's Health Study and shows that over an observation period of 11 years those who sleep on average <5h per night are at significantly higher risk of a faster decline in renal function, eGFR.

          Sleep disturbances can be associated with hypertension, metabolic syndrome/diabetes and CVD; the authors however adjusted for incident hypertension, DM and CVD and found that it did not impact on the relative increased risk associated with short sleep duration.

          Comments

          Whilst this observation is of interest, and worthy to be pursued, such analysis is always difficult to validate and interpret as:

          1. It could be counfounded by underlying co-morbidity; those who dont sleep well may have illnesses that distrub their sleep and also predispose them to declining kidney function.

          2. Sleep apnea cannot be discared as a cause of distrubed sleep; sleep apnea has been associated with impaired kidney function.

          http://www.ncbi.nlm.nih.gov/pubmed/27152260

          2. Hypertension in cohort studies is difficult to validate  as causal and occasional measurement of BP is seldom good enough to exclude underlying or incident hypertension. Also sleep disturbance may be associated with nocturnal hypertension, known to impact of CKD and its progression.

          3. Serum creatinine/eGFR occasional (twice in 11 years) measurements may also mislead and give false positive results of decline, in the absence of a truly negative slope of eGFR decline ;non-linear decline may confound the interpretation of the renal functional data in this study.

          http://www.ncbi.nlm.nih.gov/pubmed/22284441

          4. Sleep disturbance may also be associated with medication, to alleviate the underlying cause or the associated symptoms including headaches, analgesics and others, that could in turn be instrumental in impacting negatively on renal function.

          In conclusion, the association of sleep disturbances with CKD progressionmay be difficult to untangle by just counting sleep hours through a self reported questionaire.

          CKD, Hypertension and diabets in the adult population of Morocco. Gharbi et al.

          This is the publicationof the MAREMAR study that showed the prevalence of NCD and CKD in samples of the Moroccan adult population. CKD prevalence was around 5%. The study showed the importance of re-testing for proteinuria and eGFR in population screening studeis as the prevalence falls significantly upon validation of the initial positive testing...It also showed the important finding of underdiagnosis of CKD in the younger population and overdiagnosis in the older population when relying on one size fit all eGFR cut off of 60 ml/min comapred to teh more age-senstive cut-off of below the third age adjusted percentile.

          Comments:

          This is an example of how epidemiological studies on CKD detection and prevalence should be conducted.

          It also shows the serious limitations of eGF <60 ml/min to define CKD in all age groups.

          Underestimation, in younger patients whereby a 25 year old with a GFR of 70 ml/min would be considered as no suffering from CKD in the absence of proteinuira/hematuria, in spite of a significant reduction in kidney function...

          Overestimation, by using an inappropriate and age-insensitiev cut off of 60 ml/min for a 75 year odl when 45 ml/min would be much more appropriate.

          http://www.ncbi.nlm.nih.gov/pubmed/27057075

          http://www.ncbi.nlm.nih.gov/pubmed/26932693

          It is time for a rethink of the KDOQI/KDIGO CKD classification with a single defining cut off of 60 ml/min for all ages!

           

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

          Comments

             
            Picture of Meguid El Nahas
            by Meguid El Nahas - Monday, 13 June 2016, 11:09 AM
            Anyone in the world

            Are modern days nephrologists becoming Don Quixotes fighting delusionary fights...?!

            Don Quixote in the novel of Cervantes looses his mind after so much reading....and goes on a self assigned mission to fight illusionary enemies...including windmills....

            Have modern days nephrologists, also lost their sense falling prey to the brainwashing unslaught of publications on CKD definition, classification, detection and prevalence...leading them to beleive that CKD, the ultimate foe is everywhere...beleiving that up to 1 in 2 of living humans will fall to that disease...and its growing "epidemic"... are they also off to fight a delusionary battle "against CKD"...

            When will nephrologists stop referring to CKD (Chronic Kidney Disease) as a "disease" ?

            when in reality we use functional criteria that imply a reduction in function rather than a "disease" entity...in fact, there isnt an epidemic of "CKD"... there is just a deliberate misrepresentation of what is generically termed CKD...

            And, how can we label all those with a reduced kidney function as suffering from the same "Disease" when in reality they suffer from a number of underlying causes or diseases...ranging from glomerulonephritis, diabetes, hypertension, vasculitis, interstitial nephritis or hereditart kidney diseases including cystic malformations... not to mention a majority labelled as "diseased' when in reality all they suffer from is the "disease" of old age...and the associated reduction in the function of most organs including the kidneys...

            Worse still, how can we have a classification that pretends a staging and continuity from CKD1 to 5...when those suffering from CKD 1 to 3a...mostly older people, seldom progress to CKD 4 or 5...whilst those who end up in CKD4 and5 often present acutely with severe renal dysfunction as in glomerulobnephritis, vasculitis, and acute kidney injury... and never go through stages 1 and 2...

            Consequently, research shows that early detection to prevent CKD progression is a myth and an illusion...you would need to detect and unecessarily treat thousands for years to prevent 1 ESRD...as we are not detection and treating those who progress to ESRD...

            http://www.ncbi.nlm.nih.gov/pubmed/24424348

            Proteinuria changes the detection-prevention risk v benefit ratio, but then proteinuria identifies those with true disease compared to those who are labelled as "diseased"... those with glomerulonephritis, diabetic nephropathy or advanced hypertensive nephrosclerosis... compared to the community elders labelled with a "disease" they dont have...

            Is it therefore time to drop this generic and misleading term "CKD"...or leave it to epidemiologists to collect and compile meaningless information on population they never saw or truly investigated...for the sake of publishing repetitive papers on the prevalence of "CKD" in communities... leave it to the Don Quixotes of Nephrology...

            and revert to identify patients by their true renal abnormalities: hematuria, proteinuria, glomerulonephritis, vasculitis, lupus nephritis, diabetic nephropathy, etc...and tailor approach and treatment accordingly.

            This would allow for an individualisation of management approach instead of the one size fits all current generic "CKD" prevention, diagnosis and management approach...

            http://www.ncbi.nlm.nih.gov/pubmed/22189037

            It is often difficult to rail against the wind...even when the wind blows in the wrong direction...but then if we dont, we get also blown off in the wrong direction...and continue for the next decades to chase and treat a "disease" that doesnt exist...Don Quixote's style...fighting delusionary windmills...those of modern day "CKD"...

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

            Comments

               
              Picture of Meguid El Nahas
              by Meguid El Nahas - Tuesday, 24 May 2016, 6:32 AM
              Anyone in the world

              An growing controversy is buidling around the use of steroids in IgA Nephropathy.

              Pozzi and Locatelli showed that high dose steroids slow the progression of the nephropathy. http://www.ncbi.nlm.nih.gov/pubmed/10093981

              The large STOPIGAN study showed no benefit of immunosuppresion; steroids and/or cyclophosphamide. http://www.ncbi.nlm.nih.gov/pubmed/?term=STOPIGAN%2C+NEJM

              Now a Chinese study (TESTING) reported at the congress of the ERA-EDTA suggests a benefit of treatment with methylprednisolone given orally at doses of 0.6-0.8mg/kg/day for 2 months then tapering over 6-8 months; proteinuria reduction and GFR slowed down...

              All these studies rely on creatinine derived measurements of GFR and NEVER a MEASURED GFR....???!!!!

              They seem to overlook the effect of prolonged corticotherapy on muscle mass potentially contributing to a fall in serum creatinine and consequently an apparent improvement in estimated GFR...an unbeleivable AMNESIA of the effects of steroid therapy on the muscle and serum creatinine?!

              Finally, why should immunosuppression or steroids benefit a nephropathy with little or no inflammtory reaction; mesangial proliferation is seldom associated with a glomerular inflammtory reaction...

              As to the notion of IgAN being an auto-immune disease with anti-IgA autoantibodies...well, this has weak support and such auto-antobody is seldom mentioned or measured in RCTs pertaining to impact on it...?!

              IgAN is a metabolic abnormality that leads to abnormal traffic and or overproduction of an aberrantly glycosylated IgA1 characterized by galactose deficiency of some hinge-region O-linked glycans. This IgA1 subequently sticks ro is uptaked by the mesangium and leads to glomerular damage with hematuria, proteinuria and progressive CKD in a minority: http://www.ncbi.nlm.nih.gov/pubmed/27189177

              Therapies based on the manipulation of the abnormal glycosylation of IgA1 would make better sense that this nephrological obssession with immunosuppression...

              Selective depletion of Gd-IgA1-producing cells via glycan engineering may be a more logical approach...vindicating 30 years of research in the field, rather than ignoring that research and hanging one's hat on a doubtful concept of clinical relevance namely auto-immunity...

              http://www.ncbi.nlm.nih.gov/pubmed/25604055

              STOP TESTING FLAWED HYPOTHESIS AND BUILD ON RESEARCH FINDINGS TO COME UP WITH PLAUSIBLE ALTERNATIVE THERAPIES FOR IgA NEPHROPATHY!

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

              Comments

                 
                Picture of Meguid El Nahas
                by Meguid El Nahas - Tuesday, 24 May 2016, 6:32 AM
                Anyone in the world

                An growing controversy is buidling around the use of steroids in IgA Nephropathy.

                Pozzi and Locatelli showed that high dose steroids slow the progression of the nephropathy. http://www.ncbi.nlm.nih.gov/pubmed/10093981

                The large STOPIGAN study showed no benefit of immunosuppresion; steroids and/or cyclophosphamide. http://www.ncbi.nlm.nih.gov/pubmed/?term=STOPIGAN%2C+NEJM

                Now a Chinese study (TESTING) reported at the congress of the ERA-EDTA suggests a benefit of treatment with methylprednisolone given orally at doses of 0.6-0.8mg/kg/day for 2 months then tapering over 6-8 months; proteinuria reduction and GFR slowed down...

                All these studies rely on creatinine derived measurements of GFR and NEVER a MEASURED GFR....???!!!!

                They seem to overlook the effect of prolonged corticotherapy on muscle mass potentially contributing to a fall in serum creatinine and consequently an apparent improvement in estimated GFR...an unbeleivable AMNESIA of the effects of steroid therapy on the muscle and serum creatinine?!

                Finally, why should immunosuppression or steroids benefit a nephropathy with little or no inflammtory reaction; mesangial proliferation is seldom associated with a glomerular inflammtory reaction...

                As to the notion of IgAN being an auto-immune disease with anti-IgA autoantibodies...well, this has weak support and such auto-antobody is seldom mentioned or measured in RCTs pertaining to impact on it...?!

                IgAN is a metabolic abnormality that leads to abnormal traffic and or overproduction of an aberrantly glycosylated IgA1 characterized by galactose deficiency of some hinge-region O-linked glycans. This IgA1 subequently sticks ro is uptaked by the mesangium and leads to glomerular damage with hematuria, proteinuria and progressive CKD in a minority: http://www.ncbi.nlm.nih.gov/pubmed/27189177

                Therapies based on the manipulation of the abnormal glycosylation of IgA1 would make better sense that this nephrological obssession with immunosuppression...

                Selective depletion of Gd-IgA1-producing cells via glycan engineering may be a more logical approach...vindicating 30 years of research in the field, rather than ignoring that research and hanging one's hat on a doubtful concept of clinical relevance namley auto-immunity...

                http://www.ncbi.nlm.nih.gov/pubmed/25604055

                 

                 

                 

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

                Comments

                   
                  Picture of Meguid El Nahas
                  by Meguid El Nahas - Tuesday, 24 May 2016, 6:32 AM
                  Anyone in the world

                  An growing controversy is buidling around the use of steroids in IgA Nephropathy.

                  Pozzi and Locatelli showed that high dose steroids slow the progression of the nephropathy. http://www.ncbi.nlm.nih.gov/pubmed/10093981

                  The large STOPIGAN study showed no benefit of immunosuppresion; steroids and/or cyclophosphamide. http://www.ncbi.nlm.nih.gov/pubmed/?term=STOPIGAN%2C+NEJM

                  Now a Chinese study (TESTING) reported at the congress of the ERA-EDTA suggests a benefit of treatment with methylprednisolone given orally at doses of 0.6-0.8mg/kg/day for 2 months then tapering over 6-8 months; proteinuria reduction and GFR slowed down...

                  All these studies rely on creatinine derived measurements of GFR and NEVER a MEASURED GFR....???!!!!

                  They seem to overlook the effect of prolonged corticotherapy on muscle mass potentially contributing to a fall in serum creatinine and consequently an apparent improvement in estimated GFR...an unbeleivable AMNESIA of the effects of steroid therapy on the muscle and serum creatinine?!

                  Finally, why should immunosuppression or steroids benefit a nephropathy with little or no inflammtory reaction; mesangial proliferation is seldom associated with a glomerular inflammtory reaction...

                  As to the notion of IgAN being an auto-immune disease with anti-IgA autoantibodies...well, this has weak support and such auto-antobody is seldom mentioned or measured in RCTs pertaining to impact on it...?!

                  IgAN is a metabolic abnormality that leads to abnormal traffic and or overproduction of an aberrantly glycosylated IgA1 characterized by galactose deficiency of some hinge-region O-linked glycans. This IgA1 subequently sticks ro is uptaked by the mesangium and leads to glomerular damage with hematuria, proteinuria and progressive CKD in a minority: http://www.ncbi.nlm.nih.gov/pubmed/27189177

                  Therapies based on the manipulation of the abnormal glycosylation of IgA1 would make better sense that this nephrological obssession with immunosuppression...

                  Selective depletion of Gd-IgA1-producing cells via glycan engineering may be a more logical approach...vindicating 30 years of research in the field, rather than ignoring that research and hanging one's hat on a doubtful concept of clinical relevance namley auto-immunity...

                  http://www.ncbi.nlm.nih.gov/pubmed/25604055

                   

                   

                   

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

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                    Anyone in the world

                    Two decades ago, Hales and Barker reported the association between hypertension (HTN) in adult life and birth weight. They suggested that intrauterine environmental factors, mainly nutrition, could lead to permanent metabolic and structural changes in the fetus, influencing BP in adult life and increasing the risk of CVD in adulthood.

                    An inverse association exists between low birth weight (LBW) and higher blood pressures in infancy and childhood, and overt HTN in adulthood.

                    Impaired kidney development in an adverse intrauterine environment results in a low nephron number, which predisposes individuals to hypertension and kidney disease in adulthood. The main factors that predispose individuals to impaired kidney development are protein and calorie malnutrition, placental malfunction and maternal hyperglycemia. Complex processes with yet to be identified cellular and molecular mechanisms presumably contribute to impaired nephrogenesis. Growing evidence suggests that epigenetic modifications might explain many of the changes noted in perinatal programming.

                    What can we do then to ameliorate the effect of adverse fetal programming?

                    Prenatal care is transitioning to incorporate goals of optimizing maternal, fetal, and neonatal health to prevent or reduce adult-onset diseases including HTN and CVD morbidities.

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

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