Nephron News
Nephron NEWS
(Updated on Dec.25.2009)
Issue 9 [December 2009]
I take the opportunity of the December issue of Nephron Digest to send all the readers of Nephron Digest the warmest seasonal greetings and wish you a Happy New Year.
Professor Meguid El Nahas, PhD, FRCP
Editor, Nephron Clinical Practice
nephron@sheffield.ac.uk
m.el-nahas@sheffield.ac.uk
Digest of issue 113/4/2009
Locatelli and colleagues (Nephron Clin Pract 2009;113:c286-c293) provide a critical appraisal of the literature on the use of inhibitors of the RAAS system in CKD. They warn against misuse of these agents, either alone or in combination, in the elderly and those with ischaemic nephropathies. This coincides with a recent publication showing that stopping inhibitors of the RAAS system in patients with CKD5 can be beneficial, with reversal of previously relentless renal functional decline and delaying onset of ESRD (Ahmed et al, Nephrol Dial Transplant 2009 Oct 10).
Thuraisingham and Yaqoob (Nephron Clin Pract 2009;113:c294-c300) examine the evidence upon which guidelines for the management of hypertension in CKD are based. They also take a critical look at the use of ACE inhibitors/ARBs in CKD, highlighting sudden or progressive deterioration of kidney function in some patients treated with these agents. On the other hand, they report a favourable response when RAAS inhibitors were discontinued and go on to stress that treatment decisions should primarily rely on efficacy of BP lowering, tolerability and cost-benefit ratio. They caution against uncritical and indiscriminate applications of guidelines, reminding the reader that most of the current guidelines are based on expert opinion and little supporting evidence.
Vij et al. (Nephron Clin Pract 2009;113:c281-c285) conclude that urine culture should be requested to confirm UTIs in dialysis patients. Alternate tests such as pyuria (low specificity), urinary nitrites levels (very poor sensitivity) are much less reliable.
Yoon and colleagues (Nephron Clin Pract 2009;113:c241-c249) report the outcomes of renal allografts coming from spousal, emotionally related donors compared to living unrelated donors (LUDs). Spousal donor kidneys compare favourably, showing a similar outcome to kidneys taken from better HLA-matched and younger LUDs. It is important to caution against LUDs as the Istanbul declaration of 2008 takes a very strong stand against LUDs, they often being the victims of organ trafficking and abuse (Am J Transplant 2009;9:2466-2469).
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Nephron NEWS
(Updated on Nov.11.2009)
Issue 8 [November 2009]
I strongly encourage the readers of Nephron Digest to engage in a dialogue by emailing me to discuss issues of global nephrological interest. These would be addressed by expert members of the editorial board of Nephron. Also readers are encouraged to request topics that they would like to be updated upon through the Mini Review series of Nephron Clinical Practice.This issue of Nephron Digest, based on papers from Nephron Clinical Practice issue 113/3/09, contains a minireview on drug development, a critical review of the 2008 UK NICE CKD Guidance and introduces the new series on Kidney Disease and Population Health.
Professor Meguid El Nahas, PhD, FRCP
Editor, Nephron Clinical Practice
nephron@sheffield.ac.uk
m.el-nahas@sheffield.ac.uk
Digest of issue 113/3/2009
The minireview by Tamimi and Ellis, UK (Nephron Clin Pract 2009;113:c125-c131) explains the stages of drug development, going through details of regulatory approval. It also reminds the reader of the huge and often prohibitive cost of developing new drugs, explaining why thousands of new potentially promising products never make it to the bedside. The review also clarifies sensitive issues relevant to the relationship between the pharmaceutical industry and the medical profession.
Khwaja and Throssel, UK, (Nephron Clin Pract 2009;113:c207-c213) review and appraise the 2008 UK National Institute of Health and Clinical Excellence (NICE) CKD guidance. The NICE guidelines are the first to recommend a subdivision of CKD stage 3 into CKD3a (GFR:59-45ml/min) and CKD3b (44-30ml/min). They also recommend adding the suffix "p" after the CKD stage to denote proteinuria (PCR>50mg/mmol or 500mg/g; ACR >30mg/mmol). The NICE CKD modification of the KDOQI 2002 classification takes into consideration the different risk profiles of patients within the CKD3 stage. It also stratifies, for the first time, CKD according to albuminuria/proteinuria. Albuminuria is known to be a major renal, cardiovascular and mortality risk marker. For more details refer to the UK NICE website.
In this issue, Nephron Clinical Practice also introduces the new series of Kidney Disease and Population Health. Zoccali (Italy), Jager, Dekker (The Netherlands) and their colleagues introduce and explain cohort studies and study designs in clinical research (Nephron Clin Pract 2009;113:c214-c217) and (Nephron Clin Pract 2009;113:c218-c221). All too often Nephrologists, through lack of knowledge of such important topics, fail to appreciate the quality of publications. They also fail to undertake meaningful clinical research as they lack the basic tools. Nephron Clinical Practice hope that this new series of publications (11 in total) will guide those who wish to embark on clinical research and inform those who read publications as to their true value.
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Nephron News
(Updated on Sep.24.2009)
Issue 7 [September 2009]
This issue of Nephron Digest, based on papers from Nephron Clinical Practice issue 113/2/09, focuses on RAAS inhibition and the progression of CKD, endothelial dysfunction and ADPKD, arterial stiffness and fetuin A in CKD, and volume control and reduction of cardiac biomarkers.I strongly encourage the readers of Nephron Digest to engage in a dialogue by emailing me to discuss issues of global nephrological interest. These would be addressed by expert members of the editorial board of Nephron.
Professor Meguid El Nahas, PhD, FRCP
Editor, Nephron Clinical Practice
nephron@sheffield.ac.uk
m.el-nahas@sheffield.ac.uk
Digest of issue 113/2/2009
RAAS inhibition and the progression of CKD. In this paper, Onuigbo, USA (Nephron Clin Pract 2009;113:c63-c70), critically evaluates the literature pertaining to the therapeutic advantage to the progression of CKD of the inhibition of the renin-angiotensin-aldosterone system (RAAS). He draws attention to the limitations of published evidence and stresses the risks associated with ACE inhibitors/ARBs in CKD in the elderly. This mini review should stimulate a re-evaluation of the risk/benefit ratio of inhibition of the RAAS in CKD.
Endothelial dysfunction and ADPKD. Ramunni and colleagues, Italy (Nephron Clin Pract 2009;113:c71-c75), report on microvascular/endothelial dysfunction in ADPKD patients. They postulate that systemic endothelial dysfunction precedes hypertension and impaired kidney function. Nitric oxide (NO) dysfunction has been implicated in defective vascular reactivity in ADPKD. These observations are of interest as emerging data link polycystins to NO signalling (W.A. AbouAlaiwi et al., Circ Res 2009;104:860-469). Within the kidney, a defect in polycystins affects tubule cilia and may contribute to cystogenesis whilst an endothelial defect in polycystins may contribute to vascular dysfunction (S.M. Nauli et al., Circulation 2008;117:1161-1171). Polycystin abnormalities may thus underlie the systemic pathology of ADPKD.
Arterial stiffness and fetuin A in CKD. Porazko and co-authors, Poland and USA, (Nephron Clin Pract 2009;113:c81-c87), attempt to link the increased arterial stiffness observed in CKD patients to decreased circulating fetuin A levels and raised CRP and IL-6. A growing body of data links fetuin deficiency to vascular, valvular and soft-tissue calcifications in CKD. In CKD, a number of bone regulatory proteins, including fetuin, are involved in both bone demineralisation and vascular calcifications (K.A. Hruska et al., Semin Nephrol 2009;29:156-165). Recognition of the links between bones and vascular calcifications in CKD should optimise management.
Volume control and reduction of cardiac biomarkers. Ortega and colleagues, Spain (Nephron Clin Pract 2009;113:c96-c103), undertook a short-term prospective study that showed that strict fluid and salt restriction in HD patients may impact on biomarkers of cardiovascular prognosis such as CRP and NT-proBNP. Clearly, longer term studies are required to ascertain whether changes in biomarkers impact CVD morbidity and mortality. More emphasis should be put on the temporal evolution of key biomarkers during HD rather than on single cross-sectional values (P. Kotanko et al., Blood Purif 2009;27:38-47). This study also highlights the often overlooked importance of salt and water restriction in HD patients (F. Raimann et al., Hemodial Int 2008;12:395-405).
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Nephron NEWS
(Updated on Aug.03.2009)
Issue 6 [July 3, 2009]
This issue of Nephron Digest, based on papers from Nephron Clinical Practice issue 113/1/09, focuses on transplant glomerulopathy, obesity and CKD progression, albuminuria/microalbuminuria, and secondary hyperparathyroidism and CKD progression.I strongly encourage the readers of Nephron Digest to engage in a dialogue by emailing me to discuss issues of global nephrological interest. These would be addressed by expert members of the editorial board of Nephron.
Professor Meguid El Nahas, PhD, FRCP
Editor, Nephron Clinical Practice
nephron@sheffield.ac.uk
m.el-nahas@sheffield.ac.uk
Digest of issue 113/1/2009
Transplant glomerulopathy. The minireview by Fotheringham and colleagues from the Sheffield Kidney Institute (Nephron Clin Pract 2009;113:c1-c7) is a comprehensive update on transplant glomerulopathy (TG). This term has replaced that of chronic allograft nephropathy, placing more emphasis on glomerular changes. Tubular interstitial changes are labelled as Interstitial Fibrosis and Tubular Atrophy. Pathology also focuses on vascular, peritubular capillary, changes including the deposition of the complement fragment C4d suggesting a humoral, anti-donor antibody-mediated injury.
Fotheringham and his colleagues review the range of available therapies for TG. Amongst the novel therapies that might prove effective in the future are anti-C5 monoclonal antibodies inducing an accommodation state in endothelial cells. Also,co-stimulation blockade with interference with the CD40-CD154 pathway may prove effective. It is likely that this area of nephrology/immunology will see major advances over the next few years (Cosio et al., Am J Transplant 2008;8:492-496).
Obesity and CKD Progression. A study from the UK by Othman and his coworkers (Nephron Clin Pract 2009;113:c16-c23) reinforces the increasingly held impression that obesity is a major risk factor for CKD. A large body of evidence is now linking obesity with initiation and progression of CKD (Ting et al., Nephron Clin Pract 2009;112:c121-127). Othman and his colleagues have noted that baseline BMI at presentation to a Nephrology service is a strong and independent predictor of the rate of CKD progression. They also report that changes in BMI during the follow-up period do not affect the rate of decline in GFR. Previous observations by the same group showed that weight loss reduces microalbuminuria in a general population cohort study (Bello et al., Nephrol Dial Transplant 2007;22:1619-1627).
High Normal Albuminuria and risk. Cotter and colleagues from Porto in Portugal (Nephron Clin Pract 2009;113:c8-c15) identify high normal albuminuria, poor blood pressure control as well as dyslipidemia as risk factors for the onset of microalbuminuria. This observation agrees with observations made in the general population by the PREVEND group who identified high normal albuminuria as a CVD risk marker as well as those made in people with diabetes where poor glycemia and blood pressure control, dyslipidemia and smoking have all been implicated in the onset of microalbuminuria. Of note the majority of individuals in this study (70%) were diabetics. However, this study re-emphasises that the risk associated with albuminuria is a linear one starting within the upper normal range. This observation reinforces the call for a reassessment of the artificial separation of albuminuria into high normal and microalbuminuria.
Secondary Hyperparathyroidism (SHPT) and CKD progression. Schumock and associates from Chicago and Torrance (Nephron Clin Pract 2009;113:c54-c61) report the predictive value of SHPT in relation to outcomes of patients with CKD. They note that diabetic pre-dialysis CKD patients with higher levels of PTH are at increased risk of disease progression to ESRD, requiring dialysis, and also at higher risk of death. This study identifies SHPT as a CKD risk factor; future research will determine whether there is a causal link and whether control of SHPT with agents such as calcimimetics will delay CKD progression. It would also be interesting to know whether the observed association is independent of underlying changes in vitamin D levels. The latter is increasingly singled out, along with FGF-23, as a major renal and cardiovascular risk factor (Judd and Tangpricha, Am J Med Sci 2009;338:40-44).
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Nephron NEWS
(Updated on May.25.2009)
Issue 4 [May 20, 2009]
For the current Nephron Digest, I have chosen three papers from Nephron Clinical Practice, issue 112/2/09: One article deals with Balkan Endemic nephropathy, one focuses on kidney disease as a negative predictor of 30-day survival after acute ischaemic stroke, and the third investigates cardiorenal risk prevalence in sickle cell hemoglobinopathy.
Many of the topics discussed in this issue of Nephron Clinical Practice will undoubtedly feature prominently at the forthcoming World Congress of Nephrology in Milan, Italy.
Hope to see you there!
Professor Meguid El Nahas, PhD, FRCP
Editor, Nephron Clinical Practice
nephron@sheffield.ac.uk
m.el-nahas@sheffield.ac.uk
Digest of issue 2/2009
The review by Stefanovic and Polenakovic (Nephron Clin Pract 2009;112:c51-c56), two leading experts on Balkan Endemic Nephropathy (BEN), reminds readers of the link between BEN, uroepithelial cancer and toxins such as aristolochic acid (AA). In the Balkans, BEN may be associated with consumption of flour derived from wheat contaminated with Aristolochia clematitis which contains high levels of AA. Of note, in Asian countries, the complexity of processing of Chinese herbal remedies and the common substitution of botanical products by AA-containing herbs represents the major risk for AA-associated nephropathy. In Taiwan, regular users of Chinese herbal medicines have a 20% increased risk of developing CKD (Wen et al., Lancet 2008;371:2173-82).
The study by Szymon Brzosko and colleagues from Bialystok, Poland (Nephron Clin Pract 2009;112:c79-c85) showed that decreased eGFR and presence of dipstick proteinuria were strong negative predictors of 30-day survival after ischemic stroke. This study confirms the negative cardiovascular disease (CVD) prognostic implications of CKD. It supports the growing impression that decreased kidney function and/or proteinuria in the elderly identify a subgroup with underlying subclinical atherosclerosis. A recently devised predictive scoring system, SCORED (SCreening for Occult REnal Disease), was shown to reliably predict recurrent CVD in heart attack and stroke patients, (Bang et al., Nephrol Dial Transplant 2009; March 26 - Epub ahead of print; doi:10.1093/ndt/gfp124).
Abo-Zenah and colleagues from the Kingdom of Saudi Arabia (Nephron Clin Pract 2009;112:c98-c106) showed that markers of cardio-kidney-damage, such as albuminuria and atherosclerosis, were common findings in patients of Arabic descent with sickle cell haemoglobinopathies. They suggested that albuminuria could prove to be a useful screening tool to identify sicklers at risk for cardiovascular and renal events. Albuminuria is proving to be a useful marker of the well-known diffuse vascular endothelial dysfunction of patients with SCD (Morris, Hematology Am Soc Hematol Educ Program 2008;177-185).
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Nephron NEWS
(Updated on Apr.09.2009)
Special Issue [April 8, 2009]
Dear Nephron Digest Reader
This is to draw your attention to the online publication of the UK Renal Registry Report (UKRR) 2008. This is an annual publication summarizing and commenting on all the UK renal activities, with emphasis on renal replacement therapy statistics as well as a thorough comparative analysis of UK renal unit's performance in a number of key target areas of clinical governance. The UKRR is an excellent example of clinical governance and monitoring of renal services delivery of quality nephrological care. By naming and comparing performances across UK renal units, the UKRR leads the way internationally in auditing activities and highlighting high and low performers. Undoubtedly, the UKRR has raised the standards of nephrological care in the UK. Unfortunately, the majority of countries doesn't have a renal registry to report and monitor renal services activities. Efforts should be made to improve the documentation and outcomes of renal services worldwide. National and regional renal registries should be fostered by local and regional governmental and non-governmental organizations. A global renal registry reporting on World Kidney Day may one day become a reality.
THE UKRR report has been published in Nephron Clinical Practice as a free electronic supplement.
Professor Meguid El Nahas, PhD, FRCP
Editor, Nephron Clinical Practice
nephron@sheffield.ac.uk
m.el-nahas@sheffield.ac.uk
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Nephron NEWS
(Updated on Feb.04.2009)
Issue 2, 2009 [February 4, 2009]
Nephron News
has changed its name to
Nephron Digest
The February issue of Nephron Digest concentrates on the following topics discussed in Nephron Clinical Practice Vol. 111, No. 2, 2009: Encapsulating peritoneal sclerosis; Management of severe secondary hyperparathyroidism (sHPT) and the associated renal osteodystrophy, and predictors of erythropoiesis-stimulating agents (ESA) use in non-dialysis CKD.
I would like to point out that nephrologists worldwide need to be aware that the management of anemia and bone and mineral disorders in CKD patients impact on patients' morbidity, QoL and mortality. Optimization of care is therefore essential to improve outcomes.
Professor Meguid El Nahas, PhD, FRCP
Editor, Nephron Clinical Practice
nephron@sheffield.ac.uk
m.el-nahas@sheffield.ac.uk
Augustine and colleagues from the UK (2009;111:c149-c154) address an important, serious and often underestimated complication of long-term CAPD, namely encapsulating peritoneal sclerosis (EPS): In their review, they highlight the clinical, pathological as well as radiological features of EPS and discuss the pathophysiology of peritoneal fibrosis which shares common pathways with other forms of fibrosis including a putative important role attributed to transforming growth factor-beta1. Moreover, the authors not only introduce a list of recommendations and guidelines for early detection and management of EPS, but they also draw attention to the recently formed UK EPS registry and DNA bank to foster clinical collaboration and research in the field. This registry is supported by the International Society of Peritoneal Dialysis (ISPD) and the Kenyon Gilson Fund. Readers with an interest in the field should contact Dr Martin Wilkie at the Sheffield Kidney Institute, Sheffield, UK. (martin.wilkie@sth.nhs.uk)
Silvia Stracke and her colleagues from Ulm, Germany (2009;111:c102-c109) make a case for total parathyroidectomy (tPTx) without autotransplantation for the management of severe secondary hyperparathyroidism (sHPT) and the associated renal osteodystrophy.
Their data is of interest, but caution should be exerted when advocating tPTx in ESRD patients treated by dialysis as this can lead to severe suppression of PTH release and adynamic bone disease. Of concern is the risk of vascular calcifications associated with adynamic bone in the face of vitamin D therapy and calcium supplementation. It is now well established that bone, mineral and vascular disease form a continuum in patients with ESRD, whereby loss of bone mineralization is often associated with a shift of calcium deposition away from the bone into soft tissues and vessels. It is important to apply a holistic approach to the management of bone, vascular and mineral disorders in ESRD patients, thus avoiding to treat the bones at the expense of the vessels.
After all, ESRD patients die from cardiovascular disease precipitated in many instances by severe and accelerated vascular calcifications.
Allan Collins and his colleagues from Minneapolis, Minn. (2009;111:c141-c148) discuss the predictors of erythropoiesis-stimulating agents (ESA) use in non-dialysis CKD.
Their study shows the low use of ESA in US CKD patients not on RRT (7%),at the same time highlighting the fact that referral to CKD-specific care is an important predictor of ESA use.
A recent publication by Finkelstein et al. from Yale, New Haven, Conn. (CJASN 2009;4:33-38) also demonstrates that increasing hemoglobin (Hb) levels impact on Quality of Life (QoL) parameters including energy/vitality and the general health score. The most dramatic QoL improvements occurred between the <11g/dl when compared to the 11 to 12g/dl group. These findings have implications for the care of CKD patients in terms of the initiation of ESA therapy. However, issues related to the use of ESA in CKD have recently focused on target Hb levels with suggestions that high Hb levels (>12.5g/dl) may be detrimental to patients with CKD/ESRD and/or that high levels of administered ESA may be associated with increased risk including that of malignancies. The US Food and Drug Administration has inserted a boxed warning for ESAs and, along with the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI), decreased recommended target Hb ranges for ESA therapy. Caution may be warranted when prescribing ESAs in patients with ESRD and a recent history of cancer.
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Nephron NEWS
(Updated on Jan.07.2009)
Issue 1, 2009 [January 7, 2009]
The January issue of Nephron Clinical Practice (Vol. 111, No. 1, 2009) features a number of interesting original articles as well as some outstanding reviews and commentaries. The current issue of Nephron News highlights three articles: The mini review by Courtney and Maxwell, Belfast, on the challenges facing global renal transplantation and organ retrieval; the first of a series of critiques of current nephrological guidelines by Connolly and Woolfson, London; and the article by Takemoto et al., Japan, on the prognostic value of the serum adiponectin level for coronary heart disease in hemodialysis patients.
Please do not hesitate to write to me and share your views and experiences of topics related to these publications.
Professor Meguid El Nahas, PhD, FRCP
Editor, Nephron Clinical Practice
nephron@sheffield.ac.uk
m.el-nahas@sheffield.ac.uk
The timely review by Courtney and Maxwell (2009;111:c62-c68) discusses issues related to the challenge of equity in the allocation of organs for kidney transplantation. Globally, the shortage in kidney transplants has challenged national healthcare authorities to come up with policies addressing this issue without compromising ethics and human rights. The authors examine some of the allocation schemes and discuss related ethical considerations, all in the spirit of the Istanbul declaration (2008) that concluded that organ trafficking and transplantation tourism violate the principles of equity, justice and respect for human dignity and that such practices should be prohibited. It is also important to bear in mind that geographical and socio-economic factors, along with cultural influences, impact on transplantation worldwide. I just hope that the current global financial crisis does not put even more pressure on those living in conditions of deprivation to jeopardize their health through dangerous and unethical renal transplantation practices.
In their thorough and considerate review (2009;111:c69-c73) , Connolly and Woolfson highlight the limitations of the current CKD classification and guidelines. They also raise reservations regarding the limitations of current formulae, in particular MDRD, for the calculation of GFR in the general population and in ethnic minorities where it has not been fully validated. Of note, efforts have been made to come up with correction factors for the MDRD formula to make it more accurate in predicting GFR in Asian CKD patients including those from Japan. Improving the accuracy and precision of the calculation of GFR may enhance future applicability.
The nephrology community needs to appreciate that KDIGO is committed to regular reviews of the definition and classification of CKD and that more data is needed to refine them, with emphasis on the prognostic implications of CKD stages in terms of progression to ESRD, but also in relation to the high CVD mortality that plagues CKD patients.
The Japanese study by Takemoto et al. (2009;111:c12-c20) confirms the prognostic value of low adiponectin in ESRD patients. A number of studies have shown that low circulating levels of this adipokine, known to be decreased in obesity, has negative CVD prognostic implications. Adiponectin is a multifunctional adipokine with anti-inflammatory properties. Low serum levels of adiponectin have been associated with increased CVD mortality in the general population, in patients with CKD as well as in those with ESRD. Adiponectin, along with brain natriuretic peptide (BNP), is emerging as a reliable prognostic indicator in hemodialysis patients. The mechanisms of the cardioprotective effect of adiponectin remain poorly understood, although an increase in HDL cholesterol and a direct effect on myocardial contractibility have been postulated. In the general population, another adipokine leptin known to be raised in obesity has also been associated with increased CVD risk in men. Moreover, published data link low adiponectin levels with raised blood pressure and associated vascular stiffness; these are also known to impact CVD morbidity and mortality in hemodialysis. Clearly, the relationship between adipokines and CVD outcomes in ESRD patients is a hot topic that warrants further investigations. This is all the more intriguing since increased weight in HD patients is associated with improved survival.
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