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糖尿病肾病分子机制及个性化医疗

Nephrol

Dial Transplant(2015)30:iv105–iv112

doi:10.1093/ndt/gfv210

Full Review

Drugs meeting the molecular basis of diabetic kidney disease:bridging from molecular mechanism

to personalized medicine

Hiddo https://www.wendangku.net/doc/1a16346551.html,mbers Heerspink1,Rainer Oberbauer2,Paul Perco3,Andreas Heinzel3,Georg Heinze4,Gert Mayer5 and Bernd Mayer3

1Department of Clinical Pharmacy and Pharmacology,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands,2Department of Internal Medicine III,Medical University of Vienna,Vienna,Austria,3Emergentec biodevelopment GmbH,Vienna, Austria,4Center for Medical Statistics,Informatics and Intelligent Systems,Medical University of Vienna,Vienna,Austria and5Department of Internal Medicine IV,Medical University of Innsbruck,Innsbruck,Austria

Correspondence and offprint requests to:Bernd Mayer;E-mail:bernd.mayer@https://www.wendangku.net/doc/1a16346551.html,

A B S T R AC T

Diabetic kidney disease(DKD)is a complex,multifactorial dis-ease and is associated with a high risk of renal and cardiovascu-lar morbidity and mortality.Clinical practice guidelines for diabetes recommend essentially identical treatments for all pa-tients without taking into account how the individual responds to the instituted therapy.Yet,individuals vary widely in how they respond to medications and therefore optimal therapy dif-fers between individuals.Understanding the underlying mo-lecular mechanisms of variability in drug response will help tailor optimal therapy.Polymorphisms in genes related to drug pharmacokinetics have been used to explore mechanisms of response variability in DKD,but with limited success.The complex interaction between genetic make-up and environ-mental factors on the abundance of proteins and metabolites renders pharmacogenomics alone insuf?cient to fully capture response variability.A complementary approach is to attribute drug response variability to individual variability in underlying molecular mechanisms involved in the progression of disease. The interplay of different processes(e.g.in?ammation,?brosis, angiogenesis,oxidative stress)appears to drive disease progres-sion,but the individual contribution of each process varies. Drugs at the other hand address speci?c targets and thereby interfere in certain disease-associated processes.At this level, biomarkers may help to gain insight into which speci?c patho-physiological processes are involved in an individual followed by a rational assessment whether a speci?c drug’s mode of ac-tion indeed targets the relevant process at hand.This article de-scribes the conceptual background and data-driven work?ow developed by the SysKid consortium aimed at improving char-acterization of the molecular mechanisms underlying DKD at the interference of the molecular impact of individual drugs in order to tailor optimal therapy to individual patients. Keywords:drug,personalized medicine,prediction,systems biology,type2diabetes

I N T RO D U C T I O N

About one of three patients with diabetes mellitus develops some degree of chronic kidney disease(CKD)[1].Given that the prevalence of type2diabetes mellitus is approximately 8%in industrialized countries[2],diabetic kidney disease (DKD)has become a huge global health burden.For example the US government(via the National Center for Chronic Dis-ease Prevention and Health Promotion)has recently issued an initiative to provide comprehensive public health strategies for promoting kidney health in diabetes[3].These plans are de-signed to raise awareness and control renal risk factors in order to prevent end-stage renal disease(ESRD)and maintain quality of life of affected individuals.Haemodialysis as treat-ment modality of most ESRD patients with diabetes consumes about1–3%of the national health care budgets although the

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prevalence is only 0.1%[4,5].There is thus a strong economic imperative to improve the outcomes of type 2diabetes as well as a strong personal and societal health rationale.Risk factors and intervention studies predominantly ad-dressed established cardiovascular risk pro ?les such as arterial hypertension,hyperlipidaemia and poor glucose control.Al-though these risk factors predict renal function decline on a population level,the individual prediction of the course of glomerular ?ltration rate (GFR)decline remains poor.Of the novel promising predictive biomarkers,only very few have been validated in large prospective cohorts,and thus the ex-plained variability of GFR loss on top of established clinical risk factors remains elusive in the everyday clinical setting.Past intervention studies have addressed the established car-diovascular risk factors and demonstrated the importance of HbA1c control and blood pressure control in delaying the pro-gression of DKD.Blood pressure control with drugs intervening in the renin-angiotensin-aldosterone-system (RAAS)is particu-larly effective and remain so far the only established prevention strategy in already proteinuric patients with type 2diabetes [6–8].Even in these successful studies,the number needed to treat for prevention of ESRD averages about 60patients suggesting that the absolute risk reduction is only 1–2%.Thus the obvious question is why some patients experience a progressive loss of renal function whereas others do not.Accordingly,treatment is bene ?cial in some patients but fails in many others.There are several potential explanations for the lack of treat-ment effect.Besides low adherence to therapy due to polyphar-macy and prescription of drugs for many years without an immediate positive effect,the complex and heterogenic patho-physiology of DKD is likely another key reason.Morphological features of DKD range from predominantly atherosclerosis to severe podocyte injury and subsequently partial obliteration of the glomerular tuft to full glomerulosclerosis.Many deregu-lated molecular pathways have been identi ?ed in different stages of DKD,but the integration of these data into a wider molecular network to better discern the key mediators of pro-gression of DKD and how drugs intervene in these processes in individual patients only recently started [9,10].Given the large heterogeneity in pathophysiology of DKD and the substantial variability in response to renoprotective drugs,the SysKid consortium developed a data-centric work-?ow to improve molecular phenotyping and characterization of the underlying molecular mechanisms of DKD on the level of individual patients in order to develop novel treatment ap-proaches with a special emphasis on personalized medicine.T R E AT M E N T O F D I A B E T I C K I D N E Y D I S E A S E Optimal blood pressure and HbA1c control are the mainstay of treatment for diabetic nephropathy.HbA1c control is particu-larly important to prevent microvascular complications as shown in landmark clinical trials such as the United Kingdom Prospective Diabetes Study (UKPDS)and Action in Diabetes and Vascular disease:preterAx and diamicroN-MR Controlled Evaluation (ADV ANCE)trials [11,12].Blood pressure control with intervention in the RAAS is vital at any stage of nephropathy and slows the progression of renal disease [13].The success of these strategies is illustrated by a recent study of Andrésdóttir et al.,who showed that intensi ?ed RAAS block-ade,metabolic control and improved cholesterol treatment re-sults in an almost 50%reduction in mortality in both type 1and type 2diabetic subjects with CKD [14].However,despite much progress has been made still many patients progress to ESRD,or are confronted with cardiovascular complications.There is thus an urgent need for tailoring medication or identifying novel drugs to mitigate the complications of diabetes.In the last dec-ade,several novel drugs and strategies have been tested,without success however [15].First,intensi ?cation of RAAS blockade by combinations of Angiotensin-Converting-Enzyme-inhibitors (ACEi),ARBs or direct renin inhibitors did not lead to the expected improve-ment in renal and cardiovascular outcome.The ALiskiren TrIal in Type 2diabetes Using carDiorenal End points (ALTI-TUDE)and Veterans Affair Nephropathy in Diabetes trials (V A NEPHRON-D)were stopped early because of more cases of worsening of renal function and hyperkalemia in the dual RAAS blockade treatment arm [16,17].In addition,in the ALTITUDE trial dual RAAS blockade did not confer renal or cardiovascular protection,in fact it showed a trend towards more stroke events,despite additional blood pressure and albu-minuria lowering.In the NEPHRON-D trial,blood pressure and albuminuria also decreased and dual RAAS blockade caused a 34%risk reduction of ESRD,but this was not statistic-ally signi ?cant (P =0.07)possibly due to the early discontinu-ation of the trial.Endothelin receptor blockade represents another promising therapeutic strategy because of the powerful blood pressure and albuminuria lowering effects [18].However,the hard outcome study with one of the ?rst endothelin receptor antagonists

(ERA)in this class (avosentan)demonstrated that its use was associated with increased incidence of oedema and hospitaliza-tion for heart failure which led to the premature discontinu-ation of the trial [19].The high risk of heart failure was attributed to the drug ’s sodium retaining effects.Key aspects of DKD pathogenesis include oxidative stress,in ?ammation and ?brosis.A recent phase III trial with bardox-olone methyl addressed in ?ammation and oxidative stress in order to delay ESRD.However,this trial also had to be stopped early due to increased incidence of heart failure and mortality in the bardoxolone methyl treatment arm [20].

Thus,various trials with different drugs and targets failed to demonstrate the ef ?cacy and safety of new interventions for

DKD.In fact,some trials even showed a higher risk of compli-

cations,mainly stroke and heart failure.The recent failures in

developing novel treatments for DKD reveal a fundamental

problem in drug research and development productivity.Bring-

ing a new molecular entity to the patient takes approximately 13years with costs exceeding 1billion US dollars [21].Despite the enormous investments in human and ?nancial recourses to de-velop new drugs still approximately 50%of all drugs fail in late stage drug development as clearly exempli ?ed by past clinical trials in diabetic nephropathy [22].Apparently the ef ?ciency of the current drug development process needs conceptual im-provements to successfully deliver new drugs to the patient.F U

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Large variability between individuals in drug response The design of past clinical trials focussed on the drug effect on the overall population.The trial designs did not take into ac-count the variable drug effects in individual patients.However,it is known for many years already that individual patients show

a large variability in response to many drugs.For example,in the Reduction of End points in noninsulin-dependent dia-betes mellitus with the Angiotensin II Antagonist Losartan (RENAAL)trial,a large variation in albuminuria was observed (Figure 1).This response variation is also observed in the above-mentioned trials in diabetic nephropathy.Careful post-hoc analyses from these trials have suggested that a sub-group of patients may have bene ?tted from therapy or in contrast were prone to side effects such as heart failure and should not have been exposed to the investigational drug.A post-hoc analysis in the ALTITUDE trial showed that in-dividuals with a larger albuminuria reduction during the ?rst months of therapy had fewer renal events compared with pa-tients with no reduction in albuminuria.These data suggest that enrichment of the population with albuminuria responders will result in a larger treatment effect.Since many trials were stopped early because of side effects,early identi ?cation of pa-

tients who do not tolerate the therapy is warranted.In the Bar-doxolone Methyl Evaluation in patients with CKD and type 2diabetes mellitus:the Occurrence of Renal Events (BEACON)trial patients with a brain natriuretic peptide (BNP)>200pg/mL or previous heart failure were at highest risk of heart failure [23].After exclusion of these patients,the risk of heart failure was similar in the bardoxolone methyl and placebo arm.In the ASCEND trial,the risk of heart failure during avosentan therapy was particularly pronounced in patients who had a rise in body weight more than 1.0kg during the ?rst weeks of therapy [24].Thus,careful selection of patients (e.g.BNP cri-teria in BEACON)and patient monitoring (e.g.body weight in ASCEND)during the ?rst weeks of treatment may help to identify patients who do not tolerate the study drug.These post-hoc analyses (albeit post-hoc and only hypothesis generating)indicate that a large,individually determined response variabil-ity exists suggesting that the current ‘one-size ?ts all ’approach in drug development is no longer sustainable.Hence,alternative strategies by for example using biomarkers to predict and monitor the individual drug response have to be considered and implemented to resolve the fundamental problems in drug development for DKD.

New interventions

In the context of DKD a broad spectrum of targets addres-sing diverse mechanisms are presently undergoing preclinical or early clinical evaluation,including further NOX inhibitors,interference with protein kinase C,chemokine receptor 2an-tagonists and inhibitors of TGFB-linked SMAD2signalling ac-tivation,or direct inhibition of TGFbeta.A PubMed scienti ?c literature search provided 104protein coding genes implicated as potential drug targets in DKD [25].From this plethora of drug candidates the key question is how to successfully bring drugs addressing these targets to the right patients.A strategy of tailoring these drugs to individual patients using biomarkers to select the right drug for the right patient seems the most lo-gical and fruitful approach.Obviously,such an approach is not only limited to new drugs but should also be considered for already registered drugs.

Precision medicine as a concept

As outlined by Klonoff in the context of managing diabetes precision medicine aims at tailoring medication with respect to a speci ?c clinical presentation [26].Precision medicine may be seen as successor of personalized medicine.Personalized

medicine conceptually refers to the development of speci ?c drugs which are speci ?cally targeted to one individual.These drugs thus vary for each patient.An example is the de-velopment of an autologous vaccine utilizing tumour cells of an individual.A less extreme example of personalization is the strati ?cation of patients based on clinical parameters or dis-ease biomarkers and tailoring therapies to speci ?c sub-group of patients [27].

Hence,precision medicine rests on phenotype pro ?ling and allows selection of a sub-group of patients who are more likely to respond or tolerate a speci ?c treatment.This concept is cer-tainly not new,and has been applied in clinical trials focussing on delaying the progression of DKD.For example,past clinical

trials selected patients with a high albuminuria level or low

eGFR in order for suf ?cient ESRD end points to occur without

the need for an extremely large clinical trial of long duration.

However,with respect to treatment response,applying albu-

minuria and eGFR thresholds did not lead to the identi ?cation

of responder patients (e.g.in the RENAAL trial)or identifying

patients prone to side effects (e.g.in the BEACON trial)[6,20].

It therefore appears that readily available clinical risk markers

for disease development and progression (e.g.albuminuria/

eGFR)are insuf ?cient to predict the individual ’s response to

treatment and are therefore unlikely to be used in the context

of precision medicine for selecting responder and non-

responder patients.Optimally,precision medicine requires a

match between the drug ’s molecular mechanism of action

and the molecular pathophysiology of a sub-group of patients.

Therefore,the entire concept of precision medicine is based on

the molecular mechanisms of drugs and disease.Risk factors for disease progression as well as indicators of organ

(dys)function F I G U R E 1:Cumulative distribution of changes in albuminuria after 6months treatment with losartan or placebo in the RENAAL trial.F U L L R E V I E W T r a n s l a t i o n o f d r u g c a n d i d a t e s t o p e r s o n a l i z e d m e d i c i n e iv107 at University of California, Santa Barbara on July 27, 2015

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may serve as proxy for such speci ?c molecular match.However,the currently used markers for renal disease progression appear not to re ?ect a drug ’s molecular mode of action and therefore do not predict the response to therapy.Following this line of argument a different strategy may be pursued in which the interference at the molecular level of a drug mode of action is established against the background of an individual patient ’s or sub-group of patient ’s pathophysi-ology.At such interference,biomarkers can be selected that can be used to monitor the drug effect in the background of a speci ?c (individually determined)DKD mechanism.For im-plementing such an approach at ?rst a detailed molecular pro-cess and mechanism map of DKD needs to be retrieved allowing for annotation of a molecular pathway representation of DKD pathophysiology.Second,biomarker candidates are to be determined serving as proxy for such individual molecular mechanisms.The biomarker thus serves as a proxy for a given status of a selected mechanism,and the biomarker panel covers all mechanisms considered relevant for character-izing disease presentation.Then such candidate biomarkers need to be individually tested as to whether they improve pre-diction of renal function decline.This leads to a (sub)set of prognostic renal biomarkers for progressive disease.As the bio-markers were derived on the basis of their mechanisms,these prognostic biomarkers seamlessly provide insight in the me-chanisms associated with progressive disease.In turn,having established such biomarker panel provides enhanced molecular insight in the phenotype on a patient-speci ?c level.As drugs need to address mechanisms associated with progressive dis-ease the above-described phenotype pro ?ling in turn allows cat-egorization of patient strata for which speci ?c drugs indicate bene ?cial interference.Implementing such approach is inher-ently data-driven.A D

ATA -D R

I V

P E R S P E C T I V E O N

S T R AT I F I E D M E D I C I N E I N D I A B E T I C K I D N E Y D I S E A S E In order to identify individuals who will respond and bene ?t from therapy,various types of data in a biological interaction context have to be considered such as the genetic background with direct impact on drug absorption,distribution,metabol-ism and excretion (ADME),and on top biomarkers re ?ecting disease presentation and progression including genetic back-ground impacting speci ?c disease mechanisms together with in ?uence of environmental factors.Genetic background in ?uencing drug effect and variability in drug response The genetic background of an individual may impact on drug ADME and thereby contribute to variability in drug re-sponse.Polymorphisms in genes af ?icted in pharmacokinetic processes can result in drug therapy resistance for example in case of rapid drug metabolism,or can increase the susceptibility to side effects [28].This is illustrated by a study demonstrating that polymorphisms in CYP2C9impact on the pharmacokinet-ics of Angiotensin Receptor Blockers [29].Further,sequence variation resulting from gene polymorphism may be involved in the drug target itself.Some of these variations may be func-tional with respect to drug binding resulting in variability in pharmacodynamic response.A link between genetic poly-morphisms and variability in drug response is illustrated by polymorphisms in the angiotensinogen 235Met/Thr which seems to relate to RAAS activity and variability in drug re-sponse to Angiotensin Receptor Blockers [30].However,poly-morphisms in this gene and response variability were not consistently observed in all studies hampering development of genetic testing on ACE/ARB response in clinical practice [31].Thus,pharmacogenomic studies have clearly demon-strated that variability in drug response can in part be attrib-uted to variability of the genetic background of an individual.Yet,it is unlikely that drug response variability is entirely captured by gene polymorphisms which can alter drug disposition.Systems medicine to unravel individual differences in drug response A complementary view is that drug response variability can also be attributed to individual variability in underlying molecular mechanisms involved in the progression of nephro-pathy.Indeed,it is known that type 2diabetes is a heteroge-neous disease involving multiple pathophysiological processes.Accordingly,recent studies have shown that panels of biomar-kers that capture at least several of the pathophysiological pro-cesses improve prediction of DKD progression [32–34].Drugs may interfere in one or more of the processes that drive DKD progression in an individual.At this level,biomarkers may help to gain insight,which speci ?c processes are involved in progres-sion of disease in an individual and whether a drug indeed im-pacts on that process.In other words,a biomarker can serve (i)

as a proxy of a key mechanistic factor characterizing the presen-

tation and progression of disease in a certain individual and (ii)

as an indicator for interference of a drug with such process.To identify biomarkers that meet these two requirements,two components are needed.First,a detailed model characterizing

the molecular mechanisms of DKD is required,and second,details on how these mechanisms interfere with a drug ’s molecular mode of action is to be factored in.Studies have shown that an Omics-based pro ?ling approach combining sev-eral sources of data (genomics,transcriptomics,metabolomics,proteomics)at the same time taking molecular interactions into consideration is a successful strategy to generate these components.

First,a DKD model characterizing the pathways and pro-

cesses of DKD progression was developed within the SysKid programme through integrating Omics pro ?ling data from

the genetic up to the metabolite level combined with scienti ?c

literature mining for deriving a set of molecular features asso-ciated with DKD.In total,>2000molecular features have pro-vided ample information for reconstruction of molecular processes and pathways being involved in diabetic nephropa-thy.Interpreted on the level of molecular pathways,the dia-betic nephropathy model includes signalling processes such as PI3-Akt,chemokines and cytokines,?brosis (TGFbeta sig-nalling),ECM receptor interaction and components of F U

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metabolic pathways.In an alternative representation resulting from mapping the DKD-associated molecular features on a protein coding gene-centric,hybrid interaction network fol-lowed by network segmentation provided a DKD molecular process model consolidating a subset of the associated mo-lecular features in more than20molecular processes resem-bling aspects of the molecular background of DKD[35].By utilizing a molecular process representation(be it on the level of molecular pathways or network process segments) biomarkers(protein coding gene-level)can be selected that are embedded in each pathway or process in order to develop a biomarker panel aimed at covering relevant aspects of the molecular landscape of DKD(in contrast to using a single bio-marker approach representing only a single process or path-way).Forwarding such panel to experimental testing regarding explaining variance of e.g.eGFR decline allows identifying the subset of markers—hence molecular mechan-isms—indeed af?icted with progressive disease.In addition, the contribution of different process units at early and late stages of disease can be assessed thereby allowing

for

F I

G U R E2:Molecular process model representation of DKD(A),mode of action of ramipril(B),(C)interference of ramipril mode of action with

the model representation of DKD,where overlapping elements of phenotype and drug are indicated in red,and zoom into a speci?c process

segment of the DKD model(D).The molecular models encode clusters of protein coding genes(nodes given in grey)and their interactions

according to an underlying hybrid interaction network.Interactions between segments(molecular processes)are omitted in display.

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delineating a model for the progression of disease at the mo-lecular mechanism level.

Second,to determine a drug’s impact on these various me-chanisms of progressive DKD in a patient-speci?c context,the drug mechanism of action must be determined.To characterize the effects of a drug on the processes of DKD,not only the drug target(s)itself should be considered but a broader description of the mode of action of drugs of interest should be obtained.In analogy to modelling disease mechanisms,molecular features associated with a drug’s effect can be obtained by combining Omics pro?ling data together with literature https://www.wendangku.net/doc/1a16346551.html,ing such drug-associated molecular data allows the construction of a molecular pathway or process landscape of a drug effect. Interference of the drug pathways with DKD progression path-ways provide hypotheses if and what speci?c pathways in DKD are indeed addressed by the effect of a drug.Biomarkers repre-senting such pathways can subsequently be selected for testing the predictive performance whether the individual will respond to the drug.Such drug mechanism of action molecular model was recently developed for ACEi,consolidating a number of speci?c drugs including ramipril,captopril or enalapril in a general ACEi model.In order to assess which of the processes of a general ACEi mode of action molecular model impact on the progression of DKD,the ACEi molecular network model was mapped on the DKD molecular process model.This re-sulted in the identi?cation of?ve processes on the DKD side signi?cantly addressed by ACEi molecular effect.Biomarkers represented in these?ve processes included amongst others the cytokine tumour growth factorβ(TGF-β),the nuclear tran-scription factor NFκB and the chemokine C-C motif ligand5 (CCL5).This study showed that ACEi impact on different mo-lecular processes,many of them also involved in the progres-sion of DKD.As speci?c example,scienti?c literature mining regarding molecular features associated with ramipril effect re-sulted in the identi?cation of about2200features which led to the development of a ramipril molecular process model consist-ing of30molecular processes including866protein coding genes(Figure2).Interference of this drug model with a DKD model identi?es a number of DKD-associated processes appar-ently affected by ramipril going beyond the direct drug target (ACE)context.A systematic analysis of the molecular processes involved in DKD coupled with a systemic analysis of the impact of ACEi on these molecular processes allows selection of a set of biomarker candidates serving for evaluating drug response. After experimental validation,such biomarkers can be used in future studies to assess which molecular processes operate at an individual patient level and whether the individual patient is more or less likely to respond to ACEi.

F U T U R E D I R E C T I O N S

Substantial Omics pro?ling data have become available over the last decade which after consolidation on interaction networks and pathways enable to study the intricate molecular compos-ition of DKD,and when combined with the large body of evi-dence from reductionist approaches?nally provides the opportunity of establishing data-driven work?ows aimed at matching clinical disease presentation and drug effect via util-izing predictive biomarkers(Figure3).

Although the above-described work?ow appears appropri-ate to develop biomarkers for individual drug prediction and monitoring,the molecular models and their biomarkers have to be validated in prospective clinical trials.To this end,bio-markers derived from the molecular models have to be mea-sured in prospective studies and their ability to predict drug response has to be ascertained.Such future studies will also help to gain more insight into the molecular processes involved in responder and non-responder patients.In addition,interfer-ence of the DKD molecular network model with a drug mode

F I

G U R E3:A data-driven work?ow for matching disease pathophysiology and drug mode of action via linked biomarkers.Step1resembles

consolidation of molecular data found as associated with a phenotype,in an iterative procedure used for deriving molecular process/pathway

models.On this basis biomarker candidates are selected for serving as proxy of the process/pathway landscape(2),subsequently forwarded to

experimental evaluation regarding association with disease progression.In analogy,molecular data found associated with a drug’s effect need

consolidation(3)for allowing delineation of a drug mechanism of action representation on a process/pathway level.Central step de?nes the match

of drug molecular effect and molecular processes seen af?icted with progressive disease(4),at this stage already knowing biomarkers allowing

monitoring such interference in the speci?c disease molecular background.

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action model can help to reposition already registered drugs from other disciplines to diabetes.Most of the registered drugs already have a large safety record which increases the like-lihood of successful new developments and evidence-based treatments for DKD.Future in-silico modelling and prospective randomized clinical trials will provide proof-of-concept of this approach.

CO N C L U S I O N S

The SysKid consortium has developed an integration scheme for providing enhanced insight into the underlying molecular mechanisms of individual renal disease progression and disease pathophysiology.Coupling this mechanistic representation to a model describing the effects of a drug on a molecular level pro-vides the possibility to develop novel drug response biomarkers which will help to tailor optimal therapy to the individual patient.

AC K N OW L E D G E M E N T S

H.J.L.H.is supported by a VENI grant from the Netherlands Organization for Scienti?c Research.The work leading to this paper received funding from the European Community’s Sev-enth Framework Programme under grant agreement no. HEALTH–F2–2009–241544(SysKid).

CO N F L I C T O F I N T E R E S T S TAT E M E N T

B.Mayer is co-founder and managing partner,A.Heinzel and P.Perco are employees of emergentec biodevelopment GmbH, a company developing methods and computational platforms for in silico biomarker,target and drug https://www.wendangku.net/doc/1a16346551.html,mbers Heerspink is consultant for Astellas,Abbvie,J&J,Reata Phar-maceuticals,Z-Pharma(honoraria paid to his institution).

R E F E R E N C E S

1.Plantinga LC,Crews DC,Coresh J et al.Prevalence of chronic kidney dis-

ease in US adults with undiagnosed diabetes or prediabetes.Clin J Am Soc Nephrol2010;5:673–682

2.Tao Z,Shi A,Zhao J.Epidemiological perspectives of diabetes.Cell Bio-

chem Biophys2015;doi:10.1007/s12013-015-0598-4

3.Promotion National Center for Chronic Disease Prevention and Health

Promotion.https://www.wendangku.net/doc/1a16346551.html,/diabetes/projects/pdfs/ckd_summary.pdf (3March2015,date last accessed)2015

4.De Vecchi AF,Dratwa M,Wiedemann ME.Healthcare systems and end-

stage renal disease(ESRD)therapies—an international review:costs and re-imbursement/funding of ESRD therapies.Nephrol Dial Transplant1999;

14Suppl6:31–41

5.Caskey FJ,Kramer A,Elliot RF et al.Global variation in renal replacement

therapy for end-stage renal disease.Nephrol Dial Transplant2011;26: 2604–2610

6.Brenner BM,Cooper ME,De Zeeuw D et al.Effects of losartan on renal and

cardiovascular outcomes in patients with type2diabetes and nephropathy.

N Engl J Med2001;345:861–869

7.Lewis EJ,Hunsicker LG,Clarke WR et al.Renoprotective effect of the

angiotensin-receptor antagonist irbesartan in patients with nephropathy

due to type2diabetes.N Engl J Med2001;345:851–860

8.Parving HH,Lehnert H,Brochner-Mortenson J et al.The effect of irbesar-

tan on the development of diabetic nephropathy in patients with type2dia-

betes.N Engl J Med2001;345:870–878

9.Komorowsky CV,Brosius FC,III,Feng Y et al.Perspectives on systems biol-

ogy applications in diabetic kidney disease.J Cardiovasc Transl Res2012;5:

491–508

10.Mischak H,Delles C,Klein J et al.Urinary proteomics based on capillary

electrophoresis-coupled mass spectrometry in kidney disease:discovery

and validation of biomarkers,and clinical application.Adv Chronic Kidney

Dis2010;17:493–506

11.Turner RC,Holman RR,Cull CA et al.Intensive blood-glucose control

with sulphonylureas or insulin compared with conventional treatment

and risk of complications in patients with type2diabetes(UKPDS33).

UK Prospective Diabetes Study(UKPDS)https://www.wendangku.net/doc/1a16346551.html,ncet1998;352:

837–853

12.Patel A,MacMahon S,Chalmers J et al.Intensive blood glucose control and

vascular outcomes in patients with type2diabetes.N Engl J Med2008;358:

2560–2572

13.Roscioni SS,Lambers Heerspink HJ,de Zeeuw D.The effect of RAAS

blockade on the progression of diabetic nephropathy.Nat Rev Nephrol

2014;10:243

14.Andresdottir G,Jensen ML,Carstensen B et al.Improved survival and renal

prognosis of patients with type2diabetes and nephropathy with improved

control of risk factors.Diabetes Care2014;37:1660–1667

https://www.wendangku.net/doc/1a16346551.html,mbers Heerspink HJ,de Zeeuw D.Novel drugs and intervention strat-

egies for the treatment of chronic kidney disease.Br J Clin Pharmacol

2013;76:536–550

16.Parving HH,Brenner BM,McMurray JJ et al.Cardiorenal end points in a

trial of aliskiren for type2diabetes.N Engl J Med2012;367:2204–2213

17.Fried LF,Emanuele N,Zhang JH et https://www.wendangku.net/doc/1a16346551.html,bined Angiotensin inhibition

for the treatment of diabetic nephropathy.N Engl J Med2013;369:

1892–1903

18.Kohan DE,Pollock DM.Endothelin antagonists for diabetic and non-

diabetic chronic kidney disease.Br J Clin Pharmacol2013;76:573–579

19.Mann JF,Green D,Jamerson K et al.Avosentan for overt diabetic nephro-

pathy.J Am Soc Nephrol2011;21:527–535

20.de Zeeuw D,Akizawa T,Audhya P et al.Bardoxolone methyl in type2dia-

betes and stage4chronic kidney disease.N Engl J Med2013;369:

2492–2503

21.Paul SM,Mytelka DS,Durwiddle CT et al.How to improve R&D product-

ivity:the pharmaceutical industry’s grand challenge.Nat Rev Drug Discov

2010;9:203–214

22.Arrowsmith J.Trial watch:phase III and submission failures:2007–2010.

Nat Rev Drug Discov2011;10:87

23.Chin MP,Wrolstad D,Bakris GL et al.Risk factors for heart failure in pa-

tients with type2diabetes mellitus and stage4chronic kidney disease trea-

ted with bardoxolone methyl.J Card Fail2014;20:953–958

24.Hoekman J,Lambers Heerspink HJ,Viberti G et al.Predictors of congestive

heart failure after treatment with an endothelin receptor antagonist.Clin J

Am Soc Nephrol2013;9:490–498

25.Heinzel A,Perco P,Mayer G et al.From molecular signatures to predictive

biomarkers:modeling disease pathophysiology and drug mechanism of ac-

tion.Front Cell Dev Biol2014;2:37

26.Klonoff DC.Precision medicine for managing diabetes.J Diabetes Sci

Technol2015;9:3–7

27.Trusheim MR,Berndt ER,Douglas FL.Strati?ed medicine:strategic and

economic implications of combining drugs and clinical biomarkers.Nat

Rev Drug Discov2007;6:287–293

28.Ingelman-Sundberg M,Rodriguez-Antona C.Pharmacogenetics of drug-

metabolizing enzymes:implications for a safer and more effective drug

therapy.Philos Trans R Soc Lond B Biol Sci2005;360:1563–1570

29.Samer CF,Lorenzini KI,Rollason V et al.Applications of CYP450testing in

the clinical setting.Mol Diagn Ther2013;17:165–184

30.Winkelmann BR,Russ AP,Nauck M et al.Angiotensinogen M235T poly-

morphism is associated with plasma angiotensinogen and cardiovascular

disease.Am Heart J1999;137(4Pt1):698–705

T r a n s l a t i o n o f d r u g c a n d i d a t e s t o p e r s o n a l i z e d m e d i c i n e iv111 at University of California, Santa Barbara on July 27, 2015https://www.wendangku.net/doc/1a16346551.html,/ Downloaded from

31.Taverne K,de Groot M,De Boer A et al .Genetic polymorphisms related to

the renin-angiotensin-aldosterone system and response to antihypertensive drugs.Expert Opin Drug Metab Toxicol 2010;6:439–460

32.Roscioni SS,de Zeeuw D,Hellemons ME et al .A urinary peptide biomarker

set predicts worsening of albuminuria in type 2diabetes mellitus.Diabeto-logia 2012;56:259–267

33.Pena M,Heinzel A,Heinze G et al .A novel panel of biomarkers to predict

eGFR decline in type 2diabetes.PLoS One 2015;10:e012099534.Niewczas MA,Sirich TL,Mathew AV et al .Uremic solutes and risk of end-stage renal disease in type 2diabetes:metabolomic study.Kidney Int 2014;85:1214–122435.Fechete R,Heinzel A,Soellner P et al .Using information content for ex-panding human protein coding gene interaction networks.J Comput Sci Syst Biol 2013;6:2Received for publication:11.3.2015;Accepted in revised form:15.4.2015

https://www.wendangku.net/doc/1a16346551.html,mbers Heerspink et al. at University of California, Santa Barbara on July 27, 2015https://www.wendangku.net/doc/1a16346551.html,/Downloaded from

糖尿病肾病的护理查房

一.病史汇报：患者张思成，男性，79岁，退休工人，入院时间：2015.04.22，供病史者：本人现病史：患者现精神尚可，双下肢轻度浮肿，生命体征平稳，血糖波动较大，入院第二晚睡前血糖3.1mmol/l，检查结果：全腹部CT：双肾多发性囊肿、胃窦间质瘤可能。超声心动图示：高血压性心脏病，心电图正常。血红蛋白107g/l，肌红蛋白1200ng/ml，Cr102.7umol/l，Bun12.71mmol/l，磷酸肌酸激酶489u/l，尿蛋白1+。既往史：T：36.7℃P：80次/分R：20次/分BP：130/60mmhg 患者既往糖尿病、高血压20余年，3年前有白内障手术史，无食物和药物过敏史，患者曾因糖尿病、高血压多次入住内分泌科，给予降糖降压治疗，血糖血压控制一般，7年前无明显诱因下体检时发现肾功能异常，肌酐160umol/l，明确为慢性肾衰，后不正规治疗，入院前在外院查肌酐170.9umol/l，同时查CT示：胃小弯占位性病灶，建议行胃镜进一步检查。故此次为进一步检查治疗入院。入院时神志清，精神可，眼睑及双下肢轻度浮肿，躯干及四肢散在暗红色斑片。二.糖尿病肾病的相关知识 1.概述糖尿病肾病：(DN ) 是糖尿病常见的并发症，是糖尿病全身性微血管病变表现之一。临床表现为蛋白尿，渐进性肾功能损害，高血压、水肿，晚期出现严重的肾功能衰竭，是糖尿病患者的主要死亡原因之一。 2.病因 ①.遗传因素 2.肾血流动力学的异常 3.高血糖症 4.高血压 3.分期一期：以肾小球滤过率增高和肾体积增大为特征。但没有病理组织学损伤。当血糖控制后可以部分缓解。是可逆的。二期：该期尿蛋白排出率正常但肾小球已出现结构改变。三期：又称早期糖尿病肾病期。四期：临床糖尿病肾病或显性糖尿病肾病。五期：终末肾功能衰竭。前3期为DN早期，适当治疗可控制病情进展；4期和5期分别为DN的中期和晚期，如病情进入这两期不管临床如何治疗都不能阻止病变的进展。 4.临床表现（1）蛋白尿：可为早期的唯一表现。期间蛋白尿呈间歇性，逐渐发展为持续性，尿液镜检可发现白细胞和管型。（2）水肿：糖尿病性肾病患者早期一般没有水肿，少数病人在血浆蛋白降低后，可出现轻度水肿。当24小时尿蛋白超过3克时，水肿就会出现。明显的水肿仅见于糖尿病性肾病迅

糖尿病肾病的发病机制

糖尿病肾病的发病机制林善锬糖尿病肾病(diabetic nephropathy, DN)是糖尿病患者最主要的微血管病变之一。据美国、日本及许多西欧国家统计资料表明，DN已跃升为终末期肾功能衰竭(ESRF)首位病因，目前在我国DN发病率亦呈上升趋势。由于DN患者机体存在极其复杂的代谢紊乱，一旦发展到ESRF，往往比其它肾脏疾病治疗更加辣手。因此进一步探索其发病机制，以便制定更加有效的防治措施，已成为当前糖尿病和肾脏病学界十分热点的课题。一、肾组织糖代谢紊乱糖尿病状态下存在肾组织局部糖代谢活跃。高糖可刺激肾组织细胞葡萄糖糖转运主要载体葡萄糖转运子1(glucose transporter 1,GluT1)表达和活性，促进葡萄糖进入细胞内，而细胞内高糖诱导的各种损伤介质如IGF-1、TGF-b1、PDGF、AngⅡ、糖皮质激素及低氧等反过来有可刺激促进GluT1表达和活性，促进更多的葡萄糖进入细胞内，形成恶性循环。另外，糖尿病状态下尚存在肾组织细胞膜胰岛素受体数目和亲和力增加，导致肾组织糖原储存和葡萄糖利用增加，产生许多中间代谢产物。高糖与这些中间代谢产物可通过非酶糖化、激活的多元醇通路、DAG-PKC途径损害肾脏。葡萄糖可以在非酶条件下形成Amadori产物，后者再经过一系列反应，形成晚期糖基化终末产物(AGEs)。AGEs损害肾脏机制包括：(1)使肾小球基底膜(GBM)成分交联增多，导致GBM增厚及孔径选择性和电荷选择性丧失，而产生蛋白尿；(2)糖化的血管基质可通过AGEs捕获渗出血管外的可溶性血浆蛋白如LDL，致富含胆固醇性LDL在局部堆积，促进动脉硬化；(3)使醛糖还原酶(AR)糖化，其活性增加，参与多元醇途径的活化；LDL糖化后则清除减少，致血浆中LDL浓度升高，渗入血管壁，促进血管并发症发生；(4)通过AGEs与细胞上特异性受体(RAGE)结合激活细胞，尤其是巨噬细胞，随后分泌大量的细胞因子和细胞介质如IL-1、TNF1、TGFb、PDGF等，引起组织损伤。此外，AGEs与RAGE结合后还会导致细胞氧化增加，产生大量氧自由基，而激活NFkB，后者可诱导ET-1及血管细胞粘附因子-1(VCAM-1)等表达。此外，在体外培养的系膜上Amadori修饰的白蛋白不仅能诱导TGFb1基因和蛋白表达，亦能上调TGFbⅡ型受体功能，因而促进ECM蛋白表达。当血糖持续升高超过了糖原合成和葡萄糖氧化能力时，可激活肾小球系膜细胞、近端肾小管上皮细胞及内髓质集合管细胞AR基因中葡萄糖反应元件(GLRES)及渗透压反应元件(ORE)，从而激活AR。葡萄糖在AR作用下转变为山梨醇，然后在山梨醇脱氢酶作用下转变为果糖。由于山梨醇不易透过细胞膜而果糖又很

糖尿病肾病健康指导

1.注意休息：肾脏病患者，在急性发作期间应适当卧床休息，症状严重时要绝对卧床休息。慢性者应劳逸结合，消除顾虑，保持身心愉快，避免劳力、劳神。如果在病情相当稳定好转时，可参加一些力所能及的工作。 2心理护理：了解病人的思想、生活和工作状况，进行必要的卫生知识和有关糖尿病知识的宣教，使病人消除对本病的恐惧心理和悲观情绪，鼓励病人增强战胜疾病的信心。 3 饮食指导：糖尿病病人的饮食护理极为重要，控制碳水化合物的摄入，以减轻胰岛β细胞的负担。多食营养丰富含多种维生素蛋白质的食物。如:瘦肉、鸡蛋、豆类及蔬菜等，三餐热量按早、午、晚各1/5、2/5、2/5分配。使病人及家属了解饮食对疾病的重要性，从而使病人自觉控制饮食。 4 监测血糖变化及正确注射胰岛素：教会患者及家属监测血糖的正确方法及血糖的正常值，使病人及家属懂得注射方法、部位、时间以及注意事项，如血糖出现较大波动应立即门诊复查，不可自行调整胰岛素剂量。如有心悸、饥饿、出冷汗等，是低血糖反应症状，应立即进食或饮糖水。 5 降糖药：按医嘱定时定量服用降糖药，并注意观察疗效及不良反应，常用的磺脲类如优降糖，双胍类如降糖灵及α-糖酐酶抑制剂、拜糖平等，前二者要饭前30min服用，用药期间如有皮疹或胃肠道症状如恶心、呕吐等应及时到医院诊治;后者应与第一口饭同时服用，主要预防餐后高血糖的发生。 6 预防感染：因糖尿病病人机体抵抗力差，容易感染，应少去公共场所，气候变化时要及时增减衣服，如有感冒等要及时治疗。 7 注意个人卫生：糖尿病病人易生疖痈等，应保持全身皮肤清洁，勤洗澡、勤换内衣内裤，保持床单清洁。如发生皮肤感染应及时治疗，并保持口腔清洁，早晚刷牙，避免口腔疾患。 8.定期到医院复查血糖，向医生汇报病情及用药情况，掌握病情变化的动态信息。

糖尿病肾病的病理生理和病理

?专题笔谈?糖尿病肾病的诊断与治疗糖尿病肾病的发病情况及危害王德全　张秀英　(山东医科大学附属医院250012) 据WHO1997年报道,全世界已诊断的糖尿病患者目前约1.35亿,估计2025年将达到3.0亿。在发达国家,特别是发展中国家,糖尿病发病率呈上升趋势。目前,糖尿病是仅次于心血管病、肿瘤而居第三位的致死性疾病。1　糖尿病肾病的发病情况自胰岛素应用以来,糖尿病患者因急性并发症(如酮症酸中毒)而死亡者已显著减少。但随着糖尿病患者寿命的延长,慢性并发症已成为糖尿病患者的主要死因,其中糖尿病肾病所致尿毒症是主要死因之一。据北京、天津糖尿病协作组调查,男、女糖尿病患者尿蛋白阳性率分别高达54.2%和55.2%。尤其是青少年起病的1型糖尿病,糖尿病肾病是其主要死因。A nder sen等对1364例1型糖尿病患者进行了长达25年的随访,39%发展为糖尿病肾病,发病率于糖尿病发病10年后迅速上升,20～30年最高,累积发病率约为40%～50%,随访结束时死亡者中的66%死于尿毒症。成年起病的Ⅱ型糖尿病患者,其糖尿病肾病发病率为5%～10%,其合并糖尿病肾病的绝对数远超过1型糖尿病。可见,必须高度重视糖尿病肾病的危害性。 2　糖尿病肾病的危害 2.1　糖尿病肾病的自身危害　糖尿病引起的肾脏病变可累及肾血管、肾小球、肾小管和间质,其中糖尿病性肾小球硬化症是糖尿病特有的肾脏并发症,称为糖尿病肾病。若在20岁以前确诊糖尿病,以后的20年内约50%患者发生糖尿病肾病,20年以上者几乎达100%。糖尿病肾病起病隐袭,进展也较缓慢。初期常无临床症状,蛋白尿也是间歇性的,易被忽视。一旦出现持续性蛋白尿,则不可逆转,肾小球滤过率由代偿性升高降至正常水平,继以大约每月1m l/min的速度下降。1～2年后出现高血压,血压升高加重尿蛋白的排泄,加速糖尿病肾病的进展,而肾脏病变本身又导致血压更为升高,形成恶性循环。6～7年后血清肌酐上升,肾功能进行性减退。一般来说,从尿蛋白到死于尿毒症平均为10年,尿蛋白> 3.0g/d者多在6年内死亡。 2.2　糖尿病肾病的社会危害　糖尿病是一种终生性疾病,长期治疗对患者的生活及精神造成很大压力,昂贵的费用是患者家庭的巨大负担。糖尿病肾病的发生和发展更加重了治疗的困难性,降低了生活质量。据统计,由糖尿病肾病导致尿毒症者较非糖尿病者高17倍。在美国,因肾功能衰竭而进行透析或肾移植治疗的患者中,由糖尿病引起者占25%～30%,是终末期肾病的最常见原因。在欧州和日本,糖尿病肾病是接受肾移植的第2位原因。糖尿病肾病患者进行血液透析治疗时常因血管病变而需多次造瘘,易形成空气栓塞,感染率亦由此升高。Jacobs等报道欧州1098例维持性血液透析患者,其第1年存活率为67%,第2年存活率为49%,1型糖尿病患者的死亡率约为非糖尿病患者的2.5～ 3.0倍。肾或胰—肾联合移植是目前治疗晚期糖尿病肾病最有效的办法。自采用环孢霉素作为免疫抑制剂以来,肾移植的5年存活率明显升高,但糖尿病患者由于心、脑血管合并症和感染率升高,肾移植的5年存活率仍较非糖尿病者低10%。且由于供体来源困难和经济等方面的原因,亦限制了应用。糖尿病肾病的病理生理和病理杜兆鹏　谌贻璞　(北京中日友好医院100029) 糖尿病肾病(D N)是糖尿病的主要长期并发症之一,其发病机理复杂,遗传易感性和长期高血糖状态导致的一些细胞因子及(或)生长因子的增多等因素可能参与其病理生理的改变。高血糖引起肾小球细胞外基质(ECM)生成增多,降解减少及ECM积聚导致的肾小球损伤,即为糖尿病肾病的病理生理和病理。 1　糖尿病肾病的病理生理 1.1　高血糖损伤肾小球的途径　高血糖通过非酶促反应与游离的氨基等基团形成Schiff碱基,经过进一步重排、脱水形成高级糖化终末产物(A GE),它通过下列途径引起肾小球损伤。A G E及糖化的低密度脂蛋白可使系膜细胞(M Sc)中的转化生长因子 (T GF- )、血小板源生长因子(P DG F)表达增多;高糖也可直接使M Sc等因有细胞产生T G F- 、PD GF以及碱性成纤维细胞生长因子(b-F G F)、血管内皮生长因子(VEG F)、生长激素(GH)/胰岛素样生长因子-1(I GF-1)等,高糖还可使M Sc产生过多的单核细胞趋化肽-1(M CP-1),使巨噬细胞(M )浸润到系膜区加重局部的炎症反应。上述因子可通过自分泌、旁分泌及内分泌途径起作用,其中T GF- 和PD GF可能作为最后的共同介质,通过二酰基甘油—蛋白激酶C及蛋白酪氨酸激酶信息传递途径,使M Sc产生过多的Ⅳ型胶原、层粘蛋白、纤粘连蛋白等,引起ECM的积聚及肾小球硬化,而且也使近曲小管上皮细胞肥大及肾间质纤维化。另外A G E、肾小球内高压、血管紧张素Ⅱ(AGⅡ)、内皮素(ET)和氧化的脂蛋白可增强上述细胞因子的表达及作用。另外,A GE通过与肾小球ECM ? 37 ? 1999年第39卷第6期山东医药

糖尿病肾病病人的健康教育

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2型糖尿病和病程5年以上的1型糖尿病患者每年应至少进行一次UACR和eGFR检测，以便早期发现DKD。（B级） 3DKD的诊断 DKD通常是根据UACR升高和（或）eGFR下降、同时排除其他CKD 而作出的临床诊断。糖尿病合并肾脏损害不一定是DKD，病因难以鉴别时可行肾穿刺病理检查。（C级）确诊后应根据eGFR进行CKD1~5期分期。（C级） DKD的防治 DKD的防治应强调积极筛查、早期发现、合理干预。（C级）重视对DKD危险因素的干预，包括高血糖、高血压、肥胖（尤其是腹型肥胖），避免肾毒性食物及药物、急性肾损伤、蛋白摄入过多。（A级）良好的生活方式、有效的血糖和血压控制是防治DKD的关键。（A级） 1一般治疗

糖尿病病人的健康教育

糖尿病病人的健康教育对于糖尿病的治疗，我们提倡“五驾马车”原则。所谓五驾马车是指糖尿病的治疗不是一个单一的治疗，而是一个综合治疗。这五驾马车包括：饮食、运动、药物、教育和自我监测。糖尿病教育被誉为“治疗教育” ，它除了能帮助建立良好的心理状态和生活方式外，还能使患者早期发现糖尿病、了解相关知识、掌握控制糖尿病的基本技能，达到提高生活质量的目的。一、什么是糖尿病？糖尿病是由多种原因引起的以慢性高血糖为特征的代谢紊乱综合征。高血糖是由于胰岛素分泌或作用缺陷，或者两者同时存在所引起的。久病导致多系统损害，特别是眼、肾、神经、心脑以及血管组织的功能缺陷及衰竭。表现为“三多一少” ：多饮、多食、多尿、体重减轻，除此之外，还可出现皮肤干燥、搔痒、饥饿感、视物不清、经常感到疲倦、劳累等。有时并无明显症状，仅于健康查体时发现高血糖。二、糖尿病有哪些并发症？我们说糖尿病可怕不仅在于糖尿病本身，而在于与糖尿病密切相关的各种急、慢性并发症，在于它的高致残率和高致死率。1、急性并发症：低血糖、糖尿病酮症酸中毒昏迷、糖尿病非酮症高渗性昏迷等。2、慢性并发症：（1）由大血管病变引起的冠心病、心肌梗塞、中风、下肢跋行等。（2）由微血管病变引起的尿毒症、失明和截肢等。尽管糖尿病的危害很大，其实只要控制好血糖，使血糖在正常范围内波动，则组织细胞处于正常环境中，并发症即不会出现，而糖尿病病人也和健康人一样可以快乐生活。三、怎样知道自己得了糖尿病？有糖尿病“三多一少”症状者，同时血糖检测结果符合以下一条件者；或无糖尿病“三多一少”症状者，而血糖结果符合以下任二条件者，即可诊断为糖尿病：1、空腹血糖≥7.0mmol/L（检查血糖的前一夜，晚餐后需禁食，次日早餐前抽取空腹血糖）2、餐后2 小时血糖或随机血糖≥11.1 mmol/L（从吃第一口饭开始计时2 小时后抽取餐后2 小时血糖，随机是指一天的任意时间而不管上次进餐时间）。3、口服葡萄糖耐量实验2 小时血糖≥11.1 mmol/L。口服葡萄糖耐量 -1- 实验：在医院中口服75g 葡萄糖溶于250～300ml 水中，抽取空腹血标本后，即在 5 分钟之内饮完，然后于30 分钟、60 分钟、120 分钟、180 分钟分别抽取血标本，检测血糖值的目的是帮助糖尿病的诊断。正常人的血糖值为空腹3.9～ 6.1mmol/L，餐后＜7.8mmol/L。如果空腹血糖＜7 mmol/L，餐后血糖介于7.8～11.1 mmol/L 之间，则为糖耐量低减，这是糖尿病的前期状态。四、哪些人群应到医院检查确定是否得了糖尿病？调查表明，大多数处于糖尿病前期和早期糖尿病的人群会仅以餐后血糖升高表现为主，而不一定合并空腹血糖升高；在此状态下的人群通常没有症状，因此，必须在高危人群中定期检测餐后血糖才能作出诊断。以下就是糖尿病的高危人群：1、有糖尿病家庭史者；2、年龄超过45 岁者，年纪越大，患糖尿病的机会越高；3、长期高热量饮食摄入者； 4、肥胖及平常缺乏运动者； 5、生产过重婴儿（4 公斤或者以上的妇女）； 6、高血压、高血脂、冠心病和痛风病人以及长期吸烟者； 7、工作高度紧张、心理负担重者。如果您或您家人身体情况符合糖尿病高危人群七项中的其中两项，就请立刻行动起来，加入到检测血糖，特别是餐后血糖的队伍中来，做到早预防、早诊断、早治疗，让大家远离糖尿病，拥有健康每一天。五、得了糖尿病怎么办？确诊患有糖尿病，您不必恐惧、失望，您要接受事实，正确对待，寻找对付它的策略。首先要和医务人员配合好，掌握基本的糖尿病知识和注意事项，其次要认识到糖尿病的严重性及治疗的必要性，它即是一种严重的全身性疾病、终身性疾病，又是一种能够治疗的疾病，俗称是“条件健康人” 。治疗结果如何，完全取决于你的努力，信心和对医务人员的依从性，要树立战胜疾病的信心。六、糖尿病能否治愈？就目前科技水平来讲，是不能治愈的疾病。有很多报纸、电视广告、广播专家的旗号和祖传秘方的幌子宣传包根治，其实是骗人的，广大的糖尿病病人及家人盲目追求“根治”而停止正规治疗，延误时机，造成不可挽回的损失。奉劝大家一定要到正规医院就治，

2型糖尿病患者合并肾病危险因素分析及护理对策

2型糖尿病患者合并肾病危险因素分析及护理对策发表时间：2016-06-27T13:46:18.247Z 来源：《医药前沿》2016年6月第18期作者：肖春芳 [导读] 本研究通过对合并及未合并DN的2型糖尿病合并DN患者进行对比，从而掌握该病的相关危险因素。肖春芳（上海市奉贤区海湾镇社区卫生服务中心上海 201419）【摘要】目的：探讨糖尿病患者罹患糖尿病肾病（diabetic nephropathy，DN）的危险因素及护理对策。方法：分析2型糖尿病患者合并肾病的相关危险因素，为预防与治疗2型糖尿病患者合并肾病提供理论依据。结果：两组在糖尿病家族病史及相关合并症方面存在差异（P均<0.05），在DM病程、甘油三酯（TG）、胆固醇（TC）、肌酐（Scr）、尿酸（UA）、脉压（PR）水平等方面有显著差异（P均 <0.05），并且两组在个人因素和社会心理行为因素等方面的情况进行比较发现两组在收缩压控制和患糖尿病后体育锻炼方面的差别有统计学意义（P均<0.05）。多因素分析结果显示DM病程时间，合并高血压以及血清肌酐水平是糖尿病患者合并肾病的危险因素。结论：DN病因系多因素参与，包括遗传背景以及多种危险因素。因此，糖尿病患者应加强健康宣教，注意控制血糖和血压，适当运动，以及合理的饮食疗法，可及时防治并延缓DN的发展。【关键词】 2型糖尿病；肾病；危险因素分析；护理对策【中图分类号】R473.5 【文献标识码】B 【文章编号】2095-1752（2016）18-0325-03 本研究通过对合并及未合并DN的2型糖尿病合并DN患者进行对比，从而掌握该病的相关危险因素，从而有助于预防2型糖尿病患者合并肾病，并延缓该病的发展。 1.资料与方法 1.1 一般资料选择2013年8月～2015年8月期间，我院收治120例2型糖尿病合并肾病患者作为研究组，入选的患者均符合1997美国糖尿病协会（ADA）的糖尿病诊断标准；其中男68例，女52例；平均年龄（60.64±12.55）岁，年龄范围42～82岁；病程时间2～15年，平均病程（6.15±4.05）年；此外，选择同期收治100例未合并DN的2型糖尿病患者作为对照组，入选的患者均符合1997美国糖尿病协会（ADA）的糖尿病诊断标准；其中男57例，女43例；年龄41～79岁，平均年龄（58.82±11.14）岁；病程时间1～10年，平均病程（3.82±2.57）年；对两组患者的一般资料进行统计学分析发现研究组和对照组的年龄、性别及病程时间比较均无显著差异（P>0.05）。 1.2 方法（1）调查内容：人口统计学资料、DM病史、DN病史、家族史、个人行为因素及临床检测指标等。（2）护理措施：①控制饮食：调节饮食结构，控制每日能量摄入以及各营养素比例，蛋白质摄入应以高生物效价的动物蛋白为主[1-2]。②运动疗法：要根据年龄而定,年龄比较大的最好根据自己的身体素质，最好是慢走为宜，每天坚持[3]。③控制血脂和血压，纠正代谢紊乱。④健康宣教：健康宣教可以确保患者良好的遵医行为，对于疾病的治疗起着至关重要。所以应根据患者的个体特点实施个体化的健康宣教。指导患者正确使用胰岛素，监测患者的血糖、蛋白尿、肾功能、尿酮体、血钾的变化[4-6]。⑤心理护理：DN是需要终生治疗的疾病，容易给患者带来焦虑、抑郁、恐惧等负性情绪，影响患者内环境的稳定，拮抗胰岛素，引起血糖升高，加重病情，使患者丧失治疗信心。因此，护理人员给予患者针对性的心理护理，使其保持良好的情绪，树立治疗的信心，促进疾病的早日康复。 1.3 统计学分析应用SPSS 13.0软件进行统计学分析，计量资料以均数±标准差（x-±s）表示，组间比较采用u检验，计数资料的比较采用χ2检验；危险因素分析采用非条件Logistic回归分析；两组间差异用P值（P=0.05）表示，计算OR值及95％置信区间。 2.结果 2.1 糖尿病病史及其他合并症分布情况由表1可知两组在糖尿病家族病史，冠心病，高血脂，高血压以及其他糖尿病合并症方面存在差异，且差异具有统计学意义（P均<0.05）。

糖尿病肾病健康教育

CRF患者饮食及健康教育 1.CRF优质低蛋白饮食患者宜选用动物性蛋白质,如鸡蛋、牛奶、瘦肉等。植物性蛋白质一般含非必需氨基酸较多,生物效价低,故应限制。主食除米饭和面条外还可以配合麦淀粉(面粉抽去蛋白质的制品,蛋白质含量仅016 %) 。同时注意全日所供给的蛋主食除米饭和面条外还可以配合麦淀粉(面粉抽去蛋白质的制品,蛋白质含量仅016 %)白质要均匀地分配在3 餐中,以利于更好的吸收及利用。若经济条件许可,同时补充α-酮酸或氨基酸,以更好地维护肾功能和提高营养状况。蛋白质的摄入量既要达到不加重氮质血症,又要满足机体代谢需求,难以确切估计,至今尚未形成一致观点[3 ] 。低蛋白饮食并不是指一味地限制蛋白质摄入,也并不是指摄入的蛋白质越少越好,一般不低于0. 5～0.6g·kg- 1·d - 1 ,否则易引起营养不良。如已开始血透或腹透,则不需要低蛋白饮食。 2.供应充足的热量保证充足的热量供应,以满足新陈代谢的需要,同时保证食入的少量蛋白质被充分利用。每天的热量至少要达到35kcal·kg - 1·d - 1其主要来源依靠糖和脂肪。如果是糖尿病患者,糖类饮食则要小心控制。含热量高的膳食有土豆、山药、芋头、藕、南瓜、粉丝、菱角粉、营养粉等。 3．低盐低钠饮食CRF 合并高血压和浮肿的病人,要限制钠盐和含钠丰富的食物, 如腌制品等。大多数CRF 患者钠盐摄入量< 3g/ d。严重呕吐或腹泻时,不应限制钠盐。 4．保持水平衡CRF 患者的水平衡非常重要,液体的入量要根据排出量而定,防止水摄入过多,排出障碍而加重浮肿。临床上CRF 患者稳定状态下(正常或接近正常血压,无明显浮肿,血钠正常) ,尿量可以指导摄水量,即水摄入量= 尿量+ 500mL (不显性出汗) 。 5．预防高血钾CRF 患者出现高血钾时,应限制含钾食物,避免食用果汁、罐装饮料和含钾高的蔬菜及水果,如橙子、蘑菇、紫菜、虾米、大葱等。 6．高钙低磷饮食在部分CRF 患者中可有血磷升高和血钙下降的现象,因此饮食中应注意提高钙的含量,降低磷的含量,含钙高的食品有牛奶、芝麻酱等。另外烹调鱼和瘦肉时, 用水煮一下捞出,再进行热炒,能够降低食物中磷的含量。 7．维生素的补充和限制CRF 患者大多数合并有消化吸收不良,另外疾病本身可导致水溶性维生素代谢改变,所以要有意识地补充维生素以满足机体代谢的需要。ARF 患者的维生素需要量未明确规定。水溶性维生素在体内无贮备,建议积极补充。脂溶性维生素,不主张常规补充。临床上对CRF 患者应补充B 族维生素、维生素C、维生素D 等,而不应补充维生素A ,其原因是体内维生素A 升高,可刺激甲状腺激素分泌而引起肾性骨营养不良,还可以引起脂肪代谢紊乱,致使胆固醇、甘油三酯水平增高。维生素D 应在有严重低钙指征的情况下进行补充,而且剂量必须个体化,避免出现高钙血症肾病患者并不需要远离肉类和鱼类，只要注意适量摄八就行。变做法一些烹调技巧可以帮助降低食物中某些成分的含量，例如土豆在烹制前先用水泡一会儿就可以去掉一部分钾元素，不吃莱汤、肉汤可以减少磷的摄入。．选种类多选择钾含量较低的蔬菜和水果，如用苹果替代香蕉。

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