Hi Biswajit, good answer.

In patients with combinstion HT and DM first line therapy are ACEI or ARB. Second line - CCB. If we used together ACET/ARB and Amlo it is does matter AE Amlo. Because comb theraphy dilate both afferent and effarent arteriols in glomerulous and have good renal protection. According guidelines Amlo is indicated... Of course new drug will be superiority to previous...

GFR is a measurement of renal function. It also varies with age. Markers of kidney damage are something else; the most important being proteinuria. In a diabetic patient/ hypertensive patient, chronic kidney disease is defined as GFR < 60ml/min/1.73m2 or proteinuria (30mg/24 hours) persisting for 3 months or more.

Dear Sheikh,

please look on this table.

Main target organ damage in HT and DM patients is Heart, Kidney and Wessel as well.

And Nataliia ask not about Markers of kidney damage... She ask if we will talk about kidney as target organ damage if GFR 60-89ml/min...

Dear Sergey, thank you for good explanation. Certainly patients with HT an DM combination are at great risk of renal dysfunction due to DM and HT nephropathy. In this case renal damage develops earlier and even in mildly decreased GFR, so we should check it every 3 month. Also we have evaluate GFR level because of polypramasia and drug interactions in hypertensive diabetics - ACE or ARB, ACCB, diuretics, metformine, statins and others which could influence GFR in hypertensive diabetics.

Hi Nataliia, very good question. In this GFR stage we should start aggressive therapy to reduce the progression of renal dysfunction. I totally agreed with your answars and the drugs you have maintained. Never L and N type calcium channel blockers cilnedepine and benidepine may also be useful in terms of renal protection in this situation . They dilate both afferent and effarent arteriols in glomerulous and have much renal protection compared to amlodepine... Some newer data are coming with these molecule in terms of reduction of prtenuria and renal protection.. Thanks

Hi Biswajit, good answer.

In patients with combinstion HT and DM first line therapy are ACEI or ARB. Second line - CCB. If we used together ACET/ARB and Amlo it is does matter AE Amlo. Because comb theraphy dilate both afferent and effarent arteriols in glomerulous and have good renal protection. According guidelines Amlo is indicated... Of course new drug will be superiority to previous...

Hi Biswajit! Thanks for your answer! It s a pity, but cilnedepine and benidepine are not registered yet in our country, but we have lercanidipine that have showed good results in BP lowering and nephroprotecive effect in several clinical trials.

I agrre with you that in HT and DM patients with GFR 60-90 doctor should prefer more agressive therapy but with drugs with

renoprotective effect.

Article Lercanidipine in Patients with Chronic Renal Failure: The ZAFRA Study

Hi Sergey, thanks for your reply and useful links. I think that kind of algorhythm is in need where the terms of GFR decrease will be explained during follow up according to the type of antyhypertensive and hypoglycemic treatment. What about statins in GFR rate 60-90?

Simplistically speaking , the eGFR is the key to monitor therapy of Htn in T2DM...CCB like amlodipin dialate only affarent arterioles in kidney as L type channel are predominant in affarent arterioles only ...But Benidipine is a balanced ccb which blocks L, T, N type channels ...T channel is presnt in juxtamed efferent nd affarent arterioles ...which decreases intraglomerular hypertension more effectively than amlodipine , ACEI or ARB also dialates efferent arterioles to have the aforementioned effect. However at this level of GFR ( 60-90 ) ( more in hyperfiltration phase ), SGLT2 inhibitors may be renoprotective as gliflozins cause to deliver more Na to macula densa, thereby increasing tubuloglomerular feedback ( TGF loop is impaired in early diabetic nefropathy leads to hyperfiltration ) that ultimately leads to Affarent arteriolar constriction and normalisation of GFR. In any case, combo of ACEI and newer CCB viz Benidipine may be beneficial at this stage of diabetic nefropathy. Thanks.

Hi Subhro! Thank You for very interesting opinion especially point about hyperfiltration phase and CCB also.

It was shown that in diabetes and hypertension, hyperfiltration should be regarded as a precursor of nephropathy.

European guidelines classify hypertensive patients with subclinical target organ damage among those with a high total cardiovascular risk. In hypertensive individuals, renal subclinical organ damage is associated with increased 10-year risk of cardiovascular events.

More extensive use of markers of early organ damage may help clinicians to reach a more timely decision about the initiation of treatment and thus delay cardiovascular complications.

As suggested by Okada et al. hyperglycaemia and high blood pressure in people with hyperfiltration should be treated earlier to prevent the progression of renal dysfunction to chronic kidney disease. Pharmacological interventions and strict glycaemic and lipid control should thus be implemented early together with a diet with sufficient intake of foods rich in antioxidants.

https://academic.oup.com/ndt/article/27/5/1708/1843853

Hi Nataliia, Efonidipine, a newer L and T ca(2+) blocker also may be useful is this situation. It has both renal and cardio protection effect. It can reduce proteinuria and has antianginal effect. It has the advantage that it does not cause reflex sympathetic tachycardia.. Thanks

Hi Biswajit! Thank you for useful information. I think all CCB which blocks L, T, N type channels in combination can may benefit is this situation.

Thanks

Hi Nataliia,, continuing with the discussion efonidipine is recently introduced in India. In Japan this this molecule was introduced in 1995 as an antihypertensive and still continuing with good results. Some unique features of this molecule are negative chronotrophic effect, increases myocardial blood flow, improves Endothelial function, decreased serum aldostetone level, increases glomerular filtration rate without increasing intraglemerular pressure. It also prevents the inflammation and hypertrophy of renal vasculature. It prevents Rho kinase induced renal fibrosis and protects kidney damage in hypertension.. Thanks

Hi Biswajit! Thank you for discussion. Unfortunately, efonidipine is not presented yet in our country, but I hope that it will be in near future because it has really many positive effects.

Thanks

At those level of GFR, age must be taken into account to avoid unuseful therapy with potential side effects.

Hi Giovanni! Thank you for reply! I agree, age must be taken in to account. GFR by CKD-EPI and other include it.

Thanks.

In a patient with hypertension & DM , even stage 1 CKD should be labelled as target organ damage . I agree with Sheik Salahudeen Ahmed that GFR is used to assess severity of CKD . Proteinuria with normal GFR is stage 1 CKD & should be treated with either ACEI / ARB's or newer calcium channel blockers . This policy would delay progression of CKD.

The inclusion og age in the formula does is not sufficiente. Afetr obtainig the GFR value, one must define the reference range of normal values for that age and that gender. One cannot use 125 ml/min as reference value for all the age groups, by considering that GFR reduces 1 ml/min per year afetr age of 40. The current classification CKD I-V puts all the older patients in class CKDIIIa and CKDIIIb even if they have no kidney disease, but only elderly.

Hi Giovanni! Thanks for your opinion! We can use another formula for GFR like MDRD though it can decrease real GFR more than CKD-EPI. Also obesity can influence GFR meaning.

https://www.kidney.org/professionals/kdoqi/gfr_calculator

So what is your proposition to evaluate renal function in real clinical practice? For example male , 70 years, height 170, weight 80. Hypertension and DM. Calculator gives GFR meaning 72 ml/min/1.73m2. What about his renal function? Thanks

Dear Singh Shivakumar,

good message. I agree with you that we should start treatment even stage 1 CKD, Because it is really as preclinical target organ damage. Also if Proteinuria with normal GFR is stage 1 CKD should be treated with first line ACEI or ARB. Main goal erly start treatment - to prevent progression of CKD. Thanks.

One shouild consider that after the age of 40 there is a decrease in GFR of about 0.7-1 ml/min per year of age. So, the expected GFR for a patient 70 year old is 30 ml/min less than the GFR of a young man.

Please see:

NDT 2008;23:2818-2826

NDT 2008;23:1117-1121

CJASN 2008;3:1563-1568;

http://www.bnms.org.uk/~bnms/images/stories/downloads/documents/gfrguidelinesv5.2.pdf

http://optn.transplant.hrsa.gov/PublicComment/pubcommentPropSub_208.pdf

Hi Giovanni! Thanks a lot for useful information.

Hi Nataliia, Because patients diabetes with hypertension are prone to develop CKD.. Wheather aggressive therapy before the target organ damage with ACE inhibitor or ARB or with newer calcium channel blockers in these patients is beneficial that needs to be tested by well design trial.. Thanks

Maybe you're right Biswajit.

From the point of view of evidence-based medicine, an RCT is necessary.

But from a practical point of view, we have enough reason (according to current recommendations) to prescribe aggressive therapy in the early period.

We have such an expression - Late drink Borjomi, when the kidneys fell off ...

Hi Biswajit!

I support your opinion about agressive treatment in diabetic patients with ACE inhibitor,ARB or with newer CCB before TOD.

Also I want to notice that in HT patients with Diabetes we shoud remember about antihyperglycemic therapy that may have renoprotective effect, for example empagliflozine.

The use of empagliflozin has been associated with a lowering of glycated hemoglobin levels in patients with type 2 diabetes, including those with stage 2 or 3a chronic kidney disease, and with reductions in weight and blood pressure, without increases in heart rate.

http://www.nejm.org/doi/full/10.1056/NEJMoa1515920#t=article

Among patients with type 2 diabetes who were at high risk for cardiovascular events, the use of empagliflozin was associated with slower progression of kidney disease when added to standard care. In this study RAAS blockers were also used in this patients.

Empagliflozin was also associated with a significantly lower risk of clinically relevant renal events.

Thanks

Hi Nataliia, I totally agree with you.Empaglifozin is an excellent molecule that that has shown great promise in terms of cardiovascular and renal protection and this benifits are independent of sugar control. This drug probably have inherent property of cardiac and renal protection. It will be interesting to see whether renal or cardiac protection of this molecule can be obtained in nondiabetic patients also? Future trial will probably can say.

Hi Nataliia,

see the enclosed file with some interesting slides.

Hi Giovanni! Thanks a lot about useful information and sorry for delay!

I want to highlight points from these interesting slides and agree with you:

1) eGFR provides information only about kidney function and nothing else

2) The stages are truly stages of kidney function (KF) than the disease and accordingly should consider classifying as stages of kidney function (KF) than stages of disease (CKD), as persons with normal function may have disease and similarly persons with decreased eGFR may not have the disease.

But if we talk about patients with Hypertension and diabetes I have no doubt that their GFR even more than 60ml/min/1.73 could be as a signal to give them antyhypertensive or antidiabetic treatment with nephroprotective properities and also they need more frequent monotoring.

Thank You!

Wish You Happy New Year!

Hi Nataliia,, thank you very much highlighting very interesting points. I also want to give thanks to Giovanni for his very interesting and relevant slides. You are absolutely right that eGFR gives an idea about the renal function only. For example patient with same eGFR with ischaemic nephropathy, chronic tubulointestinal disease, chronic glomerulonephritis and polycystic kidney disease prognosis and progression differ. But you are absolutely right that patient with diabetes and hypertension needs aggressive therapy at the earliest to prevent progression of renal dysfunction.. Thanks

Hi Biswajit! Thanks for your point of view and support in discussion. I agree with you also!

Wish You happy Holidays!