Diabetes and the kidney disease risk JM Krzesinski ULg-CHU Lige - - PowerPoint PPT Presentation

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Diabetes and the kidney disease risk JM Krzesinski ULg-CHU Lige - - PowerPoint PPT Presentation

May 23, 2023 214 likes •701 views

Diabetes and the kidney disease risk JM Krzesinski ULg-CHU Lige Service de Nphrologie- Dialyse-Transplantation DIABETIC NEPHROPATHY First cause of ESRD in the XXst century Dialysis: Incident causes of ESRD (2013) in Belgiun 23%

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Diabetes and the kidney disease risk

JM Krzesinski ULg-CHU Liège Service de Néphrologie- Dialyse-Transplantation

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DIABETIC NEPHROPATHY

First cause of ESRD in the XXst century

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Dialysis: Incident causes of ESRD (2013) in Belgiun

Congénitale/Malfor matif 7%

Vascular 27%

Glomerulonéphrite 7% Inconnu 6% Néphrite Tubulo- interticielle 8% Pyélonéphrite 3% Secondaire 18%

Diabetes 21%

Non encodée 3%

Causes of dialysis due to DM: in USA 40% in Asia 50% 23%

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60 175 60 49 65 30 153 231 27 50 100 150 200 250 300

Incident patients: Distribution according to nephropathy from 1994 - 2013

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Diabetes mellitus

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Importance of TI lesions on the rate of progression Glomerular lesions

hyperfiltration

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New paradigm of Diabetic kidney disease in the 21st century?

  • In type 2 DM, kidney disease lesions could be quite

different:

  • Association between classical DN and a mixture of

different patterns (including other primary glomerular diseases)

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37% 36% 27% Among 611 type 2 DM

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New paradigm of Diabetic kidney disease in the 21st century?

  • In type 2 DM, kidney disease lesions could be quite

different:

  • Association between classical DN and a mixture of

different patterns (including other primary glomerular diseases) or

  • Presence of decreased GFR but no proteinuria.
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Different patterns of DN according to GFR changes How identifying patients with slow or fast renal decline function trajectories?

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Renal events (dialysis, Tx, doubling s creat) 22X higher when combining UACR >300 mg/g and eGFR <60 ml/min per 1,73m²

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Fast decliner Fast decliner

10% 20% 68%

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Krolewski A et al. Diabetes Care 2012;35:2311-2316

Serum Concentration of Cystatin C and Risk of End-Stage Renal Disease in Diabetes

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Fast decliners Slow decliners ESRD

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DM patients Stage 1 or 2 CKD: prediction of risk for progressive renal decline!

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DM patients Stage 3 or higher CKD

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Management of diabetes

HbA1C according to comorbidities BP <140/85 mmHg Max dose accepted LDL<100 mg/dl If high CV risk <70

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Tight glucose control (metabolic memory) Multifactorial approach

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STENO2

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7.5% 6.5%

8yrs saved

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GLP1agonists

Bariatric surgery

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High CV DM risk population 63y, 72 % Males Most with history of CVE >75% with RASI and statins

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Potential protective mechanisms of SGlT2 inhibition

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Liraglutide (GlP1 agonist) decreases the nephropathy risk, mainly in eGFR group < 60 ml/min per 1,73 m² 9340 high CV risk type 2 DM, median FU 3.8y

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Mean Age 50 y; mean BMI 40; DM mean duration 3y

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Conclusions

  • Incidence of DM is growing and brings CV and renal

risk

  • An early identification of those who will be fast

decliners and early multifactorial treatment approach is necessary, before development of complications.

  • New treatments are urgently resquested, according to

the DN development mechanisms.

  • The most interesting protecting drugs come from new

glucose management therapies.

  • Don’t forget to apply lifestyle and diet approaches (or

bariatric surgery in severe obesity).

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NDT 2015 Clinical practice guidelines

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NDT 2015 Clinical practice guidelines

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Renal decline to ESRD

  • KDIGO guidelines have defined rapid progression by a rate
  • f eGFR decline >5 ml/min/y.
  • There are indeed fast (renal function loss with an interval
  • f 2 to less than 10y between normal function and ESRD),

moderate (between 10-20y) and slow (between 20 and 45y) decline of Kidney function.

  • In type 1(but also 2) DM, role of high HbA1C, urinary

albumin-to-creatinine ratio values, and eGFR (cystatine C) and circulating TNF1R

  • In type 2 DM, 14 biomarkers have been identified in those

with stage 3 and higher CKD who will have a rapid decline

  • f GFR .
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Strict control of glycemia and protection

  • Positive results for microvascular complications
  • It postpones their onsets by several years if applied

early

  • Less convincing results for CV protection
  • The benefit on CV disease of a HbA1C < 7% rather

than 8% decreases with - age,

  • diabetes duration and
  • comorbidities.
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Chronic hyperglycemia Vasoactive hormones (Ag II, endothelins, NO)

Metabolic Hemodynamic Albuminuria

Accumulation Of EC matrix − Intraglomerular pressure − Endothelial dysfunction ↑ Vascular permeability

Cytokines – Growth factors

(TGFβ, VEGF, IGFs,…)

PKC β ΙΙ Glycation end-products

Oxydative stress

Pathophysiology of classical DN

Interstitial fibrosis GFR

INFLAMMATION

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