Thread by @cardiomet_CE

1) Welcome to a new #accredited #tweetorial on Clinical and Laboratory Manifestations of #DKD in #T2D: From Early Identification to Monitoring Management. Your expert author is @edgarvlermamd.

2a) This activity is supported by an independent educational grant from the Boehringer Ingelheim/Lilly Alliance and is intended for healthcare providers. It is accredited for #physicians #physicianassistants #nurses #NPs #pharmacists. Check out @cardiomet_ce for more🆓CE/#CME.

2b) Past programs are still eligible for credit & can be found at cardiometabolic-ce.com. Faculty disclosures are at cardiometabolic-ce.com/disclosures/.
#FOAMed #medtwitter #diabetesmanagement #kidneydisease #diabetickidneydisease #diabetes @goKDIGO @MedTweetorials @nephondemand

3) So let's talk #histmed. Symptoms of #diabetes were recorded as far back as 400 BC.
Sushruta, an Indian physician described diabetes in an ancient Hindi document as “madhumeha” or the honeyed-urine disease.
🔓satyawahr.com/post/sushruta-…
🔓pubmed.ncbi.nlm.nih.gov/23984020/

4) Around 150 AD, the Greek physician Aretaeus of Cappadocia (attention #histmed geeks, see 🔓pubmed.ncbi.nlm.nih.gov/26037198/) wrote this about diabetes:

5) As to modern epidemiology, the increasing prevalence of DKD (also referred to as diabetic #nephropathy) parallels the dramatic worldwide rise in prevalence of diabetes. In 2016, estimates of diagnosed diabetes prevalence varied across US counties, ranging from 1.5% to 33.0%.

6) The median county-level prevalence of diagnosed diabetes ↗️↗️ from 7.8% in 2004 to 13.1% in 2016.
cdc.gov/diabetes/pdfs/…

7) Diabetes is the number one cause of kidney failure in the US.
It is responsible for fully 4⃣4⃣% of #KidneyDisease cases.
freseniuskidneycare.com/kidney-disease…

8) The driving force behind the escalating prevalence of diabetes is the global pandemic of obesity 🔓cdc.gov/diabetes/stati…

9) DKD risk factors can conceptually be classified as susceptibility factors (e.g., age, sex, race/ethnicity, family history), initiation factors (e.g., hyperglycemia, AKI), & progression factors (e.g., hypertension, dietary factors, obesity)
🔓pubmed.ncbi.nlm.nih.gov/28522654/

10) Two of the most prominent established risk factors are #hyperglycemia and #hypertension.

11) The natural history of diabetic kidney disease (#DKD) is best exemplified in patients with type 1 diabetes (#T1D) because the onset of #diabetes is more clearly definable and typically occurs at an early enough age to permit long-term follow-up.

12) Note that T1D usually afflicts a younger population that do not usually initially have comorbid conditions (#hypertension, #ASCVD, #obesity, etc.) often associated with #T2D and that may independently produce #CKD.
🔓accessmedicine.mhmedical.com/book.aspx?book…

13) Patients with either T1D or T2D may exhibit an increased glomerular filtration rate (#GFR), so-called hyperfiltration, at the initial presentation of disease.

14) This hyperfiltration is mediated by proportionately greater relaxation of the afferent arteriole than the efferent arteriole and results in increased glomerular blood flow and elevated glomerular capillary pressure.
link.springer.com/book/10.1007/9…

15) Along with this changing paradigm of the natural history of #DKD, emerging evidence suggests that the clinical presentation of DKD is altering
🔓pubmed.ncbi.nlm.nih.gov/28522654/

16) Let's talk🥼pathology. An early finding in patients with poorly controlled diabetes is enlargement of the kidneys, which represents predominantly hypertrophy of the existing structures rather than growth of new #nephrons or cellular hyperplasia.

17) Commissioned by the Research Committee of @Renalpathsoc an international consensus working group has provided a pathologic classification system (combining T1D and T2D #DKD) to address the heterogeneity of DKD presentation.

18) This system included scoring of 🔬glomerular, interstitial, & vascular lesions.
DKD was divided into 4 hierarchical glomerular lesions with a separate evaluation for degrees of interstitial and vascular involvement.
🔓pubmed.ncbi.nlm.nih.gov/20167701/

19) Renal #biopsy at the time of onset of #microalbuminuria indicates glomerular and tubular basement membrane thickening and the inception of mesangial matrix expansion.
🔓pubmed.ncbi.nlm.nih.gov/28522654/

20) Renal biopsy in patients who develop overt #proteinuria reveals diffuse or nodular (Kimmelstiel–Wilson) #glomerulosclerosis.
pubmed.ncbi.nlm.nih.gov/29398179/

21) Although the Kimmelstiel–Wilson lesion is considered pathognomonic of advanced diabetic nephropathy, only approximately 25% of patients manifest this lesion.
link.springer.com/book/10.1007/9…

22) What other diseases cause a nodular pattern of glomerulopathy?
A.AL Amyloidosis
B.AA Amyloidosis
C.Monoclonal Ig Deposition Disease (MIDD)
D.All of the above

23) Mark your response and return TOMORROW for the correct answer and more #accredited education!
@KIReports @NIDDKgov @ErinMichos @KatherineTuttl8 @polska_md @nephondemand @dguerrot
And in case you missed it, here's a good patient ed video for DKD:

24a) Welcome back! Expert author @edgarvlermamd is providing foundational knowledge on the evaluation & staging of #CKD in patients with #T2D. And YOU are earning CE/#CME! Nods to @GoggleDocs @LangoteAmit @divyaa24 @ChristosArgyrop @mvaduganathan @AgarwalRajivMD @VelezNephHepato

24b) Yesterday's poll? If you didn't vote yet, go back to tweet #22, don't miss a chance to learn something, and JUST DO IT

25) A nodular pattern of glomerulopathy mimicking Kimmelstiel-Wilson lesions may also be seen in light chain nephropathy. Historic descriptions of “diabetic nephropathy without overt hyperglycemia” based solely on light microscopy actually may have been light-chain disease.

26) Nodular glomerular lesions can also be observed in amyloidosis and membranoproliferative glomerulonephritis type 2.
🔓pubmed.ncbi.nlm.nih.gov/23128123/

27) #Microalbuminuria is more likely in patients who also have evidence of other microvascular insults, especially proliferative #retinopathy
link.springer.com/book/10.1007/9…

28) The earliest clinical sign of the development of #DKD is usually the onset of microalbuminuria.
link.springer.com/book/10.1007/9…

29) Initially, transient or intermittent microalbuminuria can be measured by radioimmunoassay, enzyme-linked immunosorbent assay, or special dipsticks, especially when induced by stress, physical exertion, concurrent illness, or poor glycemic control.

30) Albuminuria is a dynamic, fluctuating condition rather than a linearly progressive process.

31) So let's move now to pathobiology. Critical metabolic changes that alter kidney hemodynamics and promote inflammation and fibrosis in early diabetes include hyperaminoacidemia, a promoter of glomerular hyperfiltration and hyperperfusion, and #hyperglycemia.

32) Hyperglycemia & its metabolic sequelae are considered to be the proximate causative factor in development of diabetic #nephropathy. Hyperglycemia can induce numerous metabolic & structural abnormalities implicated in the pathogenesis of diabetic nephropathy, including ...

33) ..generation of reactive oxygen species, activation of the polyol pathway (leading to de novo synthesis of diacylglycerol & increased protein kinase C activity), alterations in the hexosamine pathway, & nonenzymatic protein glycation (advanced glycosylation end products).

34) Although experimental studies have indicated that each of these alterations can be causative in animal models of diabetic nephropathy, their role in human diabetic nephropathy remains incompletely determined.

35) Better glucose control does generally reduce the risk of nephropathy and other microvascular complications, especially in type 1 diabetes
pubmed.ncbi.nlm.nih.gov/29398179/

36) What about renal #hemodynamics? Glomerular hyperfiltration is a well characterized consequence of early diabetes. Overall, it is observed in 10%–40% or up to 75% of patients with #T1D and up to 40% of patients with #T2D.

37) In T2D, systemic #hypertension and #obesity also contribute to glomerular hyperfiltration via various mechanisms, such as high transmitted systemic BP and glomerular enlargement.
pubmed.ncbi.nlm.nih.gov/29654297/

38) Mechanisms underlying glomerular hyperfiltration in diabetes are incompletely understood; one plausible mechanism is⬆️proximal tubular reabsorption of glucose via #SGLT2, which⬇️distal delivery of solutes, particularly NaCl, to the macula densa.
🔓pubmed.ncbi.nlm.nih.gov/28522654/

39) The resulting⬇️in tubuloglomerular feedback may dilate the afferent arteriole to⬆️glomerular perfusion, while concurrently, high local production of angiotensin II at the efferent arteriole produces vasoconstriction.

40) The overall effect is high intraglomerular pressure and glomerular hyperfiltration.
pubmed.ncbi.nlm.nih.gov/28143897/

41) There's even more to the #pathophysiology of #DKD: #DM causes overactivation of the mineralocorticoid receptor, which⬆️the expression of proinflammatory cytokines & profibrotic proteins, leading to inflammation & fibrosis.
🔓pubmed.ncbi.nlm.nih.gov/25368026/

42) So what about screening for diagnosing #DKD? Screening should be performed annually for patients with #T1D beginning 5 years after diagnosis and annually for all patients with #T2D beginning at the time of diagnosis.
link.springer.com/book/10.1007/9…

43) So re making that diagnosis, mark your choice below and return tomorrow for the correct answer, the rest of the education in this #tweetorial, and your CE/#CME credit grab!
The diagnosis of DKD requires which of the following?