Ncbi
Ncbi
Ncbi
ability, leading to the activation of signaling cascades fa- normoalbuminuria, microalbuminuria, macroalbumin-
voring glomerulosclerosis, including pathways mediated uria, and finally ESRD (table 1). The earliest stage begins
by TGF-β, advanced glycosylation end products (AGEs), initially with glomerular hyperfiltration and increased
protein kinase C, and various cytokines and growth fac- GFR. The next stage is microalbuminuria, defined as a
No
The optimal therapy of DN continues to evolve. The key- In type 1 diabetes with persistent microalbuminuria,
stones in preventing and slowing renal progression are tight angiotensin-converting enzyme inhibitors (ACEi) reduce
glycemic control, BP and lipid control, and other adjunctive the risk of nephropathy [27]. The Collaborative Study
interventions. The following sections summarize the clini- Group [28] compared captopril with placebo in patients
cal evidence supporting current therapeutic interventions. with type 1 diabetes, urinary protein excretion >500 mg/
day and serum creatinine >1.5 mg/dl. Captopril signifi-
BP Control cantly reduced the composite risk of doubling serum cre-
BP lowering has clearly shown to be an important and atinine, death, dialysis, or transplantation. There are no
powerful intervention in slowing DN progression, reduc- equivalent large long-term clinical trials to demonstrate
ing cardiovascular disease events, and preventing prema- the efficacy of ARBs in patients with type 1 diabetes with
ture death in both type 1 and type 2 diabetic patients. nephropathy. Nevertheless, based on the similar proper-
However, the optimal lower limit for BP control in DN ties of ACEi and ARBs, there is sufficient reason to believe
remains unclear. Major guidelines published before the that both are effective in the treatment of type 1 DN.
Type 2 Diabetes concluded that tight glycemic control delays the onset of
Incretin mimetic Exenatide Ccr 30-50 ml/min: caution advised Avoid Pancreatitis, nephrotoxicity, nausea,
Ccr <30 ml/min: avoid vomiting, diarrhea
DPP-4 Inhibitors Linagliptin No dose adjustment No dose adjustment Pancreatitis, URI, diarrhea,
hyperuricemia
Saxagliptin Ccr <50 ml/min: 2.5 mg po QD HD: give dose after Lymphopenia, pancreatitis, headache,
dialysis edema, vomiting, angioedema
PD: not defined
Alogliptin Ccr 30 – 59 ml/min: 12.5 mg po QD 6.25 mg po QD Skin rash, hepatic failure,
Ccr<30 ml/min: 6.25 mg po QD PD: not defined headache, URI
Sitagliptin Ccr 30 – 49 ml/min: 50 mg po QD 25 mg po QD Skin rash, acute kidney injury, headache,
Ccr <30 ml/min: 25 mg po QD diarrhea, arthralgia
SGLT2 inhibitors Canagliflozin eGFR 49 – 59 ml/min: 100 mg po QD Avoid Renal impairment, hyperkalemia,
eGFR 30 – 44 ml/min: avoid pancreatitis, hypotension, UTI,
eGFR <30 ml/min: contraindicated hypermagnesemia, vulvovaginitis,
hyperphsophatemia
Dapagliflozin eGFR 30 – 59 ml/min: avoid Avoid Renal impairment, bladder cancer,
eGFR <30 ml/min: contraindicated orthostatic hypotension, vulvovaginits,
nasopharyngitis, increased serum
creatinine
Empagliflozin eGFR 30 – 44 ml/min: avoid Avoid Orthostatic hypotension, renal
eGFR <30 ml/min: contraindicated impairment, UTI, vulvovaginitis,
polyuria
Glycemic monitoring in CKD is complex. Advanced ject to this confounding. Other factors that limit the util-
CKD significantly alters the results of HbA1c testing (ta- ity of the HbA1c measurement in patients with ESRD or
ble 2). Elevated blood urea nitrogen causes the formation advanced CKD include a shorter erythrocyte life span,
of carbamylated hemoglobin and an increased glycosyl- iron deficiency anemia, recent transfusion, and erythro-
ation rate. Historically, the increase in urea carbamylation poietin treatment, all of which can cause an underestima-
falsely elevated the HbA1c measurement; however, newer tion of the HbA1c level. Despite these limitations, HbA1c
measures of glycosylated hemoglobin are no longer sub- is still considered a reasonable and probably still is the
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