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148 Cardio Diabetes Medicine 2017

tionary mechanism is linked to the sodium-glucose
transporter 2 (SLGT2) in the proximal tubule. SLGT2
is a low-affinity and high-capacity transporter and is
responsible for >90% of glucose reabsorption in the
proximal tubule. Animals with a genetic deficiency
of SLGT2 lose approximately 60% of their filtered
glucose into the urine. In settings of hyperglycemia,
there is upregulation of SLGT2 expression which is
believed to be of evolutionary benefit as it allows for
glucose reabsorption and hence energy conservation
for both the body and brain.

Clinical manifestations and natural history
Clinical stages of type 1 diabetes mellitus renal in-
volvement is summarized in Table-1. These stages are
also accepted for type 2 diabetic patients however
they might not always follow these steps . ESRD is
not the only major consequence of diabetic nephrop-
athy but patients have increased risk of cardiovas-
cular disease , morbidity and mortality even in the
early stages of nephropathy. Microalbuminuria (30-
300 mg/day albuminuria) is the first clinical sign
of diabetic nephropathy and this situation is highly
associated with other complications of diabetes like Despite current approaches to management of dia-
cardiovascular disease and retinopathy. 24 hour urine betes and hypertension and use of ACE inhibitors
or spot urine albumin / creatinine ratios should be and ARB, there is still large residual risk in DKD. Nov-
used for microalbuminuria follow-up. Overt protein- el agents targeting mechanisms, such as glomerular
uria is defined as >300 mg/day albuminuria and at hyperfiltration, inflammation, and fibrosis, have been
this stage total protein loss in urine might exceed 1g/ a major focus for development of new treatments.
day. 5-7 years after development of overt proteinuria Agents that have shown promise include ruboxistau-
these patients usually develop ESRD.
rin, a protein kinase C-b inhibitor; baricitinib, a se-
lective Janus kinase 1 and Janus kinase 2 inhibitor;
Treatment of DKD pentoxifylline, an anti-inflammatory and antifibrotic
Prevention of diabetic complications, particularly agent ; atrasentan, a selective endothelin A receptor
DKD, by long-term intensive glycemic control from antagonist; and finerenone, a highly selective non-
early in the course of diabetes is well established steroidal mineralocorticoid receptor antagonist. How-
for DM1 and DM2. However, intensive glucose con- ever, thus far, there are no available phase 3 clinical
trol after onset of complications or in longstanding trial data for these agents, and none are approved
diabetes has not been shown to reduce risk of DKD for use in DKD.
progression or improve overall clinical outcomes. Tar-
geting low HbA1C (6%–6.9%) compared with standard References
therapy in this population did not reduce risk of car- 1. Centers for Disease Control and Prevention. Number (in Millions)
diovascular (CV) or microvascular complications but of Civilian, Noninstitutionalized Adults Diagnosed with Diabetes, United
increased the risk of severe hypoglycemia. The Amer- States, 1980–2014. 2015..
ican Diabetes Association recommends that targets 2. Centers forDiseaseControl and Prevention,AnnualNumber (inThousands)
for glycemia should be tailored to age, comorbidities, of New Cases of Diagnosed Diabetes Among AdultsAged 18–79 Years,
and life expectancy of individual patients. United States, 1980–2011,
The KDIGO guidelines recommend use of an ACE or 3. “Salahudeen AK. Obesity and survival on dialysis. American journal of
kidney diseases. 2003 May 31;41(5):925-32.
an ARB and a BP goal ,130/80 mmHg in all patients
with CKD and albuminuria irrespective of diabetes 4. Ritz E, Rychlík I, Locatelli F, Halimi S. End-stage renal failure in type 2
diabetes: a medical catastrophe of worldwide dimensions. American journal
status (Table 1) of kidney diseases. 1999 Nov 30;34(5):795-808.
5. A. T. Reutens, “Epidemiology of Diabetic Kidney Disease,” Medical Clinics
ofNorth America, 2013vol. 97, no. 1, pp. 1–18, .

GCDC 2017