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146 Cardio Diabetes Medicine 2017

Mechanism, Clinical Presentation and

Treatment of Diabetic Kidney Diseases

Prof. Soundarajan, MD., DM., Phd., FRCP (Glasg).,
HOD Nephrology Saveetha Medical College, Chennai.

Abstract most common reason for progressing to end stage
Diabetic kidney disease develops in approximately renal disease in the US and in many parts of the
40% of patients who are diabetic and is the lead- world [3–5]. The number of people initiating treatment
ing cause of CKD worldwide. Although ESRD may for ESRD related to diabetes was 48,374 people in
be the most recognizable consequence of diabetic 2008, more than 18- fold what it was in 1980. DKD
kidney disease, the majority of patients actually die was previously known as diabetic nephropathy and
from cardiovascular diseases and infections before is defined as diabetes with albuminuria (ratio of urine
needing kidney replacement therapy. The natural albumin to creatinine ≥ 30 mg/g), impaired glomerular
history of diabetic kidney disease includes glomeru- filtration rate (<60ml/min/1.73m2) or both and is the
lar hyperfiltration, progressive albuminuria, declining single strongest predictor of mortality in patients with
GFR, and ultimately, ESRD. Metabolic changes asso- diabetes . Today, DKD encompasses not only diabet-
ciated with diabetes lead to glomerular hypertrophy, ic nephropathy but also atheroembolic disease, isch-
glomerulosclerosis, and tubulointerstitial inflamma- emic nephropathy, and interstitial fibrosis that occurs
tion and fibrosis. Despite current therapies, there is as a direct result of diabetes.
large residual risk of diabetic kidney disease onset Previously, histopathological changes seen in dia-
and progression. Therefore, widespread innovation betic kidney disease , were attributed primarily to
is urgently needed to improve health outcomes for metabolic and hemodynamic derangements seen
patients with diabetic kidney disease. Achieving this in diabetes, the latter referring to the hyperfiltration
goal will require characterization of new biomarkers, which occurs as a result of efferent arteriolar vaso-
designing clinical trials that evaluate clinically per- constriction due to an activated renin-angiotensin-al-
tinent end points, and development of therapeutic dosterone system (RAAS). However, it has become
agents targeting kidney - specific disease mecha- increasingly evident over the years that hyperglyce-
nisms (e.g., glomerular hyperfiltration, inflammation, mia in and of itself is not the sole cause of DKD,
and fibrosis) although inarguably, it plays a major role. Several
Diabetes has long been a growing epidemic in the pathophysiologic pathways are involved in the de-
United States (US) and around the world. In 2011, velopment of DKD.
there were 20.8 million people aged 18 years and
older who carried a diagnosis of diabetes in the US Mechanism of DKD
alone [1].The number of adults aged 18–79 in the US Hemodynamic Pathways of DKD
that were newly diagnosed with diabetes has more Activation of the RAS leads to increased angiotensin
than tripled from 493,000 in 1980 to over 1.5 million II levels which subsequently cause efferent arteriolar
in 2011 [2]. The increased prevalence of diabetes has vasoconstriction. Elevated levels of angiotensin II are
also led to an increase in the number of macro- and associated with increased albuminuria and nephrop-
microvascular complications of diabetes such as athy in both humans and mice [8,9,10]. ACEIs and
coronary heart disease, stroke, visual impairment, ARBs have a long track record in reducing the dou-
diabetic kidney disease (DKD), and end stage renal bling rate of creatinine, albuminuria, and progression
disease (ESRD). Additionally, diabetes remains the
to nephropathy, ESRD, and death. Another potent va-

GCDC 2017