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04-13-2018 | Nephropathy | Review | Article

CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease

Journal: Nature Reviews Nephrology

Authors: Hans-Joachim Anders, Tobias B. Huber, Berend Isermann, Mario Schiffer

Publisher: Nature Publishing Group UK

Abstract

The increasing global prevalence of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has prompted research efforts to tackle the growing epidemic of diabetic kidney disease (DKD; also known as diabetic nephropathy). The limited success of much of this research might in part be due to the fact that not all patients diagnosed with DKD have renal dysfunction as a consequence of their diabetes mellitus. Patients who present with CKD and diabetes mellitus (type 1 or type 2) can have true DKD (wherein CKD is a direct consequence of their diabetes status), nondiabetic kidney disease (NDKD) coincident with diabetes mellitus, or a combination of both DKD and NDKD. Preclinical studies using models that more accurately mimic these three entities might improve the ability of animal models to predict clinical trial outcomes. Moreover, improved insights into the pathomechanisms that are shared by these entities — including sodium–glucose cotransporter 2 (SGLT2) and renin–angiotensin system-driven glomerular hyperfiltration and tubular hyper-reabsorption — as well as those that are unique to individual entities might lead to the identification of new treatment targets. Acknowledging that the clinical entity of CKD plus diabetes mellitus encompasses NDKD as well as DKD could help solve some of the urgent unmet medical needs of patients affected by these conditions.

Diabetic kidney disease

(DKD). Also known as diabetic nephropathy. Often defined as a clinical syndrome of albuminuria in patients with diabetes mellitus but more accurately defined as a distinct histopathological pattern of kidney injury, characterized by arteriolar hyalinosis and nodular glomerulosclerosis, induced by hyperglycaemia.

Sodium–glucose cotransporter 2

(SGLT2). A transporter expressed in the S2 segment of the (convoluted) proximal tubule that reabsorbs freely filtered glucose and cotransports sodium.

GLP1 analogue

Glucagon-like peptide 1 analogues are incretin mimetics that reduce meal-related hyperglycaemia and have a low risk of causing hypoglycaemia. Liraglutide reduced cardiovascular and renal end points in patients with type 2 diabetes mellitus.

Kidney hypertrophy

A diffuse nephron hypertrophy that increases the size of the kidney.

Tubuloglomerular feedback

An autoregulatory mechanism of glomerular perfusion that maintains a submaximal single-nephron glomerular filtration rate (SNGFR) and responds to changes in intravascular fluid volume. Hyperglycaemia deactivates tubuloglomerular feedback and leads to a persistent increase in SNGFR.

Glomerular hyperfiltration

The consequence of an increase in single-nephron glomerular filtration rate due to impaired autoregulation of glomerular haemodynamics or a reduction in the nephron number:body mass ratio.

Glomerular hypertension

The increased pressure gradient across the glomerular filtration barrier that occurs, for example, when glomerular hyperfiltration is not associated with a respective increase in filtration surface.

Sterile inflammation

Non-infectious causes of inflammation such as those that occur in autoinflammatory or autoimmune disorders upon trauma or toxic tissue injury.

Spiegelmer

L-Ribonucleic acid aptamers that mirror structures of natural RNA oligonucleotides, protecting them from enzymatic degradation. Spiegelmers can bind and neutralize small proteins.

Danger-associated molecular patterns

(DAMPs). Natural cellular components, often released by dying cells, that induce inflammation via specific pattern recognition receptors of the innate immune system.

Adipokines

Cytokines secreted by the adipose tissue, including leptin, adiponectin, and apelin.

Nephron hypertrophy

The increased dimensions of nephrons, usually as a consequence of glomerular hypertension and hyperfiltration.

Total GFR

In poorly controlled diabetes, the total glomerular filtration rate (GFR) is close to maximal GFR.

Nephron number

A critical parameter for kidney function. The number of nephrons multiplied by single-nephron glomerular filtration rate (GFR) equals the total GFR.

Kimmelstiel–Wilson lesions

A lesion characterized by nodular glomerulosclerosis that is commonly found in biopsy samples from patients with diabetes mellitus.

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