Glomerular hyperfiltration is a situation where the filtration elements in the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s called

glomeruli ''Glomerulus'' (; : glomeruli) is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to ...

produce excessive amounts of pro-urine. It can be part of a number of medical conditions particularly

diabetic nephropathy Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading cause of chronic kidney disease (CKD) and end-stage renal disease ...

(kidney damage associated with

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

). There is no universally accepted definition of glomerular hyperfiltration, and little research has been done on the pathophysiological mechanisms, which are likely to change depending on the underlying ailment. Glomerular hyperfiltration can result from efferent arteriolar

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

due to activation of the renin–angiotensin–aldosterone system, which causes glomerular

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

, or afferent arteriolar

vasodilation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...

, as observed in diabetic patients or following a high-protein meal.

Causes

In healthy individuals, high protein loading causes glomerular hyperfiltration, or an absolute increase in

glomerular filtration rate Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearance (medicine), clearing toxins; absorption of glucose, amino acids, and other small molecules; reg ...

(GFR).

Risk factors

Most young Type 1 diabetic patients experience glomerular hyperfiltration, a typical functional deviation in

insulin-dependent diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone required ...

mellitus. A meta-analysis of research done on Type 1 diabetic subjects found that people with glomerular hyperfiltration have a higher chance of developing

albuminuria Albuminuria is a pathological condition of elevated albumin protein in the urine (often measured as urine albumin-to-creatinine ratio of >30 milligrams of albumin per 1 gram of creatinine per day). It is a type of proteinuria, and is the most com ...

and seeing their

worsen. Poor glycaemic control has been blamed for this finding because hyperfiltration and

HbA1c Glycated hemoglobin, also called glycohemoglobin, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose, and fructose, spontaneously (that is, non-enzymatically) bond with hemoglob ...

were found to be correlated. According to certain research, glomerular hyperfiltration happens in cases of

as well. Humans with early-stage

have demonstrated glomerular hyperfiltration during

sympathetic nervous system The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...

activation.

Mechanism

Activation of the renin–angiotensin–aldosterone system may be the mechanism underlying renal injury linked to glomerular hyperfiltration. This can result in endothelial dysfunction, increased arterial stiffness, and maladaptive renal and systemic

hemodynamic Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously ...

responses.

Diagnosis

The lack of an established definition for this clinical entity is one of the primary issues with the diagnosis of hyperfiltration. The primary cause of the lack of clarity surrounding the GFR levels that indicate hyperfiltration is their strong reliance on age. Glomerular hyperfiltration has traditionally been characterized as an elevated whole-kidney GFR, or a GFR greater than two standard deviations above the mean GFR of healthy individuals.

Treatment

In diabetic mice, proinsulin

C-peptide The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum levels ...

, a putative renoprotective agent, narrows glomerular afferent

arteriole An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillary, capillaries. Arterioles have vascular smooth muscle, muscular walls (usually only one to two layers of smoo ...

s. Therefore, proinsulin

administration should theoretically prevent glomerular hyperfiltration. An insulin-sensitizing medication called

rosiglitazone Rosiglitazone (trade name Avandia) is an antidiabetic drug in the thiazolidinedione class. It works as an insulin sensitizer, by binding to the PPAR in fat cells and making the cells more responsive to insulin. It is marketed by the pharmaceut ...

is known to treat endothelial dysfunction. It has been demonstrated that this medication reduces renal end-organ damage in patients with

type 2 diabetes Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...

and

microalbuminuria Microalbuminuria is a term to describe a moderate increase in the level of urine albumin. It occurs when the kidney leaks small amounts of albumin into the urine, in other words, when an abnormally high permeability for albumin in the glomerulus o ...

, improves

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

bioavailability, and ameliorates glomerular hyperfiltration in patients with early

. In experimental diabetes, renal nerves may play a significant role in mediating glomerular hyperfiltration. In this sense, in diabetic rats, chronic renal denervation also inhibits glomerular hyperfiltration.

References

External links

{{Glomerular disease, state=collapsed Nephrology Glomerular diseases