Glomerular hyperfiltration

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Glomerular hyperfiltration
Physiology of Nephron.png
Diagram showing a schematic nephron and its blood supply.

Glomerular hyperfiltration is a situation where the filtration elements in the kidneys called glomeruli produce excessive amounts of pro-urine. It can be part of a number of medical conditions particularly diabetic nephropathy (kidney damage associated with diabetes). [1]

Contents

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. [2]

Glomerular hyperfiltration can result from efferent arteriolar vasoconstriction due to activation of the renin-angiotensin-aldosterone system, which causes glomerular hypertension, or afferent arteriolar vasodilation, as observed in diabetic patients or following a high-protein meal. [2]

Causes

In healthy individuals, high protein loading causes glomerular hyperfiltration, or an absolute increase in glomerular filtration rate (GFR). [3]

Risk factors

Most young Type 1 diabetic patients experience glomerular hyperfiltration, a typical functional deviation in insulin-dependent diabetes mellitus. [4] A meta-analysis of research done on Type 1 diabetic subjects found that people with glomerular hyperfiltration have a higher chance of developing albuminuria and seeing their diabetic nephropathy worsen. [5] Poor glycaemic control has been blamed for this finding because hyperfiltration and HbA1c were found to be correlated. [6]

According to certain research, glomerular hyperfiltration happens in cases of hypertension as well. [7] Humans with early-stage hypertension have demonstrated glomerular hyperfiltration during sympathetic nervous system activation. [8]

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 responses. [9] [10]

Diagnosis

The lack of an established definition for this clinical entity is one of the primary issues with the diagnosis of hyperfiltration. [11] The primary cause of the lack of clarity surrounding the GFR levels that indicate hyperfiltration is their strong reliance on age. [12] 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. [2]

Treatment

In diabetic mice, proinsulin C-peptide, a putative renoprotective agent, narrows glomerular afferent arterioles. Therefore, proinsulin C-peptide administration should theoretically prevent glomerular hyperfiltration. [13]

An insulin-sensitizing medication called rosiglitazone is known to treat endothelial dysfunction. It has been demonstrated that this medication reduces renal end-organ damage in patients with type 2 diabetes and microalbuminuria, improves nitric oxide bioavailability, and ameliorates glomerular hyperfiltration in patients with early type 2 diabetes. [14]

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. [15]

See also

Related Research Articles

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<span class="mw-page-title-main">Nephron</span> Microscopic structural and functional unit of the kidney

The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure called Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 1 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the foot processes of the podocytes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged ; first with the interstitial fluid outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—urine—exits: it is composed of water, metabolic waste, and toxins.

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<span class="mw-page-title-main">Glomerulus (kidney)</span> Functional unit of nephron

The glomerulus is a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally supported by the mesangium, composed of intraglomerular mesangial cells. The blood is filtered across the capillary walls of this tuft through the glomerular filtration barrier, which yields its filtrate of water and soluble substances to a cup-like sac known as Bowman's capsule. The filtrate then enters the renal tubule of the nephron.

<span class="mw-page-title-main">Macula densa</span> A region of juxtaglomerular apparatus in nephron of kidney

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Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus. Together with the mesangial matrix, they form the vascular pole of the renal corpuscle. The mesangial cell population accounts for approximately 30-40% of the total cells in the glomerulus. Mesangial cells can be categorized as either extraglomerular mesangial cells or intraglomerular mesangial cells, based on their relative location to the glomerulus. The extraglomerular mesangial cells are found between the afferent and efferent arterioles towards the vascular pole of the glomerulus. The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the capillaries. The primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris. The contractile properties of mesangial cells have been shown to be insignificant in changing the filtration pressure of the glomerulus.

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Sickle cell nephropathy is a type of nephropathy associated with sickle cell disease which causes kidney complications as a result of sickling of red blood cells in the small blood vessels. The hypertonic and relatively hypoxic environment of the renal medulla, coupled with the slow blood flow in the vasa recta, favors sickling of red blood cells, with resultant local infarction. Functional tubule defects in patients with sickle cell disease are likely the result of partial ischemic injury to the renal tubules.

Cardiorenal syndrome (CRS) is an umbrella term used in the medical field that defines disorders of the heart and kidneys whereby "acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other". When one of these organs fails, the other may subsequently fail. The heart and the kidneys are involved in maintaining hemodynamic stability and organ perfusion through an intricate network. Patients who have renal failure first may be hard to determine if heart failure is concurrent. These two organs communicate with one another through a variety of pathways in an interdependent relationship. In a 2004 report from the National Heart, Lung and Blood Institute, CRS was defined as a condition where treatment of congestive heart failure is limited by decline in kidney function. This definition has since been challenged repeatedly but there still remains little consensus over a universally accepted definition for CRS. At a consensus conference of the Acute Dialysis Quality Initiative (ADQI), the CRS was classified into five subtypes primarily based upon the organ that initiated the insult as well as the acuity of disease.

References

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Further reading