Glomerular hyperfiltration

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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).{{cite journal|last1=Cachat|first1=F|last2=Combescure|first2=C|last3=Cauderay|first3=M|last4=Girardin|first4=E|last5=Chehade|first5=H|title=A Systematic Review of Glomerular Hyperfiltration Assessment and Definition in the Medical Literature.|journal=Clinical Journal of the American Society of Nephrology|date=7 January 2015|doi=10.2215/CJN.03080314|pmid=25568216|volume=10|issue=3|pages=382–9|pmc=4348676}}

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 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.

Causes

In healthy individuals, high protein loading causes glomerular hyperfiltration, or an absolute increase in glomerular filtration rate (GFR).{{cite journal | last1=BERGSTRÖM | first1=JONAS | last2=AHLBERG | first2=MARIANNE | last3=ALVESTRAND | first3=ANDERS | title=Influence of Protein Intake on Renal Hemodynamics and Plasma Hormone Concentrations in Normal Subjects | journal=Acta Medica Scandinavica | publisher=Wiley | volume=217 | issue=2 | date=January 12, 1985 | issn=0001-6101 | doi=10.1111/j.0954-6820.1985.tb01655.x | pages=189–196| pmid=3887848 }}

= Risk factors =

Most young Type 1 diabetic patients experience glomerular hyperfiltration, a typical functional deviation in insulin-dependent diabetes mellitus.{{cite journal | last1=Amin | first1=Rakesh | last2=Turner | first2=Charles | last3=van Aken | first3=Sara | last4=Konopelska Bahu | first4=Teresa | last5=Watts | first5=Angela | last6=Lindsell | first6=David R.M. | last7=Neil Dalton | first7=R. | last8=Dunger | first8=David B. | title=The relationship between microalbuminuria and glomerular filtration rate in young type 1 diabetic subjects: The Oxford Regional Prospective Study | journal=Kidney International | publisher=Elsevier BV | volume=68 | issue=4 | year=2005 | issn=0085-2538 | doi=10.1111/j.1523-1755.2005.00590.x | pages=1740–1749 | doi-access=free| pmid=16164650 }} 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.{{cite journal | last1=Magee | first1=G. M. | last2=Bilous | first2=R. W. | last3=Cardwell | first3=C. R. | last4=Hunter | first4=S. J. | last5=Kee | first5=F. | last6=Fogarty | first6=D. G. | title=Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis | journal=Diabetologia | publisher=Springer Science and Business Media LLC | volume=52 | issue=4 | date=February 7, 2009 | issn=0012-186X | doi=10.1007/s00125-009-1268-0 | pages=691–697 | doi-access=free| pmid=19198800 }} Poor glycaemic control has been blamed for this finding because hyperfiltration and HbA1c were found to be correlated.{{cite journal | last1=DAHLQUIST | first1=G. | last2=APERIA | first2=A. | last3=BROBERGER | first3=O. | last4=PERSSON | first4=B. | last5=WILTON | first5=P. | title=Renal Function in Relation to Metabolic Control in Children with Diabetes of Different Duration | journal=Acta Paediatrica | publisher=Wiley | volume=72 | issue=6 | year=1983 | issn=0803-5253 | doi=10.1111/j.1651-2227.1983.tb09838.x | pages=903–909| pmid=6369870 | s2cid=37840032 }}

According to certain research, glomerular hyperfiltration happens in cases of hypertension as well.{{cite journal | last1=QUASCHNING | first1=THOMAS | last2=D'USCIO | first2=LIVIUS V. | last3=SHAW | first3=SIDNEY | last4=GRÖNE | first4=HERMANN-JOSEF | last5=RUSCHITZKA | first5=FRANK | last6=LÜSCHER | first6=THOMAS F. | title=Vasopeptidase Inhibition Restores Renovascular Endothelial Dysfunction in Salt-Induced Hypertension | journal=Journal of the American Society of Nephrology | publisher=Ovid Technologies (Wolters Kluwer Health) | volume=12 | issue=11 | year=2001 | issn=1046-6673 | doi=10.1681/asn.v12112280 | pages=2280–2287| pmid=11675404 }} Humans with early-stage hypertension have demonstrated glomerular hyperfiltration during sympathetic nervous system activation.{{cite journal | last1=Schmieder | first1=R E | last2=Veelken | first2=R | last3=Schobel | first3=H | last4=Dominiak | first4=P | last5=Mann | first5=J F | last6=Luft | first6=F C | title=Glomerular hyperfiltration during sympathetic nervous system activation in early essential hypertension. | journal=Journal of the American Society of Nephrology | publisher=Ovid Technologies (Wolters Kluwer Health) | volume=8 | issue=6 | year=1997 | issn=1046-6673 | doi=10.1681/asn.v86893 | pages=893–900| pmid=9189855 }}

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.{{cite journal | last1=Cherney | first1=David Z.I. | last2=Lai | first2=Vesta | last3=Scholey | first3=James W. | last4=Miller | first4=Judith A. | last5=Zinman | first5=Bernard | last6=Reich | first6=Heather N. | title=Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness, and Endothelial Function in Humans With Uncomplicated Type 1 Diabetes | journal=Diabetes Care | publisher=American Diabetes Association | volume=33 | issue=2 | date=November 4, 2009 | issn=0149-5992 | doi=10.2337/dc09-1303 | pages=361–365 | doi-access=free| pmid=19889802 | pmc=2809283 }}{{cite journal | last1=van der Meer | first1=Irene M | last2=Cravedi | first2=Paolo | last3=Remuzzi | first3=Giuseppe | title=The role of renin angiotensin system inhibition in kidney repair | journal=Fibrogenesis & Tissue Repair | publisher=Springer Science and Business Media LLC | volume=3 | issue=1 | date=May 4, 2010 | issn=1755-1536 | doi=10.1186/1755-1536-3-7 | doi-access=free | page=7| pmid=20441574 | pmc=2888753 }}

Diagnosis

The lack of an established definition for this clinical entity is one of the primary issues with the diagnosis of hyperfiltration.{{cite journal | last=Palatini | first=P. | title=Glomerular hyperfiltration: a marker of early renal damage in pre-diabetes and pre-hypertension | journal=Nephrology Dialysis Transplantation | publisher=Oxford University Press (OUP) | volume=27 | issue=5 | date=March 19, 2012 | issn=0931-0509 | doi=10.1093/ndt/gfs037 | pages=1708–1714 | doi-access=free| pmid=22431709 }} The primary cause of the lack of clarity surrounding the GFR levels that indicate hyperfiltration is their strong reliance on age.{{cite journal | last1=Premaratne | first1=E. | last2=MacIsaac | first2=R. J. | last3=Tsalamandris | first3=C. | last4=Panagiotopoulos | first4=S. | last5=Smith | first5=T. | last6=Jerums | first6=G. | title=Renal hyperfiltration in type 2 diabetes: effect of age-related decline in glomerular filtration rate | journal=Diabetologia | publisher=Springer Science and Business Media LLC | volume=48 | issue=12 | date=November 1, 2005 | issn=0012-186X | doi=10.1007/s00125-005-0002-9 | pages=2486–2493| pmid=16261309 }} 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.{{cite journal | last1=Helal | first1=Imed | last2=Fick-Brosnahan | first2=Godela M. | last3=Reed-Gitomer | first3=Berenice | last4=Schrier | first4=Robert W. | title=Glomerular hyperfiltration: definitions, mechanisms and clinical implications | journal=Nature Reviews Nephrology | publisher=Springer Science and Business Media LLC | volume=8 | issue=5 | date=February 21, 2012 | issn=1759-5061 | doi=10.1038/nrneph.2012.19 | pages=293–300| pmid=22349487 | s2cid=5678191 }}

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.{{cite journal | last1=Nordquist | first1=Lina | last2=Lai | first2=En Yin | last3=Sjöquist | first3=Mats | last4=Patzak | first4=Andreas | last5=Persson | first5=A. Erik G. | title=Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism | journal=American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | publisher=American Physiological Society | volume=294 | issue=3 | year=2008 | issn=0363-6119 | doi=10.1152/ajpregu.00811.2007 | pages=R836–R841 | doi-access=free| pmid=18077505 }}

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.{{cite journal | last1=Pistrosch | first1=Frank | last2=Herbrig | first2=Kay | last3=Kindel | first3=Beate | last4=Passauer | first4=Jens | last5=Fischer | first5=Sabine | last6=Gross | first6=Peter | title=Rosiglitazone Improves Glomerular Hyperfiltration, Renal Endothelial Dysfunction, and Microalbuminuria of Incipient Diabetic Nephropathy in Patients | journal=Diabetes | publisher=American Diabetes Association | volume=54 | issue=7 | date=July 1, 2005 | issn=0012-1797 | doi=10.2337/diabetes.54.7.2206 | pages=2206–2211| pmid=15983223 }}

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.{{cite journal | last=Luippold | first=G. | title=Chronic renal denervation prevents glomerular hyperfiltration in diabetic rats | journal=Nephrology Dialysis Transplantation | publisher=Oxford University Press (OUP) | volume=19 | issue=2 | date=February 1, 2004 | issn=1460-2385 | doi=10.1093/ndt/gfg584 | pages=342–347 | doi-access=free| pmid=14736957 }}

References

External links

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Category:Nephrology

Category:Glomerular diseases