Information

How does ANF increase GFR?

How does ANF increase GFR?


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

ANF as we know reduce the Na+ uptake and K+ removal in the distal tubules and it also functions as a Vasodialator (?) But again it says that ANF increases the Glomerular filtrate ? But if it is acting has a Vasoldialator (ie, antagonistic to Vasopressin) how is it increasing the GFR ? Shouldnt it lower the GFR ?


ANF - Atrial Natriuretic Factor also called Atrial Natriuretic Peptide

GFR - Glomerular Filtration Rate


ANF (Atrial Natriuretic Factor more commonly known as ANP - atrial natriuretic peptide) squeezes (vasoconstricts) the efferent arteriole. This means the pressure in the glomerulus is higher (like if you squeeze the end of a hose) and so more fluid is squeezed out i.e. the glomerular filtration rate (GFR) is higher. It also dilates the afferent which means more fluid is going in, further increasing GFR (Marin-Grez et al.)


Atrial Natriuretic Peptide

atrial natriuretic hormone atrialnatriuretic polypeptide atrial peptide atriobiss atriopeptin atriumnatriuretic factor atrium natriuretic peptide atrium natriureticpolypeptide a type natriuretic peptide cardionatrin heart atrialnatriuretic factor heart atrium natriuretic extract heart atriumnatriuretic factor heart atrium peptide natriuretic atrial extract natriuretic factor,atrial atrial natriuretic factor ANF ANP(R3D,G9T,R11S,M12L,R14S,G16R) ANP atrial natriuretic polypeptide atrium natriuretic factor atrium natriuretic polypeptide heart atrial natriuretic factor heart atrium natriuretic factor


Issues of Concern

The structure of the glomerulus exerts both size and charge constraints over what will pass through. The endothelium of fenestrated capillaries permits molecules of less than 70 nM to pass through. The basement membrane also restricts by size (approximately 1 kDa) and by charge, since the negative charge of basement membrane protein repels other proteins but favors filtration of cations. Finally, podocyte food processes on the visceral layer also size selects by about 14 nM.

The forces that govern filtration in the glomerular capillaries are the same as any capillary bed. Capillary hydrostatic pressure (Pc) and Bowman’s space oncotic pressure (πi) favor filtration into the tubule, and Bowman’s space hydrostatic pressure (Pi) and capillary-oncotic pressure (㰌) oppose filtration. These terms are expressed together in the Starling force’s law equation, as a measure of J (flow):

Where Kf is the filtration coefficient, and σ is the reflection coefficient, both inherent and fixed values of the epithelium. For the kidney, flow (J) is positive, favoring filtration, meaning that plasma flows from higher hydrostatic pressure in the capillary to lower hydrostatic pressure in the tubular space, despite the unfavorable oncotic gradient (there is higher protein concentration in the capillary). In theory, therefore, GFR is highly dependent on hydrostatic pressure.

However, GFR is tightly regulated through several mechanisms. Firstly, RBF is relatively constant over a wide range of mean arterial pressures (MAP), through what is termed the myogenic response. An increase in hydrostatic pressure in the afferent arteriole stretches vascular smooth muscle, activating inward directed ion channels, leading to depolarization and contraction. This prevents pathologic increases in RBF that would damage the kidney. Notably, this is a localized effect, independent of autonomic regulation (as is the case for autoregulation in other organs). Falling blood pressure does the opposite: dilate the afferent arteriole and preserve blood flow to the kidney. Secondly, the renin-angiotensin-aldosterone system acts to preserve GFR. The juxtaglomerular cells in the afferent arteriole release renin in response to decreased stretch. Circulating renin activates liver-synthesized angiotensinogen to angiotensin I, which is further acted upon by angiotensin converting enzyme in the lung to the active angiotensin II, a potent vasoconstrictor. Angiotensin II raises systemic blood pressure and stimulates the release of aldosterone, which promotes sodium retention/potassium secretion and further increases in blood pressure, in both cases preserving renal perfusion and maintaining GFR. The third mechanism is tubuloglomerular feedback. The macula densa in the thick ascending limb senses an increase in GFR through increased delivery of electrolytes. The increased flow leads to an increased intracellular Cl concentration (sensed by Na-K-Cl transporter), depolarizing the cell, and leading to the release of ATP, adenosine, and thromboxane. These paracrine mediators contract nearby smooth muscle cells in the afferent arteriole to reduce RBF and, thus, return GFR to normal. The macula densa can also independently stimulate the juxtaglomerular cells to release renin, activating the RAAS. We know that this transporter is implicated because the effect can be attenuated by loop diuretics that block the Na-K-Cl channel.

Clearance is the virtual plasma volume from which a solute is removed per unit time, expressed in ml per minute. It can be calculated for any substance given steady-state, known concentrations as [urine concentration] x (urine flow rate) / [plasma concentration], or more simply, C = UV/P. Therefore, it is an indicator of GFR (also ml per minute) for solutes that are freely filtered (not size/charge restricted) and which are not significantly reabsorbed, secreted, synthesized or metabolized in the kidney. Experimentally, inulin, a plant polysaccharide that is indigestible and administered exogenously is used. This requires time to reach a steady state and is not feasible in the clinical setting. Practically, we use creatinine, a breakdown product of creatine phosphate in skeletal muscle. Under normal adult metabolism (catabolic and anabolic in equilibrium), a constant amount of creatinine is released. Under those conditions, any change in creatinine is due to changes in clearance (and therefore GFR). Nonrenal factors that influence the plasma creatinine are strenuous exercise, endogenous consumption (muscle-building supplements), rapid muscle growth, or injury to a skeletal muscle (rhabdomyolysis, burns). We standardize clearances by comparing them to inulin/creatinine which is assigned clearance of 1. Substances that are reabsorbed will have a clearance of less than 1, and those that are secreted will have a clearance greater than 1. We can use the clearance of another compound to look at renal plasma flow. Para-amino hippuric acid (PAH) is filtered and secreted such that, in one pass, it is entirely cleared by the kidney. Therefore, its clearance approximates RPF. We now have the required calculations to describe another measure of kidney function: filtration fraction (FF). This is the portion of plasma entering the kidney (RPF) that ends up as filtrate (GFR). FF = GFR / RPF and is approximately 20% for a healthy individual.


The renal tubule is a long and convoluted structure that emerges from the glomerulus and can be divided into three parts based on function. The first part is called the proximal convoluted tubule (PCT) due to its proximity to the glomerulus it stays in the renal cortex. The second part is called the loop of Henle, or nephritic loop, because it forms a loop (with descending and ascending limbs ) that goes through the renal medulla. The third part of the renal tubule is called the distal convoluted tubule (DCT) and this part is also restricted to the renal cortex. The DCT, which is the last part of the nephron, connects and empties its contents into collecting ducts that line the medullary pyramids. The collecting ducts amass contents from multiple nephrons and fuse together as they enter the papillae of the renal medulla.

The capillary network that originates from the renal arteries supplies the nephron with blood that needs to be filtered. The branch that enters the glomerulus is called the afferent arteriole. The branch that exits the glomerulus is called the efferent arteriole. Within the glomerulus, the network of capillaries is called the glomerular capillary bed. Once the efferent arteriole exits the glomerulus, it forms the peritubular capillary network , which surrounds and interacts with parts of the renal tubule. In cortical nephrons, the peritubular capillary network surrounds the PCT and DCT. In juxtamedullary nephrons, the peritubular capillary network forms a network around the loop of Henle and is called the vasa recta .


What is Estimated Glomerular Filtration Rate (eGFR)?

eGFR (Estimated Glomerular Filtration Rate) is a calculated value based on filtration marker (basically, serum creatinine) concentration to assess the kidney function. Estimated GFR can vary with age even in a healthy population. Age-based average eGFR for healthy population is listed below

Average eGFR

eGFR is basically performed to diagnose CKD (Chronic Kidney Disease) and currently it is classified into five stages based on eGFR as recommended by professional guidelines.

Description

Kidney damage with normal kidney function

Kidney damage with mild loss of kidney function

Mild to moderate loss of kidney function

Moderate to severe loss of kidney function

Severe loss of kidney function

Equations for Calculating eGFR

In the past, a 24-hour creatinine clearance has been considered as the sensitive method of measuring kidney function. But due to practical limitations of collecting timed urine samples and failure to collect the entire specimen, National Kidney Foundation Disease Outcomes Quality Initiative (K-DOQI) recommends the use of eGFR calculated from prediction equation based on plasma/serum creatinine.

This offered an easy and practical approach for calculating eGFR taking into consideration factors like patient’s age, sex, weight and ethnicity (depending on the type of equation). The commonly used equations are Modification of Diet in Renal Disease [(MDRD) (1999)] and Chronic Kidney Disease Epidemiology Collaboration [(CKD-EPI) (2009)]

For estimating GFR in patients under age 18 years, the Bedside Schwartz equation can be used.

MDRD Equation

MDRD eGFR = 186×[Plasma Creatinine (μmol/L)×0.0011312]−1.154 ×[age (years)]−0.203 ×[0.742 if female]×[1.212 if black]

This equation was validated in patients with diabetic kidney disease, renal transplant recipients and African Americans with non-diabetic kidney disease. But it has not been validated in children age under 18 years, pregnant women and patients over 70 years of age.

CKD-EPI Equation

White or other

Female with Creatinine≤0.7mg/dL use eGFR=144×(Cr/0.7)^−0.329×(0.993)Age

Female with Creatinine>0.7mg/dL use eGFR=144×(Cr/0.7)^−1.209×(0.993)Age

Male with Creatinine≤0.9mg/dL use eGFR=141×(Cr/0.9)^−0.411×(0.993)Age

Male with Creatinine>0.9mg/dL use eGFR=141×(Cr/0.9)^−1.209×(0.993)Age

Female with Creatinine≤0.7mg/dL use eGFR=166×(Cr/0.7)^−0.329×(0.993)Age

Female with Creatinine>0.7mg/dL use eGFR=166×(Cr/0.7)^−1.209×(0.993)Age

Male with Creatinine≤0.9mg/dL use eGFR=163×(Cr/0.9)^−0.411×(0.993)Age

Male with Creatinine>0.9mg/dL use eGFR=163×(Cr/0.9)^−1.209×(0.993)Age

CKD-EPI equation minimizes the over diagnosis of CKD with MDRD equation. This includes log serum creatinine model with gender, race and age on natural scale.


Effect of protein on glomerular filtration rate and prostanoid synthesis in normal and uremic rats

Normal and uremic conscious rats that had been maintained on a low-protein diet were given oral protein or carbohydrate loads, and clearance studies were performed. Both the normal and uremic animals demonstrated a approximately 30% increase in glomerular filtration rate (GFR) in response to the protein bolus, but no significant increase in GFR was seen following the carbohydrate bolus. Similar studies were performed in uremic rats on a standard protein diet. The changes in GFR that were seen after an albumin bolus were similar but not as pronounced as those noted in the animals on the low-protein diet. Pretreatment with either aspirin or meclofenamate, cyclooxygenase inhibitors, completely blocked the protein-induced rise in GFR. The rats of glomerular production of prostaglandin (PG) E2 and 6-keto-PGF1 alpha (a stable metabolite of prostacyclin, PGI2) were determined by radioimmunoassay in a similar group of normal rats. The synthetic rates of PGE2 and 6-keto-PGF1 alpha following the protein bolus were 40 and 52% greater, respectively, than those observed following the carbohydrate load (P less than 0.005). Aspirin decreased glomerular prostanoid production in protein-treated animals by greater than 60%. Thus it appears that in the setting of protein restriction, the percent increase in GFR following a protein load is similar in both the normal and uremic rats, the increase in GFR in uremic rats is attenuated when animals were allowed to ingest a normal protein diet prior to study, and the increase in GFR seen in response to a protein load may be related to an increase in the synthesis of one or more vasodilatory glomerular prostanoids.


Discussion

In this study, we demonstrate that renal function can improve sustainably over time in a subgroup of patients followed and treated for CKD. Given the reputedly relentless nature of CKD, the existence of our group of improvers may appear surprising, but the methods we used attest to its reality. First, we measured GFR in all patients, using 51 Cr-EDTA renal clearance, a gold standard method to assess renal function [23]. Similar trends were obtained based on MDRD or CKD-EPI eGFR. Second, all subjects were outpatients, in stable condition, without any recent therapeutic modifications. Given the length of the follow-up, neither extracellular volume expansion nor hemodynamic changes can account for the repeated GFR improvement. The median of four annual visits in the two study groups rules out any transient renal improvement or iatrogenic bias. Third, and most importantly, we demonstrated that the observed increase in mGFR was associated with a decrease in the number of metabolic complications such a decrease reflects a true improvement in mGFR.

The 15.3% prevalence of GFR improvement observed in this cohort is consistent with the few reports previously published. In the 2-year follow-up of the MDRD study, GFR remained stable in 19% of patients and improved in 11% [3]. In the AASK trial, however, over a longer period of 8.8 years and with Bayesian models, eGFR improved among only 3.3%, with a mean slope of +1.06 ml/min/1.73 m 2 per year [19]. This study also emphasized that many patients with CKD have a nonlinear GFR trajectory or a prolonged period of nonprogression [24]. In a population with mild CKD receiving primary care through a large integrated health care system between 2004 and 2009, eGFR rose over time among 41.3% [25]. In a retrospective study of patients before nephrology referral, eGFR did not progress among 16% of those with stages 3–5 of CKD [26]. After referral, the eGFR decline slowed to less than 1 ml/min/1.73 m 2 /year in 55% of patients, including those with an improving slope. Others have emphasised the beneficial effect of nephrology referral and reported a positive slope for eGFR (more than +1 ml/min/1.73 m 2 /year) in 18% of patients in stages 2 and 3 of CKD and in 24% of those in stage 4 [26]. Most of those studies, however, used estimated GFR and did not describe in detail the features of the subgroup with this positive slope.

A second important finding is that this favourable disease course occurred in patients with various initial nephropathies. The notable exceptions were diabetic and polycystic kidney diseases, not seen in any improvers. Both those nephropathies are well known for their relatively poorer prognosis. Polycystic kidney disease has been reported to be resistant to ACE inhibitor treatment and to progress relentlessly even after inhibition of cyst development [27], [28]. Diabetic glomerulopathy is characterized by high urinary albumin excretion, a major negative prognostic factor, even though renal decline appears similar in diabetic and non-diabetic patients at comparable levels of albuminuria [29], [30]. Our data, like those of others, emphasize the importance of albuminuria as a prognostic factor of renal function. We should specify that the diagnosis of diabetic glomerulopathy in the NephroTest cohort was based on either renal biopsy or clinical data (diabetes, renal failure, high urinary albumin excretion, and/or other microvascular complications).

Surprisingly, GFR also improved in some patients with advanced CKD: 24.2% of the improvers had advanced CKD, in stage 4 or 5. Our results suggest that the ability to heal persists in some conditions in advanced CKD. This is consistent with previous evidence from the REIN study demonstrating that the tertile with the lowest GFR at inclusion had the most ESRD events prevented [31]. Mechanisms of this improvement in renal function remain unknown, but might involve renal tissue remodeling during follow-up, perhaps mediated by angiotensin II blockers. Certainly, more than 90% of our cohort takes ARBs or ACE (>90%), and they are known to induce regression of renal fibrosis in experimental models [32]–[34].

We assessed the number of achieved recommended treatment targets, based on the main established modifiable risk factors for CKD, including systolic and diastolic blood pressure, proteinuria or albuminuria, and use of angiotensin blockers. We observed a higher number of achieved targets in improvers than in nonimprovers at all visits, despite a lower need for antihypertensive and antiproteinuric treatments. The use of a higher number of treatments in nonimprovers may clearly reflect indication bias. However, it is important to note that the number of achieved targets was significantly associated with mGFR improvement independent of baseline or mean mGFR and of progression risk factors. Thus our results confirm the value of achieving recommended therapeutic targets to preserve renal function. Improvers also differed from nonimprovers in their CKD metabolic complications. This finding underlines the possible deleterious role of metabolic complications on GFR progression. We considered CKD metabolic complications to include hyperphosphatemia, metabolic acidosis, anemia, hyperkalemia, and elevated parathormone, as previously reported [21]. High serum phosphate has also been recognized as an independent risk factor for renal disease progression in several observational studies [35], [36]. In the REIN trial, patients with phosphate levels in the two highest quartiles progressed significantly faster to a composite endpoint of doubled serum creatinine or ESRD compared with patients whose phosphate levels were below the median [37]. Moreover, the renoprotective effect of ACE inhibitor decreased as serum phosphate increased. The authors hypothesized that fibroblast growth factor-23 (FGF-23) might activate the renin-angiotensin system (RAS).

Metabolic acidosis is another risk factor for renal disease progression, and its correction with sodium bicarbonate slows renal function decline in stage 2–5 CKD [38]. However, after adjusting for mGFR, we found no difference between groups for metabolic complications considered individually, with the notable exception of native vitamin D level We nonetheless cannot rule out the possibility that we lack the necessary statistical power.

We found that native vitamin D deficiency was less prevalent in improvers than nonimprovers. This result is important because vitamin D deficiency is very common in CKD patients, and its prevalence increases as GFR declines [39]. Although there is not yet any proof that an insufficient 25(OH)D level contributes to GFR impairment, a few studies have reported similar results. In a community-based cohort of ambulatory older adults, lower serum 25(OH)D concentrations were associated with faster eGFR loss, particularly when 25(OH)D was lower than approximately 30 ng/ml [40]. Moreover, lower levels of 25(OH)D were related to higher risks of ESRD and mortality in patients with stage 2–5 CKD [41]. In NHANES III, a 25(OH)D concentration <15 ng/ml was associated with an increased risk of incident ESRD in black subjects [42]. These findings suggest that effective treatment of CKD metabolic complications and 25(OH)D deficiency could limit GFR loss.

Major strengths of this study include the quality of the patient phenotype, including repeated GFR measures with a reference method, and the variety of nephropathy types. Its principal limitation is that data could be confounded by a regression to the mean (RTM) phenomenon. RTM is indeed a concern when the outcome is the evolution of a continuous variable over time. However, it is considerably reduced when the evolution is studied with several measurements, which we did by selecting patients with at least 3 measurements. Moreover, we performed several sensitivity analyses and found RTM was limited. In addition, our classification of patients was not based on mGFR slopes estimated from linear regression, but on the examination of mGFR trajectories by four independent nephrologists. While we cannot rule that this qualitative method may have slightly overestimated the number of improvers, it is outweighted by strong agreement between nephrologists in their evaluation. Another limitation is that this is an observational study, and observed associations cannot be presumed to be causal relations. Moreover, as with all studies of change in GFR, our study is subject to potential survival bias, which may result in overestimating the prevalence of mGFR improvement. Finally, despite careful data collection, we cannot exclude unrecognized therapeutic modifications for some patients that could be responsible for bias.

In conclusion, our data show that renal function can improve over time in a significant proportion of CKD patients, even at a severe stage. It is noteworthy that the observed GFR increase is associated with a decrease in the number of metabolic complications over time, thus demonstrating true renal function improvement. Achievement of the current targets of nephroprotection is essential for preserving renal function. Our results also suggest that treating metabolic complications and 25(OH)D deficiency more effectively could promote improvement in renal function. Prospective replication of these findings during intervention trials is now required.


What would cause an increase in glomerular filtration rate (GFR) & renal plasma flow (RPF)?

This would cause an increase in glomerular filtration rate (GFR) & renal plasma flow (RPF).One of the major reasons behind this scenario is that the renal vascular resistance is lessened while the hydrostatic pressure is heightened if afferent arteriole gets dilated.

M. Klose

The answer to this is option C. Dilation of the afferent arteriole will increase the renal plasma flow and glomerular filtration rate. The reasons for this are the following: the renal vascular resistance is lessened while the hydrostatic pressure is heightened.

If the dilation of the efferent arteriole occurs, the RPF will increase but the glomerular filtration rate will be decreased. Hyperproteinemia will decrease the glomerular filtration rate. This is also the same as the other choice, ureteral stone. It will also decrease the glomerular filtration rate.


What should I do if I get abnormal test results?

Your healthcare provider will discuss your test results with you and tell you what to do next. You may need to have other tests. If you have chronic kidney disease, you will need regular GFR tests to monitor your condition. You will also need to receive treatment for kidney disease.

Care Agreement

© Copyright IBM Corporation 2021 Information is for End User's use only and may not be sold, redistributed or otherwise used for commercial purposes. All illustrations and images included in CareNotes® are the copyrighted property of A.D.A.M., Inc. or IBM Watson Health


Natriuretic Hormones

Natriuretic hormones are peptides that stimulate the kidneys to excrete sodium—an effect opposite that of aldosterone. Natriuretic hormones act by inhibiting aldosterone release and therefore inhibiting Na + recovery in the collecting ducts. If Na + remains in the forming urine, its osmotic force will cause a concurrent loss of water. Natriuretic hormones also inhibit ADH release, which of course will result in less water recovery. Therefore, natriuretic peptides inhibit both Na + and water recovery. One example from this family of hormones is atrial natriuretic hormone (ANH), a 28-amino acid peptide produced by heart atria in response to over-stretching of the atrial wall. The over-stretching occurs in persons with elevated blood pressure or heart failure. It increases GFR through concurrent vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole. These events lead to an increased loss of water and sodium in the forming urine. It also decreases sodium reabsorption in the DCT. There is also B-type natriuretic peptide (BNP) of 32 amino acids produced in the ventricles of the heart. It has a 10-fold lower affinity for its receptor, so its effects are less than those of ANH. Its role may be to provide “fine tuning” for the regulation of blood pressure. BNP’s longer biologic half-life makes it a good diagnostic marker of congestive heart failure.


Cushing's syndrome, glucocorticoids and the kidney

Glucocorticoids (GCs) affect renal development and function in fetal and mature kidneys both indirectly, by influencing the cardiovascular system, and directly, by their effects on glomerular and tubular function. Excess GCs due to endogenous GC overproduction in Cushing's syndrome or exogenous GC administration plays a pivotal role in hypertension and causes increased cardiac output, total peripheral resistance and renal blood flow. Glucocorticoids increase renal vascular resistance (RVR) in some species and experimental settings and decrease RVR in others. Short term administration of adrenocorticotrophic hormone or GCs causes an increased glomerular filtration rate (GFR) in humans, rats, sheep and dogs. Interestingly, chronic exposure may cause a decreased GFR in combination with a higher cardiovascular risk in human patients with Cushing's syndrome. Glomerular dysfunction leads to proteinuria and albuminuria in canine and human Cushing's patients, and some cases also show histological evidence of glomerulosclerosis. Tubular dysfunction is reflected by an impaired urinary concentrating ability and disturbed electrolyte handling, which can potentially result in increased sodium reabsorption, hypercalciuria and urolithiasis. Conversely, chronic kidney disease can also alter GC metabolism. More research needs to be performed to further evaluate the renal consequences of Cushing's syndrome because of its implications for therapeutic aspects as well as the general well-being of the patient. Because there is a high incidence of Cushing's syndrome in canines, which is similar to the syndrome in humans, dogs are an interesting animal model to investigate the link between hypercortisolism and renal function.