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Interaction Of Fluid Status And Residual Renal Function In Peritoneal Dialysis Patients

The preservation of residual renal function in peritoneal dialysis patients could improve the quality of life and survival. To preserve it, various protective methods have been applied.

Dr. Cooney Blades
Jan 19, 20241634 Shares31417 Views
Residual renal function(RRF) means the function of residual healthy nephrons.
RRF includes the clearance of molecular-solute, regulation of water-electrolyte and acid-base balance, and iatrogenic substitution of endogenous hormones.
Just as in chronic kidney disease (CKD) patients, preservation of RRF is one of the primary goals in the management of peritoneal dialysis (PD) patients.
RRF was associated with survival in PD patients.
Loss of RRF in PD patients has been linked with:
  • overhydration
  • left ventricular hypertrophy
  • increased arterial stiffness
  • cardiovascular comorbidity in general
  • mortality
Careful volume control to prevent dehydration has been used to minimize loss of RRF in PD patients.
Dehydration is known to lead to a loss in residual renal function.
This phenomenon of volume depletion has led some clinicians to run their patients to ‘overhydration.’
On the other hand, overhydration is associated with:
  • hypertension
  • left ventricular hypertrophy
  • excess mortality
Hypertension has been reported to lead to the loss of residual renal function.
Based on this evidence, some clinicians run their patients to ‘dehydration.’
It is necessary to highlight the relationship between RRF and fluid status in PD patients, which does not simply indicate causality.
However, it leads to a hypothesis that RRF and fluid status could interact as both cause and effect.
Our paper intends to discuss the interaction of fluid status and residual renal function in peritoneal dialysis patients.

Fluid Status Of PD Patients

Hydration status is usually assessed by clinical parameters, such as:
  • extremities edema
  • changes in body weight
  • blood pressure
This method is simple and useful.
However, multi-frequency bioelectrical impedance analysis (BIA) is a much more accurate technique in estimation of hydration status.
The following can be estimated by BIA:
  • extracellular water (ECW)
  • intracellular water (ICW)
  • total body water (TBW)
  • excess body fluid
It is indicated that overhydration is a common complication in peritoneal dialysis (PD) patients.
Likewise, in a large cohort of PD patients, overhydration is a prevalent finding compared to a normal reference population using Body Composition Monitor.
An epidemiological analysis showed that 66.8% in 307 continuous ambulatory peritoneal dialysis (CAPD) patients were attacked by overhydration, defined by ECW/TBW of more than 0.4.
The first step to maintaining normal hydration in PD patients is dietary salt restriction.
Moreover, the use of any of these three may also contribute to maintain volume homeostasis:
  • loop diuretics
  • icodextrin
  • hypertonic glucose peritoneal dialysis solutions

Residual Renal Function In PD Patients

As residual renal function (RFF) is such a strong predictor of outcome in peritoneal dialysis (PD) patients, it is significant to preserve RRF in PD patients.
Here are some methods for protection of RRF:

Sodium Restriction

Dietary salt restriction, as mentioned before, is an effective strategy to preserve volume homeostasis in PD patients.
Besides, it has potential benefits on protection of RRF as well.
In their study published in 1998 by the American Journal of Physiology, Wei-Zhong Ying and Paul W. Sanders testified that high glomerular sodium exposure will induce the up-regulation of TGF-β, and TGF-β has a positive correlation with glomerulosclerosis, and thus leads to the deterioration of residual renal function.

Avoid Peritonitis

Better preservation of residual renal function may lead to a reduced rate of peritonitis.
On the other hand, In a study published in 2009 by the journal Nephrology Dialysis Transplantation, the authors, with Chia-Te Liao as lead author, indicated that increased episodes of peritonitis may result in declining RRF.
This might be explained by peritonitis’ association with:
  • hypotension
  • systemic inflammation
  • the use of nephrotoxic antibiotics
These factors do harm the preservation of residual renal function.

Avoid Nephrotoxic Agents

The avoidance of nephrotoxic drugs is beneficial in preserving residual renal function, such as:
  • nonsteroidal anti-inflammatory agents
  • nonsteroidal aminoglycosides
  • radiocontrast agents
Therefore, In a study published in 2003 by the American Journal of Kidney Diseases, the authors, with Richard J. Baker as lead author, proved that the following can reduce the nephrotoxic effect of aminoglycoside:
  • once-daily dosing
  • avoiding the use of concomitant nephrotoxins
  • monitoring of drug concentration
  • using the least nephrotoxicity aminoglycosides

Use Of Renin-Angiotensin-Aldosterone System (RAAS) Inhibition

Inhibitors of the RAAS have been well described to be associated with preservation of residual renal function by a number of studies.
In a prospective study by Li et al., the residual renal function deterioration rate of PD patients prescribed with ramipril was slower than the control group.
In another study by Suzuki et al., there’s no significant difference in blood pressure between the valsartan group and control group, but it is clear that valsartan can slow the deterioration of residual renal function.

Use Of Loop Diuretics

In a comparative study published in 2003 by Peritoneal Dialysis International, its authors, with Rudolf W. van Olden as lead author, observed that the use of loop diuretics in peritoneal dialysis (PD) patients would increase the renal excretion of water and sodium without impact on residual renal function.
In their comparative study published in 2001 by the journal Kidney International, James F. Medcalf, Kevin P. G. Harris, and John Walls proved that using loop diuretics for 12 months resulted in higher levels of urinary volume compared with a placebo group.
However, no significant changes were found in preservation of residual renal function.

Use Of Biocompatible Solutions

The Euro-Balance Trial provides positive expectations on the protective effect of new biocompatible solutions on residual renal function using a neutral pH and low-glucose degradation product (GDP) fluid.
However, in a randomized controlled trial published in 2008 by journal Kidney International, the authors, with S. L. S. Fan as lead author, found no difference in the decline of RRF between high-GDP and low-GDP solutions.
The variable findings of these studies are probably due to the difference in the:
  • study period
  • baseline residual renal function
  • baseline fluid status, and so on
Still, no clear association pattern was identified.

APD Versus CAPD

It is automated peritoneal dialysis (APD) versus continuous ambulatory peritoneal dialysis (CAPD).
In some preliminary reports, a faster decline of residual renal function was associated with APD.
This faster decline might be explained by the increase of total glucose exposure and the intermittent nature of APD.
In a comparative study published in 2011 by the Clinical Journal of the American Society of Nephrology, the authors, with Wieneke Marleen Michels as lead author, reported the worse preservation of RRF in those starting on APD than CAPD.
Although we haven’t got a definitive conclusion yet, it is still important to take their different features in consideration when choosing and observing modality options.
Fluid status of PD patients has proved to play a role in the protection of residual renal function.
However, the different views of volume control strategies have been put forward to maintain RRF overhydration or dehydration.
The details will be discussed in the next section.

The Effect Of Fluid Status To RRF

In an attempt to maintain residual renal function, some authors suggested keeping patients overhydrated.
So far, there is a lack of evidence from interventional trials that hypervolemia, compared with euvolemia or hypovolemia, may lead to better protection of RRF.
Substantial fluid overload is a common problem for peritoneal dialysis (PD) patients, but early observational studies did not find a determinate association between overhydration and preservation of RRF.
From a clinical trial conducted by Andrew Davenport, Rabya Hussain Sayed, and Stanley Fan and published in 2011 by the journal Blood Purification, a close relationship was observed between fluid status and RRF based on analysis relating 24-hour urine output to ratio of ECW/TBW.
They suggested that ECW volume expansion may result in better preservation of residual renal function in PD patients.
In a study in PD patients published in 2014 by the journal Kidney International, in which fluid status was assessed by multifrequency bioimpedance, authors Kieran McCafferty, Stanley Fan, and Andrew Davenport found that overhydration, as identified by increased ECW/TBW, was not linked to improved protection of residual renal function.
On the other hand, overhydration may result in:
  • hypertension
  • left ventricular hypertrophy
  • cardiac disease
  • intradialytic hypertension
In a cross-sectional study in 2002 and published by the journal Kidney International, its authors, with Maarten A. M. Jansen as lead author, found that those complications induced by overhydration could lead to a steeper decline of residual renal function.
Moreover, in a study by Hiromi Hidaka and Toshiyuki Nakao and published in 2003 by the journal Nephrology (Carlton), hypertension and a high level of atrial natriuretic peptide (ANP), as a marker of overhydration, were found as independent negative predictors for decline in residual renal function.
In a study published in by the American Journal of Kidney Diseases, the authors, with Ana Rodriguez-Carmona as lead author, found that automated peritoneal dialysis (APD) had lower levels of sodium and water removal compared with continuous ambulatory peritoneal dialysis (CAPD), and thus bringing about the result of hypertension.
In addition to overhydration, decline of residual renal function was faster in the APD group.
This also brings the suspicion that there may be a relationship between overhydration and decline of residual renal function.
Overhydration influences the loss of residual renal function from some other approaches as well.
In a study published in 2011 by the journal PLoS One, the authors, with Wim Van Biesen as lead author, demonstrated that overhydrated patients were more likely to be diabetic and had worse glycemic control.
And of note is that worse glycemic control intensifies microvascular damage, especially in the kidney.
In other words, diabetic changes induced by overhydration will accelerate the damage of residual nephrons and result in loss of residual renal function.
In a study published in 1999 by the journal Clinical Cardiology, its authors, with Dr. Yukihito Sato as lead author, observed that hypervolemia induces inflammation.
Also, Chung et al. demonstrated that inflammation is associated with an accelerated deterioration of preserved residual renal function.
Dehydration can cause acute kidney injury (AKI) and loss of residual renal function.
This may be attributed to the functional reduction of aquaporins, renal vasoconstriction and structural changes in the tubular system in the condition of hypovolemia.
Jansen et al. and Liao et al. demonstrated that intravascular volume insufficiency and hypotension play important roles in the decline of residual renal function.
Volume depletion may induce ischemic injury of nephridial tissue, and thus lead to the decrease of glomerular filtration rate (GFR).
In a study published in 2001 by the American Journal of Kidney Diseases, the authors, with Ali Ihsan Gunal as lead author, reported that strict volume control with restriction of sodium and water and/or elevated ultrafiltration resulted in a 2.8kg weight loss and a 10% reduction in weekly Kt/V urea.

The Effect Of RRF To Fluid Status

Preservation of residual renal function contributes to an improved fluid balance.
In a study published in 2001 by the journal Nephrology Dialysis Transplantation, the authors, with Murali K. Menon as lead author, demonstrated that the blood pressure of peritoneal dialysis (PD) patients increased notably with the decrease of residual renal function, and this may be associated with the decline of volume removal.
In a study published in 2003 by the journal Nephrology Dialysis Transplantation, its authors, with Constantijn J. A. M. Konings as lead author, PD patients with GFR<2ml/min were certified to have increased volume of extracellular fluid compared with those who had better preserved residual renal function.
This effect of residual renal function to fluid status may be realized by the following pathology and physiology mechanism.
Volume homeostasis is one of the fundamental roles of kidneys and it plays an important role in PD patients’ clinical management.
Kidneys regulate the circulating volume status by its excretory function.
Volume overload will lead to increased clearance of sodium and water.
This increase can be realized through a series of mechanisms, such as:
a. stimulating the secretion of natriuretic peptide
b. the generation of arachidonate metabolites
c. inhibiting the secretion of:
  • renin-angiotensin-aldosterone
  • arginine vasopressin (AVP)
  • sympathetic activation of kidney

Stimulating The Secretion Of Natriuretic Peptide

Water-sodium retention will increase the excretion of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by irritating atrial cells and ventricular cells.
The receptors of ANP and BNP are NPRa and NPRb, and they are distributed widely in the:
  • glomerulus
  • renal tubules
  • collecting tubules
Thus, diuretic and natriuretic effects will be realized through the combination of these natriuretic peptides with their receptors.

Stimulating The Secretion Of Arachidonate Metabolites

PGE2, PGI2, and CYP-450 are metabolites of arachidonic acid.
The combination of PEG2 and its receptor, EP3, can inhibit the reabsorption of sodium.
PGI2 also possesses a similar effect.
A metabolite of cytochrome P450 (CYP-450), 5,6-Epoxyeicosatrienoic acid (5,6-EET) can inhibit transference of sodium by its effect on proximal tubule and cortical collecting tubule.
Water-sodium retention will:
  • promote the anabolism of these arachidonate metabolites
  • increase nephric excretion of natrium and urine

Inhibiting The Secretion Of Renin-Angiotensin-Aldosterone

Renin is mainly secreted by a juxtaglomerular cell in the afferent glomerular arteriolar wall.
With the increase of renal blood filtration, under the circumstance of water-sodium retention, the pressure of the afferent glomerular arteriolar wall and/or the sodium concentration in the distal tubule is elevated.
As the macula densa cell is stimulated, the secretion of renin by the juxtaglomerular cell is suppressed, and this proceeds to the decreased generation of angiotensin II and aldosterone.
Aldosterone can bind with its receptor in the distal tubule and collecting tubule to enhance water-sodium reabsorption.
On the contrary, water-sodium retention will lead to decreased secretion of aldosterone and contribute to the diuretic and natriuretic effect of the kidney.
Angiotensin II can bind with the angiotensin I receptor in the:
  • glomerular arteriole
  • mesangial cell
  • proximal tubular epithelial cell
It also plays a part in regulation of:
  • kidney blood flow volume
  • glomerular filtration rate
  • sodium reabsorption of the tubule
Conversely, the reduced generation of angiotensin II will make for diuresis of the kidney.

Inhibiting The Secretion Of Arginine Vasopressin (AVP)

AVP, which is produced by the hypothalamus and released by the posterior pituitary, can bind to the V2 receptor in the collecting tubule to increase its water permeability.
It also binds to the V2 receptor in the medullary loop ascending limb to increase sodium reabsorption.
Accordingly, expansion of circulation volume caused by water-sodium retention can:
  • inhibit the secretion of AVP by negative feedback
  • strengthen nephric diuretic and natriuretic effects

Inhibiting The Secretion Of Sympathetic Activation Of The Kidney

Noradrenaline released by sympathetic nerves can combine with an α-adrenoceptor in the kidney to:
  • arouse vasoconstriction
  • reduce renal blood flow
  • enhance sodium reabsorption of the proximal tubule
This will ultimately result in water-sodium retention.
At the time when circulation volume is enlarged, baroreceptor will:
  • restrain sympathetic activation of kidney reflexively
  • promote the nephric excretion of natrium and urine
In a dehydration condition, nephridial tissue will exert its sodium and water-sparing function by performing the above-mentioned mechanisms reversely.
Therefore, residual renal function is extremely important with its function to regulate fluid status rather than additional solute clearance.
This statement is well demonstrated by the reanalysis of the CANUSA data.

Discussion

The relationship between residual renal function and fluid status in peritoneal dialysis (PD) patients has already attracted a lot of attention, but there’s still less evidence based on randomized trials about their interaction with each other.
On account of existing studies, successful management of hydration status will enhance the protection of residual renal function.
However, what is successful hydration management still needs further study.
Present experiments tend to support the opinion that hypervolemia compared with euvolemia or hypovolemia may not lead to better preservation of residual renal function, and hypovolemia may also accelerate the decline of RRF.
The deterioration of residual renal function might result in a worse control of fluid status, and thus, build up a vicious cycle.
This vicious cycle will compromise the prognosis of PD patients.

Conclusion

Appropriate fluid status is important to the preservation of residual renal function in peritoneal dialysis (PD) patients.
The greatest challenge in hydration management might be removing the correct amount of fluid to keep PD patients away from fluid excess or fluid depletion.
The increasing cognition of the significance of optimal fluid status may lead to a better protection of residual renal function and achieve appropriate hydration management in return.
And the preserved residual renal function is helpful to maintain the optimal fluid status.
Appropriate fluid status and protection of residual renal function could form a vicious cycle and improve the final prognosis of PD patients.
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