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Chapter 35
Renal Functional Reserve and Renal
Recovery After Acute Kidney Injury
Gabriele Guglielmetti and Sara Samoni
Introduction
Renal functional reserve (RFR) stands at the forefront of contemporary nephrology,
offering critical insights into kidney health, acute kidney injury (AKI), and renal
recovery. As our understanding of renal physiology evolves, the assessment of RFR
emerges as a pivotal parameter in delineating the susceptibility to kidney damage,
prognosticating postoperative kidney dysfunction, and defining the trajectory of
renal recovery. Living kidney donation and transplantation represent one of the
prominent domains where the utilization of RFR holds significant promise. Studies
evaluating the safety and feasibility of preoperative RFR evaluation during living
kidney transplantation shed light on its potential applications. These investigations
underscore the importance of understanding the dynamic interplay between baseline
renal function, stress-induced responses, and the suscep tibility to postoperative
complications. Beyond the realm of transplantation, the clinical utility of RFR
extends to the broader spectrum of renal diseases, including AKI and chronic kidney
disease (CKD). With conventional markers offering limited insights into renal
function and prognosis, the early detection and quantification of RFR emerge as
vital components in the comprehensive nephrological evaluation. In this review, we
Supplementary Information The online version contains supplementary material available at
https://doi.org/10.1007/978-3-031-66541-7_35.
G. Guglielmetti
Nephrology and Kidney Transplantation Unit, Department of Translational Medicine,
University of Piemonte Orientale, “Maggiore della Carità” University Hospital, Novara, Italy
e-mail: g.guglielmetti@maggioreosp.nova ra.it
S. Samoni (
Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda, Ospedale
Maggiore Policlinico, Milan, Italy
e-mail: sara.samoni@policlinico.mi.it
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A.
https://doi.org/10.1007/978-3-031-66541-7_35
✉)
411
Cotoia et al. (eds.), Nutrition, Metabolism and Kidney Support,
412 G. Guglielmetti and S. Samoni
delve into the multifaceted role of RFR in nephrology, exploring its significance in
living kidney donation, AKI, and renal recovery post-AKI. We examine the current
understanding of RFR assessment, its implications in clinical practice, and the
challenges and opportunities in defining renal recovery. By elucidating the intricate
nuances of RFR, we aim to foster a deeper comprehension of renal physiology and
enhance patient care in the realm of kidney health and diseas
e.
Renal Functional Reserve
Renal functional reserve is defined as the capability of the kidney to increase
glomerular filtration rate (GFR) in response to certain physiological or pathological
stimuli requiring a higher functional demand. These stimuli include high protein
intake, pregnancy, AKI episodes, sepsis, unilateral nephrectomy, CKD, and congestive heart failure [
2, 3]. Currently, a single method or a single dose of the stress needed to
RFR [
quantify RFR in an easy and accurate way is not known. Furthermore, kidneys
present a glomerular and tubular functional reserve capacity. In the presence of
appropriate stimuli, a subject with inta ct nephron mass can increase both GFR and
tubular secretion. The ability to test RFR may represent an excellent diagnostic
possibility to reveal subclinical disease or silent loss of nephron mass. In healthy
subjects, baseline GFR (bGFR) varies from 110 to 130 mL/min/1.73 m
and males, respectively, depending also on age, body size, diet, and other variables.
Moreover, it changes during the day based on physiological requirements. Normal
subjects display a significant capacity to increase GFR under physiological stimuli
(e.g., pregnancy, solitary kidney) or in pathological states (e.g., diabetes and arterial
hypertension). Glomerular RFR (RFR-G) is the capacity to increase GFR in
response to stimuli, such as an acute oral protein load, intravenous amino acid, or
dopamine infusion. The difference between maximum GFR and bGFR represents
the RFR-G. Weight-adjusted doses of protein of 1–2 g/kg are equally effective in
increasing GFR compared to intravenous amino a cid or dopamine infusion [
subjects with intact RFR-G, the increase of GFR varies between 20 and 70 mL/min/
2
1.73 m
during glomerular stress tests [3, 7–9]. RFR-G is lower in the elderly and in
the initial CKD stages, although serum creatinine (sCr) level is still normal [10]. Different theories have been proposed to explain the increase in GFR during a glomerular stress test. Glomerular hyperfiltration may occur, leading to an increase in the
filtration fraction [
blood flow is the main mechanism, rather than a temporary variation in filtration
fraction [12]. This theory seems to be supported by the observation of the decrease in
renal vascular resistance with afferent arteriolar vasodilation in response to protein
load [13]. Another theory is that the GFR increases by recruiting the “dormant
cortical nephrons,” not working during resting conditions but potentially available
under stress [
and thus a limited RFR, may have an increased susceptibility to develop AKI.
1]. Since the 1980s, several methods have been tested to quantify
2
In 1993, Woods suggested that an overall increase in renal
11].
According to this theory, solitary kidneys, with fewer nephrons
14].
in females
4–6].
In
35 Renal Functional Reserve and Renal Recovery After Acute Kidney Injury 413
Although RFR testing has been established for decades, it has not yet entered
routine clinical practice. Until now, probably the most important study showing the
potential clinical meaning of RFR has been performed by Husain-Syed et al. They
demonstrated that, in elective cardiac surgery patients with GFR >60 ml/min/
2
1.73 m
, preoperative RFR was highly predictive of AKI. Therefore, a reduced
RFR appears to be a novel risk factor for AKI, and preoperative measurement of
RFR can identify patients who are likely to benefit from preventive meas ures or to
select for the use of biomarkers for early detection of AKI [15].
Another potential area of use for RFR is in living kidney donation and kidney
transplantation. In 2017, Spinelli et al. conducted a study examining the safety and
feasibility of preoperative RFR evaluation using a protein load during living kidney
transplantation. They administered a protein loading test to kidney donors before
donation and after transplantation, comparing basal and stress renal function in both
donors and recipients. Following kidney transplantation, stressed GFR resembled
basal GFR for both donors and recipients, indicating a limited RFR. In the context of
living kidney transplantation, RFR determination has been suggested to assess the
original global filtration capacity of the donor’s kidneys (stressed GFR) and to gauge
the susceptibility of donors and recipients to postoperative kidney dysfunction [16].
However, recent findings by Van Londen et al. suggest that RFR, as assessed by the
renal response to dopamine infusion, predicts short-term GFR after living kidney
donation but not long-term kidney function [17 ].
Baseline eGFR offers limited insights into patients’ renal function, especially in
acute kidney injury (AKI), during renal recovery post-AKI, and in the early stage s of
chronic kidney disease (CKD). Moreover, diagnostic and prognostic tools to identify
patients at risk of AKI and the transition from AKI to CKD are lacking. RFR serves
as an early indicator of renal impairment, and its quantification can contribute to a
comprehensive nephrological evaluation.
Renal Functional Reserve and Renal Recovery After Acute Kidney Injury
Susceptibility to kidney damage is influenced by various patient-related factors,
including age, baseline renal function, and comorbidities. Baseline renal function,
encompassing both baseline sCr/GFR and RFR, plays a crucial role. With a normal
GFR and intact RFR, kidney damage may remain subclinical even with repeated
exposure to potentially nephrotoxic agents. Conversely, impaired GFR and/or loss of
RFR can lead to AKI even with mild exposure, potentially due to nephron loss after
AKI episodes, nephrotoxic agent administration, or underlying pathological conditions reducing functioning nephron mass (Fig. 35.1). The multifaceted nature of AKI
is acknowledged, evolving from an acute event to acute kidney disease and potentially CKD, with loss of functioning nephrons affecting RFR and eGFR hypothesized as an underlying mechanism (Fig. 35.2 ) [18].
414 G. Guglielmetti and S. Samoni
Fig. 35.1 Renal susceptibility to injury in relation to glomerular filtration rate (GFR) and renal
functional reserve (RFR). In the presence of a normal glomerular filtration rate (GFR) and intact
renal functional reserve (RFR) (green line), even in the case of repeated and intense potentially
nephrotoxic exposure, renal damage may remain subclinical. Conversely, if GFR is compromised
(red line) or if RFR is lost (yellow line), even mild exposure can lead to acute kidney injury (AKI).
Following an AKI episode, a reduction in GFR or RFR may occur, thus increasing renal susceptibility to further insults
There is currently no standardized definition of renal recovery from AKI. Previous definitions primarily focused on recovery from dialysis-requiring AKI, with less
severe stages often overlooked. The Acute Disease Quality Initiative (ADQI) group
proposed clinical renal recovery from AKI as the absence of evidence of damage or
functional loss post-AKI episode [
18], but even these patients may be susceptible to
further kidney damage and adverse events [15]. Defining full renal recovery necessitates consideration of biomarkers of kidney damage, imaging outputs, and RFR,
requiring further investigation. Recovery patterns post-AKI vary significantly,
highlighting the importance of assessing both baseline and post-AKI renal function
accurately [
Preadmission sCr, often considered the gold standard for defining
19].
baseline sCr/eGFR, may be unreliable, with dynamic tests assessing RFR offering
greater accuracy [20]. Additionally, while sCr levels are commonly used, they are
late markers of renal function [21], influenced by various nonrenal factors [20, 22].
Plasma Cystatin C has been proposed as an alternative marker for renal recovery,
though routine clinical adoption is pending [23].
Even with clinical renal recovery
from AKI, subclinical damage may persist, as evidenced by new-onset or worsened
proteinuria, arterial hypertension, or a drop in RFR [18, 24]. Patients whose sCr levels
return to baseline remain susceptible to further kidney damage and adverse events
25]. Future studies should consider incorporating dynamic kidney tests to assess RFR
[
for a comprehensive evaluation of renal function and prognostic insights.
35 Renal Functional Reserve and Renal Recovery After Acute Kidney Injury 415
Fig. 35.2 Renal function and susceptibility to acute kidney injury (AKI) in relation to glomerular
filtration rate (GFR) and renal functional reserve (RFR). Renal function consists of both the
glomerular filtration rate (GFR) and the renal functional reserve (RFR). Nephrotoxic agents (e.g.,
nonsteroidal anti-inflammatory drugs, NSAIDs) and various diseases (such as diabetes, congestive
heart failure, sepsis, etc.) can reduce the functioning nephron mass, either acutely or chronically.
However, as long as the RFR is present, the GFR remains normal. Conversely, if the RFR is lost,
acute kidney injury (AKI) can become clinically evident and initiate the continuum toward chronic
kidney disease (CKD)
Conclusion
In conclusion, the RFR holds promise as a crucial parameter in various aspects of
nephrological evaluation and clinical practice. Its significance spans from assessing
susceptibility to kidney damage to predicting postoperative kidney dysfunction in
living kidney transplantation. While recent studies have shed light on its role in
short-term GFR prediction after kidney donation, its long-term implications remain
under scrutiny.
In summary,
significance as a dynamic parameter in nephrology, offering avenues for enhanced
risk assessment, early intervention, and personalized care in the realm of kidney
health and disease.
the evolving landscape of renal functional reserve underscores its
416
G. Guglielmetti and S. Samoni
References
1. Sharma A, Mucino MJ, Ronco C. Renal functional reserve and renal recovery after acute kidney
injury. Nephron Clin Pract. 2014;127(1–4):94–100.
2. Koyner JL, Chawla LS. Use of stress tests in evaluating kidney disease. Curr Opin Nephrol
Hypertens. 2017;26:31–5.
3. Ronco C, Chawla LS. Glomerular and tubular kidney stress test: new tools for a deeper
evaluation of kidney function. Nephron. 2016;134:191–4.
4. Bosch JP, Saccaggi A, Lauer A, Ronco C, Belledonne M, Glabman S. Renal functional reserve
in humans. Effect of protein intake on glomerular filtration rate. Am J Med. 1983;75:943–50.
5. Graf H, Stummvoll HK, Luger A, Prager R. Effect of amino acid infusion on glomerular
filtration rate. N Engl J Med. 1983;308:159–60.
6. ter Wee PM, Rosman JB, van der Geest S, Sluiter WJ, Donker AJ. Renal hemodynamics during
separate and combined infusion of amino acids and dopamine. Kidney Int. 1986;29:870–4.
7. Barai S, Gambhir S, Prasad N, Sharma RK, Ora M. Functional renal reserve capacity in
different stages of chronic kidney disease. Nephrology (Carlton). 2010;15:350–3.
8. Fliser D, Zeier M, Nowack R, Ritz E. Renal functional reserve in healthy elderly subjects. J Am
Soc Nephrol. 1993;3:1371–7.
9. Ronco C, Brendolan A, Bragantini L, Chiaramonte S, Fabris A, Feriani M. Renal functional
reserve in pregnancy. Nephrol Dial Transplant. 1988;3:157–61.
10. Pecly IM, Genelhu V, Francischetti EA. Renal functional reserve in obesity hypertension. Int J
Clin Pract. 2006;60:1198–203.
11. Rodriguez-Iturbe B, Herrera J, Garcia R. Relationship between glomerular filtration rate and
renal blood flow at different levels of protein-induced hyperfiltration in man. Clin Sci (Lond).
1988;74:11–5.
12. Woods LL. Mechanisms of renal hemodynamic regulation in response to protein feeding.
Kidney Int. 1993;44:659–75.
13. Samoni S, Nalesso F, Meola M, Villa G, De Cal M, De Rosa S, et al. Intra-parenchymal renal
resistive index variation (IRRIV) describes renal functional reserve (RFR): pilot study in
healthy volunteers. Front Physiol. 2016;7:286.
14. ter Wee PM, Geerlings W, Rosman JB, Sluiter WJ, van der Geest S, Donker AJ. Testing renal
reserve filtration capacity with an amino acid solution. Nephron. 1985;41:193–9.
15. Husain-Syed F, Ferrari F, Sharma A, Danesi TH, Bezerra P, Lopez-Giacoman S, et al.
Preoperative renal functional reserve predicts risk of acute kidney injury after cardiac operation.
Ann Thorac Surg. 2018;105(4):1094–101.
16. Spinelli A, Sharma A, Villa G, Samoni S, Ramponi F, Brocca A, et al. Rationale for the
evaluation of renal functional reserve in living kidney donors and recipients: a pilot study.
Nephron. 2017;135(4):268–76.
17. van Londen M, Kasper N, Hessels NR, Messchendorp AL, Bakker SJL, Sanders JS, et al. Renal
functional reserve capacity before and after living kidney donation. Am J Physiol Renal
Physiol. 2018;315(6):F1550–4.
18. Chawla LS, Bellomo R, Bihorac A, Goldstein SL, Siew ED, Bagshaw SM, et al. Acute kidney
disease and renal recovery: consensus report of the acute disease quality initiative (ADQI) 16
workgroup. Nat Rev Nephrol. 2017;13(4):241–57.
19. Kellum JA, Sileanu FE, Bihorac A, Hoste EAJ, Chawla LS. Recovery after acute kidney injury.
Am J Respir Crit Care Med. 2017;195(6):784–91.
20. De Rosa S, Samoni S, Ronco C. Creatinine-based definitions: from baseline creatinine to serum
creatinine adjustment in intensive care. Crit Care. 2016;20:69.
21. Delanaye P, Schaeffner E, Ebert N, Cavalier E, Mariat C, Krzesinski J, et al. Normal reference
values for glomerular filtration rate: what do we really know? Nephrol Dial Transplant. 2012
Jul;27(7):2664–
72.
35 Renal Functional Reserve and Renal Recovery After Acute Kidney Injury 417
22. Ostermann M, Bellomo R, Burdmann EA, Doi K, Endre ZH, Goldstein SL, et al. Controversies
in acute kidney injury: conclusions from a kidney disease: improving global outcomes
(KDIGO) conference. Kidney Int. 2020;98(2):294–309.
23. Mårtensson J, Martling C, Oldner A, Bell M. Impact of sepsis on levels of plasma cystatin C in
AKI and non-AKI patients. Nephrol Dial Transplant. 2012;27(2):576–81.
24. Prowle JR, Kolic I, Purdell-Lewis J, Taylor R, Pearse RM, Kirwan CJ. Serum creatinine
changes associated with critical illness and detection of persistent renal dysfunction after
AKI. Clin J Am Soc Nephrol. 2014;9(6):1015–23.
25. Forni LG, Darmon M, Ostermann M, Oudemans-van Straaten HM, Pettilä V, Prowle JR, et al.
Renal recovery after acute kidney injury. Intensive Care Med. 2017;43(6):855–66.
Part V
Renal Replacement Therapy
Chapter 36
Nomenclature for Renal Replacement
Therapy
Gianluca Villa and Dario Degl’Innocenti
Background
Management of patients with AKI may include kidney support therapies (KST).
Among these, continuous renal replacement therapy (CRRT) is the most widely used
for those who are critically ill. CRRT is a blood purification therapy in which the
patient’s blood is driven from a vascular access device through a hemodiafilter.
Fluids and waste molecules are removed by the membrane through several physicochemical mechanisms, and the purified blood is then pumped back into the patient
through a dedicated line. The slow and continuous nature of the process, compared
to intermittent hemodialysis, allows critical care patients to better tolerate the blood
purification process [1]. The use of CRRT has become widespread and has evolved
significantly over the last few decades. Its management often requires a
multidisciplinary approach in both clinical practice and research, underscoring the
importance of understanding and using shared terminology. The terminology used to
describe CRRT and other KST modalities can be confusing and sometimes variable.
In 1995, a panel of experts in San Diego developed a nomenclature to establish
standardized language in KST [2]. In 2016, an international consensus of experts in
Vicenza (Nomenclature Standardization Initiative) organized a consensus conference to develop standard defi nitions for components, techniques, and operation of
Supplementary Information The online version contains supplementary material available at
https://doi.org/10.1007/978-3-031-66541-7_36.
G. Villa (
Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of
Florence, Florence, Italy
e-mail: gianluca.villa@unifi.it
D. Degl’Innocenti
Department
© The
A. Cotoia et al. (eds.), Nutrition, Metabolism and Kidney Support,
https://doi.org/10.1007/978-3-031-66541-7_36
✉)
of Cardiothoracovascular Medicine, Careggi Hospital, Florence, Italy
Author(s), under exclusive license to Springer Nature Switzerland AG 2024
421
422 G. Villa and D. Degl’Innocenti
machines for acute KST [3, 4]. A correct understanding and harmonization of CRRT
terminology is paramount in both clinical and research fields.
Membrane and Filter Characteristics
Geometric Characteristics
Surface area, priming volume, and membrane porosity are the main
multidimensional characteristics of hollow fiber membranes used for KST
(Table 36.1). These parameters are crucial during the prescription phase, as they
direc
tly impact treatment efficacy. The surface area plays a significant role in
extracorporeal clearance, with larger surface areas generally associated with higher
clearance rates. For adult patients, membranes with larger surface areas, typically
around 1.5 m
require membranes with around 0.5 m
typically treated with shorter hemodiafilters due to lower blood flow rates achievable
through pediatric vascular access devices and the increased risk of membrane
fouling. In the event of membrane fouling during treatment, the CRRT monitor
promptly halts blood restitution before patient disconnection. The amount of blood
lost within the circuit equals the priming volume of blood compartments. Furthermore, membrane porosity influences the profile of extracorporeal clearance for
solutes of varying dimensions and molecular shapes [5].
2
, are often required compared to pediatric patients, who typically
2
of surface area. Pediatric membranes are also
Performance Characteristics
The ultrafiltration coefficient (Kuf) quantifies the water permeability of a membrane,
representing the flow of water crossing the membrane per unit of pressure. It is
expressed in ml/h/mmHg and is calculated by multiplying the hydraulic permeability
(Lh) by the surface area (A). In clinical practice, the Kuf for a specific hemodiafilter
is determined by divi ding the ultrafiltration rate (Quf) by the transmembrane
pressure (TMP). Kuf values help categorize membranes into low flux
Table 36.1 Membrane properties (Neri et al. [4])
Multidimensional characteristics Symbol Formula
Surface area A = 2∙N
Filter priming volume Vb
Total priming volume Vb
Membrane porosity ρ = N∙π ∙ r־
L membrane length,
fibers, r־ mean inner radius of the pores
number of fibers, N number of pores in the filter, r־i mean inner radius of the
N
f
A
f
tot
ρ
∙L∙π∙r
f
i
Vb
= Nf∙L∙π r־
f
= Vbf + volume of tubes
Vb
tot
2
i