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E. M. Ebin and V. N. Tholakanahalli
vation. Larger studies have focused on the symptomatic congenital Long QT Syndrome as well as CPVT [9, 10]. More
recently, retrospective analyses have been published looking
at cardiac sympathetic denervation for structural heart disease demonstrating a modest benet as an adjunct to ICD
and catheter ablation [4]. Perhaps some of the best evidence
for denervation leading to decreased ventricular arrhythmia
burden comes from orthotopic heart transplants where the
incidence of ventricular arrhythmias is low [11] and when it
does occur it is more commonly associated with acute ischemia or severe allograft rejection [12].
Renal Denervation andtheAnimal Model
We have established both that increased sympathetic tone is
implicated in VAs as well as the benets of CSD.We have
demonstrated this with ablative and surgical approaches to
the myocardium and sympathetic chains. As aforementioned and demonstrated in other chapters of this book, the
downstream effects of RDN, either by surgical or ablative
approach, lead to decreased sympathetic inputs to the heart.
In turn, this leads to a decrease in VAs. Prior animal studies
have demonstrated the benets of sympathetic denervation
on cardiac arrhythmias [13–15]. This section will detail
two animal studies that focus on RDN as a mitigation strategy for VAs.
Zhang etal. [16] investigated the impacts of RDN on
myocardial brosis and VAs in a rat-model with ischemic
cardiomyopathy. In this elaborate experiment, an ischemic
cardiomyopathy was induced by ligating the left-anterior
descending artery (LAD) via a surgical approach. The rats
were administered medications to eliminate pain. A control
group went through a similar thoracoscopic surgical procedure without coronary artery ligation. Two weeks after
induced myocardial infarction, bilateral RDN was performed using a surgical approach and severing visible
nerves. The control group underwent a similar surgical procedure without manipulation or damage to the nerves.
Echocardiography was performed at two and 6weeks to
assess for ejection fraction. At 4weeks, all rats underwent
an electrophysiologic study with programmed electrical
stimulation until failure to capture a second coupled ventricular stimulus. After the rats were sacriced, histologic
examination was performed. Echocardiographic analysis at
2 weeks conrmed successful induction of myocardial
infarction. When comparing two groups, one with MI and
RDN contrasted with a group that had an MI without RDN,
ventricular tachycardia (VT) and ventricular brillation
(VF) were more inducible during an EP study in the animals that had not undergone RDN.In addition, circulating
levels of BNP, a marker of poor outcomes was reduced in
the group with RDN.Lastly, cardiac function was partially
restored when comparing the two groups.
Linz etal. [17] tested suppression of Vas in the acute ischemic setting in the porcine model. A total of 13 pigs were
randomized, seven to receive a surgical RDN procedure with
the remaining six undergoing a sham procedure. One hour
after the procedure, a thoracotomy was performed with ligation of the LAD for 20min before reperfusion was allowed.
During the rst 10mins of ligation, there was a signicant
decrease in ventricular ectopy in the denervated group compared with the control group. All of the control group animals suffered VF during LAD ligation whereas only 14% of
the denervated pigs suffered VF.However, VF occurred in all
animals during reperfusion regardless of denervation status.
This is congruent with current literature where the observed
arrhythmias during acute ischemia are often associated with
increased sympathetic tone and the fascicular electrical system mediated Vas. Contrastingly, the reperfusion arrhythmias are more closely associated with activation of
sodium-proton exchangers [18].
Renal Denervation inHumans
We have previously discussed rationale for sympathetic
denervation. We briey examined the sympathetic innervation in the myocardium and how RDN can aid in refractory
ventricular arrhythmias in the animal model. We will discuss
some case reports and series of RDN in humans as further
justication of its utility as an adjunct to current treatment
modalities.
Vaseghi etal. demonstrated in a well-crafted retrospective
analysis that sympathetic denervation, particularly bilateral
cardiac denervation resulted in a signicant reduction in
implantable cardioverter-debrillator shocks compared with
preprocedural shocks. Data from 41 patients who had
VT-storm or refractory VT were collected. All patients
underwent either left sided or bilateral CSD.At a median of
1 year follow-up, the shock burden was reduced from
19.6±19 shocks to 2.3±2.9 shocks. Additionally, at 1year
follow-up, 30% of the patients who underwent left-sided
denervation had no ICD interventions whereas, 48% of the
bilateral denervation group had no ICD interventions.
Although a retrospective analysis, these data help substantiate the need for sympathetic denervation as an adjunct to
standard catheter ablation and antiarrhythmic therapy.
In 2012, Ukena etal. published a case-report on renal
sympathetic denervation for electrical storm [19]. Two
patients with refractory ventricular arrhythmias and underlying cardiomyopathies (hypertrophic and dilated, respectively) were selected for the treatment protocol. Renal
arterial catheter ablation was performed in both patients
with up to six ablations at 8 W for 2 mins. In the rst
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patient, with hypertrophic cardiomyopathy, coronary disease was excluded before proceeding to multiple EP studies
demonstrating monomorphic VTs arising from the basal
left ventricle. On arrival to the hospital, he had multiple
episodes of VAs that could be terminated by anti-tachypacing. He was started on lidocaine with restoration to sustained sinus rhythm, although attempts at weaning resulted
in recurrence of VAs. After RDN, the patient was weaned
from lidocaine without issue. Approximately 3weeks later,
he had an episode of ventricular tachycardia resulting in
successful anti- tachycardia pacing. He had no further
events for 4months although developed VA secondary to
hypokalemia. The second patient with dilated cardiomyopathy refused suggested catheter ablation although was
amenable to experimental RDN.Within 24-h of his ablation, he developed 12 episodes of VF although, however, no
further episodes were recorded following the rst 24 h.
These cases demonstrate the success of RDN for ventricular arrhythmias although also highlight early data suggesting that effects of the procedure are not immediately
apparent and are sustained with time.
Aksu etal. [20] demonstrated the bets of RDN in refractory CPVT.A 46-year-old male with known CPVT presented
to the hospital with ventricular arrhythmias refractory to
beta-blockers and ecainide therapies. He was brought to the
electrophysiology lab for planned ablation of premature ventricular beats thought to be the cause of his VT.Three PVC’s
were targeted although multiple others were seen. RDN was
performed to decrease sympathetic tone on the heart.
Immediately after RDN, all episodes of polymorphic VT disappeared. He did, however, have sustained monomorphic VT
that was amenable to VT ablation. Although there existed
prior published data for sympathetic denervation for CPVT,
this was the rst published case of RDN as an adjunctive
therapy.
Hoffman etal. [21] published a case report with a 6year
old gentleman who presented to the ED with an acute myocardial infarction in the LAD territory. After reperfusion,
he had many episodes of monomorphic VT and an episode
of sustained VF refractory to medical management. He
underwent a catheter ablation that rendered the arrhythmia
non- inducible. However, despite ablation, he had recurrent
fast VT and VF. He subsequently underwent RDN with
immediate decrease in his arrhythmia burden. At day 23, no
more VT or VF episodes were recorded. This is the rst
case published with VAs as a consequence of acute ischemia. Interestingly, here too, despite immediate benet
with decreased burden of arrhythmia, complete arrhythmic
burden only ceased after a period of a few weeks. Similar to
this case, Feyz etal. [22] published a similar case with a
patient that was plagued with ventricular arrhythmias due
to vasospastic angina. He too, remained free of arrhythmia
after RDN.
The last two case series are reported by Jiang etal. [23]
and Armaganijan etal. [24] The former is a retrospective
analysis of eight patients with an ICD who underwent
RDN.The latter was a prospective look at 10 patients who
underwent RDN to assess for a response in arrhythmia burden. In the former series studying the Asian population with
a predominance of non-ischemic cardiomyopathy, ventricular arrhythmia decreased from an average 3.17 episodes per
month to 0.10 episodes per month over an average of
15months follow up. In the latter series, with a predominance of Chagasic cardiomyopathy, the median ventricular
arrhythmic burden was 28.5 episodes in the 6months leading
to RDN procedure. This was decreased to 1 and subsequently
0 at 1 and 6months, respectively.
Ablation Techniques Using anEP RF Catheter
forRDN
To date, a single technique for catheter ablation of the renal
arteries has not been established. Larger trials looking at
RDN to control hypertension helped establish some of the
protocol. However, minor variations exist between each center. Table 12.1 outlines many of the published data on
catheter- based ablation of the renal arteries. In brief, all procedures had been performed under moderate to heavy sedation and often under general anesthesia. After obtaining
femoral arterial access, heparin is generally administered to
achieve an ACT of 200–250s. A pigtail catheter is advanced
into the abdominal aorta at the level of the renal arteries.
Contrast angiography is performed to visualize the renal
Table 12.1 Renal artery ablation techniques using an EP catheter
#
Study
Esler etal [25] 52 <8 Up to six 60–120 Not specied Not specied
Ahmed etal
[26]
Qui etal [27] 21 10 15 60 7.1 Not specied
Remo etal.
[28]
Jiang etal. [23] 8 10 4–10 60 Not specied Not specied
Patients
10 17±3 4.5 26.6 14±5 Only when spasm was
4 6–12 Not specied 60 Not specied Not specied
Power / Temp
(W/°C)
# of lesions per
artery
Duration
(s)
Fluoroscopy time
(mins) Nitroglycerin administered
observed.
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E. M. Ebin and V. N. Tholakanahalli
arteries. An ablation catheter is then advanced through a
45cm support sheath into the bilateral renal arteries. Most of
the published data utilized an irrigation-cooled-catheter and
advanced into the renal arteries. A series of circumferential
lesions are applied between 6–20 W for 20–90 s. In one
series, a 10–20% drop in impedance was utilized as a marker
of successful ablation. After each lesion, the catheter is withdrawn 5mm and another lesion is applied. Some operators
empirically injected nitroglycerin (200mcg) into each renal
artery while others only injected in response to spasm.
Minimal adverse outcomes were reported in all case series
and the procedure were relatively well tolerated.
Future Directions
We have outlined many of the important published case
series and reports on the implications of RDN as an adjunct
therapy to current therapies including medications and catheter ablation. Published data suggests that not only is RDN
effective, but it can be utilized in situations where other
modalities have failed. While the scope of the procedure was
not discussed in this chapter, as more providers become procient in the skills involved in catheter ablation of renal
arteries to achieve RDN, we would expect to see more data,
both retrospective and more importantly, prospective studies
looking at the long-term benets of RDN to reduce VAs. It is
conceivable that, if effective, it would provide an adjunct
modality as a rst line treatment to catheter ablation in the
ventricles.
Disclosures No relevant disclosure all authors.
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Renal Denervation andKidney Pain
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Syndromes
LeslieMarisolLugo-Gavidia, MárcioGalindoKiuchi,
RevathyCarnagarin, andMarkusP.Schlaich
13
Abbreviations
ADPKD Autosomal dominant polycystic kidney disease
ESRD End-stage renal disease
LPHS Loin pain hematuria syndrome
LRV Left Renal Vein
NCS Nutcracker Syndrome
NSAID nonsteroidal anti-inammatory drugs
RAAS Renin-angiotensin aldosterone system
RDN Renal denervation
RF radiofrequency
TBM Thin basement membrane nephropathy
Introduction
Kidney-related pain syndromes are chronic debilitating
conditions impacting the patient’s quality of life. Chronic
pain syndromes require a thorough assessment to identify
the underlying pathology which will dictate the appropriate
treatment. Multiple conditions can cause chronic ank pain
and these have to be investigated as part of the workup for
differential diagnosis (Table 13.1). Specic consideration
should be given to differentiate kidney-related painsyndromes from non-renal pathologies presenting with diffuse visceral pain or dermatomal pattern (gastric, pancreatic,
and aortic pathology can present an unusual ank pain distribution) [1]. The renal causes can be categorized as vascular, parenchymal, and post-renal. (Table13.1) [1, 2].
Among the renal causes loin pain hematuria
syndrome(LPHS), autosomal dominant polycystic kidney
disease (ADPKD), and nutcracker syndrome (NCS) are of
particular interest for their overlapping features and complexity in their diagnosis and treatment [2] as discussed in
the clinical scenarios below.
L. M. Lugo-Gavidia (*) · M. G. Kiuchi · R. Carnagarin
Dobney Hypertension Centre, School of Medicine- Royal Perth
Hospital Unit, University of Western Australia,
Perth, WA, Australia
e-mail: marcio.galindokiuchi@uwa.edu.au;
revathy.carnagarin@uwa.edu.au
M. P. Schlaich
Dobney Hypertension Centre, School of Medicine- Royal Perth
Hospital Unit, University of Western Australia,
Perth, WA, Australia
Departments of Cardiology and Nephrology, Royal Perth Hospital,
Perth, WA, Australia
Neurovascular Hypertension and Kidney Disease Laboratory,
Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
e-mail: markus.schlaich@uwa.edu.au
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
R. R. Heuser et al. (eds.), Renal Denervation, https://doi.org/10.1007/978-3-031-38934-4_13
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Table 13.1 Causes of kidney pain syndromes [1, 2]
Renal Causes Extra renal Causes
Vascular Parenchymal Post-renal Endometriosis
Fibromuscular dysplasia Polycystic kidney disease Ureteral obstruction Visceral pain derived from liver, gallbladder, ovary/
tetis, pleura, etc.
Renal artery aneurysm/
dissection
Perinephric hemorrhage Glomerular disease Retroperitoneal
Nutcracker syndrome Xanthogranulomatous inammation
Arteriovenous stula Pyelonephritis/pyonephrosis Familial Mediterranean fever
Renal thromboembolism Benign or malignant neoplasms Sickle cell disease
Loin pain hematúria syndrome Nephrolithiasis Post herpetic neuralgia
Radiculopathy
brosis
Nephroptosis Acute intermittent porphyria
(XGI)
L. M. Lugo-Gavidia et al.
Clinical andPathophysiologic
Considerations
Loin Pain Hematuria Syndrome
Loin pain hematuria syndrome (LPHS) is a relatively rare
syndrome with a reported prevalence of ~0.012% in general
population [2–5]. The literature suggests a predominance
within caucasian population, affecting mostly women (70%),
during the third decade of life, but its onset can vary widely
and has been reported to occur from the rst to sixth decade
[2, 6–9]. A previous history of nephrolithiasis is common in
patients with LPSH (~50%) [2, 7, 9]. Several conditions have
been associated with LPSH including psychological aspects,
raising the possibility that LPHS at least in part could represent a somatoform disorder [7, 10]. Data on its exact etiology
and epidemiology however is still limited, as most of the data
is derived from case reports and small series and might be
underestimating the real size of the problem.
Multiple hypotheses have been proposed to explain the
underlying pathophysiology including renal capsular distension due to intratubular obstruction by erythrocytes (glomerular hemorrhage) or microcrystals (by hypercalciuria or
hyperuricosuria) causing subsequent interstitial edema and
intraglomerular hypertension. [2, 3, 7, 9] Other potential
contributors include renal vascular disease, vasospasm,
venocalyceal stula, hypersensitivity type III (deposition of
C5b-9 complexes and C3in arterioles), [2, 3, 11] coagulopa-
thy (abnormal platelet aggregation and brin deposition) [2,
3, 12], and abnormal ureteral peristalsis [2, 3, 13, 14].
Furthermore, an association with glomerular disease, in particular IgA glomerulonephritis, and thin membrane glomerular (TBM) disease have been proposed [2, 3, 7]. Clinically,
LPHS can be classied as primary (idiopathic) or secondary
if it occurs in the presence of glomerular diseases with IgA
nephropathy being most frequent (Table 13.2) [2, 7, 9]. A
kidney biopsy is usually required to conrm the diagnosis of
secondary LPHS [2]. It is important to note that TBM and
IgA nephropathy are common causes of asymptomatic
hematuria. An additional classication has been proposed
with Type 1 LPSH being dened by the presence of an attributable etiology (Table 13.2) in contrast to Type 2 LPSH
where no other etiology can be determined [5].
Severe to invalidating episodes of ank pain sometimes
with radiation to the groin or iliac fossa for at least 6months,
associated with hematuria (gross or microscopic) are the
dening features of the syndrome [2–4, 7, 13]. At the time of
the rst presentation the pain is typically unilateral, but in
most cases, bilateral pain develops over time [7, 15].
Hematuria can present either continually or intermittently,
often associated with pain exacerbations [2, 8, 15]. There is
a wide variation of the severity, frequency (twice per year to
incessant), and duration (hours to weeks) of the pain exacerbations [8, 15]. The episodes, can be accompanied by mild
fever, nausea, vomiting, increased urinary frequency, and
dysuria [2, 3, 7, 8, 15].
Interestingly, hypertension and chronic kidney disease as
such do not seem to be directly associated with
LPSH.Although proteinuria is not a characteristic feature of
LPSH, mild proteinuria can be present during the exacerbations of pain [2, 5, 7]. The diagnosis of LPHS is sometimes
challenging as LPHS is mainly a diagnosis of exclusion, as
discussed in morr detail below [2, 4].
Autosomal Dominant Polycystic Kidney
Disease
Autosomal dominant polycystic kidney disease (ADPKD) is
the most common hereditary renal cystic disease, with a
worldwide prevalence of 1:800 to 1:1000 [16–19]. It is characterized by the formation of multiple renal cysts, producing
progressive enlargement of the kidneys and renal failure.
ADPKD often presents when the patient is in their forties to
sixties [17, 20]. Contrary to LPSH, kidney failure is common
in ADPKD, it represents a leading cause of end-stage renal
disease (ESRD), ~10% of the total ESRD patients, and the
fourth cause of renal replacement therapy worldwide [20–
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Table 13.2 Classication of LPHS
Classication Denition Associated pathology Relevant investigations and ndings
Primary LPSH No acquired underlying
glomerular disease identied
Secondary
LPSH
Type 2 LPSH LPSH is attributed to another
Type 2 LPSH No other etiology can explain
LPSH is caused by an underlying
glomerular process
pathology
LPSH
NA NA
Glomerulopathies
IgA nephropathy (Berger’s disease)
Thin or thick basement membrane
nephropathy
Urinary infection Urine culture
Nephrolithiasis Cystoscopy or computed tomography
Tumors (renal cell carcinoma)
Renal artery dissection Angiography or CT angiography
Recurrent renal thromboembolism
A-V malformation
Hemangioma
Nutcracker syndrome
Ureteral pathology (papillary necrosis with
ureteral obstruction)
Polycystic kidney disease Ultrasonography
Coagulopathy Low heparin thrombin clotting times
NA NA
Urinalysis (hematuria with RBC cast,
proteinuria >500mg/24h)
FBC (dysmorphic RBC)
Serum creatinine (>1.2mg/dl women
and>1.4mg/dl men)
Kidney biopsy
Electron microscopy
Flexible ureteroscopy
Low factor XII levels
High b-thromboglobulin
Increased platelet aggregation
Higher levels C-reactive protein
High levels of D-dimmer
127
23]. The renal manifestations are correlated with the devel-
opment and cyst enlargement and include pain, early onset of
hypertension, and renal failure. [24] Of them, pain is the
most prominent symptom affecting 60% of ADPKD patients,
which can be severe and difcult to manage with a substantial impact on the quality of life [13, 16–19, 25–29]. The
presumed mechanisms causing pain include cyst hemorrhage or infection, nephrolithiasis, cyst-induced compression of the surrounding tissues, traction on the pedicle of the
kidney, and distension of the renal capsule that leads to the
transmission of pain signal through the afferent renal sensory
nerves [18, 19, 26, 30, 31].
Detection and management of hypertension in early
stages is important to minimize the cardiovascular complications (proteinuria, hematuria, faster decline of renal function,
left ventricular hypertrophy (LVH) [24].
Other clinical features include cysts in extrarenal organs
such as liver (30%), seminal vesicles and pancreas, nephrolithiasis, proteinuria, hematuria, intracranial or other arterial
aneurysms, dilatation of the aortic root, dissection of the thoracic aorta, aortic insufciency, mitral valve prolapse, LVD,
diverticulitis, and cyst infections [16, 24, 25]. A thorough
revision of the extrarenal manifestation of ADPKD is beyond
the scope of this manuscript.
Nutcracker Syndrome
Nutcracker syndrome refers to the clinical manifestations
associated with the compression of the left renal vein (LRV)
between the aorta and the superior mesentery artery [2, 32–
34] or less frequently with the vertebral body (0.8–7.1%). A
combination of both has also been reported [32]. This causes
the subsequent distal dilatation of the LRV and pelvic congestion [32]. The precise prevalence of NCS is not well
dened, but it has been reported with higher prevalence in
females [32, 33]. It can manifest during childhood, the peak
prevalence has been reported to occur in the patients of age
twenty through forty [33]. The clinical features include
mainly otherwise unexplained micro or macro-hematuria,
pelvic and/or ank pain that increases with physical activity,
orthostatic proteinuria, and gonadal vein syndrome [2,
32–34].
Diagnosis
A number of conditions must be investigated to determine
the cause of kidney-related pain syndromes. Urinalysis
should be done to evaluate glomerular disease [2]. A concur-
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L. M. Lugo-Gavidia et al.
rent urinary infection must be ruled out by urine culture [2,
7, 8]. A series of imaging techniques (cystoscopy, computed
tomography, angiography, CT angiography, exible ureteroscopy) are often required to determine specic causes as
listed in Table13.2 [2, 7].
LPSH generally exhibits unremarkable laboratory parameters and radiologic images, even though vascular variations
have been described in renal angiograms including widened
bifurcations of interlobar arteries, tortuosity, and focalized
avascular areas [7]. A kidney biopsy can be relevant to discriminate specic forms of glomerulopathy. Other possible
ndings include tubular atrophy, interstitial brosis, subcapsular cortical ischemia [7, 15].
In ADPKD the diagnosis is based on the identication of
multiple bilateral renal or extrarenal cysts by ultrasonography or MRI in accordance to age-specic criteria. ADPKD
inherited in an autosomal dominant manner, a genetic testing
(heterozygous pathogenic variant in PKD1, PKD2, GANAB,
or DNAJB11) or a rst-degree relative with ADPKD are
required to establish the diagnosis [16, 24].
Management Strategies forKidney-Related
Pain Syndromes
been shown in some studies to be effective in several pain
conditions [30, 35].
Systemic Treatment
Analgesic strategies are the cornerstone of pain management, these include a large variety of drugs that are recommended in a step-wise approach including acetaminophen,
nonsteroidal anti-inammatory drugs(NSAID), which
should be limited for acute episodes, COX-2 inhibitors, nonopioid analgesics, anti-epileptic, antidepressants, muscle
relaxants, opioids, and others. Side effects are a concern particularly if long-term treatment is required and must be taken
into consideration regarding chronic use of medications, specically opioids such as habituation, and addiction [10, 14,
17, 19, 26, 30].
Some patients can display somatoform pain disorders,
which underline the need to emphasize conservative measures, including psychological support and potentially
antidepressant treatment (tricyclics and serotonin-norepinephrine reuptake inhibitors [SNRIs]), antiepileptic
drugs can also be used (gabapentin, pregabalin, and other
anticonvulsants) [1, 36].
The treatment strategy for these complex pain syndromes is
commonly based on interdisciplinary approaches. Current
approaches focus on the identication of any potential underlying causes that can be targeted specically, and symptomatic treatment is mainly focused on pain relief. Importantly,
spontaneous remission could occur, [2, 3, 7] therefore, symp-
toms should be present for at least 6months under appropriate pain control therapies before considering invasive
interventions.
Regardless of the underlying condition causing chronic
ank pain, its management remains a clinical challenge and
a step-wise approach must be used in all cases. Table 13.3
summarizes the therapeutic mechanisms implicated in different pain management approaches.
Conservative Treatment
Conservative treatment is recommended as a rst-line treatment for control of mild-to-moderate pain. It consists of a
combination of psychotherapy and physiotherapy (adjuvants
of ice, heating pads, whirlpool, etc) to decrease intermittent
spasms. Additionally, the potential impact of body posture
on the musculature implicated in kidney-related pain syndromes makes cognitive behavioral therapy to modify postures and movements that induce pain a safe, non-invasive
intervention [19, 26]. The Alexander technique, which
focuses on adequate posture during daily life activities, has
LPSH
In patients with LPSH the use of NSAID should be
restricted if hematuria is present due to its antiplatelet
effect. Early approaches included antibiotics, antiplatelet,
and anticoagulation therapies, however, these are no longer
recommended as there was no evidence for benet [2, 7,
37]. Targeting the renin-angiotensin system with ACEi has
also been tested as a therapeutic target, through its effects
on reducing the intraglomerular hydrostatic pressure, it was
associated with better control of pain and hematuria, yet the
evidence is limited [2, 38].
Russell etal. reported the off-label use of tadalal in one
case for ureter relaxation and reduce intrarenal spasms.
Although complete relief of pain wasn’t achieved, it showed
a decrease in pain and reduced need for background therapy [39].
ADPKD In patients with ADPKD it is important to keep in
mind that they tend to develop early renal failure and 50%
evolve to end-stage renal disease by age 60, therefore the
long-term of use medications interfering with renal metabolism is discouraged due to nephrotoxicity [22]. The use of
NSAID must be limited to the pain exacerbations especially
if renal function is compromised. Previous studies support
the role of the renin-angiotensin-aldosterone system (RAAS)
in the pathogenesis of hypertension and promotion of renal
cysts [19, 38, 40–42]. The angiotensin-converting–enzyme
inhibitors (ACEi) or an angiotensin-receptor blockers (ARB)
13 Renal Denervation andKidney Pain Syndromes
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129
Effectiviness in pain
relief References
[2, 7]
Related
pharmacodinamic
Nephrotoxicity Short-term
[2, 7]
Short-term
[38]
Related
pharmacodynamics
Medium-term
Addiction
Favorable response
(57%)
NA [19, 40]
Dizziness
Electrolyte imbalance
Dizziness
Electrolyte imbalance
[43]
a
Long-term
3years
Polydipsia
Electrolyte-free water excretion
[2, 7,
50–54]
Short-medium term
~2weeks to 5months
Urinary tract infection
Worsening of renal pain
Fibrotic constriction
Nephrotoxicity
Renal function deterioration (~29%).
[26]
~6months −1year
19, 24]
[56]
[
a
~6months
NA Short-medium
(continued)
term~18months
Short-medium term
~28.5months
Microhematuria, localized pain,
transient
Surgery related Medium-long term [19, 26]
Fever, and systemic absorption of the
alcohol
Table 13.3 Summary of pain kidney syndrome management strategies
Procedure Mechanistic description and considerations Contraindications/Cautions Complications/side effects
nephrotoxicity
Episodes of hematuria due to
None No safety concerns Shot-term [2, 7, 35]
Decrease intermittent spasms None None NA [19]
Physcotherapy
movement habits
&Physiotherapy
Alexander Thechnique Guidance to diminish damaging postural and
antiplatelet effect
Systemic analgesia Compromised renal function due to
Nonsteroidal Anti-
inammatory drugs
Opioids Systemic analgesia Intolerance Tolerance
Hypotension Renal blood ow decline
pressure, decrease rupture of glomerular
RAASi LPSH: Decrease glomerular hydrostatic
capillaries
ADPKD: hypertension control, renal protection NA Renal blood ow decline
NA Not reported NA [39]
NA Polyuria
spasms, improve ureter blood perfusion
Tadalal LPSH: Ureter relaxation, decrease ureter
Tolvaptan ADPKD: Decrease uid production, Decrease
NA Severe bladder pain
cystic pressure, decrease kidney volume
bres)
Ablative effect in nocioceptive afferences
Capsaicin Blockage of pain transmission (sympathetic C
NA Not reported Short-medium term
Nerve blockage Nerve blockage of intercostal nerve, splanchnic
NA Not reported Short-medium term
nerve, and celiac plexus nerve with an
anesthetic or neurolytic agent.
Neuromodulation Implantation of electrodes as a stimulation
reaccumulation
More effective for small number of
system at L3-L4 level.
ADPKD:Sclerotherapy using ethanol,
Decompression ADPKD:Cyst aspiration Cyst frequently reform due to uid
High bleeding risk
cysts
minocycline or n-butyl cyanoacrylate to prevent
uid reacumulation
Chronic renal disease
Circumferential dissection of peri-arterial
nerves through thoracoscopic, videothoracic, or
Surgical
RDN
laparoscopic approach
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L. M. Lugo-Gavidia et al.
81]
Effectiviness in pain
relief References
Medium-long term [55, 66,
Puncture site complications (femoral
hematoma,
Mild wound infection, dissections,
pseudoaneurysms)
Renal artery dissection
Progression of preexistent renal stenosis
Intima and media transmural thermal
injury
2
[7, 55]
Medium-long term [62]
Medium-long term [63]
hematoma, Mild wound infection,
dissections, pseudoaneurysm)
Medium-long term
10 to 25% recurrence
Vessel dissection
Severe sclerosis
Renal artery occlusion
Renal vein thrombosis
Infections
Nerve entrapment
Mechanical complications
Nephrectomy
Procedure-related Long-term [19]
Procedure-related Long-term [19]
Procedure Mechanistic description and considerations Contraindications/Cautions Complications/side effects
Table 13.3 (continued)
eGFR <45mL/min/1.73m
Previous RA angioplasy
Previous RA stent implantation
Anatomic variants (aneurysms,
severe RA stenosis, excessive
tortuosity)
Aortic aneurysm
Pregnancy
As above Puncture site complications (femoral
area accross each RA
Multiple renal arteries and branches should be
treated
Radiofrequency RDN RF energy increases temperature in a localized
Thermal circumferentiaablation by ultrasound
Ultrasound
As above Microleaks
energy
Single ablation in RA
Microneedle delivery of alcohol into the
peri-adventicial space
Single ablation in RA
RDN
Alcohol
RDN
Previous surgical renal denervation
as scarring could affect the success
of the procedure
Excision of kidney and upper ureter with
ex-situ excision of renal innervation,
capsulotomy, and reimplantation
Surgical
Autotransplantation
Last resource in patients with
Nephrectomy ADPKD: Unilaterally or bilaterally followed by
end-stage kidney disease total
removal of the kidney
Suitable in patients with end-stage
kidney who are poor surgical
candidates
dialysis
ADPKD: Reduction of kidney volume (47%)
and decreased compression.
Thranscatheter arterial
embolization
RAASi Renin-angiotensin aldosterone inhibitors, ADPKD Autosomal dominant polycystic kidney disease, LPHS Loin pain hematuria syndrome, RND renal denervation
a
time of study follow up
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