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Successful kidney transplantation from a deceased donor to a recipient with chronic intradialytic hypotension (clinical case report)
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Successful kidney transplantation from a deceased donor to a recipient with chronic intradialytic hypotension. (Clinical case report) A.V. Pinchuk , N.S. Zhuravel , A.G. Balkarov , A.S. Kondrashkin PII: DOI: Reference:
S2451-9596(19)30029-0 https://doi.org/10.1016/j.tpr.2019.100036 TPR 100036
To appear in:
Transplantation Reports
Received date: Accepted date:
7 October 2019 6 November 2019
Please cite this article as: A.V. Pinchuk , N.S. Zhuravel , A.G. Balkarov , A.S. Kondrashkin , Successful kidney transplantation from a deceased donor to a recipient with chronic intradialytic hypotension. (Clinical case report), Transplantation Reports (2019), doi: https://doi.org/10.1016/j.tpr.2019.100036
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Successful kidney transplantation from a deceased donor to a recipient with chronic intradialytic hypotension (Clinical case report) A.V. Pinchuk¹²³, N.S. Zhuravel¹, A.G. Balkarov¹, A.S. Kondrashkin¹ ¹ N.V. Sklifosovsky Research Institute for Emergency Medicine, 3 Bolshaya Sukharevskaya Sq., Moscow, Russia, 129090 ² Department of Transplantology and Artificial Organs MSMU n. a. A.I. Evdokimov, Delegatskaya Street, 20/1, Moscow, Russia, 127473 ³ Research Institute of Healthcare and Medical Management, Bol'shaya Tatarskaya Street, 30, Moscow, Russia, 115184 Corresponding author: Dr. Nikita Zhuravel, +7 (906) 703-05-42, e-mail: [email protected]
Abstract Intradialytic hypotension is a frequent complication of chronic kidney disease. According to different authors, the incidence of this condition varies in severity and being recorded in 10–70% of cases during chronic intermittent hemodialysis. The development of severe chronic intradialytic hypotension in most cases is considered as a relative contraindication to kidney transplantation due to the risk of the graft dysfunction and loss in the early postoperative period. Meanwhile, there is no consensus on the lower limit of blood pressure, which would be an absolute contraindication for kidney transplantation. In addition, patients with intradialytic hypotension have the dialysis session reduced which leads to inadequate dialysis; also, they often have such complications as thrombosis of an arteriovenous fistula, as a result of which further dialysis sessions become impossible. In such cases, renal transplantation is a risky, but lifesaving operation. We present a clinical case report of kidney allotransplantation in a female patient with a history of bilateral nephroectomy, who had been suffering from severe chronic intradialytic hypotension for three years before the operation. After allograft transplantation, her blood pressure was normalized to reference values, and the graft function fully recovered. Keywords: kidney transplantation, intradialytic hypotension, end-stage renal disease, bilateral nephrectomy. Abbreviation AVF, arteriovenous fistula BP, blood pressure DSA, donor-specific antibodies ESRD, end stage renal disease HD, hemodialysis HR, heart rate IDH, intradialytic hypotension K-DOQI, Kidney Disease Outcomes Quality Initiative NKF, National Kidney Foundation, Inc. RI, resistivity index RRT, renal replacement therapy
1. Introduction Intradialytic hypotension (IDH) is a common complication in patients on chronic hemodialysis (HD). According to estimates of various authors, the IDH incidence makes as high as 10–70%, varying in hypotension severity. This variability in the incidence rate is associated with various definitions of this nosology. National Kidney Foundation, Inc. (NKF) defines IDH as a systolic blood pressure (BP) decrease by over 20 mm Hg or a mean blood pressure decrease by over 10 mm Hg with clinical manifestations (fainting, dizziness, muscle cramps, etc.). [1] According to the NKF/K-DOQI estimates, IDH occurs in approximately 20–30% of dialysis sessions. [2]
IDH may occur in the form of acute (episodic), recurring (in at least 50% of dialysis sessions) or, in rare cases, chronic dialysis hypotension, which is manifested by a decrease in systolic blood pressure <100 mmHg between HD sessions in 5–10 % of patients. IDH is more common in elderly patients with cardiovascular disease, on prolonged dialysis, in patients with diabetes, low albumin, a high body mass index in women, as well as in patients with low blood pressure before dialysis. The clinical consequences of IDH include, first of all, a deterioration in the quality of life and an increase in mortality from cardiovascular complications. [3] IDH manifestations may also arise due to inadequate dialysis resulting from the reduction in dialysis session. Complications associated with vascular access also develop more often due to frequent arteriovenous fistula (AVF) thrombosis. [4,5]
To date, the pathophysiology of IDH is not fully understood. One of the IDH causes is a decrease in the response of the cardiovascular system to vasopressor agents. So, the blood norepinephrine level is elevated while the density of both α1, α2 and β1, β2 adrenergic receptors is reduced. A long-term dialysis treatment leads to an impaired baroreceptor function. Another significant factor influencing the onset of IDH is an increased level of vasodilators (adrenomodulins and nitric oxide) as a result of the activation of proinflammatory cytokines. Hypotension episodes and, as a consequence, hypoperfusion lead to an increased production of pro-inflammatory cytokines, the oxidative stress, and the endothelial cell dysfunction. [4, 6]
Another cause of IDH may be bilateral nephrectomy leading to removal of sympathetic stimulus from native kidneys [7]
The occurrence of chronic severe IDH in most cases is considered as a contraindication to kidney transplantation and leads to the exclusion of patients from the waiting list. It is considered that even short periods of intraoperative mean blood pressure decrease by less 55-60 mm Hg carry the risk of developing postoperative acute tubular necrosis. [8] Nowadays, in the world literature, there are few reports of successful kidney transplantation with the restoration of blood pressure to normal values in patients with chronic IDH.
2. Clinical case.
Patient C., 51 years old, female, was diagnosed with polycystic liver and kidney disease in 1988. In the 3rd trimester of pregnancyб when she was 30 years old, she noted the occurrence of leg edema, blood pressure increases to 140-150/90-100 mm Hg. Proteinuria was noted in urinalysis. After childbirth, arterial hypertension persisted with episodic increases in blood pressure to 160/100 mm Hg, and therefore, she took antihypertensive drugs irregularly. From that time, the episodic increases in blood creatinine had been noted. In 2008, the patient underwent a laparoscopic removal of the suppurated cysts from the right kidney.
In June 2015, and end stage renal disease (ESRD) was diagnosed. An examination revealed anemia, critical hyperkalemia (potassium being 8.9 mmol/L), azotemia (creatinine of 472 mmol/L, urea of 45 mmol/L), glomerular filtration rate of 14 ml/min. The patient started renal replacement therapy (RRT).
In October 2015, AVF was formed in the patient, and in March 2016, she was diagnosed with fistular vein thrombosis. In order to perform RRT, a double-lumen cuff tunnel catheter was implanted as a permanent vascular access. In early September 2016, the patient first noted the blood pressre instability (systolic blood pressure was below 90 mm Hg).
To consider the need in kidney transplantation, the patient was referred to the Sklifosovsky Institute for Emergency Medicine. Having persistent oliguria, the patient underwent laparoscopic bilateral nephrectomy aimed at sanitizing the chronic focus of infection and preparing for transplantation in November 2016.
The estimated blood pressure was at a level of 70/40 mm Hg against the renoprival state of the patient, while during the HD sessions, there were regular decreases to 50/20 mm Hg. The patient regularly took midodrine, 5 mg x 3 times a day, to correct blood pressure.
A 24-hour blood pressure monitoring was undertaken for an additional pre-transplant examination. According to its results, the mean daily blood pressure was 69/44 mm Hg (no hemodialysis session was performed on the day of monitoring). (Monitoring data are presented in Figure 1).
Figure 1 Daily monitoring of blood pressure (BP) and heart rate (HR) According to the examination results, the patient was included in the waiting list for kidney transplantation, despite the risk of an unsuccessful outcome of surgery due to a high risk of developing a primary graft nonfunction.
On September 01, 2019, under combined endotracheal anesthesia using an inhaled desflurane anesthetic (4-5 vol%), the patient underwent the left kidney transplantation in the right iliac region from a deceased donor. The data of a cadaveric donor were as follows: a female of 45 years old, height 165 cm, body mass 65 kg; the donor's death was ascertained based on a stroke diagnosis with the brain death. The donor was compatible with the recipient by the blood group, showing a HLA allele mismatch at HLA-A, -A, -B. The donor's renal function was satisfactory: diuresis was 3900 ml for the latest day, urea was 3.9 mmol/L,
creatinine was 36.1 mmol/L, potassium was 3.6 mmol/L, and sodium was 141 mmol/L. Cold ischemia time was 11 hours.
During transplantation, the blood pressure correction was performed using dopamin at a dose of 5-9 μg/kg/min, and norepinephrine at a dose of 0.15-0.3 μg/kg/min. Vascular anastomoses were alternately formed: the graft renal artery was connected with the recipient's right external iliac artery, and the graft renal graft vein was anastomosed "end-to-side" to the recipient's external iliac vein. Blood pressure was 105/50 mm Hg at the time of reperfusion. The graft turned pink and turgor was slightly reduced after the restart of blood flow. Ureterine mild urination was recorded. We also noted a satisfactory pulsation of the renal arteries and the function of the vascular anastomosis retained. The induction immunosuppression was carried out with 20 mg of basiliximab, 500 mg of methylprednisolone, diuresis was stimulated using furosemide 200 mg. The surgery duration was 120 minutes.
In the postoperative period, blood pressure was maintained at an average daily level of 85/55 mm Hg, and a heart rate was 110 beats/min with the administration of norepinephrine 0.15-0.2 μg/kg/min, and dobutamine 2-4 μg kg/min. The administered immunosuppressive therapy included tacrolimus, ext. release, 10 mg once a day, mycophenolic acid 720 mg x 2 times per day, methylprednisolone 250 mg, intravenously, once a day with a gradual dose reduction. According to the ultrasound examination of the graft, the arterial blood flow in the parenchyma was traceable slightly depleted in all departments to the capsulethe, the resistivity index (RI) was recorded at the level of 0.70-0.75 on the segmental arteries and 0.78-0.82 on the arch arteries.
Vasopressor support was canceled completely on the fourth day. In addition, anticoagulant therapy was given with heparin 5 000 units x 2 times per day, and the infusions of alprostadilum 40 mg per day, and of 20% albumin solution 200 ml/day. Daily diuresis remained at a level of less than 100 ml for a long time (up to 34 days), intermittent HD procedures were performed.
On the 21st day after surgery, a fine-needle aspiration biopsy of the renal graft was performed that detected no signs of rejection, however, there were the signs of acute tubular necrosis and moderate ischemic damage to the renal allograft.
The therapy was continued contributing to a gradual decrease in creatinine and urea levels. Body weight averaged 59 kg (57.8; 62.1 kg) (“dry weight” was 56 kg). General patient's condition was satisfactory. From the 34th day of the postoperative period, the urination volume increased and began to exceed 100 ml/day. At the same time, there was a tendency to some spontaneous increase in blood pressure, up to an average daily level of 105/70 mm Hg.
On the 50th day after surgery, daily diuresis exceeded 1000 ml, ultrasonography exminations also demonstrated positive changes over time (RI 0.7-0.8). Pharmacological stimulation of diuresis with loop diuretics was started. On the 58th day, diuresis was about 1700 ml/day; a decrease in creatinine level to 302 mmol/L was also noted. The changes in diuresis, creatinine and blood pressure levels over time are shown in Figures 2 and 3.
Gradually, the patient's diuretic therapy was completely canceled, while the average daily diuresis exceeded 1700 ml. On the 70th day, the patient being in satisfactory condition was transferred to the outpatient treatment under the supervision of the specialists from the Moscow City Nephrology Center, in accordance with the standard practice of the capital healthcare system.
Figure 2 Dynamics of the creatinine level in the blood and diuresis level in the postoperative period
*- vasopressors
Figure 3 Dynamics of postoperative level of blood pressure (BP) 3. Discussion. In our clinical case, the decision on kidney transplantation was rather difficult to make. On the one hand, there was a high risk of developing a primary graft non-function due to refractory hypotension with the average daily blood pressure of 70/40 mm Hg before surgery and frequent episodes of its fall to critical values of 50/25 mm Hg.
On the other hand, prior AVF thrombosis and, as a result, a high risk of losing the tunnel CVC (central venous catheter) being the only remaining option for permanent vascular access, would have been very likely leading to death due to the impossibility of adequate RRT by means of dialysis methods.
We assumed that successful kidney transplantation will lead to the recovery of the renin-angiotensinaldosterone system, and this one will normalize the level of blood pressure. In addition, the administration of immunosuppressive therapy, namely tacrolimus, with its side effect of causing hypertension, in our case would also contribute to the blood pressure normalization.
A similar case was demonstrated by Taiwan authors [9]. They described a 59-year-old woman with hypertension and diabetes, who developed intradialytic hypotension (in the range 80–100/50–60 mm Hg) over the course of 6 years on HD. Blood pressure increased to the range of 120–140/60–80 mm Hg on the
1st day after transplantation. In another study, Muscroft et al. [10] assessed the BP normalization after successful kidney transplantation in eight patients with IDH. They were high-risk patients with donorspecific antibodies (DSA), and had previously undergone appropriate desensitization procedures. Only one of eight patients underwent a deceased donor kidney transplant; the rest of them underwent a living donor transplant. It should be noted that only four patients in that group had had hypotension <100 mm Hg between hemodialysis sessions. The authors draw attention to a large соmplication rates before transplantation (central retinal vein thrombosis) and during the treatment (bleeding, intestinal ischemia). One patient who received a cadaveric kidney died from complications of ischemic bowel disease. In these patients, various combinations of pressor amines, including norepinephrine, were also used during transplantation to achieve a normal blood pressure level [10].
The unique nature of our clinical case lied in patient’s having refractory hypotension with a blood pressure decrease to 50/25 mm Hg in association with the undertaken bilateral nephrectomy that was undoubtedly advisable from the point of the recipient's infection control, but, meanwhile, being hemodynamically a highly probable aggravating factor for kidney transplantation. A similar case was reported by Ewa Ignacak. She studied a 44 year old female patient with severe refractory hypotension (mean BP was 60/30 mm Hg, the lowest values being 48/28 mm Hg) who underwent bilateral laparoscopic nephrectomy of infected native kidneys. Her kidney transplantation was performed from a deceased donor with the infusion of two pressor amines (dopamine and dobutamine). The surgery was technically uneventful, BP values were 100120 / 70-80 mm Hg. The immunosuppression regimen was chosen according to the classical scheme: tacrolimus + mycophenolate mofetil and steroids. The infusion of pressor amines was discontinued on the 18th day after transplantation. Four HD session were performed due to a delayed graft function. The patient was discharged from the hospital on the 22nd day having an adequate transplant function (serum creatinine concentration 117 μmol/L). [11]
It was also extremely important in our severe case that the graft was obtained from a standard criteria donor without hypertension in the previous history who had preserved urinary and nitrogen excretory functions. Such a lucky coincidence was very positive for the success of the patient’s surgical treatment. Unfortunately, when selecting an optimal donor-recipient pair in the routine current transplant practice in Moscow clinics, only the following parameters are considered: donor and recipient compatibility by blood group, histocompatibility by HLA-system and the period of being on the waiting list. [12] In our opinion, these parameters are clearly not enough to select a truly optimal recipient for an available kidney graft with a certain set specific characteristics, since very often, organs from posthumous extended criteria donors are used for transplantation; and first of all, from donors with a long, overt or latent, hypertensive history. In
some cases, only the cause of the donor's death, such as an acute cerebrovascular accident or a brain aneurysm rupture, may indirectly indicate the presence of renal damage with hypertensive nephroangiosclerosis of various severity. Moreover, this such organ can (and must) be successfully transplanted to many other patients in need who do not have serious concomitant pathology and who would have a reasonable prognosis of satisfactory graft functioning for a long time. [13-21] However, transplantation of such an organ to a patient with severe hemodynamic impairments (as in our case) might be associated with an extremely high risk of the graft loss immediately after surgery despite an impeccable immunological selection of a donor-recipient pair. The currently adopted, insufficiently comprehensive approach to the selection of kidney transplant recipients sometimes impedes the surgery success and may even result in a poor long-term transplantation outcome, which dictates the necessity in immediate revision of the existing patient selection guidelines in the transplantation practice of Moscow healthcare.
4. Conclusion. Nowadays, the world experience of kidney transplantation in patients with intradialytic hypotension have not been sufficiently summarized and there are no clear-cut recommendations on the intra- and postoperative management of such kidney transplant recipients. Refractory hypotension due to bilateral nephrectomy should not be considered as an absolute contraindication for surgical treatment using transplant methodology. In our case, we demonstrated the possibility of a successful transplantation with an efficient perioperative management. Kidney transplantation in this case not only significantly improved the quality of life of the recipient, but as evaluated in the short term, was a life-saving operation. It is important to address the need for an integrated multifactorial approach to the recipient selection for an available donor organ and to make a revision of the existing authorized guidelines in this field. Immunological compatibility is undoubtedly an important factor in the long-term graft survival. But the paramount goal is still a complete functional recovery of the graft function in the recipient’s body. This is possible only with the hemodynamic compatibility of the graft and the recipient, especially in modern conditions when the age and nosological composition of deceased donors has greatly changed. The revision of the criteria for the donor-recipient selection and graft allocation taking into account all the individual characteristics of both the graft and the recipient will significantly increase the number of successful transplants. Also, the hospital length of stay and the treatment costs will also significantly decrease.
Conflict of interests. Authors declare no conflict of interest.
Financing. The study was performed without external funding.
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Successful kidney transplantation from a deceased donor to a recipient with chronic intradialytic hypotension. (Clinical case report) A.V. Pinchuk , N.S. Zhuravel , A.G. Balkarov , A.S. Kondrashkin PII: DOI: Reference:
S2451-9596(19)30029-0 https://doi.org/10.1016/j.tpr.2019.100036 TPR 100036
To appear in:
Transplantation Reports
Received date: Accepted date:
7 October 2019 6 November 2019
Please cite this article as: A.V. Pinchuk , N.S. Zhuravel , A.G. Balkarov , A.S. Kondrashkin , Successful kidney transplantation from a deceased donor to a recipient with chronic intradialytic hypotension. (Clinical case report), Transplantation Reports (2019), doi: https://doi.org/10.1016/j.tpr.2019.100036
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Successful kidney transplantation from a deceased donor to a recipient with chronic intradialytic hypotension (Clinical case report) A.V. Pinchuk¹²³, N.S. Zhuravel¹, A.G. Balkarov¹, A.S. Kondrashkin¹ ¹ N.V. Sklifosovsky Research Institute for Emergency Medicine, 3 Bolshaya Sukharevskaya Sq., Moscow, Russia, 129090 ² Department of Transplantology and Artificial Organs MSMU n. a. A.I. Evdokimov, Delegatskaya Street, 20/1, Moscow, Russia, 127473 ³ Research Institute of Healthcare and Medical Management, Bol'shaya Tatarskaya Street, 30, Moscow, Russia, 115184 Corresponding author: Dr. Nikita Zhuravel, +7 (906) 703-05-42, e-mail: [email protected]
Abstract Intradialytic hypotension is a frequent complication of chronic kidney disease. According to different authors, the incidence of this condition varies in severity and being recorded in 10–70% of cases during chronic intermittent hemodialysis. The development of severe chronic intradialytic hypotension in most cases is considered as a relative contraindication to kidney transplantation due to the risk of the graft dysfunction and loss in the early postoperative period. Meanwhile, there is no consensus on the lower limit of blood pressure, which would be an absolute contraindication for kidney transplantation. In addition, patients with intradialytic hypotension have the dialysis session reduced which leads to inadequate dialysis; also, they often have such complications as thrombosis of an arteriovenous fistula, as a result of which further dialysis sessions become impossible. In such cases, renal transplantation is a risky, but lifesaving operation. We present a clinical case report of kidney allotransplantation in a female patient with a history of bilateral nephroectomy, who had been suffering from severe chronic intradialytic hypotension for three years before the operation. After allograft transplantation, her blood pressure was normalized to reference values, and the graft function fully recovered. Keywords: kidney transplantation, intradialytic hypotension, end-stage renal disease, bilateral nephrectomy. Abbreviation AVF, arteriovenous fistula BP, blood pressure DSA, donor-specific antibodies ESRD, end stage renal disease HD, hemodialysis HR, heart rate IDH, intradialytic hypotension K-DOQI, Kidney Disease Outcomes Quality Initiative NKF, National Kidney Foundation, Inc. RI, resistivity index RRT, renal replacement therapy
1. Introduction Intradialytic hypotension (IDH) is a common complication in patients on chronic hemodialysis (HD). According to estimates of various authors, the IDH incidence makes as high as 10–70%, varying in hypotension severity. This variability in the incidence rate is associated with various definitions of this nosology. National Kidney Foundation, Inc. (NKF) defines IDH as a systolic blood pressure (BP) decrease by over 20 mm Hg or a mean blood pressure decrease by over 10 mm Hg with clinical manifestations (fainting, dizziness, muscle cramps, etc.). [1] According to the NKF/K-DOQI estimates, IDH occurs in approximately 20–30% of dialysis sessions. [2]
IDH may occur in the form of acute (episodic), recurring (in at least 50% of dialysis sessions) or, in rare cases, chronic dialysis hypotension, which is manifested by a decrease in systolic blood pressure <100 mmHg between HD sessions in 5–10 % of patients. IDH is more common in elderly patients with cardiovascular disease, on prolonged dialysis, in patients with diabetes, low albumin, a high body mass index in women, as well as in patients with low blood pressure before dialysis. The clinical consequences of IDH include, first of all, a deterioration in the quality of life and an increase in mortality from cardiovascular complications. [3] IDH manifestations may also arise due to inadequate dialysis resulting from the reduction in dialysis session. Complications associated with vascular access also develop more often due to frequent arteriovenous fistula (AVF) thrombosis. [4,5]
To date, the pathophysiology of IDH is not fully understood. One of the IDH causes is a decrease in the response of the cardiovascular system to vasopressor agents. So, the blood norepinephrine level is elevated while the density of both α1, α2 and β1, β2 adrenergic receptors is reduced. A long-term dialysis treatment leads to an impaired baroreceptor function. Another significant factor influencing the onset of IDH is an increased level of vasodilators (adrenomodulins and nitric oxide) as a result of the activation of proinflammatory cytokines. Hypotension episodes and, as a consequence, hypoperfusion lead to an increased production of pro-inflammatory cytokines, the oxidative stress, and the endothelial cell dysfunction. [4, 6]
Another cause of IDH may be bilateral nephrectomy leading to removal of sympathetic stimulus from native kidneys [7]
The occurrence of chronic severe IDH in most cases is considered as a contraindication to kidney transplantation and leads to the exclusion of patients from the waiting list. It is considered that even short periods of intraoperative mean blood pressure decrease by less 55-60 mm Hg carry the risk of developing postoperative acute tubular necrosis. [8] Nowadays, in the world literature, there are few reports of successful kidney transplantation with the restoration of blood pressure to normal values in patients with chronic IDH.
2. Clinical case.
Patient C., 51 years old, female, was diagnosed with polycystic liver and kidney disease in 1988. In the 3rd trimester of pregnancyб when she was 30 years old, she noted the occurrence of leg edema, blood pressure increases to 140-150/90-100 mm Hg. Proteinuria was noted in urinalysis. After childbirth, arterial hypertension persisted with episodic increases in blood pressure to 160/100 mm Hg, and therefore, she took antihypertensive drugs irregularly. From that time, the episodic increases in blood creatinine had been noted. In 2008, the patient underwent a laparoscopic removal of the suppurated cysts from the right kidney.
In June 2015, and end stage renal disease (ESRD) was diagnosed. An examination revealed anemia, critical hyperkalemia (potassium being 8.9 mmol/L), azotemia (creatinine of 472 mmol/L, urea of 45 mmol/L), glomerular filtration rate of 14 ml/min. The patient started renal replacement therapy (RRT).
In October 2015, AVF was formed in the patient, and in March 2016, she was diagnosed with fistular vein thrombosis. In order to perform RRT, a double-lumen cuff tunnel catheter was implanted as a permanent vascular access. In early September 2016, the patient first noted the blood pressre instability (systolic blood pressure was below 90 mm Hg).
To consider the need in kidney transplantation, the patient was referred to the Sklifosovsky Institute for Emergency Medicine. Having persistent oliguria, the patient underwent laparoscopic bilateral nephrectomy aimed at sanitizing the chronic focus of infection and preparing for transplantation in November 2016.
The estimated blood pressure was at a level of 70/40 mm Hg against the renoprival state of the patient, while during the HD sessions, there were regular decreases to 50/20 mm Hg. The patient regularly took midodrine, 5 mg x 3 times a day, to correct blood pressure.
A 24-hour blood pressure monitoring was undertaken for an additional pre-transplant examination. According to its results, the mean daily blood pressure was 69/44 mm Hg (no hemodialysis session was performed on the day of monitoring). (Monitoring data are presented in Figure 1).
Figure 1 Daily monitoring of blood pressure (BP) and heart rate (HR) According to the examination results, the patient was included in the waiting list for kidney transplantation, despite the risk of an unsuccessful outcome of surgery due to a high risk of developing a primary graft nonfunction.
On September 01, 2019, under combined endotracheal anesthesia using an inhaled desflurane anesthetic (4-5 vol%), the patient underwent the left kidney transplantation in the right iliac region from a deceased donor. The data of a cadaveric donor were as follows: a female of 45 years old, height 165 cm, body mass 65 kg; the donor's death was ascertained based on a stroke diagnosis with the brain death. The donor was compatible with the recipient by the blood group, showing a HLA allele mismatch at HLA-A, -A, -B. The donor's renal function was satisfactory: diuresis was 3900 ml for the latest day, urea was 3.9 mmol/L,
creatinine was 36.1 mmol/L, potassium was 3.6 mmol/L, and sodium was 141 mmol/L. Cold ischemia time was 11 hours.
During transplantation, the blood pressure correction was performed using dopamin at a dose of 5-9 μg/kg/min, and norepinephrine at a dose of 0.15-0.3 μg/kg/min. Vascular anastomoses were alternately formed: the graft renal artery was connected with the recipient's right external iliac artery, and the graft renal graft vein was anastomosed "end-to-side" to the recipient's external iliac vein. Blood pressure was 105/50 mm Hg at the time of reperfusion. The graft turned pink and turgor was slightly reduced after the restart of blood flow. Ureterine mild urination was recorded. We also noted a satisfactory pulsation of the renal arteries and the function of the vascular anastomosis retained. The induction immunosuppression was carried out with 20 mg of basiliximab, 500 mg of methylprednisolone, diuresis was stimulated using furosemide 200 mg. The surgery duration was 120 minutes.
In the postoperative period, blood pressure was maintained at an average daily level of 85/55 mm Hg, and a heart rate was 110 beats/min with the administration of norepinephrine 0.15-0.2 μg/kg/min, and dobutamine 2-4 μg kg/min. The administered immunosuppressive therapy included tacrolimus, ext. release, 10 mg once a day, mycophenolic acid 720 mg x 2 times per day, methylprednisolone 250 mg, intravenously, once a day with a gradual dose reduction. According to the ultrasound examination of the graft, the arterial blood flow in the parenchyma was traceable slightly depleted in all departments to the capsulethe, the resistivity index (RI) was recorded at the level of 0.70-0.75 on the segmental arteries and 0.78-0.82 on the arch arteries.
Vasopressor support was canceled completely on the fourth day. In addition, anticoagulant therapy was given with heparin 5 000 units x 2 times per day, and the infusions of alprostadilum 40 mg per day, and of 20% albumin solution 200 ml/day. Daily diuresis remained at a level of less than 100 ml for a long time (up to 34 days), intermittent HD procedures were performed.
On the 21st day after surgery, a fine-needle aspiration biopsy of the renal graft was performed that detected no signs of rejection, however, there were the signs of acute tubular necrosis and moderate ischemic damage to the renal allograft.
The therapy was continued contributing to a gradual decrease in creatinine and urea levels. Body weight averaged 59 kg (57.8; 62.1 kg) (“dry weight” was 56 kg). General patient's condition was satisfactory. From the 34th day of the postoperative period, the urination volume increased and began to exceed 100 ml/day. At the same time, there was a tendency to some spontaneous increase in blood pressure, up to an average daily level of 105/70 mm Hg.
On the 50th day after surgery, daily diuresis exceeded 1000 ml, ultrasonography exminations also demonstrated positive changes over time (RI 0.7-0.8). Pharmacological stimulation of diuresis with loop diuretics was started. On the 58th day, diuresis was about 1700 ml/day; a decrease in creatinine level to 302 mmol/L was also noted. The changes in diuresis, creatinine and blood pressure levels over time are shown in Figures 2 and 3.
Gradually, the patient's diuretic therapy was completely canceled, while the average daily diuresis exceeded 1700 ml. On the 70th day, the patient being in satisfactory condition was transferred to the outpatient treatment under the supervision of the specialists from the Moscow City Nephrology Center, in accordance with the standard practice of the capital healthcare system.
Figure 2 Dynamics of the creatinine level in the blood and diuresis level in the postoperative period
*- vasopressors
Figure 3 Dynamics of postoperative level of blood pressure (BP) 3. Discussion. In our clinical case, the decision on kidney transplantation was rather difficult to make. On the one hand, there was a high risk of developing a primary graft non-function due to refractory hypotension with the average daily blood pressure of 70/40 mm Hg before surgery and frequent episodes of its fall to critical values of 50/25 mm Hg.
On the other hand, prior AVF thrombosis and, as a result, a high risk of losing the tunnel CVC (central venous catheter) being the only remaining option for permanent vascular access, would have been very likely leading to death due to the impossibility of adequate RRT by means of dialysis methods.
We assumed that successful kidney transplantation will lead to the recovery of the renin-angiotensinaldosterone system, and this one will normalize the level of blood pressure. In addition, the administration of immunosuppressive therapy, namely tacrolimus, with its side effect of causing hypertension, in our case would also contribute to the blood pressure normalization.
A similar case was demonstrated by Taiwan authors [9]. They described a 59-year-old woman with hypertension and diabetes, who developed intradialytic hypotension (in the range 80–100/50–60 mm Hg) over the course of 6 years on HD. Blood pressure increased to the range of 120–140/60–80 mm Hg on the
1st day after transplantation. In another study, Muscroft et al. [10] assessed the BP normalization after successful kidney transplantation in eight patients with IDH. They were high-risk patients with donorspecific antibodies (DSA), and had previously undergone appropriate desensitization procedures. Only one of eight patients underwent a deceased donor kidney transplant; the rest of them underwent a living donor transplant. It should be noted that only four patients in that group had had hypotension <100 mm Hg between hemodialysis sessions. The authors draw attention to a large соmplication rates before transplantation (central retinal vein thrombosis) and during the treatment (bleeding, intestinal ischemia). One patient who received a cadaveric kidney died from complications of ischemic bowel disease. In these patients, various combinations of pressor amines, including norepinephrine, were also used during transplantation to achieve a normal blood pressure level [10].
The unique nature of our clinical case lied in patient’s having refractory hypotension with a blood pressure decrease to 50/25 mm Hg in association with the undertaken bilateral nephrectomy that was undoubtedly advisable from the point of the recipient's infection control, but, meanwhile, being hemodynamically a highly probable aggravating factor for kidney transplantation. A similar case was reported by Ewa Ignacak. She studied a 44 year old female patient with severe refractory hypotension (mean BP was 60/30 mm Hg, the lowest values being 48/28 mm Hg) who underwent bilateral laparoscopic nephrectomy of infected native kidneys. Her kidney transplantation was performed from a deceased donor with the infusion of two pressor amines (dopamine and dobutamine). The surgery was technically uneventful, BP values were 100120 / 70-80 mm Hg. The immunosuppression regimen was chosen according to the classical scheme: tacrolimus + mycophenolate mofetil and steroids. The infusion of pressor amines was discontinued on the 18th day after transplantation. Four HD session were performed due to a delayed graft function. The patient was discharged from the hospital on the 22nd day having an adequate transplant function (serum creatinine concentration 117 μmol/L). [11]
It was also extremely important in our severe case that the graft was obtained from a standard criteria donor without hypertension in the previous history who had preserved urinary and nitrogen excretory functions. Such a lucky coincidence was very positive for the success of the patient’s surgical treatment. Unfortunately, when selecting an optimal donor-recipient pair in the routine current transplant practice in Moscow clinics, only the following parameters are considered: donor and recipient compatibility by blood group, histocompatibility by HLA-system and the period of being on the waiting list. [12] In our opinion, these parameters are clearly not enough to select a truly optimal recipient for an available kidney graft with a certain set specific characteristics, since very often, organs from posthumous extended criteria donors are used for transplantation; and first of all, from donors with a long, overt or latent, hypertensive history. In
some cases, only the cause of the donor's death, such as an acute cerebrovascular accident or a brain aneurysm rupture, may indirectly indicate the presence of renal damage with hypertensive nephroangiosclerosis of various severity. Moreover, this such organ can (and must) be successfully transplanted to many other patients in need who do not have serious concomitant pathology and who would have a reasonable prognosis of satisfactory graft functioning for a long time. [13-21] However, transplantation of such an organ to a patient with severe hemodynamic impairments (as in our case) might be associated with an extremely high risk of the graft loss immediately after surgery despite an impeccable immunological selection of a donor-recipient pair. The currently adopted, insufficiently comprehensive approach to the selection of kidney transplant recipients sometimes impedes the surgery success and may even result in a poor long-term transplantation outcome, which dictates the necessity in immediate revision of the existing patient selection guidelines in the transplantation practice of Moscow healthcare.
4. Conclusion. Nowadays, the world experience of kidney transplantation in patients with intradialytic hypotension have not been sufficiently summarized and there are no clear-cut recommendations on the intra- and postoperative management of such kidney transplant recipients. Refractory hypotension due to bilateral nephrectomy should not be considered as an absolute contraindication for surgical treatment using transplant methodology. In our case, we demonstrated the possibility of a successful transplantation with an efficient perioperative management. Kidney transplantation in this case not only significantly improved the quality of life of the recipient, but as evaluated in the short term, was a life-saving operation. It is important to address the need for an integrated multifactorial approach to the recipient selection for an available donor organ and to make a revision of the existing authorized guidelines in this field. Immunological compatibility is undoubtedly an important factor in the long-term graft survival. But the paramount goal is still a complete functional recovery of the graft function in the recipient’s body. This is possible only with the hemodynamic compatibility of the graft and the recipient, especially in modern conditions when the age and nosological composition of deceased donors has greatly changed. The revision of the criteria for the donor-recipient selection and graft allocation taking into account all the individual characteristics of both the graft and the recipient will significantly increase the number of successful transplants. Also, the hospital length of stay and the treatment costs will also significantly decrease.
Conflict of interests. Authors declare no conflict of interest.
Financing. The study was performed without external funding.
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