Renal autotransplant as a definitive treatment for nutcracker syndrome: A multicenter retrospective study.

Conception and design: JP, JS, JM, EP, TN, DF, TP Analysis and interpretation: JP, JS, EM, TS, JM, EP, TN, DF, TP Data collection: JP, EM, TS, KL Writing the article: JP, JS, JM, TN, DF, TP Critical revision of the article: JP, JS, EM, TS, KL, EP, TN, DF, TP Final approval of the article: JP, JS, EM, TS, KL, JM, EP, TN, DF, TP Statistical analysis: JS, JM, JP Obtained funding: Not applicable Overall responsibility: DF DF and TP contributed equally to this article and share senior authorship.

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This retrospective, chart included patients who underwent renal autotransplantation for definitive treatment of nutcracker syndrome at two US transplant centers, the University of Wisconsin, Madison (UW; n = 73) and the University of Colorado Hospital (CU; n = 32) between 2011 and 2022. The diagnosis of nutcracker syndrome was determined by the treating physician after in-person evaluation where symptoms were assessed and review of ancillary testing. The primary reason for referral for patients was left flank pain. Evaluations included serum and urine laboratory testing, history, physical examination, as well as computed tomography (CT) imaging to rule out other causes of left flank pain with or without hematuria, including nephrolithiasis. The primary radiographic study used to determine left renal vein compression was the abdominal CT scan. Patients typically underwent at least one of two confirmatory tests: invasive diagnostic venography or the UW loin pain hematuria syndrome (LPHS) test. The UW-LPHS test is a temporary local anesthetic test, which involves ureteral lidocaine injection, designed to help predict resolution of pain with renal autotransplantation. 10 Resolution of left flank pain with ureteral lidocaine injection was considered a positive result to confirm the diagnosis of nutcracker syndrome. Invasive diagnostic venography included direct measurements of the pressure gradient across the left renal vein and quantification of degree of compression using intra-vascular ultrasound. Venograms were considered positive if there was a pressure gradient of ≥3 mm Hg higher across the renal vein and/or evidence of left renal vein narrowing or compression as determined by the radiologist performing the procedure. Evaluating providers determined which invasive confirmatory test was used if the testing had not been completed before referral. Typically, only one confirmatory test was performed per patient. The presence of left flank pain, CT evidence of left renal vein compression, and a positive confirmatory test were considered necessary for physicians to make the diagnosis of nutcracker syndrome. Patients who were determined to have a diagnosis of nutcracker syndrome and who did not have any medical or surgical contraindications to surgery were offered renal autotransplantation. For patients with comorbidities, including endometriosis, median arcuate ligament syndrome (MALS), and superior mesenteric artery syndrome (SMAS), these conditions were treated fully either medically surgically and patients were optimized medically and nutritionally before proceeding with autotransplantation. Patient demographic data, medical history, mode of nutcracker syndrome diagnosis, surgical details, and complications at 30 days and 1 year after the operation were collected. Morphine milligram equivalents (MMEs) were calculated from data abstracted from the medical records at baseline, 30 days, 90 days, 6 months, and 12 months after the operation. Left flank pain was self-reported by each patient and recorded in the medical record at each of these timepoints, per clinical protocols. The estimated glomerular filtration rate (eGFR) was calculated using Modification of Diet in Renal Disease equation from the medical record at baseline and 1-year follow-up. All data were collected under local institutional review board approval. The primary outcomes of this study were resolution of left flank pain at 30 days, 90 days, and 6 and 12 months after the operation. Secondary outcomes included MMEs at 30 days, 90 days, and 6 and 12 months after the operation, as well as complications at 30 days and 1 year of follow-up and eGFR at the 1-year follow-up. Summary statistics were performed on all data. Data are presented as mean ± standard deviation or number (%). Comparisons were made between cohorts from each transplant center (UW vs CU) or between patients who reported opioid use before renal autotransplantation or those without prior opioid use, in the case of MMEs. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t test for categorical and continuous variables, respectively. The paired McNamar's test was used to determine differences in the proportion of patients with left flank pain or opioid use at every timepoint. A related-samples Friedman's two-way analysis of variance by ranks summary was used to analyze differences across time points for MMEs and an independent-samples Mann-Whitney U test was performed to test the statistical differences in MMEs between patients who were on opioids at baseline compared with those who were not at each timepoint.

A total of 105 patients were included in this study. Seventy-three patients (69.5%) were treated at UW. There were no statistically significant differences between the demographics of the cohort between the two centers ( Table I ). Combined, 104 patients (99.0%) were female with a mean age of 33 years and predominantly of White race (102 patients [97.1%]). Fifty-nine patients (56.2%) had documented microscopic hematuria at the time of evaluation as defined by >3 red blood cells per high power field. The percentage of patients with hematuria was slightly higher in the group of patients who had undergone prior intervention for nutcracker syndrome (n = 21 [67%]), as it was for those who had no prior intervention; however, this difference was not statistically significant ( P  = .29). All patients had normal renal function as measured by eGFR. As expected, the number of concomitant medical diagnoses were high. Fifty-one patients (48.6%) had a previous diagnosis of pelvic congestion syndrome, 32 patients (30.5%) had a diagnosis of May-Thurner syndrome, 24 patients (22.9%) had a diagnosis of nephrolithiasis, and 33 patients (31.4%) had a diagnosis of a urinary tract infection (UTI). There was also a high number of patients with a diagnosis of MALS, SMAS, and endometriosis (20%, 17.1%, and 18.1%, respectively). Table I Demographics and medical history All (n = 105) CU (n = 32) UW (n = 73) P value Age, years 33.9 ± 12.3 31.6 ± 9.7 34.9 ± 13.3 .1 Sex, female 104 (99.0) 32 (100) 72 (98.6) 1.0 Race  White 102 (97.1) 31 (96.9) 71 (97.3) 1.0  Black 0 (0.0) 0 (0.0) 0 (0.0) 1.0  Hispanic 8 (7.6) 2 (6.3) 6 (8.2) 1.0  Other 3 (2.9) 1 (3.1) 2 (2.7) 1.0 Preoperative renal parameters  Microscopic hematuria - yes 59 (56.2) 19 (59.4) 40 (54.8) .07  Creatinine 0.733 ± 0.148 0.754 ± 0.166 0.742 ± 0.140 .3  eGFR 101.30 ± 23.03 95.62 ± 26.15 103.70 ± 21.30 .1 History of NCS intervention 31 (29.5%) 8 (25%) 23 (31.5%) .5  Renal vein stent 15 (14.3) 2 (6.3) 13 (17.8) .1  Renal vein transposition 13 (12.4) 3 (9.4) 9 (12.3) 1.0  Other surgical procedure 13 (12.4) 3 (9.4) 10 (13.7) .8 History of other vascular intervention  Left iliac vein stent 14 (13.3) 5 (15.6) 9 (12.3) .8  Surgery for MALS/SMAS 18 (17.1) 5 (15.6) 13 (17.8) 1.0  Gonadal vein coils/embolization 22 (21.0) 6 (18.8) 16 (21.9) .8 Other medical diagnosis  Pelvic congestion syndrome 51 (48.6) 12 (37.5) 39 (53.4) .1  May-Thurner syndrome 32 (30.5) 8 (25.0) 24 (32.9) .5  MALS diagnosis 21 (20.0) 3 (9.4) 18 (24.7) .1  SMAS diagnosis 18 (17.1) 7 (21.9) 10 (13.7) .4  Endometriosis 19 (18.1) 5 (15.6) 14 (19.2) .8  Nephrolithiasis 24 (22.9) 9 (28.1) 15 (20.5) .5  UTI 33 (31.4) 16 (50.0) 17 (23.3) .01 CU , University of Colorado Hospital; eGFR , estimated glomerular filtration rate; MALS , median arcuate ligament syndrome; NCS , nutcracker syndrome; SMAS , superior mesenteric artery syndrome; UTI , urinary tract infection; UW , University of Wisconsin, Madison. Data presented as number (%) or mean ± standard deviation. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t test. Demographics and medical history CU , University of Colorado Hospital; eGFR , estimated glomerular filtration rate; MALS , median arcuate ligament syndrome; NCS , nutcracker syndrome; SMAS , superior mesenteric artery syndrome; UTI , urinary tract infection; UW , University of Wisconsin, Madison. Data presented as number (%) or mean ± standard deviation. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t test. Thirty-one of the 105 patients (29.5%) had undergone at least one prior intervention specifically for nutcracker syndrome ( Table I ). A renal vein stent was placed in 15 patients (14.3%) and renal vein transposition was undertaken in 13 patients (12.4%). Some patients presented with a history of multiple prior interventions for nutcracker syndrome. All patients with a history of prior intervention for nutcracker syndrome had a patent renal vein at the time of evaluation and autotransplantation. All of the patients with prior renal vein stenting had imaging findings of either in-stent stenosis or migration of stent with compression of left renal vein in the preaortic position. Similarly, all patients with prior renal vein transposition or other surgical procedure for nutcracker syndrome had imaging evidence of recurrent renal vein compression at time of autotransplantation. Many patients also had a history of prior vascular interventions for pelvic congestion syndrome, May-Thurner syndrome, or other vascular compression syndromes. Gonadal vein embolization was the most common procedure, performed in 22 patients (21%). Left iliac vein stents had been placed in 14 patients (13.3%). Eighteen patients (17.1%) had prior MALS or SMAS surgery. Between the two centers, there was no difference in the type of radiological studies used in aiding the diagnosis of nutcracker syndrome ( Table II ). Ninety-nine of the 105 patients (94.3%) had CT imaging consistent with the finding of left renal vein compression. Fifty-six patients (53.3%) had undergone invasive diagnostic venography. The use of ultrasound examination and magnetic resonance imaging was minimal in this cohort. Preoperative use of the UW-LPHS test, a temporary local anesthetic test designed to help predict the resolution of pain with renal autotransplantation, demonstrated a statistical difference between the two centers. 10 CU used it in 93.8% of their patients and UW used it 60.3% of their patients ( P  < .001). Table II Diagnosis of nutcracker syndrome All (n = 105) CU (n = 32) UW (n = 73) P value Diagnostic imaging modality  CT 99 (94.3) 30 (93.8) 69 (94.5) .5  Ultrasound examination 8 (7.6) 1 (3.1) 7 (9.6) .20  MRI 7 (6.7) 0 (0.0) 7 (9.6) .09  Invasive venography 56 (53.3) 11 (34.4) 45 (61.6) .01 UW-LPHS test 74 (70.5) 30 (93.8) 44 (60.3) <.001  Pain relief - yes 69 (93.2) 30 (100.0) 39 (88.6) .08  Pain relief duration, hours 11.3 ± 15.2 12.0 ± 18.0 10.9 ± 13.0 .8 CT , Computed tomography; CU , University of Colorado Hospital; MRI , magnetic resonance imaging; UW , University of Wisconsin, Madison. Data presented as number (%) or mean ± standard deviation. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t test. Diagnosis of nutcracker syndrome CT , Computed tomography; CU , University of Colorado Hospital; MRI , magnetic resonance imaging; UW , University of Wisconsin, Madison. Data presented as number (%) or mean ± standard deviation. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t test. Between the two centers, renal autotransplantation was performed independently by five different surgeons over a 12-year period. The surgical approach (open nephrectomy/open implant, laparoscopic nephrectomy/open implant, robotic nephrectomy/robotic implant) was chosen at the treating surgeon's discretion ( Table III ). All patients with a prior intervention for nutcracker syndrome underwent open nephrectomy and autotransplantation. Inferior vena cava control was obtained as necessary for renal vein stents that extended into the inferior vena cava with primary closure or patch repair of the renal vein orifice. Stents were removed from the renal vein during the back table flush and preparation of the kidney for reimplantation. This maneuver was able to be done by everting the vein with preservation of enough renal vein length for autotransplantation in all cases. Statistically significant differences were noted between the two centers in surgical approach, length of operation, and length of stay. Fifty-nine percent of the renal autotransplants performed at CU were done robotically and likely contributed to these differences as compared with UW, which performed 95.9% using standard open techniques ( Table III ). The rate of major complications was low after nephrectomy with autotransplantation. There were no deaths and only two graft losses within the follow-up period. Overall, 8 of the 105 patients had return to the operating room in the first 30 days. Reasons for reoperation were bleeding (n = 3), bowel injury or compromise (n = 3), and vascular compromise of the autotransplant requiring nephrectomy (n = 2). Across both centers and all surgical techniques, the highest rate of complications at 30 days were hospital readmission (21%), incision paresthesia (18%), and UTI (13%) ( Table IV ) The reasons for readmissions were small bowel obstruction/ileus (n = 6), perinephric/abdominal fluid collection (n = 6), pain control (n = 5), UTI (n = 3), and deep vein thrombosis (n = 1). Follow-up complications at 1 year demonstrated a 30.4% UTI rate with only 5.7% of patients having three or more UTIs and 7.6% rate of pyelonephritis despite the kidney being replaced anatomically next to the bladder with a very short ureter. Forty-four percent of patients who had UTIs in the first year developed them in the immediate postoperative period and 30% of patients had a history of UTI before autotransplantation ( Table I ). Table III Surgical details All (n = 105) CU (n = 32) UW (n = 73) P value Surgery type <.001  Laparoscopic a 11 (10.5) 8 (25.0) 3 (4.1)  Open b 75 (71.4) 5 (15.6) 70 (95.9)  Robotic c 19 (18.1) 19 (59.4) 0 (0.0) Length of operation, minutes 347.5 ± 106.2 465.3 ± 82.7 295.8 ± 66.8 <.001 Length of hospital stay, days 7.1 ± 5.7 5.0 ± 2.3 8.0 ± 6.4 <.001 CU , University of Colorado Hospital; UW , University of Wisconsin, Madison. Data presented as number (%) or mean ± standard deviation. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t  test. a Laparoscopic nephrectomy and open transplant. b Open nephrectomy and open transplant. c Robotic nephrectomy and robotic transplant. Table IV Complications at 30 days and 1 year follow-up All (n = 105) CU (n = 32) UW (n = 73) P value 30-Day follow-up  UTI 14 (13.3) 5 (15.6) 9 (12.3) .8  Lymphocele 4 (3.8) 2 (6.3) 2 (2.7) .6  Lymphocele requiring intervention 3 (2.9) 2 (6.3) 1 (1.4) .2  Ileus 10 (9.5) 0 (0.0) 10 (13.7) .03  SBO 10 (9.5) 0 (0.0) 10 (13.7) .03  Paresthesia 19 (18.1) 3 (9.4) 16 (21.9) .2  Hernia 1 (1.0) 1 (3.1) 0 (0.0) .3  SSI 2 (1.9) 0 (0.0) 2 (2.7) 1.0  Nonsurgical procedure 7 (6.7) 3 (9.4) 4 (5.5) .4  Return to OR 8 (7.6) 4 (12.5) 4 (5.5) .2  Readmission 21 (20.0) 7 (21.9) 14 (19.2) .8 1-Year follow-up  Graft loss 2 (1.9) 1 (3.1) 1 (1.4) .5  Hernia 6 (5.7) 0 (0.0) 6 (8.2) .2  UTIs (≥1) 32 (30.4) 9 (28.1) 23 (31.5) .6  Pyelonephritis 8 (7.6) 2 (6.3) 6 (8.2) 1.0  Creatinine 0.773 ± 0.194 0.884 ± 0.296 0.732 ± 0.120 .03  eGFR 95.0 ± 21.7 83.8 ± 22.2 99.1 ± 20.1 .004  Delta creatinine −0.048 ± 0.180 −0.156 ± 0.187 −0.006 ± 0.160 <.001  Delta eGFR 6.2 ± 26.3 4.6 ± 27.7 6.8 ± 26.0 .7 CU , University of Colorado Hospital; eGFR , estimated glomerular filtration rate; NCS , nutcracker syndrome; OR , operating room; SBO , small bowel obstruction; SSI , surgical site infection; UTI , urinary tract infection; UW , University of Wisconsin, Madison. Data presented as number (%) or mean ± standard deviation. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t  test. Delta is the difference between the baseline and 12-month creatinine and eGFR. Surgical details CU , University of Colorado Hospital; UW , University of Wisconsin, Madison. Data presented as number (%) or mean ± standard deviation. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t  test. Laparoscopic nephrectomy and open transplant. Open nephrectomy and open transplant. Robotic nephrectomy and robotic transplant. Complications at 30 days and 1 year follow-up CU , University of Colorado Hospital; eGFR , estimated glomerular filtration rate; NCS , nutcracker syndrome; OR , operating room; SBO , small bowel obstruction; SSI , surgical site infection; UTI , urinary tract infection; UW , University of Wisconsin, Madison. Data presented as number (%) or mean ± standard deviation. Comparisons between CU and UW cohorts were performed with Pearson's χ 2 test or t  test. Delta is the difference between the baseline and 12-month creatinine and eGFR. By the 1-year follow-up, only four patients (3.8%) were lost to follow-up ( Fig 1 , A ). Excluding those patients lost to follow-up at 12 months, 93.1% of the patients reported complete resolution of their left flank pain. Nearly one-half (48.6%) of the entire cohort were using opioids before renal autotransplantation ( Fig 1 , B ) and there was a statistically significant decrease to 17% of the cohort by 12 months. A small portion of patients (n = 11) who reported resolution of left flank pain were still using opioids at the 12-month follow-up. These patients had chronic pain separate from their left flank pain owing to nutcracker syndrome, which was not impacted by nephrectomy and autotransplantation. Fig 1 Reported flank pain and opioid use over 12 months following renal autotransplant. The percentage of patients who reported flank pain (A) and opioid use (B) are depicted in black (yes). White bars (no) show those who did not have flank pain or opioid use and gray bars (missing) show the number of patients that had missing data. Paired McNamar's test was used to determine differences in the proportion of patients in each category at every timepoint. ∗∗∗ P  < .001. Reported flank pain and opioid use over 12 months following renal autotransplant. The percentage of patients who reported flank pain (A) and opioid use (B) are depicted in black (yes). White bars (no) show those who did not have flank pain or opioid use and gray bars (missing) show the number of patients that had missing data. Paired McNamar's test was used to determine differences in the proportion of patients in each category at every timepoint. ∗∗∗ P  < .001. Across the entire cohort the mean MMEs per day was 33.4 ± 8.0 at baseline, which decreased by 69.2%, to a mean of 12.6 ± 5.4 per day, at the 12-month follow-up ( Fig 2 , A ). In those patients using opioids before renal autotransplantation, the baseline MMEs were 68.9 ± 15.0 per day ( Fig 2 , B ). A statistically significant decrease to 25.0 ± 11.02 MMEs per day (67.9% decrease) was observed in this at-risk subgroup. Importantly, 100% of patients who did not report opioid use at baseline were completely off opioids by 12 months after the operation. Fig 2 Pain medication use over 12 months after renal autotransplant. Morphine milligram equivalents ( MMEs ) per day were calculated from the medical records at each timepoint (baseline and postoperatively) and displayed as the mean ± standard error. (A and B) A related-samples Friedman's two-way analysis of variance by ranks summary was used to analyze differences across time points. To test the statistical differences in MME between patients who were on opioids (solid line) at baseline compared with those who were not ( B, dotted line ) at each timepoint, an independent-samples Mann-Whitney U test was performed. For each timepoint, statistical significance was achieved at P  < .001 or P = .002 as indicated. Pain medication use over 12 months after renal autotransplant. Morphine milligram equivalents ( MMEs ) per day were calculated from the medical records at each timepoint (baseline and postoperatively) and displayed as the mean ± standard error. (A and B) A related-samples Friedman's two-way analysis of variance by ranks summary was used to analyze differences across time points. To test the statistical differences in MME between patients who were on opioids (solid line) at baseline compared with those who were not ( B, dotted line ) at each timepoint, an independent-samples Mann-Whitney U test was performed. For each timepoint, statistical significance was achieved at P  < .001 or P = .002 as indicated.

Nutcracker syndrome is an uncommon but challenging disorder that primarily effects young women. Owing to the severe left flank pain associated with nutcracker syndrome and the difficulties with diagnosis, there is a high prevalence of self-reported opioid use in these women. 5 This study examined the characteristics, flank pain resolution, and opioid cessation or reduction from the largest multicenter cohort to date of patients diagnosed with nutcracker syndrome who were treated definitively with renal autotransplantation. Nearly one-third of this cohort had undergone at least one prior vascular intervention or surgery for nutcracker syndrome, without resolution. Notably, 93.1% of our patients treated with renal autotransplantation had durable and complete flank pain relief at 12 months with a 62% decrease in the mean MMEs across cohorts. These results occurred despite statistically significant differences in the surgical approach used and the operation being performed by five different surgeons over the study period. No patient in this series has required reintervention for recurrent left renal vein obstruction and there was no clinical decrease in renal function as measured by the eGFR at 12 months. The complication profile associated with renal autotransplantation in this study seems to be acceptable and comparable with other surgical treatment options described in the literature. 4 , 8 The primary referral reason for this cohort was flank pain, with nearly half of the cohort already using opioids for pain relief. Of those patients, the mean MMEs before renal autotransplantation were in excess of 65 MMEs per day. For perspective, a MMEs of >50 per day doubles the risk of opioid overdose death as compared with 20 MMEs per day. 1 Collectively, these data suggest that renal autotransplantation is an acceptable definitive cure for the flank pain associated with nutcracker syndrome, either as a primary treatment or a salvage therapy, with simultaneous total cessation or dramatic decrease in the amount of opioid dosage after surgical recovery. It is important to note that even in this highly selected cohort representing two high-volume transplant centers, 7% of patients did not experience relief of flank pain and 11% of patients with self-reported resolution of left flank pain remained on opioids at 12 months after autotransplantation. Thus, discussion of treatment failure rate and complication profiles with patients are necessary when considering renal autotransplantation. Left renal vein transposition (LRVT) is often cited as the standard of care for patients with severe symptoms of nutcracker syndrome with a reported 80% to 90% resolution or improvement of flank pain. 4 , 11 , 12 Those series also suggest a portion (27%-32%) of patients will require reintervention owing to stenosis and/or recurrence of symptoms. 11 , 12 Several reports of ongoing chronic flank pain after LRVT or left renal vein stent placement, despite normal findings and no evidence of left renal vein obstruction, have also been published. 13 , 14 In our series, 21.9% of patients had undergone a previous LRVT or left renal vein stent placement, but were still experiencing flank pain at the time of referral without evidence of vein occlusion. This discrepancy in radiographic findings after treatment with LRVT or left renal vein stent and patient-reported symptoms suggests that nutcracker syndrome must also have an underappreciated neuropathic component. Indeed, the nomenclature of nutcracker phenomena vs nutcracker syndrome suggests that not all patients with radiographic findings of severe left renal vein compression will experience pain. 12 The kidney's sympathetic, parasympathetic, and sensory innervation has largely been elucidated after years of research in the areas of nephrolithiasis related renal colic and renal hypertension. 15 With a specific focus on the somatic nerves of the kidney, the pioneering animal studies by the Ammons' series provide the most insight into neurophysiology of renal pain. 15 , 16 , 17 These studies demonstrated that the thoracolumbar spinal nerves receive the renal A delta- and C-fiber sensory inputs with the convergence of nearby somatic nerves. These signals ultimately get interpreted in the ventrolateral medulla. Thus, a noxious insult perceived by renal afferent A-delta and C-sensory fibers, be it a from ureteral obstruction or renal vein obstruction, is most likely the neurophysiological basis for patient perceived renal pain. 15 , 16 , 17 It is possible that these afferent sensory fibers can become damaged in the setting of venous hypertension from nutcracker syndrome, resulting in pain that persists in some patients after relief of venous outflow obstruction via LVRT or left renal vein stenting. It is also likely that there are neurological etiologies of left flank pain owing to the left kidney that are independent of venous hypertension, but may present very similarly. LPHS is one example of such a syndrome that is characterized primarily by hematuria and left flank pain. 18 These neurological etiologies of pain provide another explanation for why pain may persist even after a decrease in left renal vein pressures after LVRT or left renal vein stenting. The presumed underlying neurophysiology of the renal somatic system is the basis for using the UW-LPHS test before surgery. 10 Seventy percent of the patients in this study had the UW-LPHS test used as confirmatory test before surgery by blocking the renal afferent sensory fibers to see who would experience complete pain relief. This test had previously been shown to be the predictor of clinical success of renal autotransplantation following a failed LRVT in a small case series. 13 Our data suggest that renal autotransplantation may be a better treatment option with regard to the neuropathic component of nutcracker syndrome by definitively and completely denervating the somatic nerves of the kidney upon its removal from its orthotopic location. Treating patients with nutcracker syndrome with minimal morbidity and maximal efficacy is the objective of anyone managing this debilitating condition. Recently, at the forefront of minimally invasive approaches, is endovascular and extravascular stent placements. A recent systematic meta-analysis review of extravascular (n = 63) and endovascular stent placements (n = 170), demonstrated symptom relief between 76% to 83% in a predominantly male population (62%). 9 In the included studies, pain was not necessarily the primary symptom for intervention. The predominantly male population in those studies had higher incidences of concomitant hematuria, varicoceles, and infertility issues. 9 Thus, it is difficult to compare those results with our results because it seems that these are different subsets of the nutcracker syndrome population. Minimally invasive robotic autotransplantation surgery in the treatment of nutcracker syndrome is also showing promise as acceptable minimally invasive alternative to open surgery, with potential lower morbidity and hospital length of stay. 19 Close to 20% of the renal autotransplants performed in this study were done robotically with no difference in the primary outcome of pain relief and cessation or decreased use of opioids. This study has several important limitations. All the data were collected retrospectively by review of clinical records. The primary outcome of pain was self-reported and likely subject to some bias. Given that we report follow-up out to 1 year for >95% of the cohort and that the primary indication for intervention was also self-reported pain, subjective reporting of pain is an important patient-centered outcome for this population. We hope that future prospective studies can include more robust standardized pain and quality-of-life questionnaires, but this was not possible in this study owing to the retrospective nature. Evaluation of opioid use by MMEs does provide a quantitative and medically relevant outcome given the harmful impact of long-term opioid use. Additionally, our study is limited by only having follow-up out to 1 year. This time point was chosen because it is the standard postoperative follow-up interval used by our clinical centers and there was no consistent follow-up for patients beyond this time point. Although longer term follow-up would add additional information, 1 year of follow-up is well beyond most standard surgical follow-up intervals and does provide strong evidence regarding the durability of the positive impacts of renal autotransplantation for nutcracker syndrome. We hope to evaluate 5- and 10-year outcomes in future studies. Finally, similar to many of the previous studies evaluating interventions for nutcracker syndrome, there is only one intervention included in our study. This study presents a large, multi-institutional cohort demonstrating that renal autotransplantation is a safe and effective treatment for nutcracker syndrome. nutcracker syndrome is a debilitating pain syndrome primarily impacting women. Our study demonstrates durable resolution of flank pain and statistically significant reduction in opioid use in patients with nutcracker syndrome after renal autotransplantation. Although these results are impactful, future work is needed to further characterize the impact of flank pain in nutcracker syndrome on quality of life as well as to evaluate durability of renal autotransplantation results in longer term follow-up.

None.