MAUDE Adverse Event Report: Q-MED DEFLUX; AGENT, BULKING, INJECTABLE FOR GASTRO-UROLOGY USE

Device Problem Adverse Event Without Identified Device or Use Problem (2993)

Patient Problems Calcium Deposits/Calcification (1758); Obstruction/Occlusion (2422); Abdominal Distention (2601); Renal Impairment (4499); Appropriate Clinical Signs, Symptoms, Conditions Term / Code Not Available (4581)

Event Type  Injury  

Manufacturer Narrative

Company comment: the serious events of hydronephrosis, urethral obstruction, implant site calcification and renal impairment, and the non-serious event of abdominal distension were considered expected and possibly related to the treatment.Serious criteria included required intervention in form of left uvj dilation with left ureteral stent placement and left simple nephrectomy to prevent permanent damage.Potential root cause include product calcification leading to ureteral obstruction and its manifestations.Alternative etiology for renal impairment could include potential antibiotic use for prophylaxis of recurrent utis.The case meets the criteria for expedited reporting to the regulatory authorities.Product note:routine investigations have been performed and provide sufficient information to assess the potential root cause and indicate a possible association to the treatment procedure.Lot number was not reported and the product could not be verified.The information in this case does not indicate a non-conforming product or malfunction.The performed investigations are therefore considered adequate and no additional investigations will be conducted.No corrective or preventive actions are deemed necessary based on the outcome of the performed investigations.

Event Description

Case reference number us(b)(4) is a literature report identified on 16-may-2022 during literature screening.This case was described in the literature article hannah pham, jason au, eric jones, deflux calcification leading to delayed obstruction and loss of renal function: a case report, urology (2022), doi: https://doi.Org/10.1016/j.Urology.2022.04.025.Abstract dextranomer/hyaluronic acid (deflux) has been widely used in the treatment of vesicoureteral reflux in the pediatric population.It has demonstrated acceptable early efficacy with minimal morbidity.Early complications from deflux have been reported to occur in approximately 1% of cases.However, late complications from deflux use, including calcification and delayed ureteral obstruction, are less well understood.We present the case of an asymptomatic 11 year old girl with severe ipsilateral hydroureteronephrosis, identified nearly 8 years after treatment.This case details a rare instance of loss of renal function after deflux use in a patient with no apparent risk factors.Introduction we discuss such a case, with dramatic loss of ipsilateral renal function that resulted in nephrectomy.Case report this is the case of a 11-year-old girl with trisomy 21, who initially presented at 18 months of age with recurrent febrile urinary tract infections.Initial imaging studies included a renal ultrasound and voiding cystourethrogram (vcug).The kidneys appeared normal on ultrasound.The vcug demonstrated left grade 3 vur.She was followed non-operatively on trimethoprim-sulfamethoxazole for uti prophylaxis.On repeat vcug at 2 ½ years of age, she had persistent left grade 3 vur.The pre-deflux renal ultrasound demonstrated similar renal length (right kidney was 6cm and left kidney was 6.1cm), no hydronephrosis, and normal corticomedullary differentiation of both kidneys.With normal renal size and volume, the patient was presumed to have normal renal function prior to the procedure.She underwent endoscopic therapy for her vur.A total of 0.8ml of deflux was injected into the left subureteric space using a standard sub-trigonal injection technique (sting).A renal ultrasound was performed 6 weeks after the procedure and was normal.Antibiotic prophylaxis was discontinued with follow-up arranged at one year post procedure.The patient was unfortunately lost to follow-up.Eight years later, she had an abdominal ultrasound obtained for abdominal fullness and was incidentally noted to have severe left hydroureteronephrosis.Prior to the study, she had no evidence of recurrent utis or obstructive urinary symptoms.Dedicated renal ultrasound demonstrated society of fetal urology (sfu) grade 4 hydronephrosis and a 1.4cm echogenic focus at the left uvj concerning for a calculus.Mag3 renal scan with lasix showed obstructive parameters on the left, and differential renal function of 15% left and 85% right.Serum creatinine was 0.76 (egfr 63), and cystatin c was 1.1.The patient initially underwent left uvj dilation with left ureteral stent placement.The left ureteral orifice was noted to be orthotopically located however significantly deformed from the prior deflux procedure.Three weeks later, the patient had a repeat mag3 renal scan with lasix.The differential renal function was 7.5% left (previously 15%) and 92.5% right (previously 85%).The patient subsequently underwent an uneventful left simple nephrectomy and has done well.Discussion vesicoureteral reflux is seen in approximately 1.8% of children with many of these patients managed endoscopically with deflux injection.Early experience with deflux demonstrated a low initial complication rate, and success rates as high as 93% with lower grade vur.Unfortunately with longer follow-up, a number of troubling late complications have been reported, including delayed vur recurrence, calcification of the deflux mound, and ureteral obstruction.We report a rare case of a calcified deflux mound associated with delayed ureteral obstruction resulting in severe hydronephrosis and ultimately kidney removal.Delayed calcification of deflux has been widely reported and occurs with an incidence of approximately 2% after 4 years.Only a few cases have reported the association of deflux calcification and ureteral obstruction.While it is impossible to prove causality between calcification and ureteral obstruction in the case presented above, deflux injection does have the capacity to cause an extensive foreign body reaction, granuloma formation, and calcification leading to ureteral obstruction.The various injection techniques of deflux may contribute to ureteral obstruction.There are three common injection techniques for the treatment of vur: sting, hit, and double-hit.The sting technique has been reported in several cases of ureteral obstruction, however ureteral obstruction has been observed following each of these injection techniques.Currently, there is no clear evidence of increased risk of ureteral obstruction with a specific injection technique.In our case, the pre-deflux kidney appeared normal, and was presumed to possess normal function.Pre-nephrectomy ureteral stenting allowed decompression of the kidney and more accurate assessment of function.As the cohort of deflux-treated patients ages, we are likely to see more cases of delayed ureteral obstruction.Papagiannopoulos et al.Recently reported a small cohort of patients with delayed obstruction from deflux, also resulting in loss of renal function.In contrast to our report, deflux was used in an off-label fashion in all cases.Each patient had risk factors for ureteral obstruction.Ours is the first case reporting renal loss after on-label use of deflux and without risk factors.While deflux may be a reasonable treatment option for select patients with vur, open ureteral reimplantation still remains the gold standard with better success rates and acceptably low complication rates.Ureteral obstruction is a well-recognized complication of reimplantation with a rate of up to 5%, however the literature on late/delayed obstruction remains scarce and there have been no recent reports other than transient obstruction with pregnancy.Ours is a cautionary tale of renal loss attributed to unilateral deflux injection.It is possible that this complication could have been prevented with better follow-up, and it highlights the importance of sonographic evaluation beyond the immediate post-op period.Unfortunately, obstruction and renal loss after deflux injection can be insidious and asymptomatic.Fortunately, it appears to be an exceedingly rare complication.Conclusion delayed ureteral obstruction from calcified deflux can be silent and lead to irreversible damage to the kidney.Patients should have long-term follow up with upper tract imaging to rule out obstruction and ensure preservation of kidney function.

Manufacturer Narrative

Company comment: the serious events of hydronephrosis, urethral obstruction, implant site calcification and renal impairment, and the non-serious event of abdominal distension were considered expected and possibly related to the treatment.Serious criteria included required intervention in form of left uvj dilation with left ureteral stent placement and left simple nephrectomy to prevent permanent damage and hospitalization.Potential root cause include product calcification leading to ureteral obstruction and its manifestations.Alternative etiology for renal impairment could include potential antibiotic use for prophylaxis of recurrent utis.The case meets the criteria for expedited reporting to the regulatory authorities.Product note:routine investigations have been performed and provide sufficient information to assess the potential root cause and indicate a possible association to the treatment procedure.Lot number was not reported and the product could not be verified.The information in this case does not indicate a non-conforming product or malfunction.The performed investigations are therefore considered adequate and no additional investigations will be conducted.No corrective or preventive actions are deemed necessary based on the outcome of the performed investigations.

Event Description

Case reference number (b)(4) is a literature report identified on 16-may-2022 during literature screening.This case was described in the literature article pham h, au j, jones e, deflux calcification leading to delayed obstruction and loss of renal function: a case report.Urology 2022;166:246-249.Abstract: dextranomer/hyaluronic acid (deflux) has been widely used in the treatment of vesicoureteral reflux in the pediatric population.It has demonstrated acceptable early efficacy with minimal morbidity.Early complications from deflux have been reported to occur in approximately 1% of cases.However, late complications from deflux use, including calcification and delayed ureteral obstruction, are less well understood.We present the case of an asymptomatic 11 year old girl with severe ipsilateral hydroureteronephrosis, identified nearly 8 years after treatment.This case details a rare instance of loss of renal function after deflux use in a patient with no apparent risk factors.Introduction: we discuss such a case, with dramatic loss of ipsilateral renal function that resulted in nephrectomy.Case report: this is the case of a 11-year-old girl with trisomy 21, who initially presented at 18 months of age with recurrent febrile urinary tract infections.Initial imaging studies included a renal ultrasound and voiding cystourethrogram (vcug).The kidneys appeared normal on ultrasound.The vcug demonstrated left grade 3 vur.She was followed non-operatively on trimethoprim-sulfamethoxazole for uti prophylaxis.On repeat vcug at 2 ½ years of age, she had persistent left grade 3 vur.The pre-deflux renal ultrasound demonstrated similar renal length (right kidney was 6cm and left kidney was 6.1cm), no hydronephrosis, and normal corticomedullary differentiation of both kidneys.With normal renal size and volume, the patient was presumed to have normal renal function prior to the procedure.She underwent endoscopic therapy for her vur.A total of 0.8ml of deflux was injected into the left subureteric space using a standard sub-trigonal injection technique (sting).A renal ultrasound was performed 6 weeks after the procedure and was normal.Antibiotic prophylaxis was discontinued with follow-up arranged at one year post procedure.The patient was unfortunately lost to follow-up.Eight years later, she had an abdominal ultrasound obtained for abdominal fullness and was incidentally noted to have severe left hydroureteronephrosis.Prior to the study, she had no evidence of recurrent utis or obstructive urinary symptoms.Dedicated renal ultrasound demonstrated society of fetal urology (sfu) grade 4 hydronephrosis and a 1.4cm echogenic focus at the left uvj concerning for a calculus.Mag3 renal scan with lasix showed obstructive parameters on the left, and differential renal function of 15% left and 85% right.Serum creatinine was 0.76 (egfr 63), and cystatin c was 1.1.The patient initially underwent left uvj dilation with left ureteral stent placement.The left ureteral orifice was noted to be orthotopically located however significantly deformed from the prior deflux procedure.Three weeks later, the patient had a repeat mag3 renal scan with lasix.The differential renal function was 7.5% left (previously 15%) and 92.5% right (previously 85%).The patient subsequently underwent an uneventful left simple nephrectomy and has done well.Discussion: vesicoureteral reflux was seen in approximately 1.8% of children with many of these patients managed endoscopically with deflux injection.Early experience with deflux demonstrated a low initial complication rate, and success rates as high as 93% with lower grade vur.Unfortunately with longer follow-up, a number of troubling late complications have been reported, including delayed vur recurrence, calcification of the deflux mound, and ureteral obstruction.We report a rare case of a calcified deflux mound associated with delayed ureteral obstruction resulting in severe hydronephrosis and ultimately kidney removal.Delayed calcification of deflux has been widely reported and occurs with an incidence of approximately 2% after 4 years.Only a few cases have reported the association of deflux calcification and ureteral obstruction.While it is impossible to prove causality between calcification and ureteral obstruction in the case presented above, deflux injection does have the capacity to cause an extensive foreign body reaction, granuloma formation, and calcification leading to ureteral obstruction.The various injection techniques of deflux may contribute to ureteral obstruction.There are three common injection techniques for the treatment of vur: sting, hit, and double-hit.The sting technique has been reported in several cases of ureteral obstruction, however ureteral obstruction has been observed following each of these injection techniques.Currently, there is no clear evidence of increased risk of ureteral obstruction with a specific injection technique.In our case, the pre-deflux kidney appeared normal, and was presumed to possess normal function.Pre-nephrectomy ureteral stenting allowed decompression of the kidney and more accurate assessment of function.As the cohort of deflux-treated patients ages, we are likely to see more cases of delayed ureteral obstruction.Papagiannopoulos et al.Recently reported a small cohort of patients with delayed obstruction from deflux, also resulting in loss of renal function.In contrast to our report, deflux was used in an off-label fashion in all cases.Each patient had risk factors for ureteral obstruction.Ours is the first case reporting renal loss after on-label use of deflux and without risk factors.While deflux may be a reasonable treatment option for select patients with vur, open ureteral reimplantation still remains the gold standard with better success rates and acceptably low complication rates.Ureteral obstruction is a well-recognized complication of reimplantation with a rate of up to 5%, however the literature on late/delayed obstruction remains scarce and there have been no recent reports other than transient obstruction with pregnancy.Ours is a cautionary tale of renal loss attributed to unilateral deflux injection.It is possible that this complication could have been prevented with better follow-up, and it highlights the importance of sonographic evaluation beyond the immediate post-op period.Unfortunately, obstruction and renal loss after deflux injection can be insidious and asymptomatic.Fortunately, it appears to be an exceedingly rare complication.Conclusion: delayed ureteral obstruction from calcified deflux can be silent and lead to irreversible damage to the kidney.Patients should have long-term follow up with upper tract imaging to rule out obstruction and ensure preservation of kidney function.Tracking list: v.0 initial.V.1 fu received on 16-aug-2022 from the same reporter: seriousness criteria of hospitalization added.Outcome of the events urethral obstruction, implant site calcification and hydronephrosis was updated from resolved to resolving.Laboratory test information was updated.

• Brand Name: DEFLUX
• Type of Device: AGENT, BULKING, INJECTABLE FOR GASTRO-UROLOGY USE
• Manufacturer (Section D): Q-MED; seminariegatan 21; uppsala, SE-75 228; SW SE-75228
• Manufacturer (Section G): Q-MED; seminariegatan 21; uppsala, SE-75 228; SW SE-75228
• Manufacturer Contact: randy russell ; 14501 n. freeway; fort worth, TX 76177
• MDR Report Key: 14649236
• MDR Text Key: 294839755
• Report Number: 9710154-2022-00034
• Device Sequence Number: 1
• Product Code: LNM
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: P000029
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Literature,Health Professional
• Reporter Occupation: Physician
• Type of Report: Initial,Followup
• Report Date: 09/07/2022

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Initial Date Manufacturer Received: 05/16/2022
• Initial Date FDA Received: 06/09/2022
• Supplement Dates Manufacturer Received: 08/16/2022
• Supplement Dates FDA Received: 09/07/2022
• Was Device Evaluated by Manufacturer?: No
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Unknown
• Patient Sequence Number: 1
• Treatment: ANTIBIOTICS; COTRIMOXAZOLE (SULFAMETHOXAZOLE, TRIMETHOPRIM)
• Patient Outcome(s): Required Intervention; Hospitalization
• Patient Age: 11 YR
• Patient Sex: Female