Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis.

Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.

Solid organ transplant recipients can be highly immune suppressed, and infection with Coccidioides (valley fever) after transplant can lead to severe infections in these patients. Our study showed that fluconazole was safe and effective for preventing Coccidioides in kidney transplant recipients.

Deep cutaneous mycoses in kidney transplant recipients: Diagnostic and therapeutic challenges.

Deep cutaneous mycoses (DCMs) are rare infections that extend throughout the dermis and subcutis, often occurring after inoculation with pathogenic fungi. Trends toward a growing incidence have been observed that may be partially related to an increasing population of solid organ transplant patients. The aim of this study is to describe the diagnostics and the outcomes of DCM among kidney transplant recipients so as to optimize their management. We performed a retrospective review of cases of DCM occurring among kidney transplant recipients in our institution over 12 years. Twenty cases were included. Lesions were only located on the limbs and presented mainly as single (10/20, 50%) nodular lesions (15/20, 75%), with a mean size of 3 cm. Direct mycological examination was positive for 17 patients (17/20, 85%) and the cultures were consistently positive. Thirteen different fungal species were observed, including phaehyphomycetes (n = 8), hyalohyphomycetes (n = 3), dermatophytes (n = 1), and mucorale (n = 1). The (1-3) beta-D-glucan antigen (BDG) was also consistently detected in the serum (20/20, 100%). Systematic imaging did not reveal any distant infectious lesions, but locoregional extension was present in 11 patients (11/14, 79%). Nineteen patients received antifungal treatment (19/20, 95%) for a median duration of 3 months, with surgery for 10 (10/20, 50%). There is a great diversity of fungal species responsible for DCMs in kidney transplant recipients. The mycological documentation is necessary to adapt the antifungal treatment according to the sensitivity of the species. Serum BDG positivity is a potentially reliable and useful tool for diagnosis and follow-up.

Effect of metastatic calcification on complication rate and survival in 74 renal transplant cats (1998-2020).

OBJECTIVE: To report the incidence of metastatic calcification in cats with renal failure presenting for renal transplantation, and to determine if metastatic calcification detected prior to renal transplantation is associated with complication rates and patient survival. STUDY DESIGN: Retrospective case series. SAMPLE POPULATION: Seventy-four cats. METHODS: In imaging studies, 178 feline renal transplant recipients from 1998 to 2020 were evaluated for metastatic calcification. Demographic, clinicopathological data, intraoperative complications, postoperative complications, need for hemodialysis, and survival times were recorded. Exclusion criteria were cats lacking imaging reports and cats with gastric, renal, or tracheal/bronchial calcification alone. Univariable and multivariable analyses were performed to determine variables that were independently associated with survival. Kaplan-Meier analysis was used to generate survival plots and estimate median survival times with a 95% confidence interval (CI). RESULTS: Seventy four of 178 cats met the inclusion criteria. Fifteen of 74 (20.3%) cats had metastatic calcification prior to renal transplantation. Twelve of 74 (16.2%) cats developed calcification following transplantation, and 47 of 74 (63.5%) cats had no calcification during the study period. Median follow-up time was 472 days, with a range of 0-1825 days. Cats with pretransplant calcification had shorter median survival times (147 days) than cats without calcification (646 days) (p = .0013). Metastatic calcification pretransplant was associated with an increased risk of death by 240% (95% CI, 1.22-4.71). CONCLUSION: Metastatic calcification in renal transplant cats is a negative prognostic indicator and is associated with decreased survival times. CLINICAL SIGNIFICANCE: These findings may help guide therapeutic recommendations and owner expectations in cats undergoing renal transplantation.

Characterization of preoperative cardiovascular status and association with outcome following feline renal allograft transplantation: 166 cases.

OBJECTIVES: To retrospectively evaluate preoperative historical, biochemical, and cardiovascular screening data for predictors of survival to discharge and long-term survival in feline renal allograft recipients from 1 institution. ANIMALS: 166 cats that underwent renal transplantation at the University of Pennsylvania between 1998 and 2018. PROCEDURES: Medical records were reviewed for preoperative historical information, biochemical data, and cardiac assessment including auscultation findings, pre- and postoperative systolic blood pressure measurements, thoracic radiographic evaluation, and echocardiographic measurements. The need for hemodialysis, the number of surgical procedures, native kidney biopsy diagnosis and survival time was also recorded. Kaplan-Meier analysis was used to generate survival plots and estimate median survival times with a 95% CI. Univariable and multivariable analysis were performed to determine variables that were independently associated with survival to discharge and long-term survival. RESULTS: The patient population primarily consisted of adult male DSH cats (70%) diagnosed with IRIS stage 4 CKD (66.3%). Abnormalities identified on preoperative cardiac assessment, including hypertension, the presence of a murmur, echocardiographic changes, and radiographic signs of congestive heart failure, were not associated with survival to discharge or long-term survival. Age was the only single significant variable associated with survival, and the risk of death increased by 11% (95% CI, 6% to 17%) for every 1 year in patient age. CLINICAL RELEVANCE: The presence of cardiac abnormalities identified during the screening process of cats presenting for transplantation should not immediately exclude a potential candidate for the procedure. Owners considering transplantation should be educated on the impact of age on survival following surgery.

Retroperitoneal fibrosis as a postoperative complication following renal transplantation in cats.

OBJECTIVES: The aim of this report was to describe the clinical signs, diagnostic imaging findings, surgical management, histopathological findings, outcome and possible risk factors for cats that developed retroperitoneal fibrosis (RPF) following renal transplantation. METHODS: Medical records of cats that underwent renal transplantation and developed clinically significant RPF between 1995 and 2019 were reviewed. RESULTS: Eighty-one cats underwent 83 renal transplantations. Of these 81 cats, six developed clinically significant RPF. For all six cats, renal transplantation was performed using cold organ preservation solution and ureteral papilla implantation. Immunosuppression protocol included ciclosporin and prednisolone. All cats had at least one subtherapeutic trough ciclosporin level (<250 ng/ml) in the postoperative period. Cats presented with moderate-to-severe azotemia 39-210 days following renal transplantation. Abdominal ultrasonography and contrast pyelography revealed various degrees of hydroureter and hydronephrosis of the transplanted kidney. Surgical examination revealed a layer of dense fibrous tissue surrounding the transplanted kidney, ureter and bladder resulting in ureteral obstruction. Ureteral obstruction was managed by reimplantation of the proximal ureter or renal pelvis to the bladder. Histopathologic examination of the fibrous tissue and affected portion of the distal ureter revealed fibrous connective tissue with lymphoplasmacytic infiltration and perivascular inflammation suggestive of an autoimmune type reaction. Of the six cats, two died within 5 days after revision surgery, two developed signs consistent with recurrent partial ureteral obstruction (40 and 41 days after revision), one was euthanized 6 years later for an unrelated disease and one was lost to follow-up. CONCLUSIONS AND RELEVANCE: The incidence of RPF in this population of cats was relatively low (7%), but still represents a significant cause of morbidity and mortality. The cause of RPF remains unknown, although investigation into suboptimal immunosuppression as a potential cause for local rejection reaction is warranted.

Renal Osteodystrophy due to Secondary Hyperparathyroidism in a Cat.

A 6 yr old neutered male mixed-breed cat presented for renal transplantation (RTx) for chronic kidney disease. Severe periodontal disease was identified, and before initiation of immunosuppressive therapy, a comprehensive oral health assessment and treatment procedure was performed to reduce the burden of existing oral infection. Dental radiography revealed diffuse, severe bone demineralization across the mandible and maxilla, with thinning of the cortices. Nasal turbinates were easily visualized owing to the decreased opacity of maxillary bone. Generalized bone resorption left teeth to appear minimally attached. A Vitamin D panel revealed a severely elevated parathyroid hormone level. Full mouth extractions were performed. Seven days following this procedure, RTx was performed. Serum creatinine concentration was within normal limits by 48 hr after surgery and remained normal until discharge 12 days after RTx. At 3.5 mo after RTx, the cat was mildly azotemic, and the parathyroid hormone level was elevated but significantly decreased from the original measurement. Secondary hyperparathyroidism is a common abnormality in cats with chronic kidney disease. However, clinical manifestations of hyperparathyroidism are rare in this species. This is a novel presentation of a cat demonstrating bone loss in the oral cavity as a result of renal secondary hyperparathyroidism.

Toxoplasma gondii infection in feline renal transplant recipients: 24 cases (1998-2018).

OBJECTIVE: To evaluate the effects of Toxoplasma gondii infection in feline renal transplant recipients with a preoperative seronegative or unknown serostatus (SN-UNK) for T gondii and the efficacy of lifelong prophylactic treatment of T gondii infection in feline renal transplant recipients with a preoperative seropositive serostatus (SP) for T gondii. ANIMALS: 24 cats with various serostatuses for T gondii before undergoing renal transplantation. PROCEDURES: Medical records of cats that had undergone renal transplantation from 1998 through 2018 were reviewed. Two groups of cats were identified. Before renal transplantation, the SN-UNK group cats were seronegative for T gondii (n = 4) or serostatus for T gondii was unknown (4). The SN-UNK group cats received immunosuppressive therapy but were not maintained on prophylactic treatment of T gondii infection. The SP group cats were seropositive for T gondii (n = 16) prior to initiation of immunosuppressive therapy and renal transplantation and were managed after surgery with prophylactic treatment of T gondii infection. RESULTS: All 8 SN-UNK group cats developed T gondii infections after initiation of immunosuppressive therapy and renal transplantation; T gondii infections were fatal in 6 cats. Of 16 SP group cats, 1 developed a nonfatal T gondii infection resulting in an allograft rejection episode. No SP group cats, which were managed postoperatively with prophylactic treatment, developed a fatal T gondii infection. CONCLUSIONS AND CLINICAL RELEVANCE: T gondii infection resulted in morbidity and death in immunosuppressed cats not receiving prophylactic treatment of T gondii infection after renal transplantation. Seropositive cats were acceptable candidates for renal transplantation when lifelong prophylactic treatment of T gondii infection was provided.

Evaluation of a microvascular anastomotic coupler for end-to-side arterial and venous anastomosis for feline renal transplantation.

OBJECTIVE: To describe the technique and determine the feasibility of an end-to-side (ETS) anastomosis of the renal vein to vena cava and renal artery to aorta using a microvascular anastomotic coupler (MAC) for feline renal transplantation. STUDY DESIGN: In vivo experimental study. ANIMALS: Six purpose-bred domestic shorthair cats. METHODS: The left kidney was autotransplanted using a MAC for ETS vascular anastomosis. Outcomes included intraoperative hemorrhage from the anastomosis sites, duration of anastomoses, surgical complications, postoperative renal perfusion (including resistive index (RI)) measured by Doppler ultrasonography and computed tomography angiography, and histopathological examination of the left kidney and anastomosis sites (30 days). RESULTS: Anastomosis was successful in all cats, and intraoperative hemorrhage was negligible. Intraoperative renal perfusion was considered excellent. Venous and arterial anastomoses were completed in 11 minutes 20 seconds (range, 6:38-13:27) and 21 minutes 50 seconds (range, 11:05-30:24), respectively. Vascular occlusion time was 32 minutes (17:43-42:03). One cat was euthanized 5 hours postoperatively because of bleeding from a muscular arterial branch of the dorsal aorta causing hemoabdomen. Renal perfusion and RI of the remaining five cats were within normal range (<0.8) and similar to the contralateral kidney at all time points. Endothelialization of the anastomosis was complete with mild-to-moderate fibrosis surrounding the MAC in all cats. CONCLUSION: End-to-side anastomosis of the renal vein and artery to the vena cava and aorta, respectively, was consistently achieved in all six cats with the MAC. CLINICAL SIGNIFICANCE: The use of the MAC may be considered as an alternative to hand suturing for ETS anastomoses for feline renal transplantation.

Fatal SV40-associated pneumonia and nephropathy following renal allotransplantation in rhesus macaque.

Recrudescence of latent and dormant viruses may lead to overwhelming viremia in immunosuppressed hosts. In immunocompromised hosts, Simian virus 40 (SV40) reactivation is known to cause nephritis and demyelinating central nervous system disease. Here, we report SV40 viremia leading to fatal interstitial pneumonia in an immunosuppressed host following renal allotransplantation.

Pilot study: use of contrast-enhanced ultrasonography in feline renal transplant recipients.

Objectives The study aims were to evaluate the feasibility of contrast-enhanced ultrasonography in feline renal transplant recipients in the post-transplantation period and to report findings in a case with presumptive delayed allograft ischemia. Methods Cats were imaged postoperatively using contrast harmonic ultrasonography after a bolus injection of a microbubble contrast medium. Time/mean pixel intensity curves were generated for cortical and medullary regions of interest in the renal allograft in each cat. Arrival time, time to peak, wash-in slope, wash-out slope, mean transit time and renal blood flow were calculated for each area. Results Within the renal cortices of cats without ureteral obstruction 1 day post-transplantation, arrival time was 2.0-6.3 s, time to peak was 3.6-30.1 s, wash-in rate was 2.45-41.14 mean pixel intensity (MPI)/s, wash-out rate was -2.01 to -0.47 MPI/s and blood flow was 6.1-106.5 MPI/s. Ratio mean transit time was 0.29-1.29. Typical cortical and medullary perfusion patterns were observed in these cats. In one cat with delayed graft ischemia followed by presumptive acute transplant rejection, dynamic and heterogeneous cortical and medullary perfusion was demonstrated. Decreases in cortical blood flow were paralleled by elevated serum creatinine. Conclusions and relevance Contrast-enhanced ultrasonography can be used in feline renal transplant recipients and provides both qualitative and quantitative data regarding renal allograft perfusion.

A Carrel patch technique for renal transplantation in cats.

OBJECTIVE: To evaluate the feasibility of a Carrel patch method in feline renal transplantation. STUDY DESIGN: Descriptive case series. ANIMALS: Nine healthy donor cats and 9 client recipient cats with chronic renal failure. METHODS: Renal transplantation was performed in 9 cats with chronic renal failure after collection of a donor's left kidney with a Carrel patch technique. A patch of donor aortic wall was removed with either 2 or 1 renal artery (ies) (n = 1 and 8 cats, respectively) central to the patch, with a cuff of tissue (≤1 mm) protruding from the base of the vessels. The Carrel patch was implanted in recipient cats with an end-to-side artery-to-aorta anastomosis, in a simple-continuous pattern of 9-0 nylon. The renal vein and ureter were implanted as previously described. RESULTS: All donors and recipients survived surgery without vascular complication. CONCLUSION: The Carrel patch is a novel approach allowing the harvest of kidneys with multiple renal arteries. The technique also simplified the implant procedure, potentially decreasing the risks of bleeding and thrombosis.

Effect of cold storage on immediate graft function in an experimental model of renal transplantation in cats.

OBJECTIVE To assess the effect of cold storage (CS) on immediate posttransplantation function of renal autografts in cats. ANIMALS 15 healthy 1-year-old cats. PROCEDURES Cats were assigned to 2 groups and underwent autotransplantation of the left kidney followed by nephrectomy of the right kidney. The left kidney was autotransplanted either immediately (IT group; n = 6) or after being flushed with a cold sucrose phosphate solution and stored on ice while the implant site was prepared (CS group; 9). Serum creatinine and BUN concentrations were monitored daily and autografts were ultrasonographically examined intermittently for 14 days after surgery. RESULTS Mean duration of CS was 24 minutes for the CS group. Posttransplantation serum creatinine and BUN concentrations for the CS group had lower peak values, returned to the respective reference ranges quicker, and were generally significantly lower than those for the IT group. Mean posttransplantation autograft size for the CS group was smaller than that for the IT group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that immediate posttransplantation function of renal autografts following a short period of CS was better than that of renal autografts that did not undergo CS, which suggested CS protected grafts from ischemic injury and may decrease perioperative complications, speed recovery, and improve the long-term outcome for cats with renal transplants. IMPACT FOR HUMAN MEDICINE Cats metabolize immunosuppressive drugs in a manner similar to humans; therefore, renal transplantation in cats may serve as a desirable model for investigating the effects of renal transplantation in human patients.

Update on the Current Status of Kidney Transplantation for Chronic Kidney Disease in Animals.

Kidney transplantation is a novel treatment option for cats suffering from chronic renal failure or acute irreversible renal injury. Improvement in quality of life as well as survival times of cats that have undergone transplantation has helped the technique to gain acceptance as a viable treatment option for this fatal disease. This article reviews information regarding the optimal time for intervention, congenital and acquired conditions that have been successfully treated with transplantation, recipient and donor screening, immunosuppressive therapy, recent advances in anesthetic and surgical management, postoperative monitoring and long-term management, and troubleshooting perioperative and long-term complications.

Kidney transplants in cats: RCVS considers its guidance.

■ Guidance on renal transplantation in cats ■ Reforms to the governance of the RCVS ■ Tackling non-compliance with CPD requirements. These were among matters discussed by the RCVS Council at its meeting on March 3. The RCVS President, Bradley Viner, chaired the meeting, which was held at Belgravia House, London SW1P.

Ureteral Papilla Implantation as a Technique for Neoureterocystostomy in Cats Undergoing Renal Transplantation: 30 Cases.

OBJECTIVE: To describe the clinical outcome of donor and recipient cats undergoing ureteral papilla harvest and implantation as a technique for neoureterocystostomy in clinical kidney transplant. STUDY DESIGN: Retrospective case series. ANIMALS: Donor (n=31) and recipient (n=30) cats that underwent kidney harvest and transplantation using ureteral papilla implantation technique for neoureterocystostomy. METHODS: Medical records for donor and recipient cats presented to the University of Wisconsin Veterinary Teaching Hospital from January 2003 to December 2014 were reviewed. Data recorded included complete blood count, serum chemistry panel, surgical technique, diagnostic imaging results, short- and long-term complications, and anesthetic survival. RESULTS: All 30 recipients recovered from anesthesia. Four died within 24 hours and 26 survived to hospital discharge. Serum creatinine was within the reference interval by 72 hours in 22/26 cats (85%). Complications related to the ureteral papilla implantation technique were seen in only 1 cat (3%). Uroabdomen diagnosed on day 3 ultimately resolved over the following 24 hours without surgical intervention. All 31 donor cats survived to discharge. Four donors (13%) experienced mild, transiently increased serum creatinine. CONCLUSION: Ureteral papilla implantation is a viable technique for neoureterocystostomy in cats undergoing kidney transplantation. Proposed benefits for the recipient include a less technically challenging anastomosis, decreased risk of ureteral obstruction at the anastomosis site, and reduced risk of leakage compared to previous reports. Benefits for recipients should be weighed against risks to donors, including a more complex ureteral harvest, increased surgical time, and potential injury or obstruction of the contralateral ureteral papilla.

FIRST STEPS TOWARDS ORGAN BANKS: VITRIFICATION OF RENAL PRIMORDIAL.

BACKGROUND: Kidney transplantation from deceased or living human donors has been limited by donor availability as opposed to the increasing demand, by the risks of allograft loss rejection and immunosuppressive therapy toxicity and by limitations of organ preservation protocols, which is essential to organise staff and facilities, transport organs, and perform necessary laboratory tests. However, the cryopreservation of composite tissues poses technical challenges beyond those seen in the preservation of single tissue types or organs. OBJECTIVE: The purpose of our study was to establish a protocol for long-term storing of renal primordia, that generates new adult kidneys after transplant into a syngeneic non-immunosuppressed host. MATERIALS AND METHODS: Metanephroi from 16-days-old embryos were microdissected and vitrified following the minimum essential volume method and using Cryotop as a device and VM3 as vitrification solution. After 3 months of storage in liquid nitrogen (-196 degree C), 20 metanephroi were warmed and transplanted using minimally invasive laparoscopic surgery into retroperitoneal fat of 5-month-old immune-competent New Zealand rabbits. In the same way, 22 fresh metanephroi were transplanted. Twenty-one days after transplantation, hosts were euthanized and developed kidneys were recovered and evaluated morphologically and histologically. RESULTS: Significant growth and fully differentiated mature glomeruli and tubule were observed in all kidney graft explants recovered. In total, 5 metanephroi (25.0%) were successfully grown after vitrification. In the same way, 12 metanephroi (54.5%) were successfully grown in the fresh group. CONCLUSION: These encouraging results reported that metanephroi not only survive vitrification, but they vascularized and developed morphologically normal glomeruli after their allotransplantation. These results suggest that it's possible to create a long-term biobank of kidney precursors as an unlimited source of organs for transplantation, and open new therapeutic possibilities for the patients with chronic renal failure.

Perioperative morbidity and long-term outcome of unilateral nephrectomy in feline kidney donors: 141 cases (1998-2013).

OBJECTIVE To evaluate the outcome associated with unilateral nephrectomy in feline kidney donors. DESIGN Retrospective case series. ANIMALS 141 cats. PROCEDURES Medical records of cats that underwent nephrectomy for renal donation were reviewed for information on signalment, date of renal donation, results of blood and urine analyses, infectious disease history, anesthetic protocols, intra- and postoperative complications, and postoperative analgesic protocols. Long-term follow-up data were obtained via client telephone interview and review of referring veterinarian medical records. RESULTS All donors were healthy young adult cats with a median age of 1.5 years (range, 0.8 to 2 years). No cats died or were euthanized during the perioperative period. Intraoperative complications occurred in 2 cats, and postoperative complications occurred in 17. Median time from nephrectomy to hospital discharge was 3.6 days (range, 2 to 8 days). Long-term follow-up information was available for 99 cats, with a median interval between nephrectomy and follow-up of 10 years (range, 0.25 to 15 years). Six cats had a history of urinary tract disease including stable chronic kidney disease (n = 3), acute kidney injury (2), and cystitis (1). Nine cats were dead at follow-up; death was attributed to chronic renal failure in 2 and acute ureteral obstruction in 4. CONCLUSIONS AND CLINICAL RELEVANCE Feline donor nephrectomy had an acceptably low perioperative morbidity in this series. Most cats (84%) for which follow-up information was available had no associated long-term effects. However, a small subset (7%) developed renal insufficiency or died of urinary tract disease.

Surgical management of vesicoureteral reflux with recurrent urinary tract infection after renal transplantation in a dog.

CASE DESCRIPTION A 3-year-old male Cocker Spaniel renal transplant recipient was readmitted 39 weeks after transplantation because of acute clinical signs of pollakiuria, intermittent vomiting, decreased appetite, lethargy, and mild fever. CLINICAL FINDINGS Hydronephrosis and hydroureter were observed with ultrasonography and contrast cystography, and a diagnosis of vesicoureteral reflux (VUR) was made. Urinary tract infection (UTI) caused by Escherichia coli was also diagnosed on the basis of results of urine culture. TREATMENT AND OUTCOME Despite treatment of the UTI with an appropriate antimicrobial for 6 weeks, the VUR persisted and the UTI recurred 9 weeks after cessation of antimicrobial treatment. Therefore, surgical correction by means of revision extravesicular ureteroneocytostomy was performed. Both VUR and hydronephrosis resolved after surgery. No recurrences of clinical signs of urinary tract complications were observed during the subsequent 22-month follow-up period. CLINICAL RELEVANCE Results suggested that ureteral reimplantation with an extravesicular technique incorporating a long submucosal tunnel may be an effective treatment for VUR when medical management fails in canine renal transplant recipients with recurrent UTIs.