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Volume: 16 Issue: 6 December 2018

FULL TEXT

ARTICLE
Timing and Predictors of Early Urologic and Infectious Complications After Renal Transplant: An Analysis of a New York Statewide Database

Objectives: The most common complications after renal transplant are urologic and are a cause of significant morbidity in a vulnerable population. We sought to characterize the timing and predictors of urologic complications after renal transplant using a statewide database.

Materials and Methods: We queried the New York Statewide Planning and Research Cooperative System database to identify patients who underwent renal transplant from 2005 to 2013. Postoperative com-plications included hydronephrosis, ureteral stricture, vesicoureteral reflux, nephrolithiasis, and urinary tract infections. Cox proportional hazards model was used to assess independent predictors of urologic com-plications.

Results: In total, 9038 patients were included in the analyses. Urologic complications occurred in 11.3% of patients and included hydronephrosis (12.0%), nephrolithiasis (2.8%), ureteral stricture (2.4%), and vesicoureteral reflux (1.5%). We found that 23% experienced at least one urinary tract infection. On multivariate analysis, predictors of urologic com-plications included medicare insurance, hypertension, and prior urinary tract infection. Graft recipients from living donors were less likely to experience urologic complications than deceased-donor kidney recipients (P < .001).

Conclusions: Urologic complications occur in a significant proportion of renal transplants. Further study is needed to identify risk factors for com-plications after renal transplantation to decrease morbidity in this vulnerable population.


Key words : Hydronephrosis, Kidney, Nephrolithiasis, Transplantation, Urinary tract infections, Vesicoureteral reflux

Introduction

As of January 2014, there were more than 660 000 patients living with end-stage renal disease (ESRD) in the United States; of these, 29.2% had a functioning renal transplant.1 Renal transplant is the criterion standard treatment for patients with ESRD, with a total of 17 500 renal transplant procedures taking place in the United States in 2012 alone.2

Urologic complications occur in 2.5% to 14% of renal transplants and are the most common technical adverse events after renal transplant.3-7 These complications may result in significant morbidity and graft loss, especially given the patients’ immuno-suppression and chronic comorbidities.8-10 A number of posttransplant urologic complications have been identified and may be categorized as immediate or delayed complications. Immediate urologic com-plications include hematuria, urinary extravasation, and urinary obstruction. Potential long-term com-plications include nephrolithiasis, vesicoureteral reflux (VUR), and ureteral stricture disease.11

The timing at which patients are at risk for urologic complications is not well characterized, thus potentially limiting targeted follow-up care.12,13 Although the role of the urologist in the renal transplant population has diminished over time, the preoperative urologic assessment is crucial to identify potential issues that may lead to graft dysfunction or complications. During the post-transplant period, technical complications may require specialized care by urologists as well.

A number of studies have investigated urologic complications after renal transplant as well as risk factors for the aforementioned complications. However, these are generally limited to single institution studies with few transplant surgeons included in the analyses. In this study, we sought to utilize a statewide administrative database to investigate the rate and timing of urologic complications after renal transplant surgery in the state of New York.

Materials and Methods

Patients
We utilized the New York Statewide Planning and Research Cooperative System administrative database, which collected data from 1994 to 2014 on all inpatient stays and outpatient visits (ambulatory surgery, emergency department, and outpatient services) in the state of New York. We identified all patients who underwent renal transplant surgery between 2005 and 2014 using International Classification of Disease, 9th edition (ICD-9) CM procedure codes 00.91, 00.92, and 00.93. To define a standard follow-up period for each patient, we tracked patients for up to 2 years after their initial presentation. Patients > 18 years old with at least 1 year of follow-up were included in the analysis.

Outcomes
The primary outcome analyzed was urologic complication rate after renal transplant. Urologic complications were identified by ICD-9 codes and included ureteral strictures, hydronephrosis, VUR, and nephrolithiasis ( Table 1). Urinary tract infections (UTIs) within 2 years of transplant were similarly abstracted. We relied on complications in the inpatient, ambulatory, and emergency departments for our analyses. Patients who did not develop a complication within 2 years of transplant were censored at the 24-month mark, and those with less than 24 months of follow-up were censored at the last follow-up visit. Because only the month and year of admission were available, the date of admission was normalized to the 15th of the month for each patient.

Independent variables
Patient comorbidity was defined using the Elixhauser Comorbidity Index and specific conditions associated with the development of ESRD were identified using ICD-9 codes. These included history of UTIs, history of nephrolithiasis, history of hypertension, history of diabetes, history of polycystic kidney disease, and history of glomerulonephritis. Patient characteristics such as age, sex, race, ethnicity, and geographic region were also included in the analysis.

Statistical analyses
Follow-up time was calculated from date of renal transplant, and patients were censored at a maximum of 2 years. A Cox proportional hazards model was used to identify predictors of urologic complications by 2 years after renal transplant. Variables included donor of the transplanted kidney (deceased donor, living related donor, or living unrelated donor), history of UTI, glomerulonephritis, polycystic kidney disease, hypertension, and diabetes mellitus in addition to demographic characteristics, including age, race, and insurance status. Hazard ratios (HR) and 95% confidence intervals (CI) were reported. P < .05 was considered significant. All statistical analyses were performed using SPSS software (SPSS: An IBM Company, version 23.0, IBM Corporation, Armonk, NY, USA).

Results

A total of 9038 patients were included in the final analysis. Patient characteristics are listed in Table 2. Mean age at the time of transplant was 51.5 ± 13.8 years, and our data showed that 61% of patients were male. Most of the cohort were white (54%), with 22% having African American (AA) ethnicity. Medicaid was the primary insurance in 58% of patients, and most transplants were performed in the New York City area (67%). Most of the sample had an Elixhauser Comorbidity Index of 1 or higher (74%), with 21% having a score over 10. Deceased donor renal transplant was performed in most of the patients (57%). A total of 32% of patients had a history of hypertension and 31% had a history of diabetes. Polycystic kidney disease was found in 4% and history of glomerulonephritis in 17%.

Overall, 11.3% of patients developed a urologic complication (Table 3) with a median follow-up of 2 years. Hydronephrosis was found in 9.3% (843 patients), with 67.7% of those episodes diagnosed within the first year after transplant. Ureteral stricture, nephrolithiasis, and vesicoureteral reflux were detected in 1.9% (174 patients), 1.6% (142 patients), and 1.1% (99 patients), respectively. Almost a quarter of patients (23.2%) experienced a UTI, with 88% occurring within the first year after transplant. Figure 1, A-E, shows Kaplan Meier curves of the various urologic complications after transplant. Most urologic complications occurred within the first year after transplant.

On multivariate analysis, Medicare insurance versus commercial insurance (HR 1.25; 95% CI, 1.01-1.53), history of UTI (HR 1.57; 95% CI, 1.37-1.80), and history of hypertension (HR 1.16; 95% CI, 1.05-1.27) were significant predictors of urologic complications. Living related renal transplant (HR 0.74; 95% CI, 0.66-0.83) and living unrelated renal transplant (HR 0.72; 95% CI 0.63-0.82) were associated with a significantly lower risk of urologic complications (Table 4). Significant predictors of the development of UTI after renal transplant included increasing age (HR 1.01; 95% CI, 1.09-1.01), female sex (HR 1.74; 95% CI, 1.59-1.90), commercial pretransplant history of UTI (HR 3.37; 95% CI, 3.03-3.75), history of hypertension (HR 1.14; 95% CI, 1.04-1.26), and history of type 2 diabetes mellitus (HR 1.22; 95% CI, 1.11-1.35). Similar to the urologic complications, living donor grafts were protective against UTIs (Table 4).

Discussion

Urologic and infectious complications after trans-plant are essential to identify and treat given the risk of graft failure and immunosuppressed state of transplant patients. To our knowledge, we are the first group to identify and characterize urologic and infectious complications after renal transplant using a population-level dataset. This has several advan-tages over single-institution studies as it pools data from all transplant centers in New York State, allowing the analysis of a large sample of renal transplant recipients and the creation of a standard methodology to capture urologic complications.

Several single institution studies have inves-tigated predictors of urologic complications using different outcome measures. An analysis of 634 patients found that 4.6% of patients experienced a urine leak or urinary obstruction after transplant, requiring intervention.14 The median follow-up was 1012 days, and the median time to complication was 40 days. On multivariate analysis, only renal artery multiplicity was found to be significantly associated with developing complications. Similarly, in another cohort of 2500 renal transplants, a 5.5% complication rate was observed, including VUR in 3%, stricture disease in 1.3%, urine leak in 0.9%, and ureteropelvic junction obstruction in 0.3%.15 Of the 9038 patients in our study, we found slightly lower rates of VUR (1.5%) and higher stricture rates (2.4%). Englesbe and colleagues retrospectively reviewed a cohort of 1698 renal transplants and identified an overall incidence of urologic complications, defined as urine leak and ureteral stricture, of 6.2%.10 On multivariate analysis, they identified male sex, AA ethnicity, and “U” stitch technique (vs Lich-Gregoir) as independent predic-tors of complications. Our analyses also identified male sex and AA as significant predictors of any urologic complication.

Hydronephrosis of the graft is reported to occur in 3% to 6.5% of cases with a variety of causes, including extraluminal (hematoma or lymphocele) or intraluminal (reflux, obstruction, or blood clot) causes.3,7 Timing of this complication is dependent on the associated cause. We were not able to identify these secondary causes of hydronephrosis given the limitations of the ICD-9 coding system. However, within our cohort, most hydronephrosis comp-lications occurred within 1 year of transplant and the overall rate was 12%, a rate higher than previously reported.

The incidence of urolithiasis in patients after renal transplant is reported to be 0.23% to 3%.16-19 In a single institution retrospective study of 2085 renal transplants, 21 (1.0%) were found to be diagnosed with urolithiasis at a mean follow-up of 3.7 years (0.17-18 y).17 Most of these patients were successfully treated with extracorporeal shock wave lithotripsy, and all patients were found to be stone free on follow-up. This incidence estimate is comparable to our own of 1.6%. Predisposing risk factors for urolithiasis in patients after renal transplant include metabolic abnormalities such as hypocitraturia, hyperparathyroidism, hypophosphatemia, and hypercalcemia in addition to gout, female sex, and recurrent UTI.16,17

Ureteral strictures are reported to occur in 0.6% to 12.5% of renal transplant procedures.20-23 Previously identified risk factors include male sex, deceased donor grafts, and the Politano-Leadbetter technique.21 In a study of 1298 renal transplant patients, 3.1% developed ureteral stenosis, with 75% diagnosed within the first year of surgery and 65% within the first 3 months of surgery.24 A similar analysis of 1000 renal transplant patients found an overall incidence of 3.6% ureteral strictures with a median time to presentation of 16 weeks after transplant.5 There have been several proposed mechanisms driving the development of this complication, including ischemia, technical issues, rejection, infection, and external compression.5,23,24 Although our stricture rate of 2.4% is slightly lower than quoted above, many patients will still require surgical intervention for this complication. Treatments include endoscopic approaches (balloon dilation, chronic stenting, laser/cold knife incision), which have a success rate of 60%, and open surgical procedures (ureteral reimplantation or ureteropelvic anastomosis), which have success rates of 80% to 100%.20

The reported incidence of VUR ranges from 3.0% to 12.4%, although notably several of these studies involved the pediatric population.25-28 In a single institution study of 2500 transplants over a 16-year period by a single transplant urologist, symptomatic VUR was reported in 3% (78 patients).21 The average time to presentation was 3.5 years (0.5-15 y), and the most common presentation was recurrent UTI. Most of these patients were female (80%). A minority (11.5%) was initially treated with antibiotic therapy alone, with the remaining patients undergoing deflux injection or reconstructive surgery. We reported a VUR of 1.1% of total patients (n = 99), almost 2% lower than previously reported. Despite the lower percentage of patients with VUR in our study, the associated risk of pyelonephritis with VUR makes it important to monitor these immunosup-pressed patients.26

The incidence of UTI has significant variability, ranging from 23% to 75%,29-31 with 2.9% to 27% experiencing recurrent UTI.29,32 Identification of patients at risk for UTI may help improve outcomes as it is associated with increased posttransplant morbidity and worse graft and patient survival.32-34 In our study, the rate of UTI was 23%, similar to previously reported rates. We identified risk factors for UTI development including increasing age, female sex, nonwhite race, pretransplant history of UTI, hypertension, and type 2 diabetes mellitus, which are factors similar to those previously reported.32,35,36 Living donor transplant is associated with a decreased risk of infectious complications, which has also been reported.37 Although the reason for increased UTI risk and complication rate remains to be determined for deceased donor transplants, this may be due to colonization in the deceased donor graft, whereas living donors are extensively evalu-ated before donation.

It is important to point out the limitations of this study. The retrospective nature of the analysis precludes from identifying causal relations between the risk factor and the urologic complication at question. Donor characteristics and operative variables (technique of ureteral anastomosis, stitch technique, placement of ureteral stents, and so forth) could not be abstracted and may be associated with the development of complications.10,14 Our study did not capture complications that may have been treated in the outpatient setting. Instead, we relied on treatment of complications in the inpatient, ambulatory, and emergency department settings. This may affect the rate of capture of complications that may be managed in an outpatient setting. In addition, the database did not capture medication information such as steroid use, which may have also affected postoperative complications. This study also relied on accurate documentation of postoperative complications, which have been shown to be reliable but may underestimate the comorbid condition.38,39 Finally, there is missing preoperative baseline urologic information such as work-up completed for voiding dysfunction or if patients required inter-mittent catheterization. These uncaptured factors may affect risk of infection. Despite its limitations, this study identifies several important factors asso-ciated with increased posttransplant complication risks.

Conclusions

We identified specific demographic and socio-economic factors associated with urologic com-plications in patients undergoing renal transplant, including insurance type and history of hypertension or UTI. This information can be used to help improve care in this specific patient population and potentially limit the morbidity associated with such complications. Future studies identifying solutions to decrease complications in this vulnerable population are needed.


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Volume : 16
Issue : 6
Pages : 665 - 670
DOI : 10.6002/ect.2016.0357


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From the Department of Urology, Columbia University Medical Center, New York, New York, USA
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Sven Wenske, Department of Urology, Columbia University Medical Center, Herbert Irving Pavilion 11th Floor, 161 Fort Washington, New York, NY 10032, USA
Phone: +1 212 305 6408
E-mail: sw2510@columbia.edu