Objectives: Although the extraperitoneal approach is standard in renal transplant, intraperitoneal placement is utilized in pediatric recipients and select adult cases. Concerns exist regarding the safety of percutaneous allograft biopsy in intraperitoneally placed kidneys due to potential visceral injury. We aimed to compare biopsy-related complication rates between intraperitoneal and extraperitoneal kidney transplant recipients.
Materials and Methods: This retrospective cohort study (2022-2024) compared biopsy-related complications in 100 transplant recipients (50 intraperitoneal, 50 extraperitoneal) at Labbafinezhad Hospital. Only 23 patients underwent ultrasonography-guided allograft biopsy (13 intraperitoneal, 10 extraperitoneal) for clinical indications. Demographic, clinical, and transplant-related variables and postbiopsy complications were evaluated.
Results: The intraperitoneal group (mean age 39 ± 12 years, 69% male) and the extraperitoneal group (mean age 37 ± 13 years, 60% male) were demographically comparable (P > .⁰⁵). All transplants were from living donors. No significant differences were observed in baseline characteristics, including cause of end-stage renal disease, dialysis vintage, or number of previous transplants. Postbiopsy complications were rare and of minor severity in both cohorts. One patient (7.7%) in the intraperitoneal group developed a small hematoma (grade 3), and 1 patient (7.7%) had a minor perinephric collection (40 mL). No such events occurred in the extraperitoneal group, but this difference was not significant (P = .⁵⁶⁵). No instances of gross hematuria, clinically significant hemoglobin drop, transfusion requirement, hypotension, fistula, or need for angioembolization were recorded in either group.
Conclusions: Ultrasonography-guided renal allograft biopsy appears to be a safe procedure with a similarly low complication profile in both intraperitoneal and extraperitoneal transplant recipients. Despite theoretical risks associated with intraperitoneal organ placement, our study found no evidence of increased major or minor complications, supporting the safety of percutaneous biopsy in this population when performed with image guidance.

Key words : Allograft biopsy, Arteriovenous fistula, End-stage renal disease, Kidney transplantation, Safety

Introduction
Kidney transplant is the preferred therapy for end-stage renal disease (ESRD), with surgical approach tailored to patient factors The surgical technique for renal allograft implantation has evolved, and the extraperitoneal (EP) placement in the iliac fossa has been established as the gold standard for adult recipients due to its technical simplicity, ease of postoperative monitoring, and access for potential biopsies.¹ Intraperitoneal placement (ie, positioning the graft within the peritoneal cavity) is conventionally reserved for very small children or repeat transplants, where space is limited.^2,3 Recent published studies of pediatric series have shown that intraperitoneal (IP) transplants in young children (range, 1.6-10 years) can achieve excellent long-term graft survival (≥93% at 7 years) and complication rates comparable to standard approaches.² This approach may also be employed in adult recipients with extensive prior abdominal surgeries or significant peritoneal fibrosis or during a combined liver-kidney transplant.⁴ The percutaneous renal allograft biopsy is a critical diagnostic procedure to evaluate graft dysfunction. Although biopsy is generally considered to be a safe procedure, biopsy has also been characterized as invasive and complicated by bleeding (eg, gross hematuria, hematoma) and vascular injury.⁵ Reported complication rates in large cohorts are low but not trivial; major complications (requiring transfusion, intervention, or surgery) occur in approximately 1% to 2% of renal transplant biopsies. For example, in a previously published series of 2514 biopsies, results showed a 1.9% major complication rate (transfusion in 1.3%), and a national registry reported 1.4% major complication incidence in transplant biopsies.⁶ Minor complications (subclinical hematomas, transient hematuria) are more common. Arteriovenous fistulas (AVF) occur in ~8% to 17% of transplant biopsies, although most are asymptomatic and often resolve spontaneously.⁷ The biopsy procedure on an IP graft raises theoretical concerns that are not present with an EP graft. Previously published studies have offered limited direct comparative data on this specific issue, and most previous studies have focused on surgical outcomes rather than postbiopsy complications.⁸ Our present study was designed to address this knowledge gap. We hypothesized that, due to the anatomic adjacency of IP allografts to mobile abdominal viscera, ultrasonography-guided biopsy could be associated with a higher rate of complications versus biopsies of EP grafts. To test this hypothesis, we conducted a retrospective cohort study to compare the incidence and severity of biopsy-related complications between adult recipients of IP and EP kidney transplants at a single tertiary care center.

Materials and Methods

Study design and population
This was a single-center, retrospective cohort study conducted at the Labbafinezhad Hospital Transplant Center. The study protocol was reviewed and approved by the Institutional Review Board (No. IR.SBMU.UNRC.REC.¹⁴⁰³.010). The need for informed consent was waived due to the retrospective nature of the analysis. We reviewed the medical records of all patients who underwent kidney transplant at our center from January 2022 to December 2024. Patients were categorized into 2 groups based on the surgical approach documented in the operative report, that is, the IP group and the EP group. From each of these broader cohorts, we identified all patients who subsequently underwent a percutaneous ultrasonography-guided renal allograft biopsy for clinical indications during the follow-up period. The indication for biopsy was at the discretion of the treating nephrologist, typically for unexplained graft dysfunction (eg, an increase in serum creatinine ≥20% from baseline), proteinuria, or suspected rejection based on donor-specific antibodies.

Inclusion and exclusion criteria
Inclusion criteria for the biopsy analysis were (1) age ≥18 years at the time of biopsy, (2) receipt of a living donor kidney transplant, (3) availability of a complete procedural note and postbiopsy monitoring records, and (4) at least 1 follow-up visit within 1 week after biopsy. Exclusion criteria included (1) presence of severe uncorrected coagulopathy (international normalized ratio >1.5; platelets <50 000 platelets/μL), (2) active perigraft or systemic infection, (3) biopsy performed for research purposes only (protocol biopsy), and (4) incomplete medical records.

Biopsy procedure
All biopsies were performed by experienced transplant nephrologists proficient in ultrasonography-guided procedures. A standardized protocol was followed. Prior to the procedure, a baseline complete blood count, coagulation profile, and urinalysis were obtained. Blood pressure was controlled to <140/90 mm Hg. Under strict aseptic conditions, real-time ultrasonography (using a high-frequency linear probe) was used to localize the upper pole of the allograft, identify a safe cortical needle path to avoid large vessels and the renal pelvis, and mark the entry site. Local anesthesia (1%-2% lidocaine) was administered. A 16-gauge or 18-gauge automated spring-loaded biopsy needle (Bard Max-Core disposable core biopsy instrument or equivalent) was used to obtain 2 cores of renal tissue under direct ultrasonography visualization. Postprocedure manual compression was applied for 5 to 10 minutes, followed by a pressure dressing. Patients were instructed to maintain bed rest in a supine position for 4 to 6 hours, with close monitoring of vital signs and continuous pulse oximetry.

Data collection and outcome measures
Data were extracted from electronic medical records via a standardized data collection form. Variables collected included demographic information and baseline data (age, sex, body mass index, primary cause of ESRD); transplant details (living donor type, cold ischemia time, warm ischemia time, graft side); and biopsy indication (documented clinical reason, eg, creatinine rise, de novo donor-specific antibodies, proteinuria). Primary outcomes (complications) were the following complications assessed within 72 hours after biopsy. (1) Hematoma was defined as a perinephric or subcapsular fluid collection with internal echoes on follow-up ultrasonography, categorized by size (grade 1 was <2 cm; grade 2 was 2-4 cm; and grade 3 was >4 cm or required intervention). (2) Symptomatic fluid collection was defined as any perigraft collection causing pain or mass effect. (3) Gross hematuria was defined as visibly bloody urine persisting >24 hours. (4) Hemoglobin drop was defined as a decrease >1 g/dL from prebiopsy baseline. (5) Blood transfusion was a requirement for packed red blood cells after biopsy. (6) Hypotension was defined as a systolic blood pressure <90 mm Hg with symptoms attributable to blood loss. (7) Occurrence of AVF was defined by the detection of a new focal area of turbulent flow with aliasing on color Doppler ultrasonography. (8) Angioembolization was a primary outcome if radiographic intervention was required to control bleeding.

Statistical analyses
We used SPSS software (version 28.00; IBM) for all statistical analyses. Continuous variables are presented as mean values ± SD or median values (with IQR), as appropriate. Categorical variables are presented as frequencies (with percentages). Normality was assessed using the Shapiro-Wilk test. We analyzed differences between the IP group and the EP group with independent samples t test or Mann-Whitney U test for continuous variables and the χ2 test or the Fisher exact test for categorical variables. A 2-tailed P < .⁰⁵ was considered statistically significant.

Results

Baseline characteristics of the biopsied cohort
From the initial 100 transplant recipients (50 IP, 50 EP), 23 patients (13 in the IP group, 10 in the EP group) met the inclusion criteria and underwent a clinically indicated allograft biopsy. The baseline characteristics of these 23 patients are summarized in Table 1. The cohorts comprised well-matched participants. The mean age was 38.5 ± 12.5 years overall, with 65.2% male participants. All patients received living donor grafts. The most common causes of ESRD were glomerulonephritis (21.7%) and hypertension (21.7%). The median time from transplant to biopsy was 6 months (range, 1-161 months). No significant differences were shown between the IP group and the EP group with regard to age, sex distribution, body mass index, cause of ESRD, dialysis vintage, number of prior transplants, or graft side (all P > .⁰⁵). The primary indications for biopsy were similar between groups and were predominantly a rising serum creatinine (50% of biopsied cases) and ruling out antibody-mediated rejection (33.3%).

Biopsy-related complications
The incidence of complications after biopsy is detailed in Table 2. The overall complication rate was low. In the IP group, 1 patient (7.7%) developed a grade 3 perinephric hematoma (>4 cm), which was managed conservatively with observation and serial hemoglobin checks without the need for transfusion or intervention. Another patient in the IP group (7.7%) had a small (40 mL), asymptomatic perinephric fluid collection noted on routine postbiopsy ultrasonography, which resolved spontaneously. No patients in the EP group experienced a hematoma or symptomatic collection requiring documentation. This numerical difference was not significant (P = .¹ for both hematoma and collection). Critically, no major complications occurred in either group. The incidence rate was zero for gross hematuria, clinically significant hemoglobin drop (>1 g/dL), requirement for blood product transfusion, procedure-related hypotension, formation of a detectable AVF on Doppler ultrasonography, or requirement for angioembolization. All biopsies yielded adequate tissue for diagnosis.

Discussion
This retrospective comparative study provided reassuring data regarding the safety of percutaneous renal allograft biopsy in intraperitoneally placed grafts. Contrary to our initial hypothesis, we found no significant increase in the rate of biopsy-related complications, whether minor or major, versus the standard EP approach. The only 2 minor complications (a hematoma and a small collection) occurred in the IP group, but the event rate was too low to draw definitive conclusions about increased risk, and both resolved with conservative management. Our findings align with the broader scope of previously published studies on the safety of ultrasonography-guided native and transplant kidney biopsies, which have consistently reported major low complication rates with modern techniques. Studies on kidney transplant complications in adults have reported that only 3.2% of allograft biopsies required transfusion and that AVF may arise at a rate of 1.5% (mostly asymptomatic).⁹ Our zero incidence rate for hemorrhagic complications agrees with such previously reported low rates. Similarly, a previously published study of a large multicenter series has reported a low rate of ~1.9% for major complications.⁶ Our findings are well within this safety range. Although no prior study has directly contrasted IP versus EP biopsy safety in adults, our results align with related evidence. Pediatric series have found that IP transplants (commonly used in small children) achieve graft survival rates and patient survival rates comparable to the rates in EP cases.² In the context of renal biopsies in children, a meta-analysis has reported hematoma rates between 11% and 18%, with a blood transfusion requirement of 0.9% (95% CI, 0.5%-1.4%). Notably, no significant difference was observed in transfusion needs for native kidneys versus transplant kidneys.¹⁰ Another study of 183 pediatric renal biopsies identified hematoma requiring transfusion (rate of rates of 2%) and AVF (rate of 0.5%) as the primary complications at values that are low and consistent with those reported in adults who predominantly receive EP grafts.¹¹ In a report from 2022, Gerzina and colleagues reported 46 pediatric with IP grafts (mean weight ≈18 kg) who had surgical complication rates that were not higher than shown in other published data in pediatric transplant, with 7-year graft survival of 93%.² Our data suggest that theoretical concerns related to IP positioning, such as bowel injury or graft torsion, do not translate into increased biopsy-related morbidity. In support of our conclusions, Ghidini and colleagues noted that although IP placement may expose grafts to risks such as intestinal obstruction or vascular twisting, the long-term outcomes remain similar between both surgical approaches (IP and EP).³ In a recent study of 239 pediatric patients, AVF was identified as the most common biopsy complication, but no difference in complication rates was shown between native and transplant kidneys based on anatomic location. Although biopsy in children is generally safe, younger age, lower glomerular filtration rate, and anemia were identified as factors that may increase complication risk.¹² The comparable safety profile between the 2 groups in our study may be attributed to several factors. Intraperitoneal grafts, although mobile, often lie adjacent to the anterior abdominal wall, allowing clear sonographic visualization. Under continuous ultrasonography guidance, we were able to avoid the intervening bowel loops and visceral structures. Both surgical approaches (IP and EP) in our cohort presented at similar cortical depths beneath the skin, and needle trajectories through the flank musculature were technically analogous. Meticulous technique, including real-time needle tracking, controlled advancement, and careful postprocedure hemostasis, likely contributed to reduction of risk in both groups. Routine postbiopsy imaging, as recommended in prior work,¹³ further allowed for early detection of subclinical bleeding. The absence of AVF formation in our series, in sharp contrast to a reported incidence of up to 10% in some previously published studies, may reflect our limited sample size or effective tissue tamponade following biopsy. These results provide practical reassurance that intraperitoneally placed renal allografts can be biopsied without undue risk. In adult recipients with IP grafts, such as those with prior abdominal surgeries or repeat transplants, clinicians may hesitate to perform biopsies due to perceived peritoneal hazards. Our data suggested that standard ultrasonography-guided biopsy remains safe when performed by experienced operators, even in IP locations. Although EP placement remains preferable when feasible to avoid potential long-term risks such as torsion or adhesive disease,¹⁴ an IP surgical approach should not preclude necessary diagnostic biopsy, particularly in pediatric or anatomically complex cases.² This study had several limitations. The primary constraints were the small sample size of biopsies (n = 23) and the retrospective, single-center design. The incidence of rare but serious complications, such as graft loss, was too low to be reliably assessed in our cohort, and subtle differences between groups might emerge in a larger study. Our cohort was also relatively homogeneous, consisting entirely of living donor organ recipients with predominantly adult body habitus; therefore, our results may not be generalizable to very-low-weight pediatric patients or to recipients of deceased donor grafts. The follow-up period in our study was limited to 2 weeks after biopsy, which may have missed late-presenting complications such as delayed AVF, although clinically significant late events are uncommon.

Conclusions
Our study found no significant difference in complication rates following renal allograft biopsy between IP transplant recipients and EP transplant recipients. Despite theoretical concerns, IP grafts were safely biopsied with outcomes comparable to the outcomes of EP grafts. These findings support the feasibility of IP graft placement when clinically indicated and affirm that diagnostic biopsy can be performed safely without need for additional precautions beyond standard ultrasonography-guided technique. Future prospective, multicenter studies including larger pediatric and adult cohorts are warranted to further validate these results.