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Vol. 42. Issue. 1.January - February 2022
Pages 1-112
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Vol. 42. Issue. 1.January - February 2022
Pages 1-112
Original article
Open Access
No effect of desmopressin administration before kidney biopsy on the risk of major post-biopsy bleeding
Ausencia de efecto de la administración de desmopresina antes de una biopsia renal sobre el riesgo de hemorragia mayor tras la biopsia
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Minseon Cheong, Tae Yeon Lee, Jongmin Lee, Soon Bae Kim
Corresponding author
sbkim@amc.seoul.kr

Corresponding author.
Division of Nephrology, Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea
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Tables (6)
Table 1. Summary of studies on the effects of desmopressin on post-kidney biopsy bleeding.
Table 2. Baseline characteristics before kidney biopsy and kidney biopsy information.
Table 3. Bleeding events within 7 days.
Table 4. Propensity score matching for comparison of differences according to whether desmopressin was administered or not.
Table 5. Outcome comparison after propensity score matching.
Table 6. Subgroup analysis of matched data for major bleeding events.
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Abstract
Background/Aims

The most important complication of kidney biopsy is bleeding, and it is unclear whether desmopressin is effective in preventing it. Thus, the study was conducted to compare post-biopsy bleeding with or without desmopressin prescription prior to percutaneous kidney biopsy.

Methods

In this single-centered, retrospective, and observational study, 3,018 adult patients who underwent kidney biopsy between January 1, 2003 and March 31, 2019 at our institute were recruited. Of these, 776 patients received desmopressin. To compare the differences in major bleeding events between patients administered and not administered with desmopressin, propensity score matching was performed.

Results

Before propensity score (PS) matching, it was observed that patients in the desmopressin group were significantly older (p<0.001) and had a higher blood pressure (p<0.001), higher serum creatinine (p<0.001), lower hemoglobin levels (p<0.001), and lower platelet counts (p=0.001) than those in the no-desmopressin group. Furthermore, the incidence of renal artery embolization was not significantly different between the two groups (p=0.077); however, blood transfusions occurred significantly more frequently in the desmopressin group (p<0.001). A comparison of the two groups after PS matching did not reveal any differences in the incidence of renal artery embolization (p=0.341), blood transfusion (p=0.579), and total major bleeding events (p=0.442). Furthermore, there was no difference in the incidence of perinephric hematoma on computed tomography or ultrasound (p=0.120).

Conclusions

We do not recommend desmopressin administration before kidney biopsy.

Keywords:
Desmopressin
Renal biopsy
Renal artery embolization
Blood transfusion
Perinephric hematoma
Propensity score matching
Resumen
Antecedentes/objetivos

La complicación más importante de la biopsia renal es la hemorragia y no está claro si la desmopresina es eficaz en su prevención. Por lo tanto, el estudio se realizó para comparar la hemorragia tras una biopsia renal percutánea con o sin prescripción de desmopresina previa a esta.

Métodos

En este estudio unicéntrico, retrospectivo y observacional se seleccionaron 3.018 pacientes adultos que se sometieron a una biopsia renal entre el 1 de enero de 2003 y el 31 de marzo de 2019 en nuestro instituto. De ellos, 776 pacientes recibieron desmopresina. Para comparar las diferencias en los acontecimientos de hemorragia mayor entre los pacientes que recibieron desmopresina y los que no, se realizó un emparejamiento por puntuación de propensión.

Resultados

Antes del emparejamiento por puntuación de propensión, se observó que los pacientes del grupo con desmopresina tenían una edad significativamente mayor (p<0,001) y presentaban una presión arterial más alta (p<0,001), una creatinina sérica más alta (p<0,001), niveles de hemoglobina más bajos (p<0,001) y recuentos de plaquetas más bajos (p=0,001) que los del grupo sin desmopresina. Además, la incidencia de embolización de la arteria renal no fue significativamente diferente entre los 2 grupos (p=0,077); sin embargo, las transfusiones de sangre se produjeron con una frecuencia significativamente mayor en el grupo con desmopresina (p<0,001). Una comparación de los 2 grupos tras el emparejamiento por puntuación de propensión no reveló diferencias en la incidencia de embolización de la arteria renal (p=0,341), la transfusión de sangre (p=0,579) y los acontecimientos de hemorragia mayor totales (p=0,442). Además, no se observaron diferencias en la incidencia de hematomas perinéfricos en la tomografía computarizada o la ecografía (p=0,120).

Conclusiones

No se recomienda la administración de desmopresina antes de una biopsia renal.

Palabras clave:
Desmopresina
Biopsia renal
Embolización de la arteria renal
Transfusión de sangre
Hematoma perinéfrico
Emparejamiento por puntuación de propensión
Full Text
Introduction

Percutaneous kidney biopsy is an important modality for diagnosing and treating glomerular disease. Complications in biopsies can be major (those that require interventions such as a blood transfusion or procedure to stop bleeding) and minor (those that do not require special interventions, for e.g., hematuria or perinephric hematoma).1

Desmopressin is a long-acting synthetic analog of vasopressin, and was originally designed to treat diabetes insipidus.2 It is now used to treat bleeding disorders as well, because it can induce an increase in the plasma levels of factor VIII and the von Willebrand factor, thereby shortening the prolonged activated partial thromboplastin time (aPTT) and the bleeding time.3

The effect of desmopressin on the risk of post-kidney biopsy bleeding remains controversial (Table 1). Two studies revealed that desmopressin decreased the bleeding risk,4,5 while one study revealed that it did not decrease the bleeding risk.6 Two additional studies also reported controversial results.7,8

Table 1.

Summary of studies on the effects of desmopressin on post-kidney biopsy bleeding.

Study ID  Number of patients  Study design  Results 
Manno et al.4 (2011)  162 patients undergoing native kidney biopsy  Randomized, controlled, single-center study; Italy  Desmopressin significantly decreased post-biopsy bleeding (13.7% vs. 30.5%, p=0.01). 
Radhakrishnan et al.6 (2014)  43 patients (22 with native kidney biopsy and 21 with central line placement)  Retrospective single-center study; Canada  No difference in the bleeding complications between desmopressin and no-desmopressin groups (23% vs. 27%, p=1.0). 
Peters et al.5 (2018)  576 patients with serum creatinine above 150μmol/L (≥1.7mg/dl) undergoing native kidney biopsy  Most prospective multicenter study; Sweden  Multiple logistic regression revealed that desmopressin showed lesser major (OR: 0.38) and overall complications (OR: 0.36). 
Athavale et al.7 (2019)  269 patients undergoing percutaneous kidney biopsy  Retrospective single-center study; United States of America  Desmopressin decreased bleeding risk in patients with serum creatinine ≥1.8mg/dL (OR: 2.11, p=0.09), but increased the risk when serum creatinine was <1.8mg/dL (OR: 9.72, p<0.001). 
Leclerc et al.8 (2020)  413 patients undergoing native kidney biopsies  Retrospective single-center study; Canada  Despite a higher bleeding risk, patients using desmopressin had a similar likelihood of symptomatic hematomas (OR: 0.39) and a lower need for urgent radiologic studies (OR: 0.33). 
Cheong et al.  3018 patients undergoing native kidney biopsy  Retrospective single-center study; South Korea  No differences in the incidence of renal artery embolization (p=0.341), blood transfusion (p=0.579), and total major bleeding events (p=0.442). 

We previously reported that intravenous desmopressin significantly reduced the level of collagen/epinephrine and collagen/adenosine diphosphate closure time in uremic patients.2 We also reported that a single injection of desmopressin prior to invasive procedures in uremic patients using antiplatelet agents ameliorated platelet dysfunction (measured by in vitro collagen/epinephrine occlusion time).9 Based on these studies, over the past 17 years, we have administered desmopressin to some patients prior to kidney biopsy.

This study was performed to compare major post-biopsy bleeding between patients who were prescribed with desmopressin prior to percutaneous kidney biopsy and patients who were not.

Material and methodsPatients

A retrospective single-center study was conducted to compare the incidence of severe post-kidney biopsy bleeding between adult patients who were administered with desmopressin and patients who were not. Patients who underwent kidney biopsy at our institute from January 1, 2003 to March 31, 2019 were included. The exclusion criteria were as follows: (1) transplanted kidney biopsy (when kidney transplant was performed a day prior to the kidney biopsy or kidney transplant disease codes were available), (2) open kidney biopsy, (3) age <18 years at the time of kidney biopsy, and (4) mass biopsy for cancer diagnosis. A search using our center's Biomedical Research Environment revealed that 6877 patients underwent a kidney biopsy during the period specified above. Among these, 6518 patients were aged 18 years or above. After excluding for transplant kidney biopsy and open kidney biopsy, 4051 patients were identified; of these, 3018 patients were selected as the final study subjects. The patient‘s informed consent was not necessary because the data obtained was collected from clinical practice.

Data collection

The following data were collected:

  • 1.

    Desmopressin administration: Yes/No

  • 2.

    Consumption of anticoagulants or antiplatelet drugs before kidney biopsy: Yes/No

  • 3.

    Baseline characteristics at the time of kidney biopsy: age, sex, weight, height, and body mass index (BMI)

  • 4.

    Comorbidities: diabetes mellitus, hypertension

  • 5.

    Blood pressure just before and after the kidney biopsy

    • 1)

      Systolic blood pressure (SBP) (mmHg)

    • 2)

      Diastolic blood pressure (DBP) (mmHg)

    • 3)

      Mean arterial pressure (MAP) (mmHg)

  • 6.

    Blood and urine test results obtained just before and after the kidney biopsy

    • 1)

      Hemoglobin (g/dL), platelet (×103/μL), hematocrit (%)

    • 2)

      Prothrombin time (PT international normalized ratio [INR]), activated partial thromboplastin time (sec)

    • 3)

      Serum creatinine (mg/dL), estimated glomerular filtration rate (eGFR) (ml/min/1.73m2), blood urea nitrogen (BUN) (mg/dL)

    • 4)

      Spot urine albumin/creatinine ratio (g/g), spot urine protein/creatinine ratio (g/g)

  • 7.

    Kidney biopsy data

    • 1)

      Number of needle passes, number of biopsy segments

    • 2)

      Clinical indication for kidney biopsy

      • (i)

        Hematuria and/or non-nephrotic range proteinuria

      • (ii)

        Azotemia

      • (iii)

        Nephrotic syndrome

    • 3)

      Histological diagnosis

      • (i)

        Glomerulonephritis

      • (ii)

        Nephrosclerosis

      • (iii)

        Tubulo-interstitial nephritis

      • (iv)

        Lupus nephritis

      • (v)

        Diabetic nephropathy

      • (vi)

        Vasculitis

      • (vii)

        Amyloidosis

      • (viii)

        Others

    • 4)

      Department that performed biopsy

      • (i)

        Nephrology

      • (ii)

        Rheumatology

      • (iii)

        Allergy

      • (iv)

        Others

  • 8.

    Bleeding events

    • (1)

      Renal artery embolization

    • (2)

      Blood transfusion (limited to red blood cell transfusion)

    • (3)

      Perinephric hematoma on computed tomography (CT) or ultrasound (US), Size of the hematoma

    • (4)

      Nephrectomy due to bleeding

    • (5)

      Length of hospital stay

The eGFR presented in our electronic medical record was estimated using the modification of diet in renal disease (MDRD) equation (MDRD eGFR) and the chronic kidney disease epidemiology collaboration (CKD-EPI) equation (CKD eGFR). In the old data at our institute, it was often expressed as either MDRD eGFR or CKD-EPI eGFR alone. The difference between the two was considered insignificant and the two data were applied together and used to evaluate eGFR statistics. If data for the computation of both were available, then the MDRD equation (which has data from more patients) was applied.

In order to identify bleeding events, cases where renal artery embolization and blood transfusion were performed within 7 days from the biopsy were investigated. Furthermore, in cases where CT or US was performed within 7 days from the biopsy, the presence of perinephric hematoma was investigated. Hematoma size data were included only when it was described in the official reading. The major bleeding events were defined as cases that underwent renal artery embolization and blood transfusion.

Biopsy procedure and desmopressin administration

In all kidney biopsies, patients were provided with a detailed explanation of the protocol and informed consent was obtained. Prior to the procedure, the patient's complete blood count (CBC) and coagulation profile were checked. Transfusions were recommended for patients with hemoglobin levels lower than 10g/dL or with platelet counts lower than 100,000/μL. Patients who consumed anticoagulants or antiplatelet drugs prior to kidney biopsy underwent a period of discontinuation. Furthermore, aspirin and clopidogrel consumption was skipped for 7 days, cilostazol for 3 days, and warfarin until the PT INR was normal.

There was no standardized hospital protocol for the administration of desmopressin in this study. Desmopressin was administered to subjects who were deemed to have a high risk of bleeding by the attending physician; these subjects were typically those with a known high risk of bleeding, i.e., patients with impaired renal function and elevated BUN, old age, high blood pressure, low hemoglobin levels, and low platelet counts. Patients in the desmopressin group received a dose of 0.3μg/kg desmopressin (Minirin®, Ferring, Saint-Prex, Switzerland) in 100cc normal saline 30min before the procedure.

A 16- or 18-gauge semiautomated, side-notch disposable biopsy needle was used for the biopsy (STARCUT®, TSK Laboratory, Tochigi, Japan). To reduce the risk of bleeding, 18-gauge needles (9–12cm in length) were used in most cases.10 By using needles of a gauge thinner than that of the usual ones, the risk of bleeding was reduced. Therefore, even in patients with a relatively high bleeding tendency, punctures were repeated several times to obtain sufficient tissue. For native kidney biopsy, we aimed to collect more than 25 glomeruli and obtain an average of about three segments. The biopsies were conducted using real-time ultrasound guidance. After the procedure, a sandbag was placed on the biopsy site for 3h and the patient rested in a supine position. Then, after being transferred to the ward, the blood pressure and pulse rate were measured periodically, and the CBC was checked the next morning. If vital signs became unstable or other bleeding complications, such as gross hematuria or severe abdominal pain, were detected, CT or US was performed and renal artery embolization and blood transfusion were undertaken as required. CT or US was not performed routinely after kidney biopsy in patients without any symptoms.

Ethics statements

This study was conducted in accordance with the ethical standards of the Declaration of Helsinki (as revised in Brazil, 2013). This research protocol was approved by the Institutional Review Board of our institute (No. 2019-0427).

Statistical analysis

When numerical data satisfied normality, they were expressed as mean±standard deviation, and a Student's t-test was performed to compare the means of the two independent groups. The chi-square test and Fisher's exact test were performed to compare categorical data between the two groups. The frequency of occurrence was expressed as a percentage (%). To compare the difference according to whether desmopressin was administered or not, propensity score matching (PS matching) was performed. After performing multiple imputations, the average of PSs estimated from each completed dataset was used. In case of a 2:1 or 3:1 matching, several patients in the desmopressin group were lost; thus, a 1:1 matching was performed. Post-matching outcome comparison was performed using logistic regression, with correlation allowed within the matching pair and a robust estimator. PS matching was performed using the R software, version 3.6.1, while the remaining tests were performed using IBM SPSS Statistics for Windows, version 23 (IBM Corp., Armonk, N.Y., USA). In addition, p<0.05 was considered statistically significant.

ResultsComparison of baseline characteristics before kidney biopsy

There were no significant differences in the weight, height, and BMI between the two groups; however, the age was significantly higher in the desmopressin group than in the no-desmopressin group (p<0.001). Furthermore, the SBP, DBP, and MAP were also significantly higher in the desmopressin group than in the no-desmopressin group (p<0.001). The hemoglobin, platelet, and hematocrit levels were significantly lower in the desmopressin group than in the no-desmopressin group (p<0.001, p=0.001, and p<0.001, respectively). The PT (p<0.001) and aPTT (p=0.025) were significantly higher in the desmopressin group than in the no-desmopressin group. Serum creatinine and BUN were significantly higher (p<0.001), while eGFR was significantly lower (p<0.001) in the desmopressin group than in the no-desmopressin group. The urine protein/creatinine ratio (p=0.007) was also significantly higher in the desmopressin group than in the no-desmopressin group. The use of anticoagulants or antiplatelet drugs before renal biopsy was significantly more in the desmopressin group as compared to in the no-desmopressin group (p<0.001) (Table 2).

Table 2.

Baseline characteristics before kidney biopsy and kidney biopsy information.

  Desmopressin group  No-desmopressin group  p 
  N=776 (25.7%)  N=2242 (74.3%)   
Age (years)  50.2±16.8  43.5±16.1  <0.001 
Men/women (women %)  432/344 (44.3%)  1087/1155 (51.5%)  0.001 
Weight (kg)  64.2±12.6  64.1±13.0  0.869 
Height (cm)  163.9±8.9  163.7±9.1  0.690 
Body mass index (kg/m2)  23.9±3.6  23.8±3.8  0.581 
Systolic blood pressure (mmHg)  126±19  121±17  <0.001 
Diastolic blood pressure (mmHg)  79.6±11.7  77.3±10.8  <0.001 
Mean arterial pressure (mmHg)  95.1±12.9  91.9±11.9  <0.001 
Blood parameters
Hemoglobin (g/dL)  11.3±2.6  12.6±2.3  <0.001 
Platelet (×103/μL)  243±93  256±82  0.001 
Hematocrit (%)  33.7±7.4  37.7±6.4  <0.001 
Prothrombin time (INR)  1.02±0.11  0.98±0.09  <0.001 
aPTT (sec)  29.2±5.8  28.6±4.3  0.025 
Serum creatinine (mg/dL)  2.87±2.68  1.24±1.25  <0.001 
eGFR (ml/min/1.73m245.0±34.5  73.6±28.2  <0.001 
BUN (mg/dL)  33.5±22.9  19.3±13.1  <0.001 
Spot urine tests
Urine albumin/creatinine ratio (g/g)  1.8 (0.5, 4.5)  1.5 (0.5, 3.9)  0.161 
Urine protein/creatinine ratio (g/g)  2.4 (1.0, 5.8)  1.7 (0.7, 4.1)  0.007 
Comorbidities
Diabetes mellitus  202 (26.0%)  233 (10.4%)  <0.001 
Hypertension  315 (40.6%)  637 (28.4%)  <0.001 
Anticoagulant/antiplatelet use before biopsy  264 (34.0%)  601 (26.8%)  <0.001 
Number of needle passes  4.08±1.11  3.73±1.09  <0.001 
Number of biopsy segments  3.33±0.82  3.20±0.80  0.003 
Clinical indication for kidney biopsy<0.001 
Hematuria and/or non-nephrotic range proteinuria  421 (54.3%)  1507 (67.2%)   
Azotemia  282 (36.3%)  300 (13.4%)   
Nephrotic syndrome  73 (9.4%)  435 (19.4%)   
Histologic diagnosis<0.001 
Glomerulonephritis  518 (66.8%)  1307 (58.3%)   
Nephrosclerosis  16 (2.1%)  34 (1.5%)   
Tubulo-interstitial nephritis  50 (6.4%)  67 (3.0%)   
Lupus nephritis  47 (6.1%)  334 (14.9%)   
Diabetic nephropathy  24 (3.1%)  101 (4.5%)   
Vasculitis  40 (5.2%)  99 (4.4%)   
Amyloidosis  8 (1.0%)  33 (1.5%)   
Others  73 (9.4%)  267 (11.9%)   
Department that performed the biopsy<0.001 
Nephrology  675 (87.0%)  1722 (76.8%)   
Rheumatology  42 (5.4%)  157 (7.0%)   
Allergy  7 (0.9%)  140 (6.2%)   
Others  52 (6.7%)  223 (9.9%)   

Note: Data are expressed as mean±standard deviation, medians (25th and 75th percentile), or absolute frequencies and percentiles. aPTT, activated partial thromboplastin time; eGFR, estimated glomerular filtration rate; BUN, blood urea nitrogen.

Comparison of kidney biopsy indications and results

The incidence of clinical indications for kidney biopsy were significantly different between the desmopressin and no-desmopressin groups (p<0.001). Hematuria and/or non-nephrotic range proteinuria (54.3% in the desmopressin group, 67.2% in the no-desmopressin group) were the most common indications. The incidence of azotemia as an indication was higher in the desmopressin group than in the no-desmopressin group (36.3% vs. 13.4%), while the incidence of nephrotic syndrome as an indication was higher in the no-desmopressin group than in the desmopressin group (19.4% vs. 9.4%). The histological diagnosis also differed between the two groups (p<0.001): Glomerulonephritis was the most common (66.8% in the desmopressin group, 58.3% in the no-desmopressin group), while lupus nephritis was more common in the no-desmopressin group (14.9% vs. 6.1%). The departments where the biopsy was performed differed significantly between the two groups (p<0.001); however, the nephrology department was the most common in both groups (87.0% in the desmopressin group, 76.8% in the no-desmopressin group) (Table 2).

Bleeding events within 7 days before PS matching

The incidence of renal artery embolization did not differ significantly between the two groups (p=0.077); however, blood transfusions occurred significantly more frequently in the desmopressin group than in the no-desmopressin group (p<0.001). The frequency of perinephric hematoma (detected by CT and US) was significantly higher in the desmopressin group than in the no-desmopressin group (p<0.001). In both groups, there was no case in which nephrectomy was performed due to complications from renal biopsy. After biopsy, hemoglobin levels were significantly lower in the desmopressin group than in the no-desmopressin group (p<0.001); moreover, hemoglobin reduction was significantly higher in the desmopressin group (p<0.001). The size of the hematoma was significantly larger in the desmopressin group as compared to in the no-desmopressin group (p=0.016). Post-biopsy SBP (p<0.001) and MAP (p=0.002) were higher in the desmopressin group than in the no-desmopressin group; moreover, the reduction in SBP was significantly greater in the desmopressin group (p=0.007). Hospital stay was significantly longer in the desmopressin group than in the no-desmopressin group (p<0.001) (Table 3).

Table 3.

Bleeding events within 7 days.

  Desmopressin group  No-desmopressin group  OR (95% CI)  p 
  N=776 (25.7%)  N=2242 (74.3%)     
Bleeding events
Renal artery embolization  4 (0.5%)  3 (0.1%)  3.87 (0.86, 17.32)  0.077 
Blood transfusion  85 (11.0%)  63(2.8%)  4.26 (3.04, 5.96)  <0.001 
Perinephric hematoma on CT  34 (4.4%)  36 (1.6%)  2.81 (1.74, 4.52)  <0.001 
Perinephric hematoma on US  13 (1.7%)  4 (0.2%)  9.53 (3.10, 29.32)  <0.001 
Perinephric hematoma (total)  42 (5.4%)  39 (1.7%)  3.23 (2.07, 5.04)  <0.001 
Hemoglobin after biopsy (g/dL)  10.5±2.3  12.5±2.3    <0.001 
Hemoglobin reduction (g/dL)  0.79±0.99  0.17±0.89    <0.001 
Size of hematoma (mm)a  32.0±14.0 (N=16)  18.2±15.9 (N=15)    0.016 
Post-biopsy blood pressure
SBP after biopsy (mmHg)  120±18  116±16    <0.001 
DBP after biopsy (mmHg)  74.2±11.3  73.4±10.3    0.116 
MAP after biopsy (mmHg)  89.3±12.4  87.8±11.4    0.002 
SBP reduction (mmHg)  6.34±16.24  4.53±14.54    0.007 
Length of hospital stay (day)  10.5±15.2  6.4±11.1    <0.001 

OR, odds ratio; CI, confidence interval; CT, computed tomography; US, ultrasound; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure.

a

Maximal thickness.

Comparison of bleeding events after PS matching

The age, sex, BMI, SBP, MBP, hemoglobin, platelet count, hematocrit, PT, aPTT, serum creatinine, eGFR, and BUN were chosen as variables that could influence bleeding events. Following PS matching for these variables, there were no differences in the variables between the two groups, as the standardized mean difference (SMD) was less than 0.1 (Table 4).

Table 4.

Propensity score matching for comparison of differences according to whether desmopressin was administered or not.

  Before matching desmopressin    After matching desmopressin 
  (+)  (−)  p  SMD  (+)  (−)  SMD 
Number of patients  776  2242      627  627   
Age (years)  50.2±16.8  43.5±16.1  <0.001  0.405  49.0±16.7  49.2±16.0  0.014 
Women (%)  344 (44.3%)  1155 (51.5%)  0.001  0.144  290 (46.3%)  297 (47.4%)  0.022 
Body mass index (kg/m223.9±3.6  23.8±3.8  0.581  0.024  24.1±3.7  23.9±3.9  0.044 
Systolic blood pressure (mmHg)  126±19  121±17  <0.001  0.286  124±19  123±18  0.095 
Mean arterial pressure (mmHg)  95.1±12.9  91.9±11.9  <0.001  0.260  94.2±12.8  93.2±12.4  0.076 
Hemoglobin (g/dL)  11.3±2.6  12.6±2.3  <0.001  0.543  11.8±2.6  11.8±2.5  0.009 
Platelet (×103/μL)  243±93  256±82  0.001  0.144  247±91  247±84  0.001 
Hematocrit (%)  33.7±7.4  37.7±6.4  <0.001  0.576  35.1±7.2  35.2±7.0  0.006 
Prothrombin time (INR)  1.02±0.11  0.98±0.09  <0.001  0.349  1.00±0.10  1.00±0.09  0.003 
aPTT (sec)  29.2±5.8  28.6±4.3  0.025  0.104  29.0±6.1  28.7±4.7  0.040 
Serum creatinine (mg/dL)  2.87±2.68  1.24±1.25  <0.001  0.782  2.10±1.93  2.10±2.06  0.002 
eGFR (ml/min/1.73m245.0±34.5  73.6±28.2  <0.001  0.907  53.0±33.6  54.6±31.6  0.046 
BUN (mg/dL)  33.5±22.9  19.3±13.1  <0.001  0.765  28.5±20.2  28.4±19.3  0.002 

SMD, standardized mean difference; INR, international normalized ratio; aPTT, activated partial thromboplastin time; eGFR, estimated glomerular filtration rate; BUN, blood urea nitrogen.

Comparison of the two adjusted groups revealed no intergroup differences in the incidence of renal artery embolization (p=0.341), blood transfusion (p=0.579), and total major bleeding events (p=0.442). Furthermore, total bleeding events (including perinephric hematoma on CT/US) did not differ between the two groups (p=0.239) (Table 5).

Table 5.

Outcome comparison after propensity score matching.

  DesmopressinOR (95% CI)  p 
  (+)  (−)     
Number of patients  627  627     
Renal artery embolization (%)  3 (0.5%)  1 (0.2%)  3.01 (0.31, 29.01)  0.341 
Blood transfusion (%)  46 (7.3%)  41 (6.5%)  1.13 (0.73, 1.75)  0.579 
Total major bleeding (%)  48 (7.7%)  41 (6.5%)  1.19 (0.77, 1.83)  0.442 
Perinephric hematoma on CT/US (%)  26 (4.1%)  16 (2.6%)  1.65 (0.88, 3.11)  0.120 
Total bleeding events (%)  63 (10.0%)  51 (8.1%)  1.26 (0.86, 1.86)  0.239 
Serum sodium reduction (mmol/L)  3.83±4.33  1.91±3.79  1.92a (1.45, 2.40)  <0.001 
Significant hyponatremia (<125mmol/L) (%)  34 (6.0%)  15 (2.7%)  2.33 (1.25, 4.32)  0.008 

OR, odds ratio; CI, confidence interval; CT, computed tomography; US, ultrasound.

a

Beta (difference in mean).

The degree of serum sodium reduction was significantly greater in the desmopressin group than in the no-desmopressin group by an average of 1.92 (p<0.001). Furthermore, the incidence of significant hyponatremia of less than 125mmol/L was significantly higher in the desmopressin group than in the no-desmopressin group (p=0.008) (Table 5).

Subgroup analysis on matched data for major bleeding events

Comparison of the two groups based on a creatinine level of 1.8mg/dL revealed that desmopressin did not significantly change the major bleeding risk in both groups (p=0.808 for serum creatinine less than 1.8mg/dL, p=0.482 for more than 1.8mg/dL, and p=0.870 indicating the difference between the two groups) (Table 6).

Table 6.

Subgroup analysis of matched data for major bleeding events.

  Levels  Number of patients  Desmopressin OR (95% CI)  p  p for interaction 
Serum creatinine (mg/dL)<1.8  771  1.11 (0.48, 2.54)  0.808  0.870 
≥1.8  483  1.21 (0.72, 2.03)  0.482   

OR, odds ratio; CI, confidence.

Discussion

This is the largest study to investigate the effect of desmopressin on major bleeding risk (requiring renal artery embolization and blood transfusion) following kidney biopsy. To investigate the major bleeding events, of the 3018 patients analyzed, 776 and 2242 were categorized into the desmopressin and no-desmopressin groups, respectively. After adjusting the two groups by PS matching, we concluded that there was no difference in the major bleeding risk after desmopressin administration. Regarding major post-biopsy bleeding, Peters et al.5 reported that multiple logistic regression revealed that prophylaxis using desmopressin prior to native kidney biopsy led to lesser major complications (for example, bleeding, acute hydronephrosis, and septicemia that requires transfusion and/or an invasive intervention; odds ratio [OR]: 0.38). Furthermore, Leclerc et al.8 reported that patients who received desmopressin had a likelihood of symptomatic hematomas similar to those who did not (OR: 0.39) and a need for urgent radiologic studies lower than those who did not (OR: 0.33). Regarding minor post-biopsy bleeding in this study, there was no difference in the incidence of perinephric hematoma on CT or US between the two groups (p=0.120).

The Caring for Australians with Renal Impairment (CARI) guidelines (2018) recommended that as there is a lack of evidence to support the benefit or harm of desmopressin administration prior to renal biopsy, care units should continue their existing practice until a higher level of evidence is available.11 In 2011, Whittier suggested that although desmopressin may play a role in patients at a high risk of bleeding (which deserves a study in itself), administering desmopressin off-label to all patients undergoing percutaneous kidney biopsy is premature and possibly hazardous.1 In this study as well, we observed a greater sodium reduction in the desmopressin group than that observed in the no-desmopressin group. Considering the increased risk of thrombotic events or hyponatremia associated with desmopressin use,11 we do not recommend desmopressin use before kidney biopsy.

Previous studies reported that the serum creatinine, blood pressure, age, gender, hemoglobin, and platelet count were the risk factors of bleeding after kidney biopsy. In a study by Corapi et al.10 that compared and analyzed 34 studies through meta-analysis of bleeding complications of native kidney biopsy, the transfusion rate was significantly higher in women (≥50%) (p=0.03) and when the mean serum creatinine level was ≥2.0mg/dL (p=0.02). Furthermore, although age ≥40 years (p=0.2) and mean SBP ≥130mmHg (p=0.09) were not significant risk factors, they were associated with a tendency for high transfusion requirements. Moreover, Xu et al.12 also reported that a low platelet count significantly increased the risk of severe bleeding after renal biopsy. In our study, compared to the no-desmopressin group, the desmopressin group was older and had a higher blood pressure and serum creatinine level and lower hemoglobin and platelet levels. As a result, blood transfusions were significantly more common in the desmopressin group before PS matching. A striking observation was the higher number of transfusions in the desmopressin group than in the no-desmopressin group (11% vs. 2.8%) with an average hemoglobin reduction of 0.79±0.99g/dL and a mean post-biopsy hemoglobin level of 10.5g/dL.

Therefore, PS matching was performed to reduce selection bias and compare the bleeding events in the two groups. The SMD13,14 was calculated by comparing all variables deemed to affect bleeding, and was found to be less than 0.1 after correction. Because there were some variables with many missing values, we performed multiple imputations and used the average of PSs from all completed data sets. Because there were fewer patients in the desmopressin group, after matching, the two groups were organized based on those who had the potential to receive desmopressin, and reflected the “average treatment effect on the treated patients” rather than the “average treatment effect” (Table 4). On comparing the bleeding events between the two adjusted groups, no intergroup differences were noted in the incidence of both, renal artery embolization and blood transfusion.

The major limitation of this study is its retrospective and observational nature, which may have inherent selection bias. In our hospital, there was no protocol for administering desmopressin; therefore, desmopressin was administered to people at a high risk of bleeding, as judged by the attending physician. Furthermore, the predominant use of small caliber needles in a generalized way (usually 18-gauge) or a large number of punctures (4 passes and 3.7 passes) could be confounders and influence the absence of differences between the desmopressin and no-desmopressin groups.

Conclusions

We do not recommend desmopressin administration before kidney biopsy.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

None.

Acknowledgements

We would like to thank to our institute's statistics department for helping with statistics. Also, thank you to Editage for English language editing.

References
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Nefrología (English Edition)

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