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CJASN ePress. Published on October 15, 2020 as doi: 10.2215/CJN.

04710420
Article

Systematic Review and Meta-Analysis of Native Kidney


Biopsy Complications
Emilio D. Poggio,1 Robyn L. McClelland ,2 Kristina N. Blank,2 Spencer Hansen,2 Shweta Bansal,3 Andrew S. Bomback,4
Pietro A. Canetta,4 Pascale Khairallah ,4 Krzysztof Kiryluk,4 Stewart H. Lecker,5 Gearoid M. McMahon,6
Paul M. Palevsky ,7,8 Samir Parikh,9 Sylvia E. Rosas ,10,11,12 Katherine Tuttle,13 Miguel A. Vazquez ,14
Anitha Vijayan,15 and Brad H. Rovin ,16 for the Kidney Precision Medicine Project*

Due to the number of


Abstract
contributing authors,
Background and objectives Native kidney biopsies are commonly performed in the diagnosis of acute kidney the affiliations are
diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not listed at the end of
uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney this article.
Diseases–sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy;
therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using Correspondence:
Dr. Brad H. Rovin, The
automated devices under kidney imaging.
Ohio State University
Wexner Medical
Design, setting, participants, & measurements This is a systematic review and meta-analysis of the literature Center, Nephrology
published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using Division, 395 West
predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta- 12th Avenue, Ground
Floor, Columbus, OH
analysis for proportions was used to obtain combined estimates of complication rates. Freeman–Tukey double- 43210. Email: Rovin.
arcsine transformations were used to stabilize variance as complications were rare. [email protected]

Results A total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of
patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of
biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%,
bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are
estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an
estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in
hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of
study type and geographic location.

Conclusions Although the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding
complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after
kidney biopsies of hospitalized patients with AKI.
CJASN 15: ccc–ccc, 2020. doi: https://doi.org/10.2215/CJN.04710420

Introduction than a half century, but it is of limited quality due to


The native kidney biopsy was introduced into clinical study heterogeneity, variability in the definition of
practice in the 1950s, but the technique has evolved complications, and reporting bias. Most studies de-
over time. Since the late 1980s, kidney biopsies have scribed single-center experiences from different re-
been done with the assistance of automated biopsy gions of the world. From the numerous available
devices and imaging of the kidneys, mostly ultraso- publications, there has been one meta-analysis and
nography. This evolution of the procedure has there- systematic review of 34 studies (9474 biopsies) that
fore changed the type and severity of postbiopsy focused on bleeding complications after biopsies that
complications. The primary complications of native were performed under kidney imaging with an
kidney biopsies are related to hemorrhagic events that automated biopsy device (1).
can manifest in the form of pain, hematuria, peri- In the Kidney Precision Medicine Project (KPMP),
nephric bleeding that is self-contained as a hematoma, protocol kidney biopsies will be performed for re-
or active bleeding requiring red blood cell transfu- search purposes. The overarching goal of the KPMP is
sions or interventions to control the bleed. Albeit rare, to conceptually change the paradigms of CKD and
the most serious adverse event is death. acute kidney disease by integrating deep molecular
The medical literature on complications related to phenotyping of kidney tissue with patient character-
native kidney biopsies is vast and dates back more istics and disease outcomes. Native kidney biopsies

www.cjasn.org Vol 15 November, 2020 Copyright © 2020 by the American Society of Nephrology 1
2 CJASN

from such patients will undergo regional and single-cell a possible 5290 comparisons. The disagreements were sent
interrogation with a variety of techniques, including RNA back as queries to the original two reviewers who then
sequencing, proteomics, and metabolomics. The current discussed and resolved via consensus. This protocol was not
meta-analysis was undertaken to obtain an estimate of registered online.
percutaneous native kidney biopsy complications in order
to provide patients in the KPMP with accurate risk in- Statistical Methods
formation during the informed consent process. We did an We conducted a meta-analysis of proportions on the
intentional and detailed review of the literature describing basis of a random effects model (2). This model divides the
the risks and complications associated with native kidney heterogeneity into two components: the between-study
biopsies. The KPMP Kidney Biopsy Working Group ex- variance due to the true variation among different studies,
panded upon the prior meta-analysis by adding relevant and the within-study variance due to sampling error. The
publications from June 2011 to 2017 (1). The focus of this between-study variance is denoted by t2 . We tested the null
investigation was again on complication rates of native hypothesis H0 : t 2 50 using Cochran Q and a chi-squared
kidney biopsies performed using automated devices in test to determine P values. Heterogeneity was quantified by
conjunction with kidney imaging for acute kidney dis- the I 2 statistic, which is the percentage of total variation
eases and CKD. across studies that is due to heterogeneity rather than
chance (3). We estimated the random effects model using
the restricted maximum likelihood (4) for all complications
Materials and Methods except death. Because of the number of zero proportions,
Search Strategy and Review Process we used the Freeman–Tukey double-arcsine transforma-
Our initial literature search captured articles published tion (5) to avoid bias and stabilize the variance for the
from January 1983 to March 2018 and used MEDLINE, estimated effect sizes (6). We used back transformation (7)
Embase, and the Cochrane Library; it was restricted to to find the estimated proportion for the total effect estimate.
publications in English. The following medical subject Because of the rarity of death, the random effects model
headings terms were used to identify potential papers: was unable to provide a stable estimate for the true
kidney, biopsy/kidney, biopsy/fine needle, biopsy/ad- proportion of death. Thus, we used a b-binomial model
verse effects, and biopsy/complication. Each medical sub- to model the number of deaths using a binomial distribu-
ject heading term was then combined with “biopsy” tion and the underlying proportion of deaths with a
and “kidney.” b-distribution (8). We did not report any heterogeneity
This search strategy identified 1139 potential papers. The statistics for this approach as it was not comparable with
review of these papers was conducted in three phases. In the other analyses. This is because we do not calculate a
the first phase, the papers were randomly divided among value for t 2 in this approach. Outlier studies were iden-
16 reviewers. The title and abstract for each paper were tified on the basis of visual inspection of forest plots and
evaluated by a single reviewer. Papers were eliminated on absolute residuals more than two. Influential studies were
the basis of one or more of the following criteria: abstract identified on the basis of leave-one-out analysis. We
only (no accompanying paper); ,50 biopsies; non-native conducted subgroup analysis for all complications except
biopsies included and unable to be excluded; pediatric death. We assumed common between-study variance for
patients included and unable to be excluded; no image subgroups and used an omnibus test to examine if there
guidance; no complication data provided; biopsy for was a significant difference between subgroup estimates.
kidney mass; open kidney biopsy; nonkidney biopsy; All analyses were conducted using R version 3.6.1 with the
review or editorial; patient report; and use of a transjugular Meta, Metafor, and Forestplot packages.
approach. In the first round of review, 936 papers were
eliminated, leaving 203 papers for full-text review. In the
full-text review, the 203 papers were again randomly Results
divided and evaluated by a single reviewer. The entire After extensive review of the English literature and
paper was assessed, and the reasons for exclusion (same as application of the selection process described in Figure 1, 87
the first round) were recorded in detail for each paper. In papers were used for this meta-analysis. These studies were
this phase, 88 additional papers were excluded. published between 1983 and March 2018 and included
For full data abstraction, the remaining 115 papers were 182,546 kidney biopsies. The largest study comprised
randomly assigned to two reviewers. The reviewers en- 118,064 biopsies, and the smallest had 50 biopsies. Most
tered general descriptive data from the paper (e.g., country of these investigations described clinical cohorts, but seven
of origin, number of patients, number of biopsies, number were randomized controlled trials. The average age of the
of sites, study design, average age, percent women), the patients included in each study ranged from 30 to 79 years,
procedures (e.g., needle gauge, average number of passes, and 45% were women. The details of the reported studies
duration of monitoring), and the complications reported are given in Supplemental Table 1.
from our prespecified list of complications (pain, hemato- The biopsy complications of interest were pain, kidney
mas, macroscopic hematuria, need for transfusion, need for hematoma, macroscopic hematuria, red blood cell trans-
interventions to stop bleeding, and death). All extracted fusion, need for surgical/radiologic intervention to control
data elements (n546) were then compared between the two bleeding from the kidney, and death. Not all of these
reviewers by an independent third reviewer. Of 115 papers, domains were specifically examined in each investigation.
90 had at least one data element for which the two reviewers There was significant heterogeneity between studies in the
disagreed. There were a total of 185 disagreements overall, of various domains (Table 1). Heterogeneity for all of the
CJASN 15: ccc–ccc, November, 2020 Complications of Native Kidney Biopsies, Poggio et al. 3

Initial publications identified through


database search N=1139. Titles and
Abstracts were reviewed for these.

936 Excluded Due to one or more criteria


(see exclusion list below)

Full text review of 203 Papers

Exclusions (not mutually exclusive) N=88


Abstract only 32
<50 biopsies 12
Non-native biopsy 21
115 Papers Included for Data Pediatric patients 13
Abstraction No image guidance 8
No complications data 7
Biopsy for mass 5
Open biopsy 3
Not about kidney bx 3
Review or editorial 3
Case report 6
Transjugular 4
Mainly transplant 2
Unable to find article 7
Duplicate 1

N=28 excluded in final abstraction phase


Transplant Biopsy 12
Subjects Under 14 yrs included 12
N=87 Papers Included in Meta- Liver Biopsies Included 1
Analysis No complications Data 1
Can’t separate complications data 1
Complication data does not match # subjects 1

Figure 1. | This flow chart describes the number of papers reviewed at each of the three rounds of review. At each stage, papers were excluded
from further review on the basis of one or more of the exclusion criteria. The final meta-analysis was conducted on the basis of data from 87 papers.
bx, biopsy.

complication domains is visually depicted through forest Europe had a lower incidence of macroscopic hematuria
plots of the proportion of events found in each study than the United States and Asia. There were more pain
contributing to that domain (Supplemental Figures 1–6). events when a smaller needle (18 versus 16 gauge) was
The proportion of patients who experienced one or more used, but this analysis included ,1500 biopsies. There was
of these biopsy complications is summarized in Table 1. For also a numerical trend toward more hematomas and
each complication domain except death, a more detailed transfusions with the smaller needle, but statistical signif-
examination of occurrence stratified by geographical re- icance was not reached.
gion, biopsy vintage, and biopsy needle gauge is given in The most serious complication, death, was highly influ-
Tables 2 and 3. The overall incidence of complications was enced by one study (8). This study investigated over
low, especially for the serious adverse events of interven- 100,000 patients and recorded 2125 deaths. All of the other
tions to stop bleeding and death. These interventions and studies together reported only 15 deaths in 42,066 biopsies.
red blood cell transfusions occurred significantly less Unlike any of the other studies, the investigation of Al Turk
frequently in Asia than the United States or Europe, and et al. (8) interrogated a nationwide inpatient database to

Table 1. Summary of kidney biopsy complications

All Studies Influential Studies Excluded


Complication Domain
Proportion 95% Confidence Interval I2 , % Proportion 95% Confidence Interval I2 , %

Pain 0.043 0.02 to 0.07 94


Hematoma 0.11 0.07 to 0.15 99 0.088 0.06 to 0.12 98
Hematuria 0.035 0.03 to 0.04 99
Transfusion 0.016 0.01 to 0.02 99 0.014 0.01 to 0.02 88
Intervention 0.003 0.00 to 0.01 73
Death 0.0006 0.00 to 0.00 0.0003 0.00 to 0.00
4 CJASN

Table 2. Pain, hematoma, and macroscopic hematuria complications stratified by region, year, and needle gauge

Papers, Pain or Biopsies, 95% I 2, Modifier Test:


Subgroup Estimate
n Hematoma, n n Confidence Interval % P Value

Pain
America 3 10 1440 0.0110 [0.00 to 0.06] 76.5
Asia 7 118 1485 0.0596 [0.02 to 0.11] 94.6
Europe 8 66 1488 0.0455 [0.02 to 0.09] 88.3 0.24
Pre-2000 6 57 763 0.0728 [0.03 to 0.13] 84.1
2000–2009 6 115 1938 0.0427 [0.01 to 0.09] 96.2
2010–2018 6 22 1712 0.0212 [0.00 to 0.06] 85.3 0.21
16 Gauge 3 13 612 0.0230 [0.00 to 0.08] 85.6
18 Gauge 3 106 812 0.1274 [0.06 to 0.22] 93.7 0.02
Overall 18 194 4413 0.0429 [0.02 to 0.07] 93.8
Hematoma
America 15 428 5012 0.0947 [0.03 to 0.18] 95.7
Asia 19 1136 6658 0.1319 [0.07 to 0.22] 99.3
Europe 26 877 15,989 0.0924 [0.04 to 0.16] 98.6 0.67
Pre-2000 12 257 2053 0.1249 [0.04 to 0.24] 97.4
2000–2009 16 765 5639 0.1060 [0.04 to 0.20] 99.3
2010–2018 34 1419 19,967 0.0980 [0.05 to 0.16] 98.9 0.88
16 Gauge 23 420 8423 0.0574 [0.02 to 0.11] 95.9
18 Gauge 9 534 1728 0.1614 [0.07 to 0.29] 99.1 0.06
Overall 62 2441 27,659 0.1050 [0.07 to 0.15] 98.9
Macroscopic
hematuria
America 14 15,466 122,779 0.0481 [0.03 to 0.07] 97.3
Asia 25 280 7321 0.0397 [0.03 to 0.05] 84.4
Europe 25 722 27,511 0.0244 [0.02 to 0.04] 93.5 0.05
Pre-2000 14 138 2389 0.0518 [0.03 to 0.07] 43.5
2000–2009 16 449 9543 0.0318 [0.02 to 0.05] 94.1
2010–2018 34 15,881 145,679 0.0305 [0.02 to 0.04] 99.3 0.10
16 Gauge 22 232 8614 0.0249 [0.01 to 0.04] 88.9
18 Gauge 9 78 1659 0.0351 [0.02 to 0.06] 68.5 0.37
Overall 64 16,468 157,611 0.0347 [0.03 to 0.04] 98.8

identify patients who had a kidney biopsy at some point decreased the meta-analyzed estimated proportions of
during their hospitalization. Deaths occurred during the death from 0.0006 to 0.0003. Similarly, the need for blood
hospitalizations and could not necessarily be attributed to transfusion postbiopsy was influenced by the study by Al
the kidney biopsy. Excluding the study of Al Turk et al. (8) Turk et al. (8), but removing that study did not change the

Table 3. Transfusion and surgical/radiologic intervention complications stratified by region, year, and needle gauge

95%
Papers, Transfusion or Biopsies, I 2, Modifier Test:
Subgroup Estimate Confidence
n Intervention, n n % P Value
Interval

Transfusion
America 15 31,029 123,864 0.0460 [0.03 to 0.07] 99.5
Asia 23 195 22,141 0.0075 [0.00 to 0.02] 85.9
Europe 21 187 16,800 0.0103 [0.00 to 0.02] 65.0 ,0.001
Pre-2000 7 33 1231 0.0172 [0.00 to 0.04] 69.0
2000–2009 17 119 6759 0.0108 [0.00 to 0.02] 81.3
2010–2018 35 31,259 154,815 0.0187 [0.01 to 0.03] 99.8 0.49
16 Gauge 21 219 10,711 0.0574 [0.02 to 0.11] 95.9
18 Gauge 9 31 2777 0.1614 [0.07 to 0.29] 99.1 0.06
Overall 59 31,411 162,805 0.0160 [0.01 to 0.02] 99.8
Surgical/radiologic
intervention
America 19 216 124,630 0.0047 [0.00 to 0.01] 80.3
Asia 23 43 21,897 0.0006 [0.00 to 0.00] 59.5
Europe 24 74 17,467 0.0052 [0.00 to 0.01] 62.8 0.04
Pre-2000 9 9 1645 0.0033 [0.00 to 0.01] 0.0
2000–2009 17 34 6654 0.0029 [0.00 to 0.01] 35.2
2010–2018 40 290 155,695 0.0036 [0.00 to 0.01] 77.6 0.80
16 Gauge 24 55 10,799 0.0024 [0.00 to 0.01] 39.8
18 Gauge 11 12 2994 0.0005 [0.00 to 0.00] 23.7 0.28
Overall 66 333 163,994 0.0033 [0.00 to 0.01] 72.8
CJASN 15: ccc–ccc, November, 2020 Complications of Native Kidney Biopsies, Poggio et al. 5

proportion of transfusions needed or study heterogeneity hematoma. Although the overall incidence of hematoma
much (Table 1). was 11%, this was derived from a mixture of studies that
Another common complication of kidney biopsy was routinely imaged the kidney after biopsy to look for
perinephric hematoma. Two studies were identified as bleeding and studies that only imaged the kidney if there
influential for hematoma occurrence, each finding hema- was a clinical indication, such as pain or a fall in hemoglo-
tomas in over 80% of the cohort (9,10). Excluding these bin. We speculate that if hematomas are specifically sought
studies only decreased the proportion of hematomas from by imaging the kidney postbiopsy, they will be found often.
11% to 8.8% (from one in nine to one in 11) and had little However, many hematomas will be small and of arguable
effect on study heterogeneity (Table 1). In both of these clinical significance. In many of the reviewed papers, the
studies, kidney imaging was done postbiopsy to prospec- size of the hematoma was not reported, so size of a clinically
tively assess for hematomas as opposed to waiting for a relevant hematoma is unclear.
clinical indication to do postbiopsy imaging. Most hema- A particularly difficult complication to assess was pain
tomas were small (,2 cm). Several other studies reported related to the kidney biopsy. Only 18 papers attempted to
relatively high hematoma rates (.30%), and postbiopsy quantify pain, and only 194 pain events were reported in
imaging was also done routinely in these studies. nearly 4400 biopsies. No standard method of assessing pain
was used across studies, and an accepted amount of pain
after an uncomplicated kidney biopsy has not been de-
Discussion termined. Therefore, the pain domain is the least accurately
This analysis was done to obtain an estimate of percu- evaluated complication. The development of a standard-
taneous native kidney biopsy complications in order to ized pain assessment is needed.
provide patients undergoing research biopsies for the Death and need for red blood cell transfusion were
KPMP with accurate risk information during the informed highly influenced by one study that interrogated the US
consent process. We determined the occurrence of adverse Nationwide Inpatient Sample database between 2008 and
events using six biopsy complication domains of impor- 2012 (9). All included patients (n5118,064) were identified
tance to patients and clinicians. The most severe adverse by the International Classification of Disease code for
event was death, with an incidence of 0.008% (one in percutaneous native kidney biopsy. In general, these
12,500), followed by an intervention to stop bleeding with patients may have been sicker than typical patients having
an incidence of 0.3% (one in 333). The need for a red blood elective outpatient diagnostic kidney biopsies. For exam-
cell transfusion was 1.6% (one in 62.5). Gross hematuria ple, only 27% of these patients had a diagnosis of GN on the
developed in 3.5% of patients (one in 29), and pain basis of administrative codes. Notably, two thirds of the
developed in 4.3% of patients (one in 23). The incidence patients had AKI, and 15% had a pathologic diagnosis of
of perinephric hematoma was 11% (one in nine). acute tubular necrosis. Administrative codes were also
These risk estimates were on the basis of available data used to identify complications. Mortality in this cohort was
largely from retrospective reports of patient series for 1.8%, but it was twice as high (2%) in patients admitted to
biopsies performed for clinical indications. As such, the the hospital nonelectively compared with electively
overall data quality was modest, and the studies were not (0.99%). Red blood cell transfusions were administered
large. Although the ranges of patients and kidney biopsies to a quarter of the patients. These complication rates are
assessed were wide, the median number of patients per greater than those reported in other studies of native
study was 210. There were no studies that were both kidney biopsy. The findings may be explained by the acuity
prospective and designed specifically to identify compli- of illness for many of the hospitalized patients, including
cation rates. Additionally, many of the studies did not the presence of comorbidities such as coagulopathies or BP
assess the full range of biopsy complication domains instability, and inability to accurately attribute complica-
considered important for the KPMP. Although several tions to the biopsy itself as opposed to other conditions
biopsy complications were readily quantified, such as occurring during hospitalization. These results are similar
death, interventions to stop bleeding, red blood cell to those from a recent investigation that examined native
transfusions, and presence of macroscopic hematuria, the kidney biopsy complications in patients with acute kidney
postbiopsy observation period was highly variable; there- disease that was mainly AKI (11). Mortality was 3% in this
fore, events could have been missed, and rules for attri- cohort, but none of the deaths were directly attributed to
bution to the biopsy procedure were not in place. Pain and the kidney biopsy. Red blood cell transfusions were re-
hematoma were more difficult to assess. Pain is subjective, quired in 8% of patients, and 2% needed an intervention to
and no uniform pain assessment standard was applied in stop bleeding; these adverse events were biopsy compli-
the few studies that reported pain. Similarly, there was no cations. These higher complication rates may more accu-
uniform approach to the identification or measurement of rately reflect risk of performing native kidney biopsies in
perinephric hematomas. These issues produced significant patients with AKI in the KPMP who are often hospitalized
heterogeneity between studies, at least in part due to with significant comorbidities, as opposed to those un-
reporting bias. Because of this heterogeneity, we suggest dergoing elective, outpatient kidney biopsies.
that it is reasonable to use the upper limit of the confidence Difficulty arises when analyzing the mortality end point
intervals provided for each complication domain (Table 1) due to the rarity of the event. The paper by Al Turk et al. (8),
to provide patients with the most conservative esti- which has a much higher death rate then all of the other
mate of risk. studies where death was reported, caused issues in the
The most frequent complication of the percutaneous initial analysis (9). Furthermore, with many studies report-
native kidney biopsy seems to be a postbiopsy perinephric ing zero deaths, the preferred analysis that uses random
6 CJASN

effects could not be used. Instead, we fit a b-binomial experiences in the United States and abroad, the presented
model, a method that has been shown to be useful in estimates most likely reflect current practice by minimizing
the setting of meta-analysis of proportions for very single-center biases.
rare outcomes (8). In conclusion, this meta-analysis has considered the best
Since performing this systematic analysis, four addi- available data to guide clinicians and patients to make an
tional investigations of complications in adults undergo- informed decision regarding the safety of a kidney biopsy.
ing a native kidney biopsy have been published (12–15). Overall, the data suggest the percutaneous native kidney
Death was examined in three studies and occurred in one biopsy, when done for diagnostic and prognostic purposes,
of 17,125 biopsies, less than the one in 1667 we found in is usually very safe and, by extension, is expected to be
our meta-analysis (12,14,15). The need for blood trans- correspondingly safe in the setting of biopsies being done
fusion postbiopsy was variable. The rate was below 0.5% electively for research purposes, such as the KPMP. How-
in an all-outpatient cohort (12), but it was 4.3% in a mixed ever, patients who are hospitalized may be at higher risk for
outpatient-inpatient cohort and 5.7% in an all-inpatient complications than patients undergoing an elective out-
cohort (13,15). Importantly, the mixed cohort observed a patient biopsy.
57% transfusion rate among inpatients who needed an
urgent kidney biopsy (15). The all-inpatient cohort data Disclosures
were obtained from the Nationwide Inpatient Sample S. Bansal reports other from Home Therapy Institutes, Osprey
database using diagnostic codes and included 35,183 Medical, and UpToDate outside the submitted work. K. Kiryluk
biopsies (13). Most biopsies (70%) were done for AKI, and reports employment by Columbia University and grants from the
28% of the patients had diabetes. The meta-analysis National Institutes of Health (the National Institute of Diabetes and
found an overall need for blood transfusion in 1.6% of Digestive and Kidney Diseases, the National Center for Advancing
patients, but when stratified by region, transfusions were Translational Sciences, the National Human Genome Research In-
needed in 4.6% of patients from America, perhaps stitute) during the conduct of the study and reports other from
reflecting a large number of inpatient biopsies. This Goldfinch Bio and nonfinancial support from AstraZeneca outside
estimate may be more relevant when discussing biopsy the submitted work. G.M. McMahon reports receiving nonfinan-
complications with potential research subjects who are cial support from GSK. P.M. Palevsky reports receiving personal
inpatients. Finally, the need for angiography or surgical fees from Baxter and grants from BioPorto and Dascena outside
intervention to control bleeding was 0.6% or less in all the submitted work. S. Parikh reports receiving grant U01:
four studies, a bit higher than the meta-analysis rate of IN4687813OSU from the National Institute of Diabetes and Di-
0.3%. A meta-analysis of 23 investigations of kidney gestive and Kidney Diseases/the National Institutes of Health
biopsy complications in pediatric patients also demon- during the conduct of the study. E.D. Poggio reports receiving
strated a low incidence of major bleeding events (16). consulting fees from CareDx. S.E. Rosas reports attending one sci-
Blood transfusions were required in 0.6% of patients, and entific advisory board each for Bayer HealthCare Pharmaceuticals
an intervention to control bleeding was needed in 1.2% Inc. and Reata in 2019, for which she was compensated. She has
of patients. received grant support from Bayer HealthCare Pharmaceuticals Inc.
Relevant to the underlying question of whether an extra and is about to start a study with MedImmune Limited, a wholly-
research core of kidney tissue can be safely obtained during owned subsidiary of AstraZeneca AB; both are clinical trials related
native kidney biopsy, the Transformative Research in to diabetic nephropathy. B.H. Rovin reports receiving personal fees
Diabetic Neproplathy (TRIDENT) study recently reported from AstraZeneca, Aurinia, Bristol Myers Squibb, Callidatis, Che-
its initial biopsy experience (17). The TRIDENT is exam- mocentryx, EMD Serono, Janssen, Morphosys, Novartis, Omeros,
ining the molecular pathology of diabetic kidney disease. and Retrophin; nonfinancial support from the Lupus Foundation of
In the first 160 biopsies, 11 patients (7%) had complications, America; and grants from the National Institutes of Health outside
including three patients who needed a blood transfusion, the submitted work. K. Tuttle reports receiving personal fees from
three patients who had gross hematuria, and seven patients AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, and
who had large (.5-cm) hematomas. Importantly, no pa- Novo Nordisk and grants and personal fees from Goldfinch Bio
tient required an invasive procedure to control bleeding, outside the submitted work. A. Vijayan reports receiving personal
and there were no deaths. fees from Boeringher Ingelheim, NxStage, and Sanofi Aventis out-
This analysis did not find an advantage of using an 18- side the submitted work. All remaining authors have nothing
gauge biopsy needle over a 16-gauge needle for any of the to disclose.
complication domains; however, we cannot exclude the
possibility that the 18-gauge needles were used for a Funding
specific indication in these observational studies. None- The KPMP is funded by National Institute of Diabetes and
theless, this suggests that a 16-gauge biopsy needle may Digestive and Kidney Diseases grants UH3DK114861, UH3DK114866,
be safely used to comfortably obtain enough tissue for UH3DK114870, UH3DK114908, UH3DK114915, UH3DK114926,
histologic diagnosis and research purposes. UH3DK114907, UH3DK114920, UH3DK114923, UH3DK114933,
This large meta-analysis of all published literature re- and UH3DK114937.
lated to native kidney biopsies is limited to some extent by
the heterogeneity of the available literature, but its strength Supplemental Material
relies in the comprehensive approach taken by the KPMP to This article contains the following supplemental material online at
evaluate all complication domains that are clinically rele- http://cjasn.asnjournals.org/lookup/suppl/doi:10.2215/CJN.
vant. By systematically reviewing and evaluating all 04710420/-/DCSupplemental.
reported complications, especially from recent single-center Supplemental Figure 1. Overall pain forest plot.
CJASN 15: ccc–ccc, November, 2020 Complications of Native Kidney Biopsies, Poggio et al. 7

Supplemental Figure 2. Overall hematoma forest plot. TRIDENT Study Investigators: The feasibility and safety of ob-
Supplemental Figure 3. Overall macroscopic hematuria forest plot. taining research kidney biopsy cores in patients with diabetes: An
Supplemental Figure 4. Overall erythrocyte transfusion forest plot. interim analysis of the TRIDENT study. Clin J Am Soc Nephrol 15:
1024–1026, 2020
Supplemental Figure 5. Overall surgical/IR intervention forest plot.
Supplemental Figure 6. Overall death forest plot. Received: April 9, 2020 Accepted: July 21, 2020
Supplemental Material. References.
Supplemental Table 1. Study characteristics. *The Kidney Precision Medicine Project members are as follows:
American Association of Kidney Patients, Tampa, FL: Richard
Knight; Beth Israel Deaconess, Boston, MA: Stewart Lecker, Isaac
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Wadhwani S, Townsend RR, Palmer MB, Susztak K, Mottl AK; pages xxx and xxx–xxx, respectively.
8 CJASN

AFFILIATIONS

1
Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
2
Department of Biostatistics, University of Washington, Seattle, Washington
3
Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas
4
Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York
5
Division of Nephrology and Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
6
Division of Nephrology, Brigham and Women’s Hospital, Boston, Massachusetts
7
Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
8
Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
9
Division of Nephrology, Ohio State University Wexner Medical Center, Columbus, Ohio
10
Kidney and Hypertension Unit, Joslin Diabetes Center, Boston, Massachusetts
11
Nephrology Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts
12
Harvard Medical School, Boston, Massachusetts
13
Division of Nephrology, Providence Medical Research Center, Sacred Heart Medical Center, Spokane, Washington
14
Division of Nephrology, UT Southwestern Medical Center, Dallas, Texas
15
Division of Nephrology, Washington University in St. Louis, St. Louis, Missouri
16
Division of Nephrology, Ohio State University Wexner Medical Center, Columbus, Ohio
Supplemental Material
Supplemental Table 1. Study Characteristics

Supplemental Figure 1. Overall Pain Forest Plot

Supplemental Figure 2. Overall Hematoma Forest Plot

Supplemental Figure 3. Overall Macroscopic Hematuria Forest Plot

Supplemental Figure 4. Overall Erythrocyte Transfusion Forest Plot

Supplemental Figure 5. Overall Surgical/IR Intervention Forest Plot

Supplemental Figure 6. Overall Death Forest Plot

Supplemental References
Supplemental Table 1. Study Characteristics * Outlier Study ^ Influential Study

Macroscopic Erythrocyte Surgical


Study Average % Biopsies Pain Hematomas Death
First Author Country Year Hematuria Transfusion Intervention
Design Age Female (n) (n) (n) (n)
(n) (n) (n)

Al Turk*^1 USA 2018 Cohort 55 48 118064 NR NR 15230* 30815*^ 165 2125*^


Altindal2 Turkey 2015 CC 40 40 290 NR NR NR 6 2 1
3
Arora India 2012 RCT NR NR 50 NR 1 1 0 0 0
4
Azhar Pakistan 2005 Cohort NR NR 200 NR NR NR NR NR 0
5
Bataille France 2012 Cohort 55 41 535 NR 2 NR 2 3 0
Branger6 France 1985 RCT NR NR 108 2 2 2 NR NR NR
Carrington7 Wales 2011 Cohort 52 2 192 1 2 4 2 2 0
8
Castoldi Italy 1993 Cohort NR NR 230 7 96 16 NR 2 0
9
Chen USA 2012 Cohort 37 86 219 NR NR NR 5 3 0
Chikamatsu*10 Japan 2017 Cohort 62 39 252 NR NR 36* 12 2 0
11
Chunduri* USA 2015 Cohort 47 68 137 NR 44 1 10 4* 0
12
Cluzel France 2000 CC 49 26 400 NR 1 2 1 3 0
13
Cozens UK 1992 Cohort 47 41 154 23 NR 7 3 2 0
Cui14 USA 2016 Cohort 56 49 86 NR 25 NR NR 2 0
15
DiPalma Italy 2010 Cohort 68 36 110 NR 10 1 0 0 0
16
Doyle USA 1994 Cohort 32 50 155 NR 10 8 NR 1 0
17
Eiro, M Japan 2005 Cohort 44 NR 394 27 149 29 0 0 0
Elahi18 Pakistan 2017 Cohort 36 36 75 NR 20 5 NR NR 0
19
Esposito Italy 2018 Cohort 58 30 337 NR NR NR NR NR 0
20
Fisi* Hungary 2012 Cohort 49 42 353 NR 160 NR 2 8* 0
21
Gesualdo Italy 2008 Cohort 45 NR 110 NR NR NR NR 1 0
Granata22 Italy 2011 CC NR 43 561 NR 15 21 2 1 0
Guerrero23 Spain 2014 Cohort 56 NR 180 NR 9 4 NR 3 0
24
Helenius Finland 1983 RCT 39 50 57 NR 7 NR NR NR 0
25
Hojs Slovenia 2004 Cohort 45 45 144 NR 2 4 0 0 0
Ilsam26 USA 2010 Cohort 44 38 56 NR 11 5 4 0 0
27
Ishikawa*^ Japan 2009 Cohort 45 46 317 67* 273*^ 12 1 0 0
28
Jordan* UK 2014 Cohort 35 86 215 NR 29 3 8 6* 1
29
Joseph USA 2010 Cohort 41 73 170 NR 44 NR 13 NR 0
Khajehdehi30 USA 1999 Cohort NR 45 59 NR NR 3 NR NR NR
Kitterer31 Germany 2015 Cohort 58 39 205 NR 37 NR 3 1 0
32
Kohli India 2006 Cohort 39 32 210 NR 1 11 4 0 NR
33
Korbet USA 2014 Cohort 46 62 1055 3 92 76 56 11 1
Kriegshauser34 USA 2015 Cohort 59 43 293 NR NR NR NR NR 0
35
Lees Scotland 2017 Cohort 57 43 2563 NR NR NR 46 9 1
36
Lin Taiwan 2006 Cohort 46 NR 330 2 55 21 2 NR 0
37
Lubomirova Bulgaria 2014 Cohort 46 48 230 NR 15 NR NR NR NR
Mackinnon38 UK 2008 Cohort 56 40 1120 NR 2 4 15 2 0
39
Mai Australia 2013 Cohort NR 47 934 NR 19 13 8 0 0
Maixnerova40 Czech Rep 2015 Cohort 45 42 9051 NR 133 138 NR NR NR
41
Manno Italy 2011 RCT 41 NR 162 2 36 0 0 0 0
Manno42 Italy 2004 RCT 39 41 471 12 157 2 2 4 0
Margaryan43 USA 2010 Cohort 44 56 146 NR 4 2 1 0 0
44
Marwah USA 1996 Cohort 44 2 394 NR 11 23 22 3 0
45
Mauer USA 2002 RCT 30 53 285 5 4 8 NR 0 0
Maya46 USA 2009 Cohort 42 60 100 NR 13 NR 0 0 0
McMahon47 USA 2012 Cohort 49 NR 105 NR 4 5 NR 1 0
48
Mendelssohn Canada 1995 Cohort NR NR 305 NR 13 27 NR 0 0
49
Mishra Libya 2011 Cohort NR 73 86 NR 2 2 NR 1 0
Miura50 Japan 1984 Cohort 38 46 52 NR 14 3 0 0 0
51
Munib Pakistan 2017 Cohort 28 32 120 9 2 9 2 0 0
52
Nadium Sudan 2013 Cohort 34 44 83 5 NR 4 2 0 0
Saudi
Nyman53 Arabia 1997 Cohort NR 57 168 NR NR NR NR NR 0
54
Ori Israel 2002 Cohort 53 47 85 NR 7 1 4 0 0
55
Paivansalo* Finland 1984 Cohort 41 44 70 12 46* NR NR NR 0
56
Pendon-Ruiz Spain 2014 Cohort 49 3 241 NR NR 19 9 2 NR
Pincon57 France 2010 Cohort 77 48 150 NR 5 1 3 0 0
58
Prasad India 2015 Cohort 34 31 2138 NR NR NR NR NR 0
59
Preda Netherlands 2003 Cohort NR NR 170 NR 30 3 4 NR 0
60
Rao India 2018 CC 37 40 307 NR 10 19 2 4 0
Richards61 UK 1994 Cohort 41 NR 276 NR 1 8 2 NR 0
Roccatello62 Italy 2017 Cohort 55 39 462 NR 15 12 NR 6 0
63
Rollino Italy 1994 RCT NR NR 201 NR 44 21 NR NR 0
64
Rollino Italy 2014 Cohort 79 45 131 NR 8 3 NR 1 0
Rychlik65 Czech Rep 2004 Cohort 42 41 4004 NR NR 273 NR NR NR
Sakaci66 Turkey 2015 Cohort 71 38 78 NR NR 1 0 0 0
67
Sakhuja India 1990 Cohort NR NR 150 NR NR 9 1 0 0
68
Sethi USA 2013 Cohort 47 59 100 2 NR NR 8 1 0
Shah69 Singapore 1993 Cohort 32 NR 100 6 NR 4 NR NR 0
70
Shidam USA 2005 Cohort 42 50 645 NR 6 12 16 4 0
71
Soares USA 2008 Cohort NR 44 289 NR NR NR 6 5 0
72
Sosa-Barrios Spain 2017 Cohort 44 58 175 NR NR NR NR NR 0
Tabatabai73 USA 2009 CC NR 61 1116 NR NR NR 24 8 0
Tan74 China 2017 Cohort 40 50 400 NR 9 1 NR NR 0
75
Tanaka*^ Japan 2017 Cohort 50 47 462 NR 386*^ 5 2 0 0
76
Tang Hong Kong 2002 Cohort NR NR 141 2 2 5 2 2 0
Tikkakoski77 Finland 1994 Cohort 43 47 101 7 11 3 2 0 0
Tondel78 Norway 2012 Cohort 51 NR 8573 NR NR 167 78 17 NR
Torres-
Munoz79 Mexico 2011 Cohort 34 71 623 NR 96 10 11 3 0
80
Tung UK 1992 Cohort 45 38 104 NR 2 4 3 1 0
Wang81 China 2015 Cohort 40 41 1985 NR 84 57 71 16 0
Werner82 Israel 2007 Cohort 46 38 77 NR 12 6 0 0 0
83
Whittier USA 2004 Cohort NR NR 750 NR 51 56 38 5 2
Yamamoto84 Japan 2015 Cohort 45 48 15191 NR NR NR 76 15 9
Yang85 China 2015 Cohort 67 39 288 NR 5 4 0 0 0
86
Yesudas India 2010 Cohort 43 44 65 NR 1 2 0 1 0
87
Zhang China 2011 Cohort 40 44 280 NR 84 20 0 0 0
Supplemental Figure 1. Overall Pain Forest Plot
Supplemental Figure 2. Overall Hematoma Forest Plot
Supplemental Figure 3. Overall Macroscopic Hematuria Forest Plot
Supplemental Figure 4. Overall Erythrocyte Transfusion Forest Plot
Supplemental Figure 5. Overall Surgical/IR Intervention Forest Plot
Supplemental Figure 6. Overall Death Forest Plot
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