Safety and Complications of Percutaneous Kidney Biopsies in 715 Children and 8573 Adults in Norway 1988–2010

Discussion

The main finding in the present study is that a renal biopsy should be regarded as a safe procedure (both in adults and children) provided that general contraindications are respected, and the overall rate of major complications was less than 1% (Table 2). Of note, the relative risk was even lower in children, and only 2 of 715 children (0.3%) were affected. Importantly, the lowest complication rates were seen in centers performing more than 30 biopsies/yr, indicating the best clinical routines occur when biopsies are done approximately on a weekly basis.

To our knowledge, the current study is the only nationwide registry-based and largest report of renal biopsy complications, and our findings confirm the general impression of low complication rates and improved safety of modern renal biopsy procedures (19). Similar low complication rates have been reported in recent studies (16,19,20) in contrast to earlier studies (reporting 5%–7% complication rates) (21–25). The crucial safety evaluation of kidney biopsies is characterized by the overall risk and frequency of major complications, which in our study, are defined as need of blood transfusion and/or surgery or catheter-based intervention (embolization) secondary to bleeding, and they should not be jeopardized by procedural events of minor clinical relevance. Therefore, the description of kidney biopsy complications should be restrained to clinically meaningful complications, especially because there often is an unfounded skepticism toward biopsies because of many reports of frequent occurrence of clinically less relevant events, like microscopic hematuria, transient gross hematuria, and asymptomatic minor perirenal hematoma. The latter should, in fact, be regarded as an epiphenomenon because of the high incidence (reported in up to 60%–90% of cases after examination prospectively with ultrasonography or computertomography). Of note, several authors found that a hematoma alone is not a reliable predictor of a serious adverse outcome (7,16,26,27). Perirenal hematomas should not be regarded as a clinical significant complication in the absence of significant bleeding or persisting pain necessitating delayed hospitalization. The number of hematomas in the present study was significantly higher in children, probably because of a more systematic use of routine ultrasonographic examination, and this finding must, therefore, be interpreted with caution. Such a view is supported by several studies. The work by Kersnik Levart et al. (16) found mostly small perinephritic hematoma in 63.2% of 87 children, and 10 of the hematomas (11.5%) were more than 2 cm in diameter. Other authors report that the majority of hematomas are less than 2 cm, and about 1%–2% are described as symptomatic (15,28,29).

In the present large study, gross hematuria was seen in less than 2%, and the benign course supports the view that such events should not be considered serious complications unless bleeding is of a magnitude causing a significant decline in hemoglobin concentration or delayed hospitalization. The great majority of the patients (97.9%) had neither macroscopic hematuria nor blood transfusion or surgery/embolization. These findings are in line with other studies (27,30–32).

In the current study, the risk factors for major complications were older age, low eGFR, systolic hypertension, acute renal failure, and smaller center size (<30 biopsies/yr) in the unadjusted analyses. Only low eGFR and smaller center size were associated with increased risk in the adjusted analyses. In fact, the relative risk was 16 times higher when eGFR was below 30 ml/min per 1.73 m² (Table 4). Although elevated risk has been shown previously, the increased risk incurred by kidney failure may be underscored in many reports (14,21,33,34), and the work by Whittier and Korbet (25) found that serious complications were about two times as common in patients with serum creatinine above 5.0 mg/dl. It is conceivable that this observation is associated with the general increased bleeding tendency seen in kidney failure patients (33). Similarly, acute renal failure more than doubled the risk of major complications in our study, and the reason for this finding is probably also related to increased bleeding tendency (Table 4). As a consequence, careful recognition of reduced kidney function before the procedure is important. To minimize biopsy risk, meticulous control of clinical routines (to avoid inappropriate use of anticoagulant medication 1 week before as well as after the biopsy procedure) is mandatory, especially in patients with reduced eGFR.

An overview of studies from many centers shows the wide variation in complication rates (27). In the current nationwide registry study, we found the lowest complication rates in the most active and experienced centers (e.g., university hospitals performing biopsies, on average, on a weekly basis or >30 biopsies/yr). This finding is a reassuring observation that strengthens the importance of introducing adequate training programs (27) and supports the view that modern biopsy procedures are safe in experienced hands. Furthermore, the general low complication rate indicates similar adequate clinical practice among our centers. This finding is in contrast to two recent nationwide surveys from the United Kingdom (19) and France (35) showing relatively great variability in clinical practice and complication rates among centers and highlighting the importance of establishing safe procedural standards.

Although there has been a change in practice (fewer patients with isolated microscopic hematuria and more elderly patients undergo a biopsy), the total frequency of renal biopsies in Norway has remained stable for the last 20 years and was 10.9/100,000 in 2009 (13/100,000 in adults and 3.8/100,000 in children). Other reports have shown a range of biopsy frequencies between 3.3 and 23 per 100,000 inhabitants (36,37).

In many centers, the numbers of kidney biopsies are relatively low in children because of a traditional view of many nephrologists and pediatricians that the procedure is associated with an unacceptable high complication risk. General skepticism to the routine use of anesthesia is probably also contributing to the restraint of kidney biopsies. In our cohort, kidney biopsies in children below the age of 15 years were usually performed with short-lasting general anesthesia (sedation) without intubation. Our experience supports the findings in the work by Mauer and Drummond (38) that general anesthesia often can be avoided in patients above the age of 12 years (9). No complications caused by general anesthesia were reported in our study. Hence, the present encouraging findings should contribute to attenuating unfounded skeptic attitudes against kidney biopsies in children as long as general clinical safety routines are respected (14).

Valid biomarkers are generally lacking in many renal diseases, and several important studies have shown the role of kidney morphology as an important prognostic and therapeutic guide in common renal diseases (e.g., IgA nephritis [39], lupus nephritis [40], and diabetes nephropathy [41]); potential prognostic capacity has been shown in orphan diseases like Fabry disease (42). Furthermore, modern therapies of kidney diseases include potent and potentially toxic drug intervention in many common as well as a rapidly increasing number of rare diseases identified by genetic molecular techniques. The latter is mirrored by an increasing general focus from biotechnology companies on development of orphan drugs (43). Importantly, the Food and Drug Administration and the European Medical Association have recently presented guidelines that highlight the importance of meticulous safety and follow-up control of tolerance and side effects of new medical treatment in children (44). Hence, this fundamental change of attitude should also be reflected in the use of evidence-based risk evaluation when it comes to indications of renal biopsy.

It has been suggested that the complication rate is lower with the use of thin biopsy needles (27,45). However, valid comparative studies on needle size and complications in native kidneys are lacking. In the current study, the shift of needle size from 14 to 16 G over time (Figure 2) and the dominance of 16- and 18-G needles (Table 3) may be seen as a result of higher focus, in general, on minimizing risk factors and the acceptance of less tissue per needle pass. The median number of glomeruli per subject in our study (10, range=0–86) was comparable with the median number in other studies (7) and significantly higher by use of both 14- and 16-G needles compared with 18-G needles (P<0.001). However, the percentage of biopsies characterized as representative tissue was in the same level irrespective of needle size. Surprisingly, there was a significantly higher rate of gross hematuria by use of 18 compared with 16 G. This finding has not been reported previously and may be because of the tendency of thinner needles to deviate from the lower pole sector in a proximal direction (where vessel density is higher), with subsequent bleeding into the pelvis. Of note, serious complications, like surgery/embolization and blood transfusions, were of the same order in all needle sizes (Tables 3 and 4).

Interestingly, we did not observe any influence of number of needle passes on the rate of serious complications. The reason for this finding is not known, but it may be related to restraint with multiple needle insertions in high-risk patients and children. In our study, the majority of the biopsy cases (85.4%) had one or two needle passes, and the percentage of patients with three or more passes was low (14.6%). This finding is in contrast to the recent British audit, where the standard target of >80% needing three or less passes was achieved in 86.4% (19). No difference in complication rate was seen between different medical specialists. In our study, most biopsies were performed by a radiologist, whereas 33.4% were done by a nephrologist; the latter percentage has been decreasing over the last decade as reported previously, and it represents an educational challenge in nephrology (27).

Limitations of this study are potential underreporting, reporting bias, and lack of detailed information about other potential complications not prespecified in the registry report form. All GFR analyses were based on eGFR, although imprecision of eGFR is well known in subgroups of patients.

In conclusion, we have shown that kidney biopsies are safe procedures with low complication rates in children and adults when contraindications are respected. Lower eGFR and biopsies performed in smaller centers are risk factors.