Conditions that impede a kidney biopsy.
\r\n\tThis book is intended to provide a series of peer reviewed chapters that the guest editor believe will aid in increasing the quality of the research focus across the growing field of grain and seeds compound functionality research. Overall, the objective of this project is to serve as a reference book and as an excellent resource for students, researchers, and scientists interested and working in different functional aspects of grain and seed compounds, and particularly for the scientific community to encourage it to continue publishing their research findings on grain and seed and to provide basis for new research, and the area of sustainable crop production.
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Recognition of familiar people can be based on three main sources of information: the face, the voice and the name, but the face has usually the greatest impact on this important social skill.
For this reason the study of ‘prosopagnosia’, considered as a form of visual agnosia, specifically concerning the recognition of familiar people through their face, has represented, since the proposal of this term by Bodamer (1947), the dominant and almost exclusive line of research in this field of inquiry. For the same reason, the first cognitive model that has tried to analyse the cognitive and subjective/behavioural stages involved in recognition and identification of familiar people is the Bruce et Young’s (1986) model of familiar faces recognition. The first cognitive step of this model is the formation of a view independent structural description of a seen face, which can be compared with all the known faces stored in the Face Recognition Units (FRUs). A similar process was afterwards hypothesized for other sources of person recognition, such as voices and names, by several authors (Brédart et al., 1995; Burton et al., 1990; Burton et al., 1999; Valentine et al., 1996; Young & Burton, 1999), who assumed that the outcome of the corresponding perceptual processing could be matched with information stored in correlative Voice (VRUs) or Name Recognition Units (NRUs). According to all these models, the second step of the people identification process requires the convergence of information stored in these modality-specific units into person-identity nodes (PINs), allowing identification of a particular person and retrieval of the corresponding semantic (biographical) information. The PINs (or the accessed person-specific knowledge) could, in turn, activate the phonological codes underlying the production of the person\'s proper name.
In spite of the general similarities existing among the model proposed by Bruce and Young (1986) and those offered by following authors, there are also important differences among these models, which concern the locus in which familiarity feelings for the addressed person are generated and in which person-specific information is stored. As for the first point, the Bruce and Young (1986) model assumed that familiarity feelings are generated in the modality-specific recognition units where (for instance) the structural description of a seen face is compared to the familiar faces stored in the FRUs. On the contrary, in the Burton et al. (1990, 1999), Brédart et al. (1995) and Valentine et al. (1996) models, decisions about familiarity are taken at a supra-modal level, namely the PINs, where information from different modalities is combined in person identity nodes. Furthermore, the Bruce and Young\'s (1986) model assumes that PINs store semantic information, whereas Burton et al. (1990, 1999), Brédart et al. (1995) and Valentine et al. (1996) maintain that PINs do not store semantic information, but provide a modality-free gateway to a single semantic system, where information about people is stored in an amodal format.
Main differences between the original Bruce & Young (1986) model and the subsequent, more complex models of familiar people recognition.
Figure 1 reports in a schematic manner the main differences existing between the Bruce and Young (1986) model and the following models (e.g. Burton et al., 1990) with respect to the locus of generation of familiarity feelings and to the relations between PINs and person-specific semantic information.
But even the Burton et al.’s (1990, 1999), Brédart et al.’s (1995) and Valentine et al.’s (1996) statement that information about people is stored in an amodal format in the person-specific semantic system is open to controversies, because some authors (e.g. Snowden et al., 2004; Gainotti et al., 2003 and 2010; Gainotti, 2007aand 2011) maintain that this information is stored in a different format at the hemispheric level, i.e. in a multisensory/pictorial format in the right hemisphere and in a verbally-coded format in the left hemisphere.
Coming back from these general models and controversies to the dominance of face recognition in the identification of famous (or personally familiar) people, it is necessary to clearly distinguish ‘prosopagnosia’ (a defect of face/people recognition, restricted to the visual modality) from multimodal disorders in familiar people recognition, but this distinction has not been systematically made in the literature, because many patients who showed a multimodal disorder in familiar people recognition have been described as affected by prosopagnosia. This failure to distinguish prosopagnosia from multimodal familiar people recognition disorders is probably due to the dominance of faces in the recognition of known people and can be observed both in anatomo-clinical observations and in group studies. To stress the frequency with which patients affected by a multimodal people recognition defect have been considered as instances of prosopagnosia, and to underline the anatomical locus of lesion that subsume the multimodal forms of familiar people recognition disorders, we will limit ourselves to quote two classical anatomo-clinical observations, and two recent group studies of patients affected by right temporal variant of fronto-temporal degeneration (Hodges, 2000; Snowden et al., 1996; Tyrrel et al., 1990). The first anatomo-clinical observation, originally reported by Bouduresque et al. (1979) and afterwards studied in more details by Sergent & Poncet (1990), concerned a patient (M.me V.) who, after a Herpes Simples Encephalitis (HSE), complained of severe difficulties to recognize familiar people by face, in the absence of intellectual, memory, linguistic or visual defects.
The claim that M.me V’s defective recognition of familiar people was not due to a subtle disorder of visual perception was documented by the fact that she showed no problems in the treatment of unknown faces during administration of a test similar to the Benton and Van Allen (1968) face matching test. Bouduresque et al. (1979) also noted that their patient repeatedly claimed being able to identify her family members, by hearing their voice, but that her performance was very poor when voice identification was investigated with an objective procedure. As for the lesion location, she showed on CT scan, a massive damage of the anterior parts of the right temporal lobe (RTL), in keeping with the usual localization of lesions caused by HSE (Gitelman et al., 2001).
The second anatomo-clinical observation concerned a man (LP) reported by De Renzi (1986) and De Renzi et al. (1987), who had also suffered from a previous HSE. This patient showed a widespread semantic disorder, but was unimpaired from the attentional, linguistic and visual point of view (including tests performed with unknown faces) and was considered as a case of ‘associative prosopagnosia’ (De Renzi et al.,1991), even if he also showed a multimodal defect of familiar people identification. As in the Bouduresque et al. (1979) patient, the anatomical lesion involved the antero-mesial parts of the temporal lobes, but this time with a left-sided prevalence. The two group studies relevant to the distinction between prosopagnosia and multimodal familiar people recognition disorders have been reported by Josephs et al. (2008) and by Chan et al. (2009). The first authors, starting from the description of a ‘progressive prosopagnosia’ in two SD patients (Evans et al., 1995; Joubert et al., 2003), tried to assess with the ‘voxel-based morphometry’ (VBM) the patterns of gray matter atrophy in SD patients with and without prosopagnosia. Results of this study showed that in SD patients with prosopagnosia atrophy mainly affects the antero-mesial parts of the RTL, whereas in those without prosopagnosia the lesion mainly involves the left temporal lobe. Chan et al. (2009), on the other hand, tried to identify the clinical profile associated with predominantly RTL atrophy and observed that prosopagnosia was reported by 60% of these patients. Note that, just as Bouduresque et al. (1979) and De Renzi (1986), also Josephs et al. (2008) were aware of having made an inappropriate use of the term ‘prosopagnosia’, because, contrary to what happens in real prosopagnosia, in their patients the person recognition defect was not confined to the visual (face) modality, but also concerned the voice and the name of the known person.
In any case, the just mentioned anatomo-clinical observations and the results of the group studies show that in patients with multimodal familiar people recognition disorders, the lesion lies outside the posterior temporo-occipital network involved in face processing. This network spans, indeed, from the inferior occipital areas (‘Occipital Face Area/OFA of Gauthier et al., 2000) to the lateral portion of the mid-fusiform gyrus where is located the Face Fusiform Area (FFA/Kanwisher et al., 1997), whereas in patients showing a multimodal familiar people recognition disorder the lesion mainly involves the anterior parts of the TL.
Since in patients with multimodal familiar people recognition disorders the lesion can involve both the right (as in the Bouduresque et al. (1979 patient) and the left anterior TL (as in the case reported by De Renzi, 1986), it became necessary to assess if familiar people recognition disorders are similar or different in patients with right and left TL lesions and to evaluate if these differences are relevant with respect to the controversies among theoretical models that we have summarized in the first part of the introduction. The first important contribution in this direction has been provided by Snowden et al. (2004), who have argued that a fine-grained investigation of the person-specific semantic impairment obtainable from visual (face) and verbal (name) stimuli in patients with degenerative lesions of the right and left TL could contribute: (a) to evaluate if different patterns of familiar people recognition disorders can be observed in patients with right and left TL lesions and (b) to clarify the debate concerning the ‘unitary’(abstract-amodal) or ‘non-unitary’ (concrete-multisensory vs verbally-coded) format of semantic representations.
One of the cornerstones of this debate turns, in fact, around the hypothesis that dissociations in access to the semantic representation through the visual and the verbal modalities may be due to the ‘perceptual affordances’ of objects, namely to the perceptual features that could "suggest" which actions can be performed with those objects (Norman, 1988), allowing ‘privileged accessibility’ from vision to part of the semantic representation (Caramazza et al., 1990). Snowden et al. (2004) reasoned that, since people’s faces and names are arbitrary, the study of person-specific semantic information obtainable from visual (face) and verbal (name) stimuli in patients with degenerative lesions of the right and left TL could represent a potentially valuable means of addressing the unitary vs non-unitary semantic systems controversy, ruling out the possible influence of the perceptual affordances of objects. Results of their study showed that semantic information accessed through face and name are different according to the prevalent side of atrophy. Semantic dementia patients with predominantly left temporal lobe atrophy identified faces better than names and performed better on the picture than on the word version of the semantic memory ‘Pyramids and Palm Trees’ test (Howard & Patterson, 1992), whereas patients with right temporal lobe atrophy showed the opposite pattern of performance. These data were considered as incompatible with a unitary abstract model of semantic memory. A problem with this study consisted of the fact that, due to the rarity of this disease, the number of patients reported by Snowden et al. (2004) was relatively small and that paired comparisons between patients with right and left TL atrophy did, therefore, seldom reach significance. Since studies of semantic dementia patients typically involve single case studies, we thought that a strategy allowing to further check the Snowden et al.’s (2004) hypothesis could consist in systematically reviewing all the published individual cases of patients with a prevalent damage to the anterior parts of the right or left TL, in whom disorders of person recognition were on the foreground. Results of our review (Gainotti, 2007a) confirmed the findings of Snowden et al. (2004) and offered data provided of theoretical significance, since they were consistent with the Bruce and Young (1986) model, and inconsistent with the alternative models of Burton et al. (1990 and 1999), Bredart et al. (1995) and Valentine et al. (1996), with respect both to the locus of generation of familiarity feelings and to the functions of the PINs.
As for the first point, two main findings suggested that familiarity judgements were generated at the level of the modality-specific recognition units rather than at the PINs level. The first was that familiarity judgements were much more impaired in right than in left TL patients and the second that in patients with RTL lesions familiarity defects were modality-specific, concerning more famous faces than famous names. These findings suggested that familiarity feelings, being modality-specific, should be generated at the level of recognition units and in particular of the FRUs, that could be more represented in the RTL due to the major role played by the right hemisphere in face processing (De Renzi, 1986; De Renzi et al., 1994; Michel et al., 1989).
As for the second point, results of our review were inconsistent for two main reasons with the hypothesis assuming that PINs provide a modality-free gateway to a single system, where semantic information about people is stored in an amodal format. The first was that in patients with a RT damage the loss of person-specific semantic information, was clearly greater from face than from name. The second was that an important imbalance between the amount of person-specific information available from faces and names was also found in right and left TL patients who, showing intact or mildly impaired familiarity judgments, should have (according to the previously mentioned cognitive models) no defect at the PINs level.
A factor that could weaken the relevance of results obtained in our review, with respect to the models of familiar people recognition, was the Haslam et al.’s (2004) observation that in normal subjects both familiarity judgements and access to biographical information are more accurate in response to names than to faces. Now, since in studies considered in our review there were often no normative data, that considered separately familiarity judgement and biographical information obtainable from faces and from names, it was possible that the greater loss of familiarity feelings and of biographical information obtained from faces by RTL patients was in part due to this methodological pitfall. To check if differences observed in our review between patients with right and left anterior TL atrophy were due to the ‘normal’ differences about familiarity judgements and access to biographical information in response to names and faces reported by Haslam et al. (2004), we conducted a new research (Gainotti et al., 2010) in which we made use of two very well controlled normative studies, recently conducted by Bizzozero et al. (2005) and by Bizzozero, et al. (2007) on Italian participants. In the Bizzozero et al. (2005 and 2007) norms, the influence of age, education and gender on familiarity recognition and on person identification from faces and names had been controlled by means of covariate linear models, removing the effect of each variable and calculating from each subject’s raw score the corresponding adjusted score. In a second step, the adjusted scores had been classified into five equivalent scores categories, ranging from 0 (= scores lower than the outer 5% inferential tolerance limits) to 4 (= scores higher than the median value of the sample). Furthermore, in the Bizzozero et al.’s (2005 and 2007) data, the semantic interviews aiming to assess the person identification were restricted to the faces and names correctly judged as familiar by the patient and therefore to people whose PINs should be unimpaired. Possible discrepancies between results obtained from faces and names with this procedure should, therefore, point to a different format of the semantic representation accessed through these different channels and could not be explained on the basis of methodological inconsistencies. The Bizzozero et al. (2005 and 2007) tests of face and name recognition and identification were administered to two patients, showing a selective mild difficulty of familiar people identification and naming due to a predominantly right and left TL atrophy, to see if the conclusions of our previous review were confirmed even with this highly controlled material. If the conclusions of our previous review were correct, the right TL patient should again show a greater impairment of familiarity feelings and of access to person-specific semantic information from faces, whereas, if results of our previous review were biased by a ‘normal’ advantage of names over faces we should observe in this patient no name advantage in familiarity judgment or access to person-specific semantic information. Data obtained in the right TL patient by Gainotti et al. (2010) confirmed the results of the previous review, since this patient showed: (1) a very impaired familiarity for faces, contrasting with a spared familiarity for names, indicating that familiarity judgments are generated at the level of modality-specific recognition units and not of a supramodal PIN; (2) a prevalent impairment of person-specific information available from faces rather than from names also for people that (being recognized as familiar from their face and name), should be normally represented at the PINs level.
Results of our previous review (Gainotti, 2007a) and behavioural data (Gainotti et al., 2010) obtained in a right TL patient, affected by a selective defect of familiar people identification, had a third implication, besides the fact of showing: (a) that familiarity feelings are generated at the level of modality-specific recognition units and (b) that PINs cannot be simply considered as a modality-free gateway to the person-specific semantic system, because they also suggested (c) that semantic information about people is stored in a different format at the level of the right and left temporal lobes. These data, therefore, confirmed the previous results of Snowden et al. (2004) who had shown that semantic dementia patients with predominantly right temporal lobe atrophy are more impaired with faces than with names, whereas patients with left TL atrophy show the opposite pattern of performance. Taken together, data obtained by Snowden et al. (2004) and our results strongly suggested that semantic representations of famous people are not represented in an ‘amodal format’ in both temporal lobes, but in a pictorial format in the right and in a verbal format in the left temporal lobe. Furthermore the Snowden et al.’s (2004) observations that semantic dementia patients with predominantly right temporal lobe atrophy perform worse on the picture than on the word version of the semantic memory ‘Pyramids and Palm Trees’ test (Howard & Patterson, 1992), suggest that this different format is not limited the semantic representation of famous people, but also extends to other conceptual domains. This suggestion is supported by both behavioural and neuroimaging data.
Behavioural data in line with the assumption of a prevalent involvement of the left TL in verbal and of the right TL in pictorial aspects of conceptual knowledge, have been obtained by Damasio et al. (1996 and 2004) and Tranel et al. (1997) in patients with focal lesions of the left and right temporal lobes. Damasio et al. (1996 and 2004) showed that defective retrieval of words denoting entities from various conceptual domains (such as famous people, animals or artefacts) was associated with lesions encroaching upon different parts of the left temporal lobe, whereas Tranel et al. (1997) demonstrated that impaired recognition of pictures representing persons, animals or tools was associated with lesions of the homologous areas of the right temporal lobe. According to these authors, both the left and the right temporal lobes play a mediational role in concept retrieval, but in the left hemisphere the activation of the “word” intermediary region promotes the retrieval of lexical knowledge required for word production, whereas in the right hemisphere the recollection of the perceptual properties of a given stimulus promotes the concrete sensorimotor representation of knowledge pertaining to that object.
Other behavioural data consistent with the hypothesis of a different involvement of the left and right temporal lobes in verbal and pictorial aspects of conceptual knowledge have been obtained in SD patients by Ikeda et al. (2006). These authors tested 10 SD patients and 10 matched controls on an object recognition task in which they were invited to choose (from a four-item array) the picture representing “the same thing” as an object picture that they had just inspected and attempted to name. The target in the response array was never physically identical to the studied picture but differed from it for various aspects. The patients whose structural brain imaging revealed major right-temporal atrophy were more impaired than those with an asymmetric pattern characterised by predominant left-sided atrophy, showing that they had a selective defect in the retrieval of the pictorial properties of objects.
A different role of the right and left ATL has been documented by functional neuroimaging investigations that have taken into account different aspects of familiar people recognition or of conceptual knowledge. Thus, several authors have documented a prevalent activation of the right temporal lobe for famous faces (Ishai et al., 2005), for famous - contrasted with newly learned - faces (Leveroni et al., 2000), during association between faces and person-specific semantic information (Tsukiura et al., 2008) or during a semantic categorization task of famous faces (Brambati et al., 2010). On the other hand, Tsukiura et al. (2008) have shown that the left ATL may mediate associations between names and person-related semantic information and similar results have been obtained by Brambati et al. (2010), who have shown an increased activation of the left anterior TL when subjects were asked to determine whether a stimulus photograph matched with the label of a profession category. Consistent with these results obtained studying different aspects of familiar people recognition are results of investigations which have assessed the correlations between neuroimaging data and conceptual impairment in the verbal and pictorial modality.
Thus, Acres et al. (2009) and Butler et al. (2009), evaluating conceptual knowledge with verbal and pictorial material, and the severity of temporal lobe atrophy with voxel-based measures, have shown that verbal semantic defects are on the foreground when the atrophy mainly affects the left temporal lobe, whereas non-verbal conceptual disorders tend to prevail when the right inferior temporal structures are preferentially disrupted. Similar data have been recently obtained by Mion et al. (2010), who examined with FDG-PET the neural correlates of verbal and non-verbal semantic measures in SD. The semantic verbal task was a picture naming task, whereas the non-verbal semantic task was the ‘Camel and Cactus test’ (Bozeat et al., 2000), similar to the pictorial version of the semantic memory ‘Pyramids and Palm Trees’ test (Howard & Patterson, 1992). Regions of interest (ROIs) were the left and right anterior fusiform gyri and the temporal poles. The left anterior fusiform activity predicted performance on the verbal semantic tasks, whereas the right anterior fusiform metabolism predicted performance on the non-verbal semantic task. Furthermore, an additional behavioural study, performed on a wider cohort of SD patients, confirmed that patients with more extensive right TL atrophy are significantly more impaired on tests of non-verbal semantics.
We will conclude this chapter by reporting in a schematic manner in Figure 2 the implications that data concerning: (a) the patterns of familiar people recognition shown by right and left TL patients and (b) the different format of (person-specific or conceptual) knowledge represented in the right and left temporal lobes could have for models of familiar people recognition.
Two main conclusions are suggested by results of investigations surveyed in the previous sections of this chapter and summarized in Figure 2. The first is that results concerning (a) the locus of generation of familiarity feelings, (b) the relationships between PINs and person-specific semantic knowledge and (c) the format of this kind of knowledge are much more consistent with the simpler and older model of Bruce and Young’s (1986) than with the more recent and complex models of familiar people recognition proposed by Burton et al. (1990, 1999), Brédart et al. (1995) and Valentine et al. (1996). The second is that, to give a plausible account of data obtained in brain-damaged patients, these models cannot ignore some basic inter-hemispheric differences, such as the critical role of the right hemisphere in the generation of face familiarity feelings and the different format of person-specific semantic knowledge at the level of the right and left hemisphere.
Both these issues have been thoroughly discussed in previous reviews (Gainotti, 2007b and 2011) and will be only shortly considered here as two sides of a unitary phenomenon, namely the more primitive (sensori-motor) organization of the right hemisphere and the more complex, language-mediated organization of the left hemisphere.
Within this context, it is possible to assume that the early familiarity feelings may be automatically elicited through a right-hemisphere subcortical route, allowing a first, unconscious, global recognition of familiar faces and fostering the subsequent distinction of known faces (unconsciously detected) from unfamiliar faces.
From the theoretical point of view, this possibility has been suggested by De Haan et al. (1991) with the following expression: ‘When a FRU is activated it will signal that the face is familiar and instigate the retrieval of semantic knowledge concerning the bearer of the face’. Within the same framework, it seems logical to assume that, far from being represented in an abstract amodal format, every kind of person-specific and conceptual knowledge may consist of a more primitive perceptual-motor knowledge (more represented in the right hemisphere) and of a more complex language-mediated and language-structured knowledge, more represented in the left hemisphere. From this point of view, the prevalent impairment of person-specific information available from faces, that we have documented in patients with a right TL atrophy, could be considered as the most impressive manifestation of the disruption of the multi-sensory/pictorial knowledge that seems typical of the right hemisphere.
Renal lesions are subdivided based on duration as acute kidney injury (AKI) and chronic kidney disease (CKD). AKI has numerous hemodynamic, inflammatory, toxic, and obstructive causes, which, when diagnosed and treated early, can be reversed, thereby avoiding permanent damage [1, 2]. CKD, however, is the clinical detection of a progressive, irreversible loss of kidney function, for which the aim of therapy is to minimize the progression of the disease [2].
Percutaneous kidney biopsy has become part of clinical practice in nephrology, as it enables the diagnosis, prognostic assessment, and therapeutic guidance of kidney diseases [3, 4]. Since its advent in the 1950s, advances have been achieved in the technique to improve the diagnostic yield and minimize complications [5].
The indication for a kidney biopsy is determined mainly by signs and symptoms [4]. The global rate of biopsy (number of procedures per million [ppm]) in native kidneys ranges from more than 250 ppm in Australia to less than 75 ppm in the United States. This divergence in kidney biopsy rates is influenced by the prevalence of kidney disease as well as different opinions regarding the value of the procedure in terms of diagnosis, prognosis, and therapy [6].
The main objectives that lead to the indication for kidney biopsy are the need for a precise diagnosis and treatment, the need to determine the degree of activity and chronicity of the lesion in order to establish the prognosis and possible response to treatment, and the evaluation of genetic diseases [6]. The diagnostic contribution of a kidney biopsy is undeniable in cases of nephrotic syndrome, systemic disease kidney failure, unexplained AKI, and transplanted kidney dysfunction [7].
For cases of idiopathic nephrotic syndrome in adults and children older than 6 years of age, the indication for a kidney biopsy is extremely important, as the findings often influence therapeutic decision-making [8]. In a prospective study involving 276 biopsies of native kidneys, the diagnosis resulting from the biopsy influenced the management of 86% of cases of nephrotic syndrome [9]. However, there is a variety of clinical situations of nephrotic syndrome for which a kidney biopsy is not generally performed at the time of diagnosis, such as in cases of children between 1 and 6 years of age due to the high prevalence of minimal change disease [10, 11]. In such situations, corticotherapy is indicated and biopsy is only performed in cases of therapeutic failure or the appearance of another sign or symptom not associated with minimal change disease [11]. Biopsy is also not performed initially in cases of secondary nephrotic disease clearly associated with the introduction of a medication known to cause this condition, such as non-steroidal anti-inflammatory drugs, gold salts, pamidronate, penicillamine, and lithium. This group includes patients with longstanding diabetes with gradual proteinuria progression, those with morbid obesity and slowly increasing proteinuria accompanied or not by diabetes and worsening kidney function, those with systemic diseases such as primary or secondary amyloidosis in which the diagnosis can be made through less invasive methods, such as adipose tissue biopsy, and patients known to have malignant diseases involving nephrotic syndrome [6]. Patients with nephrotic syndrome generally exhibit hematuria, proteinuria, hypertension, and renal dysfunction, and the condition is also often associated with systemic diseases. Therefore, kidney biopsy contributes to the diagnosis, therapeutic decision-making, and classification of the disease (e.g., systemic lupus erythematosus). In suspected cases of post-streptococcal glomerulonephritis, biopsy is only recommended when a gradual worsening in serum levels of creatinine, prolonged hypocomplementemia, and recurring hematuria are observed [6, 7].
Cases of systemic diseases with kidney failure include non-nephrotic proteinuria, isolated glomerular hematuria, and unexplained CKD. Protein is a marker and factor related to the progression of kidney disease. Studies have demonstrated a relation between the degree of proteinuria and the progression of CKD in cases of non-nephrotic proteinuria [7]. Thus, many nephrologists routinely perform a kidney biopsy in patients with higher non-nephrotic proteinuria (1–2 g/day) in the absence of another clinical condition that might explain the findings (e.g., diabetes mellitus or hypertension). However, in situations of low-grade proteinuria (500–1000 mg/day) in the absence of glomerular hematuria, altered kidney function, and clinical/serological evidence of a systemic disease, a biopsy is generally not performed [6]. Biopsy in cases of isolated glomerular hematuria remains controversial, as the procedure exerts little influence on therapeutic decision-making. When performed, the conditions most often encountered are Alport syndrome, thin basement membrane nephropathy, and immunoglobulin A nephropathy. In a prospective analysis, biopsy influenced the therapeutic decision-making in only one of the 36 procedures performed [9]. For patients with unexplained CKD, a kidney biopsy can provide important information, despite the greater risk of complication. In cases of exacerbated CKD, a biopsy may reveal lesions that can be treated and reversed. Moreover, a biopsy can contribute important knowledge to clinical management in cases of the need for a kidney transplant [7].
For patients with unexplained AKI, biopsy is indicated in cases of an uncertain etiology and can influence clinical management in 71% of cases [9]. Biopsy is also particularly useful for early or late-onset dysfunction of a renal graft. In cases of acute graft dysfunction, the procedure enables confirming the diagnosis of rejection and specifying the pathological mechanism (acute cellular rejection or anti-body mediated rejection). Late biopsies also furnish essential information to assist in differentiating the causes of chronic nephropathy of the graft, such as chronic rejection, transplant glomerulopathy, nephrotoxicity, viral disease, lymphoproliferative diseases, and relapse of the base disease. The simplicity of the technical procedure and richness of the diagnostic and prognostic information make biopsy indispensable to the follow-up of renal grafts [7].
Contraindications for kidney biopsy may be absolute or relative. For percutaneous kidney biopsies, absolute contraindications include uncontrolled severe hypertension, the inability of the patient to cooperate with the biopsy, having only one kidney, and uncontrollable hemorrhagic diathesis, whereas relative contraindications include severe azotemia, anatomic kidney abnormalities, anticoagulation, pregnancy, and urinary tract infection [3].
Kidney biopsies can be guided by different imaging methods, the most common of which are ultrasound (US) and computed tomography (CT) due to their good performance and broad availability. In contrast, magnetic resonance is employed little due to the greater cost and need for specific material. The choice between US and CT should be individualized and based on the physician’s experience, kidney volume, location of the biopsy site, patient’s clinical condition, and the availability of the equipment. US is generally the imaging method of choice for guiding a kidney biopsy, since it enables obtaining samples from virtually any site and visualizing the needle in real time. It also does not expose the patient to radiation, can be performed in any environment, including at the bedside, and enables the continual monitoring of any pre-operative complications. It is also the method of choice for post-procedure follow-up, enabling the early detection of complications [4].
To be successful, US-guided kidney biopsy requires specific conditions. The patient must be placed in ventral decubitus on the examining table and the procedure must be performed in a sterile environment. The transducer should be covered with a sterile film. There are specific transducer covers on the market, but a sterile glove can be used in cases of emergency. Antisepsis should be performed on the entire side of the back corresponding to the kidney to be biopsied. The selection of the puncture site is determined by US considering the best path (least distance between the skin and renal capsule and the absence of vascular structures and/or interposed intestinal loops). This region in the center of the US image ensures the safest path for the biopsy and provides better control and resolution of the image.
Once the region to be punctured has been defined, the skin at the puncture site is anesthetized and the area of anesthesia is then extended to the deep layers, preferably reaching the perirenal layers, including adjacencies external to Gerota’s fascia and the renal capsule. An alternative is the use of a long 18G peripheral intravenous catheter with the administration of 20 ml of anesthetic solution (10 ml of 2% xylocaine with no vasoconstrictor +10 ml of 0.9% saline solution or bi-distilled water). The entire anesthetic procedure as well as the subsequent steps should be guided by US. Some authors prefer performing a biopsy with their hands free. The two techniques (with or without US) have the same rates of minor and major complications and obtain adequate material for analysis, but the hands-free method requires greater experience and has a somewhat slower learning curve [1, 12]. Next, the biopsy needle is aligned with the transducer (when US is used) and introduced at a 45° angle to the skin. To ensure the safety of the procedure and control of complications, both the needle and its path should be kept within the US viewing field. The path to follow with the needle in the renal parenchyma should only involve the renal cortex (glomerular region), without transfixing the renal medulla, which contributes little to the study and has large-caliber vessels that could be associated with vascular complications; this also avoids the occurrence of injury to the renal calyces and pelvis [4, 13]. The number of fragments to collect depends on the number and types of exams requested as well as the presence of the pathologist during the exam, who may express opinions regarding the quality of the specimen collected. In procedures without the presence of a pathologist, two fragments are normally collected for each exam solicited.
Different needle calibers, lengths, and tip shapes are available on the market for the collection of material for microscopic analysis. Thin-needle punctures are performed with calibers ranging from 20 to 25, whereas thick-needle biopsies are performed with 14- to 19-gauge needles. Authors state that thin needles provide smaller fragments for analysis, but the fragments have similar quality and anatomopathological interpretation to those obtained with thick needles. Nonetheless, larger fragments enable a more complete study of renal pathologies. Moreover, although a smaller caliber is related to a lower rate of complications stemming from the procedure, it does not assist in the renal evaluation [14]. Along with a core biopsy needle (thick needle), coaxial needles can be used, which have a larger diameter with sufficient inner diameter to enable the navigation of the core biopsy needle in its interior. The use of coaxial needle kits avoids multiple punctures of the capsule, as this mechanism enables acquiring several tissue samples with a single perforation, which reduces the procedure time. However, portions of the organ cannot be sampled with this method and the use of such needles increases the cost of the procedure. The use of coaxial needles enables the operator to easily embolize the needle path with an absorbable gelatin sponge when removing the outer needle at the end of the procedure. This embolization promoted by the coaxial method is believed to reduce the risks of post-biopsy bleeding, but this characteristic is reported to not be an advantage of the method. Thus, both the coaxial and non-coaxial techniques do not appear to influence the bleeding complication rate [15]. The use of spring-loaded tools is currently recommended. These needles are classified based on the form of discharge into the tissue: automatic or semi-automatic (disposable). Such tools are reported to be more effective and safer than classic percutaneous renal biopsies that use the Tru-Cut or Vim-Silverman needle. Automatic tools are more economical, since only part of the kit is disposable. However, the disadvantage is the lower control over the progression of the needle during discharge and capture of the fragment as well as the longer procedure time due to the increase in the number of preparation steps of the needle/spring-loaded tool with the risk of contamination. Semi-automatic tools are more costly due to the fact that the entire system is disposable. The advantages are the security in maintaining all material sterile throughout all steps of the procedure, greater control over the advancing of the needle for the extraction of the fragment, the possibility of checking the intralesional position prior to discharge, and the reduction in procedure time, since no preparation of the needle and spring-loaded tool is needed.
Prior to presenting the biopsy technique to the patient or legal guardian, it is advisable to consult with the physician in charge of the procedure. This moment orientates the patient and family regarding the risks, benefits, and preparation for the procedure. It is also possible to identify possible techniques linked to the peculiarities of each patient, such as having a physical disability that precludes the standard position, deforming kyphoscoliosis, scars, skin diseases, and anxiety disorders. To ensure a successful examination, it is of extreme importance to evaluate recent laboratory exams (within the previous 30 days) and determine the patient’s health condition. Patients should meet basic criteria before being submitted to the procedure (Table 1). If a patient does not meet the minimum requirements, the procedure should be rescheduled until after the base disorder has been corrected. For patients with an urgent need for the procedure, immediate corrective measures should be assessed. For instance, plasma and platelet transfusion may be options in cases of a high international normalized ratio (INR) and low platelet count, respectively. An imaging study should be performed prior to the kidney biopsy to gain knowledge on renal anatomy and determine the presence of ectopias, congenital dysplasia, or polycystic kidneys.
Criteria that impede a kidney biopsy |
---|
Clotting disorders characterized by prothrombin activity <60% |
INR > 1.3 |
Platelet count <60,000/mm3 |
Use of anticoagulant |
Systolic BP > 140 mm Hg |
Urinary infection |
Acute persistent cough |
Skin lesions at puncture site |
Altered mental state |
Conditions that impede a kidney biopsy.
A kidney biopsy is an important diagnostic tool and considered the “gold standard” for the best definition of the majority of nephropathies. It is capable of changing the clinical diagnosis approximately 50% of the time and changing the therapy to be administered approximately 40% of the time [16]. For this to happen, however, an adequate sample must be obtained.
A 19-gauge needle generally furnishes very small, narrow specimens that are often inadequate for the assessment of vessels. Thus, smaller needles, such as 18 or 16 gauge, are advisable [17, 18]. Depending on the needle used, the difference in the obtainment of glomeruli can be as high as 300% [19]. The quantity of glomeruli needed for a secure diagnosis depends mainly on the diagnostic hypothesis and the clinical condition of the patient. For virtual exclusion (with greater than 95% certainty) of the diagnosis of focal segmental glomerulosclerosis, it is essential to have at least 25 glomeruli representing the juxtamedullary portion, as the focal disease affects some glomeruli while sparing others of morphological abnormalities seen with light microscopy and a good sample is important to the best definition of the disease [20]. In contrast, the diagnosis can be confirmed with a single glomerulus for other diseases, such as membranous glomerulopathy, in which diffuse morphological changes are similar in all glomeruli. For still other diseases, such as myeloma nephropathy, the diagnosis is essentially confirmed with representation of the medullary portion. In the analysis of transplanted kidney tissue, the aim is to achieve at least two core fragments exhibiting at least 7–10 glomeruli, two arteries, and the medullary portion (minimum assessment criteria defined by the Banff Meeting) [21].
In the evaluation of most glomerulopathies by light microscopy or immunofluorescence microscopy, 8–10 glomeruli are needed [22]. During the US-guided removal of the fragment, the evaluation of a pathologist is very important, as he/she is capable of determining the adequacy of the sample. The examination of the fresh material determines its sufficiency (quantity of glomeruli) for testing the main clinical hypotheses and provides information on medullary representation as well as the representation of larger vessels (Figure 1).
Ultrasound-guided kidney biopsy. Fragment stored in 0.9% NaCl and analyzed under a light microscope. Renal medulla with medullary rays and characteristic striation. Multiple small round structures (glomeruli) distributed in renal cortex—some paler, others congested with numerous red blood cells (details of two glomerular structures).
After determining the ideal amount of material and its representation of the renal parenchyma, the pathologist stores the samples in specific solutions for different analyses. The solutions should not come into contact with each other, as this would render the subsequent analyses unviable. The largest portion of the fragments should be allocated to light microscopy analysis. The most widely used fixatives are 10% neutral buffered formalin, paraformaldehyde, and Bouin’s solution. In these media, the sample remains viable for analysis for several days. However, earlier histological processing results in analyses of better quality. For the analysis of antigens, such as IgG, IgM, IgA, complement components C3 and Cq1, fibrinogen as well as κ and λ chains, immunofluorescence microscopy should be used. Therefore, the sample should be stored in 0.9% saline solution—if the collection site is near the analysis site—and kept chilled (but not frozen) to obtain the best possible results. If rapid analysis (within several hours) is not possible, the sample should be placed in a transport solution, such as Michel’s or Zeus solution. Although this solution preserves the sample for several days, better results are achieved the earlier the sample is taken for analysis, with poor or even impossible results if the sample is analyzed 5–7 days after being collected [23]. For transmission electron microscopy, a small portion is needed of the cortical parenchyma, with two glomeruli. This analysis is essential to the evaluation of podocytopathies, thin basement membrane disease, and metabolic disease. The fragments should be fixed within minutes after collection in a specific solution (glutaraldehyde or Karnovsky’s solution). In the presence of a pathologist, a small portion may be acquired (1 and 2 mm) and fragmented until obtaining the quantity of glomeruli needed. This material should be placed in a buffered solution after fixation (1–2 days after collection), as the aim of the analysis is to examine the ultrastructure, such as the cytoplasmic membrane, reticulum, and immune deposits, which are lost if not fixed soon enough.
When a biopsy is performed without the presence of a nephropathologist, it is advisable to remove at least one fragment (if possible, two) from the renal parenchyma for each solution. Immunohistochemical analysis for the study of C4d, polyomavirus, adenovirus, cytomegalovirus, PLA2R, IgG4, etc. should be performed with material embedded in paraffin, which is preserved for light microscopy.
A kidney biopsy is considered a minimally invasive method but is not without complications. Depending on the severity, such events are classified as minor and major, which require different forms of treatment (Table 2). Minor complications include hematuria, small perirenal hematomas, arteriovenous fistulas, and pain, all of which normally resolve spontaneously [24]. Major complications include massive bleeding with hemodynamic instability, voluminous perirenal hematomas with refractory disabling pain, and important hematuria with obstruction of the urinary tract by clots. In such cases, management is normally necessary.
Complications | Management |
---|---|
Major complications | |
Disabling intense pain | Optimization of analgesia (use of opioids) |
Hemodynamic instability with blood transfusion | Endovascular treatment (embolization) |
Clot obstructing urinary tract | Irrigation with three-way probe |
Minor complications | |
Arteriovenous fistula | Conservative |
Hematuria | Hydration |
Post-biopsy complication and proper management for each.
Among all forms of complication, bleeding is the most frequent and occurs mainly within the first 12–24 hours after the procedure in nearly all patients [4, 25]. Microscopic hematuria, mild low back pain, and a slight drop in the hemoglobin concentration are frequent findings and should not be considered complications [25]. However, the persistence of these symptoms for more than a week may require a detailed investigation with imaging exams. Post-biopsy chronic hypertension, the puncture of other organs, and perirenal soft part infections have been described but are very rare.
The literature reports variable complication rates, generally ranging from 5 to 16%, with macroscopic hematuria in 3–9% of cases and the need for transfusions in 0.1–3.0% of cases [14, 26, 27, 28, 29]. In such cases, an exploratory ultrasound examination should be performed (Figure 2). Burstein et al. found post-biopsy complications in 14.3% of patients, with 6.6% considered minor and another 7.7% considered major (hemorrhages requiring blood transfusion or another approach) [28]. González-Michaca et al. found major complications in 2.4% of patients and minor complications in 8.65%, the most frequent of which was perirenal hematoma [30, 31]. Native kidneys tend to have a lower complication rate than transplanted kidneys (13.9 and 24.4%, respectively) [32].
Exploratory ultrasound performed on patient with gross hematuria, 24 hours after percutaneous native kidney biopsy. (A and B) Multiple pelvic blood clots (arrow) after renal biopsy.
After a kidney biopsy, patients should remain in observation for at least 4 hours. They are placed at absolute rest in dorsal decubitus and are monitored in this period with the constant evaluation of vital signs. It is also advisable to perform renal ultrasound 1 hour after the procedure in all patients submitted to percutaneous kidney biopsy. The aim of this measure is to evaluate the biopsied area and anticipate possible post-procedure complications, thereby enabling immediate, effective therapeutic support (Figure 3 and Figure 4).
Perirenal hematoma, an hour after percutaneous native kidney biopsy. Computed tomography (CT) scan slices of the abdomen revealed voluminous perirenal hematoma (yellow circle), on the left side. (A and B) Axial scan slices. (C) Coronal scan slice. (D) Coronal scan slice.
Post-biopsy procedures and management.
The volume of the perirenal hematoma formed and the complication rates associated with this procedure have a direct relation of proportionality. Hematomas formed in the first hour after the procedure with volumes greater than 40 ml are related to a greater risk of developing major complications [14] (Figure 5). For cases of minor complications, the patient should receive clear orientation regarding the expected benign evolution of the case and receive medication for the symptoms based on individual need. These patients should be required to return after 7 days for a follow-up ultrasound and definitive discharge of the case if no imaging abnormalities are found and there are no new complaints. In cases of hemodynamic instability, the patient should receive adequate clinical measures at an intensive care unit, followed by an angiographic study. Digital angiography remains the gold standard for the anatomic study of the renal arteries, but computed tomography angiography (angiotomography) has gained popularity, offering comparable accuracy and the advantage of evaluating not only the lumen, but its walls and other visceral changes [32].
Perirenal hematoma, observed an hour after percutaneous native kidney biopsy. (A) Longitudinal ultrasonography exhibiting hematoma area near the posteroinferior border of the left kidney. (B and C) Longitudinal (line 1) and transversal dimension on ultrasound (line 2 and 3) estimated the final volume of 216.73 ml of hematoma area. LK, left kidney; H, hematoma.
After renal vascular mapping and if signs of active bleeding are identified (active escape of contrast medium, pseudoaneurysms, or arteriovenous fistulas), endovascular treatment is indicated, which is a minimally invasive procedure that should be performed by an interventionist radiologist or professional who is duly trained and certified in endovascular techniques (Figure 6). The procedure can be performed through femoral or radial artery access, always initiated with an anatomic study of the renal arteries and respective variations. When a probable focal hemorrhage is identified, superselective arteriography is performed in a coaxial system with a microcatheter and microguide, followed by superselective embolization techniques performed on the compromised vessel. For interventional treatment, the selection of appropriate embolic agents for superselective embolization is the key to achieving desirable outcomes (Figure 7). Embolic agents include PVA particles, coils, and gelatin sponge strips, which can be used either alone or in combination [33]. The de-vascularized area will suffer infarction, which could cause a momentary change in renal function. Thus, more selective catheterism leads to a lower risk of this complication. Pseudoaneurysms are pulsating masses at puncture sites due to the rupture of the arterial wall and extravasation of blood, generally associated with local pain and hematoma. Hemodynamic instability and a drop in hemoglobin concentration may be related to the rupture of pseudoaneurysms. The treatment for pseudoaneurysms and arteriovenous fistulas is recommended for persistent bleeding for more than 72 hours or in cases of the accentuated loss of kidney function after the procedure. It should be stressed that most pseudoaneurysms less than 2.0 cm and arteriovenous fistulas progress with thrombosis and spontaneous resolution within 4 weeks, making conservative treatment the conduct of choice in cases without hemodynamic instability. Patients should remain in intensive care for at least 24 hours after the procedure and a follow-up imaging method should be performed prior to the decision regarding the discharge of these patients.
Renal arteriography, 2 hours after percutaneous native kidney biopsy. (A) Pre-embolization arteriography revealed pseudoaneurysm in a lower renal pole (yellow arrow). (B) Post-embolization superselective arteriography revealed absence of pseudoaneurysm with preservation of the local vasculature (yellow arrow).
Endovascular embolization. (A) A catheter is inserted into femoral artery, by the groin area to access vessels of the kidney and into vascular rupture site. (B) Rupture in arterial blood vessel, which will receive a catheter and embolization material to achieve occlusion.
Imaging-guided renal biopsy is a useful tool for the evaluation and management of renal diseases. This chapter summarizes that percutaneous ultrasound-guided renal biopsy is a safe technique which allows the evaluation of renal disease but is associated with post-biopsy complications. We discuss indications and approach to imaging-guided percutaneous renal biopsies as well as complications and management associated with this.
We thank Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Hospital Santa Casa de Belo Horizonte, Brazil and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.
The authors declare no conflict of interest.
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",metaTitle:"Conflicts of Interest Policy",metaDescription:"As an Open Access publisher, IntechOpen is dedicated to maintaining the highest ethical standards and principles in publishing. In addition, IntechOpen promotes the highest standards of integrity and ethical behavior in scientific research and peer-review.",metaKeywords:null,canonicalURL:"/page/conflicts-of-interest-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"In each instance of a possible Conflict of Interest, IntechOpen aims to disclose the situation in as transparent a way as possible in order to allow readers to judge whether a particular potential Conflict of Interest has influenced the Work of any individual Author, Editor, or Reviewer. IntechOpen takes all possible Conflicts of Interest into account during the review process and ensures maximum transparency in implementing its policies.
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\n\nA Conflict of Interest is a situation in which a person's professional judgment may be influenced by a range of factors, including financial gain, material interest, or some other personal or professional interest. For IntechOpen as a publisher, it is essential that all possible Conflicts of Interest are avoided. Each contributor, whether an Author, Editor, or Reviewer, who suspects they may have a Conflict of Interest, is obliged to declare that concern in order to make the publisher and the readership aware of any potential influence on the work being undertaken.
\n\nA Conflict of Interest can be identified at different phases of the publishing process.
\n\nIntechOpen requires:
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\n\nAll Authors are obliged to declare every existing or potential Conflict of Interest, including financial or personal factors, as well as any relationship which could influence their scientific work. Authors must declare Conflicts of Interest at the time of manuscript submission, although they may exceptionally do so at any point during manuscript review. For jointly prepared manuscripts, the corresponding Author is obliged to declare potential Conflicts of Interest of any other Authors who have contributed to the manuscript.
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