Early Conversion to Prednisolone/Everolimus as an Alternative Weaning Regimen Associates With Beneficial Renal Transplant Histology and Function: The Randomized-Controlled MECANO Trial.

In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open-label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL). Primary outcomes were renal fibrosis and inflammation. Secondary outcomes were estimated glomerular filtration rate (eGFR) and incidence of rejection at 24 months. The P/MPS arm was prematurely halted. The trial continued with P/CsA (N = 89) and P/EVL (N = 96). Interstitial fibrosis and inflammation were significantly decreased and the eGFR was significantly higher in the P/EVL arm. Cumulative rejection rates were 13% (P/EVL) and 19% (P/CsA), (p = 0.08). A post hoc analysis of HLA and donor-specific antibodies at 1 year after transplantation revealed no differences. An individualized immunosuppressive strategy of early CNI elimination to dual therapy with everolimus was associated with decreased allograft fibrosis, preserved allograft function, and good efficacy, but also with more serious adverse events and discontinuation. This can be a valuable alternative regimen in patients suffering from CNI toxicity.

Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection.

Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium-binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid-derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell-mediated acute rejection.

EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.

In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

Diagnosis of early pancreas graft failure via antibody-mediated rejection: single-center experience with 256 pancreas transplantations.

Early pancreas graft loss is usually attributed to technical failure while the possibility of antibody-mediated rejection (AMR) is generally overlooked. To investigate the role of AMR in early pancreas graft loss, we retrospectively assessed 256 patients with simultaneous pancreas-kidney transplantation (SPK) between 1985 and 2010 at our institute. We included 33 SPK patients who lost their pancreas graft <1 year after transplantation. AMR was diagnosed based on donor-specific antibodies, C4d and histology in 7 cases, 8 cases were suspicious for AMR and 18 pancreas graft losses were not due to AMR. Acute AMR occurred >1 month after transplantation in 6/7 cases, whereas all other causes typically led to loss <1 month after transplantation. Thrombotic lesions occurred equally among the 33 cases. In 12/18 concurrent kidney specimens, the diagnostic results paralleled those of the pancreas graft. All patients with acute AMR of the pancreas graft lost their renal grafts <1 year after transplantation. In the setting of a thrombotic event, histopathological analysis of early pancreas graft loss is advisable to rule out the possibility of AMR, particularly because a diagnosis of acute AMR has important consequences for renal graft outcomes.

Increased metallothionein expression reflects steroid resistance in renal allograft recipients.

Steroid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We aimed to gain insight into the mechanisms underlying steroid resistance by identifying novel molecular markers of steroid-refractory acute rejection. Eighty-three kidney transplant recipients (1995-2005), who were treated with methylprednisolone during a first acute rejection episode, were included in this study. Gene expression patterns were investigated in a discovery cohort of 36 acute rejection biopsies, and verified in a validation cohort of 47 acute rejection biopsies. In the discovery set, expression of metallothioneins (MT) was significantly (p < 0.000001) associated with decreased response to steroid treatment. Multivariate analysis resulted in a predictive model containing MT-1 as an independent covariate (AUC = 0.88, p < 0.0000001). In the validation set, MT-1 expression was also significantly associated with steroid resistance (p = 0.029). Metallothionein expression was detected in macrophages and tubular epithelial cells. Parallel to the findings in patients, in vitro experiments of peripheral blood mononuclear cells from 11 donors showed that nonresponse to methylprednisolone treatment is related to highly elevated MT levels. High expression of metallothioneins in renal allografts is associated with resistance to steroid treatment. Metallothioneins regulate intracellular concentrations of zinc, through which they may diminish the zinc-requiring anti-inflammatory effect of the glucocorticoid receptor.

Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving inflammation of the joints. Among the autoantibodies described in RA, anticitrullinated protein antibodies (ACPAs) are highly specific and predictive for RA. In addition, ACPAs have been implicated in the pathogenesis of RA. However, a direct functional response of immune cells from ACPA(+) RA patients toward citrullinated proteins has not been demonstrated. In this study, we show that exposure to citrullinated antigens leads to activation of basophils from ACPA(+) RA patients within 20 minutes. This was not observed after exposure of basophils to noncitrullinated control antigens or after stimulation of basophils from ACPA(-) RA patients and healthy controls. Basophil activation was correlated with the binding of citrullinated proteins to basophils. Furthermore, serum from ACPA(+) RA patients in contrast to that from ACPA(-) RA patients could specifically sensitize human FcepsilonRI expressing rat basophil cells (RBL), enabling activation by citrullinated proteins. Mast cell degranulation products such as histamine levels were enhanced in synovial fluid of ACPA(+) RA patients as compared with ACPA(-) RA and osteoarthritis patients. In addition, histamine levels in synovial fluid from ACPA(+) RA patients correlated with IgE levels, suggesting degranulation of mast cells by cross-linking IgE. Immunohistochemistry on synovial biopsies demonstrated an increased number of degranulated CD117(+) mast cells in ACPA(+) RA patients; IgE and FcepsilonRI expression in synovial mast cells from ACPA(+) RA patients was increased. In conclusion, our results show an immunological response of immune cells from ACPA(+) RA patients in a citrulline-specific manner. Moreover, these data indicate a role for IgE-ACPAs and FcepsilonRI-positive cells in the pathogenesis of RA.

Mannan-binding lectin mediates renal ischemia/reperfusion injury independent of complement activation.

Ischemia/reperfusion injury (IRI) remains a major problem in renal transplantation. Clinical studies have identified that high serum levels of Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, are associated with inferior renal allograft survival. Using a rat model, we identified an entirely novel role for MBL in mediating renal IRI. Therapeutic inhibition of MBL was protective against kidney dysfunction, tubular damage, neutrophil and macrophage accumulation, and expression of proinflammatory cytokines and chemokines. Following reperfusion, exposure of tubular epithelial cells to circulation-derived MBL resulted in internalization of MBL followed by the rapid induction of tubular epithelial cell death. Interestingly, this MBL-mediated tubular injury was completely independent of complement activation since attenuation of complement activation was not protective against renal IRI. Our identification that MBL-mediated cell death precedes complement activation strongly suggests that exposure of epithelial cells to MBL immediately following reperfusion is the primary culprit of tubular injury. In addition, also human tubular epithelial cells in vitro were shown to be susceptible to the cytotoxic effect of human MBL. Taken together, these data reveal a crucial role for MBL in the early pathophysiology of renal IRI and identify MBL as a novel therapeutic target in kidney transplantation.

Presence of CD163+ macrophages in DCD kidneys with high DGF reduces the risk for acute cellular rejection in 6 months after kidney transplantation.

Acute cellular rejection (ACR) occurs in 10% of renal allograft recipients and is characterized by leukocyte infiltration as observed in needle biopsies. ACR onset is subject to several risk factors, including delayed graft function (DGF). As the impact of DGF on the etiology of ACR remains unclear, this study analyzed the association between presence of leukocyte subsets and ACR onset, in DCD kidney biopsies with extensive DGF following transplantation. Immunohistochemical analysis of protocol biopsies taken 10 days after kidney transplantation revealed that patients with high levels of renal CD163+ macrophages have a decreased risk (OR = 0.021, P = 0.008) for ACR in the first 6 months after transplantation. In pre-transplant biopsies of a comparable DCD cohort, with >80% DGF, presence of donor CD163+ macrophages showed no effect on ACR risk. Therefore, leukocyte infiltrate present during the inflammatory response at the time of DGF may contain anti-inflammatory macrophages that exert a protective effect against ACR development.

Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema.

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.

Pathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis.

What drives human beings to classify? It seems as if it is within our nature to do so. Clinical classification systems for the systemic vasculitides were composed a long time ago, and they are constantly being revised and altered. The histopathological features of many diseases are so diverse that classification is called for. The histopathological classification for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis was the culmination of results produced from a number of clinicopathological studies conducted within the European Vasculitis Study Group (EUVAS). The classification scheme has four general categories, named focal, crescentic, sclerotic and mixed. The first three categories are based on the predominance of normal glomeruli, glomeruli with cellular crescents and globally sclerotic glomeruli. The mixed category represents a heterogeneous phenotype of biopsies in which none of the aforementioned features is dominant. Results from a validation study incorporating 100 patients with at least 1-year follow-up showed that the phenotypical order of the four classes corresponded to the severity of renal function impairment. The new histopathological classification for ANCA-associated glomerulonephritis provides a logical structure for the categorization of patients into four subgroups defined according to glomerular features. This classification will be of use for future studies, such as clinical trials.

Pancreas allograft biopsies with positive c4d staining and anti-donor antibodies related to worse outcome for patients.

C4d+ antibody-mediated rejection following pancreas transplantation has not been well characterized. Therefore, we assessed the outcomes of 27 pancreas transplantation patients (28 biopsies), with both C4d staining and donor-specific antibodies (DSA) determined, from a cohort of 257 patients. The median follow-up was 50 (interquartile range [IQR] 8-118) months. Patients were categorized into 3 groups: group 1, patients with minimal or no C4d staining and no DSA (n = 13); group 2, patients with either DSA present but no C4d, diffuse C4d+ and no DSA or focal C4d+ and DSA (n = 6); group 3, patients with diffuse C4d+ staining and DSA (n = 9). Active septal inflammation, acinar inflammation and acinar cell injury/necrosis were significantly more abundant in group 3 than in group 2 (respective p-values: 0.009; 0.033; 0.025) and in group 1 (respective p-values: 0.034; 0.009; 0.002). The overall uncensored pancreas graft survival rate for groups 1, 2 and 3 were 53.3%, 66.7% and 34.6%, respectively (p = 0.044). In conclusion, recipients of pancreas transplants with no C4d or DSA had excellent long-term graft survival in comparison with patients with both C4d+ and DSA present. Hence, C4d should be used as an additional marker in combination with DSA in the evaluation of pancreas transplant biopsies.

Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel.

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

[Arthroscopic lavage plus corticosteroids is more effective than joint aspiration plus corticosteroids in patients with arthritis of the knee]. / Artroscopische lavage met toediening van corticosteroïden effectiever dan gewrichtsaspiratie met toediening van corticosteroïden bij artritis van de knie.

OBJECTIVE: To compare the efficacy of arthroscopic lavage plus corticosteroids (ALC), arthroscopic lavage plus placebo (ALP), and joint aspiration plus corticosteroids (JAC) in patients with arthritis of the knee, and to identify clinical or histological factors that predict outcome. DESIGN: Prospective, randomised. METHOD: Patients with arthritis of the knee (not due to gout, osteoarthritis or septic arthritis) were randomised to 1 of 3 treatment arms: ALC, ALP or JAC. The primary endpoint was time to recurrence; recurrence was defined as recurrent or persistent symptomatic knee swelling requiring local treatment, and/or non-improvement in knee joint score. Synovial tissue specimens were collected for histological analysis. RESULTS: Of the 78 patients enrolled, 3 did not receive the intended therapy and 3 were lost to follow-up. The median time to recurrence was 9.6 months in the ALC group, 3.0 months in the JAC group and 1.0 month in the ALP group. Compared with ALC, the relative risk of recurrence of arthritis (RR) was 2.2 for JAC (95% CI: 1.2-4.2; p = 0.02) and 4.7 for ALP (95% CI: 2.3-9.4; p < 0.0001). In the ALC group, extensive synovial fibrosis was associated with a higher risk of recurrence (RR 5-7; 95% CI: 1.6-20.5; p < 0.01). CONCLUSION: Arthroscopic lavage plus corticosteroids was more effective than arthroscopic lavage plus placebo or joint aspiration plus corticosteroids. The absence of synovial fibrosis predicted a beneficial response.

Erythropoietin, progenitors, and repair.

The erythropoietin-erythropoietin-receptor (EPO-EPO-R) system has recently been identified as an important cellular survival pathway. Its presence has also been demonstrated in the kidney and identified as a therapeutic target to prevent loss of renal function. Part of the protective effects may be related to the action of erythropoietin on endothelial function and expansion of endothelial progenitor cells. This paper reviews current evidence for involvement of these mechanisms in EPO-mediated renoprotection.

Effect of prolonged warm ischemia and pneumoperitoneum on renal function in a rat syngeneic kidney transplantation model.

BACKGROUND: Laparoscopic donor nephrectomy is associated with several advantages for the donor. However, graft function may be impaired due to use of pneumoperitoneum and prolonged warm ischemia. This study investigated the impact of pneumoperitoneum and prolonged warm ischemia on long-term graft function in a syngeneic rat renal transplant model. METHODS: A total of 27 Brown Norway rats were randomized for transplantation of kidneys after three different procedures: no insufflation and no warm ischemia (group 1), no insufflation with 20 min of warm ischemia (group 2), and CO2 insufflation and 20 min of warm ischemia (group 3). Glomerular filtration rate (GRF), serum creatinine, urine volume, urine creatinine, and proteinuria were determined monthly for 1 year. One year after transplantation, the grafts were removed for histomorphologic analysis. RESULTS: No significant differences in GRF, serum creatinine, urine volume, and proteinuria were found among the three groups. Histologic analysis also showed no differences between the groups. CONCLUSION: Warm ischemia in combination with CO2 pneumoperitoneum, as used in laparoscopic donor nephrectomy, does not result in a negative effect on long-term graft function.

Stability and Species Specificity of Renal VEGF-A Splicing Patterns in Kidney Disease.

Vascular endothelial growth factor A (VEGF-A) is essential for maintaining the glomerular filtration barrier. Absolute renal levels of VEGF-A change in patients with diabetic nephropathy and inflammatory kidney diseases, but whether changes in the renal splicing patterns of VEGF-A play a role remains unclear. In this study, we investigated mRNA splicing patterns of pro-angiogenic isoforms of VEGF-A in glomeruli and whole kidney samples from human patients with kidney disease and from mouse models of kidney disease. Kidney biopsies were obtained from patients with acute rejection following kidney transplantation, patients with diabetic nephropathy, and control subjects. In addition, kidney samples were obtained from mice with lupus nephritis, mice with diabetes mellitus, and control mice. The relative expression of each VEGF-A splice variant was measured using RT-PCR followed by quantitative fragment analysis. The pattern of renal VEGF-A splice variants was unchanged in diabetic nephropathy and lupus nephritis and was stable throughout disease progression in acute transplant rejection and diabetic nephropathy; these results suggest renal VEGF-A splicing stability during kidney disease. The splicing patterns were species-specific; in the control human kidney samples, VEGF-A 121 was the dominant isoform, whereas VEGF-A 164 was the dominant isoform measured in the mouse kidney samples.

Distribution of renal lesions in idiopathic systemic vasculitis: A three-dimensional analysis of 87 glomeruli.

Extracapillary proliferation and fibrinoid necrosis are the main diagnostic glomerular lesions in renal biopsy specimens of patients with idiopathic systemic vasculitis. Neither the incidence nor the correlation between extracapillary proliferation and fibrinoid necrosis in renal biopsy specimens from patients with systemic vasculitis has been systematically evaluated. By means of a three-dimensional analysis, we made a topographic reconstruction of the distribution of extracapillary proliferation and fibrinoid necrosis in affected glomeruli and tested different biopsy-processing protocols to optimize histopathologic analysis in clinical practice. Paraffin blocks of renal biopsy specimens from six patients diagnosed with systemic vasculitis were completely and serially sectioned in 2-microm thick sections and stained with the Gomori trichrome method. Glomeruli were scored per section for the presence of fibrinoid necrosis and extracapillary proliferation. Subsequently, a three-dimensional reconstruction was obtained for 87 glomeruli. In only one glomerulus did fibrinoid necrosis occur without extracapillary proliferation; in 51%, a combination of the two lesions was found; in 22%, extracapillary proliferation occurred in the absence of fibrinoid necrosis; and 26% did not show either lesion. Using the standard protocol from our department (ie, evaluation of 20 consecutive sections in various stainings), the chance of finding extracapillary proliferation was 100% and that of finding fibrinoid necrosis was 73%. If 5 sections stained with the Gomori trichrome were added, the latter percentage increased to 86%. Using skip-serial sections, even better results (87% to 92%) were obtained, with four skips as the best option (92%). In conclusion, our finding that fibrinoid necrosis rarely occurs in the absence of extracapillary proliferation may imply that both lesions are etiologically related. In addition, our observations indicate that the incidence of fibrinoid necrosis may be underestimated in clinical practice, depending on the number of sections evaluated.

Short-term impact of carbon dioxide, helium, and gasless laparoscopic donor nephrectomy on renal function and histomorphology in donor and recipient.

BACKGROUND: Laparoscopic donor nephrectomy has the potential to increase the number of living kidney donations by reducing donor morbidity. However, studies have shown that raised intraabdominal pressure can result in transient renal dysfunction. Therefore, laparoscopically procured kidneys might be at higher risk for suffering a period of ischemia during pneumoperitoneum. The objective of this study was to investigate the short-term impact of pneumoperitoneum used for laparoscopic donor nephrectomy on renal function and histomorphology in donor and recipient. METHODS: EXPERIMENT 1: KIDNEY DONOR: Initially, 36 brown Norway (BN) rats were randomized for three procedures: 2 h of carbon dioxide (CO2) insufflation (8 mmHg), 2 h of helium insufflation (8 mmHg), and 2 h of gasless technique (0 mmHg). After this, a unilateral nephrectomy was performed in all the animals. EXPERIMENT 2: RECIPIENT: Subsequently, 36 donor BN rats were subjected to a similar insufflation protocol, but after nephrectomy, a syngeneic kidney transplantation (BN-BN) was performed. Urine and blood samples were collected on postoperative days 1, 3, 7, and 14 for determination of renal function. Subsequently, donor and recipient kidneys were removed for histomorphologic and immunohistochemical analysis. RESULTS: In both donors and recipients, no significant changes in serum creatinine, proteinuria, or glomular filtration were detected between the CO2, the helium, and the gasless control groups. In both experiments, histologic analysis of Kidney specimens did not show any deleterious effects from abdominal gas insufflation. Although kidney grafts exposed to CO2 showed significantly higher numbers of CD45+ leukocytes 3 days after transplantation, immunohistochemical analysis did not show significant differences in number of infiltrating cells (CD4, CD8, ED1, OX6, OX62) between the two insufflation groups and the gasless control subjects. CONCLUSIONS: Abdominal gas insufflation does not have an adverse effect on the renal function of the kidney donor 1 week after laparoscopic donor nephrectomy. No differences in renal function or histomorphology were detected between syngeneic kidney grafts exposed to pneumoperitoneum and gasless control subjects.

Renal granulomas in systemic vasculitis. EC/BCR Project for ANCA-Assay Standardization.

Renal granulomas are a relatively infrequent finding in the kidney biopsy. They have been described in a number of syndromes such as Wegener's granulomatosis, anti-GBM glomerulonephritis, and sarcoidosis, and are commonly believed to be indicative of a fulminant clinical course. In leading textbooks, diverse definitions of renal granulomas are presented, which has led to controversies in identifying them. This, in combination with their rare occurrence, makes it difficult for the general pathologist to identify them. We present the clinical data of 16 patients with renal granulomas, from a total group of 157 patients with systemic vasculitis. Their renal functioning was not significantly different from the other 141 patients in whose renal biopsies renal granulomas were present. Furthermore, we present two practical definitions for the recognition of renal granulomas in the kidney biopsy, and we show a number of examples of their various histopathological shapes.