Renal Biopsy Findings in Acute Renal Failure in the Cohort of Patients in the Spanish Registry of Glomerulonephritis

Juan M. Lo´pez-Go´mez* and Francisco Rivera,† on behalf of Spanish Registry of Glomerulonephritis *Servicio de Nefrologıá, Hospital Universitario Gregorio Maranõń, Madrid, and †Seccioń de Nefrologıá, Hospital General de Ciudad Real, Ciudad Real, Spain

Background and objectives: Renal biopsy in acute renal failure of unknown origin provides irreplaceable information for diagnosis, treatment, and prognosis. This study analyzed the frequency and clinicopathologic correlations of renal native biopsied acute renal failure in Spain during the period 1994 through 2006. Design, setting, participants, & measurements: Acute renal failure was defined as a rapid deterioration of glomerular filtration rate, with or without oligoanuria or rapidly progressive renal insufficiency, including acute-on-chronic renal failure. Patients who were younger than 15 yr were considered children, those between 15 and 65 yr adults, and those >65 elderly. Results: Between 1994 and 2006, data on 14,190 native renal biopsies were collected from 112 renal units in Spain. Of these, 16.1% (2281 biopsies) were diagnosed with acute renal failure. The prevalence of the main clinical syndromes was different in the three age groups: Biopsy-confirmed acute renal failure in children was 5.7%, in adults was 12.5%, and in elderly increased significantly to 32.9%. The prevalence of biopsy-confirmed acute renal failure according to cause was as follows: Vasculitis, 23.3%; acute tubulointerstitial nephritis, 11.3%; and crescentic glomerulonephritis types 1 and 2, 10.1%. The prevalence of the different causes differed significantly according to age group. Conclusions: The Spanish Registry of Glomerulonephritis provides useful information about renal histopathology in biopsy-confirmed acute renal failure. The prevalence of vasculitis and crescentic glomerulonephritis is high, especially in elderly patients. These data obtained from a national large registry highlight the value of renal biopsy in undetermined acute renal failure. Clin J Am Soc Nephrol 3: 674-681, 2008. doi: 10.2215/CJN.04441007

he study of the epidemiology of biopsy-confirmed re- Materials and Methods nal disease provides useful information about the prev- We analyzed the frequency and clinicopathologic correlations of ARF T alence of renal disease and its clinical manifestations. confirmed by native renal biopsy in Spain and the distribution of the Although there are several renal biopsy registries around the different clinicopathologic findings according to age. Patients who world, most describe the distribution of histopathologic find- were younger than 15 yr were classified as children, those between 15 ings, and very few analyze in detail the main clinical pictures and 65 yr as adults, and those older than 65 as elderly. that indicate renal biopsy, yet knowledge of the epidemiology We analyzed the results of renal biopsies during the period 1994 of renal syndromes is of paramount importance in clinical through 2006 and completed one questionnaire for each patient. ARF was defined as a rapid deterioration of the GFR, with or without nephrology. oligoanuria or rapidly progressive renal insufficiency, including acute- The Spanish Registry of Glomerulonephritis has recorded on-chronic renal failure. Nephrotic syndrome was defined as protein- individual patient data for all renal biopsies performed since uria Ͼ3.5/g per d/1.73 m2 and serum albumin Ͻ2.5 g/dl. Nephritic 1994 (1,2). This information enables us to study the epidemiol- syndrome was defined as hematuria, hypertension, oliguria, edema, ogy of renal syndromes and histopathologic data. Renal biopsy and reduced GFR. Asymptomatic urinary abnormalities were defined in acute renal failure (ARF) of unknown origin provides irre- as proteinuria Ͻ3.5 g/d and/or hematuria with more than three red placeable information for diagnosis, treatment, and prognosis. blood cells and no clinical manifestations, hypertension as BP Ͼ140/90 In this report, we analyze the frequency and clinicopathologic mmHg or antihypertensive treatment, and chronic renal failure as correlations of renal native biopsied ARF in Spain during the serum creatinine levels persistently Ͼ1.5 mg/dl. Each questionnaire period 1994 through 2006. recorded the following variables: Name, hospital, date of birth, gender, presence of arterial hypertension and/or antihypertensive treatment, serum creatinine (mg/dl), creatinine clearance (ml/min), proteinuria (g/d), urinary sediment, main defined clinical syndrome, study meth- Received October 18, 2007. Accepted February 15, 2008. ods, and number of glomeruli obtained. Primary glomerulonephritis Published online ahead of print. Publication date available at www.cjasn.org. (GN) is classified into eight groups: Minimal-change disease; FSGS; proliferative endocapillary GN; crescentic GN (presence of crescents in Correspondence: Dr. Francisco Rivera, Seccio´n de Nefrologı´a, Hospital General Ͼ de Ciudad Real, C/Tomelloso, s/n, 13005 Ciudad Real, Spain. Phone: 00-34- 50% of glomeruli) types 1, 2, and 3; membranoproliferative types 1 629678901; Fax: 00-34-926257585; E-mail: [email protected] and 2 GN; membranous GN, IgA nephropathy; and mesangioprolifera-

Copyright © 2008 by the American Society of Nephrology ISSN: 1555-9041/303–0674 Clin J Am Soc Nephrol 3: 674-681, 2008 Renal Biopsy Findings in ARF 675 tive non-IgA nephropathy. Secondary GN has also been classified into eight groups: Fibrillary, lupus nephritis, collagenosis (scleroderma and other connective tissue diseases not included in another diagnosis), vasculitis, Goodpasture syndrome, cryoglobulinemic GN, amyloidosis, and light-chain nephropathy. Crescentic type 3 and pauci-immune rapidly progressive GN were included in the vasculitis group. Nonin- flammatory renal pathology has been classified into eight groups: Diabetic nephropathy, nephroangiosclerosis, atheroembolic disease, acute tubular necrosis, myeloma kidney, thrombotic microangiopathy, acute tubulointerstitial nephritis (ATIN), and chronic interstitial nephropathy. The remaining causes have been classified into three groups: Unclassified nephropathies, sclerotic kidney, and other miscel- laneous pathologies. Biopsies of transplant kidneys were not studied (1,2). Testing for antineutrophil cytoplasmic autoantibodies (ANCA) Figure 2. Percentages of acute renal failure (ARF) as the main and anti–glomerular basement membrane in serum was not requested indication for renal biopsy during the study period. in this study, and we did not collect outcome or follow-up information.

Statistical Analysis cally different in the three age groups. For children, ARF rep- Data were stored in a database (Microsoft Access; Microsoft Corp., resented 5.7% of all renal syndromes, and for adults and elderly Redmond, WA). Statistical analysis was by SPSS for Windows 10.0.6 (SPSS Systat Inc., Chicago, IL). The normal distribution was determined patients, this figure increased to 12.5 and 32.9%, respectively using the Kolmogorov-Smirnov test. The values are expressed as me- (Table 1). When we consider all biopsied ARF, the distribution dians when the parameters did not follow a normal (Gaussian) distri- according to age was also different: 1.9% in children, 52.8% in bution. The ␹2 and Fisher exact test were used to compare qualitative adults, and 45.3% in elderly patients. variables. P Ͻ 0.05 (by two-tailed testing) was considered to indicate Ninety percent of the patients with biopsy-confirmed ARF statistical significance. had abnormal urinary sediment, mainly hematuria (Figure 3). Men predominated in every age group with an overall ratio of Results 1.5, and the prevalence of hypertension was high. The median Between 1994 and 2006, we collected 14,190 native renal age, proteinuria levels, number of glomeruli obtained, and biopsies from 112 renal units in Spain, 99 of which had at least statistical significance are shown in Table 2. The most impor- one case of ARF. The renal units are listed in the Acknowledg- tant causes of ARF were secondary GN (32.5%), followed by ments. nonglomerular pathology (30.4%), primary GN (28.8%), and Sixteen percent (2281 biopsies) were diagnosed with ARF, other or unclassified nephropathies (8.3%). which is the third indication for renal biopsy after nephrotic The histologic categories of the biopsies are listed in Table 3 syndrome (35.4%) and asymptomatic urinary abnormalities and Figure 4. This distribution differs significantly in the three (21.4%), as indicated in Figure 1. The prevalence of ARF over age groups (P Ͻ 0.001). Vasculitis (including pauci-immune total syndromes as a main indication for renal biopsy increased crescentic or type 3 GN with or without angiitis) was the first significantly during the study period (P Ͻ 0.0001; Figure 2). The cause (23.3%), followed by ATIN (11.3%) and crescentic GN average incidence of ARF was 175 biopsies per year. types 1 and 2 (10.1%). Crescentic GN type 1 (anti–glomerular The prevalence of the main clinical syndromes was statisti- basement membrane antibodies) constituted 12.5% of all crescentic glomerular diseases; type 2 (immune complex related), 20.2%; and type 3, 67.2%. The percentage distribution of the different types of crescentic GN was similar in the three age groups (P ϭ 0.11, data not shown). The prevalence of acute tubular necrosis in our registry is low: 5% of all renal biopsies, with minor differences in the three age groups (Table 3). In children (n ϭ 43), the predominant conditions were thrombotic microangiopathy (20.9%), followed by crescentic GN types 1 and 2, IgA nephropathy, and vasculitis (11.6% each). The predominant conditions in adults (n ϭ 1191) were vasculitis (18.3%), followed by ATIN (11.8%), IgA nephropathy (11.3%), and crescentic GN types 1 and 2 (9.3%; Table 3, Figure 5). This prevalence did not change during the study period. Finally, in elderly patients (n ϭ 1023), there was an even greater prevalence of vasculitis that increased to 29.6%, followed by other forms of crescentic GN types 1 and 2 (10.9%) and ATIN (10.9%; Table 3, Figure 6). These values did not Figure 1. Frequency of the main renal syndromes that required change during the study period. These results are summarized renal biopsy during the study period. in Figure 7, which shows that the prevalence of vasculitis 676 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 3: 674-681, 2008

Table 1. Distribution of renal syndromes according to age: 1994 through 2006 dataa

Asymptomatic Chronic Nephrotic Nephritic Urinary Hypertension ARF Renal Hematuria Age (yr) Syndrome Syndrome Abnormalities (%) (%) Failure (%) (%) (%) (%) (%)

Ͻ15 (n ϭ 748) 47.3 6.8 22.9 0.3 5.7 3.5 13.5 15 to 65 (n ϭ 9494) 36.5 5.1 26.9 2.8 12.5 12.3 3.8 Ͼ65 (n ϭ 3111) 36.8 5.8 9.1 0.8 32.9 13.9 0.7 Total 37.2 5.4 22.5 2.4 16.9 12.2 3.6

aP Ͻ 0.0001 (␹ 2 test). ARF, acute renal failure.

reported 748 cases of ARF with an incidence of 209 cases per million people. The most frequent causes of ARF were acute tubular necrosis (45%), prerenal failure (21%), acute-onset chronic renal failure (12.7%), and obstructive ARF (10%). Al- though the number of renal biopsies performed was low (6.1% of all cases of ARF), it allowed us to diagnose several renal diseases by histopathology. The use of renal biopsy for patients with ARF is usually reserved for the following conditions: (1) absence of an obvious cause; (2) extrarenal manifestations com- patible with a systemic disease; (3) proteinuria, hematuria, or cylindruria; (4) ARF of more than 3 wk duration or prolonged Figure 3. Urinary sediment. anuria; and (5) suspicion of a parenchymatous origin excluding acute tubular necrosis. In our patients, urinary sediment was increased significantly in the three age groups: Thrombotic normal in only 10% of cases and hematuria, cylindruria, and microangiopathy decreased in adults and elderly patients and non-nephrotic proteinuria were present in most cases. More- ATIN was slightly lower in children but similar in adults and over, hypertension was more common than in other cases of elderly patients. ARF. Thus, we assumed that in ARF with hypertension, proteinuria, and altered urinary sediment (mainly hematuria) and Discussion after excluding obvious cases of acute deterioration of renal This observational study is the first description of the epide- function, biopsy provided essential information on histopathol- miology of biopsy-confirmed ARF in native kidneys from a ogy, pathogenesis, and classification (7,8). Although renal bi- large national registry. Most of the patients have glomerular opsy is much safer nowadays thanks to new biopsy guns and disease, and our analysis is made only for patients from whom ultrasonic guidance, it is necessary to tailor indications and biopsies have been taken because of clinical suspicion of GN or evaluate potentially severe risks (9). other renal diseases that merit histologic confirmation. Despite Although there are many renal biopsy registries around the the biases common to national registries—biopsy studied by world, most describe the incidence and prevalence of his- different pathologists, nonhomogeneous biopsy policy, and in- topathologic findings. Very few analyze in detail the main terpretation of histopathologic findings—the data offered by clinical syndromes that indicate renal biopsy. Renal biopsy the Spanish Registry of Glomerulonephritis are representative registries in Australia (10), Denmark (11,12), Macedonia (13), of histologic findings in ARF. Moreover, the large number of Hungary (14), Thailand (15), Peru (16), Korea (17), China (18), renal biopsies (2281) and the long period of data collection (13 New Zealand (19), Brazil (20), Saudi Arabia (21), and the Czech yr) reinforce the value of this database. In all renal syndromes, Republic (22) do not provide information about ARF as a particularly in ARF, histopathologic findings are of paramount separate clinical syndrome at the time of renal biopsy. In the importance for correct diagnosis, prognosis, and even choosing Singaporean (23), Dutch (24), Uruguayan (25), and Japanese therapy (3,4). Haas et al. (5) reported that in patients who were (26) registries, the clinical indication for renal biopsy was ARF aged Ն60 yr and underwent renal biopsy, ARF was the main in 7 to 13.6% of cases; however, the definition of clinical syn- indication of biopsy in 24.3%; moreover, prebiopsy clinical dromes is not clear, and, in most cases, ARF is referred to as diagnosis was correct in only 33% of cases, biopsy enabled a nephritic syndrome or rapidly progressive GN. These discrep- specific diagnosis to be reached in Ͼ90%, and a diagnosis ancies may arise because the definition of ARF is problematic offering the potential for improved outcomes with treatment and a precise operational definition of ARF is not available (27). was made in 73% of cases. The design of our study did not Thus, the term ARF was recently replaced by acute kidney include outcome or follow-up data. injury, and ARF should be restricted to patients who have acute Curiously, the epidemiology of ARF has not been studied in kidney injury and need renal replacement therapy (28). More- detail. In one of the most interesting studies, Lian˜o et al. (6) over, the new Acute Kidney Injury Network has proposed Clin J Am Soc Nephrol 3: 674-681, 2008 Renal Biopsy Findings in ARF 677

Table 2. Distribution of clinical data in biopsied ARF according to agea

Serum Age (yr) Male/Female Hypertension Age Creatinine GFR Proteinuria No. of Ratio (%) (yr) (mg/dl) (ml/min) (g/24 h) Glomeruli

Ͻ15 (n ϭ 43) 1.3 37.2 9 2.9 18.0 1.0 18 15 to 65 (n ϭ 1191) 1.7 53.0 50 5.0 16.0 1.7 12 Ͼ65 (n ϭ 1023) 1.3 58.3 73 5.5 11.0 1.4 11 Total 1.5 53,1 63 5.1 13.1 1.5 12 P 0.0007b Ͻ0.003b – Ͻ0.001c Ͻ0.001c Ͻ0.001c Ͻ0.0001c

aData are medians. b␹2 test. cKruskal-Wallis nonparametric test.

Table 3. Distribution of histopathologic diagnoses in biopsied ARFa

Age (yr) Diagnosis Total (%) (n ϭ 2281) Ͻ15 (%) 15 to 65 (%) Ͼ65 (%) (n ϭ 43) (n ϭ 1191) (n ϭ 1023)

Type 3 crescentic GN ϩ vasculitis 23.3 11.6 18.3 29.6 Acute tubulointerstitial nephritis 11.3 9.3 11.8 10.9 Types 1 and 2 crescentic GN 10.1 11.6 9.3 10.9 IgA nephropathy 8.8 11.6 11.3 6.0 Acute tubular necrosis 5.0 2.3 4.3 6.0 Benign nephrosclerosis 3.8 – 4.8 2.6 Lupus nephritis 3.3 4.7 5.0 1.4 Others 3.3 9.3 4.0 2.2 Unclassifiable 3.0 2.3 2.9 3.1 Thrombotic microangiopathy 2.8 20.9 3.4 1.2 Light-chain cast nephropathy (myeloma kidney) 2.8 – 1.8 4.0 Membranoproliferative GN 2.7 – 3.2 2.2 Endocapillary GN 2.5 4.7 2.1 2.8 Chronic tubulointerstitial nephritis 2.2 – 2.2 2.4 FSGS 2.1 – 2.6 1.4 Sclerotic kidney 2.1 4.7 2.1 1.9 Amyloidosis 2.0 – 1.5 2.4 Anti–glomerular basement membrane antibody 2.0 – 2.4 1.6 (Goodpasture disease) Diabetic nephropathy 1.8 – 1.7 2.0 Non-IgA mesangial GN 1.1 2.3 1.4 0.7 Membranous nephropathy 1.1 – 1.3 0.9 Atheroembolism 0.8 – 0.4 1.3 Light-chain disease 0.7 – 0.4 1.2 Cryoglobulinemia 0.7 2.3 0.8 0.6 Minimal-change disease 0.5 2.3 0.3 0.6 Collagenosis 0.4 0.4 0.3 Fibrillary GN 0.1 – 0.2 –

aGN, glomerulonephritis.

uniform standards for diagnosis and classification, which were ARF is more imprecise than the current definition, the results of published in 2007 (29). Unfortunately, according to these stan- our investigation are representative. dards, our definition of ARF is flawed, thus reflecting the Other large national registries include detailed data on renal problem of this type of definition in national registries during syndromes and allow comparison with other registries of the the study period (1994 to 2006). Although our consideration of importance of renal biopsy in undetermined ARF. A survey by 678 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 3: 674-681, 2008

Figure 7. Renal histopathology by age group.

Figure 4. Causes in all age groups. GN, glomerulonephritis. ARF was necrotizing vasculitis (20.1%) followed by crescentic GN (14%), ATIN (11.3%), and acute tubular necrosis (7.9%). In the French registry (32), ARF constitutes 20% of renal biopsy indications, with a decrease in the last period studied. In the United Arab Emirates, a study of renal diseases (33) revealed that biopsied ARF represents 3.5% of all ARF, although the low number of renal biopsies does not permit comparisons with other larger registries. In more recent reports, the frequency of ARF varied from 2.5 to 12.4%. In Romania (34), ARF was present in 12.4% of the population, although this percentage was significantly lower (9.2%) in patients who were younger than 60 yr than in patients who were older than 60 yr (26.6%). Brazilian data (35) showed that ARF affects 2.5% of the population and rapidly progressive GN affects 7.1%; when the two entities are taken as one, the real incidence of ARF is 9.6%. In the Portuguese renal biopsy registry, ARF affected 9.7% (36), and in the large Indian registry (37), ARF affected 9.3 and 5.2% Figure 5. Causes of biopsy-confirmed ARF in adults. during the two study periods (1971 to 1985 and 1986 to 2002); the decrease may be due to improved health care. In most of these investigations, ARF was preceded by nephrotic syndrome (35), urinary abnormalities (30), recurrent macrohematuria, or nephritic syndrome (34). In our registry (1,2), the main indication was nephrotic syndrome, although ARF constitutes the third indication for renal biopsy (16%). We also found in our database that ARF as a main indication of renal biopsy increased during the last few years of the study; this was probably because biopsy began to be indicated for elderly patients as a consequence of the increase in life expectancy. Thus, in our experience, the percentage of ARF as an indication for renal biopsy increases from 5.4% in children to 11.9% in adults and 31.6% in elderly patients. Many renal diseases are not diagnosed in elderly patients because of comorbidity and the results of serologic tests (ANCA and others), thus creating a new bias in our knowledge of the epidemiology of renal diseases in this age group. Figure 6. Causes of biopsy-confirmed ARF in elderly patients. When we analyze histopathology results, there is consensus on two points: (1) The different patterns according to the age group studied and (2) the elevated incidence of systemic or the Italian registry (30,31), which collected 15,461 biopsies, limited renal vasculitis, especially in the elderly. Thus, the revealed the incidence of ARF as a clinical syndrome in the report of the Italian National Registry of Renal Biopsies in study of renal biopsies to be 9.2%. The most frequent cause of Children (38) confirms that onset of ARF occurs at Ͻ15 yr in Clin J Am Soc Nephrol 3: 674-681, 2008 Renal Biopsy Findings in ARF 679

5.3% of cases (very similar to our results) and that this is clearly acute tubular necrosis and of developing updated guidelines preceded by isolated hematuria, proteinuria, and nephrotic for renal biopsy (44). syndrome. In this group of patients, the most frequent diseases The Spanish Registry of Glomerulonephritis provides useful are crescentic GN, ATIN, and hemolytic-uremic syndrome. Our information about renal histopathology in biopsy-confirmed results are similar, although we found that hemolytic-uremic ARF. ARF associated with proteinuria and/or hematuria is syndrome was predominant in children. The Italian registry produced by several renal diseases other than acute tubular (30) reported that renal biopsy was indicated as a result of necrosis, with important prognostic and therapeutic conse- necrotizing vasculitis, chronic GN, acute tubulointerstitial ne- quences. The prevalence of vasculitis and crescentic GN is high, phritis, and acute tubular necrosis, in percentages similar to especially in elderly patients. These data, obtained from a na- ours; however, that study made no distinctions between adult tional large registry, stress the value of renal biopsy in unde- and elderly patients. termined ARF. The follow-up, prognosis, and outcome of this In our registry, crescentic proliferation (with or without an- type of ARF must be studied in the future. giitis) appears in one third (34.7%) of all renal biopsies; these findings are even more evident in the elderly (42.2%) and are consistent with those reported in elderly patients in the detailed Acknowledgments The following are the participating renal units: A´ lava: Hospital San- investigations of Haas et al. (5) and Uezono et al. (39). When we tiago Apo´stol, Txagorritxu Ospitalea; Albacete: Hospital General de consider the results of all renal biopsies in Spain during the Albacete; Alicante: Hospital de Villajoyosa-Benidorm, Hospital General same period, we see that crescentic GN and vasculitis take sixth de Elda, Hospital General Universitario de Alicante, Hospital General place (6.8%), preceded by IgA nephropathy (14.5%), membra- Universitario de Elche, Hospital Virgen de los Lirios, Hospital Perpetuo nous nephropathy (10.6%), FSGS (9.4%), lupus nephritis (9.2%), Socorro; Almerıá: Hospital Torreca´rdenas; Asturias: Hospital Central and minimal-change disease (7.4) (1,2). In the Italian registry, de Asturias, Hospital Central de Asturias (Infantil), Hospital Valle there was an increase in the percentage of patients who were Naloń; A´ vila: Hospital Nuestra Senõra de Sonsoles; Badajoz: Hospital older than 65 yr and required renal biopsy (40). These findings Universitario Infanta Cristina; Baleares: H. Son Llatzer, Hospital Son highlight the role of crescentic proliferation in the acute dete- Dureta, Policlıńica Miramar; Barcelona: Clıńica Quiront, Consorci Hos- pitalari del Parc Taulı´, Fundacioń Puigvert, H. Althaia, Hospital Clinic rioration of renal failure; however, it is widely known that i Provincial, Hospital de Bellvitge, Hospital de la Cruz Roja, Hospital de pauci-immune crescentic GN is a form of renal limited vascu- Terrassa, Hospital del Mar, Hospital General Vall d’Hebroń, Hospital litis generally associated with ANCA. Here, the prompt diag- San Joan de Deu, Hospital Universitari Germans Trias i Pujol; Burgos: nosis with renal biopsy is a key procedure when initiating Hospital General Yaguë;Caćeres: Complejo Hospitalario San Pedro de immunosuppressive treatment to prevent irreversible glomer- Alcańtara; Ca´diz: Hospital de Jerez, Hospital Puerta del Mar, Hospital ulosclerosis. In our registry, testing to determine the presence Universitario de Puerto Real; Cantabria: Hospital Universitario of ANCA was not requested to simplify the data collected and Marque´s de Valdecilla; Castelloń: Hospital General de Castelloń; facilitate participation. The second cause of ARF is acute tubu- Ciudad Real: Hospital General de Ciudad Real; Co´rdoba: Complejo lointerstitial nephritis, which must be confirmed in severe cases Hospitalario Universitario Reina Sofıá; Corunã, A: Complejo Hospita- lario Universitario de Santiago; Hospital Universitario Juan Canalejo; by renal biopsy so that treatment with steroids and/or immu- Cuenca: Hospital Virgen de la Luz; Girona: Hospital Dr. Josep Trueta; nosuppressive drugs can be started. It is interesting that IgA Granada: Ciudad Sanitaria Virgen de la Nieves, Hospital Universitario nephropathy is a significant cause of biopsy-confirmed ARF in de Granada; Guadalajara: Hospital General Universitario de Guadala- adults (approximately 11%), probably caused by hematuria jara; Guipu´zcoa: Hospital Nuestra Sra. de la Antigua; Huelva: Hospital and/or crescentic proliferation. Finally, it is also important to General Juan Ramoń Jimeńez; Huesca: Hospital San Jorge; Jaeń: emphasize that the incidence of necrotizing crescentic GN has Complejo Hospitalario Princesa de Espanã, Hospital General de Espe- increased in recent years. In a UK study (41), pauci-immune cialidades Ciudad de Jaeń; Las Palmas de Gran Canaria: Hospital rapidly progressive GN accounted for nearly 8% of ARF ad- Nuestra Sra. del Pino, Hospital Universitario Insular de Las Palmas; Leoń: Hospital Virgen Blanca; Lleida: Hospital Arnau de Vilanova; missions. Apart from the clinical picture, crescentic GN is the Lugo: Complejo Hospitalario Xeral Calde; Madrid: Clıńica Puerta de third cause of renal disease, preceded only by membranous GN Hierro, Clıńica Ruber, Fundacioń Hospital Alcorcoń, Fundacioń Jime´- and IgA nephropathy (42); however, the spectrum of intrinsic nez Dıáz, Hospital 12 de Octubre (Adultos), Hospital del Aire, Hospital ARF could be different in less developed countries (43). del Ninõ Jesu´s, Hospital General Universitario Gregorio Maranõń The percentage of cases of acute tubular necrosis in our (Adultos), Hospital General Universitario Gregorio Maranõń (Infantil), registry is very low (5% of all renal biopsies), because most Hospital Militar Go´mez Ulla, Hospital Universitario de Getafe, Hospi- cases are diagnosed with clinical data and we analyzed only the tal Universitario de la Princesa, Hospital Universitario La Paz, Hospital cases of biopsy-confirmed ARF; however, even profound acute Universitario La Paz (Infantil), Hospital Universitario Severo Ochoa; tubular necrosis often has limited pathologic changes, so some Ma´laga: Hospital Carlos Haya (Adultos), Hospital Carlos Haya (Infan- til), Hospital Clıńico Universitario Virgen de la Victoria, Hospital Re- cases with acute tubular necrosis might end up being classified gional de Ma´laga (Infantil); Murcia: Hospital Universitario Virgen de la under their underlying pathology, such as nephrosclerosis or Arrixaca; Navarra: Hospital de Navarra; Ourense: Hospital Cristal diabetes. Nevertheless, several cases of acute allergic interstitial Pinõr; Palencia: Hospital General Rıó Carrioń; Pontevedra: Complejo nephritis, atheroembolism, or another renal disease could have Hospitalario Xeral Cıés, Hospital Montecelo, Hospital Provincial de been confused with acute tubular necrosis. This fact stresses the Pontevedra; Rioja, La: Hospital San Millań y San Pedro; Salamanca: importance of carefully indicating renal biopsy in “atypical” Hospital Clıńico Universitario de Salamanca; Segovia: Hospital General 680 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 3: 674-681, 2008 de Segovia; Sevilla: Hospital General Virgen del Rocıó, Hospital Uni- of Macedonia: Long-term follow-up. Nephrol Dial Trans- versitario Virgen Macarena, Hospital Virgen del Rocıó (Infantil); Soria: plant 18[Suppl 5]: v26–v27, 2003 Hospital General de Soria; Tarragona: Hospital Joan XXIII; Tenerife: 14. Sipiczki T, Ondrik Z, Abraham G, Pokorny G, Turi S, Complejo Hospitalario Nuestra Sra. de la Candelaria, Hospital Nuestra Sonkodi S, Kemeny E, Ivanyi B: The incidence of renal Sra. de la Candelaria (Infantil), Hospital Universitario de Canarias; diseases as diagnosed by biopsy in Hungary. Orv Hetil 145: Teruel: Hospital Obispo Polanco; Toledo: Hospital Virgen de la Salud; 1373–1379, 2004 Valencia: Hospital Clıńico Universitario de Valencia, Hospital Dr. Peset 15. Parichatikanond P, Chawanasuntorapoj R, Shayakul C, Aleixandre, Hospital General Universitari, Hospital San Francesc de Choensuchon B, Vasuvattakul S, Vareesangthip K, Chan- Borja, Hospital Universitario La Fe (Adultos), Hospital Universitario La chairujira T, Sritippayawan S, Vongwiwatana A, Prema- Fe (Infantil); Valladolid: Hospital del Rıó Ortega, Hospital Universita- sathian N, Kiattisunthorn K, Larpkitkachorn R, Onga- rio de Valladolid; Vizcaya: Hospital de Basurto, Hospital de Cruces, jyooth L: An analysis of 3,555 cases of renal biopsy in Hospital de Cruces (Infantil), Hospital de Galdakao; Zamora: Hospital Thailand. J Med Assoc Thai 89[Suppl 2]: S106–S111, 2006 Virgen de la Concha; Zaragoza: Hospital Clıńico Universitario de Zara- 16. Hurtado A, Escudero E, Stromquist CS, Urcia J, Hurtado goza, Hospital Miguel Servet, Hospital Miguel Servet (Infantil). ME, Gretch D, Watts D, Russell K, Asato C, Johnson RJ: Distinct patterns of glomerular disease in Lima, Peru. Clin Nephrol 53: 325–332, 2000 Disclosures 17. Choi IJ, Jeong HJ, Han DS, Lee JS, Choi KH, Kang SW, Ha None. SK, Lee HY, Kim PK: An analysis of 4514 cases of renal biopsy in Korea. Yonsei Med J 42: 247–254, 2001 18. Li LS, Liu ZH: Epidemiologic data of renal diseases from a References single unit in China: Analysis based on 13 519 renal biop- 1. Rivera F, Lo´pez-Go´mez JM, Pe´rez-Garcıá R: Frequency of sies. Kidney Int 66: 920–923, 2004 renal pathology in Spain 1994–1999. Nephrol Dial Trans- 19. The New Zealand Glomerulonephritis Study: Introductory plant 17: 1594–1602, 2002 report. Clin Nephrol 31: 239–246, 1989 2. Rivera F, Lo´pez-Go´mez JM, Pe´rez Garcıá R: Clinicopatho- 20. Bahiense-Oliveira M, Saldanha LB, Mota EL, Penna DO, logical correlations of renal pathology in Spain. Kidney Int Barros RT, Romao-Junior JE: Primary glomerular diseases 66: 898–904, 2004 in Brazil (1979–1999): Is the frequency of focal and seg- 3. Risler T, Braun N, Ittel TH: Multi-centre glomerulonephri- mental glomerulosclerosis increasing? Clin Nephrol 61: 90– tis registry: Basis for optimised therapy. Kidney Blood Press 97, 2004 Res 20: 184–187, 1997 21. Mitwalli AH, Wakeel JSA, Mohaya SSA, Malik HG, Abu- 4. Andreucci VE, Fuiano G, Stanziale P, Andreucci M: Role of Aisha H, Hassan OS, Akhtar M: Pattern of glomerular renal biopsy in the diagnosis and prognosis of acute renal disease in Saudi Arabia. Am J Kidney Dis 27: 797–802, 1996 failure. Kidney Int Suppl 66: S91–S95, 1998 22. Rychlı´k I, JaneòvaÉ, Tesaø V, Kolsky A, Laćha J, Stejskal J, 5. Haas M, Spargo BH, Wit EJ, Meehan SM: Etiologies and Stejskalova´ A, Dusˇek J, Herout V: The Czech registry of outcome of acute renal insufficiency in older adults: A renal biopsies: Occurrence of renal diseases in the years renal biopsy study of 259 cases. Am J Kidney Dis 35: 433– 1994–2000. Nephrol Dial Transplant 19: 3040–3049, 2004 447, 2000 23. Woo KT, Chiang GS, Pall A, Tan PH, Lau YK, Chin YM: 6. Lianõ F, Pascual J: Epidemiology of acute renal failure: A The changing pattern of glomerulonephritis in Singapore prospective, multicenter, community-based study. Madrid over the past two decades. Clin Nephrol 52: 96–102, 1999 Acute Renal Failure Study Group. Kidney Int 50: 811–818, 24. Tiebosch AT, Wolters J, Frederik PF, van der Wiel TW, 1996 Zeppenfeldt E, van Breda Vriesman PJ: Epidemiology of 7. Richards NT, Darby S, Howie AJ, Adu D, Michael J: idiopathic glomerular disease: A prospective study. Kidney Knowledge of renal histology alters patient management Int 32: 112–116, 1987 in over 40% of cases. Nephrol Dial Transplant 9: 1255–1259, 25. Mazzuchi N, Acosta N, Caorsi H, Schwedt E, Di Martino 1994 LA, Mautone M, Gadola L, Petraglia A, Noboa O, Pro- 8. Fuiano G, Mazza G, Comi N, Caglioti A, De Nicola L, grama de Prevencion y Tratamiento de las Glomerulopa- Iodice C, Andreucci M, Andreucci VE: Current indications tias: Frequency of diagnosis and clinic presentation of glo- for renal biopsy: A questionnaire-based survey. Am J Kid- merulopathies in Uruguay. Nefrologia 25: 113–120, 2005 ney Dis 35: 448–457, 2000 26. Iseki K, Miyasato F, Uehara H, Tokuyama K, Toma S, 9. Solez K, Racusen LC: Role of the renal biopsy in acute renal Nishime K, Yoshi S, Shiohira Y, Oura T, Tozawa M, failure. Contrib Nephrol 132: 68–75, 2001 Fukiyama K: Outcome study of renal biopsy patients in 10. Briganti EM, Dowling J, Finlay M, Hill PA, Jones CL, Okinawa, Japan. Kidney Int 66: 914–919, 2004 Kincaid-Smith PS, Sinclair R, McNeil JJ, Atkins RC: The 27. Biesen WV, Vanholder R, Lameire N: Defining acute renal incidence of biopsy-proven glomerulonephritis in Austra- failure: RIFLE and beyond. Clin J Am Soc Nephrol 1: 1314– lia. Nephrol Dial Transplant 16: 1364–1367, 2001 1319, 2006 11. Heaf J: The Danish Renal Biopsy Register. Kidney Int 66: 28. Molitoris BA, Levin A, Warnock DG, Joannidis M, Mehta 895–897, 2004 RL, Kellum JA, Ronco C, Shah SV, on behalf of the Acute 12. Heaf J, Løkkegaard H, Larsen S: The epidemiology and Kidney Injury Network working group: Improving out- prognosis of glomerulonephritis in Denmark 1985–1997. comes of acute kidney injury: Report of an initiative. Nat Nephrol Dial Transplant 14: 1889–1897, 1999 Clin Pract Nephrol 3: 439–442, 2007 13. Polenakovic MH, Grcevska L, Dzikova S: The incidence of 29. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, biopsy-proven primary glomerulonephritis in the Republic Warnock DG, Levin A, and the Acute Kidney Injury Net- Clin J Am Soc Nephrol 3: 674-681, 2008 Renal Biopsy Findings in ARF 681

work: Acute Kidney Injury Network: Report of an initia- adults: towards a renal biopsy registry. J Nephrol 19: 205– tive to improve outcomes in acute kidney injury. Crit Care 210, 2006 11: R31, 2007 38. Coppo R, Gianoglio B, Porcellini MG, Maringhini S: Fre- 30. Schena FP, Italian Group of Renal Immunopathology: Sur- quency of renal diseases and clinical indications for renal vey of the Italian Registry of Renal Biopsies: Frequency of biopsy in children (report of the Italian National Registry the renal diseases for 7 consecutive years. Nephrol Dial of Renal Biopsies in Children). Group of Renal Immuno- Transplant 12: 418–426, 1997 pathology of the Italian Society of Pediatric Nephrology 31. Gesualdo L, Di Palma AM, Morrone LF, Strippoli GF, and Group of Renal Immunopathology of the Italian Soci- Schena FP, Italian Immunopathology Group, Italian Soci- ety of Nephrology. Nephrol Dial Transplant 13: 293–297, ety of Nephrology: The Italian experience of the national 1998 registry of renal biopsies. Kidney Int 66: 890–894, 2004 39. Uezono S, Hara S, Sato Y, Komatsu H, Ikeda N, Shimao Y, 32. Simon P, Rame´e MP, Boulahrouz R, Stanescu C, Charasse Hayashi T, Asada Y, Fujimoto S, Eto T: Renal biopsy in C, Seng Ang K, Leonetti F, Cam G, Laruelle E, Autuly V, elderly patients: A clinicopathological analysis. Ren Fail 28: Rioux N: Epidemiologic data of primary glomerular dis- 549–555, 2006 eases in western France. Kidney Int 66: 905–908, 2004 40. Stratta P, Segoloni GP, Canavese C, Sandri L, Mazzucco G, 33. Yahya TM, Pingle A, Boobes Y, Pingle S: Analysis of 490 Roccatello D, Manganaro M, Vercellone A: Incidence of kidney biopsies: Data from the United Arab Emirates Re- biopsy-proven primary glomerulonephritis in an Italian nal Diseases Registry. J Nephrol 11: 148–150, 1998 province. Am J Kidney Dis 27: 631–639, 1996 34. Covic A, Schiller A, Volovat C, Gluhovschi G, Gusbeth- 41. Hedger N, Stevens J, Drey N, Walker S, Roderick P: Inci- Tatomir P, Petrica L, Caruntu ID, Bozdog G, Velciov S, dence and outcome of pauci-immune rapidly progressive Trandafirescu V, Bob F, Gluhovschi C: Epidemiology of glomerulonephritis in Wessex, UK: A 10-year retrospective renal disease in Romania: A 10 year review of two regional study. Nephrol Dial Transplant 15: 1593–1599, 2000 renal biopsy databases. Nephrol Dial Transplant 21: 419– 42. Vendemia F, Gesualdo L, Schena FP, D’Amico G: Renal 424, 2006 Immunopathology Study Group of the Italian Society of 35. Malafronte P, Mastroianni-Kirsztajn G, Betoˆnico GN, Ro- Nephrology: Epidemiology of primary glomerulonephritis mao JE Jr, Alves MA, Carvalho F, Neto OM, Cadaval RA, in the elderly. Report from the Italian Registry of Renal Be´rgamo RR, Woronik V, Sens YA, Marrocos MS, Barros Biopsy. J Nephrol 14: 340–352, 2001 RT: Paulista registry of glomerulonephritis: 5-Year data 43. Prakash J, Sen D, Kumar NS, Kumar H, Tripathi LK, Sax- report. Nephrol Dial Transplant 21: 3098–3105, 2006 ena RK: Acute renal failure due to intrinsic renal diseases: 36. Carvalho E, Faria MdS, Nunes JPL, Sampaio S, Valbuena Review of 1122 cases. Ren Fail 25: 225–233, 2003 C: Renal diseases: A 27-year renal biopsy study. J Nephrol 44. Cagnoli L, Italian Society of Nephrology: Instructions and 19: 500–507, 2006 implementations for percutaneous renal biopsy: Guide- 37. Narasimhan B, Chacko B, John GT, Korula A, Kirubakaran lines for the therapy of glomerular nephropathies. G Ital MG, Jacob CK: Characterization of kidney lesions in Indian Nefrol 20[Suppl 24]: S3–S47, 2003

See related editorial, “Renal Biopsies in Acute Kidney Injury: Who Are We Missing?” on pages 647–648.