Frequency of renal pathology in Spain 1994–1999

Francisco Rivera1,, Juan Manuel López-Gómez2 and Rafael Pérez-García2 representing the Spanish Registry of Glomerulonephritis

1 Sección de Nefrología, Complejo Hospitalario, Ciudad Real and 2 Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, Spain



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Appendix I
 Appendix II
 References
 
Background. There are not enough large epidemiological population-based studies of biopsy-proven nephropathies with detailed clinical and histopathological data.

Methods. The Glomerulonephritis Registry of the Spanish Society of Nephrology has obtained data from 7016 patients with biopsied renal diseases between 1994 and 1999, investigating prevalence, incidence and clinical and histopathological data. Biopsies of transplant kidneys have not been considered.

Results. The observed biopsy rate for all ages is 4.8 per 100 000 inhabitants. A male predominance is seen for all age groups. The most common clinical syndrome at any age is nephrotic syndrome. The prevalence of hypertension is higher in adults and elderly patients. The most common pathologies are IgA nephropathy, focal glomerulosclerosis, membranous nephropathy and lupus nephritis. The mean annual incidence (per million of population) of the most common nephropathies is IgA nephropathy 7.9, focal segmental glomerulosclerosis 6.4, membranous nephropathy 6.2, lupus nephritis 5.6, minimal-change disease 4.8, nephroangiosclerosis 4.6, vasculitis 4.3, membranoproliferative glomerulonephritis 3.6 and amyloidosis 3.3. In children, the most frequent causes are minimal-change disease, IgA nephropathy and focal glomerulosclerosis. In adults, the most common diagnoses are IgA nephropathy, lupus nephritis, and focal glomerulosclerosis. In elderly patients, the most frequently reported pathologies are vasculitis, membranous nephropathy and amyloidosis. Membranous nephropathy has increased in incidence in recent years.

Conclusions. We provide representative population-based descriptive data on native biopsy-proven renal diseases in Spain.

Keywords: epidemiology; glomerulonephritis; nephropathy; pathology; registry; renal biopsy



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Appendix I
 Appendix II
 References
 
The Spanish Registry of Glomerulonephritis was established in 1987 as a result of several epidemiological retrospective studies on primary glomerulonephritis (GN) that were published in the journal of the Spanish Society of Nephrology Nefrología, and that investigated the needs and usefulness of epidemiological multicentric studies. The study of renal biopsies between 1970 and 1986, with a sample size of 8545 cases in adults and 1364 in children, described the high incidence of IgA nephropathy and the decrease of membranoproliferative glomerulonephritis in Spain [1,2]. An editorial published in Nefrología in 1987 [3] discussed this study, and since then representative data have been repeatedly reported [4].

The Spanish Registry of Glomerulonephritis is one of the largest and most reliable of the registries of biopsied renal pathologies that are published world-wide, perhaps surpassed only by those based in Italy [57] and the UK [8,9]. Considering the number of renal biopsies in relation to the general population in those countries, our results are representative of biopsied renal diseases. Other registries, like those in France [10], United States [11,12], Brazil [13], Australia [14,15], India [16], Estonia [17], Sweden [18], Denmark [19], Singapore [20], Japan [21] and Korea [22], are also representative and permit epidemiological comparisons.

In this report we describe the frequency and clinicopathological correlations of biopsy-proven native renal diseases in Spain during 1994–1999.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Appendix I
 Appendix II
 References
 
We analysed the results of renal biopsies during the years 1994–1999. We recorded the following variables for each patient: name, hospital, population served by each renal unit, date of birth, gender, presence of arterial hypertension, serum creatinine (mg/dl), creatinine clearance (ml/min), proteinuria (g/day), urinary sediment (normal, haematuria, leukocyturia, casts), known interval between diagnosis and renal biopsy (years), main clinical syndrome (nephrotic, nephritic, asymptomatic urinary abnormalities (AUA), arterial hypertension, acute renal failure (ARF), chronic renal failure (CRF), and macroscopic haematuria), histological methods (optic microscopy, immunofluorescence, electron microscopy and number of glomeruli obtained).

Primary GN has been classified into eight groups: minimal-change disease (MCD), focal and segmental glomerulosclerosis (FSGS), proliferative endocapillary GN, crescentic GN (CRESGN) (presence of crescents in more than 50% of glomeruli) types I, II and III according to standard classification [23], membranoproliferative GN (MPGN) types I and II, membranous GN (MN), IgA nephropathy (IgAN), mesangioproliferative non-IgAN (nonIgAN).

Secondary GN has been classified into another eight groups: fibrillar, lupus nephritis (LN), collagenosis (scleroderma and other connective-tissue disease not included in other diagnoses), vasculitis (VAS), Goodpasture's syndrome, cryoglobulinaemic GN, amyloidosis (AMYL) and light-chain nephropathy. The CRESGN type III or pauci-immune, rapidly progressive GN were included in the VAS group.

Non-inflammatory renal pathology has been classified into eight groups: diabetic nephropathy, nephroangiosclerosis (NA) (benign and malignant), atheroembolic disease, acute tubular necrosis, myeloma kidney, thrombotic microangiopathy, acute interstitial nephropathy (ATIN) and chronic interstitial nephropathy (CTIN).

The remaining causes have been classified into three groups: unclassified nephropathies (UN), sclerotic kidney (ESKD) and other miscellaneous pathologies (MIS). Biopsies of transplant kidneys have not been studied in this review.

Patients <15 years of age were considered as children, those >=15 and <65 years as adults, and those >=65 years were classified as elderly individuals.

Nephrotic syndrome was defined as proteinuria greater than 3.5 g/day/1.73 m2 and serum albumin less than 2.5 g/dl. Nephritic syndrome was defined as haematuria, hypertension, oliguria, oedema and reduced glomerular filtration rate. Urinary abnormalities consisted of persistent non-nephrotic proteinuria, with or without microscopic haematuria, and hypertension consisted of blood pressure higher than 140/90 mmHg. ARF was defined as a rapid deterioration of glomerular filtration rate, while CRF was considered when serum creatinine levels were persistently above 1.5 mg/dl.

Spanish regions have been classified into four groups: Northern (Galicia, Asturias, Cantabria, País Vasco, Navarra), Central (La Rioja, Aragón, Castilla-León, Castilla-La Mancha, Madrid, Extremadura), Eastern (Cataluña, Valencia, Murcia and Baleares Islands) and Southern (Andalucia and Canary Islands).

Statistical analysis
Each year's data were stored on a database file (MS Access 2000). Data were tested for normal distribution with the Kolmogorov–Smirnov test. The values are expressed as medians when the parameters did not fit into a normal (Gaussian) distribution. {chi}2 and Fisher's tests were used to compare qualitative variables. A P value <0.05 (by two-tailed testing) was considered significant. The annual incidence was defined as the total number of new cases per year related to the mean total population of the year, taking into account the fact that the data provided by the renal units gave us the size of the population served. It was expressed as per million of population (p.m.p.). The statistical calculations were performed by means of the statistical package SPSS for Windows 10.0.6 (SPSS Systat Inc., Chicago, Illinois, USA).



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Appendix I
 Appendix II
 References
 
General data
Records from 7016 renal biopsies, obtained from 93 renal units (81 adult and 12 paediatric) were studied for the period 1994–1999, as indicated in Figure 1AGo, with a participation of 70.4%. Thirty-six per cent of the cases came from the Eastern region, 33.3% from the Central region, 19.6% from the Southern region and the remaining 11.1% from the Northern region (Figure 1BGo).



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Fig. 1.  (A) Number of renal biopsies in Spain. (B) Regional distribution.

 
Seventy-one per cent of the biopsies came from adults, 7% from children and 22% from elderly patients. The rate of renal biopsy for all ages is 4.8 per 100 000 inhabitants per year.

Figure 2Go shows the results of all renal biopsies in the years 1994–1999. IgAN is the most frequent diagnosis, and together with MN, LN and the variants of idiopathic nephrotic syndrome constitutes 50% of all biopsies. Type III is the most frequent form of CRESGN (65.1%), followed by types II and I at 20 and 14.6% respectively. Most MPGN (88%) is of type I. The secondary form of AMYL comprises 62% of that diagnostic category.



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Fig. 2.  Frequency of different forms of biopsy-proven nephropathies in Spain during 1994–1999; see abbreviations (Appendix I).

 
Table 1Go shows the mean annual incidence of the most frequent nephropathies. The number of hospitals that serve well-documented populations is 39 and the total population is 17056120 inhabitants. Thus the annual average of IgAN is 7.9 p.m.p, FSGS 6.4 p.m.p, MN 6.2 p.m.p. and LN 5.6 p.m.p.


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Table 1.  Annual incidence of biopsied renal diseases in Spain (1994–1999)

 

Clinical data
A male predominance is seen for all age groups, with a male/female ratio in children of 1.2, in adults of 1.5 and in the elderly of 1.4 (P=NS, {chi}2 test). The percentage of patients with arterial hypertension is high and increases significantly with age (children 14.1, adults 47.4 and elderly 56.4%). Table 2Go shows the representative values for age, renal function, proteinuria, evolution time and number of glomeruli obtained on biopsy. The most frequent clinical syndrome is nephrotic syndrome, followed by AUA in children and adults, and by ARF in the elderly, with an increase in the prevalence of ARF and CRF with age (Table 3Go). The most frequent finding in urinary sediment is haematuria (Table 4Go). Most of the cases in all ages are based on the first biopsy (children 94.6%, adults 92.3% and elderly 96.3%). Most of the material obtained is evaluated through MO and IF, complemented by electron microscopy in 17–32% of the cases (Table 5Go).


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Table 2.  Data of the patients with renal biopsy in 1994–1999

 

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Table 3.  Predominant renal syndromes according to age (%)

 

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Table 4.  Urinary sediment according to age (%)

 

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Table 5.  Method of histological study according to age (%)

 

Histopathological data
Primary GN is predominant across age groups. However, secondary GN and non-glomerular pathology are more common in adults and the elderly (Table 6Go).


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Table 6.  Major groups of renal diseases (%)

 
In children, the most frequent renal diseases are: MCD (24.2%), IgAN (19.5%) and FSGS (15.2%), as shown in Figure 3Go. We did not find significant variations in prevalence during the years studied; however, there were some significant variations in regional distribution. In the Eastern region there is a higher incidence of the variants of idiopathic nephrotic syndrome, in the Central region there is a higher prevalence of MPGN, MN and VAS, and in the Northern region more IgAN and LN are found.



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Fig. 3.  Frequency of different forms of biopsy-proven nephropathy in children in Spain during 1994–1999. ENDOGN, endocapillary GN; see abbreviations (Appendix I).

 
In adults, the most common diseases are IgAN (17.2%), followed by LN (11.5%) and FSGS (10.8%), as shown in Figure 4Go. We have not found differences in the evolution of glomerular pathology between the observed years. Some variations in regional distribution are also found: in the Eastern region there is a higher prevalence of NA and IgAN, in the Central region more FSGS and IgAN, in the Northern region there is a higher prevalence of idiopathic nephrotic syndrome, and in the Southern region more MPGN and LN.



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Fig. 4.  Frequency of different forms of biopsy-proven nephropathy in adults in Spain during 1994–1999; see abbreviations (Appendix I).

 
In the elderly, the most frequent diagnoses are VAS (18.3%), MN (12.4%), AMYL (8.3%), IgAN (6.2%) and NA (6.1%), as shown in Figure 5Go.



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Fig. 5.  Frequency of different forms of biopsy-proven nephropathy in the elderly in Spain during 1994–1999. DN, diabetic nephropathy; see abbreviations (Appendix I).

 
Figure 6Go shows the evolution of renal pathologies in recent years in this age group, where we see a moderate increase of MN, with less prevalence of AMYL and MCD.



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Fig. 6.  Evolution of the percentages of RB in the elderly in Spain during 1994–1999; see abbreviations (Appendix I).

 
This is applicable to the primary forms, where the increase of MN is more apparent in the last year of data collection, with a decrease of the CRESGN forms (Figure 7Go). We did not find significant differences in regional distribution.



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Fig. 7.  Evolution of the percentages of primary GN in the elderly in Spain during 1994–1999; see abbreviations (Appendix I).

 



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Appendix I
 Appendix II
 References
 
The epidemiology of GN has certain geographic connotations, and in this sense the data of a national registry provide a more accurate picture of the different incidences in our country and permit certain comparisons with other registries. The data of the GN Registry of the Spanish Society of Nephrology from 1994 to 1999 disclose interesting aspects of the epidemiology of biopsied native renal diseases. In contrast with other registries, we have included all the renal pathologies, glomerular and non-glomerular diseases, because some of them could present with similar clinical syndromes. As can occur in this type of national epidemiological study, the following biases will attenuate the value of the study: (i) incomplete participation of the renal units (30% of them did not contribute to our data); (ii) incomplete knowledge of the size of the served population to calculate (in p.m.p.) the exact incidence of renal pathologies, as 58% of the participating renal units did not tell us the population served by them; (iii) absence of strict national uniform indications for renal biopsies, at least in certain situations such as urinary abnormalities, acute renal or chronic renal failure, and several forms of nephrotic syndrome (especially in children); and (iv) absence of a central review of the histopathology. In order to minimize these biases we have repeatedly emphasized the importance of increasing the participation. On the other hand, the policy of renal biopsies could differ from centre to centre, and curiously its indications are still ill defined [24]. Finally, the existence of a central review of renal biopsies is desirable but difficult to organize in a national registry. A renal pathology external quality assessment scheme, as found in the UK [25], does not, unfortunately, exist in Spain. Some general conclusions can be reached, however, in spite of these limitations, and our study could be representative of the range of renal diseases, as we have data on an average of 1170 biopsies per year. In the Italian Registry an average of 2000 renal biopsies per year were collected over 7 years (1987–1993), with a very high participation percentage [5], even though Italy has 60 million inhabitants as against the 40 million in Spain. The average annual rate of renal biopsy we found in our review, 4.8 per 100 000 per year, is comparable to that of the Italian registry. However, our rate is less than that observed in France [10] and recently in Australia [15].

In our results there is a small percentage of renal re-biopsies, and the number of glomeruli obtained is consistent at all ages. Nevertheless, the number of biopsies studied by electron microscopy is only 23%, meaning that some biopsies will be considered as unclassifiable. Undoubtedly, the incorporation of ultrastructural techniques should be increased for a better classification of some renal diseases. As is customary in our country, the largest percentage of renal biopsies (71%) were performed on adults, and the elderly group contains triple the number of cases compared to children. This fact may show the ageing of the population served by most of the nephrology units [4,6,26] and may also reflect that many children were classified and treated based only on clinical data (idiopathic nephrotic syndrome, isolated microhaematuria and others).

As occurs with many renal diseases, men outnumber women. The prevalence of hypertension was high, particularly in the adult and elderly groups. Moreover, renal function impairment and the intensity of proteinuria increase with age. In fact, most of the cases over 15 years of age present with renal failure or nephrotic proteinuria. These data could indicate that renal biopsy is performed more frequently in the more severe form of each nephropathy. In fact, the most common causes of biopsy-proven glomerulonephritis were also the most common causes of end-stage renal disease due to glomerulonephritis [15].

The most frequent clinical syndrome at any age is nephrotic syndrome, followed by AUA in children and adults, and ARF in the elderly. These data agree with one Japanese study in which nephrotic syndrome is the most frequent clinical manifestation among 1850 cases [21]. As expected, the incidence of renal failure, acute or chronic, increases significantly with the age. Conversely, in the Italian registry, AUA is more common than nephrotic syndrome, perhaps expressing a tendency to biopsy asymptomatic haematuria or proteinuria [5].

Renal pathology is clearly different in different age groups, and thus we have separately analysed data from children, adults and the elderly. In children primary GN predominates, whereas in adults and the elderly, these primary GN decrease, with an increase of secondary forms and non-glomerular pathology, renal sclerosis and unclassified pathologies.

In children, the pathologies most frequent in our study are the variants of idiopathic nephrotic syndrome and IgAN, without change of their incidence in the studied years, as has been reported [7,15]. However, we were not able to confirm the high incidence of LN in this age group.

In adults, as has been repeatedly reported by our Registry, idiopathic IgAN is the most frequent biopsied renal pathology [4]. These data are similar to those found in Italy [5,6], Japan [21] and Victoria in Australia [15] where IgAN constitutes the most frequent diagnosis. However, its prevalence is significantly lower in the Registries of Kentucky [11], Brazil [13] and New Caledonia in Australia [14]. In adults, our annual incidence of IgA disease has been similar to that observed in other studies [5,10,27]. While true variation may exist between populations, differences in biopsy policies, particularly in AUA, and classification criteria for histological diagnosis of renal biopsies may explain, at least in part, the observed geographical variations. LN is very frequent in our environment and is the second cause of renal disease in adults. The third cause is FSGS, and in several studies its incidence has been reported between 0.1 and 0.9 per 100 000, with a tendency to increase [5,10,12,27], probably due to genetic, socio-economic or environmental causes, or obesity [22,2830]. Our observations did not show this tendency.

In our country the prevalence of MPGN is low and remains constant since the historical decrease of the 1980s [1,2]. However, in northern Italy [6] and in Japanese children [31] the incidence of MPGN has decreased, probably due to changes in microbiological milieu.

In the elderly, the predominant renal pathologies in our study are VAS that includes extracapillary GN type III, because this disease is considered a part of a continuum of VAS illness [32], followed by membranous nephropathy and amyloidosis, as observed by the majority of elderly registries. In our results, there is a definite increase in the membranous type in the last year, as has been experienced by other registries [5,15]. The annual incidence of primary renal VAS in the elderly seems to be increasing [32,33].

To conclude, the information obtained from the Spanish Glomerulonephritis Registry is an important contribution to the understanding of the frequency of renal diseases in Spain, and permits comparisons with other active Renal Biopsy Registries in the world. Thus, we firmly believe in the usefulness of this Registry and we would like to develop the following areas: (i) an increase in participation, to obtain accurate knowledge of the population cared for in each renal unit, with a view to calculating annual incidences; (ii) the saving of data with specific software to facilitate dissemination via the Internet; (iii) inclusion of the data on the Web page of the Spanish Society of Nephrology (www.senefro.org); and (iv) contribution to studies and multicentre clinical trials on specific renal pathologies.



   Appendix I
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Appendix I
 Appendix II
 References
 
Abbreviations

AMYL amyloidosis
ARF acute renal failure
ATIN acute tubulointerstitial nephritis
AUA asymptomatic urinary abnormalities
CRESGN crescentic glomerulonephritis
CTIN chronic tubulointerstitial nephritis
ESKD end-stage kidney disease
FSGS focal and segmental glomerulosclerosis
GN glomerulonephritis
IgAN IgA nephropathy
LN lupus nephropathy
MCD minimal-change disease
NA nephroangiosclerosis
MCD minimal-change disease
MIS miscellaneous
MN membranous glomerulonephritis
MPGN membranoproliferative glomerulonephritis
Non-IgAN non-IgA mesangioproliferative glomerulonephritis
UN unclassified nephropathy
VAS vasculitis



   Appendix II
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Appendix I
 Appendix II
 References
 
Participating renal units

Hospital

Province

Medical participants

Hospital Santiago Apóstol Álava F. Viana, J. C. Anitúa
Txagorritxu Ospitalea Álava R. Ruiz de Gauna
Hospital General de Albacete Albacete E. Olivas, E. Gallego
Hospital de Villajoyosa-Benidorm Alicante M. Perdiguero, J. Ma. Gas
Hospital General de Elda Alicante V. Valverde, E. Bosque
Hospital General Universitario de Alicante Alicante F. Rivera, C. M. Gil, Ma. T. Gil, J. Torralba,
   J. J. Egea, A. Crespo, J. Olivares
Hospital General Universitario de Elche Alicante R. Enríquez, C. González, J. Cabezuelo, A. Reyes, A. Sirvent
Hospital Virgen de los Lirios Alicante C. Del Pozo, L. Sánchez, Ma. D. Albero
Sanatorio Perpetuo Socorro Alicante Ma. D. Arenas
Hospital Torrecárdenas Almeria Ma. García Valverde, M. Real
Hospital Central de Asturias Asturias J. Álvarez Grande, J. Baltar, R. Álvarez, F. Ortega
Hospital Central de Asturias (Infantil) Asturias S. Málaga
Hospital Nuestra Señora de Sonsoles Ávila J. Martín, J. C. Chacón, A. Fidalgo
Hospital Universitario Infanta Cristina Badajoz R. Robles, M. Arrobas
Hospital Son Dureta Baleares A. Morey, X. Molina, D. Tura, J. Gascó, J. Bernabeu, P. Losada
Policlínica Miramar Baleares C. Piza, M. del Río, X. Vidal, P. Serrano
Consorci Hospitalari del Parc Taulí Barcelona A. Rodríguez Jornet
Fundación Puigvert Barcelona F. Calero, J. Ballarín
Hospital de Bellvitge Barcelona R. Poveda, L. Carreras
Hospital del Mar Barcelona M. Mir
Hospital San Joan de Deu Barcelona L. García García
Hospital Universitari Germans Trias i Pujol Barcelona A. Serra
Hospital General Yagüe Burgos P. Abaigar, G. Torres
Complejo Hospitalario San Pedro de Alcántara Cáceres A. Covarsí, R. Novillo
Hospital de Jerez Cádiz M. Ramos, M. Almaraz, G. Salgado, G. Velasco, Ma. L. Alcalá
Hospital Puerta del Mar Cádiz M. Ribero, T. García
Hospital Universitario de Puerto Real Cádiz E. Fernández Ruiz
Hospital General de Castellón Castellón J. Hernández Jaras, V. Navarro, X. Calvo, F. Maduell
Complejo Hospitalario Córdoba F. Gómez Carrasco
   Universitario Reina Sofía
Complejo Hospitalario Coruña, A X. M. Lens, D. Sánchez Guisande, D. Güimil
   Universitario de Santiago
Hospital Universitario Juan Canalejo Coruña, A M. Adeva, F. Valdés, E. Vázquez Martull
Hospital Virgen de la Luz Cuenca L. Lozano, F. Tornero, J. Usón, B. Rincón
Hospital Dr Josep Trueta Girona X. Bromsons
Ciudad Sanitaria Virgen de la Nieves Granada J. M. Osorio, C. Asensio, X. Peinado, F. J. González,
   M. González
Hospital General Universitario Guadalajara Ma. D. Jarillo, M. Sánchez
   de Guadalajara
Hospital Nuestra Sra de la Antigua Guipuzcoa J. J. Ruiz Laiglesia, A. Argoitia
Hospital General Juan Ramón Jiménez Huelva X. Onaindía, C. Suárez
Hospital San Jorge Huesca J. M. Logroño, X. Gonzáñez, X. Virto, C. Laviades
Complejo Hospitalario Princesa de España Jaén F. Fernández Montero
Hospital General de Especialidades Jaén J. Borrego, P. Serrano
   Ciudad de Jaen
Hospital Nuestra Sra del Pino Las Palmas C. Plaza
Hospital Universitario Insular de Las Palmas Las Palmas Ma. D. Checa, S. Suría, N. Esparza, A. Moreno
Hospital Virgen Blanca León M. Granda
Hospital Arnau de Vilanova Lleida Ma. L. Amoedo, J. Zonas, J. Mardares
Complejo Hospitalario Xeral Calde Lugo M. Ranero
Clínica Ruber Madrid M. Dapena
Fundación Hospital Alcorcón Madrid K. López Revuelta, V. Barrio
Fundación Jiménez Díaz Madrid S. Casado
Hospital 12 de Octubre (Adultos) Madrid M. Praga, E. Hernández
Hospital del Aire Madrid G. Gónzález Parra, A. Méndez
Hospital del Niño Jesús Madrid M. Vázquez
Hospital General Universitario Gregorio Madrid J. M. López-Gómez, R. Pérez García, F. Gómez Campderá
   Marañón (Adultos)
Hospital General Universitario Gregorio Madrid M. Luque
   Marañón (Infantil)
Hospital Militar Gómez Ulla Madrid G. Vázquez
Hospital Universitario de Getafe Madrid V. Giner
Hospital Universitario de la Princesa Madrid C. Bernis
Hospital Universitario La Paz Madrid J. Martínez Ara, C. Díaz
Hospital Universitario La Paz (Infantil) Madrid A. Peña, Ma. J. Martínez
Hospital Universitario Severo Ochoa Madrid A. Vigil
Hospital Carlos Haya (Adultos) Málaga M. A. de Frutos, G. Martín, E. López de Novales, J. M. Martínez
Hospital Clínico Universitario Virgen de la Victoria Málaga A. Valera
Hospital Regional de Málaga (Infantil) Málaga X. Peña, M. Millán, A. Bueno
Hospital Universitario Virgen Murcia S. Alegría, E. López Guillén, F. Pérez Silva, R. Rodado,
   de la Arrixaca    A. J. Andreu
Hospital Cristal Piñor Ourense J. Esteban, E. Armada, A. Otero, C. Pérez
Hospital General Río Carrión Palencia Ma. Salva, F. Sousa, E. Hernández García, J. M. Monfá
Complejo Hospitalario Xeral Cíes Pontevedra L. González, J. Sobrado, B. Pazos, R. Alonso
Hospital Montecelo Pontevedra E. Peláez, A. Pereira
Hospital San Millán y San Pedro Rioja M. Sierra
Hospital Clínico Universitario de Salamanca Salamanca J. Ma. Tabernero
Hospital General de Segovia Segovia M. Fernández Reyes, J. Álvarez-Ude
Hospital Universitario Virgen Macarena Sevilla C. Jarava
Hospital Virgen del Rocío (Infantil) Sevilla J. Martín Govantes, J. Fernández,
   Ma. J. Gutiérrez, A. Sánchez
Hospital General de Soria Soria M. Asensio
Hospital Joan XXIII Tarragona J. A. Oliver
Complejo Hospitalario Nuestra Sra de la Candelaria Tenerife J. J. García Pérez, A. Rivero
Hospital Nuestra Sra de la Candelaria (Infantil) Tenerife V. García Nieto
Hospital Universitario de Canarias Tenerife D. Hernández Marrero, E. de Bonis, B. Martín,
   A. Hernández, A. Rodríguez
Hospital Obispo Polanco Teruel J. J. Belvis, X. Bedisa, X. Bergasa
Hospital Virgen de la Salud Toledo J. J. Ahijado, J. Sierra, X. Hormigós
Hospital Clínico Universitario de Valencia Valencia J. S. Pons, X. Abarca
Hospital Dr Peset Aleixandre Valencia E. Alcoy, L. Pallardó
Hospital General Universitari Valencia A. Pérez García, J. Ma. Escobedo
Hospital Universitario La Fé (Infantil) Valencia I. Zamora, J. M. Simón
Hospital del Río Ortega Valladolid A. Molina, A. de Paula, A. Rodrigo, Ma. E. Plagaro
Hospital Universitario de Valladolid Valladolid J. Briso, J. Bustamante
Hospital de Basurto Vizcaya R. J. Ortiz-Vigón
Hospital de Cruces Vizcaya S. Zárraga, F. Gainza
Hospital de Cruces (Infantil) Vizcaya A. Vallo
Hospital de Galdakao Vizcaya J. Montenegro, I. Martínez, R. Saracho
Hospital Virgen de la Concha Zamora J. Grande, J. Deira
Hospital Clínico Universitario de Zaragoza Zaragoza J. Cebollada, J. Usón
Hospital Miguel Servet Zaragoza J. A. Gutiérrez Colón
Hospital Miguel Servet (Infantil) Zaragoza C. Loris, M. Heras



   Acknowledgments
 
We gratefully acknowledge the invaluable assistance of Lucía Llaneras, María Guardiola, Carmen Ma Gil, José Manuel Sierra, Roberto Alcázar and Marcial García-Rojo.



   Notes
 
Correspondence and offprint requests to: Dr Francisco Rivera Hernández, Seccion de Nefrología, Hospital Alarcos, Avenida Pío XII, s/n, E-13002 Ciudad Real, Spain. Email: francisco.rivera{at}wanadoo.es Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Appendix I
 Appendix II
 References
 

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Received for publication: 29. 9.01
Accepted in revised form: 2. 4.02