[Frequency of diagnosis and clinic presentation of glomerulopathies in Uruguay]. / Frecuencia de diagnóstico y de presentación clínica de las glomerulopatías en el Uruguay.

UNLABELLED: The Uruguayan Registry of Glomerulopathies began its activity in 1974 and since 1985 is a national registry. The aim of this report is to analyze the incidence and the variations in frequencies of the histological diagnosis and clinical presentation during the 1980-2003 period. PATIENTS AND METHODS: From the 2,058 patients with renal biopsy in the whole period, we analyzed the histological diagnosis and the following data has been collected when the patients were registered: age, gender, clinical syndrome, proteinuria, hematuria, serum creatinine, blood pressure and time from the first symptom. Four periods of registry entry were considered: 1980-1989, 1990-1994, 1995-1999 and 2000-2003. Chi-square and Student test for independent samples were used to evaluate the differences among the variables frequencies in the four periods. RESULTS: The incidence of registered glomerulopathies per million population (pmp) increased from 13 (1980-1989) to 43 (2000-2003). In the 2000-2003 period, the incidences pmp were: primary glomerulopathy (PG), 25.3 and secondary glomerulopathy, 14.2. The highest incidences pmp were: focal and segmental glomeruloesclerosis (FSGS) 6.4; vasculitis 5.4; lupus nephritis 4.6; minimal change disease (MCD) 4.6; IgA nephropathy (IgAN) 4.5; and membranous nephropathy (MN) 4.0. The most frequent PG were the FSGS (29.3%) and the MCID (19.6%). The FSGS frequency decreased from 36.3% in 1995-1999 to 19.1% in 2000-2003. The IgAN frequency increased from 5.2% in 1980-1989 to 17.5% in 2000-2003. Nephrotic syndrome was the most frequent clinical presentation; its frequency was over 30% in the four periods. Asymptomatic urinary abnormality frequency increased from 14.0% in 1980-1989 to 22.7% in 2000-2003. The frequency of serum creatinine under 1.5 mg/dl, increased from 42.2% in 1980-1989 to 67.2% in 2000-2003 (p = 0.001). The frequency of serum creatinine over 6.0 mg/dl, decreased from 19.3% in 1990-1994 to 7.2% in 2000-2003. The percentage of patients referred since the first month of the apparent onset of the disease increased from 24.0% in 1980-1989 to 40.1% in 2000-2003 (p < 0.001). CONCLUSIONS: In Uruguay, the incidence of glomerulopathies with histological diagnosis has increased and the frequency of the different types has changed. Several indicators seem to show that the reference of patients to the nephrologist tended to be earlier in the last years.

Different patterns of renal osteodystrophy in Iberoamerica.

The various forms of renal osteodystrophy are predominant hyperparathyroid bone disease, mixed uremic osteodystrophy, low turnover osteomalacia, and adynamic bone disease. The present study analyses a total number of 1,209 bone biopsies from 5 different countries (Brazil, Uruguay, Argentina, Portugal, and Spain). Low turnover osteomalacia and mixed uremic osteodystrophy were more common in Brazil, Uruguay, and Argentina than in Portugal and Spain whereas predominant hyperparathyroid bone disease was seen more often in Portugal and Spain. In all centers, independent of the aluminum staining technique used, the extent of aluminum deposited in bone was greater in patients presenting with low bone turnover, whether from low turnover osteomalacia or adynamic bone disease, than in the predominant hyperparathyroid bone disease. In summary, even though recent reports have indicated that, over the last decade, the incidence of aluminum-induced toxicity was reduced, aluminum still seems to be implicated in a great percentage of symptomatic low bone remodelling lesions in Iberoamerica.

The role of imaging techniques in the study of renal osteodystrophy.

Secondary hyperparathyroidism is the most common form of this condition found in renal osteodystrophy. Enlarged parathyroid glands are the rule in severe secondary hyperparathyroidism because of a marked parathyroid cell hyperplasia. For several years, ultrasonography, computed tomography, and scintigraphy with thallium201-technetium99 have been useful techniques to identify enlarged parathyroid glands. More recently, ultrasonography with color Doppler and parathyroid scintigraphy with 99mTc-sestamibi have proved to be useful as well. Computed tomography and magnetic resonance imaging can be used, but their sensitivity is similar to ultrasonography and they cost more. Ultrasonography with color Doppler signals has made it possible to evaluate tissue blood supply, an aid in differentiating thyroid nodules. The degree of blood supply may be an indirect index of cell proliferation when there is neither necrosis nor calcification, because an enriched blood supply suggests vigorous cell growth and nodule formation. Scintigraphy with 99mTc-sestamibi allows identification of ectopic glands, including those located in the mediastinum, and also provides functional information. Sestamibi uptake is closely related to both parathyroid hormone levels and to the histological type of parathyroid proliferation. In our experience, when hyperparathyroidism is not too severe, 2 weeks after 2 g of calcitriol is administered intravenously, these scintigraphic images can disappear (inhibition test). This suggests a possibility for a medical treatment. By contrast, when parathyroid hormone levels are higher, parathyroid sestamibi uptake remained unchanged. In such patients, parathyroidectomy or ethanol injection should be the best treatment. These glands would correspond to the most actively functioning glands; they would have a lesser expression of vitamin D receptors, rendering them refractory to medical treatment with calcitriol.

Are there any differences in the parathyroid response in the different types of renal osteodystrophy?

With the purpose of studying the curve of parathyroid response to variations of serum calcium during dialysis, we studied 20 patients on haemodialysis: 10 women and 10 men, with different forms of bone disease diagnosed by bone biopsy (adynamic bone disease, mild hyperparathyroidism, severe hyperparathyroidism). In all patients, we performed parathyroid stimulation by 4 h dialysis with 1 mEq/l of Ca2+ in the dialysate, and an inhibition test in another dialysis session with 4 mEq/l of Ca2+, with a 48 h interval. Ca2+ and intact parathyroid hormone (iPTH) were measured prior to dialysis and every hour subsequently, to obtain a Ca2+-iPTH for each patient. The analysis of the curves was made using Brown's four-parameter model. Stimulation and inhibition levels were similar in all groups, but basal iPTH and the response profiles obtained varied in the different histological groups. Basal, maximal and minimal iPTH were lower in adynamic forms than in the other two groups (P<0.04), and basal calcium was higher than basal calcium of severe hyperparathyroidism, expressing a basal inhibition status. In severe hyperparathyroidism, basal calcium was lower than the set-point, showing a permanent stimulation, and the slope was higher than in other groups, showing more sensitivity to serum calcium variations. The set-point of severe hyperparathyroidism was significantly higher than the set-point of mild and adynamic forms. In conclusion, the functional parathyroid study showed a different response in the different forms of renal osteodystrophy.

[(99m)Tc]-sestamibi parathyroid scintigraphy in chronic haemodialysis patients: static and dynamic explorations.

BACKGROUND: The place of parathyroid gland imaging by [(99m)Tc](technetium)-sestamibi scintigraphy in uraemic patients with secondary hyperparathyroidism remains a matter of debate. The purpose of the present study was (i) to assess its value with respect to plasma intact parathyroid hormone (iPTH) levels and to surgical parathyroidectomy (PTx), and (ii) to explore the possibility of suppressing parathyroid [(99m)Tc]-sestamibi uptake by calcitriol. METHODS: In a first cross-sectional, static study 52 chronic haemodialysis (HD) patients with plasma iPTH levels between 14 and 2791 pg/ml (normal, 10-65 pg/ml) had a [(99m)Tc]-sestamibi scan, and 21 of them underwent surgical PTx. In a second longitudinal, dynamic study 14 chronic HD patients with advanced secondary hyperparathyroidism received short-term calcitriol treatment in an attempt to suppress [(99m)Tc]-sestamibi imaging of parathyroid glands. Calcitriol was given intravenously for 2 weeks, 2 microg after each haemodialysis session. Scintigraphy was carried out before and at the end of this inhibition test. RESULTS: [(99m)Tc]-Sestamibi scan led to imaging of one or more (maximum three) parathyroid glands in most, but not all, HD patients with plasma iPTH values >600 pg/ml. Based on surgical findings, overall sensitivity of [(99m)Tc]-sestamibi scan in correctly locating parathyroid glands was only 50%, whereas specificity was 100%. In contrast, its sensitivity was 100% in locating single glands in the subgroup of five patients with recurrent hyperparathyroidism. The calcitriol inhibition test showed suppression of [(99m)Tc]-sestamibi uptake by at least one parathyroid gland in eight patients (57%), with complete suppression in five of them (36%). Basal plasma iPTH or decrease of plasma iPTH in response to calcitriol was not predictive of suppressible [(99m)Tc]-sestamibi uptake in the individual case, although mean iPTH was markedly higher in patients with non-suppressible parathyroid glands. CONCLUSION: Because of its relatively low sensitivity the [(99m)Tc]-sestamibi scan is of limited help in the exploration of uraemic patients with severe secondary hyperparathyroidism before a first surgical PTx. However, it is very useful in locating the remaining parathyroid gland(s) in case of reoperation. The novel calcitriol inhibition test of [(99m)Tc]-sestamibi uptake could help to better distinguish parathyroid glands with non-suppressible, autonomous activity from glands whose activity might be amenable to long-term suppression.

Can we use 99mTc-MIBI in functional studies of the parathyroid gland?

The usefulness of technetium-99m-sestamibi (99mTc-MIBI) in patients with secondary hyperparathyroidism on haemodialysis was assessed. We studied 33 patients with parathyroid scintigraphy with i.v. (99mTc-MIBI). Static images in a scintillation camera were taken at 15 and 120 min after the injection. With P x Ca<80, we performed an inhibition test with calcitriol i.v. 2 microg, three times a week, for 2 weeks. The MIBI study and assessment of intact parathyroid hormone (iPTH) were performed before (baseline study) and after inhibition. A 'focal positive study' corresponded to one or more areas of abnormal hypercaptation in relation to surrounding thyroid tissue seen in early images and persisting in later images, and a 'negative study' did not correspond to the previous image. In the baseline study, iPTH in the positive MIBI group was significantly greater than in the negative group. Eight positive MIBI patients had a bone biopsy; six corresponded to severe osteitis fibrosa and two to mild osteitis fibrosa. In the negative MIBI group, four of the six patients who had bone biopsy had mild forms of osteitis fibrosa (Fisher=0.03); the other two had low turnover forms. A positive inhibition test was defined when the basal uptake disappeared after calcitriol administration. In these patients, we observed a significant decrease of iPTH, not observed in the negative inhibition test. In 10 patients who had been parathyroidectomized, those with alpha positive basal MIBI result had a nodular parathyroid hyperplasia. We conclude that a scintigraphic parathyroid study with 99mTc-MIBI showed a good correlation with functional parathyroid status. With the same inhibition test, only some glands were inhibited, suggesting that this could be the expression of different vitamin D receptor densities in inhibited glands and/or a different kind of proliferation in those glands. This test would be of value in functional studies when a therapeutic decision must be made.

Frecuencia de diagnóstico y de presentación clínica de las glomerulopatías en el Uruguay / Frequency of diagnosis and clinic presentation of glomerulopathies in Uruguay

El Registro Uruguayo de Glomerulopatías ha registrado en el período 1980-2003,datos de 2.058 pacientes con biopsia renal. El objetivo del presente informe es analizarla incidencia y las variaciones de la frecuencia de los diagnósticos y de la presentaciónclínica en dichos pacientes.Pacientes y métodos: En los 2.058 pacientes registrados se analizaron el diagnósticoy los siguientes datos correspondientes a la fecha de la primera biopsia renal(BR): edad, sexo, síndrome clínico, proteinuria, hematuria, creatinininemia, presiónarterial y tiempo de evolución desde el primer síntoma. Se consideraron cuatro períodos:1980-1989, 1990-1994, 1995-1999 y 2000-2003 y las diferencias de frecuenciasde las distintas variables se valoraron con chi-cuadrado y con test de Studentpara muestras independientes.Resultados: La incidencia de las glomerulopatías registradas por millón de población(pmp) aumentó de 13 (1980-1989) a 43 (2000-2003). En el período 2000-2003 las incidencias pmp fueron: glomerulopatía primaria (GP) 25,3 y glomerulopatíasecundaria (GS) 14,2. Las mayores incidencias pmp fueron: esclero-hialinosisfocal y segmentaria (EHFS) 6,4, vasculitis 5,4, lupus eritematoso sistémico 4,6,lesión glomerular mínima 4,6, nefropatía a IgA (NIgA) 4,5 y glomerulopatía membranosa4,0.Las GP más frecuentes fueron la EHFS (29,3%) y la LGM (19,6%). La frecuenciade la EHFS descendió de 36,3% en 1995-1999 a 27,1% en 2000-2003 y la de laNIgA aumentó de 5,2% en 1980-1989 a 17,5% en 2000-2003.La presentación clínica más frecuente fue el síndrome nefrótico, mayor de 30%en todos los períodos. La frecuencia de la alteración urinaria asintomática aumentóde 14,0% en 1980-1989 a 22,7% en 2000-2003. La frecuencia de creatinina séricamenor de 1,5 mg/dl aumentó de 42,2% en 1980-1989 a 67,2% en 2000-2003 (p =0,001). El porcentaje de pacientes referidos dentro del primer mes de evoluciónaumentó de 24,0% en 1980-1989 a 40,1% en 2000-2003.Conclusiones: La incidencia de glomerulopatías con BR en el Uruguay ha aumentadomodificándose algunas frecuencias. Algunos indicadores muestran que lospacientes son referidos más tempranamente al nefrólogo en los últimos años

The Uruguayan Registry of Glomerulopathies began its activity in 1974 and since1985 is a national registry. The aim of this report is to analyze the incidence and thevariations in frequencies of the histological diagnosis and clinical presentation duringthe 1980-2003 period.Patients and methods: From the 2,058 patients with renal biopsy in the wholeperiod, we analyzed the histological diagnosis and the following data has been collectedwhen the patients were registered: age, gender, clinical syndrome, proteinuria,hematuria, serum creatinine, blood pressure and time from the first symptom. Fourperiods of registry entry were considered: 1980-1989, 1990-1994, 1995-1999 and2000-2003. Chi-square and Student test for independent samples were used to evaluatethe differences among the variables frequencies in the four periods.Results: The incidence of registered glomerulopathies per million population (pmp)increased from 13 (1980-1989) to 43 (2000-2003). In the 2000-2003 period, the incidencespmp were: primary glomerulopathy (PG), 25.3 and secondary glomerulopathy,14.2. The highest incidences pmp were: focal and segmental glomeruloesclerosis(FSGS) 6.4; vasculitis 5.4; lupus nephritis 4.6; minimal change disease (MCD) 4.6;IgA nephropathy (lgAN) 4.5; and membranous nephropathy (MN) 4.0.The most frequent PG were the FSGS (29.3%) and the MCID (19.6%). The FSGSfrequency decreased from 36.3% in 1995-1999 to 19.1% in 2000-2003. The lgANfrequency increased from 5.2% in 1980-1989 to 17.5% in 2000-2003.Nephrotic syndrome was the most frequent clinical presentation; its frequency wasover 30% in the four periods.Asymptomatic urinary abnormality frequency increasedfrom 14.0% in 1980-1989 to 22.7% in 2000-2003. The frequency of serum creatinineunder 1.5 mgldi, increased from 42.2% in 1980-1989 to 67.2% in 2000-2003 (p =0.001). The frequency of serum creatinine over 6.0 mgldl, decreased from 19.3% in1990-1994 to 7.2% in 2000-2003.The percentage of patients referred since the first month of the apparent onset ofthe disease increased from 24.0% in 1980-1989 to 40.1% in 2000-2003 (p < 0.001).Conclusions: In Uruguay, the incidence of glomerulopathies with histological diagnosishas increased and the frequency of the different types has changed. Several indicatorsseem to show that the reference of patients to the nephrologist tended to beearlier in the last years