Nephrogenic systemic fibrosis: a case series suggesting gadolinium as a possible aetiological factor.

Nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy is a rare fibrotic condition that presents in patients with a history of renal disease. The aetiology is unknown, but it has recently been proposed that gadolinium, a paramagnetic contrast agent, may be a trigger of this disease. We report three patients with NSF with a history of use of gadolinium in magnetic resonance angiography a few weeks before the onset of symptoms. In the future, gadolinium should probably be avoided as much as possible in renal insufficiency patients until its role in the development of NSF is clarified.

Sistema renina-angiotensina-aldosterona. Su utilidad clínica / The renin-angiotensin-aldosterone system: its clinical utility

Después de una breve introducción sobre el sistema renina-angiotensina-aldosterona, se resaltan las circunstancias tanto fisiológicas como patológicas que modifican el sistema, así como también los fármacos que estimulan e inhiben la secreción de renina y aldosterona, que servirán al lector de guía para la interpretación de los resultados. La utilidad clínica de la determinación de la actividad renina plasmática (ARP) y la aldosterona se centra en el diagnóstico de algunas hipertensiones secundarias (hipertensión vasculorrenal, tumores secretantes de renina, hipermineralocorticismos y ciertas tubulopatías hereditarias infrecuentes), para el estudio de las alteraciones del metabolismo del potasio (hipo e hiperpotasemia), y para la evaluación pronóstica y/o terapéutica de ciertos estados edematosos (cirrosis hepática y síndrome nefrótico)

After a brief introduction on the renin-angiotensin-aldosterone system, the article analyses the physiological and pathological circumstances which modify it, and the drugs which stimulate or inhibit the release of renin and aldosterone. This analysis is intended as a guide to interpret results. In order to establish the medical effectiveness of determining the plasmatic renin activity (PRA) and the aldosterone, the article focuses on the diagnosis of some secondary hypertensions (vascularrenal hypertension, renin releasing tumours, hypermineralcorticisms and certain infrequent hereditary tubular pathologies), on the analysis of the alterations of potassium metabolism (hypo- and hyperpotassaemia), and on the prognostic and therapeutic evaluation of certain oedematous states (cirrhosis of the liver and nephritic syndrome)

Especificidad de acción de la aldosterona e hipertensión arterial / Specificity of the action of aldosterone and arterial hypertension

La enzima 11 beta-hidroxiesteroide deshidrogenasa tipo 2 (11 HSD2) confiere la especificidad de la acción de la aldosterona respecto a otros corticoides circulantes (cortisol) en los tejidos que deben responder de forma específica a los mineralocorticoides. Esta especificidad debe darse sobre todo en ciertos epitelios transportadores de sodio como el túbulo distal del riñón y en el colon. Esta enzima, poco conocida hasta hace unos años, se está revelando como de gran importancia, ya que interviene en la regulación de la presión arterial. En primer lugar, mutaciones del gen que codifica la enzima causan una forma rara de hipertensión sal sensible de herencia mendeliana autosómica recesiva conocida como exceso aparente de mineralocorticoides (AME). En segundo lugar, se ha determinado que en la población normal, polimorfismos genéticos en 11 HSD2 se asocian con una reducción de la actividad de la enzima in vivo. Esta reducción de la actividad enzimática así como los polimorfismos genéticos que la determinan se han relacionado con un incremento de la respuesta presora a la ingestión elevada de sal, fenómeno conocido como sensibilidad a la sal, tanto en sujetos sanos como en pacientes con hipertensión arterial esencial. Por tanto, es un gen candidato que intervendría en la patogenia de la hipertensión arterial (HTA) "esencial", sobre todo sensible a la sal y que debe aún ser estudiado en mayor profundidad (AU)

Elevación de los niveles de creatinfosfoquinasa como marcador de enfermedad aterombólica renal

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Focal segmental glomerular sclerosis in two patients with Addison's disease: any more than fortuitous development of glomerular disease?

Adjustment of the mineralocorticoid activity under substitution therapy is of primary importance in Addison's disease. We report the clinical and biological conditions of 2 patients with Addison's disease who developed nephrotic proteinuria during their deficient mineralocorticoid state. Renal biopsy was performed and the specimens processed using conventional histochemistry, Congo red staining, and indirect immunofluorescence. The renal biopsy specimens showed focal segmental glomerular sclerosis and nodular deposits of IgM and C3. Negative for Congo red staining. Serum complement, circulating immune complexes, and anti-DNA and hepatitis B and C and human immunodeficiency virus antibodies were all normal or negative. Absence of vesicoureteral reflux was assessed by X-ray studies. Our observations suggest that deficiency in mineralocorticoid substitution therapy inducing a status of hyperreninemia could play a role in the development of focal segmental glomerulosclerosis in patients with Addison's disease.

Rabdomiolisis masiva asociada al uso de cerivastatina en monoterapia / No disponible

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Genetic variation of the gamma subunit of the epithelial Na+ channel and essential hypertension. Relationship with salt sensitivity.

We evaluated the association of a common polymorphism in gammaENaC, consisting in a C to G transversion in codon 649, with essential hypertension and to the pressor response to salt in whites. Two hundred fifteen essential hypertensive patients, and 137 normotensive controls were genotyped for the gamma649 ENaC polymorphism by polymerase chain reaction method and diagnostic restriction enzyme digestion. The genotype distribution of the gamma649 ENaC polymorphism in the hypertensives, 129 CC (60%) and 86 CG/GG (40%) was not significantly different from that of the control group, 84 CC (61%) and 53 CG/GG (39%) (P = .81). Salt sensitivity was assessed in a group of 48 patients by 24-h mean blood pressure response to changes in salt intake. Nineteen patients were diagnosed as salt sensitive, whereas 29 had salt-resistant hypertension. The gamma649 ENaC genotype distribution in salt-sensitive patients was 12 CC (63%) and 7 CG/GG (37%), not significantly different from the distribution in the salt-resistant group, 19 CC (65%) and 10 CG/GG (35%), P = .87. The changes in systolic, diastolic, and mean blood pressure as measured by ambulatory blood pressure monitoring, and in plasma renin activity and plasma aldosterone induced by high salt diet were not different among the gamma649 ENaC genotypes. In the present study we found no association between the gamma649 ENaC polymorphism and essential hypertension or salt sensitivity. Although these data do not support a major causative role for this polymorphism, we cannot exclude that a functional mutation elsewhere in ENaC might be associated with essential hypertension.

Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment.

Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells. It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli (not secreted or reabsorbed as an intact molecule). Because serum cystatin C concentration is independent of age, sex, and muscle mass, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with serum creatinine level. We compared serum cystatin C level with other markers of GFR, such as serum creatinine level and creatinine clearance, and analyzed their variations based on iothalamate labeled with iodine 125 ((125)I-iothalamate) clearance ((125)I-ICl), used as the gold standard for GFR. The concentrations of the two different markers of GFR in patients with impaired renal function were classified according to (125)I-ICl. Twenty individuals with normal renal function ((125)I-ICl, 128 +/- 23 mL/min/1.73 m(2)) were used as the control group. Serum cystatin C level showed a greater sensitivity (93.4%) than serum creatinine level (86.8%). Also, serum cystatin C showed the greatest proportion of increased values in patients with impaired renal function (100%) compared with serum creatinine level (92.15%). Serum cystatin C levels started to increase to greater than normal values when GFR was 88 mL/min/1.73 m(2), whereas serum creatinine level began to increase when GFR was 75 mL/min/1.73 m(2). These data suggest that measurement of serum cystatin C may be useful to estimate GFR, especially to detect mild reductions in GFR, and therefore may be important in the detection of early renal insufficiency in a variety of renal diseases for which early treatment is critical.

High prevalence of antithyroid antibodies in anti-glomerular basement membrane antibody-mediated disease.

Anti-glomerular basement membrane antibody (anti-GBM Ab)-mediated disease and autoimmune thyroiditis are characterized by the presence of organ-specific antibodies. The diagnosis of autoimmune thyroiditis is usually based on the presence of serum antithyroid antibodies. Few studies have addressed the relationship between anti GBM-Ab mediated disease and autoimmune thyroid pathology. Given that this disorder is often asymptomatic, associations of the two pathologies may be under-diagnosed. This study investigated the prevalence of serum antithyroid antibodies (antithyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO)) in patients with anti-GBM Ab-mediated disease. Antithyroid antibodies presence was investigated in sera from 35 patients in whom anti-GBM Ab-mediated disease had been diagnosed. Anti-glomerular basement membrane antibodies and anti-thyroid antibodies (anti-TG and anti-TPO) were assayed using an enzyme-linked immunosorbent assay. Forty-five percent of patients with anti-GBM Ab-mediated disease (16/35) had positive antithyroid antibody titers. Eighteen percent (3/16) suffered from subclinical hypothyroidism. In conclusion, the high prevalence of antithyroid antibodies in these patients suggests a possible pathogenic link between autoimmune thyroiditis and anti GBM Ab-mediated disease.

[Genetic polymorphisms of the renin-angiotensin system and essential hypertension]. / Polimorfismos genéticos del sistema renina-angiotensina e hipertensión arterial esencial.

BACKGROUND: The renin-angiotensin system (RAS) plays an important role in blood pressure (BP) regulation. A number of RAS polymorphisms have been linked to essential hypertension (EH), but there is uncertainty about this association in other studies. We examined whether the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the M235T and T174M polymorphisms of the angiotensinogen (AGT) gene are associated with EH in a Spanish sample of hypertensive patients. MATERIAL AND METHODS: We studied 75 patients with EH (BP > 160/100 mmHg), aged 55 (8.5) years, 30 males, systolic BP (SBP) 182 +/- (22.1) mmHg, diastolic BP (DBP) 109 +/- (9.9) mmHg (mean [SD]) and a strong family history of the disease. As a control group, 75 healthy subjects with no family history of cardiovascular disease were studied. The polymorphisms were determined by PCR amplification of genomic DNA, followed by enzyme digestion for the AGT gene polymorphisms. RESULTS: The genotype distribution and the frequencies of the alleles of the three RAS polymorphisms were similar in hypertensive and control subjects. In addition, we did not find any compound effect of the I/D ACE gene and M235T AGT gene polymorphisms on BP levels in hypertensive and control subjects. CONCLUSIONS: In this sample, the contribution of the ACE I/D polymorphism and the AGT M235T and T174M polymorphisms in the development of EH seems to be less important than previously estimated.

Angiotensin converting enzyme gene I/D polymorphism in essential hypertension and nephroangiosclerosis.

An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene significantly influences circulating ACE levels and plays a role in the development of target organ damage, that is, left ventricular hypertrophy in essential hypertension (EH), and microalbuminuria in diabetes mellitus. We have examined the role of the I/D polymorphism in essential hypertensive patients with renal involvement. The study was divided in two independent protocols. In protocol 1, we retrospectively analyzed the ACE genotypes in 37 essential hypertensive patients with a clinical and histopathological diagnosis of nephroangiosclerosis. In protocol 2, ACE genotypes as well as microalbuminuria and renal hemodynamic parameters were investigated in 75 patients with EH with normal renal function and a strong family history of hypertension. As control group, 75 healthy subjects with BP < 130/85 mm Hg and no family history of cardiovascular diseases were studied. The ACE variants were determined by PCR and the genotypes were classified as DD, DI and II. In protocol 1, patients with nephroangiosclerosis displayed a significant difference in the genotype distribution (57% DD, 27% DI, 16% II) when compared to the control population (25% DD, 64% DI, 11% II; P < 0.001). There was no significant difference in genotype distribution between hypertensive patients with normal renal function (protocol 2; 33% DD, 59% DI, 8% II) and the control group. There were no differences in age, blood pressure, microalbuminuria and duration of the disease among the three genotypes in the EH group from protocol 2. Taken together, these findings suggest that the DD genotype of ACE is associated with histopathologic-proven kidney involvement in patients with EH and that this polymorphism could be a potential genetic marker in hypertensives at risk of renal complications.

Angiotensinogen gene M235T and T174M polymorphisms in essential hypertension: relation with target organ damage.

The molecular variants M235T and T174M of the angiotensinogen gene have been linked to essential hypertension in some populations, but there are discrepancies about this association in other studies. We studied 75 patients with essential hypertension (BP > 160/100 mm Hg) from our outpatient clinic, aged 55+/-1 years, 30 men, systolic BP 182+/-2.5, diastolic BP 109+/-1 mm Hg (mean +/- SEM), and a family history of the disease. Target organ damage was evaluated by measuring urinary albumin excretion rate, left ventricular hypertrophy, and fundoscopy. As a control group, 75 healthy subjects with BP < 130/85 mm Hg and with no family history of cardiovascular disease were selected. M235T and T174M angiotensinogen genotypes were determined by PCR and subsequent digestion of the products with SfaNI and NcoI, respectively. The frequency (q) of genotypes of the variant M235T in the patients with essential hypertension was MM 0.31, MT 0.41, and TT 0.28, not significantly different (P = .93) from that of the controls (MM 0.28, MT 0.44, and TT 0.28). For the variant T174M, the genotype frequencies in hypertensives were TT 0.83, TM 0.15, and MM 0.02, which was not significantly different (P = .89) from that of the controls (TT 0.86, TM 0.12, and MM 0.02). Similarly, there was no evidence for association between angiotensinogen genotypes and hypertension in subjects aged < or = 40 years old (n = 24) or with severe (stage III) hypertension (n = 31). Within the group of patients with essential hypertension, there were no differences in genotype distribution between patients with and without retinopathy (n = 31), left ventricular hypertrophy (n = 37), or microalbuminuria (n = 14). This study shows that M235T and T174M variants are not associated either with essential hypertension or with target organ damage in a Spanish sample.