The role of molecular genetics in diagnosing familial hematuria(s)

Familial microscopic hematuria (MH) of glomerular origin represents a heterogeneous group of monogenic conditions involving several genes, some of which remain unknown. Recent advances have increased our understanding and our ability to use molecular genetics for diagnosing such patients, enabling us to study their clinical characteristics over time. Three collagen IV genes, COL4A3, COL4A4, and COL4A5 explain the autosomal and X-linked forms of Alport syndrome (AS), and a subset of thin basement membrane nephropathy (TBMN). A number of X-linked AS patients follow a milder course reminiscent of that of patients with heterozygous COL4A3/COL4A4 mutations and TBMN, while at the same time a significant subset of patients with TBMN and familial MH progress to chronic kidney disease (CKD) or end-stage kidney disease (ESKD). A mutation in CFHR5, a member of the complement factor H family of genes that regulate complement activation, was recently shown to cause isolated C3 glomerulopathy, presenting with MH in childhood and demonstrating a significant risk for CKD/ESKD after 40 years old. Through these results molecular genetics emerges as a powerful tool for a definite diagnosis when all the above conditions enter the differential diagnosis, while in many at-risk related family members, a molecular diagnosis may obviate the need for another renal biopsy

Evaluación del dolor crónico en una población de pacientes hemodializados

[eng]Pain is a frequent symptom in patients undergoing dialysis, having a negative effect on their quality of life. Greater access to dialysis therapy, more time spent by patients on haemodialysis programmes and aging population have contributed to the habitual presence of pain in the life of these people. This study evaluates chronic pain in a population of patients on haemodialysis using validated valuation instruments used in other disciplines, which have been used recently in haemodialysis patients. 82.1% of our patients indicated that they felt pain at home, only 7 patients denied having pain and only in 28.12% of cases the Visual Analogue Scale (VAS) used to determine the intensity of pain was zero. Non-pharmacological measures such as heat, massages or changes in posture showed similar efficiency to treatment with drugs. The time spent on haemodialysis and the value of PTHi were related statistically to the intensity of the pain and the qualitative description of it, frequently altering the activities of patients' daily lives, mainly moving/walking and general activity. These connections, described for the first time in scientific literature, could explain in part the high prevalence of this symptom and the high percentage of muscular-skeletal pain referred by our patients. [spa]El dolor es un síntoma frecuente en los pacientes sometidos a hemodiálisis, influyendo negativamente en su calidad de vida. La mayor accesibilidad a la terapia dialítica, el mayor tiempo de permanencia de los pacientes en los programas de hemodiálisis y el envejecimiento de la población han contribuido a la presencia habitual del dolor en la vida de estas personas. En el presente estudio se evalúa el dolor crónico en una población de hemodiálisis usando instrumentos de valoración validados procedentes de otras disciplinas, que han sido recientemente utilizados en pacientes de hemodiálisis. Un 82.1% de nuestros pacientes afirmaron tener dolor en casa, únicamente 7 pacientes lo negaron, y sólo en el 28.12% de los casos, la Escala Visual Analógica (EVA) usada para averiguar su intensidad, fue 0. Medidas no farmacológicas como el calor, masajes o cambios posturales mostraron una eficacia similar a la del tratamiento con fármacos. El tiempo de permanencia en hemodiálisis y el valor de PTHi se relacionaron estadísticamente con la intensidad del dolor y la descripción cualitativa del mismo, alterando frecuentemente las actividades de la vida diaria de los pacientes, principalmente el desplazamiento/caminar y la actividad general. Estas relaciones, descritas por primera vez en la literatura científica, podrían explicar, en parte, la alta prevalencia de este síntoma y el alto porcentaje de dolor músculo-esquelético referido por nuestros pacientes

Evaluación y manejo del dolor intradiálisis

[eng]Pain is a frequent symptom in patients who undergo haemodialysis (HD), directly affecting their quality of life. However, its characteristics in this type of patient are not well known and there are no publications prior to this study dedicated exclusively to assessing pain during a haemodialysis session. This study assesses the characteristics of intradialysis pain, including its prevalence, intensity, qualitative characteristics and measures applied to control it. For these purposes, validated valuation scales widely used in the control of oncological pain were used, which were extended with a specific survey that evaluated aspects of pain related to the dialysis itself, including timing, frequency or influence of the treatment parameters. The entire information compilation process took place during the haemodialysis sessions. The prevalence of pain in HD was 92.1%, only in 3 cases (7.89%) was the pain level zero. 28.9% of patients identified the procedure itself as the cause of the pain, the second most frequent cause after pain of ischemic origin. The Pain Management Index (PMI) showed clear under treatment, which was most marked the more intense the pain described by the patient. However, the measures taken during haemodialysis for the control of the episodes of pain detected were efficient in a reasonable percentage of cases, which indicates that most of the pain episodes are not perceived by us. [spa]El dolor es un síntoma frecuente en los pacientes sometidos a hemodiálisis (HD), afectando directamente su calidad de vida. Sin embargo, sus características en este tipo de pacientes son poco conocidas y no existen publicaciones previas a este estudio en las que se valore de forma exclusiva el dolor durante una sesión de hemodiálisis. El presente estudio evalúa las características del dolor intradiálisis, incluyendo su prevalencia, intensidad, características cualitativas y medidas aplicadas para su control. Se utilizan para ello escalas de valoración validadas y ampliamente usadas en el control del dolor oncológico, que fueron ampliadas con una encuesta específica en la que se valoran aspectos del dolor relacionados con la propia diálisis, incluyendo temporalidad, frecuencia o influencia de los parámetros del tratamiento. Todo el proceso de recogida de información se realizó durante las sesiones de hemodiálisis. La prevalencia de dolor en HD fue de un 92,1%, sólo en 3 casos (7,89%) el nivel de dolor fue 0. Un 28,9% de los pacientes identificaron el propio procedimiento como causa del dolor, segunda causa más frecuente tras el dolor de origen isquémico. El Índice de Manejo del Dolor (PMI) indicó un claro infratratamiento, tanto más acentuado cuanto más intenso era el dolor descrito por el paciente. Sin embargo, las medidas llevadas a cabo durante la hemodiálisis para el control de los episodios de dolor detectados fueron eficaces en un porcentaje razonable, lo que indica que la mayor parte de los episodios de dolor pasan desapercibidos ante nuestros ojos

Familial C3 Glomerulopathy Associated with CFHR5 Mutations: Clinical Characteristics of 91 Patients in 16 Pedigrees

Background and objectives Complement factor H and related proteins (CFHR) are key regulators of the alternative complement pathway, where loss of function mutations lead to a glomerulopathy with isolated mesangial C3 deposits without immunoglobulins. Gale et al. (12) reported on 26 patients with the first familial, hematuric glomerulopathy caused by a founder mutation in the CFHR5 gene in patients of Cypriot descent living in the United Kingdom. CFHR5 nephropathy is clinically characterized by continuous microscopic hematuria whereas some patients present with additional episodes of synpharyngitic macrohematuria, associated with infection and pyrexia. A subgroup of patients, particularly men, develop additional proteinuria, hypertension, and chronic renal disease or ESRD.Design, setting, participants, & measurements We herewith expand significantly on the study by Gale et al., reporting on histologic, molecular, and clinical findings in 91 patients from 16 families with the same founder mutation.Results Eighty-two patients (90%) exhibited microscopic hematuria; 51(62%), exhibited only microscopic hematuria, whereas the remaining 31 additionally had proteinuria (38%); 28 proteinuric patients developed chronic renal failure (CRF). Among carriers of CFHR5 mutation aged >50 years, 80% of the men and 21% of the women developed CRF; 18 developed ESRD (14 men [78%], 4 women [22%]).Conclusions The diagnosis of CFHR5-related, isolated C3 glomerulopathy was established in 2009 using newly described mutation analysis after decades of follow-up with unclear diagnoses, occasionally confused with IgA nephropathy. This larger patient cohort establishes the clinical course, significant variable expressivity, and marked gender difference regarding the development of CRF and ESRD. Clin J Am Soc Nephrol 6: 1436-1446, 2011. doi: 10.2215/CJN.0954101