Hypertension in autosomal-dominant polycystic kidney disease (ADPKD)

Cardiovascular (CV) complications are the major cause of death in autosomal-dominant polycystic kidney disease (ADPKD) patients. Hypertension is common in these patients even before the onset of renal insufficiency. Blood pressure (BP) elevation is a key factor in patient outcome, mainly owing to the high prevalence of target organ damage together with a poor renal prognosis when BP is increased. Many factors have been implicated in the pathogenesis of hypertension, including the renin-angiotensin-aldosterone system (RAAS) stimulation. Polycystin deficiency may also contribute to hypertension because of its potential role in regulating the vascular tone. Early diagnosis and treatment of hypertension improve the CV and renal complications of this population. Ambulatory BP monitoring is recommended for prompt diagnosis of hypertension. CV risk assessment is mandatory. Even though a nonpharmacological approach should not be neglected, RAAS inhibitors are the cornerstone of hypertension treatment. Calcium channel blockers (CCBs) should be avoided unless resistant hypertension is present. The BP should be <140/90 mmHg in all ADPKD patients and a more intensive control (<135/85 mmHg) should be pursued as soon as microalbuminuria or left ventricle hypertrophy is present

Concentrating defect in experimental nephrotic syndrome: Altered expression of aquaporins and thick ascending limb Na+ transporters

Concentrating defect in experimental nephrotic syndrome: Altered expression of aquaporins and thick ascending limb Na+ transporters.BackgroundSeveral pathophysiological states associated with deranged water balance are associated with altered expression and/or intracellular distribution of aquaporin water channels. The possible role of dysregulation of thick ascending limb NaCl transporters, which are responsible for countercurrent multiplication in the kidney, has not been evaluated.MethodsSemiquantitative immunoblotting and immunocytochemistry were carried out in the kidneys of rat with adriamycin-induced nephrotic syndrome and in vehicle-injected control rats.ResultsPreliminary studies confirmed the presence of a severe concentrating defect. Semiquantitative immunoblotting of outer medullary homogenates demonstrated a marked decrease in the abundance of three thick ascending limb Na+ transporters in nephrotic rats, namely the bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), the type 3 Na/H exchanger (NHE-3), and the α1-subunit of the Na-K-ATPase. These results are predictive of a decrease in the NaCl transport capacity of the medullary thick ascending limb and therefore a decrease in countercurrent multiplication. Immunocytochemistry of outer medullary thin sections demonstrated broad (but highly variable) suppression of BSC-1 expression in the outer medullas of adriamycin-nephrotic rats. There was also a large decrease in outer medullary expression of two collecting duct water channels (aquaporin-2 and -3) and the major water channel of the thin descending limb of Henle’s loop (aquaporin-1).ConclusionThe concentrating defect in adriamycin-induced nephrotic syndrome in rats is a consequence of multiple defects in water and solute transporter expression, which would alter both the generation of medullary interstitial hypertonicity and osmotic equilibration in the collecting duct. Whether a similar widespread defect in transporter expression is present in idiopathic nephrotic syndrome in humans is, at this point, untested

Influencia de la edición de los valores de presión arterial (PA) en la interpretación de la monitorización ambulatoria de la PA (MAPA)

En este trabajo se recogieron 115 MAPAs realizados a pacientes hipertensos, y se investigó la influencia que la edición de los valores de PA en el periodo que rodea al inicio del sueño y la vigilia podía tener en la interpretación de la prueba. Se observó que el porcentaje de pacientes con PA controlada con o sin la edición de valores fue similar. Sin embargo, la edición de la MAPA condicionó cambios en la clasificación del perfil circadiano, observándose una disminución de perfiles reductores, reclasificados hacia perfiles menos fisiológicos como no-reductor y reductor extremo, ambos asociados a un peor pronóstico cardiovascular.En aquest treball es van recollir 115 MAPAs realitzats a pacients hipertensos, i es va investigar la influencia que la edició dels valors de PA en el període que envolta l'inici de la son i la vigília podia tenir en la interpretació de la prova. Es va observar que el percentatge de pacients amb PA controlada amb o sense la edició dels valors va ser similar. Però, la edició de la MAPA va condicionar canvis en la classificació del perfil circadiari, observant-se una disminució de perfils reductors, reclassificats cap a perfils menys fisiològics com no-reductor o reductor extrem, ambdós associats a un pitjor pronòstic cardiovascular

Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis

Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as ‘severe’ or ‘mild’ using this in silico approach. Our results suggest an earlier onset of the disease in patients with two ‘severe’ mutations compared to patients with at least one ‘mild’ mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease

Hypertension in autosomal-dominant polycystic kidney disease (ADPKD)

Cardiovascular (CV) complications are the major cause of death in autosomal-dominant polycystic kidney disease (ADPKD) patients. Hypertension is common in these patients even before the onset of renal insufficiency. Blood pressure (BP) elevation is a key factor in patient outcome, mainly owing to the high prevalence of target organ damage together with a poor renal prognosis when BP is increased. Many factors have been implicated in the pathogenesis of hypertension, including the renin-angiotensin-aldosterone system (RAAS) stimulation. Polycystin deficiency may also contribute to hypertension because of its potential role in regulating the vascular tone. Early diagnosis and treatment of hypertension improve the CV and renal complications of this population. Ambulatory BP monitoring is recommended for prompt diagnosis of hypertension. CV risk assessment is mandatory. Even though a nonpharmacological approach should not be neglected, RAAS inhibitors are the cornerstone of hypertension treatment. Calcium channel blockers (CCBs) should be avoided unless resistant hypertension is present. The BP should be <140/90 mmHg in all ADPKD patients and a more intensive control (<135/85 mmHg) should be pursued as soon as microalbuminuria or left ventricle hypertrophy is present

Prevalence of Cysts in Seminal Tract and Abnormal Semen Parameters in Patients with Autosomal Dominant Polycystic Kidney Disease

Background and objectives: Autosomal dominant polycystic kidney disease is a systemic disorder with a wide range of extrarenal involvement. The scope of this study was to analyze the prevalence of seminal cysts and to correlate these findings with the sperm parameters in patients with autosomal dominant polycystic kidney disease

Study of candidate genes affecting the progression of renal disease in autosomal dominant polycystic kidney disease type 1.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder with a wide spectrum of renal involvement. Differences in the age at onset of end-stage renal disease (ESRD) are partially explained by the genetic heterogeneity of the disease but intrafamilial variability remains to be explained. Modifier genes may play a role in disease severity. METHODS: A total of 355 PKD1 patients from 131 families belonging to three different European centres were analysed. According to the age at onset of ESRD patients were classified into two groups: early and late onset. Two different cut-offs were used. Based on literature, early onset was firstly considered when ESRD was reached before 40 years of age and late onset after 60 years of age. Secondly, according to the bimodal distribution of age at onset of ESRD in our population we established two groups with similar variability and the cut-offs were assigned before 48 years of age and after 56 years of age. These groups of patients were then analysed by two different complementary perspectives: (i) using ESRD onset as a quantitative trait when performing survival analysis and Cox regression analysis, and (ii) considering it a qualitative trait. The candidate genes (and polymorphisms) studied were the following: NOS3 (T-786C and E298D), BDKRB1 (-699 G > C), BDKRB2 (R14C), TGFB1 (-509 C > T, R25P and L10P), ACE (I/D), EGFR (IVS1CA) and PKD2 (-9780 G > A, -718 A > G and 83 C > G). RESULTS: The results disclosed that the ACE polymorphism had a slight influence on the age of onset of ESRD in ADPKD patients and the NOS3 and BDKBR1 polymorphisms showed a very slight involvement in renal outcome. CONCLUSIONS: Our results discard the most prominent functional genes suggested to date, to have a major effect on ADPKD progression in this cohort. Genes strongly implicated in disease severity are yet to be identified. The description of such genes would allow us to establish a prognosis for ADPKD and eventually to develop therapeutic interventions

Cuff-based oscillometric central and brachial blood pressures obtained through ABPM are similarly associated with renal organ damage in arterial hypertension

BACKGROUND/AIMS: Central blood pressure (BP) has been suggested to be a better estimator of hypertension-associated risks. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of renal organ damage in hypertensive patients. METHODS: Brachial and central (calculated by an oscillometric system through brachial pulse wave analysis) office BP and ambulatory BP monitoring (ABPM) data and aortic pulse wave velocity (PWV) were measured in 208 hypertensive patients. Renal organ damage was evaluated by means of the albumin to creatinine ratio and the estimated glomerular filtration rate. RESULTS: Fifty-four patients (25.9%) were affected by renal organ damage, displaying either microalbuminuria (urinary albumin excretion ≥30 mg/g creatinine) or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Compared to those without renal abnormalities, hypertensive patients with kidney damage had higher values of office brachial systolic BP (SBP) and pulse pressure (PP), and 24-h, daytime, and nighttime central and brachial SBP and PP. They also had a blunted nocturnal decrease in both central and brachial BP, and higher values of aortic PWV. After adjustment for age, gender, and antihypertensive treatment, only ABPM-derived BP estimates (both central and brachial) showed significant associations with the presence of renal damage. Odds ratios for central BP estimates were not significantly higher than those obtained for brachial BP. CONCLUSION: Compared with peripheral ABPM, cuff-based oscillometric central ABPM does not show a closer association with presence of renal organ damage in hypertensive patients. More studies, however, need to be done to better identify the role of central BP in clinical practice

Influencia de la edición de los valores de presión arterial (PA) en la interpretación de la monitorización ambulatoria de la PA (MAPA)

En este trabajo se recogieron 115 MAPAs realizados a pacientes hipertensos, y se investigó la influencia que la edición de los valores de PA en el periodo que rodea al inicio del sueño y la vigilia podía tener en la interpretación de la prueba. Se observó que el porcentaje de pacientes con PA controlada con o sin la edición de valores fue similar. Sin embargo, la edición de la MAPA condicionó cambios en la clasificación del perfil circadiano, observándose una disminución de perfiles reductores, reclasificados hacia perfiles menos fisiológicos como no-reductor y reductor extremo, ambos asociados a un peor pronóstico cardiovascular.En aquest treball es van recollir 115 MAPAs realitzats a pacients hipertensos, i es va investigar la influencia que la edició dels valors de PA en el període que envolta l'inici de la son i la vigília podia tenir en la interpretació de la prova. Es va observar que el percentatge de pacients amb PA controlada amb o sense la edició dels valors va ser similar. Però, la edició de la MAPA va condicionar canvis en la classificació del perfil circadiari, observant-se una disminució de perfils reductors, reclassificats cap a perfils menys fisiològics com no-reductor o reductor extrem, ambdós associats a un pitjor pronòstic cardiovascular