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

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Relación entre el perfil de presión arterial y el tamaño renal con la afectación subclínica de órgano diana en pacientes normotensos con poliquistosis renal autosómica dominante y sin insuficiencia renal

La poliquistosis renal autosómica dominante (PQRAD) es la enfermedad genética con afectación renal más común. Se caracteriza por la aparición y progresivo crecimiento de quistes renales, que alteran la estructura normal del parénquima renal conduciendo a la insuficiencia renal avanzada. Representa la entrada en tratamiento sustitutivo renal del 10 % de los pacientes que lo requieren. La principal causa de mortalidad de los pacientes poliquísticos es la enfermedad cardiovascular, muy ligada a una aparición precoz de hipertensión arterial (HTA) y de lesión subclínica de órgano diana. Tanto la HTA como el volumen renal son dos de los factores de progresión más importantes de la enfermedad. El volumen renal se correlaciona de forma estrecha con la HTA y con la pérdida de función renal, especialmente cuando ya existe alteración de la misma. Sin embargo, existe poca información sobre la relación en fases iniciales de la enfermedad entre el volumen renal, la presión y la lesión subclínica de órgano diana en pacientes poliquísticos normotensos. La hipótesis de trabajo de esta tesis doctoral es que incluso en estadios muy precoces de la PQRAD cuando todavía no hay insuficiencia renal y la presión arterial (PA) es normal, el volumen renal y la PA se relacionan con mayor afectación subclínica de órgano diana y que ésta es mayor que en la población sana. Además, se pretende estudiar si la elevación de las cifras de PA en esta población se relacionan con una mayor activación del sistema reninaangiotensina (SRA) y si la determinación de cistatina C permitiría detectar pérdidas precoces de la función renal no detectadas mediante la creatinina sérica y las fórmulas de estimación de filtrado glomerular derivadas de la misma. Se han estudiado 62 pacientes con PQRAD y 28 controles sanos. Los pacientes presentaron de manera significativa mayores cifras de PA (a pesar de estar en el rango de normalidad) y mayor afectación subclínica de órgano diana a nivel vascular, cardíaco y renal sin objetivarse diferencias en la función renal entre ambos grupos. Cuando se estratificaron los pacientes poliquísticos por terciles de volumen renal, se objetivó como con volumen renal levemente aumentado (inferior a 546 ml), los poliquísticos ya presentan mayor afectación subclínica a nivel renal y vascular sin que ello esté relacionado con mayores niveles de PA respecto de los controles sanos. El incremento del volumen renal se acompaña de un aumento de las cifras de PA y de un agravamiento en la lesión subclínica de órgano diana. Así, el volumen renal superior a 800 ml se asocia a un empeoramiento global de la situación cardiovascular de los pacientes con PA significativamente más elevada y mayor afectación subclínica de órgano diana a nivel vascular, cardíaco y renal) respecto de los controles sanos pero también respecto de los poliquísticos con menor volumen renal (inferior a 546 ml). Por otro lado, el incremento del volumen renal se acompaña de mayores variaciones en la cistatina C (y fórmulas derivadas de la misma) que en la creatinina (y fórmulas derivadas de la misma), sin que la fuerza de la asociación entre volumen renal y cistatina C resultara significativamente mayor que la de volumen renal y creatinina. En relación a la activación del SRA, en los pacientes poliquísticos únicamente se objetivó una mayor actividad de la enzima de conversión de la angiotensina (ECA) sérica respecto de los controles sin objetivarse correlación entre los distintos componentes del SRA y el volumen renal. No se observó correlación entre poliquistosis precoz, HTA y marcadores de inflamación.Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. New formation and progressive enlargement of tubular cysts that disrupt the normal renal architecture lead to end-stage renal disease. ADPKD accounts for the 10% of patients that require renal replacement therapy. Cardiovascular disease is the leading cause of death in ADPKD patients, linked to an early onset of hypertension and target organ damage (TOD). Both hypertension and renal volume represent two of the major progression factors of the disease and they both correlate with each other especially when renal function starts its decline. There is only few data on the relationship between renal volume and hypertension with target organ damage in normotensive ADPKD patients. The aim of this work was to determine whether in spite of normotension and normal renal function blood pressure and renal volume correlate with TOD and whether TOD is greater than in healthy population. Whether or not greater blood pressure values may be linked to a higher renin angiotensin system activation and if C cystatin could better identify early renal function decline respect to creatinine or eGFR formulas dependent on creatinine was also assessed. Sixty-two ADPKD patients and 28 healthy subjects were studied. ADPKD patients showed greater blood pressure values (even though within the normal range) and major vascular, renal and cardiac TOD. When ADPKD patients were stratified into tertiles according to their renal volume, greater vascular and renal organ damage was noticed in very early stages, with a renal volume of less than 546 ml. No differences in blood pressure were found between those patients and healthy controls. Renal enlargement was linked to an increase in blood pressure values and aggravation of TOD. A renal volume above 800 ml was associated with a worse cardiovascular situation due to significant higher blood pressure values and greater vascular, cardiac and renal TOD when compared to healthy subjects and also when highest renal volume patients were compared to lowest renal volume tertile patients. Greater changes in plasmatic C cystatin and cystatin-derived estimated glomerular filtration rate (eGFR) fomulas were found respect to changes in creatinine or creatinine-derived eGFR fomulas along the three renal volume tertiles. The strength of the association between C cystatin and renal volume was not greater than the association between creatinine and renal volume. Higher serum angiotensin converting enzyme (ECA) activity was found in ADPKD patients compared to controls but no correlation was found between renal volume and the renin angiotensin system components. Early ADPKD and hypertension were not associated with inflammation biomarkers

Tolvaptan in the treatment of autosomal dominant polycystic kidney disease: patient selection and special considerations

Standard of care therapies for autosomal dominant polycystic kidney disease (ADPKD) may limit morbidity and mortality due to disease-related complications, but they do not delay disease progression. Tolvaptan, a selective vasopressin V2 receptor antagonist, delays the increase in kidney volume (a surrogate marker for disease progression), slows the decline in renal function, and reduces pain in ADPKD patients with relatively preserved renal function. The most common adverse events of tolvaptan are linked to its aquaretic effect, and rare cases of idiosyncratic hepatitis were observed. Additional ongoing studies will determine whether the benefits are sustained over time, whether they can be observed in patients with advanced kidney disease, and whether they can be translated in terms of quality of life and cost/effectiveness parameters. Tolvaptan is currently approved in Europe and several countries throughout the world. In real-life conditions, selection of patients that would be good theoretical candidates to tolvaptan is a key but complex question. Eligibility criteria slightly differ from one country to another, and several models (based on conventional data, genetics, renal volume) were recently proposed to identify patients with evidence or risk of rapid disease progression. Eligible patients will ultimately make the decision to start tolvaptan, after complete information, consideration, and balancing of benefits, adverse events, and risks

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

Relación entre el perfil de presión arterial y el tamaño renal con la afectación subclínica de órgano diana en pacientes normotensos con poliquistosis renal autosómica dominante y sin insuficiencia renal

La poliquistosis renal autosómica dominante (PQRAD) es la enfermedad genética con afectación renal más común. Se caracteriza por la aparición y progresivo crecimiento de quistes renales, que alteran la estructura normal del parénquima renal conduciendo a la insuficiencia renal avanzada. Representa la entrada en tratamiento sustitutivo renal del 10 % de los pacientes que lo requieren. La principal causa de mortalidad de los pacientes poliquísticos es la enfermedad cardiovascular, muy ligada a una aparición precoz de hipertensión arterial (HTA) y de lesión subclínica de órgano diana. Tanto la HTA como el volumen renal son dos de los factores de progresión más importantes de la enfermedad. El volumen renal se correlaciona de forma estrecha con la HTA y con la pérdida de función renal, especialmente cuando ya existe alteración de la misma. Sin embargo, existe poca información sobre la relación en fases iniciales de la enfermedad entre el volumen renal, la presión y la lesión subclínica de órgano diana en pacientes poliquísticos normotensos. La hipótesis de trabajo de esta tesis doctoral es que incluso en estadios muy precoces de la PQRAD cuando todavía no hay insuficiencia renal y la presión arterial (PA) es normal, el volumen renal y la PA se relacionan con mayor afectación subclínica de órgano diana y que ésta es mayor que en la población sana. Además, se pretende estudiar si la elevación de las cifras de PA en esta población se relacionan con una mayor activación del sistema reninaangiotensina (SRA) y si la determinación de cistatina C permitiría detectar pérdidas precoces de la función renal no detectadas mediante la creatinina sérica y las fórmulas de estimación de filtrado glomerular derivadas de la misma. Se han estudiado 62 pacientes con PQRAD y 28 controles sanos. Los pacientes presentaron de manera significativa mayores cifras de PA (a pesar de estar en el rango de normalidad) y mayor afectación subclínica de órgano diana a nivel vascular, cardíaco y renal sin objetivarse diferencias en la función renal entre ambos grupos. Cuando se estratificaron los pacientes poliquísticos por terciles de volumen renal, se objetivó como con volumen renal levemente aumentado (inferior a 546 ml), los poliquísticos ya presentan mayor afectación subclínica a nivel renal y vascular sin que ello esté relacionado con mayores niveles de PA respecto de los controles sanos. El incremento del volumen renal se acompaña de un aumento de las cifras de PA y de un agravamiento en la lesión subclínica de órgano diana. Así, el volumen renal superior a 800 ml se asocia a un empeoramiento global de la situación cardiovascular de los pacientes con PA significativamente más elevada y mayor afectación subclínica de órgano diana a nivel vascular, cardíaco y renal) respecto de los controles sanos pero también respecto de los poliquísticos con menor volumen renal (inferior a 546 ml). Por otro lado, el incremento del volumen renal se acompaña de mayores variaciones en la cistatina C (y fórmulas derivadas de la misma) que en la creatinina (y fórmulas derivadas de la misma), sin que la fuerza de la asociación entre volumen renal y cistatina C resultara significativamente mayor que la de volumen renal y creatinina. En relación a la activación del SRA, en los pacientes poliquísticos únicamente se objetivó una mayor actividad de la enzima de conversión de la angiotensina (ECA) sérica respecto de los controles sin objetivarse correlación entre los distintos componentes del SRA y el volumen renal. No se observó correlación entre poliquistosis precoz, HTA y marcadores de inflamación.Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. New formation and progressive enlargement of tubular cysts that disrupt the normal renal architecture lead to end-stage renal disease. ADPKD accounts for the 10% of patients that require renal replacement therapy. Cardiovascular disease is the leading cause of death in ADPKD patients, linked to an early onset of hypertension and target organ damage (TOD). Both hypertension and renal volume represent two of the major progression factors of the disease and they both correlate with each other especially when renal function starts its decline. There is only few data on the relationship between renal volume and hypertension with target organ damage in normotensive ADPKD patients. The aim of this work was to determine whether in spite of normotension and normal renal function blood pressure and renal volume correlate with TOD and whether TOD is greater than in healthy population. Whether or not greater blood pressure values may be linked to a higher renin angiotensin system activation and if C cystatin could better identify early renal function decline respect to creatinine or eGFR formulas dependent on creatinine was also assessed. Sixty-two ADPKD patients and 28 healthy subjects were studied. ADPKD patients showed greater blood pressure values (even though within the normal range) and major vascular, renal and cardiac TOD. When ADPKD patients were stratified into tertiles according to their renal volume, greater vascular and renal organ damage was noticed in very early stages, with a renal volume of less than 546 ml. No differences in blood pressure were found between those patients and healthy controls. Renal enlargement was linked to an increase in blood pressure values and aggravation of TOD. A renal volume above 800 ml was associated with a worse cardiovascular situation due to significant higher blood pressure values and greater vascular, cardiac and renal TOD when compared to healthy subjects and also when highest renal volume patients were compared to lowest renal volume tertile patients. Greater changes in plasmatic C cystatin and cystatin-derived estimated glomerular filtration rate (eGFR) fomulas were found respect to changes in creatinine or creatinine-derived eGFR fomulas along the three renal volume tertiles. The strength of the association between C cystatin and renal volume was not greater than the association between creatinine and renal volume. Higher serum angiotensin converting enzyme (ECA) activity was found in ADPKD patients compared to controls but no correlation was found between renal volume and the renin angiotensin system components. Early ADPKD and hypertension were not associated with inflammation biomarkers

Changes in central 24-h ambulatory blood pressure and hemodynamics 12 months after bariatric surgery: the BARIHTA study

Background: Weight loss is associated to blood pressure (BP) reduction in obese patients. There is no information on central 24-h BP changes after bariatric surgery (BS). Methods and results: In this study, we analyzed changes in 24-h BP 12 months following BS, with intermediate evaluations at 1, 3, and 6 months, in severely obese adults. The primary endpoint was aortic (central) 24-h systolic BP changes. Circadian BP patterns and hypertension resolution were also assessed. As secondary endpoints, we analyze changes in central 24-h diastolic BP as well as in all office and ambulatory peripheral BP parameters. Obese adults scheduled for BS as routine clinical care were recruited. We included 62 patients (39% with hypertension, 77% women, body mass index, 42.6 ± 5.5 kg/m2). Reduction in body weight was mean (IQR) 30.5% (26.2-34.4) 1 year after BS. Mean (95% CI) change in central 24-h systolic BP was - 3.1 mmHg (- 5.5 to - 0.7), p = 0.01 after adjustment for age, sex, and baseline hypertensive status. BP parameter changes were different between normotensives and hypertensives. Mean (95% CI) change in central 24-h systolic BP was - 5.2 mmHg (- 7.7 to - 2.7), p < 0.001, in normotensives and - 0.5 mmHg (- 5.1 to 4.0), p = 0.818, in hypertensives. There was a remission of hypertension in 48% of patients. Most patients had a reduced dipping pattern, similarly at baseline and 12 months after BS. Conclusions: Among patients with severe obesity, there was a substantial central 24-h systolic BP decrease 12 months following BS. Importantly, this change was observed in those patients with normal BP at baseline

Improvement of arterial stiffness one month after bariatric surgery and potential mechanisms

Arterial stiffness (AS) is an independent predictor of cardiovascular risk. We aimed to analyze changes (Δ) in AS 1-month post-bariatric surgery (BS) and search for possible pathophysiological mechanisms. Patients with severe obesity (43% hypertensives) were prospectively evaluated before and 1-month post-BS, with AS assessed by pulse-wave velocity (PWV), augmentation index (AIx@75) and pulse pressure (PP). Ambulatory 24 h blood pressure (BP), anthropometric data, renin-angiotensin-aldosterone system (RAAS) components and several adipokines and inflammatory markers were also analyzed. Overall reduction in body weight was mean (interquartile range (IQR)) = 11.0% (9.6-13.1). A decrease in PWV, AIx@75 and PP was observed 1-month post-BS (all, p < 0.01). There were also significant Δ in BP, RAAS components, adipokines and inflammatory biomarkers. Multiple linear regression adjusted models showed that Δaldosterone was an independent variable (B coeff.95%CI) for final PWV (B = -0.003, -0.005 to 0.000; p = 0.022). Angiotensin-converting enzyme (ACE)/ACE2 and ACE were independent variables for final AIx@75 (B = 0.036, 0.005 to 0.066; p = 0.024) and PP (B = 0.010, 0.003 to 0.017; p = 0.01), respectively. There was no correlation between ΔAS and anthropometric changes nor with Δ of adipokines or inflammatory markers except high-sensitivity C-reactive protein (hs-CRP). Patients with PWV below median decreased PWV (mean, 95%CI = -0.18, -0.25 to -0.10; p < 0.001) and both AIx@75 and PP at 1-month, but not those with PWV above median. In conclusion, there is an improvement in AS 1-month post-BS that correlates with ΔBP and Δrenin-angiotensin-aldosterone components. The benefit is reduced in those with higher PWV

Recommendations for the management of renal involvement in the tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a rare, hereditary, multisystemic disease with a broad phenotypic spectrum. Its management requires the collaboration of multiple specialists. Just as in the paediatric age, the paediatric neurologist takes on special importance; in adulthood, renal involvement is the cause of the greatest morbidity and mortality. There are several recommendations on the general management of patients with TSC but none that focuses on renal involvement. These recommendations respond to the need to provide guidelines to facilitate a better knowledge and diagnostic-therapeutic management of the renal involvement of TSC through a rational use of complementary tests and the correct use of available treatments. Their elaboration has been based on consensus within the hereditary renal diseases working group of the SEN/REDINREN (Spanish Society of Nephrology/Kidney Research Network). It has also counted on the participation of non-nephrologist specialists in TSC in order to expand the vision of the disease

Risk factors associated with major complications after ultrasound-guided percutaneous renal biopsy of native kidneys

Introduction: Percutaneous renal biopsy (PRB) of native kidneys is an important tool for diagnosis and management of renal disease. In this study, we analyzed the success, safety, and risk complications of PRB in our center. Methods: A retrospective review of ultrasound-guided PRB done at our institution from January 1998 to December 2017 was performed. Clinical and laboratory data were collected for 661 PRBs. Statistical analysis was performed using the Mann-Whitney U test for continuous variable and chi-square test for categorical variables. Multivariate analysis using logistic regression was performed to assess factors associated with increased risk of complications after PRB. Results: The median age was 56 (42-68) years old, the majority were male (64%) and white (82%). Ten glomeruli were present in 63.5% of PRBs. Overall, the rate of complications was 16.6%, where 15.1% of them were minor complications and 1.5% were major complications. Perinephritic hematoma accounted for the minor complication that occurred most frequently, whereas the need of a blood transfusion was the prevalent for major complications. By multivariate analysis, increased activated partial thromboplastin time (aPTT; OR 1.11, 95% CI 1.035-1.180) and prebiopsy lower hemoglobin (Hgb; OR 1.61, 95% CI 1.086-2.304) were identified as independent risk factors for major complications. In addition, older patients (OR 1.057, 95% CI 1.001-1.117) were identified as an independent risk factor for blood transfusion requirement. Conclusion: The current risk of complications after native PRB is low. Major complications are most common in case of increased aPTT and decreased Hgb baseline level