Measured and Estimated Glomerular Filtration Rate to Evaluate Rapid Progression and Changes over Time in Autosomal Polycystic Kidney Disease: Potential Impact on Therapeutic Decision-Making.

Autosomal polycystic kidney disease (ADPKD) is the most common genetic form of kidney failure, reflecting unmet needs in management. Prescription of the only approved treatment (tolvaptan) is limited to persons with rapidly progressing ADPKD. Rapid progression may be diagnosed by assessing glomerular filtration rate (GFR) decline, usually estimated (eGFR) from equations based on serum creatinine (eGFRcr) or cystatin-C (eGFRcys). We have assessed the concordance between eGFR decline and identification of rapid progression (rapid eGFR loss), and measured GFR (mGFR) declines (rapid mGFR loss) using iohexol clearance in 140 adults with ADPKD with ≥3 mGFR and eGFRcr assessments, of which 97 also had eGFRcys assessments. The agreement between mGFR and eGFR decline was poor: mean concordance correlation coefficients (CCCs) between the method declines were low (0.661, range 0.628 to 0.713), and Bland and Altman limits of agreement between eGFR and mGFR declines were wide. CCC was lower for eGFRcys. From a practical point of view, creatinine-based formulas failed to detect rapid mGFR loss (-3 mL/min/y or faster) in around 37% of the cases. Moreover, formulas falsely indicated around 40% of the cases with moderate or stable decline as rapid progressors. The reliability of formulas in detecting real mGFR decline was lower in the non-rapid-progressors group with respect to that in rapid-progressor patients. The performance of eGFRcys and eGFRcr-cys equations was even worse. In conclusion, eGFR decline may misrepresent mGFR decline in ADPKD in a significant percentage of patients, potentially misclassifying them as progressors or non-progressors and impacting decisions of initiation of tolvaptan therapy.

The error of estimated GFR in predialysis care.

The error of estimated glomerular filtration rate (eGFR) and its consequences in predialysis are unknown. In this prospective multicentre study, 315 predialysis patients underwent measured GFR (mGFR) by the clearance of iohexol and eGFR by 52 formulas. Agreement between eGFR and mGFR was evaluated by concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). In a sub-analysis we assessed the impact of eGFR error on decision-making as (i) initiating dialysis, (ii) preparation for renal replacement therapy (RRT) and (iii) continuing clinical follow-up. For this sub-analysis, patients who started RRT due to clinical indications (uremia, fluid overload, etc.) were excluded. eGFR had scarce precision and accuracy in reflecting mGFR (average CCC 0.6, TDI 70% and cp 22%) both in creatinine- and cystatin-based formulas. Variations -larger than 10 ml/min- between mGFR and eGFR were frequent. The error of formulas would have suggested (a) premature preparation for RTT in 14% of stable patients evaluated by mGFR; (b) to continue clinical follow-up in 59% of subjects with indication for RTT preparation due to low GFRm and (c) to delay dialysis in all asymptomatic patients (n = 6) in whom RRT was indicated based on very low mGFR. The error of formulas in predialysis was frequent and large and may have consequences in clinical care.

Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods: This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results: Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions: SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study.

INTRODUCTION: Inflammation is a risk factor for diabetes in the general population. The role of inflammation in prediabetes or post-transplant diabetes mellitus (PTDM) is not clear. We evaluated the association between inflammatory markers in patients on the waiting list for renal transplantation and the onset of prediabetes and PTDM 12 months after transplantation. METHODS: This is a post hoc analysis of a prospective study that included nondiabetic patients on the waiting list for kidney transplantation who underwent an oral glucose tolerance test (OGTT) and were followed up to 12 months after transplantation. At this time, those patients without PTDM underwent another OGTT. At pre-transplantation, five cytokines: TNFα, IL6, IL1ß, CRP, MCP1 were determined. The association between inflammation and prediabetes/PTDM was evaluated using multiple regression models. RESULTS: 110 patients on the waiting list were enrolled: 74 had normal glucose metabolism and 36 had prediabetes or occult diabetes. At 12 months, 53 patients had normal glucose metabolism, 25 prediabetes, and 32 PTDM. In multiple regression analysis, pre-transplant inflammation was not a risk factor for prediabetes or PTDM. This was attributed to the high interrelation between obesity, prediabetes, and inflammation: about 75% of the cases had these conditions. In a sub-analysis, we analyzed only patients without prediabetes and occult diabetes on the waiting list and found that TNFα levels and BMI at pre-transplantation were independently associated with the onset of prediabetes or PTDM 1 year after transplantation. CONCLUSIONS: Pre-transplant inflammation and BMI are risk factors for prediabetes and PTDM in patients without glucose metabolism alterations.

Efficacy and Safety of Eculizumab in Kidney Transplant Patients With Primary Atypical Hemolytic-Uremic Syndrome.

The atypical hemolytic-uremic syndrome (aHUS) is characterized by the triad of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The aHUS is related to complement dysregulation; since the approval of eculizumab for this entity (a monoclonal antibody that inhibits C5 activation and blocks the formation of the membrane attack complex) the prognosis has improved. The recurrence of aHUS after kidney transplantation is frequent and implies loss of the graft in a high percentage of cases. Eculizumab prophylaxis to prevent recurrence has allowed successful kidney transplantation in this group of patients. We present a series of kidney transplant patients with chronic kidney disease secondary to aHUS and the use of eculizumab for prevention of recurrence.

Characteristics, management and outcomes of atypical haemolytic uraemic syndrome in kidney transplant patients: a retrospective national study.

BACKGROUND: Kidney transplantation (KTx) is a strong trigger for the development of either recurrent or de novo atypical haemolytic uraemic syndrome (aHUS). According to previous studies, eculizumab (ECU) is effective for prophylaxis and for treatment of recurrence. METHODS: We evaluated the experiences of Spanish patients with recurrent and de novo aHUS associated with KTx, treated or not treated with ECU. In the de novo group, we classified patients as having early de novo (during the first month) or late de novo aHUS (subsequent onset). RESULTS: We analysed 36 cases of aHUS associated with KTx. All of the 14 patients with pre-KTx diagnosis of aHUS were considered to have high or moderate risk of recurrence. Despite receiving grafts from suboptimal donors, prophylactic ECU was effective for avoiding recurrence. The drug was stopped only in two cases with low-moderate risk of recurrence and was maintained in high-risk patients with no single relapse. There were 22 de novo aHUS cases and 16 belonged to the early de novo group. The median time of onset in the late group was 3.4 years. The early group had a better response to ECU than the late group, probably due to earlier diagnosis and use of the drug. No genetic pathogenic variant was detected in de novo aHUS cases, suggesting a secondary profile of the disease. ECU was stopped in all de novo patients with no relapses. ECU was well tolerated in all cases. CONCLUSIONS: Both groups (pre-aHUS and de novo) presented different clinical profiles, management approaches and outcomes. One should consider aHUS regardless of time after KTx. Genetic studies are crucial to stratify risks of relapse and to determine necessary lengths of treatment. We suggest short ECU treatment for de novo cases without pathogenic mutation and that ECU treatment be considered pre-emptively for patients with moderate or high risk of recurrence.

Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion.

Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact of NRP on the short-term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012-2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n = 865) or RR (n = 1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high-volume centers (≥90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p = .261) and mortality at 1 year (p =  .111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 [95% CI 1.43-2.72]; p < .001) and 1-year graft loss (OR 1.77 [95% CI 1.01-3.17]; p = .034). In conclusion, compared with RR, NRP appears to improve the short-term outcomes of cDCDD kidney transplants.

Extending the Battery Life of the ZigBee Routers and Coordinator by Modifying Their Mode of Operation.

Wireless sensor networks proliferate more and more in all social scopes and sectors. Such networks are implemented in smart homes, smart cities, security systems, medical resources, agriculture, automotive industry, etc. Communication devices and sensors of such networks are powered with batteries: the enlarging of battery life is a hot research topic. We focus on wireless sensor networks based on ZigBee technology. While sleep standard operation mode is defined for end devices, it is not the case for the rest of devices (routers and Coordinator), which usually always remain in active mode. We designed a formal optimization model for maximizing the enlarging of the battery life of routers and Coordinator, allowing us to delimit practical successful conditions. It was successfully tested with a standard ZigBee datasheet comprising technical data for sensors, routers, and coordinators. It was tested in a practical wireless sensor network assembly with XBee S2C devices. We derived, from the previous model, a novel but simple protocol of communication among routers and coordinators. It was tested in different use cases. We showed that when end devices generate traffic at regular intervals, the enlarging of the battery life of routers and Coordinator was possible only under certain use cases.

Interference Effects Redress over Power-Efficient Wireless-Friendly Mesh Networks for Ubiquitous Sensor Communications across Smart Cities.

Ubiquitous sensing allows smart cities to take control of many parameters (e.g., road traffic, air or noise pollution levels, etc.). An inexpensive Wireless Mesh Network can be used as an efficient way to transport sensed data. When that mesh is autonomously powered (e.g., solar powered), it constitutes an ideal portable network system which can be deployed when needed. Nevertheless, its power consumption must be restrained to extend its operational cycle and for preserving the environment. To this end, our strategy fosters wireless interface deactivation among nodes which do not participate in any route. As we show, this contributes to a significant power saving for the mesh. Furthermore, our strategy is wireless-friendly, meaning that it gives priority to deactivation of nodes receiving (and also causing) interferences from (to) the rest of the smart city. We also show that a routing protocol can adapt to this strategy in which certain nodes deactivate their own wireless interfaces.

Spanish modified version of the palliative care outcome scale-symptoms renal: cross-cultural adaptation and validation.

BACKGROUND: Patients with chronic kidney disease (CKD) have a high symptoms burden that is related to a poor health-related quality of life (HRQoL) and high costs of care. Validated instruments may be useful for assessing the symptoms and monitoring outcomes in these patients. The Palliative care Outcome Scale-Symptoms Renal (POS-S Renal) is a patient-reported outcome measure for assessing symptoms in CKD stage 4-5. This study is the first cross-cultural adaptation and psychometric analysis of this clinical tool. The purpose of this study is to carry out a cross-cultural adaptation of the POS-S Renal for Spanish-speaking patients, and to perform an analysis of the psychometric properties of this questionnaire. METHODS: The English version of the POS-S Renal was culturally adapted and translated into Spanish using a double forward and backward method. An expert panel evaluated the content validity. The questionnaire was pilot-tested in 30 patients. A total of 200 patients with CKD stage 4-5 filled in a modified Spanish version of the POS-S Renal and the MSAS-SF. Statistical analysis to evaluate the psychometric properties of the questionnaire was carried out. RESULTS: The content validity index (CVI) was 0.97, which indicated that the content of the instrument is an adequate reflection of the symptoms in advanced CKD (ACKD). The factor analysis indicated a two-factor solution explaining 35.05% of total variance. The confirmatory factor analysis (CFA) demonstrated that the two factor model was well supported (comparative fit index = 0.98, root mean square error of approximation = 0.068). This assessment tool demonstrated a satisfactory test-retest reliability (r = 0.909 to factor 1, r = 0.695 to factor 2, r = 0.887 to total score), good internal consistency to factor 1 (α = 0.78) and moderate internal consistency to factor 2 (α = 0.56). Concurrent criterion-related validity with MSAS-SF was also demonstrated, with r = 0.860, which indicated a high degree of correlation with a validated instrument that has been used in patients with ACKD. CONCLUSIONS: The Spanish modified version of the POS-S Renal is a reliable and valid instrument that can be used to assess symptoms in Spanish patients with CKD stage 4-5.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study) / Alteraciones del metabolismo mineral, fracturas vertebrales, y calcificaciones aórticas en receptores estables de trasplante renal: papel del género (estudio EMITRAL)

Antecedentes y objetivos: La relación entre las alteraciones del metabolismo mineral, las fracturas óseas y las calcificaciones vasculares en receptores de un trasplante renal no han sido establecidas. Método: Realizamos un estudio transversal en 727 receptores estables procedentes de 28 centros de trasplante españoles. Se determinaron de manera centralizada los parámetros del metabolismo mineral; también se centralizó la semicuantificación de las fracturas vertebrales y de las calcificaciones de la aorta abdominal. Resultados: La deficiencia de vitamina D (25OHD3 < 15ng/ml) fue más frecuente en mujeres y en los estadios CKD-T I-III (29,6 vs. 44,4%; p=0,003). La relación inversa y significativa observada entre los niveles de 25OHD3 y PTH fue modificada por el género de tal manera que la pendiente fue mayor en las mujeres que en los hombres (p=0,01). Un 15% de los receptores mostró alguna fractura vertebral (VFx) con un grado de deformidad ≥2. Los factores relacionados con la VFx diferían en función del género: en los hombres, la edad (OR: 1,04; IC 95%: 1,01-1,06) y el tratamiento con CsA (OR: 3,2; IC 95: 1,6-6,3); en las mujeres la edad (OR: 1,07; IC 95%: 1,03-1,12) y los niveles de PTH (OR per 100pg/ml increase: 1,27; IC 95%: 1,043-1,542). Las calcificaciones de la aorta abdominal fueron comunes (67,2%) y se relacionaron con los factores de riesgo clásicos, pero no con los parámetros del metabolismo mineral. Conclusiones: La deficiencia de vitamina D es más frecuente en las mujeres receptoras de un trasplante renal y en los estadios más tempranos de la CKD-T, y es un factor que contribuye al desarrollo de hiperparatiroidismo secundario. Las VFx prevalentes están relacionadas con unos niveles más elevados de PTH solamente en las mujeres (AU)

Background and objectives: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. Method: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. Results: Vitamin D deficiency (25OHD3 < 15 ng/ml) was more common in female recipients at CKD-T stages I–III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100 pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. Conclusions: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients (AU)

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.

Influencia de los genotipos del sistema renina-angiotensina en la respuesta antiproteinúrica a dosis altas de olmesartán en nefropatías proteinúricas no diabéticas / The influence of renin-angiotensin system genotypes on the antiproteinuric response to high doses of olmesartan in non-diabetic proteinuric nephropathies

Objetivo: Evaluar la respuesta antiproteinúrica a un tratamiento multifactorial basado en dosis elevadas de antagonistas de los receptores de la angiotensina II (ARAII) (olmesartán) en pacientes con nefropatías proteinúricas no diabéticas, según tres de los polimorfismos del sistema renina-angiotensina (SRA): inserción/deleción del gen de la enzima convertidora de angiontensina (ECA), M235T del gen del angiotensinógeno y A1166C del receptor AT1 (rAT1) para la angiotensina II. Material y métodos: Se estudiaron 53 pacientes con nefropatía proteinúrica no diabética, con un tiempo medio de evolución de 84,4 ± 15 meses. Género varón en 41 (77,4 %); edad media 49,7 ± 3 años; índice de masa corporal 30 ± 6 kg/m2. Todos recibieron olmesartán (40 mg/12 h) asociado a un promedio de 2,4 ± 1,6 fármacos antihipertensivos durante una mediana de tiempo de 13 meses (rango intercuartil 7-25 meses). Resultados: La presión arterial (PA) sistólica descendió de 145 ± 14 hasta 128 ± 14 mmHg (p < 0,001) y la PA diastólica desde 85 ± 11 a 79 ± 7 mmHg (p < 0,01). La presión de pulso pasó de 53,5 ± 14 a 48 ± 12 mmHg (p < 0,05). La proteinuria se redujo de 2,74 ± 1,6 a 0,9 ± 1 g/24 h (p < 0,001), representando un descenso promedio del 67,1 %. Según los polimorfismos del SRA, la respuesta antiproteinúrica fue: polimorfismo del gen del angiotensiógeno: genotipo TT: 76,8 %; genotipo MM: 67,3 %; genotipo MT: 65,8 %, significativamente mayor (p < 0,05) para genotipo TT respecto de MM y MT. Polimorfismo del gen de la ECA: genotipo DD: 71,4 %; genotipo ID: 60,6 %, genotipo II: 34,8 %, significativamente mayor (p < 0,05) para genotipo DD respecto a ID e II, y asimismo (p < 0,05) para el genotipo ID respecto a II. Polimorfismo del gen del rAT1: genotipo AC: 85,2 %; genotipo CC: 73,7 %; genotipo AA: 62,7 %; significativamente mayor para el genotipo AC (p < 0,05) respecto a AA y CC. Las diferencias entre la proteinuria inicial y final del período de seguimiento fueron significativas (p < 0,01) para las asociaciones genotípicas: DD/AA, DD/MT, DD/MM, DD/TT y DD/AC, si bien la asociación con mayor efecto antiproteinúrico fue DD/AC (89,9 %, p < 0,05 %). Conclusiones: La administración de dosis altas de olmesartán en pacientes con nefropatía proteinúrica no diabética comporta reducciones significativas en la proteinuria. Este descenso fue independiente del control tensional y de otros factores de confusión. Los polimorfismos del SRA pueden modular la respuesta antiproteinúrica al tratamiento con ARAII

Objective: To assess the antiproteinuric response to multifactorial treatment based on high doses of angiotensin II receptor antagonists (ARBs) (olmesartan) in patients with non-diabetic proteinuric nephropathies, according to three renin-angiotensin system (RAS) polymorphisms: insertion/deletion of the angiotensin converting enzyme (ACE) gene, the angiotensinogen gene M235T and the angiotensin II type 1 receptor (AT1R) A1166C. Material and method: We studied 53 patients with non-diabetic proteinuric nephropathy with a mean progression time of 84.4±15 months. 41 were males (77.4%); mean age 49.7±3 years, body mass index 30±6kg/m2. All received olmesartan (40mg/12h) associated with a mean of 2.4±1.6 antihypertensive drugs for a median period of 13 months (interquartile range 7-25 months). Results: Systolic blood pressure (BP) decreased from 145±14mmHg to 128±14mmHg (P<.001) and diastolic BP from 85±11mmHg to 79±7mmHg (P<.01). Pulse pressure decreased from 53.5±14mmHg to 48±12mmHg (P<.05). Proteinuria decreased from 2.74±1.6g/24h to 0.9±1g/24h (P<.001), representing a mean decrease of 67.1%. According to RAS polymorphisms, antiproteinuric response was: angiotensinogen gene polymorphism: genotype TT: 76.8%; genotype MM: 67.3%; genotype MT: 65.8%, significantly higher (P<.05) for genotype TT compared to genotypes MM and MT. Polymorphism of the ACE gene: genotype DD: 71.4%; genotype ID: 60.6%, genotype II: 34.8%, significantly higher (P<.05) for genotype DD compared to genotypes ID and II, and also (P<.05) for genotype ID compared to II. AT1R gene polymorphism: genotype AC: 85.2%; genotype CC: 73.7%; genotype AA: 62.7%; significantly higher for genotype AC (P<.05) compared to genotypes AA and CC. The differences between initial and final proteinuria for the follow-up period were significant (P<.01) for genotypic associations DD/AA, DD/MT, DD/MM, DD/TT and DD/AC, although the association with the highest antiproteinuric effect was DD/AC (89.9%, P<.05%). Conclusions: Administering high doses of olmesartan in patients with non-diabetic proteinuric nephropathy results in significant reductions in proteinuria. This decrease was independent of blood pressure control and other confounding factors. RAS polymorphisms may modulate the antiproteinuric response to treatment with ARBs

The influence of renin-angiotensin system genotypes on the antiproteinuric response to high doses of olmesartan in non-diabetic proteinuric nephropathies.

OBJECTIVE: To assess the antiproteinuric response to multifactorial treatment based on high doses of angiotensin II receptor antagonists (ARBs) (olmesartan) in patients with non-diabetic proteinuric nephropathies, according to three renin-angiotensin system (RAS) polymorphisms: insertion/deletion of the angiotensin converting enzyme (ACE) gene, the angiotensinogen gene M235T and the angiotensin II type 1 receptor (AT1R) A1166C. MATERIAL AND METHOD: We studied 53 patients with non-diabetic proteinuric nephropathy with a mean progression time of 84.4±15 months. 41 were males (77.4%); mean age 49.7±3 years, body mass index 30±6kg/m2. All received olmesartan (40mg/12h) associated with a mean of 2.4±1.6 antihypertensive drugs for a median period of 13 months (interquartile range 7-25 months). RESULTS: Systolic blood pressure (BP) decreased from 145±14mmHg to 128±14mmHg (P<.001) and diastolic BP from 85±11mmHg to 79±7mmHg (P<.01). Pulse pressure decreased from 53.5±14mmHg to 48±12mmHg (P<.05). Proteinuria decreased from 2.74±1.6g/24h to 0.9±1g/24h (P<.001), representing a mean decrease of 67.1%. According to RAS polymorphisms, antiproteinuric response was: angiotensinogen gene polymorphism: genotype TT: 76.8%; genotype MM: 67.3%; genotype MT: 65.8%, significantly higher (P<.05) for genotype TT compared to genotypes MM and MT. Polymorphism of the ACE gene: genotype DD: 71.4%; genotype ID: 60.6%, genotype II: 34.8%, significantly higher (P<.05) for genotype DD compared to genotypes ID and II, and also (P<.05) for genotype ID compared to II. AT1R gene polymorphism: genotype AC: 85.2%; genotype CC: 73.7%; genotype AA: 62.7%; significantly higher for genotype AC (P<.05) compared to genotypes AA and CC. The differences between initial and final proteinuria for the follow-up period were significant (P<.01) for genotypic associations DD/AA, DD/MT, DD/MM, DD/TT and DD/AC, although the association with the highest antiproteinuric effect was DD/AC (89.9%, P<.05%). CONCLUSIONS: Administering high doses of olmesartan in patients with non-diabetic proteinuric nephropathy results in significant reductions in proteinuria. This decrease was independent of blood pressure control and other confounding factors. RAS polymorphisms may modulate the antiproteinuric response to treatment with ARBs.

Trasplante renal con injertos procedentes de donantes en parada cardíaca Maastricht tipo III / Kidney transplantation with grafts from type III Maastricht non-beating-heart donors

El trasplante renal (TR) con riñones de donantes fallecidos en parada cardíaca (PC) está creciendo en nuestro país. La mayoría procede de donantes con los criterios de Maastricht tipo II, si bien en los últimos años el donante fallecido tras limitación de tratamientos de soporte vital (LTSV) es una realidad en algunos países europeos y norteamericanos y constituye el Maastricht tipo III. Se presenta una serie de 6 TR con riñones de donantes fallecidos tras PC como consecuencia de LTSV en tres hospitales del Sector Málaga. Tras consensuar protocolo de actuación en el que la valoración como donante fue siempre posterior a la decisión de LTSV, se planteó a las familias la opción de donación. La preservación de los riñones se realizó mediante sonda de doble balón tipo Porges que se colocó antes de la PC. En dos casos la LTSV se realizó en la Unidad de Cuidados Intensivos y en el tercero en quirófano. Los tiempos desde inicio LTSV hasta la PC oscilaron entre 15 y 40 minutos, con un tiempo de parada circulatoria antes del inicio de la (..) (AU)

Kidney transplantation (KT) with kidneys from non-beating-heart donors (NBHD) is a growing trend in Spain. The majority of these kidneys come from type II Maastricht patients, although in recent years, organ donations from patients deceased due to cardiac arrest following limitation of life-sustaining therapy has already been in practice in certain European and North American countries, and it involves type III Maastricht patients. We present a series of 6 KT using kidneys from NHBD as a consequence of limitation of life-sustaining therapy in three different hospitals in the sector of Malaga. After agreeing upon a protocol for evaluating the potential of a patient for organ donation, which was always after deciding to limit life-sustaining therapy, the patients' families were given the option of organ donation. Kidneys were preserved using a Porges double balloon catheter, which was placed prior to cardiac arrest. In two cases, the limitation of life-sustaining therapy took place in the intensive care unit, and in the third case, in the operating room. The interval between limitation of life-sustaining therapy and cardiac (..) (AU)

Kidney transplantation with grafts from type III Maastricht non-beating-heart donors.

Kidney transplantation (KT) with kidneys from non-beating-heart donors (NBHD) is a growing trend in Spain. The majority of these kidneys come from type II Maastricht patients, although in recent years, organ donations from patients awaiting cardiac arrest following limitation of life-sustaining therapy has already been in practice in certain European and North American countries, involving type III Maastricht patients. We present a series of 6 KT using kidneys from NHBD as a consequence of limitation of life-sustaining therapy in three different hospitals in the sector of Malaga. After agreeing upon a protocol for evaluating the potential of a patient for organ donation after the decision for limiting life-sustaining therapy, the patients' families were given the option of organ donation. Kidneys were preserved using a Porges double balloon catheter, which was placed prior to cardiac arrest. In two cases, the limitation of life-sustaining therapy took place in the intensive care unit, and in the third case, in the operating room. The interval between limitation of life-sustaining therapy and cardiac arrest ranged between 15 minutes and 40 minutes, with an interval of circulatory arrest prior to perfusion of 5-11 minutes. Perfusion-cooling of the kidneys was initially carried out using saline solution, followed by organ preservation solution (Celsior or Belzer) and extraction of the kidney using a rapid surgical technique. True or functional hot ischaemia times were 60 minutes, 59 minutes, and 50 minutes, respectively, for each of the three donors. Kidneys were evaluated for viability using time intervals for the procedure (including hypotension prior to cardiac arrest), macroscopic appearance, and histopathology of a sample taken from each kidney. The recipients of these 6 kidneys had given their consent to receive organs from expanded-criteria donors. Cold ischaemia lasted between 9 hours and 20 hours (mean: 14.6 hours). One recipient developed haemorrhagic complications during the immediate postoperative period and required a transplantectomy. The other five currently retain functioning grafts. All had delayed graft function, necessitating haemodialysis. The range of estimated glomerular filtration rates at the most recent follow-up evaluation was 23.0-106 ml/min/1.73 m(2). In conclusion, type III Maastricht donors provide valid kidneys for transplantation, although this series showed that supported functional hot ischaemia was very important, the consequence of accumulated ischaemic damage starting in the agonal phase, circulatory arrest, and organ preservation using cold solutions. As such, to improve the quality of results obtained using kidneys from these types of donors would involve a very careful selection of optimal donors and minimisation of total functional ischaemia times.

Papel de la denervación simpática de arterias renales en un paciente con hipertensión arterial refractaria / Role of renal sympathetic denervation in a refractory arterial hypertension patient

A pesar de los progresos en el tratamiento farmacológico de la hipertensión arterial (HTA) y el empleo de múltiples fármacos antihipertensivos, un pequeño pero significativo porcentaje de los pacientes con HTA refractaria severa verdadera continúa sin alcanzar su objetivo de control tensional. En estos casos, la denervación simpática renal (DNSR) parece mostrarse como un método seguro y eficaz para aquellos pacientes hipertensos severos refractarios al tratamiento farmacológico múltiple. Presentamos el caso de un paciente de 52 años de edad diagnosticado de HTA esencial refractaria a tratamiento con 7 fármacos antihipertensivos. Tras 10 ingresos hospitalarios sin conseguir un adecuado control de las cifras de presión arterial, decidimos plantear la DNSR como coadyuvante al tratamiento médico. El procedimiento se realizó sin complicaciones a corto y medio plazo, consiguiéndose una mejoría significativa de las cifras tensionales, con el objetivo de disminuir su riesgo vascular global (AU)

Despite advances in the pharmacological treatment of arterial hypertension (AHT) and the use of multiple antihypertensive drugs, a small but significant percentage of true severe refractory arterial hypertension patients are still not reaching their target blood pressure. In these cases, renal sympathetic denervation (RSD) seems to be a safe and effective method for severe hypertensive patients who are resistant to multiple drug treatment. We present the case of a 52-year-old patient diagnosed with essential hypertension, resistant to treatment with seven antihypertensive drugs. After 10 hospitalisations without achieving adequate blood pressure control, we decided to propose renal sympathetic denervation as an addition to medical treatment. The procedure was performed without complications in the short to medium-long term, achieving a significant improvement in blood pressure with the intention of reducing overall vascular risk (AU)