Effect of Immunosuppressive Treatments on Kidney Outcomes After Gross Hematuria-Related Acute Kidney Injury in Older Patients With IgA Nephropathy.

Introduction: Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. Methods: This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. Results: The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Conclusions: Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.

The role of copeptin in kidney disease.

Copeptin is a 39-amino acid glycopeptide that is secreted equimolecularly with arginine-vasopressin (AVP) from the prepro-hormone AVP in the posterior pituitary. While AVP is a very unstable molecule and is accompanied by significant technical troubles in its quantification, copeptin is a stable and easily quantifiable molecule. For this reason, circulating copeptin is currently used as a surrogate for AVP in different pathological conditions, including renal diseases. In recent years it has been shown that copeptin is associated with an increased risk of developing chronic kidney disease in the general population. In addition, copeptin has also been associated with multiple renal diseases with relevant clinical consequences and potential therapeutic implications. In the present review, we update and summarize the clinical significance of copeptin as a surrogate marker for AVP concentrations in different kidney diseases, as well as in renal replacement therapy (hemodialysis and peritoneal dialysis) and renal transplantation.

Essential Role of Enzymatic Activity in the Leishmanicidal Mechanism of the Eosinophil Cationic Protein (RNase 3).

The recruitment of eosinophils into Leishmania lesions is frequently associated with a favorable evolution. A feasible effector for this process is eosinophil cationic protein (ECP, RNase 3), one of the main human eosinophil granule proteins, endowed with a broad spectrum of antimicrobial activity, including parasites. ECP was active on Leishmania promastigotes and axenic amastigotes (LC50's = 3 and 16 µM, respectively) but, in contrast to the irreversible membrane damage caused on bacteria and reproduced by its N-terminal peptides, it only induced a mild and transient plasma membrane destabilization on Leishmania donovani promastigotes. To assess the contribution of RNase activity to the overall leishmanicidal activity of ECP, parasites were challenged in parallel with a single-mutant version, ECP-H15A, devoid of RNase activity, that fully preserves the conformation and liposome permeabilization ability. ECP-H15A showed a similar uptake to ECP on promastigotes, but with higher LC50's (>25 µM) for both parasite stages. ECP-treated promastigotes showed a degraded RNA pattern, absent in ECP-H15A-treated samples. Moreover ECP, but not ECP-H15A, reduced more than 2-fold the parasite burden of infected macrophages. Altogether, our results suggest that ECP enters the Leishmania cytoplasm by an endocytic pathway, ultimately leading to RNA degradation as a key contribution to the leishmanicidal mechanism. Thus, ECP combines both membrane destabilization and enzymatic activities to effect parasite killing. Taken together, our data highlight the microbicidal versatility of ECP as an innate immunity component and support the development of cell-penetrating RNases as putative leishmanicidal agents.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

IgA Nephropathy in Elderly Patients.

BACKGROUND AND OBJECTIVES: Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS: We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS: The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Helicobacter pylori pathogenicity and primary antimicrobial resistance in Northern Spain.

BACKGROUND: Helicobacter pylori infection is associated with chronic gastritis, ulcers and gastric cancer. Antimicrobial resistance has increased worldwide affecting the efficacy of current treatments. Most guidelines recommend implementation of regional surveillance of primary antibiotic resistance of H pylori. Only a fraction of individuals infected with H pylori develop gastric diseases which are related to virulence factors of the bacteria. The aims of the study were to determine the primary antimicrobial resistance rates of H pylori and to know the virulence factors prevalence of strains circulating in Southern Europe. MATERIALS AND METHODS: Susceptibility testing by Etest to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline was performed in 102 isolates (99 naïve patients). The prevalence of virulence factors (cagA, vacA, oipA, babA and dupA) was evaluated in 102 H pylori isolates from patients with mild-disease symptoms and in 22 isolates from patients with severe-disease symptoms. RESULTS: Primary resistance rates were 12.1% to clarithromycin, 13.1% to levofloxacin, 24.2% to metronidazole and 0% to amoxicillin and tetracycline. Combined resistance to clarithromycin and levofloxacin was 3% and to clarithromycin and metronidazole 4%. Prevalence of virulence factors in the mild- and severe-disease group was 35.3% and 81.8% for cagA, 20.6% and 54.5% for cagA/vacAs1m1, 94.1% and 95.4% for babA2, 78.4% and 100% for oipA and 30.4% and 18.2% for dupA. CONCLUSIONS: Primary antimicrobial resistance rates were under 15% for clarithromycin and levofloxacin. The prevalence of H pylori carrying the virulent genotype cagA/vacAs1m1 was higher than 20% in the mild-disease and 54% in the severe-disease symptom group.

Enfermedad renal «oculta» en ancianos: ¿deja de ocultarse a los 10 años de seguimiento? / Hidden renal disease in the elderly is not longer buried after 10 years of follow up

No disponible

Concentraciones séricas de potasio: importancia de la normopotasemia / Serum potassium concentrations: Importance of normokalaemia

Las anomalías en las concentraciones de potasio se asocian con morbimortalidad. En los últimos años se está considerando que pequeñas variaciones en las concentraciones séricas de potasio dentro del intervalo de la normalidad también pueden asociarse con mortalidad. Las estrategias para conseguir la normopotasemia incluyen medidas dietéticas, limitar el uso de fármacos que retienen potasio y emplear resinas de intercambio catiónico clásicas (poliestireno sulfonato cálcico/sódico) o el nuevo polímero no absorbible de intercambio catiónico (patiromer) (AU)

Abnormalities in potassium concentrations are associated with morbidity and mortality. In recent years it has been considered that small variations in serum potassium concentrations within normal intervals may also be associated with mortality. Strategies for achieving normokalaemia include dietary measures, limiting the use of potassium retaining drugs, and use of conventional cation exchange resins (calcium/sodium polystyrene sulfonate) and/or the new non-absorbed cation exchange polymer (patiromer) (AU)

Serum potassium concentrations: Importance of normokalaemia. / Concentraciones séricas de potasio: importancia de la normopotasemia.

Abnormalities in potassium concentrations are associated with morbidity and mortality. In recent years it has been considered that small variations in serum potassium concentrations within normal intervals may also be associated with mortality. Strategies for achieving normokalaemia include dietary measures, limiting the use of potassium retaining drugs, and use of conventional cation exchange resins (calcium/sodium polystyrene sulfonate) and/or the new non-absorbed cation exchange polymer (patiromer).

Clarithromycin resistance in Helicobacter pylori and its molecular determinants in Northern Spain, 2013-2015.

OBJECTIVES: Clarithromycin resistance (CLR-R) is the main reason for failure of Helicobacter pylori infection treatment, which is frequently empirically prescribed due to the erroneous belief that culture for susceptibility testing is difficult. The aim of this study was to determine CLR-R in a region of southern Europe and to evaluate the utility of a PCR sequencing assay applied on gastroduodenal biopsies in detecting H. pylori and clarithromycin (CLR) susceptibility. METHODS: The susceptibility of all H. pylori isolates obtained by culture during 2013-2015 was determined by Etest. During 2014-2015, H. pylori detection and CLR susceptibility were also studied by PCR followed by sequencing performed on gastroduodenal biopsies. Point mutations in the 23S rRNA gene were studied in all CLR-resistant isolates in 2014. RESULTS: Of 1986 H. pylori isolates obtained by culture (63 from children and 1923 from adults), 349 (17.6%) were CLR-resistant [21/63 (33.3%) in children and 328/1923 (17.1%) in adults; P<0.001], of which 31.5% were also resistant to levofloxacin. The main mutations detected were A2147G (79.8%), A2146G (17.2%) and A2146C (2%). Concordance between the PCR sequencing assay on biopsies and CLR susceptibility by Etest after culture was 89.8%. CONCLUSIONS: CLR-R was high in Gipuzkoa, northern Spain. The molecular PCR method performed directly on biopsies was a good alternative to the traditional Etest susceptibility method and was an aid when culture was non-viable.

La ecuación berlin initiative study, una herramienta útil y específica para estimar el filtrado glomerular en centenarios / The berlin initiative study equation: a useful and specific tool for estimating glomerular filtration rate in centenarian patients

No disponible

SOX9 Elevation Acts with Canonical WNT Signaling to Drive Gastric Cancer Progression.

Gastric cancer remains one of the leading causes of global cancer mortality due to therapy resistance, with Helicobacter pylori (H. pylori) infection being a major risk factor. In this study, we report the significance of an elevation of the stem cell regulator SOX9 in bacteria-infected human gastritis and cancer samples, paralleling increased levels of TNFα SOX9 elevation was more intense in specimens containing the pathogenically significant cagA+ strains of H. pylori Notably, we found that SOX9 was required for bacteria-induced gastric cancer cell proliferation, increased levels of ß-catenin, and acquisition of stem cell-like properties. Analysis of three large clinical cohorts revealed elevated SOX9 levels in gastric cancer with advanced tumor stage and poor patient survival. Functionally, SOX9 silencing in gastric cancer cells enhanced apoptosis and senescence, concomitantly with a blockade to self-renewal and tumor-initiating capability. Paralleling these effects, we also found SOX9 to mediate cisplatin chemoresistance associated with reduced disease-free survival. Mechanistic interactions between SOX9 and ß-catenin expression suggested the existence of a regulatory role for SOX9 targeting the WNT canonical pathway. Taken together, our findings establish the significance of SOX9 in gastric cancer pathobiology and heterogeneity, with implications for targeting WNT-SOX9 signaling as a rational therapeutic strategy. Cancer Res; 76(22); 6735-46. ©2016 AACR.

Fracturas de cadera en una cohorte de ancianos con filtrado glomerular disminuido (no diálisis) / Hip fractures in an elderly cohort with decreased glomerular filtration rate (non-dialysis)

No disponible

Remisión completa de síndrome nefrótico en mujer con amiloidosis renal por fiebre mediterránea familiar / Complete remission of nephrotic syndrome in a woman with renal amyloidosis due to familial mediterranean fever

No disponible

Nuevas herramientas para abordar la función renal en ancianos: la ecuación Berlin Initiative Study y la fórmula hematocrito, urea y género / New tools for the management of renal function in the elderly: Berlin Initiative Study equation and hematocrit, urea and gender formulae

En los últimos años se ha generado un debate sobre el rango normal de función renal en el anciano, y si todo anciano con filtrado glomerular estimado por fórmulas (Cockroft-Gault, MDRD, CKD-EPI) menor de 60 ml/min/1,73 m2 tiene una enfermedad renal. En esta revisión analizamos, con base en los datos del estudio Ancianos con enfermedad renal crónica del Hospital de Segovia, las nuevas ecuaciones para medir la función renal en ancianos: la Berlin Initiative Study, diseñada para estimar el filtrado glomerular en personas de 70 años o más, y la fórmula hematocrito, urea y género para diferenciar si un anciano con FG menor de 60 ml/min/1,73 m2 tiene enfermedad renal (AU)

In the last few years a debate has emerged on the range of normal renal function in the elderly, and if every elderly person with a glomerular filtration rate estimated using formulas (Cockroft-Gault, MDRD, CKD-EPI) of less than 60 ml/min/1.73 m2 has kidney disease. In this review we analysed, based on the results of the study Elderly people with chronic kidney disease of the Hospital de Segovia, the new equations to measure kidney function in the elderly: the Berlin Initiative Study equation designed to estimate the glomerular filtration rate in people aged 70 or more, and the hematocrit, urea and gender formula to establish whether an elderly person with a glomerular filtration rate lower than 60 mL/min/1.73 m2 has kidney disease (AU)

Cómo debemos analizar y describir la mortalidad de nuestros pacientes: experiencia del Grupo Centro Diálisis Peritoneal / How should we analyze and present mortality in our patients?: A multicentre GCDP experience

Introducción: Existen distintas estrategias para analizar la mortalidad en diálisis peritoneal (DP), con diferentes definiciones de caso, evento, tiempo en riesgo y análisis estadístico. Un método común entre los distintos registros permitiría compararlos adecuadamente y entender mejor las diferencias reales de mortalidad de nuestros pacientes. Métodos: Revisamos y describimos las estrategias de análisis de los registros autonómicos, nacional e internacionales. Incluimos análisis de supervivencia actuarial, Kaplan-Meier (KM) y riesgos-competitivos (RC). Aplicamos los diferentes enfoques a la misma base de datos (GCDP), lo que permite mostrar las diferencias aparentes con cada método. Resultados: Se incluyeron 1.890 pacientes incidentes en DP en el periodo 2003-2013 (55 años; 64,2% varones), con FRR inicial de 7ml/min; el 25% presentaba diabetes y un índice de Charlson de 3 [2-4]. Fallecieron 261 pacientes, 380 pasaron a hemodiálisis (HD) y 682 recibieron trasplante. Las tasas de mortalidad anual llegan a variar hasta un 20% en números relativos (6,4 vs. 5,2%) según el sistema aplicado. La estimación de probabilidad de mortalidad por RC es inferior a KM en todos los años: 3,6 vs. 4,0% el 1.er año; 9,0 vs. 11,9%; 15,6 vs. 28,3% y 18,5 vs. 43,3% los siguientes. Conclusiones: Aunque cada método pueda ser correcto en sí mismo y expresar diferentes enfoques, la impresión final que queda en el lector es un número que sobrestima la mortalidad. El modelo de RC expresa mejor la realidad en DP, donde el número de pacientes que pierden seguimiento (trasplante, paso a HD) cuadruplica al de los fallecidos y solo una cuarta parte continúa en DP al final del seguimiento (AU)

Introduction: There are different strategies to analyse mortality in peritoneal dialysis (PD) with different definitions for case, event, time at risk, and statistical tests. A common method for the different registries would enable proper comparison to better understand the actual differences in mortality of our patients. Methods: We review and describe the analysis strategies of regional, national and international registries. We include actuarial survival, Kaplan-Meier (KM) and competitive risk (CR) analyses. We apply different approaches to the same database (GCDP), which show apparent differences with each method. Results: A total of 1,890 incident patients in PD from 2003-2013 were included (55 years; men 64.2%), with initial RRF of 7 ml/min; 25% had diabetes and a Charlson index of 3 [2-4]; 261 patients died, 380 changed to haemodialysis (HD) and 682 received a transplant. Annual mortality rates varied up to 20% in relative numbers (6.4 vs. 5.2%) depending on the system applied. The estimated probability of mortality measured by CR progressively differs from the KM over the years: 3.6 vs. 4.0% the first year, then 9.0 vs. 11.9%, 15.6 vs. 28.3%, and 18.5 vs. 43.3% the following years. Conclusions: Although each method may be correct in themselves and express different approaches, the final impression left on the reader is a number that under/overestimates mortality. The CR model better expresses the reality of PD, where the number of patients lost to follow-up (transplant, transfer to HD) it is 4 times more than deceased patients and only a quarter remain on PD at the end of follow up (AU)

[New tools for the management of renal function in the elderly: Berlin Initiative Study equation and hematocrit, urea and gender formulae]. / Nuevas herramientas para abordar la función renal en ancianos: la ecuación Berlin Initiative Study y la fórmula hematocrito, urea y género.

In the last few years a debate has emerged on the range of normal renal function in the elderly, and if every elderly person with a glomerular filtration rate estimated using formulas (Cockroft-Gault, MDRD, CKD-EPI) of less than 60ml/min/1.73m(2) has kidney disease. In this review we analysed, based on the results of the study Elderly people with chronic kidney disease of the Hospital de Segovia, the new equations to measure kidney function in the elderly: the Berlin Initiative Study equation designed to estimate the glomerular filtration rate in people aged 70 or more, and the hematocrit, urea and gender formula to establish whether an elderly person with a glomerular filtration rate lower than 60mL/min/1.73m(2) has kidney disease.