How should we analyze and present mortality in our patients?: A multicentre GCDP experience

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.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 7 ml/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 siguiente

Enfermedad renal crónica: la carga sanitaria invisible para los organismos que

REDINREN RD16/0009.The uptake of the current concept of chronic kidney disease (CKD) by the public, physicians and health authorities is low. Physicians still mix up CKD with chronic kidney insufficiency or failure. In a recent manuscript, only 23% of participants in a cohort of persons with CKD had been diagnosed by their physicians as having CKD while 29% has a diagnosis of cancer and 82% had a diagnosis of hypertension. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. A prevalent view is that for those in whom kidneys fail, the problem is "solved" by dialysis or kidney transplantation. However, the main burden of CKD is accelerated aging and all-cause and cardiovascular premature death. CKD is the most prevalent risk factor for lethal COVID-19 and the factor that most increases the risk of death in COVID-19, after old age. Moreover, men and women undergoing KRT still have an annual mortality which is 10-100-fold higher than similar age peers, and life expectancy is shortened by around 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 global cause of death by 2040 and the second cause of death in Spain before the end of the century, a time when 1 in 4 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 CIBER network research structure in Spain. Leading Spanish kidney researchers grouped in the kidney collaborative research network REDINREN have now applied for the RICORS call of collaborative research in Spain with the support of the Spanish Society of Nephrology, ALCER and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true. However, only the highest level of research funding through the CIBER will allow to adequately address the issue before it is too late.El impacto del concepto actual de enfermedad renal crónica (ERC) en la población, médicos y autoridades sanitarias ha sido bajo. Los médicos aún confunden la ERC con la insuficiencia renal crónica. En un manuscrito reciente, en una cohorte de personas con ERC, solo el 23% de los participantes fueron diagnosticados de ERC por sus médicos mientras que el 29% estaban diagnosticados de cáncer y el 82% de hipertensión. Para el público en general y las autoridades sanitarias, la ERC evoca la terapia de reemplazo renal (TRR). En España, la prevalencia de TRR es del 0,13%. La opinión predominante es que para aquellos en los que fallan los riñones, el problema se “resuelve” mediante diálisis o trasplante de riñón. Sin embargo, la principal carga sanitaria de la ERC es el envejecimiento acelerado y la muerte prematura de causa cardiovascular o de cualquier causa. La ERC es el factor mas prevalente de riesgo de mortalidad por COVID-19 después de la edad avanzada. Además, los hombres y mujeres que se someten a TRR todavía tienen una mortalidad anual que es de 10 a 100 veces superior a sus pares de edades similares, y la esperanza de vida se reduce en alrededor de 40 años para jóvenes en diálisis y en 15 años para jóvenes con un injerto renal funcionante. Se espera que la ERC se convierta en la quinta causa mundial de muerte para 2040 y la segunda causa de muerte en España antes de fin de siglo, época en la que 1 de cada 4 españoles tendrá ERC. Sin embargo, para 2022, la ERC se convertirá en la única causa de muerte entre las 15 principales a nivel mundial que no cuenta con el respaldo de una estructura de investigación CIBER en España. Los Principales grupos de investigación renal en España agrupados en la red de investi- gación colaborativa renal REDINREN han solicitado la convocatoria RICORS de investigación colaborativa en España con el apoyo de la Sociedad Española de Nefrología, ALCER y ONT: RICORS 040 tiene como objetivo evitar que se hagan realidad las terribles predicciones sobre la carga mundial de ERC para 2040. Sin embargo, solo el más alto nivel de financiación de la investigación a través del CIBER permitirá abordar adecuadamente el problema antes de que sea demasiado tarde.REDINREN RD16/000

CKD: The burden of disease invisible to research funders.

The uptake of the current concept of chronic kidney disease (CKD) by the public, physicians and health authorities is low. Physicians still mix up CKD with chronic kidney insufficiency or failure. In a recent manuscript, only 23% of participants in a cohort of persons with CKD had been diagnosed by their physicians as having CKD while 29% has a diagnosis of cancer and 82% had a diagnosis of hypertension. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. A prevalent view is that for those in whom kidneys fail, the problem is "solved" by dialysis or kidney transplantation. However, the main burden of CKD is accelerated aging and all-cause and cardiovascular premature death. CKD is the most prevalent risk factor for lethal COVID-19 and the factor that most increases the risk of death in COVID-19, after old age. Moreover, men and women undergoing KRT still have an annual mortality which is 10-100-fold higher than similar age peers, and life expectancy is shortened by around 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 global cause of death by 2040 and the second cause of death in Spain before the end of the century, a time when 1 in 4 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 CIBER network research structure in Spain. Leading Spanish kidney researchers grouped in the kidney collaborative research network REDINREN have now applied for the RICORS call of collaborative research in Spain with the support of the Spanish Society of Nephrology, ALCER and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true. However, only the highest level of research funding through the CIBER will allow to adequately address the issue before it is too late

Analysis of spontaneous resolution of cytomegalovirus replication after transplantation in CMV-seropositive patients with pretransplant CD8+IFNG+ response.

This prospective study evaluates whether CMV-seropositive (R+) transplant patients with pretransplant CD8+IFNG+ T-cell response to cytomegalovirus (CMV) (CD8+IFNG+ response) can spontaneously clear the CMV viral load without requiring treatment. A total of 104 transplant patients (kidney/liver) with pretransplant CD8+IFNG+ response were evaluable. This response was determined using QuantiFERON-CMV assay. The incidence of CMV replication and disease was 45.2% (47/104) and 6.7% (7/104), respectively. Of the total patients, 77.9% (81/104) did not require antiviral treatment, either because they did not have CMV replication (n = 57) or because they had asymptomatic CMV replication that could be spontaneously cleared (n = 24). Both situations are likely related to the presence of CD8+IFNG+ response to CMV, which has a key role in controlling CMV infection. However, 22.1% of the patients (23/104) received antiviral treatment, although only 7 of them did so because they had symptomatic CMV replication. These patients developed symptoms in spite of having pretransplant CD8+IFNG+ response, thus suggesting that other immunological parameters might be involved, such as a dysfunctional CD4+ response or that they might have become QFNon-reactive due to the immunosuppression. In conclusion, around 80% of R+ patients with pretransplant CD8+IFNG+ response to CMV did not require antiviral treatment, although this percentage might be underestimated. Nevertheless, other strategies such as performing an additional CD8+IFNG+ response determination at posttransplant time might provide more reliable information regarding the patients who will be able to spontaneously clear the viremia

Oral fosfomycin for the treatment of lower urinary tract infections among kidney transplant recipients-Results of a Spanish multicenter cohort.

Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram-negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended-spectrum β-lactamase-producing Enterobacteriaceae [14%] or carbapenem-resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5-2) was administered for a median of 7 days (IQR: 3-10). Clinical cure (remission of UTI-attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow-up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98-112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs