Coronavirus infectious disease 2019 (COVID-19) pandemic has posed at risk the kidney transplant (KT) population. We describe clinical pictures, risk factors for death, and chances to recovery in a ...large cohort of KT recipients with COVID-19.
Inclusion in a Spanish prospectively filled registry was allowed for KT cases with confirmed COVID-19. Outcomes were assessed as in-hospital mortality or recovery.
The study population comprised of 414 patients. Fever, respiratory symptoms, and dyspnea were the most frequent COVID-19-related symptoms, and 81.4% of them had pneumonia. More than one-third of patients showed digestive symptoms at diagnosis, combinations of nausea, vomiting, and diarrhea. Most patients were hospitalized, 12.1% in intensive care units, and 17.6% needed ventilator support. Treatment for COVID-19 included frequently hydroxychloroquine, azithromycin, high-dose steroids, lopinavir/ritonavir, and tocilizumab. After a mean follow-up of 44 days, the fatality rate was 26.3%. Pneumonia without gastrointestinal symptoms was associated with a 36.3% mortality (respiratory phenotype), and gastrointestinal symptoms without pneumonia with a 5.3% mortality (gastrointestinal phenotype). The mixed pneumonia and gastrointestinal phenotype showed an intermediate mortality of 19.5% (mixed phenotype). Multivariate Cox regression analysis showed that age and pneumonia were independently associated with death, whereas the gastrointestinal phenotype was associated with recovery.
COVID-19 is frequent among the KT population. Advanced age and pneumonia are the main clinical features associated with a high-mortality rate. Gastrointestinal disease is associated with a more benign course and lower mortality.
Background
Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although available evidence is ...conflicting. It has been suggested that (val)ganciclovir therapy may increase the risk of BKPyV viremia and BKPyV‐associated nephropathy (BKPyVAN) as a result of drug‐induced T‐cell impairment.
Methods
We investigated whether CMV replication and/or (val)ganciclovir exposure (either as prophylaxis or treatment) were associated with the development of BKPyV viremia or BKPyVAN in a prospective cohort of 399 KT recipients. CMV infection (any level or high‐level viremia and area under the curve of DNAemia) and (val)ganciclovir exposure (any duration of therapy and cumulative days of treatment) during the first post‐transplant year were explored through separate landmark survival analyses.
Results
Cumulative incidence of BKPyV viremia and BKPyVAN after a median follow‐up of 551 days was 23.1% and 2.5%, respectively. One‐year rates of CMV infection and (val)ganciclovir therapy were 47.4% and 54.1%, respectively. No differences were observed in BKPyV viremia‐ or BKPyVAN‐free survival according to previous CMV infection or (val)ganciclovir exposure in any of the landmark analyses. Adjusted Cox models confirmed this lack of association.
Conclusion
Our findings do not confirm the existence of a relevant impact of CMV infection or (val)ganciclovir therapy on the risk of post‐transplant BKPyV events.
The importance of submicroscopic malaria infections in high-transmission areas could contribute to maintain the parasite cycle. Regarding non-endemic areas, its importance remains barely understood ...because parasitaemia in these afebrile patients is usually below the detection limits for microscopy, hence molecular techniques are often needed for its diagnosis. In addition to this, the lack of standardized protocols for the screening of submicroscopic malaria in immigrants from endemic areas may underestimate the infection with Plasmodium spp. The aim of this study was to assess the prevalence of submicroscopic malaria in afebrile immigrants living in a non-endemic area.
A prospective, observational, multicentre study was conducted. Afebrile immigrants were included, microscopic observation of Giemsa-stained thin and thick blood smears, and two different molecular techniques detecting Plasmodium spp. were performed. Patients with submicroscopic malaria were defined as patients with negative blood smears and detection of DNA of Plasmodium spp. with one or both molecular techniques. Demographic, clinical, analytical and microbiological features were recorded and univariate analysis by subgroups was carried out with STATA v15.
A total of 244 afebrile immigrants were included in the study. Of them, 14 had a submicroscopic malaria infection, yielding a prevalence of 5.7% (95% confidence interval 3.45-9.40). In 71.4% of the positive PCR/negative microscopy cases, Plasmodium falciparum alone was the main detected species (10 out of the 14 patients) and in 4 cases (28.6%) Plasmodium vivax or Plasmodium ovale were detected. One patient had a mixed infection including three different species.
The prevalence of submicroscopic malaria in afebrile immigrants was similar to that previously described in Spain. Plasmodium vivax and P. ovale were detected in almost a third of the submicroscopic infections. Screening protocols for afebrile immigrants with molecular techniques could be useful for a proper management of these patients.
Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms ...of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc.
The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units.
The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered.
Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.
•Massive vaccination has greatly improved the outcomes of the COVID-19 pandemic.•Suboptimal responses to vaccines have been observed in transplant recipients.•Health care strategic plans are necessary in these vulnerable populations.•The best practices contained in this expert panel report may aid to their broader implementation.•Pretransplant, peritransplant and postransplant new practices are proposed.
Purpose
To report our experience on third kidney transplantation, analyzing the complications and graft survival rates as compared to previous transplants.
Methods
Retrospective study of third renal ...transplants performed at our center. Outcomes were compared with a cohort of first and second transplants.
Results
Of a total of 4143, we performed 72 third transplants in 46 men and 26 women with an average age of 46 years and mean time on dialysis of 70 months. Thirty-seven patients were hypersensitized panel-reactive antibody (PRA) > 50%. They were all from deceased donors, with a mean cold ischemia time of 19.2 h. The extraperitoneal heterotopic approach was used in 88.8%, transplantectomy was performed in 80.6% and vascular anastomoses were realized mostly to external iliac vessels, using the common iliac artery in 15 cases, and the inferior vena cava in 16. The main ureteral reimplantation technique was the Politano-Leadbetter (76.4%).
Third transplantation reported a significantly higher incidence of lymphocele (13.9% vs. 3.2% in first and 4.5% in second transplants;
p
< 0.001), rejection (34.7% vs. 14.9% and 20.5%,
p
< 0.001) and urinary obstruction (11.1% vs. 3.6% and 6.3%,
p
0.002). Graft survival rates for first, second and third transplants were 87%, 86% and 78% at 1 year, 83%, 82% and 74% at 3 years and 80%, 79% and 65% at 5 years, respectively.
Conclusion
Iterative transplantation constitutes a valid therapeutic option with adequate surgical and survival results compared to previous transplants. It is a challenging procedure which must be performed by experienced surgeons.
Resumen: Introducción: La nefropatía diabética (ND) es una complicación frecuente de la diabetes mellitus (DM), y su diagnóstico suele ser clínico. Sin embargo, en numerosas ocasiones la enfermedad ...renal que presentan los pacientes diabéticos es debida a otras causas cuyo diagnóstico es histológico. El objetivo del estudio fue determinar los datos clínicos y analíticos predictores de ND y enfermedad renal no diabética (ERND), y elaborar un modelo predictivo (score) para confirmar o descartar ND. Material y métodos: Estudio observacional, transversal y retrospectivo de biopsias renales realizadas en pacientes diabéticos tipo 2 entre 2000 y 2018. Resultados: Se incluyeron 207 pacientes diabéticos con una edad media de 64,5 ± 10,6 años; el 74% eran varones. La biopsia mostró ND en 126 (61%) y en 81 ERND (39%). La retinopatía diabética estaba presente en el 58% de los pacientes con ND y en el 6% del grupo con ERND (p < 0,001). Histología encontrada en la ERND: glomerulopatías primarias (52%), nefroangioesclerosis (16%), nefritis intersticial inmunoalérgica (15%) y vasculitis (8,5%). En el análisis multivariable, la retinopatía (OR 26,7; IC 95%: 6,8-104,5), la isquemia crónica de miembros inferiores (OR 4,37; IC 95%: 1,33-14,3), la insulinoterapia (OR 3,05; IC 95%: 1,13-8,25), una evolución de la DM ≥ 10 años (OR 2,71; IC 95%: 1,1-6,62) y la proteinuria nefrótica (OR 2,91; IC 95%: 1,2-7,1) fueron predictores independientes de ND. La microhematuria, definida como ≥ 10 hematíes/campo (OR 0,032; IC 95%: 0,01-0,11) y el sobrepeso (OR 0,21; IC 95%: 0,08-0,55) lo fueron de ERND. Según el modelo predictivo resultante del estudio multivariable para ND, el rango de puntuación varió de −6 a 8 puntos. Todos los pacientes con un score > 3 era tenían ND, y el 94% de los casos con score ≤ 1 punto fueron ERND. Conclusiones: La ERND es frecuente en pacientes con DM (39%). La etiología más frecuente son las glomerulonefritis primarias. La ausencia de retinopatía y la presencia de microhematuria son altamente sugestivas de ERND. La utilización de un sistema de puntuación facilita la indicación de biopsia renal en pacientes diabéticos. Abstract: Introduction: Diabetic nephropathy (DN) is one of the most frequent complications in patients with diabetes mellitus (DM) and its diagnosis is usually established on clinical grounds. However, kidney involvement in some diabetic patients can be due to other causes, and renal biopsy might be needed to exclude them. The aim of our study was to establish the clinical and analytical data that predict DN and no-diabetic renal disease (NDRD), and to develop a predictive model (score) to confirm or dismiss DN. Material and methods: We conducted a transversal, observational and retrospective study, including renal biopsies performed in type 2 DM patients, between 2000 and 2018. Results: Two hundred seven DM patients were included in our study. The mean age was 64.5 ± 10.6 years and 74% were male. DN was found in 126 (61%) of the biopsies and NDRD in 81 (39%). Diabetic retinopathy was presented in 58% of DN patients, but only in 6% of NDRD patients (P < .001). Patients with NDRD were diagnosed of primary glomerulopathies (52%), nephroangiosclerosis (16%), inmunoallergic interstitial nephritis (15%) and vasculitis (8.5%). In the multivariate analysis, retinopathy (OR 26.7; 95% CI: 6.8-104.5), chronic ischaemia of lower limbs (OR 4,37; 95% CI: 1.33-14.3), insulin therapy (OR 3.05; 95% CI: 1.13-8.25), time course of DM ≥ 10 years (OR 2.71; 95% CI: 1.1-6.62) and nephrotic range proteinuria (OR 2.91; 95% CI: 1.2-7.1) were independent predictors for DN. Microhaematuria defined as ≥ 10 red blood cells per high-power field (OR 0.032; 95% CI: 0.01-0.11) and overweight (OR 0.21; 95% CI: 0.08-0.5) were independent predictors of NDRD. According to the predictive model based on the multivariate analysis, all patients with a score > 3 had DN and 94% of cases with a score ≤ 1 had NDRD (score ranked from −6 to 8 points). Conclusions: NDRD is common in DM patients (39%), being primary glomerulonephritis the most frequent ethology. The absence of retinopathy and the presence of microhematuria are highly suggestive of NDRD. The use of our predictive model could facilitate the indication of performing a renal biopsy in DM patients. Palabras clave: Diabetes mellitus, Biopsia renal, Nefropatía diabética, Enfermedad renal no diabética, Modelo predictivo, Keywords: Diabetes mellitus, Renal biopsy, Diabetic nephropathy, Non-diabetic renal disease, Predictive model
Diabetic nephropathy (DN) is one of the most frequent complications in patients with diabetes mellitus (DM) and its diagnosis is usually established on clinical grounds. However, kidney involvement ...in some diabetic patients can be due to other causes, and renal biopsy might be needed to exclude them. The aim of our study was to establish the clinical and analytical data that predict DN and no-diabetic renal disease (NDRD), and to develop a predictive model (score) to confirm or dismiss DN.
We conducted a transversal, observational and retrospective study, including renal biopsies performed in type 2 DM patients, between 2000 and 2018.
Two hundred seven DM patients were included in our study. The mean age was 64.5±10.6 years and 74% were male. DN was found in 126 (61%) of the biopsies and NDRD in 81 (39%). Diabetic retinopathy was presented in 58% of DN patients, but only in 6% of NDRD patients (p<0.001). Patients with NDRD were diagnosed of primary glomerulopathies (52%), nephroangiosclerosis (16%), inmunoallergic interstitial nephritis (15%) and vasculitis (8.5%). In the multivariate analysis, retinopathy (OR 26.7; 95% CI: 6.8–104.5), chronic ischemia of lower limbs (OR 4.37; 95% CI: 1.33–14.3), insulin therapy (OR 3.05; 95% CI: 1.13–8.25), time course of DM ≥10 years (OR 2.71; 95% CI: 1.1–6.62) and nephrotic range proteinuria (OR 2.91; 95% CI: 1.2–7.1) were independent predictors for DN. Microhaematuria defined as ≥10 red blood cells per high-power field (OR 0.032; 95% CI: 0.01–0.11) and overweight (OR 0.21; 95% CI: 0.08–0.5) were independent predictors of NDRD. According to the predictive model based on the multivariate analysis, all patients with a score >3 had DN and 94% of cases with a score ≤1 had NDRD (score ranked from −6 to 8 points).
NDRD is common in DM patients (39%), being primary glomerulonephritis the most frequent ethology. The absence of retinopathy and the presence of microhematuria are highly suggestive of NDRD. The use of our predictive model could facilitate the indication of performing a renal biopsy in DM patients.
La nefropatía diabética (ND) es una complicación frecuente de la diabetes mellitus (DM), y su diagnóstico suele ser clínico. Sin embargo, en numerosas ocasiones la enfermedad renal que presentan los pacientes diabéticos es debida a otras causas cuyo diagnóstico es histológico. El objetivo del estudio fue determinar los datos clínicos y analíticos predictores de ND y enfermedad renal no diabética (ERND), y elaborar un modelo predictivo (score) para confirmar o descartar ND.
Estudio observacional, transversal y retrospectivo de biopsias renales realizadas en pacientes diabéticos tipo2 entre 2000 y 2018.
Se incluyeron 207 pacientes diabéticos con una edad media de 64.5±10,6años; el 74% eran varones. La biopsia mostró ND en 126 (61%) y en 81 ERND (39%). La retinopatía diabética estaba presente en el 58% de los pacientes con ND y en el 6% del grupo con ERND (p<0,001). Histología encontrada en la ERND: glomerulopatías primarias (52%), nefroangioesclerosis (16%), nefritis intersticial inmunoalérgica (15%) y vasculitis (8,5%). En el análisis multivariable, la retinopatía (OR26,7; IC95%: 6,8-104,5), la isquemia crónica de miembros inferiores (OR4,37; IC95%: 1,33-14,3), la insulinoterapia (OR 3,05; IC95%: 1,13-8,25), una evolución de la DM ≥10años (OR2,71; IC95%: 1,1-6,62) y la proteinuria nefrótica (OR2,91; IC95%: 1,2-7,1) fueron predictores independientes de ND. La microhematuria, definida como ≥10hematíes/campo (OR0,032; IC95%: 0,01-0,11) y el sobrepeso (OR0,21; IC95%: 0,08-0,55) lo fueron de ERND. Según el modelo predictivo resultante del estudio multivariable para ND, el rango de puntuación varió de −6 a 8 puntos. Todos los pacientes con un score >3 era tenían ND, y el 94% de los casos con score ≤1punto fueron ERND.
La ERND es frecuente en pacientes con DM (39%). La etiología más frecuente son las glomerulonefritis primarias. La ausencia de retinopatía y la presencia de microhematuria son altamente sugestivas de ERND. La utilización de un sistema de puntuación facilita la indicación de biopsia renal en pacientes diabéticos.
Abstract Background and Aims This study explores a personalized delisting strategy enabling kidney transplantation in highly sensitized patients with preformed donor-specific anti-HLA antibodies ...(DSA) trying to minimize the risk of antibody-mediated rejection (ABMR). Method Retrospective single-centre analysis of 50 kidney transplant recipients with preformed DSA (preDSA) after employing a delisting strategy to enhance their access to transplantation, and without received a pre-transplant or immediate post-transplant desensitization protocol. The delisting approach focused on allowing less deleterious antibodies according to their mean fluorescence intensity (MFI), anti-HLA class and C1q study results. The strategy consisted on eliminating as prohibited HLA antigens those recognized by antibodies with the lowest MFI in the following order: 1st- MFI < 5000; 2nd- MFI < 10000; 3rd-Any MFI. Additionally, delisting prioritized a single locus in the following order: 1st- one of the HLA class I loci (A, B, or Cw); 2nd- the rest of the class I loci; 3rd- HLA-DP, followed by DR. C1q studies were performed before delisting and transplantation was contraindicated in the presence of DSA detected in the C1q assay. Two comparative cohorts included 50 sensitized recipients without pre-transplant DSA (SwoDSA) and 50 non-sensitized recipients (NS). Results The delisting strategy allowed transplantation with preformed DSA and demonstrated comparable rejection rates to SwoDSA and NS groups (16%, 14% and 8%, respectively; log-rank = 0.28). However, the occurrence of acute ABMR was 12% in the preDSA group, significantly higher than in SwoDSA (1%) and NS (0%) (log-rank = 0.0093). The immunological risk assumed in delisting correlated with ABMR incidence (patients with ABMR had significantly higher sum MFI mean ± SD: 9301 ± 6340 vs 4492 ± 5641; p = 0.049), emphasizing the importance of tailored strategies. DSA persistence after transplantation correlated with higher MFI and increased ABMR risk. Of note, 16% of preDSA patients developed de novo DSA versus only the 4% of SwoDSA and 0% of NS patients (p = 0.004). After a mean follow-up of 3.1 ± 2.1 years, the 1-, 3- and 5-year death-censored allograft survival rates were 100%, 90% and 78%, respectively, in the preDSA group; 98%, 84% and 84% in the SwoDSA group and 100% in NS group (log-rank = 0.02). Conclusion The present study demonstrates the feasibility and acceptable outcomes of kidney transplantation in highly sensitized patients with preformed DSA through a personalized delisting strategy without using desensitization protocols.
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