Derivation and external validation of the SIMPLICITY score as a simple immune-based risk score to predict infection in kidney transplant recipients.

Existing approaches for infection risk stratification in kidney transplant recipients are suboptimal. Here, we aimed to develop and validate a weighted score integrating non-pathogen-specific immune parameters and clinical variables to predict the occurrence of post-transplant infectious complications. To this end, we retrospectively analyzed a single-center derivation cohort of 410 patients undergoing kidney transplantation in 2008-2013 in Madrid. Peripheral blood lymphocyte subpopulations, serum immunoglobulin and complement levels were measured at one-month post-transplant. The primary and secondary outcomes were overall and bacterial infection through month six. A point score was derived from a logistic regression model and prospectively applied on a validation cohort of 522 patients undergoing kidney transplantation at 16 centers throughout Spain in 2014-2015. The SIMPLICITY score consisted of the following variables measured at month one after transplantation: C3 level, CD4+ T-cell count, CD8+ T-cell count, IgG level, glomerular filtration rate, recipient age, and infection within the first month. The discrimination capacity in the derivation and validation cohorts was good for overall (areas under the receiver operating curve of 0.774 and 0.730) and bacterial infection (0.767 and 0.734, respectively). The cumulative incidence of overall infection significantly increased across risk categories in the derivation (low-risk 13.7%; intermediate-risk, 35.9%; high-risk 77.6%) and validation datasets (10.2%, 28.9% and 50.4%, respectively). Thus, the SIMPLICITY score, based on easily available immune parameters, allows for stratification of kidney transplant recipients at month one according to their expected risk of subsequent infection.

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.

Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in Chronic Kidney Disease: A Clinical Approach.

Asymmetric dimethylarginine (ADMA) and its enantiomer, Symmetric dimethylarginine (SDMA), are naturally occurring amino acids that were first isolated and characterized in human urine in 1970. ADMA is the most potent endogenous inhibitor of nitric oxide synthase (NOS), with higher levels in patients with end-stage renal disease (ESRD). ADMA has shown to be a significant predictor of cardiovascular outcome and mortality among dialysis patients. On the other hand, although initially SDMA was thought to be an innocuous molecule, we now know that it is an outstanding marker of renal function both in human and in animal models, with ESRD patients on dialysis showing the highest SDMA levels. Today, we know that ADMA and SDMA are not only uremic toxins but also independent risk markers for mortality and cardiovascular disease (CVD). In this review, we summarize the role of both ADMA and SDMA in chronic kidney disease along with other cardiovascular risk factors.

Multicenter Long-Term Real World Data on Treatment With Lumasiran in Patients With Primary Hyperoxaluria Type 1.

Introduction: The RNA interference (RNAi) medication lumasiran reduces hepatic oxalate production in primary hyperoxaluria type 1 (PH1). Data outside clinical trials are scarce. Methods: We report on retrospectively and observationally obtained data in 33 patients with PH1 (20 with preserved kidney function, 13 on dialysis) treated with lumasiran for a median of 18 months. Results: Among those with preserved kidney function, mean urine oxalate (Uox) decreased from 1.88 (baseline) to 0.73 mmol/1.73 m2 per 24h after 3 months, to 0.72 at 12 months, and to 0.65 at 18 months, but differed according to vitamin B6 (VB6) medication. The highest response was at month 4 (0.55, -70.8%). Plasma oxalate (Pox) remained stable over time. Glomerular filtration rate increased significantly by 10.5% at month 18. Nephrolithiasis continued active in 6 patients, nephrocalcinosis ameliorated or progressed in 1 patient each. At last follow-up, Uox remained above 1.5 upper limit of normal (>0.75 mmol/1.73 m2 per 24h) in 6 patients. Urinary glycolate (Uglyc) and plasma glycolate (Pglyc) significantly increased in all, urine citrate decreased, and alkali medication needed adaptation. Among those on dialysis, mean Pox and Pglyc significantly decreased and increased, respectively after monthly dosing (Pox: 78-37.2, Pglyc: 216.4-337.4 µmol/l). At quarterly dosing, neither Pox nor Pglyc were significantly different from baseline levels. An acid state was buffered by an increased dialysis regimen. Systemic oxalosis remained unchanged. Conclusion: Lumasiran treatment is safe and efficient. Dosage (interval) adjustment necessities need clarification. In dialysis, lack of Pox reduction may relate to dissolving systemic oxalate deposits. Pglyc increment may be a considerable acid load requiring careful consideration, which definitively needs further investigation.

Silent challenge: Early kidney transplant failure and cardiomyopathy.

Differentiation of hypertrophic cardiomyopathy phenotypes is challenging but crucial for appropriate management. We report a case of myocardial oxalate deposition as an infrequent cause of infiltrative cardiomyopathy.

Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.

INTRODUCTION: Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients. METHODS: We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. RESULTS: Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug. CONCLUSION: In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.

Advanced chronic renal failure (ACRF) study. Baseline characteristics, evaluation of the application of the structured information for the election of renal replacement therapy and one-year evolution of the incident patients in the ACRF medical office. / Estudio ERCA. Características basales, evaluación de la aplicación de la información estructurada para la elección de tratamiento renal sustitutivo y evolución a un año de los pacientes incidentes en la consulta ERCA.

BACKGROUND AND OBJECTIVES: Analyze evolution Renal Chronic Failure stage 4-5 (ACRF) patients and influence information they receive (educational process, EP) in modality Renal Replacement Therapy (RRT) or conservative treatment (CT) in multidisciplinar ACRF Office. MATERIAL AND METHODS: Prospective, multicenter study (3 centers). Inclusion: from June-01-2014 to October-01-2015; observation: 12 months or until start RRT or death if they occur before 12 months; ends October-01-2016. RESULTS: 336 patients were included (60% males), median and intercuartile rank 71.5 (17), 55% ≥ 70 years; Follow up initiation eGFR CKD-EPI: 21 (9) ml / min / 1.73m2; Charlson Index (ChI) with / without age 8 (3) / 4 (2); Diabetic patients: 52,4%. The EP was carried out in 168, eGFR 15 (10) ml / min / 1.73m2. The initial treatment election: 26% peritoneal dialysis (PD), 45% hemodyalisis (HD), 26% CT, kidney trasplant 3%; 60 patients started RRT: 3.3% kidney traspant; 30% PD, 66% HD; 104 admissions in 73 patients, the most frequent cause: cardiovascular disease (42%). Fallecimiento: 23 patients (6.8%). Age was higher (78.4 (6) vs. 67.8 (13.4), P<.001), higher ChI 9.8 (2.1) vs. 7.4 (2.5), P<.001). All deceased who received EP had chosen CT; 61% of deceased had at least one hospital admission vs. 39% alive (P<0.001). Cox regression: age and Charlson index were the predictive mortality variables. CONCLUSIONS: The population of ACRF patients is elder, comorbid, with high rate hospitalizations rate. The PD election is higher than usual. The EP has been very useful tool and has favored the PD choice.

Anaemia and fever in Kidney transplant. The role of human parvovirus B19. / Anemia y fiebre en el postrasplante renal: su relación con el parvovirus humano B19.

Infections remain an issue of particular relevance in renal transplant patients, particularly viral infections. Human parvovirus B19 infection causes severe refractory anaemia, pancytopenia and thrombotic microangiopathy. Its presence is recognized by analysing blood polymerase chain reaction (PCR) and by the discovery of typical giant proerythroblasts in the bone marrow. We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence.

Renal Replacement Therapy: Purifying Efficiency of Automated Peritoneal Dialysis in Diabetic versus Non-Diabetic Patients.

BACKGROUND: In order to reduce the cardiovascular risk, morbidity and mortality of peritoneal dialysis (PD), a minimal level of small-solute clearances as well as a sodium and water balance are needed. The peritoneal dialysis solutions used in combination have reduced the complications and allow for a long-time function of the peritoneal membrane, and the preservation of residual renal function (RRF) in patients on peritoneal dialysis (PD) is crucial for the maintenance of life quality and long-term survival. This retrospective cohort study reviews our experience in automatic peritoneal dialysis (APD) patients, with end-stage renal disease (ESRD) secondary to diabetic nephropathy (DN) in comparison to non-diabetic nephropathy (NDN), using different PD solutions in combination. DESIGN: Fifty-two patients, 29 diabetic and 23 non-diabetic, were included. The follow-up period was 24 months, thus serving as their own control. RESULTS: The fraction of renal urea clearance (Kt) relative to distribution volume (V) (or total body water) (Kt/V), or creatinine clearance relative to the total Kt/V or creatinine clearance (CrCl) decreases according to loss of RRF. The loss of the slope of RRF is more pronounced in DN than in NDN patients, especially at baseline time interval to 12 months (loss of 0.29 mL/month vs. 0.13 mL/month, respectively), and is attenuated in the range from 12 to 24 months (loss of 0.13 mL/month vs. 0.09 mL/month, respectively). Diabetic patients also experienced a greater decrease in urine output compared to non-diabetic, starting from a higher baseline urine output. The net water balance was adequate in both groups during the follow up period. Regarding the balance sodium, no inter-group differences in sodium excretion over follow up period was observed. In addition, the removal of sodium in the urine output decreases with loss of renal function. The average concentration of glucose increase in the cycler in both groups (DN: baseline 1.44 ± 0.22, 12 months 1.63 ± 0.39, 24 months 1.73 ± 0.47; NDN: baseline 1.59 ± 0.40, 12 months 1.76 ± 0.47, 24 months 1.80 ± 0.46), in order to maintain the net water balance. The daytime dwell contribution, the fraction of day and the renal fraction of studies parameters provide sustained benefit in the follow-up time, above 30%. CONCLUSIONS: The wet day and residual renal function are determinants in the achievement of the objective dose of dialysis, as well as in the water and sodium balance. The cause of chronic kidney disease (CKD) does not seem to influence the cleansing effectiveness of the technique.

The occurrence or fibrillary glomerulonephritis in patients with diabetes mellitus may not be coincidental: a report of four cases.

Although clinical presentation of fibrillary glomerulonephritis is similar to most forms of glomerulonephritis, it is usually difficult to make the diagnosis. Clinical manifestations include proteinuria, microscopic haematuria, nephrotic syndrome, and impairment of renal function. A diagnosis of fibrillary glomerulonephritis is only confirmed by renal biopsy and it must comprise electronmicroscopy-verified ultrastructural findings. We report four cases between 45-50 years old with documented type 2 diabetes mellitus (T2DM) and arterial hypertension. All patients were found to have fibrils on kidney biopsy. The differential diagnosis of fibrils in the setting of diabetes mellitus is also discussed.

Anemia y fiebre en el postrasplante renal: su relación con el parvovirus humano B19 / Anaemia and fever in Kidney transplant. The role of human parvovirus B19

Las infecciones continúan siendo un problema relevante en el paciente trasplantado renal, en especial las infecciones virales. La infección por el parvovirus humano B19 causa anemia refractaria grave, pancitopenia y microangiopatía trombótica. Dicha infección se diagnostica mediante el análisis de la reacción en cadena de la polimerasa (PCR) en sangre y por la presencia de proeritroblastos gigantes típicos en la médula ósea. Presentamos el caso clínico de un varón de 65 años con trasplante renal de donante cadáver en septiembre de 2014. A los 38 días del trasplante comienza con anemia progresiva y resistente a los agentes estimulantes de la eritropoyesis. A los 64 días se produce hipertermia, con deterioro progresivo de su estado general. La serología vírica resultó negativa, al igual que la PCR inicial en sangre del parvovirus humano B19. A los 4 meses y 19 días se realiza una biopsia de médula ósea en la que se observan eritroblastos gigantes con inclusiones víricas nucleares compatibles con parvovirus, por lo que se realiza una PCR en dicho tejido que confirma el diagnóstico. Una segunda PCR en sangre resultó positiva. Tras el tratamiento con inmunoglobulinas intravenosas (IGIV) y la suspensión temporal del micofenolato de mofetilo, se produce una remisión completa de la enfermedad, aunque persistía positiva la PCR para el parvovirus B19 en sangre, lo que hace necesario vigilar probables recidivas (AU)

Infections remain an issue of particular relevance in renal transplant patients, particularly viral infections. Human parvovirus B19 infection causes severe refractory anaemia, pancytopenia and thrombotic microangiopathy. Its presence is recognized by analysing blood polymerase chain reaction (PCR) and by the discovery of typical giant proerythroblasts in the bone marrow. We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence (AU)

Estudio ERCA. Características basales, evaluación de la aplicación de la información estructurada para la elección de tratamiento renal sustitutivo y evolución a un año de los pacientes incidentes en la consulta ERCA / Advanced chronic renal failure (ACRF) study. Baseline characteristics, evaluation of the application of the structured information for the election of renal replacement therapy and one-year evolution of the incident patients in the ACRF medical office

ANTECEDENTES Y OBJETIVOS: Conocer evolución de pacientes ERC estadios 4 y 5 (ERCA) e influencia de la información (proceso educativo [PE]) que reciben para elección de la modalidad de tratamiento renal sustitutivo (TRS) o tratamiento conservador (TC) en consulta multidisciplinar de ERCA. MATERIAL Y MÉTODOS: Estudio prospectivo, multicéntrico (3 centros españoles). Pacientes incidentes: consulta ERCA desde el 1 de junio del 2014 al 1 de octubre del 015; observación: 12 meses o inicio del TRS o fallecimiento si antes de los 12 meses; finaliza el 1 de octubre del 2016. RESULTADOS: Trescientos treinta y tres pacientes (60% varones), mediana y rango intercuartil: edad 71,5 (17) años (55% ≥ 70 años), FGe CKD-EPI inicio 21 (9) ml/min/1,73 m2, índice de Charlson (ICh) con/sin edad 8 (3)/4 (2). Pacientes diabéticos: 52,4%. Recibieron PE 168 pacientes, FGe al inicio 15 (10) ml/min/1,73 m2. Tratamiento inicial elegido: 26% diálisis peritoneal (DP), 45% hemodiálisis (HD), 26% TC, trasplante renal 3%; 60 pacientes iniciaron TRS: 3,3% trasplante renal, 30% DP, 66% HD. Ingresos: 104 en 73 pacientes, la causa más frecuente fue por enfermedad cardiovascular (42%). Fallecimiento: 23 pacientes (6,8%), de mayor edad (78,4 [6] vs. 67,8 [13,4], p < 0,001), ICh más elevado 9,8 [2,1] vs. 7,4 [2,5], p < 0,001). Todos los fallecidos con PE habían decidido TC; el 61% de los fallecidos tenían al menos un ingreso hospitalario vs. 39%vivos (p < 0,001). Regresión Cox: variables predictivas mortalidad: edad e ICh. CONCLUSIONES:La población de ERCA es añosa, comórbida y con elevado índice de ingresos hospitalarios. La incidencia de DP es mayor a la habitual. El PE ha sido una herramienta de gran utilidad y favorece la elección de DP

BACKGROUND AND OBJECTIVES: Analyze evolution Renal Chronic Failure stage 4-5 (ACRF) patients and influence information they receive (educational process, EP) in modality Renal Replacement Therapy (RRT) or conservative treatment (CT) in multidisciplinar ACRF Office. MATERIAL AND METHODS: Prospective, multicenter study (3 centers). Inclusion: from June-01-2014 to October-01-2015; observation: 12 months or until start RRT or death if they occur before 12 months; ends October-01-2016. RESULTS: 336 patients were included (60% males), median and intercuartile rank 71.5 (17), 55% ≥ 70 years; Follow up initiation eGFR CKD-EPI: 21 (9) ml / min / 1.73m2; Charlson Index (ChI) with / without age 8 (3) / 4 (2); Diabetic patients: 52,4%. The EP was carried out in 168, eGFR 15 (10) ml / min / 1.73 m2. The initial treatment election: 26% peritoneal dialysis (PD), 45% hemodyalisis (HD), 26% CT, kidney trasplant 3%; 60 patients started RRT: 3.3% kidney traspant; 30% PD, 66% HD; 104 admissions in 73 patients, the most frequent cause: cardiovascular disease (42%). Fallecimiento: 23 patients (6.8%). Age was higher (78.4 (6) vs. 67.8 (13.4), P < .001), higher ChI 9.8 (2.1) vs. 7.4 (2.5), P < .001). All deceased who received EP had chosen CT; 61% of deceased had at least one hospital admission vs. 39% alive (P < 0.001). Cox regression: age and Charlson index were the predictive mortality variables. CONCLUSIONS: The population of ACRF patients is elder, comorbid, with high rate hospitalizations rate. The PD election is higher than usual. The EP has been very useful tool and has favored the PD choice