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BackgroundC3 glomerulopathy associated with monoclonal gammopathy (C3G-MIg) is a rare entity. Herein we analysed the clinical and histologic features of a cohort of C3G-MIg patients.MethodsWe conducted a retrospective, multicentre, observational study. Patients diagnosed with C3G-MIg between 1995 and 2021 were enrolled. All had genetic studies of the alternative complement pathway. The degree of disease activity and chronicity were analysed using the C3G histologic index. Descriptive statistics and propensity score matching (PSM) analysis were used to evaluate the main outcome of the study [kidney failure (KF)].ResultsThe study group included 23 patients with a median age 63 of years [interquartile range (IQR) 48–70], and 57% were males. Immunoglobulin G kappa was the most frequent MIg (65%). The diagnosis of C3G-MIg was made in transplanted kidneys in seven patients (30%). Five (22%) patients had C3 nephritic factor and five (22%) had anti-factor H antibodies. One patient carried a pathogenic variant in the CFH gene. During a follow-up of 40 months (IQR 14–69), nine patients (39%) reached KF and these patients had a significantly higher total chronicity score on kidney biopsy. Patients who received clone-targeted therapy had a significantly higher survival compared with other management. Those who achieved haematological response had a significantly higher kidney survival. Outcome was remarkably poor in kidney transplant recipients, with five of them (71%) reaching KF. By PSM (adjusting for age, kidney function, proteinuria and chronicity score), no significant differences were observed in kidney survival between C3G patients with/without MIg.ConclusionsThe C3G histologic index can be used in patients with C3G-MIg to predict kidney prognosis, with higher chronicity scores being associated with worse outcomes. Clone-targeted therapies and the development of a haematological response are associated with better kidney prognosis.

Background Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. Methods We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. Results Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). Conclusions The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.

BACKGROUND AND AIMS Persistent chronic hypotension affects 5–10% of dialysis patients, and it is associated with high morbidity and mortality [1]. Although data regarding the influence of this hemodynamic condition on kidney transplantation are scarce, some studies suggest a negative impact on kidney transplant outcomes [2-3]. We decided to analyze the evolution of patients with chronic hypotension in dialysis who undergo kidney transplantation in our center. METHOD A retrospective observational study was conducted. We evaluated 2308 consecutive kidney transplants performed at Hospital Doce de Octubre between 2004 and 2020. Sixty-six patients with chronic hypotension (defined as systolic blood pressure ≤ 100 mmHg at the time of transplantation) were identified. A control group of 66 non-hypotensive patients was assigned, matched for the source of organs and age (using as control, whenever possible, the recipient of the other kidney from the same donor). The evolution of both groups was compared in terms of primary graft function, graft thrombosis, delay in graft function, serum creatinine at the end of follow-up and renal graft survival. RESULTS Patients with chronic hypotension had higher rates of primary non-function (18.2% versus 6.1%, P = 0.033) mainly due to venous thrombosis of the renal graft (15.2% versus 3%, P = 0.015). Delayed graft function was also more common in patients with chronic hypotension (68.2% versus 50%, P< 0001). Mean graft survival was lower in the group of patients with chronic hypotension (81.1 months) compared to the control group (104.1 months) (P = 0.012). At the end of follow-up, there were 67.7% of functioning grafts within the hypotensive group compared with 86.4% in the control group (P = 0.013). Serum creatinine at the end of follow-up was slightly higher in patients with chronic hypotension (1.76 ± 0,70mg/dL versus 1.50 ± 0.49 mg/dL, P = 0.04). Median follow-up time was 37 months (1–122). In multivariate analysis, chronic hypotension was an independent risk factor for renal graft loss [RR = 2.8 (1.3–6.4), P = 0012]. CONCLUSION Chronic hypotension in dialysis has a negative impact in short and long-term kidney transplant outcomes. It is associated with higher rates of primary non-function due to venous graft thrombosis, higher rates of delayed graft function, a higher serum creatinine at the end of follow-up and a worse renal graft survival. It seems crucial to identify this subgroup of patients in order to implement measures aimed to ameliorate transplant results.

Background Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis is a chronic relapsing and remitting autoimmune disease. Urinary soluble CD163 (usCD163) has been proposed as a biomarker of active renal vasculitis. We aimed to assess the potential usefulness of usCD163 for diagnosing renal relapse in patients with ANCA-associated glomerulonephritis. Methods One hundred and fifty-six samples from 47 patients with ANCA-associated glomerulonephritis belonging to two different cohorts (incident and prevalent) and 20 healthy controls were studied. Patients from the incident cohort were prospectively followed up, and usCD163 concentrations were measured every 3 months. Renal relapses were identified and changes in usCD163 concentrations were analysed. Results Normalized usCD163 concentrations were elevated at disease onset in all patients with active renal vasculitis, with a median concentration of 601 ng/mmol (interquartile range 221–1404 ng/mmol). On the other hand, usCD163 concentrations were undetectable among control patients with renal vasculitis in remission. Except for non-responders, usCD163 concentrations progressively decreased in all patients after treatment. In the presence of vasculitis relapse, there was a consistent increase in usCD163 concentrations, compared with previous values. The area under the receiver-operating characteristic curve of absolute and relative changes in usCD163 concentrations to identify relapse of ANCA-associated glomerulonephritis was 0.96 [95% confidence interval (CI) 0.91–1.00; P = 0.001] and 0.95 (95% CI 0.90–1.00; P = 0.001), respectively. Sensitivity and specificity for a relative increase of 20%, or an absolute increase of 20 ng/mmol, in usCD163 concentrations were 100% for both, and 89.3% and 87.5%, respectively. Urinary sCD163 concentrations significantly correlated with Birmingham Vasculitis Activity Score scores at Month 6 (r = 0.737; P = 0.006) and Month 12 (r = 0.804; P = 0.005). Conclusions usCD163 represents an accurate biomarker for the detection of active renal vasculitis and relapse. Its close association with disease activity provides additional information for monitoring treatment response.

Background Recently, renal risk score on the basis of three clinicopathologic features to predict end-stage renal disease (ESRD) in antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis has been proposed. The aim of this multi-centre study was to validate this renal risk score in a large cohort of southern European patients. Methods Data were retrospectively collected from the time of diagnosis by systematic review of medical records from 147 patients with renal vasculitis recruited from three Spanish centres. The renal risk score was calculated in every patient, and renal and global outcomes were analysed according to the risk group assessment. Results ANCA serology was positive in 76.2% of patients: 64.6% showed activity against myeloperoxidase (MPO) and 12.2% against proteinase 3 (PR3). The median (interquartile range) follow-up period was 41 months (9.6–104). Forty-eight patients (32.7%) reached ESRD. Patients were classified into the three groups according to the risk of progression to ESRD: 21.8% of patients were classified into low risk, 52.4% were classified into moderate risk and the remaining 25.9% were classified into high risk. The cumulative proportion of renal survival at 2, 5 and 10 years was 100, 100 and 82% in the low-risk group, 79, 77 and 77% in the medium-risk group and 63, 53 and 40% in the high-risk group (P, Graphical Abstract

C3 glomerulopathy (C3G) is a clinicopathologic entity secondary to dysregulation of the alternative complement pathway in plasma and the glomerular microenvironment. The current consensus definition of C3G relies on immunofluorescence staining criteria. However, due to its high clinical variability, these criteria may not be accurate enough in some clinical scenarios. Thus, a new pathogenic classification based on a cluster analysis of clinical, histologic, and genetic data has recently been proposed, which could also help identify patients at higher risk of progression. Several pathogenic abnormalities in complement genes have been described, and the role of autoantibodies in the disease is increasingly recognized, but still the genotype-phenotype correlations in C3G are poorly understood. C3G may be diagnosed in both children and adults. The spectrum of clinical manifestations is wide, although one of the most common clinical presentations is proteinuria with relatively preserved kidney function. In order to standardize the evaluation of kidney biopsies from these patients, a histopathologic index was recently proposed, including both parameters of activity and chronicity. However, this index has not yet been validated in independent cohorts. Currently, no targeted therapies are available in clinical settings for the treatment of C3G, although several new molecules are under investigation. Treatment with corticosteroids plus mycophenolate mofetil has been shown to be associated with improved renal outcomes, as compared to other immunosuppressive regimens. Yet, the main determinants of treatment response with this regimen and the influence of the underlying pathogenic drivers have not been extensively studied. The therapeutic response to eculizumab, an anti-C5 monoclonal antibody, has been shown to be highly heterogeneous. Thus, its current clinical indication in C3G is restricted to rapidly progressive forms of the disease. To summarize, in recent years, several important advances have taken place in the understanding of C3G, but still further studies are warranted to elucidate the best therapeutic strategies that could improve prognosis of this entity.

Anticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. A total of 26 patients were included with a median age of 75 years (62-80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8-8.2), median international normalized ratio (INR) 2.4 (1.5-3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis. IgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

Dysregulation of the alternative complement pathway is a major pathogenic mechanism in two rare renal diseases: atypical haemolytic uraemic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN). We report on a 66-year-old male with chronic hepatitis C virus (HCV) infection and a combined liver–kidney transplant that was diagnosed with MPGN at the age of 63 years and a 5-year-old boy who presented with aHUS at the age of 21 months following a Streptococcus pneumoniae infection. Both patients carried similar frameshift variants in the complement CFHR5 gene that segregate with reduced levels of factor H–related 5 (FHR-5). We conclude that low FHR-5 levels may predispose to viral and bacterial infections that then trigger different renal phenotypes.

Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short-term outcomes similar to those obtained from donation after brain death (DBD) donors. However, heterogeneous results in the long term have been reported. We compared 10-year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death-censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P .01), although glomerular filtration rates at the end of follow-up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10-year death-censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age 50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long-term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation.

Background and Aims Acute kidney injury (AKI) secondary to glomerular hemorrhage in the context of overanticoagulation, commonly known as anticoagulant-related nephropathy (ARN), is a relatively novel recognized entity. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to examine underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Method Spanish retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. The main outcome was to describe pathologic findings in kidney biopsy specimens of patients with clinical suspicion of ARN. The secondary outcome was to assess kidney outcomes during follow-up. Results Twenty-four patients were included with a median age of 76 years (interquartile range [IQR] 64-81) and a follow-up period of 10.1 (IQR 1.3-41.1) months. 79% were male, 22 (91%) had hypertension and 9 (37%) were diabetic. Most cases (91%) were on anticoagulation with vitamin K antagonists. At admission, 87% of cases presented gross hematuria with a median serum creatinine (SCr) of 4.2 mg/dl and a median INR of 2.3. During follow-up, median highest (peak) SCr was 6.3 mg/dl and 11 (45%) patients required acute dialysis. Kidney biopsy showed that all patients except one had an underlying nephropathy (confirmed IgA nephropathy in 16 [66.7%], probable IgA nephropathy in 2, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1). Tubules filled with red cells and red cell casts were observed in 66.7% of the cases and acute tubular necrosis in 70.8%. Management included anticoagulation withdrawal in 14 cases (58.3%) and immunosuppressive treatment with corticosteroids (n = 17 [70.8%]) and mycophenolic acid (n = 5 [20.8%]). At 12 weeks after discharge, 11 patients had >50% decrease in SCr (with respect to peak SCr), 6 had Conclusion IgA nephropathy was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

Background and Aims Atypical haemolytic uremic syndrome (aHUS) is a clinical entity characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. There are several cases of AHUS in non-renal solid organ transplants described in the literature, included lung transplant. Kidney and patient survival are compromised by this complication because of the lack of an effective treatment. Eculizumab is C5 complement factor specific blocker already administered in another kind of secondary aHUS with encouraging results Method We analys six lung transplants in a retrospective single-center study between 2018-2020 who developed an aHUS and were treated with eculizumab. Clinical and analytical data were collected along the follow-up. Principal outcome was to explore haematologycal and renal response after treatment with eculizumab. Results We included a total of six patients (83% were female) with a median age of 57 years at the time of transplantation. Aetiologies of lung transplantation were chronic obstructive pulmonary disease in 2 patients, interstitial lung disease in another 2, and cystic fibrosis in the remaining two. Induction and maintenance immunosuppressive therapy were based on tacrolimus, mycophenolate and prednisone in all cases. Baseline serum creatinine after lung transplantation was 1.1 mg/dl (0.9-2.4). Two patients developed an aHUS in the immediate post-transplant, one of them died because of surgical complications. Another four patients developed an aHUS 59 months (33-95) after transplantation. Previously of thrombotic microangiopathy, three patients were on treatment with everolimus instead of mycophenolate and two lung transplants have cytomegalovirus reactivation. At the aHUS onset, median serum creatinine was 4mg/dl (2.4-5-7) and acute dialysis was performed in 50% of patients. Median hemoglobin was 7.2g/dl (6.9-7.7), platelet count was 32x1000/µL (17-58), and DHL was 1343 U/L (581-1597) at the start of eculizumab despite having treated the trigger. After a median of 6 doses of eculizumab, the five surviving patients had haematologycal and renal response. No patients underwent chronic dialysis. Serum creatinine was 2.2 mg/dl (1.7-2.3), hemoglobin 9.8 g/dl and platelet count 159x1000/µL at the end of follow-up. Conclusion AHUS is a critical complication in lung transplantation, shortly related with immunosuppressive therapy. Patients are at risk of end stage renal disease. Eculizumab treatment appears promising.

Background and Aims Thin basement membrane nephropathy (TBMN), the most common cause of persistent microhaematuria (mH), is due to mutations in genes codifying alfa-3 and alfa-4 collagen IV chains (COL4A4/COL4A3). Initially considered as a benign condition, subsequent studies have shown that an important number of patients develop proteinuria and CKD. We reported in a previous small study the presence of multicystic kidney disease (MCD) in some TBMD patients. In this study we aimed to evaluate the presence of MCD in a larger cohort of TBMD patients and analyze its association with renal outcomes. Method We collected 50 patients with a diagnosis of TBMD based on the presence of persistent mH (>5 erythocytes per high power field in more than 90% of urinary sediments and radiological examinations to exclude other causes of mH) and at least one first-degree relative with persistent mH. TBMD diagnosis was confirmed by renal biopsy (glomerular basement membrane thickness less than 150nm) in 18 patients and by genetic test (pathogenic mutations in COL4A3/COL4A4) in 6 patients. MCD was diagnosed by the presence of uncountable cysts on renal ultrasonography. Results Mean age at diagnosis was 43.7 years, 34% were males and 18% had hypertension. At baseline, serum creatinine (SCr) was 0.9 mg/dL, proteinuria 0.48 gr/24h and 9 patients (18%) had CKD (estimated glomerular filtration rate -eGFR- lower than Conclusion MCD is frequently observed in TBMD patients and is a risk factor for the progression of CKD.

8 p.-2 fig.-3 tab., 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., This project was co-founded by Public Research Network REDinREN ISCIII 16/009/009 and the SENTRA group. S.R.d.C. is supported by the Spanish Ministerio de Economía y Competitividad-FEDER (SAF2015-66287R) and the Autonomous Region of Madrid (S2017/BMD-3673).

12 p.-4 fig.-4 tab., Rationale & objective: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population., Study design: Multicenter, retrospective cohort study., Setting & participants: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN)., Predictors: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score., Outcome: Time to kidney failure., Analytical approach: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines., Results: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure., Limitations: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding., Conclusions: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure., Work in this study was supported by the Instituto de Salud Carlos III /Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to MP), the Autonomous Region of Madrid (S2017/BMD-3673) (to MP); EGdeJ is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades" (RYC-2013-13395 and RTI2018-095955-B-100).

The increase in demand for medical care for renal complications associated with neoplastic diseases is a reality in most nephrology departments. In response to this overall situation, the creation of healthcare models such as monographic consultations and develop training programs in Onconephrology could improve the care of these patients.Through an exploratory and descriptive study, we identified current situation of kidney involvement in cancer patients. The objective of the present study is to establish the criteria for specific assistance in the field of Onconephrology. For this, we have reviewed key aspects and analyzed the current situation in our country, through a survey addressed to all nephrologists through the Spanish Society of Nephrology., together with the experience of two Spanish centers. From this information, we have established some requirements and recommendations for the start-up of these consultations. Resumen: El incremento de la demanda asistencial de patología renal asociada a enfermedades neoplásicas es una realidad en la mayoría de servicios de nefrología. Para dar respuesta a esta situación, debe considerarse la creación de modelos asistenciales como consultas monográficas y desarrollar programas de formación en Onconefrologia que permitan optimizar la atención de estos pacientes.A través de un estudio exploratorio y descriptivo, identificamos cual es la situación actual de la afectación renal en pacientes con cáncer. El objetivo del presente estudio es establecer los criterios para la asistencia específica en el ámbito de la Onconefrologia. Para ello hemos revisado aspectos clave y analizado la situación actual en nuestro entorno, mediante una encuesta dirigida a todos nefrólogos a través de la S.E.N., junto a la experiencia de dos centros españoles. A partir de esta información hemos establecido una serie de requisitos y recomendaciones para la puesta en marcha de estas consultas.

Resumen El sindrome hemolitico uremico (SHU) se caracteriza por una anemia hemolitica microangiopatica con deterioro de funcion renal. Actualmente se clasifica en SHU asociado a toxina Shiga y SHU atipico, y el mecanismo comun consiste en un dano grave del endotelio vascular que origina una microangiopatia trombotica. Dentro del SHU atipico se engloban formas primarias, secundarias y debidas a enfermedades metabolicas. En la gran mayoria de casos de SHU atipico, la hiperactividad de la via alternativa del complemento juega un papel patogenico central. El tratamiento se basa en el bloqueo de la formacion del complejo de ataque de membrana, molecula final de la via alternativa del complemento, con eculizumab, que ha revolucionado la historia natural de la enfermedad. La recidiva de la enfermedad en el trasplante es frecuente y con muy mal pronostico para la supervivencia renal.

Introduction Perigraft fluid collection (PFC) is a common complication after kidney transplant. Its etiology is not clear and not all the causes have been identified. The influence of the type of donor has never been evaluated. Our aim was to compare the incidence, severity and management of PFC in recipients of grafts from uncontrolled donors after circulatory death (DCD) with normothermic extracorporeal membrane oxygenation (NECMO) versus recipients of grafts from donors after brain death (DBD). Material and methods We conducted a retrospective cohort study of 300 kidney transplants performed in our center between 2007 and 2012. Patients were divided in two groups: 150 recipients of Maastricht II DCD graft and 150 recipients of the DBD graft. Incidence, severity according to Clavien scale and management were analyzed in both groups, and comparison was carried out using Chi-square. Results Of the 300 kidney recipients analyzed, 93 (31.4%) suffered PFC, showing no difference between DBD (32.0%) and DCD (30.8%) groups (p = 0.9). Complicated PFC rate (defined as a PFC generating vascular compression, fever or urinary tract obstruction) was 22.9% in the DBD group versus 22.2% in the DCD group (p = 1); most complicated PFC were due to urinary tract obstruction (81%), with no difference between the groups (p = 1). Concerning Clavien scale, 78.5% of the PFC in our series were Clavien I, 19.4% Clavien IIIa and 2.2% Clavien IIIb, with no difference between both groups (p = 1). Conclusions PFC is a frequent complication that appears in a third of our patients, showing no difference in the incidence or severity between DBD and uncontrolled DCD graft recipients.

9 p.-1 fig.-7 tab. Cavero, Teresa et al., Background. Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab., Methods. We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 109/L) and haemoglobin, disappearance of all the markers of microangiopathichaemolytic anaemia (MAHA), and improvement of renal function,with a 25% reduction of serum creatinine from the onset of eculizumab administration., Results. Twenty-nine patients with secondary aHUS (15 druginduced,8 associated with systemic diseases, 2 with postpartum,2 with cancer-related, 1 associated with acute humoral rejectionand 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a _>50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses., Conclusion. Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition., Work in this report was funded by the Instituto de Salud Carlos III: REDinREN (RD 016/009 Feder Funds), the Fondo de Investigaciones Sanitarias (13/02502 and ICI14/00350), the Ministerio de Economia y Competitividad (SAF2015-66287R) and the Autonomous Region of Madrid (S2010/BMD-2316;Grupo de Investigación Complemento-CM). SRdeC is funded by the Seventh Framework Programme European UnionProject EURenOmics (305608).

The Canal of Aragon and Catalonia (CAC) is 134 km long and irrigates 105,000 ha (131 irrigation user communities) and it is own by the River Ebro’s Water Agency. The aqueducts are located between km 67 and 71 of the canal and were designed by the Civil Engineer Félix de los Ríos Martín in 1907. The cross-section of both aqueducts, Coll de Foix and Capedevila, was extended within the framework of the project by Fernando Hué Herrero in 1962 in order to reach design flows of 26.1 m3/s and 25.7 m3/s, respectively. The structural performance of the aqueducts has been satisfactory, nevertheless the hydraulic capacity has reduced over the years. As a result, the irrigation user communities have expressed the need to extend the cross-section of the aqueducts to meet the irrigation demands. Given the age of the structure and the different design considerations at the time, it is paramount to verify the structural reliability of the aqueducts in the new load configuration. Therefore, the objective of the paper is to present the structural safety analysis conducted and describe the new extended cross-section for both aqueducts (maintaining the original structural typology).

Several studies have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis. We aimed to assess the association between baseline serum C3 (sC3) levels and long-term outcomes in patients with renal vasculitis. This retrospective study included 111 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Serum levels of C3 were measured at the onset and the study population was divided into three tertiles according to sC3 concentrations (tertile 1106 mg/dl; tertile 2 106-128 mg/dl; tertile 3128 mg/dl). Patients with lower sC3 (tertile 1) were compared with those having higher levels of sC3 (tertile 2 and tertile 3). Histological, clinical, and laboratory data were recorded for analysis. The primary end point was the composite of end-stage renal disease (ESRD) and death from any cause. Lower sC3 levels were associated with a higher need for dialysis and lower response rate to treatment (p = 0.04 and p = 0.007, respectively). Renal and global survival at 1 and 5 years was 53 and 46 % in patients with lower sC3 (tertile 1) compared with 72 and 65 % in patients with higher sC3 (upper two tertiles) (p = 0.04). In a multivariate Cox-regression model, when adjusted by renal function and histopatholologic categories, lower sC3 remained as an independent predictor of ESRD and death (HR, 1.9; 95 % CI, 1.1 to 3.4; p = 0.02). Baseline serum C3 levels have an independent prognostic value in predicting long-term renal and global survival in patients with renal vasculitis.

34 p.-2 fig.-3 tab., Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) refers to the thrombotic microangiopathy resulting from uncontrolled complement activation during pregnancy or the postpartum period. Pregnancy-associated aHUS is a devastating disease for which there is a limited clinical understanding and treatment experience. Here we report a retrospective study to analyze the clinical and prognostic data of 22 cases of pregnancy-associated aHUS from the Spanish aHUS Registry under different treatments. Sixteen patients presented during the first pregnancy and as many as nine patients required hemodialysis at diagnosis. Identification of inherited complement abnormalities explained nine of the 22 cases, with CFH mutations and CFH to CFHR1 gene conversion events being the most prevalent genetic alterations associated with this disorder (66%). In thirteen of the cases, pregnancy complications were sufficient to trigger a thrombotic microangiopathy in the absence of genetic or acquired complement alterations. The postpartum period was the time with highest risk to develop the disease and the group shows an association of cesarean section with pregnancy-associated aHUS. Seventeen patients underwent plasma treatments with a positive renal response in only three cases. In contrast, ten patients received eculizumab with an excellent renal response in all, independent of carrying or not inherited complement abnormalities. Although the cohort is relatively small, the data suggest that pregnancy-associated aHUS is not different from other types of aHUS and suggest the efficacy of eculizumab treatment over plasma therapies. This study may be useful to improve prognosis in this group of aHUS patients., Work in this report was funded by the Instituto de Salud Carlos III: REDinREN (RD016/009 and RD012/0021) and Fondo de Investigaciones Sanitarias (ISCIII/FEDER) ref 13/02502 and ref 16/01685. SRdeC is supported by the Spanish “Ministerio de Economía y Competitividad-FEDER” (SAF2015-66287R), the Seventh Framework Programme European Union Project EURenOmics (305608) and the Autonomous Region of Madrid (S2010/BMD-2316).

Haemolytic uraemic syndrome (HUS) is characterized by microangiopathic haemolytic anaemia with acute kidney injury. It is currently classified into two main categories: Shiga-toxin producing E. coli-haemolytic uraemic syndrome (STEC-HUS) and atypical haemolytic uraemic syndrome (aHUS). Endothelial cell damage is the common pathway in HUS to developing thrombotic microangiopathy. Atypical HUS includes primary, secondary and aHUS due to metabolic diseases. In the majority of aHUS cases, hyperactivity of the alternative complement pathway plays a central role. Therefore, treatment is based on complement inhibitors like eculizumab, a drug that has revolutionized the natural history of the disease. Relapses are frequent after kidney transplant and thus confer a poor prognosis.

Hematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0.75 or ≤0.75 g/d). The proportion of patients reaching ESRD or a 50% reduction of renal function was significantly greater among patients with persistent hematuria than patients with minimal or negative hematuria (30.4% and 37.0% versus 10.6% and 15.2%, respectively; P=0.01). Multivariable analysis revealed time-averaged hematuria, time-averaged proteinuria, renal function at baseline, and the presence of tubulointerstitial fibrosis on renal biopsy as independent predictors of ESRD. After hematuria disappearance, which occurred in 46% of the patients, the rate of renal function decline changed from -6.45±14.66 to -0.18±2.56 ml/min per 1.73 m2 per year (P=0.001). Patients with time-averaged proteinuria >0.75 g/d had significantly poorer renal survival than those with time-averaged proteinuria ≤0.75 g/d. However, on further classification by time-averaged hematuria, only those patients with time-averaged proteinuria >0.75 g/d and persistent hematuria had significantly worse renal survival than those in the other three groups. In conclusion, remission of hematuria may have a significant favorable effect on IgA nephropathy outcomes.

Renal failure secondary to ANCA-associated vasculitis represents a clinical and therapeutic challenge. In this study, we aimed to assess the treatment response rates and long-term outcomes of vasculitis patients presenting with renal failure. This retrospective study included 151 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Patients with renal failure which required dialysis at the onset were compared to those presenting with more preserved renal function. The primary end point was treatment response and patient surivival. Patients with severe renal involvement had a lower response to treatment compared to those having preserved renal function (26.6 versus 93.4%; p