Teresa Cavero

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis

C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

Eculizumab in secondary atypical haemolytic uraemic syndrome

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 microangiopathic haemolytic 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 drug‐induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer‐related, 1 associated with acute humoral rejection and 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.

The predictive value of kidney biopsy in renal vasculitis: a multicenter cohort study

The histopathologic classification of antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated to have prognostic value in small cohorts of patients with pauci-immune extracapillary glomerulonephritis. We aimed to validate this histologic subgrouping system in a large cohort of patients with renal vasculitis from 3 Spanish centers. The additional value of several histologic parameters for predicting renal outcome was investigated. A total of 151 biopsies of patients with renal vasculitis were reviewed and classified as follows: 41% crescentic, 24% mixed, 21% focal, and 14% sclerotic. The cumulative proportions of renal survival at 5 years were 83.2%, 81.2%, 60.5%, and 50.7% for the focal, mixed, crescentic, and sclerotic categories, respectively (P < .05). In the crescentic category, patients with less than 75% of glomeruli showing crescents had better survival at 1 and 5 years compared with those having greater than or equal to 75% of crescents (77.9% and 70.6% versus 51.3% and 45.6%; P = .02). When adjusted by renal function and other histologic parameters, the percentage of extracapillary proliferation and glomerulosclerosis remained as significant predictors for renal survival (hazard ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .001, and hazard ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .002, respectively). In conclusion, patients with pauci-immune crescentic glomerulonephritis experienced different outcomes depending on the percentage of crescents observed, so that extensive extracapillary proliferation was associated with the poorest renal survival. These findings validate the prognostic utility of the histologic classification scheme in antineutrophil cytoplasmic antibody positive and negative patients and suggest a subdivision of crescentic category (<75% and ≥75% of crescents) based on the different survival rates observed among these subgroups.

A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome

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.

Remission of Hematuria Improves Renal Survival in IgA Nephropathy

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.

Cuándo debe sospechar un nefrólogo una enfermedad mitocondrial

Mitochondrial diseases, taking into account those that affect the processes of the respiratory chain (RC) and mitochondrial oxidative phosphorylation system (OXPHOS), make up a relatively frequent group within rare diseases that usually have multisystem involvement, a very variable phenotypic expression and a complex genetic base. Renal involvement is uncommon, with the tubule being the most affected, specifically its proximal portion, developing into full Toni-Debré-Fanconi syndrome in the most serious cases. However, in some cases the glomerulus is involved, fundamentally in focal segmental glomerulosclerosis form (FSGS), expressed by proteinuria and renal failure. It is important that the Nephrologist keeps in mind the possibility of a mitochondrial disease in patients with this type of renal involvement that present clinical data with these characteristics, especially diabetes mellitus and deafness. In cases with FSGS, a correct diagnosis will avoid the inappropriate use of immunosuppressive medication. Specific treatments do not exist for the majority of mitochondrial diseases, but it is likely that the intense research that currently exists for these diseases will eventually produce effective treatment possibilities.

Results of Kidney Transplantation in Very Old Age Recipients Using Kidneys from Very Old Donors

Background Kidney transplantation is the best option for elderly patients with end stage renal disease. The major limitation in this group of patients is shortage of donors since kidneys from young donors are assigned to younger recipients. Spain had 43,4 donors pmp in 2016, 30% of them were aged over 70 years. Kidneys from these donors can be assigned to older patients without detriment to young recipients. Aim Identify clinical factors associated with worse outcomes in very old recipients of grafts from very old donors. Methods Retrospective analysis of pretransplant clinical factors associated with graft and recipient survival in elderly patients (≥70 years) that received a kidney transplant from a very old donor (≥70 years) at our institution from October 2004 to December 2013 (n = 155). Results Median age of donors and recipients was 77 (74-79) and 75 (73-78) years, respectively. The 3-year and 5-year patient survival was 73.1% and 67.1%, respectively. Mortality in the first year was 15.9%. Primary nonfunction was 13.6%. Early graft thrombosis was 7.7%. Death censored graft survival was 83.4% at year 3 and 80.8% at year 5. History of cerebrovascular disease in the recipient was the only factor associated with patient survival (HR 5.12, p=0.027), while history of diabetes melliuts in the recipient was the only factor associated with the risk of graft loss (HR 4.40, p=0.0001). Conclusion Kidney transplantation in patients over 70 years offers a survival advantage over staying on dialysis. History of cerebrovascular disease in the recipient was associated with an increased risk of recipient mortality, while history of diabetes in the recipient was associated with increased risk of graft loss. Further studies are needed to identify pretrasplant clinical factors associated with increased risk of graft failure and recipient mortality in this population in order to improve allocation of these old allografts in the elderly patients. Fundación Mutua Madrileña.

FP723RESULTS OF KIDNEY TRANSPLANTATION IN VERY OLD RECIPIENTS

INTRODUCTION AND AIMS: Kidney transplantation is the best option for elderly patients with end stage renal disease. The major limitation in this group of patients is shortage of donors since kidneys from young donors are assigned to younger recipients. Spain had 43,4 donors pmp in 2016, 30% of them were aged over 70 years. Kidneys from these donors can be assigned to older patients without detriment to young recipients.Aims: To describe the outcomes of very old recipients using kidneys from very old donors. To identify clinical factors associated with worse outcomes in this population.

Kidney transplant from uncontrolled donation after circulatory death donors maintained by nECMO has long-term outcomes comparable to standard criteria donation after brain death

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.