Effect of Immunosuppressive Treatments on Kidney Outcomes After Gross Hematuria-Related Acute Kidney Injury in Older Patients With IgA Nephropathy.

Introduction: Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. Methods: This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. Results: The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Conclusions: Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.

Practical implementation and clinical benefits of the new automated dialysate sodium control biosensor.

Background: A key feature of dialysis treatment is the prescription of dialysate sodium (Na). This study aimed to describe the practical implementation of a new automated dialysate Na control biosensor and to assess its tolerance and the beneficial clinical effects of isonatraemic dialysis. Methods: A prospective study was carried out in 86 patients who, along with their usual parameters, received the following five consecutive phases of treatment for 3 weeks each: phase 0: baseline 5008 machine; phases 1 and 2: 6008 machine without activation of the Na control biosensor and the same fixed individualized Na dialysate prescription or adjusted to obtain similar conductivity to phase 0; phases 3 and 4: activated Na control to isonatraemic dialysis (Na dialysate margins 135-141 or 134-142 mmol/L). Results: When the Na control was activated, the few episodes of cramps or hypotension disappeared when the lower dialysate Na margin was increased by 1 or 2 mmol/L. The activated Na control module showed significant differences compared with baseline and the non-activated Na module in final serum Na values, diffusive Na balance, and changes in pre- to postdialysis plasma Na values. The mean predialysis systolic blood pressure value was significantly lower in phase 4 than in phase 1. There were no significant differences in total Na balance in the four 6008 phases evaluated. Conclusions: The implementation of the automated dialysate Na control module is a useful new tool, which reduced the diffusive load of Na with good tolerance. The module had the advantages of reducing thirst, interdialytic weight gain and intradialytic plasma Na changes.

Efficacy and Safety of the Medium Cut-Off Elisio HX Dialyzer.

INTRODUCTION: The medium cut-off Elisio HX dialyzer by Nipro became commercially available in Europe in 2021, but there are still no reports of in vivo data. This study aimed to evaluate the safety and efficacy of it compared with previously evaluated hemodialysis (HD), expanded HD (HDx), and postdilution hemodiafiltration (HDF) treatments. METHODS: A prospective study was carried out on 18 patients who underwent 5 dialysis sessions: FX80 Cordiax in HD, Elisio H19 in HD, Elisio HX19 in HDx, Theranova 400 in HDx, and FX80 Cordiax in HDF. The reduction ratios of urea, creatinine, ß2-microglobulin, myoglobin, kappa FLC, prolactin, α1-microglobulin, α1-acid glycoprotein, lambda FLC, and albumin were compared. Dialysate albumin loss was measured. RESULTS: The comparison between the different dialysis modalities revealed no difference for small molecules, but HDx and HDF were significantly more efficient than HD for medium and large molecule removal. The efficacy of Elisio HX19 dialyzer in HDx was similar to the Theranova 400, superior to both dialyzers in HD, and slightly lower than HDF. Albumin losses in dialysate with HD dialyzers were less than 1 g, but between 1.5 and 2.5 g in HDx and HDF. The global removal score (GRS) values with HDx treatments were statistically significantly higher than those with HD. The highest GRS was obtained with the helixone dialyzer in HDF. CONCLUSIONS: The new MCO dialyzer, Elisio HX, performs with excellent behavior and tolerance. It represents an upgrade compared to their predecessor and is very close to the removal capacity of HDF treatment.

Conductivity variations and changes in serum sodium concentration during dialysis related to monitor switching.

INTRODUCTION: The sodium gradient during hemodialysis sessions is one of the key factors in sodium balance in patients with dialysis-dependent chronic kidney disease; however, until the appearance of the new monitors with sodium modules, the differences between prescribed and measured sodium have been understudied. The present study aimed to compare the impact on the measured conductivity and the initial and final plasma sodium after changing the 5008 Cordiax to the new 6008 Cordiax monitor. MATERIAL AND METHODS: 106 patients on hemodialysis were included. Each patient underwent 2 dialysis sessions in which only the monitor was varied. The variables collected were dialysate, sodium and bicarbonate prescribed, real conductivity, initial and final plasma sodium measured, and the calculated sodium gradient (ΔPNa). RESULTS: The change of dialysis monitor showed small but statistically significant differences in the initial (138.14mmol/L with 5008 vs. 138.81mmol/L with 6008) and final plasma sodium (139.58mmol/L vs. 140.97mmol/L), as well as in the actual conductivity obtained (13.97 vs. 14.1mS/cm). The ΔPNa also increased significantly. CONCLUSION: The change from 5008 to 6008 monitor is associated with increased conductivity, leading the patient to end the sessions with higher plasma sodium and ΔPNa. Knowing and confirming this change will allow us to individualize the sodium prescription and avoid possible undesirable effects. It could be the preliminary study to explore the new sodium biosensor incorporated into the new generation of monitors.

Incidence of severe breakthrough SARS-CoV-2 infections in vaccinated kidney transplant and haemodialysis patients.

INTRODUCTION: Given the increased COVID-19 observed in kidney transplant recipients (KTRs) and haemodialysis patients, several studies have tried to establish the efficacy of mRNA vaccines in these populations by evaluating their humoral and cellular responses. However, there is currently no information on clinical protection (deaths and hospitalizations), a gap that this study aims to fill. METHODS: Observational prospective study involving 1,336 KTRs and haemodialysis patients from three dialysis units affiliated to Hospital Clínic of Barcelona, Spain, vaccinated with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccines. The outcomes measured were SARS-CoV-2 infection diagnosed by a positive RT-PCR fourteen days after the second vaccine dose, hospital admissions derived from infection, and a severe COVID-19 composite outcome, defined as either ICU admission, invasive and non-invasive mechanical ventilation, or death. RESULTS: Six per cent (18/302) of patients on haemodialysis were infected, of whom four required hospital admission (1.3%), only one (0.3%) had severe COVID-19, and none of them died. In contrast, 4.3% (44/1034) of KTRs were infected, and presented more hospital admissions (26 patients, 2.5%), severe COVID-19 (11 patients, 1.1%) or death (4 patients, 0.4%). KTRs had a significantly higher risk of hospital admission than HD patients, and this risk increased with age and male sex (HR 3.37 and 4.74, respectively). CONCLUSIONS: The study highlights the need for booster doses in KTRs. In contrast, the haemodialysis population appears to have an adequate clinical response to vaccination, at least up to four months from its administration.

Extracapillary proliferation scoring correlates with renal outcome and contributes to stratification in adult patients with immunoglobulin A nephropathy.

BACKGROUND: The revised Oxford classification of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate the histological crescents and interstitial fibrosis and tubular atrophy (IFTA) subgrouping, and to investigate the additional value of the proportion of crescents (CatPE) in the prediction of renal outcome. METHODS: Data were retrospectively collected over 10 years, from the time of diagnosis, by systematic review of medical records from 90 patients with renal biopsies recruited to cohorts from two hospitals in Spain. Patients were classified into three groups for the analysis: CatPE >25% (C2), CatPE <25% (C1) and without this type of lesion (C0). The end point was renal survival defined by either >50% reduction in glomerular filtrate rate or end-stage renal disease. RESULTS: Renal survival at 5 years was 90% in group C0, 81% in group C1 and 31% in group C2 (P = 0.013). The presence of >25% crescents in the sample was associated with more severe disease when compared with <25%, as demonstrated by more interstitial fibrotic change and by lower estimated glomerular filtration rate at diagnosis, as well as worse renal function at 2 and 5 years. At the time of diagnosis and at 24 months, the group with IFTA >50% had poorer renal function compared with the other groups. CONCLUSIONS: We have confirmed the predictive value for renal survival of the revised Oxford classification in a two-centre study. We found worse renal outcome in patients with severe tubulointerstitial fibrosis and atrophy. Patients with extracapillary lesions >25% and IFTA >50% had a worse renal prognosis due to more severe kidney injury. These results contribute to patient stratification in immunoglobulin A nephropathy for therapeutic, epidemiological and basic research.

IgA Nephropathy Recurrence after Kidney Transplantation: Role of Recipient Age and Human Leukocyte Antigen-B Mismatch.

BACKGROUND: Recurrence of immunoglobulin (Ig)A nephropathy (rIgAN) is a growing cause of kidney allograft dysfunction. This study was aimed at investigating factors associated with rIgAN and the subsequent progression to end-stage renal disease (ESRD). METHODS: Retrospective study including consecutive patients with IgA nephropathy (IgAN) who received a kidney transplant in our center between 1992 and 2016 and had a renal biopsy by clinical indication. The date of detection of chronic kidney disease (CKD) 5 was used as renal outcome. RESULTS: Eighty-six kidney transplants were performed in patients with IgAN, 38 (44%) were from living donors (related n = 26). rIgAN was diagnosed in 23 allografts (27%). Renal function and proteinuria at the end of the follow-up period were worst in the rIgAN patients compared to those without rIgAN (2.2 vs. 1.4 mg/dL, p = 0.014, and 1.16 vs. 0.49 g/day, p = 0.005, respectively). Risk of rIgAN and progression to CKD 5 decreased with patient's age (hazard ratio [HR] 0.95, 95% CI 0.92-0.98, p = 0.002, and HR 0.97, 95% CI 0.83-0.97, p = 0.008 per year, respectively). Patients with rIgAN had a higher risk of progression to CKD 5 (HR 6.7, 95% CI 1.3-35.7, p = 0.025). Full donor-recipient mismatch in the human leukocyte antigen (HLA)-B loci decreased the risk of rIgAN (HR 0.22, 95% CI 0.06-0.76, p = 0.017). CONCLUSIONS: rIgAN was an independent risk factor for ESRD after renal allograft. Younger age increased the risk of rIgAN and CKD 5. Conversely, HLA-B mismatching was a potential protective factor for rIgAN of this glomerular disease.

Antiphospholipase 2 receptor antibody levels to predict complete spontaneous remission in primary membranous nephropathy.

BACKGROUND: M-type phospholipase A2 receptor (APLA2R) is considered the major antigen involved in the pathogenesis of adult primary membranous nephropathy (MN), which is the leading cause of non-diabetic nephrotic syndrome. Antibodies to this antigen have been proved to be an excellent biomarker of disease activity in primary MN. In fact, preliminary data suggest that the higher the antibody level the more proteinuria, and that a decrease in antibody level precedes the remission of proteinuria, but more solid evidence is needed. METHODS: The present work aims to characterize the predictive value of the level of antibodies against PLA2R as a biomarker of disease course and treatment response in a well-defined cohort of 62 patients from University Hospitals Clinic of Barcelona and Josep Trueta in Girona. The primary outcome was the appearance of a spontaneous complete remission (CR), defined as induction of a CR without the use of immunosuppressive agents. RESULTS: In common with other reports, this work confirms that spontaneous CR is more frequent in patients with low titre of APLA2R at diagnosis, but strikingly, in this cohort we found that spontaneous CR was achieved in patients with APLA2R levels <40 UI/mL. Furthermore, spontaneous CR were less frequently observed in patients with proteinuria >8 g/day. CONCLUSIONS: In conclusion, these findings point out the important role of APLA2R as a tool to predict the disease course and establish personalized therapeutic options at the moment of diagnosis of primary MN. Specifically, patients with low titre of APLA2R (<40 UI/mL) and proteinuria <4/day could obtain benefit of a longer period of follow-up with conservative treatment after diagnosis.

The utility of phospholipase A2 receptor autoantibody in membranous nephropathy after kidney transplantation.

Membranous nephropathy (MN) is estimated to cause end-stage renal disease in ∼ 5% of patients, in whom renal transplantation is the therapy of choice. Among patients receiving a transplant for MN, the disease will recur in the graft in 30-50%; among these, graft loss will occur in 50% within 10 years. Several studies have suggested that phospholipase A2 receptor autoantibody (aPLA2R) levels before transplantation might be useful in predicting recurrence, and their titration after transplantation is clinically relevant to assess the risk of recurrence and progression, to guide treatment indications and to monitor treatment response. In this review we describe the evolving role of aPLA2R as a biomarker in primary MN and its current usefulness in predicting recurrence of this autoimmune podocytopathy after renal transplantation.

Histopathological evaluation of pretransplant donor biopsies in expanded criteria donors with high kidney donor profile index: a retrospective observational cohort study.

There is no consensus on the allocation of renal transplants from expanded criteria donors (ECD). The Kidney Donor Profile Index (KDPI) is used without the need for pretransplant donor biopsies (PTDB). We explored whether PTDB based on Remuzzi Score (RS) allows identification of those marginal kidneys in the highest calculated KDPI risk group (>91%) that appropriate for single transplantation. A retrospective study was conducted of 485 consecutive kidneys procured from a single center and transplanted if the RS was ≤4. We compared 5-year kidney and patients survival between KDPI groups and between RS <4 or =4 in the highest KDPI group. The median KDPI (interquartile range) was 71 (66-76) for KDPI <80% (n = 77), 86 (81-90) for KDPI 81-90% (n = 82), and 97 (94-100) for KDPI >91% (n = 205). Patient survival at 5 years was 85.7%, 85.3%, and 76.09% (P = 0.058) and death-censored graft survival was 84.4%, 86.5%, 73.6% (P = 0.015), respectively for each KDPI group. In >91% calculated KDPI group, there were no differences in graft survival depending on the RS (<4 vs. =4) (P = 0.714). The implementation of PTDB based on RS used for allocation of organs with the highest KDPI range could support to the acceptance of suitable organs for single transplantation with good patient and graft survival rate.

ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis.

BACKGROUND: The phenotype of renal involvement in anti-neutrophil cytoplasmic antibodies (ANCA) vasculitis has a major influence on survival, and histological subgrouping of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate this histological subgrouping and to investigate the additional value of ANCA serotype in the prediction of renal outcome. METHODS: Data were retrospectively collected from the time of diagnosis by systematic review of medical records from 136 patients with renal biopsies recruited to cohorts from the UK and Spain, over 15 years. The end point, renal survival, was the composite of end-stage renal disease (ESRD) or death from any cause. The occurrence of ESRD, Stage 4 Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease, was assessed separately, in order to establish a severity index risk of chronic kidney disease. RESULTS: Renal survival at 5 years was 96% in the focal, 86% in the crescentic, 81% in the mixed and 61% in the sclerotic subgroups (P = 0.03). Myeloperoxidase (MPO)-ANCA was associated with more severe disease when compared with PR3-ANCA, as demonstrated by a lower frequency of focal and higher frequency of sclerotic subgroups, by more advanced interstitial fibrotic change and by lower glomerular filtration rate at diagnosis and worse renal function at 1 and 2 years. CONCLUSIONS: We have confirmed the predictive value for renal survival of the ANCA vasculitis histology classification in a multi-centre study. We found a worse renal outcome in patients with tubulointerstitial fibrosis and atrophy. MPO-ANCA positive patients had a worse renal prognosis due to more severe glomerular injury. These results contribute to patient stratification in renal vasculitis for therapeutic, epidemiological and basic research.