Hemodialysis-Associated Immune Dysregulation in SARS-CoV-2-Infected End-Stage Renal Disease Patients.

Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1ß, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1ß and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.

Role of non-alcoholic fatty liver disease in the evolution of renal function in patients with diabetes mellitus.

BACKGROUND: The increasing prevalence of type 2 diabetes mellitus (T2DM) has influenced in an increasing prevalence of chronic kidney disease (CKD). Little is known about the influence of non-alcoholic fatty liver disease (NAFLD) on the progression of CKD. The aim of this study was to analyse the role of NAFLD and its severity in the progression of renal function in patients with T2DM. METHODS: We conducted a retrospective and observational study including patients with T2DM and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2. NAFLD was defined as the presence of compatible ultrasonography and/or the presence of fibrosis using the NAFLD score. Patients were classified into three groups according to the NAFLD score: Group 1: <-1.85; Group 2: -1.85-0.18 and Group 3: >0.18. RESULTS: A total of 102 patients were included [67.6% males, median age 59 years [interquartile range (IQR) 53-64)], with a median time of T2DM evolution of 70 months (IQR 39-131). Group 3 had lower eGFR (84.8 ± 40.4 versus 71.4 ± 30.6 mL/min/1.73 m2; P = 0.03) and higher proteinuria at baseline (0.56 ± 0.77 versus 1.59 ± 2.70 g/24 h; P = 0.05). After a follow-up time of 75.8 ± 23.9 months, Group 3 had a significant decrease in eGFR (66.6 ± 33.3 versus 36.8 ± 23.1 mL/min/1.73 m2; P ≤ 0.01) and a higher risk of CKD progression [odds ratio 7.50 (95% confidence interval 2.76-20.35); P ≤ 0.001] defined as a decrease in eGFR of >50%. CONCLUSIONS: The presence of NAFLD with high-risk fibrosis confers higher risk of CKD progression in patients with T2DM. Therefore NAFLD should be a risk factor evaluated in these patients to optimize treatment.

Something new about prognostic factors for lupus nephritis? A systematic review.

BACKGROUND: Lupus nephritis (LN) affects 30-45% of patients with systemic lupus erythematosus (SLE) and causes great morbidity and mortality. About 10-25% of patients will develop chronic kidney disease (CKD), and it has been described a mortality of 10-20% at 10 years. The contribution of clinical and biological markers to the prediction of outcome is unclear. OBJECTIVE: To describe the factors, with measures of association, that predict the main outcomes of LN. MATERIAL AND METHODS: We have conducted a systematic review. Medline, Embase, and Cochrane Library were systematic searched from inception up to Oct 2019, with a strategy that included synonyms of all targeted outcomes of LN: (kidney failure, response to treatment, cardiovascular events, and mortality). Only studies with longitudinal prospective design or with warranties of unbiased recollection of the prognostic factors, where LN was confirmed by biopsy were included. Risk of bias was assessed with the New Castle Ottawa scale. Predictive factors and their effect measures were collected from each study. RESULTS: From 1221 studies identified, 25 studies were included, of which 15 were retrospective, nine prospective, and one was a trial extension study (range from 3 months to 11 years). The main predictive factors of renal response were serum creatinine (SCr) and glomerular filtration rate C3 levels, titer of anti-C1q, and anti-dsDNA antibodies. Renal histological findings such as class type (IV or V), tubulointerstitial or vascular lesions and chronicity index were risk factors for development of chronic kidney disease. The factors associated with persistence of activity were proteinuria, anti-dsDNA, anticardiolipin, anti C1q antibodies, and complement values. The factors associated to cardiovascular events and mortality were age, smoking, amount of proteinuria, and histological findings, such as vascular lesions. Meta-analysis was precluded given the heterogeneity of designs definitions and effect measures. CONCLUSIONS: Nowadays, we do not have new biomarkers that establish the renal prognosis of patients with LN. Classical clinical, renal, and histological markers are used in most studies. It is worth noting the heterogeneity of studies in the definition of renal outcomes, which complicates risk stratification in these patients.

Pre-transplant dialysis modality does not influence short- or long-term outcome in kidney transplant recipients: analysis of paired kidneys from the same deceased donor.

Previous studies have reported contradictory results regarding the effect of pre-transplant dialysis modality on the outcomes after kidney transplantation (KT). To minimize the confounding effect of donor-related variables, we performed a donor-matched retrospective comparison of 160 patients that received only one modality of pre-transplant dialysis (peritoneal dialysis [PD] and hemodialysis [HD] in 80 patients each) and that subsequently underwent KT at our center between January 1990 and December 2007. Cox regression models were used to evaluate the association between pre-transplant dialysis modality and primary study outcomes (death-censored graft survival and patient survival). To control for imbalances in recipient-related baseline characteristics, we performed additional adjustments for the propensity score (PS) for receiving pre-transplant PD (versus HD). There were no significant differences according to pre-transplant dialysis modality in death-censored graft survival (PS-adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [95% CI]: 0.25-1.68) or patient survival (aHR: 0.58; 95% CI: 0.13-2.68). There were no differences in 10-year graft function or in the incidence of post-transplant complications either, except for a higher risk of lymphocele in patients undergoing PD (odds ratio: 4.31; 95% CI: 1.15-16.21). In conclusion, pre-transplant dialysis modality in KT recipients does not impact short- or long-term graft outcomes or patient survival.

Predictors of response and relapse in patients with idiopathic membranous nephropathy treated with tacrolimus.

BACKGROUND: Although tacrolimus is recommended by KDIGO Clinical Practice Guideline for Glomerulonephritis for the treatment of idiopathic membranous nephropathy (MN), little is known about factors that influence response and relapse of the disease after tacrolimus therapy. METHODS: Multicentre study that collected 122 MN patients with nephrotic syndrome and stable renal function treated with tacrolimus. Duration of treatment was 17.6 ± 7.2 months, including a full-dose and a tapering period. RESULTS: The percentage of remission was 60, 78 and 84% after 6, 12 and 18 months of treatment, respectively. The amount of proteinuria at baseline significantly predicted remission, the lower the baseline proteinuria the higher the probability of remission. Only 10 patients (8%) received concomitantly corticosteroids, and their rate of remission was similar (80% at 18 months). Among responders, 42% achieved complete remission (CR) and 58% partial remission (PR). Almost half (44%) of the responder patients relapsed. The amount of proteinuria at the onset of tacrolimus tapering was significantly higher in relapsing patients. By multivariable analysis, the presence of a PR versus CR at the onset of tacrolimus tapering and a shorter duration of the tapering period significantly predicted relapses. Tolerance was good and the number of adverse events low. CONCLUSIONS: Tacrolimus monotherapy is an effective and safe option for the treatment of MN with stable renal function. Relapses are frequent in patients with PR and can be partially prevented by a longer tapering period.

Renoprotective effects of mineralocorticoid receptor blockers in patients with proteinuric kidney diseases.

BACKGROUND: Several studies have demonstrated a short-term antiproteinuric effect of mineralocorticoid receptor blockers (MRB) on proteinuric kidney diseases, but no information is available about the long-term persistence (>1 year) of such reduction in proteinuria and the long-term effects of MRB on renal function. METHODS: We prospectively studied the effects of adding spironolactone (25 mg/day) to 87 patients who maintained proteinuria higher than 1 g/day in spite of renin-angiotensin system blockade. The mean follow-up was 25 ± 15 (1-84) months. RESULTS: Estimated glomerular filtration rate (eGFR) showed an acute fall in the first month of treatment (5.1 ± 9.4 mL/min/1.73 m(2)), but it remained stable thereafter (+0.04 ± 0.7 mL/min/1.73 m(2)/month), with a significant difference with respect to the eGFR slope during the 12-month pre-treatment period. The initial eGFR fall predicted a more stable course of renal function, the higher the eGFR initial fall, the better the long-term evolution of eGFR. Proteinuria showed an important and sustained reduction since the first month of treatment. At the end of follow-up, it had decreased by 61% (43-77%) with respect to baseline values. The antiproteinuric and renoprotective influence of spironolactone was also observed in diabetic patients and in patients with renal function impairment, although tolerance was poorer among the latter. CONCLUSIONS: Spironolactone induces an initial acute fall in eGFR that predicts a later favourable influence on the course of renal function and a remarkable and sustained reduction in proteinuria.

[Atheroembolic renal disease: analysis of clinical and therapeutic factors that influence its progression]. / Enfermedad renal ateroembólica: un análisis de los factores clínicos y terapéuticos que influyen en su evolución.

Cholesterol embolism is a disease caused by distal showering of cholesterol crystal released from disintegration of arterial atheromatous plaques. It may occur spontaneously or more often after invasive vascular procedures or thrombolytic/anticoagulant agents. Forty five cases were diagnosed between 1989 and 2005 in three Spanish hospitals. The diagnosis was confirmed by histology or diagnostic ophthalmoscopic findings. The majority were male (93.3%), elder (55.5% were older than 70 years), smoker (91.1%), had hypertension (95.6%), with high prevalence of cardiovascular risk factors. At the time of diagnosis all patients presented acute renal failure. Mean serum creatinine at diagnosis was 4.3+/- 2.4 mg/dl. The acute renal failure was accompanied with eosinophilia (64.4%) and cutanous lesions (57.7%). 20% of cases occur spontaneously and 46.7% after endovascular manipulation (coronary angiography/arteriography) and only 8% after changes in anticoagulant treatment. After a follow-up of 12 +/- 16.3 months the 55.6% of patients need chronic dialysis, 64.4% died, 8 of them after the beginning of dialysis. Nine patients recovered renal function, with a mean creatinine of 3 +/- 1.7 mg/dl at the end of follow-up. The cardiovascular comorbididy and the clinical severity of the embolism don t have impact in the renal or patient survival. Renal survival (Kaplan-Mier) were better in spontaneous than in iatrogenic cholesterol embolism. Fifteen of 45 patients were treated with steroids. In treated patients we observed a high incidence of death (73.3% versus 60%) and fewer recovery of renal function (13.3% versus 23%), without statistical significance. The mean time to dialysis was shorter in treatment patients (p= 0.017). Statins treatment was not associated with outcome (renal or individual). In summary, atheroembolic renal disease represents an acute renal failure with special characteristics. Renal and individual outcome is poor, but some patients have spontaneous recovery of renal function. Renal survival was significantly better in spontaneous disease. We don t observe beneficial effect of steroid treatment.

Malignant hypertension in HIV-associated glomerulonephritis.

BACKGROUND: Glomerular diseases other than HIVAN (HIV-associated nephropathy) are common among HIV patients but the information about their clinical characteristics and prognosis is very scarce. We have observed several HIV patients with glomerulonephritis in whom malignant hypertension (MHT) was the first clinical manifestation. METHODS: All HIV-infected individuals with a biopsy-proven glomerulonephritis at our hospital were reviewed. Information about clinical characteristics, histopathologic data and outcome was collected. The incidence of MHT among HIV and non-HIV patients with glomerulonephritis was studied. RESULTS: Thirty HIV patients with glomerulonephritis were identified. Ten of them (33%) presented with MHT (severe hypertension and grade III hypertensive retinopathy). In comparison with patients without MHT, they showed a significantly higher blood pressure at presentation, a higher finding of IgA nephropathy (50% versus 15%; P < 0.05) and of malignant nephrosclerosis (60% versus 0%; P < 0.05) in renal biopsies, a higher viral load and a lower CD4+ cell count at the end of follow-up and a worse patient and renal survival: six patients (60%) started chronic dialysis and seven (70%) died after a follow-up of 11.8 +/- 16.2 and 39 +/- 35 months, respectively. Co-infection by HCV (hepatitis C virus) and HBV (hepatitis B virus) was very frequent among patients with malignant hypertension. The incidence of malignant hypertension among non-HIV patients with glomerulonephritis was significantly lower than that among HIV-infected patients. CONCLUSIONS: Malignant hypertension is a common presentation of patients with HIV-associated glomerulonephritis, particularly in those with IgA nephropathy, and is associated with a very poor patient and renal survival.

Hepatitis C-induced renal disease in patients with AIDS: an emergent problem.

Cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) is the more characteristic renal disease associated with hepatitis C virus (HCV) infection. Patients infected with human immunodeficiency virus (HIV) can present, in addition to HIV-associated nephropathy, different types of immune complex glomerulonephritis, including MPGN, IgA nephropathy, non-collapsing focal segmental glomerulosclerosis, membranous nephropathy and lupus-like glomerulonephritis. On the other hand, the incidence of hypertensive nephrosclerosis, diabetic nephropathy and decreased renal function similar to that of elderly patients is increasingly recognized among HIV-infected patients. In spite of the fact that HCV coinfection in HIV patients is a very common problem, affecting approximately 30% of HIV-infected patients, information about the role of HCV in renal diseases of HIV-infected patients is scant. A large proportion of HIV patients with glomerular diseases are coinfected with HCV, and the latter is likely the responsible agent in those cases of cryoglobulinemic MPGN reported in HIV-infected patients. Participation of HCV in other types of HIV-related glomerular diseases is uncertain. Patient and renal survival in glomerular diseases of patients coinfected with HIV and HCV is very poor, but some studies suggest that antiretroviral therapy might change this dismal prognosis. Information about the effect of specific anti-VHC therapy or immunosuppressive agents in these patients is very limited.

Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients.

BACKGROUND AND OBJECTIVES: Calcineurin inhibitors (CNIs) induce remission of proteinuria in most nephrotic patients with membranous glomerulonephropathy (MGN). However, 60% of patients become treatment dependent and are at risk of chronic nephrotoxicity. The aim of this study was to evaluate the efficacy of rituximab in patients with long-term dependence on CNIs. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Thirteen patients with MGN, normal renal function, and proven dependence on CNIs, despite previous treatment with other immunosuppressant drugs, received a single trial of four weekly doses of rituximab (375 mg/m(2)). Outcome measures were the percentage of patients with CNI withdrawal and no evidence of relapse and the percentage of patients with complete or partial remission 30 mo after CNI withdrawal. RESULTS: After rituximab, proteinuria decreased significantly (2.5 +/- 0,76 basal versus 0.85 +/- 0.17 at 6 mo; P = .0003). CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse. After CNI withdrawal, GFR increased significantly (90.3 +/- 15 basal to 106.4 +/- 20 at 3 mo with a mean increase of 15.3% [range 0-20]). Three patients suffered a relapse of nephrotic proteinuria 19, 23, and 28 mo after rituximab treatment; all were successfully treated with a second course of rituximab. At 30 mo, all patients were in remission. CONCLUSIONS: In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.