Tubular biomarkers and histology in lupus nephritis.

INTRODUCTION: The relevance of tubulo-interstitial involvement for kidney prognosis has recently been emphasized, but validated biomarkers for predicting histology are still lacking. The aim of our study was to evaluate different serum and urinary markers of tubular damage in patients with lupus nephritis (LN) and to correlate them with kidney histopathology. METHODS: A single-center retrospective study was conducted from January 2016 to December 2021. Serum and urine samples were collected on the same day of kidney biopsy and correlated with histologic data from a cohort of 15 LN patients. We analyzed the following urinary markers, adjusted for urine creatinine: beta 2-microglobulin, alpha 1-microglobulin, NGAL, uKIM-1, MCP-1, uDKK-3, and uUMOD. The serum markers sKIM-1 and sUMOD were also analyzed. RESULTS: A positive and strong correlation was observed between the degree of interstitial fibrosis (rho = 0.785, p = .001) and tubular atrophy (rho = 0.781, p = .001) and the levels of uDKK3. uUMOD also showed an inverse and moderate correlation with interstitial fibrosis (rho = -0.562, p = .037) and tubular atrophy (rho = -0.694, p = .006). Patients with >10% cortical interstitial inflammation had higher levels of uKIM-1 [4.9 (3.9, 5.5) vs. 0.8 (0.6, 1.5) mcg/mg, p = .001], MCP-1 [3.8 (2. 3, 4.2) vs. 0.7 (0.3, 1.2) mcg/mg, p = .001], sKIM-1 [9.2 (5.9, 32.7) vs. 1.4 (0, 3.5) pg/mL, p = .001], and lower sUMOD [8.7 (0, 39.7) vs. 46.1 (35.7, 53) ng/mL, p = .028]. CONCLUSION: The use of specific urinary and serum biomarkers of tubular dysfunction or injury may help to predict certain histologic parameters in LN patients.

Tubular biomarkers in proteinuric kidney disease: histology correlation and kidney prognosis of tubular biomarkers.

Background: Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes. Methods: A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: beta 2 microglobulin (ß2-mcg), alpha 1 microglobulin (α1-mcg), neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (MCP-1), urinary Dickkopf-3 (uDKK3), uromodulin (urinary uUMOD), serum kidney injury molecule-1 (sKIM-1) and serum uromodulin (sUMOD). A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months. Results: Multivariate regression analysis identified sUMOD (ß-0.357, P < .001) and uDKK3 (ß 0.483, P < .001) as independent predictors of interstitial fibrosis, adjusted for age, estimated glomerular filtration rate (eGFR) and log proteinuria. Elevated levels of MCP-1 [odds ratio 15.61, 95% confidence interval (CI) 3.52-69.20] were associated with a higher risk of cortical interstitial inflammation >10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (hazard ratio 2.26, 95% CI 1.04-4.94) after adjustment for interstitial fibrosis, eGFR and proteinuria. Conclusions: Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.

Impact of preoperative exercise in not initially candidates to native arteriovenous fistulas.

BACKGROUND: Native autologous arteriovenous fistula (AVFn) is the preferred vascular access for hemodialysis due to its long term patency and low complication rate. A challenging limitation is the anatomical inability to perform AVFn and failure of maturation. Preoperative isometric exercise (PIE) can increase vascular calibers and improve the rate of distal AVF. However, it is unknown whether PIE might enhance the performance of AVFn in patients who are not initially candidates. METHODS: A retrospective observational study was conducted over a population of 45 patients evaluated in vascular access clinic, 23 were not initially candidates for radiocephalic (NRC-AVF) and 22 were not candidates for autologous fistula at all (NA-AVF). They were assigned to perform PIE with handgrip device and revaluated. RESULTS: After 4-8 weeks of PIE, a AVFn was performed in 16 patients from NA-AVF group and a radiocephalic AVFn was performed in 21 patients from NRC-AVF group. Both groups experienced a significant and similar increase in venous caliber 0.91 ± 0.43 mm in NA-AVF versus 0.76 ± 0.47 mm in NRC-AVF (p = 0.336) and arterial caliber 0.18 ± 0.24 mm versus 0.18 ± 0.21 mm (p = 0.928), respectively. Nevertheless, primary failure rate was significantly higher in NA-AVF (n = 8, 50%) than in NRC-AVF group (n = 3, 14.3%) (p = 0.030). After 6 months, the fistula usability for dialysis was only 50% in NA-AVF, while 86.7% were dialyzed by fistula in NRC-AVF group (p = 0.038). CONCLUSIONS: PIE allowed the allocation of an AVFn in patients not initially candidates, but entailed a high rate of maturation failure. Patients not candidates to radiocephalic AVF benefited from PIE and preserved a long term usability of AVF for dialysis.

Direct-acting antiviral therapy improves kidney survival in hepatitis C virus-associated cryoglobulinaemia: the RENALCRYOGLOBULINEMIC study.

BACKGROUND: Direct-acting antiviral agents (DAAs) have shown high rates of sustained virological response in chronic hepatitis C virus (HCV) infection. However, the influence of DAAs on the course of kidney involvement in HCV-associated mixed cryoglobulinaemia (HCV-MC) has been little studied. The aim of this study was to analyse the effects of antiviral treatment on kidney prognosis and evolution in patients diagnosed with HCV-MC. METHODS: The RENALCRYOGLOBULINEMIC study is an observational multicentre cohort study of 139 patients with HCV-MC from 14 Spanish centres. Clinical and laboratory parameters were measured before and after antiviral treatment. Primary endpoints were kidney survival and mortality after HCV-MC diagnosis. Secondary endpoints were clinical, immunological and virological responses after antiviral treatment. RESULTS: Patients were divided into three groups based on the treatment received: treatment with DAAs (n = 100) treatment with interferon (IFN) and ribavirin (RBV) (n = 24) and no treatment (n = 15). Patients were followed up for a median duration of 138 months (interquartile range 70-251. DAA treatment reduced overall mortality {hazard ratio [HR] 0.12 [95% confidence interval (CI) 0.04-0.40]; P < 0.001} and improved kidney survival [HR 0.10 ( 95% CI 0.04-0.33); P < 0.001]. CONCLUSIONS: Results from the RENALCRYOGLOBULINEMIC study indicated that DAA treatment in patients with HCV-MC improves kidney survival and reduces mortality.

Body composition and ventricular function in hemodialysis patients.

There is no evidence about the potential role of body composition on cardiovascular mortality in dialysis patients. The aim of this study was to assess the relationship between body composition and changes in ventricular function. We conducted an observational study over a population of 78 patients on chronic hemodialysis. A transthoracic echocardiogram and a bioimpedance were performed at the beginning and at the end of the study. The mean follow-up time was 30.6 months. Patients who had a higher fat tissue index (FTI > 9.20 kg/m2 ) experienced a worsening in right and left ventricular function. They developed a greater fall in tricuspid annular plane systolic excursion (TAPSE) (-1 ± 4.3 mm) and left ventricular ejection fraction (LVEF)(-4.2 ± 6.8%), compared to those with lower FTI (p = 0.032 and p = 0.045, respectively). No associations were found between any other echocardiography or body composition parameters and overall mortality. Patients with right ventricular dysfunction (determined as TAPSE) experienced a tendency to higher mortality rate along the study (HR for mortality of 13.5 (95% CI, 1.1-166.7; p = 0.041)]. A higher fat tissue index could be associated with a deleterious effect over right and left ventricular function in dialysis patients.

Thrombotic Microangiopathy in a Kidney Transplant Patient With COVID-19.

Kidney transplant recipients are at increased risk for infection, including coronavirus disease 2019 (COVID-19), given ongoing immunosuppression. In individuals with COVID-19, complications including thrombosis and endothelial dysfunction portend worse outcomes. In this report, we describe a kidney transplant recipient who developed severe thrombotic microangiopathy with a low platelet count (12 ×109/L), anemia (hemoglobin, 7.5 g/dL with 7% schistocytes on peripheral-blood smear), and severe acute kidney injury concurrent with COVID-19. The clinical course improved after plasma exchange. Given this presentation, we hypothesize that COVID-19 triggered thrombotic microangiopathy.

COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.

Molecular Regulation of Notch Signaling by Gremlin.

Gremlin is a member of the TGF-ß superfamily that can act as a BMP antagonist, and recently, has been described as a ligand of the vascular endothelial growth factor receptor 2 (VEGFR2). Gremlin shares properties with the Notch signaling pathway. Both participate in embryonic development and are reactivated in pathological conditions. Gremlin is emerging as a potential therapeutic target and biomarker of renal diseases. Here we review the role of the Gremlin-VEGFR2 axis in renal damage and downstream signaling mechanisms, such as Notch pathway.

Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome.

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.

Glomerulonefritis postinfecciosa IgA dominante secundaria a infección cutánea por Staphylococcus aureus resistente a meticilina / IgA dominant postinfectious glomerulonephritis secondary to cutaneous infection by methicillin-resistant Staphylococcus aureus

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Pentoxifylline, progression of chronic kidney disease (CKD) and cardiovascular mortality: long-term follow-up of a randomized clinical trial.

BACKGROUND: Pentoxifylline could reduce proteinuria and slow renal disease progression. We previously conducted a single-blind, randomized, controlled trial that showed that pentoxifylline decreases inflammatory markers and stabilizes renal function. SETTING AND PARTICIPANTS: 91 participants (46 in the pentoxifylline group and 45 in the control group) followed up for 7 additional years. STUDY DESIGN: Post hoc analysis of a long-term follow-up after completion of the 12-months trial. INTERVENTION: Pentoxifylline treatment (400 mg/twice a day) or standard treatment. OUTCOME: Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥ 50% decrease in estimated glomerular filtration rate) and cardiovascular mortality. RESULTS: During follow-up, a renal event was recorded in 24 patients from control group (13 initiated dialysis therapy and serum creatinine doubled in 11) and 11 patients from PTF group (7 initiated dialysis and serum creatinine doubled in 4) (log Rank: 5.822, p = 0.016). The possible protector effect of PTF was more significant in albuminuric patients and was independently of diabetes mellitus presence. Treatment with PTF reduced the renal events by 35% compared to the control group in a Cox model adjusted for diabetes mellitus, albuminuria and basal renal function (HR 0.65 (0.45-0.94), p = 0.022). Cardiovascular mortality was significantly reduced in PTF treatment (2 patients vs. 10 in control group) (log Rank 5.0977, p = 0.024). PTF treatment reduced cardiovascular mortality in 55% adjusted for diabetes mellitus and age (HR 0.45 (0.21-0.98), p = 0.044) (Table 3). LIMITATIONS: Small sample size, single center, not double blind and post hoc follow-up analysis. CONCLUSIONS: Long-term treatment with pentoxifylline may slow the rate of progression of kidney disease and reduce cardiovascular risk.