The role of mononuclear phagocyte system in IgA nephropathy: pathogenesis and prognosis

Although the “multiple hits” theory is a widely accepted pathogenesis in IgA nephropathy (IgAN), increasing evidence suggests that the mononuclear/macrophage system plays important roles in the progression of IgAN; however, the exact mechanism is unclear. In the present study, we explored 1,067 patients in 15 studies and found that the number of macrophages per glomerulus was positively related with the degree of hematuria, and the macrophages in the glomeruli were mainly related to mesangial proliferation (M) in renal biopsy. In the tubulointerstitium, macrophages were significantly paralleled to tubulointerstitial α-SMA and NF-kB expression, tubulointerstitial lesion, tubule atrophy/interstitial fibrosis (T), and segmental glomerulosclerosis (S). In the glomeruli and tubulointerstitium, M1 accounted for 85.41% in the M classification according to the Oxford MEST-C, while in the blood, M1 accounted for 100%, and the patients with low CD89+ monocyte mean fluorescence intensity displayed more severe pathological characteristics (S1 and T1-2) and clinical symptoms. M1 (CD80+) macrophages were associated with proinflammation in the acute phase; however, M2 (CD163+) macrophages participated in tissue repair and remodeling, which correlated with chronic inflammation. In the glomeruli, M2 macrophages activated glomerular matrix expansion by secreting cytokines such as IL-10 and tumor necrosis factor-β (TGF-β), and M0 (CD68+) macrophages stimulated glomerular hypercellularity. In the tubulointerstitium, M2 macrophages played pivotal roles in renal fibrosis and sclerosis. It is assumed that macrophages acted as antigen-presenting cells to activate T cells and released diverse cytokines to stimulate an inflammatory response. Macrophages infiltrating glomeruli destroy the integrity of podocytes through the mesangio-podocytic-tubular crosstalk as well as the injury of the tubule

Efficacy and Safety of Agents in IgA Nephropathy: An Update Network Meta-Analysis

Background/Aims: The present network meta-analysis of randomized controlled trials (RCTs) was to explore the efficacy and safety of different pharmacologic interventions in IgA nephropathy with proteinuria more than 0.75 g/d. Methods: We systematically searched the Cochrane Library, Embase, and PubMed database for studies compared the rate of clinical remission and/or serious adverse events in IgA nephropathy patients with proteinuria (> 0.75 g/d) up to August 1, 2018. We ranked the comparative effects of all drugs against placebo on the surface under the cumulative ranking area (SUCRA) probabilities. Results: There were 29 RCTs comprising 2517 participants included for the comparisons of 9 interventions. The rank of the most effective treatments for inducing clinical remission was renin-angiotensin system inhibitors (RASi) in combination with steroid, tonsillectomy combined with steroid pulse therapy, and azathioprine plus RASi with SUCRA of 82.9%, 80.5%, and 67.6%, respectively. RASi in combination with steroid (SUCRA 3.9%) was the most effective in prevention of end-stage renal disease or doubling serum creatinine, followed by RASi monotherapy (SUCRA 38.4%) and azathioprine combined with steroid (SUCRA 49.0%). As for the occurrence of serious adverse events, azathioprine combined with RASi (SUCRA 88.0%) and steroid plus RASi (SUCRA 74.6%) showed the first and second highest incidence of adverse events, respectively. Conclusion: RASi combined with steroid demonstrated the most effective therapeutic approach for IgA nephropathy patients in terms of reducing proteinuria and stabilizing renal function

New-Onset Acute Interstitial Nephritis Post-SARS-CoV-2 Infection and COVID-19 Vaccination: A Panoramic Review

Abstract The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has posed a considerable challenge to global healthcare. Acute interstitial nephritis (AIN) post SARS-CoV-2 infection and vaccination has been reported, but its clinical features and pathogenesis remained unclear. We reviewed so far the largest 22 cases of AIN post SARS-CoV-2 infection and 36 cases of AIN following COVID-19 vaccination. The onset of AIN was mainly related to messenger RNA vaccines (52.8%). Apart from fever, proteinuria (45.5%) was the main manifestation of AIN post SARS-CoV-2 infection, left acute kidney injury (AKI, 63.9%) in patients post COVID-19 vaccination. The potential mechanism of vaccination induced AIN was conjugating vaccines with proteins to form a hapten, which activated dendritic cells and promoted a cascade immunological reaction leading to AIN

New-Onset Acute Kidney Disease Post COVID-19 Vaccination

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an exceptional setback to the global economy and health. Vaccination is one of the most effective interventions to markedly decrease severe illness and death from COVID-19. In recent years, there have been increasingly more reports of new acute kidney injury (AKI) after COVID-19 vaccination. Podocyte injury, IgA nephropathy, vasculitis, tubulointerstitial injury, and thrombotic microangiopathy appear to be the main pathological phenotypes. Nonetheless, whether the link between the COVID-19 vaccine and acute kidney disease (AKD) is causal or coincidental remains to be verified. Here, we generalize some hypotheses for the emergence of AKD and its pathogenesis in response to certain COVID-19 vaccines. In fact, the enormous benefits of mass vaccination against COVID-19 in preventing COVID-19 morbidity and mortality cannot be denied. The purpose of this review is to assist in the clinical assessment and management of AKD following COVID-19 vaccination

Clinical Utility of Serum Cystatin C in Predicting Diabetic Nephropathy Among Patients with Diabetes Mellitus: a Meta-Analysis

Background/Aims: Clinically, there is lack of predictors for diabetic nephropathy (DN) in diabetes mellitus (DM) without microalbuminuria, macroalbuminuria or retinopathy. Methods: PubMed, Chinese Biomedical Database, Cochrane Library, EMBASE and Elsevier Database were searched from inception to August 13, 2016. Studies involving patients with DM and containing data on cystatin C measurements and the measured glomerular filtration rate (mGFR) were included. Pooled sensitivity, specificity, positive predictive value, negative predictive value and other diagnostic indices were evaluated using a random effect model. Results: The meta-analysis enrolled 9 studies with 1417 patients. The pooled sensitivity and specificity of serum cystatin C for predicting DN were 0.88 (95% CI 0.85 - 0.91) and 0.85 (95% CI 0.82 - 0.87), respectively. The pooled positive and negative predictive values of serum cystatin C for predicting DN were 7.04 (95% CI 4.33 - 11.43) and 0.13 (95% CI 0.09 - 0.20), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.9549, and the diagnostic odds ratio was 66.80 (95% CI 27.92 - 159.86). Conclusion: Serum cystatin C is an early predictor of DN among patients with DM

SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney disease

Abstract Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium–glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc. Simultaneous use of SGLT-2 inhibitors and renin–angiotensin–aldosterone system (RAAS) blockers are novel strategies to slow the progression of DKD via reducing inflammatory and fibrotic markers induced by hyperglycaemia more than either drug alone. The available population and animal based studies have described SGLT2 inhibitors plus RAAS blockers. The present review was to systematically review the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and especially the angiotensin-converting enzyme inhibitors/angiotensin receptor blockers

Early versus late initiation of renal replacement therapy impacts mortality in patients with acute kidney injury post cardiac surgery: a meta-analysis

Abstract Background Acute kidney injury (AKI) is a common clinical complication of cardiac surgery and increases mortality and hospitalization. We aimed to explore and perform an updated meta-analysis of qualitative and quantitative evaluations of the relationship between early renal replacement therapy (RRT) and mortality. Methods We searched the Chinese Biomedical Database, the Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed. Results Fifteen studies (five randomized controlled trials (RCTs), one prospective cohort and nine retrospective cohorts) including 1479 patients were identified for detailed evaluation. The meta-analysis suggested that early RRT initiation reduced 28-day mortality (odds ratio (OR) 0.36; 95% confidence interval (CI) 0.23 to 0.57; I 2 60%), and shortened intensive care unit (ICU) length of stay (LOS) (mean difference (MD) -2.50; 95% CI -3.53 to -1.47; I 2 88%) and hospital LOS (MD -0.69; 95% CI -1.13 to -0.25; I 2 88%), and also reduced the duration of RRT (MD -1.18; 95% CI -2.26 to -0.11; I 2 69%), especially when RRT was initiated early within 12 hours (OR 0.23; 95% CI 0.08 to 0.63; I 2 73%) and within 24 hours (OR 0.52; 95% CI 0.28 to 0.95; I 2 58%) in patients with AKI after cardiac surgery. Conclusions Early RRT initiation decreased 28-day mortality, especially when it was started within 24 hours after cardiac surgery in patients with AKI

Glycated Albumin Versus HbA1c in the Evaluation of Glycemic Control in Patients With Diabetes and CKD

Introduction: It is inaccurate to assess blood glucose with glycated hemoglobin (HbA1c) in patients with diabetes and chronic kidney disease (CKD), and whether glycated albumin (GA) is better than HbA1c in these patients remains unclear. Methods: We searched PubMed, Embase, Web of Science, Scopus, the Cochrane Library, and MEDLINE to July 2017 for studies that investigated the correlation between GA or HbA1c and the average glucose levels (AG) relevant to this theme. Statistical analysis was performed using RevMan5.3 and Stata12.0. The outcome was the correlation coefficient between GA or HbA1c and AG. For the first time, we made a comparison of GA and HbA1c in different CKD stages. Results: A total of 24 studies with 3928 patients were included. Early stages of CKD refer to CKD stage 1 to 3. Advanced CKD refer to CKD stage 4 and 5 including patients receiving dialysis. The meta-analysis suggested that in early stages of CKD, the pooled R between GA and AG was 0.61 (95% CI = 0.49−0.73) and 0.71 (95% CI = 0.55−0.87) for HbA1c (P > 0.05). In advanced CKD patients, the pooled R between GA and AG was 0.57 (95% CI = 0.52−0.62), and 0.49 (95% CI = 0.45−0.52) for HbA1c (P = 0.0001). Conclusion: GA is superior to HbA1c in assessing blood glucose control in diabetes patients with advanced CKD. Keywords: chronic kidney disease, diabetes mellitus, glycated albumin, HbA1

New-Onset and Relapsed Membranous Nephropathy post SARS-CoV-2 and COVID-19 Vaccination

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak and COVID-19 vaccination, new-onset and relapsed clinical cases of membranous nephropathy (MN) have been reported. However, their clinical characteristics and pathogenesis remained unclear. In this article, we collected five cases of MN associated with SARS-CoV-2 infection and 37 related to COVID-19 vaccination. Of these five cases, four (4/5, 80%) had acute kidney injury (AKI) at disease onset. Phospholipase A2 receptor (PLA2R) in kidney tissue was negative in three (3/5, 60%) patients, and no deposition of virus particles was measured among all patients. Conventional immunosuppressive drugs could induce disease remission. The underlying pathogenesis included the subepithelial deposition of viral antigens and aberrant immune response. New-onset and relapsed MN after COVID-19 vaccination generally occurred within two weeks after the second dose of vaccine. Almost 27% of patients (10/37) suffered from AKI. In total, 11 of 14 cases showed positive for PLA2R, and 20 of 26 (76.9%) presented with an elevated serum phospholipase A2 receptor antibody (PLA2R-Ab), in which 8 cases exceeded 50 RU/mL. Conventional immunosuppressive medications combined with rituximab were found more beneficial to disease remission for relapsed patients. In contrast, new-onset patients responded to conservative treatment. Overall, most patients (24/37, 64.9%) had a favorable prognosis. Cross immunity and enhanced immune response might contribute to explaining the mechanisms of MN post COVID-19 vaccination