Development and Validation of a Nomogram for the Early Prediction of Iga Nephropathy in Primary Glomerulonephritis

Background: To make early prediction of immunoglobulin A nephropathy (IgAN) before renal biopsy, we developed and validated a new non-invasive nomogram for the early prediction of IgAN in primary glomerulonephritis (GN) in south China. Methods: A total of 431 patients were included in this study and additional 113 patients were included as the independent test cohorts to validate our results. A stepwise regression model was used for features selection. Multivariate logistic regression analysis with 5-fold cross validation was used to validate the result of the stepwise selection. Performance of the logistic regression model was assessed with respect to its calibration, discrimination, and clinical usefulness. Independent test was assessed. Results: We developed a model incorporating age of patients and four clinical chemistry signatures, including serum IgA, serum albumin (ALB), serum phosphorus (P) and 24-hour urinary protein (24hUpro) and presented with a nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) reached 0.89 (95% CI: 0.86–0.92) and 0.88 (95%: 0.85-0.92) in the training set and validation set, respectively. The model also had good performance in independent test cohorts (AUC of 0.82, 95% CI: 0.75–0.90). The DCA and calibration plot of the model also shows good performance. Conclusions: The logistic regression model presented in this study incorporates age of patients, IgA, ALB, P and 24hUpro and can be conveniently used to facilitate the individualized prediction of IgAN.

Pregnancy and delivery in women receiving maintenance hemodialysis in Japan: analysis of potential risk factors for neonatal and maternal complications

Introduction Average dialysis vintage in Japan is among the longest in the world, providing a unique opportunity to characterize pregnancy under conditions of long dialysis vintage. In 2017, we carried out a nationwide survey following up on a similar survey in 1996, in which we investigated the prevalence and outcomes of pregnancy in women undergoing dialysis and assessed risk factors associated with neonatal and maternal complications. Methods The target population was women aged 15–44 years undergoing maintenance dialysis between 2012 and 2016. The survey was conducted in 2693 dialysis units. Results A response was obtained from 951 dialysis units, yielding a target population of 1992 women of childbearing age receiving hemodialysis or peritoneal dialysis. Pregnancy occurred only among women receiving hemodialysis, with 25 pregnancies (1.26% in 5 years) being reported for 20 women. Detailed information about 19 pregnancies (mean age 34.6 ± 5.7 years at conception, mean dialysis vintage 8.4 ± 7.3 years) indicated 4 spontaneous abortions, 1 elective abortion, no neonatal deaths, and 14 surviving infants, including 5 full-term (≥ 37 weeks at birth), 2 late preterm (34–36), and 3 extremely preterm (< 28) cases. Neonatal complications occurred in the offspring of 3 mothers who had end-stage renal disease (ESRD) caused by primary glomerulonephritis and serum albumin levels (sAlb) ≤ 3.2 mg/dL in the first trimester. These mothers had started dialysis at 12, 17, and 30 years of age. ESRD caused by diabetic nephropathy or primary glomerulonephritis, age at conception ≥ 38 years, and sAlb ≤ 3.2 mg/dL were associated with maternal complications, although not significantly. Conclusions In this study, the pregnancy rate of Japanese women with ESRD was 0.25% per year. The study generates the hypothesis that ESRD caused by diabetic nephropathy and age at conception ≥ 38 years are potential risk factors for maternal complications but not for neonatal complications in dialysis patients, and that hypoalbuminemia is a potential risk factor for both kinds of complications. Graphic Abstract

History of IgA Nephropathy Mouse Models

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.

The Non-Coding RNA Landscape in IgA Nephropathy—Where Are We in 2021?

IgA nephropathy (IgAN) is the most commonly diagnosed primary glomerulonephritis worldwide. It is a slow progressing disease with approximately 30% of cases reaching end-stage kidney disease within 20 years of diagnosis. It is currently only diagnosed by an invasive biopsy and treatment options are limited. However, the current surge in interest in RNA interference is opening up new horizons for the use of this new technology in the field of IgAN management. A greater understanding of the fundamentals of RNA interference offers exciting possibilities both for biomarker discovery and, more importantly, for novel therapeutic approaches to target key pathogenic pathways in IgAN. This review aims to summarise the RNA interference literature in the context of microRNAs and their association with the multifaceted aspects of IgA nephropathy.

MO295RESULTS OF 30 YEARS OF RENAL BIOPSIES IN THE GENERAL HOSPITAL OF CIUDAD REAL. WHAT HAS CHANGED?

Background and Aims The renal biopsy (RB) has been performed in the General Hospital of Ciudad Real (HGUCR) since the year 1989. It allows kidney diseases to be diagnosed and treated and pronostics to be made. We will analyse the results of these 30 years as well as the evolution of the various parameters studied. Method Descriptive study of the RB carried out in the HGUCR between 1989 and 2019. Age, sex, clinical syndrome (CS) at the time of the RB, number of glomeruli and histological diagnosis will be analysed. The patients are divided into 3 groups according to age: children (&lt;15), adults (15-65) and the elderly (&gt;65). We will establish three periods of 10 years: period A (1989-1998), period B (1999-2008) and period C (2009-2019). The categorical variables are expressed as percentages and the quantitative variables average ± standard deviation. Statistical analysis with SPSS 25.0. Results 898 RB have been performed, average number of glomeruli 16, 70% of the RB with more than 10 glomeruli. The average age of the patients was 53±19 years old, 58% male. The most frequent CS was acute kidney failure (AKF) (35%), followed by nephrotic syndrome (NS) (30.5%), asymptomatic urinary disorders (19%), chronic kidney disease (11%), nephritic syndrome (3.6%), haematuria (0.7%) and arterial hypertension (0.7%). The most common in children were asymptomatic urinary disorders (50%), in adults NS (34%) and in the elderly AKF (55.5%). The predominant primary glomerulonephritis (GN): IgA nephropathy (IgAN) (15%), followed by membranous nephropathy (MN) (12%) and focal segmental glomerulosclerosis (FSGS) (11%). The most frequent secondary GN: vasculitis (11%) and lupus nephropathy (10%). 164 RB were performed in period A, 370 in period B and 346 in period C. In all three periods the predominant sex was male and the average age increased: 48 years old in A, 51 years old in B and 56 years old in C. Together with the increase in age, the indication of RB changes: NS in the first two periods and AKF in period C. The most frequent pathology in period A: FSGS (17%), IgAN (16%) in period B and IgAN (15%) followed by vasculitis (11%) in period C. Conclusion In the HGUCR the most common biopsied kidney pathology is IgAN, followed by MN. There has been an increase in the age of the patients as well as an increase in AKF and vasculitis. The KB constitutes a highly useful diagnostic test that allows us to establish prognostics and appropriate treatments.

MO311THE ASSOCIATION BETWEEN NEPHROTIC-RANGE PROTEINURIA AND OXALATE METABOLISM VIOLATION IN PATIENTS WITH PRIMARY GLOMERULONEPHRITIS

Background and Aims There is a general lack of scientific research on oxalate metabolism in primary glomerulonephritis (PGN) patients. The present study aimed to evaluate plasma oxalic acid (POx) concentration and urinary oxalate (UOx) excretion in PGN patients and determine the role of nephrotic syndrome in oxalate metabolism, which has never before been reported. Method A total of 100 participants were enrolled in this cross-sectional single-center study, including 76 PGN patients aged 41 ± 1.83 years and 24 healthy volunteers on a free-choice diet who served as a control reference group to evaluate POx concentration. Among the patients were 53 (69.7 %) patients with nephrotic syndrome (NS) and biopsy-proven PGN and 23 (30.3 %) patients with a clinical diagnosis of PGN. All patients were treated according to KDIGO Clinical Practice Guidelines for Glomerulonephritis. In addition to routine hematological and biochemical tests, POx concentration and UOx excretion were found in all study participants. POx was measured spectrophotometrically using a commercially available kit (MAK315, Sigma, Spain). Daily UOx excretion was determined using an oxalate oxidase/peroxidase reagent (BioSystems, Spain). Urine protein excretion (UPE) was measured in a 24-h urine collection. The glomerular filtration rate (GFR) was calculated using the CKD-EPI formula. The data were presented as the median and the interquartile ranges [Me (Q25-Q75)] and compared using the Mann-Whitney test. The Spearman correlation test and the partial correlation coefficient were used to evaluate the association between the examined markers. Results POx concentration was significantly higher in the patients with PGN compared with the healthy volunteers: 29.9 (14.9-51.7) vs 18.9 (16.2-23.8) µmol/L, p = 0.01. Although the patients with NS demonstrated a statistically higher GFR level compared with the patients with mild proteinuria [70.5 (47-87) vs 50 (22-76.2) mL/min/1.73 m2, p = 0.01], these patients also had the highest POx level (Fig. 1). Moreover, POx concentration was significantly associated with GFR (r = -0.27, p = 0.005), serum phosphate (r = 0.26, p = 0.007) and UPE (Fig. 2) levels. No significant differences were found in UOx excretions between the groups. However, the higher level of UPE was, the higher level of UOx was observed in the PGN patients with NS (Fig. 3). The partial correlation analysis confirmed a strong association between UPE and POx concentration independently of the patients’ age, gender, GFR and serum phosphate levels (r = 0.22, p = 0.04). Conclusion Nephrotic-range proteinuria was significantly associated with the elevation of POx concentration and UOx excretion in the PGN patients. More research with a larger cohort is needed to confirm this preliminary evidence and validate NS as a risk factor for oxalate metabolism violation in PGN patients.

Crosstalk between proteinuria, plasma oxalic acid and inflammation in glomerulonephritis patients: an exploratory study

In the present exploratory cross-sectional cohort study, we evaluated whether plasma and urine oxalate concentrations in patients with primary glomerulonephritis depend not only on the glomerular filtration rate but also on the proteinuria level and influence the inflammatory response. Methods. We enrolled 100 participants, including 76 patients with glomerulonephritis having chronic kidney disease stage (CKD) 1–3b (69.7% of them with nephrotic syndrome) and 24 healthy volunteers. We excluded patients with diabetes, cardiovascular disease and those with glomerulonephritis with an estimated GFR (eGFR) < 30 mL/min/1.73 m2. In addition to routine hematological and biochemical tests, plasma oxalate concentration, urinary oxalate excretion, and serum interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) levels were assessed in all study participants. Results. We observed that plasma oxalic acid concentration was significantly higher in patients with glomerulonephritis (19.0 [5.9–45.2] µmol/L) than in healthy volunteers (5.5 [3.8–7.3] µmol/L, p < 0.0001). Moreover, nephrotic proteinuria was significantly associated with plasma oxalic acid elevation independent of the patients’ age, sex, glomerular filtration rate, and body mass index (odds ratio = 1.42, 95% confidence interval = 1.13–1.77, p = 0.002). In turn, the increased plasma oxalic acid concentration was associated with high levels of serum IL-6 and MCP-1, which may be cardiovascular risk factors in patients with primary glomerulonephritis. Conclusions. Nephrotic proteinuria was significantly associated with the elevation of plasma oxalic acid concentration and hyperoxaluria in glomerulonephritis patients with CKD stages 1–3b. Plasma oxalate at least partly promotes inflammation, which may be a cardiovascular risk factor in patients with glomerulonephritis in the early stages of CKD. Future studies should recruit at least 156 participants to confirm our preliminary results, validate nephrotic proteinuria as a risk factor for oxalate metabolism violation or determine the role of impaired oxalate homeostasis in clinical outcomes in patients with glomerulonephritis.

Paraneoplastic immunoglobulin A nephropathy in a patient with lung adenocarcinoma: A case report and literature review

Immunoglobulin A nephropathy (lgAN) is a common primary glomerulonephritis, but paraneoplastic IgAN has been rarely reported. This current case report describes a 49-year-old male patient that was referred with proteinuria, oedema and hypoproteinaemia after lung cancer surgery and before the first cycle of chemotherapy. Renal biopsy confirmed lgAN. The patient received four cycles of chemotherapy (first cycle: pemetrexed + nedaplatin; second to fourth cycle: pemetrexed + carboplatin). The symptoms of IgAN were gradually relieved with additional cycles of chemotherapy. At the latest follow-up on 10 February 2020, there was no evidence of lung cancer recurrence and all symptoms of lgAN had disappeared. lgAN combined with lung adenocarcinoma is quite rare, which suggests that IgAN might be a paraneoplastic manifestation of lung adenocarcinoma.