Clinical significance of massive proteinuria in primary IgA nephropathy with and without nephrotic syndrome: a single center cohort study.

BACKGROUND: Both primary IgA nephropathy (IgAN) with and without nephrotic syndrome (NS) can present massive proteinuria (24-h urinary protein ≥3.5 g/d). The clinical significance of massive proteinuria may be different in the two entities and needs further research. METHODS: Data of 1870 patients with biopsy-proven IgAN in our hospital from January 2011 to December 2022 was retrospectively reviewed. A total of 242 IgAN patients with massive proteinuria were enrolled. Patients who presented with nephrotic syndrome at renal biopsy were included in the IgAN with NS cohort (IgAN-NS). The IgAN with nephrotic-range proteinuria cohort (IgAN-NR) consisted of 1:1 matched cases from the remaining according to age, gender, estimated glomerular filtration rate (eGFR) at baseline, and follow-up time. The clinical and pathological characteristics between the two cohorts were analyzed. RESULTS: The IgAN-NS had a significantly higher proteinuria level than the IgAN-NR (p < .001). Cluster analysis revealed that proteinuria was associated with lipids in IgAN-NS, while it was associated with inflammatory indicators in IgAN-NR. When the complete remission of proteinuria (CR) was not achieved, the Kaplan-Meier analysis showed the prognosis of IgAN-NS was significantly worse than that of IgAN-NR (p = .04). Then, our GLMM model and line chart showed that the serum albumin level of the IgAN-NR was always evidently higher than that of the IgAN-NS while the significant difference in urinary albumin/creatinine ratio between the two cohorts gradually disappeared during the short-term follow-up (1 year). Moreover, the Cox regression analysis showed that the increased serum albumin was an independent protective factor for the poor outcomes (eGFR decreased from the baseline ≥ 30% continuously or reached end-stage renal disease [ESRD]). CONCLUSION: The IgAN-NS had poorer clinicopathologic manifestation than IgAN-NR, including severer massive proteinuria. When the CR was not achieved, the prognosis of IgAN-NS was inferior to that of the IgAN-NR.

Clinical Significance of Persistent Hematuria Degrees in Primary IgA Nephropathy: A Propensity Score-Matched Analysis of a 10-Year Follow-Up Cohort.

INTRODUCTION: The clinical significance of persistent hematuria degrees has not been expounded in primary IgA nephropathy (IgAN) and requires further research. METHODS: From January 2003 to May 2022, a total of 684 IgAN patients with persistent hematuria were enrolled to conduct a retrospective single-center study. Patients whose hematuria degree at baseline was higher than the second tertiles of the whole were included in the high-degree hematuria cohort (Hh), and the low-degree hematuria cohort (Lh) was constructed with 1:1 matched cases from the rest according to age, gender, and estimated glomerular filtration rate (eGFR) at baseline and follow-up time. Survival was determined using the Kaplan-Meier method (K-M) and generalized linear mixed-effects model (GLMM). Risk factors for survival were determined according to the Cox proportional hazards model. RESULTS: Both the Hh and Lh consisted of 228 cases. While the demographic data and the renal function at baseline were matched, both the K-M (p = 0.02) and GLMM (p = 0.04) proved that the prognosis of the Hh was significantly worse than that of the Lh within 10 years of follow-up. The higher persistent hematuria degree was an independent risk factor (3.93; 95% confidence interval, 1.33-11.6) associated with reaching the endpoint (eGFR decreased from the baseline ≥30% continuously or reached end-stage renal disease [ESRD]). The Hh had a significantly higher proportion of crescent (p = 0.003). The prognosis of the Hh was significantly worse than that of the Lh when accompanied by the crescent and presented an indistinct difference if the crescent was absent. CONCLUSIONS: The clinicopathologic manifestation of IgAN patients with persistent high-degree hematuria was severer, and the prognosis was worse than those with persistent low-degree hematuria.

Clinical significance of intrarenal vascular lesions in non-hypertensive patients with IgA nephropathy.

BACKGROUND: The clinical significance of intrarenal vascular lesions has not been elucidated in primary IgA nephropathy (IgAN), especially in non-hypertensive subjects. METHODS: From January 2003 to December 2020, data of 3435 patients with biopsy-proven IgAN were reviewed. Two hundred-forty non-hypertensive patients who met the criteria for IgAN and had intrarenal vascular lesions (IgAN-vas) were selected. The control cohort was constructed with 1:1 matched cases of non-hypertensive IgAN patients without vascular lesions according to age, gender, estimated glomerular filtration rate (eGFR) and follow-up time. RESULTS: The IgAN-vas cohort had significantly higher serum uric acid levels than the control IgAN cohort (P < 0.05); glomerulosclerosis was more common in IgAN-vas patients. Moreover, cluster analysis indicated that the serum uric acid level was associated with serum creatinine (s-Cr) levels in IgAN-vas while it was associated with serum lactate dehydrogenase (LDH) levels in control cases with IgAN. Both Kaplan-Meier analysis and generalized linear mixed-effects models revealed that the prognosis of the IgAN-vas cohort was significantly worse than that of the IgAN cohort after > 5 years of follow-up. Intimal thickening was an independent risk factor associated with reaching the endpoint (eGFR decrease ≥ 30% from the baseline or reaching end-stage renal disease [ESRD] or death). CONCLUSIONS: The prognosis of non-hypertensive patients with IgAN-vas was worse than that of matched individuals with IgAN. The clinicopathologic manifestation of IgAN-vas was more severe, and included a higher proportion of glomerulosclerosis, and a higher serum uric acid level correlated with renal function impairment.

Clinicopathologic and Prognostic Study of Primary IgA Nephropathy With Light Chain λ Restriction in the Mesangial Deposits.

Introduction: Primary IgA nephropathy (IgAN) with light chain λ restriction in the mesangial deposits (IgAN-λ) has unique immunofluorescence (IF) features. Nevertheless, its clinicopathology and prognosis are still ambiguous. Methods: From January 2002 to December 2020, the clinical and pathologic data of 3872 patients who were diagnosed with having primary IgAN by renal biopsy in our hospital were reviewed. A total of 187 patients who met the selection criteria for IgAN-λ were enrolled to conduct a retrospective single-center study. The selection criteria were that IF features conform to light chain λ restriction in the mesangial deposits. According to age, sex, renal function (estimated glomerular filtration rate [eGFR]), and follow-up time, the control group was constructed with 1:3 matched cases of IgAN. The clinicopathologic and prognostic differences between the 2 groups were analyzed. Results: Compared with that in the IgAN group, the serum fibrinogen level in the IgAN-λ group was significantly higher (P < 0.001). Furthermore, cluster analysis indicated the different clusters involved in fibrinogen between the IgAN-λ and IgAN groups and that fibrinogen is associated with factors reflecting renal function in IgAN-λ but proteinuria levels in IgAN. The light chain λ deposit in the mesangium is associated with the formation of crescents in those with IgAN-λ, but complement C3 deposition in those with IgAN. Our Kaplan-Meier analysis revealed that the prognosis of the IgAN-λ group was significantly worse than that of the IgAN group within >6 years of follow-up (P = 0.02). The multi-Cox analysis revealed that the light chain λ restriction in the mesangial deposits was an independent risk factor for poor outcomes (eGFR decreased from the baseline ≥ 30% continuously or reached end-stage renal disease [ESRD] or died). Conclusion: The prognosis of those with IgAN-λ was worse than that of those with IgAN, which may be attributed to the light chain λ restriction in the mesangial deposits inducing a significant systemic inflammation manifested as severe clinical features and frequent crescent.

Dysregulation of tRNA-derived small RNAs and their potential roles in lupus nephritis.

OBJECTIVE: Lupus nephritis (LN) is a major end-organ complication of systemic lupus erythematosus (SLE), and the molecular mechanism of LN is not completely clear. Accumulating pieces of evidence indicate the potential vital role of tRNA-derived small RNAs (tsRNAs) in human diseases. Current study aimed to investigate the potential roles of tsRNAs in LN. METHODS: We herein employed high-throughput sequencing to screen the expression profiles of tsRNAs in renal tissues of the LN and control groups. To validate the sequencing data, we performed quantitative real-time PCR (qRT-PCR) analysis. Correlational analysis of verified tsRNAs expression and clinical indicators was conducted using linear regression. The potential target genes were also predicted. The biological functions of tsRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: Our findings revealed that the expression profiles of tsRNAs were significantly altered in the kidney tissues from LN patients compared with control. Overall, 160 tsRNAs were significantly dysregulated in the LN group, of which 79 were upregulated, whereas 81 were downregulated. Subsequent qRT-PCR results confirmed the different expression of candidate tsRNAs. Correlation analysis results found that expression of verified tsRNAs were correlated to clinical indicators. The target prediction results revealed that verified tsRNAs might act on 712 target genes. Further bioinformatics analysis uncovered tsRNAs might participate in the pathogenesis of LN through several associated pathways, including cell adhesion molecules, MAPK signaling pathway, PI3K-Akt signaling pathway and B cell receptor signaling pathway. CONCLUSION: This study provides a novel insight for studying the mechanism of LN.

Clinicopathological and prognostic study of IgA-dominant postinfectious glomerulonephritis.

BACKGROUND: The clinicopathological and prognostic features of IgA-dominant postinfectious glomerulonephritis and its difference from the primary IgA nephropathy remains to be investigated. METHODS: The clinical and pathological data of 6542 patients who underwent renal biopsy from 2009 to 2020 in our hospital were reviewed and 50 patients who met the selection criteria of IgA-dominant postinfectious glomerulonephritis were enrolled to conduct a retrospective and observational single-center study. The selection criteria were: meet the characteristics of IgA dominance or codominance in immunofluorescence, and conform to 3 of the following 5 criteria: 1.Clinical or laboratory evidence show that there is infection before or at the onset of glomerulonephritis; 2.The level of serum complement decreased; 3.Renal pathology is consistent with endocapillary proliferative glomerulonephritis; 4. Glomerular immunofluorescence staining showed complement C3 dominance or codominance; 5. Hump-like subepithelial immune complex deposition was observed under electron microscopy. According to age, sex, renal function (estimated glomerular filtration rate, eGFR) and follow-up time, the control group was constructed with 1:3 matched cases of primary IgA nephropathy. The clinicopathological and prognostic differences between the two groups were analyzed. RESULTS: The most common histological pattern of IgA-dominant postinfectious glomerulonephritis was acute endocapillary proliferative glomerulonephritis and exudative glomerulonephritis. Immunofluorescence showed mainly IgA deposition or IgA deposition only, mainly deposited in the mesangial area (deposition rate 100 %), with typical C3 high-intensity staining (intensity++~+++), mainly deposited in the mesangial area (deposition rate 92.0 %). The fluorescence intensity of kappa is usually not weaker than lambda. The probability of the appearance of typical hump-like electron deposition under electron microscopy is low. Compared to primary IgA nephropathy, patients with IgA-dominant postinfectious glomerulonephritis had higher proportion of crescents (p = 0. 005) and endocapillary hypercellularity (p < 0.001) in pathological manifestations. Using serum creatinine level doubled of the baseline or reached end-stage renal disease as the endpoint, the prognosis of IgA-dominant postinfectious glomerulonephritis patients was worse than that of primary IgA nephropathy patients (p = 0.013). CONCLUSIONS: The clinicopathological features of patients with IgA-dominant postinfectious glomerulonephritis was different from that of primary IgA nephropathy, and the prognosis was worse.

Sources and burial fluxes of sedimentary organic carbon in the northern Bering Sea and the northern Chukchi Sea in response to global warming.

The Arctic and subarctic seas are the major CO2 sink areas on earth. In this study, the vertical variation characteristics of organic carbon, total nitrogen and their ratio (Corg/Nt), stable isotopes δ13C and δ15N, and BIT (branched and isoprenoid tetraether) index of GDGTs (glycerol dialkyl glycerol tetraethers) in combination with 210Pb-dating were used to analyze the changes in the marine and terrestrial sources of organic carbon in the northern Bering Sea (site 1), western Beaufort Sea slope (site 2) and northern Chukchi Sea (site 3). Organic carbon burial fluxes (OCBF) in the context of global warming were also explored at sites 1 and 3. The results showed that organic matter in these sediments were a mixed input of marine and terrestrial sources, and the BIT index and δ13C of site 2 suggested that the terrestrial soil organic matter was dominant. Based on a combination of 210Pb dating and Corg, the sedimentary OCBF at site 1 was 2.29-3.65 mg cm-2 y-1, and at site 3 was 0.00-0.41 mg cm-2 y-1. The temperature anomalies and sea ice changes in the Arctic in the past 100 years were compared with the burial fluxes of the terrestrial organic carbon. At site 1, the results indicated that fast melting of seasonal sea ice led to earlier arrival of ice algae bloom, enhanced zooplankton feeding and reduced carbon burial from 1947 to 2010, and the sudden increase in carbon burial after 2010 was attributed to an increase in primary productivity and terrestrial organic matter input due to an accelerated melting of sea ice. There was a smaller change in marine organic carbon content in site 3, but OCBF increased after a pre-1965 decrease, mainly controlled by terrestrial organic matter input associated with temperature rising and sea ice melting during recent decades.

Simple Cysts in Donor Kidney Contribute to Reduced Allograft Function.

BACKGROUND: Simple renal cysts may be an early marker of renal disease. We investigated whether simple cysts in donor kidney are associated with the decline of allograft function in living donor kidney transplantation. METHODS: We retrospectively reviewed records of donors and recipients from 716 living donor kidney transplants performed between April 2007 and April 2015 in our hospital. Ninety-one donors with renal cysts and 64 recipients with cysts in donor kidney were noted. We compared these 64 cases to 128 no cyst-bearing controls matched for the donor gender, recipient gender, donor baseline serum creatinine (sCr), donor/recipient body surface area ratio, donor age, recipient age and the date of kidney transplantation in turn. RESULTS: The presence of cysts was interrelated with age, gender and renal function independently in donors. Pathological findings of time-zero biopsy revealed that donor kidney harboring cysts existed more glomerular sclerosis compared with no cyst-bearing controls (p = 0.040). The estimating glomerular filtration rate levels of recipients were 80.82 ± 26.61 vs. 88.21 ± 23.12, 66.95 ± 17.42 vs. 72.15 ± 16.42 and 60.92 ± 22.17 vs. 68.72 ± 14.43 ml/min· 1.73 m2 in cyst-bearing and no cyst-bearing group on day 7, month 6 and year 5, respectively, after surgery (p < 0.05). The mean sCr were 112.14 ± 48.32 vs. 98.75 ± 29.71 and 126.28 ± 42.32 vs. 115.05 ± 26.35 µmol/l on the 7th day and a half year after transplant, respectively (p < 0.05). The 2 groups did not significantly differ in terms of the other characteristics. CONCLUSION: Simple cysts in donor kidney can influence the early and long-term allograft function. In living donor transplantation, kidney presenting cysts should be considered carefully at the time of donor selection.

The Effect of Histological CD20-Positive B Cell Infiltration in Acute Cellular Rejection on Kidney Transplant Allograft Survival.

Background. It is controversial whether lymphocyte infiltration exhibited in biopsy specimens is associated with transplant outcomes. This study focused on the effect of CD20-positive B cell infiltration in biopsy specimens from allografts with acute cellular rejection (ACR) in a Chinese population. Methods. Altogether, 216 patients transplanted from Sep. 2001 to Dec. 2014 with biopsy-proved ACR (Banff I or Banff II) were included in the analysis. Biopsies were immunostained for CD20 and C4d. Baseline information, serum creatinine and GFR before and after treatment, steroid resistance, response to treatment, graft loss, and survival were analyzed. Results. Eighty-three patients were classified into CD20-negative group, and 133 patients were classified into CD20-positive group. Significantly more CD20-negative patients (49/83, 59.0%) received steroid plus antibody therapy compared with the CD20-positive group (52/133, 39.1%) (P = 0.004). The response to treatment for ACR did not differ between these two groups. The CD20-positive group had less graft loss (18.8% versus 32.5%, P = 0.022) and a better graft survival rate. Further exploration of the infiltration degree suggested that it tended to be positively related to graft survival, but this did not reach statistical significance. Conclusion. CD20-positive B cell infiltration in renal allograft biopsies with ACR is associated with less steroid resistance and better graft survival. The presence of CD20-positive B cells is protective for renal allografts.