Glomerulonephritis Patients Research Articles

Primary Membranous Glomerulonephritis: The Role of Serum and Urine Biomarkers in Patient Management.

The detection of phospholipase A2 receptor (PLA2R) and thrombospondin domain containing 7A THSD7A among primary membranous glomerulonephritis (MGN) patients transformed the diagnosis, treatment monitoring, and prognosis. Anti-PLA2R can be detected in 70–90% of primary MGN patients while anti-THSD7A in 2–3% of anti-PLA2R negative primary MGN patients depending on the technique used. Serum and urine samples are less invasive and non-invasive, respectively, and thus can detect the presence of anti-PLA2R and anti-THSD7A with higher sensitivity and specificity, which is significant in patient monitoring and prognosis. It is better than exposing patients to a frequent biopsy, which is an invasive procedure. Different techniques of detection of PLA2R and THSD7A in patients’ urine and sera were reviewed to provide newer and alternative techniques. We proposed the use of biomarkers (PLA2R and THSD7A) in the diagnosis, treatment decision, and follow-up of patients with primary MGN. In addition, other prognostic renal biomarkers like retinol binding protein (RBP) and beta-2 microglobulin were reviewed to detect the progression of renal damage for early intervention.

Comparison of cancer prevalence between patients with glomerulonephritis and the general population at the time of kidney biopsy.

Glomerulonephritis (GN) has been associated with many solid and hematologic malignancies. However, cancer prevalence at the time of GN diagnosis has been rarely examined. We aimed to evaluate the cancer prevalence in patients with GN at the time of kidney biopsy and to compare the results to those of the general population. A total of 1,155 patients who underwent kidney biopsy between 2003 and 2017 were included. We investigated patients diagnosed with cancer within one month of kidney biopsy. The occurrence of cancer was compared with that of the Korean general population using the observed-to-expected rates (O/E ratio). Twenty-nine patients with GN had cancer. The mean age of patients with and without cancer was 49 and 66 years old, respectively. The proportion of male patients with and without cancer was 49.4% and 58.6%, respectively. The glomerular filtration rate was different between the groups (78.1 ± 37.0, 58.0 ± 43.6 ml/min/1.73 m2, p = 0.006), but the urine protein/creatinine ratio was not (3.21 ± 4.01, 5.38 ± 7.47 g/gCr, p = 0.172). Immunoglobulin A nephropathy (IgAN) was the most common GN (37.9%), followed by membranous GN (13.5%), focal segmental glomerulosclerosis (9.7%), minimal change disease (9.2%), amyloidosis (1.2%). Amyloidosis was the most common GN associated with malignancy (20.7%). In patients with amyloidosis, cancer was observed almost 28 times more than expected and these patients showed higher cancer occurrence than patients with other GN (Relative Risk [RR]: 15.73; 95% confidence interval [CI]: 4.82–51.30; p < 0.01). Cancer occurrence was three times greater in GN patients aged > 50 years compared to the general population (O/E ratio: 3.42; 95% CI: 1.37–5.46; p = 0.027). Patients with GN, especially amyloidosis, have higher risk of cancer than the general population at the time of GN diagnosis. Older age (> 50 years) was one of the major determinants of the presence of cancer in GN patients.

3237 CMV Gastric Ulcer in a Patient With Pauci Immune Cresenteric Glomerulonephritis on Rituximab: A Rare Combination

INTRODUCTION: CMV infections are asymptomatic in immunocompetent patients but in immunocompromised patients, CMV have varying manifestations depending on their location. Patient who are organ transplant recipients, taking immunosuppressive therapy for a long time are at increased risk of CMV infections. CMV induced gastric ulcer is very rare but many cases have been reported in the literature. No case describing association between CMV related gastric ulcer and glomerulonephritis has not been reported in the literature so far. CASE DESCRIPTION/METHODS: In this manuscript, we describe a case of pauci immune cresenteric glomerulonephritis in a patient who was on rituximab and long-term steroid therapy and found to have CMV related gastric ulcer. The association of small vessel vasculitis and CMV related gastrointestinal infection has not been studied in the literature. DISCUSSION: Pauci immune cresenteric glomerulonephritis is a subtype of rapidly progressive glomerulonephritis manifested by continuous loss of renal functions with features of dysmorphic red blood cells and glomerular proteinuria. Treatment of such condition is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen known as Rituximab. We also discussed the pathogenesis of CMV induced gastric ulcer after rituximab therapy. This case emphasizes the importance of opportunistic infections in glomerulonephritis patients and raises the awareness that glomerunephritis patients are at increased risk of opportunistic infections as well. Rituximab was considered to be a safer drug but over the years, the incidence if opportunistic infections in patients on rituximab has been increasing.

SUN-038 RECOVERY OF KIDNEY FUNCTION IN GLOMERULONEPHRITIS WITH RAPIDLY PROGRESSIVE RENAL FAILURE AT CHO RAY HOSPITAL

It is uncommon for patients with glomerulonephritis (GN) who require hemodialysis (HD) to recover renal function. Lupus nephritis (LN) is one of the common GN in Vietnam. Our aim was to describe the renal outcome of 64 GN patients with rapidly progressive renal failure (RPRF) on HD at Cho Ray Hospital, Ho Chi Minh City, Vietnam. A prospective study was conducted in 64 GN patients with RPRF requiring HD from 2014 to 2018. RPRF was defined as a progression to renal failure within a period of 1 week to three months. A definitive diagnosis of the kidney disease was established by history, clinical examination, lab tests, and renal biopsy. The patients had received standard therapy for their primary medical condition. We followed the patients after initiation of HD (3 months min, 18 months max) to evaluate recovery sufficient to discontinue HD Patient median age 25 (Inter-quartile range 21,32); 49 females; 59/64 pts with lupus nephritis (LN) (54 class III or IV, 1 class V, and 1 unclassified). 3 patients had IgA nephropathy; 1 Anti-glomerular basement membrane GN; 1 idiopathic membranoproliferative GN. Thrombotic microangiopathy (TMA) was clinically diagnosed based on Coombs negative hemolytic anemia, thrombocytopenia, D-Dimer >600 ng/mL, LDH >600 U/L, schistocytes on blood smear, with or without kidney biopsy. TMA was found in 56 pts, of which 19 were biopsy proven. Six LN patients with TMA were tested for ADAMTS13, all of whom were negative. Patients with TMA were treated with therapeutic plasma exchange (26 cases) or plasma infusion (30 cases) and heparin anticoagulation. All 64 pts were on oral methylprednisolone (median 32mg/day, IQR 16, 48mg) for the first month then tapered. 41 pts (39 LN, 2 non Lupus GN) received median of 6 doses of monthly intravenous cyclophosphamide 0.5g/m2 over median 12 months follow up. 36/59 (61%) of LN pts recovered kidney function, and discontinued HD after median 39 days (IQR 24;72 days). They remained dialysis independent for a median of 10 months (IQR 6 ,11 months) follow up. Median of the last serum creatinine in patients who recovered function was 1.4 mg/dL (IQR 1.2; 1.7 mg/dL). In the 28 patients who failed to recover kidney function, 4 died and 24 continued HD after median 4 months. Recovery of renal function was more common in LN pts with TMA or patients with length on HD of less than 3. Recovery of function was not associated with age, gender, body mass index, hypertension, 24h proteinuria, hematuria, isolated TMA diagnosis, anemia, or serum albumin on admission). TableComparison between patients who recovered and failed to recover functionTotal (N=64)Recovered kidney function (N=36)Non recovered kidney function (N=28)pLupus nephritis5936 (61%)230.03Nonlupus GN50 (0%)5TMAneg/LNpos85 (62.5%)30.01TMApos/LNpos5131(60.7%)20TMApos/LNneg50(0%)5Length on HD ≤ 3 months4632(69.5%)140.005Length on HD > 3 months184(22.2%)14 Open table in a new tab RPRF in lupus nephritis patients with or without TMA had a good likelihood of function recovery after requiring hemodialysis.

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

BackgroundA novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers.MethodsA total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated.ResultsHigh levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2—which is not reliable because of the small number of cases—strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3–4 had worse renal survival than patients in Clusters 1–2.ConclusionsOur results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.

Mercury-associated glomerulonephritis: a retrospective study of 35 cases in a single Chinese center

BackgroundLong-term exposure of mercury may induce glomerulonephritis. Clinical and pathological features of mercury-associated glomerulonephritis are not fully clear. This study retrospectively analyzed 35 cases of mercury-associated glomerulonephritis in a single Chinese center.MethodsThirty-five patients of mercury-associated glomerulonephritis were enrolled. Clinical data on diagnosis and during follow-up were collected. Plasma anti-phospholipase A2 receptor (PLA2R) antibody, glomerular PLA2R and glomerular IgG subclasses deposition were detected in the cases with membranous nephropathy (MN).ResultsMercury exposure was caused by skin lighting cream (20 patients), mercury-containing pills (9 patients), hair-dyeing agents (4 patients), and unidentified reasons (2 patients). All patients presented with proteinuria and normal renal function. The median of urinary protein was 4.6 (range 1.6~19.7) g/24 h. Twenty-two patients (62.9%) had nephrotic syndrome. Renal histopathology showed minimal change disease (MCD) in 21 patients (60.0%), MN in 13 (37.1%) and focal segmental glomerular sclerosis (FSGS) in 1 patient (2.9%). The proportion of MCD increased along with urinary mercury concentration (P = 0.024). In 13 cases of MN, all patients were negative for plasma anti-PLA2R antibody and glomerular PLA2R antigen. IgG1 (61.5%) and IgG4 (46.2%) deposits were noted along the glomerular capillary loops. Among the 16 patients received mercury detoxification monotherapy, 14 patients received 4.5 ± 2.8 (range 1~12) rounds of regimen and achieved complete remission in 4.5 (range 0.3~23.0) months, 2 patients stayed no remission.ConclusionsMCD was the most common pathological type of mercury-associated glomerulonephritis, followed by MN. The proportion of MCD increased along with the increase of urinary mercury concentration. Most patients could achieve complete remission after mercury detoxification.

Ultrasound Elastography Evaluations in Patient Populations With Various Kidney Diseases.

Renal elastography is an ultrasonographic method that has been recently found to provide information on renal functions and fibrosis. In this study, we aimed to investigate the relationship between elastography scores and renal functions and proteinuria levels in patient populations with various kidney diseases. Seventy-five diabetic nephropathy patients, 66 kidney transplant patients, and 45 glomerulonephritis patients were included in the study. The amount of proteinuria was measured according to the protein-to-creatinine ratio in spot urine samples. The estimated glomerular filtration rate (eGFR) was calculated according to the Modification of Diet in Renal Disease formula. Ultrasound elastography scores were measured in each patient group by a radiologist. The mean age of diabetic nephropathy patients was 61 ± 10 years. The mean elastography score was 0.96 ± 0.30. Elastography score was positively correlated with serum blood urea nitrogen and creatinine levels and was negatively correlated with eGFR value. The mean age of kidney transplant patients was 42 ± 12 years. The mean elastography score was 1.10 ± 0.38. There was a significant relationship between elastography score and proteinuria level. The mean age of glomerulonephritis patients was 37 ± 13 years. The mean elastography score was 0.91 ± 0.41. Elastography score was positively correlated with serum blood urea nitrogen and creatinine levels. However, there was no relationship between elastography score and eGFR value and proteinuria level. Although renal elastography provides information on renal functions and proteinuria in patients with diabetic nephropathy, renal transplant, and glomerulonephritis, there is a need for studies with a larger number of patients on this subject.

Plasma Exchange Is Highly Effective for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Patients With Rapidly Progressive Glomerulonephritis Who Have Advanced to Dialysis Dependence: A Single-Center Case Series.

Plasma exchange (PEX) can be an effective treatment in anti-neutrophil cytoplasmic antibody-associated vasculitis with severe renal damage; however, it is still controversial. Among cases of newly diagnosed AAV with rapidly progressive glomerulonephritis at our department from 2008 onward, 11 patients who received PEX (seven cases for severe renal damage [R-PEX] and four cases for lung hemorrhage [L-PEX]) were retrospectively analyzed. All cases of R-PEX were dependent on hemodialysis at the beginning of PEX and all received seven sessions of PEX (50 mL/kg or 1.3 plasma volume per exchange) within 2 weeks. All cases became dialysis-independent within 8 weeks, with 3- and 12-month cumulative renal survival rates of 100% and 80%, respectively. All cases of L-PEX retained their renal function. In rapidly developing, newly dialysis-dependent antibody-associated vasculitis with rapidly progressive glomerulonephritis patients with normal renal function before disease onset, standard PEX can be expected to induce sufficient renal recovery to establish dialysis independence.

Effectiveness of cinacalcet treatment for secondary hyperparathyroidism on hospitalization: Results from the MBD-5D study.

ObjectivesTo elucidate the effect of cinacalcet use on all-cause and cause-specific hospitalization outcomes using a prospective cohort of maintenance hemodialysis patients.MethodsWe used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism and examined baseline characteristics as well as longitudinal changes. All patients were cinacalcet-naïve at study enrollment. Further, we used a marginal structural model to account for time-varying confounders on cinacalcet initiation and hospitalization outcomes, and an Andersen-Gill–type recurrent event model to account for any recurring events of hospitalization in the outcome analysis using the weighted dataset.ResultsAmong the 3,276 patients, cinacalcet treatment was initiated in 1,384 patients during the entire follow-up. Cinacalcet users were slightly younger, included more patients with chronic glomerulonephritis and fewer patients with diabetes, were more likely to have a history of parathyroidectomy, and were more often used receiving vitamin D receptor activator, phosphate binders, and iron supplements. The overall hospitalization analysis yielded a hazard ratio (HR) of 0.97 (95% confidence interval [CI]: 0.80, 1.18). A trend toward a mild protective association was observed for cardiovascular-related hospitalizations (HR: 0.85; 95% CI: 0.64, 1.14). In the subgroup analysis, a protective association was seen due to cinacalcet use for infection-related hospitalizations in the lowest intact parathyroid hormone group (HR: 0.36; 95% CI: 0.14, 0.95).ConclusionsCinacalcet initiation in patients on maintenance hemodialysis had no effect on all-cause and cause-specific hospitalizations. Although the overall association was statistically not significant, cinacalcet may have a protective association on cardiovascular-related hospitalization in all patients and infection-related hospitalization in patient with low intact parathyroid hormone.

Serum levels of DNAJB9 are elevated in fibrillary glomerulonephritis patients

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease. Kidney biopsy is required to establish the diagnosis. Recent studies have identified abundant glomerular deposition of DNAJB9 as a unique histologicalmarker of FGN. We developed an immunoprecipitation-based multiple reaction monitoring method to measure serum levels of DNAJB9. We detected a 4-fold higher abundance of serum DNAJB9 in FGN patients when compared to controls, including patients with other glomerular diseases. Serum DNAJB9 levels were also negatively associated with estimated glomerular filtration rate in patients with FGN. Serum DNAJB9 levels accurately predicted FGN with moderate sensitivity (67%) and with high specificity (98%) and positive and negative predictive value (89% and 95%, respectively). A receiver operating curve analysis demonstrated an AUC of 0.958. These results suggest that serum levels of DNAJB9 could be a valuable marker to predict FGN, with the potential to complement kidney biopsy for the diagnosis of FGN.

Commentary on the Current Guidelines for the Diagnosis of Lupus Nephritis Flare.

Lupus nephritis flare is a frequent complication in patients with systemic lupus erythematosus. Recognizing disease activity is crucial in lupus nephritis management. Proteinuria magnitude and urine sediment change are major clinical indicators of lupus nephritis activity. This work updates these insights in light of recent findings regarding proteinuria quantification and urine sediment analyses. Currently, BILAG and SLEDAI estimate proteinuria magnitude based on the protein/creatinine ratio of "spot" (single void collections) or "intended" 24-h urine collections without specifying the extent to which the collection approaches a 24-h collection. As discussed here, and based on our recently published work, these approaches often incur serious errors that can adversely affect SLE patient management. Also incorporated into this work is a new analysis of the clinical significance of urine sediment hematuria and pyuria changes with regard to recent-onset SLE glomerulonephritis (GN) flare. This analysis is based on a prospective study of urine sediment changes in the Ohio SLE Study, which was an NIH-sponsored prospective observational study of SLE GN patients with SLE flare of recent onset. We propose that BILAG and SLEDAI renal flare criteria can be made more rigorous by incorporating recently published insights into proteinuria quantification using the protein/creatinine ratio of an intended 24-h urine collection that is at least 50% complete based on its creatinine content. Also proposed are new insights into the interpretation of urine sediment hematuria and pyuria based on findings from the Ohio SLE Study.

Small Red Blood Cell Fraction on the UF-1000i Urine Analyzer as a Screening Tool to Detect Dysmorphic Red Blood Cells for Diagnosing Glomerulonephritis.

BackgroundDysmorphic red blood cells (dRBCs) are first-line biomarkers for detecting glomerulonephritis (GN) in patients with hematuria. The UF-1000i system (Sysmex, Kobe, Japan), based on flow cytometry, provides small red blood cell (RBC) values (UF-1000i [UF]-%sRBCs). We evaluated the clinical application of UF-%sRBCs for detecting %dRBCs and GN.MethodsUrine samples of 103 patients (47 with GN; 56 without GN [NGN]) were analyzed using UF-1000i urinalysis, phase-contrast microscopy (PCM), and urine chemistry. Serum creatinine (mg/dL), serum albumin (g/dL), serum protein (mg/dL), urine protein (mg/dL), and urea nitrogen (mg/dL) levels were measured using an automated chemical analyzer. To determine the cut-off level of predicting GN, ROC curve was analyzed.ResultsUF-%sRBCs, %dRBCs, urine protein, serum creatinine, and estimated-glomerular filtration rate differed between the GN and NGN groups, with the greatest differences detected for UF-%sRBCs and %dRBCs (P<0.0001). In ROC curve analysis, urine protein had the highest area under the curve (0.828), followed by %dRBCs (0.771) and UF-%sRBCs (0.745). To screen for GN, the best cut-off values of UF-%sRBCs and %dRBCs were >40.5% and >6.7%, respectively. %dRBCs (P=0.0001) and UF-%sRBCs (P=0.0006) differed between the GN and NGN groups in patients with isolated hematuria but without proteinuria.ConclusionsUF-%sRBCs had similar diagnostic power to %dRBCs determined by PCM for identifying patients with GN. UF-%sRBCs may be more useful for diagnosing GN in patients with isolated hematuria. Predicting %dRBCs using UF-1000i will provide information on possible GN in patients presenting with asymptomatic hematuria.

Pathological spectrum of glomerular disease in patients with renal insufficiency: a single-center study in Northeastern China

Background: To investigate the pathological spectrum of glomerular disease in patients with renal insufficiency (RI) from 2008 to 2017.Methods and results: We calculated the estimated glomerular filtration rate (eGFR) with the Chronic Kidney Disease Epidemiology Collaboration creatinine (CKD-EPI) equation and defined RI as an eGFR <60 ml/min/1.73 m2. A total of 969 RI patients were included in our study. IgA nephropathy (IgAN) was the most common subtype of primary glomerulonephritis (37.2%). The frequencies of IgAN and non-IgA mesangioproliferative glomerulonephritis decreased from 27.3% and 9.5% during 2008–2012 to 20.7% and 2.6% during 2013–2017, respectively. However, the frequency of membranous nephropathy increased from 6.8% to 16.2%. Lupus nephritis was the most common subtype of secondary glomerulonephritis (32.1%). The frequencies of both ANCA-associated systemic vasculitis and diabetic nephropathy increased from 3.8% to 7.6% and from 4.3% to 7.6%, respectively. The number of elderly patients (≥60 years) in our study increased sharply, from 15.6% in 2008 to 35.0% in 2017. Membranous nephropathy, minimal change disease, membranoproliferative glomerulonephritis, lupus nephritis and renal amyloidosis are more frequently observed in the elderly patients than in nonelderly patients (<60 years) (p < .05). Excluding those with acute kidney injury, IgAN was the leading cause of RI (24.9%), followed by membranous nephropathy (13.3%) and lupus nephritis (12.0%).Conclusions: IgAN and lupus nephritis were the most prevalent primary glomerulonephritis and secondary glomerulonephritis in patients with RI, respectively. The frequencies of membranous nephropathy, ANCA-associated systemic vasculitis and diabetic nephropathy increased significantly. The number of elderly patients with RI increased sharply.

Hormonal disorders in acute glomerulonephritis in patients of young age

Goal: To study and asses the role of hormone imbalance (blood TSH, T3, T4, their antibodies, prolactin, cortisol and testosterone levels) in the development of acute glomerulonephritis in adaptational problems in the contingent of the Armed Forces of the Republic of Armenia. Material and methods. To achieve the goal of the study 150 military servicemen (conscripts), aged 18-22, who were hospitalized for acute glomerulonephritis during the first 6 months of their service, were examined. The control group consisted of 50 practically healthy servicemen. Apart from common clinical and laboratory and instrumental examinations, blood serum levels of cortisol, testosterone, prolactin, TTG, T3, T4, antiTG and antiTPO were determined by immuno-fermentative analysis taking into account their circadian rhythms in young organism. Results. In patients with acute glomerulonephritis with acute nephritic syndrome and isolated urinary syndrome extensive increase in prolactin levels, cortisol levels and in T4 levels was observed in relation to comparison group. In both study groups, other data were within normal range in relation to comparison group. Conclusion. In acute glomerulonephritis the adaptation process of young organism is accompanied by certain phase shifts in endocrine system, which manifests with hyperprolactinemia, increased cortisol and thyroxine levels. Prolonged duration of these increased levels can lead to overexertion of the protective adaptation reactions of body and ultimately to their exhaustion. Taking into consideration the abovementioned changes, we consider it necessary to carry out hormonal tests when examining patients with acute glomerulonephritis, and in case of detecting deviations - take the patients under endocrinologist’s follow-up.

Decreased α7nAChR mRNA levels in peripheral blood monocytes are associated with enhanced inflammatory cytokine production in patients with lupus nephritis

The cholinergic anti-inflammatory pathway modulates cytokine release by activating alpha-7 nicotinic acetylcholine receptors (α7nAChR) in monocytes/macrophages. We aimed to determine the role of α7nAChR in lupus nephritis (LN). We enrolled 36 inactive and 35 active LN patients, 34 primary glomerulonephritis patients, and 35 healthy controls. Peripheral blood monocytes were isolated, and mRNA expression of α7nAChR, interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α) in monocytes was measured. α7nAChR and IL-10 mRNA levels were significantly decreased, but IL-6 was increased, in LN patients compared with healthy controls or glomerulonephritis patients (all P < 0.01). Interestingly, α7nAChR mRNA levels were negatively correlated to SLEDAI (r = −0.68, P < 0.01), anti-dsDNA (r = −0.38, P < 0.05), and proteinuria (r = −0.49, P < 0.01) levels, and positively correlated to serum complement C3 levels (r = 0.38, P < 0.05) in patients with active LN. Furthermore, α7nAChR mRNA levels were negatively correlated to TNF-α (r = −0.50, P < 0.01), IL-1β (r = −0.42, P < 0.05), IL-6 (r = −0.69, P < 0.01) mRNA levels, and positively correlated to IL-10 (r = 0.45, P < 0.01). TNF-α, IL-1β, and IL-6 protein levels in the supernatant of cultured monocytes from active LN patients were significantly higher, while IL-10 was lower, than that of healthy controls. PNU-282987, an α7nAChR agonist, significantly decreased TNF-α, IL-1β, and IL-6 but increased IL-10 in the monocyte culture supernatant of active LN patients, which were abolished by an α7nAChR antagonist methyllycaconitine. The effects of PNU-282987 were confirmed in lipopolysaccharides-stimulated monocytes. Taken together, these findings suggest that decrease in α7nAChR mRNA levels may play a role in LN and that activation of α7nAChR may inhibit inflammation in LN.

Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis

Background: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. Methods: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. Results: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15–34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9–19) mL/min/1.73 m². Over a median (IQR) follow-up of 33.5 (17–82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). Conclusions: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

Clinical and pathologic characteristics of pauci-immune anti-myeloperoxidase antibody associated glomerulonephritis with nephrotic range proteinuria

Background: Heavy proteinuria in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is usually considered to be associated with immune deposits in renal biopsy. Nephrotic ANCA GN without immune deposits (pauci-immune) is rare and has not been studied specially. In this study characteristics of these patients are to be investigated. Methods: Clinical and pathological characteristics from 20 kidney biopsy-proven pauci-immune anti-myeloperoxidase antibody-associated GN patients with nephrotic proteinuria were analyzed and were compared with ANCA GN patients without nephrotic proteinuria. Results: Acute kidney injury (AKI) and gross hematuria were much prevalent but extra-renal involvement was less prevalent in pauci-immune ANCA GN with nephrotic proteinuria than in pauci-immune ANCA GN without nephrotic proteinuria. No more severe hypoalbuminemia, hypercoagulability, hyperlipidemia or higher thrombosis incidence were found between two groups. Compared with patients without nephrotic proteinuria, patients with nephrotic proteinuria had more prevalent crescentic category in histopathology. Proteinuria decreased quickly after treatment but much poorer renal prognosis was found in pauci-immune ANCA GN with nephrotic proteinuria. The results of urinary albumin to total protein ratio and urinary protein electrophoresis showed pauci-immune ANCA GN with nephrotic proteinuria had obvious non-selective proteinuria. Conclusions: Pauci-immune ANCA GN with nephrotic proteinuria do not have more severe hypoalbuminemia, hypercoagulability or hyperlipidemia than patients without nephrotic proteinuria. Non-selective proteinuria might be the reason. However, pauci-immune ANCA GN with nephrotic proteinuria have more prevalent crescentic category in histopathology, higher incidence of AKI, gross hematuria and poorer renal prognosis despite of good sensitivity to therapy of proteinuria.

Comparing outcomes of biopsy-proven anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis patients treated with cyclophosphamide in the 20th and 21st centuries: a 23-year study.

BackgroundAnti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disorder associated with significant morbidity and mortality. Approximately 80–90% of patients have circulating ANCAs. Long-term outcomes appear to be improving. This retrospective study analyses the incidence and patient outcomes over a period of 23 years at a single tertiary centre.MethodsOutcomes of patients diagnosed with AAV between 1 January 1988 and 31 December 2010 were collected retrospectively. Data including patient demographics, age of diagnosis, dates of starting renal replacement therapy, death and biochemistry results were collected. Patients were divided into two cohorts (1988–99 and 2000–10) and analysed using Stata software (StataCorp, College Station, TX, USA).ResultsA complete dataset was obtained for 273 patients. Of these patients, 101 were diagnosed between 1988 and 1999 while 172 were diagnosed between 2000 and 2010. The number of patients diagnosed with AAV increased from 2.2/million in 1988 to 10.3/million in 2010. A higher proportion of patients (56.4%) in the earlier cohort presented with creatinine >500 μmol/L compared with the later cohort (30.2%; P < 0.001). Overall patient survival improved significantly between the two cohorts. Cohort 1 had a median survival of 59 months compared with 125 months for Cohort 2 (P = 0.003).ConclusionsThis study shows that AAV is being diagnosed at an earlier stage, resulting in improved outcomes. This may be because of improvements in the management of AAV and chronic kidney disease.

Urinary fibrin/fibrinogen degradation products measured using an anti-fibrinogen antibody predict orthostatic proteinuria.

The aim of this study was to assess the diagnostic value of urinary fibrin/fibrinogen degradation products (uFDP) measured using an anti-fibrinogen antibody in patients with orthostatic proteinuria (OP), and their use in differentiating between OP and glomerulonephritis (GN). uFDP were measured using first urine in the morning (supine) and non-first urine during a hospital visit (upright) and then normalized to urine creatinine (uFDP/Cr, ng/mgCr). We compared (i) OP patients (n = 16); (ii)those in remission from nephrotic syndrome (NS, n = 14) and from GN (IgA nephropathy [IgAN], n = 14; Henoch-Schönlein purpura nephritis [HSPN], n = 12); and (iii) those with active GN (IgAN, n = 12; HSPN, n = 19). The uFDP/Cr ratio increased from supine to upright urine in patients with OP (P < 0.001), but decreased in one case. uFDP were excreted in supine urine in 94% of OP patients, with no excretion in NS remission patients or in 92% of GN remission patients (P < 0.001 for both). uFDP/Cr in supine urine was similar between the OP and active GN patients (P = 0.40), whereas proteinuria in supine urine was in the normal range in all OP patients, but was significantly higher in upright urine in the OP patients (P < 0.001). In upright urine, urinary protein/creatinine ratio was significantly lower in patients with OP than in those with active GN (P = 0.005). A uFDP/Cr ratio cut-off of 1,108ng/mgCr in upright urine correctly differentiated OP from active GN, with a sensitivity of 87.5% and a specificity of 100%. Comparison of uFDP levels in supine/upright urine can be reliable for diagnosing OP and for differentiating it from active GN.

Epidemiology and risk factors for cytomegalovirus infection in glomerular diseases treated with immunosuppressive therapy.

Cytomegalovirus (CMV) infections are associated with morbidity and mortality. We aimed to describe the epidemiology, risk factors and outcomes of CMV infection among patients with glomerulonephritis (GN) who received potent immunosuppressants (IS). Single-centre retrospective study of adults with biopsy-proven GN prescribed methylprednisolone (MP), cyclophosphamide (CYC) or rituximab (RTX). Primary endpoint was CMV infection defined by significant CMV antigenaemia (>10 positive cells in 106 cells) or viraemia (>2000 copies/mL). Death was related to CMV if CMV infection occurred within the same hospitalization as death. Ninety-four patients were studied. CYC was prescribed in 65% and MP in 71% of the cohort. Only two patients received RTX and 15 patients received plasma exchanges (PEX). Median follow up was 31.9 (IQR: 13.7, 53.6) months. CMV infection occurred in 13 patients (13.8%) at 1.3 (0.6, 3.0) months from biopsy. Patients with CMV infection had higher serum creatinine [404 (272, 619) vs. 159 (93, 317) μmol/L, P < 0.001] and greater proteinuria [UPCR 7.5, (4.8, 11.8) vs. 4.2 (2.3, 8.4) g/g, P = 0.02] than those who did not have CMV infection. Also, more patients received CYC (92% vs. 60%, P = 0.03), RTX (15% vs. 0, P = 0.02) and PEX (38% vs. 12%, P = 0.01) than those who did not have CMV infection. Two patients had CMV-related deaths. Cytomegalovirus infection is common in GN patients receiving potent IS. Surveillance and possibly anti-viral prophylaxis should be considered for high-risk patients.