Immunoglobulin A glomerulonephropathy:A review

In this editorial,we comment on the article by Meng et al published in the World Journal of Clinical Cases.We comprehensively review immunoglobulin A nephro-pathy(IgAN),including epidemiology,clinical presentation,diagnosis,and management.IgAN,also known as Berger's disease,is the most frequent type of primary glomerulonephritis(GN)globally.It is mostly found among the Asian population.The presentation can be variable,from microscopic hematuria to a rapidly progressive GN.Around 50%of patients present with single or recurring episodes of gross hematuria.An upper respiratory infection and tonsillitis often precede these episodes.Around 30%of patients present microscopic hematuria with or without proteinuria,usually detected on routine examination.The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy.We focus on risk stratification and management of IgAN.We provide a review of all the landmark studies to date.According to the 2021 KDIGO(kidney disease:Improving Global Outcomes)guidelines,patients with non-variant form IgAN are first treated conservatively for three to six months.This approach consists of adequate blood pressure control,reduction of proteinuria with renin-angiotensin system blockade,treatment of dyslipidemia,and lifestyle modifications(weight loss,exercise,smoking cessation,and dietary sodium restrictions).Following three to six months of conservative therapy,patients are further classified as high or low risk for disease progression.High-risk patients have proteinuria≥1 g/d or<1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy.Some experts consider proteinuria≥2 g/d to be very high risk.Patients with high and very high-risk profiles are treated with immunosuppressive therapy.A proteinuria level of<1 g/d and stable/im-proved renal function indicates a good treatment response for patients on immu-nosuppressive therapy.

Echerichia coli Infection—Associated Glomerulonephritis in a Kidney Transplant Patient: A Case Report

Post infectious Glomerulonephritis (PIGN) in renal allograft is a rare entity. Only a few Cases have been described in the literature. The post streptococcal glomerulonephritis is the classic example in native kidney. A wide variety of organism has been associated with PIGN in renal allograft such as Staphylococcus, Cytomegalovirus and Polyomavirus. We describe one case of Infection associated glomerulonephritis due to Echericha Coli, developed 5 years after kidney transplantation, in 47 years old female patient. The Clinical presentation was characterized by a peripheral edema and high blood pressure, and biological tests showed a nephrotic syndrome, an acute kidney injury, a consumption of Complement fractions. The renal biopsy revealed a diffuse endocapillary cell proliferation with preponderant deposits of C3. Total recovery was achieved 4 months after Methyprednisolone pulse and Cyclophasphamid with antimicrobial treatment.

Immunoglobulin A vasculitis nephritis:Current understanding of pathogenesis and treatment

The clinical spectrum of immunoglobulin A vasculitis nephritis(IgAVN)ranges from the relatively common transitory microscopic hematuria and/or low-grade proteinuria to nephritic or nephrotic syndrome,rapidly progressive glomerulonephritis,or even renal failure.Clinical and experimental studies have shown a multifactor pathogenesis:Infection triggers,impaired glycosylation of IgA1,complement activation,Toll-like-receptor activation and B cell proliferation.This knowledge can identify IgAVN patients at a greater risk for adverse outcome and increase the evidence for treatment recommendations.

Infection related membranoproliferative glomerulonephritis secondary to anaplasmosis:A case

BACKGROUND Anaplasmosis is a tick-borne disease with a range of clinical manifestations,from a flu-like illness with fever and myalgias to a severe systemic disease with multisystem organ failure.Although renal involvement is not a common presentation,there have been few cases reporting acute kidney injury from Anaplasmosis.CASE SUMMARY We present a 55-year-old female with anaplasmosis who developed acute kidney injury due to membranoproliferative glomerulonephritis(MPGN).The patient originally presented with cough and shortness of breath.She was admitted to the hospital with a diagnosis of community acquired pneumonia and received antibiotics.During the hospital course she developed severe acute renal failure.Initial serological work up didn’t provide any conclusive diagnosis.Hence,she underwent kidney biopsy which showed MPGN pattern suggesting autoimmune,multiple myeloma or infectious etiology.Extensive work up was undertaken which was negative for autoimmune diseases,vasculitis panel,paraproteinemias but tested positive for IgG anaplasma with high titers indicating Anaplasmosis.CONCLUSION Our case shows a unique presentation of severe acute renal failure from MPGN from tick borne illness.MPGN is usually seen with autoimmune diseases,hepatitis C virus infections,paraproteinemias.Hence,we suggest that tick borne illness should also be considered when evaluating acute renal failure cases in tick borne prevalent regions.

Novel COL4A3 synonymous mutation causes Alport syndrome coexistent with immunoglobulin A nephropathy in a woman:A case report

BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which is often accompanied by hearing impairments and ocular abnormalities.Histopathologically,AS shows mesangial proliferation and sometimes incidental immunoglobulin A(IgA)deposition.Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features.CASE SUMMARY Herein,we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for>2 years.This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS(ADAS)and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing,which suggested that the patient carried a novel heterozygous variation(c.888G>A:p.Gln296Gln)in the COL4A3 gene that enriches the mutation spectrum of ADAS.The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established.After one year of therapy,a significant reduction in proteinuria was observed.The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels.Renal function also maintained well during the follow-up.CONCLUSION Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits in a young woman: A case report

BACKGROUND Proliferative glomerulonephritis with monoclonal immunoglobulin G(IgG)deposits(PGNMID)is a newly recognized rare disease.The renal pathology is characterized by prominent manifestations of membranous hyperplasia,which are easy to misdiagnose.The clinical symptoms are severe.Massive proteinuria and hypoproteinemia are conspicuous,and most patients are accompanied by renal insufficiency and microscopic hematuria.CASE SUMMARY A 27-year-old woman was admitted to a hospital for macroscopic hematuria and proteinuria 4 years prior,and renal biopsy in the hospital suggested moderate-tosevere mesangial proliferating glomerulonephritis(MsPGN).She had taken a glucocorticoid,cyclophosphamide,mycophenolate mofetil,and other treatments and achieved brief partial remission.Recently,the patient visited our hospital due to massive proteinuria.Repeated renal biopsy and re-evaluation of the first biopsy obtained 4 years previously revealed monoclonal immunoglobulin deposition in the glomeruli.A bone marrow examination was performed to exclude hematologic malignancy,and a diagnosis of PGNMID was established.The patient showed remission after four cycles of a bortezomib+cyclophosphamide+dexamethasone scheme.CONCLUSION PGNMID is usually misdiagnosed as MsPGN or membranoproliferative glomerulonephritis.Although it often occurs in middle-aged and elderly individuals,it cannot be readily excluded in young people,even when serum immunofixation electrophoresis is negative.IgG subtype and light chain staining are necessary when this disease is highly suspected.An accurate diagnosis at the earliest stage may avoid the overuse of glucocorticoids and immunosuppressants.

Exploring the Protective Effect of the Ethanolic Extract of Rosa laevigata Michx.Fruit on Rats with Mesangial Proliferative Glomerulonephritis Based on NLRP3 Inflammasome Pathway

Objective:To investigate the effect of the ethanolic extract of Rosa laevigata Michx.fruit on rats with mesangial proliferative glomerulonephritis based on the NLRP3 inflammasome pathway.Methods:Thirty Wistar rats were divided into three groups,a blank control group,a diabetic nephropathy(DN)model group,and an ethanolic extract intervention group,according to the random number table method,with 10 rats in each group.One day before the experiment,basic feeding was initiated for all the rats;the changes in activity and weight of each group of rats were observed and recorded after 7 d,and a rat model of renal function injury was established after 1 d.Results:Compared with the control group,the model group had significantly higher kidney/body ratio,24 h urine protein,serum creatinine(SCr),blood urea nitrogen(BUN),glomerular mesangial cell(GMC)count,and extracellular matrix(ECM)positive area ratio(P<0.05);the same indicators were significantly lower in the intervention group than in the model group(P<0.05).The NLRP3 inflammasome pathway in renal intrinsic cells was activated in the intervention group.The overactivation of NLRP3 inflammasome is known to promote interleukin(IL)-1βrelease,which was inhibited in the intervention group.Conclusion:The ethanolic extract of Rosa laevigata Michx.fruit has a protective effect on renal intrinsic cells and may be related to NLRP3 inflammasome pathway,suggesting that the fruit of Rosa laevigata Michx.has a potential role in protecting renal intrinsic cells from inflammatory damage.NLRP3 inflammasomes are involved in the development of various chronic inflammatory diseases,such as acute and chronic glomerulonephritis and renal fibrosis.

Triple hit to the kidney-dual pathological crescentic glomerulonephritis and diffuse proliferative immune complexmediated glomerulonephritis: A case report

BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis.It has been described in association with other glomerulonephritides[such as anti-neutrophilic antibody(ANCA)-glomerulonephritis,membranous nephropathy,and immunoglobulin(Ig)A nephropathy].CASE SUMMARY Herein we present an unusual case of concurrent anti-GBM disease,ANCAassociated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence.The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL,proteinuria,and hematuria.He rapidly deteriorated and became anuric.He was found to have high anti-GBM antibodies titers(151 units)and high anti-neutrophil cytoplasmic-ANCA.Despite prompt and early treatment,the patient’s condition worsened,and he succumbed to his illness.CONCLUSION Our case emphasizes the importance of a renal biopsy in anti-GBM disease,even in the presence of positive serum anti-GBM antibodies,to identify other potential causes of rapidly progressive glomerulonephritis.The challenge in treating such cases lies in the different therapy modalities.

Autoimmune hepatitis in a patient with immunoglobulin A nephropathy:A case report

BACKGROUND Immunoglobulin A nephropathy(IgAN)is the most commonly encountered glomerular disease in Asian countries.It has a broad clinical presentation,and it is frequently associated with other conditions.Chronic liver disease is well recognized as the leading cause of secondary IgAN.However,cases of IgAN associated with autoimmune hepatitis(AIH)have seldom been reported.CASE SUMMARY A 63-year-old Korean woman was admitted to Pusan National University Hospital for an evaluation of abdominal pain and elevated liver enzymes.Two weeks prior,she had presented to our hospital with proteinuria of approximately 1350 mg/d and hematuria and was diagnosed with IgAN.Autoimmune profiles were highly positive for antinuclear antibodies,and symptoms related to portal hypertension including ascites and peripheral edema were present.A diagnosis of AIH was made according to the simplified scoring system of the International Autoimmune Hepatitis Group.Despite immunosuppression with prednisolone and azathioprine,rapid deterioration of liver function led to end-stage liver disease.After a living-donor liver transplantation,liver function gradually improved,and she had maintained stable liver and kidney function at the six months follow-up.CONCLUSION Cases of secondary IgAN with chronic liver disease have been frequently reported in the literature but are rarely associated with AIH.We encountered an IgAN patient with concurrent progressive liver failure due to AIH.

Treatment of hepatitis B virus-associated glomerulonephritis:A meta-analysis

AIM:To evaluate the efficacy of antiviral or corticosteroid treatment on hepatitis B virus-associated glomerulonephritis(HBV-GN) . METHODS:Six and five trials were used respectively to evaluate the efficacy of either antiviral or corticosteroid treatment on HBV-GN.Pediatric patients were pooled separately to assess their response to the above treatment modalities.The primary and secondary outcomes were remission of proteinuria and clearance of Hepatitis B e-antigen(HBeAg) ,respectively.A fixed or random effect model was established to collect the data. RESULTS:The remission rate of proteinuria(RR=1.69,95%CI:1.08-2.65) and the clearance rate of HBeAg(RR =6.44,95%CI:3.11-13.35) were significantly higher in antiviral treatment group than in control group.The proteinuria remission was significantly associated with HBeAg clearance(P=0.002) .However,the difference in proteinuria remission rate was not statistically significant between corticosteroid treatment group and controlgroup(RR=1.45,95%CI:0.68-3.11) .Antiviral therapy could significantly promote the HBeAg clearance in pediatric patients,but neither antiviral nor corticosteroid therapy could significantly decrease proteinuria in pediatric patients compared to controls. CONCLUSION:Antiviral but not corticosteroid treatment can decrease proteinuria and promote HBeAg clearance in HBV-GN patients.

Recurrence of primary glomerulonephritis:Review of the current evidence

In view of the availability of new immunosuppression strategies,the recurrence of allograft glomerulonephritis(GN) are reported to be increasing with time post transplantation.Recent advances in understanding the pathogenesis of the GN recurrent disease provided a better chance to develop new strategies to deal with the GN recurrence.Recurrent GN diseases manifest with a variable course,stubborn behavior,and poor response to therapy.Some types of GN lead to rapid decline of kidney function resulting in a frustrating return to maintenance dialysis.This subgroup of aggressive diseases actually requires intensive efforts to ascertain their pathogenesis so that strategy could be implemented for better allograft survival.Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis after renal transplantation was evaluated using data from various registries,and pathogenesis of individual glomerulonephritis is discussed.The following review is aimed to define current protocols of the recurrent primary glomerulonephritis therapy.

Study on Localization Factors of Coagulation and Fibrinolysis in Glomerulonephritis

The intraglomerular distribution of alpha 2-plasmin inhi-bitor (α2-PI), plasminogen (PLG), fibronectin (FN) andfibrinogen related antigen (FRA), were examined in 118 ca-ses of primary or secondary glomerular disease by immuno-fluorescence method. The plasma concentrations of α2-PI,PLGand FRA were also measured simultaneously. The results ofthis study indicated that there was significant correlationbetween the deposition of α2-PI, PLG, FN, FRA and thedegree of histopathological changes in patients with severeglomerulonephritis. There was no significant correlation be-tween the intensity of α2-PI, PLG, FN and FRA depositionin glomeruli and the serum levels of α2-PI, PLG and FRA.

Homocysteine, Vitamin B12 and Folic Acid in Children with Acute Glomerulonephritis

Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and cofactors. It is deleterious to blood vessel including glomeruli. Kidney is a major organ that metabolizes Hcy. More than 80% of patients with chronic renal disease develop hyperhomocysteinemia (hHcy). Accessible data of plasma Hcy in nephritic syndrome (NS) patients are controversial with increased, decreased and unchanged values reported. In renal patients, plasma Hcy concentration can be reduced by administration of folic acid. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Therefore, plasma Hcy, folic acid, vitamin B6, and vitamin B12 in children with acute glomerulonephritis (AGN) were accessed in this study. Hcy, folic acid vitamin B12, B6 and renal function such as blood urea nitrogen (BUN), creatinine (Cr) were analyzed 12 pediatric patients with AGN and 15 age and sex matched healthy children served as controls. The results revealed that a?significant increase in plasma Hcy in children with acute AGN when compared with controls. For simple regression analysis, Hcy was positively correlated with BUN, Cr, ferritin and uric acid but negatively correlated with serum glutathione. This research indicated hHcy suggests enhanced risks for inflammation and endothelial injury,?which lead to kidney disease. Folic acid has also been shown to improve endothelial function, suggesting an alternative explanation for the effect of folic acid on endothelial function. Careful considerations of not only dietary measures are necessary but also folate and vitamin B supplementation for reducing hHcy in AGN need to be investigated.

Post-Infectious Acute Glomerulonephritis in Child: Epidemiological, Clinical and Evolutionary Aspects in Gabriel TouréTeaching Hospital in Mali

Introduction: Acute post-infectious glomerulonephritis (APIGN) can be serious due to its complications that still occur in our countries. In this work, we aimed to study the epidemiological, clinical, biological and evolutionary aspects of APIGN. Patients and methods: We conducted a retrospective, descriptive study from January 1st, 2015 to December 31st, 2017 in the pediatric ward of the Gabriel Touré Teaching Hospital in Bamako. All children hospitalized for APIGN were included. Results: In two years, we included 10 children aged 7 years old on average;all from low socioeconomic backgrounds. The sex ratio was 1.5. On average, the children spent 15.8 days before our consultation. Edema was the main reason for consultation. We found a history of infection and high blood pressure in 30% each, and renal failure in 10% of the children. Hematuria and proteinuria were detected in 100% and 90%, respectively. Hypocomplementemia was observed in 66.6%. One third of the children had a positive antistreptolysin O. The average duration of hospital stay was 11.2 days. The evolution was favorable in 90%. Kidney failure was the leading cause of death. Conclusion: Acute post-infectious glomerulonephritis is still a reality in our context. Emphasis should be put on its prevention by improving the hygienic conditions, detection and the management of infections.

Correlations of Serological Markers with Development of Systemic Involvement in Adult Immunoglobulin A Vasculitis:A Retrospective Study of 259 Patients in Central China

Objective:Although relatively rare,adult immunoglobulin A vasculitis(IgAV)can lead to severe complications and longer hospitalization,and result in poor prognosis,when compared to childhood IgAV.Hence,early identification and prevention for patients prone to develop systemic involvement are essential.The purpose of this study was to explore the correlations of common serological markers with the development of systemic involvement in adult IgAV.Methods:A retrospective analysis was performed for adult IgAV patients,who were hospitalized in Wuhan Union Hospital between January 2016 and December 2019.A total of 259 patients were enrolled,and the pre-treatment serological markers were comprehensively assessed.Results:In the present study,49.0% and 33.2% of patients developed renal and gastrointestinal(GI)involvement,respectively.Furthermore,the elevated levels of white blood cells count,D-Dimer(D-D),C-reactive protein(CRP)and neutrophil granulocyte ratio(NE%)>60% were significantly associated with GI involvement in the univariate analysis,while the decrease in high density lipoprotein level,and the elevated D-D and CRP levels were significantly associated with renal involvement(P<0.05).Moreover,a prediction model that combined multiple markers was established by performing a logistic regression analysis,and this presented a more favorable value of prediction than the individual serological markers.Conclusion:The present study suggests that common serological markers have close correlations with systemic involvement in adult IgAV,and that the establishment of a prediction model for systemic involvement may be helpful in facilitating personalized therapeutic strategies and clinical management for IgAV patients.

DETECTION AND SIGNIFICANCE OF HBV IN RENAL TISSUE OF HBV ASSOCIATED GLOMERULONEPHRITIS PATIENTS

Objective To study the pathogenesis of hepatitis B virus ( HBV ) on kidney tissues. Methods HBsAg and HBcAg in paraffin-embedded renal biopsy tissues from 27 cases of glomerulonephritis with positive serum HBV markers were observed by using immunohistochemistry. In addition, in situ polymerse chain reaction (IS-PCR) was performed in 5 cases with positive HBsAg and HBcAg in renal tissue of the 27-case glomerulonephritis to reveal the state of renal HBV DNA. Results Twenty cases (20/27,74.07%) were positive with HBAg which were mainly diffusely distributed in epithelial cells of renal tubule. Four cases (4/5,80% ) were positive with HBV DNA whose distribution was the same of that of HBAg. Conclusion Renal lesions due to HBV are not only the results of immunologic response, but also the outcome of direct invasion and duplication of HBV in epithelial cells of renal tubule.

THE STUDY ON RELATION BETWEEN CD1a^+ CELLS AND INFILTRATIVE CD3 ^+ AND CD8 ~ + CELLS IN RENAL TISSUE OF GLOMERULONEPHRITIS

Objective To discuss the role of dendritic cell s (DCs) in cellular immunity pathogenesis of glomerulonephritis (GN). Meth ods 114 patients with GN were selected randomly and divided into two gr oups, primary GN (pGN) and secondry GN (sGN). CD1a +, CD3 + and CD8 + cells in bioptic renal tissues were examined immunohistochemically. The di stribution of CD1a + cells and the infiltration of CD3 + and CD8 + cells in renal tissues were observed. Results There was no si gnificant difference of CD1a +, CD3 +, and CD8 + cells between pG N and sGN group (P>0.05). CD1a + cells had significant positive correla tion with the infiltrative CD3 + and CD8 + cells, respectively (P< 0.01). The infiltrative CD3 + cells had significant positive correlation wi th the CD8 + cells in the same area, respectively (P<0.01). CD1a + cells, CD3 + cells infiltrating in both glomeruli and renal interstitial t issues, and CD8 + cells only infiltrating in renal interstitial tissues, al l of them had significant positive correlation with the degree of glomerular pro liferation, respectively (P<0.05). The infiltrative CD3 + and CD8 + cells in renal interstitial tissues had significant positive correlation with the degree of glomerular sclerosis and the lesion degree of renal tubule and in terstitial, respectively (P<0.05). There were significant positive correlati on between CD1a + cells and the lesion degree of renal interstitial (P< 0.05). Conclusion DCs could activate T lymphocyte by presenting antigen, then the activated T lymphocyte participate in the pathogenesis of GN through releasing cytokine and/or directly damaging the renal tubule and interst itial, which produce more serious glomerular lesion.

Comparison of total immunoglobulin A levels in different samples in Leghorn and broiler chickens

Objective: To standardize an ELISA protocol to quantify total immunoglobulin A(IgA)from different biological samples.Methods: Two independent experiments were conducted. In Experiment 1, total IgA levels were quantified from the lachrymal fluid, tracheal swab, and cloacal swab at various time points from Days 30 to 89 in white Leghorn chickens. Experiment 2 was conducted to evaluate the effect of 50 or 500 ppb of aflatoxin B1(AFB1) on total IgA quantified in samples from the lachrymal fluid, tracheal swab, gut content and cloacal swab in broiler chickens at 21 days of age.Results: Lachrymal fluid contained the highest level of IgA; however, the sampling procedure was time consuming and stressful to the bird, and the sample volume depends largely on the size of the chicken. Cloacal swabs also contained a high concentration of IgA; this sampling procedure was faster than lachrymal fluid sampling and was not affected by the age of the bird. Tracheal sampling was more difficult than cloacal sampling; the age of the bird limited the sampling, and the IgA concentration was the lowest detected at all sampling ages. 500 ppb of AFB1 significantly reduced total IgA concentration in the gut content compared with control or 50 ppb of AFB1 treated groups.Interestingly, a significant reduction in total IgA was also observed in those chickens that received 50 ppb of AFB1 in gut rinse when compared with cloacal swabs.Conclusions: The results of this study suggest that cloacal swab is an easy and reliable way to evaluate mucosal IgA concentration in both Leghorn and broiler chickens.

Experimental Studies on immune－Complex in Situ Type Glomerulonephritis in Rabbits Treated with Mai－Luo－Tong and Natural Indig

(孙世澜)(易惠萍)(汪琼玲)(黄寿珍)(刘晓城)ＥｘｐｅｒｉｍｅｎｔａｌＳｔｕｄｉｅｓｏｎｉｍｍｕｎｅ－ＣｏｍｐｌｅｘｉｎＳｉｔｕＴｙｐｅＧｌｏｍｅｒｕｌｏｎｅｐｈｒｉｔｉｓｉｎＲａｂｂｉｔｓＴｒｅａｔｅｄｗｉｔｈＭａｉ－Ｌｕｏ－ＴｏｎｇａｎｄＮａｔｕｒａｌ...

Rituximab therapy for primary glomerulonephritis: Report on two cases

The evidence in the medical literature on the efficacy and safety of rituximab therapy for primary glomerulonephritis is limited and controversial. We describe two male Caucasian patients with rapidly progressive kidney failure due to primary proliferative glomerulonephritis. Both of them received high-dose intravenous corticosteroids and oral cyclophosphamide with limited benefit. The first patient(hepatitis C virus-negative mixed cryoglobulinemia) underwent plasma-exchange with intravenous immunoglobulins; he showed significant benefit on kidney function(he became dialysis independent with serum creatinine going back to 1.6 mg/d L) after one rituximab pulse even if urinary abnormalities were still present. No improvement in renal function or urinary changes occurred in the second patient. Both these individuals developed sepsis over the follow-up, the first patient died two months after rituximab therapy. This report is in keeping with the occurrence of severe infections after rituximab therapy in patients with renal impairment at baseline and concomitant high-dose steroids.