Gaps in kidney stone disease management: From clinical theory to patient reality.

With nephrolithiasis projected to affect 25% of the global population in the next three decades, there is an urgent call for innovative management strategies to prevent and reduce stone recurrence. This study aims to explore the evolving management needs in nephrolithiasis from both patient and healthcare provider perspectives. An expert-collaborative online survey comprising 10 targeted questions on kidney stone management was developed and disseminated. This survey was designed to gather comprehensive insights from patients, physicians and dietician and other person in the field of nephrolithiasis. Analysis of responses from 120 participants, including 45 nephrologists, 38 dieticians, 11 urologists, and 14 kidney stones patients followed in our hospital, revealed critical insights. A significant 97.5% emphasized the necessity of optimizing daily water intake, and 94.1% recognized the need for practical dietary modifications. Additionally, 88.3% of respondents found timely hydration reminders beneficial. Notably, monitoring urine color and pH was valued by 85% and 84.3% of the participants, respectively. A striking disparity emerged in the perception of fatigue and wellness monitoring, with 65% of patients prioritizing fatigue monitoring, a view less shared by healthcare professionals. Similarly, 71% of patients deemed wellness monitoring essential, highlighting a gap in understanding between patients and their caregivers. This study underscores the critical need for more tailored guidance on hydration strategies and the promise of remote urine parameters monitoring in nephrolithiasis management. The findings strongly advocate for a patient-centered approach, aligning medical recommendations with patient lifestyles and experiences, to enhance the effectiveness of nephrolithiasis management.

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

International Alliance of Urolithiasis (IAU) guidelines on the metabolic evaluation and medical management of urolithiasis.

The aim of this study was to construct the fourth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the metabolic evaluation, prevention, and follow-up of patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of the literature in the PubMed database from January 1976 to June 2022. Each generated recommendation was graded using a modified GRADE methodology. Guideline recommendations were developed that addressed the following topics: initial evaluation, metabolic testing, dietary measures, medical management, and follow-up of recurrent stone formers. It was emphasized by the Panel that prevention of new stone formation is as important as the surgical removal of the stones. Although general preventive measures may be effective in reducing stone recurrence rates in some patients, specific medical and dietary management should be well considered and eventually applied in an individualized manner based on the outcomes of metabolic work-up, stone analysis and some certain patient related factors. A detailed follow-up of each case is essential depending on the metabolic activity of each individual patient.

Clinical management of a granulomatous tubulointerstitial nephritis associated with a bilateral granulomatous anterior uveitis: A challenging case report and review of the literature.

Acute granulomatous tubulointerstitial nephritis (GTIN) is a rare finding in renal biopsy. Differential diagnosis is facilitated when GTIN is associated with granulomatous bilateral anterior uveitis (GBAU). Nevertheless, differentiation between a rare form of granulomatous tubulointerstitial nephritis and uveitis syndrome (TINU) and sarcoidosis can be challenging. We report a case of biopsy-proven GTIN with concomitant GBAU, leading to a dead-end diagnosis. We discuss workup and propose a diagnostic algorithm based on a literature review. We also report a successful treatment of ophthalmologic and renal relapse using mycophenolate mofetil.

Kidney Stones, Proteinuria and Renal Tubular Metabolic Acidosis: What Is the Link?

Kidney stone disease represents a rare cause of chronic kidney disease (2−3%) but has severe clinical consequences. Type 1 renal tubular acidosis is a strong lithogenic condition mainly related to primary Sjögren syndrome. This study aimed to illustrate an unusual presentation of Sjögren syndrome to improve the knowledge about rare kidney stone diseases, and to provide clues for the diagnostic approach in this specific condition. We report the case of a 35-year-old Indian woman with severe nephrocalcinosis and chronic kidney disease with tubular proteinuria who presented for metabolic assessment. We found advanced chronic kidney disease, low serum bicarbonate, permanent alkaline urine with pH at ~7.1, and severe hypocitraturia corresponding to type 1 renal tubular acidosis. The erythrocyte sedimentation rate was high. Serological screening for HAV, HBV, HCV, HIV, EBV was negative and complement was normal. Autoimmune screening showed antinuclear antibodies (>1/1.280) with anti-SSA, anti-SSA/Ro52 and anti-SSB antibodies. Genetic testing excluded an inherited cause of renal tubular acidosis. A renal biopsy showed moderate chronic tubulo-interstitial nephritis without any glomerular involvement. Primary Sjögren syndrome with significant renal involvement was considered, and corticosteroids were then subsequently initiated in combination with potassium citrate with vitamin D substitution. Only partial improvement was observed in electrolytes disturbance. After 15 months, her renal function remained stable. In conclusion, nephrocalcinosis could be the first manifestation of severely impacting diseases such as primary Sjögren syndrome. Chronic kidney disease, bilateral nephrocalcinosis, and metabolic acidosis can be linked through type 1 renal tubular acidosis. Therefore, autoimmune screening for Sjögren syndrome should be considered in such cases.

Experimental Aristolochic Acid Nephropathy: A Relevant Model to Study AKI-to-CKD Transition.

Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial nephritis caused by the intake of aristolochic acids (AA) contained in Chinese herbal remedies or contaminated food. AAN is characterized by tubular atrophy and interstitial fibrosis, characterizing advanced kidney disease. It is established that sustained or recurrent acute kidney injury (AKI) episodes contribute to the progression of CKD. Therefore, the study of underlying mechanisms of AA-induced nephrotoxicity could be useful in understanding the complex AKI-to-CKD transition. We developed a translational approach of AKI-to-CKD transition by reproducing human AAN in rodent models. Indeed, in such models, an early phase of acute tubular necrosis was rapidly followed by a massive interstitial recruitment of activated monocytes/macrophages followed by cytotoxic T lymphocytes, resulting in a transient AKI episode. A later chronic phase was then observed with progressive tubular atrophy related to dedifferentiation and necrosis of tubular epithelial cells. The accumulation of vimentin and αSMA-positive cells expressing TGFß in interstitial areas suggested an increase in resident fibroblasts and their activation into myofibroblasts resulting in collagen deposition and CKD. In addition, we identified 4 major actors in the AKI-to-CKD transition: (1) the tubular epithelial cells, (2) the endothelial cells of the interstitial capillary network, (3) the inflammatory infiltrate, and (4) the myofibroblasts. This review provides the most comprehensive and informative data we were able to collect and examines the pending questions.

Subclinical Choroidal Inflammation Revealed by Indocyanine Green Angiography in Tubulointerstitial Nephritis and Uveitis Syndrome.

PURPOSE: To describe subclinical chorioretinal lesions revealed by indocyanine green angiography (ICGA) and their evolution under systemic treatment in tubulointerstitial nephritis and uveitis (TINU) patients. METHODS: Retrospective case series of three patients with TINU syndrome. Choroidal and retinal involvement were assessed by fluorescein angiography (FA) and ICGA. RESULTS: Three patients were analyzed. FA demonstrated hot disc, associated in two cases with retinal vascular leakage, and ICGA revealed subclinical chorioretinal dots in all three cases. Given the presence of posterior uveitis and deterioration of kidney function, asystemic treatment by oral methylprednisolone was started. Persistence of retinal and choroidal inflammations under systemic corticosteroids required association with immunosuppressive agent to control the disease activity. CONCLUSION: Multimodal imaging and more precisely ICGA is useful to assess subclinical choroidal inflammation and monitor treatment response in TINU syndrome. Immunosuppression needs to be revised and adapted when uveitis and/or kidney function are unresponsive to systemic steroids. ABBREVIATIONS: TINU: tubulointerstitial nephritis and uveitis; TIN: tubulointerstitial nephritis; ACE: angiotensin-converting enzyme; RF: rheumatoid factor; Uß2M: urinary ß-2microglobulin; AMPPE: acute multifocal placoid pigment epitheliopathy; FA: fluorescein angiography; ICGA: indocyanine green angiography; CT: computed tomography.

In Search of an Efficient Complexing Agent for Oxalates and Phosphates: A Quantum Chemical Study.

Limiting gastrointestinal oxalate absorption is a promising approach to reduce urinary oxalate excretion in patients with idiopathic and enteric hyperoxaluria. Phosphate binders, that inhibit gastrointestinal absorption of dietary phosphate by the formation of easily excretable insoluble complexes, are commonly used as a treatment for hyperphosphatemia in patients with end-stage renal disease. Several of these commercially available phosphate binders also have affinity for oxalate. In this work, a series of metallic cations (Li+, Na+, Mg2+, Ca2+, Fe2+, Cu2+, Zn2+, Al3+, Fe3+ and La3+) is investigated on their binding affinity to phosphate and oxalate on one side and anionic species that could be used to administer the cationic species to the body on the other, e.g., acetate, carbonate, chloride, citrate, formate, hydroxide and sulphate. Through quantum chemical calculations, the aim is to understand the competition between the different complexes and propose possible new and more efficient phosphate and oxalate binders.

Lanthanum carbonate to control plasma and urinary oxalate level in type 1 primary hyperoxaluria?

INTRODUCTION: The therapy to reduce urinary oxalate excretion in primary hyperoxaluria type 1 is still required. CASE PRESENTATION: A 37-year-old hemodialyzed man suffered from systemic oxalosis secondary to primary hyperoxaluria type 1 exhibited a drastic plasma oxalate decrease from 110 to 22 µmol/L two months after adjunction of lanthanum carbonate to classical treatment (intensive hemodialysis with pyridoxine). A 34-year-old woman with normal kidney function presented 10 years of bilateral kidney stones due to primary hyperoxaluria type 1 [hyperoxaluria (109.2 mg/24 h), plasma oxalate (56.0 µmol/L)]. The oxalate level remained uncontrolled despite of low oxalate-normal calcium diet, pyridoxine and increased water intake though the lanthanum carbonate adjunction resulted in significant decrease in plasma oxalate and oxaluria. CONCLUSION: We report the lanthanum efficacy in reducing circulating and urinary oxalate levels in type 1 primary hyperoxaluria. Possible mechanism of observed falls in oxalate concentration would be a decrease in the intestinal absorption of oxalate.

Molecular classification of membranous nephropathy.

PURPOSE OF REVIEW: Continuous expansion of our knowledge in the pathogenesis of membranous nephropathy possible by the identification of antibodies recognized specific podocytes antigens results in unprecedent patient management strategy. RECENT FINDINGS: Circulating anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin domain 7A (THSD7A) antibodies strongly relate with the modifications of podocytes biology leading to the new molecular diagnosis of membranous nephropathy. Immunization against THSD7A involves extra-renal mechanism. However, the pathway of anti-PLA2R immunization still remains unresolved. Experimental data highlight the crucial role of THSD7A in the attachment of podocytes to the glomerular basement membrane, rewarding the THSD7A pathogenicity, whereas the third of Koch's postulates is still not fulfilled for anti-PLA2R antibodies. The anti-PLA2R antibodies epitope spreading will possibly be even more specific marker improving the molecular classification of membranous nephropathy. Two immune epitopes have been identified in the N-terminal tail of THSD7A but without evidence of epitope spreading as for anti-PLA2R. SUMMARY: In 2019, the Kidney Diseases: Improving Global Outcomes guidelines recognized anti-PLA2R antibodies (but not anti-THSD7A antibodies) as a valuable molecular risk factor for the pejorative evolution of kidney function and recommended their monitoring for the diagnosis and the assessment of membranous nephropathy immune activity. Screening for malignancy is particularly advised in THSD7A-mediated membranous nephropathy.

A preliminary survey of practice patterns across several European kidney stone centers and a call for action in developing shared practice.

Currently an evidence-based approach to nephrolithiasis is hampered by a lack of randomized controlled trials. Thus, there is a need for common platforms for data sharing and recruitment of patients to interventional studies. A first step in achieving this objective would be to share practice methods and protocols for subsequent standardization in what is still a heterogeneous clinical field. Here, we present the results of a pilot survey performed across 24 European clinical kidney stone centers. The survey was distributed by a voluntary online questionnaire circulated between June 2017 and January 2018. About 46% of centers reported seeing on average 20 or more patients per month. Only 21% adopted any formal referral criteria. Centers were relatively heterogeneous in respect of the definition of an incident stone event. The majority (71%) adopted a formal follow-up scheme; of these, 65% included a follow-up visit at 3 and 12 months, and 41% more than 12 months. In 79% of centers some kind of imaging was performed systematically. 75% of all centers performed laboratory analyses on blood samples at baseline and during follow-up. All centers performed laboratory analyses on 24-h urine samples, the majority (96%) at baseline and during follow-up. There was good correspondence across centers for analyses performed on 24-h urine samples, although the methods of 24-h urine collection and analysis were relatively heterogeneous. Our survey among 24 European stone centers highlights areas of homogeneity and heterogeneity that will be investigated further. Our aim is the creation of a European network of stone centers sharing practice patterns and hosting a common database for research and guidance in clinical care.

Meeting report of the "Symposium on kidney stones and mineral metabolism: calcium kidney stones in 2017".

A symposium on kidney stones and mineral metabolism held on December 2017 in Brussels, Belgium was the first international multidisciplinary conference of the International Collaborative Network on Kidney Stones and Mineral Metabolism. This meeting addressed epidemiology, underlying pathophysiological mechanisms, genetics, pathological, as well as clinical and research topics. The participants included clinicians and recognized experts in the field from Europe and the United States interacted closely during the symposium which promoted a chance to explore new frontiers in the field of kidney stone disease. This manuscript summarizes some of the major highlights of the meeting.

New insights into immune cells cross-talk during IgG4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) is a newly acknowledged entity, characterized by an immune-mediated fibro-inflammatory process affecting virtually all organs, with infiltration of IgG4+ bearing plasma cells. Until today the pathogenesis of IgG4-RD remains unknown. Treatment with anti-CD20 monoclonal antibodies efficiently induced remission and attenuated the secretory phenotype of myofibroblasts responsible of uncontrolled collagen deposition. This supports the pathogenic role of the adaptive immunity, particularly B cell compartment and B cell/T cell interaction. Latest studies have also highlighted the importance of innate immune system that has been underestimated before and the key role of a specific T cell subset, T follicular helper cells that are involved in IgG4-class-switching and plasmablast differentiation. In this review, we aim to review the most recent knowledge of innate immunity, T and B cells involvement in IgG4-RD, and introduce tertiary lymphoid organs (TLO) as a potential marker of relapse in this condition.

Membranous Nephropathy and Anti-Podocytes Antibodies: Implications for the Diagnostic Workup and Disease Management.

The discovery of circulating antibodies specific for native podocyte antigens has transformed the diagnostic workup and greatly improved management of idiopathic membranous nephropathy (iMN). In addition, their identification has clearly characterized iMN as a largely autoimmune disorder. Anti-PLA2R1 antibodies are detected in approximately 70% to 80% and anti-THSD7A antibodies in only 2% of adult patients with iMN. The presence of anti-THSD7A antibodies is associated with increased risk of malignancy. The assessment of PLA2R1 and THSD7A antigen expression in glomerular immune deposits has a better sensitivity than measurement of the corresponding autoantibodies. Therefore, in the presence of circulating anti-podocytes autoantibodies and/or enhanced expression of PLA2R1 and THSD7A antigens MN should be considered as primary MN (pMN). Anti-PLA2R1 or anti-THSD7A autoantibodies have been proposed as biomarkers of autoimmune disease activity and their blood levels should be regularly monitored in pMN to evaluate disease activity and predict outcomes. We propose a revised clinical workup flow for patients with MN that recommends assessment of kidney biopsy for PLA2R1 and THSD7A antigen expression, screening for circulating anti-podocytes antibodies, and assessment for secondary causes, especially cancer, in patients with THSD7A antibodies. Persistence of anti-podocyte antibodies for 6 months or their increase in association with nephrotic proteinuria should lead to the introduction of immunosuppressive therapies. Recent data have reported the efficacy and safety of new specific therapies targeting B cells (anti-CD20 antibodies, inhibitors of proteasome) in pMN which should lead to an update of currently outdated treatment guidelines.

Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients.

OBJECTIVES: To assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients. METHODS: Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model. RESULTS: Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients. CONCLUSION: RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.

Circulating (CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)) Plasmablasts: A Promising Cellular Biomarker for Immune Activity for Anti-PLA2R1 Related Membranous Nephropathy?

Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX), efficacy is still needed to improve clinical outcome of patient with MN. We evaluated the modification of plasmablasts (CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)), a useful biomarker of RTX response in other autoimmune diseases, and memory (CD3(-)CD19(+)CD20(+)IgD(-)CD27(+)CD38(-)) and naive (CD3(-)CD19(+)CD20(+)IgD(+)CD27(-)CD38(low)) B cells by fluorescence-activated cell sorter analysis in PLA2R1 related MN in one patient during the 4 years of follow-up after RTX. RTX induced complete disappearance of CD19(+) B cells, plasmablasts, and memory B cells as soon as day 15. Despite severe CD19(+) lymphopenia, plasmablasts and memory B cells reemerged early before naive B cells (days 45, 90, and 120, resp.). During the follow-up, plasmablasts decreased more rapidly than memory B cells but still remained elevated as compared to day 0 of RTX. Concomitantly, anti-PLA2R1 Ab increased progressively. Our single case report suggests that, besides monitoring of serum anti-PLA2R1 Ab level, enumeration of circulating plasmablasts and memory B cells represents an attractive and complementary tool to assess immunological activity and efficacy of RTX induced B cells depletion in anti-PLA2R1 Ab related MN.

Blocking TGF-ß Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRß+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats.

BACKGROUND: The platelet-derived growth factor receptor ß (PDGFRß)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target. AIMS: In this regard, we first confirmed the presence of PDGFRß+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor ß (TGFß) inhibition in a rat model of AAN. MATERIALS AND METHODS: Neutralizing anti-TGFß antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily. RESULTS: At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro. CONCLUSIONS: The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRß+ pericytes-derived myofibroblasts accumulation.

Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN.

Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m(2) Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m(2)with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death.