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The ANCA associated vasculitides (AAV) include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and churgstrauss syndrome (eosinophilic granulomatosis with polyangiitis, EGPA). Renal involvement is present in 20-50% of patients at presentation; 70-80% of patients will in time have renal involvement during the course of GPA and MPA. The typical histopathology is a pauci-immune focal and necrotizing crescentic glomerulonephritis [1]. Therapy consists of a staged treatment approach involving two treatment phases: remission induction, and remission maintenance. Treatment response is evaluated both clinically and by measurement of serum creatinine, inflammatory markers and urinary markers.

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are mostly limited to individuals who are immunosuppressed. In transplant recipients, BKV has been associated with ureteral stenosis, interstitial nephritis, and hemorrhagic cystitis. The role of BKV in the development of human tumors is intriguing but uncertain. BKV has been identified in various tumor types including urothelial carcinoma, but the ubiquitous presence of BKV as a latent infection has confounded efforts to validate any causal role in cancer development. We report the case of a simultaneous pancreas and kidney transplant recipient who developed BKV interstitial nephritis and carcinoma of the bladder with widespread metastases. High level expression of BKV large T antigen in the primary and metastatic carcinoma, but not in the nonneoplastic urothelium, implicates BKV as an etiologic agent in the development of this tumor.

Despite major advances in the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) achieved in the last decades, a large proportion of AAV patients still develop end-stage renal disease. The survival of AAV patients dependent on dialysis is significantly worse compared with dialysis-independent AAV patients, but is comparable to other non-diabetic patients requiring dialysis. Renal transplantation (RTx) is the method of choice among renal replacement therapies and there has been increasing evidence that it is a suitable method with favorable patient- and graft-survival also in AAV patients. It is recommended to perform RTx after ≥12 months of remission, and ANCA positivity at the time of RTx is generally not considered a contraindication. Even though the risk of relapse after RTx is relatively low with current post-transplant immunosuppressive regimens, disease recurrence may occur. Besides cyclophosphamide, rituximab might become a therapeutic alternative for post-transplant AAV recurrence in the near future but its efficacy and safety in this setting needs to be confirmed in larger studies.

Granulomatosis with polyangiitis and microscopic polyangiitis are anti-neutrophil cytoplasmic antibody-associated vasculitides (AAVs) that are prone to cycles of remission and relapse. The introduction of cytotoxic therapy has changed the prognosis for these diseases from typically fatal to manageable chronic illnesses with a relapsing course. Despite improvements in outcomes, recurrence of disease and drug-related toxicity continue to produce significant morbidity and mortality. Better understanding of the pathogenesis of AAV and the mechanism of action of cyclophosphamide has led to investigation of therapies that target B cells. Two randomized controlled trials have shown that rituximab is not inferior to cyclophosphamide for induction of remission in severe AAV, with no significant difference in the incidence of overall adverse events in rituximab- versus cyclophosphamide-treated patients. Data from ongoing clinical trials will determine the role of rituximab in the maintenance of remission.

Human Parvovirus B19 (PV B19) is one of the several recently described ‘emerging viruses’ and has been identified as the etiological agent of ‘fifth disease’ in childhood. Human PV B19, which is the etiological agent of transient erythroblastopenia in hemolytic anemia, is also a recognized rare cause of red cell aplasia in immunocompromised patients, including transplant recipients. To date, 26 cases of PV B19-induced red cell aplasia have been reported in solid organ transplant recipients. Twelve patients had cyclosporine-based immunosuppression and 14 had tacrolimus-based immunosuppression. Sixteen of these patients required treatment with commercial intravenous immunoglobulin alone, 1 required treatment with intravenous immunoglobulin and plasmapheresis, 4 required intravenous immunoglobulin and erythropoietin, 1 required treatment with intravenous immunoglobulin and conversion of tacrolimus to cyclosporine, 1 had improvement in hematocrit with erythropoietin alone and in 3 patients the disease was self-limiting. Herein, we report a case of pure red cell aplasia caused by acute PV B19 infection in a renal transplant recipient in whom the immunosuppressive regimen included prednisone, mycophenolate mofetil and tacrolimus and the red cell aplasia resolved with discontinuation of mycophenolate mofetil.

Pauci-immune glomerulonephritis is rare in African Americans (AA) and the clinical presentation and treatment outcomes of vasculitis have not been well described.We identified patients who were 2-92 years of age between 1983 and 2011 with a diagnosis of biopsy-proven pauci-immune glomerulonephritis (GN) at any point during their disease course. Comparing AA to Caucasian patients, we examined demographics, clinical features at presentation, treatment and outcomes of relapse, end-stage renal disease (ESRD), and death.Of the 672 patients, 75 were AA with the remainder being Caucasian. Compared to Caucasians, disease onset in AA was at an earlier age (52 vs. 57 years, p = 0.05) and was more often myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positive (71% vs. 54%, p = 0.01). AA patients had a shorter median time between onset of symptoms and biopsy compared to Caucasians [median (IQR): 0.23 (0.00, 1.22) months vs. 0.66 (0.00, 3.62) months, p = 0.003]. Median [Interquartile range (IQR)] follow-up in months was 28 (5, 52) in AA and 26 (10, 55) in Caucasian patients. Median estimated glomerular filtration rate was similar at presentation (21 vs. 22 ml/min/m(2)). Both groups had similar induction treatment regimens. There was less favorable treatment response among AA compared to Caucasians for initial treatment resistance (28% vs. 18%, p = 0.05) and complete remission (72% vs. 82%, p = 0.05). There were no differences in the number of renal relapses or number of deaths between the 2 groups. Overall, in multivariable analyses controlling for age, race, ANCA type, and entry serum creatinine, there were not differences by race in treatment response, renal relapse, ESRD, or death over the entire time of follow-up.AA patients with pauci-immune GN are younger and more often MPO-ANCA positive compared to Caucasians. Despite a shorter time to diagnosis for AA patients, there were no differences compared to Caucasians in treatment response, ESRD, renal relapse, or death rates by race over the entire duration of follow-up.

Hematuria is considered a marker of active renal disease in ANCA-associated glomerulonephritis (ANCA-GN) with induction immunosuppression often continued until hematuria has resolved. We aim to determine whether longer hematuria duration is associated with lower estimated glomerular filtration rate (eGFR) at 1 year.We conducted a retrospective study of 55 patients with biopsy-proven ANCA-GN. Linear regression models were constructed to determine predictors of eGFR at 1 year. The primary exposure was hematuria (5 rbc/hpf) duration, defined as90 days vs. ≥ 90 days following renal biopsy. Covariates included age, gender, ANCA type, baseline eGFR, and baseline proteinuria.Mean age at diagnosis was 58 years (53% male, 80% Caucasian, 38% PR3-ANCA, and 45% MPO-ANCA). At baseline, all patients had hematuria, 95% had proteinuria, and mean serum creatinine was 3.1 [standard deviation (SD) = 2.3]mg/dL. Overall, 93% were treated with steroids in combination with either cyclophosphamide or rituximab. Mean hematuria duration was 92 (SD = 77) days with 34 (62%) patients having hematuria resolution within 90 days. Older age and lower baseline eGFR were associated with lower eGFR at 1 year (p = 0.03 and p0.001, respectively). Hematuria resolution (90 days vs. ≥ 90 days) was not predictive of eGFR at 1 year (p = 0.93).In ANCA-GN, hematuria duration does not predict eGFR at 1 year. Our findings provide support that among individuals who are otherwise considered to be in clinical remission, the persistence of hematuria should not delay transition from induction to maintenance immunosuppression.

Kidney transplantation (KTX) is the treatment of choice for patients with end-stage renal disease (ESRD) due to ANCA-associated vasculitis (AAV). Recurrent ANCA-associated glomerulonephritis (GN) occurs after KTX and may adversely affect allograft survival. Cyclophosphamide (CYC) combined with glucocorticoids has been the cornerstone of treatment for recurrent GN. Rituximab (RTX), a B-cell-depleting monoclonal antibody, is approved for remission induction in AAV. We report the clinical presentation and outcomes of five KTX recipients treated with RTX for biopsy-confirmed recurrent GN. The median age at the time of KTX was 26 years (four Caucasian, three females). All patients were in remission with four being ANCA positive at time of KTX. Recurrent GN occurred at a median of 26 months post-KTX. All relapses were treated with RTX and glucocorticoids. Four patients achieved disease remission; the fifth patient was refractory to treatment with RTX and CYC. Follow-up biopsies (n = 3) showed resolution of active GN in two patients and persistent active GN in one patient. RTX is an alternative to CYC for remission induction in recurrent AAV-associated GN in KTX patients.

The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown.In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months.A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide-azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P=0.01) and at 12 months (P=0.009) but not at 18 months (P=0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events.In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, NCT00104299.)

Women of reproductive age who have received a solid-organ transplant are at risk for unplanned pregnancy. Fertility can return as soon as 1 month after transplantation, and the baseline unplanned pregnancy rate in the United States is approximately 50%. Pregnancy, although not absolutely contraindicated in this population, carries risk greater than the general population and should be timed with regard to medication regimen and organ function. The Centers for Disease Control categorizes every form of contraception as Category 2-benefits outweigh risks-in women with an uncomplicated transplantation. There is a large range of contraceptive options, varying in drug formulation, route of delivery, and discrepancy between "perfect" and "typical" use. Long-acting reversible contraceptive methods include intrauterine devices (IUDs) and subdermal implants and show great promise for women with solid-organ transplant. These methods have excellent efficacy, eliminate user error, and, in the case of IUDs, have extremely low or no systemic drug absorption. Providers have historical concerns regarding the association of IUD and infection; however, modern studies have shown their safety in both immunocompetent and immunocompromised patients. Women with a history of solid-organ transplantation can be safely offered a wide range of contraceptive options to suit their individualized needs.

The anti-neutrophil cytoplasmic antibody-associated vasculitides include granulomatosis with polyangiitis (Wegener’s granulomatosis) and microscopic polyangiitis. The introduction of therapy with cytotoxic agents such as cyclophosphamide transformed these diseases from fatal diagnoses to chronic conditions characterized by cycles of relapse and remission. Modern treatment strategies have focused on minimizing cyclophosphamide exposure or eliminating its use altogether. Two randomized clinical trials have shown that rituximab is not inferior to cyclophosphamide for induction of remission in patients with severe granulomatosis with polyangiitis (Wegener’s) or microscopic polyangiitis. For patients with non-life threatening disease, methotrexate may be used to induce and maintain remission, although some patients may have a higher long-term risk of relapse as a result. For patients with life-threatening disease, plasma exchange may be an effective adjuvant therapy. This article reviews seminal studies from the past decade that have contributed to the current standard of care.

Objective.Hematuria is considered a sign of active renal disease in patients with small-vessel vasculitis. In patients who are in apparent clinical remission, presence of persistent or new-onset microscopic hematuria may reflect active vasculitis, damage, or other glomerular pathology.Methods.We identified 74 patients from the Johns Hopkins Renal Pathology database between 1995 and 2009 with the diagnosis of pauciimmune glomerulonephritis (GN). Among them we identified 9 who were in clinical remission and underwent a renal biopsy for evaluation of persistent or new-onset hematuria.Results.Nine patients with small-vessel vasculitis, 8 antineutrophil cytoplasmic antibody (ANCA)-positive and 1 ANCA-negative, underwent a renal biopsy at variable time periods after remission of vasculitis (6 to 164 months) for persistent microscopic hematuria (n = 6) or new-onset microscopic hematuria (n = 3). All patients were in apparent clinical remission at the time of renal biopsy. Of the 3 patients presenting with new-onset hematuria, 2 had crescentic IgA nephropathy and 1 had healed crescentic pauciimmune GN. Of the 6 patients with persistent hematuria, 2 had arteriosclerosis, 2 had focal segmental glomerulosclerosis, and 2 had global and segmental glomerulosclerosis and healed crescentic GN, and none had active vasculitis.Conclusion.Microscopic hematuria in patients with renal vasculitis otherwise in remission could represent chronic glomerular injury from prior episode of vasculitis or may represent new glomerular pathology. Renal biopsy should be considered in these patients to guide therapy.

ABO-incompatible kidney transplant recipients may have a higher incidence of BK virus allograft nephropathy (BKVAN) compared with ABO-compatible recipients. It is unclear whether HLA-incompatible recipients share this risk or whether this phenomenon is unique to ABO-incompatible recipients. DESIGN, SETTING, PARTICIPATION, MEASUREMENTS: This study analyzed adult incompatible kidney transplant recipients from 1998 to 2010 (62 ABO-incompatible and 221 HLA-incompatible) and identified patients in whom BKVAN was diagnosed by biopsy (per protocol or for cause). This was a retrospective analysis of a prospectively maintained database that compared BKVAN incidence and outcomes between ABO- and HLA-incompatible recipients, respectively. BKVAN link to rejection and graft accommodation phenotype were also explored. The Johns Hopkins Institutional Review Board approved this study.Risk for BKVAN was greater among ABO-incompatible than HLA-incompatible patients (17.7% versus 5.9%; P=0.008). Of BKVAN cases, 42% were subclinical, diagnosed by protocol biopsy. ABO-incompatibility and age were independent predictors for BKVAN on logistic regression. C4d deposition without histologic features of glomerulitis and capillaritis (graft accommodation-like phenotype) on 1-year biopsies of ABO-incompatible patients with and without BKVAN was 40% and 75.8%, respectively (P=0.04). Death-censored graft survival (91%) and serum creatinine level among surviving kidneys (1.8 mg/dl) were identical in ABO- and HLA-incompatible patients with BKVAN (median, 1399 and 1017 days after transplantation, respectively).ABO-incompatible kidney recipients are at greater risk for BKVAN than HLA-incompatible kidney recipients. ABO-incompatible recipients not showing the typical graft accommodation-like phenotype may be at heightened risk for BKVAN, but this observation requires replication among other groups.

Polyomavirus-associated nephropathy (PVAN) is an increasing cause of renal allograft dysfunction, but the optimal management of immunosuppression for these patients is unclear. We examined the clinical course of 58 patients with biopsy-proven PVAN diagnosed from 1997 to 2008 at Johns Hopkins Medical Institutions. Immunosuppression management was analyzed as 2 different immunosuppression reduction strategies, the first centered on eliminating a single immunosuppressive drug and reducing the doses of all other immunosuppressive drugs (Strategy A, n = 40), compared with the second, centered on reducing the doses of all immunosuppressive drugs and eliminating none (Strategy B, n = 18). Primary outcome was graft failure, defined as a 50% reduction in estimated glomerular filtration rate, or the need for dialysis within 2 years of PVAN diagnosis. Graft failure developed in 17 (29%) patients during follow-up. In unadjusted and adjusted Cox models, both strategies of immunosuppression reduction had similar efficacy in preventing graft failure (hazard ratio [HR], 0.61; 95% confidence interval, 0.18-2.06; p = 0.43). Rejection after PVAN occurred in 24 of 58 patients and was associated with a 3-fold higher risk of graft failure (HR, 2.99; p = 0.005). Ancillary therapies (cidofovir or leflunomide) were associated with a trend toward faster clearance of viremia (p = 0.65) but were not predictive of outcome.In conclusion, the 2 strategies of immunosuppression reduction had similar efficacy in preventing graft failure. Post-PVAN rejection leads to graft failure. Early repeat allograft biopsy should be considered in the management of PVAN with persistent graft dysfunction.

Fibrillary glomerulonephritis (GN) is an uncommon cause of rapidly progressive kidney failure. We report a case of rapidly progressive kidney failure with kidney biopsy showing crescentic GN on light microscopy and immunofluorescence showing linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G and C3, consistent with anti-GBM disease. However, electron microscopy showed fibrillary deposits in the GBM, suggesting a diagnosis of fibrillary GN. As exemplified by this case, it is important to consider fibrillary GN in the differential diagnosis of crescentic GN with linear immunoglobulin G deposits within the GBM. Electron microscopy is crucial to make this diagnosis.

Pauci-immune crescentic glomerulonephritis remains the most common cause of rapidly progressive renal failure (1). The majority of cases are associated with the presence of circulating antineutrophil cytoplasmic antibodies (ANCA) (2). The two major subtypes of ANCA-associated vasculitis (AAV) are Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA). Notwithstanding the advances in diagnosis and treatment of AAV, 20% to 40% of patients developed end-stage renal disease (ESRD) (3–6). Kidney transplantation (KTX) has been shown to improve survival and quality of life among patients with ESRD, and several studies have demonstrated that KTX offers a survival benefit compared with maintenance dialysis (7, 8). Transplanted AAV patients also have lower vasculitis relapse rates compared with those who remain on dialysis (6, 9–12). A mean 10-year graft survival of 65.4% has been reported for patients with WG, which compares favorably with graft survival observed in other nonsystemic inflammatory conditions (13); however, as many as 50% of cases have been said to suffer a vasculitis relapse after KTX, and this may adversely affect allograft outcome (3, 4, 14–21). A pooled analysis of 127 patients reported in 1999 indicated that AAV recurred in 17.3% of patients after KTX (22). The majority of these patients (65%) received cyclosporine. In contrast, a much lower vasculitis relapse rate was observed in two single-center series published in recent years on AAV patients using modern immunosuppressive agents (23, 24). Gera et al. (23), in a single-center series of 35 transplant recipients with diagnoses of AAV reported nonrenal relapses in three patients (8.6%). No clear risk factor to relapse emerged and no detrimental effect to renal function was found. In addition, another single-center analysis of 17 patients with AAV who underwent KTX identified relapses in three patients over a median follow-up of 37 months (24). More recently, Little et al. (25) reported relapses in only 5 of 107 transplanted AAV patients (4.7%). Overall graft survival was 70% after 10 years. ANCA status per se was not significantly associated with graft failure, and the strongest predictor of death was transplantation less than 1 year from the time of vasculitis remission (25). This study included patients transplanted over a 20-year period and did not have details of posttransplant immunosuppression. These discrepancies and the paucity of information regarding long-term transplant outcomes for AAV in the modern era of immunosuppression led us to extend our previous observations by conducting this multicenter study to address questions regarding the influence of waiting period after remission is achieved before KTX, influence of disease subtypes, ANCA status at the time of KTX, and the effect antirejection regimen on graft outcome and vasculitis relapse rate in this patient population.

Background Cyclophosphamide and glucocorticoids have been the cornerstone of remissioninduction therapy for severe antineutrophil cytoplasmic antibody (ANCA)−associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. Methods We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. Results Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P

Objective.Antineutrophil cytoplasmic antibody-associated vasculitis is an important cause of endstage renal disease. Our aim was to investigate how the underlying vasculitis diagnosis may influence outcomes following renal transplant.Methods.We undertook a retrospective cohort study of patients who underwent renal transplant at the Johns Hopkins Hospital between 1999 and 2008.Results.Detailed followup data were available for 11 patients with Wegener’s granulomatosis (WG) and 6 with microscopic polyangiitis (MPA), representing 799 patient-months of observation. Patients with WG remained on hemodialysis longer (and may have had slightly worse renal outcomes following transplant) than patients with MPA. Four patients with WG experienced adverse events following renal transplant: 2 experienced rejection and 2 vasculitis flare. Among the patients with MPA, there was 1 episode of rejection and no vasculitis flare.Conclusion.Whether outcomes following renal transplant may be influenced by the underlying diagnosis of vasculitis merits further study.

Kidney transplantation should be considered the treatment of choice for patients with end-stage renal disease due to antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). However, relapses of AAV have been reported to occur in 9-40% of cases following kidney transplantation and may adversely affect allograft outcome. These relapses are usually treated with cyclophosphamide (CYC) and glucocorticoids, but the repeated use of CYC carries a risk of substantial toxicity that may limit or prohibit its use in some patients. B lymphocytes have been implicated in the pathogenesis of AAV, and their depletion has been effective as salvage therapy for refractory disease in the nontransplant setting. We report the successful induction of remission using rituximab in two patients who suffered relapse of AAV post-kidney transplant. Given the substantial morbidity and adverse effects of CYC, rituximab appears to be a suitable alternative agent to treat relapses of AAV posttransplantation.

Despite advances in the diagnosis and treatment of the antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides, renal morbidity is common. End-stage renal disease occurs in up to 20% of patients with these diagnoses, which include Wegener's granulomatosis and microscopic polyangiitis. As the mortality of patients with ANCA-associated vasculitis continues to improve, our ability to address the consequences of renal failure in this patient population becomes paramount. Renal transplantation is an important therapeutic option for these patients. Graft and patient survival rates among patients with ANCA-associated vasculitis are comparable to those observed in nondiabetic patients. This review summarizes our current knowledge of indications and contraindications for renal transplantation in these patients, the recurrence of vasculitis after transplantation and the impact of posttransplant immunosuppression on the clinical course of these patients.

Polyomavirus virus nephropathy (PVN) is an important cause of renal allograft dysfunction. The risk factors for the development of PVN have not been completely elucidated. We investigated the hypothesis that ureteral trauma caused by placement of indwelling stents is an independent risk factor for PVN. Twenty cases of PVN were compared with 46 controls. Logistic regression was used to calculate odds ratios and to construct multivariate models. A total of 75% of cases and 35% of controls had stents placed during renal transplantation. In both univariate and multivariate logistic regression analyses adjusting for age, gender, deceased donor transplant, delayed graft function, tacrolimus and exposure to antibodies, the placement of a ureteral stent at the time of kidney transplantation was found to have a statistically significant association with developing PVN. Our findings reveal that the presence of a ureteral stent is associated with an increase in the risk of PVN.

Granulomatosis with polyangiitis and microscopic polyangiitis are small vessel vasculitides characterized by circulating antineutrophil circulating antibodies. Standard treatment for active severe disease has consisted of cyclophosphamide with glucocorticoids with or without plasmapheresis, which achieves approximately 75% sustained remission, but carries significant adverse effects such as malignancy, infertility, leukopenia, and infections. The role of B cells in the pathogenesis of anti-neutrophil circulating antibodies-associated vasculitis has been established, and as such, rituximab, a monoclonal anti-CD20 antibody, has been studied in treatment of active granulomatosis with polyangiitis and microscopic polyangiitis (induction) and in maintaining remission. Rituximab has been shown to be effective in inducing remission in several retrospective studies in patients with refractory disease or cyclophosphamide intolerance. The RAVE and RITUXVAS trials demonstrated rituximab is a noninferior alternative to standard cyclophosphamide-based therapy; however, its role in elderly patients and patients with severe renal disease warrants further investigation. Rituximab has been compared with azathioprine for maintaining remission in the MAINRITSAN trial and may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction. Rituximab is not without risks and carries a similar adverse event risk rate as cyclophosphamide in randomized control trials. However, its use can be considered over cyclophosphamide in patients who have relapsing or refractory disease or in young patients seeking to preserve fertility.

Background Renal biopsies provide important diagnostic and prognostic information in ANCA associated glomerulonephritis. A new classification for prognostication of pauci-immune glomerulonephritis (GN) based on four categories (Mixed, Crescentic, Sclerotic and Focal) was proposed by an international working group of renal pathologists (IWGRP). The goal of our study was to apply the proposed classification system to a United States cohort of vasculitis patients and determine the association of IWGRP class with estimated glomerular filtration rate (eGFR) at one year. Methods Seventy-six cases of pauci-immune glomerulonephritis diagnosed from 1995 to 2011 from a single center were identified for this retrospective study. Clinical data were collected by abstraction from medical records. Histology was reviewed by a pathologist and classified according to the new classification. MDRD formula was used to calculate eGFR. We correlated IWGRP class to renal function at presentation and at one year. ×2, ANOVA, and linear regression analysis were performed as appropriate. Results Renal biopsies were categorized as focal: n = 20, crescentic: n = 18, mixed: n = 27, sclerotic: n = 11. The baseline e-GFR was lowest in the crescentic class and highest in the focal class. In linear regression analysis investigating e-GFR at 1 year; age and baseline e-GFR were independent predictors of e-GFR at 1 year. Conclusions The e-GFR at diagnosis and age were predictors of e-GFR at 1 year. Pathologic class at diagnosis may also be a helpful tool in risk stratification at diagnosis.

Background ANCA-associated vasculitis (AAV) with renal involvement is not uncommon in older individuals. Unfortunately, this can be catastrophic requiring hemodialysis (HD) and may lead to end stage renal disease (ESRD). However, more than 50 % of patients with AAV who require HD initially have renal recovery and discontinue HD. The aim of this study was to describe a retrospective cohort of older patients with AAV and severe renal involvement which required hemodialysis. Methods Between 1995 and 2013 a total of 30 patients with histologic evidence of pauci-immune glomerulonephritis who required HD were evaluated at a single university center. The association of demographic and clinical parameters with age was assessed. Older age of disease onset was defined as age ≥60 years. The risk of developing ESRD at 3 months was examined using univariate logistic regression analysis. Results Among 30 patients with AAV who required HD, the mean age of disease onset was 59 ± 17 years (range 22-88 years). Twelve patients were in the older age group, and 18 were in the younger group. Three months after diagnosis, 43 % of the cohort had ESRD with a statistically similar proportion of older (n = 9, 50 %) versus younger (n = 4, 33 %) patients (p = 0.367). Most patients (93 %) received immunosuppressive therapy. There was not a statistically significant association between age and ESRD. Conclusions These data suggest that age alone does not predict renal recovery among individuals on HD due to AAV. Renal recovery is a realistic expectation and outcome, if patients are treated, even among older patients with AAV who require HD initially.

Background Provision of exceptional medical care is a goal for the medical profession because this is what the public needs and deserves. Academic medical centers that value excellent clinicians may have the best chance to recruit and retain these faculty members. When our institution hoped to launch the Miller Coulson Academy of Clinical Excellence to measure and reward master clinicians, a critical first step was to use rigorous methods to develop a definition of clinical excellence. Published papers have illustrated that this general definition of clinical excellence is applicable to fields of psychiatry, cardiology, and pediatrics. Summary In this manuscript, we apply the definition of clinical excellence to nephrology. Using the same framework, we reviewed the literature to find clinical cases and exemplary nephrologists that highlight the specific domains. This collection of reports in nephrology illustrates that the definition of clinical excellence set forth by the Miller Coulson Academy is highly applicable to physicians caring for individuals with kidney disease. Relating the definition of clinical excellence to renal medicine is worthwhile in that it can help to exemplify the model to which physicians and trainees may seek to aspire. Key message Many examples of clinical excellence in renal medicine can be found in the published medical literature. The domains of clinical excellence, described by the Miller-Coulson Academy of Clinical Excellence, apply very well to the field of nephrology.

Background. In anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, antigen specificity varies between myeloperoxidase (MPO) and proteinase 3 (PR3). This has been reported to vary in relation to age, gender, geography and extrarenal manifestations. However, studies are difficult to compare as criteria for inclusion vary. The aim of this study was to investigate the relationship between ANCA serotype, latitude, ultraviolet (UV) radiation levels, age, gender and renal function at diagnosis in a large study with uniform inclusion criteria. Methods. Patients with biopsy-proven ANCA-associated glomerulonephritis were identified from regional or nationwide registries in 14 centres in Norway, Sweden, the UK, the Czech Republic, Croatia, Italy and the USA during the period 2000-13. UV radiation levels for 2000-13 in Europe were obtained from the Swedish Meteorological and Hydrological Institute. Results. A total of 1408 patients (45.2% PR3-ANCA) were included in the study. In univariable analysis, PR3-ANCA was significantly associated with male gender {odds ratio [OR] 2.12 [95% confidence interval (CI) 1.71-2.62]}, younger age [OR per year 0.97 (95% CI 0.96-0.98)] and higher glomerular filtration rate [OR per mL/min 1.01 (95% CI 1.01-1.02); Pamp;lt;0.001] at diagnosis but not with latitude or UV radiation. In multivariable logistic regression analysis, latitude and UV radiation also became significant, with higher odds for PR3-ANCA positivity at northern latitudes/lower UV radiation levels. However, the latitudinal difference in MPO: PR3 ratio is smaller than differences previously reported concerning microscopic polyangiitis and granulomatosis with polyangiitis. Conclusions. The ratio between PR3-ANCA and MPO-ANCA varies in glomerulonephritis with respect to age, gender, renal function and geographic latitude/UV radiation levels. Funding Agencies|Ingrid Asp Foundation; Swedish Renal Foundation; Swedish Society of Medicine (Svenska Lakaresallskapet); Swedish Rheumatism Association (Reumatikerforbundet); National Institute for Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, Bethesda, MD, USA [P01-DK5-30834]