HLA-B8, DR3: a new risk factor for graft failure after renal transplantation in patients with underlying immunoglobulin A nephropathy

Abstract: Background: The HLA‐B8, DR3 haplotype has been associated with high immune reactivity. In this study, we have tested whether this haplotype has differential effect on graft survival in patients with IgAN compared with control patients. Methods: From the Eurotransplant Registry we analyzed graft survival of 1207 recipients with IgAN and 7935 control patients with non‐glomerular diseases. Death‐censored graft loss according to the HLA‐B8, DR3 haplotype was calculated with Kaplan–Meier analysis and Cox‐regression model was used to correct for various risk factors. Results: The frequency of the HLA‐B8, DR3 haplotype was significantly lower in IgAN patients compared with controls (10.3% vs. 15.4%, p < 0.001). Ten‐year graft survival was identical in the control group with and without the HLA‐B8, DR3 haplotype (71.1% and 70.2%, respectively), but significantly worse in IgAN patients carrying the HLA‐B8, DR3 haplotype compared with patients without it (52.5% vs. 69.1%, respectively, p = 0.009). The risk of graft loss was increased by 66% (HR 1.6, 95% CI 1.14, 2.29) in IgAN with the HLA‐B8, DR3 haplotype and independent of well‐known risk factors. Conclusions: We have identified a new risk factor for graft loss unique to patients with IgAN. This finding emphasizes the exclusive immune characteristics of IgAN patients after transplantation.     

Impact of recurrent disease and chronic allograft nephropathy on the long‐term allograft outcome in patients with IgA nephropathy

Although recurrent IgA nephropathy (IgAN) may lead to graft dysfunction after transplantation, donation from living related donor (LRD), with whom the risk of recurrence may be higher, is not a contraindication. Herein, we evaluated the natural history of allograft in recipients with IgAN and the risk factors influencing long‐term allograft outcome. Recurrence rate and graft survival were assessed retrospectively in 221 IgAN patients, including transplants from 139 LRDs (62.9%). Ten‐year cumulative rate for recurrent IgAN was 30.8%. The operation at younger age and donation from LRD were significant for the recurrence by multivariate analysis. Ten‐year graft survival was affected by recurrent IgAN (61.0% in recurrent IgAN group vs. 85.1% in nonrecurrent, P < 0.01). However, transplants from LRDs did not show poor graft survival when compared with those from other types of donors. In transplants from LRDs, the incidence of chronic allograft nephropathy (CAN) was lower than those in grafts from deceased donors (10.8% vs. 19.5%, P < 0.05). When CAN was considered in addition to recurrence, the variance of graft survival was affected significantly by the development of CAN than by the recurrence. These results suggest that the detection and adequate management of CAN could improve graft outcome in transplant recipients with IgAN.     

Recurrent IgA nephropathy after renal transplantation despite immunosuppressive regimens with mycophenolate mofetil.

BACKGROUND: Transplantation offers an excellent option for patients with immunoglobulin-A nephropathy (IgAN) with severe renal dysfunction. However, IgAN frequently recurs in allografts treated with azathioprine. We examined the impact of mycophenolate mofetil immunosuppression on recurrence of IgAN. METHODS: We reviewed the charts of patients transplanted for IgAN at our institution in the cyclosporin era. Patients were excluded from further analysis if follow-up was <12 months or if immunosuppression at engraftment did not include azathioprine or mycophenolate mofetil. Laboratory data, medications and allograft biopsy findings were compiled. RESULTS: 152 kidney transplantations met the study criteria. At engraftment, 61 allografts were treated with azathioprine and 91 with mycophenolate mofetil. By 3 years post-transplant, IgAN developed in six of 60 (10.0%) azathioprine-treated allografts and five of 62 (8.1%) mycophenolate mofetil-treated allografts (P = 0.76). Overall, 13 azathioprine-treated and seven mycophenolate mofetil-treated allografts showed recurrence. As expected in this retrospective study, the duration of observation was longer in the azathioprine group. The interval between engraftment and diagnosis of recurrent disease was also longer. Survival of allografts with recurrent IgAN was similar in the two groups. Survival of allografts with recurrent IgAN was worse than for allografts without recurrence or allografts transplanted into patients with non-IgAN renal failure. Neither switching azathioprine to mycophenolate mofetil nor using an angiotensin-converting enzyme inhibitor or angiotensin-II type 1 receptor blocker ameliorated the clinical course after a biopsy documented recurrent IgAN. CONCLUSIONS: Mycophenolate mofetil, compared with azathioprine, did not lessen the recurrence of IgAN or its clinical impact.     

Efficacy of tonsillectomy for patients with recurrence of IgA nephropathy after kidney transplantation

Abstract:  From January 2007, we started to perform the tonsillectomy for every patient with recurrent IgA nephropathy (IgAN) after kidney transplantation. Up to September 2008, four recipients with primary IgAN had biopsy-proven recurrent IgAN. They had also progressive hematuria or proteinuria from on the average 14.3 months after transplantation. Then their specimens diagnosed as recurrent IgAN were collected and they underwent tonsillectomies on the average 52.3 months after transplantation. Abnormal urinary findings of all patients favorably improved after tonsillectomy. All cases but one had mild renal injury, where the severity of glomerular lesions, glomerular hypercellularity, segmental lesions, and sclerosis was mild, and no deteriorated serum creatinine (SCr) before their tonsillectomies. Even the case with exacerbated SCr and severe renal injury, where the severity of glomerular lesions was severe, had her urinary findings ameliorated promptly after tonsillectomy likely as others. At present, they have almost no symptoms after tonsillectomy and no remarkable change of SCr level compared with before and after tonsillectomy and maintain ameliorated urinary findings continuously. Tonsillectomy had possibility to be a favorable treatment of hematuria or proteinuria in recurrent IgAN recipients.     

Renal transplantation in Slovenia after joining Eurotransplant.

BACKGROUND: This report presents data on renal transplantation in Slovenia before and after joining Eurotransplant (ET). METHODS: Slovenia (population: 2 million) has one renal transplant centre. The establishment of an appropriate national transplantation organization resulted in an increase in transplantations and the acceptance of Slovenia into ET at the beginning of 2000. Current immunosuppression is composed of cyclosporin (Neoral), mycophenolate mofetil, methylprednisolone and anti-interleukin-2 receptor monoclonal antibodies. RESULTS: By the end of 2004, 607 renal transplantations had been performed. From 1970 to 1998, 124 patients were given living related donor kidneys. From 1986 to 1999, 239 patients received renal grafts from deceased donors. From 2000 to 2004, 244 patients were transplanted from deceased donors. In 2004, 55 renal transplantations were carried out. One hundred and forty one (57.8%) renal grafts were shipped from other ET countries. The HLA-antigen mismatch of 2.8+/-1.1 was not significantly different from what it was before 2000. Up to 31 December 2004, the 1- and 3-year patient survival rates were 98.3% and 96.0%, respectively. The concomitant graft survival rates were 95.8% and 93.5%, respectively. CONCLUSIONS: In the ET era, the number of deceased donor renal transplants per year was 2.8 times higher than in the 14 years before. In 2004, we reached the average number of deceased donor renal transplants per million population of ET. Although tissue compatibility in these recipients was not significantly better than it was before the ET era, it would have been much worse had we not joined ET. Short- and medium-term results in the ET era have been entirely comparable to those in large reports.     

Pre-transplant course and risk of kidney transplant failure in IgA nephropathy patients

Bjørneklett R, Vikse BE, Smerud HK, Bostad L, Leivestad T, Hartmann A, Iversen BM. Pre‐transplant course and risk of kidney transplant failure in IgA nephropathy patients.
Clin Transplant 2011: 25: E356–E365. © 2011 John Wiley & Sons A/S. Abstract: Background: There is lack of knowledge to what degree clinical/morphological presentation and course of IgA nephropathy (IgAN) prior to end‐stage renal disease are risk factors for graft loss after kidney transplantation. Material and Methods: Patients with IgAN between 1988 and 2006 (registered in the Norwegian Kidney Biopsy Registry) who later received a kidney transplant (registered in the Norwegian Renal Registry) were included. The cohort was followed up regarding death‐censored graft loss throughout 2008. Graft survival with a rapid progressive (RP) vs. a slow progressive (SP) course of pre‐Tx IgAN (annual GFR > or <30 mL/min/1.73 m²) was studied. Results: Among 106 included patients, there were 14 graft losses giving a graft loss rate of 1.9/100 patient years. Follow‐up until the first kidney transplant was 6.9 ± 4.4 (range 0.1–19) yr. Patients with pre‐Tx RP had a higher graft loss rate compared with SP patients (6.3 vs.1.3/100 patient years, p < 0.001). Graft loss rate with living‐related donor (LRD) was similar to unrelated donor (UD) grafts. Most RP patients had received LRD grafts, and in SP patients, graft survival with LRD grafts was better than UD grafts (0.3 vs.2.1/100 patient years, p = 0.055). Conclusions: A rapid pre‐transplant course is a strong risk factor for transplant failure in patients with IgAN.     

IgA serology in recurrent and non-recurrent IgA nephropathy after renal transplantation

BACKGROUND: This study investigated whether abnormal circulation of macromolecularIgA and IgA with altered glycosylation or electrical chargeplays a role in the recurrence of IgA nephropathy (IgAN) aftertransplantation. STUDY DESIGN: A total of 92 renal transplant patients were enrolled; 52 IgANpatients and 40 with other non-IgAN. The IgAN group included10 patients showing IgA mesangial deposits in the grafted kidneys(recurrent group) and 10 who did not (immunohistochemicallyproven non-recurrent group). In addition another 22 IgAN transplantpatients were clinically free of recurrent disease. METHODS: The analyses included macromolecular IgA (IgAIC) detected bythe conglutinin assay (K), heavy IgA precipitated in 2.5% polyethyleneglycol (PEG), IgA-fibronectin aggregates (IgA/F Aggr), mixedIgA/IgGIC, IgA binding to mesangial matrix components (fibronectin,laminin, type IV collagen) or polycations (poly-L-lysine) andIgA with altered glycosylation (Jacalin-binding assay). RESULTS: After transplantation, IgAN patients displayed significantlyhigher mean levels for each variable measured than non-IgAN(ANOVA, P <0.05). By stepwise regression analysis, the bindingof IgA to fibronectin had the highest coefficient. By comparingdata in recurrent and clinically non-recurrent IgAN, we observedthat two groups could be distinguished by the results of thetwo assays for macromolecular IgA (conglutinin IgAIC and IgA-fibronectinaggregates) and IgA with increased affinity for type IV collagen(P <0.05). When the selected group of immunohistochemicallyproven non-recurrent IgAN was compared to the recurrent one,a statistically significant difference was found only for thebinding of IgA to type IV collagen (P<0.05). Data from thistest were significantly related with proteinuria (P<0.05)and microscopic haematuria (P <0.04). CONCLUSION: Even though the IgA serology of renal transplant IgAN patientsshows peculiar features and recurrent and non-recurrent IgANdiffer in many aspects, the prevalence of positive data in thetwo groups had no predictive value. This suggests that the recurrenceof IgAN is modulated by factors affecting the interaction betweencirculating abnormal IgA and mesangial cells and/or matrix.     

Recurrent IgA nephropathy after renal transplantation and steroid withdrawal

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis; the reported recurrence rate of IgAN after renal transplantation is as high as 13%‐50%. The impact of immunosuppressive therapy and steroid withdrawal on the risk of recurrence of IgAN is still under debate. We performed a retrospective single‐center study, selecting 123 kidney transplants (rtx) in 120 patients, between January 1995 and December 2012, with IgAN on the native kidney. In 51 of 123 transplants, at least one post‐transplantation biopsy for clinical indication was performed; in 28 of 51 transplants, IgAN recurrence (IgANr) was demonstrated. This group (G1; N = 28) was compared with a group without IgANr (G2; N = 23). In our study, clinically evident IgANr rate was 54.9% (28/51) on biopsied patients. At discharge, the use of the immunosuppressant drugs (tacrolimus, cyclosporine A, mycophenolate mofetil, azathioprine, mTor inhibitors) was not associated with an increased risk of IgANr (P = NS). At discharge, all patients were steroid treated. Neither the use of tacrolimus, mycophenolate mofetil, nor mTor inhibitors (mTori) at biopsy time were associated with IgANr. However, IgANr was significantly higher in patients who experienced steroid withdrawal at any post‐transplantation time (OR 7.7 P = .03). The median time to recurrence after steroid withdrawal was 59 months (min 4.18, max 113.2).     

Serological and genetic factors in early recurrence of IgA nephropathy after renal transplantation

BACKGROUND: The relative role of IgA anomalies and genetic factors in IgA nephropathy (IgAN) recurrence after transplantation has never been investigated in a single cohort. METHODS: Sixty-one transplanted patients who had IgAN as an original disease (30 with biopsy-proved early recurrence, median 2.9 yr post-transplant), and 120 controls, were investigated for aberrantly glycosylated IgA1, IgA binding to mesangial matrix, macromolecular IgA (IgA/fibronectin and uteroglobulin/IgA/fibronectin complexes), and polymorphisms of cytokines [tumor necrosis factor alpha (TNFalpha), interleukin 10 (IL-10), IL-6, interferon gamma and transforming growth factor beta 1] and renin-angiotensin system (angiotensinogen converting enzyme, angiotensin II receptor 1, and angiotensinogen) genes. RESULTS: At multivariate logistic regression analysis, recurrence showed a border-line association with aberrantly glycosylated IgA1 [odds ratio (OR) 8.172, p = 0.077], and was significantly less frequent in carriers of -308 AG/AA TNF-alpha"high producer" genotype (OR 0.125, p = 0.036) and -1082, -819, -592 ACC/ATA IL-10 "low producer" (OR 0.038, p = 0.009) genotypes. CONCLUSION: High levels of aberrantly glycosylated IgA1 do not appear to play a strong crucial role in recurrence of IgAN. Polymorphisms of TNFalpha and IL-10 known to condition Th1 prevalence were associated with protection from early recurrence of IgAN.     

Age-matching in renal transplantation.

BACKGROUND: So far, the combined influence of donor age and recipient age on renal allograft survival has not been investigated sufficiently. In this retrospective single-centre study we analysed whether the influence of donor age and recipient age on renal allograft survival are dependent on each other. METHODS: Data from 1269 cadaveric renal allograft transplantations were evaluated. Paediatric donors (<15 years) and paediatric recipients (<15 years) were excluded. Donors and recipients were divided by age: young donors (yd, 55 years, n=176), young recipients (yr, 55 years, n=211). Functional and actual long-term graft survival (8 years) within the four resulting groups was determined: yd/yr (n=926), yd/or (n=167), od/yr (n=132), and od/or (n=44). RESULTS: Univariate analysis showed that long-term graft survival of both, kidneys from young donors (functional, 66.1 vs 52.2%, P=0.004; actual, 53.3 vs 46.2%, P=0.065) and kidneys from old donors (functional, 68.7 vs 22.5%, P=0.07; actual, 57.1 vs 20.8%, P=0.15) was better in old recipients as compared to young recipients. Multivariate regression analysis revealed that actual graft survival of kidneys from old donors was significantly reduced in young recipients (od/yr) as compared to all other groups (P=0.001; RR, 1. 97; 95% CI, 1.32-2.94). In this group of patients, graft loss was mainly due to acute (33.7%) and chronic (24.0%) rejection. CONCLUSION: Transplantation of kidneys from 'old' donors into 'young' recipients should be avoided, and these kidneys should be given to age-matched recipients.     

Polyomavirus nephropathy after renal transplantation: a single centre experience

BACKGROUND: Polyomavirus associated nephropathy (PVN) in renal transplant recipients has been observed with increasing frequency recently and has emerged as a cause of allograft failure linked to highly potent new immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). METHODS: Polyomavirus associated nephropathy was identified in nine out of 182 patients who received renal transplantation between October 1998 and July 2003. PVN was confirmed by allograft biopsy. The clinical records of these nine patients were reviewed, as were all of the allograft biopsies. Electron microscopy was performed in all nine cases. After the diagnosis of PVN, maintenance immunosuppression was reduced. The clinical course and outcome of the PVN patients were reviewed in relation to manipulation of immunosuppressive agents. RESULTS: There were nine cases of PVN in renal transplant recipients and the incidence of PVN was 4.9%. All patients with PVN were under triple immunosuppression comprising tacrolimus and MMF. The mean time to a diagnosis of PVN was 7.8 months after transplantation. Three of the nine patients received antirejection therapy prior to PVN. Seven out of nine PVN patients presenting acute allograft dysfunction were initially treated with high-dose intravenous steroid pulse or OKT3 before reduction of the immunosuppression. After reduction of the immunosuppression, seven patients stabilized their renal function. Two (22%) lost their grafts due to persistent PVN and chronic rejection. Two (22%) patients later developed acute rejection after reduction of the immunosuppression. CONCLUSION: PVN can cause allograft dysfunction and graft loss. Renal allograft recipients who are at risk of PVN should be routinely screened with urine cytology and quantitative measurements of viral load in the blood, particularly patients who had graft dysfunction. Early diagnosis and judicious alteration of immunosuppressive agents might permit a superior prognosis and reduce the graft loss from PVN in renal transplant recipients.     

Recurrent mesangial IgA nephritis following renal transplantation

Recurrence of mesangial IgA deposits in renal allografts ofpatients whose original disease was primary IgA nephropathy(IgAN) has been studied. Forty-six patients with primary IgANreceived 51 renal allografts and have been followed for 3–183months. A prospective study of 11 patients (11 biopsies) anda retrospective analysis of 17 patients (16 biopsies; 2 nephrectomyspecimens) have been combined. Seventeen of the 29 allograftshad recurrent mesangial IgA deposits and of these three patientshave negative urinalysis, normal glomeruli by light microscopy,and stable renal function; six patients have microhaematu-ria,mesangial proliferative nephritis, but at present stable renalfunction; and five have mesangial proliferative glomerulonephritiswith microhaematuria, heavy proteinuria, hypertension, and progressiveallograft failure secondary to IgA disease alone, and one ofthese is now back on dialysis. Three other grafts with recurrentdeposits are failing because of transplant glomerulopathy orrejection. The only predictor identified for recurrence of mesangial IgAdeposits was length of time post-transplantation, with allografttissue being studied at 45.9±10.0 versus 15.3±4.8months (P = 0.008) post-transplantation in patients with andwithout recurrent deposits respectively. Cyclosporin A did notprevent recurrence. By virtue of a longer follow-up of patientspost-transplantation than all other reported series, these resultssuggest that with increasing time post-transplantation recurrenceof mesangial IgA disease will become increasingly importantas a cause of progressive allograft dysfunction and failureunless effective treatment is found for the primary disease.     

Successful Treatment of Recurrent Henoch–Schönlein Purpura in a Renal Allograft with Plasmapheresis

Acute and severe cases of Henoch–Schönlein purpura (HSP) nephritis have been treated with plasmapheresis (PA) in both adults and children. It has been used either alone or with steroids, antiplatelets or cytoxic drugs. Generally, renal function has been shown to improve when PA is utilized. The role of PA in recurrent HSP after renal transplantation is unclear and has not been well described in the literature. We report a 29-year-old female with HSP who developed end-stage renal disease and subsequently underwent a renal transplantation with eventual loss of the allograft 5 years later due to recurrent HSP nephritis. Retransplantion was performed and the patient developed active HSP nephritis in her second allograft within a week after transplantation. In an effort to preserve her allograft, four cycles of PA were performed. Her proteinuria resolved and renal biopsies afterwards demonstrated marked reduction in mesangial IgA deposition. We conclude that PA may be useful in recurrent HSP nephritis, especially when used early. The risk of additional immunosuppression caused by PA needs to be considered. More studies need to be done to evaluate the efficacy of PA in this setting as well as to define the optimal treatment regimen.     

Segmental glomerulosclerosis in IgA nephropathy after renal transplantation: relationship with proteinuria and therapeutic response to enalapril

INTRODUCTION: Although graft dysfunction has been increasingly reported in post-transplant IgA nephropathy (Tx-IgAN), intragraft morphological changes have been largely overlooked. We evaluated glomerular changes in Tx-IgAN to identify the histological features pertaining to significant proteinuria and therapeutic response to enalapril. MATERIALS AND METHODS: Fifty-four renal allograft biopsies, diagnosed as Tx-IgAN at a median of 46 months after transplantation, were the subject of the study. In 10 patients, glomerular morphometry was performed. In 14 patients who have been treated with enalapril for more than 12 months, we correlated the therapeutic response to enalapril with allograft histology. RESULTS: No uniform pattern was found in the glomeruli of Tx-IgAN. The glomerular mesangium was mostly indistinct. Interstitial fibrosis was negative or mild in 88.9%. By morphometry, the glomerular tuft areas and mesangial areas were significantly larger in Tx-IgAN than those of the normal native kidney (p < 0.05), but were not different from transplant cases without glomerulonephritis. Proteinuria of >/=1 g/24 h was correlated with glomerulosclerosis, interstitial fibrosis and interstitial inflammation at time of biopsy (p < 0.005). The presence of segmental sclerosis (SS) correlated well with the amount of 24-h proteinuria (p < 0.001). After treatment with enalapril, the amount of proteinuria reduced in 64.3%. Therapeutic response to enalapril tended to be less effective in patients having SS (28.6 versus 71.4%), but this finding did not reach a statistical significance. CONCLUSIONS: Significant proteinuria was associated with advanced chronic injury, especially with the presence of SS in Tx-IgAN, but anti-proteinuric effect of enalapril was not affected by graft histology. It remains to be clarified whether glomerular mesangial expansion plays a role in graft dysfunction in a subset of Tx-IgAN showing prominent mesangial changes.     

Clinical risk factors for recurrence of IgA nephropathy

No clinical risk factors for recurrence of immunoglobulin A (IgA) nephropathy in kidney transplants have been defined. This is a single-centre retrospect analysis of recurrence in 104 first kidney transplant patients with biopsy-verified IgA nephropathy. Fifty patients had living donors. All but an identical twin were treated with cyclosporin A. The median follow-up time was 5 yr. Graft biopsies had been obtained from 35 grafts later than 6 months after transplantation, due to deteriorating graft function or gross proteinuria. Thirteen biopsies showed mesangial glomerulopathy proliferative in eleven cases with IgA deposits. Recurrence caused failure of six grafts. Eleven grafts with recurrence were from living donors (p = 0.005). No specific human leukocyte antigen (HLA) was identified as a risk factor. Known duration of original disease until end-stage renal failure was significantly shorter in patients with recurrence (median 5 yr, range 0-25 yr) compared with those without (median of 10 yr, range of 0-37 yr) (p = 0.015). Cumulative graft survival was not reduced in living versus cadaveric donor recipients.     

Membranous nephropathy: recurrence after kidney transplantation

BACKGROUND.: It is supposed that about 5% of dialysis patients had membranousnephropathy as a cause for their renal failure. Despite of thisprevalence, only 33 cases of recurrent membranous nephropathyafter kidney transplantation have been reported in the Englishliterature. METHODS.: Among 509 recipients of renal allografts, membranous glomerulonephritiswas the cause of renal failure in five patients, who receivedsix transplants. RESULTS.: Recurrence of the disease was observed in three allografts (50%)in three patients, all of them were on treatment with cyclosporinand low-dose prednisone. Proteinuria appeared at 2, 5 and 19months after grafting. One patient experienced a spontaneousremission after 12 months and he is free from proteinuria andwith good renal function after 5 years. The remaining two patientspresented progressive renal function deterioration and returnedto haemodialysis 24 and 17 months after the appearance of proteinuria.In these patients increasing the immunosuppression did not produceany beneficial effect. One of those patients underwent a secondtransplant; recurrence of the membranous nephropathy has notbeen observed after 3 years of follow-up. CONCLUSIONS.: In this study three new cases of recurrence of membranous nephropathyare reported. One patient experienced a spontaneous remissionof proteinuria. Recurrence of membranous nephropathy in renalallograft was very high in our series. Its appearance was associatedwith poor prognosis of the graft in most patients, althoughspontaneous remission of proteinuria is possible.     

Natural history of immunoglobulin A nephropathy and predictive factors of prognosis: a long-term follow up of 204 cases in China

Aim: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. However, its natural history and risk factors are not well understood. Our aim was to identify the clinical and pathological factors that could predict disease prognosis in Chinese patients. Methods: We studied 204 biopsy‐diagnosed IgAN patients, who were followed for an average of 6.1 years (range, 4–15 years). Chronic kidney disease (CKD) classified according to the Kidney Disease Outcomes Quality Initiative practice guidelines. Renal pathological lesions were graded single‐blindedly according to the Haas classification. The glomerular filtration rate was estimated by the Modification of Diet in Renal Disease equation for Chinese subjects. Results: Patients with CKD were classified as stage 1 (38.10%), stage 2 (35.40%), stage 3 (13.30%), stage 4 (9.90%) and stage 5 (3.30%). During the follow up, 31 patients had progressed to end‐stage renal disease. The renal survival rate following biopsy was 85.1% at the fifth year, and 77.1% at the 10th year. Univariate analysis indicated that patients who were male, had hypertension, proteinuria of more than 1 g/day, renal impairment (estimated glomerular filtration rate, <60 mL/min.1.73 m²), and a high histological grading were associated with poor prognosis. Multivariate analysis indicated that the relative risk of renal failure for patients was 3.9 (P = 0.000) for patients with renal impairment, 2.8 (P = 0.019) for patients with hypertension, and 2.0 (P = 0.003) for patients with high histological grading. Conclusion: We described the natural history of IgAN through follow ups of a relatively large cohort of patients. Most patients were biopsied at an early stage; however, the long‐term prognosis was still poor. Patients with renal impairment, hypertension and advanced histological involvement had the highest risk for disease progression.     

Emerging therapies in immunoglobulin A nephropathy

Despite advances in our understanding of immunoglobulin A nephropathy (IgAN) over the past decade, there are currently no specific therapies capable of targeting key pathways involved in the pathogenesis of the disease. Recent studies have, however, provided new insights into important molecular pathways that are likely to be amenable to therapeutic manipulation in the future. Specifically, a deeper understanding of the role of mucosal immunity, B‐cell activation and mesangial cell activation in IgAN has provided the impetus for a number of exciting phase II/III clinical trials in IgAN. In this review, we examine some of these on‐going studies, first examining studies that clarify the role of traditional immunosuppression in IgAN, then focusing on novel therapies in early clinical studies, looking closely at the rationale for these agents in relation to our current understanding of the pathogenesis of IgAN. Finally, we examine emerging pathways and therapeutic agents that have the potential to be developed as novel therapies in the coming years. It is hoped that as we continue to develop a greater understanding of IgAN, emerging therapies will soon become a reality in the day‐to‐day treatment of patients with IgAN.