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).     

Differential influence of azathioprine and mycophenolate mofetil on the disposition of basiliximab in renal transplant patients

Pharmacokinetic sampling was performed in two multicenter trials in which basiliximab (anti-CD25 monoclonal antibody) was administered with triple immunosuppression consisting of cyclosporine microemulsion, corticosteroids, and either azathioprine or mycophenolate mofetil. Blood samples were collected over 12 wk post-transplant from 31 azathioprine-treated and 66 mycophenolate mofetil-treated patients. Empirical Bayes estimates of each patient's basiliximab disposition parameters were derived and the duration of CD25 saturation was estimated as the time over which serum concentrations exceeded 0.2 microg/mL as confirmed by flow cytometry measurements. Basiliximab clearance was 29+/-14 mL/h when coadministered with azathioprine and 18+/-8 mL/h with mycophenolate mofetil. Both were significantly lower compared with a clearance of 37+/-15 mL/h from a previous study of basiliximab with dual therapy (p<0.001). As a consequence of the lower clearance of basiliximab, the durations of CD25 saturation were prolonged in the presence of azathioprine (50+/-20 d; range, 13--84) and mycophenolate mofetil (59+/-17 d; range, 28--94) compared with dual therapy (36+/-14 d; range, 12--91). A total of 27 acute rejection episodes occurred during the first 6 months in the two studies. Durations of CD25 saturation were not different in these patients compared with those who remained rejection-free in each study. A single patient among 57 who were screened developed anti-idiotype antibodies to basiliximab. The average duration of CD25 saturation was prolonged by 39 and 64% in the presence of azathioprine and mycophenolate mofetil, respectively. This graded effect was also observed for basiliximab clearance and may be due in part to a differentially reduced humoral response to basiliximab. Nonetheless, the range of CD25 saturation durations and basiliximab clearances did not extend outside the range when basiliximab was used with dual therapy in the absence of these agents. Hence, no dosing adjustment is deemed necessary when basiliximab is used in triple immunosuppressive therapy including either azathioprine or mycophenolate mofetil.     

Impact of Immunosuppressive Medication on the Risk of Renal Allograft Failure due to Recurrent Glomerulonephritis

Recurrent glomerulonephritis is a major problem in kidney transplantation but the role of immunosuppression in preventing this complication is not known. We used data from the United States Renal Data System to examine the effect of immunosuppressive medication on allograft failure due to recurrent glomerulonephritis for 41 272 patients undergoing kidney transplantation from 1990 to 2003. Ten-year incidence of graft loss due to recurrent glomerulonephritis was 2.6% (95% confidence interval [CI]: 2.3–2.8%). After adjusting for important covariates, the use of cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, sirolimus or prednisone was not associated with graft failure due to recurrent glomerulonephritis. There was no difference between cyclosporine and tacrolimus or between azathioprine and mycophenolate mofetil in the risk of graft failure due to recurrent glomerulonephritis. However, any change in immunosuppression during follow-up was independently associated with graft loss due to recurrence (adjusted hazard ratio 1.30, 95% CI: 1.06–1.58, p = 0.01). In patients with a pretransplant diagnosis of glomerulonephritis, the risk of graft loss due to recurrence was not associated with any specific immunosuppressive medication. The selection of immunosuppression for kidney transplant recipients should not be made with the goal of reducing graft failure due to recurrent glomerulonephritis.     

Renal transplantation in patients with primary immunoglobulin A nephropathy.

BACKGROUND: Opinions on the clinical course and outcome of renal transplantation in patients with primary immunoglobulin A nephropathy (IgAN) have been controversial. METHODS: We conducted a retrospective single-centre study on 542 kidney transplant recipients over the period 1984-2001. Long-term outcome and factors affecting recurrence in recipients with primary IgAN were analysed. RESULTS: Seventy-five patients (13.8%) had biopsy-proven IgAN as the cause of renal failure, and their mean duration of follow-up after transplantation was 100 +/- 5.8 months. Fourteen (18.7%) of the 75 patients had biopsy-proven recurrent IgAN, diagnosed at 67.7 +/- 11 months after transplantation. The risk of recurrence was not associated with HLA DR4 or B35. Graft failure occurred in five (35.7%) of the 14 patients: three due to IgAN and two due to chronic rejection. Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616). Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001). Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non-IgAN patients, P = 0.001). CONCLUSIONS: Our data suggested that around one-fifth of patients with primary IgAN developed recurrence by 5 years after transplantation. Recurrent IgA nephropathy in allografts runs an indolent course with favourable outcome in the first 12 years. However, the contribution of recurrent disease to graft loss becomes more significant on long-term follow up.     

Long-term outcome of renal transplantation in focal glomerulosclerosis

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) has a tendency to recur frequently after kidney transplantation. We evaluated 12 cases to examine the incidence and long-term outcomes of recurrent FSGS. MATERIALS AND METHODS: Twelve patients with renal failure caused by FSGS received kidney allografts from living related donors. Tacrolimus or cyclosporine was used in combination with prednisolone and azathioprine or mycophenolate mofetil. RESULTS: The mean graft survival was 87.4 +/- 46.8 months. The graft survival rates in FSGS recipients were at 1 year, 100%; 5 years, 79.6%; 10 years, 68.2%. Two out of four recipients experienced graft loss due to chronic rejection. The other two out of four recipients with graft loss displayed severe proteinuria diagnosed as recurrence of FSGS. To treat recurrent FSGS, plasma exchange was partially effective to reduce proteinuria. CONCLUSION: Our incidence of recurrent FSGS is 16.7% with graft survivals at 5 and 10 years of 79.6% and 68.2%, respectively. The recurrence of FSGS happened after scheduled reductions in immunosuppressants. Careful observation is required with maintenance of immunosuppression in these patients.     

Steroids and Recurrent IgA Nephropathy After Kidney Transplantation

We studied the impact of steroid use on kidney graft loss due to recurrent IgA nephropathy (IgAN). We used data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) to conduct a survival analysis of adult recipients of a first kidney transplant for IgAN who received a graft between 1988 and 2007. Predictors of graft loss due to recurrent IgAN were analyzed in a competing risk survival analysis with steroid use modeled as a time‐varying covariate. Fifteen hundred twenty‐one recipients with kidney failure due to biopsy‐proven IgAN received a first kidney transplant during the study period. Four hundred and twenty‐eight recipients experienced graft loss, of which 54 losses (12.6%) were attributed to recurrent IgAN. The overall 10‐year cumulative incidence of graft loss from recurrent IgAN was 4.3% (95% CI 3.1–5.8). Prevalence of steroid use was 92% at baseline, 84% at 1 year and 64% at 5 years. After adjusting for age, sex, HLA mismatch, dialysis duration and transplant era, steroid use was strongly associated with a reduced risk of recurrence (subhazard ratio 0.50, 95% CI 0.30–0.84). These results suggest that the risk of graft loss from recurrent disease should be considered when tailoring immunosuppression for patients with IgAN.     

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.     

Risk factors for graft loss in patients with recurrent IGA nephropathy after renal transplantation

BACKGROUND: The recurrence rate of IgA nephropathy (IgAN) in transplanted kidneys has been reported to be >50%. Although recurrent IgAN has a benign clinical course, recent data suggest that it leads to graft loss in a substantial number of patients. METHODS: We performed a retrospective single-center analysis of 34 renal transplant recipients, with biopsy-proven IgAN as the cause of end-stage renal failure. RESULTS: Renal allograft biopsies were performed in 30 patients, of whom 24 did and 6 did not have biopsy-confirmed recurrent transplant IgAN. Recurrent transplant IgAN was more often detected in men and at later timepoints after post-transplantation. Four patients with recurrent transplant IgAN progressed to graft failure. Progression to graft failure was associated with worsened renal function, higher systolic blood pressure, and the lack of presenation of angiotensin-converting enzyme inhibitors (ACEs) at the time of allograft biopsy. Immunologic factors such as frequency of acute rejection, HLA typing, and immunosuppression did not show a relation to recurrence or graft loss. CONCLUSIONS: Recurrent transplant IgAN increased with long-term graft survival and risk factors for graft loss due to recurrent IgAN were similar to those among IgAN in native kidneys.     

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.     

Peritubular Capillary Changes and C4d Deposits Are Associated with Transplant Glomerulopathy But Not IgA Nephropathy

We examined our renal transplant population for glomerular diseases demonstrated on biopsy between January 1993 and April 2002, focusing on transplant glomerulopathy (TGP). Of 1156 patients followed in our clinics during this period, glomerular disease was diagnosed in 132 cases (11.4%). Glomerulonephritis was diagnosed in 86 transplants (7.4%), with IgA nephropathy (IgAN) being the commonest diagnosis [32 cases (2.8%)]. Thirty-one cases (2.7%) of biopsy-proven TGP were analyzed for associated factors compared with 27 cases (2.3%) of recurrent IgAN. Transplant glomerulopathy was less frequent with mycophenolate mofetil (MMF) and/or tacrolimus, whereas recurrent IgAN showed no such tendency (P= 0.02). Peritubular capillary (PTC) C4d deposition was observed in six of 24 cases (25%) with TGP but none with recurrent IgAN (P= 0.02). Peritubular capillary basement membrane (BM) multilayering was significantly greater in TGP (4.92 +/- 2.94) than in recurrent IgAN (1.86 +/- 1.04) (P < 0.001). The graft survival of TGP was worse than recurrent IgAN (P= 0.05). The association of TGP with BM multilayering and C4d deposits in PTC suggests a generalized disorder of the graft microcirculation and its BM, owing to antibody-mediated rejection in at least some cases. Transplant glomerulopathy has a serious prognosis but is less frequent in patients on newer immunosuppression, unlike recurrent IgAN.     

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.     

IgA Nephropathy in Renal Allografts: Increased Frequency in Native American Patients

We investigated the frequency of IgA nephropathy in transplanted kidneys in 2 ethnic groups in New Mexico (USA). A total of 80 renal graft biopsies were obtained from 66 patients when clinically indicated for the differential diagnosis of graft dysfunction. Glomerulonephritis was present in 16 patients, in biopsies obtained after the first posttransplantation month. The frequency of IgAN in allografts was not the same in Native Americans and in Caucasians: Nondonor IgAN was observed in 4/18 biopsies from Native American patients (22.2%) but only in 4/48 biopsies from Caucasians (8.3%) (p < 0.01). This study demonstrates that in New Mexico the frequency of IgAN in transplanted kidneys in Native American patients is 2.7 times higher than in Caucasian graft recipients.     

Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial.

BACKGROUND: IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. Up to 40% progress to end-stage renal disease (ESRD) over 10-20 years. Currently, treatment is limited. We studied the use of mycophenolate mofetil (MMF) vs placebo in a group of North American IgAN patients at high risk for progressive disease. METHODS: Included were 32 patients aged 18-75 years from multiple centres who had their biopsies read at Columbia and who had at least 1 g of proteinuria per day plus at least two of the following risk factors: (i) male sex; (ii) hypertension >150/90 mmHg or requiring antihypertensive medications; (iii) creatinine clearance, measured by 24 h urine collection, <80 and >20 ml/min at time of enrolment; and (iv) presence of glomerulosclerosis or tubulointerstitial atrophy and fibrosis on renal biopsy. Patients were randomized to either 1 year of MMF, titrated up to a dose of 1000 mg bid, or placebo. Total follow-up was 2 years. All patients received angiotensin inhibition medication. The primary outcome was a 50% increase in baseline serum creatinine (SCr). Secondary outcomes were an increase of 0.5 mg/dl SCr, ESRD and a 50% reduction in proteinuria. RESULTS: The mean baseline SCr was 2.4 mg/dl. No statistically significant differences were observed for any outcome. Five of 17 who received MMF vs two of 15 patients in the placebo group reached a 50% increase in SCr (P = 0.4). In both groups, all patients who reached the primary outcome also reached ESRD. Ten who received MMF vs seven who received placebo had a 0.5 mg/dl increase in SCr (P = 0.7) Only three MMF and two placebo patients had a 50% reduction in 24 h proteinuria. No serious adverse events occurred in either group. CONCLUSION: No benefit was seen in patients who received MMF in this high risk group, probably reflecting the relatively advanced stage of disease of our population. We conclude that MMF is probably not effective in patients with IgAN who already have moderate renal insufficiency.     

Clinical remission and pathological progression after tonsillectomy in a renal transplant patient with recurrent IgA nephropathy

Abstract:  We discuss a renal transplant patient with recurrent IgA nephropathy (IgAN) before and after tonsillectomy. A 36-year-old man started on hemodialysis support in 1996 due to biopsy-proven IgAN, living related renal transplantation was then performed in 1997. Six years after transplantation, the patient presented with microhematuria and proteinuria. Graft biopsy for these urinary abnormalities showed recurrent IgAN. Tonsillectomy was subsequently performed in December 2003, proteinuria remitted 6 months after the tonsillectomy and microhematuria disappeared three years later. Protocol graft biopsy was subsequently performed twice, at 2 yr after the tonsillectomy (2005) and 4 yr after (2008). Comparing the findings of the pre-tonsillectomy biopsy and the two post-tonsillectomy biopsies, an increase in mesangial cells and matrix in 2005, and an expansion of the mesangial matrix and proliferation of mesangial interposition in 2008. In addition, global sclerosis of glomeruli increased over time, the area of tubulointerstitial damage has extended as well. While the tonsillectomy led to clinical remission of recurrent IgAN, the chronicity progressed on these protocol biopsies. This is the first report of the efficacy and the limitations of tonsillectomy in a case of recurrent IgAN in a transplant patient.     

Mycophenolate mofetil but not the type of calcineurin inhibitor (cyclosporine vs tacrolimus) influences the intragraft mRNA expression of cytokines in human kidney allograft biopsies by in situ RT-PCR analysis

The aim of the study was to assess the molecular background of the alloimmune response by the detection of low-abundance mRNA of cytokines in 34 core needle biopsies from kidney allografts with histopathological findings of acute rejection (AR). Recipients were immunosuppressed with a calcineurin inhibitor (CNI), cyclosporine or tacrolimus, and prednisone and azathioprine or mycophenolate mofetil (MMF). Tubular and glomerular expression of IL-2, IL-6, IL-10, IFN-gamma, TGF-beta1, and PDGF-B mRNA were assessed using semiquantitative evaluations of RT-PCR in situ on paraffin tissue sections. This procedure resulted in light microscopy visualization of granular precipitates at the sites of the corresponding mRNA chains. The tubular expression of mRNA for IL-6 and TGF-beta1 was significantly lower in biopsies with AR (n = 34) obtained from patients treated with MMF (n = 12) than in biopsies obtained from patients treated with azathioprine (n = 22) (P < .02). Responsiveness to corticosteroids tended to be more frequent among the MMF group (11 of 12 recipients vs 15 of 22 recipients, P = ns). Moreover, 8 of 12 recipients in the MMF-treated group displayed serum creatinine levels equal or less than 167 mmol/L 1 year after biopsy compared to 7 of 22 recipients in the azathioprine-treated group. There was no significant difference between the groups that had or had not received corticosteroids or between those treated with each type of CNI. These results suggest stronger inhibition of humoral responses and down-regulation of fibrosis by MMF among recipients with AR.     

Control of antidonor antibody production with tacrolimus and mycophenolate mofetil in renal allograft recipients with chronic rejection

BACKGROUND: In renal transplantation, chronic rejection is a major cause of late allograft loss. Recent studies indicate that a subset of chronic rejection is associated with anti-HLA donor specific antibodies (DSA) and complement C4d deposition in peritubular capillaries (PTC). Since rescue therapy with tacrolimus and mycophenolate mofetil has been found to limit antidonor B-cell responses in recipients with acute humoral rejection, we sought to determine whether a similar immunosuppressive regimen might be effective in patients with 'chronic humoral rejection'. METHODS: Four renal allograft recipients with 'chronic humoral rejection' were prospectively identified. The diagnosis was based on: (1) progressive rise in serum creatinine over 12 months; (2) typical pathologic features by light microscopy (transplant arteriopathy and glomerulopathy); (3) widespread C4d deposits in PTC by immunofluorescence; (4) detection of 'de novo' DSA at the time of biopsy. Maintenance immunosuppression was CsA, prednisone and azathioprine (n=3) or prednisone and azathioprine (n=1). Rescue therapy with tacrolimus and mycophenolate mofetil was initiated in all patients, 12 hr after cyclosporine and azathioprine discontinuation. RESULTS: At diagnosis, the mean serum creatinine was 3.9 mg/dl (range: 3.3 to 5.4 mg/dl). DSA was an IgG directed against HLA class II (n=3) or class I (n=2), that is one patient had both anti-HLA class I and class II antibodies. Pretreatment antibody titers varied between 1:8 and 1:128. Rescue therapy was associated with a rapid and sustained decrease in antibody titers. In two patients, DSA became undetectable after 9 months and a repeat biopsy performed after 12 months revealed a decrease in C4d deposition in PTC. CONCLUSION: These results suggest that a decrease in DSA production can be induced in renal allograft recipients with 'chronic humoral rejection' by using an immunosuppressive regimen that combines tacrolimus and mycophenolate mofetil. Limitation of antidonor antibody synthesis may be important for the treatment or the prevention of chronic rejection in organ transplantation.     

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.     

Intestinal microsporidiosis occurring in two renal transplant recipients treated with mycophenolate mofetil.

BACKGROUND: Intestinal microsporidiosis is a major cause of chronic diarrhea and malabsorption in patients with human immunodeficiency virus. Its occurrence in transplant recipients has exceptionally been reported to date. METHODS: We report what we believe are the first two cases of intestinal microsporidiosis in renal transplant recipients. The patients were treated with mycophenolate mofetil. RESULTS: The clinical presentation was chronic diarrhea with massive weight loss. Stool analysis revealed microsporidian spores, identified as Enterocytozoon bieneusi spores by polymerase chain reaction. The onset of this opportunistic infection in these two patients is believed to be secondary to an increase in immunosuppression after azathioprine replacement by mycophenolate mofetil. The withdrawal of mycophenolate mofetil led to clinical recovery. CONCLUSION: The incidence of microsporidiosis will probably increase in transplant recipients treated with powerful immunosuppressants. Therefore, we recommend a systematic search for microsporidian spores in stool specimens in cases of unexplained diarrhea in these patients.     

Histologic findings in protocol biopsies performed in stable renal allografts under different immunosuppressive schedules

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions. Histologic findings in protocol biopsies have been related to graft outcome. We evaluated histologic lesions observed in protocol biopsies performed in patients under different immunosuppression therapies. From June 1988 a protocol biopsy was performed at approximately 4 months in patients who fulfilled the following criteria: serum creatinine <300 micromol/L; stable renal function; and proteinuria <1 g/d. Histologic lesions were graded according to 1997 Banff criteria. For the present study we considered the following groups according to immunosuppressive schedule: (i) induction therapy with polyclonal or monoclonal antilymphocytic antibodies associated with cyclosporine and prednisone (n=201); (ii) cyclosporine, mycophenolate mofetil, and prednisone (n=127); and (iii) tacrolimus, mycophenolate mofetil, and prednisone (n=51). On protocol biopsy patients treated with tacrolimus displayed a lower acute score (0.61+/-1.01 vs 1.24+/-1.23 in group I, 1.28+/-1.41 in group II; P<.0001) and a higher proportion of normal biopsies (57.1% vs 41.9% in group I, 45.1% in group II; P=.016). A similar proportion of chronic lesions (chronic score of group I: 1.30+/-1.56; group II: 1.34+/-1.80; group III: 1.51+/-0.95; P=NS) was observed in the three groups. Protocol biopsies displayed fewer acute lesions in patients treated with tacrolimus. This result suggests that the efficacy of new immunosuppression schedules can be evaluated using the protocol biopsy as a surrogate marker of graft outcome.     

正常血压IgA肾病患者动脉病变的意义

目的:传统观点认为动脉硬化与高血压有关。然而,部分IgA肾病患者,尽管血压正常,但仍有动脉硬化的改变。本研究的目的就是比较血压正常、伴有和不伴有动脉病变的IgA肾病患者的临床病理特点,探讨正常血压IgA肾病患者肾内动脉病变的影响因素及意义。方法:所有患者均经肾活检诊断为原发性IgA肾病,无高血压病史,肾活检前血压<140/90mmHg。动脉病变的定义为活检肾组织光镜下见动脉壁增厚和(或)动脉玻璃样变。符合标准的105例患者,根据动脉病变的有无分为两组,有动脉病变组52例、无动脉病变组53例,分别比较两组的临床病理特点。肾脏动脉病变的半定量分级标准:0:无损害;1:<25%;2:≥25%,<50%;3:≥50%。统计学方法:分别比较两组的临床病理特点,将差异有统计学意义的单因素指标作为多因素分析的入选指标,采用逐步回归方法分析动脉病变的影响因素,以P<0.05作为差异有统计学意义。结果:与无动脉病变组比较,动脉病变组肾活检时的年龄、血肌酐、血尿酸、尿蛋白定量、尿NAG酶、肾小球硬化、肾小管萎缩以及肾间质纤维化的程度显著增高,尿渗透压显著下降。多因素分析的结果表明,肾活检时的血肌酐、尿渗透压、肾小管萎缩及肾间质纤维化是正常血压IgA肾病动脉病变的独立影响因素。动脉病变的程度与血肌酐、肾小管萎缩及肾间质纤维化呈正相关;与尿渗透压呈负相关。结论:血压正常IgA肾病患者的肾内动脉病变,主要与年龄、血肌酐、血尿酸增高等因素有关,常伴有肾小管间质损害。