Search

Glomerulonefritisi (GN) su treći po učestalosti uzrok terminalnog zatajenja bubrežne funkcije dok je transplantacija metoda izbora u nadomještanju bubrežne funkcije (NBF). Kod transplantiranih bolesnika postoji rizik povrata osnovne bolesti za koji se smatra da je jedan od važnijih uzroka gubitka funkcije presatka. Cilj ovog istraživanja je ustanoviti utjecaj glomerularne bolest kao primarne bolesti nativnih bubrega, kao i samog povrata osnovne bolesti, na ishod transplantacije i petogodišnje preživljenje presatka. Retrospektivno smo analizirali 120 bolesnika s biopsijom potvrđenim GN koji su transplantirani u razdoblju od 2007. do 2012. IgA nefropatija (IgAN), fokalna segmentalna glomeruloskleroza (FSGS) i membranoproliferativni glomerulonefritis (MPGN) su predstavljali 75% podtipova GN. Sumnju na povrat bolesti smo definirali proteinurijom > 1g, dok je sam povratak potvrđen biopsijom. Izolirani povrat osnovne bolesti je dokazan u 75% bolesnika od kojih je najčešći i najznačajniji povrat bolesti bio uslijed MPGN-a (44% patohistološki dokazanih povrata). U 25% ispitanika s povratom MPGN došlo je do gubitka funkcije presatka definiranog potrebom za NBF. Udio povrata FSGS-a iznosio je 33,3% patohistološki dokazanih povrata, te u ni jednom slučaju nije došlo do gubitka funkcije presatka. Povrat IgAN je dijagnosticiran u 1 bolesnika (11,1%), kao i lupus nefritis (11,1%) kod kojeg je došlo do gubitka funkcije presatka. Funkcionalan presadak nakon petogodišnjeg praćenja imalo je 70% bolesnika, dok je gubitak funkcije presatka ili graftektomija uslijedila kod 18 bolesnika (15%), od kojih su 2 (11,1%) imala povrat osnovne bolesti. Glomerulonefritisi kao primarna bolest nativnih bubrega kao i sam povrat osnovne bolesti, nemaju negativan utjecaj na ishod transplantacije i dugoročno preživljenje presatka., Glomerulonephritis (GN) is the third most common cause of end-stage kidney failure while the transplantation is a method of choice for renal replacement therapy. Transplant patients have a risk of recurrent GN which is considered to be an important cause of allograft loss. The aim of this study was to determine the effect of glomerular disease as a primary disease in native kidneys, as well as recurrence, on transplantation outcome and five-year allograft survival. We have retrospectively analyzed 120 patients with biopsy-proven glomerulonephritis, that have received a renal transplant from 2007 through 2012. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (GN) represented 75% of GN subtypes. Recurrence suspicion was defined as proteinuria >1g while the recurrence itself was confirmed by biopsy. Isolated recurrence was proved in 7,5% patients while the most common and significant recurrence was due to MPGN (44% of biopsy-proven GN). Allograft loss, defined as a need for renal replacement therapy, was found in 25% of patients with recurrent MPGN. Recurrent FSGS occurred in 33,3% of biopsy-proven recurrences, and none of the allografts was lost. IgAN recurrence was diagnosed in one patient (11,1%), as well as lupus nephritis (11,1%) which resulted in allograft loss. Functional allograft after five-year follow up was found in 70% of patients while the allograft loss or graftectomy occurred in 18 patients (15%), of whom 2 (11,1%) had a recurrence. Glomerulonephritis as a primary disease in native kidneys, as well as recurrence, don’t have a negative impact on transplantation outcome and long-term allograft survival.

No specific treatment for IgA nephropathy (IgAN) after kidney transplantation is currently available. We conducted a retrospective single-center study on 29 patients with biopsy-proven de novo and recurrent IgAN after kidney transplantation, divided into two groups. Group 1 (n = 16) received intravenous methylprednisolone 500 mg per day for three consecutive days at the beginning of months 1, 3 and 5, plus oral prednisone 0.5 mg/kg every other day for 6 months. The control group (n = 13, Group 2) received supportive therapies. The two groups were comparable for serum creatinine (sCr) and proteinuria at the time of renal biopsy, but differed significantly at the end of follow-up. sCr was 1.8 ± 0.4 mg/dl in Group 1 vs. 2.7 ± 0.9 in Group 2 (p = 0.002), and proteinuria was 0.9 g/day in Group 1 vs. 1.9 in Group 2 (p = 0.04). The composite outcome of death-censored graft loss or doubling of sCr displayed 2 events in Group 1 (12.5 % of the entire group) and 5 events in Group 2 (38.5 % of the entire group), p = 0.19, odds ratio (OR) 4.4 [95 % confidence interval (CI) 0.7–27.8]. In the absence of therapeutic guidelines for de novo or recurrent IgAN after kidney transplantation, our study reports that therapy with pulse and oral steroids for 6 months is associated with an improved renal function. Nevertheless, further randomized controlled studies in larger patient cohorts are necessary to establish the gold standard treatment.

Glomerulonephritis (GN) continues to be one of the main causes of end-stage kidney disease (ESKD) with an incidence rating from 10.5% to 38.2%. Therefore, recurrent GN, previously considered to be a minor contributor to graft loss, is the third most common cause of graft failure 10 years after renal transplantation. However, the incidence, pathogenesis, and natural course of recurrences are still not completely understood. This review focuses on the most frequent diseases that recur after renal transplantation, analyzing rate of recurrence, epidemiology and risk factors, pathogenesis and bimolecular mechanisms, clinical presentation, diagnosis, and therapy, taking into consideration the limited data available in the literature. First of all, the risk for recurrence depends on the type of glomerulonephritis. For example, recipient patients with anti-glomerular basement membrane (GBM) disease present recurrence rarely, but often exhibit rapid graft loss. On the other hand, recipient patients with C3 glomerulonephritis present recurrence in more than 50% of cases, although the disease is generally slowly progressive. It should not be forgotten that every condition that can lead to chronic graft dysfunction should be considered in the differential diagnosis of recurrence. Therefore, a complete workup of renal biopsy, including light, immunofluorescence and electron microscopy study, is essential to provide the diagnosis, excluding alternative diagnosis that may require different treatment. We will examine in detail the biomolecular mechanisms of both native and transplanted kidney diseases, monitoring the risk of recurrence and optimizing the available treatment options.

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

Posttransplant glomerulonephritis (PTGN) is the third most common cause of late allograft loss. This could be classified into recurrent or de novo PTGN. The prevalence of PTGN is about 6–8%. There are several challenges with the diagnosis of PTGN. In addition, these diseases are not common, mostly described in case reports, case series and registry analysis. The reports vary in their definitions and approach to diagnosis. There is no high quality evidence for management of these conditions. This review focuses on summarizing the current evidence on the prevalence, clinical features, risk factors and management of PTGN.

Recurrent glomerulonephritis (GN) remains an important cause of kidney allograft loss and whether rapid discontinuation of steroids (RDS) is associated with a higher risk of recurrence is not known.We studied recurrence rate, and graft and patient survival in four groups of recipients: 216 recipients with GN transplanted under RDS (group 1), 978 concurrent non-GN recipients transplanted under RDS (group 2), 260 historic comparator group transplanted for GN between 1994 and 1999 with steroid maintenance (group 3), and 950 recipients who were also transplanted between 1994 and 1999 for non-GN and also maintained on steroids (group 4). Regression analysis adjusting for donor and recipient factors, steroid and sirolimus use, and also GN type was used to address factors associated with recurrent disease.The 1-, 5-, and 7-year recurrence rate in the GN group under RDS was 6.7%, 13.7%, and 19.2% and in historic GN recipients maintained on steroids it was 2.4%, 3.8%, and 5.3%, respectively (P0.0001). RDS was associated with a higher adjusted risk of recurrent disease for all GN types (hazard ratio 4.86; 95% confidence interval 2.34-10.07; P0.0001). Graft and patient survival were similar in the two GN groups and both were highest among all groups. Notably, death-censored graft survival was not different among the groups.Steroid avoidance may be associated with a higher rate of recurrent GN but no apparent increase in risk of graft loss. This group of recipients needs to be studied more carefully, in larger numbers, and for a longer time period.

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).

Invasive aspergillosis is a serious complication in renal transplant recipients. Hepatic involvement, although seen in liver transplant recipients, has not been reported following renal transplantation. We describe here an interesting occurrence of hepatic Aspergillus infection in a renal transplant recipient. The infection responded to anti-fungal therapy, but there was re-activation following a second renal transplant. In addition, the patient had recurrence of the underlying membrano-proliferative glomerulonephritis following both transplants. The relevant existing literature relating to these problems has been reviewed.

Background/Aims: Post-renal transplant recurrent glomerulonephritis (GN) contributes to allograft loss. Rituximab treatment has been used in a multidose strategy with variable efficacy and toxicity. We investigated a novel single-dose approach. Methods: A single center, retrospective, cohort study was conducted between January 1998 and April 2012 among renal allograft recipients with recurrent GN treated with rituximab (cases) or without (controls). The primary outcome was complete response (CR, urine protein/creatinine ratio (UP/C) 50% reduction in UP/C), response relapse, treatment-response by GN type, acute rejection incidence, time to graft loss, and infection incidence. Results: The median dose of rituximab was 200 mg per patient. Of 20 rituximab cases and 13 controls, CR was achieved in eight (40%) versus four (31%), respectively (p = 0.72). Three subjects in each group achieved PR (p = 0.66). Response relapse was similar between the two groups (p = 0.47). Significantly more subjects with recurrent membranous nephropathy (MN) achieved CR with rituximab treatment (p = 0.029). Acute rejection was lower in the rituximab group versus controls (n = 0 vs. 4; p = 0.046). The mean time to graft loss was much later in the rituximab group (35 months, (95% CI 33-37)) versus controls (29 months, (95% CI 24-35)) at 36 months (p = 0.04). There was no infection increase in rituximab-treated subjects (p = 0.16). Conclusion: Single-dose rituximab for treatment of recurrent GN was associated with less subsequent rejection and longer time to graft loss without increased infection, but was no more effective than regimens not using rituximab at 36-months except those with recurrent membranous GN.

Twenty-yr patient and death-censored graft survival of 348 kidney transplant recipients with primary glomerulonephritis (GN) and of 696 matched controls were 82.2% in GN patients and 75% in controls (p = 0.037) and 49.5% and 54%, respectively (p = 0.013). GN patients had a higher incidence of graft failure than controls even considering death as a competing risk (p = 0.004). In the GN group, graft survival of deceased and of living donor recipients was similar. At multivariate analysis, GN as primary disease (RR: 1.47), delayed graft function recovery (RR: 2.34), acute rejection (RR: 2.36), and any PRA positivity (RR: 1.01) were predictive of graft loss. GN recurred in 85 of 348 grafts (24.4%), and 43 were lost for recurrence. In non-recurrent patients, graft survival at 20 yr was significantly better than in recurrent patients (59.4% vs. 24.4%, p = 0.000), but not different from that of controls (59.4 vs. 54%, p = 0.9). At multivariate analysis, young age at transplantation (RR: 0.97), shorter duration of dialysis (RR: 1.05 per each dialysis year), and graft from living donors (RR: 1.668) were independent predictors of recurrence. Patients with primary GN have reduced graft survival in comparison with controls, and this is mainly due to recurrence of original disease. However, the most frequent recurrence in living recipients does not compromise graft survival.

A spectrum of kidney diseases besides classic human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) exists in HIV-infected patients. Immune complex–mediated glomerulonephritis has emerged as a significant contributor to the burden of kidney disease in this population, particularly in patients of non-African descent. Lupus-like nephritis, a form of immune complex glomerulonephritis with histologic features identical to lupus nephritis in the absence of clinical or serologic markers of lupus, is well recognized as a cause of end-stage renal disease in HIV-infected patients. None of the HIV-associated kidney lesions, whether classic HIVAN or non-HIVAN, has been reported to recur in kidney transplants. We report here for the first time clinical and histologic recurrence of HIV-associated lupus-like nephritis after successful kidney transplantation, causing proteinuria, hematuria, and impaired kidney transplant function.

SUMMARY: The present article provides an update from the literature on the clinical significance of recurrent IgA disease in renal transplant patients, and it identifies possible reasons for the differences between the data that have been published. the clinical features of recurrent IgA nephropathy are described here, along with suggestions for the management of these patients.

La proteinuria es frecuente después del trasplante renal y afecta a más del 40% de los pacientes al año del mismo. En general, el nivel de proteinuria es bajo (

Since 1979 we have performed 669 kidney transplantations (KT) in our unit, 613 first and 56 retransplantations (KRT). Among the causes of graft loss in our first graft group, recurrence of glomerulonephritis (GN) was the fifth in importance (4%) after death with functioning graft, chronic and acute rejections and vascular thrombosis. Thus, ten patients lost their grafts after recurrent glomerulopathy: focal segmental glomerulosclerosis (FSGS) (n = 3), membranoproliferative (n = 3), IgA (n = 2) and membranous (n = 2), after a post-KT period variable from some weeks to 15 years. We have attempted KRT for three of them.

Background. Interest in the humanities in the medical school is growing; while several medical schools, mainly of Anglo-Saxon background, have developed dedicated courses, the experience in Italy is limited. Methods. Since the academic year 2000 to 2001, a discussion of ethical problems was implemented in the nephrology course (fourth year of the Medical School of Torino, Italy; overall 6 years). In 2002 to 2003, a case entitled Retransplantation of Multiple Organs (Prog Transplant 2002) was discussed in 2 hours of small-group tutorial teaching: a boy received a renal graft at age 5, failed at age 7 due to recurrent glomerulonephritis, required a heart-kidney graft at age 11, and a second heart-kidney graft at 17. Student opinions were gathered by anonymous semistructured questionnaires at the beginning of the lessons as a basis for discussion. Results. Following the lessons all students returned the questionnaires (n = 104). In the absence of competition for allocation, retransplantation was approved by 76.2%, unacceptable for 1% (22.9% uncertain-blank). With a waiting list of 10 patients, the opinions changed: 32.4% approved transplantation, 6.7% didn't approve it, 60.9% were uncertain. A theoretical categorization into deontological or utilitaristic approaches favored the first (41.9% vs 26.7%), with a high prevalence of blank-uncertain (31.5%); 21.9% of the students would change their opinion was that study head of the Transplant Department. Conclusion. Ethical aspects of the medical profession have been discussed with interest by medical school students; the high prevalence of uncertain answers and requests to develop specific tools underline the importance of this educational approach.

During the period from January 1973 to December 1990, 774 renal transplantations in 698 children were performed in our renal unit. A total of 540 grafts were examined both by light and immunofluorescence microscopy at least once. Recurrent glomerulonephritis was diagnosed in 62 grafts, de novo glomerulonephritis in 68 and allograft glomerulopathy in 38 (7%). The term allograft glomerulopathy (AGP) refers to the very specific pattern of glomerular involvement unique to renal allografts and characterized by: (1) widespread reduplication of the glomerular basement membrane due to a widening of the subendothelial space associated with (2) moderate increase in mesangial matrix and (3) interposition of mesangial matrix and cells. AGP is a glomerular manifestation of chronic rejection and is almost always associated with obliterative vascular changes. In our experience it is present in 25% of long-standing grafts (more than 10 years), but may develop early in the post-transplantation period (5 cases within the first year). In 13 of 33 patients in whom early biopsies were available, a different pattern characterized by a hypercellularity and the presence of monocytes-macrophages in the mesangial areas was observed. We suggest that this hypercellular pattern might be the early stage of the disease and could be called "acute allograft glomerulopathy" as opposed to the pattern characterized by reduplication of the glomerular basement membrane which deserves the name of "chronic allograft glomerulopathy." The exact relationship between these two patterns remains to be determined. Clinicopathologic correlations showed that chronic AGP is often associated with marked proteinuria. However, in our series proteinuria was absent or minimal in 25% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Two patients with Wegener's granulomatosis, who were in complete remission secondary to cyclophosphamide therapy but who had end-stage renal failure, were treated with renal transplantation. Neither patient has clinical evidence of recurrent glomerulonephritis 10 and 28 months after receiving the renal transplants. Cytotoxic therapy has been proved to be highly effective in inducing and maintaining remission in patients with Wegener's granulomatosis; thus increasingly larger numbers of patients will be seen who, despite being maintained in complete remission, will have markedly impaired renal function due to previous acute damage. Renal transplantation can now be considered an acceptable alternative form of therapy in such patients.

A 20-year-old patient with Henoch-Schönlein purpura leading to end-stage renal failure received a living-related renal transplant. She was treated with conventional immunosuppressive therapy. Following a quiescent period of 18 months pretransplant, at 3 months after engraftment there was recurrence of purpuric lesions with subsequent abdominal pain and glomerulonephritis. Renal and skin biopsies confirmed the immunopathologic changes of Henoch-Schönlein purpura. This case represents the second report of an adult with multiorgan recurrence of Henoch-Schönlein purpura following transplantation.

Thirty-two recipients of 33 renal allografts from related donors were divided into three groups by serotyping and genetic analysis. In the first group, eight patients inherited the same HL-A complexes as their donors. Seven have had excellent courses, with complete rehabilitation; one has recurrent glomerulonephritis. In the second group, seven patients inherited one HL-A complex in common with their donors and had very good serologic matches for the other. All had evidence of rejection, but six have had excellent courses; two have stable but subnormal function. In the third group 16 patients shared one HL-A complex with their donors but had poor serologic matches for the other; one differed by both complexes from his donor. Three patients have had excellent courses though two show decreasing creatinine clearances. Ten had unsatisfactory courses resulting in death, nephrectomy or poor rehabilitation; four have had intermediate courses. Intrafamilial donors can be selected so that the prognosis is...

Several factors, including widespread clinical renal transplantation, histopathologic recognition of glomerular disease within grafts [1–4] and elucidation of the principal immunopathogenetic mechanisms causative of glomerulonephritis in experimental animals and human renal disease [5], have combined to cause keen awareness of the potential risks of recurrent glomerulonephritis in renal grafts. This awareness has been strengthened by reported experience with renal isografts in which most patients whose underlying disease was glomerulonephritis developed glomerulonephritis in their grafts, ultimately causing death in six of the 12 patients affected [6]. Moreover, reports based on immunologic data indicated that pathogenetic autoimmune mechanisms persisting in the host could have important clinical expression in patients with renal allografts, despite immunosuppressive therapy [7].

The glomerular pathology of 634 transplant specimens (526 biopsies and 108 transplantectomies) from 410 children was studied. Three types of glomerulopathies were observed: (1) recurrent glomerulonephritis (GN) (40 of 142 patients with glomerular nephropathy), (2) de novo GN (52 grafts), and (3) transplant glomerulopathy (29 grafts). The study of recurrent GN is considered of great interest because of the possible insight into the nature of the original disease and the opportunity to observe the evolution of the disease in sequential biopsies of the transplant. The two major forms of de novo GN were membranous GN and IgG linear deposits along glomerular and tubular basement membranes. Transplant glomerulopathy, although distinctive morphologically, may resemble membranoproliferative GN (MPGN) or thrombotic microangiopathy.

Surprisingly enough no reports on urinary stone formation after kidney transplantation have been published to our knowledge. Since obstruction of a transplanted ureter appears not to cause pain, renal stone formation can be missed easily or misinterpreted as rejection or recurrent glomerulonephritis or simply urinary tract infection.

Recurrent glomerulonephritis in kidneys transplanted to glomerulonephritic recipients is becoming more obvious. It has been suggested that the disease process which caused the original disease in the recipient is also operative in the transplanted tissue. This study compared the ultrastructure and immunofluorescence of the native kidneys of four patients with their respective sequential, transplant biopsies. In each case, subepithelial humps and IgG, characteristic of a complex type of nephritis, were observed in both the original diseased kidneys and in the transplants. This would indicate that the immunopathologic process which caused the original glomerulonephritis and led to transplantation is also operative in the transplanted tissue.

• Twenty-four renal allografts functioning up to six years from the date of transplantation were retained in situ from four days to five years following return of the patient to hemodialysis. Fifteen of the 24 kidneys were removed for specific indications within four days to ten months. The reasons for allograft nephrectomy included fever, hematuria, graft pain and tenderness, and severe hypertension. Nine patients remained asymptomatic with grafts retained three months to five years (median, two years) following return to hemodialysis. It appears safe to retain nonfunctioning grafts in asymptomatic patients, thereby avoiding an unnecessary operation when failure is due to chronic rejection or recurrent glomerulonephritis. Nevertheless, in many patients complications eventually develop for which the allograft will be removed. (Arch Surg115:42-43, 1980)

In 1954 Merrill et al. first performed successful renal transplantation in man (Merrill et al. 1956). Since then, kidney grafting has become a well-accepted therapy for terminal renal failure.

Thirty-four renal transplants were performed in 32 children and adolescents between the ages of 5 and 21 over the past 3 years. Some children with unusual syndromes such as Juene's nail-patella, and congenital oxalosia were transplanted. Nineteen out of 26 (73%) living-related transplants and 4 out of 8 (50%) cadaveric transplants are functioning. Thirty-one out of 32 patients (97%) are surviving. Graft loss has been due to acute progressive rejection, chronic rejection, and recurrent membranoproliferative glomerulonephrltis. Craatinine clearance and concentrating ability is maintained in many grafts indicating prolonged survival even in some patients with recurrent glomerulonephritis. Patterns of serum complement levels and urinary protein excretion are reviewed post-transplant. Growth patterns are also reviewed in the younger children.