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In patients who have not undergone transplantation, Guillain-Barré syndrome (GBS) is typically preceded by an acute infection often sustained by Campylobacter jejuni. Thus far, in renal transplant recipients, only eight cases of GBS have been reported. In seven patients GBS was attributed to cytomegalovirus infection and in the eighth patient to cyclosporin A neurotoxicity. We report here the case of a GBS in a renal transplant recipient following C. jejuni bacteremia. The infection quickly disappeared after erythromycin and methronidazole therapy. GBS progressively evolved into a paraparesis within 1 week. After reaching a plateau phase, the clinical status improved and the patient was able to walk unassisted after 3 weeks. At this last check-up, 54 months later, the patient was doing well with a functioning graft and only minimal weakness of the lower limbs.

The treatment of renal failure in cirrhotic patients with ascites remains unsatisfactory. Recent studies have shown that the dietary supplementation with fish oil improves the renal function of normal subjects, as well as that of patients with renal failure of different etiologies. We have investigated the renal effects of a daily supplementation for 1 month of 12 g fish oil (27% C20:5 n-3 eicosapentanoic acid [EPA], and 23% C22:6 n-3 docosahexanoic acid [DHA]) in a prospective study of cirrhotic patients with ascites, nine with normal renal function (group 1) and eight with renal failure (glomerular filtration rate [GFR] < 60 mL/min, group 2). Compliance with the dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentration of EPA (from 1.5 +/- 0.7% to 3.7 +/- 0.8%, P = .024, in group 1; and from 0.53 +/- 0.3% to 2.9 +/- 0.8%, P = .03, in group 2) and of DHA (from 2.1 +/- 0.4% to 3.4 +/- 0.3%, P = .008, in group 1; and from 1.45 +/- 0.5% to 3.8 +/- 0.4%, P = .05, in group 2). At the end of the study, in patients from group 1, the glomerular filtration rate increased by 19% (from 94 +/- 8 to 113 +/- 13 mL/min, P = .039), and the urine flow increased by 39% (from 0.85 +/- 0.14 to 1.12 +/- 0.2 mL/min, P = .039), while no changes occurred in the renal function of patients from group 2. No changes were observed in the urinary excretion of prostaglandin (PG) E2 or of 6-keto prostaglandin-1-alpha (6-K-PGF1-alpha) nor in plasma renin activity (PRA) or the plasma concentration of aldosterone (PA) or antidiuretic hormone (ADH) in both groups. As far as undesirable effects of fish oils were considered, the mean arterial pressure (MAP) decreased in both groups (group 1: from 88.6 +/- 2 to 85.3 +/- 2 mm Hg, P = .015; group 2: from 88.2 +/- 3 to 82.8 +/- 3 mm Hg, P = .05), and bleeding time displayed a significant increase when patients were considered collectively (from 744 +/- 89 to 872 +/- 106 seconds, P = .0068). In conclusion, the administration of fish oil for 1 month was unable to improve renal function in cirrhotic patients with ascites and renal failure. The occurrence of undesirable effects, such as the reduction of arterial pressure and the prolongation of bleeding time, argues against the use of fish oils in these patients. (Hepatology 1997 Feb;25(2):313-6)

The influence of three different immunosuppressive regimens with cyclosporine (CsA) on the development of osteopenia in renal transplant patients was assessed. Fifty-three adults with first kidney transplants participated in a randomized trial to analyze the efficacy of three different immunosuppressive regimens: CsA alone (group 1), CsA plus steroids (group 2), and CsA plus steroids plus azathioprine (group 3). Lumbar spine bone mineral density was assessed by dual energy x-ray absorptiometry every 6 months for 18 months. The values for trabecular mass were expressed as bone mineral density and as a fraction of the standard deviation of the mean of the normal value for patient's sex and decade of age (Z-score). Statistical analysis was performed on Z-score and "Z-score change" (value after 6 months minus the basal value at transplantation). At the 18th month, the Z-score increased significantly in treatment group 1 without steroids (P=0.006) and decreased significantly in steroid-treated groups 2 (P

The patient and graft survival are the primary endpoints to evaluate safety and efficacy of the immunosuppressive treatments in renal transplantation. Today, however, the results are so good that a huge number of patients is needed to find statistically significant differences between treatments. Secondary endpoints are, therefore, used. Infections and other side effects are good endpoints for safety. Acute rejection is the best surrogate endpoint for efficacy. The diagnosis of acute rejection rests on an increase of plasma creatinine but how much the increase should be to define rejection is still unclear. Moreover, a number of noninvasive techniques can be used to exclude causes of graft dysfunction other than rejection. Thus, renal biopsy may be required to confirm the diagnosis. The severity of acute rejection may be used as a tertiary endpoint, but the criteria for assessing the severity of rejection still need to be standardized either based on clinical or histological variables.

Basiliximab is a chimeric monoclonal antibody directed against the alpha chain of interleukin-2 receptor (IL-2R). When administered intravenously at a dosage of 20 mg at the time of transplantation and 4 days later, basiliximab saturates the alpha chain of IL-2R for 4 weeks.This review evaluates the efficacy and safety of basiliximab in kidney transplantation. Randomized controlled trials showed that basiliximab can significantly reduce the incidence of acute rejection without increasing the risk of adverse events. When compared with other antibodies used for induction, basiliximab showed efficacy and safety profiles similar to daclizumab, another monoclonal antibody directed against the alpha chain of IL-2R. In comparison with rabbit anti-thymocyte globulins (rATG), basiliximab showed a similar efficacy. However, in patients at higher risk of rejection, rATG proved to be more effective. No serious safety problems related to basiliximab have been reported.There is a solid evidence that basiliximab can significantly decrease the risk of acute rejection in kidney transplant recipients without increasing adverse events. This can allow decreased dosage or avoidance of glucocorticoids and reduced dosage of calcineurin inhibitors. On the basis of efficacy, tolerability, ease of administration, and cost effectiveness, basiliximab may be considered the drug of choice for the prophylaxis of acute rejection in standard renal transplant recipients.

Whether and when is it possible to completely stop immunosuppression in patients with lupus nephritis is still poorly defined.An attempt to slowly and progressively eliminate steroids and immunosuppressive drugs was tried in 73 of 161 (45.3%) patients with lupus nephritis who achieved a stable clinical remission defined as normal serum creatinine, proteinuria0.5g/24h, inactive urine sediment, and no clinical signs of extra-renal activity of SLE for at least 12 months.Twenty-one out of the 73 patients (28.7%) who met the criteria for withdrawal of treatment developed flares during the phase of progressive reduction of therapy and their treatment was reinforced. Twenty patients entered remission again; the last patient was lost to follow-up at achievement of partial remission. In the other 52 of the 73 patients (71.2%), it was possible to completely withdraw treatment. Of these, 32 patients (group A) did not resume therapy for the subsequent follow-up (median 101.8 months); the other 20 patients (group B) had at least one flare, in median 37 months after withdrawing therapy, and had to be retreated. At the last observation, after a median follow-up of 286 months, 10 of these 20 patients were off therapy. At the last observation, two patients in group A and two in group B had died, no patient of group A and two of group B had developed renal insufficiency (serum creatinine 2.5 and 3 mg/dl, respectively). Compared to patients in group B, group A patients received longer treatment (98.1 vs. 31.0 months; p=0.01), had longer remission (52.8 vs. 12.0 months; p=0.000) before withdrawal of therapy, and continued chloroquine after stopping therapy (52% vs. 10%; p=0.004). In comparison to patients who never stopped therapy, patients who were able to interrupt treatment had lower risk of chronic renal insufficiency (3.8% vs. 28.4%; p=0.000), end-stage renal disease (0 vs. 12.8%; p=0.01), arterial hypertension (32.7% vs. 66.9%; p=0.000) and cardiovascular events (11.5% vs. 27.5%; p=0.04).Complete withdrawal of therapy is feasible in selected patients who achieved stable remission after long-term treatment. The reduction of treatment must be done in a very gradual manner, progressively and under strict medical surveillance. The withdrawal of therapy allows the patients to reduce renal and extra-renal damage accrual. Treatment with chloroquine may help to maintain remission in patients who discontinue steroids and immunosuppressive drugs.

We report three patients with well-documented renal amyloidosis who developed rapidly progressive renal failure. Renal biopsies from all three patients showed crescentic glomerulonephritis imposed on renal amyloidosis. All patients were treated with intravenous high-dose methylprednisolone pulses combined with immunosuppressive agents and oral corticosteroids. Partial recovery of renal function was obtained in two patients. For the third patient, treatment had to be stopped after a few days because of a septic arthritis. Renal function continued to deteriorate, and the patient had to be placed on regular hemodialysis. We conclude that extracapillary glomerulonephritis may occasionally complicate a preexisting renal amyloidosis and may be reversible if recognized early and treated appropriately.

This study presents the 10-yr follow-up results of a multicenter controlled trial on 108 recipients of cadaveric renal transplantation, randomized to receive cyclosporine (N = 55) or azathioprine (N = 53), both in combination with steroids. The 10-yr patient survival rate was 89% in the cyclosporine group and 83% in the azathioprine group (P = not significant [NS]); the 10-yr graft survival was 56% and 35%, respectively (log-rank test, P = 0.009). The half-life of grafts functioning after 1 yr was 15.4 +/- 3.9 versus 10.6 +/- 3.6, P = NS). The rate of early rejection in the cyclosporine group was significantly lower than that in the azathioprine group (0.30 versus 1.4, P0.01). Although the mean creatinine clearance rate was always higher in the azathioprine group, the decline in graft function from the first to the tenth yr was not significantly different between the two groups (-13.0 +/- 16.4 versus -12.3 +/- 19 mL/min, P = NS). In cadaveric renal transplantation, cyclosporine allows better graft survival than azathioprine, not only in the short term but also in the long term, with similar attrition of graft function for up to 10 yr.

Background Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic nephropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting–enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases. Methods In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 to 60 ml per minu...

Recent studies have pointed out that the incidence of primary glomerular diseases is similar in the elderly and in younger populations. However the clinical characteristics of the different subtypes may be different in the advanced age. Minimal change nephropathy responds favorably to corticosteroids and/or cyclophosphamide, but many untreated or non-responder patients progress to end-stage renal disease or die from nephrotic complications. Focal and segmental glomerulosclerosis also has a severe prognosis in older patients but some 50% of patients may attain remission of the nephrotic syndrome with a prolonged corticosteroid treatment. The responders tend to maintain normal renal function over time. Membranoproliferative glomerulonephritis and IgA nephritis have a severe prognosis and do not respond to treatment. The clinical presentation and the outcome of membranous nephropathy are similar in the elderly and in younger adults. Corticosteroids are of little benefit while a 6-month treatment with chlorambucil and methylprednisolone may obtain remission of the nephrotic syndrome in about 2/3 of older patients. Crescentic glomerulonephritis has an ominous prognosis in older patients but some patients may improve if treatment with methylprednisolone pulses is started early. Acute postinfectious glomerulonephritis is often associated with renal failure in older patients. The prognosis may be severe.

Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [EPA] and 12% C22:6 n-3 docosahexanoic acid [DHA]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsA-treated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 +/- 0.02% to 4.6 +/- 0.5%, P < .0001) and DHA (from 1.8 +/- 0.2% to 3.9 +/- 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 +/- 2% to 28.4 +/- 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% (P = .012), the glomerular filtration rate increased by 33% (P = .057), the renal blood flow increased by 17% (P = .024), and the calculated total renal vascular resistances decreased by 20% (P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during L-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been recently reported that in type 1 diabetes the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme gene is associated with the presence of diabetic nephropathy. Tissue angiotensin I-converting enzyme is determined by I/D polymorphism, and it has been speculated that in diabetes differences of local angiotensin II availability determine the risk of renal disease. Since angiotensin II is thought to play an important role in the evolution of renal disease in general, we tested whether genotype distribution of the I/D polymorphism is also different in patients with immunoglobulin A-glomerulonephritis (IgA-GN). Furthermore we compared IgA-GN patients with (1) stable renal function or (2) terminal renal failure to investigate a potential role of the I/D polymorphism in the renal prognosis. We examined 122 patients with biopsy-confirmed IgA-GN who had stable renal function and 82 dialysis-dependent or transplanted patients with biopsy-confirmed IgA-GN. Furthermore, in 134 healthy individuals used as controls we analyzed the DNA for normal distribution of genotypes and allele frequencies. The polymorphic region was amplified using polymerase chain reaction with specific primers. Alleles were detected on 2% agarose gels. Genotype distributions and allele frequencies were not significantly different between controls and patients with IgA-GN and stable renal function. Furthermore, no significant difference in genotype distribution was detected between patients with IgA-GN and stable renal function compared with patients with IgA-GN and end-stage renal failure, although a trend for a higher frequency of DD-homozygotes was noted in the latter group (P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosteroids have played a key role in the immunosuppression of organ transplantation. Unfortunately, the extensive use of these agents has resulted in disabling and life-threatening adverse effects in many patients. The advent of concomitant corticosteroid/cyclosporin regimens has allowed a reduction in the dosages of steroids administered, yet steroid-induced morbidity is still a major problem in many cyclosporin-treated renal transplant patients. After favourable initial experiences with cyclosporin monotherapy, several attempts at steroid-free immunosuppression in renal transplant patients have been undertaken, either by not starting steroids after transplantation or by stopping steroids in patients with stable graft function. Most controlled and uncontrolled trials showed that with either strategy short term graft survival was similar with or without steroids, but acute rejection was more frequent in patients not taking steroids. The percentage of patients who could be maintained steroid-free ranged from 28 to 94%, and was higher in patients who stopped steroids later than in those never receiving them. Little information is available about long term follow-up of these patients. Some studies reported late attrition of renal function in patients not taking steroids, while others reported a favourable outcome even in the long term. Steroid-free immunosuppression is feasible in renal transplant patients, but it requires careful monitoring of renal function and cyclosporin dosage. This strategy is particularly indicated in patients at high risk of cardiovascular disease or steroid-related complications, and in children. Nevertheless, several issues need to be better elucidated by further studies, namely the long term outcome of steroid-free immunosuppression, the advantages and disadvantages of steroid avoidance versus steroid withdrawal, and the criteria for selecting patients.

A large number of factors can influence the clinical out- come of kidney transplant recipients, but the active role of the patient to prevent the possible complications re- lated to transplant and its treatment is often neglected. Poor adherence to prescriptions is frequent in transplant recipients and represents a major contributor to the de- velopment of graft failure, cardiovascular disease, infec- tion and/or malignancy. Smoking can render the patient more susceptible to cancer, cardiovascular disease and infection, and can also impair renal allograft func- tion. The risk of malignancy is increased in transplant recipients. Therefore screening for cancer is of para- mount importance. Measures that can enable preven- tion or early detection of cancer include self-exams and screening, physical activity, avoidance of smoking and sun exposure, and a diet rich in fruits and vegetables but limited in fats, red meats, salt and alcohol. Regu- lar exercise can help to prevent cardiovascular disease, diabetes, obesity, osteoporosis and even some forms of cancer. Thus regular exercise is recommended. Yet, too many transplant patients remain sedentary. Weight gain is common in renal allograft recipients and may be asso- ciated with hypertension, hyperlipidemia and/or glucose intolerance or overt diabetes. To prevent these compli- cations, patients should follow diet regimens based on low fat and normal/low caloric intake. Small amounts of alcohol may be permitted in view of its potential car- dioprotective effect, but a large consumption of alcohol can be responsible for devastating side effects. Last but not least, abidance by hygienic measures may help in preventing cardiovascular and infectious complications.

De novo membranous nephropathy (MN) is an uncommon complication of kidney transplantation, which shows histological findings similar to those seen in recurrent MN, but with some distinct differences. The clinical presentation may be variable, from asymptomatic to nephrotic proteinuria. The disease may run an indolent course or may have an accelerated course leading to allograft loss. De novo membranous nephropathy (MN) can develop in transplant recipients with viral hepatitis, Alport syndrome, ureteral obstruction, renal infarction, or in conjunction with recurrent IgA nephritis. Histologic signs of allograft rejection are often associated with or can antedate de novo MN. These findings suggest that donor-specific antibodies and antibody-mediated rejection might play a pathogenetic role in some patients with de novo MN. However, signs of rejection were absent in a number of cases, and in some instances the disease developed in recipients of "full house" HLA- matched kidneys. Thus, it seems possible that de novo MN is not because of allograft rejection per se, but is triggered by different injuries that can create an inflammatory environment, activate innate immunity, and expose hidden (cryptic) antigens, probably different from those observed to be involved in idiopathic MN. These events can lead to the production of circulating antibodies and in situ formation of immune complexes (IC) and the morphological lesion of MN.

The prevalence of proteinuria at 1 year after renal transplantation ranges between 11% and 45% and is even higher in patients treated with inhibitors of the mammalian target of rapamycin (mTOR). Two main mechanisms can lead to proteinuria: an inadequate reabsorption of small proteins from proximal tubular cells damaged by ischemia-reperfusion injury, rejection, or toxic agents (tubular proteinuria) or an increased passage of albumin and/or protein with higher molecular weight (MW) because of a disruption of glomerular barrier caused by recurrent or de novo glomerulonephritis, transplant glomerulopathy, chronic rejection, or CNI toxicity (glomerular proteinuria). Proteinuric patients have worse patient and graft survival rates in comparison to non proteinuric patients. The amount of proteinuria is a reliable predictor of the allograft outcome. However, even microalbuminuria may be associated with a poor outcome. Treatment of proteinuria mainly rests on the management of the etiologic cause. Inhibitors of renin-angiotensin system (RAS) are useful in reversing microalbuminuria and can reduce proteinuria, but their efficacy in interfering with patient or graft survival is not demonstrated.

The most frequent primary glomerular diseases (PGD) associated with nephrotic syndrome (NS) in the elderly are membranous nephropathy (MN), minimal change nephropathy (MCN), and focal and segmental glomerulosclerosis (FSGS). In older patients MN may be secondary to drugs or neoplasia in 20 to 25% of cases. The natural renal outcome of idiopathic MN is similar in elderly patients and in those of the second age. However, elderly patients are more exposed to the extra-renal complications of NS. Corticosteroids alone do not seem to modify the course of the disease. A 6-month regimen with corticosteroids alternated to chlorambucil, which has proven to improve the outcome of MN in adults, may increase the chances of remission and protect renal function also in the elderly patients but side effects increase with age. Elderly patients with MCN are more prone than younger adults to the complications of the NS and to the development of renal failure. Only 60% of older patients enter remission with an 8-week course of prednisone, but about 80% can achieve complete remission with corticosteroids if treatment is prolonged to 12–16 weeks. Relapses are more rare in the elderly. In patients with contraindications to prolonged corticosteroid therapy, a course of 12 weeks with a cytotoxic agent may obtain stable remission in most cases. Little information is available about the natural course and the management of idiopathic FSGS in the elderly. A recent report showed that more than 40% of older patients may obtain stable remission after an initial treatment with corticosteroids for 6 months. For those patients who do not respond or have contraindications to steroid therapy, a cautious trial with cyclophosphamide may be tried.

For many years, acute rejection has been considered as a typical response of the adaptive immunity system. However, recent investigations have revealed a critical role for innate immunity as a pivotal trigger in adaptive immune responses. Danger signals released by cells damaged or killed by injury or disease may be intercepted by Toll-like receptors (TLRs) that alarm the dendritic cells (DCs) through the activation of transcription factors. In the presence of an inflammatory milieu created by other components of the innate immunity, DCs become mature and present the antigen to naive T cells. The activation of T cells requires both a signal engendered by the presentation of the antigen to the T cell receptor and costimulatory signals generated by the contact between molecules displayed by antigen-presenting cells (APCs) and by T cells. Once activated, T cells encode and synthesize interleukin 2 (IL-2) and other cytokines that provide the signals for cell differentiation and proliferation. Until recently, little attention was paid to the role of antibodies in renal transplantation. However, there is mounting evidence that a number of kidney allografts fail as a consequence of a rejection caused by antibodies specifically directed against major histocompatibility complex antigens, class I or II, of the recipient. A critical role in antibody-mediated rejection (AMR) is played by complement. A number of therapeutic attempts have been tried to prevent or treat AMR. The still open question is whether the antibodies we detect are those responsible for tissue damage or not.

Background: Cyclosporine nephrotoxicity negatively impacts long-term outcome after heart transplantation (HT). We previously reported 1-year results from a randomized study showing that cyclosporine-lowering strategies based on everolimus or mycophenolate mofetil (MMF) are equally effective for reducing progression of renal dysfunction. It is unknown whether this efficacy could be maintained over the long term. Methods: Thirty-four recipients 1 to 4 years after HT and with 25 to 60 ml/min of creatinine clearance (CrCl) were randomized to everolimus with a very low dose (C0: 50 to 90 ng/ml, n = 17) or MMF with low dose of cyclosporine (C0: 100 to 150 ng/ml, n = 17). Follow-up was prolonged up to 3 years, and calculated CrCl was the main efficacy measure. Results: Cyclosporine was maintained at 70% and 30% lower than baseline in the everolimus and MMF arms, respectively, throughout the 3-year study period. CrCl remained stable in the everolimus patients (+7% from baseline; p = 0.7), but improved in the MMF patients (+20% from baseline; p < 0.01), with a trend toward improved values compared with everolimus patients (46 ± 12 vs 56 ± 15 ml/min; p = 0.06). Subgroup analysis revealed that baseline proteinuria markedly influenced the renal function response to everolimus: whereas in patients with baseline proteinuria CrCl significantly worsened (-20%; p = 0.04), it improved in those without (+15%; p = 0.03). Safety was comparable between the two study arms. Conclusions: Cyclosporine nephrotoxicity improved after a prolonged dose reduction in patients receiving MMF. The everolimus-based strategy provided a similar benefit only to patients without baseline proteinuria. While raising caution against the universal use of everolimus for kidney protection, our long-term results support the need for customized approaches in the management of drug toxicities in maintenance HT recipients.

Hepatitis B virus (HBV) infection remains an important cause of liver disease in the renal transplant (RT) population, potentially diminishing survival. Consequences of HBV infection after RT include progression to decompensated cirrhosis and an increased risk of hepatocellular carcinoma. Although precautions initially recommended by the Centers for Diseases Control and Prevention 30 years ago have substantially reduced HBV transmission within hemodialysis units, acute HBV outbreaks continue to be reported in patients with chronic kidney disease on maintenance hemodialysis. In addition, immigration from areas of high HBV prevalence implies that HBV-infected organs with chronic kidney disease will continue to enter the RT pool. Fortunately, the advent of oral therapy for HBV infection now reduces the risk of HBV progression post-RT.

The risk of a posttransplant recurrence of secondary glomerulonephritis (GN) is quite variable. Histologic recurrence is frequent in lupus nephritis, but the lesions are rarely severe and usually do not impair the long-term graft outcome. Patients with Henoch-Schonlein nephritis have graft survival similar to that of other renal diseases, although recurrent Henoch-Schonlein nephritis with extensive crescents has a poor prognosis. Amyloid light-chain amyloidosis recurs frequently in renal allografts but it rarely causes graft failure. Amyloidosis secondary to chronic inflammation may also recur, but this is extremely rare in patients with Behcet's disease or in those with familial Mediterranean fever, when the latter are treated with colchicine. Double organ transplantation (liver/kidney; heart/kidney), chemotherapy, and autologous stem cell transplantation may be considered in particular cases of amyloidosis, such as hereditary amyloidosis or multiple myeloma. There is little experience with renal transplantation in light-chain deposition disease, fibrillary/immunotactoid GN, or mixed cryoglobulinemic nephritis but successful cases have been reported. Diabetic nephropathy often recurs but usually only after many years. Recurrence in patients with small vessel vasculitis is unpredictable but can cause graft failure. However, in spite of recurrence, patient and graft survival rates are similar in patients with small vessel vasculitis compared with those with other renal diseases. Many secondary forms of GN no longer represent a potential contraindication to renal transplantation. The main issues in transplantation of patients with secondary GN are the infectious, cardiovascular, or hepatic complications associated with the original disease or its treatment.

Herpes virus infections are frequent in renal transplant recipients. Some herpes viruses are not only responsible for life-threatening infections and renal graft injury but can also increase the risk of malignancy. Three herpes viruses, namely cytomegalovirus (CMV) or human herpes virus 5, Epstein-Barr virus (EBV) or herpes virus 4 and human herpes virus 8 (HHV8), may play an oncogenic role. The oncogenic role of CMV is controversial. However, there is growing evidence showing that CMV can infect cancer cells and favour their resistance to the immune system and chemotherapy. B cells infected by EBV can have uncontrolled proliferation eventually resulting in polyclonal polymorphic or monomorphic post-transplant lymphoproliferative diseases (PTLD), which are particularly frequent in children and in EBV-negative recipients. In some ethnicities, the carriers of HHV8 are susceptible to develop Kaposi's sarcoma after transplantation. The intensity of immunosuppression therapy plays a critical role in mediating infections from oncogenic herpes viruses. However, the type of immunosuppressive drugs can also influence the risk of virus-mediated neoplasias. An aggressive induction therapy aimed at depleting lymphocytes may favour the reactivation and dissemination of oncogenic herpes viruses, while anti-CD25 monoclonal antibodies have little impact on virus reactivation. Calcineurin inhibitors can increase the risk of viral infections and malignancy. Mycofenolate salts may perhaps protect from EBV-related PTLD. Finally, the inhibitors of the mammalian target of rapamycine may reduce the risk of viral disease by inhibiting the cascade of kinases that govern the proliferation and replication of oncogenic herpes viruses.

Arterial hypertension is frequently observed in renal transplant recipients. Its pathogenesis is multifactorial in most cases. Calcineurin inhibitors (CNI) can increase peripheral vascular resistance by inducing arteriolar vasoconstriction and can cause extracellular fluid expansion by reducing the glomerular filtration rate (GFR), activating the renin-angiotensin system (RAS), and by inactivating the atrial natriuretic peptide. Glucocorticoids can impair urinary water and salt excretion. Poor graft function can lead to increased extracellular volume and inappropriate production of renin. Native kidneys, older age of the donor and transplant renal artery stenosis (TRAS) may also contribute to the development of hypertension. Arterial hypertension not only can increases the risk for cardiovascular events but can also deteriorate renal allograft function. A number of studies have shown that the higher the levels of blood pressure are, the higher is the risk of graft failure. On the other hand, a good control of blood pressure may prevent many cardiovascular and renal complications. Appropriate lifestyle modification is the first step for treating hypertension. Calcium channel blockers (CCB) and renin-angiotensin system (RAS) inhibitors are the most frequently used antihypertensive agents, but in many cases, a combination of these and other drugs is required to obtain good control of hypertension.

Chyluria results from an abnormal connection between lymphatic bed and urinary tract, causing lymph leakage into the urine. The clinical picture often begins with the appearance of cloudy, milky urines accompanied by monolateral flank pain, malnutrition, weight loss and weakness. We report a case of chyluria that occurred in a young woman who was referred to our unit for nephrotic-range proteinuria. Before performing a renal biopsy, we found that urine analysis demonstrated a massive lipiduria. Therefore, we collected urine samples from each kidney with a selective ureteral catheterization, demonstrating a monolateral source of lipids and proteins. We suspended the renal biopsy and performed a lymphography that showed an inherited lymphangioma on the left lumbar lymphatic bed. Sclerosing solution instillation, renal pedicle lymphatic disconnection or laser therapy are invasive therapeutical options that may cause severe adverse effects. Instead of these procedures, a conservative therapy based on a low-fat diet supplemented with medium-chain triglycerides was chosen. This dietetic schedule was followed by complete resolution of proteinuria and lipiduria. The patient progressively gained body weight and improved quality of life. No relapses were observed after 3 years of follow-up. This case emphasizes the possible role of a noninvasive therapeutical option for patients with chyluria.

An abnormal vascular status is present in the transplanted kidney. To define whether vascular factors might influence kidney function of the graft, the renal volume, blood flow and vascular resistance of a group of healthy subjects were compared with those of a group of well functioning renal transplants by color Doppler ultrasonography. Sixty healthy subjects and 75 well functioning cadaver renal transplant recipients were compared by color Doppler ultrasonography. Subsequently, 15 couples of donors and recipients of a living related renal graft were compared to observe the differences between the two organs of the same subject in a different environment. The variables studied were: the diameters and the volume of the kindey, renal blood flow and renal resistance index (RI). The group of cadaver renal transplant patients showed higher mean blood pressure (P = 0.009), higher serum creatinine levels (P = 0.0001) and lower endogenous creatinine clearance (P < 0.0001) than healthy controls. The length (P < 0.00001) and volume (P < 0.001) of the kidneys of cadaver transplanted patients were significantly greater than those of healthy subjects, while the length and volume of the living donors kidneys were identical to those of the recipients. RI, measured on renal vessels, showed lower values in healthy subjects and in kidney donors than in transplantated patients (P < 0.00001). Well functioning transplanted kidneys showed increased renal arterial RI. This non-immunologic factor did not appear to be detrimental with renal function in time, at least until 50 months after successful grafting.

Uremic xerosis is a bothersome condition that is poorly responsive to moisturizing and emollient therapy.A randomized, double-blind, intraindividual (left versus right comparison), multicentric clinical study was performed on 100 patients with moderate to severe uremic xerosis for 7 days, during which the patients applied twice daily an emulsion combining glycerol and paraffin (test product) on one allocated lower leg, and the emulsion alone (comparator) on the other lower leg. This was followed by an open-labeled use of the test product on all of the xerotic areas for 49 days. The main efficacy parameter was treatment response on each lower leg, as defined by a reduction from baseline of at least two grades in a five-point clinical score on day 7.Among the 99 patients analyzed, the test product was highly effective with a treatment response in 72 patients (73%), whereas 44 patients (44%) responded to the comparator (P0.0001, intergroup analysis). This was associated with an objective reduction in the density and thickness of the scales on day 7 (P0.0001 compared with the comparator) and a substantial improvement of the uremic pruritus (75%) and quality of life of the patients at study end (P0.001, intragroup analysis). The test product was very well tolerated, with product-related local intolerance (exacerbated pruritus, local burning, or erythema) occurring in only five patients (5%).Uremic xerosis can be managed successfully when an appropriate emollient therapy is used.

In 212 cyclosporine-treated renal transplant recipients with stable graft function at 1 year and with potential followup of 5 years the prevalence of arterial hypertension was 81.6% at 1 year and 81.2% at 5 years. The logistic regression analysis showed that the presence of hypertension before transplantation ( P = 0.0001; odds ratio 3.5), a plasma creatinine level higher than 2 mg/dL at 1 year ( P = 0.0001; odds ratio 3.8), and a maintenance therapy with corticosteroids ( P = 0.008; odds ratio 3.3) were positively associated with hypertension at 1 year after transplantation. The mean number of graft failures between 1 and 5 years was significantly higher and the mean reciprocal of plasma creatinine was significantly worse at 1 and 5 years in patients with noncontrolled hypertension than in normotensive patients or in patients with hypertension well controlled by drugs. We also investigated the potential protective role of nifedipine. The episodes of acute tubular necrosis (four versus three), of acute rejections (28 versus 29), the mean arterial pressure at 1 year (105 ± 9 versus 104 ± 9 mm Hg) and 5 years. (105 ± 10 versus 108 ± 12 mm Hg), and the mean plasma creatinine level at 1 year (1.4 ± 0.4 versus 1.6 ± 0.4 mg/dL) and 5 years (1.8 ± 1 versus 1.9 ± 1 mg/dL) were similar in 52 patients who were given nifedipine for at least 4 years and 58 hypertensive patients who never took calcium channel blockers. To evaluate whether an early administration of nifedipine might have a protective role on the graft we separated patients who started nifedipine within 3 days (17 patients) from those who were given the drug 4 or more days after transplantation (35 patients). No case of acute tubular necrosis was seen in patients treated early, while four cases occurred in the group receiving nifedipine later. The number of rejections (nine versus 19), mean arterial pressure at 1 year (105 ± 8 versus 105 ± 9 mm Hg) and 5 years (105 ± 11 versus 104 ± 9 mm Hg), and the mean plasma creatinine level at 1 year (1.5 ± 0.5 versus 1.5 ± 0.4 mg/dL) and 5 years (1.9 ± 1.5 versus 1.9 ± 0.9 mg/dL) were similar in the two groups.

Several therapeutic approaches have been tried in patients with membranous nephropathy. Corticosteroids have been largely used, but a meta-analysis of the available controlled trials did not show any benefit of corticosteroids either in favouring remission of the nephrotic syndrome or in preventing renal dysfunction. Controversial results have been obtained with cytotoxic agents. Unfortunately, most of the available trials were small in size and had short-term follow-ups. Three controlled trials evaluated the role of a 6-month treatment with methylprednisolone and chlorambucil. The first trial showed that the 10-year renal survival rate was 92% in treated patients compared with 60% in untreated controls. A second trial compared the effects of methylprednisolone chlorambucil with those of methylprednisolone alone. The combined treatment achieved remission of nephrotic syndrome in 64% of cases vs 38% in patients given steroids alone. A third trial showed equivalent results in patients randomized to be given methylprednisolone/chlorambucil or methylprednisolone cyclophosphamide. A number of non-controlled studies and a randomized trial also showed the efficacy of cyclosporine in reducing proteinuria. In many but not all cases, proteinuria reappeared when cyclosporine was stopped. In conclusion, although the treatment of membranous nephropathy remains difficult, some therapeutical approaches have proved to favour remission and protect renal function.

Increased survival in patients with β thalassaemia major (TM) allowed for several morbidities to manifest. Renal manifestations of the disease and its treatment have been poorly evaluated. There is evidence, mainly from studies in the paediatric population, of tubular dysfunction and glomerular filtration rate abnormalities in this patient population. Long-term outcomes of these changes, however, have not been prospectively investigated. The pathogenesis of these abnormalities could be attributed to iron overload, too aggressive iron removal, and/or the underlying anaemia. These changes seem to be nonprogressive, resolve spontaneously in most part, or may require iron chelator dose modifications. Relative iron depletion may explain renal function changes attributed to chelation therapy; thus, sudden removal of iron or overchelation should be avoided. Future studies should aim to evaluate the natural history of kidney function in TM patients to help understand the mechanisms and long-term sequelae of the observed renal changes.

Glomerular diseases and renal transplantation have always been considered as independent fields of nephrology, due to the supposed prevalent role of antibody production and immune complex formation in glomerulonephritis versus a direct reaction of immune cell towards the grafted kidney. However, both conditions share common pathogenetical pathways, and possible new therapeutic approaches are being envisaged. Innate immunity, particularly Toll-like receptors, dendritic cells and complement pathways, B cells and antibody networks are involved in the development of glomerular damage as well as graft injury. Consequently, new treatments targeting previously not considered immune pathways, like nuclear factor-κB or the proteasome and B-cell activation with antibody production, are being tested in glomerular diseases and in transplanted kidneys.

archy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 2004; 104: 2752–2760 8. Bahlmann FH, de Groot K, Duckert T et al. Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin. Kidney Int 2003; 64: 1648–1652 9. Bahlmann FH, de Groot K, Spandau J-M et al. Erythropoietin regulates endothelial progenitor cells. Blood 2004; 103: 921–926 10. de Groot K, Bahlmann FH, Bahlmann E et al. Kidney graft function determines endothelial progenitor cell number in renal transplant recipients. Transplantation 2005; 79: 941–945 11. Eknoyan G, Beck GJ, Cheung AK et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347: 2010–2019 12. de Groot K, Bahlmann FH, Sowa J et al. Uremia causes endothelial progenitor cell deficiency. Kidney Int 2004; 66: 641–646 13. Krieter D, Fischer R, Merget K et al. Endothelial progenitor cells in patients on extracorporeal maintenance dialysis therapy. Nephrol Dial Transplant 2010; 25: 4023–4031 14. Carracedo J, Merino A, Nogueras S et al. On-line hemodiafiltration reduces the proinflammatory CD14CD16 monocyte-derived dendritic cells: a prospective, crossover study. J Am Soc Nephrol 2006; 17: 2315–2321 15. Swirski FK, Libby P, Aikawa E et al. Ly-6C monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 2007; 117: 195–205

Idiopathic membranous nephropathy (IMN) may have a variable course, with some patients entering spontaneous remission and others slowly progressing to renal failure. The disease is treatable, but the available treatments are not devoid of potential morbidity. We review the studies dedicated to finding prognostic markers. Although a number of clinical and histologic markers are associated with an increased risk of progression to renal failure, in many cases it is still impossible to recognize at presentation what will be the long-term outcome for a patient with IMN. More reliable are time-dependent predictors, such as the amount of proteinuria over time and complete or partial remission. However, this means that a physician should wait for months or even years before taking therapeutic decisions, with the risk of starting after renal or extrarenal complications have already developed. How to proceed will have to be dictated by a careful evaluation of the patient: Taking into consideration not only the risk of renal progression but also the possible extrarenal complications, we suggest starting a "specific" treatment for patients presenting with full-blown nephrotic syndrome or with increasing levels of serum creatinine, while specific treatment is not necessary for asymptomatic patients with subnephrotic proteinuria.

To the Editor: In his excellent review, Meyrier1 outlined the current ignorance about the pathogenesis of focal segmental glomerulosclerosis (FSGS) and hoped for new treatments aimed at counteracting the unknown factor(s) responsible for FSGS rather than pursuing trials with agents interfering with the immune system (or alternatively, acting directly on the dysfunctional podocyte).

Treatment of proliferative lupus nephritis (PLN) consists of an initial aggressive treatment aimed to quench the hectic activity of the disease (induction phase) followed by a milder therapy aimed to prevent flares (maintenance treatment). There are a number of possible options for induction treatment. Intravenous (i.v.) pulses of cyclophosphamide plus oral or i.v. steroids is very effective but can be accompanied by severe adverse events. Alternatively, i.v. pulses of methylprednisolone (MPP) followed by a 2-3-month course of oral cyclophosphamide, or mycophenolate mofetil (MMF) plus prednisone, seem to be as effective as i.v. cyclophosphamide and may be better tolerated. In cases refractory to these treatments, rituximab has been used successfully. However, the exact role of rituximab is difficult to ascertain as in most cases the drug was administered together with glucocorticoids or cyclophosphamide. Intravenous cyclophosphamide has also been prescribed for maintenance therapy with good results. However, recent trials showed that similar or even better results can be obtained with azathioprine or MMF associated with moderate doses of prednisone. Also cyclosporine can achieve good results while sparing steroids, particularly in patients with persistently elevated proteinuria. In summary, modern immunosuppression today allows us to reduce the dosage of steroids and to avoid the prolonged use of cyclophosphamide. These newer strategies may result in fewer adverse effects, better quality of life and better survival for patients with proliferative lupus nephritis.

Background and Methods. Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy. To determine whether similar results might be obtained with methylprednisolone alone, we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy. The patients were randomly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months (group 1) or methylprednisolone alone for six months at the same cumulative dosage (group 2). Results. Four of the 45 patients in group 1 (9 percent) and 1 of the 47 in group 2 (2 percent) stopped treatment because of side effects. At one, two, and three years, the percentage of patients who did not have the nephrotic syndrome was significantly higher in group 1...

Little attention has been paid by the renal literature to ureteral endometriosis, a rare and silent disorder that can eventually lead to renal failure. In endometriosis, the ureteral involvement can be limited to a single ureter, more often the left one, or both ureters with consequent urine tract obstruction and ureterohydronephrosis. In most cases, the ureteral obstruction is caused by endometrial tissue surrounding the ureter (extrinsic ureteral endometriosis). In the remaining cases, endometrial cells are located within the ureter (intrinsic ureteral endometriosis). Progressive ureteral obstruction can be insidious in onset and can ultimately lead to renal failure if a correct diagnosis is missed. The true incidence of renal failure caused by endometriosis is completely unknown, although cases have been reported in the literature. The diagnosis of ureteral endometriosis is difficult since the disease may be clinically silent or associated with non-specific symptoms. Only a high index of suspicion and radiological support may help to obtain an early diagnosis. However, while renal imaging is useful in the cases of extrinsic endometriosis, the diagnosis of intrinsic endometriosis often requires ureteroscopy or laparoscopy. The prognosis of ureteral endometriosis depends on the time of diagnosis. In too many cases of bilateral obstruction, the patient is referred to the nephrologist because of an advanced, irreversible renal failure. Although some patients may benefit from progestin or anti-arotamase therapy, in most cases of ureteral endometriosis surgery is needed, laparoscopy surgery being preferred today to laparatomy.

Chapter 1 - Symptomatic therapy Chapter 2 - Corticosteroids and immunomodulating agents Chapetr 3 - Minimal change nephropathy Chapter 4 - Focal and segmental glomerulosclerosis Chapter 5 - Membranous nephropathy Chapter 6 - Immunoglobuline nephropathy Chapter 7 - Membranoproliferative glomerulonephritis Chapter 8 - Crescentic glomerulonephritis

Minimal change nephropathy (MCN), also called ‘minimal change disease’ in the USA, is chiefly characterized by episodes of nephrotic syndrome—presenting with massive proteinuria, hypoalbuminemia, generalized edema, hyperlipidemia—and no lesions or only minimal glomerular abnormalities in the renal biopsy examined by light microscopy.

Fibrillary glomerulonephritis (FGN) and immunotactoid glomerulopathy (ITG) are both glomerular diseases characterized histologically by a diffuse increase in mesangial matrix due to deposits having a fibrillary structure by electron microscopy, which are negative for Congo-red stains but positive for immunoglobulin deposition. Most patients present with proteinuria, often in a nephrotic range, microhematuria, and hypertension. Almost half of patients have a reduced renal function at presentation. Although FGN and ITG have quite similar light microscopical and clinical features the current opinion is that they represent two separate diseases. FGN is an idiopathic (primary) condition characterized by polyclonal immune deposits with restricted gamma isotypes. Most patients present with significant renal insufficiency and have a poor outcome despite immunosuppressive therapy. By contrast, ITG very often contains monoclonal IgG deposits and has a significant association with underlying monoclonal paraproteinemia and hypocomplementemia. ITG is more properly classified as a mono-clonal immunoglobulin deposition disease (MIDD). Differentiation of FGN from the much more rare entity ITG appears justified on immunopathologic, ultrastructural, and clinical grounds (Fogo et al., 1993; Bridoux et al., 2002; Rosenstock et al., 2003). Both will be discussed together, although only FGN should be regarded as a primary glomerular disease, as defined in this monograph.

Although the rationale for an etiological treatment of primary glomerulonephritis is still lacking, a number of clinical studies have shown that some subtypes of these diseases may benefit from empirical treatment based upon the use of glucocorticoids or immunomodulating agents. In this chapter the clinical pharmacology, the mechanisms of action, and the toxic effects of these drugs will be reviewed.

Membranous nephropathy (MN) is a glomerular disease which is characterized histologically by uniform thickening of the glomerular capillary due to the presence of immunoglobulin-containing deposits on the outer or subepithelial aspect of the glomerular basement membrane (GBM). It exists in idiopathic (etiology unknown) or secondary (causally associated with another disorder) forms. Differentiation of the idiopathic membranous nephropathy (IMN) from secondary forms of MN may be difficult. It is a frequent cause of the nephrotic syndrome in adults. It is also characterized by a tendency for spontaneous remission in some patients and by persistence of proteinuria and slow progression to end-stage renal disease (ESRD) in others. Those patients with severe and un-remitting nephrotic syndrome may also suffer from disabling and even life-threatening extra-renal complications, such as thromboembolic events.

Focal and segmental glomerular sclerosis (FSGS) is a glomerular lesion which is associated with distinctive clinical features. Because it may be pathogenetically heterogeneous, it is not yet appropriate to call it a disease, yet its discovery in a renal biopsy in a patient with the nephrotic syndrome does have important connotations with respect to response to treatment and to long-term outcome. By light microscopy the characteristic finding is segmental areas of sclerosis (and hyalinosis) involving only some glomeruli. Patients with the FSGS lesion typically have proteinuria which is usually in the nephrotic range (〉3.5g/d in an adult), accompanied by the typical constellation of signs and symptoms of the nephrotic syndrome and arterial hypertension. A minority of patients may have only asymptomatic proteinuria and these patients usually do not progress to end-stage renal disease (ESRD) but the natural course of FSGS is ominous in most patients with nephrotic syndrome. However, numerous observational studies have shown that about 50–70% of patients may respond completely or partially to prolonged glucocorticoid therapy or other ‘immunosuppressive’ treatments and thus have a fair outcome in the long term.

After more than 40 years since the first demonstration that high-dose corticosteroids can modify the relentless outcome of lupus nephritis [1], the ideal treatment of lupus nephritis is still far from being established. There is some agreement that the initial treatment should be aggressive, particularly in proliferative forms (so-called induction therapy) and should be followed by a maintenance regimen aimed at preventing flares of activity while minimizing the side effects of treatment. However, there are differing views on how to use the available immunomodulating drugs in the various phases of the disease. In particular, there is still much controversy about the current therapies for maintenance [2]. Notwithstanding the different approaches used, it should be noted that the treatment of systemic lupus erythematosus (SLE) nephritis relies on three main categories of drugs, i.e. corticosteroids, alkylating agents and inhibitors of purine synthesis. However, all these drugs have a narrow therapeutic index, and their prolonged administration can cause severe iatrogenic toxicity. In this review, we will try to assess whether cyclosporine (CsA), a drug that interferes with the immune response at levels different from those of corticosteroids and immunosuppressive drugs, may have a role to play in the therapeutic armamentarium of lupus nephritis. CsA is a pro-drug that gains pharmacological activity after binding to its specific cytoplasmic receptor cyclophylin. The complex CsA–cyclophylin interferes with a complex of phosphatases called calcineurin that has a key role in the immune response. Contact with the antigen-presenting cell generates a strong influx of calcium ions into the lympho

One hundred two exit-site infections (ESI) were diagnosed in 63 of 163 (38.6%) patients, with an incidence of one episode every 23.7 patient-months in patients with a history of ESI, whereas in the overall continuous ambulatory peritoneal dialysis (CAPD) population the incidence was one episode every 48.7 patient-months. In diminishing order of frequency, the bacteria isolated were Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli. The probability of remaining free of ESI was 72% at 1 year and 45% at 5 years. The ESI that led to catheter removal were due to S aureus and gram-negative rods. In 13 (48%) of 27 S aureus ESI unresponsive to antibiotics and local care, deroofing and outer cuff shaving completely resolved the ESI. Despite this treatment, the catheters of the remaining 14 patients had to be removed because of peritonitis associated with the tunnel infection. In conclusion, ESI is a major cause of CAPD failure. In our series, shaving the cuff as a rescue treatment was effective for almost 50% of the patients with antibiotic-resistant S aureus ESI.

In a prospective trial 151 recipients of renal transplants were randomly assigned to treatment with CsA alone (74 patients) and to low dose of AZA, prednisolone, and CsA (77 patients). At two years, graft survival was 84% for the monotherapy and 90% for the triple therapy. This difference was not statistically significant. The number of rejection episodes was similar in the two groups, but the severity of rejection was significantly worse among the patients on monotherapy. More kidneys were lost because of rejection (6 versus 3), and a higher number of methylprednisolone pulses was used for treating rejection (5.2 +/- 2.3 versus 4.3 +/- 2.9; P = 0.0077). CsA nephrotoxicity episodes were more frequent among patients on monotherapy (23 versus 7; P less than 0.02). Infectious episodes were equally distributed between the two groups. Creatinine clearance was poorer in the monotherapy-treated patients at the third month (42 +/- 16 ml/min versus 48 +/- 15 ml/min; P = 0.02), but no differences were observed between the two groups since the sixth month after transplantation. Many patients on monotherapy required changes in maintenance therapy. In fact, one patient was switched to conventional immunosuppression because of Cremophor-induced anaphylaxis. Another patient who developed Kaposi's sarcoma 4 months after surgery was switched to steroids alone. Excluding 5 patients who lost their grafts a few days after transplantation, only 30 of 74 patients (40%) could be kept without steroids. We conclude that both the therapeutic protocols can give good results in renal allotransplantation; however, monotherapy could create some problems in keeping the balance between drug toxicity and significant immunosuppression. On the contrary, triple therapy is easier to handle, especially in the early posttransplant period when the differential diagnosis between acute rejection and CsA-related nephrotoxicity can be difficult even for a skilled clinician.