Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia <5 g/L. RTX could be used in cases of SOC failure or remission for early discontinuation of PP without increasing the risk of infection.

Renal transplantation is the treatment of choice of end stage renal failure. It both improves the quality and the quantity of life compared to other techniques, such as hemodialysis. These results are partly related to the use of immunosuppressive therapy more effective and whose handling has improved over time. Advances in understanding the mechanisms of lymphocyte activation and the phenomena of rejection have in fact better defined the use of these treatments and their associations. Treatments can be broadly classified according to their characteristics (biological or chemical). Among chemical treatments, steroids are widely used, although the question of their avoidance or spearing is still a matter of debate. The cornerstone of immunosuppressive regimens remains the calcineurin inhibitors, characterized by a narrow therapeutic index and the need for therapeutic drug monitoring. Inhibitors of mammalian target of rapamycin (mTOR) have interesting antiproliferative effects that could be important against chronic allograft dysfunction and/or carcinogenesis. However, their safety profile makes them difficult to handle. Inhibitors of purine synthesis are largely based on inhibitors of inosine monophosphate dehydrogenase (IMPDH). Their effectiveness makes them privileged partners of other therapeutic classes. Among biological treatments, it is possible to separate the depleting and non depleting antibodies. Among the former, antithymocyte globulins are mainly active in T cells, whereas rituximab, a monoclonal anti-CD20, is active in B cells involved in the phenomena of humoral rejection. The non depleting antibodies are represented by anti-CD25, directed against the receptor for interleukin-2. In the near future it is likely that the belatacept, a costimulation blockade fusion protein will be used to allow calcineurin inhibitors sparing. Other immunosuppressive agents, acting at different levels of the immune response are being evaluated. In addition, advances in pharmacology offered hope of a better individualization of immunosuppressive therapies and better definition of therapeutic strategies used.

THURSDAY MORNING - ORAL ABSTRACTS: Molecular and Cellular Pathology of the Kidney Allograft: PDF Only

Background. Hypertension is a risk factor for the two leading causes of death in renal transplant recipients: cardiovascular disease (CVD) and graft failure. Despite this, the optimum medication for post-transplant hypertension is unclear. Methods. The Study on Evaluation of Candesartan Cilexetil after Renal Transplantation (SECRET) was an international multicentre, double-blind, randomized investigation of the angiotensin II type 1 receptor blocker (ARB) candesartan cilexetil versus placebo in renal allograft recipients originally designed to study 700 patients for 3 years. The candesartan dose was escalated from 4 to 16 mg daily, followed by addition of co-medication, if needed, with the aim of achieving a diastolic blood pressure (BP) <85 mmHg. The primary efficacy variable was a composite of all-cause mortality, cardiovascular morbidity and graft failure. Results. SECRET was stopped prematurely as the primary event rate was much lower than expected. At that point, 502 patients were enrolled; 255 received candesartan and 247 placebo. Thirteen primary events had occurred in each group. Control of both systolic and diastolic BP was better in the candesartan group. Urinary protein excretion and protein/creatinine ratio decreased on candesartan but increased on placebo. Serum creatinine and potassium were increased in candesartan patients, but these changes were generally small. Conclusions. SECRET provides insights into the design and conduct of studies in this area and evidence for the utility of candesartan, which showed good safety and tolerability, improved BP control and decreased proteinuria in renal transplant recipients.

Large analyses have demonstrated that pre-emptive kidney transplantation (PKT) leads to significant improvements in patient and graft survival when compared with transplantation performed after a period of dialysis. We analysed 1585 patients who received a first renal transplantation from a deceased donor between 2000 and 2004 in four French transplantation centres. The objective was to compare the characteristics of the deceased donor transplantations with or without previous dialysis and to evaluate the impact of PKT and length of dialysis on patient and graft outcomes. Mean age of recipients was 48.1 ± 13.4 years, 62% were men, and 118 (7.4%) of them received a pre-emptive transplantation. For the nonpre-emptive patients, mean time on pretransplant dialysis was 3.4 ± 3.2 years. Pretransplant factors independently related to pre-emptive transplantation were year of transplantation, centre and recipients characteristics: gender, diabetes history, blood group and donor age. Patients with pretransplant dialysis were three times more likely to have delayed graft function than pre-emptive transplant patients, and were 10 times more likely to receive post-transplant dialysis. Five-year patient survival was 92.9%. Five-year graft survival was 89.0%. Neither pre-emptive transplantation nor time on dialysis was significantly associated with patient and/or graft survival.

Key words: indinavir; HIV protease inhibitor; renal started: 4 g per day sulphadiazine, 50 mg per day pyrimethamine, and 25 mg folinic acid three times failure; nephrotoxicity; crystals; AIDS weekly.At day 0 of this antitoxoplasmic treatment, serum creatinine was 0.9 mg/dl (80 mmol/l ) and proteinuria was negative.No concomitant alkaline supple-

The aim of this study was to compare the renal tolerance of cisplatin and carboplatin in euvolemic and dehydrated rats. A total of 79 euvolemic or dehydrated male rats were randomly assigned to receive cisplatin (5 mg/kg body weight, i.p.), carboplatin (40 mg/kg body weight, i.p.) or vehicle. Body weight, serum creatinine, creatinine clearance, fractional excretion of sodium and urinary NAG excretion were recorded on days 1 and 5. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and renal histology were determined on day 5. In the euvolemic and dehydrated control and carboplatin groups we observed no change in serum electrolytes, serum creatinine, creatinine clearance, GFR and ERPF. In the euvolemic and dehydrated control groups we observed no change in urinary NAG excretion. Carboplatin induced a slight but significant increase in urinary NAG excretion. In dehydrated rats carboplatin induced a significantly higher increase in urinary NAG excretion than in euvolemic rats. Cisplatin induced a marked and significant decrease in GFR and ERPF, and a significant increase in NAG. Dehydration markedly potentiated cisplatin nephrotoxicity. Euvolemic rats treated with cisplatin exhibited, slight renal lesions with a mean score which was similar to the control group. The most extensive lesions were observed in euvolemic and dehydrated cisplatin treated rats with tubular necrosis in the outer stripe of the medulla. The mean total nephrotoxicity score of dehydrated cisplatin treated rats was significantly higher than that of the euvolemic cisplatin treated rats. The results in this study indicate that carboplatin is a promising second generation platinum analog with respect to decreased renal toxicity as compared with cisplatin and may be particularly useful in patients with risk factors such as chronic renal failure or in patients who cannot bear hyperhydration.

Resistant hypertension and paroxystic hemodynamic changes are common features in patients on regular hemodialysis. We describe a hemodialyzed patient who developed malignant hypertension. The finding of elevated plasma catecholamines suggested the diagnosis of pheochromocytoma, which was confirmed by surgical removal of the tumor.

Foscarnet is a pyrophosphate analogue that has been successfully used in severe cytomegalovirus (CMV) infections. Little is known of the incidence and mechanisms of foscarnet-induced nephrotoxicity as most data comes from recipients of renal allografts or from patients with severe underlying disease or with other nephrotoxic drugs. We have retrospectively analyzed the evolution of renal function after 56 courses of foscarnet. In addition, we have prospectively studied the protective effects of hydration on foscarnet nephrotoxicity (2.5 liters of saline/day during the night before the foscarnet therapy and throughout the course of treatment). Foscarnet-induced acute renal failure was defined as a rise in serum creatinine of at least 25% from the basal value. An increase in serum creatinine occurred in 37 cases out of the 56 courses of foscarnet (66%). The mean serum creatinine prior to foscarnet was 80.5 +/- 3.3 mumol/l and the mean increase was 190 +/- 28.3 mumol/l (range 80-1,000). Peak serum creatinine was higher than 200 and 300 mumol/l in 16 and 13 patients, respectively. Kidney obtained at autopsy from a 30-year-old male with AIDS, CMV pneumonitis and acute renal failure secondary to foscarnet administration showed an extensive tubular necrosis. In the group which was prospectively hydrated only 1 patient had an acute renal failure. The mean serum creatinine at the peak (96 +/- 4 mumol/l) and at the end of the treatment (83 +/- 4 mumol/l) was significantly lower (p less than 0.05) than in non hydrated patients. In conclusion, foscarnet is a highly nephrotoxic drug which induces acute tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The syndrome of inappropriate secretion of antidi­ uretic hormone (SIADH) is characterized by hypona­ tremia primarily due to water retention and with natriuresis closely parallel to sodium intake [1]. The mecha­ nisms that govern the natriuresis in that condition have not been clearly delineated. To determine whether hu­ moral factors have a role in the natriuresis we measured plasma atrial natriuretic factor in a patient with hypo­ natremia due to SIADH that was associated with head trauma. The patient, a 51-year-old man, was investigated in the basal state under water restriction and after water loading. In the basal state the serum electrolyte levels (expressed in millimoles per liter) were as follows: so­ dium 123, potassium 4.9. and chloride 84. The plasma urea level was 2.7 mmol/1 and the creatinine clearance was 123 ml/min. Plasma and urine osmolality measured simultaneously were 250 and 754 mosm/kg, respective­ ly. The urinary sodium concentration was 130 mmol/1 and the fractional excretion of sodium was 0.51 %. Thyroid, pituitary and adrenal functions were nor­ mal. Plasma renin activity (0.6 ng/ml/h) was below the normal range. Catecholamines and plasma aldosterone level (33 pg/ml) were in the normal range. The plasma levels of AVP and of ANF were elevated at 5.4 and 60.5 pg/ml, respectively. Under water restriction the se­ rum sodium level and plasma osmolality increased to 139 and 280, respectively. Weight decreased from 55 to 52 kg. Plasma ANF decreased to 45.5 pg/ml. Plasma aldosterone level, PRA and plasma cathecholamine lev­ els remained unchanged. The response to an acute oral water load (20 ml/kg body weight in 30 min) was clearly abnormal: only 20% of the oral load was excreted in 4 h (normal excretion, 80%). The minimal urinary osmolality was 878 mosm/kg (normal value. < 100 mosm/kg); thus, free water clear­ ance remained negative throughout the test. The plasma osmolality decreased to 267 mosm/kg, a value below the