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Background: Serum cystatin C (Scyst) has been suggested as an alternative index of glomerular filtration rate (GFR) and could be useful in renal transplant patients., Methods: In a 60-subject cohort (40 +/- 12 years old), we compared the simultaneous measurements of Scyst, serum creatinine (Screat), creatinine clearance (Ccreat), Cockcroft and Gault's estimated clearance (Ccg) and GFR measured using inulin clearance (Cin). Receiver operating characteristic (ROC) analysis was performed using two Cin cut-off (60 and 90 mL/min/1.73 m2)., Results: A significant correlation was found among Cin on one hand and 1/Scyst, Ccreat, 1/Screat and Ccg on the other hand. Best fits (sensitivity/specificity) at 90 mL/min/1.73 m2 were 1.18 mg/L (0.72/0.80) for Scyst, 1.32 mg/dL (0.67/0.90) for Screat, 77 mL/min (0.80/0.70) for Ccg and 104 mL/min (0.88/0.80) for Ccreat. The areas under the ROC curves were not significantly different., Conclusions: This study provides cut-off values for Screat and Ccg for detection of renal failure in renal transplant patients. However, the results also suggest that Scyst is not a more sensitive marker than Screat or Ccg for detecting renal failure in renal transplant patients.

In the Drosophila melanogaster complex, females D. melanogaster mate relatively easily with males Drosophila simulans but the reciprocal cross is rare. The species sexual isolation is mainly based on chemical and acoustic signal exchanges between partners. The male side of this communication is investigated in this paper in order to understand the asymmetry. In D. melanogaster the acoustic signature is highly significant, and is synergistically reinforced by the chemical signal. In D. simulans the importance of the two signaling channels seems to be reversed. This could explain why D. simulans males produce less precise interpulse interval (IPI) mean value in the courtship song, which can readily overlap those of D. melanogaster. As the males of the two species use the same chemical key, D. simulans males could be recognized by D. melanogaster females as a conspecific.

There are various modes of presentation of glomerular diseases. Patients may present with edema or hypertension, isolated proteinuria, asymptomatic microhematuria or recurrent gross hematuria, nephrotic syndrome, acute nephritic syndrome, or rapidly progressive renal insufficiency. We focus on the anti-proteinuric treatment, on the complications and symptomatic management of the nephrotic syndrome, and on the early diagnosis of rapidly progressive glomerulonephritis.

Background: Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5-10 mg/day) and the beta-adrenoceptor antagonist tertatolol (5-10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension., Methods: Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n = 24) or tertatolol (n = 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure., Results: Amlodipine significantly decreased serum uric acid levels from 483 +/- 99 to 431 +/- 110 microM/l (P < 0.001), while tertatolol significantly increased uric acid from 450 +/- 98 to 476 +/-84 microM/l (P = 0.006). Amlodipine also significantly increased glomerular filtration rate (P = 0.0048) and the clearance rate of uric acid (P = 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P = 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated., Conclusions: Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients.

Background: Non-Hodgkin's lymphoma is the second most frequent neoplasia following solid-organ transplantation. The objective of this study is to describe the clinical, histologic, and radiologic features of primary posttransplantation brain lymphomas (PTBL) in addition to their outcome., Methods: Twenty-five kidney transplant patients with histologically proven PTBL from 11 French centers were retrospectively investigated., Results: Immunosuppressive regimen included induction with antithymocyte globulins (ATG) in 20 patients. Median overall delay between transplantation and lymphoma was 18 months (4-264). Six of 10 patients with late posttransplantation brain lymphomas (PTBL) occurrence (>3 years) had been recently switched from azathioprine to mycophenolate mofetil (median switch lymphoma delay 14 months). Cerebral computed tomography (CT) scans and magnetic resonance imaging (MRI) revealed multifocal lesions (n=18), with a ring contrast enhancement (n=20) similar to cerebral abscesses, as observed in HIV-related brain lymphomas. Histology showed large B-cell non-Hodgkin's lymphoma in 87.5% of cases; Epstein-Barr virus (EBV) was detected in 95%. After lymphoma diagnosis, immunosuppressive treatment was reduced in all patients, and all but one received complementary treatment by surgery (n=2), anti-CD21 antibodies (n=2), chemotherapy including high-dose intravenous methotrexate (n=7), encephalic radiotherapy (n=5), or chemotherapy plus radiotherapy (n=8). Median overall survival was 26 months. Patients with a radiotherapy-based regimen seemed to have a longer survival (36 vs. 7 months, P<0.005)., Conclusions: Our study showed that PTBL are EBV-induced large B-cell lymphomas, which mimic cerebral abscesses on imaging and whose occurrence may be influenced by immunosuppression modifications. Treatment by radiotherapy is associated with better survival.

Background: Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients., Methods: In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n=186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy., Results: Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P<0.05)., Conclusions: Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups. Significantly more hematologic and infectious adverse events were observed in both ATG induction groups.

Background: Among hereditary fevers characterized by recurrent attacks of fever and organ localized inflammation, familial Mediterranean fever (FMF), and tumour necrosis factor receptor superfamily 1A (TNFRSF1A) receptor associated periodic syndrome (TRAPS) are diseases with identified genes that can be associated with renal amyloidosis of the AA type. In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks., Methods: Mutations of the MEFV and TNFRSF1A genes, responsible respectively for FMF and TRAPS, were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing., Results: Twenty-seven patients (71%) carried mutations in MEFV (22 patients with two mutations, two patients with a single mutation) or TNFRSF1A genes (three patients). Patients with MEFV mutations belonged to the classical at-risk ethnic group for FMF: Sephardic Jews, Turks, Armenians, and Arabs from the Maghreb. The main genotype encountered was M694V/M694V (19/22), one Turkish patient was M680I/M680I, and two Arab patients from the Maghreb were M694I/M694I. We found three Caucasian patients with the C55S, C70Y, R92Q mutations in the TNFRSF1A gene., Conclusions: In this series we observed that FMF is the main cause of AA amyloidosis in Sephardic Jews and Turks. MEFV and TNFRSF1A mutations were found in only 6 of 14 Arab patients from the Maghreb. We found three families (one Caucasian and two from Maghreb) with AA amyloidosis without MEFV or TNFRSF1A mutations, suggesting that other genetic cause(s) exist(s). The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.

Acute graft rejection remains a major problem in renal transplant recipients, and there is no consensus on the optimal immunosuppressive strategy. Immunoprophylaxis with Thymoglobulin or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation. This open, randomized, multicenter study investigated the efficacy and tolerability of basiliximab (20mg day 0-day 4) plus early cyclosporine from day 0 (n = 50) compared with Thymoglobulin plus delayed cyclosporine (n = 50) in adult kidney transplant patients. In addition, all patients received steroids and mycophenolate mofetil (MMF) at standard doses from day 0. Patient and graft survival rates at 12 months were 98 and 94% in the basiliximab group, respectively, compared with 100 and 96% in the Thymoglobulin' group. The incidences of biopsy-confirmed acute rejection (8.0% in each group) and treatment failure (14% in the basiliximab group vs. 8% in the Thymoglobulin group) were comparable in the two groups. There was a non-significant tendency to more dialysis (14 vs. 6%), and fewer cytomegalovirus (CMV) infections (p = 0.005) in the basiliximab group, but the percentage of clinical CMV was not different between the two groups (6 vs. 12%). Both strategies give excellent results, despite the differences in patterns, in nonhyperimmunized patients receiving their first cadaveric renal allograft.

The courtship song of Drosophila is known to be an important signal involved in sex and species recognition. It consists of pulse song and sine song, which have been studied in a quantitative way with different parameters. For the first time the setting of both components of the acoustic signaling is described and compared for males belonging to the sibling species D. melanogaster and D. simulans. At early ages, these two species share similar interpulse interval values but maturation establishes the species specificity of this character. For D. melanogaster the variations of several acoustic parameters take place in two successive periods, whereas for D. simulans the majority of the acoustic features does not change much with age. In D. melanogaster, copulation success seems to be linked to the maturation of the acoustic performance, which is not the case for D. simulans.

Purpose: As patients with chronic renal failure are frequently referred late to nephrologists, we decided to quantify the magnitude of late referral and its consequences., Methods: We studied retrospectively an inception cohort of 62 patients starting dialysis (either hemodialysis or continuous ambulatory peritoneal dialysis) during 1993 with a 4-year follow-up., Results: The mean delay between either first symptoms of renal disease, or first evidence of renal failure and nephrologist referral was 10 years and 3 years 56 days, respectively. About 47% of the patients were referred less than 6 months before starting dialysis, and 27.5% less than 1 month. Blood pressure levels were higher in patients referred less than 6, 3 and 1 month (P < 0.05), as was creatinine concentration in patients referred less than 1 month (P < 0.05). In contrast, plasma calcium was lower for referral less than 6 months (P < 0.05) and 3 months (P < 0.005), as was bicarbonate concentration for referral less than 3 and 1 month (P < 0.05). Initial hospitalisation stay was prolonged (x1.5) for late referral less than 3 months (56.4 +/- 39 days vs 35.9 +/- 33.6 days, P < 0.05) as was 6 months hospitalisation length for referral less than 3 months (x1.6) (52.9 +/- 40.6 days vs 33.2 +/- 28.7 days, P < 0.05) and less than 1 month (x1.8) (61 +/- 45 days vs 33.9 +/- 28.7 days, P < 0.05) and < 1 month (x1.8) (61 +/- 45 days vs 33.9 +/- 28.7 days, P < 0.05). Only 44.1% of patients started hemodialysis with a functioning arteriovenous fistula, and patients requiring temporary access had a 4.4-fold longer initial (60.1 +/- 41.7 days vs 13.6 +/- 11.6 days, P < 0.005) and 6-month (59.6 +/- 39 days vs 13.6 (9.1, P < 0.005) hospitalisation stay. The four-year mortality rate was unaffected by the delayed referral but strongly and independently predicted by age, diabetes and hypoalbuminemia., Conclusion: Early nephrologic referral and timely initiated dialysis decrease morbidity at the start of dialysis and both hospitalisation length and costs.

Patients with chronic renal diseases (CRD) have a high prevalence of lipid abnormalities. Elevated levels of total and low density lipoprotein cholesterol are associated with cardiovascular diseases in patients with CRD. The 3-hydroxy-methylglutaryl co-enzyme A reductase inhibitors appear to be the most effective agents to lower LDL cholesterol in this category of patients and are generally safe if used with caution. They should be drugs of first choice in CRD but dosage reduction and close monitoring may be required to avoid side effects in case of renal failure or in combination with calcineurin inhibitors. Moreover recent studies suggest that in addition to lowering plasma LDL cholesterol, theses compounds may modify several factors implicated in the development of atherosclerosis and the progression of chronic renal failure. Such newly defined effects may contribute to extend the use of statins in the management of renal patients.

Aim: Serum cystatin C (SCyst) has been proposed as a novel indicator of GFR., Patients and Methods: We compared SCyst, serum creatinine (SCreat) and Cockcroft and Gault's estimated clearance (CCG) using inulin clearance (Cin) as gold standard. 140 subjects (161 samples; aged 39 +/- 14; male/female: 79/82) underwent simultaneous measurements., Results: A highly significant correlation r = 0.70, 0.74, 0.77 (p < 0.0001) was found between 1/SCyst, 1/SCreat, C(CG), respectively, and Cin. Receiver-operating characteristic (ROC) analysis was performed on SCyst, SCreat and C(CG) using a Cin cut-off of 90 ml/min/1.73 m2. Best fit for SCyst was 0.90 mg/l with a sensitivity of 75% and a specificity of 92%. The area under the ROC curve was not significantly greater for SCreat or C(CG) than for SCyst (p = 0.91,0.13, respectively). When relationship between Cin and SCyst was plotted, experimental data deviated from the theoretical model, suggesting that cystatin C may not be solely filtered. Additional patients were selected in our database on the basis of discordant SCreat/GFR values: false negative (n = 46 samples, 31 patients) and false positive (n = 16 samples, 9 patients). In this highly selected subgroup, 38% of the SCreat false positive had normal SCyst values and 48% of the false negative SCreat had abnormally elevated SCyst., Conclusion: This study suggests that SCyst is not more sensitive than SCreat or C(CG) for detecting renal failure, however, SCyst could be proposed as a confirmatory test for patients with elevated SCreat.

Despite multiple evidence-based data that diabetic nephropathy is largely preventable and its progression slowed by currently available interventions diabetic patients are often undertreated, especially for the lowering of blood pressure. Recent studies, (HOT Syst-Eur, SHEP, UKPDS, CAPPP, ABCD, HOPE) have confirmed the efficiency of intensively treated blood pressure in reducing morbidity-mortality in this group of patients at high risk. Low blood pressure targets are mandatory, but may not be that easy to achieve, especially in the presence of renal failure. Early prescription of a combination of antihypertensive drugs is often neccessary. Thus, the clinical question relates to the best combination of drugs. Most studies in hypertensive diabetic patients have dealt with 3 classes of antihypertensives drugs: diuretics, beta-blockers and ACE-inhibitors. Diuretics are one of the most efficient hypotensive drugs available for treatment of hypertension in diabetic patients. Their use must be encouraged early in the stepped approach since diabetes is usually associated with mid-volume expansion due to hyperinsulinism and hyperadrenergic state. In spite of the proven benefit of beta-blockers in diabetic patients, these drugs are largely underused. The indications for selective beta-blockers should probably be broadened for most diabetic patients in primary prevention. Beta-blockers are essential in secondary prevention for patients with coronary artery disease and hypertension. ACE-inhibitors are now more and more widely prescribed in diabetic patients at all stages of hypertension and nephropathy, but paradoxally their use has not been validated in Type 2 diabetic nephropathy. When the desired blood pressure target is obtained, cardiovascular outcome and probably also progression of diabetic nephropathy are significantly improved independently of a specific drug. Early combination therapy, including ACE-inhibitors, diuretics and beta-blockers, should be promptly proposed to all hypertensive diabetic patients to achieve low blood pressure and prevent high cardiovascular burden and progression of nephropathy.

Background: Colloid osmotic pressure (COP) plays a major role in transcapillary fluid shift, including in the glomerular capillary. However, COP is generally estimated by quadratic equations derived from total plasma protein and/or albumin concentrations. The aim of this study was to assess the accuracy of such equations, and to determine the potential role of liver-derived non-albumin proteins in the maintenance of COP, especially in patients presenting a nephrotic syndrome., Methods: COP was directly assessed with an osmometer in 170 patients (347 samples), and the results compared with calculated COP, using 4 previously published formulas [Brenner 1972, Canaan-Kühl 1993, Landis-Pappenheimer 1963, Navar 1977]., Results: The 4 calculated COP values were strongly correlated with measured COP (range r = 0.88 - 0.96). However, in absolute terms, measured COP differed significantly from each of the 4 calculated mean values of COP (p < 0.001). Fibrinogen exerted per se a weak oncotic effect as measured in vitro. However, fibrinogen was highly related to albumin and presumably reflected the oncotic effect of other liver-derived non-albumin proteins. Inclusion of albumin and fibrinogen in a linear model provided an excellent fit for predicted COP with a highly significant correlation (r = 0.96, p < 0.001) over a wide range of COP values. The predicted equation was: COP(mmHg) = 6.89 x (albumin + fibrinogen) (g/dl) - 5.68., Conclusion: None of the 4 most commonly used formulas correctly predicted COP, and direct measurement of COP is still preferable for research studies. The introduction of fibrinogen into the formula estimating COP leads to higher accuracy, and therefore represents a more convenient model for routine evaluation.

New immunosuppressive therapies are currently being developed in renal transplantation and their relative risk in terms of posttransplant lymphoproliferative disorders (PTLD) must be carefully evaluated. For this purpose, a French registry of PTLD occurring after renal transplantation was set up. Among 10,000 patients presently followed up in 30 French renal transplantation centers, we prospectively identified 53 new PTLD (0.5%) since January 1998. Patients (34 male, 19 female) ranged from 3 to 72 years (mean age: 46 years), and the median time between grafting and diagnosis of PTLD was 63 months (2 months to 14 years). Ninety percent of recipients were Epstein-Barr virus (EBV) positive before transplantation. Most patients received a quadruple sequential therapy with polyclonal anti-lymphocyte globulin. Sites involved in PTLD were isolated lymph nodes in 13 cases, stomach or bowel in 10 cases, allograft in 14 cases, central nervous system in 6 cases, oropharynx in 4 cases, and skin or mucosa in 4 cases. Only three PTLD expressed markers of T lineage. Out of 40 studied tumors, 31 (78%) were EBV positive. Tumors were classified as polymorph in 26 cases and monomorph in 23 cases. Genotype studies in 18 PTLD showed a monoclonal pattern in 13 cases. In most patients, treatment consisted of reduction of immune suppression, 21 patients were given additional anti-viral therapy, 13 patients had anti-CD20, 23 patients underwent chemotherapy, and 4 patients were given cerebral radiotherapy. Five patients underwent transplantectomy. Sixteen patients (30%) died within the 1st year and 7 patients returned to dialysis (13%). The outcome of patients with PTLD remains poor, and the optimal approach to therapy is largely unknown. This ongoing registry is not only a national observatory but also a task force designed to improve the treatment strategy of PTLD.

Background: Haemodialysis patients exhibit an excessive burden of atherothrombotic disease, which is not explained adequately by traditional risk factors. Hyperhomocyst(e)inaemia, a consistent finding in uraemic patients, is now widely recognized as an independent risk factor for vascular disease. The aim of this study was to examine the hypothesis that hyperhomocyst(e)inaemia is associated with cardiovascular complications in dialysed patients., Methods: In a cohort of 63 stable chronic haemodialysis patients, we examined the causal relationship between hyperhomocyst(e)inaemia and vascular endothelial and haemostatic function. All their markers were determined before and after an 8-week course of a 10 mg per day oral folate supplementation, a manoeuvre known to decrease hyperhomocyst(e)inaemia in uraemic patients., Results: History of at least one cardiovascular atherothrombotic event was present in 47.6% of the haemodialysed patients, and radiographic evidence of vascular calcifications in 70%. Hyperhomocyst(e)inaemia was found in all patients, averaging 3.5-fold the upper limit of normal values (P<0.001), despite the lack of clinical and biological evidence of malnutrition. Fibrinogen, von Willebrand factor and plasminogen activator inhibitor type 1, but not endothelin 1, were significantly higher in haemodialysis patients than in controls. After adjustment for all variables, past history of cardiovascular events was independently associated with higher levels of homocyst(e)inaemia only (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.12; P<0.026). The presence of aortic calcifications was independently and significantly associated with age (OR 1.37; 95% CI 1.07-1.75; P<0.025), homocyst(e)inaemia (OR 1.14; 95% CI 1.02-1.27; P<0.05) and fibrinogen concentration only (OR 9.74; 95% CI 1.25-75.2; P<0.05). None of the endothelial haemostatic factors was, however, related to homocyst(e)ine levels. Mid-term folate supplementation decreased plasma homocyst(e)ine levels significantly without achieving normal values. No significant change of endothelial-haemostatic markers was observed, however, despite the drop in plasma homocyst(e)ine., Conclusions: Hyperhomocyst(e)inaemia is associated with increased cardiovascular risk in haemodialysis patients. Folate supplementation was partially effective in lowering hyperhomocyst(e)inaemia, but its usefulness in terms of reduction in cardiovascular morbidity and mortality remains to be determined in prospective trials.

The objective of this study was to further characterize the clinical and immunopathologic features of heavy chain deposition disease (HCDD), a recently described entity. Four patients were diagnosed as having HCDD on a kidney biopsy. All presented with nodular glomerulosclerosis with deposition of gamma1 heavy chains lacking CH1 epitopes, but without light chains. Two different patterns were observed in the serum. First, patients 1 and 2 had a circulating monoclonal IgGlambda containing a short gamma1 heavy chain lacking CH1 epitopes, with an apparent molecular weight of 40 kD consistent with a complete CH1 deletion. Biosynthetic experiments also showed that the deleted heavy chain was produced in excess compared with light chains, and was secreted in vitro together with half Ig molecules, although these abnormal components were not detected by Western blot analysis of whole serum. Second, patients 3 and 4 had a circulating monoclonal IgG1lambda with an apparently normal, nondeleted heavy chain subunit, but serum fractionation followed by immunoblotting revealed an isolated monoclonal gamma1 chain lacking CH1 epitopes. These data strongly suggest that renal deposition of a CH1-deleted heavy chain circulating in low amounts in the serum as a free unassembled subunit is a major feature of HCDD. The CH1 deletion is most likely responsible for the premature secretion in blood of the heavy chain by a clone of plasma cells.

The AIDS pandemia in developing countries forces forth the question of women's rights in Africa and underscores their extreme physical and sociocultural vulnerability. Experience gained during a program designed to reduce mother-to-child transmission of HIV in the Ivory Coast highlights the socially imposed and therefore intricate nature of differences between men and women and of the resulting relationships. Defending a woman's right to know her serologic status empowers her in the fight for emancipation but can also make her more fragile by undermining support from medical staff and family environment. To prevent the risk of outcasting, exclusion, and fragilization, gender must be given greater emphasis in planning future programs. Careful consideration must be devoted to the special sociocultural factors that affect women in Africa.

Introduction: The importance of non-insulin-dependent diabetes mellitus (type II diabetes) as a leading cause of end-stage renal disease is now widely recognized. The purpose of this study was to assess life-prognosis and its predictors in a cohort of patients newly entering dialysis., Material and Methods: Eighty-four consecutive type II diabetes patients (40% of all patients) starting dialysis between 01/01/95 and 31/12/96 were studied retrospectively, focusing on clinical data at inception and life-prognosis after a mean follow-up of 211 days. Patients were divided into three groups, according to onset of renal failure: acute 11% (9/84), chronic 61% (51/84) and acutely aggravated chronic renal failure 28% (25/84)., Results: Patients (mean age 67 years) had long-standing diabetes (mean duration approximately 15 years), heavy proteinuria (approximately 3 g/24h) and diabetic retinopathy (67%). The average creatinine clearance (Cockcroft's formula) was 13 ml/min. Cardiovascular diseases were highly prevalent at the start of dialysis: history of myocardial infarction (26%), angina (36%) and acute left ventricular dysfunction (67%). More than 80% of the patients underwent the first session dialysis under emergency conditions, a situation in part related to late referral to the nephrology division (63% for chronic patients). A great majority of the patients were overhydrated when starting dialysis, as evidenced by the average weight loss of 6 kg, during the first month of dialysis, required to reach dry weight. Nearly 64% of the patients presented high blood pressure (> 140/90 mmHg) when starting dialysis despite antihypertensive therapy (mean: 2.3 drugs). The outcome of this type II diabetes population was dramatic: 32% (27/84) died after a mean follow-up of 211 days, mostly from cardiovascular diseases. The rate of recovery of renal function was low in both the acute and the acutely aggravated renal failure group (30% and 24%, respectively). Of note, iatrogenic nephrotoxic agents accounted for renal function impairment in nearly 30% of patients., Conclusion: Our observational study illustrates the high burden of cardiovascular diseases contrasting with sub-optimal cardiovascular therapeutic interventions in type II diabetes patients entering dialysis. Factors aggravating renal failure were mainly iatrogenic, and therefore largely avoidable. Late referral generally implied a poor clinical condition at the start of dialysis.

Early postoperative graft thrombosis remains the second cause of failure in pancreas transplantation. Thus, the aim of this study was to compare retrospectively coagulation and fibrinolysis in type I diabetic recipients of simultaneous kidney pancreas transplants having or not experienced thrombosis of their pancreatic graft. From December 1990 to August 1996, 30 simultaneous kidney pancreas transplants were performed in 30 uremic type I diabetic patients. Acute thrombosis of the pancreatic graft was observed among 6 patients (group A), whereas 24 did not develop thrombosis (group B) although 4 died from other causes. The control groups were composed of kidney transplant (group C) or haemodialysed (group D) non-diabetic patients, type I diabetics with HbA1C < 8% (group E) or > or = 8% (group F) who were not in end-stage renal failure and kidney transplant type I diabetic patients (group G). Beginning at least 6 months after transplantation, we analysed hemostatic factors (fibrinogen, thrombin, and prothrombin times), coagulation inhibitors (proteins C and S), fibrinolysis (plasminogen activator inhibitor) and endothelial cell abnormalities (Von Willebrand factor: VWf). Micro and macrovascular complications were evaluated on a score ranging from 0 to 12. Hemostatic factors, coagulation inhibitors and fibrinolysis were similar in groups A and B whereas VWf differed significantly in group A (3.49 +/- 0.93 IU/ml) as compared to group B (2.04 +/- 0.92 IU/ml) (p < 0.05). VWf was also significantly increased in group A relative to the control groups C, D, E, F, and G. The score of vascular complications was increased in groups A and B and significantly higher in group A (9 +/- 0.81 vs. 6.07 +/- 1.75) (p < 0.01), while a correlation (r = 0.812, p > 0.05) was observed between VWf levels and the severity of vascular complications. These results point out the possible involvement of VWf in the pathogenesis of pancreatic vein thrombosis in kidney-pancreas transplantation.

Post-transplant lymphoproliferative disorders (PTLD) are recognized as a devastating complication of organ transplantation. Their occurrence appears to vary according to the transplanted organ and the type and the level of administered immunosuppressive therapy. In kidney transplants the incidence is estimated between 1 and 2%. PTLD represent a clinically and morphologically heterogeneous group of lymphoid proliferations. They have been closely associated with Epstein-Barr virus (EBV), and the spectrum of manifestations after transplantation range from an infectious mononucleosis-like syndrome to more serious polyclonal or monoclonal lymphoproliferation, the treatment of which is not well defined and, relying on immuno- and chemotherapy. Oncogenicity of EBV is not yet completely understood, but may implicate latent viral gene expression of EBNA or LMP as well as Th2 cytokines. Detection and monitoring of EBV induced lymphoid abnormalities are necessary to start early efficient antiviral treatment. Prophylactic antiviral therapy has to be considered.

1. We have examined the effect of hypoalbuminaemia, a hallmark of nephrotic syndrome, on the albumin-fatty acid equilibrium in the plasma of 11 adult patients with nephrosis compared with 12 healthy subjects and six subjects with normoalbuminaemic hyperlipoproteinaemia. 2. We used a dialysis exchange rate method which allows the evaluation in relative terms of the binding affinity of albumin for plasma fatty acid and the fatty acid availability, tentatively equated with the unbound fatty acid fraction. 3. In nephrotic patients, an increase (P < 0.001) in albumin affinity for fatty acid was seen compared with healthy subjects, which was negatively correlated with albuminaemia (r = -0.69, P < 0.02). No change in fatty acid availability was seen for the group as a whole, but individual values showed a wide scatter, with the highest values in four patients with the highest fatty acid-albumin molar ratios. The increase in albumin affinity for fatty acid was specific to nephrotic syndrome since no such effect was seen in subjects with hyperlipoproteinaemia, who only showed a moderate increase (P < 0.01) in fatty acid availability. 4. The increased albumin affinity for fatty acid in nephrotic syndrome supports the hypothesis that an albumin component with lower affinity for fatty acid might filter out through the diseased glomerular membrane and leave the high-affinity albumin in plasma.

In idiopathic thrombocytopenic purpura, intravenous immunoglobulin therapy is currently a treatment of choice. It is usually effective with little side-effects. Acute renal failure has been recently identified as a potential, though rare, complication of intravenous immunoglobulins. However, the mechanism remains unclear. A 53 year-old-woman with idiopathic thrombocytopenic purpura developed oliguric renal failure after high doses of intravenous immunoglobulins. Her renal function returned to normal after dialysis and plasmapheresis. This rapid normalization suggested that acute renal failure was functional. Since laboratory tests showed an increase in protidemia concomitant to the immunoglobulin therapy, acute renal failure was likely to be related to hyperosmolar renal damage.

We examined the effects of two therapeutic oral (p.o.) doses of cicletanine (50 and 100 mg daily) on renal hemodynamics and segmental tubular handling of sodium. Six normotensive (NT) healthy subjects (group 1) received 50 mg cicletanine, and 12 moderately hypertensive (HT) patients with normal sodium diet and randomly divided into two groups of 6 were treated either with cicletanine 50 mg (group II) or with cicletanine 100 mg (group III). Studies were performed both acutely and after 4 weeks of cicletanine administration. After 28-day treatment, blood pressure (BP) was significantly reduced in HT patients. In NT subjects (group I) and HT patients (groups II and III), acute administration of cicletanine 50 or 100 mg at day 0 did not significantly modify glomerular filtration rate (GFR) or renal blood flow (RBF), but markedly increased fractional excretion of Na (FENa) by 67% in group I and by 62 and 135% in groups II and III, respectively. Fractional distal reabsorption of Na (FDRNa) was significantly reduced in the three groups after cicletanine administration. After 4-weeks treatment, GFR and RBF were not significantly modified. The increase in FeNa and decrease in FDRNa were of the same magnitude as that at day 0. No major changes occurred in hormonal profile [renin, aldosterone, atrial natriuretic factor (ANF)]. Even at low doses, cicletanine has a natriuretic effect in NT and HT subjects. Unchanged fractional reabsorption of lithium and a significant decrease in FDRNa in the three groups suggest that this natriuretic effect occurs at the distal tubule.

Goodpasture's syndrome is a rare pneumorenal syndrome. Although the antigenic target of this auto-immune disorder is now known, its etiology remains debated. We report two cases of Goodpasture's syndrome occurring in similar epidemiologic conditions concerning the moment the disease began, the age and sex of the patients, their place of residence and work and manipulation of chemicals. Thus, a common environmental factor could have been the trigger event of the Goodpasture's syndrome. The epidemiologic features of this disease are reviewed.

Improvement in erythropoiesis following renal transplantation (RT) was assessed in 74 consecutive patients by serial measurements of serum erythropoietin (EPO), hematocrit, absolute reticulocyte count (ARC) and serum creatinine during the first month after RT. The reticulocyte maturity index (RMI) which provides an objective measure of red-cell maturity was assessed in 31 patients by flow cytometry using thiazole orange. In group I (n = 39) with immediate graft function, EPO levels increased rapidly from day 2 and remained elevated at the plateau between two and three times the upper limit of normal during the first 2 months. In group II (n = 29) with delayed graft function, EPO levels increased gradually from day 10 when renal function improved significantly. No particular significant biphasic pattern of secretion was detected in group I or II. In both groups, hematocrit rose to over 35% approximately 3 months after RT. In a third group (n = 6) with immediate postoperative acute blood loss and severe anemia, a hematocrit fall was followed by a steep increase in EPO levels with a negative correlation between hematocrit and EPO levels during the first 4 days. During acute rejection, EPO diminished significantly by more than 50% either on the day of diagnosis or on the following days in 8 patients. RMI increased by 25% over the pretransplantation values by 7 days on average before the ARC rose. Thus the RMI seems to be an early sensitive predictor of erythropoiesis after RT. EPO response after RT depends on graft function, and the early transient increase in EPO observed in patients with acute blood loss may explain the apparent biphasic response previously reported.

Tumor necrosis factor-alpha (TNF alpha) likely plays a role in hemodialysis-associated complications. As TNF alpha is mainly produced by monocytes in response to endotoxins, we studied its production and the presence of circulating endotoxins in patients dialyzed on polyacrylonitrile (PAN) membrane. Spontaneous production of TNF alpha was observed in patients before the dialysis session and increased during the session. Endotoxins were present in serum from patients chronically dialyzed with PAN and increased during hemodialysis session. In addition, intradialytic decrease in CD14 antigen expression on circulating monocytes, which could be caused by endotoxins, was found. The continuous presence of low amounts of circulating endotoxins between sessions may explain the chronic increase in TNF alpha secretion, while high amounts of circulating endotoxins may account for intradialytic oversecretion of TNF alpha and downmodulation of CD14. We suggest that endotoxin-free dialysates should be a prerequisite for the use of high-flux membranes.

Renal morphological and functional changes occur in the elderly. Between the ages of 50 and 80 years the renal mass diminishes by a mean of 20 percent, to the expense of the renal cortex. Glomerular sclerosis results in a gradual fall in the number of functioning glomeruli. Simultaneously, a decrease of about 7 percent in glomerular filtration rate per decade after the age of 40 years and a 10 percent decrease in renal plasma flow per decade, and therefore an increase in filtration fraction, are observed. These haemodynamic abnormalities are accompanied by changes in tubular function, including a delay in renal adjustment to sodium overload, and above all to sodium restriction, together with a decrease in concentrating and, to a lesser extent, diluting capacity. In actual fact, the intensity of glomerular sclerosis varies considerably from one subject to another, and the decrease in glomerular filtration rate is far from being constant. These changes are perhaps not ineluctably associated with aging; they might result from pathological processes that have gone unnoticed.

We retrospectively analyzed clinical presentation, immunopathological data and renal outcome in 13 patients with glomerulonephritis (GN) and chronic lymphocytic leukemia (CLL) or related diffuse well-differentiated lymphocytic lymphoma (WDLL) of B-cell lineage. B-cell proliferation and glomerulopathy were simultaneously diagnosed in seven of the 13 patients. Nephrotic syndrome was observed in nine patients. Serum creatinine was elevated (greater than 120 mumol/liter) in 10 patients and exceeded 400 mumol/liter in three patients. A clear cut relationship between GN and hematologic disease could be established in nine cases: five patients had MPGN caused by type I or type II cryoglobulinemia; two had MPGN or mesangial hypertrophy with circulating and deposited noncryoprecipitating monoclonal IgG K and IgM K, respectively; in the two remaining patients, monotypic IgG K glomerular deposits exhibiting fibrillary organization were observed in association with MGN or MPGN, despite the absence of circulating M-component by immunofixation. The pathophysiologic link between glomerular lesions and B-cell proliferation was further evidenced by effectiveness of specific treatment of the malignancy by chlorambucil. This drug, used in the absence of steroids, induced complete remission of nephrotic syndrome in the five patients to whom it was given. Moreover, in the five patients with creatininemia greater than 200 mumol/liter who received chemotherapy, substantial improvement in renal function was observed. These overall data demonstrate that the occurrence of GN in B-CLL and related lymphoma is not fortuitous, and testify to the paraneoplastic nature of glomerular involvement mediated by deposition and possibly processing of cryoprecipitating or noncryoprecipitating M-components.

Both increased synthesis and decreased catabolism of lipoproteins may account for the severe hyperlipidemia which frequently occurs in patients with the nephrotic syndrome (NS). Nevertheless the complex relation between hyperlipidemia and proteinuria remains unclear and still debated. Increased levels of serum total cholesterol, of low-density lipoprotein and of apolipoprotein B are the most characteristic reported abnormalities placing these patients at high risks for atherosclerotic vascular disease. Moreover recent experiments have suggested that hyperlipidemia may also play a role in the progression of renal disease. Thus the reasons for using hypolipemic treatment are now growing in number and recent trials with lipid lowering medication have been successful without major side effects.

We report a case of visceral leishmaniasis in a 38-year-old renal transplant recipient living in an endemic country. Antimonial derivatives induced a rapid remission. A review of the literature disclosed 8 cases of this association with a fatal fulminant outcome in 5 cases. We suggest that the specific immunosuppression used in renal transplant patients might facilitate the development of a dormant infection and in these patients the misleading presentation may delay the diagnosis. Moreover special caution with treatment of leishmaniasis must be taken in renal transplant because of possible interactions between antimony compounds and ciclosporin metabolites. In renal transplant patients living in endemic countries, visceral leishmaniasis should be kept in mind as a potential cause of unexplained long-standing fever and considered as an opportunistic infection.