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Background: Nephrosclerosis is one of the histopathological consequences of severe or malignant hypertension (MH), some of the pathophysiology of which has been extrapolated from essential polygenetic arterial hypertension. Despite our recent description of unsuspected ciliopathies with MH, causes of MH in young patients with severe renal impairment are poorly understood., Methods: To refine and better describe the MH phenotype, we studied clinical and prognostic factors in young patients receiving a kidney biopsy following their first episode of MH. Patients were identified retrospectively and prospectively from eight centres over a 35-year period (1985-2020). Keywords were used to retrospectively enrol patients irrespective of lesions found on renal biopsy., Results: A total of 114 patients were included, 77 (67%) of whom were men, average age 34 years, 35% Caucasian and 34% African origin. An isolated clinical diagnosis of severe nephrosclerosis was suggested in only 52% of cases, with 24% primary glomerulopathies. Only 7% of patients had normal renal function at diagnosis, 25% required emergency dialysis and 21% were eventually transplanted. Mortality was 1% at the last follow-up. Independent prognostic factors significantly associated with renal prognosis (6-month dialysis) and predictive of end-stage renal disease were serum creatinine on admission {odds ratio [OR] 1.56 [95% confidence interval (CI) 1.34-1.96], P < .001} and renal fibrosis >30% [OR 10.70 (95% CI 1.53-112.03), P = .03]. Astonishingly, the presence of any thrombotic microangiopathy lesion on renal biopsy was an independent, protective factor [OR 0.14 (95% CI 0.02-0.60), P = .01]. The histopathological hallmark of nephrosclerosis was found alone in only 52% of study patients, regardless of ethnicity., Conclusions: This suggests that kidney biopsy might be beneficial in young patients with MH., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Cancer-associated thrombotic microangiopathy (TMA) is a rare disease, with a poor prognosis. The classical treatment is urgent chemotherapy. Few data are available on the efficacy of plasma exchange (PE) and eculizumab in these patients., Methods: Cases of cancer-related TMA treated between January 2008 and December 2019 in 12 French treatment centres were retrospectively analysed, excluding cases associated with chemotherapy and stem cell transplantation. Patients were divided into four groups depending on the treatment received: none, PE therapy alone, chemotherapy, with or without PE therapy, or eculizumab, with or without chemotherapy and PE therapy., Results: The data of 59 patients with cancer-associated TMA were analysed. Twenty of these cases were related to a cancer recurrence. The cancer was metastatic in 90% of cases (53/59). Bone marrow invasion was observed in 20/41 biopsies. Some laboratory results, including disseminated intravascular coagulation high ferritin and C-reactive protein, were suggestive of cancer. None of the 16 patients whose alternative complement pathway was assessed had abnormal levels of protein expression or activity. The median survival time was 27 days. Chemotherapy was significantly associated with improved survival, with a 30-day survival rate of 85% (17/20) among patients who received PE and chemotherapy, versus 20% (3/15) among patients who received PE alone. Patients treated with eculizumab in addition to chemotherapy and PE therapy did not have longer overall survival or higher haematological remission rates than those treated with chemotherapy and PE therapy alone. Renal remission rates were non-significantly higher, and times to remission non-significantly shorter, in the eculizumab group., Conclusions: Nephrologists and oncologists should make themselves aware of cancer diagnoses in patients with TMA and bone marrow biopsies should be performed systematically in these cases. All 59 patients had poor survival outcomes, but patients treated with urgent initiation of chemotherapy survived significantly longer than those who were not., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Acute kidney injury (AKI) is an often neglected but crucial element of clinical nephrology. The aim of the Nephrology and Public Policy Committee (NPPC) of the European Renal Association-European Dialysis and Transplant Association is to promote several key aspects of European nephrology. One of the targets proposed by the NPPC was to advance European nephrology involvement in AKI., Methods: We undertook a literature analysis to define the current position of European nephrology in the field of AKI compared with other regions and to determine how different European countries compare with each other., Results: It appeared that vis-à-vis countries with a comparable socio-economic status (the USA, Australia, New Zealand and Canada), the European contribution was almost 50% less. Within Europe, Central and Eastern Europe and countries with a lower gross domestic product showed lower scientific output. Nephrologists contributed to less than half of the output. There was no trend of a change over the last decade., Conclusions: There is room to improve the contribution of European nephrology in the field of AKI. We propose a model on how to promote clinical collaboration on AKI across Europe and the creation of a pan-European nephrology network of interested units to improve clinical outcomes, increase nephrologist involvement and awareness outside nephrology and stimulate research on AKI in Europe. Accordingly, we also propose a list of research priorities and stress the need for more European funding of AKI research., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas., Methods: As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT)., Results: Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups., Conclusions: These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Among the severe complications of preeclampsia (PE), acute kidney injury (AKI) is problematic if features of thrombotic microangiopathy (TMA) are present. Although a haemolysis enzyme liver low-platelets syndrome is considerably more frequent, it is vital to rule out a flare of atypical haemolytic and uraemic syndrome (aHUS). Our objective was to improve differential diagnosis procedures in post-partum AKI., Methods: A total of 105 cases of post-partum AKI, admitted to nine different regional French intensive care units from 2011 to 2015, were analysed. Analysis included initial and final diagnosis, renal features, haemostasis and TMA parameters, with particular focus on the dynamics of each component within the first days following delivery. A classification and regression tree (CART) was used to construct a diagnostic algorithm., Results: AKI was attributed to severe PE (n = 40), post-partum haemorrhage (n = 33, including 13 renal cortical necrosis) and 'primary' TMA (n = 14, including 10 aHUS and 4 thrombotic thrombocytopenic purpura). Congruence between initial and final diagnosis was low (63%). The dynamics of haemoglobin, haptoglobin and liver enzymes were poorly discriminant. In contrast, the dynamic pattern of platelets was statistically different between primary TMA-related AKI and other groups. CART analysis independently highlighted the usefulness of platelet trajectory in the diagnostic algorithm. Limitations of this study include that only the most severe cases were included in this retrospective study, and the circumstantial complexity is high., Conclusion: Trajectory of platelet count between admission and Day 3 helps to guide therapeutic decisions in cases of TMA-associated post-partum AKI. Our study also strongly suggests that during the post-partum period, there may be a risk of transient, slowly recovering TMA in cases of severe endothelial injury in women without a genetic mutation known to induce aHUS., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Although end-stage renal disease (ESRD) is frequently used as an outcome marker for primary immunoglobulin A nephropathy (IgAN), the clinical course after reaching ESRD is not well documented. This study examined patients' characteristics and survival in ESRD-related biopsy-proven IgAN in France., Methods: French Renal Epidemiology and Information Network Registry data from 2010 to 2014 were used to analyse patients' survival and outcome in incident ESRD patients >16 years of age with biopsy-proven primary IgAN, in comparison with other primary and secondary glomerulonephritis (GN), adult polycystic kidney disease (ADPKD) or diabetes. Multivariable survival analysis was adjusted for age, sex, time on dialysis and comorbidities., Results: Among 17 138 incident dialysis patients with ESRD, IgAN (242.8/10 000 dialysis initiation) represents the most common GN related to ESRD during 2010. IgAN patients were the youngest, and had the fewest comorbidities and the highest use of peritoneal dialysis (PD) (17%). In comparison with the haemodialysis group, hazard ratios for death were not different in the preemptive transplantation group [0.46, 95% confidence interval (CI) 0.17-1.28] and in the PD group (0.77, 95% CI 0.44-1.33). Mortality rates in IgAN patients with preemptive transplantation and in those receiving dialysis waiting for transplantation were 2.9% (95% CI 0.0-5.6) and 6.7% (95% CI 0.9-12.3). Mortality rates of ADPKD patients receiving dialysis waiting for transplantation were higher (18%, 95% CI 3.1-30.6)., Conclusion: IgAN has the best prognosis among primary and secondary GN. IgAN patients receiving dialysis waiting transplantation seem to have a more favourable prognosis than ADPKD patients, who usually comprise the reference population. The underlying reasons for the difference in access treatment modalities should be investigated to improve survival with respect to renal disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: The increased survival of patients with multiple myeloma (MM) raises the question of kidney transplantation (KT) in patients with end-stage renal disease (ESRD)., Methods: We included 13 patients with MM or smoldering myeloma (SMM) and ESRD transplanted between 2007 and 2015, including 7 MM with cast nephropathy, 3 with MM-associated amyloid light chain amyloidosis or light chain deposition disease and 3 SMM and compared them with 65 control-matched kidney-transplanted patients. Nine of the MM patients with KT were also compared with 63 matched MM patients on haemodialysis., Results: Pre-transplantation parameters were comparable, except for the duration of renal replacement therapy (57.8 versus 37.0 months; P = 0.029) in MM versus control patients, respectively. The median follow-up post-KT was 44.4 versus 36.4 months (P = 0.40). The median MM graft and patient survival were 80.1 and 117.2 months, respectively, and were not significantly different from control patients, although mortality tended to be higher in the 10 symptomatic MM patients (P = 0.059). MM patients had significantly more viral and fungal infections and immunosuppressive maintenance therapy modifications while they received lower induction therapy. Two MM patients relapsed and two SMM cases evolved to MM after KT. Three cast nephropathies occurred, two of them leading to ESRD. Moreover, survival of MM with KT increased relative to control haemodialysed patients (P = 0.002)., Conclusions: Selected MM patients may benefit from KT but need careful surveillance in the case of KT complications and MM evolution., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Eculizumab, a terminal complement inhibitor, is approved for atypical haemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA)., Methods: In five parent studies, eculizumab effectively prevented TMA and improved renal and haematologic outcomes in patients with aHUS; therefore, these patients could enrol in this long-term, prospective, observational and multicentre study. The primary endpoint was the TMA manifestation rate off and on eculizumab post-parent study. Post hoc analyses evaluated rates during labelled versus non-labelled dosing regimens, and in those with versus without identified complement abnormalities. Serious targeted treatment-emergent adverse events (TEAEs) were evaluated., Results: Of 87 patients in the current study, 39 and 76 had off- and on-treatment periods, respectively; 17 (44%) with off periods reinitiated eculizumab. TMA manifestation rate per 100 patient-years was 19.9 off and 7.3 on treatment [hazard ratio (HR), 4.7; P = 0.0008]; rates were highest off treatment and lowest during labelled regimens. TMA manifestations with hospitalizations/serious AEs occurred more frequently off versus on treatment. TMA rates were higher among patients with identified complement abnormalities (HR, 4.5; P = 0.0082). Serious targeted TEAEs occurred at similar rates off and on treatment., Conclusions: As expected, patients with aHUS have increased risk of TMA manifestations after discontinuation of eculizumab or in the setting of non-labelled eculizumab dosing. Collectively, results show that maintaining eculizumab treatment minimizes risk of TMA, particularly in patients with identified complement abnormalities. Future studies are needed to further characterize TMA and longer term outcomes on labelled or non-labelled eculizumab regimens and after discontinuation of treatment.

Background: The epithelial response to injury is stereotypical and reminiscent of epithelial-to-mesenchymal transitions (EMTs), such as those observed during embryogenesis and tumour metastasis. In the context of solid organ transplantation, EMT-like features are often acquired by epithelial cells and are predictive of graft fibrosis. Here, we studied the possible involvement of several major transcriptional regulators, including snail1, phospho-Smad 2/3 and zeb1, in EMT induction in human renal grafts., Methods: We used immunohistochemistry to detect the presence of these EMT transcriptional regulators along with that of two validated EMT markers (intra-cytoplasmic translocation of β-catenin, de novo expression of vimentin), in 103 renal graft biopsy samples taken for routine surveillance or for a clinical indication., Results: We observed the nuclear accumulation of snail1 and phospho-smad2/3 in tubular cells displaying EMT. The level of snail1 was significantly correlated with the scores of EMT markers (β-catenin: ρ = 0.94, P < 0.0001; vimentin: ρ = 0.93, P < 0.0001) and with deteriorated graft function and proteinuria at the time of biopsy. Furthermore, intense staining for both snail1 and vimentin in tubular cells (≥10% of tubules) was predictive of graft dysfunction 21 months post-biopsy, independently of the other known risk factor for long-term graft dysfunction. In contrast, in both normal and diseased graft, zeb1 expression was detected exclusively in the endothelial cells of glomeruli and peritubular capillaries., Conclusion: This study suggests that snail1 is closely related to the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts and predictive of graft function loss., (© The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Renal transplantation is the best option for patients with end-stage renal disease (ESRD), but its half-life is limited to a decade. Clinical and histological markers measurable within the first year of transplantation can be used to predict its outcome. These markers are important for selecting kidneys for transplantation, for identifying the main causes of late allograft loss, for therapeutic decisions and as surrogate markers in therapeutic trials. 'Basal state' markers, such as age, glomerular filtration rate and fibrotic lesions, are highly predictive of allograft loss, showing that early and stable pathological mechanisms contribute considerably to this loss. On the other hand, some more dynamic predictors such as treatment, recurrence of the initial disease, inflammation and epithelial phenotypic changes offer clinicians and researchers opportunities to influence the fate of allografts.

Background: Treatment and co-morbidities of human immunodeficiency virus (HIV)-infected individuals have changed dramatically in the last 20 years with a potential impact on renal complications. Our objective was to assess the change in distribution of the glomerular diseases in HIV patients., Methods: We retrospectively analysed demographic, clinical, laboratory and renal histopathological data of 88 HIV-infected patients presenting with a biopsy-proven glomerular disease between 1995 and 2007., Results: In our study including 66% Black patients, HIV-associated nephropathy (HIVAN) was observed in 26 cases, classic focal segmental glomerulosclerosis (FSGS) in 23 cases, immune complex glomerulonephritis in 20 cases and other glomerulopathies in 19 patients. HIVAN decreased over time, while FSGS emerged as the most common cause of glomerular diseases (46.9%) in HIV-infected individuals undergoing kidney biopsy in the last 2004-07 period. Patients with HIVAN were usually Black (97%), with CD4 <200/mL (P = 0.01) and glomerular filtration rate <30 mL/min/1.73 m(2) (P < 0.01). Compared to HIVAN, patients with classic FSGS were less often Black (P < 0.01), have been infected for longer (P = 0.03), were more often co-infected with hepatitis C virus (P = 0.05), showed more often cardiovascular (CV) risk factors (P < 0.01), had less often CD4 <200/mL (P = 0.01), lower HIV viral load (P = 0.01) and tended to be older (P = 0.06)., Conclusions: Classic FSGS associated with metabolic and CV risk factors has overcome HIVAN in HIV-infected patients. Compared with other glomerulopathies, HIVAN remains strongly associated with severe renal failure, Black origin and CD4 lower than 200/mL at presentation.

Genome-wide association studies (GWAS) have become a preferred method to identify new genetic susceptibility loci. This technique aims to understanding the molecular etiology of common diseases, but in many cases, it has led to the identification of loci with no obvious biological relevance. Herein, we show that previously unrecognized sequence homologies have caused single-nucleotide polymorphism (SNP) microarrays to incorrectly associate a phenotype to a given locus when in fact the linkage is to another distant locus. Using genetic differences between male and female subjects as a model to study the effect of one specific genomic region on the whole SNP microarray, we provide strong evidence that the use of standard methods for GWAS can be misleading. We suggest a new systematic quality control step in the biological interpretation of previous and future GWAS.

Background: Acute pulmonary oedema (APO) in patients undergoing chronic dialysis (CD), a common cause of hospital admission in this population, is poorly documented. The objective of this study was to determine the causes, profile, clinical course and outcomes of APO in CD patients admitted in an intensive care unit (ICU)., Methods: Medical charts of all CD patients consecutively admitted for APO in the renal ICU of the Tenon Hospital (Paris, France) between January 2000 and December 2007 were considered. Data collection included patient characteristics, etiologic factors for chronic renal failure and co-morbidities, past history of APO, precipitating factors, clinical evolution and outcomes., Results: Of the 112 files considered, 102 (65% men) were included in the final analysis. Patients were aged 20-88 years and had been dialysed for a median duration of 2 years. Hypertension (36.3%), chronic glomerulonephritis (25.5%) and diabetes mellitus (17.6%) were the main etiologic factors of chronic renal failure; 38.2% had a past history of APO. Acute pulmonary infection (26%), excessive interdialytic weight gain (25%) and inappropriate dry weight prescription (23%) were the leading causes of APO. The duration of hospitalization was <4 days in 60% of participants. Nine deaths (four being of cardiac origin) were recorded. Being referred from another hospital service was the main predictor of death., Conclusions: APO fuelled in part by chest infection, excessive interdialytic weight gain and inappropriate dry weight are important causes of hospitalization in CD patients. Mortality is high among those referred from other services usually in critical conditions.

Kidney involvement with immunoglobulin crystals usually relates to a light chain of the kappa type, in MGUS or smoldering myeloma, frequently causing Fanconi's syndrome with progressive renal insufficiency. We report on a case with severe myeloma featuring lambda light chain-derived crystals and acute kidney injury. Histology showed acute tubular necrosis and tubule obstruction with crystals, which were also abundant inside tubule epithelial cells, macrophages and bone marrow plasma cells. The light chain variable domain had a normal overall primary structure but included 11 somatic mutations, 3 of which likely increased the surface hydrophobicity, as observed in previously reported kappa-type crystals.

Background: Haemolytic uraemic syndrome (HUS) is a rare and severe disease of various aetiologies in adults. The effect of fresh frozen plasma (FFP) infusion in adults suffering from HUS is not well defined. The aim of this retrospective study was to analyse the causes of HUS in adults admitted in a single renal intensive care unit (ICU) and to determine the life and renal prognosis factors, while most patients (78%) received FFP infusion., Methods: We recorded clinical, biological, and histological data of 55 adults admitted in our renal ICU for HUS between 1990 and 1998, 49 of them having had a renal biopsy. By stepwise logistic regression analysis, we examined the parameters that were associated with the in-hospital mortality and renal function at discharge., Results: HUS complicated different diseases in 40 patients (HIV infection n=18, nephropathies n=10, allotransplantation n=7, malignant diseases n=5) and appeared as a primary in 15 patients. Factors influencing the in-hospital mortality were positive HIV serology (odds ratio (OR) >20, P=0.0002) and requirement for haemodialysis (OR >35, P=0.004). A pre-existing nephropathy was a bad prognosis factor for renal function (OR >99, P=0.02), while fever was associated with better renal prognosis (OR=1/10, P=0.033)., Conclusions: HUS in adults remains a severe disease, with a high mortality rate in HIV patients and in those who required haemodialysis. However, as compared with previous studies, we observed an improvement in renal outcome, particularly in patients with primary HUS, suggesting a beneficial effect of FFP infusion, at least in these forms.

Background: Idiopathic hypercalciuria (IH) is frequently associated with nephrolithiasis. As 40% of patients have a positive familial history of IH, an autosomal dominant mode of inheritance has been suggested. Numerous genes have been studied in this regard but none have been found to be linked to IH. Mutation of the calcium-sensing receptor (CaR) has never been studied. Therefore, we conducted a study to detect such mutations., Methods: Seven families with IH and nephrolithiasis were recruited in a prospective study. Forty-two family members underwent 24-h urine calcium measurement. Twenty-five of them with 24-h hypercalciuria also underwent extensive metabolic evaluation. Blood samples were collected in one or two affected family members in each family and exons 2-7 of the CaR gene were sequenced., Results: In the seven families, at least one parent and more than half of the children had hypercalciuria (21/30), consistent with autosomal dominant inheritance. Among the nine affected family members whose CaR gene has been studied, all nine had absorptive hypercalciuria, three also had fasting hypercalciuria, and one had renal phosphorous leak. No mutation of the CaR gene was detected in these seven families. Two previously reported polymorphisms were detected, each of them in five families: A986S and C-to-T change at -60 in intron 5., Conclusion: In these seven families, IH is not related to the CaR gene mutation. Although we cannot exclude that point mutations can be found in other families, familial IH does not seem to be generally associated with CaR mutation.

Background: Acute renal failure syndromes are frequently encountered in patients with human immunodeficiency virus (HIV) infection. Most reported cases of acute renal failure are related to acute tubular necrosis, but many other causes of renal failure have been described in these patients., Methods: The present work is a single-institution retrospective study of 92 HIV-infected patients with acute or rapidly progressing renal failure. In 60 cases, a renal biopsy was performed. For each patient we analysed clinical and pathological data, as well as the short-term prognosis., Results: Ten different causes of acute or rapidly progressing renal failure were documented: (i) haemolytic uraemic syndrome (32 patients); (ii) acute tubular necrosis either of ischaemic-toxic origin (18 patients) or due to rhabdomyolysis (six patients); (iii) obstructive renal failure which was either extrinsic (two patients), drug-induced (13 patients) or secondary to paraprotein precipitation (one patient); (iv) HIV-associated nephropathy (14 patients); (v) acute interstitial nephritis (two patients); (vi) various glomerulonephritis (four patients). In most cases, renal failure was severe (the mean creatinine clearance at entry was 12 ml/min). Most patients had a significant improvement in renal function with only symptomatic treatment. Eighteen per cent of the patients died within 2 months of the diagnosis of renal failure. Renal biopsy seems important for the diagnosis but also for the prognosis, at least in the cases of haemolytic-uraemic syndrome, HIV-associated nephropathy and drug-induced micro-obstructive renal failure., Conclusion: Vascular and glomerular diseases are frequent causes of acute or rapidly progressing renal failure in HIV-infected patients. Renal biopsy appears to be safe and useful for the diagnosis and the prognosis of the renal failure. High mortality rate is only observed in patients with ischaemic/toxic causes of acute renal failure.

Background: In children, haemolytic uraemic syndrome (HUS) is associated with high plasma plasminogen activator inhibitor type 1 (PAI-1), which may contribute to the persistence of renal glomerular and arteriolar thrombi. HUS has been described in HIV-infected patients, but the pathophysiology of HUS in these patients is poorly understood. The aim of the study was to investigate plasma fibrinolytic activity in 18 patients with HIV-associated HUS., Methods: We measured tissue type plasminogen activator (t-PA) and PAI-1 activities in the plasma of 18 HIV-infected patients with biopsy-proven HUS (HIV+/HUS+) and 48 HIV-infected patients without HUS (HIV+/HUS-)., Results: Patients with HUS had a significantly higher serum creatinine, a lower platelet count and an increased incidence of cytomegalovirus (CMV) infection (72% of patients HIV+/HUS+, vs 25% of patients HIV+/HUS-). Unexpectedly, plasma PAI-1 activity was similar in both groups. However, t-PA activity was significantly higher in HUS cases (11.5 vs 4.5 U/ml, P=0.001). Patients with CMV infection, with or without HUS, had significantly increased t-PA level (P=0.01). Multivariate analysis identified high t-PA (RR=9.21) and CMV infection (RR=3.36) as risk factors for HUS., Conclusion: This study provides evidence that HIV-infected patients with HUS have high plasma t-PA activity. PAI-1 plasma activity is not significantly increased, as opposed to non-HIV-associated HUS. Thus, in the setting of HIV infection, HUS cannot be attributed to decreased fibrinolytic activity.

Thrombotic microangiopathy (TMA) can occur during the course of human immunodeficiency virus (HIV) infection. Clinical and pathological data for 29 patients with TMA and HIV infection were recorded. In a retrospective case-control study, we analyzed the link between opportunistic infections or drug therapies and TMA. Twenty-five patients (mean CD4+ cell count +/- SD, 71.9 +/- 18.3/mm3) had renal impairment, and four had neurological dysfunction. In one-half the cases, the disease was progressive with isolated fragmentation anemia appearing several months before the clinical symptoms. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001). The case-control study demonstrated a link between TMA and clinical CMV infection (odds ratio, 3.9; 95% confidence interval, 1.1-14). We conclude that TMA is a late complication of HIV infection and can be associated with systemic CMV infection in this setting.

Cytomegalovirus (CMV) infection is the most frequent infectious complication observed in renal-transplant recipients and induces a significant morbidity in these patients due to CMV disease itself and to associated renal dysfunction or opportunistic superinfection. In order to evaluate the effect of gangiclovir prophylaxis we conducted an open-label prospective randomized study of ganciclovir administration in CMV seronegative recipients of a renal allograft from CMV seropositive donors. Ganciclovir (5 mg/kg b.i.d./day for 14 days) was started on day 14 after transplantation. Thirty-two patients were included in this study (15 in the control group, 17 in the ganciclovir group). There was no significant difference between the two groups for age, immunosuppressive regimen, number of rejection, steroid pulses, and OKT3 treatments. Renal and patient outcomes were similar in both groups. The rate of CMV infection and CMV disease were similar in both groups (80% and 73.3% in the control group versus 70.6% and 47.1% in the ganciclovir group; P = NS). Less severe CMV disease was observed in the ganciclovir group compared to controls. The delay between transplantation and CMV infection was significantly longer in the ganciclovir group compared to control group (68.1 +/- 5.1 versus 44.0 +/- 5.2 days, P < 0.005). Twelve group patients (80%) versus nine (53%) of the ganciclovir group required curative treatment with ganciclovir after the diagnosis of CMV infection (NS). All the patients recovered from CMV disease and no significant side effect was observed during ganciclovir administration.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine if endothelin 1 (Et1) receptors are present in human glomeruli, and which glomerular cells possess these receptors, 125I Et1 binding to isolated glomeruli and cultured glomerular mesangial and epithelial cells was studied. The latter were identified as podocytes. We demonstrated that Et1 binds specifically and reversibly to isolated human glomeruli and to cultured glomerular mesangial and epithelial cells. Scatchard analysis of competitive inhibition of 125I Et1 binding gave the following results (m +/- SEM, n = 3): isolated glomeruli, Kd = 4.2 +/- 2.1 x 10(-10) M, Bmax = 8.1 +/- 1.2 x 10(10) sites/mg protein; mesangial cells, Kd = 5.2 +/- 1.5 x 10(-10) M, Bmax = 1.87 +/- 0.49 x 10(4) sites/cell; epithelial cells, Kd = 7.2 +/- 1.5 x 10(-10) M, Bmax = 2.46 +/- 0.15 x 10(4) sites/cell. These receptors seem to be functional, since in both mesangial and epithelial cells Et1 induces a rapid and transient increase in intracellular [Ca2+]i. All these results indicate that Et1 may regulate glomerular filtration rate through an autocrine-paracrine pathway on mesangial cells and on podocytes.

Bone status, calcium and phosphate metabolism were prospectively evaluated in 98 renal transplant recipients with stable renal function. Aseptic necrosis of bone was found in 30 patients, leading to arthroplasty in 12 patients. Plasma parathyroid hormone and nephrogenic cyclic adenosine monophosphate (cAMP) values were greater and the duration of pre-transplant chronic renal failure longer in patients with aseptic necrosis of bone than in those who were not affected. Cumulative oral corticosteroid doses and the number of acute rejection episodes treated by intravenous methylprednisolone pulses were similar in patients with or without aseptic necrosis of bone. Hyperparathyroidism was confirmed histologically in 14 patients, comprising 4 cases of adenoma and 10 of diffuse hyperplasia. Serum parathyroid hormone correlated positively with serum creatinine (r = 0.47; P less than 0.001) and with cumulative corticosteroid dose (r = 0.30; P less than 0.003). This study suggests that hyperparathyroidism is a factor in the pathogenesis of aseptic bone necrosis. The frequency and severity of bone necrosis may be decreased by early detection and treatment of post-transplant hyperparathyroidism.

Rapidly progressive glomerulonephritis frequently leads to death or dialysis. In 21 cases treated by plasma exchange and immunosuppression we observed seven deaths, with 12 others progressing to chronic renal failure within 3 months. Patients who died were older than those who survived (57.5 +/- 17.7 vs 40.5 +/- 16.5 years, mean +/- SD, P = 0.05), but had similar clinical symptoms (hypertension, haematuria, proteinuria, extrarenal signs) and biochemical presentation (initial creatininaemia). They required the same degree of haemodialysis, of plasma exchanges and of bolus methylprednisolone. The causes of death were infection (three cases), cardiac arrhythmia (two cases) and gastrointestinal bleeding (two cases). Among the 14 remaining patients, only two recovered normal renal function. Twelve had chronic renal failure, six of them requiring chronic dialysis or transplantation. Severe renal failure at entry and anuria were more frequently observed in patients whose renal function did not improve during treatment. Plasma exchange and steroid bolus infusions also seemed to have a beneficial effect on renal function.