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Fadi Fakhouri

Publications and source records attributed to Fadi Fakhouri.

9 recordsLinked to original sources
PubMed2003

The expanding spectrum of renal diseases associated with antiphospholipid syndrome.

BACKGROUND: The association of thrombotic events and/or pregnancy complications with circulating antiphospholipid antibodies defines antiphospholipid syndrome (APS). In previous reports, renal involvement in APS consisted mainly of thrombotic vascular complications involving large vessels or intrarenal small-sized vessels (APS nephropathy). We report 9 cases of glomerulonephritis associated with APS. These cases are characterized by predominant pathological features distinct from vascular APS nephropathy. METHODS: We reviewed consecutive renal biopsies examined in 2 French university hospitals between 1980 and 2002 and identified renal biopsies performed in patients with primary APS. RESULTS: We identified 29 biopsies performed in patients with APS. Twenty biopsies showed characteristic features of APS nephropathy. In 9 cases, predominant pathological features distinct from vascular APS nephropathy were noted: membranous nephropathy (3 cases), minimal change disease/focal segmental glomerulosclerosis (3 cases), mesangial C3 nephropathy (2 cases), and pauci-immune crescentic glomerulonephritis (1 case). In 7 cases, the presentation of renal symptoms was subacute or chronic. Two patients experienced episodes of acute renal failure. At referral, median creatinine clearance was 50 mL/min (0.83 mL/s) (range, 18 to 117 mL/min [0.30 to 1.95 mL/s]). Proteinuria was noted in all cases (range, 1.5 to 15 g/d), with nephrotic syndrome in 4 cases. Lupus anticoagulant was present in all cases, and anticardiolipin antibodies, in 8 cases. Anti-DNA antibodies repeatedly were negative in all cases. Treatment consisted of antihypertensive therapy (6 cases), anticoagulant drugs (5 cases), steroids (4 cases), and antiplatelet drugs (3 cases). At last follow-up, renal function remained stable in 7 patients. Of 2 patients presenting with acute renal failure, 1 patient recovered normal renal function, whereas the other patient progressed to end-stage renal failure. CONCLUSION: The cases reported here represent a new aspect of the expanding spectrum of renal diseases encountered in association with APS.

Adrenal Cortex Hormones↗
PubMed2003

Lithium-induced nephropathy: Rate of progression and prognostic factors.

BACKGROUND: Long-term lithium administration in humans may lead to chronic tubulointerstitial nephritis, which develops very slowly. Its progression to end-stage renal disease (ESRD) has been rarely reported. The aim of this study is to document the rate of progression of lithium-induced nephropathy and its prognostic factors, and to provide an estimation of the percentage of lithium-induced ESRD in France. METHODS: Two groups have been studied: 54 patients with lithium-induced renal failure, nine of whom underwent renal biopsy; and 20 patients who were referred for systematic renal biopsy, 14 of whom were subsequently followed up. In addition, a survey of lithium-induced ESRD was conducted in French dialysis centers. RESULTS: The mean annual loss of creatinine clearance in patients with lithium-induced nephropathy was 2.29 mL/min. Among 74 patients, 12 reached ESRD at a mean age of 65 years. Creatinine clearance at referral and at last follow-up was inversely related to the duration of lithium therapy in both univariate and multivariate analyses adjusting for age, gender, hypertension, and proteinuria. The degree of interstitial fibrosis on renal biopsy was also related to the lithium duration and cumulative dose. It was predictive of the final creatinine clearance. About 35% of the patients tested had moderate hypercalcemia, due to hyperparathyroidism. The prevalence of lithium-related ESRD in France was estimated as two per 1000 dialysis patients. The average latency between onset of lithium therapy and ESRD was 20 years. CONCLUSION: Lithium-induced chronic renal disease is slowly progressive. Its rate of progression is related to the duration of lithium administration. Lithium-related ESRD represents 0.22% of all causes of ESRD in France. Regular monitoring of estimated creatinine clearance is mandatory in long-term lithium-treated patients.

Adult↗
PubMed2003

Steroid-sensitive nephrotic syndrome: from childhood to adulthood.

BACKGROUND: The clinical presentation, treatment, and outcome of steroid-sensitive nephrotic syndrome (SSNS) during childhood have been extensively studied. Conversely, few data regarding the outcome in adulthood of childhood SSNS have been published previously. We undertook to conduct a retrospective study of the outcome in adulthood of a large cohort of patients diagnosed with an SSNS during childhood. METHODS: We identified all children born between 1970 and 1975 who had been admitted to our institution for an SSNS. Data regarding the outcome in adulthood of these patients were obtained through mailed questionnaires or phone calls to patients and/or their parents or through attending physicians. RESULTS: One hundred seventeen patients were identified. Data regarding the outcome of SSNS in adulthood were available for 102 patients (87.2%). Forty-three patients (42.2%) experienced at least one relapse of nephrotic syndrome in adulthood. By univariate analysis, young age at onset (<6 years) and more severe disease in childhood, indicated by a greater number of relapses (12.9 for adulthood relapsers versus 5.4 for adulthood nonrelapsers; P < 0.0001) and more frequent use of immunosuppressors (74.4% versus 31.6%; P < 0.0001) or cyclosporine (42.9% versus 7.3%; P < 0.0001) were predictive of the occurrence of SSNS relapse in adulthood. Conversely, relapse rate in the first 6 months of disease was not predictive of further relapses in adulthood. By multivariate analysis, only number of relapses during childhood was predictive of adulthood relapses (P < 0.0058). Long-term side effects of steroids were found in 44.2% of adulthood relapsers; the most frequent were osteoporosis and excess weight. CONCLUSION: The incidence of childhood SSNS relapses in adulthood was relatively high in our study. Further studies are required to assess long-term complications in adults with relapses and a history of prolonged steroid and immunosuppressor use.

Adolescent↗
PubMed2002

Mesangial IgG glomerulonephritis: a distinct type of primary glomerulonephritis.

Fourteen cases of mesangial IgG glomerulonephritis characterized by exclusive or predominant mesangial IgG deposits are reported. The median age at onset was 19 yr (range, 13 to 47 yr). No patient exhibited evidence of systemic lupus erythematous or other systemic diseases. Proteinuria was present in all cases (median, 2.4 g/d; range, 1 to 13 g/d), microscopic hematuria in 12 cases, and macroscopic hematuria in two cases. Five patients were hypertensive at the time of referral. In all cases, renal biopsies revealed mesangial IgG deposits and varying degrees of mesangial matrix expansion, in the absence of significant mesangial cell proliferation. Complement component (mainly C3) deposits were present in virtually all cases. Subepithelial deposits were also noted in nine cases. IgG deposits were polyclonal and consisted mainly of IgG1 and IgG3 subclasses. In electron-microscopic analyses, deposits were electron dense and granular. Treatment was purely supportive. After a mean follow-up period of 11 yr, seven patients had experienced progression to chronic renal failure, including four who had reached end-stage renal failure. Three patients exhibited persistently normal renal function. For one patient, a symptomatic recurrence of mesangial IgG deposits in the renal graft was diagnosed 4 yr after renal transplantation. Such a recurrence highlights the specificity of this type of glomerulonephritis. Mesangial IgG glomerulonephritis is a distinct, albeit rare, type of glomerulonephritis that exhibits far from benign outcome and may recur in renal transplants.

Adolescent↗
PubMed2002

[Vasoactive peptides and the development of renal sclerosis: contribution of transgenes].

Vasoactive peptides are implied in the development of renal sclerosis as evidenced by the efficiency of their antagonists in preventing glomerulosclerosis of experimental and human nephropathies. Genetically engineered models provide a new approach to investigate the mechanisms of the renal profibrotic actions of angiotensin II and endothelin. Overexpression of the human angiotensinogen and renin genes in rats induces renal sclerosis independently of changes in systemic hemodynamics. The same results are observed when the endothelin-1 gene is overexpressed in mice. Transgenic mice harboring the luciferase gene under the control of the collagen I-alpha 2 chain promoter (procol alpha 2[1]) and made hypertensive by induction of nitric oxide (NO) deficiency were used to study the renal profibrotic actions of vasoactive peptides. In this strain of mice, luciferase activity is an early index of renal fibrosis. Luciferase activity was increased in preglomerular arterioles and glomeruli when mice were deficient in NO. The pharmacological blockade of angiotensin II and endothelin prevented the development of renal sclerosis without modifying blood pressure. Moreover, when the endothelin receptor antagonist was administered after the development of renal fibrosis, preformed glomerulosclerosis partially regressed. Acute administration of vasoactive peptides and TGF-beta in transgenic procol alpha 2[1] mice showed that the angiotensin II activation of collagen I gene requires participation and/or cooperation of endothelin and TGF-beta. Recent data suggest that the profibrotic actions of vasoactive peptides also need the activation of EGF receptor, ERK and rho kinase pathways in renal and vascular cells.

Angiotensin II↗
PubMed2001

Angiotensin II activates collagen type I gene in the renal cortex and aorta of transgenic mice through interaction with endothelin and TGF-beta.

Hypertension is frequently associated with the development of renal vascular fibrosis. This pathophysiologic process is due to the abnormal formation of extracellular matrix proteins, mainly collagen type I. In previous studies, it has been observed that the pharmacologic blockade of angiotensin II (Ang II) or endothelin (ET) blunted the development of glomerulo- and nephroangiosclerosis in nitric oxide-deficient hypertensive animals by inhibiting collagen I gene activation. The purpose of this study was to investigate whether and how AngII interacts with ET to activate the collagen I gene and whether transforming growth factor-beta (TGF-beta) could be a player in this interaction. Experiments were performed in vivo on transgenic mice harboring the luciferase gene under the control of the collagen I-alpha 2 chain promoter (procol alpha 2[I]). Bolus intravenous administration of AngII or ET produced a rapid, dose-dependent activation of collagen I gene in aorta and renal cortical slices (threefold increase over control at 2 h, P < 0.01). The AngII-induced effect on procol alpha 2(I) was completely inhibited by candesartan (AngII type 1 receptor antagonist) and substantially blunted by bosentan (dual ET receptor antagonist) (P < 0.01), whereas the ET-induced activation of collagen I gene was blocked only by bosentan. In subsequent experiments, TGF-beta (also administered intravenously) produced a rapid increase of procol alpha 2(I) in aorta and renal cortical slices (twofold increase over control at 1 h, P < 0.01) that was completely blocked by decorin (scavenger of the active form of TGF-beta). In addition, decorin attenuated the activation of collagen I gene produced by AngII (P < 0.01). These data indicate that AngII can activate collagen I gene in aorta and renal cortex in vivo by a mechanism(s) requiring participation and/or cooperation of ET and TGF-beta.

Angiotensin II↗