Antiproteinuric efficacy of verapamil in comparison to trandolapril in non-diabetic renal disease.
(9/7998)
BACKGROUND: Non-dihydropyridine calcium antagonists such as verapamil are equally effective in reducing proteinuria as ACE inhibitors in hypertensive patients with diabetic nephropathy. To date it is unknown whether verapamil elucidates such an antiproteinuric capacity in non-diabetic renal disease. METHODS: We performed a double-blind, placebo-controlled, random cross-over study which compared the antiproteinuric effect of 6 weeks treatment with verapamil SR (360 mg) to that of the ACE inhibitor trandolapril (4 mg), and their fixed combination vera/tran (180 mg verapamil SR and 2 mg trandolapril) in 11 non-diabetic patients with proteinuria of 6.6 (5.1-8.8) g/day, a creatinine clearance of 87 (74-106) ml/min, and a 24-h blood pressure of 136/85 (126/76-157/96) mmHg at baseline. RESULTS: Twenty-four-hour mean arterial pressure did not change during verapamil, whereas both trandolapril and vera/tran induced a significant reduction in MAP. Verapamil showed no significant effects on renal haemodynamics. Trandolapril and vera/tran did not significantly change GFR, but ERPF increased and FF decreased during both treatments (P<0.05). The antiproteinuric response of verapamil was significantly less compared to that of trandolapril and vera/tran (-12% (-17/-1) vs -51% (-56/-25) and -41% (-50/-19) respectively). The blood pressure and antiproteinuric response during verapamil tended to be greater in hypertensive patients than in normotensive patients, although this difference was not significant. Baseline blood pressure was related to the change in blood pressure during verapamil (r = -0.70; P < 0.02). CONCLUSIONS: The antiproteinuric and antihypertensive response of verapamil is less than that of the ACE inhibitor trandolapril in patients with non-diabetic renal disease. In contrast to the antiproteinuric response of trandolapril, the antiproteinuric reponse of verapamil seems to be completely dependent from effective blood pressure reduction. The fixed combination of verapamil and ACE inhibition at half doses has similar effects as ACE inhibition at full dose. (+info)
A murine model of renal abscess formation.
(10/7998)
We developed a murine model of kidney abscess by direct renal injection of either Escherichia coli (1 x 10(6) to 7 x 10(6) organisms) or sterile medium. Bacterial infection produced renal abscesses, bacteremia, and late-onset leukocytosis in all animals. Controls were unaffected. This model may be useful for the study of various sequelae of kidney infection. (+info)
'Common' uncommon anemias.
(11/7998)
Of the uncommon anemias, "common" types include the anemia of renal disease, thalassemia, myelodysplastic syndrome and the anemia of chronic disease. These conditions may be suggested by the clinical presentation, laboratory test values and peripheral blood smear, or by failure of the anemia to respond to iron supplements or nutrient replacement. The principal cause of the anemia of renal disease is a decreased production of red blood cells related to a relative deficiency of erythropoietin. When treatment is required, erythropoietin is administered, often with iron supplementation. In the anemia of chronic disease, impaired iron transport decreases red blood cell production. Treatment is predominantly directed at the underlying condition. Since iron stores are usually normal, iron administration is not beneficial. Thalassemia minor results from a congenital abnormality of hemoglobin synthesis. The disorder may masquerade as mild iron deficiency anemia, but iron therapy and transfusions are often not indicated. In the myelodysplastic syndrome, blood cell components fail to mature, and the condition may progress to acute nonlymphocytic leukemia. The rate of progression depends on the subtype of myelodysplasia, but the leukemia is usually resistant to therapy. (+info)
Familial Mediterranean fever--renal involvement by diseases other than amyloid.
(12/7998)
BACKGROUND: In patients with familial Mediterranean fever (FMF) renal involvement is usually in the form of AA amyloidosis. There is increasing evidence that renal involvement may be due to diseases other than amyloid as well. METHODS: Amongst 302 children with FMF we observed and followed 28 with typical clinical and laboratory features of vasculitis. The diagnosis of FMF was established according to the Tel Hashomer criteria. RESULTS: Polyarteritis nodosa, protracted febrile attacks and Henoch-Schonlein purpura were diagnosed in 4, 13, and 11 patients, respectively. The presentation was often difficult to distinguish from FMF attacks, but protracted febrile attacks lasting several weeks, hypertension, thrombocytosis, and dramatic responses to corticosteroid therapy that were observed in many cases were different from what is observed in classical FMF. CONCLUSIONS: We suggest that FMF, perhaps as a consequence of impaired control of inflammatory responses, predisposes to vasculitis with renal involvement. (+info)
In vitro effects of simvastatin on tubulointerstitial cells in a human model of cyclosporin nephrotoxicity.
(13/7998)
To investigate the possibility that 3-hydroxy-3-methylglutaryl CoA (HMGCoA) reductase inhibitors ameliorate renal disease via direct effects on the tubulointerstitium, primary cultures of human proximal tubule cells (PTC) and renal cortical fibroblasts (CF) were exposed for 24 h to simvastatin (0.1-10 micromol/l) under basal conditions and in the presence of 1,000 ng/ml of cyclosporin (CsA), which we have previously shown to promote in vitro interstitial matrix accumulation at least partially via activation of local cytokine networks. Simvastatin, in micromolar concentrations, engendered cholesterol-independent inhibition of CF and PTC thymidine incorporation and cholesterol-dependent suppression of PTC apical Na+/H+ exchange (NHE) (ethylisopropylamiloride-sensitive apical 22Na+ uptake). Similarly, CF secretion of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 were depressed, whereas CF collagen synthesis ([3H]proline incorporation) and PTC secretion of the fibrogenic cytokines, transforming growth factor-beta1, and platelet-derived growth factor were unaffected. A lower concentration (0.1 micromol/l) of simvastatin did not affect any of the above parameters under basal conditions but completely prevented CsA-stimulated CF collagen synthesis (control, 6.6 +/- 0.6; CsA, 8.3 +/- 0.6; CsA+simvastatin, 6.2 +/- 0.5%; P < 0.05) and IGF-I secretion (89.5 +/- 16.6, 204.7 +/- 57.0, and 94.6 +/- 22.3 ng. mg protein-1. day-1, respectively; P < 0.05). The results suggest that simvastatin exerts direct cholesterol-dependent and -independent effects on the human kidney tubulointerstitium. HMGCoA reductase inhibitors may ameliorate interstitial fibrosis complicating CsA therapy via direct actions on human renal cortical fibroblasts. (+info)
The intrarenal vascular lesions associated with primary antiphospholipid syndrome.
(14/7998)
Even 10 yr after the identification of the antiphospholipid syndrome (APS), renal involvement in the course of APS is still relatively unrecognized, and is probably underestimated. The association of anticardiolipin antibodies and/or lupus anticoagulant with the development of a vaso-occlusive process involving numerous organs is now confirmed. In a multicenter study, 16 cases of "primary" APS (PAPS) were found and followed for 5 yr or more, all with renal biopsy. In all 16 cases of PAPS, there was a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries (12 patients), recanalizing thrombi in arteries and arterioles (six patients), and focal cortical atrophy (10 patients). In combination, these led to progressive destruction of the kidney, accelerated by acute glomerular and arteriolar microangiopathy in five patients. Focal cortical atrophy is a distinctive lesion, present in 10 biopsies, and likely represents the histologic and functional renal analogue to the multiple cerebral infarcts detected on imaging studies. The clinical hallmark of this vascular nephropathy in PAPS is systemic hypertension, only variably associated with renal insufficiency, proteinuria, or hematuria. The ensemble of histologic renal lesions defined in this study should aid in the separation of the lesions found in cases of secondary APS, especially systemic lupus erythematosus, into those lesions related to APS and those related to the underlying disease. (+info)
A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome.
(15/7998)
The Wilms tumor-suppressor gene, WT1, plays a key role in urogenital development, and WT1 dysfunction is implicated in both neoplastic (Wilms tumor, mesothelioma, leukemias, and breast cancer) and nonneoplastic (glomerulosclerosis) disease. The analysis of diseases linked specifically with WT1 mutations, such as Denys-Drash syndrome (DDS), can provide valuable insight concerning the role of WT1 in development and disease. DDS is a rare childhood disease characterized by a nephropathy involving mesangial sclerosis, XY pseudohermaphroditism, and/or Wilms tumor (WT). DDS patients are constitutionally heterozygous for exonic point mutations in WT1, which include mutations predicted to truncate the protein within the C-terminal zinc finger (ZF) region. We report that heterozygosity for a targeted murine Wt1 allele, Wt1(tmT396), which truncates ZF3 at codon 396, induces mesangial sclerosis characteristic of DDS in adult heterozygous and chimeric mice. Male genital defects also were evident and there was a single case of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9 skipping event, implying a causal link between Wt1 dysfunction and Wilms tumorigenesis in mice. However, the mutant WT1(tmT396) protein accounted for only 5% of WT1 in both heterozygous embryonic stem cells and the WT. This has implications regarding the mechanism by which the mutant allele exerts its effect. (+info)
Effective treatment of autoimmune disease and progressive renal disease by mixed bone-marrow transplantation that establishes a stable mixed chimerism in BXSB recipient mice.
(16/7998)
Male BXSB mice spontaneously develop autoimmune disease with features similar to systemic lupus erythematosus. To determine whether this autoimmune disease can be treated as well as prevented by bone-marrow transplantation (BMT) and, at the same time, whether the immunity functions of lethally irradiated recipients can be reconstituted fully, male BXSB mice were engrafted with mixed T cell-depleted marrow (TCDM) both from fully allogeneic autoimmune-resistant BALB/c mice and from syngeneic autoimmune-prone BXSB mice, after the onset of autoimmune disease in the recipient mice. BMT with mixed TCDM from both resistant and susceptible strains of mice (mixed BMT) established stable mixed chimerism, prolonged the median life span, and arrested development of glomerulonephritis in BXSB mice. BMT with mixed TCDM also reduced the formation of anti-DNA antibodies that are observed typically in male mice of this strain. Furthermore, mixed BMT reconstituted the primary antibody production in BXSB recipients impressively. These findings indicate that transplantation of allogeneic autoimmune-resistant TCDM plus syngeneic autoimmune-prone TCDM into lethally irradiated BXSB mice can be used to treat autoimmune and renal disease in this strain of mice. In addition, this dual bone-marrow transplantation reconstitutes the immunity functions and avoids the immunodeficiencies that occur regularly in fully allogeneic chimeras after total body irradiation. This report describes an effective treatment of progressive renal disease and autoimmunity by establishing a stable mixed chimerism of TCDM transplantation from allogeneic autoimmune-resistant BALB/c mice plus syngeneic autoimmune-prone BXSB mice into BXSB mice. (+info)