Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrarenal hemodynamic and tubular function has been assessed in 16 patients who presented clinically with hypertension, hematuria and severe renal functional impairment. Twelve of these 16 patients had histopathologic classification as DPGN (3 cases), MPGN (3 cases) and FSGS (6 cases). The initial assessment of intrarenal hemodynamics in 11 patients revealed strikingly increased afferent (RA) and efferent arterioles (RE), filtration fraction (FF), intraglomerular capillary hydrostatic pressure (PG), whereas, there was marked reduction in renal plasma flow (RPF), in ultrafiltration coefficient (KFG) and in glomerular filtration rate (GFR). Tubular transporting defect as being reflected by enhanced fractional excretions of solutes was also observed. Both enhanced TXB2 production and diminished PGI2 may be in part responsible for the marked reduction of RPF and elevated intrarenal resistance. In light of the preceding intrarenal hemodynamics alteration, therapeutic intervention with vasodilators consisting of dipyridamole, calcium channel blocker and angiotensin convertase inhibitor has been accomplished with clinical improvement in glomerular and tubular functions following the improvement in intrarenal hemodynamics. Thus, this abnormal intrarenal hemodynamics renders a supportive view of the hemodynamically mediated glomerulo-tubulo-interstitial injury to be central to the pathogenetic mechanism.
 ...
PMID:Intrarenal hemodynamic abnormality in severe form of glomerulonephritis: therapeutic benefit with vasodilators. 129 54

From June 1987 to June 1991 at the Belgrade University Children's Hospital 10 patients, 5 males and 4 females, aged 2-16 years, with chronic glomerular disease, were treated with CyA. Seven patients had INS, 2 lupus nephritis and one IgA nephritis. Before initiation of CyA, all but one, were treated with classic immunosuppressive therapy, which had no effect (8/10) and/or had serious adverse effects (9/10). CyA dosage was initiated at 4-6 mg/kg/BW, and was subsequently adjusted to achieve CyA concentrations in blood at range 50-100 ng/ml. Treatment duration was 2-17 months. Patient compliance to CyA therapy was observed in 5/7 INSs: 2 cortico-sensitive (1 with FSGS was cortico-dependent and 1 had frequent relapses) and 3 cortico-resistant patients (2 with FSGS and 1 with minimal histologic changes). After drug withdrawal, only one of the patients who responded, had no relapse. One of the two patients with SLE showed improvement during CyA administration, while no response was observed in the patient with IgA nephritis. Adverse experiences with CyA therapy involved decreased renal function (2/10), arterial hypertension (1/10), hyperbilirubinaemia (1/10), transient LDH increase and hyperuricaemia (1/10).
 ...
PMID:[Cyclosporine in the treatment of glomerular diseases in children]. 146 61

The safety and tolerability of cyclosporin A (CyA, Sandimmun) in idiopathic nephrotic syndrome were analyzed in 661 patients enrolled in 10 clinical studies. The majority had minimal-change nephropathy (MCN, 34%) or focal-segmental glomerulosclerosis (FSGS, 33%). The safety experience covered 435 patient years of CyA exposure. The initial CyA dose averaged 5 mg/kg/day in adults and 6 mg/kg/day in children, and was further titrated according to efficacy or adverse reactions. Relevant CyA-induced renal dysfunction occurred almost exclusively in patients (mostly FSGS) who had abnormal baseline renal function. Renal tolerability was better in patients who had complete remission of nephrotic syndrome than in those who did not respond to treatment. However, in the latter, the risk was still relatively low if CyA treatment was stopped after three to four months of treatment. Sixty-nine patients had a renal biopsy performed after one to three years of continuous CyA therapy, and CyA-associated nephropathy, especially interstitial fibrosis, was seen in a few of these patients. Kidney biopsies may therefore be advisable in MCN patients treated successfully for one to two years and in whom further CyA therapy is indicated. Hypertension occurred in approximately 10% and was usually well controlled with conventional antihypertensive therapy. There were a few infectious complications, but the course of these was not unusual. Malignancies developed in five patients, including Hodgkin's lymphoma in two. Overall, adverse reactions resulted in CyA treatment discontinuation in 7.4% of patients, half of them because of renal dysfunction.
 ...
PMID:Safety and tolerability of cyclosporin A (Sandimmun) in idiopathic nephrotic syndrome. Collaborative Study Group of Sandimmun in Nephrotic Syndrome. 186 Feb 68

Whether or not pregnancy adversely affects the natural course of underlying primary renal disease, and whether fetal outcome is influenced by the type of renal disease per se are controversial issues. We retrospectively analyzed the fetal and maternal outcome in 148 women with various, biopsy-proven histological types of primary chronic glomerulonephritis (GN), including IgA GN (52 patients), membranous GN ([MGN] 20 patients), membranoproliferative type 1 GN ([MPGN] 58 patients), focal and segmental glomerulosclerosis ([FSGS] 13 patients), and minimal change nephrotic syndrome ([MCNS] 22 patients), who were pregnant (with a total of 290 pregnancies) after the clinical onset of GN, and in 104 women with reflux nephropathy (with a total of 254 pregnancies). Fetal outcome was poor in the presence of uncontrolled hypertension, nephrotic range proteinuria, and/or impaired renal function at conception or early in gestation, whatever the type of renal disease. An accelerated, more rapid than expected, worsening of maternal renal function was observed in five GN patients of whom four (two IgA, two MPGN) had serum creatinine (Scr) levels greater than 160 mumol/L (1.8 mg/dL) early in gestation, and in five patients with reflux nephropathy whose Scr at conception ranged from 180 to 490 mumol/L (2.0 to 5.5 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Specific controversies concerning the natural history of renal disease in pregnancy. 199 51

Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients are still significant. Cardiovascular disease accounts for much of the mortality in long-term survivors; screening before the transplant procedure and adequate control of hypertension should help improve patient survival. Many of the gastrointestinal complications are due to overimmunosuppression and sepsis. Adequate management must include withdrawal of all immunosuppressive medications in order to save the patient's life. Liver disease is usually of viral origin; patients with chronic active hepatitis or cirrhosis should remain on dialysis. Chronic rejection is the major cause of graft loss in long-term survivors; it is unresponsive to antirejection treatment and its progression may be mediated by nonimmunologic mechanisms. Correctable problems such as renal artery stenosis and ureteral obstruction should be ruled out before a late deterioration in graft function is disregarded as chronic rejection. Post-transplant diabetes, osteonecrosis, cataracts, and nephrotoxicity are directly related to the various immunosuppressive drugs currently used. The lowest dose compatible with graft acceptance should help reduce the incidence of these nonfatal but significant complications. Recurrence of disease is a common histologic finding in many transplant recipients but, except for a few diseases such as HUS, FSGS, and oxalosis, it usually does not lead to graft failure. Successful transplantation restores fertility in many uremic patients. Adequate counseling on contraception is imperative in order to avoid unwanted pregnancies and to delay parenthood for at least 1 year. Current immunosuppressive agents are not teratogenic, no dose adjustments are necessary, and an ill-advised decrease in medication may precipitate a rejection episode. Premature delivery is the major problem in these patients and can be avoided by maintaining adequate graft function and controlling hypertension and infections. It is evident from this review that most of the long-term morbidity and mortality seen in renal allograft recipients are due to overimmunosuppression with sepsis or to side effects of the individual drugs, steroids being a common denominator in almost all cases. New immunosuppressive protocols must aim not only to improve patient and graft survival but also to avoid the many complications that limit the full rehabilitation of these patients.
 ...
PMID:Problems in the long-term renal allograft recipient. 226 90

In summary, both the developing atherosclerotic and FSGS lesions seem to share certain postulated pathophysiologic mechanisms, including endothelial cell injury, macrophage infiltration, hyperlipoproteinemia, and hypertension. As depicted in Figure 1, any initial glomerular injury results in flux of macromolecular substances into the glomerular mesangium. As an adjunct to increased glomerular barrier dysfunction, hyperlipoproteinemia is believed to secondarily develop from the dramatic losses of albumin, stimulating increased hepatic lipoprotein synthesis and the loss of lipoprotein lipase-activating substance into the urine which would effectively produce a reduction in circulating chylomicra and triglyceride catabolism. Certain elevated circulating lipoproteins could, theoretically, pass through the damaged glomerular filter into the mesangium, thereby enhancing the flux of macromolecules. Also associated with certain experimental glomerular disorders is the development of glomerular hypertension, as manifested by an elevated glomerular capillary hydrostatic pressure (PGC), which can further augment macromolecular flux into the mesangium. Overloading of the glomerular mesangium by the above mechanisms is believed to be an injurious stimulus for MC to both proliferate and produce excess mesangial matrix substance. Both of these events are thought to be pathologic harbingers of glomerulosclerosis. Glomerular hypertension is also capable of damaging endothelial cells within the glomerular microcirculation, and this purportedly can activate platelets and result in glomerular thrombosis. At present, it is unclear how glomerular thrombosis produces increased mesangial cell injury; however, this process is believed to cause both systemic and glomerular hypertension which may serve as intermediary mechanisms producing the untoward effects of mesangial cell proliferation and matrix overproduction.
 ...
PMID:Focal and segmental glomerulosclerosis: analogies to atherosclerosis. 329 16

Renal biopsies from hypertensive pregnant women performed 8 to 10 days postpartum were processed by morphometric analysis. We allocated the 74 patients into four groups according to the respective forms of pregnancy hypertension, i.e. preeclampsia and gestational hypertension. Groups I and II included preeclamptic women, with (group I) or without (group II) de novo FSGS. Groups III and IV included biopsies of women with isolated gestational hypertension, appeared during the third trimester (group III) or earlier (group IV). The control group included 17 biopsies from age-matched nonpregnant women presenting with isolated hematuria. Glomerular lesions of typical preeclampsia were seen in all the biopsies of groups I and II, and in some of women with gestational hypertension of groups III and IV. Our morphometric analysis of these renal biopsies showed a progressive increase in glomerular size from early gestational hypertension, gestational hypertension of the 3rd trimester, isolated preeclampsia, and finally preeclamptic nephropathy associated with FSGS. The largest glomeruli were seen in preeclamptic women with severe hypertension and histologic lesions of preeclampsia with FSGS. Thus, both systemic hypertension and glomerular hypertrophy seem necessary to induce FSGS in this type of pathology.
 ...
PMID:Preeclampsia associated focal and segmental glomerulosclerosis and glomerular hypertrophy: a morphometric analysis. 792 75

This review compares the biopsy patterns, complications, responses to therapy, and long-term outcomes of idiopathic NS in children and adults. On first examination, distinctions between the pediatric and adult diseases seem more quantitative than absolute. However, underlying determinants of outcome, including immunocompetence, growth, maturity, and senescence, can present very different challenges for pediatricians and internists. The major biopsy patterns in pediatric NS include MCD, FSGS, and DMP. MCD is overwhelmingly the most frequent and most steroid-responsive of the three but commonly presents problems of massive edema, serious bacterial infections, and multiple relapses. Because of the prompt response of pediatric MCD to corticosteroids, steroid resistance in children has generally been defined as persistence of proteinuria after 1 month of daily followed by 1 month of intermittent prednisone administration. By this criterion, nephrotic FSGS is usually steroid-resistant and, if not controlled by more aggressive therapy, typically progresses to ESRD. DMP is commonly steroid-resistant but may slowly resolve. It is not clear to what extent remissions of DMP represent a delayed response to steroids or would have occurred without treatment. Biopsies showing a few globally obsolescent glomeruli or mild mesangial hypercellularity may be associated with greater difficulty in management but have been included in the broad category of MCD. Moreover, evolution of patterns in serial biopsies, variable steroid-responsiveness of FSGS and DMP, and progression of some cases of MCD to ESRD suggest common features in the three major categories. Among adults with idiopathic NS, FSGS is the most frequent biopsy pattern, followed by MN (which is rare in children) and then by MCD. In contrast to its pediatric counterpart, MCD in adults is less regularly and more slowly responsive to corticosteroids and in the elderly is more commonly associated with hypertension and renal failure. MCD in adults is less likely to relapse once remission is achieved. Adults with FSGS present less commonly with severe edema than do children with this lesion. Although children and adults with FSGS present similar challenges of resistance to therapy and loss of renal function, the more aggressive oral steroid regimens used by internists preclude strict comparisons between pediatric and adult series. There is insufficient information to support a systematic analysis of DMP in adults. Cytotoxic agents and cyclosporine have been used with varying success in children and adults with difficult cases of NS. In MCD, an alkylating agent can increase the likelihood and duration of remission. Cyclosporine can also improve control in MCD, but continued treatment is often needed to maintain remission. Significant control of steroid-resistant FSGS has not been achieved with limited courses of an alkylating agent or cyclosporine. Longer courses of either of these immunosuppressants, especially when combined with intermittent steroid administration, can produce more complete and/or more sustained remissions. However, cyclosporine nephrotoxicity is more severe in FSGS than in MCD and in steroid-resistant than in steroid-dependent NS, regardless of biopsy pattern. A protocol combining iv M-P pulses, alternate-day prednisone, and an alkylating agent in steroid-resistant pediatric FSGS has produced the highest percentage of sustained remissions with normal renal function, of all reported regimens. Controlled trials of this and other combined drug protocols are needed in children and adults.
 ...
PMID:Treatment of the idiopathic nephrotic syndrome: regimens and outcomes in children and adults. 917 55

Hepatitis B virus (HBV)-associated glomerulonephropathy (HBV-GN) has been increasingly reported, especially in adults. In the present study, the authors investigated the clinical and histopathology features of patients who suspected HBV-GN in 24 patients and age ranging from 23 to 74 years (mean 43 years). Asymptomatic hematuria was the most common presentation (54%); followed by edema and hypertension at equal percentages of 50%. The nephrotic syndrome was presented in 43%, the nephrito-nephrotic syndrome in 3.5%. Clinically suspected rapidly progressive GN was found in 14%. Renal insufficiency was determined in 30%. The most common pathologic finding was IgA nephropathy (IgAN 29%), followed by membranous nephropathy (21%), focal segmental glomerulo sclerosis (FSGS 11%), membranoproliferative GN (11%), post-infectious GN (11%). Liver disease activity also tended to be mild or had no symptoms of hepatitis. The authors remission rates both complete and partial were 75% (higher than the usual report), notwithstanding treatment. The authors achieved a sustained complete remission in half of the patients (3 in 6 cases) treated with steroid alone and 2 out of 7 cases (28.6%) treated with anti-viral therapy. Spontaneous remission was demonstrated in 2 (1 with IgAN + FSGS, and 1 with post infectious GN) out of 6 patients (33.3%). None of the patients in both treatment groups turned to ESRD that occurred in 2 cases receiving non-specific treatment. Of note, all of the patients who received anti-viral therapy or corticosteroid and had complete follow up were in remission either complete or partial.
 ...
PMID:Hepatitis-B virus-associated nephropathies in adults: a clinical study in Thailand. 1704 67

HIV-associated nephropathy (HIVAN) is characterized by a collapsed glomerular capillary tuft with hyperplasia and hypertrophy of podocytes. Recently generated were conditional transgenic mice (podocin/Vpr) that express one of the HIV-1 accessory genes, vpr, selectively in podocytes using podocin promoter and Tet-on system. These transgenic mice developed renal injury similar to HIVAN when treated with doxycycline for 8 to 12 wk. This study demonstrated that nephron reduction by heminephrectomy markedly enhanced phenotypic changes of podocytes and led to severe FSGS within 4 wk. Nephrotic-range proteinuria was observed already at 2 wk, together with dedifferentiation and dysregulation of podocytes, indicated by decreased expression of nephrin, synaptopodin, and Wilms' tumor 1 protein and increased expression of Ki-67. The acceleration of phenotypic changes of podocytes, proteinuria, and subsequent glomerulosclerosis by heminephrectomy was almost completely inhibited by angiotensin II type 1 receptor (AT1R) blocker olmesartan. In contrast, the renoprotective effect of the calcium channel antagonist azelnidipine was minimal, although it lowered systemic BP to the same level as olmesartan, demonstrating that the inhibitory effect of AT1R blocker was independent of systemic BP. Olmesartan also reduced proteinuria and prevented glomerulosclerosis even by the delayed treatment, which was initiated after the podocyte injury appeared. These data suggest that nephron reduction exaggerates podocyte injury and subsequent glomerulosclerosis, possibly through glomerular hypertension, in the mouse model of HIVAN. AT1R blockade could be beneficial in the treatment of HIVAN by ameliorating podocyte injury by avoiding the vicious cycle of nephron reduction and glomerular hypertension.
 ...
PMID:Angiotensin II type 1 receptor blockade inhibits the development and progression of HIV-associated nephropathy in a mouse model. 1722 13


1 2 3 Next >>