Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 38-year-old man gradually developed gait instability, dysarthria, and dysphagia over two months associated with an elevated blood pressure after starting hemodialysis therapy for diabetic nephropathy. Brain MRI studies indicated vasogenic edema in the brainstem, extending from the lower midbrain to the upper medulla oblongata. The patient's high blood pressure was refractory to treatment, and his neurological disabilities and MRI abnormalities progressed. FDG-PET, MR spectroscopy, and cerebrospinal fluid studies did not suggest neoplastic pathologies. The patient was diagnosed with a brainstem variant of reversible posterior leukoencephalopathy syndrome, and received three courses of steroid pulse therapy. After the pulse therapy, the clinical manifestations and MR findings improved. By maintaining strict management of blood pressure and body water balance during hemodialysis, he did not experience any further clinical exacerbation, and the lesion on MR images continued to regress. Ten months after the pulse therapy, T1-weighted images showed slightly hyperintense signal. This case suggests that reversible posterior leukoencephalopathy syndrome (RPLS) may take a chronic clinical course without acute onset.
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PMID:[Brainstem variant of reversible posterior leukoencephalopathy syndrome with a prolonged clinical course: a case report]. 1908 30

Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-beta1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (approximately 260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg x kg(-1) x day(-1) (D0.01, N = 14), 1 mg x kg(-1) x day(-1) (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-beta1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40%), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P < 0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P < or = 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-beta1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.
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PMID:Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats. 1909 49

A statistical survey of dialysis patients for the year 2006 was carried out for 4051 medical facilities across Japan, and responses were received from 3985 (98.37%) facilities. There were 264 473 dialysis patients (including 9003 peritoneal dialysis patients) in Japan at the end of 2006, which showed an increase of 6708 (2.6%) from the end of 2005. The number of patients per million population was 2069.9. The crude mortality rate during 2006 was 9.2%. The mean age of the patients who began dialysis (in 2006) was 66.4 years, and the mean age of the entire dialysis population was 64.4 years. The primary renal diseases of the patients who began dialysis were diabetic nephropathy (42.9%), chronic glomerulonephritis (25.6%), and nephrosclerosis (9.4%). Of the 3488 facilities that participated in the survey on the dialysate water quality, 2873 facilities (82.4%) measured the endotoxin concentration in the dialysate; and 1197 facilities (37.1%) out of 3228 measured the bacterial count in the dialysate. The mean hemoglobin concentration in the dialysis population at the end of 2006 was 10.23 +/- 1.33 g/dL, which was equal to that at the end of 2005 (10.23 +/- 1.37 g/dL). The mean concentration of serum creatinine in 15 853 patients who started dialysis during 2006 was 8.37 +/- 3.58 mg/dL. The estimated glomerular filtration rate, which was calculated with formula modified for the Japanese population from the Modification of Diet in Renal Disease (MDRD) Study equation, was 5.46 +/- 6.60 mL/min/1.73 m(2).
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PMID:Overview of regular dialysis treatment in Japan as of 31 December 2006. 1914 Aug 42

Diabetic nephropathy is the leading cause of renal failure in the United States. The obese Zucker rat (OZR; fa/fa) is a commonly used model of type 2 diabetes and metabolic syndrome (MetS), and of the nephropathy and renal oxidative stress commonly seen in these disorders. Heterozygous lean Zucker rats (LZRs; fa/+) are susceptible to high-fat diet (HFD)-induced obesity and MetS. The present study was designed to investigate whether 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), a membrane-permeable radical scavenger, could alleviate the renal effects of MetS in OZR and LZR fed a HFD, which resembles the typical "Western" diet. OZR and LZR were fed a HFD (OZR-HFD and LZR-HFD) or regular diet (OZR-RD and LZR-RD) and allowed free access to drinking water or water containing 1 mmol/l TEMPOL for 10 weeks. When compared to OZR-RD animals, OZR-HFD animals exhibited significantly higher levels of total renal cortical reactive oxygen species (ROS) production, plasma lipids, insulin, C-reactive protein, blood urea nitrogen (BUN), creatinine (Cr), and urinary albumin excretion (P < 0.05); these changes were accompanied by a significant decrease in plasma high-density lipoprotein levels (P < 0.05). The mRNA expression levels of desmin, tumor necrosis factor-alpha (TNF-alpha), nuclear factor kappaB (NFkappaB), and NAD(P)H oxidase-1 (NOX-1) were significantly higher in the renal cortical tissues of OZR-HFD animals; NFkappaB p65 DNA binding activity as determined by electrophoretic mobility shift assay was also significantly higher in these animals. The same trends were noted in LZR-HFD animals. Our data demonstrate that TEMPOL may prove beneficial in treating the early stages of the nephropathy often associated with MetS.
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PMID:Diet-induced renal changes in Zucker rats are ameliorated by the superoxide dismutase mimetic TEMPOL. 1942 63

1. Male gender is associated with higher blood pressure (BP) and more rapid loss of renal function in a spectrum of clinical and experimental renal diseases, including diabetic nephropathy. Consequently, modulation of testosterone levels could exert beneficial effects in the diabetic kidney. 2. The aim of the present study was to determine whether testosterone deficiency (orchiectomy) could influence BP and renal function in streptozotocin-diabetic rats, with or without accelerated endothelial dysfunction achieved by chronic inhibition of nitric oxide (NO) synthesis using N(G)-nitro-L-arginine methyl ester (l-NAME; 40-100 mg/L in the drinking water for 2 weeks), as well as in age-matched non-diabetic rats subjected to the same interventions. 3. Orchiectomy did not affect L-NAME-induced increases in BP in non-diabetic or diabetic rats. In non-diabetic rats, orchiectomy prevented L-NAME-induced increases in proteinuria. These effects on proteinuria were not observed in diabetic rats. In non-diabetic rats, orchiectomy had no effect on renal haemodynamics in animals receiving vehicle and did not affect L-NAME-induced changes in renal haemodynamics, characterized by reductions in renal plasma flow (RPF) and higher filtration fractions (FF). In intact diabetic rats, L-NAME treatment resulted in lower RPF. This difference was not observed in diabetic rats subjected to orchiectomy, although L-NAME-treated diabetic orchiectomized rats had lower RPF and higher FF compared with vehicle-treated intact diabetic rats. 4. In conclusion, we report modest beneficial effects of orchiectomy on proteinuria in normal, but not in diabetic, rats with inhibition of NO production. This suggests that testosterone reduction does not attenuate the deleterious impact of the diabetic metabolic milieu in the kidney.
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PMID:Effect of orchiectomy on renal function in control and diabetic rats with chronic inhibition of nitric oxide. 1947 97

Angiotensin-(1-7) (Ang-[1-7]) is a heptapeptide member of the renin-angiotensin system (RAS), and acts as a vasodilator and antagonist of angiotensin II (Ang II) in the vasculature. The role of Ang-(1-7) in regulating kidney function is not well understood. Within the kidneys, Ang-(1-7) is generated by angiotensin-converting enzyme 2 (ACE2)-mediated degradation of Ang II, sequential cleavage of the precursor angiotensin I (Ang I) by ACE2 and ACE, or the actions of brush-border membrane peptidases on Ang I. Ang-(1-7) mediates its effects via binding to kidney Mas receptors, although some actions may occur via Ang II AT1 or AT2 receptors. In vitro studies suggest that Ang-(1-7) is an intrarenal vasodilator. Ang-(1-7) has been reported to induce either natriuresis/diuresis or sodium and water retention, via modulation of sodium transporters in the proximal tubule and loop of Henle, and collecting duct water transport. In the proximal tubule, Ang-(1-7) antagonizes growth-promoting signaling pathways via activation of a protein tyrosine phosphatase, whereas in mesangial cells, Ang-(1-7) stimulates cell growth via activation of mitogen-activated protein kinases. The phenotype of the Mas gene knockout mouse suggests that Ang-(1-7)-signaling events exert cardiovascular protection by regulating blood pressure, and by limiting production of reactive oxygen species and extracellular matrix proteins. Ang-(1-7) also protects against renal injury in the renal wrap hypertension model, independent of effects on blood pressure. In diabetic nephropathy, however, the role of Ang-(1-7) on disease progression remains unclear. In summary, Ang-(1-7) and its receptor Mas have emerged as important components of the intrarenal RAS. The signaling and downstream effects of Ang-(1-7) in the kidney are complex and appear to be cell specific. The body of evidence suggests that Ang-(1-7) is protective against endothelial dysfunction or Ang II-stimulated proximal tubular injury, although the overall effects on glomerular function require further study.
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PMID:Angiotensin-(1-7) and its effects in the kidney. 1957 9

In addition to local causes--for example, leak of dialysate into an inguinal hernia sac or into the anterior abdominal wall through the track of the catheter for continuous peritoneal dialysis (CPD)--scrotal edema in CPD patients may result from generalized volume retention. We present 2 CPD patients with scrotal edema, illustrating the diagnosis and management of the mechanisms of volume retention. A man with hypertensive nephrosclerosis developed isolated scrotal edema 14 months after an uneventful course of continuous ambulatory peritoneal dialysis (CAPD). After repair of a ventral hernia and of a communicating hydrocele, he started continuous cycling peritoneal dialysis (CCPD), plus 2 daytime CAPD exchanges. After 4 months, he again developed isolated scrotal edema, which decreased at night. Peritoneal scintigraphy showed no dialysate leaks, and peritoneal equilibration test (PET) revealed high-average transport with a residual volume above, and an ultrafiltration volume below, the expected range. Abdominal radiography revealed migration of the CPD catheter. Malposition of the CPD catheter with positional retention of dialysate was diagnosed. The patient was treated with nightly peritoneal dialysis and no daytime exchanges. On this regimen, ultrafiltration improved and the scrotal edema disappeared with no recurrence for 5 months, at which point the patient underwent kidney transplantation. A man with diabetic nephropathy developed poor dialysate return, volume gain, and pronounced edema of the scrotum, penis, and both legs soon after starting CAPD. Peritoneal scintigraphy was negative, and abdominal radiography confirmed the appropriate position of the CPD catheter tip in the right lower abdominal quadrant. PET revealed high peritoneal solute transport, appropriate residual volume, and appropriate for the transport category, but relatively low (0.1 L), ultrafiltration volume. He was treated with a change in the CPD procedure to CCPD, plus 1 daytime icodextrin exchange and instruction to reduce salt intake. This patient has remained free of scrotal edema for 6 months. In men on CPD, scrotal edema can develop from generalized volume gain secondary to either CPD catheter malfunction or imbalance between total fluid removal and salt and water intake. Proper interpretation of PET findings is critical in the evaluation of scrotal edema not resulting from internal dialysate leaks in CPD.
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PMID:Scrotal edema secondary to fluid imbalance in patients on continuous peritoneal dialysis. 1988 20

The complex pathogenesis of chronic renal disease (CRD) depends on endothelin (ET) axis (ETs and ET receptors) and nitric oxide (NO) because of their vasoactive effects and their role in general modulation of vascular homeostasis. Various renal cells synthesize ETs and NO that play a significant role in renal hemodynamics as well as in water and salt excretion via urine. ET-1 is a strong vasoconstrictor. Besides its vasoactive effects, ET-1 modulates mitosis and apoptosis in a cell type-dependent manner, and may play an important role in CRD pathogenesis. The aims of this study were to emphasize the role and interactions of ET-1, Big ET-1, and NO in CRD. Concentrations of these vasoactive molecules were measured in plasma/serum and/or urine of 57 patients with diabetic nephropathy (subgroup 1), arterial hypertension (subgroup 2) or CRD with chronic renal insufficiency (subgroup 3), and in healthy control subjects (n=18). In comparison with control group, urine concentration of Big ET-1 was significantly increased (13.13 pmol/L vs. 11.34 pmol/L; P<0.001) in CRD patients, whereas plasma and urine concentrations of ET-1 did not differ significantly. NO concentrations were also significantly increased in CRD patients (serum, 72.55 micromol/L; P<0.001, and urine 141.74 micromol/L; P<0.05) as compared to control group. Study results indicated that Big ET-1 and NO could be useful diagnostic parameters in CRD for their diagnostic sensitivity and diagnostic specificity (Big ET-1 in urine: 56.1 and 88.9%, and NO in serum: 66.7 and 83.3%, respectively). In addition, Big ET-1 may prove useful in the differential diagnosis of diabetic nephropathy (78.6% diagnostic sensitivity and 88.9% diagnostic specificity).
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PMID:Endothelin-1, big endothelin-1, and nitric oxide in patients with chronic renal disease and hypertension. 1992 48

The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and tubular epithelial cell sodium chloride and water transport mechanisms. Pharmacological inhibition of the actions of the RAS are widely used in the treatment of patients with hypertension, congestive heart failure, left ventricular dysfunction, pulmonary and systemic edema, diabetic nephropathy, cirrhosis of the liver, scleroderma, and migraines. Therefore, a thorough understanding of the influences of the RAS on normal renal physiology is of major importance for first-year medical students.
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PMID:The renal renin-angiotensin system. 1994 73

The aim of this study was to test the hypothesis that paeoniflorin prevents the progression of diabetic nephropathy by modulating the inflammatory process. Sprague-Dawley rats were divided into 5 groups: nondiabetic control rats; untreated diabetic model (DM) rats; and DM rats treated with 5, 10, or 20 mg/kg paeoniflorin in drinking water once daily. Rats received a single intravenous injection of streptozotocin to induce diabetes; 9 wk after injection, rats began the 8-wk daily paeoniflorin treatment regimen. Compared with that of nonDM controls, the urinary albumin:creatinine ratio was increased significantly in untreated DM rats; this ratio was decreased in DM rats treated with 5, 10, or 20 mg/kg paeoniflorin compared with that of untreated DM rats. In addition, paeoniflorin treatment effectively suppressed glomerular hypertrophy; blood glucose; the expression of transforming growth factor beta, type IV collagen, and intercellular adhesion molecule 1; and renal infiltration of macrophages compared with levels in untreated DM rats. Furthermore, renal nuclear factor kappaB activity was increased in untreated but not paeoniflorin-treated DM rats. In conclusion, our data suggest that the preventive effects of paeoniflorin may be mediated by its antiinflammatory actions.
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PMID:Paeoniflorin prevents diabetic nephropathy in rats. 2003 31


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