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)

Angiotensin-converting enzyme inhibitors (ACEi) are a class of antihypertensive agents that decrease mortality in congestive heart failure and have established efficacy in the treatment of hypertension and the slowing of established diabetic nephropathy and other proteinuria-associated glomerulonephritides. These drugs have not gained wide acceptance in the treatment of hypertension in renal transplant recipients (RTRs) because of a potential for decreased renal blood flow and glomerular filtration rate associated with a single kidney and concomitant cyclosporine use. Experimental animal models suggest that ACEi may be of benefit in slowing the progression of chronic renal allograft rejection. We undertook a retrospective chart analysis of all RTRs in our institution who had been treated with an ACEi or an angiotensin II (AT II) antagonist, with the objectives of determining the safety, efficacy, and side effect profile of these medications. The minimum follow-up period was 6 months. One hundred seventy-seven of 642 RTRs were prescribed an ACEi or AT II antagonist. Forty-seven patients discontinued therapy, with the most common causes of discontinuation being cough (8 patients) and hyperkalemia (6 patients). The mean arterial blood pressure at each follow-up period was lower than that at the time of initiation of ACEi or AT II antagonist therapy, with a decrease from 92 +/- 12 mm Hg to 86 +/- 9 mm Hg (P < 0.05) after 3 years of treatment. The serum creatinine concentrations did not change throughout the follow-up period. There was a nonsustained increase from the baseline serum potassium of 4.4 +/- 0.5 to 4.6 +/- 0.6 mEq/L at 3 months (P < 0.05), but no further increases in potassium beyond this time. The mean hemoglobin concentration for the cohort did not change, but 13 RTRs given an ACEi for posttransplantation erythrocytosis (PTE) had a decrease in hemoglobin from 17.1 +/- 1.0 g/dL at the start of ACEi therapy to 14.8 +/- 2.2 g/dL at 3 years (P < 0.05). ACEi and AT II antagonists were generally effective antihypertensives, and were safe and well-tolerated agents in this cohort of RTRs. ACEi were also effective in the treatment of PTE.
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PMID:ACE inhibitors and angiotensin II antagonists in renal transplantation: an analysis of safety and efficacy. 1062 May 59

A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy. Serum erythropoietin level was 181 mU/mL (181 IU/L). Gastroscopy results showed rough mucosa with hemorrhaging caused by gastric cancer. The patient underwent distal gastrectomy, and serum erythropoietin level decreased to 27.1 mU/mL (27.1 IU/L) by postoperative day 8. Existence of erythropoietin in the tumor tissue was confirmed immunohistochemically. The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis.
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PMID:EPO-producing gastric carcinoma in a hemodialysis patient. 1283 Apr 87

While anemia is common in patients on chronic hemodialysis (HD), spontaneous erythrocytosis is rare and can be caused by either the same conditions causing erythrocytosis in the general population or any condition specific to chronic renal failure. We present a patient illustrating this latter circumstance. A 53-year-old man with diabetic nephropathy, with no known disease causing hypoxemia started HD in April 2001. Blood hemoglobin (Hgb) level was 13.7 +/- 2.8 g/dL while his kidney function was normal (1993-1996) and after 1997, with the development of chronic kidney disease, decreased progressively to a low of 10.2 g/dL in March 2001 when erythropoietin (EPO) injections were started. Erythropoietin requirements progressively decreased because of rising Hgb. Erythropoietin was discontinued in mid-2005. Blood hemoglobin continued to rise, however, to a high value of 17.6 g/dL in February 2006. At the same time, endogenous blood EPO level was 3.6 mIU/mL, a value consistent with primary polycythemia. White blood cell and platelet counts were normal. Several small renal cysts, including 1 complex cyst, were detected by ultrasonography and computer tomography in April 2006. He refused surgical treatment. He was treated with small phlebotomies (not returning the blood in the dialyzer at the end of dialysis) and monitoring of Hgb, which decreased toward the desired range. Repeated computer tomographic scans showed a slow increase in the size of the complex cyst and several other cysts. In late 2007 Hgb started rising again, and in February 2008, while the Hgb level was 16.4 g/dL, the endogenous serum EPO level was 726 mIU/mL (upper normal limit 31.5 mIU/mL). Intermittent phlebotomies were reinstituted. He subsequently developed multiple vascular catastrophes and expired from ischemic bowel disease in September 2008. Acquired cystic disease of the kidneys should be considered in HD patients who develop spontaneous erythrocytosis. The risks of acquired cystic disease include, in addition to the development of malignancy, vascular events from elevated Hgb.
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PMID:Spontaneous erythrocytosis in a patient on chronic hemodialysis. 1977 22

Chronic hypoxia induces sequential abnormalities in oxygen metabolism (for example, oxidative stress, nitrosative stress, advanced glycation, carbonyl stress, endoplasmic reticulum stress) in the kidneys of individuals with diabetes. Identification of these abnormalities improves our understanding of therapeutic benefits that can be achieved with antihypertensive agents, the control of hyperglycemia and/or hyperinsulinemia and the dietary correction of obesity. Key to the body's defense against hypoxia is hypoxia-inducible factor, the activity of which is modulated by prolyl hydroxylases (PHDs)-oxygen sensors whose inhibition may prove therapeutic. Renal benefits of small-molecule PHD inhibitors have been documented in several animal models, including those of diabetic nephropathy. Three different PHD isoforms have been identified (PHD1, PHD2 and PHD3) and their respective roles have been delineated in knockout mouse studies. Unfortunately, none of the current inhibitors is specific for a distinct PHD isoform. Nonspecific inhibition of PHDs might induce adverse effects, such as those associated with PHD2 inhibition. Specific disruption of PHD1 induces hypoxic tolerance, without angiogenesis and erythrocytosis, through the reprogramming of basal oxygen metabolism and decreased generation of oxidative stress in hypoxic mitochondria. A specific PHD1 inhibitor might, therefore, offer a novel therapy for abnormal oxygen metabolism not only in the diabetic kidney, but also in other diseases for which hypoxia is a final, common pathway.
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PMID:Diabetic nephropathy: a disorder of oxygen metabolism? 2001 Aug 96