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 (ACE) inhibitors decrease albuminuria in patients with diabetic nephropathy. To study the change in albuminuria in relation to changes in systemic and renal hemodynamics, nine normotensive patients with type 1 (insulin-dependent) diabetes mellitus and persistent proteinuria were given a single oral dose of 25 mg of the ACE inhibitor captopril. Blood pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and albumin excretion rate (AER) were measured in two periods of 40 minutes before and in four periods of 40 minutes after administration of captopril. A constant water diuresis was maintained. Blood pressure did not decrease significantly (130/79 +/- 4/3 v 124/74 +/- 4/3 mm Hg; mean +/- SEM), median AER decreased from 403 (interquartile range [IQR], 812) micrograms/min to 333 (707) micrograms/min (P < 0.01). GFR did not change (123 +/- 13 v 117 +/- 14 mL/min), but ERPF increased significantly from 609 +/- 56 to 714 +/- 55 mL/min (P < 0.01). Consequently, the filtration fraction (FF; quotient of GFR and ERPF) decreased from 0.20 +/- 0.014 to 0.17 +/- 0.014 (P < 0.01). A strong correlation was found between the decrease of AER and the decrease of FF (rs = 0.75; P < 0.02). No correlation was found between the decrease in AER and changes in GFR or blood pressure. In the normotensive patient with diabetic nephropathy, captopril causes an acute reduction of AER, which is probably mediated by a lowering of the intraglomerular pressure.
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PMID:Captopril acutely lowers albuminuria in normotensive patients with diabetic nephropathy. 146 82

Diabetic nephropathy leading to kidney failure is a major complication of type I (insulin-dependent) diabetes mellitus and is associated with progressive proteinuria. In the present 6-month study, effects of two structurally dissimilar aldose reductase inhibitors (sorbinil and ponalrestat or Statil) were examined on prevention of proteinuria in insulin-dependent spontaneously diabetic BB rats and compared with age-matched BB resistant controls. Prior to aldose reductase inhibitor treatment, all diabetic BB rats exhibited hyperglycemia (> 300 mg/dl), glycosuria (> 2,000 mg/dl) and 24-hour urinary protein excretion ranging from 5.01 to 11.23 mg/day. After daily administration of ponalrestat (20 mg/kg) for 3 months, 24-hour urinary protein excretion was 11.53 +/- 1.76 mg/day in ponalrestat-treated rats, despite persistence of hyperglycemia (444 +/- 31 mg/dl) and glycosuria (> 2,000 mg/dl); by contrast, urinary protein excretion was 17.76 +/- 2.59 mg/day in the control group of untreated BB diabetic rats. Ponalrestat initially protected against excretion of an array of urinary proteins having molecular weights between 30,000 and 100,000 daltons. These effects sustained throughout the 4th month of treatment, tended to change toward valves in control rats by the 5th month. At the end of 6 months, ponalrestat-treated diabetic rats excreted 18.73 +/- 3.20 mg/day of protein, similar to valves in untreated BB diabetic rats; both demonstrated a 4-fold increase in urinary protein excretion when compared to age-matched BB resistant controls. Proteinuria was attributed to an increase in albumin and an array of proteins having molecular weights between 30,000 and 100,000 daltons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of sorbinil and ponalrestat (Statil) diminution of proteinuria in the BB rat. 146 75

Between September 1984 and August 1991, 265 whole pancreaticoduodenal transplants were done at our institution, with bladder drainage of exocrine secretions through a duodenocystostomy. Seventeen patients subsequently underwent conversion from bladder to enteric drainage at 2 to 64 months after transplant. Eight conversion procedures were done to correct chronic intractable metabolic acidosis due to bicarbonate loss from the allograft: seven to alleviate severe dysuria, presumed secondary to the action of graft enzymes on uroepithelium; one to prevent recurrent allograft pancreatitis, presumed secondary to back pressure from the bladder; and one because of graft duodenectomy for severe cytomegalovirus duodenitis with perforation. None were done to correct technical complications from the initial transplant operation. The conversions were done by dividing the graft duodenocystostomy, then re-establishing drainage through a graft duodenal-recipient jejunal anastomosis. A simple loop of recipient jejunum was used for the duodenojejunostomy in 15 cases, and a Roux limb in two. One of those two cases had a previously created Roux limb that was available for use. The other was in the patient who underwent graft duodenectomy and subsequent mucosa-to-mucosa anastomosis of the pancreatic duct to a newly created Roux limb of jejunum. All patients experienced relief of their symptoms after operation. Two patients had surgical complications (12%), an enterotomy in one case, which was closed operatively, and an enterocutaneous fistula in the other case, which healed spontaneously with bowel rest and parenteral nutrition. The drawback to conversion is loss of urine amylase as a marker for rejection, particularly in recipients of solitary pancreas grafts (n = 5). In recipients of simultaneous pancreas-kidney (SPK) allografts (n = 12), the kidney can still be used to monitor for rejection (two with follow-up < 1 year, 10 with follow-up > 1 year). None of our solitary pancreas recipients, however, have lost graft function (follow-up, 10 to 36 months). The only pancreas allograft loss was in an SPK recipient who also rejected the kidney 6 months after conversion. She received a second SPK transplant with enteric drainage, and is insulin independent and normoglycemic 10 months after retransplantation. Patients converted for metabolic acidosis tended to have impaired renal function (mean creatinine, 2.14 +/- 0.98 mg/dL at time of conversion) due to chronic rejection, progression of native kidney diabetic nephropathy, or cyclosporine toxicity, and possibly could not compensate for bicarbonate loss from the pancreas allograft.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Conversion of exocrine secretions from bladder to enteric drainage in recipients of whole pancreaticoduodenal transplants. 146 20

To clarify the morphological changes in renal proximal tubules at the onset of diabetic nephropathy, we observed 177 biopsy samples from patients with Non-Insulin-Dependent Diabetics (NIDDM) using light and electron microscopy. Group I had no proteinuria (p.u.), group II had p.u. < or = 0.5 g/day, group III had p.u. > 0.5 g/day, group IV had serum creatine level (Cr) > 1.5 mg/dl. Twenty age-matched normal patients and 80 patients with IgA nephropathy were used as controls. In groups I and II, the following features were significantly different from those in the controls: spherical enlargement of mitochondria (MT) in proximal tubule cells, hypertrophy of proximal tubule cells and their nuclei, and thickening of both the proximal tubule basement membrane (TBM) and the glomerular basement membrane (GBM). Among the histological changes observed in group I, the thickness of the GBM and TBM indicated that the disease would lead to diabetic nephropathy. MT enlargement was positively correlated with nuclear and cytoplasmic enlargement of the proximal tubule cells in diabetic patients (p < 0.05), but was not correlated with other morphological changes or disease prognosis. Glomerular nodular lesions, glomerular sclerotic change, and cortical tubulointerstitial fibrosis became evident in groups III and IV. From the above, we concluded that MT enlargement and thickening of the TBM are possible causes of reduced active transport in the proximal tubules, causing microalbuminuria in diabetics, and initial impairment of post-tubule transport.
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PMID:Mitochondrial enlargement and basement membrane thickening of renal proximal tubules, possible initiators of microalbuminuria in non-insulin-dependent diabetics (NIDDM). 147 27

The genetically determined acetylator phenotype in diabetic children with and without increased urinary albumin excretion was investigated. Acetylator phenotype was determined according to Evans, and 24-hour albumin excretion rate (AER) was measured by immunoturbidometry in 86 children and adolescents with type 1 (insulin-dependent) diabetes mellitus and in 100 age-matched healthy controls. In diabetics, the fast acetylator phenotype was found in 36 (41.9%) patients and the slow one in 50 (58.1%); the control group had 52 (52%) fast and 48 (48%) slow acetylators. There were no significant differences in acetylator phenotypes between diabetic patients and control subjects (chi 2 = 1.0, NS). Among patients with normal albumin excretion (n = 70, mean age: 12.9 +/- 3.5 years, mean diabetes duration: 5.3 +/- 3.8 years, AER < 20 micrograms/min), 35 (50%) fast acetylators and 35 (50%) slow acetylators were found. In patients with elevated albumin excretion (n = 16, mean age: 14.0 +/- 3.2 years, mean diabetes duration: 4.9 +/- 3.0 years, AER > 20 micrograms/min), 1 (6.3%) patient was a fast acetylator and 15 (93.7%) were slow acetylators. A significant difference has been found between the two groups in the rate of fast/slow acetylators (chi 2 = 8.79, p < 0.01). The strong correlation between the slow acetylator phenotype and microalbuminuria in diabetics suggests that: (a) genetic factors may play a role in the development of diabetic nephropathy; (b) the acetylator status could be a useful tool to detect patients 'at risk' of nephropathy.
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PMID:Association of microalbuminuria with slow acetylator phenotype in type 1 diabetes mellitus. 147 91

Patients with Type 2 (non-insulin-dependent) diabetes mellitus complicated by microalbuminuria or albuminuria, have an increased risk of developing macrovascular disease and of early mortality. Because lipoprotein abnormalities have been associated with diabetic nephropathy, this study tested the hypothesis that levels of apolipoprotein (a) are elevated in patients with Type 2 diabetes and increased levels of urinary albumin loss. Levels of apolipoprotein (a) in diabetic patients with microalbuminuria (n = 26, geometric mean 195 U/l, 95% confidence interval 117-324) and albuminuria (n = 19, 281 U/l, 165-479) were higher than in non-diabetic control subjects (n = 140, 107 U/l, 85-134, p < 0.05), and in the albuminuric group than diabetic patients without urinary albumin loss (n = 58, 114 U/l, 76-169, p < 0.05). Patients with microalbuminuria and albuminuria had levels comparable with patients undergoing elective coronary artery graft surgery (n = 40, 193 U/l, 126-298). Apolipoprotein (a) levels were higher in diabetic patients with macrovascular disease than in those without (n = 49, 209 U/l, 143-306 vs n = 54, 116 U/l, 78-173, p < 0.05). These preliminary results suggest that raised apolipoprotein (a) levels of Type 2 diabetic patients with microalbuminuria and albuminuria may contribute to their propensity to macrovascular disease and early mortality.
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PMID:Plasma apolipoprotein (a) is increased in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria. 147 15

The association between diurnal blood pressure variation and diabetic nephropathy was assessed in four groups of Type 1 (insulin-dependent) diabetic patients who underwent 24-h ambulatory blood pressure monitoring using an oscillometric technique. Patients with nephropathy, who had never been treated for hypertension (group D3, n = 13), were individually matched for age, sex and diabetes duration to a group of microalbuminuric patients (D2, n = 26), to normoalbuminuric patients (D1, n = 26) and to healthy control subjects (C, n = 26). Group D3 was also compared to patients with advanced nephropathy receiving treatment for hypertension, mainly a combination of angiotensin converting enzyme inhibitors, metoprolol and diuretics (D4, n = 11). In group D3 24-h diastolic blood pressure (85 +/- 8 mm Hg) was comparable to the results obtained in D4 (85 +/- 8 mm Hg) but significantly higher than in D2 (78 +/- 7 mm Hg), D1 (73 +/- 7 mm Hg) and C (73 +/- 7 mm Hg, p < 0.05, Tukey's test). The night/day ratio of diastolic blood pressure was higher in D3 (86 +/- 5%) and D2 (85 +/- 7%) than in C (80 +/- 7%, p < 0.02). This ratio was also elevated in group D4 (94 +/- 8%) compared to D3 (p < 0.05) corresponding to a marked smoothing of the diurnal blood pressure curve. The 24-h heart rate (beats per min) was significantly elevated in D3 (84 +/- 8) and D2 (80 +/- 10) compared with C (73 +/- 11, p < 0.05 Tukey's test), suggesting the presence of parasympathetic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circadian variation of blood pressure in patients with diabetic nephropathy. 833 83

Plasma concentrations of lipids and apolipoproteins (Apo) were determined in 34 patients with long-standing type I (insulin-dependent) diabetes mellitus. Twenty-four patients had renal insufficiency (GFR 4 to 55 ml/min) due to diabetic nephropathy, while 10 patients had no clinical signs of nephropathy. Results were compared with those in 42 non-diabetic patients with comparable degree of renal insufficiency and with asymptomatic control subjects. Diabetic patients without nephropathy had plasma lipid and apolipoprotein concentrations similar to those of the control subjects. Diabetic patients with renal insufficiency had a significant increase in triglycerides (TG) and, to a lesser extent, in total cholesterol (TC). The patients also had reduced levels of ApoA-I and ApoA-II, increased levels of ApoC-II and ApoC-III, while increases in levels of ApoB and ApoE were statistically significant in patients with GFR < 20 ml/min. These lipids and apolipoprotein abnormalities were accentuated with decreasing renal function. The reduction in the ApoA-I/ApoC-III ratio characteristic of renal insufficiency was found in normo- and hyper-TG diabetic patients with nephropathy; this ratio was correlated with the GFR levels. Patients with higher HbA1C values had higher levels of ApoC-II and ApoC-III. The findings in the diabetic patients corresponded with those in non-diabetic patients with renal insufficiency. However, diabetic patients had higher ApoC-III and ApoE levels. The abnormalities of lipid metabolism in diabetic renal insufficiency seem to reflect primarily metabolic impairments characteristic of renal insufficiency, but may be further accentuated by the diabetic state and the metabolic control.
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PMID:Dyslipoproteinemia in diabetic renal failure. 147 69

We first compared glomerular charge selectivity index in two matched groups of Type 1 (insulin-dependent) diabetic patients with micro- and normoalbuminuria respectively, and secondly, investigated prospectively in a randomized clinical trial, the influence of improved metabolic control on selectivity index in diabetic patients with microalbuminuria. In Study 1, 27 patients with microalbuminuria (albumin excretion > or = 15 micrograms/min in at least two out of three overnight urine samples) were matched (age, diabetes duration, mean 1-year HbA1c, gender) with normoalbuminuria patients (n = 24), and in Study 2, 23 microalbuminuric patients were randomly allocated to either intensive (continuous subcutaneous insulin infusion) or conventional treatment. Glomerular charge selectivity index was measured as IgG/IgG4 selectivity index, i.e. total IgG/IgG4 clearance ratio in timed overnight urine samples. The microalbuminuric patients had a significantly reduced selectivity index compared to the normoalbuminuric patients: 1.20 (0.92-1.40) vs 1.68 (1.22-2.21), median and 95% confidence interval (p < 0.01). In Study 2, the HbA1c improved in the intensive-treatment group compared to the conventional-treatment group: at 2, 6 and 12 months the difference in mean percentage HbA1c between the groups was 1.1, 1.2 and 1.4, respectively (p < 0.01). A sharp 50% increment in IgG/IgG4 selectivity index was seen in the intensive-treatment group during the first 6 months (p < 0.05 compared to the conventional group). We conclude that adolescents and young adults in an early stage of diabetic nephropathy have reduced glomerular charge selectivity, which may be improved by reducing the mean blood glucose level.
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PMID:Glomerular charge selectivity and the influence of improved blood glucose control in type 1 (insulin-dependent) diabetic patients with microalbuminuria. 147 69

New treatment strategies for subjects with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are being developed. Pilot studies utilising insulin itself have been reported to prevent Type 1 diabetes in subjects likely, by immunogenetic and physiologic criteria, to develop clinically overt disease, while the results of nicoti-namide trials in these subjects remain preliminary. Immunotherapy with cyclosporin A and azathioprine can slow disease progression and may produce long-term remissions when given within two months of onset of clinically overt disease. In subjects with established disease, familial clustering of diabetic nephropathy may be related to concomitant susceptibility to hypertension and elevated rates of Na/H countertransport. Treatment of hypertension associated with the nephropathy appears to slow renal deterioration. Whether reversal of the metabolic consequences of insulin deficiency or resistance also prevents chronic diabetic complications has not been firmly established. In the presence of a reduced Beta-cell mass, moderate hyperglycaemia may itself contribute to decreased muscle glucose uptake but not glycogen synthesis in Type 1 and Type 2 diabetes. Reversal of chronic hyperglycaemia by pancreas and islet cell transplantation, vanadate, and sulphonylureas are discussed as alternate strategies to insulin treatment in establishing normoglycaemia and furthering our understanding of insulin action and secretion at the cellular level. There remains a need to develop more sensitive biochemical and genetic markers to identify subjects at increased risk for developing chronic diabetic complications.
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PMID:Treatment of diabetes mellitus. 147 80


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