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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impaired renal function occurs in about 50% of patients suffering from type 2 diabetes, and diabetic nephropathy has become the leading cause of endstage renal disease. Reduction of blood pressure to levels around 120/80 mmHg is one of the most effective way to slow progression of diabetic nephropathy. Recent meta-analyses, however, have emphasized on the fact that ACE inhibitors (ACEI) and non-dihydropyridine calcium channel blockers (NDHP-CCB) exert nephro-protective effects which go beyond the effect of blood pressure reduction. This has lately been confirmed by a prospective trial in comparison to the betablocker atenolol. Based on these data, demographics of the Swiss population, literature data on mortality rates of type 2 diabetics with impaired renal function and studies on true costs of antihypertensives, we calculated the costs of a longterm intervention (20 years) with antihypertensives in 3536 middle-aged Swiss patients with type 2 diabetes and macro-albuminuria whose antihypertensive regimen was based either on the ACEI lisinopril, or the ND-HP-CCB verapamil, or the betablocker atenolol. Under atenolol, acquisition costs were lowest, whereas faster loss of renal function over time increased mortality rate and thus reduced the number of patients to be treated. Nevertheless, due to the fact that patients reached uremia and had to be dialyzed, 20 years of atenolol-based regimen with costs of 316 millions of Swiss francs turned out to be much more expensive than the lisinopril- or the verapamil-based regimen with 121 and 38 millions of Swiss francs, respectively. Thus, low acquisition cost is not necessarily the only important determinant of overall costs of drug therapy.
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PMID:[Medicamentous kidney protection in type 2 diabetic patients--is cheaper also more economical? A model calculation for Swiss health care]. 1207 Oct 84

Calcific uremic arteriolopathy (CUA), also referred to as calciphylaxis, is a syndrome of small vessel calcification of unknown etiology causing painful violaceous skin lesions that progress to non-healing ulcers and gangrene. It is observed mainly in patients with end-stage renal disease, is associated with high morbidity and mortality and has no standard treatment at the present time. Although parathyroidectomy (PTX) has been advocated in some cases, other studies have not found this effective. Hyperbaric oxygen therapy (HOT) consists of breathing 100% O2 at higher than ambient pressure, with the patient inside a sealed chamber. HOT has been used with some success in the treatment of selected problem wounds (those that fail to respond to established medical and surgical management). They are often severely hypoxic; restoration of tissue PO2 to normal or above-normal enhances fibroblast proliferation and collagen production as well as angiogenesis. The present is the largest retrospective case series of CUA treated by means of HOT reported so far and comprises 11 chronic uremic patients on dialysis (9 hemo- and 2 peritoneal dialysis, 6 females and 5 males, mean age 56 +/- 7 SD years, time on dialysis 163 +/- 84 SD months). Four patients had biopsy-proven CUA; 3 had diabetic nephropathy as a cause of uremia; 2 were obese and 3 had a consistent increase of serum calcium x phosphorus product; 3 patients had severe secondary hyperparathyroidism (II(nd) HPTH) and two had been submitted to subtotal PTX some years before CUA; two others had already had the limb amputated. Lesions were in the legs, except for one in a hand, and were prevalently ulcers and necrosis. The number of sessions in each HOT cycle ranged from a minimum of 20 to a maximum of 108 (mean 40.6 +/- 29.0). The results of two therapies cannot be evaluated (one was interrupted by the patient after 10 sessions, and one ended with the death of the patient due to ventricular arrhythmia after eight sessions). Eight of the nine remaining had excellent results with healing of the skin ulcers, but the ninth got worse, making it advisable to amputate the foot. In conclusion, CUA appears to result from a multitude of predisposing and/or sensitizing events that are commonly present in the uremic milieu. The specific factors that induce this disorder in an individual patient are not known. The present retrospective study supports a role of HOT in many cases of CUA, especially considering that, in the absence of severe II(nd) HPTH, there are very few therapeutic options.
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PMID:Hyperbaric oxygen therapy for calcific uremic arteriolopathy: a case series. 1249 83

Renal involvement in patients with type 2 diabetes will (probably) be one of the most important clinical problems for nephrologists to face during the next few years. Unlike type 1 diabetes, in type 2 diabetes the renal damage has not yet been well defined at both clinical and pathological levels. Pathological examination of renal biopsies has displayed different patterns of renal damage including diabetic glomerulosclerosis (Class 1), mostly chronic vascular changes (Class 2) and superimposed glomerular diseases (Class 3a) or unrelated to diabetic glomerulosclerosis (Class 3b). Despite the large number of papers published in this field, the actual prevalence and outcome of the different histological classes still remain to be established. Reported discrepancies are most likely caused by ethnic and geographic factors. However, as documented by a recent study carried out on a large number of patients, the prevalence of histological patterns is also greatly influenced by the policy for performing renal biopsies adopted at the various nephrological centers. Although the natural history of type 2 glomerulosclerosis (Class 1) still remains to be defined, those patients with clinical nephropathy and impairment of renal function have very poor outcome with a high rate of mortality and progression to uremia. Moreover, when diabetic glomerulosclerosis is complicated by superimposed glomerular diseases (Class 3a) the prognosis is much worse. On the contrary, when glomerular diseases are not associated with glomerulosclerosis lesions (Class 3b) the prognosis is markedly better. During the last ten years controlled studies have shown that the outcome in type 1 diabetic nephropathy has improved as a result of the use of drugs inhibiting the renin-angiotensin system. Although it is likely that this type of drug might also favourably influence the outcome of type 2 diabetic nephropathy, any conclusive evidence is presently still lacking.
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PMID:[Renal damage in type 2 diabetes]. 1264 81

It is well known that the addition of spermine or spermidine to culture medium containing ruminant serum inhibits cellular proliferation. This effect is caused by the products of oxidation of polyamines that are generated by serum amine oxidase. Among the products, we found that acrolein is a major toxic compound produced from spermine and spermidine by amine oxidase. We then analysed the level of polyamines (putrescine, spermidine and spermine) and amine oxidase activity in plasma of patients with chronic renal failure. It was found that the levels of putrescine and the amine oxidase activity were increased, whereas spermidine and spermine were decreased in plasma of patients with chronic renal failure. The levels of free and protein-conjugated acrolein were also increased in plasma of patients with chronic renal failure. An increase in putrescine, amine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. These results suggest that acrolein is produced during the early stage of nephritis through kidney damage and also during uraemia through accumulation of polyamines in blood due to the decrease in their excretion into urine.
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PMID:Acrolein produced from polyamines as one of the uraemic toxins. 1265 41

Advanced glycation end products (AGE) are filtered by glomeruli and reabsorbed and metabolized by proximal tubule cells (PTC). In renal failure, decreased renal AGE metabolism likely accounts for the accumulation in serum that is related to uremic complications. In diabetes, AGE generation is increased, and the handling mechanisms in PTC are likely associated with the pathogenesis of tubulointerstitial injury. It is therefore important to clarify the mechanisms of the AGE metabolism to develop a strategy for removing AGE in uremia and to elucidate the pathogenesis of diabetic nephropathy. To this end, this study focused on the molecular analysis of megalin, a multi-ligand endocytic receptor, in PTC. AGE uptake analysis was performed using the rat yolk sac-derived L2 cell line system established for the analysis of megalin's endocytic functions. The cells mediated specific internalization and degradation of AGE, which were significantly blocked by anti-megalin IgG, indicating that megalin is involved in the cellular processes. However, cell surface AGE-binding assays and ligand blot analysis revealed no evidence that megalin is a direct AGE receptor. Affinity chromatography and ligand blot analysis originally revealed that 200-kD and 400-kD proteins in the cells bind to AGE and the 200-kD protein to megalin in a Ca(2+)-dependent manner. The binding of megalin with the 200-kD protein was suppressed by receptor-associated protein (RAP), a ligand for megalin. In conclusion, megalin functions for endocytosis of AGE via an indirect mechanism. L2 cells express novel AGE-binding proteins, one of which may interact with megalin.
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PMID:Role of megalin in endocytosis of advanced glycation end products: implications for a novel protein binding to both megalin and advanced glycation end products. 1270 83

Diabetic nephropathy has become the leading cause of uremia. Several lines of evidence suggest dietary factors other than protein intake have a substantial role in the progression of diabetic nephropathy to end-stage renal disease. The present investigation was initiated to evaluate whether a carbohydrate-restricted, low-iron-available, polyphenol-enriched (CR-LIPE) diet may delay and improve the outcome of diabetic nephropathy to a greater extent than standard protein restriction. To this aim, 191 diabetic patients, all with type 2 diabetes, were randomized to either CR-LIPE or standard protein restriction and the following outcomes monitored: doubling of serum creatinine, cumulative incidence of end-stage renal disease, and all cause mortality. Over a mean follow-up interval of 3.9 +/- 1.8 years, serum creatinine concentration doubled in 19 patients on CR-LIPE (21%) and in 31 control subjects (39%) (P < 0.01). Renal replacement therapy or death occurred in 18 patients on CR-LIPE (20%) and in 31 control subjects (39%) (P < 0.01). These differences were independent from follow-up interval, sex, mean arterial blood pressure, HbA(1c), initial renal dysfunction, and angiotensin system inhibitor use. In conclusion, CR-LIPE was 40-50% more effective than standard protein restriction in improving renal and overall survival rates.
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PMID:A low-iron-available, polyphenol-enriched, carbohydrate-restricted diet to slow progression of diabetic nephropathy. 1296 32

Mesangial expansion and glomerular basement membrane thickening characteristic of diabetic nephropathy recur in diabetic recipients of renal allografts from non-diabetic donors but progression to renal failure is minimally documented. Three female renal allograft recipients (aged 40, 62 and 73 yr), who developed end-stage renal disease (ESRD) due to recurrent diabetic nephropathy (two patients) and de novo diabetes (one patient) are reported. Onset of proteinuria, uncontrolled hypertension, azotemia, renal allograft pathologic findings and the need for hemodialysis were analyzed. None of the kidney donors (one cadaver, two living related) had known diabetes or perturbed glucose metabolism pre-transplantation. The three patients presented had different varieties of diabetes; type 1, type 2 and new onset diabetes after transplantation (NODAT). In each subject, proteinuria was detected by dipstick at a mean of 8.3 yr (range 8-9) post-transplantation and increased to the nephrotic range (3.7-4.8 g/day) inducing hypoalbuminemia and azotemia. A histopathologic diagnosis of allograft diabetic nephropathy was made in a mean of 11.7 yr (range 10-14), based on glomerular basement membrane thickening, nodular and diffuse intercapillary glomerulosclerosis, arteriolosclerosis, and tubular atrophy with marked tubular basement membrane thickening characteristic of advanced diabetic nephropathy. All three patients manifested uremia and resumed hemodialysis. Two patients died from sepsis within 2 months and one patient died 2.5 yr later after resumption of maintenance hemodialysis. We infer that recurrent or de novo diabetic nephropathy in renal allografts follows a clinical decade-long course irrespective of diabetes. Reports of ESRD due to allograft diabetic nephropathy (ADN) have been limited because of shorter survival of diabetic transplant recipients and few kidney biopsies performed in patients with chronic allograft dysfunction. The occurrence of allograft diabetic nephropathy in some, but not all patients, however, suggests that individual genetic variability modulates disease expression.
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PMID:Allograft diabetic nephropathy may progress to end-stage renal disease. 1526 61

In many countries, diabetic renal disease has become, or will soon become, the single most common cause of end-stage renal disease (ESRD). End-stage renal failure (ESRF) in type-2 diabetic patients is increasing worldwide. Incidence of ESRF caused by diabetic nephropathy (DN) in 1996 in the USA was 41.7% and prevalence was 32.4%. ESRD and ESRF caused by DN was 10%, 5-15% in different haemodialysis centres in adults in the year 2000 in the Republic of Macedonia. In this review article we discuss options in uraemia therapy for diabetics with ESRD. Assessment and treatment of a diabetic with ESRD must be highly individualized. Haemodialysis (HD) has emerged as the most common treatment for all forms of renal failure including diabetic nephropathy. In diabetics patients with ESRD, dialysis is started early at creatinine clearance as high as 15-20 ml/min, at serum creatinin levels as low as 3-5 mg/dl. The first choice of HD access in diabetics is an autologous a-v fistula of the Cimino-Brescia type. The A-V fistula should be created several months before starting HD when creatinine clearance is above 20-25 ml/min. When peritoneal dialysis (PD) is selected, advance planning should ensure that a suitable peritoneal catheter is in situ 2-4 weeks before starting dialysis. HD procedures should be with low ultrafiltration rates and prolonged duration of dialysis sessions. The ultrafiltration in diabetics should not exceed more than 500-600 ml/h on HD. This means dialysis sessions of more than 4h and, in larger patients, of more than 5h HD three times per week. Renal transplantation (RT) is a safe and effective treatment modality for diabetic subjects with ESRD. Cardiovascular disease and serious infections are the major causes of death in haemodialysed and transplanted diabetics. Despite recent improvement, rehabilitation of HD diabetics continues to be inferior to that of non-diabetics. Improvement of survival is a matter of reduction of cardiovascular death and infection.
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PMID:Options in uraemia therapy for diabetics with end-stage renal disease. 1573 34

There are close to 1 million people in the world who are alive simply because they have access to one form or another of renal replacement therapy (RRT). Ninety percent live in high-income countries. Little is known of prevalence and incidence of chronic kidney disease and of end-stage renal disease (ESRD) in middle-income and low-income countries, where the use of RRT is scarce or nonexistent. However, no intervention is undertaken, these people will experience progression to ESRD and death from uremia, because RRT is out of reach for them. These are the individuals for whom efforts should be focused to prevent or delay progression toward ESRD. In 1992, the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, with the cooperation of the young doctors of the Ospedale Giovanni XXIII in La Paz (Bolivia), activated a specific project titled "El Proyecto de Enfermedades Renales en Bolivia" (The Project for Renal Diseases in Bolivia). The project sought to demonstrate that in emerging countries the best strategies against renal disease are prevention and early detection. After proper training of local personnel at the Clinical Research Center "Aldo e Cele Dacco" of the Mario Negri Institute in Bergamo, Italy, an educational campaign titled "First Clinical and Epidemiological Program of Renal Diseases"-under the auspices of the Renal Sister Center Program of the International Society of Nephrology-was conducted in 3 selected areas of Bolivia, including tropical, valley, and plains areas. The goal was to define the frequency of asymptomatic renal disease in these areas by screening a large population of patients at relatively low costs. The screening was formally performed at first-level health centers (Unidad de Salud). Participants were instructed to void a clean urine specimen, and a dipstick test was performed. Patients with positive urinalysis were enrolled in a follow-up program with subsequent laboratory and clinical checks. The study was conducted by 21 clinical centers. Apparently healthy patients (14,082) were enrolled over a period of 7 months. Urinary abnormalities were found on first screening in 4261 patients, but only 1019 patients (23.9%) were available for follow-up. At second urinalysis, 35% of patients had no abnormalities. In the remaining positive group of patients, further investigations disclosed the following abnormalities: urinary tract infection (48.4%), isolated hematuria (43.9%), chronic renal failure (1.6%), renal tuberculosis (1.6%), and other diagnoses 4.3% (kidney stones, 1.3%; diabetic nephropathy, 1%; polycystic kidney diseases, 1.9%). The experience gained from this initial screening program formed the basis for a second study aimed to prevent renal disease progression in a selected Bolivian population with high altitude polycythemia. In conclusion, our studies show that mass screening of the population for renal disease is feasible in developing countries and can provide useful information on frequency of renal diseases. Also, in patients with altitude polycythemia, long-term treatment with low doses of enalapril safely prevents increase in arterial blood pressure and progressively reduces hematocrit and proteinuria. Aside from its scientific value, this last study can be taken as an example of how, by rationalizing resources and investing in research programs, renal disease progression and cardiovascular risk may eventually improve, which ultimately should translate into less demand for dialysis, and thus provide alternatives to costly RRT. The transformation of the Bolivian pilot model into a systematic program applicable to most emerging countries may be seen as a task of national nephrology societies, along with methodologic and economic support of international bodies.
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PMID:Strategies for national health care systems in emerging countries: the case of screening and prevention of renal disease progression in Bolivia. 1601 7

Advanced glycation end products (AGEs) are a heterogeneous group of protein and lipids to which sugar residues are covalently bound. AGE formation is increased in situations with hyperglycemia (e.g., diabetes mellitus) and is also stimulated by oxidative stress, for example in uremia. It appears that activation of the renin-angiotensin system may contribute to AGE formation through various mechanisms. Although AGEs could nonspecifically bind to basement membranes and modify their properties, they also induce specific cellular responses including the release of profibrogenic and proinflammatory cytokines by interacting with the receptor for AGE (RAGE). However, additional receptors could bind AGEs, adding to the complexity of this system. The kidney is both: culprit and target of AGEs. A decrease in renal function increases circulating AGE concentrations by reduced clearance as well as increased formation. On the other hand, AGEs are involved in the structural changes of progressive nephropathies such as glomerulosclerosis, interstitial fibrosis, and tubular atrophy. These effects are most prominent in diabetic nephropathy, but they also contribute to renal pathophysiology in other nondiabetic renal diseases. Interference with AGE formation has therapeutic potential for preventing the progression of chronic renal diseases, as shown from data of animal experiments and, more recently, the first clinical trials.
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PMID:Advanced glycation end products and the kidney. 1615 99


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