Optimizing antihypertensive therapy in patients with diabetic nephropathy

The number of cases of diabetic nephropathy is increasing, especially among patients with non-insulin-dependent diabetes mellitus (NIDDM). It is difficult to prevent the occurrence or progression of NIDDM, and current levels of treatment are below standard. According to one study, actuarial 5-year survival rates are only about 38% for patients with insulin-dependent diabetes mellitus and 9% for those with NIDDM receiving renal replacement therapy. Because cardiovascular diseases are responsible for more than half of these deaths, hypertension, as a major contributing factor to cardiac death, is a crucial component in the therapy for such patients. It is well established that lowering blood pressure is an important preventive measure to be taken in patients with diabetic nephropathy; blockade of the renin-angiotensin system offers benefits beyond lowering blood pressure in type I diabetic nephropathy. Two major trials are currently underway to determine the effects of angiotensin II receptor antagonists on nephropathy in patients with NIDDM. The Irbesartan Diabetic Nephropathy Trial (IDNT) has already enrolled approximately 85% of the proposed 1650 NIDDM patients to be randomly assigned to placebo, irbesartan or amlodipine. Baseline characteristics of the initial cohort are presented. In light of the well-documented case for blockade of the renin-angiotensin system in diabetes, the potentially superior blockade afforded by angiotensin II receptor antagonists, and the superior tolerability of these agents, trials such as the IDNT take on special importance for the treatment of diabetic patients. From these data may come the justification for the belief that angiotensin II receptor antagonists impart greater benefits in the treatment of diabetes than merely their well-documented role in lowering blood pressure.     

Diabetic patients with IgA nephropathy and diabetic glomerulosclerosis

Eleven diabetic patients with biopsy-proven IgA nephropathy were studied. Seven exhibited coexistence of both IgA nephropathy and diabetic glomerulosclerosis and the remaining four patients had IgA nephropathy without diabetic lesion. The clinicopathological features and follow-up of those patients with IgA nephropathy surperimposed on diabetic glomerulosclerosis were compared with a similar group of patients with diabetic glomerulosclerosis alone. Our observation suggests that the occurrence of both glomerulopathies was fortuitous with IgA nephropathy coexisting with or preceding diabetic glomerulosclerosis. There was no apparent causal relationship between the two glomerulopathies. The renal outcome is poor in both groups of patients and is possibly related to diabetic glomerulosclerosis.     

Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy

Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50 healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1, 128 (x/ divided by 3.5) U l-1 and 126 (x/ divided by 3.7) U l-1 (geometric mean (x/ divided by antilog SD)) in group 1, 2, 3 and 4, respectively. 1 U l-1 apo(a) approximates 0.7 mg l-1 Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)     

糖尿病肾病血液透析患者的临床特点及护理

目的:探讨糖尿病肾病透析患者的临床特点及护理对策.方法:选择40例糖尿病肾病及同期非糖尿病肾病血液透析患者,分别观察存活率、死亡原因、营养状况和并发症.结果:糖尿病肾病组1年和2年存活率较非糖尿病肾病组低(P<0.05,P<0.01),主要死因为心血管病变和严重感染;糖尿病肾病组Alb和Hb较非糖尿病肾病组低,差别有统计学意义(P<0.01,P<0.01);DN组血液透析中的并发症是低血压35%、低血糖35%和感染30%,与非糖尿病肾病组比较差别有统计学意义(P<0.05,P<0.01,P<0.01).结论:糖尿病肾病血液透析患者是一组高危人群,存活率低,营养状况差,应加强饮食指导;重视透析透析期间护理,降低透析中并发症的发生率,提高存活率和生活质量.     

Prevalence of diabetic nephropathy in adult patients with chronic kidney failure

Diabetic nephropathy is a frequent cause of end-stage renal failure in patients admitted for renal replacement therapy. PURPOSE: To evaluate the prevalence of DN, as the underline disease, in patients with ESRF. METHODS: 1,303 [male (M) = 767 and female (F) = 536] patients with ESRF who were on a waiting list for cadaver kidney transplant at Nephrology Unit-University Hospital (HC-UNICAMP), from August/90 to June/93--group 1--and 193 (M = 112 and F = 81) patients admitted for renal replacement therapy in a year period (April/92 to March/93), in the city of Campinas, State of S?o Paulo, Brazil, were studied. RESULTS: The prevalence of DN was 10.1% in group 1 and 17.6% in group 2 (x2 = 7.15; p = 0.007), being the third cause of ESRF in both groups, and it was preceded by glomerulonephritis and arterial hypertension. In group 1 the reduction of number of patients with increase in duration of dialysis was significantly greater in patients with diabetic nephropathy (x2 = 30.9; p < 0.001). Among patients with DN 35 (26%) in group 1 and 6 (18%) in group 2 had less than 35 years when they were admitted for renal replacement therapy and are likely to be type 1 (insulin-dependent) diabetic patients. CONCLUSION: In our studied groups DN was a frequent cause of ESRF.     

The course of kidney function in type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy

We evaluated the impact of some putative progression promoters on kidney function in albuminuric Type 2 (non-insulin-dependent) diabetic patients with biopsy-proven diabetic glomerulosclerosis. Twenty-six patients (1 female) with a mean age of 52 (standard error 2) years and a known mean duration of diabetes of 9 (1) years were followed-up prospectively for a mean of 5.2 (range 1.0-7.0) years. Twenty-one patients received antihypertensive treatment. During the observation period the glomerular filtration rate decreased from 83 (24-146) to 58 (2-145) ml.min-1 x 1.73 m-2 (mean (range)) (p < 0.001). The mean rate of decline in glomerular filtration rate was 5.7 (-3.5 to 22.0) ml/min per year. Albuminuria increased from 1.2 (0.3-7.2) to 2.3 (0.4-8.0) g/24 h (geometric mean (range)) (p < 0.001). Arterial blood pressure remained unchanged: 162/93 (SE 4/3) and 161/89 (4/2) mm Hg. Univariate analysis showed the rate of decline in glomerular filtration rate to correlate with systolic blood pressure (r = 0.71, p < 0.001), mean blood pressure (r = 0.56, p < 0.005), albuminuria (r = 0.58, p < 0.005) and the initial glomerular filtration rate (r = -0.49, p < 0.02). The rate of decline in glomerular filtration rate did not correlate significantly with dietary protein intake, total cholesterol, high-density lipoprotein cholesterol or HbA1c. Three patients died from uraemia and four patients died from cardiovascular disease. Two patients required renal replacement therapy at the end of the observation period. Our prospective observational study revealed that one-fifth of the patients developed end-stage renal failure during the 5-year observation period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.     

Increased excretion of urinary transforming growth factor beta 1 in patients with diabetic nephropathy

Two cases of double outlet right ventricle with restrictive ventricular septal defect are described. This is an uncommon presentation that causes left ventricular dysfunction because of left ventricular outflow tract obstruction. The presence of an intact atrial septum leads to severe pulmonary hypertension, which tends to aggravate the right ventricular output. In the presence of a normal left ventricle, the authors suggest the possibility of enlargement of the ventricular septal defect in order to perform a biventricular repair. The association of a supramitral valve ring in both cases, and the isolation of the left subclavian artery and an aortopulmonary fenestration in one of these cases, are also discussed. In addition we explore factors that cause restrictive ventricular septal defects as well as the mechanisms that may lead to spontaneous closure of ventricular septal defect in a double outlet right ventricle.     

Risk factors for contrast nephropathy in diabetic patients undergoing cardioangiography

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P < 0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P < 0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p < 0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.     

Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients

The immunosuppressive and antiinflammatory cytokine interleukin (IL) 10 selectively upregulates the expression of the CC chemokine receptors CCR5, 2, and 1 in human monocytes by prolonging their mRNA half-life. IL-10-stimulated monocytes display an increased number of cell surface receptors for, and better chemotactic responsiveness to, relevant agonists than do control cells. In addition, IL-10-stimulated monocytes are more efficiently infected by HIV BaL. This effect was associated to the enhancement of viral entry through CCR5. These data add support to an emerging paradigm in which pro- and antiinflammatory molecules exert reciprocal and opposing influence on chemokine agonist production and receptor expression.     

The clinical course of diabetic nephropathy

A retrospective record analysis of 112 juvenile-onset diabetics with nephropathy was conducted in order to determine their clinical course. The mean duration of diabetes at the onset of proteinuria was 17.3+/-6.0 years. Early renal failure appeared two years after the onset of protein-uria, and severe renal failure (mean serum creatinine level, 8.5+/-3.9 mg/100 ml) four years after the onset of proteinuria. The mean duration of life after the onset of severe renal failure was six months. The mortality was 53%, with 59% of the deaths attributable to renal failure and 36% to cardiovascular disease. All patients experienced progressive deterioration of renal function as well as the other complications of diabetes, the rate of progression being accelerated toward the end of the course. Juvenile onset diabetics should be considered for renal transplantation before the serum creatinine level reaches 8.5 mg/100 ml.     

High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients. Risk analysis

OBJECTIVE: Because early-onset Japanese NIDDM patients (diagnosed before age 30 years) can develop diabetic end-stage renal failure (ESRF) in their thirties, this study was performed to elucidate the incidence and determinants for the development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: The incidence of diabetic nephropathy and its relationship to baseline characteristics and long-term metabolic control were determined in 426 early-onset Japanese NIDDM patients who were followed for a mean of 6.8 years. RESULTS: Of these 426 patients, 41 developed diabetic nephropathy manifested by persistent proteinuria (incidence rate [95%CI]/1,000 person-years; 14.1 [10.4-19.1]). Among patients whose mean HbA1c (measured by a high-performance chromatography method that is standardized and comparable to the one used in the Diabetes Control and Complications Trial study) was around 7% or less, few developed nephropathy. The incidence of nephropathy increased with increasing mean HbA1c level in a dose-dependent manner (chi 2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of diabetes at entry had significant predictive effects independent of metabolic control. CONCLUSIONS:The incidence rate of diabetic nephropathy in early-onset Japanese NIDDM patients is potentially high, similar to or higher than that in Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic nephropathy in NIDDM patients aged in their thirties or forties is likely to be an early feature that leads to ESRF, and this would contribute to the marked increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a serious disease if near-normal glycemia is not achieved.     

Measurement of the extracellular matrix in glomeruli from patients with diabetic nephropathy using an automatic image analyzer

To elucidate the characteristics of glycoproteins in the mesangial matrix in glomeruli from patients with diabetic nephropathy (DN) in non-insulin-dependent diabetes mellitus (NIDDM), we examined periodic acid-Shiff (PAS) and immunofluorescence staining of types III (III-C), IV (IV-C), V (V-C) and VI (VI-C) collagen, fibronectin (FN), fibrinogen (FBG) and laminin (LN) in the glomeruli of 16 patients with DN and 12 patients with diffuse proliferative glomerulonephritis (DPGN). The percentage of positively staining areas in the glomeruli were calculated using an automatic image analyzer. The percentages of areas positive for PAS, III-C, IV-C, V-C, VI-C or FN in DN were significantly greater than those in DPGN. Moreover, the percentages of PAS-positive areas were significantly correlated with not only IV-C-positive areas, but also FN-positive areas in patients with DN. The percentages of PAS-positive areas were also significantly correlated with the levels of serum creatinine and the degree of proteinuria in these patients. It was concluded that mesangial expansion in this disease might be associated mainly with an increase in IV-C and FN. These changes appear to affect the deterioration of renal function and the appearance of proteinuria, and vice versa.     

Effects of tangshenkang capsule on diabetic nephropathy

To study the effects of Chinese herbal medicine Tangshenkang (TSK) capsule on diabetic nephropathy (DN), 57 patients with DN were randomly divided into two groups, the treated group and the control group, they were treated with TSK capsule and the conventional therapy respectively. There were serious disorders of metabolism in DN patients, that showed the TXB 2/6-keto-PGF1 alpha ratios and lipid peroxidase (LPO) levels were higher than that of healthy people. After 6 weeks treated with TSK capsule the albuminuria levels reduced obviously (decreased 51%), renal plasma flow (RPF) increased, glomerular filtration rate and the LPO levels decreased and a positive correlation was observed between albuminuria levels and TXB 2/6-keto-PGF1 alpha ratios while the clearance rate of creafinin didn't improve significantly. There were no significant difference in the above-mentioned parameters in the control group before and after treatment. These results suggested that TSK capsule possessed a significant effect in improving albuminuria and glomerular function. And the effect of TSK might be due to its adjusting TXB 2/6-keto-PGF1 alpha ratios and its lipid-peroxidation in DN patients.