Predicting Patients With Nondiabetic Renal Disease

Obviously some diabetic patients will develop non-diabetic renal disease. Therefore, are there any clinical parameters that clinicians can use to predict non-diabetic renal disease in a population that has high rates of renal insufficiency and abnormal urinary sediment Several clinical parameters have been reported to predict a high rate of non-diabetic renal disease. Haematuria occurs in diabetic nephropathy in over 50 of cases. Nevertheless some authors have suggested that its presence...

Microalbuminuria As A Risk Factor Type diabetes

The prevalence of microalbuminuria is 16 to 22 (27, 62) and the incidence over 7.3 years were recently demonstrated to be 12.6 63 . Normally no other signs of micro- or macroangiopathy are present at the first diagnosis of microalbuminuria. Later on with higher levels of microalbuminuria retinopathy will become much more frequent, and in fact microalbuminuria is a strong risk marker of severe retinopathy 20,22,23 . The blood-pressure is usually below 160 95 mmHg, but the mean blood-pressure is...

Structural Changes That May Impair Autoregulation Of

The most characteristic glomerular lesion in patients with incipient or overt nephropathy is mesangial expansion. Biopsies from patients with hypertension and or diabetic nephropathy have furthermore revealed arteriolar hyalinosis 71,72 . Arteriolar hyalinosis may impair the afferent arteriole capacity to constrict, and can thereby lead to enhanced transmission of the systemic BP into the glomerular capillary network, and lead to glomerular hypertension 19,73,74 . This haemodynamic alteration...

Generalised Endothelial Dysfunction Chronic Lowgrade Inflammation Microalbuminuria And Atherothrombosis

In both type 1 and type 2 diabetes, patients with advanced nephropathy (macroalbuminuria) have a greatly increased risk of severe retinopathy, neuropathy and atherothrombotic disease. This pattern can be observed even in early nephropathy, i.e. microalbuminuria, which has raised the question of what common mechanisms may be at work 1,2,22 . Because (micro-)albuminuria is often associated with classic risk factors for microangiopathy and atherothrombosis, notably poor glycaemic control,...

Antihypertensive Therapy In Dm More Than Just Reducing Albuminuria

Since microalbuminuria is also is a strong predictor of all-cause and in particular cardiovascular mortality 75, 76, 78 , the effects of these antihypertensive agents must include assessment of cardiovascular endpoints. In the ABCD study it was suggested that ACEI therapy was superior to dihydropyridine CCBs in conferring cardiovascular protection 89 . Similar findings were reported from the FACET study which suggested that fosinopril was associated with less cardiovascular events than...

Conclusion

Ambulatory BP is increased in NIDDM and IDDM patients with abnormal albuminuria even in the absence of a detectable difference in clinic BP. An association exist in both NIDDM and IDDM patients between impaired reduction of night BP and the two complications, autonomic neuropathy and diabetic nephropathy. This also counts for the very early phases of diabetic nephropathy in IDDM patients. It remains to be eluciated if the abnormal BP variation independently contributes to development of...

Involvement Of Pkc In Glomerular Structural Changes

One of the most important glomerular pathological changes in diabetic nephropathy is structural alterations including glomerular hypertrophy, basement membrane thickening, and mesangial expansion due to the accumulation of extracellular matrix components such as collagen and fibronectin 41 . A close relationship is also ovserved between mesangial expansion and the declining surface area available for glomerular filtration. Thus, the mechanisms responsible for mesangial expansion are closely...

Diabetic Nephropathy And Perinatal Outcome

In spite of the dramatic improvements in perinatal outcome over the last 25 years in pregnancies of diabetic women 228 , complications remain more frequent when DN is present. Examining the pooled results of 13 clinical series published in 1981-96 (table 6) 36,38, 95,96, 98, 100,101,148, 189192,229 , of 265 infants born to women with DN, nearly 2 3 were preterm deliveries prior to 37 weeks gestation, 72.5 were delivered by cesarean section, and respiratory distress syndrome was diagnosed in...

Peripheral vascular resistance

The effect of pharmachologic concentrations of insulin has been assessed in various vascular preparations (aortic rings, mesenteric arteries, cremastere arteries) and all studies agree on a direct vasodilatatory effect of insulin 3-6 . Also in humans several studies 7,8 have established that insulin infusion with maintenance of glycaemia is followed by an increase in limb blood flow in healthy, young volunteers. Typically in these studies, sustained Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION...

Low Birth Weight Glomerular Number And Diabetic Nephropathy

The variation in expression of renal disease among, for example, diabetic patients could be explained by the large variation in glomerular number and size within these patients 55, 56, 57 . The unification of the Barker and Brenner hypotheses is that intrauterine compromise, by whatever mechanism, generates LBW babies, which have smaller kidney with fewer glomeruli and or smaller glomeruli. These glomerular changes result in decreased total glomerular filtration surface area, giving rise to...

When To Intervene In Type Diabetic Patients

Based on several clinical trials 16 ACE inhibitors are now being advised for all type 1 diabetic patients with microalbuminuria, regardless of BP 10 14 . There are, however, some caveats Firstly, the range of renal disease included in studies of patients with microalbuminuria is quite broad, from those with relatively high UAE associated with advanced renal pathology, to those with only mild elevations of UAE and presumably relatively normal glomerular structure. Relatively young people may be...

TGFp In Experimental Diabetic Kidney Disease

In experimental animal models, TGF-P has been shown to play an important role in the pathogenesis of diabetic kidney disease. Several groups of investigators have demonstrated that the TGF-P level is elevated in the kidneys of insulin-dependent diabetic animals during both early and late stages of disease 67-75 . A progressive increase in the TGF- 1 mRNA and protein levels was noted in glomeruli isolated from the streptozotocin (STZ)-induced diabetic rat 67, 68 in association with an increased...

Implications For Clinical Practice

The continuous progresses in the management of patients with established cardiovascular diseases have radically changed their prognosis. This is particularly true for diabetic patients, whose rate of morbidity and mortality has been shown to be beneficially affected by a variety of interventions table 2 . Recent data from registries such as MITRA also confirm that, when used in standard clinical practice, intervention such as percutaneous coronary interventions, beta-blockers, statins and...

Glomerular Filtration Rate

An ideal marker for determination of glomerular filtration rate should fulfil the following requirements it should be freely filtered at the glomerulus, no tubular secretion or re-absorption, it should not be metabolised, and it should be physiologically inert without affecting renal function, distribute instantaneously and freely in the extracellular volume, and should be easily measured 26 . Such a marker does not exist. However the renal clearance of inulin during constant infusion has been...

References

Berkman J R.H., Unilateral nodular diabetic glomerulosclerosis Kimmelstiel-Wilson . Report of a case. Metabolism Clin Exp, 1973. 22. 715-722. 2. Mehler P.S. and Schrier R.W., Antihypertensive drugs and diabetic nephropathy. Curr Hypertens Rep, 1999. 1 2 . 170-7. 3. Schrier R.W., Treating high-risk diabetic hypertensive patients with comorbid conditions. Am J Kidney Dis, 2000. 36 3 Suppl 1 . S10-7. 4. Brenner B.M., Cooper M.E., de Zeeuw D., Keane W.F., Mitch W.E., Parving H.H., Remuzzi G.,...

Human Diabetic Kidney Disease And Tgfb

Studies performed in diabetic patients with various degrees of nephropathy also implicate the renal TGF-P system in the development of human diabetic renal disease. All three isoforms of TGF-P have been discovered to be elevated in both the glomerular and the tubulointerstitial compartments of patients with established diabetic nephropathy 68, 85, 86 . Furthermore, glomerular TGF-P1 mRNA, measured by the reverse-transcription polymerase chain reaction method, was markedly increased in renal...

Dyslipidemia

Dyslipidemia is a clear cardiovascular risk factor and lipid-lowering therapy reduces the risk of cardiovascular events in diabetic patients with coronary heart disease 29 . Moreover, there is also evidence, both in type 1 30 and type 2 DM 31 , that lipid abnormalities are associated with progressive renal function loss. Actually, hypercholesterolemia might merely be an epiphenomenon of overt proteinuria, which, in turn, would be the major independent promoter of progression because of the...

Introduction

Microalbuminuria is an early component in a continuum of progressive increases in albumin excretion rate AER associated with diabetic nephropathy. The development of microalbuminuria has been equated with incipient nephropathy but microalbuminuria is also a risk factor for macrovascular disease, especially in patients with type 2 diabetes. Recent data suggest that a substantial minority of non-diabetic and diabetic people with impaired glomerular filtration rate GFR may not pass through the...

Antimicrobial treatment

Few clinical trials have dealt with the outcome of treatment of ASB in patients with DM 40,9 . From these studies, the authors conclude that 1 two weeks of treatment is as effective as 6 weeks treatment 2 the recurrence rate is high, even after prolonged antibiotic treatment and 3 recurrences 4-8 weeks post-therapy are mostly re-infections and not relapses with the same microorganism which occur earlier . In addition, physicians should be aware of the high prevalence of underlying structural...

Intervention Programme For Treatment Of Persistent Microalbuminuria gmin

In children with microalbuminuria gt 20-200 g min blood glucose control should be improved over a period of 6 months and the status of microal-buminuria should be monitored closely. If microalbuminuria disappears or improves there is no indication for pharmacological intervention. However, if the microalbuminuria deteriorates, whether or not blood glucose control improves and blood pressure is within the normal limits, antihypertensive treatment by an ACE-inhibitor should be instituted. The ACE...

Light Microscopy Studies Heterogeneity In Renal Structure In Microalbuminuric Patients

Diabetes Efferent Hyalinosis

Microalbuminuria MA antedates clinical proteinuria in both type 1 32-34 and type 2 diabetes 35, 36 . The predictive value of MA was thought to be quite different in type 1 and type 2 diabetes in that only approximately 20 of type 2 patients with MA progressed to overt nephropathy over a decade of follow-up in contrast to over 80 of type 1 diabetic patients 36 . However, in more recent studies, approximately 30 of type 2 diabetic patients with MA progressed to overt nephropathy over a decade and...

Glomerulopathy And Antihypertensive Treatment

Glomerulopathy is observed as early as 2 years after onset of diabetes 34 and is associated with the level of nocturnal diastolic blood pressure after 10 years in children and adolelescents in whom persistent microalbuminuria has not developed 35 . Antihypertensive treatment has been shown to have a beneficial effect on the course of nephropathy. Further, several recent data present evidence that administration of this treatment regimen in the stage of microalbuminuria to normotensive patients...

Early treatment in type diabetic patients without complications

The high risks in the patients with type 2 diabetic nephropathy is in sharp contrast with the outspoken benefits of RAS blockade in the normoalbuminuric and microalbuminuric stage 60-64 . Therefore, early detection of increased urinary albumin excretion rate, followed by early treatment of microalbuminuria is imperative. Today, microalbuminuria can be measured with tests that are reproducible, acceptable, and harmless to the patient. In addition, the cost-benefit ratio in screening and early...

Angiotensin Ii And Development Of Diabetic Glomerulopathy

Angiotensin II is the dominant effector of the renin-angiotensin system RAS . Angiotensin II regulates salt and water balance, blood pressure, and the vascular tone. Several recent studies have provided clear evidence that angiotensin-converting enzyme ACE -inhibitors slow the progression of diabetic nephropathy by mechanisms mainly independent from reduction of systemic blood pressure 104,105 . Thus, angiotensin II is a renal growth factor that exerts non-hemodynamic effects on the kidney and...

The Use Of Antihypertensive Agents In Hypertensive Dm Patients With Normoalbuminuria And Microalbuminuria

Comparison of the use of ACEI versus placebo in DM2 subjects with hypertension and normoalbuminuria or microalbuminuria has not been well studied A double blind study compared captopril with conventional therapy metoprolol and hydrochlorothiazide in normoalbuminuric and microalbuminuric hypertensive DM2 subjects over a 3 year period 31 . Both regimens reduced blood pressure without altering UAE in the normoalbuminuric DM2 subjects. However, their findings in hypertensive DM2 patients with...

Actions Of Angiotensin Ii

Inhibition of Angiotensin II might be the main issue in the diabetes patient with hypertension, nephropathy or both conditions in coexistence. The effects of this active metabolite are potentially damaging to an extent superior to many other peptides and metabolites. This makes inhibition and control of Angiotensin II essential. The renin-Angiotensin system can be stimulated by stress, high sodium intake, or an increase in sympathetic activity. This stimulation results in increased renin...

Microalbuminuria In The Non Diabetic Population

Several population based studies have suggested a link between microalbuminuria , blood pressure and cardiovascular disease 29, 30 . In the Islington heart study an elevated AER was found in 9 of non - diabetic patients over 40 years of age. Those with an elevated AER had more coronary disease OR 5.7 , more peripheral vascular disease OR 7.45 and an increased mortality after 3.6 years OR 24.3 31 . Microalbuminuria is associated with rising blood pressure particularly systolic BP and increased...

Longitudinal Studies Of Gfr In Microalbuminuric Patients With Type Diabetes Figure

There are at least 3 reasons why the rate of decline of GFR may differ in microalbuminuric patients with type 2 diabetes compared with type 1 diabetes. Firstly, there is an age related GFR decline of approximately 1 ml min 1.73m2 year after the age of 40 years 74, 75 . Secondly, there is a higher prevalence of hypertension in type 2 diabetes, which may accelerate renal injury 81 . Thirdly, a proportion of microalbuminuric patients with minimal or no detectable renal structural lesions may never...

The Relation To Clinic Bp

We have found a markedly lower day time BP 147 85 mmHg than clinic BP 163 95 mmHg in 102 consecutive NIDDM and IDDM patients referred to ambulatory BP measurement because of repeated clinic BP gt 140 90 mmHg 124 . The frequency of white coat hypertension in normoalbuminuric diabetic patients is about 25 124,125 . If patients are selected for the presence of organ lesions related to hypertension diabetic nephropathy the proportion of white coat hypertension may be reduced 125 . One study...

Alternative Hypothesis For The Hspg Alterations Findings From The Atherosclerosis Prospect

The role of PGs in atherosclerosis has been the subject of intense investigations largely owing to the observation that chondroitin sulfate CS and dermatan sulfate DS PGs manly versican and decorin associate with apoB-containing lipoproteins 50 , which are major components of the atherosclerotic plaque. The increase in CS DS-PGs in the intima of atherosclerotic vessels might therefore explain an increased retention of lipoprotein. On the other hand, HS-PGs mainly perlecan are reduced in the...

The Relevance Of The Problem

Nephropathy is a major cause of illness and death of patients with type 2 diabetes mellitus DM , the excess being confined to proteinuric patients due to complications of end-stage renal disease ESRD and particularly due to cardiovascular events 1 . Diabetic nephropathy is the single most common cause of ESRD in the United States and more than one third of all patients enrolled in the Medicare ESRD program are actually diabetics 2 . It derives that costs of renal replacement therapy for...

Contents

Rationale for early screening for diabetic renal disease 1 2. Pressure-induced and metabolic alterations in the glomerulus cytoskeletal 13 changes 3. The Steno hypothesis for cardiovascular and renal disease revisited 27 Giovanni Gambaro, Monica Ceol and Augusto Antonello 4. Microalbuminuria and cardiovascular disease 45 Stephen M. Thomas and GianCarlo Viberti 5. The heart in diabetes results of trials 63 Giulio Zuanetti and Elena Sarugeri 6. Microalbuminuria and GFR in type 1 and type 2...

Concluding Remarks

The characteristic lesions of diabetic nephropathy such as renal hypertrophy, increased glomerular hypertension, and altered extracellular matrix metabolism may be intimately related to the effects of high ambient glucose on various growth factors and cytokines that are increased locally or in the circulation. Recent studies using cell culture techniques and experimental animal models have provided important insights into the pathogenetic mechanisms of diabetic nephropathy Table 1 . Much...

Evolution Of Diabetic Nephropathy

Diabetic Nephropathy Evolution

Diabetic renal disease is characterised by changes in both AER and GFR in predisposed patients. The usual sequence starts with an increase in GFR hyperfiltration , followed by an increase in AER leading to microalbuminuria. Hyperfiltration may persist through the phase of microalbuminuria or it may normalise prior to the onset of overt nephropathy macroalbuminuria , which is accompanied by further increases in AER and a declining GFR. In parallel with these changes, there is a rise in blood...

Glomerular Hyperfunction

From the onset of IDDM, kidney function is characterised by elevation of glomerular filtration rate GFR and renal plasma flow RPF for reviews see 1,2 . Using precise measurements e.g. renal clearance of inulin or iothalamate, it has been found, that mean GFR in groups of short-term IDDM patients is increased by 15-25 - to approximately 135-140 ml min 1.73m2 during 'usual metabolic control' 3-7 . Before start of insulin treatment, but in the absence of ketoacidosis, glomerular hyperfiltration is...

Heparin And Gags Renoprotection In Diabetic Nephropathy Does It Support The Steno Hypothesis

A number of reports showed that heparin and more generally GAGs prevent and cure experimental diabetic nephropathy 16,64-67 and decrease albuminuria in type 1 and 2 diabetic patients 68,69 . Because defects in HS-GAG synthesis are believed to be so striking in diabetic nephropathy, the treatment of diabetic nephropathy with HS-GAG like substances can be viewed as an experiment to test the Steno hypothesis. However, the activity of these drugs cannot be explained, by the Steno hypothesis, only...

Hyperglycaemia And The Pathogenesis Of Diabetic Nephropathy

Diabetic Nephropathy Pathogenesis

The main metabolic disorder occuring in diabetes is hyperglycaemia. Two landmark studies, the Diabetes Control and Complications Trial DCCT and the United Kingdom Prospective Diabetes Study UKPDS showed that intensive blood glucose control clearly reduces the development or progression of diabetic nephropathy 43,44 . Thus, the impact of extracellular high glucose concentrations on renal cell gene expression was investigated in detail Ayo and coworkers reported that prolonged exposure to high...

Disparity Between Declining Gfr And Increasing

Most patients with diabetic renal disease display a decline in GFR that is preceded or accompanied by an increase in AER. However there is a growing body of evidence to suggest that some patients possibly follow an alternate, non-albuminuric pathway to renal impairment. The combination of impaired renal function in association with normoalbuminuria was first highlighted by Lane et al. 3 who identified eight women with type 1 diabetes who had low creatinine clearance but a normal AER. A recent...

Role Of Combination Therapy

It has been proposed that the combination of two or more antihypertensive agents may be beneficial in the treatment of hypertension in the diabetic patient with or without evidence of renal involvement. The various combinations have been reviewed recently 57 . Brown et al postulated in 1993, that the combination of a calcium antagonist with a converting enzyme inhibitor should result in a greater reduction in urinary protein excretion and slow progression of nephropathy, as assessed...

Emerging Concepts Regarding Albumin Handling By The Kidney

A new understanding of the role of proximal tubular cells in the degradation of filtered proteins including albumin has been reached in the last 5 years. Studies by Comper's group and ourselves have shown that albumin is normally degraded in the kidney and that albumin-derived fragments are not detectable by standard immunological methods 89 . The normal renal handling of albumin involves its degradation through lysosomal uptake from the tubular fluid and subsequent exocytosis of the peptide...

Mechanisms Of Hyperfiltration In Diabetes

The pathogenesis of diabetic hyperfiltration is multifactorial. Numerous mechanisms and mediators for this effect have been proposed Table 1 , and are briefly reviewed here. For better clarity, these mechanisms are divided in five areas separately discussed below. However, the reader should be aware of overlap between these processes, and the fact that they act in concert to promote renal hemodynamic alterations in diabetes. POTENTIAL MEDIATORS OF DIABETIC HYPERFILTRATION 1. Factors affecting...

Molecular Cell Biology Of Endothelial Dysfunction In Diabetes

High Glucose Insulin Pathway

Endothelial dysfunction in diabetes originates from three main sources 1,3,6876 . Firstly, hyperglycaemia and its immediate biochemical sequelae directly alter endothelial function. Glucose transport into endothelial and vascular smooth muscle cells is insulin-independent and is autoregulated in smooth muscle cells, but not in endothelial cells, in which an increase in blood glucose concentration will thus increase the intracellular accumulation of glucose and its metabolites. Figure 2....

Influence Of Gfr On Albuminuria

Hyperfiltration, defined as a GFR above the range observed in age matched non-diabetic subjects gt 135 ml min 1.73 m2 in young subjects occurs in approximately 20 of normo- and microalbuminuria patients with type 1 diabetes 37, 38 and 0-20 of patients with type 2 diabetes 39, 40 depending on the reference range used. Hyperfiltration occurs less commonly in some ethnic groups compared with others 40 . The increase in GFR usually starts at the stage of normoalbuminuria but may continue for...

Ciq Kidney Disease

Severe functional disorders of glomerular capillaries and renal hemodynamics in treated diabetes mellitus during childhood. Ann Paediatr, 193 129-138. 2. Ditzel J, Junker K. 1972. Abnormal glomerular filtration rate, renal plasma flow and renal protein excretion in recent and short-term diabetes. Br Med J, 2 13-19. 3. Mogensen CE, Andersen MJF. 1973. Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes, 22 706-712. 4. Berkman J,...

Classification Of Proteinuria

Measurement of urinary albumin creatinine ratio is most commonly used for diagnosing and tracking urine albumin excretion. Although collection of a 24hour urine sample might be desirable, the use of an early-morning first voided sample is common practice. Early-morning urine is more concentrated, which facilitates detection of albumin. Inclusion of the urinary creatinine factor adjusts for variation in urine volume. Use of the urinary albumin creatinine ratio has been made increasingly feasible...

The Use Of Antihypertensive Agents In Normotensive Dm With Microalbuminuria

The possibility that early therapy will postpone or retard progression of renal injury in diabetes has led to the use of antihypertensive agents in normotensive subjects. UAE has been shown to be reduced in a group of normotensive DM2 patients with microalbuminuria treated with captopril over a period of 6 months, whereas the untreated group had no change in albuminuria 50 . In the Melbourne study 43 there was no change in albuminuria after 12 months treatment with either nifedipine or...

Historical Perspective

1982-84 Three studies in patients with type 1 diabetes demonstrate that microalbuminuria predicts the subsequent development of macroalbuminuria overt diabetic nephropathy . This leads to the concept of microalbuminuria as a surrogate for diabetic nephropathy. Macroalbuminuria also becomes a surrogate for assessment of the onset of a decline in glomerular filtration rate. Despite early evidence that microalbuminuria predicts cardiovascular death to a greater extent than renal disease in type 2...

Pathogenesis Pathogenesis in general

UTIs almost exclusively result from the ascending route. Bacteria colonizing the perineum and vagina can enter the bladder and further ascend to the kidneys. The most important defense mechanisms of the host, are the urine flow from the kidneys to the bladder and the intermittent voiding, resulting in complete emptying of the bladder. Patients with urinary obstruction, stasis and reflux have more difficulty in clearing bacteria and these conditions also seem to predispose to the development of...

Autoregulation Of The Normal Kidney

Regulation of renal haemodynamics is a vital component in the overall control of renal function 23 . The ability of the kidney to maintain constancy of renal Mogensen CE ed. THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright 2004 by Martin Dunitz, a member of the Taylor amp Francis Group, plc. All rights reserved. function GFR over a wide range of renal perfusion pressures is termed autoregulation 24 figure 1. Experimental studies suggests that autoregulation of GFR is due to...

Effect Of Pregnancy On The Subsequent Progression Of Diabetic Nephropathy

For years, there has been concern that the hyperfiltration, hypertension, or heavy proteinuria of pregnancy might damage glomeruli, tubules, and interstitium and accelerate the postpartum progression of DN to end-stage renal disease. In a pooled series of 195 women experiencing pregnancies with DN and having renal function assessed 1-10 years afterwards, 23 were in renal failure and 5.6 had died table 4 . Not surprisingly, the frequency of progression to renal failure after pregnancy was 49 in...

Possibilities For Interventions

An obvious goal for therapeutic intervention is to optimize glycemic control in order to decrease the risk of late complications. Such therapy will tend to reduce hyperfiltration as discussed above. However, since the pathogenetic basis for the association between glomerular hyperfiltration and later nephropathy is still not clarified, non-glycemic therapy against glomerular hyperfiltration is not presently indicated. It seems rational though, not to prescribe higher protein content in diabetic...

Hyperglycemia And Proteinuria

The onset of microalbuminuria in patients with type 2 diabetes may be transient and related to increases in glomerular filtration rate in association with hyperglycemia. Albuminuria has been shown to decrease with decreases in glucose levels in patients with newly diagnosed type 1 or type 2 diabetes 4547 . However, other researchers reported no decline in albumin excretion with control of hyperglycemia in patients with newly diagnosed type 2 diabetes 48 . The United Kingdom Prospective Diabetes...

Results From Clinical Trials

The safety and vascular effects of LY333531 were evaluated in a one month clinical study on 29 patients with type 1 or 2 diabetes of less than 10 years, with no or minimal retinopathy. This double-blind, placebo-controlled randomized trial showed significant improvement in retinal blood flow and mean circulation time with no change in glycemic indices 84 . Results of the clinical trial of LY333531 in diabetic neuropathy have also been reported recently. A 1-year double-blind, randomized,...

Impaired Autoregulation Of Gfr In Patients With Diabetic Nephropathy

Animal studies have demonstrated impaired renal autoregulation in models of glomerulosclerosis 81 , glomerulonephritis 74 , nephrosclerosis 82,83 and nephrosis 84,85 . In humans Parving et al 68 demonstrated a wide variation in response to clonidine induced acute BP reduction ranging from normal to severely impaired GFR autoregulation in long-term Type 1 diabetic patients with nephropathy. A similar clonidine induced reduction in MABP had no impact on autoregulation in short-term...

Prevalence Of Impaired Gfr During Microalbuminuria In Type And Type Diabetes

Assessments of GFR in patients with microalbuminuria can be performed either cross-sectionally or longitudinally. The former yields data on prevalence and is heavily influenced by age, whereas the latter yields data on rate of GFR decline which is strongly influenced by blood pressure especially in type 2 diabetes. It follows that cross-sectional studies would be expected to show a higher prevalence of impaired GFR in elderly subjects with type 2 diabetes than in younger patients with type 1...

Vegf

This growth factor is implicated in the microvascular complications of diabetes, especially retinopathy, but its role in nephropathy remains speculative. VEGF, also known as vascular permeability factor VPF , is a homodimeric glycoprotein that exists in at least five different isoforms that are produced by differential exon splicing 144 . Smaller isoforms are freely soluble and larger isoforms are locally bound to extracellular matrix 145 . Virtually all cell types produce VEGF an increase in...

Renal Autoregulation In Patients With Diabetes

In the first human study of renal autoregulation Parving et al. 68 studied Type 1 diabetic patients with and without diabetic nephropathy. They found no significant change in GFR during acute lowering of BP with clonidine in patients without clinical signs of microangiopathy. The patients had mean blood glucose less than 13 mmol l during the investigation 68 . In the first study of Type 2 diabetic patients with and without diabetic nephropathy 69 no significant change in GFR during acute...

Alternative Views And Future Directions

Current guidelines for the general care of patients with diabetes emphasize lower than usual blood pressure goals typically 130 80 mm Hg , smoking cessation, and the best possible glycemic control 7 . Hence, within the armamentarium for treating early renal disease, the finding of microalbuminuria leads only to the addition of an ACEI or ARB to the recommended regimen. Other issues such as low protein diets, phosphate control, and anemia management are in the province of more established renal...

Which Agent To

A large body of evidence has been collected as to the beneficial effects of various antihypertensive agents in DM1 and DM2 patients with abnormal albuminuria 4, 6, 37, 53, 107, 108 . It has been postulated that ACEI and ARB may possess beneficial effects over and above simple blood pressure control, although till recently most studies have involved small numbers of subjects and thereby introduced a potential Type II statistical error. Several meta-analyses of trials involving patients with...

Overnight Albumin Excretion Rate And Blood Glucose Control

Several previous reports have suggested a relationship between poor blood glucose control and increased urinary albumin excretion 39,41,42,43 . In our study 14 we found that only females with microalbuminuria had significantly elevated HbA1c values compared with diabetic patients with normoalbuminuria. Blood glucose control tends to be poorer during puberty, particularly in girls, which may be explained by changes in hormonal and or lifestyle factors 44,45,46,47,48 . In recent studies 49,50,102...

Overnight Albumin Excretion Rate And Arterial Blood Pressure

The normal range for diastolic blood pressure in diabetic boys Figure 3 and girls Figure 4 aged 8 to 18 years with normoalbuminuria was determined in a study of the relationship between blood pressure and urinary albumin excretion in young Danish Type 1 diabetic patients 69 . Figures 3 and 4 also include data from patients diagnosed with micro- and macroalbuminuria 69 . Ten out of 16 boys with microalbuminuria had diastolic blood pressure above the upper quartile while eight out of 14 girls...

The Central Role Of The Heparan Sulfate Proteoglycan And The Steno Hypothesis Of Diabetic Micro And Macroangiopathy

It has been suggested that the first change in the extracellular matrix in diabetes might be an undersulphation of HS- proteoglycans PGs 10 , followed by an absolute decrease of HS 11 . These alterations in HS-PG metabolism have been identified as the possible molecular basis for the abnormal permselectivity of glomerular and extrarenal capillaries in diabetes mellitus. HS-PGs consist of a central core protein to which HS-GAG side chains are linked. These HS-GAG side chains are formed by...

The Brenner Hypothesis

Glomerular number shows wide biological variation in both humans 400,000 -1,200,000 27, 28 and rats 20,000 - 35,000 11, 29 . Brenner et al, proposed that individuals with a mean glomerular number at the lower end of or below the physiological range are at increased risk of developing hypertension 5 , due to a reduction in total filtration surface area. During the growth phase of a human being, hypertension may result in glomerular capillary hypertension and later on in glomerular sclerosis,...

Bacteriology

The bacteria isolated from diabetic patients with a UTI are similar as found in nondiabetic patients with a complicated UTI 31 . As in uncomplicated UTIs, E. coli causes the majority of infections. However, other strains are relatively more frequently cultured in these patients. For example, one study reported E. coli to be the causative uropathogen in 47 of the UTIs in diabetic patients and in 68 of the UTIs in nondiabetic patients 32 . Non-E. coli uropathogens, found in patients with DM,...

The Steno Hypothesis For Cardiovascular And Renal Disease Revisited

Giovanni Gambaro, Monica Ceol, and Augusto Antonello Division of Nephrology, Dept. of Medical and Surgical Sciences, School of Medicine, University of Padova, Padova, Italy It is well known that diabetic patients are at increased risk of vascular disease, and that atherosclerosis is their main cause of death. Also, patients with diabetic nephropathy have an even higher risk of cardiovascular mortality. In a 10 year follow-up study, 15 of IDDM patients with normoalbuminuria, 25 with...

Glomerulonephritis And Other Complicating Diseases

Glomerulonephritis has been thought to occur more frequently in patients with diabetic renal disease than could be explained by mere coincidence 39, 40 . Autopsy studies have, however, shown that complicating glomerular disease is rare and probably not exceeding prevalence in the general population 41 . In biopsy studies of patients with IDDM glomerulonephritis seems to be comparatively rare 42, 43 , probably around 2-3 in unselected cases with proteinuria and duration of diabetes of more than...

The nodular lesion

As the volume of the mesangial matrix increases, some mesangial regions become more prominent than others and may take on a globular shape figure 2 . The mesangial nodule is thus created by a gradual increase of the diffuse lesion and the distinction between them is arbitrary. Several nodules may be present in each glomerulus, but usually only a few of the mesangial regions are affected in this way The nodules are distributed in a horseshoe-shaped area corresponding to the peripheral mesangium...