Proteinuria reduction

Some clinicians believe that ACEI and ARB medications should be titrated to achieve tight blood pressure control and that this will automatically result in optimal proteinuria reduction. 

ACE inhibitors can rednce proteinnria in patients with IgA nephropathy through their effect on the filtration barrier in the glomerular membrane. Several randomized trials and a large retrospective trial demonstrated that ACEIs moderately rednced proteinuria without improving renal function. Combined use of ACEIs and ARBs may have an additive effect on proteinuria reduction. However, their effects on renal function preservation is not known. Because hypertension is a negative prognostic indicator of IgA nephropathy and many of these patients already have left ventricular diastolic malfunction, despite being normotensive, early antihypertensive intervention with ACEIs or ARBs should be instimted. ... 

The main evidence for renoprotective action of RAS blockade is perhaps provided by its well-documented antiproteinuric action, which cannot completely be attributed to the reduction in BP. Proteinuria reduction during therapy is the single most important factor predicting both the renal and the cardiovascular prognosis in diabetic patients, and ACE-1 and ARB are well-tolerated, effective drugs in both respects. 

The nondihydropyridine calcium channel blockers have been shown to also decrease protein excretion in patients with diabetes,20 but the reduction in proteinuria appears to be related to the reductions in blood pressure. The maximal effect of nondihydropyridine calcium channel blockers on proteinuria is seen with a blood pressure reduction to less than 130/80 mm Hg and no additional benefit is seen with increased doses. Dihydropyridine calcium channel blockers, however, do not have the same effects on protein excretion, and may actually worsen protein excretion.17... 

Hyperkalemia The principal risk of epierenone is hyperkalemia. Hyperkalemia can cause serious, sometimes fatal arrhythmias. This risk can be minimized by patient selection, avoidance of certain concomitant treatments, dose reduction of epierenone, and monitoring. The rates of hyperkalemia increase with declining renal function. Treat patients with CHF post-MI who have serum creatinine levels greater than 2 mg/dL (males) or greater than 1.8 mg/dL (females), patients who have Ccr 50 mL/min or less, and diabetic patients with CHF post-MI, including those with proteinuria, with caution. 

This consists of weight reduction, physical activity, moderation of dietary sodium and high dietary potassium intake. Implementation of lifestyle modifications should not delay the start of effective antihypertensive drug therapy. Patients with renal insufficiency with proteinuria greater than 1 g/day should be treated to a BP goal of 125/75 mmHg ... 

ACE inhibitors have a particularly useful role in treating patients with chronic kidney disease because they diminish proteinuria and stabilize renal function (even in the absence of lowering of blood pressure). This effect is particularly valuable in diabetes, and these drugs are now recommended in diabetes even in the absence of hypertension. These benefits probably result from improved intrarenal hemodynamics, with decreased glomerular efferent arteriolar resistance and a resulting reduction of intraglomerular capillary pressure. ACE inhibitors have also proved to be extremely useful in the treatment of heart failure, and after myocardial infarction, and there is recent evidence that ACE inhibitors reduce the incidence of diabetes in patients with high cardiovascular risk (see Chapter 13). 

The compound damages the pars recta portion of the proximal tubule with the loss of the brush border. The result is renal failure detected as glycosuria, proteinuria, loss of concentrating ability, and reduction in the clearance of inulin, p-aminohippuric acid, and tetraethylammonium ion. 

Hypercholesterolemia in the patients with persistent nephrotic syndrome should be treated. Statins are similarly effective as in nonnephrotic subjects and are able to reduce total and LDL cholesterol by about 30% (M2). Reduction of proteinuria by inhibitors of angiotensin-converting enzyme is also able to reduce LDL cholesterol (M2). Dietary therapy seems to be less effective. 

Hypoproteinemia may result in low levels of serum calcium, ceruloplasmin, and transferrin. Because losses of iron are at most 0.5-1.0 mg/24 hr, even with the heaviest proteinuria, other factors must operate to produce iron deficiency and microcytic hypochromic anemia. Although the copper-binding protein ceruloplasmin is lost in the urine in nephrotic subjects and its plasma levels are low, plasma and red cell copper concentrations are usually normal. Zinc circulates mainly bound to albumin and also to transferrin, and thus the reported reduction zinc concentration in plasma, hair, and white cells in nephrotic patients is not surprising. 

Persistent nephrotic syndrome is a life-threatening disease (mainly due to the risk of thromboembolic and infectious complications) and clearly confers a high risk of progression into end-stage renal failure, which is related to the degree of proteinuria (Jl). The therapeutic goal is therefore the remission of nephrotic syndrome, or at least reduction of proteinuria. In patients with persistent nephrotic syndrome, symptomatic treatment (or prevention) of hyperlipidemia, hypercoagulability, and sodium and water retention is also warranted. 

The main function of albumin in the plasma is to provide colloid osmotic pressure. It is of major importance in maintaining blood volume and in the exchange of fluid between blood and the tissues. Heavy proteinuria may involve the loss of >3.5 g of albumin per day and this, in turn, causes a reduction in plasma oncotic pressure. When plasma oncotic pressure is reduced, fluid is not completely reabsorbed from the tissues at the venous end of capillaries. The fluid is retained within the tissues, causing oedema. The effects of gravity on fluid accumulation in the body causes oedema to be more marked in the lower body than in the upper parts, so oedema is often noticed first around the ankles. 

Three trials compared an angiotensin blocker with other blood pressure lowering drugs, and found a 20% reduction in the proportion of patients in whom proteinuria worsened or serum creatinine doubled during follow-up ... 

Biochemical effects of interleukin-6 included asymptomatic increases in liver function tests, transient proteinuria, and increased serum creatinine concentrations. Reductions in serum albumin and cholesterol concentrations, and increases in blood glucose concentrations were dose-related (SEDA-21, 376) (2). 

There was a significant reduction in proteinuria in ten children with idiopathic nephrotic syndrome after pefloxacin therapy (mean dose 2-4.6 mg/kg/day for 4—8 weeks) (1). AH had received a conrse of cyclophosphamide at least 6 months before. One patient discontinned pefloxacin within 2 weeks becanse of nansea and vomiting, one complained of arthralgia, and one developed nail discoloration. 

---