Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-ß antibody in \u3ci\u3edb/db\u3c/i\u3e diabetic mice

Emerging evidence suggests that transforming growth factor-(TGF-β) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-antibody (αT) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of αT prevents renal insufficiency and glomerulosclerosis in the db/db mouse, model of type 2 diabetes that develops overt nephropathy. Diabetic db/db mice and nondiabetic db/m littermates were treated intraperitoneally with α or control IgG, 300 µg three times per week for 8 wk. Treatment with αT, but not with IgG, significantly decreased the plasma TGF-β1 concentration without decreasing the plasma glucose concentration. The IgG-treated db/db mice developed albuminuria, renal insufficiency, and glomerular mesangial matrix expansion associated with increased renal mRNAs encoding α 1(IV) collagen and fibronectin. On the other hand, treatment with α completely prevented the increase in plasma creatinine concentration, the decrease in urinary creatinine clearance, and the expansion of mesangial matrix in db/db mice. The increase in renal matrix mRNAs was substantially attenuated, but the excretion of urinary albumin factored for creatinine clearance was not significantly affected by α treatment. We conclude that chronic inhibition of the biologic actions of TGF-with neutralizing monoclonal antibody in db/db mice prevents the glomerulosclerosis and renal insufficiency resulting from type diabetes

Evaluation of oxidative stress biomarkers in patients with chronic renal failure: a case control study

<p>Abstract</p> <p>Background</p> <p>Oxidative stress is related to several diseases, including chronic renal insufficiency. The disequilibrium in the oxidant-antioxidant balance is the result of several metabolic changes. The majority of studies to-date have evaluated the grade of oxidative stress with a single biomarker, or a very limited number of them.</p> <p>Findings</p> <p>The present study used several important biomarkers to establish a score relating to oxidative stress status (glutathione S-transferase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced and oxidized glutathione, thiobarbituric acid reactive substances and hemolysis test). The score of oxidative stress (SOS) was then applied to a group of patients with renal insufficiency not on hemodialysis, and compared to healthy control individuals.</p> <p>The score for patients with chronic renal insufficiency was significantly different from that of the healthy control group (0.62 ± 1.41 vs. -0.05 ± 0.94; p < 0.001). The comparison between patients with chronic renal insufficiency and control individuals showed significant differences with respect to changes in the enzymatic antioxidant systems (glutathione S-transferase, glutathione reductase), non-enzymatic antioxidant system (oxidized glutathione) and oxidizability (hemolysis test) indicating significant oxidative stress associated with chronic renal insufficiency.</p> <p>Conclusions</p> <p>Patients with chronic renal insufficiency not on hemodialysis are susceptible to oxidative stress. The mechanisms that underlie this status are the consequence of changes in glutathione and related enzymes. The SOS scoring system is a useful biochemical parameter to evaluate the influence of oxidative stress on the clinical status of these patients.</p

Hyperkalemia: An adaptive response in chronic renal insufficiency

Hyperkalemia: An adaptive response in chronic renal insufficiency.BackgroundHyperkalemia is a common feature of chronic renal insufficiency, usually ascribed to impaired K+ homeostasis. However, various experimental observations suggest that the increase in extracellular [K+] actually functions in a homeostatic fashion, directly stimulating renal K+ excretion through an effect that is independent of, and additive to, aldosterone.MethodsWe have reviewed relevant studies in experimental animals and in human subjects that have examined the regulation of K+ excretion and its relation to plasma [K+].ResultsStudies indicate that (1) extracellular [K+] in patients with renal insufficiency correlates directly with intracellular K+ content, and (2) hyperkalemia directly promotes K+ secretion in the principal cells of the collecting duct by increasing apical and basolateral membrane conductances. The effect of hyperkalemia differs from that of aldosterone in that K+ conductances are increased as the primary event. The changes in principal cell function and structure induced by hyperkalemia are indistinguishable from the effects seen in adaptation to a high K+ diet.ConclusionsWe propose that hyperkalemia plays a pivotal role in K+ homeostasis in renal insufficiency by stimulating K+ excretion. In patients with chronic renal insufficiency, a new steady state develops in which extracellular [K+] rises to the level needed to stimulate K+ excretion so that it again matches intake. When this new steady state is achieved, plasma [K+] remains stable unless dietary intake increases, glomerular filtration rate falls, or drugs are given that disrupt the new balance

Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy

Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy. To determine the effect of chronic exercise training on renal function in animals with moderate renal insufficiency, rats with 75% renal ablation were either exercise trained by swimming for two months or remained sedentary. Glomerular filtration rate was significantly higher in trained (1.89 ± 0.07 ml/min) than in sedentary rats (1.52 ± 0.11 ml/min). No change was observed in renal blood flow or the degree of hypertension. Proteinuria was reduced in trained (13.6 ± 4.9 mg/24 hr) compared to sedentary animals (33.5 ± 9.2 mg/24 hr). The degree of glomerulosclerosis was much less prominent in trained animals. Plasma, low-density lipoprotein cholesterol-levels and total triglycerides were reduced in trained compared to sedentary rats. This study suggests that chronic exercise training ameliorates the progression of renal disease and improves plasma lipids in rats with moderate renal insufficiency. The mechanism for this improvement in renal function appears to be independent of the influence of systemic blood pressure

Dialysotherapy effect on the quality of life for renal patients

The purpose of this essay is to examine how dialysis treatment affects patients' quality of life at the Department of Nephrology. The course of chronic renal disease and its management greatly influence the standard of living for dialysis patients. Renal insufficiency consequently results in numerous restrictions on patients' social, intellectual, and physical activities. Patients with chronic kidney disease have longer lifespans thanks to renal replacement therapy

The role of chemokine genes in the formation of terminal stage of chronic renal failure

The data on the role of chemokine genes (+1931A/T CCL4, A/G CXCL11 (rs4512021), -403A/G CCL5, C/G CCL2 (rs2857657), -801G/A CXCL12) in the formation of terminal stage of chronic renal failure, in patients with chronic glomerulonephritis, is presented in the work. It was established, that the allele A CXCL11 (rs4512021) (OR = 1.65) was the marker for the development of terminal stage of chronic renal insufficiency, and the genotype GG CXCL11was a protective factor for the development of terminal stage of chronic renal failure (OR = 0.22

Effects of initiating chronic renal replacement therapy in children, now and later in life: Data from the LERIC cohort and ERA-EDTA Registry

This thesis describes the most important results of LERIC (Late Effects of Renal Insufficiency in Children), a very a long-term follow-up study to the late somatic and psychosocial consequences of renal insufficiency in children. LERIC is a comprehensive study to evaluate the late effects of renal insufficiency in all Dutch children who had started chronic renal replacement therapy (RRT) between 1972 and 1992 at an age less than 15 years and who were born before 1979. We established the actual health status of patients, especially focusing on cardiovascular abnormalities, infections, malignancies and quality of life. Since the literature over the last decades has indicated that infections and malignancies form potentially lethal comorbidity in end-stage renal disease (ESRD), we broadened our study by using data from the European Renal Association - European Dialysis and Transplantation Association (ERA-EDTA) Registr

Recent Experience with Hemodialysis in Acute Renal Failure, Chronic Renal Disease with Reversible Features, and in Conjunction with Renal Homotransplants

Hemodialysis is a safe acceptable method of treatment for drug intoxication, and acute renal failure. It is also useful in the management of patients with chronic renal disease either on a periodic basis or, intermittantly, for acute exacerbations superimposed on chronic renal insufficiency. The great majority of dialysis at MCV has been done in conjunction with the ongoing renal homotransplantation program. Here dialysis has proven to be an innocuous procedure and has contributed significantly to the success of this program

Renal and suprarenal insufficiency secondary to familial Mediterranean fever associated with amyloidosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Familial Mediterranean fever is an autosomal recessive disease that predominantly affects people of the Mediterranean coast. One of the most frequent complications of the disease is amyloidosis. This clinical entity is known as secondary (also called AA) amyloidosis.</p> <p>Case presentation</p> <p>In this report, we describe the case of a 33-year-old Turkish man with familial Mediterranean fever and chronic renal insufficiency. He was admitted to our clinic with symptoms of suprarenal insufficiency. The patient died three months later as a result of cardiac arrest.</p> <p>Conclusion</p> <p>Our aim is to make a contribution to the literature by reporting a case of combined insufficiency due to the accumulation of renal and adrenal amyloid in a patient with familial Mediterranean fever, which has very rarely been described in the literature. We hope that adrenal insufficiency, which becomes fatal if not diagnosed and treated rapidly, will come to mind as easily as chronic renal failure in clinical practice.</p