Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated insulin-like growth factor (IGF)-I and -II mRNA expression in peripheral blood mononuclear cells (PBMC) and T cells obtained from 31 patients with IgA nephropathy (IgAN), 43 patients with other types of glomerulonephritis and 16 health age-matched controls. The majority of patients with IgAN showed elevated IGF-I and -II mRNA expression in PBMC, while no IGF-I and -II mRNA expression was detected in PBMC obtained from patients with other types of glomerulonephritis or normal controls. In T cells obtained from IgAN, other types of glomerulonephritis and normal controls, however, IGF-I and -II mRNA expression was not detected. A positive correlation was noted between IGF-I and -II mRNA levels and urinary protein excretion. IGF-I and -II mRNA expression also correlated with the histopathological findings in the renal tissue of patients with IgAN. Sixty-nine percent of patients with more than 1.0 g/day proteinuria showed strong [more than (++)] IGF-I and -II mRNA expression in their PBMC. Eighty-one and 76% of patients with grade III and IV histopathological findings, respectively, showed strong IGF-I and -II gene expression in their PBMC. We also studied the clinical course of 11 patients with IgAN during hospitalization. The IGF-I and -II mRNA levels in these patients decreased gradually, as did proteinuria, after treatment. These studies suggest that abnormal regulation of IGF-I and -II gene expression in PBMC may be associated with the progression of IgAN and may be useful as an indicator of disease activity.
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PMID:Abnormal regulation of insulin-like growth factor gene expression in peripheral blood mononuclear cells from patients with IgA nephropathy. 128 88

At present the pathogenesis of diabetic nephropathy remains unresolved. Clearly lack of insulin, with its associated disorders of carbohydrate, protein, and/or lipid metabolism, initiates the process which eventually leads to the characteristic histologic picture of diabetic nephropathy. The disturbance in cellular metabolism per se could directly injure the kidney by altering the energy needs of the cell or by leading to the accumulation of cellular toxins (ie, polyols) or by causing the deficiency of key cellular metabolites (ie, myoinositol). Elevation of the plasma glucose concentration enhances the glycosylation of proteins, which in turn can lead to glomerular basement membrane thickening, loss of charge selectivity, and direct cellular damage. The multiple disturbances in intermediary metabolism are associated with increased levels of and/or enhanced sensitivity to a variety of growth factors, including IGF-I and angiotensin, and this could lead to glomerular hypertrophy. An increase in the filtered load and subsequent reabsorption of electrolytes and metabolites also could contribute to renal hypertrophy. In all animal models of nephropathy, including diabetes, glomerular hypertrophy has been shown to be the best correlate of glomerular sclerosis, proteinuria, and progressive renal deterioration. The potential mechanisms by which glomerular hypertrophy can lead to renal histologic damage were discussed previously. By increasing the luminal diameter, glomerular hypertrophy also would be expected to augment wall tension and thereby increase intraglomerular pressure. Derangements in cellular metabolism or altered sensitivity to angiotensin also can directly elevate the intraglomerular pressure and lead to structural renal damage. In this schema, elevated intraglomerular pressure is but one of many pathogenic factors that contribute to the development of diabetic glomerulopathy and albuminuria. The precise role of increased glomerular pressure in the evolution of diabetic nephropathy remains uncertain at present. In rats, severe diabetic nephropathy can occur without an increase in Pgc, while in humans, hyperfiltration does not appear to be a predictor of proteinuria and renal dysfunction. Lastly, it is likely that a variety of other factors, including the coagulation system, plasma/cell lipid levels, prostaglandins, etc, also play a role in the pathogenesis of diabetic nephropathy. According to the outline presented in Figure 1, it is unlikely that any single factor will be sufficient to explain the development of diabetic glomerulosclerosis. Ultimately, the origin of diabetic nephropathy in IDDM must be traced to insulin lack, with its associated derangements in cellular metabolism. Therefore, the importance of tight glucose control should not be underemphasized.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hyperfiltration and diabetic nephropathy: is it the beginning? Or is it the end? 219 Feb 80

Growth failure appears to be a major problem for nephrotic children who fail to respond to steroid therapy. Recently altered serum insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) profiles are reported in renal failure and glomerulonephritis. In this study, the serum IGFBP profile was evaluated by Western ligand blot and RIA in 22 patients with the nephrotic syndrome. Serum IGFBP-3 was decreased, whereas IGFBP-2 was increased in most patients with the nephrotic syndrome. The mean serum IGFBP-3 level was 2123 +/- 531 ng/mL in active states and was increased to a normal level (3593 +/- 407 ng/mL) in remission states. We also measured serum IGF-I by RIA. The serum concentration of IGF-I (mean +/- SD) was 67.4 +/- 23.2 ng/mL in active states and was increased to 127.1 +/- 21.8 ng/mL in remission states, but was still lower than that in control subjects (180.4 +/- 15.8 ng/mL). IGF-I and IGFBP-3 levels were not correlated with primary renal diseases or the amount of proteinuria. For serum IGF-IGFBP complexes, 150-kDa complexes were significantly decreased in patients with the nephrotic syndrome compared with those in control subjects. In urine from nephrotic syndrome patients, 150- and 50-kDa complexes were found, whereas these complexes did not exist in the urine of control subjects. We speculate that low serum IGF-I and IGFBP-3 levels would be partially due to the increased urinary losses of serum IGF-IGFBP complexes, especially that of 150 kDa, and these changes may contribute to growth failure in persistent nephrotic syndrome.
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PMID:Insulin-like growth factor-I (IGF-I) and IGF-binding proteins in children with nephrotic syndrome. 862 47

We recently demonstrated that recombinant hGH exacerbates renal functional and structural injury in chronic puromycin aminonucleoside (PAN) nephropathy, an experimental model of glomerular disease. Therefore, we examined whether recombinant human (rh) IGF-I is a safer alternative for the treatment of growth failure in rats with chronic PAN nephropathy. The glomerulopathy was induced by seven serial injections of PAN over 12 wk. Experimental animals (n = 6) received rhIGF-I, 400 micrograms/d, whereas control rats (n = 6) received the vehicle. rhIGF-I improved weight gain by 14% (p < 0.05), without altering hematocrit or blood pressure in rats with renal disease. Urinary protein excretion was unaltered by rhIGF-I treatment in rats with chronic PAN nephropathy. After 12 wk, the inulin clearance was higher in rhIGF-I-treated rats, 0.48 +/- 0.08 versus 0.24 +/- 0.06 mL/min/100 g of body weight in untreated PAN nephropathy animals, p < 0.05. The improvement in GFR was not associated with enhanced glomerular hypertrophy or increased segmental glomerulosclerosis, tubulointerstitial injury, or renal cortical malondialdehyde content. In rats with PAN nephropathy, administration of rhIGF-I increased IGF-I and GH receptor gene expression, without altering the steady state level of IGF-I receptor mRNA. In normal rats with intact kidneys, rhIGF-I administration (n = 4) did not alter weight gain, blood pressure, proteinuria, GFR, glomerular planar area, renal cortical malondialdehyde content, or glomerular or tubulointerstitial damage, compared with untreated animals (n = 4). rhIGF-I treatment reduced the steady state renal IGF-I mRNA level but did not modify gene expression of the IGF-I or GH receptors. We conclude that: 1) administration of rhIGF-I improves growth and GFR in rats with chronic PAN nephropathy and 2) unlike rhGH, long-term use of rhIGF-I does not worsen renal functional and structural injury in this disease model.
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PMID:The effect of recombinant human insulin-like growth factor-I on chronic puromycin aminonucleoside nephropathy in rats. 882 80

Circumstantial evidence from clinical and pathologic correlations in patients with glomerular diseases and proteinuria suggest that glomerular protein ultrafiltration contributes to tubulointerstitial injury. A series of studies was performed to examine the hypothesis that in rats with adriamycin-induced nephropathy or with diabetic nephropathy (but not in normal rats) high molecular wt. growth factors are ultrafiltered into tubular fluid and act on tubular cells through apical membrane receptors. Analysis of proximal tubular fluid that was collected by nephron micropuncture indicates ultrafiltration of IGF-I, TGF-beta and HGF. Respective receptors are also expressed in apical membranes in some parts of the nephron as examined by immunohistochemistry. In vitro cell culture experiments using proximal tubular fluid obtained from rats with experimental glomerular diseases indicate that ultrafiltered IGF-I may contribute to increased distal tubular Na-absorption. Indirect evidence also suggests that this growth factor may increase the secretion of collagen types I and IV in proximal tubular cells. TGF-beta and HGF cause increased expression and basolateral secretion of MCP-1 in proximal tubular and collecting duct cells. There may be other biologic effects on tubules that are caused by apical exposure to ultrafiltered growth factors. These studies suggest that the glomerular ultrafiltration of bioactive proteins causes or contributes to tubulo-interstitial pathology in glomerular proteinuria.
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PMID:Pathophysiologic glomerulotubular growth factor link. 1068 46

Dent disease, an X-linked recessive renal tubular disease, results from loss-of-function mutations in the CLCN5 chloride channel gene. The effects of Dent disease on growth have not been described. We report siblings who presented with proteinuria, calciuria, and phosphaturia and growth failure who responded to growth hormone (GH) treatment. Genotyping revealed a novel c.2179delG frameshift mutation at codon 727, exon 12 of the CLCNS gene. Two years after initial presentation, linear growth had slowed, and evaluation revealed isolated GH deficiency. GH therapy resulted in more than two-fold increases in height velocity and serum IGF-I levels. There was no net change in estimated glomerular filtration rate, proteinuria or calciuria in response to GH therapy, but there was a delayed improvement in phosphaturia. These cases provide insight into the effects of GH on growth and renal function in Dent disease. Furthermore, we have reported a novel CLCN5 mutation.
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PMID:Growth hormone improves growth rate and preserves renal function in Dent disease. 1854 Feb 56

The growth hormone-insulin-like growth factor-insulin-like growth factor binding protein (GH-IGF-IGFBP) axis plays a critical role in the maintenance of normal renal function and the pathogenesis and progression of chronic kidney disease (CKD). Serum IGF-I and IGFBPs are altered with different stages of CKD, the speed of onset, the amount of proteinuria, and the potential of remission. Recent studies demonstrate that growth failure in children with CKD is due to a relative GH insensitivity and functional IGF deficiency. The functional IGF deficiency in CKD results from either IGF resistance due to increased circulating levels of IGFBPs or IGF deficiency due to increased urinary excretion of serum IGF-IGFBP complexes. In addition, not only GH and IGFs in circulation, but locally produced IGFs, the high-affinity IGFBPs, and low-affinity insulin-like growth factor binding protein-related proteins (IGFBP-rPs) may also affect the kidney. With respect to diabetic kidney disease, there is growing evidence suggesting that GH, IGF-I, and IGFBPs are involved in the pathogenesis of diabetic nephropathy (DN). Thus, prevention of GH action by blockade either at the receptor level or along its signal transduction pathway offers the potential for effective therapeutic opportunities. Similarly, interrupting IGF-I and IGFBP actions also may offer a way to inhibit the development or progression of DN. Furthermore, it is well accepted that the systemic inflammatory response is a key player for progression of CKD, and how to prevent and treat this response is currently of great interest. Recent studies demonstrate existence of IGF-independent actions of high-affinity and low-affinity-IGFBPs, in particular, antiinflammatory action of IGFBP-3 and profibrotic action of IGFBP-rP2/CTGF. These findings reinforce the concept in support of the clinical significance of the IGF-independent action of IGFBPs in the assessment of pathophysiology of kidney disease and its therapeutic potential for CKD. Further understanding of GH-IGF-IGFBP etiopathophysiology in CKD may lead to the development of therapeutic strategies for this devastating disease. It would hold promise to use of GH, somatostatin analogs, IGFs, IGF agonists, GHR and insulin-like growth factor-I receptor (IGF-IR) antagonists, IGFBP displacer, and IGFBP antagonists as well as a combination treatment as therapeutic agents for CKD.
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PMID:The insulin-like growth factor system in chronic kidney disease: Pathophysiology and therapeutic opportunities. 2688 6