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)

Sickle cell anemia and the related hemoglobinopathies are associated with a large spectrum of renal abnormalities. The patients have impaired urinary concentrating ability, defects in urinary acidification and potassium excretion, and supranormal proximal tubular function. The latter is manifest by increased secretion of creatinine and by reabsorption of phosphorus and beta(2)-microglobulin. Young patients with sickle cell disease (SCD) have supranormal renal hemodynamics with elevations in both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). These parameters decrease with age as well as following the administration of prostaglandin inhibitors. Proteinuria, a common finding in adults with sickle cell disease, may progress to the nephrotic syndrome. Proteinuria, hypertension, and increasing anemia predict end-stage renal disease (ESRD). While ESRD can be managed by dialysis and/or renal transplantation, there may be an increased rate of complications in renal transplant recipients with SCD. Hematuria is seen in individuals with all of the SCDs as well as with sickle cell trait. In most cases the etiology of the hematuria turns out to be benign. However, there does appear to be an increased association between SCD and renal medullary carcinoma. Therefore, those SCD patients who present with hematuria should initially undergo a thorough evaluation in order to exclude this aggressive neoplasm. Papillary necrosis may occur due to medullary ischemia and infarction. Erythropoietin levels are usually lower than expected for their degree of anemia and decrease further as renal function deteriorates. An abnormal balance of renal prostaglandins may be responsible for some of the changes in sickle cell nephropathy. Acute renal failure is a component of the acute multiorgan failure syndrome (MOFS). Finally, progression of sickle cell nephropathy to ESRD may be slowed by adequate control of hypertension and proteinuria. However, the prevention of the renal complications of SCD will require a cure for this genetic disorder.
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PMID:Renal abnormalities in sickle cell disease. 1142 1

Pre-eclampsia is the main cause of fetal and maternal morbidity and death associated with hypertension during complicating pregnancy. During physiological pregnancy, the immunological system undergoes secondary modifications, with an "exchange" between mother and fetus. Cytokines play an important role in the complex condition of partial fetal "rejection". It has suggested that the condition depend on immunological factors. In line with this hypothesis, apoptosis appear to play a key role in the pathophysiology of placental ischemia and the mechanism underlying this condition may be influenced by substances such as Bcl-2 which inhibits apoptosis. Neither aspirin nor calcium appear to improve maternal hypertension and proteinuria, although late ongoing trials may alter this view. At present, the condition can be resolved only by the end of pregnancy. Further studies are required in order to improve our understanding of these immunological mechanisms underlying hypertension during pregnancy, as the key to effective therapy may be their ability to "manipulate" them in an appropriate way.
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PMID:Is apoptosis cause of pre-eclampsia? 1071 Aug 17

Rats recovering from acute renal ischemia exhibit tubule loss and interstitial fibrosis followed by development of proteinuria and glomerular sclerosis. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and interstitial fibrosis was assessed in rats studied for 35 d after right nephrectomy and transient occlusion of the left renal artery. One group of rats received no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GFR (2.04 +/- 0.30 ml/min treated, 2.16 +/- 0.21 ml/min untreated), reduce the fraction of glomeruli that were no longer connected to normal tubule segments (42 +/- 9% treated, 42 +/- 13% untreated), or limit expansion of the interstitial volume fraction (25 +/- 3% treated, 25 +/- 4% untreated). The contribution of AngII to progressive glomerular injury following initial recovery from ischemia was assessed in similarly prepared rats studied for 140 d. One group of rats received no treatment, while a second group received enalapril beginning at 35 d following ischemia. Enalapril markedly reduced proteinuria (78 +/- 17 mg/d treated, 229 +/- 52 mg/d untreated) and the prevalence of segmental glomerular sclerosis (14 +/- 9% treated, 45 +/- 10% untreated). Untreated rats developed sclerotic lesions in glomeruli not connected to normal tubules, as well as in glomeruli connected to normal tubules. Enalapril prevented injury in both classes of glomeruli. These results indicate that AngII does not contribute to interstitial fibrosis during recovery from ischemic injury. Reduction of AngII activity, can, however, prevent secondary glomerular injury in kidneys initially damaged by ischemia.
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PMID:Contribution of angiotensin II to late renal injury after acute ischemia. 1086 84

As a consequence of an advancing discrepancy between supply of suitable grafts and demand from potential recipients, less than optimal organs are increasingly being used. Although clinical studies demonstrate the involvement of various risk factors, including donor age and duration of ischemia on long-term graft outcome, their individual contribution and correlation has not been followed experimentally. After cold ischemic times of 5, 60, and 120 min, kidney allografts of 3-, 12-, and 18-mo-old Fischer 344 donors were transplanted into 3-mo-old Lewis rats. Age-related changes were examined in matched native uninephrectomized controls. Proteinuria and creatinine clearance were determined, and histologic and immunohistologic studies were assessed and quantified at the end of the observation period (20 wk). All grafts functioned satisfactorily with the exception of one graft each from 12- and 18-mo-old donors with prolonged ischemia (120 min). Functional deterioration and structural changes progressed in parallel to increasing donor age and prolonged ischemia. The impact of expanded ischemia was particularly detrimental in grafts from older donor animals. Donor age and duration of ischemia act in a synergistic manner in our model. Brief ischemic times seem of particular relevance when grafts from older donors are being used.
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PMID:Contribution of prolonged ischemia and donor age to chronic renal allograft dysfunction. 1086 89

Reactive oxygen species are generated during ischemia-reperfusion tissue injury. Oxidation of thymidine by hydroxyl radicals (HO*) causes formation of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol excreted in urine can be used as a biomarker of oxidative DNA damage. The aim of this study was to investigate the oxidative DNA damage in patients showing immediate allograft function after kidney transplantation, and to find out whether this damage correlates with glomerular and tubular lesions. Time dependent changes in urinary excretion rates of thymidine glycol, but also of total protein, albumin, low molecular weight (alpha1-microglobulin, beta2-microglobulin) and high molecular weight proteins (transferrin, IgG, alpha2-macroglobulin) were analyzed quantitatively and by polyacrylamide-gel electrophoresis in six patients. Urinary thymidine glycol was determined by a fluorimetric assay in combination with affinity chromatography and HPLC. After kidney transplantation the urinary excretion rate of thymidine glycol increased gradually reaching a maximum within the first 48 hours (16.56+/-11.3 nmol/m mol creatinine, ref. 4.3+/-0.97). Severe proteinuria with an excretion rate of up to 7.2 g/mmol creatinine was observed and declined within the first 24 hours of allograft function (0.35+/-0.26 g/mmol creatinine). The gel-electrophoretic pattern showed a nonselective glomerular and tubular proteinuria. The initial nonselective glomerular proteinuria disappeared within 48 hours, changing to a mild selective glomerular proteinuria. In this period (12-48 hours) higher levels of thymidine glycol excretion were observed, when compared to the initial posttransplant phase (13.66+/-9.76 vs. 4.31+/-3.61 nmol/mmol creatinine; p<0.05). An increased excretion of thymidine glycol is seen after kidney transplantation and is explained by the ischemia-reperfusion induced oxidative DNA damage in the kidney. In the second phase higher levels of excretion were observed parallel to the change from a nonselective to a selective glomerular and tubular proteinuria. An explanation may be sought in the repair process of DNA in the glomerular and tubular epithelial cells, appearing simultaneously with functional recovery.
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PMID:Urinary thymidine glycol as a biomarker for oxidative stress after kidney transplantation. 1090 Nov 87

The present study examined the long-term consequences of warm renal ischemia (WRI) with or without renal ablation. Male Sprague-Dawley rats (250-300 g) were subjected to 60 min of complete WRI by pedicle clamping and then followed for 52 wk. Animals were organized into four groups: rats in which both kidneys were subjected to warm ischemia (2WIK); rats with left WRI and right nephrectomy (1WIK); uninephrectomized rats with a left nonischemic kidney (1NK); and sham-operated rats (2NK). Additional animals were studied at 24 h, 7 days, and 16 and 32 wk. In the first week after WRI, rats from the 2WIK and 1WIK groups displayed a similar degree of acute renal damage. After recovering from acute renal failure, 1WIK rats developed progressive and severe proteinuria, whereas it was mild in the 2WIK group, as well as in the 1NK and 2NK groups. Only animals from the 1WIK group developed severe chronic renal failure, glomerulosclerosis, interstitial fibrosis, and upregulation of transforming growth factor-beta(1) (TGF-beta(1)) gene, which was associated with increased TGF-beta(1) protein expression in tubular epithelial cells, arterioles, and in areas of mononuclear interstitial cell infiltrate. On the contrary, long-term renal TGF-beta(1) expression, function, and histology were similar in 2WIK and 2NK rats. The present study shows that prolonged bilateral WRI, when both kidneys are retained in place, induces very mild long-term renal lesions as opposed to the severe renal scarring observed when WRI is combined with contralateral nephrectomy.
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PMID:Influence of nephron mass in development of chronic renal failure after prolonged warm renal ischemia. 1091 44

In unraveling the pathogenesis of chronic transplant dysfunction (CTD), non-alloantigen specific factors, as ischemia/reperfusion and renal mass have been suggested to play a role in the process. The aim of the present study was to investigate the effect of the transplantation procedure per se on the development of CTD in a syngeneic kidney transplant model in the rat. Kidney transplantation was performed with the BN rat as donor and recipient, the recipient kidneys having been removed. Unilaterally nephrectomized (UNx) and native BN rats served as controls. Renal function was determined monthly (proteinuria and glomerular filtration rate/100 g body weight; GFR). The follow-up period was until 52 weeks post-transplantation. Histomorphological analysis of CTD according to the BANFF criteria was carried out. Immunohistochemical staining was performed to identify infiltrating cells (CD4, CD8, and ED1) and the expression of MHC class II and ICAM-1. Isografts had a minor, constant proteinuria during follow-up, which did not differ from that of UNx: 27 +/- 10 vs. 29 +/- 2 mg/24 h at week 52. Unilateral nephrectomy led to a significant reduction of the GFR, which was about 80% of that of native rats. The GFR of isografts did not differ from that of UNx rats. Histomorphology of renal isografts was comparable to UNx and native kidneys; some glomerulopathy and tubular atrophy leading to a total BANFF-score of 2.6 +/- 0.5. In native BN kidneys, few CD4+ cells and ED-1+macrophages (mphi) were found; MHC class II was constitutively expressed on the proximal tubules and ICAM-1 on the glomeruli and peritubular capillaries. UNx-kidneys showed a similar pattern. Isografts had significantly more CD4+ cells and Mphi, mainly localized in the glomeruli, and a more intense ICAM-1 expression in the glomeruli and interstitium. Transplantation of one kidney in itself does not lead to CTD.
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PMID:Transplantation of a single kidney per se does not lead to late graft dysfunction. 1126 54

We report our experience with a 62-year-old Japanese man with cholesterol crystal embolism after angiographic procedures performed because of intermittent claudication. In addition to progressive renal failure and nephrotic-range proteinuria, cutaneous ischemia, consisting of livedo reticularis in the lower limbs and digital necrosis at the tip of the right toe, and fundoscopic findings showing several white spots in the branches of retinal artery were also observed. Progressive renal failure and nephrotic-range proteinuria were halted just after treatment with simvastatin. Thus, simvastatin can exert a beneficial therapeutic effect on renal cholesterol embolism.
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PMID:Potential therapeutic effect of simvastatin on progressive renal failure and nephrotic-range proteinuria caused by renal cholesterol embolism. 1146 48

Acute episodes of severe renal ischemia result in acute renal failure (ARF). These episodes are followed by a characteristic recovery and repair response, whereby tubular morphology and renal function appear completely restored within approximately 1 mo. However, the chronic effects of such an injury have not been well studied. Male rats were subjected to 60-min bilateral ischemia followed by reperfusion, yielding a characteristic injury. Postischemic animals manifested severe diuresis, peaking at 1 wk postinjury (volume: >45 ml/day, ARF vs. 18 ml/day, sham; P < 0.05). Urine flow subsequently declined but remained significantly elevated vs. sham animals for a 40-wk period. The prolonged alteration in urinary concentrating ability was attributable, in part, to a diminished capacity to generate a hypertonic medullary interstitium. By week 16, proteinuria developed in the post-ARF group and progressed for the duration of the study. Histological examination revealed essentially normal tubular morphology at 4 and 8 wk postinjury but the development of tubulointerstitial fibrosis at 40 wk. Transforming growth factor (TGF)-beta1 expression was elevated at 40 wk, but not at 4 and 8 wk postinjury. Microfil analysis revealed an approximately 30-50% reduction in peritubular capillary density in the inner stripe of the outer medulla at 4, 8, and 40 wk in post-ARF groups vs. sham animals. In addition, post-ARF rats manifested a significant pressor response to a low dose of ANG II (15 ng x kg(-1) x min(-1)). We hypothesize that severe ischemic injury results in a permanent alteration of renal capillary density, contributing to a urinary concentrating defect and the predisposition toward the development of renal fibrosis.
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PMID:Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. 1159 47

Renal biopsy specimens from patients with systemic lupus erythematosus (SLE) rarely show changes that are pathogenetically and morphologically unrelated to SLE. The morphology and behavior of these nonlupus nephritides are not well known. Two hundred fifty-two renal biopsies performed on 224 patients with SLE collected from 3,036 native kidney biopsies performed between 1975 and 1998 were reviewed, and those that showed nonlupus nephritides (index biopsies) were selected for studies. Thirteen biopsy specimens with nonlupus nephritides were identified in 13 patients, who belonged to 3 clinically distinct groups. Group I included 6 patients in whom SLE was diagnosed at the time of index biopsies. The index biopsies in these patients showed focal segmental glomerusclerosis (FSGS; 3 cases), Immunoglobulin (Ig) M nephropathy (1 case), and thin basement membrane disease (1 case). The diagnostic features for FSGS included segmental sclerosis involving at least 1 glomerulus, absence of lupus nephritis or other conditions that may cause nonspecific segmental sclerosis of glomeruli such as ischemia or nephrosclerosis, and nephrotic-range proteinuria. There was uniform, global, diffuse and marked thinning of the glomerular basement membrane in the case of thin basement membrane disease. Group II included 3 patients in whom SLE was diagnosed 2 to 9 years before the time of index biopsies and SLE was active at the time of biopsy. The index biopsies in these patients showed FSGS (2 cases) and hypertensive nephrosclerosis (1 case). Group III included 4 patients in whom SLE was diagnosed 5 to 36 years before the time of index biopsies and SLE was inactive at the time of biopsy. The index biopsies in these patients showed 1 case each of amyloidosis, FSGS, hypertensive nephrosclerosis, and allergic acute tubulointerstitial nephritis. Previous renal biopsies, performed in 5 patients, showed IgM nephropathy (1 case), diffuse proliferative lupus GN (1 case), focal proliferative lupus GN (1 case), and mesangial proliferative lupus GN (2 cases). Follow-up biopsies, performed in 3 patients, confirmed the diagnosis of FSGS (2 cases) and hypertensive nephrosclerosis (1 case) noted in the index biopsies. Nonlupus nephritides may occasionally be encountered in SLE patients, regardless of clinical or serologic disease activity. These renal lesions display a broad morphologic spectrum in which FSGS seems most frequent. Renal biopsy plays a crucial role in identifying these lesions, which may have prognostic and therapeutic implications distinct from those of lupus nephritis.
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PMID:Nonlupus nephritides in patients with systemic lupus erythematosus: a comprehensive clinicopathologic study and review of the literature. 1167 48


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