Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Linezolid is a recent oral antibiotic used in drug-resistant Gram-positive cocci infections. Herein, we report on the first case of linezolid-related acute renal failure in a kidney-transplant patient. A 60-year-old male having autosomic polycystic kidney disease with liver involvement, on cyclosporin A, mycophenolate mofetil and very low dose prednisolone, presented with an Enterococcus faecium abscess of a huge liver cyst, which was treated by percutaneous drainage and linezolid therapy. Eight days after starting linezolid, he presented with acute renal failure, i.e. serum creatinine increased from 136- 221 micromol/l, associated with mild hypereosinophilia, anemia and thrombocytopenia. There was no skin rash, arthralgia, eosinophiluria or proteinuria. The transplant kidney biopsy, performed 15 days after the beginning of linezolid therapy, showed interstitial nephritis and focal tubular atrophy. After linezolid withdrawal and increasing prednisolone daily dose to 20 mg/d, within a few days, serum creatinine had decreased; after 2 and 4 weeks post linezolid withdrawal, his serum creatinine was 166 and 159 micromol/l, respectively. Because of the potential side effects of linezolid, i.e. myelosuppression and possibly nephrotoxicity, we recommend close monitoring of these parameters when linezolid therapy is attempted in kidney transplant patients.
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PMID:Linezolid-induced interstitial nephritis in a kidney-transplant patient. 1804 66

Polycystin-2 (PC-2), a cation channel of the Trp family, is involved in autosomal dominant polycystic kidney disease (ADPKD) type 2 (ADPKD2). This protein has recently been localized to the primary cilium where its channel function seems to be involved in a mechanosensory phenomenon. However, its biological function is not totally understood, especially in tubule formation. In the present paper, we describe a mouse model for human PC-2 overexpression, obtained by inserting a human bacterial artificial chromosome (BAC) containing the PKD2 gene. Three lines were generated, expressing different levels of PKD2. One line, PKD2-Y, has been explored in more detail and we will present physiological and molecular exploration of these transgenic animals. Our data demonstrate that transgenic animals older than 12 months present tubulopathy with proteinuria and failure to concentrate urine. Moreover, the kidney cortex has been found disorganized. Finally, we observe that extracellular matrix protein expression is downregulated in these animals. In conclusion, overexpression of human PKD2 leads to anomalies in tubular function, probably due to abnormalities in tubule morphogenesis.
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PMID:Overexpression of PKD2 in the mouse is associated with renal tubulopathy. 1804 22

Nephronophthisis (NPHP) is a disease characterized by a genetic cause of chronic renal failure in children and adolescents, complicated with several extra-renal manifestations such as retinal defect and/or liver fibrosis. Although it is difficult to establish the correct diagnosis, mutations in six genes (NPHP 1-6) have recently been identified. Here we report the case of a 25-year-old male with NPHP with congenital hepatic fibrosis. He showed microscopic hematuria and moderate proteinuria at 20 years. Renal biopsy revealed severe interstitial fibrosis, diffuse tubular atrophy and microcysts at this time with chronic kidney disease stage III (Cr 2.43 mg/dl). C3c was positive in glomeruli in direct immunofluorescent study. Although his mother belongs to a family with polycystic kidney disease, he did not have a novel genetic background of Arg585Cys mutation in exon 8 of the PKD1 gene. Magnetic resonance angiography (MRA) showed typical portal hypertension with spleno-renal shunt caused by biopsy-proven liver fibrosis. Thus, we diagnosed him as having undetermined renal cystic or tubulo-interstitial disease complicated with membranoproliferative glomerulonephritis (MPGN). Renal transplantation was performed in January 2005 after 2 years of dialysis therapy. He was transported to our emergency room because of severe abdominal pain in December 2005. A computed tomographic scan showed massive ascites, which were caused by rupture of the splenic artery. Despite full intensive care including intraluminal coiling of the ruptured aneurysm and extensive blood transfusion, we failed to rescue him on the next day. The autopsy findings revealed severe atrophy of the bilateral kidney with multiple cysts along the cortico-medullary border. Obvious portal hypertension, resulting from congenital hepatic fibrosis, could account for the rupture of the splenic artery with aneurysm formation under pressure/volume overload. This is the first report of a NPHP patient with the complication of hepatic fibrosis emerging from an ADPKD family. As it remains elusive on the phenotype-genotype of the Japanese NPHP population, a registration system of cystic disease of the kidney is required.
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PMID:Nephronophthisis complicated with hepatic fibrosis: an autopsy case with rupture of the splenic artery after renal transplantation. 1817 55

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease characterized by a prolonged subclinical course of gradual renal cyst expansion, resulting in massively enlarged kidneys and renal failure by the fifth to sixth decade. Renal cyst expansion results in intrarenal ischemia and activation of the renin-angiotensin-aldosterone system (RAAS) and relates to the development and maintenance of hypertension in ADPKD. Hypertension relates to disease progression in ADPKD with regard to renal volume, proteinuria, cardiovascular complications, and progression to end-stage renal disease. Novel magnetic resonance imaging methods developed in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) provide accurate estimates of change in renal volume over a short period of time in ADPKD patients with intact renal function. In CRISP an increase in renal volume of 63.4 ml/yr was found. PKD1 status, male gender, hypertension, reduced renal blood flow, and proteinuria are associated with increased renal volume and change in renal volume over time. HALT-Polycystic Kidney Disease (HALT-PKD) is designed to test whether blockade of RAAS and/or rigorous blood pressure control play a role in slowing renal progression during early (using magnetic resonance imaging methods developed in CRISP) and during late (using measures, including composite of time to doubling of serum creatinine, onset of end-stage renal disease, or death) phases in ADPKD. Findings from CRISP and the rationale for interventions in ADPKD are described, and the design of the HALT-PKD clinical trial is outlined.
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PMID:Approaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies. 1857 74

Adults with autosomal dominant polycystic kidney disease (ADPKD) and PKD1 mutations have a more severe disease than do patients with PKD2 mutations. The aim of this study was to compare phenotypes between children with mutations in the PKD1/PKD2 genes. Fifty PKD1 children and ten PKD2 children were investigated. Their mean age was similar (8.6 +/- 5.4 years and 8.9 +/- 5.6 years). Renal ultrasound was performed, and office blood pressure (BP), ambulatory BP, creatinine clearance and proteinuria were measured. The PKD1 children had, in comparison with those with PKD2, significantly greater total of renal cysts (13.3 +/- 12.5 vs 3.0 +/- 2.1, P = 0.004), larger kidneys [right/left kidney length 0.89 +/- 1.22 standard deviation score (SDS) vs 0.17 +/- 1.03 SDS, P = 0.045, and 1.19 +/- 1.42 SDS vs 0.12 +/- 1.09 SDS, P = 0.014, successively] and higher ambulatory day-time and night-time systolic BP (day-time/night-time BP index 0.93 +/- 0.10 vs 0.86 +/- 0.05, P = 0.021 and 0.94 +/- 0.07 vs 0.89 +/- 0.04, P = 0.037, successively). There were no significant differences in office BP, creatinine clearance or proteinuria. Prenatal renal cysts (14%), hypertension defined by ambulatory BP (27%) and enlarged kidneys (32%) were observed only in the PKD1 children. This is the first study on genotype-phenotype correlation in children with ADPKD. PKD1 children have more and larger renal cysts, larger kidneys and higher ambulatory BP than do PKD2 children. Renal cysts and enlarged kidneys detected prenatally are highly specific for children with PKD1.
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PMID:Genotype-phenotype correlation in children with autosomal dominant polycystic kidney disease. 1919 29

Sirolimus is a member of a novel class of immunosuppressant drug that potently suppresses T cell proliferation and expansion by inhibition of the Target of Rapamycin Complex 1 (TORC1) protein kinase. Sirolimus also has anti-proliferative effects on intrinsic cells of the kidney, and increasing evidence suggests that it may have a therapeutic role in non-transplant renal diseases. In the normal kidney, sirolimus is considered to be non-nephrotoxic. In the diseased kidney, sirolimus may be beneficial or detrimental, depending on the type of renal injury. In polycystic kidney disease, TORC1 activation mediates renal tubular epithelial cell (TEC) proliferation and cyst growth in animals, and Phase III clinical trials are underway to determine the effect of sirolimus in attenuating disease progression in humans. In contrast, in acute kidney injury, sirolimus transiently impairs proximal TEC regeneration and delays renal recovery. In animal models of lupus nephritis and diabetic kidney disease, sirolimus prevents disease progression. However, the efficacy of sirolimus in human glomerulonephritis as well as in diabetic chronic kidney disease remains unclear, as it paradoxically exacerbates renal dysfunction when the baseline glomerular filtration rate is low (< 40 ml/min/1.73 m(2)) and there is heavy proteinuria (> 300 mg/day). This may, in part, be due to inhibition of compensatory glomerular capillary repair through the suppression of endothelial cell proliferation and angiogenic growth factor production by podocytes. Therefore, at present, polycystic kidney disease is the most promising therapeutic application for sirolimus in non-transplant renal diseases, and further studies are needed to clarify its role in other situations.
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PMID:Therapeutic role of sirolimus in non-transplant kidney disease. 1937 18

Some calcium channel blockers (CCBs) have renoprotective effects. Our aim was to compare the effects of different subclasses of CCBs on the deterioration of renal function in chronic kidney disease (CKD). This is a prospective, observational cohort study in a single center. The subjects were 107 nondiabetic CKD patients. The rate of deterioration of estimated glomerular filtration rate (DeltaeGFR) was calculated by [last visit eGFR - baseline eGFR/follow-up duration]. Multivariate analysis was performed using the change in urinary protein (DeltaUP) and DeltaeGFR during follow-up as response variables. CCB subclasses were L-type in 76 patients, T- and L-type in 28 patients, and nondihydropyridines in 6 patients. Multiregression analysis indicated that higher baseline proteinuria (UP) and the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers were associated with the decrease of UP, while the use of L-type CCBs, prednisolone, and probucol was associated with the increase of UP. The use of T- and L-type CCBs, ACEIs and diuretics was associated with a good outcome in terms of DeltaeGFR, whereas chronic glomerulonephritis, polycystic kidney disease, and higher baseline eGFR and UP were associated with a poor outcome. It is suggested that the use of T- and L-type CCB among other subclasses may improve the outcome of patients with nondiabetic CKD in terms of renal function.
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PMID:Influence of T-calcium channel blocker treatment on deterioration of renal function in chronic kidney disease. 1962 4

Hypertension is very common in patients with chronic kidney disease (CKD); it causes early loss of kidney function and accelerated cardiovascular morbidity and mortality. African American patients with hypertension and genetic disposition are at an even higher risk for renal disease and ultimately renal failure. Hypertensive patients with CKD should aim for stringent blood pressure (BP) control (target < 130/80 mm Hg) requiring more than one drug with renin-angiotensin-aldosterone system blockade as a component of therapy targeting both hyper-tension and proteinuria. Management of hypertension in the dialysis population should focus on ambulatory measurements of BP and the use of longer-acting antihypertensive drugs, with their dosage and timing adjusted according to their dialytic clearances. Hypertension is also common among kidney transplant recipients and contributes to graft loss and premature death. The target BP in transplant recipients is the same as in the CKD population, with no preference for one drug group over another. Unless contraindicated, angiotensin-converting enzyme inhibitors remain the drugs of choice for hypertension in patients with autosomal-dominant polycystic kidney disease, in whom diastolic cardiac dysfunction is a prominent feature.
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PMID:Hypertension in patients with chronic kidney disease. 1973 49

The efficacy of mammalian target of rapamycin (mTOR) inhibitors is currently tested in patients affected by autosomal dominant polycystic kidney disease. Treatment with mTOR inhibitors has been associated with numerous side effects. However, the renal-specific effect of mTOR inhibitor treatment cessation in polycystic kidney disease is currently unknown. Therefore, we compared pulse and continuous everolimus treatment in Han:SPRD rats. Four-week-old male heterozygous polycystic and wild-type rats were administered everolimus or vehicle by gavage feeding for 5 wk, followed by 7 wk without treatment, or continuously for 12 wk. Cessation of everolimus did not result in the appearance of renal cysts up to 7 wk postwithdrawal despite the reemergence of S6 kinase activity coupled with an overall increase in cell proliferation. Pulse everolimus treatment resulted in striking noncystic renal parenchymal enlargement and glomerular hypertrophy that was not associated with compromised kidney function. Both treatment regimens ameliorated kidney function, preserved the glomerular-tubular connection, and reduced proteinuria. Pulse treatment at an early age delays cyst development but leads to striking glomerular and parenchymal hypertrophy. Our data might have an impact when long-term treatment using mTOR inhibitors in patients with autosomal dominant polycystic kidney disease is being considered.
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PMID:Pulse mTOR inhibitor treatment effectively controls cyst growth but leads to severe parenchymal and glomerular hypertrophy in rat polycystic kidney disease. 1977 71

Autosomal dominant polycystic kidney disease is a multiorgan hereditary disorder. It is responsible for 7-10% of cases of end stage renal failure. It is caused by mutations in the genes PKD1 and PKD2. The diagnosis of this disease can be performed through ultrasounds, but the molecular diagnosis offers some advantages, such as the early detection of asymptomatic individuals who carry this genetic defect, in order to perform a preventive monitoring and genetic counselling. In this work, we present the results of the clinical analysis of 48 patients diagnosed with autosomal dominant polycystic kidney disease. The objectives of this work were to analyze the main clinical aspects of the disease. The average age of appearance of the first symptoms was 41.17 +/- 13.41 years in women and 49.91 +/- 12.52 years in men (p < 0.05). Arterial hypertension was the first sign of the disease (68.42%), with more cases in men than in women (p < 0.05), followed by chronic renal failure (68.29 %). The most common renal symptom during the evolution of the disease was chronic renal failure, which was present in all the patients of the study, followed by proteinuria (92.31%), end-stage renal failure (89.58%) and arterial hypertension (87.23%). In summary, our results reveal a high prevalence of patients with polycystic kidney disease who received a late diagnosis. This could possibly explain the high morbi-mortality associated to this condition. Given the high prevalence of chronic renal failure and endstage renal failure secondary to polycystic kidney disease in our study, the early diagnostic of the disease would carry better prognostic in relation with a more strict clinical followup. The arterial hypertension was the most frequent clinical manifestation of the disease in our study by what this entity should be included in all the hypertense patients of unknown etiology and on the other hand, the infectious complications should be a sign of alert in every patient with polycystic kidney disease.
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PMID:[Clinical analysis of a population with autosomal dominant polycystic kidney disease]. 2009 73


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