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)

A 16-month-old boy was admitted to the clinic because of vomiting and growth failure. His weight and height measurements were under the fifth percentile. He had fair hair and skin, enlarged wrists and rachitic rosaries. The presence of metabolic alkalosis, hypokalemia, hypochloremia, and high renin and aldosterone levels were suggestive of Bartter syndrome. However, in view of the growth failure, fair hair and skin, proteinuria, polyuria and active rickets, cystinosis was considered. Bone marrow smear examination was normal, despite the existence of suspicious crystals in the cornea. Cystine crystals were seen in the conjunctiva biopsy and increased leukocyte cystine level was measured; therefore, definitive cystinosis diagnosis was made. Renal Fanconi syndrome with metabolic acidosis is prominent in cystinosis; however, in rare instances, if sodium-dependent trans-tubular transport defect is present, patients could have Bartter syndrome findings such as hypochloremic metabolic alkalosis. Our case is a good example demonstrating that metabolic alkalosis should not exclude cystinosis and the other signs and symptoms of the patient should be thoroughly evaluated.
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PMID:A patient with cystinosis presenting transient features of Bartter syndrome. 1717 73

Functional nephrons can be lost through a process of glomerulotubular disconnection. Progressive development of atubular glomeruli seems to play a major role in a number of renal disorders, including glomerular diseases, ascribed to injury to the glomerulotubular junction as a result of proteinuria; however, formation of atubular glomeruli is even more common in tubulointerstitial disorders, such as obstructive nephropathy. Toxic nephropathy is also associated with the formation of atubular glomeruli, suggesting susceptibility of the glomerulotubular junction to toxic injury. Narrowing or other abnormalities of the glomerulotubular junction are described as precursors of glomerulotubular disconnection. Cystinosis represents a dramatic example of progressive injury to the glomerulotubular junction, with formation of the "swan-neck deformity" following degenerative tubular cell changes attributable to apoptosis. Significant numbers of atubular glomeruli have been reported in chronic pyelonephritis and renal allograft rejection; this suggests interstitial inflammation as a stimulus for the formation of atubular glomeruli. Because of difficulties in morphologic recognition, it is likely that glomerulotubular disconnection is an underappreciated mechanism in the progression of renal disease. A better understanding of the vulnerability of the glomerulotubular junction and its protection from injury should lead to better strategies for preserving renal function in many nephropathies.
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PMID:Generation and evolution of atubular glomeruli in the progression of renal disorders. 1819 96

Renal transplantation (Tx) is the treatment of choice for end-stage renal disease. The incidence of acute rejection after renal Tx has decreased because of improving early immunosuppression, but the risk of disease recurrence (DR) is becoming relatively high, with a greater prevalence in children than in adults, thereby increasing patient morbidity, graft loss (GL) and, sometimes, mortality rate. The current overall graft loss to DR is 7-8%, mainly due to primary glomerulonephritis (70-80%) and inherited metabolic diseases. The more typical presentation is a recurrence of the full disease, either with a high risk of GL (focal and segmental glomerulosclerosis 14-50% DR, 40-60% GL; atypical haemolytic uraemic syndrome 20-80% DR, 10-83% GL; membranoproliferative glomerulonephritis 30-100% DR, 17-61% GL; membranous nephropathy approximately 30% DR, approximately 50% GL; lipoprotein glomerulopathy approximately 100% DR and GL; primary hyperoxaluria type 1 80-100% DR and GL) or with a low risk of GL [immunoglobulin (Ig)A nephropathy 36-60% DR, 7-10% GL; systemic lupus erythematosus 0-30% DR, 0-5% GL; anti-neutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis]. Recurrence may also occur with a delayed risk of GL, such as insulin-dependent diabetes mellitus, sickle cell disease, endemic nephropathy, and sarcoidosis. In other primary diseases, the post-Tx course may be complicated by specific events that are different from overt recurrence: proteinuria or cancer in some genetic forms of nephrotic syndrome, anti-glomerular basement membrane antibodies-associated glomerulonephritis (Alport syndrome, Goodpasture syndrome), and graft involvement as a consequence of lower urinary tract abnormality or human immunodeficiency virus (HIV) nephropathy. Some other post-Tx conditions may mimic recurrence, such as de novo membranous glomerulonephritis, IgA nephropathy, microangiopathy, or isolated specific deposits (cystinosis, Fabry disease). Adequate strategies should therefore be added to kidney Tx, such as donor selection, associated liver Tx, plasmatherapy, specific immunosuppression protocols. In such conditions, very few patients may be excluded from kidney Tx only because of a major risk of DR and repeated GL. In the near future the issue of DR after kidney Tx may benefit from alternatives to organ Tx, such as recombinant proteins, specific monoclonal antibodies, cell/gene therapy, and chaperone molecules.
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PMID:Disease recurrence in paediatric renal transplantation. 1924 94

A five-year-old boy was referred to our pediatric clinic for evaluation of failure to thrive, headache, intermittent high fever, restlessness, polyuria, and polydipsia. His weight and height measurements were under the 3rd percentile. Clinical findings consisted of frontal bossing, carious teeth, O-bain deformity of the lower extremities, and moderate dehydration. The presence of metabolic alkalosis, hypokalemia, hypochloremia, and high renin and aldosterone levels were suggestive of Bartter syndrome and a treatment regimen for Bartter syndrome was started. At follow-up, the polyuria and hyponatremia were found to persist. A reassessment of the patient revealed findings consistent with proximal renal tubular acidosis such as metabolic acidosis with a high urinary pH, proteinuria, aminoaciduria with phosphaturia and hypercalciuria. Based on the presence of parental consanguinity as well as polyuria, proteinuria, low tubular reabsorption of phosphorus, generalized aminoaciduria, light yellow skin and hair color, the probable diagnosis of cystinosis was established and was confirmed by slit-lamp examination of the cornea showing cystine crystal deposition. Our case is a good example demonstrating that development of metabolic alkalosis does not exclude cystinosis and that all findings of the patient should be thoroughly evaluated.
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PMID:Cystinosis presenting with findings of Bartter syndrome. 2175 Jun 41

We report the molecular findings for the CTNS gene in 12 Turkish cystinosis patients aged 7-29 years. All presented initially with severe failure to thrive, polyuria, and polydipsia. Cystinosis was diagnosed at age 1 month to 9 years. Seven patients reached end-stage renal failure at ages ranging from 6.5 to 15 years. Whereas three of the remaining five have renal Fanconi syndrome with proteinuria, two have had kidney failure of varying degrees. Molecular analyses involved an initial multiplex polymerase chain reaction (PCR) to determine the presence or absence of the 57-kb northern European founder deletion in CTNS, followed by sequencing of the ten coding exons of CTNS. Comprehensive mutation analysis verified that none of the 12 patients carried the common 57-kb deletion. We identified four previously reported nucleotide variations associated with cystinosis and five new variants: a 10-kb deletion, three missense variants, and a nucleotide substitution in a potential branch point site of intron 4. This study is the first molecular analysis of Turkish cystinosis patients and provides guidance for the molecular diagnosis of cystinosis in this population.
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PMID:Genetic basis of cystinosis in Turkish patients: a single-center experience. 2178 42

Cystinosis is the major cause of inherited Fanconi syndrome, and should be suspected in young children with a failure to thrive and with signs of renal proximal tubular damage. This is a study of a case report of cystinosis revealed by a growth failure and chronic dehydration. A 9-month-old boy was referred to our department for evaluation of polyuria and polydipsia. Clinical examination showed dehydration and enlarged wrists and rachitic rosaries. The presence of metabolic acidosis, hypokalemia, hypochloremia with proteinuria, polyuria, and hypercalciuria was suggestive of inherited Fanconi syndrome. The diagnosis of cystinosis was confirmed by an increased leukocyte cystine level.
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PMID:Nephropathic infantile form of cystinosis about one case. 2249 86

Patients with renal tubular acidosis (RTA) usually have tubular or low molecular weight proteinuria. The authors present a rare case of a 6-y-old girl with Fanconi syndrome secondary to cystinosis, who at presentation had nephrotic range proteinuria along with rickets and failure to thrive. Although hypoalbuminemia and massive proteinuria are characteristics of nephrotic syndrome, there are other conditions which can present with massive proteinuria.
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PMID:Nephrotic range proteinuria as a presenting feature of classical nephropathic cystinosis. 2377 3

Nephropathic cystinosis, a lysosomal storage disease caused by mutations in the CTNS gene encoding the lysosomal cystine transporter cystinosin, is characterized by generalized proximal tubule (PT) dysfunction that progresses, if untreated, to end-stage renal disease. The pathogenesis of defective PT cellular transport in nephropathic cystinosis remains unclear. We characterized a recently generated line of C57BL/6 Ctns mice and analyzed endocytic uptake, lysosome function, and dedifferentiation and proliferation markers using primary cultures of PT epithelial cells derived from Ctns(-/-) and Ctns(+/+) littermates. Metabolic studies revealed that Ctns(-/-) mice show a progressive PT dysfunction characterized by low-molecular-weight (LMW) proteinuria, glucosuria and phosphaturia, before structural damage and in the absence of renal failure. These changes are related to decreased expression of the multi-ligand receptors megalin and cubilin and to increased dedifferentiation (ZONAB transcription factor) and proliferation (PCNA and Cyclin D1) rates. Studies on PT cells derived from Ctns(-/-) kidneys confirmed cystine overload, with accumulation of enlarged, dysfunctional lysosomes and reduced expression of endocytic receptors reflected by decreased uptake of specific ligands. These changes were related to a loss of integrity of tight junctions with a nuclear translocation of ZONAB and increased proliferation, as observed in Ctns(-/-) kidneys. These data reveal that the absence of cystinosin in PT cells triggers aberrations of the endolysosomal compartment, transport defects and an abnormal transcription program in the early stage of nephropathic cystinosis. Insights into the early manifestations of cystinosis may offer new targets for intervention, before irreversible renal damage.
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PMID:Dedifferentiation and aberrations of the endolysosomal compartment characterize the early stage of nephropathic cystinosis. 2431

Measurement of retinol-binding protein 4 in urine (uRBP4) is arguably the most sensitive biomarker for loss of function of the human proximal renal tubule. Megalin- and cubilin-receptor-mediated endocytosis normally absorbs > 99% of the approximately 1.5 g/24 h of protein filtered by the renal glomerulus. When this fails there is "tubular proteinuria," comprising uRBP4, albumin, and many other proteins and peptides. This tubular proteinuria is a consistent feature of the renal Fanconi syndrome (FS) and measurement of uRBP4 appears to be an excellent screening test for FS. FS occurs in rare inherited renal diseases including cystinosis, Dent disease, Lowe syndrome, and autosomal dominant FS. Acquired FS occurs in paraproteinemias, tubulointerstitial renal disease, oncogenic osteomalacia, Chinese herbs nephropathy, and Balkan endemic nephropathy. Though poorly understood, FS may be associated with HIV disease and antiretroviral treatment; cadmium poisoning may cause FS. In addition to FS, uRBP4 measurement has a different role: the early detection of acute kidney injury. Urine RBP4 comprises several isoforms, including intact plasma RBP4, MW 21.07 kDa, and C-terminal truncated forms, des-L- and des-LL-RBP4, also probably plasma derived. In FS, uRBP4 levels are about 104-fold above the upper limit of normal and small increments are frequently seen in carriers of some inherited forms of FS and in acquired disease. The very high levels in disease, frequent assay nonlinearity, lack of defined calibrants, and multiple uRBP4 isoforms make accurate assay challenging; top-down mass spectrometry has brought advances. Assays for uRBP4 with defined molecular targets allowing good interlaboratory comparisons are needed.
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PMID:Urine retinol-binding protein 4: a functional biomarker of the proximal renal tubule. 2478 52

Nephropathic cystinosis is a rare lysosomal storage disorder caused by mutations in the CTNS gene ncoding the lysosomal cystine transporter cystinosin. Cystinosin deficiency leads to accumulation of cystine in the lysosomes of cells throughout the body and deregulation of endocytosis, trafficking of intracellular vesicles and related cell signalling processes. One of the early features of the disease is renal Fanconi syndrome characterized by polyuria, proteinuria and urinary loss of various solutes. Later in life, extrarenal complications become apparent, and decline of kidney function leads to the development of end-stage renal disease. Modern therapy of the disease is based on treatment with cystine-lowering drug cysteamine, which helps to postpone the disease progression and development of extra-renal pathologies, but offers no cure for the Fanconi syndrome. Besides the improvement of cystine-lowering therapy based on new formulations of cysteamine, further development of therapy is necessary. Some steps forward were done in the recent years, including studies of cell signalling abnormalities in cystinosis and development of stem cell and gene therapy approaches.
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PMID:Cystinosis: clinical presentation, pathogenesis and treatment. 2534


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