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 report here the case of a 9-year-old Japanese boy with nephrotic syndrome caused by focal segmental glomerulosclerosis, which was refractory to treatment. Although aggressive immunosuppressive therapy consisting of methylprednisolone pulse therapy combined with cyclosporine A (CsA) and intermittent low density lipoprotein apheresis was effective in overcoming his steroid-resistant state, the child became persistently steroid-dependent, that is, more than 0.75 mg/kg per day of prednisolone combined with CsA was required to maintain a negative test for proteinuria. Since adverse effects of prednisolone, such as short stature, obesity, osteoporosis and cataract, were noted, CsA in his treatment regimen was replaced with tacrolimus at the dose of 0.1 mg/kg per day, with the trough blood level of the drug maintained at around 10 ng/ml. Within 4 months of the inclusion of tacrolimus in the treatment regimen, complete remission was achieved, with no recurrence of the proteinuria, while the prednisolone dose could be tapered to 0.3 mg/kg per day. No adverse effects of tacrolimus were observed. These clinical results suggest that tacrolimus may be the drug of choice in selected patients with refractory nephrotic syndrome, even if pediatric-onset cases, at least those in whom the steroid-sparing effects of CsA is unsatisfactory.
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PMID:Effective therapy of a child case of refractory nephrotic syndrome with tacrolimus. 1550 24

The oculo-cerebro-renal syndrome of Lowe is a rare X-linked disorder, caused by the inositol biphosphate 5-phosphatase deficiency, localized to the Golgi complex. Several mutations were reported in patient's OCRL gene leading to enzyme deficiency. We report a Moroccan case of OCRL syndrome of Lowe with a neo mutation in exon 10. The patient aged of 19 months was referred to our medical centre because of a psychomotor retardation. He had a medical history of eye abnormalities including cataract and bilateral glaucoma, diagnosed when he was 5 weeks old. Cataract has been treated after chirurgical therapy but ocular hypertonia persisted. Physical examination revealed an axial hypotonia and walking difficulties. Laboratory tests revealed a moderate acidosis (20 mmol/L), a slight decrease of serum phosphate level (24 mg/L) and an increased serum phosphatase activity. Further studies showed mild proteinuria, urinary bicarbonates loosing and generalised hyperaminoaciduria. Based on both clinical and biological data, Lowe syndrome has been suggested. In this context, molecular investigation has been performed using dHPLC/sequencing techniques which allow identifying an original mutation c.776T>C (p.Phe259Ser), localized on the exon 10 of the OCRL gene. The mutation was not found in the probant's mother suggesting a neo mutation. Lowe syndrome is a rare hereditary X-linked disorder resulting from a variety of heterogeneous mutations of OCRL gene. Indeed, numerous mutations have been reported, variations were noted concerning their localization as well as their type. To our knowledge, this is the first report of the neo mutation c.776T>C of OCRL gene and the first published case report of the Lowe syndrome in a Moroccan patient.
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PMID:[Oculo-cerebro-renal Lowe syndrome: clinical, biochemical and molecular studies in a Moroccan patient]. 1642 Sep 90

A retrospective study was performed in 68 patients diagnosed as having idiopathic nephrotic syndrome with steroid-dependent, steroid-resistant or frequent relapse subtypes at the Department of Pediatrics, Siriraj Hospital during Jan 1996-Dec 2004. Male to female ratio was 3.3:1 and mean age (+/- SD) was 8.4 +/- 3.5 years. Mean follow up time (+/- SD) was 47.4 +/- 30.5 months. Renal biopsy was done in 60 patients, showing IgM nephropathy in 73.3%. Fifty-four patients (79.4%) received cyclophosphamide at a dose (+/- SD) of 2.2 +/- 0.5 mg/kg/d for 11.6 +/- 3.4 weeks. Negative proteinuria at 1 year was found in 70% and prednisolone was discontinued in 52%. Leucopenia was found in 9.2%. At last follow up, 34% of the patients were still in remission. Enalapril was prescribed in 50 patients for 12.4 +/- 10.0 months. Thirty-six patients also received cyclophosphamide. Remission at 1 year was achieved in 66% and prednisolone discontinued in 28%. Twelve patients (24%) were still in remission at last follow up. The results of 3 regimens: cyclophosphamide, enalapril, and cyclophosphamide plus enalapril were compared using chi-square test. Remission was significantly better in cyclophosphamide group (p = 0.014). Dipyridamole was prescribed in 14 patients due to thrombocytosis. Only 2 of 14 patients achieved remission although 11 patients received cyclophosphamide plus enalapril, and another 2 patients received only cyclophosphamide. Complications included hypertension (44%), cataract (40%), glaucoma (15%), short stature (17.6%), and obesity (5.9%). Recurrent infection was found in 69%, including dental caries (16.29%), urinary tract infection (14.7%), intestinal parasitic infestration (10.3%), respiratory tract infection (8.8%), and skin infection (7.4%). Chronic renal failure was found in 3 patients and portal vein thrombosis was found in 1 patient. We suggest that cyclophosphamide should be used as first line drug in difficult-to-treat nephrotic syndrome patients. Enalapril may be beneficial in some patients. Thrombocytosis may be associated with poor response to both medications. Difficult-to-treat patients also need long-term follow up and surveillance for complications due to disease and/or treatment.
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PMID:Difficult-to-treat nephrotic syndrome: management and outcome. 1685 34

The goals of this study were to ascertain damage in patients with systemic lupus erythematosus (SLE) from five rheumatologic centres in Argentina and to examine overall damage, damage by domain and damage by item within each domain. We performed a retrospective observational study including patients with SLE (ACR 1997 revised and modified criteria) from five rheumatology centres in Argentina. Organ damage was scored using the SLICC/ACR DI (SDI), ascertained at years 1, 2, 5 and 10. Three centres provided information up to the fifth year. Of the 197 patients, 88.3% were women and their mean age was 33.2 years. The mean disease duration and follow-up were 7.6 and 5.3 years, respectively. Damage accrued gradually over time with SDI ranging from 0.52 (+/-1.1) at year 1 up to 2.46 (+/-2.1) at year 10. The renal system was the most involved system, followed by the neuropsychiatric, the cardiovascular and the musculoskeletal systems. Proteinuria, cognitive impairment, pericarditis, avascular necrosis, cataract and alopecia were the predominant items in their respective systems. Systems such as peripheral vascular, pulmonary, gastrointestinal, diabetes, malignancy and premature gonadal failure were not frequent. Overall SDI had a gradual increase over time. Damage in each domain of SDI, except for diabetes, had a similar behaviour. Behaviour of items in each domain varied.
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PMID:Accrual of organ damage over time in Argentine patients with systemic lupus erythematosus: a multi-centre study. 1741 6

A proportion of patients with refractory nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS) often require long-term hospitalization, which results in the loss of quality of life (QOL) of the patients. An-11-year-old girl was brought to a regional hospital with an 8-day history of generalized edema. Laboratory studies revealed massive proteinuria without hematuria and marked hypoalbuminemia associated with hyperlipidemia. A percutaneous renal biopsy revealed lesions characteristic of FSGS. Although methylprednisolone pulse therapy was administered followed by oral prednisolone combined with cyclosporine A, heavy proteinuria persisted for the next 4 months. The patient was referred subsequenthy to our hospital for further examinations. High-dose intermittent mizoribine pulse therapy, LDL-apheresis, cyclosporine A, tacrolimus and intravenous cyclophosphamide pulse therapy proved to be partially effective. As a result, long-term hospitalization and intravenous administration of albumin, diuretics and immunoglobulin was required for this patient. Also, she developed severe steroid toxicity such as obesity, cataract and osteoporosis. A third renal biopsy revealed an advanced stage of FSGS lesions, suggesting subsequent development of end-stage renal disease (ESRD). Since the patient suffered from long-term hospitalization over 3 years and significant loss of QOL, we therefore proposed early initiation of peritoneal dialysis (PD), as in cases of congenital NS, in order to preserve the patient's general condition without intravenous drug administrations and for the preparation of a future renal transplantation. After obtaining informed consent from the patient and her family, the initiation of PD was performed at the age of 15 years before the ESRD state(serum creatinine level 2.0 mg/dL). The patient was successfully free from intravenous drug administrations and hospitalization, and the QOL was significantly improved thereafter. We, therefore, suggest that early initiation of PD might be a treatment of choice for elected patients with severe refractory nephrotic syndrome such as this presented case.
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PMID:[Early initiation of peritoneal dialysis for the treatment of a patient with refractory nephrotic syndrome]. 1923 11

The Spontaneously Diabetic Torii-Lepr(fa) (SDT-fa/fa) rat, a new model of obese type 2 diabetes, shows obesity, hyperglycemia, and hyperlipidemia from 6 weeks of age. Diabetic complications such as nephropathy and cataract are observed with aging; however, blood pressure change with age has not previously been examined. In this study, blood pressure was periodically measured and the change was investigated. Blood pressure in male SDT-fa/fa rats was elevated at 8, 16, and 24 weeks of age, whereas the heart rate was not changed. In addition to hyperglycemia, hyperlipidemia, and proteinuria, hyperleptinemia and increased urine angiotensinogen were observed in SDT-fa/fa rats. Blood pressure and heart rate in the male original SDT (SDT-+/+) rat did not significantly change. In conclusion, the SDT-fa/fa rat is a promising model, showing significant hypertension with diabetes mellitus.
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PMID:Evaluation of blood pressure in Spontaneously Diabetic Torii-Lepr(fa) rats. 2066 Oct

The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.
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PMID:[Application of guidelines in clinical practice: a multicenter analysis of the treatment of membranous glomerulonephritis in Piedmont, Italy]. 2113 46

The incidence of type 1 diabetes is rising all over the world. Furthermore, the increased life-expectancy of type 1 diabetic patients is likely to cause a higher number of diabetes-related micro- and macrovascular complications in the years to come. In order to examine the level of long-term complications in type 1 diabetes as well as potential markers of micro- and macroangiopathy, a population-based cohort of Danish type 1 diabetic patients was examined in order to achieve the following aims: 1. To evaluate diabetic retinopathy as a long-term marker of all-cause mortality in type 1 diabetes (Paper I). 2. To estimate the long-term incidence and associated risk factors of blindness (Paper II) and cataract surgery (Paper III) in type 1 diabetes. 3 To use retinal vascular analyses in order to investigate the associations of long-term micro- and macrovascular complications and retinal vascular diameters (Paper IV) and retinal fractals (Paper V) in type 1 diabetes. 4. To examine N-terminal pro brain natriuretic peptide (Paper VI) and osteoprotegerin (Paper VII) as non-invasive markers of micro- and macrovascular complications in type 1 diabetes. In Paper I it was a major finding that, despite a mean age of only 38.3 years at baseline, 44.7% of the patients died during the 25-year follow-up. Patients who had proliferative retinopathy as well as proteinuria at the baseline examination had a significantly higher mortality. For these, the 10-year survival was only 22.2%. As demonstrated in Paper II, blindness is an important issue in type 1 diabetes. The 25-year cumulative incidence of blindness was 7.5%. Glycaemic regulation and maculopathy at baseline were both identified as risk factors of blindness. Finally, mortality was higher in patients who went blind during the follow-up. Cataract surgery is quite common in type 1 diabetes. In Paper III a 25-year cumulative incidence of 20.8% was found. Adjusted for mortality, this was even higher (29.4%). As compared to patients without diabetes, cataract surgery takes place approximately 20 years earlier in type 1 diabetic patients. Age and maculopathy at baseline were both identified as predictors of cataract surgery. In Paper IV it was demonstrated that patients with retinal arteriolar narrowing were 2.17 and 3.17 times more likely to have nephropathy and macrovascular disease, respectively. This was an important finding that suggests that retinal fundus photos may be used in order to predict the risk of non-ophthalmological complications in type 1 diabetes. Retinal fractal analysis is another way to evaluate the vascular system of the retina. In Paper V we found associations between retinal fractal and microvascular - but not macrovascular--disease. For instance, patients with lower fractal dimensions were more likely to have proliferative retinopathy (OR 1.45, 95% CI 1.04-2.03) and neuropathy (OR 1.42, 95% CI 1.01-2.01). NT-proBNP is likely to be a future predictor of diabetes-related complications. In Paper VI higher levels of NT-proBNP were related to nephropathy (OR 5.03, 95% CI 1.77-14.25), neuropathy (OR 4.08, 95% CI 1.52-10.97) and macrovascular disease (OR 5.84, 95% CI 1.65-20.74). These associations should be confirmed in future prospective studies. As opposed to NT-proBNP, osteoprotegerin is less likely to be a predictor of either micro- or macrovascular disease in type 1 diabetes. As demonstrated in Paper VII, even though association between higher levels of OPG and nephropathy were found in an age- and sex-adjusted model (OR 2.54, 95% CI 1.09-5.90), this was no longer statistically significant when other factors were taken into account. Overall, it was demonstrated that various complications such as mortality, blindness and cataract surgery were high in type 1 diabetes. Furthermore, retinal arteriolar narrowing, decreased retinal fractals and plasma NT-proBNP were associated with various micro- and macrovascular complications. If confirmed by prospective studies, these modalities may be used in order to identify patients at risk of diabetes-related complications. This could, ultimately, lead to decreased mortality and morbidity in type 1 diabetic patients.
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PMID:Eye complications and markers of morbidity and mortality in long-term type 1 diabetes. 2144 78

We report on a rare case of an exon 16 mutation of the MYH9 gene in a 23-year-old woman. This gene encodes for non-muscular myosin IIA, which acts as a cytoskeletal contractile protein in diverse cell types. This disorder led to sensorineural hearing loss, macrothrombocytopenia, and proteinuria. MYH9 gene mutation can lead to diverse organ manifestation like pre-senile cataract or renal failure which are progressive in course. Due to the current lack of causal treatment, diagnostic steps, advice for follow-up examinations and symptomatic therapy approaches are presented.
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PMID:[Hereditary sensorineural hearing impairment and macrothrombocytopenia: a rare MYH9 gene mutation]. 2322 19

Two siblings, from a consanguineous Iraqi family, were investigated to identify the underlying genetic cause of their high myopia, esotropia, vitreous changes and cataract. Subsequent investigation identified low molecular weight proteinuria as part of their syndrome. Exome sequencing of one of the probands revealed a new non-synonymous variant in the LRP2 gene. Sanger sequencing confirmed the mutation and segregation in the family. No mutation was identified in COL9A1/2, COL11A1/2, or COL2A1 genes. The variant (c.11483A>G; p.Asp3828Gly) is predicted to be damaging and is conserved among vertebrate species. Mutations in LRP2 have been shown to cause the Donnai-Barrow syndrome (DBS) or facio-oculo-acoustico-renal (FOAR) syndrome, a syndrome associated with facial dysmorphism, ocular anomalies, sensorineural hearing loss, low molecular weight proteinuria, and diaphragmatic hernia and absent corpus callosum, although there is variability in the expression of some features. This family shows a milder phenotype with a predominant eye phenotype similar to the Stickler syndrome and only a few features of the DBS, including microglobulinuria. The presence of microglobulinuria was only detected after molecular results were known. In conclusion, with the identification of a new mutation in LRP2 associated with a predominant eye phenotype similar to the Stickler syndrome, we have broadened the phenotypic spectrum of LRP2 mutations.
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PMID:Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome. 2399 33


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