RESUMO
Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.
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Serum uric acid is determined by a balance between production and renal excretion. Luminal reabsorption of urate by the proximal tubule from the glomerular ultrafiltrate involves coupling between sodium-anion cotransport and urate-anion exchange. Apical sodium-coupled cotransport of lactate, ketoacids, nicotinate, and pyrazinoate increases intracellular levels of these anions in proximal tubular cells, stimulating the apical absorption of luminal urate via anion exchange. Hyperuricemia occurs when plasma levels of these anions increase; for example, hyperuricemia is a well-recognized concomitant of lactic acidosis and ketoacidosis. Relevant developments in the molecular and renal physiology of urate homeostasis are reviewed.
Assuntos
Gota/metabolismo , Túbulos Renais Proximais/metabolismo , Ácido Úrico/metabolismo , Animais , Transporte Biológico Ativo , Proteínas de Transporte/metabolismo , Gota/fisiopatologia , Humanos , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions OrgânicosRESUMO
BACKGROUND: Serum cystatin C (Cys C) has been proposed as a simple, accurate, and rapid endogenous marker of glomerular filtration rate (GFR) in research and clinical practice. However, there are conflicting reports regarding the superiority of Cys C over serum creatinine (Cr), with a few studies suggesting no significant difference. METHODS: We performed a meta-analysis of available data from various studies to compare the accuracy of Cys C and Cr in relation to a reference standard of GFR. A bibliographic search showed 46 articles until December 31, 2001. We also retrieved data from eight other studies presented and published in abstract form. RESULTS: The overall correlation coefficient for the reciprocal of serum Cys C (r = 0.816; 95% confidence interval [CI], 0.804 to 0.826) was superior to that of the reciprocal of serum Cr (r = 0.742; 95% CI, 0.726 to 0.758; P < 0.001). Similarly, receiver operating characteristic (ROC)-plot area under the curve (AUC) values for 1/Cys C had greater identity with the reference test for GFR (mean ROC-plot AUC for Cys C, 0.926; 95% CI, 0.892 to 0.960) than ROC-plot AUC values for 1/Cr (mean ROC-plot AUC for serum Cr, 0.837; 95% CI, 0.796 to 0.878; P < 0.001). Immunonephelometric methods of Cys C assay produced significantly greater correlations than other assay methods (r = 0.846 versus r = 0.784; P < 0.001). CONCLUSION: In this meta-analysis using currently available data, serum Cys C is clearly superior to serum Cr as a marker of GFR measured by correlation or mean ROC-plot AUC.
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Creatinina/sangue , Cistatinas/sangue , Rim/fisiologia , Biomarcadores/sangue , Cistatina C , Taxa de Filtração Glomerular/fisiologia , Humanos , Testes de Função Renal , Nefelometria e Turbidimetria/métodosRESUMO
We reviewed neurologic complications after renal transplantation in children over a 20-year period. Neurologic complications were classified as early (within 3 months) and delayed (beyond 3 months). Of 115 children, 10 (8.7%) had complications. Early complications were found in 4.35% of patients: seizures in 4 (posterior reversible leukoencephalopathy syndrome due to immunosuppressant toxicity, sepsis/presumed meningitis, and indeterminate) and headaches in 1. One patient with seizures received levetiracetam for 6 months and 1 with headaches received amitriptyline prophylaxis. Late complications were noted in 4.35% of patients: seizures in 3 (posterior reversible leukoencephalopathy syndrome due to hypertension, hypertensive encephalopathy), headaches in 2, and tremors in 1. Two patients with seizures were treated with anti-epilepsy medications; 1 with migraine received cyproheptadine prophylaxis. Neurologic complications develop in children after renal transplantation. Seizures due to posterior reversible leukoencephalopathy syndrome were the commonest complication. Early detection and appropriate management of these complications is important.
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Transplante de Rim/efeitos adversos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Adolescente , Encéfalo/patologia , Criança , Eletroencefalografia , Feminino , Humanos , Nefropatias/cirurgia , Estudos Longitudinais , Masculino , Neuroimagem , Exame Neurológico , Estudos Retrospectivos , Adulto JovemRESUMO
The novel 2009 H1N1 influenza virus has been reported to have increased severity in patients with underlying cardiovascular and lung disease. Pediatric patients also appear to have an increased incidence of infection. The impact on cardiothoracic transplant recipients, especially in pediatric recipients, has not been established. We report the case of a 12-year-old boy with history of congenital heart disease who was transplanted in June 2001. In October 2009, it was found that he had developed severe acute respiratory distress syndrome (ARDS) secondary to novel 2009 H1N1 influenza virus. Extracorporeal membrane oxygenation (ECMO) was given as support. Importantly, the initial specimen evaluated by real-time reverse transcriptase-polymerase chain reaction was negative for novel 2009 H1N1 influenza virus. The patient was successfully weaned from ECMO after 24 days, extubated at 6 weeks, and continues to make steady rehabilitative progress. Early suspicion for infection and initiation of treatment, even with negative testing, is essential for cardiothoracic transplant recipients during the current pandemic of novel 2009 H1N1 influenza virus.
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Oxigenação por Membrana Extracorpórea , Transplante de Coração/fisiologia , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/terapia , Infecções Oportunistas/terapia , Complicações Pós-Operatórias/terapia , Síndrome do Desconforto Respiratório/terapia , Antivirais/uso terapêutico , Criança , Terapia Combinada , Humanos , Influenza Humana/diagnóstico , Influenza Humana/fisiopatologia , Unidades de Terapia Intensiva Pediátrica , Masculino , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/fisiopatologia , Oseltamivir/uso terapêutico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Síndrome do Desconforto Respiratório/diagnósticoRESUMO
Sulfate is required for proper cell growth and development of all organisms. We have shown that the renal sulfate transport system has dual roles in euryhaline eel, namely, maintenance of sulfate homeostasis and osmoregulation of body fluids. To clarify the physiological roles of sulfate transporters in teleost fish, we cloned orthologs of the mammalian renal sulfate transporters Slc13a1 (NaSi-1) and Slc26a1 (Sat-1) from eel (Anguilla japonica) and assessed their functional characteristics, tissue localization, and regulated expression. Full-length cDNAs coding for ajSlc13a1 and ajSlc26a1 were isolated from a freshwater eel kidney cDNA library. Functional expression in Xenopus oocytes revealed the expected sulfate transport characteristics; furthermore, both transporters were inhibited by mercuric chloride. Northern blot analysis, in situ hybridization, and immunohistochemistry demonstrated robust apical and basolateral expression of ajSlc13a1 and ajSlc26a1, respectively, within the proximal tubule of freshwater eel kidney. Expression was dramatically reduced after the transfer of eels from freshwater to seawater; the circulating sulfate concentration in eels was in turn markedly elevated in freshwater compared with seawater conditions (19 mM vs. 1 mM). The reabsorption of sulfate via the apical ajSlc13a1 and basolateral ajSlc26a1 transporters may thus contribute to freshwater osmoregulation in euryhaline eels, via the regulation of circulating sulfate concentration.
Assuntos
Proteínas de Transporte de Ânions/fisiologia , Enguias/fisiologia , Água Doce , Homeostase/fisiologia , Rim/metabolismo , Sulfatos/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/fisiologia , Enguias/sangue , Enguias/metabolismo , Túbulos Renais Proximais/metabolismo , Dados de Sequência Molecular , RNA Mensageiro/metabolismo , Água do Mar , Cotransportador de Sódio-Sulfato , Sulfatos/sangue , Simportadores/genética , Simportadores/fisiologia , Distribuição TecidualRESUMO
Multiple renal adverse effects have been anecdotally reported with the ingestion of 3,4-methylenedioxymethamphetamine (Ecstasy), a widely used recreational drug. These side effects include acute renal failure, necrotizing vasculitis, and hyponatremia, the mechanisms for which are unknown. We report a case of transient acute proximal tubular injury and hyponatremia associated with Ecstasy use. An 18-year-old woman presented with new onset seizures and polydipsia. Her initial laboratory evaluation revealed hyponatremia (Na 117 mEq/L), polyuria (urine output >400 mL/h for several hours), renal glycosuria (blood glucose 120 mg/dL, urine glucose >1,000 mg/dL), and solute diuresis (urine osmolality 552 mOsm/kg H2O). Urine electrolyte values reflected a low tubular reabsorption of phosphorus (TRP) of 68.1% (expected TRP >85% at serum P 2.3 mg/dL) with an appropriate transtubular potassium gradient of 3.0 (serum K 3.7 mEq/L). Her hyponatremia was slowly corrected. A repeat TRP after 48 h had normalized to 86.5%, and her glycosuria resolved. An extensive toxin screen was later reported positive for Ecstasy. To our knowledge, this is the first example of an acute and transient proximal tubular injury with Ecstasy ingestion. This complication may become more apparent with increasing use of this drug.