Proximal Renal Tubular Dysfunction Research Articles

The clinical and pathological features of adefovir dipivoxil-related renal impairment .

To investigate the clinicopathological features and outcomes of adefovir dipivoxil (ADV)-related renal impairment in Chinese patients. Clinical, pathological, and follow-up data from 15 patients with ADV-related renal impairment were studied. Proximal renal tubular dysfunction (PRTD) was defined by the presence of at least two of the following four abnormalities: hypophosphatemia, hypouricemia, nondiabetic glucosuria, and proteinuria. All patients were treated for 3 - 15 (mean 6.7) years with daily ADV of 10 mg. Renal impairment manifested as PRTD (12, 80%), elevated serum creatinine (12, 80%), and hematuria (2, 13.3%). Mild to moderate tubulointerstitial injury primarily affecting the proximal tubules by light microscopy, and enlarged, dysmorphic mitochondria with loss and disorientation of cristae by electron microscope were identified in all of our cases. Four patients had pathological evidence of IgA nephropathy. The phosphorus, serum uric acid, and creatinine levels were normalized after ADV cessation in 66.7% (8/12) of affected patients, 27.3% (3/11) of affected patients, and 25% (3/12) of affected patients, respectively; proteinuria was eliminated in 7 of 13 affected patients (53.8%); and glucosuria and hematuria both disappeared in all affected patients. These abnormalities had hardly any recovery, and even aggravated with new-onset glucosuria, new-onset hematuria in 3 patients who replaced ADV with tenofovir. Nephrotoxicity developed in patients undergoing long-term ADV treatment and was partially reversible after drug cessation. Tubulointerstitial lesions and heteromorphic mitochondria were the predominant pathological changes. Patients with ADV-induced renal impairment should replace ADV with other antiviral agents other than tenofovir. .

Management of Renal Disease: utility of a joint HIV-renal clinic

Although there has been a decrease in the incidence of HIV-associated nephropathy, the incidence of chronic kidney disease (CKD) is increasing in patients attending HIV clinics. Traditional risk factors for CKD, including diabetes, hypertension and coinfection with hepatitis C virus, are overrepresented in this population, making it difficult to distinguish the contribution of HIV infection 1. HIV-infected patients are at risk of renal dysfunction caused by HIV and by antiretroviral treatment (ART) toxicity. In particular, tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubular dysfunction 2. In 2014 locally in Brighton we had a cohort of 2150 HIV-infected patients, 90% of whom were on ART with 910 of 1935 (47.0%) on regimens including TDF. In addition to using a written protocol for monitoring renal function in patients on antiretrovirals (ARVs) and a standardized operating policy for investigation of abnormal blood tests and urinalysis, we run a ‘one-stop shop’ HIV-renal specialist clinic with an HIV physician and renal physician working together seeing referrals from the general HIV clinic. This study aimed to investigate the utility of this clinic and to describe renal disease in this cohort. We reviewed all patient records of patients seen in a specialist HIV-renal clinic between 2012 and 2014. Demographics, HIV history, number of visits, the indication for referral and outcome information were collected using a standardized proforma. Sixty-five patients, with a median age of 51 years (28–88 years) and a median duration of HIV infection of 163 months (20–335 months), were seen. Forty-two were taking TDF for a mean of 55.8 months (9–122 months). A total of 42 of 65 patients were reviewed once with a median number of visits of 1 (1–4). There were 98 appointments, 54 of which were virtual. The did-not-attend (DNA) rate was 11.4%. Referred patients were categorized as having: proteinuria on TDF (38 of 65 patients; 59%), proteinuria not on TDF (12 of 65 patients; 18%) and raised creatinine without proteinuria (15 of 65 patients; 23%). Of the 38 patients on TDF with proteinuria, five (13.2%) had TDF toxicity diagnosed and TDF was discontinued immediately, and 27 continued with close monitoring with a further seven subsequently discontinuing; the total number discontinuing was 12 of 38 (32%). Addition or up-titration of medications for poorly controlled hypertension was the commonest intervention overall in the joint HIV-renal clinic (23 of 65 patients; 35.4%), in particular in the non-TDF proteinuria group (eight of 12 patients; 66.7%). Renal calculi were a frequent contributor to renal dysfunction and four of 65 patients (6%) had a new glomerular diagnosis after undergoing renal biopsy [two had focal segmental glomerulosclerosis, one had immunoglobulin A (IgA) nephropathy and one had glomerulonephritis with granulomata]. In four patients (6%), the creatinine rise was attributed to nonsteroidal anti-inflammatory drug (NSAID), creatine or protein supplement usage. TDF toxicity was the commonest reason for referral but only a minority of referred patients (13.2%) needed to discontinue immediately. Optimizing blood pressure control was the most frequent outcome, suggesting that this is an underappreciated priority among HIV physicians.

Modeling the neuropsychiatric manifestations of Lowe syndrome using induced pluripotent stem cells: defective F-actin polymerization and WAVE-1 expression in neuronal cells

BackgroundLowe syndrome (LS) is a rare genetic disorder caused by loss of function mutations in the X-linked gene, OCRL, which codes for inositol polyphosphate 5-phosphatase. LS is characterized by the triad of congenital cataracts, neurodevelopmental impairment (primarily intellectual and developmental disabilities [IDD]), and renal proximal tubular dysfunction. Studies carried out over the years have shown that hypomorphic mutations in OCRL adversely affect endosome recycling and actin polymerization in kidney cells and patient-derived fibroblasts. The renal problem has been traced to an impaired recycling of megalin, a multi-ligand receptor that plays a key role in the reuptake of lipoproteins, amino acids, vitamin-binding proteins, and hormones. However, the neurodevelopmental aspects of the disorder have been difficult to study because the mouse knockout (KO) model does not display LS-related phenotypes. Fortunately, the discovery of induced pluripotent stem (iPS) cells has provided an opportunity to grow patient-specific neurons, which can be used to model neurodevelopmental disorders in vitro, as demonstrated in the many studies that have been published in the past few years in autism spectrum disorders (ASD), schizophrenia (SZ), bipolar disorder (BD), and IDD.MethodsWe now report the first findings in neurons and neural progenitor cells (NPCs) generated from iPS cells derived from patients with LS and their typically developing male siblings, as well as an isogenic line in which the OCRL gene has been incapacitated by a null mutation generated using CRISPR-Cas9 gene editing.ResultsWe show that neuronal cells derived from patient-specific iPS cells containing hypomorphic variants are deficient in their capacity to produce F-filamentous actin (F-actin) fibers. Abnormalities were also found in the expression of WAVE-1, a component of the WAVE regulatory complex (WRC) that regulates actin polymerization. Curiously, neuronal cells carrying the engineered OCRL null mutation, in which OCRL protein is not expressed, did not show similar defects in F-actin and WAVE-1 expression. This is similar to the apparent lack of a phenotype in the mouse Ocrl KO model, and suggests that in the complete absence of OCRL protein, as opposed to producing a dysfunctional protein, as seen with the hypomorphic variants, there is partial compensation for the F-actin/WAVE-1 regulating function of OCRL.ConclusionsAlterations in F-actin polymerization and WRC have been found in a number of genetic subgroups of IDD and ASD. Thus, LS, a very rare genetic condition, is linked to a more expansive family of genes responsible for neurodevelopmental disorders that have shared pathogenic features.

Renal dysfunctions/injury in adult epilepsy patients treated with carbamazepine or valproate

ABSTRACTObjectives: Clinical and subclinical laboratory evidence of renal proximal tubular dysfunction had been reported in children with epilepsy as an adverse effect of some antiepileptic drugs (AEDs). This study aimed to determine kidney function in adult patients with monosymptomatic epilepsy of unknown etiology and treated with valproate (VPA) or carbamazepine (CBZ).Methods: This study included 60 patients [mean age of 33.97 ± 6.70 years and treated with VPA (n = 24) or CBZ (n = 36) for mean duration of treatment of 6.03 ± 2.81years. Measurements of serum creatinine (sCr), urinary creatinine, creatinine clearance (CrCl) and serum kidney injury molecule 1 (KIM-1), markers of renal dysfunction/injury were done.Results: Compared to controls, patients had higher sCr, KIM-1 and lower CrCl levels. Compared to patients on VPA, those on CBZ had relatively higher KIM-1 and lower CrCl levels. We reported only significant correlations between KIM-1 with sCr (r = 0.324, p = 0.001) and duration of treatment with AEDs (r = 0.301, p = 0.02).Conclusion: Chronic VPA and CBZ therapy may be associated with subclinical renal glomerular and/or proximal tubular dysfunctions or injuries. The treating neurologist have to consider this while selection of AED on start treating patients or modifying the AED for patients at high risk of kidney injury.

Lowejev sindrom - prikaz primera

Lowe syndrome is a rare X-linked multisystemic disorder, caused by mutation of the OCRL gene which encodes OCRL-1 protein. The disease is characterized by the triad of congenital cataracts, intellectual disability, and Fanconi-like proximal renal tubular dysfunction. Lifespan is short due to end-stage renal disease and other earlier complications and it rarely exceeds 40 years. The treatment is symptomatic, aimed at improving the clinical evolution of the patients and postpone the onset of terminal renal disease. The paper describes a case of a boy with Lowe syndrome with a novel genetic mutation.

Fanconi syndrome and neonatal diabetes: phenotypic heterogeneity in patients with GLUT2 defects.

Fanconi-Bickel syndrome, caused by mutations in SLC2A2 encoding the glucose transporter 2 (GLUT2), is characterized by generalized proximal renal tubular dysfunction manifesting in late infancy. We describe phenotypic heterogeneity of Fanconi-Bickel syndrome in three siblings, including early and atypical presentation with transient neonatal diabetes mellitus in one. The second-born of a non-consanguineous couple, evaluated for polyuria and growth retardation, had rickets, hepatomegaly and proximal tubular dysfunction from 4 to 6 months of age. A male sibling, who expired at 4 months, also had hepatomegaly and growth retardation. The third sibling had polyuria, glucosuria and mild proteinuria on day 3 of life. Hyperglycemia was detected 2 weeks later, which required therapy with insulin for 3 months. Mild metabolic acidosis was present at 2 weeks; hypercalciuria, phosphaturia and aminoaciduria were seen at 6 months. Sanger sequencing showed a homozygous missense mutation in SLC2A2 (exon 7, c.952G > A), causing glycine to arginine substitution; both parents were heterozygous carriers. Patients with SLC2A2 mutations may present either with isolated neonatal diabetes or with hepatomegaly and the renal Fanconi syndrome. Fanconi-Bickel syndrome shows phenotypic heterogeneity and may manifest early with subtle or atypical features, mandating a high index of suspicion.

Risk factors for sodium valproate-induced renal tubular dysfunction.

To explore the risk factors for the development of sodium valproate (VPA)-induced renal tubular dysfunction for early diagnosis and treatment. The subjects were selected from patients who were diagnosed with epilepsy and administered VPA. Blood and spot urine samples were collected and measured the concentration of VPA, the level of serum phosphorus, serum uric acid, serum free carnitine, serum cystatin-c, and urine β2-microglobulin (BMG). Patients with urine BMG/creatinine levels above 219.2 were treated as renal proximal tubular dysfunction (RTD), with all others treated as non-RTD. Eighty-seven patients, 4-48years, 53 men and 34 women, were studied. RTD group is 17 patients and non-RTD group is 70 patients. Univariate analyses revealed that the RTD patients were more likely to be bedridden, receiving enteral tube feeding, taking more anticonvulsants, and demonstrating significantly lower serum levels of free carnitine, uric acid, and phosphorus. Among them, bedridden, free serum carnitine, and phosphorus levels were associated with the development of RTD by multivariate analysis. Bedridden patients receiving VPA are susceptible to hypocarnitinemia, which can cause RTD and may lead to FS. Therefore, urinary BMG should be measured regularly in all patients receiving VPA to assess renal tubular function. An additional measurement of serum free carnitine level should be considered in patients who developed RTD. Supplementation of carnitine for those patients to prevent such complication deserves for further study.

Renal Injury and Dysfunction among HIV Positive Patients Receiving Tenofovir Based Anti-Retroviral Therapy

The rate of renal disease among patients with HIV has decreased significantly since the introduction of highly active antiretroviral therapy (HAART). Patients receiving tenofovir, disoproxil, fumarate (TDF) had an increased prevalence of proximal renal tubular dysfunction and injury but its clinical significance remain controversial. To difine the renal tubulopathy injury among patients with HIV with and without TDF. A cross-sectional study was conducted among HIV positive patients receiving TDF (N= 176) and non TDF regimen (N= 146) at outpatient clinic. All patients were evaluated regarding serum creatinine, electrolytes, phosphate and differing urinary parameters (proteinuria, glycosuria and pyuria). Estimated glomerular filtration rate (GFR) was calculated using CKD-EPI equation. Of 322 participants with mean age of 41.6+-11.4 years and HIV duration of 7.2+-4.3 years, the TDF and non TDF groups were similar on most clinical and demographic factors. GFR was 100.6+- 17.8 mL/min/1.73 m2 in TDF group and 97.5+- 19.6 mL/min/1.73 m2 in non-TDF group (p= 0.143). During evaluation, 3.4% of TDF patients vs. none of the non TDF-patients had hypophosphataemia (< 2.5 mg/dL), 3.9% of TDF-patients vs. 1.3% of non TDF had hypokalemia (< 3.5 mg/dL), and 0.68% of TDF-patients vs. none of non TDF patients had acidosis (< 18 mEq/L) with no statistically significant difference between groups. The proportion of patients with evidence of urine abnormalities was also similar in the two groups (Dipstick proteinuria > 1+, TDF: 17.6% vs. non-TDF 20.5%, p= 0.568, and pyuria; TDF: 27.3% vs. non TDF 20.5%, p= 0.192). Renal impairment, electrolyte disturbances and renal tubulopathy were uncommon among HIV positive patients receiving TDF-based antiretroviral therapy and did not significantly differ between TDF and non TDF regimens

C-terminal fragment of agrin (CAF) levels predict acute kidney injury after acute myocardial infarction

BackgroundPatients with acute myocardial infarction are at high risk for acute kidney injury. Novel biomarkers that can predict acute kidney injury in AMI may allow timely interventions. C-terminal fragment of agrin (CAF), a proteoglycan of the glomerular and tubular basement membrane, have been recently associated with rapid renal function deterioration and proximal tubular dysfunction. It is unknown whether elevated CAF levels may serve as a novel AKI biomarker in patients presenting with AMI.MethodsIn 436 persons enrolled in a multicenter prospective observational cohort study of patients with acute myocardial infarction, we measured plasma and urine levels of several kidney injury biomarkers including CAF, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and cystatin-C.The relationship between biomarker levels at baseline and the development of AKI and long-term mortality were analyzed after adjustment for demographic and clinical variables.ResultsAKI incidence was up to 15% during hospitalization. The predictive accuracy for AKI of urinary CAF was similar to NGAL and superior to other tested kidney injury biomarkers. In a multivariate model that included all possible confounding variables only urinary CAF continued to be an independent marker for AKI (OR 1.35 95%CI 1.05 -1.74). During the 2 years follow-up, only plasma CAF levels remained a significant independent predictor of mortality (OR 2.5 95%CI 1.02-6.2; P = 0.04).ConclusionsElevated CAF levels are associated with AKI in patients with acute myocardial infarction. Our study provides preliminary evidence that CAF levels may predict AKI and mortality after AMI in low risk patients with relative preserved kidney function at baseline.

Higher Prevalence and Faster Progression of Chronic Kidney Disease in Human Immunodeficiency Virus-Infected Middle-Aged Individuals Compared With Human Immunodeficiency Virus-Uninfected Controls.

Human immunodeficiency virus (HIV)-infected individuals are at increased risk of chronic kidney disease (CKD). Human immunodeficiency virus infection, traditional CKD risk factors, and combination antiretroviral therapy (cART) may all contribute. We compared prevalence of renal impairment (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2), albuminuria (albumin/creatinine ratio ≥3 mg/mmol), and proximal renal tubular dysfunction (retinol-binding protein/creatinine ratio >2.93μg/mmol and/or fractional phosphate excretion >20% with plasma phosphate <0.8 mmol/L) in 596 HIV-infected and 544 HIV-uninfected AGEhIV Cohort Study participants. We also assessed whether being HIV-infected on cART, with follow-up censored when cART regimen was modified, was associated with greater eGFR decline or worsening albuminuria (increase ≥10%/year with change in albuminuria category). Human immunodeficiency virus infection was independently associated with renal impairment (adjusted odds ratio [aOR] = 2.1; 95% confidence interval [CI] = 1.0-4.4), albuminuria (aOR = 5.8; 95% CI = 3.7-9.0), and proximal renal tubular dysfunction (aOR = 7.0; 95% CI = 4.9-10.2]). Among 377 HIV-infected and 479 HIV-uninfected individuals (median follow-up = 3.9/4.1 years, respectively) included in longitudinal analyses, being HIV-infected and remaining on unmodified cART was independently associated with greater eGFR decline (-0.56; 95% CI = -0.87 to -0.24 mL/min/1.73m2/year) and worsening albuminuria (aOR = 2.3; 95% CI = 1.3-4.0). In these middle-aged individuals, HIV infection was independently associated with renal impairment, albuminuria, and proximal renal tubular dysfunction. Human immunodeficiency virus-infected individuals on cART (predominantly containing tenofovir disoproxil fumarate) were also more likely to experience eGFR decline and worsening albuminuria compared with HIV-uninfected individuals.

Glycosuria and hyperglycemia in the neonatal period as the first clinical sign of Fanconi-Bickel syndrome

Fanconi-Bickel syndrome is a rare inherited disease characterized by the combination of hepatorenal glycogen accumulation, proximal renal tubular dysfunction and impaired utilization of glucose and galactose. The first symptoms of the disorder are recognized in late infancy as clinical characteristics appear. Therapeutic approach is mainly conservative with supplements of calcium, phosphate and vitamin D and small frequent feedings to avoid hypoglycemia. We report 1 clinical case of very early diagnosis, a 19 days old baby girl, in which the first clinical sign of the disease was the detection of glycosuria and vomits. Serum alkaline phosphatase levels were very high without rickets. The patient presented postprandial hyperglycemia and fasting hypoglycemia. A complete 24-hour glucose profile was obtained using a continuous glucose monitoring system in real time, which was fundamental not only for the diagnosis but also for the prevention of hypoglycemia. She received frequent small meals, galactose-free milk diet, and oral intakes of calcium, phosphorum, bicarbonate and vitamin D supplements with good evolution and normal height and weight gain.

Dentova bolezen

Dent disease is an x-linked disorder of proximal renal tubular dysfunction that occurs almost exclusively in males. It is characterized by significant, mostly low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and chronic kidney disease. Signs and symptoms of this condition appear in early childhood and worsen over time. There are two forms of Dent disease, which are distinguished by their genetic cause and pattern of signs and symptoms (type 1 and type 2). Dent disease 2 is characterized by the features described above and also associated with extrarenal abnormalities (they include mild intellectual disability, hypotonia, and cataract). Some researchers consider Dent disease 2 to be a mild variant of a similar disorder called Lowe syndrome.We represent a case of a 3-year old boy with significant proteinuria in the nephrotic range and hypercalciuria. We confirmed Dent disease type 1 by genetic analysis.

Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue Withdrawal in Chronic Hepatitis B.

Aims Proximal renal tubular dysfunction (PRTD) is an infrequent complication after nucleotide analogue therapy. We evaluated the outcomes of PRTD and nephrotoxicity after nucleotide analogue withdrawal in chronic hepatitis B (CHB). Methods A longitudinal follow-up study was performed in patients with PRTD after nucleotide analogue discontinuation. Serum and urine were collected at baseline and every 3 months for one year. The fractional excretion of phosphate (PO4), uric acid (UA), and potassium and tubular maximal reabsorption rate of PO4 to glomerular filtration rate (TmPO4/GFR) were calculated. Renal losses were defined based on the criteria of substance losses. Subclinical PRTD and overt PRTD were diagnosed when 2 and ≥3 criteria were identified. Results Eight subclinical and eight overt PRTD patients were enrolled. After nucleotide analogue withdrawal, there were overall improvements in GFR, serum PO4, and UA. Renal loss of PO4, UA, protein, and β2-microglobulin reduced over time. At one year, complete reversal of PRTD was seen in 13 patients (81.2%). Improvements in PRTD were seen in all but one patient. Conclusion One year after nucleotide analogue withdrawal, PRTD was resolved in most patients. Changes in TmPO4/GFR, urinary protein, and β2-microglobulin indicate that urinary biomarkers may represent an early sign of PRTD recovery.

A Fanconi-Bickel syndrome patient with a novel mutation and accompanying situs inversus totalis.

Taştemel-Öztürk T, Bilginer-Gürbüz B, Tekşam Ö, Sivri S. A Fanconi-Bickel syndrome patient with a novel mutation and accompanying situs inversus totalis. Turk J Pediatr 2017; 59: 693-695. Fanconi-Bickel syndrome is a rare autosomal recessive disorder of carbohydrate metabolism, caused by mutations in the SLC2A2 gene, that codes for the glucose transporter protein 2 (GLUT2). The disease is characterized by proximal renal tubular dysfunction, impaired glucose and galactose utilization, and accumulation of glycogen in the liver and kidney. Signs and symptoms of Fanconi-Bickel syndrome begin in infancy and include failure to thrive, hepatomegaly, hypophosphatemic rickets, and short stature. Here in we report a Turkish Fanconi-Bickel syndrome case who also has situs inversus totalis and a novel mutation that has not been described before.

Loss of OCRL increases ciliary PI(4,5)P2 in Lowe oculocerebrorenal syndrome.

Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P2, cause Lowe syndrome. Previously we showed that OCRL localizes to the primary cilium, which has a distinct membrane phospholipid composition, but disruption of phosphoinositides in the ciliary membrane is poorly understood. Here, we demonstrate that cilia from Lowe syndrome patient fibroblasts exhibit increased levels of PI(4,5)P2 and decreased levels of PI4P. In particular, subcellular distribution of PI(4,5)P2 build-up was observed at the transition zone. Accumulation of ciliary PI(4,5)P2 was pronounced in mouse embryonic fibroblasts (MEFs) derived from Lowe syndrome mouse model as well as in Ocrl-null MEFs, which was reversed by reintroduction of OCRL. Similarly, expression of wild-type OCRL reversed the elevated PI(4,5)P2 in Lowe patient cells. Accumulation of sonic hedgehog protein in response to hedgehog agonist was decreased in MEFs derived from a Lowe syndrome mouse model. Together, our findings show for the first time an abnormality in ciliary phosphoinositides of both human and mouse cell models of Lowe syndrome.

Changes in Kidney Function and in the Rate of Tubular Dysfunction After Tenofovir Withdrawal or Continuation in HIV-Infected Patients.

Longitudinal data on the changes in kidney function and tubular abnormalities in case of tenofovir disoproxil fumarate (TDF) withdrawal or continuation are scarce. Prospective study of 228 patients receiving TDF, with 3 sequential determinations of serum creatinine, estimated glomerular filtration rate (eGFR), phosphatemia, and different urinary parameters (protein, albumin, phosphaturia, uricosuria, and glycosuria). Changes were analyzed in patients who interrupted TDF as compared to those who continued the same regimen. Proximal renal tubular dysfunction (PRTD) was defined as ≥2 tubular abnormalities. After a median follow-up of 59.5 months, 78 patients (34%) had PRTD, mainly proteinuria (40%) and phosphaturia (61%), and time on TDF explains the severity of tubular alterations and eGFR slopes. In 35 switching patients, there was a rapid and significant eGFR improvement (median +4.1 ml/min per 1.73 m; P = 0.02), leading to a 39%-83% reduction in the prevalence of tubular abnormalities and of PRTD in less than 1 year (66%-39%). In comparison, 193 patients continuing the same regimen for 21.2 months had a small but significant and progressive eGFR decrease (-2.9 mL·min·1.73 m; P < 0.01), and a progressive rise in the prevalence of phosphaturia, uricosuria, and glycosuria (+9%-56%). In linear mixed-effect model, subsequent eGFR impairment was associated with proteinuria and time on TDF, and eGFR improvement with TDF discontinuation. Our data support the role of use and time on TDF in eGFR decline and tubular dysfunction. In contrast, TDF withdrawal is followed by a rapid and significant, although partial, recovery of eGFR and tubular abnormalities.

Late Diagnosis of Fanconi-Bickel Syndrome

Fanconi-Bickel syndrome (FBS), also known as glycogen storage disease type XI (GSD XI), is a rare autosomal recessive disorder of carbohydrate metabolism. It is caused by mutations in the gene SLC2A2, which encodes for the facilitative glucose transporter GLUT2. Diagnosis of FBS is often delayed since the clinical features and laboratory markers often overlap with other disorders whose characteristic features include short stature, fasting hypoglycemia, postprandial hyperglycemia, hepatomegaly, hypophosphatemic rickets, and proximal renal tubular dysfunction. In this article, we present a case of FBS and its management in an African American female who initially presented with persistent proximal tubulopathy, hypercalciuria, and metabolic acidosis. We also include a recent literature review on FBS and discuss other metabolic disorders that should be considered in the differential diagnosis.

Proximal tubular nephropathy in two dogs diagnosed with lead toxicity

Lead toxicity was diagnosed in two dogs presenting with vague clinical symptoms. Complete blood count, biochemical testing and imaging changes showed a metarubricytosis in dog 1, but were largely normal in dog 2. Both dogs had glucosuria and proteinuria on urinalysis consistent with damage to the proximal renal tubules. Both animals returned elevated blood lead levels. A history of ingestion of lead was reported by the owner in one dog and elucidated from the second owner once the animal had recorded elevated blood lead levels. Lead toxicity is rarely reported in the human literature as a cause of proximal tubular dysfunction. To the author's knowledge this is the first case report specifically examining this in the dog. The clinical awareness that lead is a potential cause of proximal renal tubular dysfunction offers another tool to assist the clinician in the diagnostic process. This is particularly important given that the clinical signs and minimum database findings in animals with lead toxicosis are highly variable. Evidence of proximal tubular dysfunction should trigger the clinician to closely examine the history for a potential source of lead exposure and consider submitting samples to test blood lead levels.

Outcome of renal proximal tubular dysfunction with Fanconi syndrome caused by sodium valproate.

Although Fanconi syndrome is rare in patients with epilepsy treated with sodium valproate (VPA), the prevalence might be higher in children with severe motor and intellectual disabilities (SMID). VPA-induced Fanconi syndrome usually has a favorable outcome, but the long-term outcome of renal tubular dysfunction in SMID patients remains unknown. The aim of this study was therefore to investigate the long-term outcome of renal proximal dysfunction in SMID children with Fanconi syndrome caused by VPA. The records of six children with SMID and Fanconi syndrome caused by VPA were retrospectively reviewed to assess long-term proximal renal tubular function after discontinuation of VPA. All six patients had intractable epilepsy and required tube feeding. Proximal tubular dysfunction improved in almost all patients after VPA discontinuation, although abnormal uric acid reabsorption persisted in three patients. Five patients had hypocarnitinemia. After carnitine supplementation, one of these three patients with decreased ability to reabsorb uric acid had a normal serum level and improved fractional excretion of uric acid. Secondary carnitine deficiency may cause prolonged tubular dysfunction in some SMID patients with VPA-induced Fanconi syndrome. Fanconi syndrome caused by VPA is a usually reversible dysfunction of the proximal tubules, but can be permanent. Although not effective for all patients, carnitine is recommended for patients with VPA-induced Fanconi syndrome, especially children with SMID.

809 Reversal of Proximal Renal Tubular Dysfunction After Nucleotide Analogue Withdrawal in Chronic Hepatitis B

809 Reversal of Proximal Renal Tubular Dysfunction After Nucleotide Analogue Withdrawal in Chronic Hepatitis B