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Journal of Veterinary Emergency and... Jul 2022To describe the clinical presentation and management of a critically ill dog with profound renal tubular acidosis (RTA) with proximal and distal renal tubular...
OBJECTIVE
To describe the clinical presentation and management of a critically ill dog with profound renal tubular acidosis (RTA) with proximal and distal renal tubular dysfunction.
CASE SUMMARY
A 3-year-old neutered female Border Terrier was presented with frequent regurgitation resulting from acute pancreatitis with severe ileus. Venous acid-base analysis and complete urinalysis confirmed the presence of normal anion gap metabolic acidosis with inappropriately alkaline urine (pH 8), consistent with distal RTA. Urinalysis, urine amino acids, and urinary fractional excretion of electrolytes revealed glycosuria (with normoglycemia), aminoaciduria, and increased fractional excretion of sodium, calcium, and phosphate consistent with generalized proximal renal tubulopathy or Fanconi syndrome. The dog responded well to supportive care and alkaline therapy and made a complete recovery.
NEW OR UNIQUE INFORMATION PROVIDED
To the authors' knowledge, this is the first description of RTA with proximal and distal renal tubular dysfunction in the veterinary literature. Furthermore, the authors hypothesize that the transient RTA was a manifestation of acute kidney injury secondary to acute pancreatitis, the first report of this in the literature.
Topics: Acidosis; Acidosis, Renal Tubular; Acute Disease; Acute Kidney Injury; Animals; Dog Diseases; Dogs; Female; Pancreatitis
PubMed: 35129879
DOI: 10.1111/vec.13186 -
The Journal of Antimicrobial... Mar 2022Data evaluating the risk of proximal tubular dysfunction in women receiving tenofovir disoproxil fumarate for the prevention of mother-to-child transmission (PMTCT) of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Data evaluating the risk of proximal tubular dysfunction in women receiving tenofovir disoproxil fumarate for the prevention of mother-to-child transmission (PMTCT) of HBV are scarce.
OBJECTIVES
To assess the risk of proximal tubulopathy in pregnant women receiving tenofovir disoproxil fumarate for PMTCT of HBV.
PATIENTS AND METHODS
We used urine samples collected from HBV monoinfected pregnant women who participated in a Phase III, multicentre, randomized, double-blind, placebo-controlled clinical trial assessing a tenofovir disoproxil fumarate short course from 28 weeks gestational age (28-wk-GA) to 2 months post-partum (2-months-PP) for PMTCT of HBV in Thailand. Markers of tubular dysfunction, including retinol binding protein, kidney injury molecule-1, α1-microglobuin and β2-microglobulin, were assayed at 28- and 32-wk-GA and 2-months-PP visits. Proximal tubulopathy was defined as the presence of ≥2 of the following: tubular proteinuria, euglycaemic glycosuria and increased urinary phosphate.
RESULTS
A total of 291 women participated in the study. No kidney-related adverse events were severe, and none led to tenofovir disoproxil fumarate discontinuation. At 2-months-PP, 3 of the 120 (3%) evaluated women in the tenofovir disoproxil fumarate group experienced proximal tubulopathy versus 3 of 125 (2%) in the placebo group (P = 1.00). None of the six women met the criteria for proximal tubulopathy at 12-months-PP but proteinuria persisted in three of them. No growth abnormalities were found at 1 year of age in infants born to mothers with proximal tubulopathy at 2-months-PP.
CONCLUSIONS
In these HBV-infected pregnant and breastfeeding women, tenofovir disoproxil fumarate administered from 28-wk-GA to 2-months-PP was not associated with a higher risk of proximal tubulopathy.
Topics: Antiviral Agents; Child, Preschool; Female; Hepatitis B virus; Humans; Infant; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Pregnant Women; Tenofovir
PubMed: 35045168
DOI: 10.1093/jac/dkab490 -
Children (Basel, Switzerland) Dec 2021Deferasirox is a first-line therapy for iron overload that can sometimes cause kidney damage. To better define the pattern of tubular damage, a systematic literature... (Review)
Review
Deferasirox is a first-line therapy for iron overload that can sometimes cause kidney damage. To better define the pattern of tubular damage, a systematic literature review was conducted on the United States National Library of Medicine, Excerpta Medica, and Web of Science databases. Twenty-three reports describing 57 individual cases could be included. The majority ( = 35) of the 57 patients were ≤18 years of age and affected by thalassemia ( = 46). Abnormal urinary findings were noted in 54, electrolyte or acid-base abnormalities in 46, and acute kidney injury in 9 patients. Latent tubular damage was diagnosed in 11 (19%), overt kidney tubular damage in 37 (65%), and an acute kidney injury in the remaining nine (16%) patients. Out of the 117 acid-base and electrolyte disorders reported in 48 patients, normal-gap metabolic acidosis and hypophosphatemia were the most frequent. Further abnormalities were, in decreasing order of frequency, hypokalemia, hypouricemia, hypocalcemia, and hyponatremia. Out of the 81 abnormal urinary findings, renal glucosuria was the most frequent, followed by tubular proteinuria, total proteinuria, and aminoaciduria. In conclusion, a proximal tubulopathy pattern may be observed on treatment with deferasirox. Since deferasirox-associated kidney damage is dose-dependent, physicians should prescribe the lowest efficacious dose.
PubMed: 34943300
DOI: 10.3390/children8121104 -
Molecular Genetics and Metabolism Dec 2021Glutaric aciduria type I (GA-I, OMIM # 231670) is an autosomal recessive inborn error of metabolism caused by deficiency of the mitochondrial enzyme glutaryl-CoA...
Glutaric aciduria type I (GA-I, OMIM # 231670) is an autosomal recessive inborn error of metabolism caused by deficiency of the mitochondrial enzyme glutaryl-CoA dehydrogenase (GCDH). The principal clinical manifestation in GA-I patients is striatal injury most often triggered by catabolic stress. Early diagnosis by newborn screening programs improved survival and reduced striatal damage in GA-I patients. However, the clinical phenotype is still evolving in the aging patient population. Evaluation of long-term outcome in GA-I patients recently identified glomerular filtration rate (GFR) decline with increasing age. We recently created the first knock-in rat model for GA-I harboring the mutation p.R411W (c.1231 C>T), corresponding to the most frequent GCDH human mutation p.R402W. In this study, we evaluated the effect of an acute metabolic stress in form of high lysine diet (HLD) on young Gcdh rats. We further studied the chronic effect of GCDH deficiency on kidney function in a longitudinal study on a cohort of Gcdh rats by repetitive Ga-EDTA positron emission tomography (PET) renography, biochemical and histological analyses. In young Gcdh rats exposed to HLD, we observed a GFR decline and biochemical signs of a tubulopathy. Histological analyses revealed lipophilic vacuoles, thinning of apical brush border membranes and increased numbers of mitochondria in proximal tubular (PT) cells. HLD also altered OXPHOS activities and proteome in kidneys of Gcdh rats. In the longitudinal cohort, we showed a progressive GFR decline in Gcdh rats starting at young adult age and a decline of renal clearance. Histopathological analyses in aged Gcdh rats revealed tubular dilatation, protein accumulation in PT cells and mononuclear infiltrations. These observations confirm that GA-I leads to acute and chronic renal damage. This raises questions on indication for follow-up on kidney function in GA-I patients and possible therapeutic interventions to avoid renal damage.
Topics: Animals; Computational Biology; Disease Models, Animal; Female; Gene Knock-In Techniques; Glomerular Filtration Rate; Glutarates; Glutaryl-CoA Dehydrogenase; Humans; Infant, Newborn; Kidney; Male; Metabolism, Inborn Errors; Neonatal Screening; Oxidative Phosphorylation; Protein Interaction Maps; Rats; Vacuoles
PubMed: 34799272
DOI: 10.1016/j.ymgme.2021.10.003 -
Indian Journal of Endocrinology and... 2021Reversible proximal tubular dysfunction associated with distal renal tubular acidosis (dRTA) mimics type 3 RTA, a condition classically associated with features of both...
PURPOSE OF THE STUDY
Reversible proximal tubular dysfunction associated with distal renal tubular acidosis (dRTA) mimics type 3 RTA, a condition classically associated with features of both proximal RTA (pRTA) and dRTA. Proximal tubulopathy has been reported in children with primary dRTA, but the data in adults are lacking.
STUDY DESIGN
In this hospital record-based retrospective study, data from 66 consecutive cases of RTA, between January 2016 to December 2018, were retrieved and analyzed.
RESULTS
Mean age of the study population was 25.3 years (range: 3 months to 73 years). Six (9.1%) of them had pRTA, 58 (87.9%) had dRTA, 1 (1.5%) had type 3 RTA, and the remaining 1 (1.5%) had type 4 RTA. Ten patients (17.2%) with dRTA and 3 patients of pRTA (50%) had underlying secondary etiologies. Data on proximal tubular dysfunction were available for 30 patients with dRTA, of whom 1 had isolated dRTA, and the rest 29 patients had accompanying completely reversible proximal tubular dysfunction. Among the 10 cases of secondary dRTA, 6 were not evaluated for proximal tubular dysfunction. Of the remaining 4, 3 had reversible form of proximal tubular abnormality. Fifty-two patients with dRTA came from a population, indigenous to the "Rarh" region of India.
CONCLUSIONS
Proximal tubular dysfunction often accompanies dRTA; 75% of the children with primary dRTA, at least 29% of adults with primary dRTA, and at least 30% of adults with secondary dRTA manifest such completely reversible form of proximal tubulopathy. "Rarh' region of India probably is a hotspot for endemic dRTA.
PubMed: 34660240
DOI: 10.4103/ijem.IJEM_785_20 -
Andes Pediatrica : Revista Chilena de... Aug 2021Treatment with iron chelators is essential for patients with iron overload secondary to repeated trans fusions. Deferasirox is the first once-daily oral active iron...
INTRODUCTION
Treatment with iron chelators is essential for patients with iron overload secondary to repeated trans fusions. Deferasirox is the first once-daily oral active iron chelator. As a result, therapeutic adherence has improved, reducing the complications of iron overload, especially heart failure. However, it is not exempt from possible side effects, such as kidney involvement, which is more frequent in children.
OBJECTIVE
To report 2 patients with Diamond-Blackfan anemia (DBA) who developed impaired renal function secondary to the administration of Deferasirox.
CLINICAL CASES
Case 1. A 15-year-old adolescent diagnosed with DBA undergoing treatment with periodic transfusions and Deferasirox. During an acute gastroenteritis, she developed acute renal failure along with complex proximal tubu- lopathy. Case 2. A 5-year-old boy diagnosed with DBA receiving periodic transfusions and treatment with Deferasirox. He presented polyuria with laboratory abnormalities compatible with acute renal failure and proximal tubular dysfunction. In both cases, they were adequately hydrated and Deferasi rox was temporarily suspended, improving renal function.
CONCLUSION
Based on these cases, close monitoring of renal and tubular function, as well as ferritin levels, is recommended in patients recei ving Deferasirox. In the presence of intercurrent processes, adequate hydration should be performed, and an early dose reduction or drug administration interruption should be considered in cases of kidney involvement.
Topics: Acute Kidney Injury; Adolescent; Anemia, Diamond-Blackfan; Benzoates; Child, Preschool; Deferasirox; Female; Humans; Iron Chelating Agents; Iron Overload; Kidney; Male; Triazoles
PubMed: 34652377
DOI: 10.32641/andespediatr.v92i4.3154 -
Antioxidants (Basel, Switzerland) Aug 2021The clinical utility of the chemotherapeutic drug cisplatin is significantly limited by its nephrotoxicity, which is characterized by electrolytic disorders, glomerular...
The clinical utility of the chemotherapeutic drug cisplatin is significantly limited by its nephrotoxicity, which is characterized by electrolytic disorders, glomerular filtration rate decline, and azotemia. These alterations are consequences of a primary tubulopathy causing injury to proximal and distal epithelial cells, and thus tubular dysfunction. Oxidative stress plays a role in cisplatin nephrotoxicity and cytotoxicity, but its relative contribution to overall toxicity remains unknown. We studied the relation between the degree of oxidative reduction (provided by antioxidant treatment) and the extent of nephrotoxicity amelioration (i.e., nephroprotection) by means of a regression analysis of studies in animal models. Our results indicate that a linear relation exists between these two parameters, and that this relation very nearly crosses the value of maximal nephroprotection at maximal antioxidant effect, suggesting that oxidative stress seems to be a pivotal and mandatory mechanism of cisplatin nephrotoxicity, and, hence, an interesting, rationale-based target for clinical use. Our model also serves to identify antioxidants with enhanced effectiveness by comparing their actual nephroprotective power with that predicted by their antioxidant effect. Among those, this study identified nanoceria, erythropoietin, and maltol as highly effective candidates affording more nephroprotection than expected from their antioxidant effect for prospective clinical development.
PubMed: 34572987
DOI: 10.3390/antiox10091355 -
Stem Cell Research Oct 2021Dent disease (DD) is a rare X-linked proximal tubulopathy associated with low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and phosphoruria,...
Establishment of an induced pluripotent stem cell line (NCKDi003-A) from a patient with X-linked Dent disease (X-Dent) carrying the hemizygote mutation p. T277P (c. 829A > C) in the CLCN5 gene.
Dent disease (DD) is a rare X-linked proximal tubulopathy associated with low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and phosphoruria, which may progress to chronic kidney disease (CKD). About 60% of cases are caused by the mutation in CLCN5 gene. Recently, we identified a mutation in the sequence of homodimer of CLCN5 gene in a patient with DD. The Peripheral Blood Mononuclear Cells (PBMCs) of the patient were obtained and a line of induced pluripotent stem cells (iPSCs) was successfully generated. The iPSC line will be useful for further study of the pathogenesis and drug screening for DD.
Topics: Chloride Channels; Dent Disease; Hemizygote; Humans; Induced Pluripotent Stem Cells; Leukocytes, Mononuclear; Mutation
PubMed: 34547705
DOI: 10.1016/j.scr.2021.102538 -
Nefrologia Sep 2021Gout is recurrent inflammatory arthritis caused by the deposition of monosodium urate crystals in the joints. The risk factors that predispose to suffering from gout... (Review)
Review
Gout is recurrent inflammatory arthritis caused by the deposition of monosodium urate crystals in the joints. The risk factors that predispose to suffering from gout include non-modifiable factors such as gender, age, ethnicity and genetics, and modifiable factors such as diet and lifestyle. It has been shown that the heritability of uric acid levels in the blood is greater than 30%, which indicates that genetics play a key role in these levels. Hyperuricaemia is often a consequence of reduced renal urate excretion since more than 70% is excreted by the kidneys, mainly through the proximal tubule. The mechanisms that explain that hyperuricaemia associated with reduced renal urate excretion is, to a large extent, a proximal renal tubular disorder, have begun to be understood following the identification of two genes that encode the URAT1 and GLUT9 transporters. When they are carriers of loss-of-function mutations, they explain the two known variants of renal tubular hypouricaemia. Some polymorphisms in these genes may have an opposite gain-of-function effect, with a consequent increase in urate reabsorption. Conversely, loss-of-function polymorphisms in other genes that encode transporters involved in urate excretion (ABCG2, ABCC4) can lead to hyperuricaemia. Genome-wide association study (GWAS) methods have made it possible to locate new gout-related loci associated with reduced renal urate excretion (NIPAL1, FAM35A).
PubMed: 34503865
DOI: 10.1016/j.nefro.2021.03.013 -
BMC Medical Genomics Sep 2021Oculocerebrorenal syndrome of Lowe is a rare X-linked disorder characterized by congenital cataracts, mental retardation, and proximal tubulopathy. This condition is...
BACKGROUND
Oculocerebrorenal syndrome of Lowe is a rare X-linked disorder characterized by congenital cataracts, mental retardation, and proximal tubulopathy. This condition is caused by a mutation of OCRL gene (located at chromosome Xq26.1), which encodes an inositol polyphosphate 5-phosphatase.
CASE PRESENTATION
We identified two novel OCRL mutations in two unrelated Chinese boys, each with a severe phenotype of Lowe syndrome. A novel de novo deletion (hemizygous c.659_662delAGGG, p.E220Vfs*29) was present in patient 1 and a novel splicing mutation (hemizygous c.2257-2A > T) that was maternally inherited was present in patient 2. A renal biopsy in patient 2 indicated mild mesangial proliferative glomerulonephritis, mild focal mononuclear cells infiltration, and interstitial focal fibrosis. Moreover, renal expression of OCRL-1 protein in patient 2 was significantly reduced compared to a control patient with thin basement membrane disease.
CONCLUSIONS
This study reports two novel OCRL variants associated with severe ocular and neurologic deficiency, despite only mild renal dysfunction. Based on our two patients and a literature review, the genotype-phenotype correlation of OCRL mutations with this severe phenotype of Lowe syndrome suggest a possible clustering of missense, deletion, and nonsense mutations in the 5-phosphatase domain and Rho-GAP domain in the Chinese population.
Topics: Oculocerebrorenal Syndrome
PubMed: 34488756
DOI: 10.1186/s12920-021-01069-9