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A 12-year-old boy with Donnai-Barrow syndrome diagnosed intra-uterus presented esotropia, high myopia, nystagmus, and optic disk staphyloma in an ophthalmologic examination. The patient had associated Fanconi syndrome and sensorineural hearing loss as well as facial manifestations as hypertelorism, downward slanting of palpebral fissures and low ear implantation. Magnetic resonance imaging revealed agenesis of the corpus callosum. To our knowledge, this is the first reported case associated with esotropia, nystagmus, and optic disk staphyloma. [ABSTRACT FROM AUTHOR]

Fanconi's syndrome is a disorder that results in generalized involvement of the proximal tubule of the kidney. It is characterized by variable degrees of phosphate, glucose, and amino acid wasting in the urine and a hyperchloremic normal anion gap metabolic acidosis – secondary to defective hydrogen ion excretion and bicarbonate ion absorption. There are hereditary variants such as cystinosis (most common), hereditary fructose intolerance, galactosemia, tyrosinemia, Dents disease, and acquired variants of Fanconi's syndrome. Toxins, drug-induced diseases, and systemic diseases (multiple myeloma, Sjogren's syndrome) are the most common acquired causes of Fanconi's syndrome. The case report describes a middle-aged female patient, a known case of human immunodeficiency virus (HIV)-positive status who developed tenofovir disoproxil fumarate-induced Fanconi's syndrome, an increasingly recognized cause of acquired Fanconi's syndrome in HIV-positive patients. [ABSTRACT FROM AUTHOR]

Tenofovir disoproxil fumarate is part of the first-line antiretroviral therapy and can lead to Fanconi syndrome, acute kidney injury, chronic kidney disease, and reduced bone mineral density. We report the first case of simultaneous occurrence of nephrolithiasis, urolithiasis, Fanconi syndrome, and bone fracture in a 54-year-old lady who presented with pain and inability to bear weight on the right lower limb following a trivial fall. She was diagnosed with human immunodeficiency infection in the year 2000 and was on tenofovir, lamivudine, and efavirenz for the past 6 years. On evaluation, she had azotemia, glycosuria, proteinuria, normal anion gap metabolic acidosis, multiple renal stones, and a proximal ureteric calculus causing right-sided hydroureteronephrosis. The patient developed sepsis following the double "J" stenting procedure. She was managed with intravenous bicarbonate therapy and the substitution of tenofovir to abacavir with a favorable outcome. [ABSTRACT FROM AUTHOR]

A quiz concerning the Fanconi syndrome, nephrotic‑range proteinuria, and hypoalbuminemia in a newborn including diferential diagnosis for renal Fanconi syndrome in a newborn and performing the additional testing.

Introduction: This study assessed the performance of a new fully automated immunoassay for fibroblast growth factor (FGF) 23 (Determinar CL FGF23 CL) among healthy individuals and those with chronic hypophosphatemia compared with the previous assay (Kainos FGF23 KI). Materials and methods: A total of 380 serum samples from healthy participants were collected to determine the reference range of FGF23 levels with CL. A total of 200 serum samples from 22 hypophosphatemic patients were collected simultaneously to compare the difference in FGF23 levels between CL and KI. The Mann–Whitney U test and linear regression analysis were adopted to assess the differences and linearity between the two assays. Results: The median FGF23 levels among healthy individuals was 31.7 (interquartile: 26.4–37.5) pg/mL. When the reference range was calculated as the mean ± 2 standard deviation (2SD), it was 16.1–49.3 pg/mL. A total of 363 individuals (96%) among normal cases fell in this range. Among 200 samples from patients with chronic hypophosphatemic disorder, the median FGF23 levels analyzed by CL and KI were 123.0 (90.2–237.7) and 172.5 (115.8–290.7) pg/mL. KI yielded significantly higher FGF23 values than CL (p < 0.001). A linear regression model revealed the correlation between KI (x) and CL (y), which had a slope of 0.76 with a y-intercept of −0.32 and high linearity (R2 = 0.99). Conclusion: The new measurement kit yielded lower FGF23 values when compared with the previous assay. Clinicians should consider this discrepancy when they assay intact FGF23 values with CL. [ABSTRACT FROM AUTHOR]

Tenofovir Disoproxil Fumarate (TDF) is one of the drugs in the initial first-line antiretroviral regimen for the treatment of hepatitis B and HIV infections. Despite its effectiveness and few adverse effects, it is related to renal and bone toxicity. We described two cases of HIVpositive middle-aged women who had been using TDF for two and four years (cases 1 and 2, respectively) and were admitted to the emergency room. Case 1 presented with metabolic ileum and diffuse bone pain while case 2 presented with bilateral coxo-femoral pain after a fall from standing height. Both cases had similar laboratory tests: hyperchloremic metabolic acidosis, hypophosphatemia, hypokalemia, hypouricemia and elevated plasma creatinine. In urinary exams, there was evidence of renal loss of electrolytes, justifying the serum alterations, in addition to glucosuria and proteinuria. The bone pain investigation identified bone fractures and reduced bone mineral density, together with increased levels of parathyroid hormone, alkaline phosphatase and vitamin D deficiency. These two cases illustrate the spectrum of adverse renal and bone effects associated with TDF use. TDF was discontinued and treatment was focused on correcting the electrolyte disturbances and acidosis, in addition to controlling the bone disease through vitamin D and calcium supplementation. The renal changes found in both cases characterized the Fanconi's syndrome, and occurred due to TDF toxicity to proximal tubule cells mitochondria. Bone toxicity occurred due to direct interference of TDF in bone homeostasis, in addition to vitamin D deficiency and phosphaturia resulting from tubulopathy. During the follow-up, both cases evolved with chronic kidney disease and in one of them, the Fanconi's syndrome did not revert. We emphasize the need to monitor markers of bone metabolism and glomerular and tubular functions in patients using TDF. [ABSTRACT FROM AUTHOR]

Abstract Background The nucleotide reverse transcriptase inhibitor Tenofovir Alafenamide (TAF) is a novel pro-drug of tenofovir (TFV) and possesses a superior renal safety profile compared with tenofovir disoproxil fumerate (TDF). Due to unique pharmacokinetic characteristics, treatment with TAF is not associated with significant renal proximal tubular accumulation of TFV. TAF is associated with a lower risk of acute kidney injury, chronic kidney disease, proteinuria and renal proximal tubular dysfunction than treatment with TDF. No cases of Fanconi syndrome have been reported in clinical trials of TAF. It is unknown whether treatment with TAF can lead to accumulation of TFV in proximal tubular cells and cause nephrotoxicity under certain clinical circumstances. Case presentation Here we report the case of a patient on stable TAF-based antiretroviral therapy with for HIV-1 infection who developed proximal tubulopathy when treated with gentamicin for febrile neutropenia in the context of relapsed Hodgkin lymphoma. Eighteen days after commencing chemotherapy for relapsed Hodgkin lymphoma the patient presented to hospital with fevers, hypotension and neutropenia. The patient was commenced on piperacillin, tazobactam and gentamicin. Within 24 h the patient developed marked hypokalaemia and hypophosphataemia requiring intravenous replacement therapy. There was proteinuria, glycosuria and evidence of marked urinary electrolyte wasting, consistent with acute proximal tubular dysfunction. Eleven days after the gentamicin was stopped the serum biochemistry normalised. The urinary electrolyte wasting and proteinuria had improved, and the glycosuria had resolved. Conclusion This is the first case report to describe acute renal proximal tubulopathy in an HIV-infected patient treated with TAF and gentamicin. As the number of patients prescribed TAF outside the clinical trial setting increases, so too does the potential for previously unreported drug interactions and adverse events. Clinicians need to be aware of potential unreported adverse drug reactions as the use of TAF becomes increasingly common in clinical practice.

Background: Pain in patients with hemophilia is common and usually a result of arthropathy. Clinicians should, however, consider a wide range of etiologies for pain in patients with hemophilia including infection, osteoporotic fractures, arthritis, and osteomalacia. Aims: This case demonstrates an instance of poorly localized back and hip pain, severe enough to prevent ambulation, caused by hypophosphatemic osteomalacia due to tenofovir treatment for blood transfusion acquired Human Immunodeficiency Virus (HIV) in a patient with hemophilia A. Methods: Case Report. Results: With termination of tenofovir treatment, this patient returned to baseline function. Conclusion: This report serves to emphasize the need for accurate diagnosis of pain in hemophilia patients, especially among the aging demographic of people with hemophilia in which there is a significant likelihood of an HIV infection and among patients who may be on Pre-exposure Prophylaxis (PrEP) or clinical trials involving tenofovir.

Introduction: Nephrotoxicity is one of the major side effects of the chemotherapeutic drug, ifosfamide (IFO). In this study, IFO was solubilized in nanoemulsion (NE) containing salvia (SAL) essential oil to investigate its adverse side effects in mice. Methods: One hundred female Swiss albino mice (n = 20/group) were split into five groups. Group I (Normal) received saline solution (0.9% (w/v) NaCl) while groups II-V were intraperitoneally (I.P.) injected with 2.5 × 106 Ehrlich ascetic carcinoma (EAC) cells/mouse. Group II (EAC) represented the untreated EAC-bearing mice. Group III (IFO) was treated with IFO at a dose of 60 mg/kg/d (I.P. 0.3 mL/mouse). Group IV (SAL) was treated with 0.3 mL blank NE-based SAL oil/mouse. Group V (SAL-IFO) was treated with IFO, loaded in 0.3 mL of blank SAL-NE, at a dose of 60 mg/kg/d (I.P. 0.3 mL/mouse). Groups III-V were treated for three consecutive days. Results: There was a double increase in the survival percentage of the SAL-IFO group (60%) relative to the IFO group (30%). Renal damage with the presence of Fanconi syndrome was indicated in the IFO group through a significant elevation in the levels of serum creatinine, blood urea nitrogen, urine bicarbonate, and phosphate in addition to a reduced level of glucose compared to the normal group. On the other hand, the administration of SAL-IFO into the mice reversed this effect. Additionally, the oxidative stress in the kidney tissues of the SAL-IFO group was ameliorated when compared to the IFO group. Conclusion: Incorporating IFO into SAL-NE has protected the kidneys from the damage induced by IFO.

Red yeast rice has been highlighted as a health-food ingredient that reduces serum cholesterol levels. Recently, an increased number of cases of renal impairment induced by a supplement containing red yeast rice have been reported in Japan. A 42-year-old man with no history of chronic kidney disease developed renal dysfunction with proximal tubular damage after supplementation with red yeast rice. An 83-year-old woman with advanced diabetic kidney disease experienced further deterioration of her renal function after supplementation with red yeast rice. We herein report cases of acute kidney injury likely induced by a supplement containing red yeast rice.

Numerous health concerns, primarily kidney injury, have been reported with the use of Beni-kōji CholesteHelp, a functional food containing red yeast rice. Here, we describe 2 cases of kidney injury caused by beni-kōji. The first case had normal kidney function before consuming the product. After several months of use, she developed hypertension. After 6 months of supplement consumption, her estimated glomerular filtration rate (eGFR) dropped to 22.5 mL/min/1.73 m 2 . A spot urine sample showed a urinary protein-to-creatinine ratio of 2.03 g/g, leading to the diagnosis of Fanconi syndrome. Kidney biopsy showed tubular degeneration. Thirty-five days after discontinuing the supplement, proteinuria resolved and the eGFR returned to baseline level. The second case, who had diabetes and normal kidney function, experienced severe kidney injury (eGFR, 3.5 mL/min/1.73 m 2 ) after 4 months of Beni-kōji CholesteHelp use. He required hemodialysis for >2 weeks but recovered kidney function after the product was discontinued. Kidney biopsy showed tubular injury similar to the first case and glomeruli changes consistent with diabetic nephropathy. These cases indicate that beni-kōji use is associated with tubular toxicity. Further studies are required to identify the precise etiology and mechanism of kidney injury., (© 2024 The Authors.)

Glycosuria can be isolated or it can be associated with other tubulopathies like proximal renal tubular acidosis, Fanconi syndrome and endocrine conditions like diabetes mellitus. The SLC5A2 gene codes for the SGLT2 transporter, which is responsible for glucose reabsorption in the proximal tubule. Previously reported cases show that mutation in this gene is associated with intellectual disability, seizure disorder and renin and angiotensin system dysfunction. In his early childhood, a male child displayed persistently high urine glucose levels. We ruled out diabetes mellitus and other tubulopathies before diagnosing the child with familial renal glycosuria, with a novel mutation in the SLC5A2 gene, and screened family members for the same condition. Child's father was found to have isolated renal glycosuria and tested positive for mutation in the SLC5A2 gene., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Autosomal dominant Fanconi syndrome due to a GATM variant (GATM-FS), causes accumulation of misfolded arginine-glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM-FS presents during childhood and progresses to end-stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known GATM variant and the effect of creatine supplementation in kidney organoids. Plasma and urine metabolites were measured by mass spectrometry. Brain creatine was assessed by magnetic resonance spectroscopy (MRS). Guanidinoacetate (GAA) synthesis by the AGAT mutant was measured in patient-derived immortalized lymphocytes using stable isotopes of arginine and glycine. The effect of creatine on GATM expression was assessed in human kidney cells and organoids. Several family members from two unrelated families were diagnosed with Fanconi syndrome and had the c.1022C>T (p. P341L) variant in GATM . Two affected individuals in both families had moderately reduced plasma GAA levels. In comparison to wild-type cells, GAA synthesis by patient-derived GATM P341L+/- lymphoblastoid cell lines (LCL) was reduced, but not absent as in GATM cells from a patient with creatine deficiency syndrome. In vitro studies on human kidney organoids revealed reduced AGAT expression after treatment with creatine. Finally, we showed in one patient that creatine supplementation (5 g daily) substantially increased plasma creatine levels. We report low plasma and urine GAA in patients with autosomal dominant GATM-FS and show that creatine downregulates AGAT in human kidney cells., Competing Interests: Ignacio Portales‐Castillo, Rhea Singal, Anastasia Ambrose, Jong Hee Song, Minsoo Son, Young Ah Goo, Wen Zhou, Avram Z. Traum, Ariella Coller‐Reilly, Benjamin D. Humphreys, Roberto Civitelli, Harald Jüppner, Andrew L. Lundquist, Peter Seres, Andrew S. Allegretti and Saadet Mercimek‐Andrews declare that they have no conflict of interest., (© 2024 The Author(s). JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Fanconi syndrome (FS) is a complex disorder characterized by a reabsorption defect in the proximal renal tubule (PT), leading to urinary loss of molecules such as glucose, phosphate, calcium, amino acids, bicarbonate, potassium, and low-molecular-weight proteins. Its etiology can be genetic or acquired, with drug toxicity being a significant cause of the acquired forms. The heterogeneous manifestations of FS, whether in its partial or complete form, can pose challenges in the emergency department; nevertheless, it should be considered in certain patients, as understanding its cause is crucial for initiating effective treatment. We present the case of a 59-year-old female patient with FS who was treated with lenalidomide in the context of stage III IgG kappa multiple myeloma according to the Salmon Durie classification. We highlight the recurrent nature of this syndrome in this patient., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sharra et al.)

Monoclonal Ig crystalline nephropathies are rare lesions resulting from precipitation of monoclonal Igs in the kidney as crystalline inclusions. They can be categorized into lesions with predominant intracellular crystals (light chain [LC] proximal tubulopathy, LC crystal-storing histiocytosis, and LC crystalline podocytopathy) and lesions with predominant extracellular crystals (crystalglobulin-induced nephropathy and crystalline variant of LC cast nephropathy). The majority of these lesions are associated with low tumor burden lymphoproliferative disorders, with the exception of crystalline variant of LC cast nephropathy. Extrarenal involvement (e.g., skin and cornea) is frequent. Kidney biopsy is the cornerstone for diagnosis, which often requires electron microscopy and antigen retrieval. A thorough hematologic workup and evaluation of extrarenal involvement is mandatory for management. Treatment of these lesions is with clone-directed therapy, with the goal of achieving hematologic very good partial response or complete response, which preserves or improves kidney function. In vitro and in vivo studies, animal models, and novel sequencing techniques have been invaluable tools to understand the pathogenesis of LC proximal tubulopathy and can be used to increase our limited knowledge of the pathogenesis of the other monoclonal Ig crystalline nephropathies. This review provides an update on the pathology, renal and hematologic characteristics, extrarenal manifestations, prognosis, treatment, and pathogenesis of monoclonal Ig crystalline nephropathies., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Drug-induced tubulointerstitial injury is a common cause of renal impairment. Since the mechanisms of drug-induced tubular injury are diverse, various treatment approaches are needed according to the pathogenesis. Renal biopsy is indispensable to determine not only the pathological diagnosis, but also the underlying mechanism, and to guide appropriate treatment. Most recently, one of the red yeast supplements has been widely highlighted as a novel cause of tubular damage, mainly in Japan and Asia. However, neither detailed pathological findings nor the mechanism of renal impairment has been sufficiently reported., Case Presentation: Two cases of renal impairment after taking red yeast supplement internally are presented. Both cases showed renal dysfunction with low uric acid, potassium, and phosphorus levels, characteristic features of Fanconi syndrome. The renal biopsy findings of both cases showed severe injury to the proximal tubules with mild inflammatory cell infiltration. The proximal tubules exhibited diffuse loss of the brush border, flattening, and tubular lumen dilation. Immunofluorescence showed no deposition of immunoglobulin and complement in the glomeruli and tubules. Electron microscopic findings indicated proximal tubular damage without crystal deposition. Moreover, immunohistochemistry using the proximal tubular marker CD10 and a marker for distal tubules including the loop of Henle, E-cadherin, collectively demonstrated that the focus of renal injury in both cases was mainly the proximal tubules., Conclusions: The red yeast rice supplement itself, its metabolized product, or other unknown contaminant components might directly induce proximal tubulopathy rather than an allergic reaction-related tubulointerstitial nephritis., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Polyuria is a common problem in patients with tubular diseases, especially for those with CKD and high-output Fanconi syndrome. There are currently no guidelines on how to treat debilitating polyuria, in children or adults, and vasopressin is usually not effective. Case-diagnosis/treatment: A 13-year-old female with idiopathic Fanconi syndrome and an eGFR of 69 mL/min/1.73 m2 was severely affected by polyuria of 5 L per day (voiding at least 11 times during the day and up to 8 times at night), impacting her mood (measured by the RCADS-child) and academic performance at school. In the absence of guidelines and with literature discouraging the use of indomethacin in this condition, we attempted indomethacin treatment at a dose of 2 mg/kg divided in two doses with substantial success. Urine output dropped to 2.5L and this was accompanied by a substantial decrease of her sodium wasting from 24.6 to 7.7 mmol/kg/day. Over the course of 18 months, the patient's eGFR dropped temporarily to 60 mL/min/1.73 m2 and was 68 mL/min/1.73 m2 at last follow-up. However, a sodium-23 (23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na+ decrease in her muscle when compared to age-matched peers with normal kidney function. Conclusions: Indomethacin may be a safe and effective treatment option for polyuria in idiopathic Fanconi syndrome. [ABSTRACT FROM AUTHOR]

Dysregulation of phosphorus homeostasis resulting in hypophosphatemia is common in cancer patients and can result in serious complications and impact outcomes. Several factors, including critical illness, nutritional status, cancer type and therapy, influence the development of hypophosphatemia. Hypophosphatemia can develop as a result of phosphaturic mesenchymal tumors or as a paraneoplastic phenomenon. The clinical presentation for hypophosphatemia varies depending on the duration and severity of the hypophosphatemia and affects several organ systems. Among other serious effects, hypophosphatemia can impair tissue oxygenation and can cause hemolysis, leukocyte and platelet dysfunction, encephalopathy, seizures, arrhythmias, cardiomyopathy, rhabdomyolysis and coma. Multiple studies have demonstrated that hypophosphatemia is an adverse prognostic marker in inpatients with increased in-hospital stay, mortality and postoperative complications. The phosphate level is homeostatically regulated and maintained in a narrow range by three main hormones: parathyroid hormone, fibroblast growth factor 23 and 1,25-dihydroxyvitaminD3. Together, these hormones regulate how the intestine, kidneys and bones traffic phosphorus. Several hematological malignancies and cancer therapies are associated with proximal tubular dysfunction (Fanconi syndrome), resulting in phosphaturia. Caution should be taken with parenteral administration of phosphate salts, because secondary complications can develop, principally due to hypocalcemia. The general approach to hypophosphatemia should target the underlying cause. Early recognition and prevention are essential and the approach to hypophosphatemia in the cancer patient, because of the nuances and complexity, should be multidisciplinary. [ABSTRACT FROM AUTHOR]

Purpose: There are limited clinical studies aimed at solving the problem of the efficiency of conventional treatment with oral phosphate and calcitriol in adults with hypophosphatemic osteomalacia (HO). In addition, there still had no good non-hazardous markers to evaluate the severity of bone loss of osteomalacia before and after treatment. Therefore, the purpose of this study was to assess the efficacy of conventional treatment with a self-blended phosphate supplementation and calcitriol on patients with HO and whether bone mineral density (BMD) can be helpful for monitoring the efficacy. Patients and Methods: A total of 21 HO patients and 105 healthy controls were enrolled. All patients were tested for serum biomarkers and BMD of the lumbar spine (L1–L4), femoral neck, and total left hip. After three years of treatment, 11 of 21 HO patients were recalled for BMD measurement. According to the administration of drugs, HO patients with calcium and calcitriol were divided into three phosphate treatment groups: patients in group A (n = 3) received continuous phosphate supplementation, patients in group B (n = 5) received intermittent phosphate supplementation and patients in group C (n = 3) received no phosphate supplementation. Results: The diagnoses of 21 HO patients were 5 cases of hereditary hypophosphatemic rickets, 4 cases of Fanconi syndrome with the features of renal tubular acidosis and vitamin D deficiency, and 12 cases of hereditary vitamin D abnormality. The average initial serum phosphorus level of the patient group was approximately 50% lower than that of the control group. Lower BMD was significantly observed in the HO group than the control group at the lumbar spine and total hip. Continuous treatment with the phosphate supplement could increase BMD in the lumbar spine and total hip by 33.4– 52.3% and in the femoral neck increased by 43.2– 79.3% compared with baseline, and the effect appears to be continued once treatment is discontinued. Conclusion: These findings suggest that conventional therapy can improve bone mineral defects in patients with HO, especially in the femoral neck. Detection of BMD in HO patients is a good tool to assess the extent of bone defects and the therapeutic effect. Trial Registration: Chinese Clinical Trial Registry, ChiCTR-OOC-16010095. Registered 7 December 2016. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor and has been extensively used in the first-line treatment of viral infectious diseases such as chronic hepatitis B. Despite its good safety, the development of Fanconi syndrome is a rare adverse effect of long-term tenofovir therapy. Here, we report a case of a 62-year-old diabetic woman with a history of chronic hepatitis B who was exposed to tenofovir and developed drug-associated Fanconi syndrome. After discounting tenofovir, the patient's bone pain was markedly reduced. [ABSTRACT FROM AUTHOR]

Fanconi syndrome is one of the primary renal manifestations of mitochondrial cytopathies caused by mitochondrial DNA (mtDNA) mutation. The common 4977-bp mtDNA deletion has been reported to be associated with aging and diseases involving multiple extrarenal organs. Cases of Fanconi syndrome caused by the 4977-bp deletion were rarely reported previously. Here, we report a 6-year-old girl with growth retardation in the course of Fanconi syndrome. She had mild ptosis and pigmented retinopathy. Abnormal biochemical findings included low-molecular-weight proteinuria, normoglycemic glycosuria, increased urine phosphorus excretion, metabolic acidosis, and hypophosphatemia. Growth records showed that her body weight and height were normal in the first year and failed to thrive after the age of three. Using a highly sensitive mtDNA analysis methodology, she was identified to possess the common 4977-bp mtDNA deletion. The mutation rate was 84.7% in the urine exfoliated cells, 78.67% in the oral mucosal cells, and 23.99% in the blood sample. After three months of oral coenzyme Q10 and levocarnitine treatment in combination with standard electrolyte supplement, her condition was improved. This is a report of growth retardation as the initial major clinical presentation of Fanconi syndrome caused by the deletion of the 4977-bp fragment. Renal tubular abnormality without any other extrarenal dysfunction may be an initial clinical sign of mitochondrial disorders. Moreover, considering the heterogeneity of the phenotypes associated with mtDNA mutations, the risk of developing Kearns–Sayre syndrome (KSS) with age in this patient should be noted because she had ptosis, retinal involvement, and changes in the brain and skeletal muscle. [ABSTRACT FROM AUTHOR]

BackgroundTenofovir disoproxil fumarate (TDF) is a widely used antiretroviral agent with favorable efficacy, safety, and tolerability profiles. However, renal adverse events, including the rare Fanconi syndrome (FS), may occur in a small subset of patients treated for HIV infections.ObjectivesThe aim of this study was to identify genetic variants that may be associated with TDF-associated FS (TDF-FS).MethodsDNA samples collected from 19 cases with TDF-FS and 36 matched controls were sequenced, and genetic association studies were conducted on eight candidate genes: ATP-binding cassette (ABC) transporters ABCC2 (MRP2) and ABCC4 (MRP4), solute carrier family members SLC22A6 (OAT1) and SLC22A8 (OAT3), adenylate kinases 2 (AK2) and 4 (AK4), chloride transporter CIC-5 CLCN5, and Lowe syndrome protein OCRL. The functional effects of a single nucleotide polymorphism (SNP) predicted to alter the transport of tenofovir were then investigated in cells expressing an identified variant of ABCC4.ResultsThe case group showed a trend toward a higher proportion of rare alleles. Six SNPs in ABCC2 (three SNPs), ABCC4 (one SNP), and OCRL (two SNPs) were associated with TDF-FS case status; however, this association did not remain significant after correction for multiple testing. Six SNPs, present in OCRL (four SNPs) and ABCC2 (two SNPs), were significantly associated with increased serum creatinine levels in the cases, and this association remained significant after multiple test correction (P < 2 × 10). One synonymous SNP in ABCC2 (rs8187707, P = 2.10 × 10, β = -73.3 ml/min/1.73 m(2)) was also significantly associated with the decreased estimated glomerular filtration rate of creatinine among cases. However, these results were driven by rare SNPs present in a small number of severely affected cases. Finally, a previously uncharacterized, nonsynonymous SNP, rs11568694, that was predicted to alter MRP4 function had no significant effect on tenofovir cellular accumulation in vitro.ConclusionAlthough no single predictive genetic marker for the development of TDF-FS was identified, the findings from our study suggest that rare variants in multiple genes involved in the renal handling of tenofovir, and/or renal cell homeostasis, may be associated with increased susceptibility to TDF-FS.

INTRODUCTION: Nephropathic cystinosis is a rarely occurring inherited metabolic disorder, leading to Fanconi syndrome, progressive renal failure and a range of extra-renal manifestations including endocrinopathies. There is no definitive cure for Cystinosis. Never the less, early introduction of cysteamine treatment and other supportive measures can adequately retard the occurrence of complications and improve prognosis. CASE DESCRIPTION: An 18-year-old boy who presented with complaints of abdominal pain, vomiting, polyuria and episodes of periodic paralysis for the last 01 year to the Endocrine Unit, Medical Teaching Institution Hayatabad Medical Complex, and Peshawar, Pakistan. He was lean and wasted with a BMI of 12.9kg/m2 (weight=32.59kg, height=159cm) having frontal bossing and splaying of bones at wrist joint with normal to low blood pressure. Investigations revealed hypokalemia, alkaline urine and metabolic acidosis on arterial blood gas analysis. Consequently, his symptoms were attributed to underlying renal tubular acidosis. Later, slit lamp examination revealed Cysteine crystals in the cornea confirming the diagnosis of Cystinosis as the underlying cause. He was started on supportive therapy including potassium chloride and citrate supplements, intravenous fluids, calcium and vitamin D supplements and Indomethacin. Senior nephrologist and Nutritionist were also taken on board regarding his management. Follow up at 02 months was suggestive of marked symptomatic and biochemical improvement. CONCLUSION: Data regarding the definitive cure for Cystinosis is scarce. Never the less, early introduction of cysteamine therapy and other supportive measures can adequately retard the occurrence of complications and improvise prognosis.

Serum uric acid levels are altered by kidney disorders because the kidneys play a dominant role in uric acid excretion. Here, major kidney disorders which accompany hyperuricemia or hypouricemia, including their pathophysiology, are discussed. Chronic kidney disease (CKD) and hyperuricemia are frequently associated, but recent clinical trials have not supported the pathogenic roles of hyperuricemia in CKD incidence and progression. Diabetes mellitus (DM) is often associated with hyperuricemia, and hyperuricemia may be associated with an increased risk of diabetic kidney disease in patients with type 2 DM. Sodium-glucose cotransporter 2 inhibitors have a uricosuric effect and can relieve hyperuricemia in DM. Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an important hereditary kidney disease, mainly caused by mutations of uromodulin (UMOD) or mucin-1 (MUC-1). Hyperuricemia and gout are the major clinical manifestations of ADTKD-UMOD and ADTKD-MUC1. Renal hypouricemia is caused by URAT1 or GLUT9 loss-of-function mutations and renders patients susceptible to exercise-induced acute kidney injury, probably because of excessive urinary uric acid excretion. Hypouricemia derived from renal uric acid wasting is a component of Fanconi syndrome, which can be hereditary or acquired. During treatment for human immunodeficiency virus, hepatitis B or cytomegalovirus, tenofovir, adefovir, and cidofovir may cause drug-induced renal Fanconi syndrome. In coronavirus disease 2019, hypouricemia due to proximal tubular injury is related to disease severity, including respiratory failure. Finally, serum uric acid and the fractional excretion of uric acid are indicative of plasma volume status; hyperuricemia caused by the enhanced uric acid reabsorption can be induced by volume depletion, and hypouricemia caused by an increased fractional excretion of uric acid is the characteristic finding in syndromes of inappropriate anti-diuresis, cerebral/renal salt wasting, and thiazide-induced hyponatremia. Molecular mechanisms by which uric acid transport is dysregulated in volume or water balance disorders need to be investigated.

Background Fumaric acid esters (FAEs) are used to treat chronic plaque psoriasis. Fumarate is a crucial component of the Krebs cycle and mitochondrial function. Proximal tubule cells have high energy demands and rely on aerobic respiration. Proximal tubular dysfunction can cause renal Fanconi syndrome and acute kidney injury. We sought to better understand the mechanism for this in the context of FAE therapy. Methods We describe a case series of 10 patients with FAE-associated Fanconi syndrome. Patients were diagnosed and managed at a tertiary renal tubular disorder clinic, with examination of serum and urine biochemistry. Five patients had a renal biopsy with examination of the specimens by electron microscopy. Results The median age was 36.5 years [interquartile range (IQR) 32.25–54.25]. The median dose of FAE was 720 mg/day (IQR 390–720). There was low molecular weight proteinuria: the median urinary retinol-binding protein (RBP) at presentation was 8385 μg/mL (IQR 2793–14 600) and the RBP:creatinine ratio was 710 (IQR 390–2415). All patients had hyperphosphaturia [median fractional excretion of phosphate 24.2% (IQR 20.8–26.9), normal range <20%] as well as relative hypophosphataemia, with a median serum phosphate concentration of 0.93 mmol/L (IQR 0.83–0.97). Renal histology showed proximal tubular damage and abnormal mitochondrial morphology. Two patients had a favourable biochemical response to treatment with probenecid. Conclusions We document for the first time that FAE-associated renal Fanconi syndrome is associated with mitochondrial damage visible on electron microscopy. This effect may be ameliorated by antagonism of the organic anion transporter with probenecid. [ABSTRACT FROM AUTHOR]