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Priyadarshini S, Sinha A, Jana M, Tandon R, Sikka K, Mathur VP, Bhatt GC, Yadav M, Meena JK, Khandelwal P, Hari P, Bagga A. Etiology and outcomes of primary renal tubular acidosis. Pediatr Nephrol 2025:10.1007/s00467-025-06747-9. [PMID: 40232499 DOI: 10.1007/s00467-025-06747-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 03/08/2025] [Accepted: 03/10/2025] [Indexed: 04/16/2025]
Abstract
BACKGROUND This study investigates the etiology, outcomes, and genotype-phenotype correlations in patients with renal tubular acidosis (RTA) at a tertiary care center in New Delhi. METHODS This cross-sectional study included children and young adults with RTA who underwent clinical, biochemical, radiological and/or genetic evaluations between July 2020 and December 2024. We report clinical phenotype, anthropometry, metabolic control and progression to chronic kidney disease (CKD) in relation to genotype of distal RTA. RESULTS Of 135 patients enrolled, 69 had distal RTA. The yield of genetic testing was 72% in distal RTA and 88.7% in Fanconi syndrome. Variants in SLC4A1 (42.4%) and ATP6V1B1 (28.8%) were the most common etiologies of distal RTA. Compared to other etiologies, patients with SLC4A1 variants were older at symptom onset (P = 0.008). Hematological abnormalities were more frequent in patients with biallelic compared to heterozygous SLC4A1 variants (50% vs. 12.5%; P = 0.18). Nephrocalcinosis and metabolic control were similarly prevalent across genetic categories of distal RTA. Sensorineural hearing loss was more common with ATP6V1B1 than with ATP6V0A4 variants (61.5% vs. 22.2%, P = 0.099) and did not vary by metabolic control. At median follow-up of 5-years, 74.1% of patients with distal RTA had short stature, 74.6% had poor metabolic control and 2.9% had progressed to CKD G3-5. CONCLUSIONS This study outlines the genetic etiology and phenotype of distal RTA in south Asia. Over short-term follow-up, poor metabolic control and severe stunting were common, while CKD was uncommon.
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Affiliation(s)
- Sukanya Priyadarshini
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Aditi Sinha
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.
| | - Manisha Jana
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Radhika Tandon
- Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Kapil Sikka
- Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India
| | - Vijay Prakash Mathur
- Center for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Girish Chandra Bhatt
- Department of Pediatrics, All India Institute of Medical Sciences, Bhopal, India
| | - Menka Yadav
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Jitendra Kumar Meena
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Priyanka Khandelwal
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Pankaj Hari
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Arvind Bagga
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
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He X, Li H. Role of LncRNA in Pathogenesis, Diagnosis and Treatment of Chronic Kidney Disease. Cell Biochem Biophys 2025:10.1007/s12013-025-01698-2. [PMID: 40000585 DOI: 10.1007/s12013-025-01698-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 02/27/2025]
Abstract
Chronic kidney disease (CKD) is a clinical syndrome of metabolic disorder caused by progressive kidney impairment for more than 3 months. CKD has become a global public health problem due to its high morbidity and mortality, which is difficult to be cured for most patients. The pathogenesis of CKD is still unclear, which is closely related to glomerulosclerosis, kidney tubular injury and kidney fibrosis. LncRNA is a non-coding RNA with a length of more than 200 nucleotides. It not only participates in intracellular transcriptional regulation, post-transcriptional regulation and epigenetic activities, but also forms a regulatory network together with miRNA and mRNA, to further conduct the reticular regulation in cells. Recently, it has been found that lncRNA participates in pathophysiological mechanism of CKD by regulating glomerulosclerosis, kidney tubular injury and kidney fibrosis. This has also become a new direction of lncRNA in early diagnosis and targeted therapy of CKD.
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Affiliation(s)
- Xin He
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Han Li
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
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Fernandes PC, da Silva MD, Waddington-Cruz M, Gomes CP. Renal tubular acidosis in hereditary transthyretin amyloidosis (ATTRv). J Bras Nefrol 2024; 46:e20240016. [PMID: 39101566 PMCID: PMC11305565 DOI: 10.1590/2175-8239-jbn-2024-0016en] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/17/2024] [Indexed: 08/06/2024] Open
Abstract
INTRODUCTION Hereditary transthyretin amyloidosis (ATTRv) is a severe autosomal dominant systemic disease. It affects the peripheral and autonomic nervous systems, heart, kidneys, and eyes. Amyloid deposition has been demonstrated in the glomerular and tubulointerstitial compartments of the kidney. Therefore, urinary acidification disorders such as renal tubular acidosis (RTA) may be early manifestations of renal involvement in this population. OBJECTIVE To evaluate the prevalence of RTA in individuals with ATTRv. METHODS We included symptomatic and asymptomatic individuals with TTR mutation, older than 18 years, GFR >45 mL/min/1.73m2, without systemic metabolic acidosis. Urinary acidification protocol was performed with furosemide and fludrocortisone after 12 h of water deprivation (water deprivation test - WDT) and measurements of urine ammonium ( UNH 4 + ) and titratable acidity (UTA). Proximal RTA (pRTA) was diagnosed when FEHCO3>10%. Incomplete form distal RTA (dRTA) was diagnosed if UpH>5.3. RESULTS We selected 49 individuals with a mean age of 40 (35.5-56.5) years, 63% of which were female, 84% were Caucasian, and mean GFR was 85.5 ± 20.5 mL/min/1.73m2. 94% had the genetic variant Val50Met and 57% were symptomatic. The prevalence of pRTA was 2% and of dRTA was 16.3%. In the subgroup with dRTA, there was no significant increase in excretion of UNH 4 + and UTA. We observed a good correlation between UpH by potentiometry and UpH dipstick. A UpH<5.5 on the dipstick had 100% sensitivity and negative predictive value to exclude dRTA. CONCLUSION A high prevalence of RTA was found in individuals with TTR mutations. The UpH dipstick after WDT had good accuracy for screening for dRTA. Further studies are needed to evaluate the impact of early diagnosis and treatment of RTA in this population.
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Affiliation(s)
- Priscilla Cardim Fernandes
- Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Centro de Estudos em Paramiloidose Antônio Rodrigues de Mello, Rio de Janeiro, RJ, Brazil
| | - Moises Dias da Silva
- Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Centro de Estudos em Paramiloidose Antônio Rodrigues de Mello, Rio de Janeiro, RJ, Brazil
- Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Divisão de Nefrologia, Rio de Janeiro, RJ, Brazil
| | - Marcia Waddington-Cruz
- Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Centro de Estudos em Paramiloidose Antônio Rodrigues de Mello, Rio de Janeiro, RJ, Brazil
| | - Carlos Perez Gomes
- Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Centro de Estudos em Paramiloidose Antônio Rodrigues de Mello, Rio de Janeiro, RJ, Brazil
- Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Divisão de Nefrologia, Rio de Janeiro, RJ, Brazil
- Universidade Federal do Estado do Rio de Janeiro, Escola de Medicina e Cirurgia, Rio de Janeiro, RJ, Brazil
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Saiteja P, Krishnamurthy S, Deepthi B, Krishnasamy S, Sravani M. Distal renal tubular acidosis as presenting manifestation of Wilson disease in a 11-year-old girl. CEN Case Rep 2024; 13:93-97. [PMID: 37415038 PMCID: PMC10982190 DOI: 10.1007/s13730-023-00806-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 06/27/2023] [Indexed: 07/08/2023] Open
Abstract
A 11-year-old girl was referred to the pediatric nephrology services of our hospital for evaluation of vitamin-D-refractory rickets. She was born to second-degree consanguineous parents. On examination, she had wrist widening and bilateral genu varum. She had normal anion gap metabolic acidosis, hypokalemia, and hyperchloremia. The fractional excretion of bicarbonate was 3% and the urine anion gap was positive. She also had hypercalciuria, but no phosphaturia, glucosuria or aminoaciduria. In view of a family history of an elder sister having rigidity with cognitive and speech impairment, an ophthalmic evaluation by slit lamp examination was performed in the index case that revealed bilateral Kayser-Fleischer rings. Serum ceruloplasmin was low and 24-h urine copper was elevated in the index case. Whole exome sequencing unveiled a novel pathogenic variant in exon 2 of the ATP7B gene (chr13: c.470del; Depth: 142x) (homozygous) that resulted in a frameshift and premature truncation of the protein, 15 amino acids downstream to codon 157 (p. Cys157LeufsTer15; NM_000053.4) confirming Wilson disease. There were no mutations in the ATP6V0A4, ATP6V1B1, SLC4A1, FOXI1, WDR72 genes or other genes that are known to cause distal RTA. Therapy with D-penicillamine and zinc supplements was initiated. A low dose of 2.5 mEq/kg/day of potassium citrate supplementation normalized the serum bicarbonate levels. This case was notable for the absence of hepatic or neurological involvement at admission. Wilson disease is well known to cause proximal renal tubular acidosis and Fanconi syndrome, with relatively lesser involvement of the distal renal tubules in the literature. However, isolated distal renal tubular involvement as presenting manifestation of Wilson disease (without hepatic or neurological involvement) is rare and can lead to diagnostic confusion.
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Affiliation(s)
- Paraselli Saiteja
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Sriram Krishnamurthy
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India.
| | - Bobbity Deepthi
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Sudarsan Krishnasamy
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Madhileti Sravani
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
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Du T, Xia Y, Sun C, Gong Z, Liang L, Gong Z, Wang R, Lu D, Zhang K, Yang Y, Sun Y, Sun M, Sun Y, Xiao B, Qiu W. Clinical, genetic profile and therapy evaluation of 11 Chinese pediatric patients with Fanconi-Bickel syndrome. Orphanet J Rare Dis 2024; 19:75. [PMID: 38365697 PMCID: PMC10874070 DOI: 10.1186/s13023-024-03070-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 02/03/2024] [Indexed: 02/18/2024] Open
Abstract
BACKGROUND Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction. METHODS Clinical, biochemical, genetic, treatment, and follow-up data for 11 pediatric patients with FBS were retrospectively analysed. RESULTS Hepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO3-) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO3- and AKP (p < 0.05). At the last follow-up, 5/7 patients with elevated AKP had nephrocalcinosis. The mean height standard deviation score (Ht SDS) of eight patients with regular treatment increased from - 4.1 to -3.5 (p = 0.02). Recombinant human growth hormone (rhGH) was administered to 4/9 patients, but their Ht SDS did not improve significantly (p = 0.13). Fourteen variants of the SLC2A2 gene were identified, with six being novel, among which one was recurrent: c.1217T > G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient. CONCLUSIONS Early diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended in FBS patients who have normal GH stimulation tests. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families.
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Affiliation(s)
- Taozi Du
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Yu Xia
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Chengkai Sun
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Zhuwen Gong
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Lili Liang
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Zizhen Gong
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Ruifang Wang
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Deyun Lu
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Kaichuang Zhang
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Yi Yang
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Yuning Sun
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Manqing Sun
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Yu Sun
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
- Department of Clinical Genetics Centre, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China
| | - Bing Xiao
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China.
- Department of Clinical Genetics Centre, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China.
| | - Wenjuan Qiu
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092, Shanghai, China.
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R, Hasan S, Hamza MB. Renal calcification in children with renal tubular acidosis: What a paediatrician should know. World J Clin Pediatr 2023; 12:295-309. [PMID: 38178934 PMCID: PMC10762599 DOI: 10.5409/wjcp.v12.i5.295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/15/2023] [Accepted: 10/16/2023] [Indexed: 12/08/2023] Open
Abstract
Renal tubular acidosis (RTA) can lead to renal calcification in children, which can cause various complications and impair renal function. This review provides pediatricians with a comprehensive understanding of the relationship between RTA and renal calcification, highlighting essential aspects for clinical management. The article analyzed relevant studies to explore the prevalence, risk factors, underlying mechanisms, and clinical implications of renal calcification in children with RTA. Results show that distal RTA (type 1) is particularly associated with nephrocalcinosis, which presents a higher risk of renal calcification. However, there are limitations to the existing literature, including a small number of studies, heterogeneity in methodologies, and potential publication bias. Longitudinal data and control groups are also lacking, which limits our understanding of long-term outcomes and optimal management strategies for children with RTA and renal calcification. Pediatricians play a crucial role in the early diagnosis and management of RTA to mitigate the risk of renal calcification and associated complications. In addition, alkaline therapy remains a cornerstone in the treatment of RTA, aimed at correcting the acid-base imbalance and reducing the formation of kidney stones. Therefore, early diagnosis and appropriate therapeutic interventions are paramount in preventing and managing renal calcification to preserve renal function and improve long-term outcomes for affected children. Further research with larger sample sizes and rigorous methodologies is needed to optimize the clinical approach to renal calcification in the context of RTA in the pediatric population.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Dr. Sulaiman Al Habib Medical Group, Manama, Bahrain, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Manama, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Chest Disease, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama, Manama 26671, Manama, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
| | - Samir Hasan
- Department of Pediatrics, Faculty of Medicine, Tanta University Hospital, Tanta 31511, Algharbia, Egypt
| | - Mohamed Basiony Hamza
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
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Singhania P, Dhar A, Deshpande A, Das D, Agrawal N, Chakraborty PP, Bhattacharjee R, Roy A. Rickets in proximal renal tubular acidosis: a case series of six distinct etiologies. J Pediatr Endocrinol Metab 2023; 36:879-885. [PMID: 37434360 DOI: 10.1515/jpem-2023-0155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 06/23/2023] [Indexed: 07/13/2023]
Abstract
OBJECTIVES Proximal renal tubular acidosis (pRTA) is characterized by a defect in the ability of the proximal convoluted tubule to reabsorb bicarbonate. The biochemical hallmark of pRTA is hyperchloremic metabolic acidosis with a normal anion gap, accompanied by appropriate acidification of the urine (simultaneous urine pH <5.3). Isolated defects in bicarbonate transport are rare, and pRTA is more often associated with Fanconi syndrome (FS), which is characterized by urinary loss of phosphate, uric acid, glucose, amino acids, low-molecular-weight proteins, and bicarbonate. Children with pRTA may present with rickets, but pRTA is often overlooked as an underlying cause of this condition. CASE PRESENTATION We report six children with rickets and short stature due to pRTA. One case was idiopathic, while the remaining five had a specific underlying condition: Fanconi-Bickel syndrome, Dent's disease, nephropathic cystinosis, type 1 tyrosinemia, and sodium-bicarbonate cotransporter 1-A (NBC1-A) defect. CONCLUSIONS Five of these six children had features of FS, while the one with NBC1-A defect had isolated pRTA.
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Affiliation(s)
- Pankaj Singhania
- Department of Endocrinology and Metabolism, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India
| | - Abhranil Dhar
- Department of Endocrinology and Metabolism, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India
| | - Aditya Deshpande
- Department of Endocrinology and Metabolism, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India
| | - Debaditya Das
- Department of Endocrinology and Metabolism, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India
| | - Neeti Agrawal
- Department of Endocrinology, Medical College Kolkata, Kolkata, India
| | | | | | - Ajitesh Roy
- Department of Endocrinology, Vivekananda Institute of Medical Sciences, Kolkata, West Bengal, India
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Santos F, Gil-Peña H. Long-term complications of primary distal renal tubular acidosis. Pediatr Nephrol 2023; 38:635-642. [PMID: 35543873 DOI: 10.1007/s00467-022-05546-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 03/12/2022] [Accepted: 03/14/2022] [Indexed: 01/19/2023]
Abstract
The clinical manifestations of primary distal renal tubular acidosis usually begin in childhood, but the disease is caused by a genetic defect that persists throughout life. This review focuses on the complications of distal tubular acidosis that occur or remain long-term such as nephrocalcinosis and urolithiasis, growth impairment, bone mineralization, severe hypokalemia, kidney cysts, and progressive kidney failure, as well as other persistent manifestations that occur independent of acidosis but are associated with some inherited forms of the disease. The pathogenic factors responsible for kidney failure are discussed in particular because it is a complication to which different publications have recently drawn attention and which affects a high percentage of adults with primary distal renal tubular acidosis. The need to maintain optimal metabolic control of the disease and scheduled clinical follow-up throughout life and the importance of organizing protocols for the transition of patients to adult nephrology services are emphasized.
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Affiliation(s)
- Fernando Santos
- Department of Medicine, Pediatrics, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain.
| | - Helena Gil-Peña
- Department of Medicine, Pediatrics, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain
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Mandal A, Khandelwal P, Geetha TS, Murugan S, Meena J, Jana M, Sinha A, Kumar R, Seth A, Hari P, Bagga A. Metabolic and Genetic Evaluation in Children with Nephrolithiasis. Indian J Pediatr 2022; 89:1243-1250. [PMID: 35819704 DOI: 10.1007/s12098-022-04234-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 03/07/2022] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To evaluate metabolic and genetic abnormalities in children with nephrolithiasis attending a referral center in North India. METHODS The patients aged 1-18 y old with nephrolithiasis underwent biochemical evaluation and whole-exome sequencing. The authors evaluated for monogenic variants in 56 genes and compared allele frequency of 39 reported polymorphisms between patients and 1739 controls from the GenomeAsia 100 K database. RESULTS Fifty-four patients, aged 9.1 ± 3.7 y were included. Stones were bilateral in 42.6%, familial in 33.3%, and recurrent in 25.9%. The most common metabolic abnormalities were hypercalciuria (35.2%), hyperoxaluria (24.1%), or both (11.1%), while xanthinuria (n = 3), cystinuria (n = 1), and hyperuricosuria (n = 1) were rare. Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. Three variants in MOCOS and one in ATP7B were pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). Causality was not attributed to two SLC34A1 likely pathogenic variants, due to lack of matching phenotype and dominant family history. Compared to controls, allele frequency of the polymorphism TRPV5 rs4252402 was significantly higher in familial stone disease (allele frequency 0.47 versus 0.53; OR 3.2, p = 0.0001). CONCLUSION The chief metabolic abnormalities were hypercalciuria and hyperoxaluria. A monogenic etiology was identified in 11% with pathogenic or likely pathogenic variants using a gene panel for nephrolithiasis. Heterozygous missense variants in the sodium-phosphate cotransporter SLC34A1 were common and required evaluation for attributing pathogenicity. Rare polymorphisms in TRPV5 might increase the risk of familial stones. These findings suggest that a combination of metabolic and genetic evaluation is useful for determining the etiology of nephrolithiasis.
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Affiliation(s)
- Anita Mandal
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Kidney Diseases, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Priyanka Khandelwal
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Kidney Diseases, All India Institute of Medical Sciences, New Delhi, 110029, India
| | | | | | - Jitendra Meena
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Kidney Diseases, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Manisha Jana
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Aditi Sinha
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Kidney Diseases, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Rajeev Kumar
- Department of Urology, All India Institute of Medical Sciences, New Delhi, India
| | - Amlesh Seth
- Department of Urology, All India Institute of Medical Sciences, New Delhi, India
| | - Pankaj Hari
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Kidney Diseases, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Arvind Bagga
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Kidney Diseases, All India Institute of Medical Sciences, New Delhi, 110029, India.
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10
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Boro H, Khatiwada S, Alam S, Kubihal S, Dogra V, Mannar V, Khadgawat R. Renal Tubular Acidosis Manifesting as Severe Metabolic Bone Disease. TOUCHREVIEWS IN ENDOCRINOLOGY 2022; 17:59-67. [PMID: 35118447 DOI: 10.17925/ee.2021.17.1.59] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 02/05/2021] [Indexed: 11/24/2022]
Abstract
Renal tubular acidosis (RTA) is a condition characterized by normal anion gap metabolic acidosis. Type 1 and type 2 RTA are the most common, and are caused by defective secretion of hydrogen ions and impaired absorption of bicarbonate, respectively. Long-standing uncorrected acidosis can lead to metabolic bone disease (MBD). Rickets and osteomalacia remain the commonest manifestations of uncorrected RTA. In addition, there can be a myriad of other skeletal manifestations like fractures, pseudofractures, secondary osteoporosis and even sclerotic bone disease. The postulated mechanism for bone involvement includes acidosis-mediated exaggerated osteoclastic bone resorption. Other contributory factors include abnormal renal handling of phosphate leading to hypophosphataemia in proximal RTA, and impaired vitamin D metabolism and action. In distal RTA, hypercalciuria and secondary hyperparathyroidism may play a key role for bone involvement. Recognizing the disease in its early course is important to prevent permanent sequelae of skeletal involvement. Most of these patients may, in fact, undergo orthopaedic interventions without primary correction of acidosis. We describe five cases who presented with MBD in varied forms. While evaluating the aetiology of MBD, they were diagnosed with RTA. Subsequently, we attempted to analyse the causes of RTA. Although the common causes were ruled out, genetic aetiology could not be ascertained due to resource constraints. RTA remains an important differential diagnosis of MBD. More awareness is required to diagnose the disease early and to treat it adequately. Our case series is an attempt to provide the clinical, biochemical and skeletal spectrum of RTA. In addition, we have attempted to provide algorithms for the approach and evaluation of RTA along with their varied causes.
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Affiliation(s)
- Hiya Boro
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Saurav Khatiwada
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Sarah Alam
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Suraj Kubihal
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Vinay Dogra
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Velmurugan Mannar
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Rajesh Khadgawat
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
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11
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Muscle and Bone Impairment in Infantile Nephropathic Cystinosis: New Concepts. Cells 2022; 11:cells11010170. [PMID: 35011732 PMCID: PMC8749987 DOI: 10.3390/cells11010170] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/28/2021] [Accepted: 01/01/2022] [Indexed: 11/17/2022] Open
Abstract
Cystinosis Metabolic Bone Disease (CMBD) has emerged during the last decade as a well-recognized, long-term complication in patients suffering from infantile nephropathic cystinosis (INC), resulting in significant morbidity and impaired quality of life in teenagers and adults with INC. Its underlying pathophysiology is complex and multifactorial, associating complementary, albeit distinct entities, in addition to ordinary mineral and bone disorders observed in other types of chronic kidney disease. Amongst these long-term consequences are renal Fanconi syndrome, hypophosphatemic rickets, malnutrition, hormonal abnormalities, muscular impairment, and intrinsic cellular bone defects in bone cells, due to CTNS mutations. Recent research data in the field have demonstrated abnormal mineral regulation, intrinsic bone defects, cysteamine toxicity, muscle wasting and, likely interleukin-1-driven inflammation in the setting of CMBD. Here we summarize these new pathophysiological deregulations and discuss the crucial interplay between bone and muscle in INC. In future, vitamin D and/or biotherapies targeting the IL1β pathway may improve muscle wasting and subsequently CMBD, but this remains to be proven.
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12
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Chakraborty PP, Bhattacharjee R, Patra S, Roy A, Gantait K, Chowdhury S. Clinical and Biochemical Characteristics of Patients with Renal Tubular Acidosis in Southern Part of West Bengal, India: A Retrospective Study. Indian J Endocrinol Metab 2021; 25:121-128. [PMID: 34660240 PMCID: PMC8477733 DOI: 10.4103/ijem.ijem_785_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/30/2021] [Accepted: 06/29/2021] [Indexed: 01/25/2023] Open
Abstract
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.
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Affiliation(s)
- Partha Pratim Chakraborty
- Department of Medicine, Midnapore Medical College and Hospital, Midnapore, Kolkata, West Bengal, India
| | - Rana Bhattacharjee
- Department of Endocrinology and Metabolism, IPGME and R/SSKM Hospital, Kolkata, West Bengal, India
| | - Shinjan Patra
- Department of Medicine, Midnapore Medical College and Hospital, Midnapore, Kolkata, West Bengal, India
| | - Ajitesh Roy
- Department of Endocrinology and Metabolism, IPGME and R/SSKM Hospital, Kolkata, West Bengal, India
| | - Kripasindhu Gantait
- Department of Medicine, Midnapore Medical College and Hospital, Midnapore, Kolkata, West Bengal, India
| | - Subhankar Chowdhury
- Department of Endocrinology and Metabolism, IPGME and R/SSKM Hospital, Kolkata, West Bengal, India
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13
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Kallistrou E, Architha NN, Pal SK, Oyibo SO. Severe Hypokalemia Secondary to Transient Distal Renal Tubular Acidosis in a Previously Healthy Woman. Cureus 2021; 13:e12765. [PMID: 33500865 PMCID: PMC7817551 DOI: 10.7759/cureus.12765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Normal anion gap (non-gap) hyperchloremic acidosis with hypokalemia is a medical emergency. There are several causes of this metabolic phenomenon, of which distal renal tubular acidosis is among the very rare causes. In this report, we present an unusual case of a previously healthy woman who was admitted to the intensive care unit with a short history of severe muscle weakness. She had no significant past medical history and was not taking any regular medication. There was also no history of recent drug or herb ingestion. Investigations demonstrated a combination of severe hypokalemia, hyperchloremia, hypobicarbonatemia (non-gap metabolic acidosis), and relatively raised urinary potassium and urinary pH in the presence of severe hypokalemia and metabolic acidosis. Results suggested a diagnosis of distal renal tubular acidosis. The patient responded rapidly to a short course of electrolyte replacement therapy and the condition resolved spontaneously thereafter. This case highlights the fact that distal renal tubular acidosis can occur as a transient phenomenon in previously healthy individuals.
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Affiliation(s)
| | | | - Soubhik K Pal
- Nephrology, Peterborough City Hospital, Peterborough, GBR
| | - Samson O Oyibo
- Diabetes and Endocrinology, Peterborough City Hospital, Peterborough, GBR
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Boro H, Khatiwada S, Alam S, Kubihal S, Dogra V, Mannar V, Khadgawat R. Renal Tubular Acidosis Manifesting as Severe Metabolic Bone Disease. EUROPEAN ENDOCRINOLOGY 2021. [DOI: 10.17925/ee.2021.1.1.59] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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15
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Sinha A, Bagga A. Pediatric Nephrology: Update for Clinicians. Indian J Pediatr 2020; 87:598-599. [PMID: 32462355 DOI: 10.1007/s12098-020-03309-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 04/14/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Aditi Sinha
- Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Arvind Bagga
- Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.
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