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World Journal of Clinical Pediatrics Dec 2023Renal tubular acidosis (RTA) can lead to renal calcification in children, which can cause various complications and impair renal function. This review provides... (Review)
Review
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.
PubMed: 38178934
DOI: 10.5409/wjcp.v12.i5.295 -
Best Practice & Research. Clinical... Mar 2024Phosphate is an integral part of human cellular structure and function. Though most recognised disorders of phosphaturia are genetic in origin, phosphate loss due to... (Review)
Review
Phosphate is an integral part of human cellular structure and function. Though most recognised disorders of phosphaturia are genetic in origin, phosphate loss due to acquired conditions is commonly encountered in clinical practice. Acquired hypophosphatemia is most commonly due to renal phosphate wasting and can produce significant morbidity. It also heralds future kidney damage, and continued exposure can lead to progressive kidney injury and potentially renal failure. These conditions are a diverse group of disorders with common shared mechanisms causing loss of phosphate in the urine. Renal phosphate loss can occur as an isolated entity or as a part of generalised proximal tubular dysfunction, i.e., Fanconi's syndrome. An insight into the pathophysiological mechanisms of acquired phosphaturia can help clinicians monitor their patients better and avoid potential harms.
Topics: Humans; Fanconi Syndrome; Hypophosphatemia, Familial; Kidney Diseases; Osteomalacia; Phosphates; Paraneoplastic Syndromes
PubMed: 38007379
DOI: 10.1016/j.beem.2023.101839 -
Progres En Urologie : Journal de... Nov 2023The morphological-compositional analysis of urinary stones allows distinguishing schematically several situations: dietary, digestive, metabolic/hormonal, infectious and... (Review)
Review
The morphological-compositional analysis of urinary stones allows distinguishing schematically several situations: dietary, digestive, metabolic/hormonal, infectious and genetic problems. Blood and urine testing are recommended in the first instance to identify risk factors of urinary stone disease in order to avoid recurrence or progression. The other objective is to detect a potential underlying pathology associated with high risk of urinary stone disease (e.g. primary hyperparathyroidism, primary or enteric hyperoxaluria, cystinuria, distal renal tubular acidosis) that may require specific management. Lifestyle-diet measures are the basis of the management of all stone types, but pharmacological treatments may be required. METHODOLOGY: These recommendations were developed using two methods: the Clinical Practice Recommendation (CPR) method and the ADAPTE method, depending on whether the question was considered in the European Association of Urology (EAU) recommendations (https://uroweb.org/guidelines/urolithiasis) [EAU 2022] and their adaptability to the French context.
Topics: Humans; Lithiasis; Urolithiasis; Urinary Calculi; Urology; Risk Factors
PubMed: 37918992
DOI: 10.1016/j.purol.2023.08.004 -
International Urology and Nephrology Nov 2023Diethylene glycol (DEG) is nephrotoxic, potentially resulting in high morbidity and mortality. Its main nephrotoxic by-product is diglycolic acid (DGA). This narrative... (Review)
Review
Diethylene glycol (DEG) is nephrotoxic, potentially resulting in high morbidity and mortality. Its main nephrotoxic by-product is diglycolic acid (DGA). This narrative overview summarizes selected literature with a focus on clinical findings, pathophysiology, diagnosis including morphological features of renal biopsies, and management. The kidney injury in DEG poisoning is secondary to proximal tubular necrosis caused by DGA. Marked vacuolization and edema of epithelial cells obstruct the lumen, reducing urine flow and, consequently, resulting in anuria and uremia. The clinical alterations due to DEG poisoning are dose-dependent. Patients may present with gastrointestinal symptoms and anion gap metabolic acidosis, followed by renal failure, and, later, encephalopathy and neuropathy. Although this three-phase pattern has been described, signs and symptoms may be overlapping. Data about DEG intoxication is scarce. Sometimes the diagnosis is challenging. The management includes supportive care, gastric decontamination, correction of acid-base disorders, and hemodialysis. The understanding of the metabolic processes related to DEG poisoning may contribute to its management, preventing death, serious sequels, or irreversible lesions.
PubMed: 37186212
DOI: 10.1007/s11255-023-03604-2 -
Frontiers in Genetics 2024Nephrolithiasis (NL) is a common condition worldwide. The incidence of NL and nephrocalcinosis (NC) has been increasing, along with their associated morbidity and... (Review)
Review
Nephrolithiasis (NL) is a common condition worldwide. The incidence of NL and nephrocalcinosis (NC) has been increasing, along with their associated morbidity and economic burden. The etiology of NL and NC is multifactorial and includes both environmental components and genetic components, with multiple studies showing high heritability. Causative gene variants have been detected in up to 32% of children with NL and NC. Children with NL and NC are genotypically heterogenous, but often phenotypically relatively homogenous, and there are subsequently little data on the predictors of genetic childhood NL and NC. Most genetic diseases associated with NL and NC are secondary to hypercalciuria, including those secondary to hypercalcemia, renal phosphate wasting, renal magnesium wasting, distal renal tubular acidosis (RTA), proximal tubulopathies, mixed or variable tubulopathies, Bartter syndrome, hyperaldosteronism and pseudohyperaldosteronism, and hyperparathyroidism and hypoparathyroidism. The remaining minority of genetic diseases associated with NL and NC are secondary to hyperoxaluria, cystinuria, hyperuricosuria, xanthinuria, other metabolic disorders, and multifactorial etiologies. Genome-wide association studies (GWAS) in adults have identified multiple polygenic traits associated with NL and NC, often involving genes that are involved in calcium, phosphorus, magnesium, and vitamin D homeostasis. Compared to adults, there is a relative paucity of studies in children with NL and NC. This review aims to focus on the genetic component of NL and NC in children.
PubMed: 38606357
DOI: 10.3389/fgene.2024.1381174 -
Canadian Journal of Physiology and... Jul 2024Kidney anion exchanger 1 (kAE1) is an isoform of the AE1 protein encoded by the gene. It is a basolateral membrane protein expressed by α-intercalated cells in the... (Review)
Review
Kidney anion exchanger 1 (kAE1) is an isoform of the AE1 protein encoded by the gene. It is a basolateral membrane protein expressed by α-intercalated cells in the connecting tubules and collecting duct of the kidney. Its main function is to exchange bicarbonate and chloride ions between the blood and urine to maintain blood pH at physiological threshold. The kAE1 protein undergoes multiple post-translational modifications such as phosphorylation and ubiquitination and interacts with many different proteins such as claudin-4 and carbonic anhydrase II. Mutations in the gene may lead to the development of distal renal tubular acidosis, characterized by the failure to acidify the urine, which may result in nephrocalcinosis and in more severe cases, renal failure. In this review, we discuss the structure and function of kAE1, its post-translational modifications, and protein-protein interactions. Finally, we discuss insights gained from the study of kAE1 mutations in humans and in mice.
Topics: Humans; Animals; Protein Processing, Post-Translational; Anion Exchange Protein 1, Erythrocyte; Mutation
PubMed: 38669699
DOI: 10.1139/cjpp-2023-0482 -
Clinical Kidney Journal Apr 2024Wilson's disease (WD) is a rare inherited disease due to the mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and its pathological accumulation... (Review)
Review
Wilson's disease (WD) is a rare inherited disease due to the mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and its pathological accumulation in various organs such as the liver, the nervous system, or the kidneys. Whereas liver failure and neuropsychiatric disorders are the most common features, less is known about the renal complications. We conducted a review of the literature to define the characteristics and pathophysiology of kidney involvement during WD. This review shed light on strong evidence for direct copper toxicity to renal tubular cells. Excessive tubular copper accumulation might present with various degrees of tubular dysfunction, ranging from mild hydroelectrolytic and acid-base disorders to complete Fanconi syndrome. Proximal and distal renal tubular acidosis also favors development of nephrolithiasis, nephrocalcinosis, and bone metabolism abnormalities. Indirect complications might involve renal hypoperfusion as occurs in hepatorenal or cardiorenal syndrome, but also tubular casts' formation during acute hemolysis, rhabdomyolysis, or bile cast nephropathy. Acute kidney failure is not uncommon in severe WD patients, and independently increases mortality. Finally, specific and long-term therapy by D-penicillamin, one of the most efficient drugs in WD, can cause glomerular injuries, such as membranous nephropathy, minimal-change disease, and, rarely, severe glomerulonephritis. Altogether, our study supports the need for interdisciplinary evaluation of WD patients involving nephrologists, with regular monitoring of tubular and glomerular functions, to provide adequate prevention of renal and bone involvement.
PubMed: 38660122
DOI: 10.1093/ckj/sfae058 -
Cureus Nov 2023Tacrolimus, widely known as Prograf, has become the preferred immunosuppressant for preventing graft rejection in solid organ transplant recipients, particularly in... (Review)
Review
Tacrolimus, widely known as Prograf, has become the preferred immunosuppressant for preventing graft rejection in solid organ transplant recipients, particularly in steroid-sparing regimens. Its efficacy and reduced risk of acute and chronic rejection compared to cyclosporine have made it the preferred treatment option for transplant patients. However, tacrolimus has drawbacks as it is associated with adverse effects, such as renal tubular necrosis, kidney failure, hypertension, metabolic acidosis, and new-onset diabetes mellitus. Among the less common but potentially severe complications is thrombotic microangiopathy linked to tacrolimus usage. Identifying and addressing this condition early on is crucial given its severity and potential complications. Manifestations of this microangiopathy can vary, encompassing renal, neurological, cardiac, and respiratory symptoms, and, in some cases, presenting as pancreatitis, intestinal ischemia, or skin abnormalities. Although conventional management often involves plasma exchange as the primary therapeutic option, recent insights into the pathophysiology have led to newer drugs, such as eculizumab and belatacept, offering promising outcomes. In this narrative review, we delve deeper into the underlying pathophysiological mechanisms of tacrolimus-induced thrombotic microangiopathy and aim to provide clinicians with valuable recommendations for efficient and timely treatment strategies. By understanding the complexities of this condition and staying abreast of the latest advancements in therapeutic options, healthcare providers can optimize patient outcomes and ensure safer tacrolimus administration in solid organ transplant recipients.
PubMed: 38146570
DOI: 10.7759/cureus.49351