-
Nefrologia 2021Distal renal tubular acidosis (DRTA) is a rare disease resulting from a failure in the normal urine acidification process at the distal tubule and collecting duct level.... (Review)
Review
Distal renal tubular acidosis (DRTA) is a rare disease resulting from a failure in the normal urine acidification process at the distal tubule and collecting duct level. It is characterised by persistent hyperchloremic metabolic acidosis, with a normal anion gap in plasma, in the presence of high urinary pH and low urinary excretion of ammonium. To date, 5 genes whose mutations give rise to primary DRTA have been described. Alterations in the ATP6V1B1 and ATP6V0A4 genes are inherited recessively and are associated with forms of early onset and, in many cases, with neurosensorial deafness. Pathogenic variants in the SLC4A1 gene are habitually inherited dominantly and give rise to milder symptoms, with a later diagnosis and milder electrolytic alterations. Nonetheless, evolution to nephrocalcinosis and lithiasis, and the development of chronic kidney disease in the medium to long term has been described in a similar manner in all 3 groups. Lastly, recessive forms of DTRA associated to mutations in the FOXI1 and WDR72 genes have also been described. The clinical management of DTRA is based on bicarbonate or citrate salts, which do not succeed in correcting all cases of the metabolic alterations described and, thus, the consequences associated with them. Recently, a new treatment based on slow-release bicarbonate and citrate salts has received the designation of orphan drug in Europe for the treatment of DTRA.
Topics: Acidosis, Renal Tubular; Ammonium Compounds; Bicarbonates; Citrates; Forkhead Transcription Factors; Humans; Vacuolar Proton-Translocating ATPases
PubMed: 36165107
DOI: 10.1016/j.nefroe.2021.09.004 -
Journal of Ayub Medical College,... 2022Acute hypokalemic paralysis (AHP) is a life-threatening emergency. It is exceptionally unusual for hypothyroidism to present with AHP. This association can be either...
Acute hypokalemic paralysis (AHP) is a life-threatening emergency. It is exceptionally unusual for hypothyroidism to present with AHP. This association can be either primary or secondary through distal renal tubular acidosis. We report two cases who presented with acute quadriplegia. The succeeding investigations revealed severe hypokalemia and autoimmune hypothyroidism. The second case was found to have Sjogren's syndrome additionally. The underlying aetiology of hypokalemia in both cases was found to be dRTA. The combination of such conditions is reported sporadically. Here we also discuss the potential association of AHP with autoimmune conditions by proxy through dRTA.
Topics: Humans; Hypokalemia; Paralysis; Autoimmune Diseases; Hypothyroidism
PubMed: 36566415
DOI: 10.55519/JAMC-04-10918 -
Pediatric Nephrology (Berlin, Germany) Feb 2020Acid-base homeostasis is one of the most tightly regulated systems in the body. Maintaining the acid-base balance is particularly challenging for preterm infants and... (Review)
Review
Acid-base homeostasis is one of the most tightly regulated systems in the body. Maintaining the acid-base balance is particularly challenging for preterm infants and growing neonates. The kidney, which represents the crucial ultimate line of defense against disturbances of acid-base balance, undergoes a complex maturation process during the transition from a fetal to an extra-uterine environment. This review article summarizes the physiology of acid-base regulation by the immature human kidney and discusses disorders of acid-base balance, such as metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. In conditions of metabolic acidosis, the serum anion gap and the urinary anion gap can be useful tools to define the nature of the acidosis. Metabolic acidosis can reflect a decrease in glomerular filtration rate, or be the consequence of selective disorders of proximal or distal tubular function. Most tubulopathies associated with metabolic acidosis observed in neonates are primary, hereditary, isolated tubulopathies. Proximal renal tubular acidosis is characterized by bicarbonate wasting, while the distal types of renal tubular acidosis are secondary to distal acidification defects. All tubulopathies are associated with hypokalemia, with the exception of type 4 hyperkalemic distal renal tubular acidosis. The transporter defects in the various acid-base tubulopathies are now well defined. Treatment of the acidosis varies according to the site and mechanism of the defect. Chronic renal tubular acidosis or alkalosis severely impair growth and calcium metabolism. Early rational therapeutic intervention can prevent some of the consequences of the disorders and improves the prognosis.
Topics: Acid-Base Imbalance; Female; Humans; Infant, Newborn; Kidney; Male
PubMed: 30456666
DOI: 10.1007/s00467-018-4142-9 -
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 -
Pediatric Nephrology (Berlin, Germany) Mar 2023The clinical manifestations of primary distal renal tubular acidosis usually begin in childhood, but the disease is caused by a genetic defect that persists throughout... (Review)
Review
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.
Topics: Adult; Humans; Acidosis, Renal Tubular; Hypokalemia; Acidosis; Nephrocalcinosis; Renal Insufficiency
PubMed: 35543873
DOI: 10.1007/s00467-022-05546-w -
Seminars in Nephrology Nov 2022Immune checkpoint inhibitors (ICIs) are now established treatments for advanced cancer and their use is now ubiquitous. The high upside of ICIs is tempered by their... (Review)
Review
Immune checkpoint inhibitors (ICIs) are now established treatments for advanced cancer and their use is now ubiquitous. The high upside of ICIs is tempered by their toxicity profile affecting almost every organ, including the kidneys. Although acute interstitial nephritis is the major kidney-related adverse effect of checkpoint inhibitors, other manifestations such as electrolyte abnormalities and renal tubular acidosis have been described. With increasing awareness and recognition of these events, the focus has shifted to non-invasive identification of ICI-acute interstitial nephritis, with sophisticated approaches involving biomarkers and immunologic signatures being studied. Although the management of immune-related adverse events with corticosteroids is straightforward, there now are more data to help guide immunosuppressive regimens, ICI rechallenge, and delineate risk and efficacy in special populations such as individuals on dialysis or those who have received a transplant.
Topics: Humans; Immune Checkpoint Inhibitors; Kidney; Nephritis, Interstitial; Acute Kidney Injury
PubMed: 37137187
DOI: 10.1016/j.semnephrol.2023.151346 -
International Journal of Nephrology and... 2019Medullary Sponge Kidney (MSK) disease is a rare congenital malformation of the distal nephron where cystic dilatation is appreciable in the collecting ducts and renal...
Medullary Sponge Kidney (MSK) disease is a rare congenital malformation of the distal nephron where cystic dilatation is appreciable in the collecting ducts and renal papillae. Most cases of the malformation are thought to arise from a malfunction within neurotrophic factor and tyrosine kinase interactions. Presentation and prognosis are usually indolent; however, they include urinary tract infections (UTI), nephrolithiasis and nephrocalcinosis, distal renal tubular acidosis (dRTA) and hypocitraturia. With an insidious and asymptomatic onset, MSK is a difficult renal manifestation to both diagnose and treat. Difficulty diagnosing MSK today arises from clinical settings deviating from the usage of contrast methods when assessing the urogenital tract. Many healthcare standards for kidney disorders center diagnosis around imaging techniques rather than contrast methods. This ultimately leads to a decrease in the total number of confirmed cases of MSK. Though intra-venous urogram (IVU) remains as the current gold standard to diagnose MSK, other methods such as endoscopy and Multi-detector computed tomography (MDCT) are being put into place. Endoscopic examination and renal biopsy may allow definitive diagnosis; however, such invasive methods may be considered excessive. Moving forward, differential diagnoses for MSK can be made more precisely when patients present with other renal manifestations, especially in groups at risk. These groups include patients between the age of 20 and 30, patients with other renal malformations, high sodium diet patients, hyperparathyroid patients, and patients with family history of MSK. Basic treatment is aimed at controlling stone formation by stabilizing urinary pH. Treatment for patients, especially those prone to forming stones, includes the application of potassium citrate compounds, prophylactic water and diet control, surgical intervention or lithotripsy for removal of symptomatic kidney stones.
PubMed: 31576161
DOI: 10.2147/IJNRD.S169336 -
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 -
Frontiers in Immunology 2020Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms... (Review)
Review
Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms of dryness (xerophthalmia and xerostomia). Extraglandular features are common and may affect several organs. Renal involvement has long been known as one of the systemic complications of pSS. The most classical lesion observed in pSS is tubulointerstitial nephritis (TIN) and less frequently membranoproliferative glomerulonephritis (MPGN), which is related to cryoglobulinemia. In some cases, renal biopsy is necessary for the definitive diagnosis of kidney involvement. Patients may present with proximal renal tubular acidosis, distal renal tubular acidosis and chronic kidney disease. Response to treatment is usually favorable. However, occasionally severe and rarely lethal outcomes have been described. Recently, several case series and cross-sectional studies have been published which investigated the factors associated with renal involvement in pSS and the most accurate screening tests for early detection. The presence of xerophthalmia, anti-SSA and rheumatoid factor positivity, low C3 levels and other features have all shown either positive or inverse associations with the development of renal complications. Serum creatinine, alpha-1-microglobulin, cystatin-C have been evaluated as early detection biomarkers with variable accuracy. More advanced techniques may be necessary to confirm proximal and distal renal tubular acidosis, along with nephrogenic diabetes insipidus. The aim of the current paper is to summarize and critically examine these findings in order to provide updated guidance on serum biomarkers and further testing for kidney involvement in pSS.
Topics: Alpha-Globulins; Autoimmunity; Biomarkers; Creatinine; Diagnostic Techniques and Procedures; Glomerulonephritis, Membranoproliferative; Humans; Kidney; Nephritis, Interstitial; Risk Factors; Sjogren's Syndrome
PubMed: 33042142
DOI: 10.3389/fimmu.2020.562101 -
Revista Medica de Chile Dec 2019Toxic alcohols can produce severe poisoning with multiple organic involvement and even death. The most common form is ethylene glycol. The diagnosis can be extremely... (Review)
Review
Toxic alcohols can produce severe poisoning with multiple organic involvement and even death. The most common form is ethylene glycol. The diagnosis can be extremely difficult if there is no history of its consumption. Its clinical presentation can simulate other conditions. Ethylene glycol poisoning is characterized by an initial rise in plasma osmolal gap that decreases during the evolution, while alcohol is metabolized to acids. This last condition causes a metabolic acidosis with elevated anion gap. The clinical manifestations are diffuse neurological involvement initially, followed by hemodynamic alterations due to myocardial damage associated with hypocalcemia and acidemia. Subsequently, severe tubular renal damage appears, which may require renal replacement therapy, and finally, focal neurological alterations. To treat this poisoning, it is necessary to inhibit the transformation of alcohol into acids, increase the metabolism of the latter or withdraw them directly with hemodialysis.
Topics: Ethylene Glycols; Humans; Poisoning
PubMed: 32186622
DOI: 10.4067/S0034-98872019001201572