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Cureus Feb 2024Renal tubular acidosis (RTA) involves dysfunction of the renal tubular system, which leads to electrolyte abnormalities and acid-base dysregulation. The case we present...
Renal tubular acidosis (RTA) involves dysfunction of the renal tubular system, which leads to electrolyte abnormalities and acid-base dysregulation. The case we present here discusses a patient with a past medical history of psoriatic arthritis who presented to the emergency department with progressive generalized weakness and anorexia in the preceding four weeks. She was found to have profound hypokalemia (1.2 mmol/L), hyperchloremic metabolic acidosis, and multiple other electrolyte abnormalities. Following an extensive workup, her principle problem was deemed to be distal (type 1) RTA. She was treated with sodium bicarbonate, spironolactone, and aggressive rehydration, which eventually led to the stabilization of her electrolytes alongside clinical improvement over the course of an eight-day hospitalization. The workup did not reveal a clear etiology for the RTA. One month prior to hospitalization, she was started on apremilast, a new medication for her psoriatic arthritis. Given the limited availability of alternative explanations and the temporality of clinical manifestations, our findings raise suspicion that apremilast might be associated with her clinical presentation.
PubMed: 38440019
DOI: 10.7759/cureus.53514 -
Cureus Mar 2024The occurrence of hyperkalemic renal tubular acidosis (RTA) in the post-transplantation period is likely underestimated, and its identification remains important to...
INTRODUCTION
The occurrence of hyperkalemic renal tubular acidosis (RTA) in the post-transplantation period is likely underestimated, and its identification remains important to offer adequate medical management. Transplant recipients frequently present with clinical and biological characteristics that may be associated with the occurrence of this complication.
METHODS
This was a single-center retrospective study that compared transplanted patients with hyperkalemic RTA and a control group to identify variables associated with the occurrence of this complication. Fisher's exact test and the Mann-Whitney test, followed by multivariate logistic regression, were applied to test whether there was a significant association between hyperkalemic RTA and different variables.
RESULTS
Kidney and heart transplant recipients were at greater risk of developing RTA than lung transplant recipients (p = 0.016). There was also a significant association between the development of RTA and kalemia (p < 0.01), chloremia (p < 0.01), and bicarbonatemia (p < 0.01). The significant impact of these last three variables was confirmed by the results of the multivariate logistic regression. Residual serum tacrolimus levels (p = 0.13) and creatinine levels (p = 0.17) of renal transplant patients were not significantly associated with hyperkalemic RTA.
CONCLUSION
The type of transplanted organ, kalemia, chloremia, and bicarbonatemia were significantly associated with the occurrence of hyperkalemic RTA. This study calls into question certain approaches to managing this complication proposed in a number of case reports, such as reducing the target serum residual of tacrolimus or discontinuing trimethoprim-sulfamethoxazole (TMP-SMX) in favor of another antibiotic prophylactic agent, potentially exposing patients to graft rejection and opportunistic infections.
PubMed: 38434606
DOI: 10.7759/cureus.55379 -
Cell Communication and Signaling : CCS Feb 2024Tubulointerstitial kidney disease associated microenvironmental dysregulation, like acidification, inflammation and fibrosis, affects tubule cells and fibroblasts....
BACKGROUND
Tubulointerstitial kidney disease associated microenvironmental dysregulation, like acidification, inflammation and fibrosis, affects tubule cells and fibroblasts. Micromilieu homeostasis influences intracellular signaling and intercellular crosstalk. Cell-cell communication in turn modulates the interstitial microenvironment. We assessed the impact of acidosis on inflammatory and fibrotic responses in proximal tubule cells and fibroblasts as a function of cellular crosstalk. Furthermore, cellular signaling pathways involved were identified.
METHODS
HK-2 (human proximal tubule) and CCD-1092Sk (human fibroblasts), in mono and coculture, were exposed to acidic or control media for 3 or 48 h. Protein expression of inflammation markers (TNF, TGF-ß and COX-2), dedifferentiation markers (N-cadherin, vinculin, ß-catenin and vimentin), fibrosis markers (collagen III and fibronectin) and phospho- as well as total MAPK levels were determined by western blot. Secreted collagen III and fibronectin were measured by ELISA. The impact of MAPK activation was assessed by pharmacological intervention. In addition, necrosis, apoptosis and epithelial permeability were determined.
RESULTS
Independent of culture conditions, acidosis caused a decrease of COX-2, vimentin and fibronectin expression in proximal tubule cells. Only in monoculture, ß-Catenin expression decreased and collagen III expression increased in tubule cells during acidosis. By contrast, in coculture collagen III protein expression of tubule cells was reduced. In fibroblasts acidosis led to an increase of TNF, COX-2, vimentin, vinculin, N-cadherin protein expression and a decrease of TGF-ß expression exclusively in coculture. In monoculture, expression of COX-2 and fibronectin was reduced. Collagen III expression of fibroblasts was reduced by acidosis independent of culture conditions. In coculture, acidosis enhanced phosphorylation of ERK1/2, JNK1/2 and p38 transiently in proximal tubule cells. In fibroblasts, acidosis enhanced phosphorylation of p38 in a sustained and very strong manner. ERK1/2 and JNK1/2 were not affected in fibroblasts. Inhibition of JNK1/2 and p38 under coculture conditions reduced acidosis-induced changes in fibroblasts significantly.
CONCLUSIONS
Our data show that the crosstalk between proximal tubule cells and fibroblasts is crucial for acidosis-induced dedifferentiation of fibroblasts into an inflammatory phenotype. This dedifferentiation is at least in part mediated by p38 and JNK1/2. Thus, cell-cell communication is essential for the pathophysiological impact of tubulointerstitial acidosis.
Topics: Humans; Acidosis; Cadherins; Catenins; Collagen; Cyclooxygenase 2; Fibroblasts; Fibronectins; Fibrosis; Inflammation; p38 Mitogen-Activated Protein Kinases; Vimentin; Vinculin; Mitogen-Activated Protein Kinase 14
PubMed: 38395872
DOI: 10.1186/s12964-024-01527-8 -
Orphanet Journal of Rare Diseases Feb 2024Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular...
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 (HCO) 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 HCO 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.
Topics: Infant; Infant, Newborn; Humans; Child; Fanconi Syndrome; Hepatomegaly; Blood Glucose; Bicarbonates; Genetic Profile; Retrospective Studies; China; Transaminases
PubMed: 38365697
DOI: 10.1186/s13023-024-03070-8 -
Cureus Jan 2024Refeeding syndrome is the potentially fatal shift in fluids and electrolytes that may occur in malnourished patients after receiving artificial refeeding. Its hallmark...
Refeeding syndrome is the potentially fatal shift in fluids and electrolytes that may occur in malnourished patients after receiving artificial refeeding. Its hallmark feature is hypophosphatemia, although other electrolytes might also be affected. Fanconi syndrome is a generalized dysfunction of the proximal tubule characterized by proximal renal tubular acidosis (RTA), phosphaturia, glycosuria, aminoaciduria, and proteinuria. The etiology of Fanconi syndrome can be either acquired or inherited, and drugs, among them tenofovir, are a common acquired cause of this disease. We present the case of a patient with AIDS and polysubstance abuse who was admitted due to pneumonia, completed treatment, was then started on antiretroviral medication (ART) that included tenofovir alafenamide (TAF) and began presenting severe episodes of hypophosphatemia along with other electrolyte imbalances, leading the workup denoted in the case, severe complications and finally to the patient's demise. Most cases of tenofovir-related Fanconi syndrome are related to tenofovir disoproxil fumarate, but very few cases have been reported with TAF. Our case highlights this rare complication of therapy with TAF and how artificial feeding can contribute to severe electrolyte abnormalities and worsen outcomes.
PubMed: 38344551
DOI: 10.7759/cureus.52169 -
International Journal of Molecular... Jan 2024High dietary phosphorus intake (P-In) and high acid loads may adversely affect kidney function. In animal models, excessive phosphorus intake causes renal injury, which,...
Higher Renal Net Acid Excretion, but Not Higher Phosphate Excretion, during Childhood and Adolescence Associates with the Circulating Renal Tubular Injury Marker Interleukin-18 in Adulthood.
High dietary phosphorus intake (P-In) and high acid loads may adversely affect kidney function. In animal models, excessive phosphorus intake causes renal injury, which, in humans, is also inducible by chronic metabolic acidosis. We thus examined whether habitually high P-In and endogenous acid production during childhood and adolescence may be early indicators of incipient renal inflammatory processes later in adulthood. P-In and acid-base status were longitudinally and exclusively determined by biomarker-based assessment in 277 healthy children, utilizing phosphate and net acid excretion (NAE) measurements in 24 h urine samples repeatedly collected between the ages of 3 and 17 years. Standard deviation scores (by sex and age) were calculated for anthropometric data and for the urinary biomarkers available within age range 3-17 years. Multivariable linear regression was used to analyze the relations of phosphate excretion and NAE with the adulthood outcome circulating interleukin-18 (IL-18), a marker of inflammation and kidney dysfunction. After adjusting for growth- and adulthood-related covariates and pro-inflammatory biomarkers to rule out confounding by non-renal inflammatory processes, regression models revealed a significant positive relationship of long-term NAE ( = 0.01), but not of long-term phosphate excretion with adult serum IL-18. Similar significant positive regression results were obtained after replacing NAE with 24 h urinary ammonium excretion as the exposition variable. Our results suggest that even moderate elevations in renal ammonia production, as caused by habitually higher acid loading during growth, may affect the intrarenal pro-inflammatory system in the long-term, known to be boosted by acidosis-induced raised ammoniagenesis.
Topics: Adolescent; Adult; Animals; Child; Child, Preschool; Humans; Acidosis; Biomarkers; Interleukin-18; Kidney; Phosphates
PubMed: 38338685
DOI: 10.3390/ijms25031408 -
BJU International May 2024To assess the impact of kidney stone disease (KSD) and its treatment on the health-related quality of life (HRQOL) of high-risk stone formers with hyperparathyroidism,...
OBJECTIVE
To assess the impact of kidney stone disease (KSD) and its treatment on the health-related quality of life (HRQOL) of high-risk stone formers with hyperparathyroidism, renal tubular acidosis, malabsorptive disease, and medullary sponge kidney.
PATIENTS AND METHODS
The Wisconsin Stone Quality of Life questionnaire was used to evaluate HRQOL in 3301 patients with a history of KSD from 16 institutions in North America between 2014 and 2020. Baseline characteristics and medical history were collected from patients, while active KSD was confirmed through radiological imaging. The high-risk group was compared to the remaining patients (control group) using the Wilcoxon rank-sum test.
RESULTS
Of 1499 patients with active KSD included in the study, the high-risk group included 120 patients. The high-risk group had significantly lower HRQOL scores compared to the control group (P < 0.01). In the multivariable analyses, medullary sponge kidney disease and renal tubular acidosis were independent predictors of poorer HRQOL, while alkali therapy was an independent predictor of better HRQOL (all P < 0.01).
CONCLUSIONS
Among patients with active KSD, high-risk stone formers had impaired HRQOL with medullary sponge kidney disease and renal tubular acidosis being independent predictors of poorer HRQOL. Clinicians should seek to identify these patients earlier as they would benefit from prompt treatment and prevention.
Topics: Humans; Quality of Life; Female; Male; Kidney Calculi; Middle Aged; Adult; Aged; Acidosis, Renal Tubular; Medullary Sponge Kidney; Surveys and Questionnaires
PubMed: 38332669
DOI: 10.1111/bju.16294 -
Journal of the American Society of... May 2024Foxp1 is a key transcriptional factor for the differentiation of intercalated cells in collecting ducts. Dmrt2 and Hmx2 act downstream of Foxp1 to control the...
KEY POINTS
Foxp1 is a key transcriptional factor for the differentiation of intercalated cells in collecting ducts. Dmrt2 and Hmx2 act downstream of Foxp1 to control the differentiation of type A and type B intercalated cells, respectively. Foxp1 and Dmrt2 are essential for body acid–base balance regulation.
BACKGROUND
Kidney collecting ducts comprise principal cells and intercalated cells, with intercalated cells playing a crucial role in kidney acid–base regulation through H and HCO secretion. Despite its significance, the molecular mechanisms controlling intercalated cell development remain incompletely understood.
METHODS
To investigate the specific role of Foxp1 in kidney tubular system, we specifically deleted expression in kidney distal nephrons and collecting ducts. We examined the effects of on intercalated cell differentiation and urine acidification. RNA sequencing and Chip-seq were used to identify Foxp1 target genes. To dissect the genetic network that regulates intercalated cell differentiation, -deficient mice were generated to determine the role of Dmrt2 in intercalated cell differentiation. -deficient mice were crossed with -deficient mice to dissect the relation between Foxp1 and Notch signaling.
RESULTS
Foxp1 was selectively expressed in intercalated cells in collecting ducts. The absence of Foxp1 in kidney tubules led to the abolishment of intercalated cell differentiation in the collecting ducts, resulting in distal renal tubular acidosis. Foxp1 regulates the expression of and , two genes encoding transcription factors specifically expressed in type A and type B intercalated cell cells, respectively. Further genetic analysis revealed that Dmrt2 was essential for type A intercalated cell differentiation, and Foxp1 was necessary downstream of Notch for the regulation of intercalated cell differentiation.
CONCLUSIONS
Foxp1 is required for the renal intercalated cell differentiation and participated in acid–base regulation. Foxp1 regulated downstream transcriptional factors, Dmrt2 and Hmx2, which were involved in the specification of distinct subsets of intercalated cells.
Topics: Animals; Cell Differentiation; Forkhead Transcription Factors; Mice; Acid-Base Equilibrium; Repressor Proteins; Kidney
PubMed: 38332484
DOI: 10.1681/ASN.0000000000000319 -
International Journal of Legal Medicine Jul 2024Herein, we present the case of accidental intravenous injection of gasoline in a 62-year-old male who was admitted to a dialysis center for his regular hemodialysis. Due...
Herein, we present the case of accidental intravenous injection of gasoline in a 62-year-old male who was admitted to a dialysis center for his regular hemodialysis. Due to previous contact with another SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) positive patient, the hemodialysis was conducted in an isolated room. At the end of the procedure, the nurse, wearing all necessary personal protective equipment (PPE), in the intent to clean the dialysis catheter, applied medical gasoline, instead of 0.9% sodium chloride, intravenously to the patient. Soon afterwards, the patient's clinical condition deteriorated, and cardiopulmonary resuscitation was started. Despite the immediate reaction of the medical staff, after two successful cardiopulmonary reanimation and necessary intensive care measures, the patient suffered respiratory, metabolic, and lactic acidosis, hypotension, and tachyarrhythmia and ultimately died 7 h after the incident. The autopsy was conducted under the order of the district attorney. Main autopsy findings were marked congestion; right pleural and pericardial effusion; brain and lung edema; enlarged heart with left ventricle thickening and mild perivascular fibrosis; nephrosclerosis; tubular thyroidization; and interstitial fibrosis with inflammation. Gasoline presence was indisputably proven by conducted toxicology analysis in lung, bile, and brain samples. Traces of gasoline could be noted in the patient's blood sample in comparison to the blood that did not contain gasoline, but it was not possible to confidently claim that gasoline was present in the blood. Based on relevant findings, we concluded that the death of the patient was violent and that the cause of death was acute intoxication by gasoline.
Topics: Humans; Male; Middle Aged; Gasoline; Renal Dialysis; Fatal Outcome; COVID-19; Injections, Intravenous; Lung
PubMed: 38332349
DOI: 10.1007/s00414-024-03181-8