Comparison of chronic kidney disease progression and associated complications between geriatric and non-geriatric groups.

There is no consensus on the physiologic decline in estimated glomerular filtration rate (GFR) due to geriatric conditions related with the aging or chronic kidney disease (CKD) itself. In this study, we aimed to compare the CKD progression and associated complications in a large sample of geriatric and non-geriatric patients. The data of in 506 patients at age between 30 to 90 years and diagnosed with CKD at stage 2 and above (15 mL/min/1.73 m2 ≤ eGFR < 90 mL/min/1.73 m2) were collected retrospectively and compared among geriatric (>65 years old) and non-geriatric individuals. The rate of hypertension was higher in geriatrics compared to non-geriatrics (96.6% vs 91.9%, P = .04). Among laboratory findings, only PTH level was significantly lower and HCO3 concentration was higher in geriatrics compared to non-geriatrics (P = .02, P < .001, respectively). There was no significant difference in last measured eGFR (P = .99) while that measured 4 years ago was lower in geriatrics compared to that of non-geriatrics (P < .001). eGFR change was smaller in geriatrics compared to non-geriatrics (P < .001), and rate of progressive renal disease among non-geriatric group (39%) was found to be significantly higher than in the geriatrics (17.2%) (P < .001). The prevalence of hyperkalemia was lower in geriatrics at stage 3a (P = .02); prevalence of hyperparathyroidism was lower in those at stage 3b (P = .02) and lastly the acidosis was observed significantly lower in geriatric patients at stage 3a, 3b, and 4 compared to the non-geriatrics at corresponding stages (P < .001, P = .03, and P = .04, respectively). The eGFR change was significantly smaller in geriatrics at stage 3b and 4 (P < .001 and P = .04, respectively) while the rate of progressed renal disease was lower in geriatrics at stage 3a and 3b (21.1% vs 9.9%, P = .03 and 41.2% vs 11.1%, P < .001, respectively). eGFR change in 4-year period and the rates of progressive renal disease are higher in the non-geriatrics and also the prevalence of secondary complications of CKD, such as hyperparathyroidism, acidosis, and hyperkalemia, are higher in non-geriatrics. This may reflect that decline of GFR in geriatric individuals is at least partially related to physiological aging rather than kidney disease. Therefore, devising age related CKD definitions might be appropriate.

Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

BACKGROUND: D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. METHODS: A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. RESULTS: Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). CONCLUSION: DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

A Counterion-Free Strategy for Chronic Metabolic Acidosis Based on an Orally Administered Gut-Restricted Inorganic Adsorbent.

Chronic metabolic acidosis, arising as a complication of chronic kidney disease (CKD), not only reduces patients' quality of life but also aggravates renal impairment. The only available therapeutic modality, involving intravenous infusion of NaHCO3 , engenders undesirable sodium retention, thereby increasing hemodynamic load and seriously exacerbating the primary disease. This deleterious cascade extends to the development of cardiovascular diseases. Herein, an orally administered, gut-restricted inorganic adsorbent that can effectively alleviate chronic metabolic acidosis without causing any electrolytic derangement or superfluous cardiovascular strain is developed. The genesis of ABC-350 entails the engineering of bismuth subcarbonate via annealing, thereby yielding a partially ß-Bi2 O3 -doped (BiO)2 CO3 biphasic crystalline structure framework enriched with atomic vacancies. ABC-350 can selectively remove chloride ions and protons from the gastrointestinal tract, mimicking the physiological response to gastric acid removal and resulting in increased serum bicarbonate. Owing to its gut-restricted nature, ABC-350 exhibits commendable biosafety, averting undue systemic exposure. In two rat models of metabolic acidosis, ABC-350 emerges not only as a potent mitigator of acidosis but also effects discernible amelioration concerning proximal tubular morphology, interstitial fibrosis, and the incendiary cascades incited by metabolic acidosis. ABC-350, as the translationally relevant material, provides a promising strategy for the treatment of metabolic acidosis.

[Reversible bilateral blindness associated with alcoholic ketoacidosis: a case report].

A 51-year-old male with a history of chronic alcoholism presented to the emergency department with an abrupt onset of complete bilateral blindness lasting for one hour. Funduscopic examination yielded unremarkable findings. Systemic evaluations revealed the presence of severe ketoacidosis. The patient spontaneously regained light perception after experiencing total blindness for 3 hours; however, he subsequently developed hypothermia and entered a state of shock. Following treatment with sodium bicarbonate and aggressive fluid resuscitation, his condition stabilized, and there was a rapid improvement in his visual acuity. The diagnosis of alcoholic ketoacidosis was established based on the patient's history of chronic alcohol abuse, physical examination findings, and blood analysis results.

Predestinative role acidic cerebrospinal fluid on the destiny of central channel in spinal cord following subarachnoid hemorrhage: an experimental study.

OBJECTIVE: Acidosis is the most dangerous complication in subarachnoid hemorrhage (SAH). This study aimed to investigate the effect of acidic cerebrospinal fluid on central canal structures after SAH. MATERIALS AND METHODS: Twenty-eight hybrid rabbits were studied. Blood and cerebrospinal fluid pH values were recorded before/during/after the experimental procedures. The structures related to the central canals at the level of C5 of the cervical spinal cord were then examined histopathologically. The relationship between pH values of ependymal cells and degenerated epithelial cell densities was statistically analyzed. RESULTS: Mean blood pH values and degenerated ependymal cell density (n/mm2) were as follows: 7.351 ± 0.033/23 ± 7 in control, 7.322 ± 0.059/78 ± 13 in SHAM, and 7.261 ± 0.048/254 ± 62 in study animals. Gross examinations revealed swelling, edema, pia-arachnoid adhesions, ventral canal dilatation, arachnoiditis, central canal hemorrhage, occlusions, and dilatation in the spinal cord. CONCLUSION: Cerebrospinal fluid acidosis-induced central channel pathologies should be considered an important complication of SAH following SAH.

OBJETIVO: La acidosis es la complicación más peligrosa en la hemorragia subaracnoidea (HSA). El objetivo de este estudio fue investigar el efecto del líquido cefalorraquídeo ácido en las estructuras del canal central tras la HSA. MATERIALES Y MÉTODOS: Se estudiaron 28 conejos híbridos. Se registraron los valores de pH de la sangre y del líquido cefalorraquídeo antes, durante y después de los procedimientos experimentales. A continuación se examinaron histopatológicamente las estructuras relacionadas con los canales centrales a nivel de C5 de la médula espinal cervical. Se analizó estadísticamente la relación entre los valores de pH de las células ependimarias y las densidades de células epiteliales degeneradas. RESULTADOS: Los valores medios de pH en sangre y la densidad de células ependimarias degeneradas (n/mm2) fueron los siguientes: 7.351 ± 0.033/23 ± 7 en el control, 7.322 ± 0.059/78 ± 13 en el SHAM, 7.261 ± 0.048/254 ± 62 en los animales del estudio. Los exámenes macroscópicos revelaron hinchazón, edema, adherencias pia-aracnoideas, dilatación del canal ventral, aracnoiditis, hemorragia del canal central, oclusiones y dilatación en la médula espinal. CONCLUSIONES: Las patologías del canal central inducidas por la acidosis del líquido cefalorraquídeo deben considerarse como una complicación importante de la HSA tras una hemorragia subaracnoidea.

[Metabolische Ursachen von Dyspnoe]. / Metabolische Ursachen von Dyspnoe.

INTRODUCTION: Endocrinological or metabolic disorders often affect a wide variety of functions of the organism. This can also include an impairment of respiratory function. Diabetic ketoacidosis as a result of insulin deficiency is a typical metabolic acidosis, which the body tries to compensate by an increased exhalation of carbon dioxide. This leads to the classic picture of "Kussmaul" breathing. Due to the increased use of SGLT2 inhibitors, which can reduce the otherwise typical hyperglycemia and thus complicate diagnosis, the occurrence of diabetic ketoacidosis has remained an important differential diagnosis in recent years. Pathologies of the thyroid gland can lead to dyspnea not only by morphological changes, for example in the case of goiter (compression). Functional disorders must also be considered here. Both hypo- and hyperthyroidism affect the cardiovascular system in different ways and may ultimately lead to the clinical picture of dyspnea. If the corresponding entities are thought of, the laboratory diagnosis of the aforementioned metabolic/endocrinological disorders is then basically straightforward. Accordingly, knowledge of these disorders as a differential diagnosis of tachy- and dyspnea is important.

Diet and Metabolism in CKD-Related Metabolic Acidosis.

Metabolic acidosis is a common complication in patients with chronic kidney disease that occurs when the daily nonvolatile acid load produced in metabolism cannot be excreted fully by the kidney. A reduction in urine net acid excretion coupled with a high nonvolatile acid load may play a role in its pathogenesis. Diet is important in generation of the nonvolatile acid load. Acids are produced from metabolism of dietary protein and from the endogenous production of organic anions from neutral precursors. Acids can be balanced by alkali precursors ingested in the diet in the form of combustible organic anions. These typically are reflected indirectly by the excess of mineral cations to mineral anions in a food or diet. These principles underscore widely used methods to estimate the nonvolatile acid load from dietary intake using formulas such as the net endogenous acid production equation and the potential renal acid load equation. Empiric data largely validate these paradigms with high net endogenous acid production and potential renal acid load contributed by foods such as protein, grains, and dairy, and low net endogenous acid production and potential renal acid load contributed by fruits and vegetables along with corresponding dietary patterns. Although further studies are needed to understand the health benefits of altering nonvolatile acid load via diet, this review provides a detailed assessment on our current understanding of the role of diet in chronic kidney disease-related acidosis, providing an updated resource for researchers and clinicians.

Acid-base and electrolyte evaluation in dogs with upper GI obstruction: 115 dogs (2015-2021).

OBJECTIVES: Metabolic alkalosis, although uncommon in small animals, has been previously associated with gastrointestinal obstructions. Depending on the population and disease process evaluated, previous prevalence of metabolic alkalosis is reported as ranging from 2% to 45% in canine patients. The objective of this study was to determine the prevalence of metabolic alkalosis and other acid-base and electrolyte disorders in a cohort of dogs with a confirmed upper gastrointestinal obstruction. MATERIALS AND METHODS: Electronic medical records were reviewed to identify dogs who presented for vomiting with evidence of an upper gastrointestinal obstruction from January 2015 to October 2021. Patients were enrolled only if a preoperative venous blood gas was obtained and analysed in house. Traditional acid-base analysis was utilised to determine an acid-base status before relieving the obstruction. When available, post-operative venous acid-base status was determined within 24 hours after surgery, and compared to preoperative results. RESULTS: A total of 115 dogs were included in the study. Twenty-five out of 115 (22%) dogs displayed either a simple metabolic alkalosis or a mixed acid-base disturbance before surgery. Twenty-seven out of 115 dogs (37%) had a normal acid-base status at entry. Seventy-one dogs had pre- and post-operative venous blood gas results available. Metabolic alkalosis was resolved in nearly all patients post-operatively, with no patients displaying a simple metabolic alkalosis. A mixed metabolic acidosis and respiratory alkalosis was the most common condition post-operatively, found in 25 of 71 (35%) dogs. Severe derangements of electrolytes were infrequent preoperatively (3/115; 2.6%). A majority of patients in this study exhibited hypokalaemia (64.4%), hypochloraemia (72.8%) and hyponatraemia (77.4%) on preoperative venous blood gases. Venous pH, Pv CO2 , bicarbonate and base excess were significantly higher preoperatively when compared to the post-operative results. CLINICAL SIGNIFICANCE: This study found the prevalence of pre-operative metabolic alkalosis in dogs with a documented upper gastrointestinal obstruction to be lower than previously reported. Surgical or endoscopic alleviation of the upper gastrointestinal obstruction resulted in resolution of metabolic alkalosis in nearly all patients.

Acute Esophageal Necrosis as a Rare Complication of Metabolic Acidosis in a Diabetic Patient: A Case Report.

BACKGROUND Acute esophageal necrosis, or Gurvits syndrome, is a rare clinical process often secondary to a systemic low-flow state. It can be caused by several medical conditions, and it is thought to arise from a combination of impaired mucosal barrier and chemical and ischemic insults to the esophagus. Acute esophageal necrosis usually presents with severe complications due to delayed diagnosis and only rarely has surgical indications. We present a case of Gurvits syndrome, presumably triggered by metabolic acidosis in a diabetic patient. CASE REPORT A 61-year-old man with history of hypertension and type 2 diabetes mellitus treated with metformin, canagliflozin, glimepiride, and pioglitazone came to our attention with persistent vomiting, odynophagia, chest pain after each meal, and progressive weight loss. Arterial blood analysis showed mild metabolic acidosis, while the first esophagogastroduodenoscopy performed revealed a circumferential black appearance of the esophageal mucosa, as in concentric necrosis of the distal esophagus with possible fungal superinfection. Brushing cytology confirmed the infection by Candida spp. and the patient was treated with intravenous fluconazole. The second esophagogastroduodenoscopy, performed after 2 weeks, showed almost complete healing of the esophageal mucosa; in this case, biopsy confirmed mucosal ischemia and necrosis, without showing deep impairment of the mucosa by fungal agents. CONCLUSIONS Due to its high lethality, often caused by the underlying medical diseases, acute esophageal disease should be considered in the differential diagnosis of digestive symptoms, even without upper gastrointestinal bleeding. Prompt diagnosis and treatment of contextual collateral conditions can help clinicians to avoid the worst outcomes of the disease. Among the causative factors of metabolic acidosis leading to esophageal necrosis we recognized metformin and dapagliflozin.

An Infant Case of Transient Distal Renal Tubular Acidosis and Fanconi Syndrome Caused by Rotavirus Gastroenteritis.

We report an infant case of transient distal renal tubular acidosis and Fanconi syndrome caused by rotavirus gastroenteritis. A 10-month-old boy was admitted to the hospital because of frequent vomiting, lack of vitality, and dehydration. He was diagnosed with rotavirus gastroenteritis on account of his positive stool rotavirus antigen test. Although he presented with acidemia and severe mixed metabolic acidosis, he also had a urine pH of 6.0, indicating impaired urinary acidification. Therefore, he was diagnosed with distal renal tubular acidosis. On the third day of hospitalization, a relatively low %tubular reabsorption of phosphate level with hypophosphatemia, increased fractional excretion of uric acid with hypouricemia, and high urinary ß2-microglobulin levels were observed. Moreover, he was diagnosed with Fanconi syndrome on account of multiple proximal tubular dysfunctions. After remission of rotavirus gastroenteritis, the signs of renal tubular dysfunction improved. This was a case of rotavirus gastroenteritis-caused transient distal renal tubular acidosis and Fanconi syndrome. Severe metabolic acidosis resulted from anion-gap metabolic acidosis due to acute kidney injury by rotavirus gastroenteritis and normal anion-gap acidosis due to renal tubular acidosis. When renal tubular acidosis is associated with a disease that causes anion-gap metabolic acidosis, mixed metabolic acidosis occurs and becomes exacerbated. Furthermore, it is important to consider the complications of renal tubular acidosis in the case of severe metabolic acidosis.

Markers of Kidney Tubule Dysfunction and Major Adverse Kidney Events.

BACKGROUND: Serum creatinine and albuminuria are primary markers of glomerular function and injury, respectively. Tubular secretion, acid-base homeostasis, protein reabsorption, among other tubular functions, are largely ignored. This mini-review aimed to discuss how two tubular functions, secretion, and acid-base homeostasis are associated with major adverse kidney events (MAKEs). SUMMARY: Proximal tubular secretion is an essential function that allows the elimination of endogenous substances and drugs. Recently discovered endogenous markers in urine and plasma allow a noninvasive way of assessing tubular secretion markers. Several studies have found an association between these markers and a higher risk of chronic kidney disease (CKD) progression and mortality. In a study we recently performed among patients with CKD and at risk of cardiovascular events, lower tubular secretion was associated with an increased risk of acute kidney injury and metabolic acidosis, independent of baseline eGFR and albuminuria. The kidney tubules also play a crucial role in acid-base homeostasis. Although the standard clinical assessment of acidosis consists of measuring serum bicarbonate, urinary ammonium excretion decreases before over metabolic acidosis. Urinary ammonium excretion is associated with CKD progression, a higher risk of kidney failure, and an increased mortality risk, independent of baseline eGFR and albuminuria. KEY MESSAGES: Novel biomarkers of kidney tubular health consistently associate with MAKEs, above and beyond baseline eGFR, albuminuria, and other CKD risk factors. Tubular markers may provide new opportunities to improve kidney prognosis, drug dosing, and monitoring for adverse events.

Rickets in proximal renal tubular acidosis: a case series of six distinct etiologies.

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.

Risks of Topical Carbonic Anhydrase Inhibitors in Glaucoma Patients With Chronic Kidney Disease: A Nationwide Population-Based Study.

PURPOSE: To investigate the risks of metabolic acidosis and renal outcomes after topical carbonic anhydrase inhibitor (CAI) use in patients with both primary open-angle glaucoma (POAG) and advanced chronic kidney disease (CKD). DESIGN: Nationwide, population-based cohort study. METHODS: This study was conducted with population data from Taiwan's National Health Insurance (NHI) Research Database between January 2000 and June 2009. Patients with advanced CKD who were diagnosed with glaucoma (International Classification of Diseases, Ninth Revision [ICD-9] code 365) and had been receiving eye drops for glaucoma (including carbonic anhydrase inhibitors selected by NHI drug code) were enrolled. Using Kaplan-Meier methods, we compared the cumulative incidence of mortality, long-term dialysis, and cumulative incidence of metabolic acidosis over time between CAI users and CAI non-users. Primary outcomes comprised mortality, renal outcome (progression to hemodialysis), and metabolic acidosis. RESULTS: In this cohort, topical CAI users had a higher incidence of long-term dialysis than non-users (incidence = 1,216.85 vs 764.17 events per 100 patient-years; adjusted hazard ratio = 1.17, 95% CI = 1.01-1.37). Hospital admissions due to metabolic acidosis were higher in CAI users compared with non-users (incidence = 21.54 vs 11.87 events per 100 patient-years; adjusted hazard ratio = 1.89, 95% CI = 1.07-3.36). CONCLUSIONS: Topical CAIs may be associated with higher risks of long-term dialysis and metabolic acidosis in patients with POAG and pre-dialysis advanced CKD. Therefore, topical CAIs should be used with caution in advanced CKD patients.

Marked Metabolic Acidosis Due to a Transverse Stoma after Urethroplasty for Congenital Epispadias.

A 58-year-old woman was admitted to our hospital. At 10 years old, she had undergone bilateral uretero-sigmoid anastomosis for congenital epispadias, and at 57 years old, she had received transverse colostomy. Biochemical tests showed marked metabolic acidosis. Computed tomography showed urine stagnation in the sigmoid colon, leading to a diagnosis of metabolic acidosis associated with transverse stoma after bilateral uretero-sigmoid anastomosis. Her bone mineral density was below normal, and the bone metabolic marker levels were high, indicating high-turnover osteoporosis. Both metabolic acidosis and bone metabolism were stabilized by treatment with a transanal urinary catheter, sodium bicarbonate, and vitamin D.

Transient distal renal tubular acidosis with nephrogenic diabetes insipidus after general anaesthesia in a dog.

A 3-year-old, 3.5 kg, female spayed Pomeranian was referred due to persistent vomiting, anorexia, polyuria and polydipsia, 7 days after receiving general anaesthetic for a medial patellar luxation correction. Physical examination revealed lethargy, tachypnoea and 7% dehydration. Complete blood count and serum chemistry results were unremarkable, and venous blood gas analysis revealed hypokalaemia and hyperchloraemic metabolic acidosis with a normal anion gap. Urinalysis revealed a urine specific gravity (USG) of 1.005, pH of 7.0 and proteinuria, and the bacterial culture was negative. Based on these results, the dog was diagnosed with distal renal tubular acidosis, and potassium citrate was prescribed to correct metabolic acidosis. In addition, concurrent diabetes insipidus (DI) was suspected because the dog showed persistent polyuria, polydipsia and a USG below 1.006 despite dehydration. After 3 days of initial treatment, acidosis was corrected, and vomiting resolved. Desmopressin acetate and hydrochlorothiazide were also prescribed for DI, but the USG was not normalized. Based on the insignificant therapeutic response, nephrogenic DI was highly suspected. DI was resolved after 24 days. This case report describes the concomitant presence of RTA and DI in a dog after general anaesthesia.

Acidosis-related pain and its receptors as targets for chronic pain.

Sensing acidosis is an important somatosensory function in responses to ischemia, inflammation, and metabolic alteration. Accumulating evidence has shown that acidosis is an effective factor for pain induction and that many intractable chronic pain diseases are associated with acidosis signaling. Various receptors have been known to detect extracellular acidosis and all express in the somatosensory neurons, such as acid sensing ion channels (ASIC), transient receptor potential (TRP) channels and proton-sensing G-protein coupled receptors. In addition to sense noxious acidic stimulation, these proton-sensing receptors also play a vital role in pain processing. For example, ASICs and TRPs are involved in not only nociceptive activation but also anti-nociceptive effects as well as some other non-nociceptive pathways. Herein, we review recent progress in probing the roles of proton-sensing receptors in preclinical pain research and their clinical relevance. We also propose a new concept of sngception to address the specific somatosensory function of acid sensation. This review aims to connect these acid-sensing receptors with basic pain research and clinical pain diseases, thus helping with better understanding the acid-related pain pathogenesis and their potential therapeutic roles via the mechanism of acid-mediated antinociception.

Empagliflozin-associated postoperative mixed metabolic acidosis. Case report and review of pathogenesis.

BACKGROUND: Euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors is a rare, relatively new and potentially fatal clinical entity, characterized by metabolic acidosis with normal or only moderately elevated glycemia. The mechanisms are not fully understood but involve increased ketogenesis and complex renal metabolic dysfunction, resulting in both ketoacidosis and hyperchloremic acidosis. We report a rare case of fatal empagliflozin-associated acidosis with profound hyperchloremia and review its pathogenesis. CASE PRESENTATION: A patient with type 2 diabetes mellitus treated with empagliflozin underwent an elective hip replacement surgery. Since day 4 after surgery, he felt generally unwell, leading to cardiac arrest on the day 5. Empagliflozin-associated euglycemic diabetic ketoacidosis with severe hyperchloremic acidosis was identified as the cause of the cardiac arrest. CONCLUSIONS: This unique case documents the possibility of severe SGLT2 inhibitor-associated mixed metabolic acidosis with a predominant hyperchloremic component. Awareness of this possibility and a high index of suspicion are crucial for correct and early diagnosis.

Classification of pseudohypoaldosteronism type II as type IV renal tubular acidosis: results of a literature review.

Pseudohypoaldosteronism (PHA) type II (PHA2) is a genetic disorder that leads to volume overload and hyperkalemic metabolic acidosis. PHA2 and PHA type I (PHA1) have been considered to be genetic and pediatric counterparts to type IV renal tubular acidosis (RTA). Type IV RTA is frequently found in adults with chronic kidney disease and is characterized by hyperchloremic hyperkalemic acidosis with normal anion gap (AG). However, we recently observed that PHA1 was not always identical to type IV RTA. In this study, we focused on the acid-base balance in PHA2. Through a literature search published between 2008-2020, 46 molecularly diagnosed cases with PHA2 were identified (median age of 14 years). They comprised 11 sets of familial and 16 sporadic cases and the pathology was associated with mutations in WNK 4 (n = 1), KLHL3 (n = 17), and CUL3 (n = 9). The mean potassium (K+) level was 6.2 ± 0.9 mEq/L (n = 46, range 4.0-8.6 mEq/L), whereas that of chloride (Cl-) was 110 ± 3.5 mEq/L (n = 41, 100-119 mEq/L), with 28 of 41 cases identified as hyperchloremic. More than half of the cases (18/35) presented with metabolic acidosis. Although AG data was obtained only in 16 cases, all but one cases were within normal AG range. Both Cl- and HCO3- levels showed significant correlations with K+ levels, which suggested that the degree of hyperchloremia and acidosis reflect the clinical severity, and is closely related to the fundamental pathophysiology of PHA2. In conclusion, our study confirmed that PHA2 is compatible with type IV RTA based on laboratory findings.

Multi-organ dysfunction in infants with acidosis at birth in the absence of moderate to severe hypoxic ischemic encephalopathy.

INTRODUCTION: Infants with perinatal asphyxia are at risk for organ failure aside from the brain, regardless of the severity of the asphyxial insult. We aimed to evaluate the presence of organ dysfunction other than the brain in newborns with moderate to severe acidosis at birth, in the absence of moderate to severe hypoxic ischemic encephalopathy. MATERIALS AND METHODS: Data of 2 years were retrospectively recorded. Late preterm and term infants admitted to the intensive care unit with ph < 7.10 and BE < -12 mmol/l in the first hour were included in the absence of moderate to severe hypoxic ischemic encephalopathy. Respiratory dysfunction, hepatic dysfunction, renal dysfunction, myocardial depression, gastrointestinal problems, hematologic system dysfunction, and circulatory failure were evaluated. RESULTS: Sixty-five infants were included [39 (37-40) weeks, 3040 (2655-3380) grams]. Fifty-six (86 %) infants had one or more dysfunction in any system [respiratory: 76.9 %, hepatic: 20.0 %, coagulation: 18.5 %, renal: 9.2 %, hematologic: 7.7 %, gastrointestinal: 3.0 %, and cardiac: 3.0 %]. Twenty infants had at least two affected systems. The incidence of coagulation dysfunctions was higher in the infants with severe acidosis (n = 25, ph < 7.00) than the infants with moderate acidosis (n = 40: pH = 7.00-7.10); 32 % vs 10 %; p = 0.03. CONCLUSIONS: Moderate to severe fetal acidosis is associated with the development of extra-cranial organ dysfunctions in infants who do not require therapeutic hypothermia. A monitoring protocol is needed for infants with mild asphyxia in order to identify and manage potential complications. Coagulation system should be carefully evaluated.