Alkali Therapy Research Articles

Effects of dietary interventions for metabolic acidosis in chronic kidney disease: a systematic review and meta-analysis.

Metabolic acidosis is a common complication of kidney disease and can result in further disease progression. Alkali therapy has been used to treat metabolic acidosis for decades. However, some concerns have been raised regarding its safety and long-term tolerability. Existing data suggest that dietary interventions can be beneficial in the management of chronic kidney disease (CKD). This systematic review and meta-analysis aims to summarize findings from studies comparing dietary interventions with placebo/usual care/no treatment in the management of metabolic acidosis in outpatient adults with CKD. Medline, Embase, Cochrane Central, CINAHL, and Web of Science Core Collection were searched from inception to June 2022. Our primary outcome measure was change in serum bicarbonate. Any dietary intervention looking to manipulate dietary acid load was considered as an intervention. Data screening and extraction were performed by two independent reviewers. Random effects meta-analysis was performed to pool data. Dietary interventions resulted in clinically significant improvement in serum bicarbonate (mean difference (MD):2.98, 95% CI: [0.77, 5.19]; I2: 91%) and higher eGFR levels (MD: 3.16, 95%CI: [0.24, 6.08], I2: 67%) compared to controls. Serum potassium, albumin and body mass index remained unchanged. Dietary interventions were reported to be safe. Subgroup analyses indicated a superiority of plant-based over non-plant-based interventions in the improvement of acid-base balance and eGFR, however, these findings are from low quality and heterogenous studies. Our findings support the beneficial effects of dietary interventions aimed at reducing acid or adding base in the management of metabolic acidosis and kidney function in adults with CKD, with no adverse effects on serum potassium and nutritional status. Well-designed clinical trials looking at the treatment of metabolic acidosis with dietary interventions with a focus on adding base through fruit and vegetables are required.

Primary Distal Renal Tubular Acidosis: Toward an Optimal Correction of Metabolic Acidosis.

The term classic, type 1 renal tubular acidosis or primary distal renal tubular acidosis is used to designate patients with impaired ability to excrete acid normally in the urine as a result of tubular transport defects involving type A intercalated cells in the collecting duct. The clinical phenotype is largely characterized by the complications of chronic metabolic acidosis (MA): stunted growth, bone abnormalities, and nephrocalcinosis and nephrolithiasis that develop as the consequence of hypercalciuria and hypocitraturia. All these manifestations are preventable with early and sustained correction of MA with alkali therapy. The optimal target for plasma bicarbonate should be as close as possible to the range considered normal by current standards (between 23 and 28 mEq/L.). Most of the benefits of alkali therapy are tangible early in the course of the disease in childhood, but life-long treatment is required to prevent the vast array of complications attributable to chronic MA.

Prevalence, Risk Factors, and Management of Metabolic Acidosis in Chronic Kidney Disease Patients: A Multicenter Retrospective Study in Malaysia.

Background Metabolic acidosis in chronic kidney disease (CKD) patients has lately gained attention due to the growing evidence of its treatment benefits. This study aims to provide baseline data on the prevalence, risk factors, and current management of metabolic acidosis among the pre-dialysis adult Malaysian CKD population. Methodology This multicenter cross-sectional retrospective study involved pre-dialysis CKD patients above 18 years old on regular nephrology clinic follow-up at three Malaysian government hospitals with nephrology subspecialty. Demographic data, clinical information, laboratory data, and a list of concomitant medications were collected. Factors associated with the occurrence of metabolic acidosis were identified via multiple logistic regression. Results Six hundred and fifty-seven CKD patients were screened for this study, in which only39.4% (n=259) had available bicarbonate levels. From this, a total of 86.1% (n=223) had metabolic acidosis.Higher estimated glomerular filtration rate (odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-1.00, p=0.043) and those with cardiovascular disease (OR 0.33, 95% CI 0.15-0.73; p=0.007) were significantly associated with lower odds of metabolic acidosis. There were 43.0% (n=96) on alkali therapy with sodium bicarbonate solution being the most common (n=91, 94.8%). Among those receiving alkali therapy, only 19.8% (n=19) achieved bicarbonate levels of ≥ 22 mEq/L. Conclusion Our study showed that metabolic acidosis was highly prevalent, although few achieved target levels despite supplementation, supporting the need for focused management of metabolic acidosis in the CKD population.

Real-World Effectiveness of Preventive Pharmacological Therapy in Patients With Urolithiasis: A Retrospective Cohort Study

Data supporting the efficacy of preventive pharmacological therapy (PPT) to reduce urolithiasis recurrence are based on clinical trials with composite outcomes that incorporate imaging findings and have uncertain clinical significance. This study evaluated whether the use of PPT leads to fewer symptomatic stone events. Retrospective cohort study. Medicare enrollees with urolithiasis who completed 24-hour urine collections that revealed hypercalciuria, hypocitraturia, low urine pH, or hyperuricosuria. PPT (thiazide diuretics for hypercalciuria, alkali for hypocitraturia or low urine pH, or uric acid lowering drugs for hyperuricosuria) categorized as (1) adherent to guideline-concordant PPT, (2) nonadherent to guideline-concordant PPT, or (3) untreated. Symptomatic stone event occurrence (emergency department [ED] visit or hospitalization for urolithiasis or stone-directed surgery). Cox proportional hazards regression. Among 13,942 patients, 31.0% were prescribed PPT. Compared with no treatment, concordant/adherent PPT use was associated with a significantly lower hazard of symptomatic stone events for patients with hypercalciuria (HR, 0.736 [95% CI, 0.593-0.915]) and low urine pH (HR, 0.804 [95% CI, 0.650-0.996]) but not for patients with hypocitraturia or hyperuricosuria. These associations were largely driven by significantly lower rates of ED visits after initiating PPT among the concordant/adherent group versus untreated patients. Patients with hypercalciuria had adjusted 2-year predicted probabilities of a visit of 3.8% [95% CI, 2.5%-5.2%%] and 6.9% [95% CI, 6.0%-7.7%] for the concordant/adherent PPT and no-treatment groups, respectively. Among patients with low urine pH, these probabilities were 4.3% (95% CI, 2.9%-5.7%) and 7.3% (95% CI, 6.5%-8.0%) for the concordant/adherent PPT and no-treatment groups, respectively. Potential bias from the possibility that patients prescribed PPT had more severe disease than untreated patients. Patients with urolithiasis and hypercalciuria who were adherent to treatment with thiazide diuretics as well as those with low urine pH adherent to prescribed alkali therapy had fewer symptomatic stone events than untreated patients. Despite multiple clinical trials demonstrating the efficacy of thiazide diuretics and alkali for secondary prevention of kidney stones, they are infrequently prescribed due in part to a lack of data about their effectiveness in real-world settings. We analyzed medical claims from older adults with kidney stones for whom urine chemistry data were available. We found that patients who took prescribed thiazide diuretics for elevated urine calcium levels or alkali for low urinary pH were less likely to experience symptomatic stone recurrences than untreated patients. This benefit was expressed as lower rates of emergency department visits after initiating therapy. Our findings should inform the prescription of and adherence to treatment with thiazide diuretics and alkali for the prevention of recurrent kidney stones.

Preventive Pharmacological Therapy and Risk of Recurrent Urinary Stone Disease.

Urinary stone disease is a prevalent condition associated with a high recurrence risk. Preventive pharmacological therapy has been proposed to reduce recurrent stone episodes. However, limited evidence exists regarding its effectiveness, contributing to its underutilization by physicians. This study aimed to evaluate the association between preventive pharmacological therapy (thiazide diuretics, alkali therapy, and uric acid-lowering medications) and clinically significant urinary stone disease recurrence. Using data from the Veterans Health Administration, adults with an index episode of urinary stone disease from 2012 through 2019 and at least one urinary abnormality (hypercalciuria, hypocitraturia, or hyperuricosuria) on 24-hour urine collection were included. The primary outcome was a composite variable representing recurrent stone events that resulted in emergency department visits, hospitalizations, or surgery for urinary stone disease. Cox proportional hazards regression was performed to estimate the association between preventive pharmacological therapy use and recurrent urinary stone disease while adjusting for relevant baseline patient characteristics. Among the cohort of patients with urinary abnormalities ( n =5637), treatment with preventive pharmacological therapy was associated with a significant 19% lower risk of recurrent urinary stone disease during the 12-36-month period after the initial urine collection (hazard ratio, 0.81; 95% confidence interval, 0.65 to 1.00; P = 0.0496). However, the effectiveness of preventive pharmacological therapy diminished over longer follow-up periods (12-48 and 12-60 months after the urine collection) and did not reach statistical significance. When examining specific urinary abnormalities, only alkali therapy for hypocitraturia was associated with a significant 26% lower recurrence risk within the 12-36-month timeframe (hazard ratio, 0.74; 95% confidence interval, 0.56 to 0.97; P = 0.03). When considering all urinary abnormalities together, this study demonstrates that the use of preventive pharmacological therapy is associated with a lower risk of clinically significant recurrent episodes of urinary stone disease in the 12-36 month timeframe after urine collection, although only the association with the use of alkali therapy for hypocitraturia was significant when individual abnormalities were examined.

The impact of kidney stone disease on quality of life in high-risk stone formers.

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. 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. 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). 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.

Metabolic acidosis in pediatric kidney transplant recipients.

Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized that metabolic acidosis would be highly prevalent and associated with worse allograft function in pediatric KTRs. Pediatric KTRs at Montefiore Medical Center from 2010 to 2018 were included. Metabolic acidosis was defined as serum bicarbonate < 22mEq/L or receiving alkali therapy. Regression models were adjusted for demographic factors and donor/recipient characteristics. Sixty-three patients were identified with a median age at transplant of 10.5 (interquartile range (IQR) 4.4-15.2) years and post-transplant follow-up of 3 (IQR 1-5) years. Baseline serum bicarbonate was 21.7 ± 2.4mEq/L, serum bicarbonate < 22mEq/L was present in 28 (44%), and 44% of all patients were receiving alkali therapy. The prevalence of acidosis ranged from 58 to 70% during the first year of follow-up. At baseline, each 1-year higher age at transplant and every 10ml/min/1.73m2 higher eGFR were associated with 0.16mEq/L (95% CI: 0.03-0.3) and 0.24mEq/L (95% CI: 0.01-0.5) higher serum bicarbonate, respectively. Older age at transplant was associated with lower odds of acidosis (OR: 0.84; 95% CI: 0.72-0.97). During follow-up, metabolic acidosis was independently associated with 8.2ml/min/1.73m2 (95% CI 4.4-12) lower eGFR compared to not having acidosis; furthermore, eGFR was significantly lower among KTRs with unresolved acidosis compared with resolved acidosis. Among pediatric KTRs, metabolic acidosis was highly prevalent in the first year post-transplantation and was associated with lower eGFR during follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.

#4989 FIRST INTERIM ANALYSIS OF THE INTERNATIONAL DISTAL RENAL TUBULAR ACIDOSIS REGISTRY

Abstract Background and Aims Primary Distal Renal Tubular Acidosis (dRTA) is a rare genetic condition characterized by impaired capacity of A-type intercalated cells to excrete excess of H+ ions. The disease is caused primarily by pathogenic variants in the SLC4A1 gene encoding for the basolateral anion exchanger 1 (AE1) or the ATP6V1B1 and ATP6V0A4 genes encoding for two subunits of the apical proton ATPase. The latter also cause variable degrees of sensorineural hearing loss (SNHL). Additional genes include WDR72 that is associated with amelogenesis imperfecta and FOXI1 that also causes SNHL. To understand better the impact of alkali treatment on the natural history of dRTA, a European prospective registry has been created in collaboration with the ERKNet European Reference Network. Method We present a first interim descriptive analysis of first 182 patients that have been collected from 2019 to 2022. Treatment data are under analysis and are not included. Results To date, mostly paediatric patients (79%) have been included in the registry. A genetic diagnosis was available in 111/182 (61%) of patients and showed the following distribution of underlying genes: ATP6V0A4: 45%, ATP6V1B1: 41%, SLC4A1: 14%. Variants in WDR72 and FOXI1 were reported in one patient each. Overall, we observed no major differences in blood pressure and in urinary/blood parameters, when comparing children vs adults or proton ATPase vs AE1 defects (partially shown in tables 1 and 2). Adult patients were on average diagnosed later, had more frequently nephrolithiasis and higher BMI. In part, differences may reflect selections biases that will be assessed with the collection of longitudinal data. As expected, patients with proton pump defects were diagnosed earlier and had more frequently SNHL. The degree of nephrocalcinosis and the estimated glomerular filtration rates were similar when comparing all groups. None of the patients had developed end stage kidney disease. Conclusion This first report demonstrates successful enrolment of a cohort of patients with dRTA. Enrolment is still ongoing. Longitudinal data will allow assessing the impact of alkali therapy on the long-term outcome.

The mechanisms of alkali therapy in targeting renal diseases.

Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function and treatments aiming at stabilizing or slowing its progression may avoid or delay the necessity of kidney replacement therapy and the increased mortality associated with reduced kidney function. Metabolic acidosis, and less severe stages of the acid stress continuum, are common consequences of CKD and some interventional studies support that its correction slows the progression to end-stage kidney disease. This correction can be achieved with mineral alkali in the form of bicarbonate or citrate salts, ingestion of diets with fewer acid-producing food components or more base-producing food components, or a pharmacological approach. In this mini-review article, we summarize the potential mechanisms involved in the beneficial effects of alkali therapy. We also discuss the perspectives in the field and challenges that must be overcome to advance our understanding of such mechanisms.

A Randomized Controlled Trial to Assess the Effects of Oral Alkali Therapy in Patients with Diabetic Kidney Disease

Background: To analyze the effects of oral alkali therapy on renal function, nutritional status and bone density in patients of diabetic kidney disease. Material &amp; Methods: A randomized controlled trial was conducted on 60 patients of age&gt;18 years with diabetic kidney disease who were not on dialysis and had plasma bicarbonate levels between 16 and 20 mmol/l. Patients were randomly divided into two groups: Test group (n=30) which received oral alkali therapy as sodium bicarbonate and control group (n=30) who did not receive oral alkali therapy. The patients were followed for 12 months to compare the improvement. Results: In comparison to controls, test group showed a significant improvement in the Hb (0.7 vs. 0.25, P =0.003), significantly less decrease in eGFR (-2.25 vs. -2.9, P=0.049), non-significant less increase in creatinine (-0.26 ± 0.4 vs. -0.43 ± 0.33, P=0.09), significant improvement in bicarbonate levels (7.5 vs. 1, p&lt;0.0001), significant restoration of albumin (0.32 vs. 0.05, P&lt;.0001), significant fall in iPTH levels (50 vs. 25, p=0.007) and ALP levels (32 vs. 12, p=0.015). Bone density (0.28 ± 0.17 vs. 0.01 ± 0.13, P&lt;.0001) and clinical well-being VAS scores improved significantly among the cases (9.83 ± 5.65 vs. -1.67 ± 7.11, P&lt;.0001). Conclusion: In conclusion, oral alkali therapy slows the rate of decline of renal function and the development of end stage renal disease in patients with advanced stages of CKD. This cheap and simple strategy, which is in line with current renal consensus documents, also improves the nutritional status of patients and bone density.

Hidden Acid Retention with Normal Serum Bicarbonate Level in Chronic Kidney Disease.

Management of metabolic acidosis is crucial for preserving bone, muscle, and renal health, as evidenced by the results of several interventional studies conducted on patients with chronic kidney disease (CKD). Considering the continuity of CKD progression over time, it is reasonable to deduce that a subclinical form of metabolic acidosis may exist prior to the manifestation of overt metabolic acidosis. Covert H+ retention with normal serum bicarbonate level in patients with CKD may result in maladaptive responses that contribute to kidney function deterioration, even in the early stages of the disease. The loss of adaptive compensatory mechanisms of urinary acid excretion may be a key factor in this process. Early modulation of these responses could be an important therapeutic strategy in preventing CKD progression. However, to date, the optimal approach for alkali therapy in subclinical metabolic acidosis in CKD remains uncertain. There is a lack of established guidelines on when to initiate alkali therapy, potential side effects of alkali agents, and the optimal blood bicarbonate levels based on evidence-based practices. Therefore, further research is necessary to address these concerns and establish more robust guidelines for the use of alkali therapy in patients with CKD. Herein, we provide an overview of recent developments on this subject and examine the potential therapeutic approaches that interventional treatments may present for patients with hidden H+ retention, exhibiting normal serum bicarbonate levels - commonly described as subclinical or eubicarbonatemic metabolic acidosis in patients with CKD.

ODP043 Hypokalemia in Autoimmune Polyglandular Syndrome: A Case of Newfound Type I (Distal) Renal Tubular Acidosis

Abstract Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Type 1 (APECED) is a rare autosomal recessive disorder predisposing to early development of chronic mucosal candidiasis and progressive development of various endocrinopathies, such as Addison's disease, Primary Hypoparathyroidism, and Type 1 Diabetes (T1D). Few cases described in literature regarding renal involvement in this disorder, with most common manifestation being tubulo-interstitial nephritis, however, there is limited evidence regarding presentation of APECED with hypokalemia due to concomitant Type I Renal Tubular Acidosis (RTA). Case of a 47-year-old female with past medical history of APECED Type 1 (consisting of hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneos candidiasis), T1DM on honeymoon, hypothyroidism, and nephrolithiasis presenting to the emergency department complaining of bilateral upper and lower extremity weakness of one week in evolution, but worsening on day of admission. Denies associated constitutional symptoms. Strong positive first-degree relative history for autoimmune diseases. Physical examination: 2/5 strength in all four extremities, deep tendon reflexes grossly intact, no gross sensory or motor deficits. Patient on oral steroid therapy for her Addison's, calcitriol supplementation for hypoparathyroidism, and potassium chloride supplementation since a prior hypokalemic episode 17 years ago. Laboratory workup results remarkable for sodium: 140 mmol/L (N: 135-144 mmol/L), chloride: 110 mmol/L (N: 95-105 mmol/L), potassium: 2. 0 mmol/L (N: 3.4-4.5 mmol/L), central bicarbonate: 18mmol/L (N: 23-31 mmol / L), anion gap: 12 (N: 10-12), glycosylated hemoglobin: 5.2% (N: 4.7-6.2%) and anti-glutamic acid decarboxylase antibodies &amp;gt;25,000 U/mL (N: &amp;lt;5 U/mL). Adrenal insufficiency was ruled out by laboratory findings, but she had normal anion gap metabolic acidosis (NAGMA) and hypokalemia. Urinalysis was negative for urinary tract infection but with pH: 7. 0 (N: 4.5-8. 0). Urine spots, measured to find the cause of her NAGMA, showed urine sodium: 92 mmol/L, urine potassium: 10 mmol/L, urine chloride: 90 mmol/L, and urine anion gap of 12 mEq/L, which is positive and suggests low urinary NH4+, consistent with Type I (Distal) RTA as the main etiology. Patient started on IV potassium replacement, which increased potassium to 3.8 mmol/L, and improved acidotic state, with central bicarbonate of 29mmol/L, and overall symptoms. Patient was discharged home with alkali therapy (Sodium citrate) for Type I (Distal) RTA. RTA is an underrecognized condition that may be inherited or acquired. Diagnosis is difficult but can be verified with a thoughtful workup. RTA should be considered for any patient with otherwise unexplained hyperchloremic metabolic acidosis and may be the presenting manifestation of autoimmune diseases. Regular renal monitoring for any APECED patient should be performed. We present this case as evidence for the coexistence of several different immune-mediated diseases in the clinical context of APECED with an unusual concomitant Type I (Distal) RTA, where there is few documented evidence of association with this disorder. Presentation: No date and time listed

New mechanisms for the kidney-protective effect of alkali in chronic kidney disease.

Worldwide, more than one in ten adults are estimated to have chronic kidney disease (CKD). As CKD progresses, both the cost of treatment and associated risk of morbidity and mortality increase exponentially. As such, there is a great need for therapies that effectively slow CKD progression. Evidence from several small clinical trials indicates that alkali therapy may slow the rate of CKD progression. The biological mechanisms underlying this protective effect, however, remain unknown. In their recently published manuscript, Pastor Arroyo et al. (Clin Sci (Lond) (2022) 136(8): https://doi.org/10.1042/CS20220095) demonstrate that the alkali sodium bicarbonate protects against loss of renal function in a crystal nephropathy model in mice. Using unbiased approaches in both mice and human tissue, the authors go on to identify two novel mechanisms that may underly this protection. The first pathway is through promoting pathways of cell metabolism, which they speculate helps the remaining functional nephrons adapt to the greater metabolic needs required to maintain kidney filtration. The second pathway is by restoration of α-Klotho levels, which may limit the expression of adhesion molecules in the injured kidney. This, the authors speculate, may prevent inflammation from driving the functional decline of the kidney. Identifying these novel pathways represents an important step forward harnessing the potential benefits of alkali therapy in CKD.

Metabolic acidosis post kidney transplantation.

Metabolic acidosis, a common complication in patients with chronic kidney disease (CKD), results in a multitude of deleterious effects. Though the restoration of kidney function following transplantation is generally accompanied by a correction of metabolic acidosis, a subset of transplant recipients remains afflicted by this ailment and its subsequent morbidities. The vulnerability of kidney allografts to metabolic acidosis can be attributed to reasons similar to pathogenesis of acidosis in non-transplant CKD, and to transplant specific causes, including donor related, recipient related, immune mediated factors, and immunosuppressive medications. Correction of metabolic acidosis in kidney transplantation either with alkali therapy or through dietary manipulations may have potential benefits and the results of such clinical trials are eagerly awaited. This review summarizes the published evidence on the pathogenesis and clinical consequences of chronic metabolic acidosis in kidney transplant recipients.

Importance of Metabolic Acidosis as a Health Risk in Chronic Kidney Disease.

Human kidneys are well adapted to excrete the daily acid load from diet and metabolism in order to maintain homeostasis. In approximately 30% of patients with more advanced stages of CKD, these homeostatic processes are no longer adequate, resulting in metabolic acidosis. Potential deleterious effects of chronic metabolic acidosis in CKD, including muscle wasting, bone demineralization, hyperkalemia, and more rapid progression of CKD, have been well cataloged. Based primarily upon concerns related to nutrition and bone disease, early Kidney Disease Outcomes Quality Initiative guidelines recommended treating metabolic acidosis with alkali therapy targeting a serum bicarbonate ≥22 mEq/L. More recent guidelines have suggested similar targets based upon potential slowing of CKD progression. However, appropriately powered, long-term, randomized controlled trials to study efficacy and safety of alkali therapy for these outcomes are largely lacking. As a result, practice among physicians varies, underscoring the complexity of treatment of chronic metabolic acidosis in real-world CKD practice. Novel treatment approaches and rigorous phase 3 trials may resolve some of this controversy in the coming years. Metabolic acidosis is an important complication of CKD, and where it "falls" in the priority schema of CKD care will depend upon the generation of strong clinical evidence.

Preclinical and Clinical Evidence of Effect of Acid on Bone Health.

Acid can have ill effect on bone health in the absence of frank clinical acidosis but affecting the bone mioneral matrix and bone cells via complex pathways botyh ascute;y and chronically. While the reaction of bone to an acid load is conserved in evolution and is adaptive, the capacity can be overwhelmed resulting in dire consequences. The preclinical an clincl evidence of the acdi effect on bone is very convincing and the clinical evidence in both association and interventiopn studies are also quite credible, The adverse effects of acid on bone is underappreoicated, under-investigated, and the potential benefits of alkali therapy is not generrally known.

Longitudinal Associations between Low Serum Bicarbonate and Linear Growth in Children with CKD.

Poor linear growth is a consequence of chronic kidney disease (CKD) that has been linked to adverse outcomes. Metabolic acidosis (MA) has been identified as a risk factor for growth failure. We investigated the longitudinal relationship between MA and linear growth in children with CKD and examined whether treatment of MA modified linear growth. To describe longitudinal associations between MA and linear growth, we used serum bicarbonate levels, height measurements, and standard deviation (z scores) of children enrolled in the prospective cohort study Chronic Kidney Disease in Children. Analyses were adjusted for covariates recognized as correlating with poor growth, including demographic characteristics, glomerular filtration rate (GFR), proteinuria, calcium, phosphate, parathyroid hormone, and CKD duration. CKD diagnoses were analyzed by disease categories, nonglomerular or glomerular. The study population included 1082 children with CKD: 808 with nonglomerular etiologies and 274 with glomerular etiologies. Baseline serum bicarbonate levels ≤22 mEq/L were associated with worse height z scores in all children. Longitudinally, serum bicarbonate levels ≤18 and 19-22 mEq/L were associated with worse height z scores in children with nonglomerular CKD causes, with adjusted mean values of -0.39 (95% CI, -0.58 to -0.2) and -0.17 (95% CI, -0.28 to -0.05), respectively. Children with nonglomerular disease and more severe GFR impairment had a higher risk for worse height z score. A significant association was not found in children with glomerular diseases. We also investigated the potential effect of treatment of MA on height in children with a history of alkali therapy use, finding that only persistent users had a significant positive association between their height z score and higher serum bicarbonate levels. We observed a longitudinal association between MA and lower height z score. Additionally, persistent alkali therapy use was associated with better height z scores. Future clinical trials of alkali therapy need to evaluate this relationship prospectively.

Alkali therapy protects renal function, suppresses inflammation, and improves cellular metabolism in kidney disease.

Chronic kidney disease (CKD) affects approximately 10-13% of the population worldwide and halting its progression is a major clinical challenge. Metabolic acidosis is both a consequence and a possible driver of CKD progression. Alkali therapy counteracts these effects in CKD patients, but underlying mechanisms remain incompletely understood. Here we show that bicarbonate supplementation protected renal function in a murine CKD model induced by an oxalate-rich diet. Alkali therapy had no effect on the aldosterone-endothelin axis but promoted levels of the anti-aging protein klotho; moreover, it suppressed adhesion molecules required for immune cell invasion along with reducing T-helper cell and inflammatory monocyte invasion. Comparing transcriptomes from the murine crystallopathy model and from human biopsies of kidney transplant recipients (KTRs) suffering from acidosis with or without alkali therapy unveils parallel transcriptome responses mainly associated with lipid metabolism and oxidoreductase activity. Our data reveal novel pathways associated with acidosis in kidney disease and sensitive to alkali therapy and identifies potential targets through which alkali therapy may act on CKD and that may be amenable for more targeted therapies.

Comparison of Selective vs Empiric Pharmacologic Preventive Therapy of Kidney Stone Recurrence With High-Risk Features

ObjectiveTo compare the frequency of stone-related events among subgroups of high-risk patients with and without 24-hour urine testing before preventive pharmacological therapy (PPT) prescription. While recent studies show, on average, no benefit to a selective approach to PPT for urinary stone disease (USD), there could be heterogeneity in treatment effect across patient subgroups. Materials and MethodsUsing medical claims data from working-age adults and their dependents with USD (2008-2019), we identified those with a prescription fill for a PPT agent (thiazide diuretic, alkali therapy, or allopurinol). We then stratified patients into subgroups based on the presence of a concomitant condition or other factors that raised their stone recurrence risk. Finally, we fit multivariable regression models to measure the association between stone-related events (emergency department visit, hospitalization, and surgery) and 24-hour urine testing before PPT prescription by high-risk subgroup. ResultsOverall, 8369 adults with USD had a concomitant condition that raised their recurrence risk. Thirty-three percent (n = 2722) of these patients were prescribed PPT after 24-hour urine testing (median follow-up, 590 days), and 67% (n = 5647) received PPT empirically (median follow-up, 533 days). Compared to patients treated empirically, those with a history of recurrent USD had a significantly lower hazard of a subsequent stone-related event if they received selective PPT (hazard ratio, 0.83; 95% confidence interval, 0.71-0.96). No significant associations were noted for selective PPT in the other high-risk subgroups. ConclusionPatients with a history of recurrent USD benefit from PPT when guided by findings from 24-hour urine testing.

POS-089 DOES METABOLIC ACIDOSIS CONTRIBUTE TO THE KIDNEY FUNCTION DECLINE IN ADVANCED, NON-DIALYSIS, CHRONIC KIDNEY DISEASE?

Metabolic acidosis (MA) is commonly reported in advanced stages of chronic kidney disease (CKD) and the levels of serum bicarbonate have been correlated with faster decline in estimated glomerular filtration rate (eGFR). Since, the causal role of MA for the progression of CKD was not conclusively demonstrated and the beneficial effect of alkali therapy is still a matter of debate, the current study aimed to assess the influence of MA and its treatment with sodium bicarbonate on the risk of renal replacement therapy (RRT) initiation.