Try a new search

Format these results:

Searched for:



Total Results:


Preemptive Removal of Small, Asymptomatic Kidney Stones [Editorial]

Goldfarb, David S
PMID: 35947713
ISSN: 1533-4406
CID: 5286962

Cystinuria: an update on pathophysiology, genetics, and clinical management

D'Ambrosio, Viola; Capolongo, Giovanna; Goldfarb, David; Gambaro, Giovanni; Ferraro, Pietro Manuel
Cystinuria is the most common genetic cause of nephrolithiasis in children. It is considered a heritable aminoaciduria as the genetic defect affects the reabsorption of cystine and three other amino acids (ornithine, lysine, and arginine) in the renal proximal tubule. Patients affected by this condition have elevated excretion of cystine in the urine, and because of this amino acid's low solubility at normal urine pH, patients tend to form cystine calculi. To date, two genes have been identified as disease-causative: SLC3A1 and SLC7A9, encoding for the two subunits of the heterodimeric transporter. The clinical features of this condition are solely related to nephrolithiasis. The diagnosis is usually made during infancy or adolescence, but cases of late diagnosis are common. The goal of therapy is to reduce excretion and increase the solubility of cystine, through both modifications of dietary habits and pharmacological treatment. However, therapeutic interventions are not always sufficient, and patients often have to undergo several surgical procedures during their lives to treat recurrent nephrolithiasis. The goal of this literature review is to synthesize the available evidence on diagnosis and management of patients affected by cystinuria in order to provide physicians with a practical tool that can be used in daily clinical practice. This review also aims to shed some light on new therapy directions with the aim of ameliorating kidney outcomes while improving adherence to treatment and quality of life of cystinuric patients.
PMID: 34812923
ISSN: 1432-198x
CID: 5063522

Comparison of empiric preventative pharmacologic therapies on stone recurrence among patients with kidney stone disease

Hsi, Ryan S; Yan, Phyllis L; Crivelli, Joseph J; Goldfarb, David S; Shahinian, Vahakn; Hollingsworth, John M
OBJECTIVE:To compare the frequency of stone-related events among patients receiving thiazides, alkali citrate, and allopurinol without prior 24-hour urine testing.  It is unknown whether one preventative pharmacological therapy (PPT) medication class is more beneficial for reducing kidney stone recurrence when prescribed empirically. MATERIALS AND METHODS/METHODS:Using medical claims data from working-age adults with kidney stone disease diagnoses (2008-2018), we identified those prescribed thiazides, alkali citrate, or allopurinol. We excluded those who received 24-hour urine testing prior to initiating PPT and those with less than three years of follow-up. We fit multivariable regression models to estimate the association between the occurrence of a stone-related event (emergency department visit, hospitalization, or surgery for stones) and PPT medication class. RESULTS:Our cohort consisted of 1,834 (60%), 654 (21%), and 558 (18%) patients empirically prescribed thiazides, alkali citrate, or allopurinol, respectively. After controlling for patient factors including medication adherence and concomitant conditions that increase recurrence risk, the adjusted rate of any stone event was lowest for the thiazide group (14.8%) compared to alkali citrate (20.4%) or allopurinol (20.4%) (each p<0.001). Thiazides, compared to allopurinol, were associated with 32% lower odds of a subsequent stone event by three years (OR 0.68, 95% CI 0.53-0.88). No such association was observed when comparing alkali citrate to allopurinol (OR 1.00, 95% CI 0.75-1.34). CONCLUSIONS:Empiric PPT with thiazides is associated with significantly lower odds of subsequent stone-related events. When 24-hour urine testing is unavailable, thiazides may be preferred over alkali citrate or allopurinol for empiric PPT.
PMID: 35545149
ISSN: 1527-9995
CID: 5214482

Comparison of Selective Versus Empiric Pharmacologic Preventive Therapy of Kidney Stone Recurrence with High-Risk Features

Hsi, Ryan S; Yan, Phyllis L; Crivelli, Joseph J; Goldfarb, David S; Shahinian, Vahakn; Hollingsworth, John M
OBJECTIVE:To compare the frequency of stone-related events among subgroups of high-risk patients with and without 24-hour urine testing before PPT prescription. While recent studies show, on average, no benefit to a selective approach to preventive pharmacological therapy (PPT) for urinary stone disease (USD), there could be heterogeneity in treatment effect across patient subgroups. MATERIALS AND METHODS/METHODS:Using 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. RESULTS:Overall, 8,369 adults with USD had a concomitant condition that raised their recurrence risk. Thirty-three percent (n=2,722) of these patients were prescribed PPT after 24-hour urine testing (median follow-up, 590 days), and 67% (n=5,647) 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% CI, 0.71-0.96). No significant associations were noted for selective PPT in the other high-risk subgroups. CONCLUSIONS:Patients with a history of recurrent USD benefit from PPT when guided by findings from 24-hour urine testing.
PMID: 35182586
ISSN: 1527-9995
CID: 5163742

Plant-Based Milk Alternatives and Risk Factors for Kidney Stones and Chronic Kidney Disease

Borin, James F; Knight, John; Holmes, Ross P; Joshi, Shivam; Goldfarb, David S; Loeb, Stacy
OBJECTIVE:Patients with kidney stones are counseled to eat a diet low in animal protein, sodium, and oxalate and rich in fruits and vegetables, with a modest amount of calcium, usually from dairy products. Restriction of sodium, potassium, and oxalate may also be recommended in patients with chronic kidney disease. Recently, plant-based diets have gained popularity owing to health, environmental, and animal welfare considerations. Our objective was to compare concentrations of ingredients important for kidney stones and chronic kidney disease in popular brands of milk alternatives. DESIGN AND METHODS/METHODS:Sodium, calcium, and potassium contents were obtained from nutrition labels. The oxalate content was measured by ion chromatography coupled with mass spectrometry. RESULTS:The calcium content is highest in macadamia followed by soy, almond, rice, and dairy milk; it is lowest in cashew, hazelnut, and coconut milk. Almond milk has the highest oxalate concentration, followed by cashew, hazelnut, and soy. Coconut and flax milk have undetectable oxalate levels; coconut milk also has comparatively low sodium, calcium, and potassium, while flax milk has the most sodium. Overall, oat milk has the most similar parameters to dairy milk (moderate calcium, potassium and sodium with low oxalate). Rice, macadamia, and soy milk also have similar parameters to dairy milk. CONCLUSION/CONCLUSIONS:As consumption of plant-based dairy substitutes increases, it is important for healthcare providers and patients with renal conditions to be aware of their nutritional composition. Oat, macadamia, rice, and soy milk compare favorably in terms of kidney stone risk factors with dairy milk, whereas almond and cashew milk have more potential stone risk factors. Coconut milk may be a favorable dairy substitute for patients with chronic kidney disease based on low potassium, sodium, and oxalate. Further study is warranted to determine the effect of plant-based milk alternatives on urine chemistry.
PMID: 34045136
ISSN: 1532-8503
CID: 4888282

Update on Uric Acid and the Kidney

Ramos, Giana Kristy; Goldfarb, David S
PURPOSE OF REVIEW/OBJECTIVE:In this review, we report on new findings regarding associations of uric acid with kidney health. We discuss kidney stones, effects of uric acid in chronic kidney disease (CKD), and management of gout in CKD. Recent studies on neuroprotective effects of raising uric acid provide interesting data regarding nephrolithiasis. RECENT FINDINGS/RESULTS:Elevated urate levels have been implicated in the progression of chronic kidney disease (CKD), but the results from PERL and CKD-FIX studies did not demonstrate that allopurinol slowed CKD progression. The SURE-PD3 sought to determine if increasing uric acid would slow the progression of Parkinson's disease. Results ultimately did not support this hypothesis, but high urinary uric acid levels caused uric acid stones, not calcium stones. Low urinary pH remains the key to the formation of uric acid stones. Thiazolidinediones improve insulin resistance, which is associated with an increase in urine pH. The most recent research has not supported the hypothesis that lowering serum uric acid levels will slow the progression of CKD or provide neuroprotection in Parkinson's disease. It is still unclear as to why uric acid stone formers have a high net acid excretion. The STOP-GOUT trial demonstrates that there was a lack of significant adverse events with higher urate-lowering dosages of allopurinol and febuxostat, despite patients' kidney function. This may push other studies to administer higher dosages per ACR guidelines. Future studies could then demonstrate decreased progression of CKD.
PMID: 35420373
ISSN: 1534-6307
CID: 5204412

Extracorporeal Treatment for Methotrexate Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup

Ghannoum, Marc; Roberts, Darren M; Goldfarb, David S; Heldrup, Jesper; Anseeuw, Kurt; Galvao, Tais F; Nolin, Thomas D; Hoffman, Robert S; Lavergne, Valery; Meyers, Paul; Gosselin, Sophie; Botnaru, Tudor; Mardini, Karine; Wood, David M
Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either "strong" or "weak/conditional") were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate-related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.
PMID: 35236714
ISSN: 1555-905x
CID: 5174522

Hypernatremia in the intensive care unit

Chand, Raja; Chand, Ranjeeta; Goldfarb, David S
PURPOSE OF REVIEW/OBJECTIVE:Hypernatremia is a relatively frequent electrolyte disorder seen in critically ill patients. As many as 27% of patients in intensive care units (ICUs) develop hypernatremia of variable severity during an ICU stay. Debate among specialists often ensues as to whether to correct hypernatremia or not. Some practitioners, particularly intensivists, believe that correction of hypernatremia with fluids may cause expansion of the extracellular fluid volume (ECFV) thereby worsening ventilation and impeding extubation. Other practitioners, including many nephrologists, do not expect correction of hypernatremia to lead to clinically apparent ECFV expansion, and fear other deleterious effects of hypernatremia. In this review we address the controversy regarding appropriate practice. FINDINGS/RESULTS:There are no randomized, clinical trials (RCTs) to guide the administration of electrolyte-free fluid administration in hypernatremic patients. However, there are associations, demonstrated in the literature, suggesting that hypernatremia of any severity will increase the mortality and length of stay in these patients. These associations generally support the practice of correction of hypernatremia. In addition, our knowledge of the distribution of total body water influences us towards correcting hypernatremia as an appropriate therapy. We do not expect that adequate RCTs addressing this question will be performed. SUMMARY/CONCLUSIONS:Allowing persistence of any degree of hypernatremia is associated with increased mortality, length of stay (LOS) and postdischarge mortality. We expect that proper use of electrolyte-free water intake will avoid adverse outcomes.
PMID: 34939612
ISSN: 1473-6543
CID: 5109022

Editorial: New perspectives on estimated glomerular filtration rate and health equity

Clark-Cutaia, Maya N; Goldfarb, David S
PMID: 35086985
ISSN: 1473-6543
CID: 5154772

Comprehensive Genetic Analysis Reveals Complexity of Monogenic Urinary Stone Disease

Cogal, Andrea G; Arroyo, Jennifer; Shah, Ronak Jagdeep; Reese, Kalina J; Walton, Brenna N; Reynolds, Laura M; Kennedy, Gabrielle N; Seide, Barbara M; Senum, Sarah R; Baum, Michelle; Erickson, Stephen B; Jagadeesh, Sujatha; Soliman, Neveen A; Goldfarb, David S; Beara-Lasic, Lada; Edvardsson, Vidar O; Palsson, Runolfur; Milliner, Dawn S; Sas, David J; Lieske, John C; Harris, Peter C
Introduction/UNASSIGNED:Because of phenotypic overlap between monogenic urinary stone diseases (USD), gene-specific analyses can result in missed diagnoses. We used targeted next generation sequencing (tNGS), including known and candidate monogenic USD genes, to analyze suspected primary hyperoxaluria (PH) or Dent disease (DD) patients genetically unresolved (negative; N) after Sanger analysis of the known genes. Cohorts consisted of 285 PH (PHN) and 59 DD (DDN) families. Methods/UNASSIGNED:Variants were assessed using disease-specific and population databases plus variant assessment tools and categorized using the American College of Medical Genetics (ACMG) guidelines. Prior Sanger analysis identified 47 novel PH or DD gene pathogenic variants. Results/UNASSIGNED:accounted for 1 pedigree each. Of the 48 defined pathogenic variants, 27.1% were truncating and 39.6% were novel. Most patients were diagnosed before 18 years of age (76.1%), and 70.3% of biallelic patients were homozygous, mainly from consanguineous families. Conclusion/UNASSIGNED:Overall, in patients suspected of DD or PH, 23.9% and 7.3% of cases, respectively, were caused by pathogenic variants in other genes. This study shows the value of a tNGS screening approach to increase the diagnosis of monogenic USD, which can optimize therapies and facilitate enrollment in clinical trials.
PMID: 34805638
ISSN: 2468-0249
CID: 5063282