Diagnosis and management of primary hyperoxalurias: best practices.

The primary hyperoxalurias (PH 1, 2, and 3) are rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate. Clinical presentations that should prompt consideration of PH include kidney stones, nephrocalcinosis, and kidney failure of unknown etiology, especially with echogenic kidneys on ultrasound. PH1 is the most common and severe of the primary hyperoxalurias with a high incidence of kidney failure as early as infancy. Until the recent availability of a novel RNA interference (RNAi) agent, PH care was largely supportive of eventual need for kidney/liver transplantation in PH1 and PH2. Together with the Oxalosis and Hyperoxaluria Foundation, the authors developed a diagnostic algorithm for PH1 and in this report outline best clinical practices related to its early diagnosis, supportive treatment, and long-term management, including the use of the novel RNAi. PH1-focused approaches to dialysis and kidney/liver transplantation for PH patients with progression to chronic kidney disease/kidney failure and systemic oxalosis are suggested. Therapeutic advances for this devastating disease heighten the importance of early diagnosis and informed treatment.

Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

Acute kidney injury and percutaneous nephrolithotomy: incidence and predictive factors.

INTRODUCTION AND OBJECTIVE: Percutaneous nephrolithotomy (PCNL) is the treatment of choice for patients with large stones. The risk of acute kidney injury (AKI) has not been reported in the Western world. Our objective was to assess the frequency of AKI in patients undergoing PCNL and to identify independent predictors of AKI. METHODS: A retrospective review of PCNL cases performed between January 2014 and June 2019 was reformed. Demographic, laboratory, and intraoperative date were obtained. Perioperative AKI was defined as (1) Increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 micromol/L) within 48 h, or (2) increase in serum creatinine to ≥ 1.5 times baseline. Multivariable logistic regression analysis was performed to determine the factors influencing AKI. A p value of 0.05 was considered significant. RESULTS: A total of 566 patients were included. Mean age was 58 ± 14.4 years. The frequency of AKI was 4.4% (n = 25). The risk factors for AKI after PCNL were having a baseline creatinine > 1.54 mg/dl (p = 0.03, odds ratio [OR] = 2.66, confidence interval [CI] = 1.07-6.6), and a preoperative hemoglobin of less than 10.6 g/dL (p = 0.02, odds ratio [OR] = 2.47, confidence interval [CI] = 1.09-5.5). Patients without AKI had a median hospitalization of 2 days, while those with an AKI were hospitalized for a median of 3 days, and this difference was statistically significant (p < 0.001). CONCLUSIONS: Perioperative AKI occurs in 4.4% of patients undergoing PCNL. Preoperative hemoglobin and serum creatinine can identify those at increased risk, in whom it may be important to avoid nephrotoxic agents.

Infectious complications after allogeneic hematopoietic stem cell transplantation in children in a bone marrow transplant unit in Colombia.

OBJECTIVE: There is a relative lack of information about infections occurring in children following allogeneic hematopoietic stem cell transplants (allo-HSCT) in developing countries. Herein, we describe the incidence rates of different infections according to the transplant period and baseline condition in Colombia. METHODS: In a retrospective cohort study of all children who underwent allo-HSCTs from 2012 to 2017 in a hospital in Cali, Colombia, we reviewed medical records from the first post-transplant day until day + 365 to describe microbiologically confirmed incidence rates of infections and deaths during three post-transplant periods and according to baseline condition. RESULTS: Most allo-HSCT (n = 144, 96%) were followed by infections over the following year, mostly due to bacteria and cytomegalovirus (4.3 and 3.3 per 1000 patient-days, respectively). Children were at the highest risk for infection in the first 30 days post-HSTC, but mortality was highest after 100 days. Overall, high mortality (n = 44, 31.7%) was associated with infections, especially from extensively drug-resistant bacteria, adenovirus, and aspergillosis. Infection rates were similar independent of the baseline condition. CONCLUSION: Almost all children in this cohort developed infections post allo-HSCT. Describing the distribution of infections throughout the first post allo-HSCT year allows clinicians to narrow the differential diagnosis of infections according to the post-transplant period. This is especially useful when prioritizing interventions in children receiving HSCT in stringent healthcare systems in developing countries.

Deciphering the Dark Proteome: Use of the Testis and Characterization of Two Dark Proteins.

For the C-HPP consortium, dark proteins include not only uPE1, but also missing proteins (MPs, PE2-4), smORFs, proteins from lncRNAs, and products from uncharacterized transcripts. Here, we investigated the expression of dark proteins in the human testis by combining public mRNA and protein expression data for several tissues and performing LC-MS/MS analysis of testis protein extracts. Most uncharacterized proteins are highly expressed in the testis. Thirty could be identified in our data set, of which two were selected for further analyses: (1) A0AOU1RQG5, a putative cancer/testis antigen specifically expressed in the testis, where it accumulates in the cytoplasm of elongated spermatids; and (2) PNMA6E, which is enriched in the testis, where it is found in the germ cell nuclei during most stages of spermatogenesis. Both proteins are coded on Chromosome X. Finally, we studied the expression of other dark proteins, uPE1 and MPs, in a series of human tissues. Most were highly expressed in the testis at both the mRNA and protein levels. The testis appears to be a relevant organ to study the dark proteome, which may have a function related to spermatogenesis and germ cell differentiation. The mass spectrometry proteomics data have been deposited with the ProteomeXchange Consortium under the data set identifier PXD009598.

[Evaluation of the cost-effectiveness of an integral model of ambulatory treatment in patients with acute coronary syndrome: application of a probabilistic Markov modelAvaliação da relação custo-eficácia de um modelo integral de tratamento ambulatorial em pacientes com síndrome coronariana aguda: aplicação de um modelo probabilístico de Markov]. / Evaluación de la costo-efectividad de un modelo integral de tratamiento ambulatorio en pacientes con síndrome coronario agudo: aplicación de un modelo de Markov probabilístico.

OBJECTIVE: To evaluate the cost-effectiveness of an integral model of ambulatory treatment in patients who presented an acute coronary syndrome. METHODS: An economic evaluation was made from a quasi-experimental intervention study, which included 442 patients aged 30 to 70 years who presented an acute coronary syndrome. The intervention group (n = 165) received an integral model of ambulatory treatment based on managed care (disease management), while the control group (n = 277) received conventional cardiovascular rehabilitation. During one year of follow-up, the presentation of cardiovascular events and hospitalizations was evaluated. A probabilistic Markov model was developed. The study perspective was applied within the General System of Health Social Security in Colombia, including the direct health costs; the time horizon was 50 years with discounts of 3.42% for costs and effectiveness; and the measure of effectiveness was quality-adjusted life years (QALYs). A probabilistic and multivariate sensitivity analysis was performed using the Montecarlo simulation. RESULTS: During the year of follow-up, the direct costs related to the value paid were, on average, USD 2 577 for the control group and USD 2 245 for the intervention group. In the probabilistic sensitivity analysis, 91.3% of the simulations were located in the quadrant corresponding to incremental negative costs and positive incremental effectiveness (evaluated intervention at a lower cost, more effective). In the simulations, an average annual savings per patient of USD 1 215 per QALY was observed. CONCLUSIONS: The integral model of ambulatory treatment implemented in patients who suffered an acute coronary syndrome was found to be less expensive and more effective compared to conventional care. Considering it is a dominant alternative, it is recommended as a model of care in this population.

OBJETIVO: Avaliar a relação custo-eficácia de um modelo integral de tratamento ambulatorial em pacientes que apresentaram síndrome coronariana aguda. MÉTODOS: Uma avaliação econômica foi feita a partir de um estudo de intervenção quase experimental, que incluiu 442 pacientes com idade entre 30 a 70 anos que apresentaram síndrome coronariana aguda. O grupo de intervenção (n = 165) recebeu um modelo integral de tratamento ambulatorial com base em cuidados gerenciados (gerenciamento de doenças), enquanto o grupo controle (n = 277) recebeu reabilitação cardiovascular convencional. Durante um ano de acompanhamento, foi avaliada a apresentação de eventos cardiovasculares e hospitalizações. Um modelo probabilístico de Markov foi desenvolvido. A perspectiva do estudo foi aplicada no Sistema Geral de Segurança Social na Saúde da Colômbia, incluindo os custos diretos de saúde; o horizonte temporal foi de 50 anos com descontos de 3,42% em custos e efetividade; e a medida de eficácia foi os anos de vida ajustados pela qualidade (QALY). Uma análise de sensibilidade probabilística e multivariada foi realizada utilizando a simulação de Montecarlo. RESULTADOS: Durante o ano de acompanhamento, os custos diretos relacionados ao valor pago foram, em média, USD 2 577 para o grupo controle e USD 2 245 para o grupo de intervenção. Na análise de sensibilidade probabilística, foram localizadas 91,3% das simulações no quadrante correspondente a custos negativos incrementais e eficácia incremental positiva (intervenção avaliada a menor custo, mais efetiva). Nas simulações, observou-se uma economia anual média por paciente de US $ 1 215 por QALY. CONCLUSÕES: O modelo integral de tratamento ambulatorial implementado em pacientes que sofreram síndrome coronariana aguda foi considerado menos caro e mais eficaz em comparação com os cuidados convencionais. Por ser uma alternativa dominante, é recomendado como modelo de cuidados nesta população.

Computerized Tomography Based Diagnosis of Visceral Obesity and Hepatic Steatosis is Associated with Low Urine pH.

PURPOSE: Uric acid nephrolithiasis is associated with an elevated visceral fat area in kidney stone formers. Hepatic steatosis has also been linked to visceral obesity and nephrolithiasis. We evaluated the association of noncontrast computerized tomography based diagnosis of visceral obesity and hepatic steatosis with 24-hour urine parameters and stone composition in kidney stone formers. MATERIALS AND METHODS: A total of 98 kidney stone formers were included in study who had computerized tomography imaging and 24-hour urine studies available. For each patient a single computerized tomography axial area measurement was obtained of the visceral fat area. Hepatic steatosis was diagnosed by comparing the HU of regions from the liver and spleen. Univariate analysis was performed to compare patients with or without an elevated visceral fat area and hepatic steatosis. Multivariate linear and logistic regression was done to assess for variables associated with 24-hour urine parameters and stone composition. RESULTS: An elevated visceral fat area was associated with higher 24-hour urine sodium (175 vs 157 mg per day, p <0.036) and lower 24-hour urine pH (5.724 vs 6.478, <0.0001). Urine pH less than 6 (OR 2.52) was associated with hepatic steatosis. Low urine pH less than 6 (OR 11.1, p = 0.004) and stone volume greater than 65 mm3 (OR 5.12, p = 0.023) were associated with an elevated visceral fat area. Low urine pH less than 6 (OR 5.87) and visceral fat area greater than 48% (OR 5.33) were associated with uric acid stones. Linear regression demonstrated that the percent of visceral fat area was associated with lower 24-hour urine pH (ß-coefficient -0.438, p <0.0001). CONCLUSIONS: Noncontrast computerized tomography based diagnosis of visceral obesity is associated with low urine pH, high urinary sodium and uric acid stone formation. Hepatic steatosis is associated with low urine pH.

Steroidal Saponins from Furcraea hexapetala Leaves and Their Phytotoxic Activity.

Four new steroidal saponins (1-4) along with 13 known saponins were isolated from the leaves of Furcraea hexapetala. The new compounds were identified as (20R,22R,25R)-3ß-hydroxy-5α-spirostan-12-one 3-O-{α-l-rhamnopyranosyl-(1→4)-O-ß-d-glucopyranosyl-(1→3)-O-[ß-d-glucopyranosyl-(1→3)-O-ß-d-glucopyranosyl-(1→2)]-O-ß-d-glucopyranosyl-(1→4)-O-ß-d-galactopyranoside} (1), (25R)-3ß-hydroxy-5α-spirost-20(21)-en-12-one 3-O-{α-l-rhamnopyranosyl-(1→4)-O-ß-d-glucopyranosyl-(1→3)-O-[ß-d-glucopyranosyl-(1→3)-O-ß-d-glucopyranosyl-(1→2)]-O-ß-d-glucopyranosyl-(1→4)-O-ß-d-galactopyranoside} (2), (25R)-5α-spirostan-3ß-ol 3-O-{ß-d-glucopyranosyl-(1→2)-O-ß-d-glucopyranosyl-(1→2)-O-ß-d-glucopyranosyl-(1→4)-O-ß-d-galactopyranoside} (3), and (25R)-5ß-spirostan-3ß-ol 3-O-{ß-d-glucopyranosyl-(1→6)-O-ß-d-galactopyranoside} (4) by spectroscopic analysis, including one- and two-dimensional NMR techniques, mass spectrometry, and chemical methods. The phytotoxicity of the isolated compounds against the standard target species Lactuca sativa was evaluated. Structure-activity relationships for these compounds with respect to phytotoxic effects are discussed.

Dipstick Spot urine pH does not accurately represent 24 hour urine PH measured by an electrode.

OBJECTIVES: To determine whether spot urine pH measured by dipstick is an accurate representation of 24 hours urine pH measured by an electrode. MATERIALS AND METHODS: We retrospectively reviewed urine pH results of patients who presented to the urology stone clinic. For each patient we recorded the most recente pH result measured by dipstick from a spot urine sample that preceded the result of a 24-hour urine pH measured by the use of a pH electrode. Patients were excluded if there was a change in medications or dietary recommendations or if the two samples were more than 4 months apart. A difference of more than 0.5 pH was considered na inaccurate result. RESULTS: A total 600 patients were retrospectively reviewed for the pH results. The mean difference in pH between spot urine value and the 24 hours collection values was 0.52±0.45 pH. Higher pH was associated with lower accuracy (p<0.001). The accuracy of spot urine samples to predict 24-hour pH values of <5.5 was 68.9%, 68.2% for 5.5 to 6.5 and 35% for >6.5. Samples taken more than 75 days apart had only 49% the accuracy of more recent samples (p<0.002). The overall accuracy is lower than 80% (p<0.001). Influence of diurnal variation was not significant (p=0.588). CONCLUSIONS: Spot urine pH by dipstick is not an accurate method for evaluation of the patients with urolithiasis. Patients with alkaline urine are more prone to error with reliance on spot urine pH.

DPY19L2 deletion as a major cause of globozoospermia.

Globozoospermia, characterized by round-headed spermatozoa, is a rare (< 0.1% in male infertile patients) and severe teratozoospermia consisting primarily of spermatozoa lacking an acrosome. Studying a Jordanian consanguineous family in which five brothers were diagnosed with complete globozoospermia, we showed that the four out of five analyzed infertile brothers carried a homozygous deletion of 200 kb on chromosome 12 encompassing only DPY19L2. Very similar deletions were found in three additional unrelated patients, suggesting that DPY19L2 deletion is a major cause of globozoospermia, given that 19% (4 of 21) of the analyzed patients had such deletion. The deletion is most probably due to a nonallelic homologous recombination (NAHR), because the gene is surrounded by two low copy repeats (LCRs). We found DPY19L2 deletion in patients from three different origins and two different breakpoints, strongly suggesting that the deletion results from recurrent events linked to the specific architectural feature of this locus rather than from a founder effect, without fully excluding a recent founder effect. DPY19L2 is associated with a complete form of globozoospermia, as is the case for the first two genes found to be associated with globozoospermia, SPATA16 or PICK1. However, in contrast to SPATA16, for which no pregnancy was reported, pregnancies were achieved, via intracytoplasmic sperm injection, for two patients with DPY19L2 deletion, who then fathered three children.

Urinary podocyte excretion and proteinuria in patients treated with antivascular endothelial growth factor therapy for solid tumor malignancies.

BACKGROUND: Urinary podocyte excretion (podocyturia) may function as a more specific marker of ongoing glomerular damage. This study sought to analyze the relationship between proteinuria and podocyturia in cancer patients treated with antivascular endothelial growth factor (anti-VEGF) agents. METHODS: Thirty-seven patients treated with anti-VEGF medications were analyzed in a single-institution, cross-sectional study. Podocyte cultures were performed on random urine collections (50-100 ml), and podocytes were identified by positive podocin staining. The corresponding urine samples were analyzed for protein and creatinine (Cr) measurements. RESULTS: Proteinuria ≥0.5 g/g Cr was found in 30% of the patients (median, 0.12; interquartile range, 0.04-0.86), and 62% had podocyturia. There was a significant difference in the amount of podocyturia between patients with proteinuria ≥0.5 g/g Cr and those with a value <0.5 g/g Cr (median podocyturia, 1.08 cells/mg Cr, range, 0-14.55 vs. 0.03 cells/mg Cr, range, 0-1.64, respectively; p < 0.001). A statistically significant correlation was observed between the cumulative dose of bevacizumab and both proteinuria (r = 0.48, p = 0.004) and podocyturia (r = 0.34, p = 0.045) as well as between proteinuria and podocyturia (r = 0.63, p < 0.001), suggesting that these are mechanistically related. DISCUSSION: Ongoing podocyte loss may be mechanistically related to the onset and severity of proteinuria in patients treated with anti-VEGF agents.

Cardiac Surgery Outcomes in Patients Receiving Hemodialysis Versus Peritoneal Dialysis.

Rationale & Objective: We sought to compare outcomes of patients receiving dialysis after cardiothoracic surgery on the basis of dialysis modality (intermittent hemodialysis [HD] vs peritoneal dialysis [PD]). Study Design: This was a retrospective analysis. Setting & Participants: In total, 590 patients with kidney failure receiving intermittent HD or PD undergoing coronary artery bypass graft and/or valvular cardiac surgery at Cleveland Clinic were included. Exposure: The patients received PD versus HD (intermittent or continuous). Outcomes: Our primary outcomes were in-hospital and 30-day mortality. Secondary outcomes were length of stay, days in the intensive care unit, the number of intraoperative blood transfusions, postsurgical pericardial effusion, and sternal wound infection, and a composite of the following 4 in-hospital events: death, cardiac arrest, effusion, and sternal wound infection. Analytical Approach: We used χ2, Fisher exact, Wilcoxon rank sum, and t tests, Kaplan-Meier survival, and plots for analysis. Results: Among the 590 patients undergoing cardiac surgery, 62 (11%) were receiving PD, and 528 (89%) were receiving intermittent HD. Notably, 30-day Kaplan-Meier survival was 95.7% (95% CI: 93.9-97.5) for HD and 98.2% (95% CI: 94.7-100) for PD (P = 0.30). In total, 75 patients receiving HD (14.2%) and 1 patient receiving PD (1.6%) had a composite of 4 in-hospital events (death, cardiac arrest, effusion, and sternal wound infection) (P = 0.005). Out of 62 patients receiving PD, 16 (26%) were converted to HD. Limitations: Retrospective analyses are prone to residual confounding. We lacked details about nutritional data. Intensive care unit length of stay was used as a surrogate for volume status control. Patients have been followed in a single health care system. The HD cohort outnumbered the PD cohort significantly. Conclusions: When compared with PD, HD does not appear to improve outcomes of patients with kidney failure undergoing cardiothoracic surgery. Patients receiving PD had a lower incidence of a composite outcome of 4 in-hospital events (death, cardiac arrest, pericardial effusion, and sternal wound infections).

Patients receiving peritoneal dialysis (PD) are frequently switched to hemodialysis (HD) around the time of an open-heart surgery. More times than not, this is driven by the preference of nonkidney doctors, because HD is perceived to control toxins and fluids better. PD is, however, more advantageous and can achieve similar results while being gentler. In an effort to keep patients on their home PD, we analyzed how they fared when compared with their HD counterparts. Patients maintained on PD did just as well if not better around and after their open-heart surgery. Given the expected increase in patients treated with PD, efforts should be made to maintain them on their home modality even around major surgeries.

Resistant hypertension: A stepwise approach.

Resistant hypertension can be challenging to manage, but a stepwise approach to diagnosis, evaluation, and treatment can lead to better blood pressure control. In this article, we review the definition and prevalence of resistant hypertension and its diagnostic workup and management, including lifestyle modifications, drugs, and experimental interventional therapies.

Comparison of Radiation Exposure for Pregnant Patients Requiring Intervention for Suspected Obstructing Nephrolithiasis.

OBJECTIVE: To identify the differences in radiation exposure per suspected stone episode between percutaneous nephrostomy tube (PCN), stent, and primary ureteroscopy (URS).The incidence of nephrolithiasis in pregnancy is low; however, repercussions for both mother and fetus can be significant. In cases of suspected obstructing nephrolithiasis, intervention may be required, including ureteral stent, PCN, or URS, with the potential for multiple subsequent procedures that often utilize fluoroscopy. METHODS: Pregnant patients who required an intervention (stent, PCN, or URS) for suspected obstructing nephrolithiasis were retrospectively reviewed. The primary outcome was total fluoroscopy exposure per suspected stone episode. Secondary outcomes included fluoroscopic exposure per procedure and number of procedures required. RESULTS: After excluding patients with renal anomalies and incomplete radiation data, 78 out of 100 patients were included in the analysis. Forty patients (51.3%) underwent initial stent placement, 22 (28.2%) underwent initial PCN placement, and 16 (20.5%) underwent primary URS. Total mean radiation exposure per stone episode was significantly higher in patients who underwent PCN, (286.9 mGy vs 3.7 mGy (stent) and 0.2 mGy (URS), P <.001). In addition, patients who underwent initial PCN placement had significantly more procedures (P <.001) and mean radiation exposure per procedure was higher (P <.001). More than 40% of PCNs experienced dysfunction, and mean duration between PCN exchanges was 16.5 days. CONCLUSION: In pregnant patients with suspected obstructing nephrolithiasis requiring intervention, initial PCN placement was associated with a significantly higher number of procedures, radiation exposure per procedure, and total radiation exposure per suspected stone episode compared to stent and URS.

Combining spectral analysis and geochemical tracers to investigate surface water-groundwater interactions: A case study in an intensive agricultural setting (southern Guatemala).

An increase in the frequency of severe hydrological events has highlighted the importance of sustainable water management in intensive agricultural regions. In a warming climate, improved understanding and stewardship of water resources are needed to guarantee water supply, ensure food security, and build resilience against extreme events. In this study, we evaluate a framework that combines spectral analysis and geochemical tracers as a potential tool for (1) gaining valuable insights into surface water (SW)-groundwater (GW) interactions, and (2) providing guidance for improved water management in an intensive agricultural basin in southern Guatemala. The framework proves to be useful in revealing important water dynamics, exposing key feedback mechanisms for water availability and quality. With the use of power density functions and hydrochemistry (T, pH, EC, and major ions), two specific interaction regimes (influent and effluent) were identified and delimited for the main watercourse. These segments are estimated to interact at high rates with the shallow aquifer in the river channel proximities and would lose influence towards the basin flanks. Furthermore, the δ2H and δ18O values indicate that regional groundwater flow systems play an essential role in the basin groundwater recharge. Lastly, we established three influence zones that depict the spatial extent of the SW-GW interactions within the basin. With these zones, we provide recommendations that will allow for further investigation and application into better water management strategies regulating groundwater development and land use activities within the agricultural context of the area.

End Point Considerations for Clinical Trials in Enteric Hyperoxaluria.

Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown. Currently, there are no US Food and Drug Administration-approved therapies for enteric hyperoxaluria, and it is unclear what end points should be used to evaluate the efficacy of new drugs and biologics for this condition. This study represents work of a multidisciplinary group convened by the Kidney Health Initiative to review the evidence supporting potential end points for clinical trials in enteric hyperoxaluria. A potential clinical outcome is symptomatic kidney stone events. Potential surrogate end points include ( 1 ) an irreversible loss of kidney function as a surrogate for progression to kidney failure, ( 2 ) asymptomatic kidney stone growth/new stone formation observed on imaging as a surrogate for symptomatic kidney stone events, ( 3 ) urinary oxalate and urinary calcium oxalate supersaturation as surrogates for the development of symptomatic kidney stone events, and ( 4) plasma oxalate as a surrogate for the development of the clinical manifestations of systemic oxalosis. Unfortunately, because of gaps in the data, this Kidney Health Initiative workgroup was unable to provide definitive recommendations. Work is underway to obtain robust information that can be used to inform trial design and medical product development in this space.

Renal Genetics Clinic: 3-Year Experience in the Cleveland Clinic.

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

Endometriosis screening in patients attending an IVF clinic: a proof-of-concept retrospective cohort study.

Given that (i) endometriosis affects approximately 40% of women diagnosed with fertility problems and (ii) this condition may be an underestimated cause of idiopathic infertility, it is essential to identify high-risk patients for laparoscopic screening and reduce the diagnostic delay. We performed a retrospective analysis of 312 women (208 diagnosed with endometriosis and 104 controls) admitted to an in vitro fertilisation (IVF) unit in the city of Brest (France) between June 2007 and July 2014. As part of the women's infertility treatment, levels of cancer antigen 125 (CA-125) were assayed in blood samples collected on the day of oocyte retrieval. Surplus serum was used to set up a new sperm agglutination test. It was observed that sperm agglutination was significantly correlated with endometriosis and CA-125 levels (p < 0.01 for both). By building a decision tree, we identified a subpopulation of patients with low CA-125 levels and a high risk of endometriosis. This proof-of-concept study constitutes a first step towards a high-quality, controlled, multi-centre trial. If our preliminary results are confirmed, the decision tree should improve the medical care given to women in IVF programmes by identifying potential endometriosis sufferers for laparoscopic examination and enabling them to be counselled about precautionary measures.

The impact of smart technology on adherence rates and fluid management in the prevention of kidney stones.

Smart technology (ST) can enhance chronic disease management, yet little is known about the benefits of ST on kidney stone prevention. Our aim was to prospectively evaluate the impact of ST on follow-up adherence rates and urine output (UOP) in patients with nephrolithiasis. Kidney stone patients with low UOP (< 2.5 L/24 h) were randomized into three intervention groups: (1) standard dietary/medical counseling alone (control), (2) control + smartphone fluid management application (app), and (3) control + smart water bottle (bottle). Demographics, adherence rates, kidney stone events, and 24 h urine data were collected and analyzed at baseline, 3-6, and 12 months. We randomized 111 patients (37 per group), of which 20 (55%), 8 (26%), and 10 (33%) patients completed the 12 month follow-up in the control, app, and bottle groups respectively. Control group patients were the most likely to adhere to follow-up (p = 0.004). Overall mean UOP increased by 0.4 L in each group (p < 0.05), with no difference in mean baseline 24 h UOP (1.6 L) and 12 month 24 h UOP (2.0 L) between groups (p > 0.05). Twenty-nine percent of patients achieved a daily UOP goal of > 2.5 L across the treatment groups (p < 0.001). In this prospective study, the 24 h UOP improved across all groups compared to baseline, although adherence to follow-up remained low. Furthermore, the use of ST did not further augment UOP, underscoring the importance of dietary/medical counseling for kidney stone prevention.

Steroidal Saponins with Plant Growth Stimulation Effects; Yucca schidigera as a Commercial Source.

Plant growth-stimulation bioactivity of triterpenoid saponins is well known, especially for oleanane-type compounds. Nevertheless, a few phytotoxicity bioassays performed on some steroidal saponins have shown hormesis profiles and growth stimulation on Lactuca sativa roots. The focus of the work described here was on the use of the wheat coleoptile bioassay to evaluate plant growth stimulation, and on the search for a commercially available source of active saponins by bio-guided fractionation strategy. Selected saponins were tested and a cluster analysis showed that those saponins with a sugar chain of more than five units had a hormesis profile, while saponins with growth enhancement had fewer sugar residues. Two saponins showed similar activity to the positive control, namely the phytohormone indole-3-butyric acid (IBA). As a potential source of these metabolites, a commercial extract of Yucca schidigera used as a fertilizer was selected. Bio-guided fractionation led to the identification of two fractions of defined composition and these showed stimulation values similar to the positive control. It was observed that the presence of a carbonyl group at C-12 on the aglycone skeleton led to improved activity. A saponin-rich fraction from Y. schidigera could be proposed to enhance crop quality and production.