Thermoablative Treatment of De Novo Tumor in Kidney Allograft.

BACKGROUND: The overall cancer risk increases in transplant patients, including in kidney allografts. This study aimed to analyze the outcome of patients with kidney allograft malignant tumors who underwent percutaneous thermal ablation. METHODS: We included 26 renal allograft tumors, including 7 clear-cell renal cell carcinoma (RCCs), 16 papillary RCCs, 1 clear-cell papillary RCC, and 2 tubulocystic RCCs, treated in 19 ablation sessions. Outcomes of thermal ablation therapy were assessed, including technical success, adverse events, local tumor progression, development of metastases, survival after thermal ablation, and changes in renal function. RESULTS: Success rate was achieved in all ablation sessions (primary success rate: 96%; secondary success rate: 100%). No adverse events were observed in grades 3, 4, or 5. The median follow-up period was of 34 mo (15-69 mo). Two patients died during follow-up from a cause independent of renal cancer. The median decrease in estimated glomerular filtration rate 1 y after procedure was -4 (interquartile range, -7 to 0) mL/min/1.73 m 2 . One patient returned to dialysis within the year of the procedure. CONCLUSIONS: Percutaneous thermal ablation shows convincing results for treating malignant renal graft tumors and should be a useful treatment option. The shorter hospitalization time, the advantage of avoiding a potentially challenging dissection of the transplant, and the excellent preservation of allograft function appear encouraging to extend this indication.

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

Percutaneous Thermal Ablation for Renal Tumors in Patients with Birt-Hogg-Dubé Syndrome.

BHD syndrome is characterized by an increased risk of bilateral and multifocal renal cell carcinoma (RCCs), but is rarely metastatic. Our report aims to analyze the outcome of patients with BHD syndrome who underwent percutaneous thermal ablation (TA). The present report included six BHD syndrome patients (five men) with a mean age of 66 ± 11 (SD) years who had a proven germline FLCN gene mutation and underwent TA for a renal tumor. Nineteen renal tumors (median two tumors per patient; range: 1-3), including seven chromophobe RCCs, five clear-cell RCCs, four papillary RCCs, two clear-cell papillary RCC, and one hybrid oncocytic/chromophobe tumor were treated in 14 ablation sessions. The mean size of the tumors was 21 ± 11 (SD) mm (median: 20 mm; interquartile range (IQR): 14-25 mm) for a mean volume of 7 ± 11 (SD) mL (median: 3; IQR: 1-5 mL). Technical success was achieved in all ablation sessions (primary success rate, 100%). The procedure was well tolerated under conscious sedation with no significant Clavien-Dindo complication (grade 2, 3, 4). All patients were alive with no distant metastasis during a median follow-up period of 74 months (range: 33-83 months). No local tumor progression was observed. The mean decrease in estimated glomerular filtration rate was 8 mL/min/1.73 m2. No patients required dialysis or renal transplantation. In this case series, percutaneous TA appeared as a safe and efficient nephron-sparing treatment for treating RCCs associated with BHD syndrome, even in the case of advanced chronic kidney disease.

Efficacy of Prolonged Antibiotic Therapy for Renal Cyst Infections in Polycystic Kidney Disease.

OBJECTIVE: To determine the impact of antibiotic therapy (ATBT) on outcomes of renal cyst infection (CyI) in patients with polycystic kidney disease. PATIENTS AND METHODS: We undertook a single-center retrospective study of CyI in autosomal dominant polycystic kidney disease (January 1, 2000, through December 31, 2018). Cyst infections were classified as definite (microbiologically proven), probable (radiologic signs), or possible (clinical or biologic signs only). We studied the determinants of ATBT failure (persistence of infection beyond 72 hours of microbiologically adequate initial ATBT, with requirement for ATBT change, cyst drainage, or nephrectomy) and recurrences (>14 days after the end of ATBT). RESULTS: Among 90 patients, 139 CyIs (11 definite, 74 probable, 54 possible) were compiled. Cultures were positive in 106 of 139 (76%) episodes, with Escherichia coli found in 89 of 106 (84%). Treatment failures and recurrences within 1 year of follow-up were more frequent in definite/probable CyI (20/85 [34%] and 16/85 [19%]) than in possible CyI (2/54 [4%] and 4/54 [7%]; P<.01 and P=.08, respectively). Male sex (odds ratio [OR], 7.79; 95% CI, 1.72 to 46.68; P<.01), peak C-reactive protein level above 250 mg/L (OR, 7.29; 95% CI, 1.78 to 35.74; P<.01; to convert C-reactive protein values to nmol/L, multiply by 9.524), and cyst wall thickening (OR, 7.70; 95% CI, 1.77 to 43.47; P=.01) but not the modalities of initial ATBT were independently associated with higher risk of failure. In a Cox proportional hazards model, kidney transplant recipients exhibited higher risk of recurrence (hazard ratio, 3.76; 95% CI, 1.06 to 13.37; P=.04), whereas a total duration of ATBT of 28 days or longer was protective (hazard ratio, 0.02; 95% CI, 0.00 to 0.16; P<.001), with an inverse correlation between duration and recurrence (81% for treatment <21 days, 47% for 21 to 27 days, 2% for ≥28 days; P<.0001). CONCLUSION: Initial first-line ATBT had no significant effect on renal CyI treatment failure. Treatment duration of 28 days and longer reduced recurrences.

Long-term impact of COVID-19 among maintenance haemodialysis patients.

BACKGROUND: Maintenance haemodialysis (MHD) patients have a high risk of initial mortality from coronavirus disease 2019 (COVID-19). However, long-term consequences of this disease in the MHD population are poorly described. We report the clinical presentation, outcome and long-term follow-up of MHD patients affected by COVID-19 in a multicentric cohort from the Paris, France area. METHODS: We conducted a retrospective analysis of clinical presentation and long-term follow-up of MHD patients affected by COVID-19 in 19 MHD centres in the Paris, France area. RESULTS: In this cohort of 248 patients with an initial mortality rate of 18%, age, comorbidities, dyspnoea and previous immunosuppressive treatment were associated with death at <30 days. Among the 203 surviving patients following the acute phase, long-term follow-up (median 180 days) was available for 189 (93%) patients. Major adverse events occurred in 30 (16%) patients during follow-up, including 12 deaths (6%) after a median of 78 days from onset of symptoms. Overall, cardiovascular events, infections and gastrointestinal bleeding were the main major adverse events. Post-COVID-19 cachexia was observed in 25/189 (13%) patients. Lower initial albuminaemia was significantly associated with this cachexia. No reinfection with severe acute respiratory syndrome coronavirus 2 was observed. CONCLUSIONS: This work demonstrates the long-term consequences of COVID-19 in MHD patients, highlighting both initial and long-term severity of the disease, including severe cachexia.

COVID-19 outbreak in vaccinated patients from a haemodialysis unit: antibody titres as a marker of protection from infection.

BACKGROUND: Patients on maintenance haemodialysis (HD) have an increased risk of severe coronavirus disease 2019 (COVID-19) and a reduced response to vaccines. Data are needed to identify immune correlates of protection in this population. METHODS: Following a COVID-19 outbreak among vaccinated patients in a HD unit, clinical data and serological response to BNT162b2 vaccine were retrospectively recorded. RESULTS: Among 53 patients present in the dialysis room, 14 were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (COVID_Pos) and 39 were not. Compared with uninfected patients, COVID_Pos patients more frequently had additional causes of immunosuppression (50% versus 21%; P = .046) and were more often scheduled on the Monday-Wednesday-Friday (MWF) shift (86% versus 39%; P = .002). Moreover, COVID_Pos had lower anti-spike (S) immunoglobulin G (IgG) titres than uninfected patients {median 24 BAU/mL [interquartile range (IQR) 3-1163] versus 435 [99-2555]; P = .001} and lower neutralization titres [median 108 (IQR 17-224) versus 2483 (481-43 908); P = .007]. Anti-S and neutralization antibody titres are correlated (r = 0.92, P < .001). In multivariable analysis, an MWF schedule {odds ratio [OR] 10.74 [95% confidence interval (CI) 1.9-93.5], P = .014} and anti-S IgG titres 1 month before the outbreak [<205 BAU/mL: OR 0.046 (95% CI 0.002-0.29), P = .006] were independently associated with COVID-19 infection. None of the patients with anti-S IgG >284 BAU/mL got infected. Ten of 14 COVID_Pos patients were treated with casirivimab and imdevimab. No patient developed severe disease. CONCLUSIONS: Anti-S IgG titre measured prior to exposure correlates to protection from SARS-CoV-2 infection in HD patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19.

Kidney Biopsy in Type 2 Diabetes: A Multicenter Cross-Sectional Study.

INTRODUCTION: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. METHODS: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients' records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. RESULTS: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1-4 respectively. Conversely, no patient who underwent KB for indications 5-7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio <0.3 g/mmol, hematuria, HbA1c <7%, and diabetes duration <5 years as predictors of NDHKD, independently from the indication group. CONCLUSION: NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD.

Encrusted Urinary Tract Infections Due to Corynebacteria Species.

INTRODUCTION: Encrusted pyelitis and cystitis are peculiar disorders characterized by the calcification of the vesical, the pyelic, and/or the ureteral walls. These calcifications are composed of struvite and calcium carbonate‒apatite due to the presence of Corynebacterium urealyticum. METHODS: We have identified the clinical features and outcomes of 17 patients with encrusted pyelitis (n = 15) or encrusted cystitis (n = 2). Diagnosis was based on computed tomography scan and sonography including thickening and calcified lesions of the urinary tract. RESULTS: The main clinical presentation was suggestive of subacute urinary tract infection with fever and urologic symptoms, mostly gross hematuria. Biologic features were characterized by the presence of struvite crystals and alkaline urine. Acute kidney injury was reported in 70.6% of cases. Predisposing factors were mostly due to urologic background (82.4%) with a history of urologic procedure (71%) and prior exposure to antibiotics (59%). All patients received appropriate antibiotherapy and 15 were treated with topical urinary acidification. A significant reduction of encrusted calcifications was observed in 88% of cases. Renal function improved in 71% of the patients. Nevertheless, poor tolerance of the treatment and side effects were common, affecting 71% of patients, with Gram-negative bacilli urinary tract infections (53%) being the most frequent. At last follow-up, 4 patients (23.5%) progressed to end-stage renal disease and only 1 had a clinical relapse. CONCLUSIONS: Encrusted urinary tract infections are rare, characterized by a severe renal and overall prognosis in the absence of appropriate treatment. Topical urinary acidification and appropriate antibiotherapy are efficient but may be burdened by significant adverse events.

Ifosfamide nephrotoxicity in adult patients.

BACKGROUND: Ifosfamide, a widely prescribed antineoplasic agent, is frequently associated with kidney dysfunction. Its nephrotoxicity is well documented in children, but data are lacking in adult patients. METHODS: The aim of this retrospective study was to describe the clinical, biological and histological characteristics of ifosfamide nephrotoxicity. RESULTS: We report 34 patients (median age: 41 years) admitted in six French nephrology departments for kidney failure and/or tubular dysfunction. Fifteen patients (44.1%) received cisplatin as part of their chemotherapy. In 6 patients (17.7%), ifosfamide nephrotoxicity was revealed by a proximal tubular dysfunction (PTD), in 5 patients (14.4%) by an acute kidney injury (AKI), in 6 patients (17.7%) by a chronic kidney disease (CKD) and in 17 patients (49.7%) by an association of PTD and AKI. Fourteen renal biopsies (41.2%) were performed and revealed acute tubular necrosis (85.7%), vacuolation (78.6%) and nuclear atypias (71.4%) of renal epithelial cells, interstitial inflammation (71.4%) and fibrosis (57.1%). Electron microscopy showed mitochondrial enlargement and dysmorphic changes suggestive of mitochondrial toxicity. Ten patients (29.4%) progressed to Stage 5 CKD, six (17.6%) required haemodialysis and six patients died during a median follow-up period of 31 months. Risk factors for Stage 5 CKD were age and cisplatin co-administration.

Rationale and study protocol of ACQUIRE, a prospective, observational study measuring quality of life, treatment preference and treatment satisfaction of autosomal dominant polycystic kidney disease (ADPKD) patients in Europe.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is considered the most common inherited renal disease. Patient-Reported Outcomes (PROs) and patient experience in ADPKD are difficult to quantify and have not been well studied, particularly in the early stages of the disease. There is evidence to suggest that early-stage ADPKD patients have a lower Health-Related Quality of Life (HRQoL) than the general population due to the signs and symptoms of early-stage ADPKD. However, no research has been carried out on the HRQoL of early-stage ADPKD patients using validated ADPKD-specific PRO measures. Additionally, a new disease progression delaying treatment option has recently emerged for ADPKD. Patient preference for this treatment and unmet treatment needs have not yet been investigated. METHODS: The ACQUIRE study is a prospective, observational study investigating the influence of early-stage ADPKD-related symptoms and treatments on PROs. It aims to collect real-world data on patient demographics, treatment patterns, clinical outcomes, and PROs such as HRQoL, treatment satisfaction and treatment preference in early-stage ADPKD. Adult ADPKD patients in stages 1-3 of chronic kidney disease (CKD) with evidence of rapidly progressing disease are being recruited from seven European countries. At baseline and every 3 months, for a follow-up period of 18 months, general and disease-specific questionnaires are completed remotely to capture patients' own assessment of their overall and ADPKD-related HRQoL. A Discrete Choice Experiment (DCE) is also used to investigate the value patients place on different attributes of hypothetical treatment options (e.g. treatment outcomes, side effects) and the role each attribute plays in determining overall patient treatment preference. DISCUSSION: The results of this study will highlight the real-world effects of ADPKD-related challenges on PROs including HRQoL, treatment experience and satisfaction; and help physicians gain greater insight into likely disease outcomes based on early-stage patient symptoms and patients' experience with treatment. Data captured by the DCE may inform ADPKD treatment decision-making from a patient perspective. The DCE will also provide insights into which patients are more likely to perceive benefit from treatments based on the value and trade-offs they place on specific treatment attributes. TRIAL REGISTRATION: NCT02848521 . Protocol Number/Version: 156-303-00096/Final.

Continuous Wound Infiltration With Ropivacaine After Mastectomy: A Randomized Controlled Trial.

BACKGROUND: To evaluate the efficacy of continuous wound infiltration with ropivacaine to reduce acute postoperative pain in patients undergoing mastectomy for carcinoma of the breast. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was conducted. One hundred fifty patients were randomly assigned to receive continuous ropivacaine (0.2%) (group A, n = 74) or saline solution (0.9%) (group B, n = 76) at 10 mL/h for 48 h through a multilumen catheter placed during the surgical procedure. Postoperative morphine consumption and visual analog scale (VAS) pain scores were recorded. A quality of life score (Quality of life questionnaire Core 30) and a VAS score were obtained at 1, 3, and 6 mo after surgery. RESULTS: The difference in mean morphine consumption between the two groups was close to significance during the first 48 h postsurgery (P = 0.056; 10.8 ± 16.5 versus 4.8 ± 10.4 mg). At day 1, patients in the ropivacaine-infusion group had lower morphine consumption than the control group (P = 0.0026). The link between local ropivacaine infiltration and a decrease in mean postoperative VAS scores reached significance for the first 24 h postsurgery (P = 0.039). No significant difference was found between the two arms for VAS pain scores (P = 0.36) or for quality of life (overall QLQ-C30 score, P = 0.09) at 1, 3, or 6 mo. CONCLUSIONS: Continuous wound infiltration with ropivacaine is efficacious in reducing postoperative pain. Quality of life and chronic pain at 1, 3, and 6 mo were not improved by ropivacaine wound infiltration.

Predicting Pain Trajectories in the One Year Following Breast Cancer Diagnosis-An Observational Study.

The impact of psychosocial vulnerability on pain in the year following breast cancer diagnosis has been little studied. To identify a score of psychosocial vulnerability (cognitive, emotional, quality of life and precariousness parameters) as a predictor of a pain trajectory, we conducted an observational prospective study and included women with newly diagnosed breast cancer. One year follow-up with 3 visits (day of breast cancer diagnosis; 6 and 12 months) aimed to identify distinct pain-time trajectories. Baseline psychosocial vulnerability was characterized by z-score transformation, a higher score representing a more vulnerable patient. A total of 89 patients were included (59.3 ± 10.7 years). Two trajectories of pain were identified-"Transient Pain trajectory" (TP) (39/89 patients) and "Persistent Pain trajectory" (PP) (50/89). A significant difference of pain over time between trajectories (PP vs. TP at 6 months: 2.23 ± 0.23 vs. 0.27 ± 0.09, p < 0.001) was observed. Psychosocial vulnerability showed a large effect size (d, -0.82; 95% CI, -1.25 to -0.38; p < 0.001) and a higher score in "Persistent pain trajectory" (PP vs. TP: 0.12 ± 0.36 vs. -0.14 ± 0.26, p < 0.001). A predictive vulnerability marker of pain development is proposed and could be used at cancer diagnosis to orientate the care pathway of patients experiencing breast cancer.

[Azadirachtin, a natural pesticide with multiple effects]. / L'azadirachtine, un pesticide naturel aux effets multiples.

There are many studies devoted to the negative impact of conventional pesticides that effectively control pests, but cause widespread environmental pollution. As a result, interest is growing in pesticides of a natural origin with a lower environmental impact. Among them, azadirachtin, sold under various formulations (neem oil, Neem-Azal, Bioneem, etc.), is still the most widely recommended molecule in agricultural ecosystems. Azadirachtin has also been used in traditional medicine for centuries, and studies published over the past few years have tended to support its therapeutic use. Yet the argument that azadirachtin is harmless to the environment has been offset by its notable collateral and controversial effects on non-target organisms. The present paper summarizes the work already done in this field.

TITLE: L'azadirachtine, un pesticide naturel aux effets multiples. ABSTRACT: Une littérature abondante traite de l'impact négatif des pesticides conventionnels, très efficaces dans la gestion des ravageurs mais responsables d'une large pollution environnementale. Les pesticides d'origine naturelle qui auraient un moindre impact environnemental suscitent ainsi un intérêt majeur. Parmi ceux-ci, l'azadirachtine, commercialisée sous diverses formulations (huile de neem, Neem-Azal, Bioneem, etc.) reste la molécule la plus recommandée dans les agro-écosystèmes. L'argument d'une innocuité environnementale de l'azadirachtine est cependant nuancé par des effets collatéraux qui, bien que controversés, sont notables sur des organismes non ciblés.

A simple ATAC-seq protocol for population epigenetics.

We describe here a protocol for the generation of sequence-ready libraries for population epigenomics studies. The protocol is a streamlined version of the Assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) that provides a positive display of accessible, presumably euchromatic regions. The protocol is straightforward and can be used with small individuals such as daphnia and schistosome worms, and probably many other biological samples of comparable size, and it requires little molecular biology handling expertise.

The Epigenetics Dilemma.

This special issue of Genes demonstrates clearly that research in epigenetics has proceeded at a very rapid pace in the last decade. [...].

Acetate-free bicarbonate dialysate: Which acid in the dialysis buffer? / Nouveaux dialysats : quel acide dans le bain de dialyse ?

The mix of bicarbonate and divalent cations requires a small amount of acid to avoid insoluble precipitation in the dialysate buffer. Small doses of acetic acid (3­7 mmol/L) are commonly used. Acetic acid may be replaced by hydrochloric acid or citric acid to achieve acetate-free haemodialysis. Hydrochloric acid theoretically avoids metabolic side effects of acetate. However, additional cost generated by technical constraints probably slowed its generalization. Citric acid has been proposed as a more biocompatible acidifier than acetic acid. By binding calcium, citric acid inhibits both coagulation and complement activation and may reduce the treatment-induced inflammatory response. However, results of the study are conflicting, especially regarding impact on calcium and phosphate metabolism and acid-base metabolism. On the basis of current findings, systematic replacement of acetic acid by citric acid cannot be proposed for all the patients.

Author Correction: Targeted therapy in patients with PIK3CA-related overgrowth syndrome.

The 'Competing interests' statement of this Article has been updated; see accompanying Amendment for further details.

Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France.

OBJECTIVE: To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria. PATIENTS AND METHODS: Data from 442 patients with cystinuria were recorded retrospectively. Crystalluria was studied in 89 patients. A mixed-effects logistic regression model was used to estimate how urine pH, specific gravity and cysteine-binding thiols (CBT) correlate with risk of cystine crystalluria. RESULTS: Alkalizing agents and CBT agents were given to 88.8% (n = 381) and 55.3% (n = 238) of patients, respectively. Gastrointestinal AEs were reported in 12.3%, 10.4% and 2.6% of patients treated with potassium bicarbonate, potassium citrate and sodium bicarbonate, respectively (P = 0.008). The percentages of patients who experienced at least one AE with tiopronin (24.6%) and with D-penicillamine (29.5%) were similar (P = 0.45). Increasing urine pH and decreasing urine specific gravity significantly reduced the risk of cystine crystalluria, whereas D-penicillamine and tiopronin treatments did not reduce this risk (odds ratio [OR] 1 for pH ≤6.5; OR 0.52 [95% confidence interval {95% CI} 0.28-0.95] for 7.0 8.0, P <0.001). CONCLUSION: Adverse events were frequent with D-penicillamine and tiopronin. Alkaline hyperdiuresis was well tolerated and reduced cystine crystalluria. Urine specific gravity ≤1.005 and urine pH >7.5, while warning about calcium-phosphate crystallization, should be the goals of medical therapy.