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2.
J Clin Endocrinol Metab ; 109(10): 2553-2560, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-38497124

RESUMEN

CONTEXT: Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed. OBJECTIVE: Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones. METHODS: We took advantage of a routine calcium load test performed in patients with hypercalciuric renal stones to assess retrospectively among patients with PHPT the prevalence and characteristics of NHPT and HPHPT under a calcium-restricted diet. RESULTS: Among 1671 patients with hypercalciuria, 91 patients had a final diagnosis of PHPT (postload ionized calcium [iCa] > 1.31 mmol/L and parathyroid hormone [PTH] > 30 pg/mL). Prevalence of NHPT is 40% of all PHPT; however, according to total serum calcium, 4/35 NHPT and 7/56 HPHPT cases would have been misclassified in the other group. Eighteen of 35 NHPT and 40/56 HPHPT cases underwent parathyroidectomy. No significant characteristics relating to parathyroid weight, stone composition, or bone remodeling biomarkers were detected between groups. Although iCa is higher in HPHPT in the fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Renal calcium excretion postload increased by 303% in NHPT but only 176% in HPHPT (P = .01) likely explained by a lesser PTH decrease (P = .02). However, a strong negative association (P < .0001) detected between pooled preload and postload iCa and PTH only in the NHPT group suggests a persistent efficient PTH-CaSR control within the parathyroid glands in this group. CONCLUSION: Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones.


Asunto(s)
Calcio , Hipercalcemia , Hiperparatiroidismo Primario , Cálculos Renales , Hormona Paratiroidea , Humanos , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/sangre , Femenino , Masculino , Hipercalcemia/sangre , Hipercalcemia/etiología , Hipercalcemia/diagnóstico , Persona de Mediana Edad , Calcio/sangre , Calcio/metabolismo , Estudios Retrospectivos , Cálculos Renales/complicaciones , Cálculos Renales/etiología , Adulto , Hormona Paratiroidea/sangre , Anciano , Paratiroidectomía
3.
Sci Rep ; 14(1): 6078, 2024 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-38480876

RESUMEN

Cotrimoxazole (Trimethoprim/Sulfamethoxazole-SMX) is frequently used in critically ill and immunocompromised patients. SMX is converted to N-acetyl-sulfamethoxazole (NASM) and excreted by the kidneys. NASM may form crystals in urine, especially in acid urine, that may induce a crystalline nephropathy. However, the imputability of crystals in acute kidney injury (AKI) has not been proven. We aimed to assess whether NASM crystals may promote AKI and to investigate risk factors associated with NASM crystalline nephropathy. Patients from Ile-de-France, France who developed AKI under SMX treatment introduced during hospitalization and had a crystalluria positive for NASM crystals were selected. Patients with excessive preanalytical delay for crystalluria or missing data regarding SMX treatment were excluded. We used the Naranjo score to assess the causal relationship between SMX and the development of AKI in patients with positive NASM crystalluria. Fourteen patients were included. SMX was the probable cause of AKI for 11 patients and a possible cause for 3 patients according to Naranjo score. Patients were exposed to high doses of SMX (but within recommended ranges), and most of them had a preexisting chronic kidney disease and were hypoalbuminemic. Urine pH was mildly acid (median 5.9). AKI occured more rapidly than expected after introduction of SMX (median 4 days) and recovered rapidly after drug discontinuation in most, but not all, cases. SMX is a probable cause of crystalline nephropathy. Monitoring of crystalluria in patients exposed to SMX may be of interest to prevent the development of crystalline nephropathy. Approval number of the study: BPD-2018-DIAG-008.


Asunto(s)
Lesión Renal Aguda , Cristaluria , Humanos , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Pronóstico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Factores de Riesgo , Estudios Retrospectivos
4.
Am J Physiol Renal Physiol ; 326(2): F278-F284, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38059298

RESUMEN

The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgH2O). Plasma ADH was positively associated with plasma tonicity and natremia (P < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule.NEW & NOTEWORTHY The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria.


Asunto(s)
Anemia de Células Falciformes , Diabetes Insípida Nefrogénica , Diabetes Insípida , Diabetes Mellitus , Humanos , Poliuria , Diuresis , Concentración Osmolar , Fármacos Antidiuréticos , Agua
5.
Sci Rep ; 13(1): 85, 2023 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-36596813

RESUMEN

Biallelic pathogenic variants in the SLC34A3 gene, encoding for the NPT2c cotransporter, cause Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH). However, the associated phenotype is highly variable. In addition, mice deleted for Slc34a3 exhibit a different phenotype compared to humans, without urinary phosphate leakage. The mechanisms by which SLC34A3 variants disrupt phosphate/calcium metabolism are un-completely understood. In this study we explored these mechanisms in vitro using SLC34A3 variants identified in patients with urinary phosphate leakage. We analyzed the consequences of these variants on NPT2c function and the link with the phenotype of the patients. We studied 20 patients with recurrent nephrolithiasis and low serum phosphate concentration harboring variants in the SLC34A3 gene. Half of the patients carried homozygous or composite heterozygous variants. Three patients had in addition variants in SLC34A1 and SLC9A3R1 genes. All these patients benefited from a precise analysis of their phenotype. We generated 13 of these mutants by site-directed mutagenesis. Then we carried out transient transfections of these mutants in HEK cells and measured their phosphate uptake capacity under different conditions. Among the 20 patients included, 3 had not only mutations in NPT2c but also in NPT2a or NHERF1 genes. Phosphate uptake was decreased in 8 NPT2c mutants studied and normal for 5. Four variants were initially categorized as variants of uncertain significance. Expression of the corresponding mutants showed that one did not modify phosphate transport, two reduced it moderately and one abolished it. Co-transfection of the NPT2c mutants with the wild-type plasmid of NPT2c or NPT2a did not reveal dominant negative effect of the mutants on NPT2c-mediated phosphate transport. A detailed analysis of patient phenotypes did not find a link between the severity of the disorder and the level of phosphate transport impairment. NPT2c mutations classified as ACMG3 identified in patients with renal phosphate leak should be characterized by in vitro study to check if they alter NPT2c-mediated phosphate transport since phosphate uptake capacity may not be affected. In addition, research for mutations in NHERF1 and NPT2a genes should always be associated to NPT2c sequencing.


Asunto(s)
Raquitismo Hipofosfatémico Familiar , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIc , Animales , Humanos , Ratones , Raquitismo Hipofosfatémico Familiar/genética , Raquitismo Hipofosfatémico Familiar/patología , Riñón/metabolismo , Mutación , Fenotipo , Fosfatos/metabolismo
8.
J Clin Med ; 10(21)2021 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-34768698

RESUMEN

Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients; (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT; (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p < 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.

9.
Nutrients ; 12(9)2020 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-32867232

RESUMEN

Dietary management is a cornerstone of Chronic Kidney Disease (CKD) monitoring, and dietary surveys often difficult to perform. We studied in a CKD patient cohort with two years follow-up, whether validated 24-h urine ionogram would be a relevant tool for diet evaluation and compliance. We included 404 non-dialysis CKD patients, with three evaluations, including repeated measurements of fractional renal creatinine clearance and 24-h urine collection. Completeness of the 24-h urine collection, assessed by daily urine creatinine excretion extrapolated from fractional creatinine clearance, was 64.6%, 75.5%, and 78.2% at the first, second, and third visits, respectively. One hundred sixty-eight patients (41.6%) had three complete collections, with a measured glomerular filtration of 42.3 mL/min/1.73 m2 at baseline and prevalence of anemia and secondary hyperparathyroidism of 13.9% and 26.2%, respectively, increasing during follow-up to 15% and 31.5% (p < 0.001 and p < 0.001). The urine analysis showed at baseline a urine volume of above 2 L/day, and estimated sodium and protein intake within targets in 51.6% and 40.3% of cases, which improved during follow-up only for protein (to 45.9%, p < 0.0001). Our data suggest that a 24-h urine ionogram is an interesting, reliable tool in CKD patients for dietary monitoring to achieve target recommendation noteworthy salt and protein intake.


Asunto(s)
Dieta/métodos , Encuestas Nutricionales/métodos , Cooperación del Paciente/estadística & datos numéricos , Insuficiencia Renal Crónica/orina , Toma de Muestras de Orina/métodos , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales/estadística & datos numéricos , Reproducibilidad de los Resultados
10.
Nephrol Ther ; 14(2): 112-116, 2018 Apr.
Artículo en Francés | MEDLINE | ID: mdl-29295766

RESUMEN

We report a case of a 43 years old man who was intoxicated by a 25g vancomycin overload. An anuric acute renal failure rapidly occured. The vancomycinemia was measured as high as 360mg/L (normal range: 15-35mg/L). We started an intermittent hemodialysis program to clear out the vancomycin. The vancomycinemia decreased below the treshold of our laboratory after the eighth session. Three supplementary sessions were needed because of a persistant oliguria. The kidney function slowly improved and was back to normal (seric creatinin: 80micromol/L) 3 weeks after the patient had gone home. To our knowledge, it is the first success of this technic concerning vancomycin poisoning in adults with anuric kidney failure.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antibacterianos/envenenamiento , Diálisis Renal/métodos , Vancomicina/envenenamiento , Lesión Renal Aguda/terapia , Adulto , Antibacterianos/sangre , Humanos , Masculino , Vancomicina/sangre
11.
Medicine (Baltimore) ; 96(25): e7196, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28640105

RESUMEN

RATIONALE: BRAF and MEK inhibitors have significantly improved the prognosis of metastatic melanoma, by inhibiting both the mitogen-activated protein kinase (MAP-kinase) pathway. They are associated with infrequent adverse kidney events. Most of these are related to the use of BRAF inhibitors and involve interstitial nephritis with acute tubular necrosis. PATIENT CONCERNS: We report a unique case of glomerulonephritis with renal granulomatous vasculitis in a patient diagnosed with metastatic melanoma treated with BRAF and MEK inhibitors. The patient was a 55-year old woman, who presented a melanoma of the right thigh with pulmonary metastasis. Treatment started in November 2015, with Encorafenib and Binimetinib, new BRAF and MEK inhibitors, respectively. Two months after the beginning of the treatment, there was a worsening of her renal function with significant proteinuria. DIAGNOSES: Kidney biopsy showed extracapillary proliferation in the glomeruli with a granulomatous reaction. INTERVENTIONS AND OUTCOMES: Renal function recovered completely after withdrawal of the chemotherapy. LESSONS: All the reported kidney adverse events secondary to BRAF and MEK inhibitors in the literature are related to the use of BRAF inhibitors. Some previous reported mechanistic investigations also provide insight between BRAF inhibitors and podocytes injuries. Therefore, encorafenib most likely is the main responsible of the disease. However, evidence has emerged that inhibition of the MAP kinase pathway could also enhance autoimmunity. Thus, binimetinib may also have played a role and the combination of BRAF and MEK inhibitors may have facilitated this autoimmune kidney disease.


Asunto(s)
Antineoplásicos/efectos adversos , Glomerulonefritis/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Melanoma/tratamiento farmacológico , Vasculitis/inducido químicamente , Antineoplásicos/uso terapéutico , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Carbamatos/efectos adversos , Carbamatos/uso terapéutico , Femenino , Glomerulonefritis/sangre , Glomerulonefritis/patología , Humanos , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Riñón/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/secundario , Melanoma/sangre , Melanoma/patología , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Vasculitis/sangre , Vasculitis/patología
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