scholarly journals Fluconazole in Hypercalciuric Patients with Increased 1,25(OH)2D Levels: The Prospective, Randomized, Placebo-Controlled, Double Blind FLUCOLITH Trial.

Author(s):  
Aurélia Bertholet-Thomas ◽  
Aurélie Portefaix ◽  
Sacha Flammier ◽  
Carole Dhelens ◽  
Fabien Subtil ◽  
...  

Abstract BackgroundHypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)2D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)2D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)2D levels.MethodsThe FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double blind trial. A total of 60 patients (10-60years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (> 0.1 mmol/kg/d), increased 1,25(OH)2D levels (> 150 pmol/L) and 25-OH-D levels >20 nmol/L, will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-hour calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-hour calciuria in patients who still display at W16 a 24-hour hypercalciuria. DiscussionThe current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)2D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the “off-label” use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)2D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. Trial RegistrationClinicalTrial.gov, ID: identifier: NCT04495608. Registered on July 23rd, 2020

2020 ◽  
Vol 24 (3) ◽  
pp. 367-373
Author(s):  
Leila Malekmakan ◽  
Zeinab Karimi ◽  
Afshin Mansourian ◽  
Maryam Pakfetrat ◽  
Jamshid Roozbeh ◽  
...  

2019 ◽  
Author(s):  
Tajamul Hussain ◽  
Shaik M. Naushad ◽  
Anwar Ahmed ◽  
Salman Alamery ◽  
Arif A. Mohammed ◽  
...  

Abstract Background: The deficiency of vitamin D receptor (VDR) or its ligand, vitamin D3, is linked to the development of renal diseases. The TaqI (rs731236) and ApaI (rs7975232) polymorphisms of VDR gene are widely studied for their association with renal disease risk. However, studies have largely been ambiguous. Objectives: Here, a meta-analysis comprising 2669 renal disease cases and 3342 controls was carried out to clarify the association of TaqI and ApaI polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN) and end stage renal disease (ESRD). Methods and Results: The VDR TaqI C-allele under allele contrast and fixed effect models was significantly associated with NL and ESRD, and Apal T-allele with ESRD only under fixed effect model. Cochrane Q-test showed no evidence of heterogeneity for TaqI polymorphism and a significant heterogeneity for Apa I polymorphism. No publication bias was observed for both the polymorphisms. Interestingly, increased disease penetrance with an increase in latitude from south to north across the globe was found only in the case of Taql polymorphism but not with Apal. Conclusions and Implications: The present meta-analysis identifies TaqI and ApaI polymorphisms of VDR gene as significant risk factors for renal diseases. Besides, increased disease penetrance with Taql polymorphism from south to north may corroborate with combined effect of defective VDR expression and decreased vitamin D synthesis due shorter durations of sun exposure with increasing latitude. On the other hand, possibility of Apal polymorphism in linkage disequilibrium with an adjacent functional polymorphism and lack of their co-segregation may have resulted in reduced disease penetrance. Present findings may have implications in understanding the role of gene-environmental interaction in renal disease risk.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Tajamul Hussain ◽  
Shaik M. Naushad ◽  
Anwar Ahmed ◽  
Salman Alamery ◽  
Arif A. Mohammed ◽  
...  

Abstract Background The deficiency of vitamin D receptor (VDR) or its ligand, vitamin D3, is linked to the development of renal diseases. The TaqI (rs731236) and ApaI (rs7975232) polymorphisms of VDR gene are widely studied for their association with renal disease risk. However, studies have largely been ambiguous. Methods Meta-analysis was carried out to clarify the association of TaqI (2777 cases and 3522 controls) and ApaI (2440 cases and 3279 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN) and end stage renal disease (ESRD). Results The VDR TaqI C-allele under allele contrast was significantly associated with ESRD in both fixed effect and random effect models, and ApaI C-allele with ESRD only under fixed effect model. Cochrane Q-test showed no evidence of heterogeneity for TaqI polymorphism and a significant heterogeneity for Apa I polymorphism. No publication bias was observed for both the polymorphisms. Conclusions The present meta-analysis identifies TaqI and ApaI polymorphisms of VDR gene as risk factors for renal diseases.


2006 ◽  
Vol 63 (1) ◽  
pp. 27-30
Author(s):  
Natasa Jovanovic ◽  
Mirjana Lausevic ◽  
Biljana Stojimirovic

Background/Aim. The disturbances of active forms of vitamin D synthesis and disturbances in calcium and posphate metabolism develop early in chronic renal failure, when creatinine clearance is about 30 ml/min. Chronic hemodialysis and peritoneal dialysis only partially correct the biochemical environment of patients on chronic renal replacement therapy because of end-stage renal disease. These dialysis modalities can?t significantly affect the endocrine disturbances of chronic renal failure and they have minimal modulatory effect. The management of disturbed calcium (Ca) and phosphate (P) metabolism and the maintainance of Ca ? P product below 4.4 mmol/l thanks to the use of dialysate solutions with the appropriate calcium concentration and the careful dosage of phosphate binders, calcium and active vitamin D metabolits, are extremely important for the prevention of renal osteodystrophy, secondary hyperparathyroidism as well as low-bone turnover disease. The aim of the study was to analyze the plasma levels of calcium, phosphate, albumin, alkaline phosphatase and parathormon (PTH) in 58 patients who were treated with continuous ambulatory peritoneal dialysis (CAPD) from March to August 2003. The use of phosphate binders and the substitution with active vitamin D metabolits were also analyzed. Methods. We examined 58 patients, 30 males and 28 female, mean-age 52 years (range, 26-78 years), affected by end-stage renal disease of the different leading cause. The average time on peritoneal dialysis program was 20 months (2-66 months). Most of the patients were treated by CAPD, while only few of them performed automatic, cyclic or intermittent peritoneal dialysis. Most of the patients used a dialysate with 1.75 mmol/l calcium concentration. Results. The study showed that our patients on chronic CAPD program during several months had normal calcemia, phosphatemia and the level of alkaline phosphatase, and that they had Ca ? P product in the recommended range. PTH serum level ranged from 16 to 490 pg/l in our patients. Conclusion. The study showed that a balanced diet and a correct dosage of phosphate binders, as well as a careful substitution with active vitamin D metabolits render a good control of calcium and phosphate serum balance, as well as an effective prevention of renal osteodystrophy development in the patients on chronic peritoneal dialysis treatment.


PEDIATRICS ◽  
1983 ◽  
Vol 72 (6) ◽  
pp. 840-846
Author(s):  
Alan M. Krensky ◽  
Joseph M. Reddish ◽  
Rita Littlewood Teele

Review of 2,700 abdominal ultrasonic examinations revealed 56 patients whose kidneys showed increased echogenicity. Echogenic kidneys were associated with medical renal disease in 94% of cases (30% glomerular, 48% tubulointerstitial, 16% end-stage) and with no detectable renal disease in 6% (three patients). Patterns of increased echogenicity and renal size were evaluated. Specific patterns occurred in end-stage renal disease and polycystic kidney disease. Other medical renal diseases had overlapping ultrasonographic features. Some generalizations could be made although increased echogenicity was often nonspecific.


2021 ◽  
pp. 353-382
Author(s):  
Gopesh K. Modi ◽  
Vivekanand Jha

Assessing renal function, Urinalysis, Proteinuria, Hematuria, Chyluria, Imaging in renal disease, Kidney biopsy, Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy, End Stage Renal Disease and Dialysis, Kidney Transplantation, Glomerular diseases, Acute glomerulonephritis, Urinary schistosomiasis (bilharzia), Infections and Kidney Disease, Rapidly Progressive glomerulonephritis, Tubulointerstitial Disease, Urinary Tract Infection, Vesico-ureteric reflux, Renal Stones, Renal Disease in Pregnancy, Renal Artery Stenosis, Renal Mass, Inherited Renal Diseases


Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Shen Li ◽  
Jin-pu Li

Abstract Background IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial. Methods/design The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study. Discussion The TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients. Trial registration ClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.


2019 ◽  
Vol 20 (14) ◽  
pp. 3567 ◽  
Author(s):  
Teresa Seccia ◽  
Brasilina Caroccia ◽  
Maria Piazza ◽  
Gian Paolo Rossi

Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the ‘classic’ view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.


Sign in / Sign up

Export Citation Format

Share Document