Successful Burosumab Treatment in an Adult Patient with X-Linked Hypophosphatemia and Chronic Kidney Disease Stage 3b.

X-linked hypophosphatemic rickets (XLH) is a genetic cause of renal hypophosphatemia due to inactivation of the PHEX gene, with an inappropriate concentration of fibroblast growth factor 23 (FGF23). Burosumab, an anti-FGF23 monoclonal antibody, is a validated treatment for XLH, but its use in patients with chronic kidney disease (CKD) has not been validated. A 61-year-old man with XLH developed CKD during follow-up. Conventional treatment (phosphate salts and active vitamin D analogs) was poorly tolerated. Treatment with burosumab was decided at a multi-professional meeting. Before burosumab initiation, his measured glomerular filtration rate was 44 mL/min/1.73 m2 defining CKD stage 3b and intact FGF23 concentration was very high (4496.0 ng/mL, N: 22.7-93.1) due to both XLH and CKD. Severe hypophosphatemia was observed after the two first injections of burosumab at usual doses (1 mg/kg monthly) and concomitant discontinuation of the conventional treatment. After increasing the dose and reducing the interval between doses (1.3 mg/kg every three weeks) from the third injection, serum phosphate concentration normalized and remained around the lower limit of the normal range. A local cutaneous reaction was observed just after the second injection, but did not recur. We report for the first time the efficacy and good short-term tolerance of burosumab in a patient with XLH and CKD, subject to a higher dosage aimed at achieving a phosphatemia at the lower limit of the normal range.

Fibroblast growth factor 23 but not copeptin is independently associated with kidney failure and mortality in patients with chronic kidney disease.

Background: Copeptin and intact fibroblast growth factor 23 (iFGF23) increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. The aim of this study was to evaluate their respective associations with renal and vital outcomes in CKD patients. Methods: We included CKD patients from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and isotopic glomerular filtration rate measurement (mGFR). The primary endpoint was a composite outcome including kidney failure (KF) (dialysis initiation, pre-emptive transplantation or a 57% decrease of mGFR, corresponding to doubling of serum creatinine) or death before KF. Hazard ratios (HRs) of the primary endpoint associated with log-transformed copeptin and iFGF23 concentrations were estimated by Cox models. The slope of mGFR over time was analysed using a linear mixed model. Results: A total of 329 CKD patients (243 men, mean age 60.3 ± 14.6 years) were included. Among them, 301 with an mGFR >15 ml/min/1.73 m2 were included in survival and mGFR slope analyses. During a median follow-up of 4.61 years (quartile 1-quartile 3: 3.72-6.07), 61 KFs and 32 deaths occurred. Baseline iFGF23 concentrations were associated with the composite outcome after multiple adjustments {HR 2.72 [95% confidence interval (CI) 1.85-3.99]}, whereas copeptin concentrations were not [HR 1.01 (95% CI 0.74-1.39)]. Neither copeptin nor iFGF23 were associated with mGFR slope over time. Conclusion: Our study shows for the first time in population of CKD patients an independent association between iFGF23 and unfavourable renal and vital outcomes and shows no such association regarding copeptin, encouraging the integration of iFGF23 measurement into the follow-up of CKD.

Hydration for Adult Patients with Nephrolithiasis: Specificities and Current Recommendations.

Nephrolithiasis affects around 10% of the population and is frequently associated with impaired dietary factors. The first one is insufficient fluid intake inducing reduced urine volume, urine supersaturation, and subsequently urinary lithiasis. Kidneys regulate 24 h urine volume, which, under physiological conditions, approximately reflects daily fluid intake. The aim of this study is to synthesize and highlight the role of hydration in the treatment of nephrolithiasis. Increasing fluid intake has a preventive effect on the risk of developing a first kidney stone (primary prevention) and also decreases the risk of stone recurrence (secondary prevention). Current guidelines recommend increasing fluid intake to at least at 2.5 L/day to prevent stone formation, and even to 3.5-4 L in some severe forms of nephrolithiasis (primary or enteric hyperoxaluria or cystinuria). Fluid intake must also be balanced between day and night, to avoid urinary supersaturation during the night. Patients should be informed and supported in this difficult process of increasing urine dilution, with practical ways and daily routines to increase their fluid intake. The liquid of choice is water, which should be chosen depending on its composition (such as calcium, bicarbonate, or magnesium content). Finally, some additional advice has to be given to avoid certain beverages such as those containing fructose or phosphoric acid, which are susceptible to increase the risk of nephrolithiasis.

Comparison of 99mTc-DTPA and 51Cr-EDTA for glomerular filtration rate measurement with the continuous infusion method.

BACKGROUND: In late 2018, the production of 51Chromium-labelled ethylenediamine tetra-acetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for measuring glomerular filtration rate, was halted. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) has been validated for GFR measurement with a single bolus injection, a procedure not suitable in patients with extracellular compartment hyperhydration. In such cases, a bolus followed by continuous infusion of the tracer is required. The aim of this study was to evaluate whether 99mTc-DTPA with the infusion protocol can replace 51Cr-EDTA for GFR measurement. METHODS: We conducted a prospective single centre study during February and March 2019. All patients referred for GFR measurement received both radiotracers simultaneously: 51Cr-EDTA and 99mTc-DTPA bolus and continuous infusion were administered concomitantly through the same intravenous route. Over four and a half hours, plasma and urine samples were collected to calculate urinary and plasma clearance. RESULTS: Twenty-two patients were included (mean age 63.4 ± 17.5 years; 68% men). Mean urinary clearance of 51Cr-EDTA and 99mTc-DTPA was 52.4 ± 22.5 mL/min and 52.8 ± 22.6 mL/min, respectively (p = 0.47), with a mean bias of 0.39 ± 2.50 mL/min, an accuracy within 10% of 100% (95% CI 100; 100) and a Pearson correlation coefficient of 0.994. Mean plasma clearance of 51Cr-EDTA and 99mTc-DTPA was 54.8 ± 20.9 mL/min and 54.4 ± 20.9 mL/min, respectively (p = 0.61), with a mean bias of - 0.43 ± 3.89 mL/min, an accuracy within 10% of 77% (95% CI 59; 91) and a Pearson correlation coefficient of 0.983. CONCLUSIONS: Urinary and plasma clearance of 99mTc-DTPA can be used with the infusion protocol to measure GFR.