Renal involvement and metabolic alterations in adults patients affected by cystic fibrosis

Lai, Silvia; Mazzaferro, Sandro; Mitterhofer, Anna Paola; Bonci, Enea; Marotta, Paolo Giangreco; Pelligra, Francesco; Murciano, Manuel; Celani, Camilla; Troiani, P.; Cimino, Giuseppe; Palange, Paolo

doi:10.1186/s12967-019-02139-4

Cited by 23 publications

(24 citation statements)

References 29 publications

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“…In fact, in our study, we reported a significant difference in serum transferrin among the three groups. Additionally, as already reported by Lai et al [11], we found an increase of SUA in LRs with worse renal function. In recent years, many authors showed that high levels of SUA are associated with renal and cardiovascular diseases, mainly due to renal glomerular vasoconstriction [20].…”

Section: Discussionsupporting

confidence: 91%

“…In our study, we showed a reduced renal function (with a reduced eGFR) and an increase in serum nitrogen in LRs compared to the other groups of patients. Similarly, Degen et al [16] and Lai et al [11] reported a poorer renal function in LRs, probably due to the concurrent administration of immunosuppressive drugs, such as cyclosporine and other calcineurin inhibitors. We found no significant difference in renal function between patients on CFTR modulators and controls.…”

Section: Discussionmentioning

confidence: 89%

“…Patients were clinically stable at the time of blood sample, in the absence of exacerbations. We followed the methods of Lai et al [11].…”

Section: Patientsmentioning

confidence: 99%

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Adult Patients Affected by Cystic Fibrosis in Therapy with Cystic Fibrosis Transmembrane Regulator Modulators and Lung Transplant: Renal Function, Metabolic and Nutritional Status

Lai

Mazzaferro

Mitterhofer

et al. 2020

Journal of Nutrition and Metabolism

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Background. Cystic fibrosis (CF) is one of the most frequent genetic diseases. The discovery and implementation of new therapies prolonged the survival of CF patients in the last years. Evaluation of long-term complications could be useful to improve the outcome of these patients. Aim of the Study. To evaluate renal function, metabolic, nutritional, and inflammatory status in CF patients on cystic fibrosis transmembrane regulator (CFTR) modulators therapy as well as lung transplant recipients (LRs) and patients on conservative therapy (control group). Materials and Methods. We performed a prospective, longitudinal study on 69 CF patients. Clinical and laboratory parameters (metabolic and nutritional indices and inflammatory markers) were evaluated in all patients before starting CFTR therapy or transplant (T0) and after 3 years (T1). Results. We enrolled 69 CF patients (42 males). Patients were distributed into three groups. The average age was 35.01 ± 10.57 years for the control group (group 0), 32.47 ± 9.40 years for patients on CFTR modulators therapy (group 1), and 38.93 ± 7.14 years for LRs (group 2). At T1, we showed a significant difference among the three groups in terms of renal function indices: creatinine, eGFR, serum nitrogen as well as serum uric acid, sodium, and potassium ( p < 0.001 , p < 0.001 , p < 0.001 , p < 0.001 , p < 0.001 , and p < 0.001 , respectively), particularly in LRs patients. Significant differences were found in nutritional status parameters among the three groups: total protein, serum albumin, serum fibrinogen, serum transferrin, and white blood cell counts ( p < 0.001 , p = 0.037 , p = 0.04 , p = 0.003 , and p = 0.007 , respectively), particularly in LRs compared with other groups. Moreover, we found significant differences in metabolic profile (HbA1c, p = 0.026 ) and inflammatory status, with a significant difference in C-reactive protein values, neutrophil counts, and neutrophil-lymphocyte ratio (NLR) among the three groups ( p < 0.001 , p = 0.005 , and p = 0.026 , respectively). Conclusions. Our study showed a reduced renal function and poor nutritional status in LRs, along with worse metabolic control. Moreover, we showed a lower inflammatory status in patients on CFTR modulators therapy. Therefore, we suggest early and careful monitoring of renal function, metabolic, and nutritional parameters in CF patients, whether they are on conservative therapy, CFTR modulators therapy, and LRs patients.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 89%

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Adult Patients Affected by Cystic Fibrosis in Therapy with Cystic Fibrosis Transmembrane Regulator Modulators and Lung Transplant: Renal Function, Metabolic and Nutritional Status

Lai

Mazzaferro

Mitterhofer

et al. 2020

Journal of Nutrition and Metabolism

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“… 71 Certainly, known CVRFs for accelerated atherosclerosis are common in the CF population, including chronic inflammation, dyslipidemia (primarily low HDL-C), and nephropathy. 72 , 73 CF-related diabetes is the most common comorbidity, occurring in ∼20% of adolescents and 40% to 50% of adults. 74 Although studies of left-ventricular function in patients with CF have been inconclusive, recent echocardiographic-strain analysis revealed significant biatrial enlargement, impaired left-atrial conduit and reservoir functions, and abnormal atrial volume indexes, which were significant predictors of mortality.…”

Section: Pediatric Risk Conditionsmentioning

confidence: 99%

Incorporating Risk Stratification Into the Practice of Pediatric Preventive Cardiology

Khoury

Kavey

St-Pierre

et al. 2020

Canadian Journal of Cardiology

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Atherosclerosis in its earliest stages is associated with the same traditional cardiovascular disease (CVD) risk factors as are associated with manifest CVD events in adulthood. Clustering of risk factors is associated with exponential increases in atherosclerotic burden from a young age. Some medical conditions and risk behaviours occurring in children can either increase the likelihood of higher levels of risk factors (such as chronic kidney disease) or the presence of risk factor clustering (such as obesity and cardiometabolic syndrome) or are associated with acquired coronary artery pathology (such as Kawasaki disease). This creates a milieu for—or increases the impact of—accelerated atherosclerosis that, in turn, increases the likelihood of premature CVD. This review highlights the importance of considering the total risk factor and risk-condition profile of pediatric patients. An algorithm is provided for stratifying patients into high-, moderate-, and at-risk categories, and practical examples are provided as to how the evaluation and management of 1 risk factor or risk condition might need to be intensified in the context of additional risk factors or risk conditions. For example, for treatment of an adolescent with familial hypercholesterolemia, the target low-density lipoprotein cholesterol level might be lowered by the concomitant presence of low high-density lipoprotein cholesterol or elevated lipoprotein(a) levels. As awareness of cardiovascular risk and atherosclerosis in pediatric patients increases, new at-risk conditions that warrant consideration are emerging. The identification and management of high-risk individuals is an important part of the overall practice of pediatric preventive cardiology.

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“…In a subset of patients who had undergone lung transplants, the eGFR was significantly lower than in nontransplanted patients (P < .001). 8 Dose adjustment for renally eliminated drugs is common practice for patients with renal impairment, with antibiotics, beta blockers, and diuretics being several examples. 9 Individualized dose adjustment targets optimal exposure that achieves therapeutic goals while avoiding potential safety risks associated with drug accumulation in renal impairment (RI).…”

mentioning

confidence: 99%

Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX‐02 in Patients With Nephropathic Cystinosis

Haverty

Wyatt

Porter

et al. 2021

The Journal of Clinical Pharma

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The aim of this study was to assess the pharmacokinetics (PK) and safety of ELX‐02 in a renally impaired population and apply these findings to the individualized dosing of patients with nephropathic cystinosis. This phase 1 renal impairment (RI; mild, moderate, or severe), single‐dose, PK, and safety evaluation included 6 participants assigned to each RI group. Six healthy controls with normal renal function were matched to participants with renal impairment. All received a single subcutaneous dose of 1‐mg/kg ELX‐02 on day 1 and were monitored for 72 hours after dosing with serial blood and urine samples. An estimated glomerular filtration rate (eGFR)‐PK model of ELX‐02 was developed from the RI study data and used to implement individualized dosing in a phase 2a study in patients with nephropathic cystinosis to achieve a weekly targeted exposure (area under the plasma concentration–time curve [AUC]). In participants with RI, ELX‐02 clearance decreased, and exposure increased with severity of RI. ELX‐02 plasma exposure was similar to healthy controls in participants with mild RI, but increasing severity of RI resulted in significantly decreased clearance, increased maximum plasma concentration, AUC from time zero to infinity, and half‐life compared to controls. ELX‐02 urinary clearance showed a similar pattern. Relationships between eGFR and exposure were defined supporting individualized dose determination for prediction of dose and AUC in patients with nephropathic cystinosis, achieving overall mean 110.7% of AUC targets. ELX‐02 was well tolerated by RI and nephropathic cystinosis populations. ELX‐02 exhibits a consistent PK profile across increasing degrees of RI with reduced clearance, increased exposure, and prolonged renal elimination proportional to reductions in eGFR. The defined relationship between eGFR and plasma exposure enabled individualized dose adjustment in patients with nephropathic cystinosis.

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Renal involvement and metabolic alterations in adults patients affected by cystic fibrosis

Cited by 23 publications

References 29 publications

Adult Patients Affected by Cystic Fibrosis in Therapy with Cystic Fibrosis Transmembrane Regulator Modulators and Lung Transplant: Renal Function, Metabolic and Nutritional Status

Adult Patients Affected by Cystic Fibrosis in Therapy with Cystic Fibrosis Transmembrane Regulator Modulators and Lung Transplant: Renal Function, Metabolic and Nutritional Status

Incorporating Risk Stratification Into the Practice of Pediatric Preventive Cardiology

Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX‐02 in Patients With Nephropathic Cystinosis

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