Papers by Maria Rosa Caruso
Journal of Nephrology, Jun 23, 2023
eClinicalMedicine, 2022
Summary Background Standard diet with normal calcium and reduced animal proteins and salt content... more Summary Background Standard diet with normal calcium and reduced animal proteins and salt content reduces stone recurrence in calcium oxalate nephrolithiasis. Whether lemon juice supplementation further reduces recurrence rate is unknown. Methods In this single-centre, prospective, randomised, open, blinded endpoint trial (Clinical Trials gov NCT01217372) we evaluated the effects of fresh lemon juice supplementation (60 mL twice daily) versus no supplementation, on time to stone recurrence in 203 patients with recurrent idiopathic calcium oxalate nephrolithiasis who were all prescribed a standard diet. Patients were included between July 2009 and March 2017 at the Nephrology Unit of the Papa Giovanni XXIII hospital in Bergamo, Italy. Time to stone recurrence at 2 years of follow-up was the primary outcome. Analyses were by intention-to-treat. Findings During two years of follow-up 21 of 100 patients randomised to lemon juice supplementation and 32 of 103 controls randomised to no supplementation had stone recurrence [HR (95% CI): 0·62 (0·35–1·07), p = 0·089]. Patient adherence to lemon juice supplementation, however, progressively decreased from 68% at one-year to 48% at two-year follow-up. At explorative analyses restricted at one-year follow-up, ten patients with supplementation versus 22 controls had stone recurrence [0·43 (0·20–0·89), p = 0·028]. After adjustment by age, sex and normo or hypocitraturia, the HR (95%) was still significant [0·45 (0·20–0·93), p = 0·036]. At six months, 24 hour urinary sodium excretion decreased by 8·60±65·68 mEq/24 h in patients receiving lemon juice supplementation and increased by 3·88±64·78 mEq/24 h in controls. Changes significantly differed between groups (p = 0·031). This difference was subsequently lost. Treatment was safe. In patients with lemon juice supplementation gastrointestinal disorders were more frequent (p<0·001). Renal and urinary tract disorders were similar between groups (p = 0·103). Interpretation Explorative analyses suggest that fresh lemon juice supplementation to standard diet might prevent stone recurrence in patients with calcium-oxalate nephrolithiasis. However, treatment effect was likely reduced by progressively declining adherence to lemon juice supplementation. Funding This study received no funding.
Nephrology Dialysis Transplantation, 2018
del 49° Congresso Nazionale SIN Rimini 8-11 Ottobre, 2008 S124 © Società Italiana di Nefrologia I... more del 49° Congresso Nazionale SIN Rimini 8-11 Ottobre, 2008 S124 © Società Italiana di Nefrologia IL TRATTAMENTO CRONICO CON Ac-SDKP MODULA I PROFILI PROTEICI RENALI NEL RATTO DIABETICO Castoldi G1, Galbusera C2, Bombardi C1, Sarto C3, Brambilla P2,3, Di Gioia C4, Corradi B1, Zerbini G5, Magni F2, Galli-Kienle M2, Stella A1 1 Clinica Nefrologica, Osp. San Gerardo Monza, DIMEP, Univ. Milano-Bicocca; 2 Dip. Medicina Sperimentale, Univ. Milano-Bicocca, Monza, Milano; 3 Dip. Laboratorio di Medicina, Osp. di Desio, Univ. Milano-Bicocca, Milano; 4 Dip. Medicina Sperimentale, Univ. La Sapienza. Roma; 5 Unità di Fisiopatologia Renale del Diabete, Istituto Scientifico San Raffaele, Milano Introduzione. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) è un tetrapeptide fisiologicamente presente nel plasma e idrolizzato dall’enzima di conversione dell’ angiotensina. È stato dimostrato che Ac-SDKP riduce l’escrezione urinaria di albumina e la fibrosi renale nel ratto diabetico (1). Scopo. Valutare...
Scientific Reports, 2019
Renal Cysts and Diabetes Syndrome (RCAD) is an autosomal dominant disorder caused by mutations in... more Renal Cysts and Diabetes Syndrome (RCAD) is an autosomal dominant disorder caused by mutations in the HNF1B gene encoding for the transcriptional factor hepatocyte nuclear factor-1B. RCAD is characterized as a multi-organ disease, with a broad spectrum of symptoms including kidney abnormalities (renal cysts, renal hypodysplasia, single kidney, horseshoe kidneys, hydronephrosis), early-onset diabetes mellitus, abnormal liver function, pancreatic hypoplasia and genital tract malformations. In the present study, using capillary electrophoresis coupled to mass spectrometry (CE-MS), we investigated the urinary proteome of a pediatric cohort of RCAD patients and different controls to identify peptide biomarkers and obtain further insights into the pathophysiology of this disorder. As a result, 146 peptides were found to be associated with RCAD in 22 pediatric patients when compared to 22 healthy age-matched controls. A classifier based on these peptides was generated and further tested on...
Nephrology Dialysis Transplantation, 2018
Kidney international, May 20, 2017
Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, a... more Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly described in association with mutations in one gene instead of the others. Nevertheless, the diagnosis of distal renal tubular acidosis is essentially based on clinical and laboratory findings, and the series of patients described so far are usually represented by small cohorts. Therefore, a strict genotype-phenotype correlation is still lacking, and questions about whether clinical and laboratory data should direct the genetic analysis remain open. Here, we applied next-generation sequencing in 89 patients with a clinical diagnosis of distal renal tubular acidosis, analyzing the prevalence of genetic defects in SLC4A1, ATP6V0A4, and ATP6V1B1 genes and the clinical phenotype. A...
Inherited acidosis may result from a primary renal defect in acid-base handling, emphasizing the ... more Inherited acidosis may result from a primary renal defect in acid-base handling, emphasizing the central role of the kidney in control of body pH; as a secondary phenomenon resulting from abnormal renal electrolyte handling; or from excess production of acid elsewhere in the body. Here, we review our current understanding of the inherited renal acidoses at a genetic and molecular level.
Journal of the American Society of Nephrology, 2014
Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paric... more Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 mg/d for 3 months and then uptitrated to 2 mg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8-152.0) to 63.3 (52.0-79.7) pg/ml (P,0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P,0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P,0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P,0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P,0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Longterm studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.
Nephrology Dialysis Transplantation, 2009
Background. Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse e... more Background. Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilation of precalyceal collecting tubules. Although its patho-genesis is unknown, the association with various congenital diseases suggests that it could be a developmental disorder. In addition to the typical clinical features of nephrocalcinosis and urolithiasis, patients with MSK show tubular ence of mutations of the H + proton pump ATP6V1B1 and ATP6V0A4 genes. Conclusions. These observations, including a previous description of a similar case in the literature, indicate that MSK could be a consequence of the proton pump defect, thus can potentially provide new insights into the pathogenesis of MSK.
Clinical Genetics, 2009
To the Editor : Dent disease (DD) 1 (OMIM 300009) is an X-linked disorder of renal tubular functi... more To the Editor : Dent disease (DD) 1 (OMIM 300009) is an X-linked disorder of renal tubular function, characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis and progressive renal failure, and associated with mutations in the ClC-5 Cl−/H+ endosomal exchanger all located in the coding region of the CLCN5 gene (1, 2). We report here the identification of 15 novel mutations including a complex allele and a nucleotide substitution in the 5′UTR region of the CLCN5 gene. Thirty patients with clinical suspicion of DD were screened by single-strand conformation polymorphism (SSCP) analysis and direct sequencing for the presence of mutations in the coding sequence and the exon-intron boundaries as well as in the 5′untranslated exons of the CLCN5 gene. All the patients were of Italian origin, except 1 from the United Kingdom. Sixteen of the 30 patients presented CLCN5 mutations of which 15 were novel and 1 recurrent (S244L). The phenotypic characteristics of patients with and without CLCN5 mutations are reported in Table 1. The table shows that LMWP, hypercalciuria and nephrocalcinosis, represent the triad of manifestations most relevant for the diagnosis of DD 1. Table 2 reports the 15 novel CLCN5 mutations identified in DD patients. Each of the missense and deletion–insertion mutations predicts a structurally significant alteration to the ClC-5 Cl−/H+ exchanger, and is thus likely to be of importance in the aetiology of the disease. The three frameshift mutations, leading to premature termination codons (PTC), can induce either a truncated ClC-5 product or mRNA degradation through nonsense-mediated decay which are likely to result in a loss of antiporter function and chloride conductance. The two in-frame codon deletion and the insertion are thought to alter the ClC-5 α-helices H and I, which are two of the four major helices involved in the formation of dimer interface (3). All the missense mutations, except one located in the C-terminal domain, are at or near the ClC-5 dimer interface. Moreover they involved amino acids conserved among different species or present in all known ClCs and were predicted with a high confidence to affect protein function by both the web program SIFT (4) and PolyPhen (5). For four out of six missense mutations (W58L, G512D, V519D, P621L) and for T277_L278 ins S mutation it was possible to establish that they segregated with DD trait in family members. Three intronic mutations affecting the canonical consensus splicing donor site of intron 4, 8 and 11 were detected in three patients. In two of them, the presence of an aberrantly spliced ClC-5 mRNA in leukocytes, leading to a truncated or absent protein, confirmed the functional significance of the mutations (Fig. 1). The presence of an aberrantly spliced mRNA due to the IVS4 +4 A>G could not be proved by transcription polymerase chain reaction (RT-PCR) analysis because the patient’s RNA was not available. The Automated Splice-Site Analysis program (ASSA; (6)), however, predicts that this variant would lower the strength of the donor splice-site leading probably to exon 4 skipping. We identified a complex allele (S386F and S388fsX434) in one patient from North Italy, inherited from his mother and grandmother. Since both the web program SIFT and PolyPhen predicted that the missense mutation S386F did not affect protein function, and the search for potential exonic splicing enhancer (ESE) motifs using ESE finder (7), RESCUE-ESE (8) and ASSA did not evidence any modification, we wondered if the mutation was indeed a polymorphism. The substitution was not found in our series of 69 patients affected by DD and in 311 X chromosomes from umbilical cord DNA samples thus
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Papers by Maria Rosa Caruso