cohort, NPHS2 p.R229Q was identified in 5 patients (6%), but only with pathogenic significance in... more cohort, NPHS2 p.R229Q was identified in 5 patients (6%), but only with pathogenic significance in 3 patients, and APOL1 high risk haplotype was coidentified with COL4 variants in 3 patients. Conclusion: The genetic study of a cohort of patients suspected of genetic FSGS allowed the identification of genetic variants in the genes of interest in a high percentage of cases. The most frequently implicated genes were COL4A3, COL4A4 e COL4A5, NPHS2, INF2 and APOL1 high risk haplotype. The high percentage of gene variants identified in our cohort is probably due to the selection of a population with a high likelihood of genetic FSGS. Further studies will clarify the causal and/or modifier effect of some genes, namely COL4A3, COL4A4 e COL4A5. The future use of WES in cases of high likelihood of genetic cause will probably allow the identification on novel candidate genes and increase the clinical benefits of a genetic diagnosis of FSGS.
Background and Aims Denosumab is a fully human monoclonal antibody to the receptor activator of n... more Background and Aims Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL), an osteoclast differentiating factor. It inhibits osteoclast formation, decrease bone resorption, increase bone mineral density (BMD), and reduce the risk of fracture. There is no restriction of its use in patients with renal disease, for whom biphosphonates are considered controindicated. The aim of our study was to evaluate the effectiveness in reducing facture risk and safety of Denosumab in patients with Osteoporosis and renal disease. Method This is a prospective analysis of 17 patients with Osteoporosis (average T-score below -2.5) admitted to our Nephrology Department for CKD in the last four years. in Vasculitis, Renal Allograft Recipients. Patients with severe Hyperparatiroidism were excluded. We estimated creatinine clearance (eGFR) using Cockcroft-Gault and classified levels of kidney function using the modified National Kidney Foundation ...
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia
Sarcoidosis is a granulomatous disorder with multiorgan involvement which may appear in an isolat... more Sarcoidosis is a granulomatous disorder with multiorgan involvement which may appear in an isolated form but more often as a systemic disease. We report the case of a 53-year-old woman presenting with acute renal failure, hypercalcemia, elevated 1.25 dihydroxycholecalciferol, and a history of fatigue, weight loss and arthralgia of several months. Kidney biopsy had revealed interstitial noncaseating granulomas, so sarcoidosis was considered as a potential diagnosis after exclusion of other granulomatous disorders. Granulomatous tubulo-interstitial nephritis (GIN) is an uncommon disease with a low, but perhaps underestimated incidence: only about 100 cases have been described in the literature. In these cases it was found that the disease may lead to deterioration of renal function and irreversible progress to end-stage renal disease. The treatment of choice is the administration of steroids.
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia
Polyomavirus BK nephropathy is emerging as a significant cause of interstitial nephritis and allo... more Polyomavirus BK nephropathy is emerging as a significant cause of interstitial nephritis and allograft dysfunction (1-2). Two patients with renal transplants from cadaveric kidneys were treated with Tacrolimus plus Mycophenolate Mofetil (MMF) and Cyclosporine plus MMF, respectively. Their renal function gradually deteriorated eight to twelve months after the transplant. The renal biopsy of the first patient showed signs of significant interstitial tubulite, which necessitated the anti-rejection therapy with intravenous steroid pulses. After the pulses there was an additional dramatic increase in plasmatic creatinine, which suggested a revaluation of the kidney biopsy because of suspected Polyomavirus BK (BKV) nephropathy. In fact, after a more careful review, the suspicion of BKV infection was confirmed by the presence of intranuclear inclusions of tubular epithelium cells and marked denudation of the tubular basal membrane. The subsequent screening in both cases confirmed the prese...
Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypo... more Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypoxic parenchymal stress during HD sessions. The oxygen extraction ratio (OER), an estimate of the oxygen claimed by peripheral tissues, might represent a new prognostic factor in HD patients. This study evaluated whether the intradialytic change in OER (ΔOER) identified patients with higher mortality risks. We enrolled chronic HD patients with permanent central venous catheters with available central venous oxygen saturation (ScvO2) measurements; the arterial oxygen saturation was measured with peripheral oximeters (SpO2). We measured OER before and after HD at enrolment; deaths were recorded during two-years of follow-up. In 101 patients (age: 72.9 ± 13.6 years, HD vintage: 9.6 ± 16.6 years), 44 deaths were recorded during 11.6 ± 7.5 months of follow-up. Patients were divided into two groups according to a 40% ΔOER threshold (ΔOER < 40%, n = 56; ΔOER ≥ 40%, n = 45). The ΔOER ≥ 40% gro...
randomly 20 patients (12 females and 8 males, average age 23±14) were treated with Pn (2 gm/day i... more randomly 20 patients (12 females and 8 males, average age 23±14) were treated with Pn (2 gm/day if body weight was less than 50 Kg and 4 gm/day if body weight was over 50 Kg) and the others 20 patients (12 females and 8 males, average age 20 ±12) were treated with placebo (control group), for 3 months (Table 1). We applied the student test t to compare
Background Data on serum soluble Klotho levels in chronic kidney disease are contradictory and ev... more Background Data on serum soluble Klotho levels in chronic kidney disease are contradictory and even less is known after renal transplantation. Experimental studies demonstrated that recombinant human erythropoietin (rhEPO) treatment mitigates Klotho reduction caused by renal damage. Therefore, this study aimed to determine serum Klotho levels in a cohort of kidney transplant recipients (KTR) and to evaluate whether rhEPO treatment can modulate, in vivo and in vitro, soluble Klotho. Methods 117 KTR and 22 healthy subjects (HS) were enrolled. In 17 KTR, rhEPO was discontinued for 5 weeks and Klotho levels were compared to 34 propensity scorematched controls. Moreover, we evaluated Klotho mRNA expression and protein secretion in HK-2 tubular cells treated with cyclosporin A (CyA) and rhEPO, alone or in combination. Results Serum Klotho levels in KTR were significantly higher than in HS (0.68 vs. 0.37, p = 0.002) and significantly associated with estimated glomerular filtration rate (r =-0.378, p = 0.003) and fibroblast growth factor 23 (r =-0.307, p \ 0.0001). After 5 weeks of rhEPO discontinuation, treated KTR showed a sharper reduction of Klotho levels than controls (-0.56 vs.-0.11 ng/ml, p \ 0.0001). In HK-2 cells CyA treatment induced a Klotho down-regulation that was mitigated by rhEPO pretreatment. In the same experimental conditions, our results revealed that cells treated with CyA ? rhEPO secreted higher soluble Klotho levels than those exposed to CyA or rhEPO alone. Conclusions Our results demonstrate that KTR have higher serum Klotho levels than HS and that rhEPO treatment modulates these concentrations, suggesting a link between rhEPO and soluble Klotho in KTR.
We selected patients converted to a calcineurin inhibitor due to neoplasia and who were exclusive... more We selected patients converted to a calcineurin inhibitor due to neoplasia and who were exclusively maintained on an mTOR-is. We studied the incidence and characteristics of the neoplasia, the median time of immunosuppression, and the survival of patients after diagnosis. We studied the graft and patient survival according to their trough levels of mTOR-is at 6 months, 1 year, 2 years and 3 years post-transplant. RESULTS: 70 patients were included, 93% were transplanted with a deceased donor. Medium age at diagnosis of neoplasia was 58,5 years (6 12,6) with a medium time post-transplant of 3,4 years 6 3,5. Ninety percent were solid neoplasia. Skin and genitourinary cancers were the most frequently diagnosed, but lung cancer was associated with the worst survival. The incidence of acute rejection after conversion was 10% (n=7). The incidence of neoplasia recurrence was 4%. Everolimus was the mTOR-Is chosen for conversion in 97% of cases. Median graft survival (censored for death) was 112,9 months (6 3,6). There was a significant difference in outcomes between patients according to their everolimus trough levels at 3 years after conversion (AUROC was 0,64). Patients who maintained everolimus trough levels of 3-4,9 ng/ml vs 5-8 ng/ml, at 3 years post conversion had superior graft survival (rhos= 0,502, p= 0,009). There were no other significant differences acknowledged at the remaining time points. Comparison between the group of patients with trough levels 3-4,9 ng/ml vs 5-8 ng/ml at 3 years post transplant did not show differences in loss of function or increased proteinuria (p>0,05 for all variables). We didn't find an association between acute rejection and lower trough Mtor-Is levels (Pearson chi2 test, p=0,412). There was one recurrence of neoplasia (squamous cell carcinoma). 7% of patients were diagnosed with a second neoplasia while on mTOR-is. CONCLUSIONS: We found that mTOR-is levels of 3-4,9 ng/ml are associated with better outcomes (better graft survival and function) at 3 years post-conversion. Further studies are needed in this specific population to determine the best immunosuppressors to use and how to use them.
Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and de... more Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkANTR and p75NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells comb...
clear evidence of ACEi efficacy on the progression of chronic kidney disease in children with hyp... more clear evidence of ACEi efficacy on the progression of chronic kidney disease in children with hypodysplastic nephropathy—report
cohort, NPHS2 p.R229Q was identified in 5 patients (6%), but only with pathogenic significance in... more cohort, NPHS2 p.R229Q was identified in 5 patients (6%), but only with pathogenic significance in 3 patients, and APOL1 high risk haplotype was coidentified with COL4 variants in 3 patients. Conclusion: The genetic study of a cohort of patients suspected of genetic FSGS allowed the identification of genetic variants in the genes of interest in a high percentage of cases. The most frequently implicated genes were COL4A3, COL4A4 e COL4A5, NPHS2, INF2 and APOL1 high risk haplotype. The high percentage of gene variants identified in our cohort is probably due to the selection of a population with a high likelihood of genetic FSGS. Further studies will clarify the causal and/or modifier effect of some genes, namely COL4A3, COL4A4 e COL4A5. The future use of WES in cases of high likelihood of genetic cause will probably allow the identification on novel candidate genes and increase the clinical benefits of a genetic diagnosis of FSGS.
Background and Aims Denosumab is a fully human monoclonal antibody to the receptor activator of n... more Background and Aims Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL), an osteoclast differentiating factor. It inhibits osteoclast formation, decrease bone resorption, increase bone mineral density (BMD), and reduce the risk of fracture. There is no restriction of its use in patients with renal disease, for whom biphosphonates are considered controindicated. The aim of our study was to evaluate the effectiveness in reducing facture risk and safety of Denosumab in patients with Osteoporosis and renal disease. Method This is a prospective analysis of 17 patients with Osteoporosis (average T-score below -2.5) admitted to our Nephrology Department for CKD in the last four years. in Vasculitis, Renal Allograft Recipients. Patients with severe Hyperparatiroidism were excluded. We estimated creatinine clearance (eGFR) using Cockcroft-Gault and classified levels of kidney function using the modified National Kidney Foundation ...
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia
Sarcoidosis is a granulomatous disorder with multiorgan involvement which may appear in an isolat... more Sarcoidosis is a granulomatous disorder with multiorgan involvement which may appear in an isolated form but more often as a systemic disease. We report the case of a 53-year-old woman presenting with acute renal failure, hypercalcemia, elevated 1.25 dihydroxycholecalciferol, and a history of fatigue, weight loss and arthralgia of several months. Kidney biopsy had revealed interstitial noncaseating granulomas, so sarcoidosis was considered as a potential diagnosis after exclusion of other granulomatous disorders. Granulomatous tubulo-interstitial nephritis (GIN) is an uncommon disease with a low, but perhaps underestimated incidence: only about 100 cases have been described in the literature. In these cases it was found that the disease may lead to deterioration of renal function and irreversible progress to end-stage renal disease. The treatment of choice is the administration of steroids.
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia
Polyomavirus BK nephropathy is emerging as a significant cause of interstitial nephritis and allo... more Polyomavirus BK nephropathy is emerging as a significant cause of interstitial nephritis and allograft dysfunction (1-2). Two patients with renal transplants from cadaveric kidneys were treated with Tacrolimus plus Mycophenolate Mofetil (MMF) and Cyclosporine plus MMF, respectively. Their renal function gradually deteriorated eight to twelve months after the transplant. The renal biopsy of the first patient showed signs of significant interstitial tubulite, which necessitated the anti-rejection therapy with intravenous steroid pulses. After the pulses there was an additional dramatic increase in plasmatic creatinine, which suggested a revaluation of the kidney biopsy because of suspected Polyomavirus BK (BKV) nephropathy. In fact, after a more careful review, the suspicion of BKV infection was confirmed by the presence of intranuclear inclusions of tubular epithelium cells and marked denudation of the tubular basal membrane. The subsequent screening in both cases confirmed the prese...
Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypo... more Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypoxic parenchymal stress during HD sessions. The oxygen extraction ratio (OER), an estimate of the oxygen claimed by peripheral tissues, might represent a new prognostic factor in HD patients. This study evaluated whether the intradialytic change in OER (ΔOER) identified patients with higher mortality risks. We enrolled chronic HD patients with permanent central venous catheters with available central venous oxygen saturation (ScvO2) measurements; the arterial oxygen saturation was measured with peripheral oximeters (SpO2). We measured OER before and after HD at enrolment; deaths were recorded during two-years of follow-up. In 101 patients (age: 72.9 ± 13.6 years, HD vintage: 9.6 ± 16.6 years), 44 deaths were recorded during 11.6 ± 7.5 months of follow-up. Patients were divided into two groups according to a 40% ΔOER threshold (ΔOER < 40%, n = 56; ΔOER ≥ 40%, n = 45). The ΔOER ≥ 40% gro...
randomly 20 patients (12 females and 8 males, average age 23±14) were treated with Pn (2 gm/day i... more randomly 20 patients (12 females and 8 males, average age 23±14) were treated with Pn (2 gm/day if body weight was less than 50 Kg and 4 gm/day if body weight was over 50 Kg) and the others 20 patients (12 females and 8 males, average age 20 ±12) were treated with placebo (control group), for 3 months (Table 1). We applied the student test t to compare
Background Data on serum soluble Klotho levels in chronic kidney disease are contradictory and ev... more Background Data on serum soluble Klotho levels in chronic kidney disease are contradictory and even less is known after renal transplantation. Experimental studies demonstrated that recombinant human erythropoietin (rhEPO) treatment mitigates Klotho reduction caused by renal damage. Therefore, this study aimed to determine serum Klotho levels in a cohort of kidney transplant recipients (KTR) and to evaluate whether rhEPO treatment can modulate, in vivo and in vitro, soluble Klotho. Methods 117 KTR and 22 healthy subjects (HS) were enrolled. In 17 KTR, rhEPO was discontinued for 5 weeks and Klotho levels were compared to 34 propensity scorematched controls. Moreover, we evaluated Klotho mRNA expression and protein secretion in HK-2 tubular cells treated with cyclosporin A (CyA) and rhEPO, alone or in combination. Results Serum Klotho levels in KTR were significantly higher than in HS (0.68 vs. 0.37, p = 0.002) and significantly associated with estimated glomerular filtration rate (r =-0.378, p = 0.003) and fibroblast growth factor 23 (r =-0.307, p \ 0.0001). After 5 weeks of rhEPO discontinuation, treated KTR showed a sharper reduction of Klotho levels than controls (-0.56 vs.-0.11 ng/ml, p \ 0.0001). In HK-2 cells CyA treatment induced a Klotho down-regulation that was mitigated by rhEPO pretreatment. In the same experimental conditions, our results revealed that cells treated with CyA ? rhEPO secreted higher soluble Klotho levels than those exposed to CyA or rhEPO alone. Conclusions Our results demonstrate that KTR have higher serum Klotho levels than HS and that rhEPO treatment modulates these concentrations, suggesting a link between rhEPO and soluble Klotho in KTR.
We selected patients converted to a calcineurin inhibitor due to neoplasia and who were exclusive... more We selected patients converted to a calcineurin inhibitor due to neoplasia and who were exclusively maintained on an mTOR-is. We studied the incidence and characteristics of the neoplasia, the median time of immunosuppression, and the survival of patients after diagnosis. We studied the graft and patient survival according to their trough levels of mTOR-is at 6 months, 1 year, 2 years and 3 years post-transplant. RESULTS: 70 patients were included, 93% were transplanted with a deceased donor. Medium age at diagnosis of neoplasia was 58,5 years (6 12,6) with a medium time post-transplant of 3,4 years 6 3,5. Ninety percent were solid neoplasia. Skin and genitourinary cancers were the most frequently diagnosed, but lung cancer was associated with the worst survival. The incidence of acute rejection after conversion was 10% (n=7). The incidence of neoplasia recurrence was 4%. Everolimus was the mTOR-Is chosen for conversion in 97% of cases. Median graft survival (censored for death) was 112,9 months (6 3,6). There was a significant difference in outcomes between patients according to their everolimus trough levels at 3 years after conversion (AUROC was 0,64). Patients who maintained everolimus trough levels of 3-4,9 ng/ml vs 5-8 ng/ml, at 3 years post conversion had superior graft survival (rhos= 0,502, p= 0,009). There were no other significant differences acknowledged at the remaining time points. Comparison between the group of patients with trough levels 3-4,9 ng/ml vs 5-8 ng/ml at 3 years post transplant did not show differences in loss of function or increased proteinuria (p>0,05 for all variables). We didn't find an association between acute rejection and lower trough Mtor-Is levels (Pearson chi2 test, p=0,412). There was one recurrence of neoplasia (squamous cell carcinoma). 7% of patients were diagnosed with a second neoplasia while on mTOR-is. CONCLUSIONS: We found that mTOR-is levels of 3-4,9 ng/ml are associated with better outcomes (better graft survival and function) at 3 years post-conversion. Further studies are needed in this specific population to determine the best immunosuppressors to use and how to use them.
Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and de... more Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkANTR and p75NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells comb...
clear evidence of ACEi efficacy on the progression of chronic kidney disease in children with hyp... more clear evidence of ACEi efficacy on the progression of chronic kidney disease in children with hypodysplastic nephropathy—report
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