IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN) represent important causes of chronic kidney disease. They belong to the immune-mediated glomerulonephritis (GNs), and ...have distinct pathogenesis, distinct clinical courses, and variable responses to treatment. Therefore, specific diagnostic procedures are necessary for more effective patient management. Recently, a role for oxidative stress has been proposed in various renal disorders. Thus, molecules related to oxidative stress, such as 2-Cys-peroxiredoxins (PRDXs), may represent plausible candidates for biomarkers in renal pathologies. The aim of this study was to assess whether there are differences between individual GNs and healthy controls in the context of PRDXs serum concentration. We enrolled 108 patients with biopsy-proven IgAN (47), MN (26), LN (35) and 30 healthy age- and sex-matched controls. The serum concentrations of PRDX 1–5 were measured with ELISA assays and correlated with demographic and clinical data. The PRDXs’ concentration varied depending on the GN type. We also observed an association of PRDXs with lower estimated glomerular filtration rates, complement, hemoglobin, and body mass index. Our study indicates that individual PRDX can play roles in pathophysiology of selected GNs and that their serum concentrations may become useful as a new supplementary diagnostic markers in IgAN, MN as well as LN. The results of this study open a new avenue for prospective research on PRDXs in renal diseases.
Membranous nephropathy is a glomerulopathy that causes nephrotic syndrome and, in at least a third of cases, lasting end-stage kidney disease (ESKD). It is also a rare case of revolutionary changes ...in our understanding of the disease, that translates from scientific findings to real diagnosis and treatment recommendations in less than ten years. In this review we present: (1) a short history and traditional approach to patients with membranous nephropathy, (2) current recommendations and treatment options that have emerged in recent years, (3) findings of new studies, with a particular focus on serological/immunological methods, genomic and proteomic studies, still requiring validation. With further development in this field, membranous nephropathy may become one of the first nephrological conditions that apply a truly personalized approach with the omission of invasive measures such as kidney biopsy.
The BNT162b2 vaccine is reportedly effective in preventing severe disease in more than 90% of the general population, but its efficacy in transplant recipients remains controversial. We aimed to ...determine the immune response to the BNT162b2 vaccine in kidney (KTRs) and liver transplant recipients (LTRs). In this retrospective cohort study, we included randomly 65 KTRs and 65 LTRs, who received two 30 μg doses of BNT162b2 vaccine in 3-to6-week intervals. We analyzed the anti-SARS-CoV-2 spike protein IgG antibody (anti-S1 Ab) titer, biochemical liver and renal tests, immunosuppressive drug trough level, and clinical follow up 4-6 weeks after the first dose and 4-8 weeks after the second dose. The level of protective antibodies was 57.1% in KTRs and 88.9% in LTRs after the second dose. The anti-S1 Ab response was significantly associated with sex, age, and history of COVID-19. A tacrolimus dose at vaccination but not its trough level was significantly correlated with the increase in anti-S1 Ab titer after the second vaccine dose in LTRs. Rejection episodes did not occur after vaccination. Our results showed a higher than previously reported humoral response to the BNT162b2 vaccine in KTRs and LTRs, which was dependent upon age, type of transplanted organ, and immunosuppression.
Many potential biomarkers in nephrology have been studied, but few are currently used in clinical practice. One is osteopontin (OPN). We compared urinary OPN concentrations in 80 participants: 67 ...patients with various biopsy-proven glomerulopathies (GNs)-immunoglobulin A nephropathy (IgAN, 29), membranous nephropathy (MN, 20) and lupus nephritis (LN, 18) and 13 with no GN. Follow-up included 48 participants. Machine learning was used to correlate OPN with other factors to classify patients by GN type. The resulting algorithm had an accuracy of 87% in differentiating IgAN from other GNs using urinary OPN levels only. A lesser effect for discriminating MN and LN was observed. However, the lower number of patients and the phenotypic heterogeneity of MN and LN might have affected those results. OPN was significantly higher in IgAN at baseline than in other GNs and therefore might be useful for identifying patients with IgAN. That observation did not apply to either patients with IgAN at follow-up or to patients with other GNs. OPN seems to be a valuable biomarker and should be validated in future studies. Machine learning is a powerful tool that, compared with traditional statistical methods, can be also applied to smaller datasets.
Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases. Glucocorticoid receptor gene (
) single nucleotide polymorphisms (SNPs) are implicated in differences in ...predisposition to autoimmunity and steroid sensitivity. The aim of this study was to evaluate the frequency of the
SNPs-rs6198, rs41423247 and rs17209237-in 72 IgA nephropathy (IgAN) and 38 membranous nephropathy (MN) patients compared to 175 healthy controls and to correlate the effectiveness of treatment in IgAN and MN groups defined as a reduction of proteinuria <1 g/24 h after 12 months of treatment. Real-time polymerase chain reactions and SNP array-based typing were used. We found significant rs41423247 association with MN (
= 0.026); a significant association of rs17209237 with eGFR reduction after follow-up period in all patients with GNs (
= 0.021) and with the degree of proteinuria after 1 year of therapy in all patients with a glomerulopathy (
= 0.013) and IgAN (
= 0.021); and in the same groups treated with steroids (
= 0.021;
= 0.012). We also observed the association between rs41423247 and IgAN histopathologic findings (
= 0.012). In conclusion, our results indicate that
polymorphisms may influence treatment susceptibility and clinical outcome in IgAN and MN.
Abstract Background and Aims Multiple factors may contribute to development and progression of glomerulopathies (GN), one of them is oxidative stress (OS). 2-cysteine-peroxiredoxins (PRDXs) possess ...the ability to reduce excessive levels of OS mediators and are crucial for cellular OS regulation. In our pilot study, we found that PRDXs 1-5 are differentially changed in patients with IgA nephropathy (IgAN), lupus nephritis (LN) and membranous nephropathy (MN). Thus, the aim of the current study was to evaluate if PRDXs 1-5 may be a prognostic marker for these 3 types of GN. Method We followed-up (5-year observation) 80 previously recruited patients with: IgAN (n = 36); MN (n = 23) and LN (n = 21). Patients were classified, based on the eGFR change (decline vs. stable and/or increase) and baseline PRDXs 1-5 levels (Table 1). The Mann Whitney-U, Kruskal-Wallis Test and Pearsons’ correlation were used for statistical analysis, the p-values <0.05 were considered significant. Results Baseline measurements indicated that the mean serum PRDXs 1-5 concentrations differ between the GN types. During the follow-up, we observed the significant association of eGFR decline with low baseline PRDX-2 level (p = 0.049) in patients with IgAN (Fig. 1). Conclusion We suggest the possible link between peroxiredoxins and deterioration of kidney function, particularly in IgAN patients.
Abstract
Background and Aims
Oxidative stress (OS) is known as a disturbance between pro- and antioxidant factors, that may lead to DNA or protein oxidation, resulting in cellular damage. ...Peroxiredoxins (PRDXs) are enzymes with an antioxidant properties. They play dominant role in regulation of cellular peroxide levels, which is crucial in maintaining organisms’ oxidative balance. PRDXs types 1-5 are involved in the pathophysiology of various diseases (e.g. cancer, inflammatory, or renal). We aim to study their role as a prognostic marker of eGFR changes in IgA nephropathy (IgAN), lupus nephritis (LN) and membranous nephropathy (MN) patients.
Method
This is a retrospective 5-year-follow-up study of 108 IgAN, MN and LN patients, in whom PRDX 1-5 serum levels were assessed with ELISA in 2017. In 2022, we were able to collect the data out of 80 patients: IgAN (n=36); MN (n=22) and LN (n=22). The remaining 28 were considered as lost-to-follow-up, namely: lack of any medical results within last 2 years (n=23); on dialysis (n=2); after renal transplantation (n=2); deceased (n=1). We classified patients depending on the changes of eGFR (decline/stable/increase; Fig. 1) between baseline and after 5 year follow-up and the PRDX levels (high/medium/low; Table 1). The Mann Whitney-U, Kruskal-Wallis and Chi-Square Test were used for statistical analysis, the p-values <0.05 were considered significant.
Results
Baseline PRDX measurements indicated, that the mean concentrations of serum PRDX 1-5 differ between the glomerulonephropathies (GN). In 2022, we observed significantly different (P = .012) change of eGFR depending on the GN type. 16/80 individuals had eGFR decline and 75% of them were diagnosed with IgAN. The MN and LN groups had increase of eGFR in the last 5 years in most cases, probably as a result of the treatment. We verified if follow-up eGFR was associated with baseline PRDX levels. The 2022 eGFR differed significantly between the GNs depending on the level of serum PRDX 2, 4 and 5 at baseline (P = .002; P = .009; P = .006, respectively, Table 1).
Conclusion
Our results showed the link between serum PRDXs concentration and IgAN, MN and LN follow-up. Importantly, selected PRDXs’ might be used to predict eGFR decline, particularly in IgAN and LN.
Abstract
Background and Aims
Liver transplantation (LT) requires patients to take immunosuppression (IS). Long term IS leads to hypertension and chronic kidney disease (CKD). Calcineurin inhibitors ...(CNi) are known to have nephrotoxic effects. Thus, liver transplant recipients (LTRs) that are taking either long-term or high cumulative doses of CNi are at a significantly higher risk of developing CKD. This study aimed to find predictive factors for development of CKD post-LT. Furthermore, it introduced IS minimization protocol in LTRs with clinical or laboratory indications with the aim to prevent the CKD progression and decrease the burden of other comorbidities.
Method
212 out of all 870 LTRs from our center were screened for eligibility and 93 were recruited in 2018 for IS minimization after obtaining informed consent. They were deemed eligible if the primary cause of LT was a non-autoimmune disease and the graft function was stable. At the time of screening, patients were on IS either triple-, dual- or monotherapy (Table 1). The IS were reduced in 3 months intervals and was minimized until monotherapy with subtherapeutic serum levels (tacrolimus <5mg/ml or cyclosporine <50mg/ml).
Results
The indications for IS minimization were hypertension (73.87%), CKD (35.87%), cardiovascular diseases (32%), diabetes mellitus (23.91%) or malignancies (6.52%). It was found that LTRs with CKD were older (61.8 CKD vs. 49.6 non-CKD) and predominantly male (84.85% male; 15.15% female) when compared to non-CKD patients (33.9% male; 66.1% female). Another risk factor for post-LT CKD development was higher BMI (27.57 vs. 25.35). Time from transplantation of LTR with CKD was 129.12 months while for non-CKD was 150.19 months, suggesting that longer time since transplantation is not a predictive factor for development of CKD after LT. LTRs with CKD concomitantly had hypertension (84.85% vs. 67.80%) and DM (48.48% vs. 27.12%) more often than non-CKD LTRs. It was found that CKD-LTRs at the beginning of the IS minimization were more commonly taking IS polytherapies (triple 6.06% and dual 45.45% vs. triple 0% and dual 33.9%) than monotherapy (48.48% vs. 67.80%). In the first 12 months of the study, 22 out of the 33 patients with CKD safely reached monotherapy, 11 of those reached subtherapeutic levels of CNi (50,0%). Moreover, when kidney function was compared before and after IS reduction any progression of CKD was observed. Liver function tests were elevated in 4 patients with CKD, but return to the previous dose of IS resulted in normalization of liver function.
Conclusion
Minimization of IS should be considered in patients after LT who suffer from IS related comorbidities, particulary CKD. Its incidence post-LT was found to be associated with male gender, BMI and IS polytherapy. Our protocol of IS minimization seems to be safe in respect to graft rejection.
Table 1.
Comparison of CKD and non-CKD LTRs.
CKD
NON- CKD
n=33
%
n=59
%
Age
61.8
49.6
Gender
Female
5
15.15
39
66.10
Male
28
84.85
20
33.90
Months from Tx
129.12
150.19
Concomitant diseases
BMI at baseline
27.57
25.35
BMI after 12 mo.
27.90
25.84
Hypertension
28
84.85
40
67.80
Diabetes Mellitus
16
48.48
16
27.12
GFR
At baseline
51.16
92.95
After 12 month
50.21
90.37
IS at Baseline
Monotherapy
16
48,48
39
66,10
Dualtherapy
15
45.45
20
33.90
Tripletherapy
2
6.06
0
0
IS After 12 month
Monotherapy
22
66.67
49
83.05
Dualtherapy
9
27.27
10
16.95
Tripletherapy
2
6.06
0
0.00
Number of LTRs taking CNi
At baseline
29
87.88
54
91.53
After 12 mo.
28
84.85
55
93.22
Renal cell carcinoma (RCC) comprises 2‑3% of all malignant tumors in adults. Many studies have established the key roles of smoking, hypertension and other components of metabolic syndrome in the ...occurrence of RCC. Diabetes mellitus (DM), one of the main consequences of metabolic syndrome, appears much more often in patients with RCC. The prognosis for patients suffering from both diabetes and RCC is worse than for those with kidney cancer only. Diabetes is linked to higher rate of recurrence and a greater number of distant metastases. These factors contribute to a reduction in overall survival (OS) and cause‑specific survival (CSS). Diabetes can also occur as a paraneoplastic syndrome. Tyrosine kinase inhibitors (TKIs), which are agents used in the therapy of metastatic RCC, may have unexpected effects when administered to patients with diabetes. Studies and case reports have shown that they influence blood glucose levels (BGLs) in diabetic patients, sometimes causing dangerous episodes of hypoglycemia. Hyperinsulinemia and hyperglycemia can be considered independent carcinogenic factors, as they increase the amount of pro‑inflammatory cytokines, reactive oxygen species and lipid peroxidation. TKIs have yet to be re‑evaluated as to their safety of use in patients with diabetes.
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