IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more \'Complement-Pathic\' subset of patients.

BACKGROUND: Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF).
METHODS: Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127).
RESULTS: Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0% vs. 85.5%, p < 0.001) and 24 months (61.0% vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4% vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6% vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9% vs. 18.6%, p = 0.003, OR = 0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406 vs. 813 days, p = 0.001) without an increased risk of complications.
CONCLUSIONS: CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications.

Diabetic neuropathy and nephropathy are common complications of type 1 diabetes (T1D). The symptoms are often elusive in the early stages, and available diagnostic methods can be improved using biomarkers. Matrix metalloproteinase 3 (MMP-3) has been identified in the kidneys and is thought to be involved in diabetic nephropathy. Growth differentiation factor 15 (GDF-15) has been suggested to have positive effects in diabetes, but is otherwise associated with adverse effects such as cardiovascular risk, declined kidney function, and neurodegeneration. This study aims to investigate plasma MMP-3 and GDF-15 as systemic biomarkers for diabetic neuropathy and nephropathy in T1D. The study involves patients with childhood-onset T1D (n = 48, age 38 ± 4 years) and a healthy control group (n = 30, age 38 ± 5 years). Neurophysiology tests, evaluations of albuminuria, and measurements of routine biochemical markers were conducted. The neuropathy impairment assessment (NIA) scoring system, where factors such as loss of sensation and weakened reflexes are evaluated, was used to screen for symptoms of neuropathy. MMP-3 and GDF-15 concentrations were determined in heparinized plasma using ELISA kits. In total, 9 patients (19%) had albuminuria, and 25 (52%) had diabetic neuropathy. No significant differences were found in MMP-3 concentrations between the groups. GDF-15 levels were higher in T1D, with median and interquartile range (IQR) of 358 (242) pg/mL in T1D and 295 (59) in controls (p < 0.001). In the merged patient group, a positive correlation was found between MMP-3 and plasma creatinine, a negative correlation was found between MMP-3 and estimated glomerular filtration rate (eGFR; rho = -0.358, p = 0.012), and there was a positive correlation between GDF-15 and NIA (rho = 0.723, p < 0.001) and high-sensitive C-reactive protein (rho = 0.395, p = 0.005). MMP-3 was increased in macroalbuminuria and correlated positively with NIA only in the nine T1D patients with albuminuria (rho = 0.836, p = 0.005). The present study indicates that high MMP-3 is associated with low eGFR, high plasma creatinine, and macroalbuminuria, and that GDF-15 can be a biomarker for diabetic neuropathy in T1D. MMP-3 may be useful as biomarker for neuropathy in T1D with albuminuria.

The Goldblatt model of hypertension (2K-1C) in rats is characterized by renal sympathetic nerve activity (rSNA). We investigated the effects of unilateral renal denervation of the clipped kidney (DNX) on sodium transporters of the unclipped kidneys and the cardiovascular, autonomic, and renal functions in 2K-1C and control (CTR) rats. The mean arterial pressure (MAP) and rSNA were evaluated in experimental groups. Kidney function and NHE3, NCC, ENaCβ, and ENaCγ protein expressions were assessed. The glomerular filtration rate (GRF) and renal plasma flow were not changed by DNX, but the urinary (CTR: 0.0042 ± 0.001; 2K-1C: 0.014 ± 0.003; DNX: 0.005 ± 0.0013 mL/min/g renal tissue) and filtration fractions (CTR: 0.29 ± 0.02; 2K-1C: 0.51 ± 0.06; DNX: 0.28 ± 0.04 mL/min/g renal tissue) were normalized. The Na+/H+ exchanger (NHE3) was reduced in 2K-1C, and DNX normalized NHE3 (CTR: 100 ± 6; 2K-1C: 44 ± 14, DNX: 84 ± 13%). Conversely, the Na+/Cl- cotransporter (NCC) was increased in 2K-1C and was reduced by DNX (CTR: 94 ± 6; 2K-1C: 144 ± 8; DNX: 60 ± 15%). In conclusion, DNX in Goldblatt rats reduced blood pressure and proteinuria independently of GRF with a distinct regulation of NHE3 and NCC in unclipped kidneys.

BACKGROUND: Acute kidney injury (AKI) incidence is extremely high worldwide, and patients who develop AKI are at increased risk of developing chronic kidney disease (CKD), CKD progression, and end-stage kidney disease (ESKD). However, there is no established treatment strategy for AKI. Based on the idea that exercise has a stabilizing effect on hemodynamics, we hypothesized that rehabilitation would have beneficial renal outcomes in patients with AKI associated with cardiovascular disease. Therefore, the purpose of this study was to determine whether rehabilitation can stabilize hemodynamics and positively impact renal outcomes in patients with AKI associated with cardiovascular disease.
METHODS: In total, 107 patients with AKI associated with cardiovascular disease were enrolled in this single-center retrospective study and were either assigned to the exposure group (n = 36), which received rehabilitation at least once a week for at least 8 consecutive weeks, or to the control group (n = 71). Estimated glomerular filtration rate was assessed at baseline before admission, at the lowest value during hospitalization, and at 3, 12, and 24 months after enrolment. Trends over time (group × time) between the two groups were compared using generalized estimating equations. Moreover, congestive status was assessed by amino-terminal pro-B-type natriuretic peptide (NT-proBNP), and the effect of rehabilitation on congestion improvement was investigated using logistical regression analysis.
RESULTS: The time course of renal function after AKI, from baseline to each of the three timepoints suggested significant differences between the two groups (p < 0.01). However, there was no significant difference between the two groups at any time point in terms of percentage of patients who experienced a 40% estimated glomerular filtration rate reduction from that at baseline. The proportion of patients with improved congestion was significantly higher in the exposure group compared with that in the control group (p = 0.018). Logistic regression analysis showed that rehabilitation was significantly associated with improved congestion (p = 0.021, OR: 0.260, 95%CI: 0.083-0.815).
CONCLUSIONS: Our results suggest that rehabilitation in patients with AKI associated with cardiovascular disease correlates with an improvement in congestion and may have a positive effect on the course of renal function.

Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR decline < 15% and ≥ 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR decline ≥ 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR decline < 15% and 88 in the group with a three-year eGFR decline ≥ 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR decline ≥ 15% (P = .039, P < .001, and P = .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR decline ≥ 15% (P = .004; OR = 2.316). There was a significant linear relationship between the eGFR decline and TG level (P = .002). Patients with a TG concentration > 1.7 mmol/L had a more apparent decrease in the eGFR (P < .05). For elderly patients with T2DM and an eGFR < 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide, but few studies are available on CKD in Cote d\'Ivoire. We aimed to assess the prevalence of CKD and identify its associated factors in the general population in Abidjan in 2016 in a cross-sectional study that included 1418 subjects. We did not receive laboratory data for 38 subjects, including serum creatinine data. Of the 1380 remaining subjects, 138 cases of CKD were included in the study (10% prevalence). We observed a female predominance (sex ratio = 0.81), and the mean age was 43.7 ± 14.5 years. Histories of hypertension (HTN) (29.7%) and diabetes (10.1%) were reported. The main clinical signs were high blood pressure (51.4%), obesity (21%), proteinuria (37.9%), and hematuria (37.4%). The glomerular filtration rate (GFR) was <60 mL/min in 8.2% of cases according to the Modification of Diet in Renal Disease equation, in 8.6% according to the CKD Epidemiology Collaboration equation, and in 12.6% according to the Cockroft-Gault (CG) equation. The other laboratory signs were hyperglycemia (51.4%), hypercholesterolemia (34.1%), and hyperlipidemia (21%). In the multivariate analysis, factors such as female sex (P = 0.013), age >55 years (P = 0.02), a history of HTN (P = 0.001), hypercholesterolemia (P = 0.010), and hyperlipidemia (P = 0.009) were associated with the risk of CKD. The prevalence of CKD was high in our study. The CG equation should not be used to estimate the GFR in the general population. Prevention involves managing modifiable risk factors.

Renal failure is a common feature of multiple myeloma (MM) that occurs in 20%-40% of newly diagnosed patients with MM and is the result of monoclonal immunoglobulin light chains. Many studies have examined the effect of autologous stem cell transplantation (ASCT) in MM patients with renal impairment and the safety of performing the transplantation in patients with renal failure. This study aimed to compare renal function before and after ASCT in Egyptian MM patients with renal insufficiency to evaluate the effect of ASCT on renal recovery. Our study included 31 MM patients with renal impairment out of 400 patients who met the criteria of the International Myeloma Working Group for symptomatic MM. The estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease formula was compared before and after the transplant. Only four patients (12.9%) were dependent on dialysis. Six of those with a history of hemodialysis (HD) who were either dependent on dialysis or dialyzed according to need achieved independence from HD. There was no significant correlation between the degree of renal impairment and the disease\'s status at the time of transplantation (P = 0.86). The study showed significant improvements in serum creatinine levels compared with its value before the transplant (P = 0.016) and in eGFR (P = 0.004). In total, 45% of patients achieved renal improvement, shown by a 25% increase in GFR above the baseline. There was a significant improvement of renal function after ASCT in MM patients with renal impairment.

UNASSIGNED: To assess the association between kidney function and odds of having low skeletal muscle mass (LSMM) in Chinese adults on the basis of a community study.
UNASSIGNED: In this cross-sectional study, we included 3726 Chinese older persons who participated in an ongoing prospective study, the China Health and Retirement Longitudinal Study(CHARLS). Fasting blood samples were collected in 2012 and analyzed for serum creatinine. Estimated glomerular filtration rate(eGFR) was computed using serum creatinine, gender, and age, according to the 2021 race-free Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). We classified the target population into three categories according to eGFR (normal eGFR;90mL/min/1.73m2, mildly-impaired eGFR;60 to < 90 mL/min/1.73 m2, moderate to severve impaired eGFR;<60 mL/min/1.73 m2). BMI-adjusted muscle mass was used to measure skeletal muscle mass.The association between eGFR(per interquartile range(IQR) increment) and the risk of low skeletal muscle mass was assessed using logistic regression model.
UNASSIGNED: Worsening renal function was associated with being high risk for LSMM after adjusting for potential confounders:the odds ratios (ORs) 95% confidence intervals (CIs) were 0.76 (95% CI = 0.63 - 0.88) for male, and [0.71, (0.61-0.82)]in female, p < 0.001. Specifically, male participants with mildly renal impairment were more prone to develop LSMM (multiadjusted OR, 1.43, 95% CI(0.92 to 2.09), p = 0.1) than femal(multiadjusted OR, 1.32, 95% CI(0.85 to 2.00), p = 0.2), the gender difference was not significant in severe renal dysfunction.However, there was a non-linear relationship between eGFR(per IQR increment) and risk of LSMM(eGFR/IQR =5.42, knot = 4 OR =1, p for non-linear <0.001).
UNASSIGNED: Lower levels of eGFR had a high likelihood of being high risk for LSMM. Older male patients with mildly renal insufficiency are more likely to experience a decrease in skeletal muscle mass compared to female.

UNASSIGNED: There is a lack of real-world evidence regarding the impact of concomitant metformin and renin-angiotensin system inhibitors (RASis) on sodium-glucose cotransporter-2 inhibitor (SGLT2i)-associated kidney outcomes. This study was aimed to investigate whether SGLT2i-associated kidney outcomes were modified by the concomitant use of metformin or RASis in patients with type 2 diabetes.
UNASSIGNED: SGLT2i users were identified from three electronic health record databases during May 2016 and December 2017 and categorized into those with and without concomitant use of metformin or RASis. Propensity score matching was performed to minimize baseline differences between groups. Study outcomes were mean estimated glomerular filtration rate (eGFR) change and time to 30%, 40%, and 50% eGFR reductions. A meta-analysis was performed to combine the estimates across databases.
UNASSIGNED: After matching, there were 6,625 and 3,260 SGLT2i users with and without metformin, and 6,654 and 2,746 SGLT2i users with and without RASis, respectively. The eGFR dip was similar in SGLT2i users with and without metformin therapy, but was greater in SGLT2i users with RASis compared to those without RASis. Neither metformin nor RASi use had a significant effect on SGLT2i-associated eGFR reductions, as evidenced by the hazard ratios (95% CIs) of 30% eGFR reductions for SGLT2is with versus without metformin/RASis, namely 1.02 (0.87-1.20)/1.09 (0.92-1.31). Such findings were also observed in the outcomes of 40% and 50% eGFR reductions.
UNASSIGNED: Using metformin or RASis did not modify SGLT2i-associated kidney outcomes in type 2 diabetes.