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IgA nephropathy (IgAN) accounts for a far higher proportion of end-stage renal disease (ESRD) in Asia compared with North America. It is not known whether this is entirely because of differences in disease prevalence or a higher risk of disease progression. The lack of a racially diverse population cohort followed longitudinally has previously precluded the ability to address this question. To determine whether Asians in North America with IgAN are at higher risk for ESRD, we analyzed a cohort of 202 patients of self-reported Pacific Asian origin and 467 of other origin from the Toronto GN Registry followed up for a median of 46.4 months. The primary outcome of ESRD (dialysis, transplantation, or eGFR below 15) was analyzed using Cox regression analysis. Baseline eGFR was 59.6ml/min/1.73m2, and median proteinuria was 1.8g/day. ESRD occurred in 213 patients. By univariable analysis, the risk of ESRD was similar between the two groups (hazard ratio 0.98, 95% CI 0.73, 1.31); however, after adjusting for age, gender, eGFR, medication use, blood pressure, and proteinuria, the risk of ESRD was significantly higher in Pacific Asian individuals (hazard ratio 1.56, 95% CI 1.10, 2.22). This was supported by a significant 1.62ml/min/1.73m2/year faster rate of eGFR decline (95% CI –3.19, –0.5) and an increased risk of a reduction in eGFR by half (hazard ratio 1.81, 95% CI 1.25, 2.62). Thus, in a large multiracial cohort of patients with IgAN, individuals of Pacific Asian origin have a higher risk of progression to ESRD.

Chronic kidney disease (CKD), defined as the presence of irreversible structural or functional kidney damages, increases the risk of poor outcomes due to its association with multiple complications, including altered mineral metabolism, anemia, metabolic acidosis, and increased cardiovascular events. The mainstay of treatments for CKD lies in the prevention of the development and progression of CKD as well as its complications. Due to the heterogeneous origins and the uncertainty in the pathogenesis of CKD, efficacious therapies for CKD remain challenging. In this review, we focus on the following four themes: first, a summary of the known factors that contribute to CKD development and progression, with an emphasis on avoiding acute kidney injury (AKI); second, an etiology-based treatment strategy for retarding CKD, including the approaches for the common and under-recognized ones; and third, the recommended approaches for ameliorating CKD complications, and the final section discusses the novel agents for counteracting CKD progression.

The aim of the study was to assess the association between the geriatric nutritional risk index (GNRI) and incidence of CKD progression, all-cause mortality, and cardiovascular events in the elderly patients with chronic kidney disease (CKD) before dialysis initiation. We performed a post hoc analysis of the CKD-ROUTE database, which included 538 pre-dialysis CKD patients aged ≥65 years in this prospective cohort study. Associations between GNRI and clinical outcomes were estimated using Cox proportional hazards model analysis. Multivariable linear mixed regression models with random intercepts were used to assess the association between GNRI and estimated glomerular filtration rate (eGFR) decline per year. During the median follow-up period of 2.92 years, there were 123 (22.86%) CKD progression events, 44 (8.18%) deaths, and 76 (14.13%) cardiovascular events. After adjusting for multiple confounding factors, the hazard ratios (HRs) for CKD progression in patients with GNRI <92 were 1.99 (95% CI, 1.34-2.97;  < 0.001), when compared with a GNRI of ≥92. Patients with a lower GNRI also had a significantly greater rate of eGFR decline over time than well-nourished patients (mean annual difference, -1.69; 95% CI, -2.62 to -0.77;  < 0.001). In the secondary outcomes, this association was consistent for all-cause mortality. Moreover, the associations were generally consistent across several subgroup and sensitivity analyses. The lower GNRI is significantly associated with higher risks of renal prognosis and all-cause mortality in elderly patients with CKD.

The use of selective COX-2 (sCOX-2) inhibitors with acute kidney injury, salt water retention, and cardiovascular events have been correlated in subjects with normal kidney function, but sCOX-2 inhibitor use concerning the progression of chronic kidney disease (CKD) remains uncertain. To determine the progression of renal function and electrolyte abnormalities among CKD patients after using sCOX-2 inhibitors during short- and long-term periods. The study employed a retrospective cohort design comprising all types of CKD patients with and without sCOX-2 inhibitors (celecoxib and etoricoxib). Data collected included medical data, estimated glomerular filtration rate (eGFR), and serum electrolytes at 3 and 6 months between January 2009 and January 2014. Subjects attended the outpatient clinic and were then followed up until discontinuation of the drugs at years 1 and 2 until May 2016. Ninety-two CKD patients on sCOX-2 inhibitors and 92 CKD patients without sCOX-2 inhibitors were included. The sCOX-2 inhibitor group showed more decline in eGFR than the control group at 3 and 6 months of follow-up (-8.27±9.75 vs -1.64±6.05 mL/min/1.73 m , <0.001 and -12.36±6.48 vs -4.31±5.11 mL/min/1.73 m , =0.001, respectively) and at 1 and 2 years of follow-up after subjects discontinued sCOX-2 (-6.84±10.34 vs -1.61±8.93 mL/min/1.73 m , =0.004 and -10.26±10.19 vs -5.12±8.61 mL/min/1.73 m , =0.005, respectively). In addition, the sCOX-2 inhibitor group had significantly more increased serum potassium during the study follow-up than the control group. The sCOX-2 inhibitors are associated with an increased risk for rapid eGFR decline and hyperkalemia in both the short term and in the long term after sCOX-2 inhibitors were terminated in the setting of a community-based CKD population. For CKD patients, these results suggest that sCOX-2 inhibitors should be closely monitored and chronic exposure to any sCOX-2 inhibitors should be avoided.

Diabetic kidney disease (DKD) affects approximately one-third of patients with diabetes and taking into consideration the high cardiovascular risk burden associated to this condition a multifactorial therapeutic approach is traditionally recommended, in which glucose and blood pressure control play a central role. The inhibition of renin–angiotensin–aldosterone RAAS system represent traditionally the cornerstone of DKD. Clinical outcome trials have demonstrated clinical significant benefit in slowing nephropathy progression mainly in the presence of albuminuria. Thus, international guidelines mandate their use in such patients. Given the central role of RAAS activity in the pathogenesis and progression of renal and cardiovascular damage, a more profound inhibition of the system by the use of multiple agents has been proposed in the past, especially in the presence of proteinuria, however clinical trials have failed to confirm the usefulness of this therapeutic approach. Furthermore, whether strict blood pressure control and pharmacologic RAAS inhibition entails a favorable renal outcome in non-albuminuric patients is at present unclear. This aspect is becoming an important issue in the management of DKD since nonalbuminuric DKD is currently the prevailing presenting phenotype. For these reasons it would be advisable that blood pressure management should be tailored in each subject on the basis of the renal phenotype as well as related comorbidities. This article reviews the current literature and discusses potentials and limitation of targeting the RAAS in order to provide the greatest renal protection in DKD.

Complex factors are involved in the development and progression of immunoglobulin A nephropathy (IgAN), a common primary glomerulonephritis worldwide. Autoimmunity and inflammation have been considered to be the basic mechanisms; however, the exact pathogenesis remains unclear. As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. Whether the NLR can predict the renal outcome of patients with IgAN remains unclear. We evaluated the relationships between the NLR and renal function, pathologic lesions, renal progression, and prognosis in patients with IgAN. This retrospective study involved 966 patients with biopsy-proven IgAN. They were divided into two groups based on the cut-off value of the NLR: the high group (NLR ≥ 2.67, n = 384) and the low group (NLR < 2.67, n = 582). The endpoint was end-stage renal disease [estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73 m or performance of renal replacement therapy]. A correlation test was conducted to explore the relationship between the NLR and other important parameters (eGFR, serum creatinine, proteinuria, hypertension and renal pathologic lesions). The predictive value was determined by the area under the receiver operating characteristics curve (AUROC). Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate renal progression and prognosis. The NLR had the highest AUROC, which was 0.633 (p < 0.001). The correlation test revealed that the NLR was positively correlated with serum creatinine (r = 0.127, p < 0.001) and 24-hour urine protein (r = 0.18, p < 0.001) and negatively correlated with eGFR (r = 0.14, p < 0.001). Patients with IgAN who had a high NLR were more likely to have hypertension (p = 0.003). Multivariate Cox regression analysis indicated that a high NLR was an independent risk factor for IgAN even after adjustment for important clinical and pathological parameters (p = 0.043, HR = 1.74, 95%CI: 1.02-2.97). Kaplan-Meier analysis showed that a high NLR was significantly associated with the renal prognosis of patients with IgAN (p < 0.001), especially patients with stage 3 to 4 chronic kidney disease (p = 0.028) or 24-hour urine protein of >1 g/day (p < 0.001). An elevated NLR affects the renal progression and prognosis in patients with IgAN and could be a marker for evaluation of renal function and pathologic lesions.

The majority of our insight about glomerulonephritis (GN) is from observational research. Because proteinuria is an important element of outcome in GN, the validity of observational analyses is dependent on the metric used to model proteinuria. Previous metrics of proteinuria included the value at baseline, the average of all values over the entire follow-up (time-averaged), the instantaneous value at each time point (time-varying), or the average of all values prior to each time point, and each of these standardized to body surface area. It was not known which of these metrics best accounts for the risk of renal outcome and should be used in GN research. To address this, we studied 1351 adult patients with IgA nephropathy, focal segmental glomerulosclerosis, and membranous nephropathy from the Toronto GN Registry. Cox regression models for the risk of end-stage renal disease or a halving of estimated glomerular filtration rate included each proteinuria metric and were compared using model fit and discrimination. Proteinuria did not need to be standardized to body surface area. Time-varying proteinuria was the best metric to account for the prognostic effects of proteinuria over time, especially in focal segmental glomerulosclerosis and IgA nephropathy over the majority of follow-up, and in membranous nephropathy earlier in the disease course. Using alternate proteinuria metrics biased analyses up to 30.3%. These findings can improve the validity and design of future observational and prediction modeling studies in GN.

To explore the association between serum fibrinogen (FIB) and clinicopathological features and renal prognosis in type 2 diabetic nephropathy (T2DN), and develop a web-based dynamic model to predict renal progression. This paper retrospectively enrolled 173 biopsy-proven T2DN patients and stratified them by the optimal FIB cutoff. Renal progression was defined as a >50% decline in eGFR, doubling of creatinine, or onset of end-stage renal disease (ESRD). Cox regression analysis was used to screen out the independent predictors of T2DN progression; a web-based dynamic prediction model was established and evaluated using time-dependent receiver operating characteristic (Time-ROC) curves, calibration curves, and decision curve analysis (DCA). Of the 173 patients, 81 (46.82%) experienced the renal endpoint event. Multifactorial Cox regression analysis showed that eGFR, hemoglobin, FIB, parathyroid hormone, and interstitial fibrosis and tubular atrophy (IFTA) scores were independent risk factors for T2DN progression (P < 0.05). Among the three models constructed based on these factors, model 3 had the highest areas under the curve (AUC) (90.42; 95% CI, 85.80-95.04). The AUC of the risk prediction model constructed by the nomogram was 0.846, 0.752, and 0.754 at 1, 3, and 5 years, showing good discrimination, and the Web-based dynamic nomogram demonstrated good calibration. FIB is an independent predictor of T2DN progression. A web-based dynamic model was developed to predict renal progression risk in T2DN.

BackgroundChronic kidney disease (CKD) is associated with increased risk of renal and cardiovascular events. It has been claimed that endogenous methylarginines, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are contributing factors. However, earlier studies were partly contradictory and mainly focused on prevalent dialysis patients. Moreover, the potential contribution of degradation products, such as acetylated ADMA and SDMA (AcADMA and AcSDMA) and other methylarginines including L-NG-monomethylarginine (LNMMA) remains unknown. To better understand their potential pathophysiological contribution to renal and cardiovascular events, we aimed to provide a comprehensive analysis of methylarginines in a cohort of patients with non-dialysis CKD.MethodsBlood samples of 528 patients with CKD KDIGO G2 to G4 were obtained from the CARE FOR HOMe study. Baseline plasma levels of ADMA, SDMA, AcADMA, AcSDMA, and LNMMA were measured by liquid chromatography—tandem mass spectrometry. All patients were followed annually for CKD progression and for incident atherosclerotic cardiovascular events.ResultsDuring 5.1 ± 2.1 years follow-up, 80 patients displayed CKD progression and 145 patients developed incident atherosclerotic cardiovascular events. In univariate Cox regression analyses, elevated plasma levels of all five metabolites were associated with both CKD progression and atherosclerotic cardiovascular disease. However, adjustment for confounders attenuated the prognostic implications of ADMA, LNMMA, AcADMA and AcSDMA. In contrast, patients in the highest tertile of plasma SDMA remained at highest risk for CKD progression and incident atherosclerotic cardiovascular events in fully adjusted Cox regression analyses.ConclusionOur results underline a potential pathophysiological role of SDMA in CKD progression and atherosclerotic cardiovascular disease among non-dialysis CKD patients. SDMA predicts CKD progression and future atherosclerotic cardiovascular events more consistently than other methylarginines. Future experimental and clinical studies should therefore focus upon SDMA rather than upon ADMA.

Inflammation plays a crucial role in the progression of autosomal dominant polycystic kidney disease (ADPKD). While tolvaptan is primarily known for its vasopressin V2 receptor antagonism, its potential anti-inflammatory effects remain under investigation. This study aimed to evaluate the impact of tolvaptan on inflammatory markers and renal progression in ADPKD patients. This retrospective, two-center cohort study included 80 ADPKD patients, with 40 receiving tolvaptan and 40 serving as controls. Inflammatory markers, including C-reactive protein (CRP), systemic inflammatory index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and renal function parameters such as glomerular filtration rate (GFR) and proteinuria, were analyzed over a 1-year follow-up period. In the tolvaptan group, CRP, SII, PLR, proteinuria, and uric acid levels significantly decreased, whereas these markers increased in the control group. GFR remained stable in the tolvaptan group but declined significantly in the control group ( p  < 0.001). No significant correlation was found between GFR and inflammatory markers in either group. Our findings suggest that tolvaptan may contribute to reducing systemic inflammation in ADPKD patients while preserving renal function. These results align with previous studies indicating a link between inflammation and ADPKD progression.