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Dual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P = .02) and donors had a higher KDPI score (median 96% vs. 91%, P < .0001). DKT operative time was higher compared to SKT (+1.4 hours, P < .0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P = .77) and hospital length of stay (median 4.0 vs. 3.0 days, P = .21) between DKT and SKT. Grade I Clavien-Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P = .008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P = .04), interstitial fibrosis (P = .02), tubular atrophy (P = .01), and arterial thickening (P = .03) on 1-year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1- (P = .004) and 2-years post-transplant (P = .01). There were no differences in patient (HR 1.3, 95% CI .5-3.3, P = .58) or graft (HR 1.1, 95% CI .5-2.3, P = .83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In patients with kidney disease, nephrotic syndrome can lead to several complications including progressive kidney dysfunction. Proteinuria may lead to the formation of cellular or fibrous crescents with reciprocal development of rapidly progressive glomerulonephritis or focal glomerulosclerosis. Proteinuria may also cause overload and dysfunction of tubular epithelial cells, eventually resulting in tubular atrophy and interstitial fibrosis. Hypoalbuminemia is usually associated with increased risk of mortality and kidney dysfunction. Dyslipidemia may increase the risk of atherosclerotic complications, cause podocyte dysfunction and contribute to vascular thrombosis. Urinary loss of anticoagulants and overproduction of coagulation factors may facilitate a hypercoagulable state. Edema, hypogammaglobulinemia, loss of complement factors, and immunosuppressive therapy can favor infection. Treatment of these complications may reduce their impact on the severity of NS. Nephrotic syndrome is a kidney disorder that can worsen the quality of life and increase the risk of kidney disease progression., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Hypertension is a risk factor for acute kidney injury. In this study, we aimed to identify the optimal blood pressure (BP) targets for CKD and non-CKD patients. We analyzed the data of the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) to determine the nonlinear relationship between BP and renal disease development using the Generalized Additive Model (GAM). Optimal systolic BP/diastolic BP (SBP/DBP) with lowest renal risk were estimated using GAM. Logistic regression was employed to find odds ratios (ORs) of adverse renal outcomes by three BP groups (high/medium/low). Both study trials have demonstrated a "U"-shaped relationship between BP and renal outcomes. For non-CKD patients in SPRINT trial, risk of 30% reduction in eGFR among intensive group patients with DBP ≤ 70 mmHg was significantly higher than the group with DBP between 71 and 85 mmHg (OR = 2.31, 95% CI = 1.51-3.53). For non-CKD patients in ACCORD trial, risk of doubling of serum creatinine (SCr) or >20 mL/min decrease in eGFR among intensive group patients with DBP ≤ 70 mmHg was significantly higher than the group with DBP between 71 and 85 mmHg (OR = 1.49, 95% CI = 1.12-1.99). For CKD patients in SPRINT trial, there are no significant differences in renal outcomes by different SBP/DBP levels. Our analysis of both SPRINT and ACCORD datasets demonstrated that lower-than-optimal DBP may lead to poor renal outcomes in non-CKD patients. Healthcare providers should be cautious of too low DBP level in intensive BP management due to poor renal outcomes for non-CKD patients., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objectives: Despite improvement of short-term graft survival over recent years, long-term graft survival after kidney transplantation has not improved. Studies in the general population suggest the Mediterranean diet benefits kidney function preservation. We investigated whether adherence to the Mediterranean diet is associated with kidney outcomes in kidney transplant recipients., Design, Setting, Participants, & Measurements: We included 632 adult kidney transplant recipients with a functioning graft for ≥1 year. Dietary intake was inquired using a 177-item validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed using a nine-point Mediterranean Diet Score. Primary end point of the study was graft failure and secondary end points included kidney function decline (doubling of serum creatinine or graft failure) and graft loss (graft failure or death with a functioning graft). Cox regression analyses were used to prospectively study the associations of the Mediterranean Diet Score with study end points., Results: During median follow-up of 5.4 (interquartile range, 4.9-6.0) years, 76 participants developed graft failure, 119 developed kidney function decline, and 181 developed graft loss. The Mediterranean Diet Score was inversely associated with all study end points (graft failure: hazard ratio [HR], 0.68; 95% confidence interval [95% CI], 0.50 to 0.91; kidney function decline: HR, 0.68; 95% CI, 0.55 to 0.85; and graft loss: HR, 0.74; 95% CI, 0.63 to 0.88 per two-point increase in Mediterranean Diet Score) independent of potential confounders. We identified 24-hour urinary protein excretion and time since transplantation to be an effect modifier, with stronger inverse associations between the Mediterranean Diet Score and kidney outcomes observed in participants with higher urinary protein excretion and participants transplanted more recently., Conclusions: Adherence to the Mediterranean diet is associated with better kidney function outcomes in kidney transplant recipients., (Copyright © 2020 by the American Society of Nephrology.)

Background: Despite extensive research on proteinuria's impact on chronic kidney disease progression, there is no direct comparison of outcomes in biopsy-diagnosed glomerular disease (GD) patients with nephrotic syndrome (NS) or nephrotic range proteinuria (NRP). Our study addresses this gap, comparing long-term outcomes between NS and NRP. Methods: We conducted a retrospective study on 240 kidney biopsy-proven GD patients, tracked from 2010 to 2015 until end-stage kidney disease (ESKD), death, or the study end in January 2022. Results: The median follow-up was 8.8 years. Diagnoses were predominantly nonproliferative (53%), proliferative (25%) nephropathies, diabetic nephropathy (12%), and paraprotein diseases (10%). NS was observed in 141 (59%) patients, presenting more frequently with arterial hypertension, higher eGFR, increased proteinuria, and dyslipidemia than NRP patients. NRP patients often had proliferative GD and diabetic nephropathy; their renal chronicity score was higher. The ESKD endpoint occurred in 35% NS and 39% NRP patients (p 0.4). The cohort's mean kidney survival time was 8.2 years. In a multivariate analysis, NS, lower eGFR, a higher renal chronicity score, and diabetic nephropathy were associated with ESKD. A total of 64 patients (27%) died, 73% post-kidney replacement therapy initiation, and mostly from cardiovascular disease (63%). Mortality between proteinuria forms showed no difference. The multivariate analysis found lower eGFR, a higher Charlson comorbidity score, and diabetic nephropathy associated with mortality. Conclusions: Our study found no difference in all-cause mortality between NS and NRP in glomerular diseases. However, an adjusted analysis revealed poorer kidney survival for NS patients, emphasizing the need for personalized management to improve renal prognoses. [ABSTRACT FROM AUTHOR]

Hypertensive nephropathy continues to be a major cause of end-stage renal disease and poses a significant global health burden. Despite the staggering development of research in hypertensive nephropathy, scientists and clinicians can only seek out useful information through articles and reviews, it remains a hurdle for them to quickly track the trend in this field. This study uses the bibliometric method to identify the evolutionary development and recent hotspots of hypertensive nephropathy. The Web of Science Core Collection database was used to extract publications on hypertensive nephropathy from January 2000 to November 2023. CiteSpace was used to capture the patterns and trends from multi-perspectives, including countries/regions, institutions, keywords, and references. In total, 557 publications on hypertensive nephropathy were eligible for inclusion. China (n = 208, 37.34%) was the most influential contributor among all the countries. Veterans Health Administration (n = 19, 3.41%) was found to be the most productive institution. Keyword bursting till now are renal fibrosis, outcomes, and mechanisms which are predicted to be the potential frontiers and hotspots in the future. The top seven references were listed, and their burst strength was shown. A comprehensive overview of the current status and research frontiers of hypertensive nephropathy has been provided through the bibliometric perspective. Recent advancements and challenges in hypertensive nephropathy have been discussed. These findings can offer informative instructions for researchers and scholars. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic kidney disease (CKD) is a major health problem with a rising prevalence due to comorbidities like diabetes and hypertension. The aim of this research was to audit the assessment and therapeutic management of proteinuria in CKD patients at the Cantonal Hospital Baselland (KSBL) in Switzerland and determine associations between patient comorbidities, rehospitalisation, death, and the quality of therapeutic management. Methods: We analysed data from 427 adults with CKD (eGFR < 45 mL/min/1.73 m2) hospitalised on the internal medicine ward in 2022. Results: The mean age was 85 years (range: 79–89), 45.9% were female, and the median eGFR was 32.8 mL/min/1.73 m2 (range: 25–40). Proteinuria assessment was performed in 120 (28.1%) patients (the ProtU group), and a corresponding treatment was prescribed in 59%. The ProtU group had a higher quota of patients with diabetes (44.1% vs. 33%, p = 0.048) and obesity (21.2% vs. 12.5%, p = 0.039) when compared to the group without proteinuria assessment (the Ustix group). Twelve-month survival was not significantly different between the groups (HR: 0.75; 95% CI: 0.488–1.154; p-value = 0.191). However, survival was significantly better in patients who received an antiproteinuric treatment compared to those who did not (HR: 0.30; 95% CI: 0.121–0.0761; p = 0.011). Conclusions: Improvements need to be made in managing CKD at the KSBL in accordance with the guidelines. [ABSTRACT FROM AUTHOR]

Premenopausal women generally exhibit lower blood pressure and a lower prevalence of hypertension than men of the same age, but these differences reverse postmenopause due to estrogen withdrawal. Sexual dimorphism has been described in different components of kidney physiology and pathophysiology, including the renin–angiotensin–aldosterone system, endothelin system, and tubular transporters. This review explores the sex-specific differences in kidney function and blood pressure regulation. Understanding these differences provides insights into potential therapeutic targets for managing hypertension and kidney diseases, considering the patient's sex and hormonal status. [ABSTRACT FROM AUTHOR]

Many kidney diseases are associated with proteinuria. Since proteinuria is independently associated with kidney function loss, anti-proteinuric medication, often in combination with dietary salt restriction, comprises a major cornerstone in the prevention of progressive kidney failure. Nevertheless, complete remission of proteinuria is very difficult to achieve, and most patients with persistent proteinuria slowly progress toward kidney failure. It is well-recognized that proteinuria leads to kidney inflammation and fibrosis via various mechanisms. Among others, complement activation at the apical side of the proximal tubular epithelial cells is suggested to play a crucial role as a cause of progressive loss of kidney function. However, hitherto limited attention is given to the pathophysiological role of tubular complement activation relative to glomerular complement activation. This review aims to summarize the evidence for tubular epithelial complement activation in proteinuric kidney diseases in relation to loss of kidney function. [ABSTRACT FROM AUTHOR]

Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age-related proteinuria. However, these studies have not explored CR in established renal disease. Therefore, this study aimed to investigate the impact of CR on established proteinuria. Rats, aged 12 ± 2 weeks, were administered 2.1 mg/kg of Adriamycin. Six weeks after injection, protein excretion was measured, and a [13N]ammonia positron emission tomography (PET) scan was conducted to assess kidney perfusion. After 7 weeks rats were divided into four groups: ad libitum (AL) and CR groups fed either a 12% or a 20% protein diet. All groups were treated for 12 weeks. Blood pressure was measured and a second PET scan was acquired at the end of the study. The animals subjected to CR exhibited a 20.3% decrease in protein excretion (p = 0.003) compared to those in the AL groups. Additionally, blood pressure in the CR group was 21.2% lower (p < 0.001) than in the AL groups. While kidney function declined over time in all groups, the 20% CR group demonstrated the smallest decline. Thus CR effectively reduces urinary protein excretion and lowers blood pressure in rats with established proteinuria. [ABSTRACT FROM AUTHOR]

Renin-Angiotensin-System (RAS) inhibitors remained the only effective nephro-protective treatments until recent landmark trials showed that sodium-glucose co-transporter 2 (SGLT2) inhibitors and non-steroid mineral receptor antagonists added-on RAS inhibitor therapy dramatically slowed renal disease progression in patients with chronic kidney disease (CKD). However, despite this impressive advancement, a substantial proportion of patients remains at high risk of renal and cardiovascular events. Thus, we are still far from achieving the therapeutic ceiling in CKD. However, we are entering a new era in the management of patients with CKD with innovative methodological approaches to test disease-modifying medications in the context of personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes, with the incidence rate increasing yearly, which is the leading cause of chronic kidney disease (CKD) and endstage kidney disease. Abelmoschus Manihot capsule, as a proprietary Chinese patent medicine, is widely used for treating CKD in China. Currently, the combination of Abelmoschus Manihot (AM) capsule and renin-angiotensinaldosterone system inhibitor (RASI) has gained popularity as a treatment option for DKD, with more and more randomized control trials (RCTs) in progress. However, the high-quality clinical evidence supporting its application in DKD is still insufficient. Aim of the study: To comprehensively and systematically evaluate the efficacy and safety of AM capsule combined with RASI in the treatment of DKD. Materials and methods: English and Chinese databases such as Pubmed, Cochrane Library, Embase, CNKI, SinoMed, WF, and VIP were searched to collect the RCTs of AM capsule in treatment of DKD. Then Two investigators independently reviewed and extracted data from the RCTs which met the inclusion criteria. The quality of the data was assessed using the Cochrane risk of bias assessment tool, and meta-analysis was performed using RevMan 5.4 software. Results: 32 RCTs with a total of 2,881 DKD patients (1,442 in the treatment group and 1,439 in the control group) were included. The study results showed that AM capsule combined with RASI could be more effective in decreasing 24h-UTP [MD = -442.05, 95% CI (-609.72, -274.38), p < 0.00001], UAER [MD = -30.53, 95% CI (-39.10, -21.96), p < 0.00001], UACR [MD = -157.93, 95% CI (-288.60, -27.25), p < 0.00001], Scr [MD = -6.80, 95% CI (-9.85, -3.74), p < 0.0001], and BUN [MD = -0.59, 95% CI (-1.07, -0.12), p = 0.01], compared to using RASI alone. According to the subgroup analyses, the combination of AM and ARB seems to be more effective in reducing UAER than the combination of ACEI, and the addition of AM may achieve a more significant clinical effect on decreasing Scr for DKD patients with 24h-UTP>2 g or Scr>110--133 μmol/L and >133 μmol/L. Furthermore, no additional adverse reactions were observed in the combination group [OR = 1.06; 95%CI: (0.66, 1.69), p = 0.82]. Conclusion: Combining AM with RASI may be a superior strategy for DKD treatment compared to RASI monotherapy. However, due to significant heterogeneity, the results should be interpreted with great caution, and more high-quality RCTs with multi-centers, different stages of DKD, large sample sizes, and long follow-up periods are still needed to improve the evidence quality of AM for DKD in the future. [ABSTRACT FROM AUTHOR]

Introduction: High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease, whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN. Methods: A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus and kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline or kidney failure, was evaluated using Cox models. Results: Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238–5.400, p = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783–0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756–0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95% CI, 1.791–14.944; p = 0.002). Conclusion: Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression. [ABSTRACT FROM AUTHOR]

Rituximab (RTX) has been the first option in idiopathic membranous nephropathy (IMN). However, the clinical effect was not very satisfactory. This study aimed to explore the clinical efficacy and safety of the combination of RTX and glucocorticoids (GC) in anti-phospholipase A2 receptor (anti-PLA2R) antibody positive IMN. Sixty-six patients were randomly divided into RTX/GC group (RTX infusion plus short-term oral GC) and RTX group (RTX infusion alone) in this prospective cohort study. Complete remission (CR) and partial remission (PR) were the primary outcomes. Adverse events were the secondary outcomes. The laboratory index including serum albumin, 24 h urinary protein, serum creatinine, estimated glomerular filtration rate, and anti-PLA2R antibody titer were also monitored. All patients were followed for at least 12 months. During the 12-month follow-up, the composite remission rates in RTX/GC and RTX groups were 74.3% and 67.7%, and the CR rates were 34.3% and 19.4%, respectively. The median time of remission in RTX/GC group was shorter than the RTX group (P < 0.001). Compared with RTX monotherapy, the combination of RTX and GC significantly decreased the anti-PLA2R antibody titer (P = 0.028). No significant difference was observed in the incidence of adverse events. The results of the Kaplan–Meier survival analysis indicated that the cumulative CR rate and cumulative composite remission rate in RTX/GC group were all better than the RTX group (P = 0.043, P = 0.040, respectively). The combination of RTX and GC was better than RTX monotherapy without increasing the adverse events in the treatment of IMN. [ABSTRACT FROM AUTHOR]

Recent studies suggest that disruptions in intestinal homeostasis, such as changes in gut microbiota composition, infection, and inflammatory-related gut diseases, can be associated with kidney diseases. For instance, genomic investigations highlight how susceptibility genes linked to IgA nephropathy are also correlated with the risk of inflammatory bowel disease. Conversely, investigations demonstrate that the use of short-chain fatty acids, produced through fermentation by intestinal bacteria, protects kidney function in models of acute and chronic kidney diseases. Thus, the dialogue between the gut and kidney seems to be crucial in maintaining their proper function, although the factors governing this crosstalk are still emerging as the field evolves. In recent years, a series of studies have highlighted the significance of enteroendocrine cells (EECs) which are part of the secretory lineage of the gut epithelial cells, as important components in gut-kidney crosstalk. EECs are distributed throughout the epithelial layer and release more than 20 hormones in response to microenvironment stimuli. Interestingly, some of these hormones and/or their pathways such as Glucagon-Like Peptide 1 (GLP-1), GLP-2, gastrin, and somatostatin have been shown to exert renoprotective effects. Therefore, the present review explores the role of EECs and their hormones as regulators of gut-kidney crosstalk and their potential impact on kidney diseases. This comprehensive exploration underscores the substantial contribution of EEC hormones in mediating gut-kidney communication and their promising potential for the treatment of kidney diseases. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) and its downstream complications (i.e. cardiovascular) are a major source of morbidity worldwide. Additionally, deaths due to CKD or CKD-attributable cardiovascular disease account for a sizeable proportion of global mortality. However, the advent of new pharmacotherapies, diagnostic tools, and global initiatives are directing greater attention to kidney health in the public health agenda, including the implementation of effective strategies that (i) prevent kidney disease, (ii) provide early CKD detection, and (iii) ameliorate CKD progression and its related complications. In this Review, we discuss major risk factors for incident CKD and CKD progression categorized across cardiovascular (i.e. hypertension, dyslipidemia, cardiorenal syndrome), endocrine (i.e. diabetes mellitus, hypothyroidism, testosterone), lifestyle (i.e. obesity, dietary factors, smoking), and genetic/environmental (i.e. CKDu/Mesoamerican nephropathy, APOL1, herbal nephropathy) domains, as well as scope, mechanistic underpinnings, and management. [ABSTRACT FROM AUTHOR]

Sodium‐glucose cotransporter (SGLT)‐2 inhibitors have recently been approved for chronic kidney disease (CKD) based on their ability to lower proteinuria and slow CKD progression independent of diabetes status. In diabetic renal disease, modulation of tubuloglomerular feedback (TGF) leading to lower intraglomerular pressure has been postulated as one of the mechanisms of renal protection with SGLT2 inhibition; however, this mechanism has not been sufficiently explored in non‐diabetic CKD. We hypothesized that SGLT2 inhibition exerts renoprotection in CKD through increasing TGF despite normoglycemia. To test this hypothesis, we used an integrative mathematical model of human physiology, HumMod. Stage 3 CKD conditions were simulated by reducing nephron mass which was associated with hypertension, low glomerular filtration rate (GFR) (55 mL/min), hyperfiltration of remnant nephrons, elevated albuminuria (500 mg/day), and minimal levels of urinary glucose (0.02 mmol/L). SGLT2 inhibition was associated with acute reductions in GFR associated with afferent arteriolar vasoconstriction due to TGF. After 12 months, glomerular pressure, nephron damage, and chronic GFR decline were reduced with SGLT2 inhibition with additional SGLT1 inhibitory effects further enhancing these effects. This model supports the use of SGLT2 inhibitors to reduce hyperfiltration in CKD and mitigate renal disease progression, even in the absence of diabetes. [ABSTRACT FROM AUTHOR]

Background: The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes. Methods: The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow‐up period. Results: Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person‐years of follow‐up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person‐years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause‐specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60–0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13–1.64) for BP above both targets, compared with BP controlled within 2012 target only. Conclusion: The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline. [ABSTRACT FROM AUTHOR]

Autosomal-Dominant Polycystic Kidney Disease (ADPKD) is a monogenic disorder initiated by mutations in either PKD1 or PKD2 genes, responsible for encoding polycystin 1 and polycystin 2, respectively. These proteins are primarily located within the primary cilia. The disease follows an inexorable progression, leading most patients to severe renal failure around the age of 50, and extra-renal complications are frequent. A cure for ADPKD remains elusive, but some measures can be employed to manage symptoms and slow cyst growth. Tolvaptan, a vasopressin V2 receptor antagonist, is the only drug that has been proven to attenuate ADPKD progression. Recently, autophagy, a cellular recycling system that facilitates the breakdown and reuse of aged or damaged cellular components, has emerged as a potential contributor to the pathogenesis of ADPKD. However, the precise role of autophagy in ADPKD remains a subject of investigation, displaying a potentially twofold impact. On the one hand, impaired autophagy may promote cyst formation by inducing apoptosis, while on the other hand, excessive autophagy may lead to fibrosis through epithelial to mesenchymal transition. Promising results of autophagy inducers have been observed in preclinical studies. Clinical trials are warranted to thoroughly assess the long-term safety and efficacy of a combination of autophagy inducers with metabolic and/or aquaferetic drugs. This research aims to shed light on the complex involvement of autophagy in ADPKD, explore the regulation of autophagy in disease progression, and highlight the potential of combination therapies as a promising avenue for future investigations. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a modern epidemic worldwide. Introducing renin–angiotensin system (RAS) inhibitors (i.e., ACEi or ARB) not only as blood-pressure-lowering agents, but also as nephroprotective drugs with antiproteinuric potential was a milestone in the therapy of CKD. For decades, this treatment remained the only proven strategy to slow down CKD progression. This situation changed some years ago primarily due to the introduction of drugs designed to treat diabetes that turned into nephroprotective strategies not only in diabetic kidney disease, but also in CKD unrelated to diabetes. In addition, several drugs emerged that precisely target the pathogenetic mechanisms of particular kidney diseases. Finally, the role of metabolic acidosis in CKD progression (and not only the sequelae of CKD) came to light. In this review, we aim to comprehensively discuss all relevant therapies that slow down the progression of non-diabetic kidney disease, including the lowering of blood pressure, through the nephroprotective effects of ACEi/ARB and spironolactone independent from BP lowering, as well as the role of sodium–glucose co-transporter type 2 inhibitors, acidosis correction and disease-specific treatment strategies. We also briefly address the therapies that attempt to slow down the progression of CKD, which did not confirm this effect. We are convinced that our in-depth review with practical statements on multiple aspects of treatment offered to non-diabetic CKD fills the existing gap in the available literature. We believe that it may help clinicians who take care of CKD patients in their practice. Finally, we propose the strategy that should be implemented in most non-diabetic CKD patients to prevent disease progression. [ABSTRACT FROM AUTHOR]

The current trial investigates the effect of renal diet therapy and nutritional education on the estimated glomerular filtration rate (eGFR), blood pressure (BP) and depression among patients with chronic kidney disease (CKD). A total of 120 CKD patients (stages 3–4) (15

The development of acute kidney injury after surgery is associated with significant mortality and morbidity and with worse short and long-term outcomes. Patients who develop acute kidney injury are at an increased risk of developing long-term renal dysfunction, which leads to lower quality of life and greater financial burden on the healthcare system. Although there are various systems to classify the severity of acute kidney injury, most systems only measure components that deteriorate after significant renal damage, such as urine output and serum creatinine. Surgical trauma and stress trigger acute kidney injury development, in addition to multiple co-morbidities, cardiovascular disease, and postoperative factors. The pathophysiology of acute kidney injury is complex, and this is reflected in the heterogenous population that is affected. Treatment is largely supportive and focuses on ensuring adequate renal perfusion, correcting electrolyte abnormalities and avoiding further renal injury. Current research focuses on novel biomarkers that detect decreased renal function earlier and that the deteriorating renal function can be treated before long-lasting damage occurs. This review discusses the epidemiology, aetiology, risk factors, and short and long-term surgical outcomes of acute kidney injury. Treatment, prevention, and recent developments in future research are also discussed. [ABSTRACT FROM AUTHOR]

Kidney fibrosis is a common pathophysiological mechanism of chronic kidney disease (CKD) progression caused by several underlying kidney diseases. Among various contributors to kidney fibrosis, transforming growth factor-β1 (TGF-β1) is the major factor driving fibrosis. TGF-β1 exerts its profibrotic attributes via the activation of canonical and non-canonical signaling pathways, which induce proliferation and activation of myofibroblasts and subsequent accumulation of extracellular matrix. Over the past few decades, studies have determined the TGF-β1 signaling pathway inhibitors and evaluated whether they could ameliorate the progression of CKD by hindering kidney fibrosis. However, therapeutic strategies that block TGF-β1 signaling have usually demonstrated unsatisfactory results. Herein, we discuss the therapeutic concepts of the TGF-β1 signaling pathway and its inhibitors and review the current state of the art regarding regarding TGF-β1 inhibitors in CKD management. [ABSTRACT FROM AUTHOR]

Background: A growing number of studies have reported a close relationship between high serum calcium (Ca)/low serum magnesium (Mg) and vascular calcification. Endothelial dysfunction and vascular inflammation seem plausible risk factors for the enhanced progression of kidney disease. The aim of this study was to evaluate the role of the Ca/Mg ratio as a predictor of the early onset of renal replacement therapy (RRT). Methods: This was a prospective study conducted in an outpatient low-clearance nephrology clinic, enrolling 693 patients with stages 4–5 of CKD. Patients were divided into two groups according to the start of renal replacement therapy (RRT). Results: The kidney's survival at 120 months was 60% for a Ca–Mg ratio < 6 and 40% for a Ca–Mg ratio ≥ 6 (p = 0.000). Patients who started RRT had lower levels of Hb, Ca, Mg, albumin, and cholesterol and higher values of phosphorus, the Ca/Mg ratio, and PTH. High values of phosphorus and the Ca/Mg ratio and low levels of Mg and GFR were independent predictors of entry into RRT. A high Ca/Mg ratio, high phosphorus levels, and low levels of GFR were associated with a cumulative risk for initiation of RRT. Conclusions: In our population, the Ca/Mg ratio is an independent predictive factor for the initiation of a depurative technique. [ABSTRACT FROM AUTHOR]

Background: In glomerular disease, the degree of proteinuria is closely related to the progression of chronic kidney disease, and its reduction is associated with a slower decline in the glomerular filtration rate (eGFR) and consequent improvement in the renal prognosis. The aim of this study was to evaluate the impact of proteinuria reduction on the decline of the eGFR in patients with glomerular disease, during the first year after the diagnosis. Methods: This was a retrospective analysis of patients with primary glomerular disease, followed at the Nephrology Department of Centro Hospitalar Universitário Lisboa Norte, during 2019. We analyzed demographic, clinical and laboratorial characteristics (creatinine, GFR, urine analysis and quantification of proteinuria determined by the proteinuria/creatinuria ratio, in the first morning urine or a 24 h urine sample). The outcome assessed was the decline in renal function, defined as a reduction in the GFR ≥ 25%, during the follow-up period. Results: We analyzed 197 patients with glomerular disease, with a mean age of 41.7 ± 19.7 years and follow-up time of 6.5 ± 5.3 years. At the time of the diagnosis, the eGFR was 81.5 ± 49.8 mL/min/1.73 m2 and proteinuria was 3.5 g/24 h (IQR 5.8). At one-year follow-up, median proteinuria was 0.9 g/24 h (IQR 2.4). At the end of the follow-up, mean eGFR was 72.1 ± 43.3 mL/min/1.73 m2. Proteinuria (p = 0.435) and the eGFR (p = 0.880) at the time of diagnosis did not correlate with long-term decline in the eGFR. Proteinuria < 1 g/24 h (HR 0.45 (95% CI 0.25–0.83) p = 0.011) after the first year was protective against long-term decline in the eGFR. It maintained this association with the long-term eGFR decline, independently of the duration of the follow-up (HR 0.30 (95% CI 0.17–0.52) p < 0.001). Conclusions: Proteinuria reduction to lower than 1 g/24 h, during the first year after diagnosis, was a protective factor for the long-term decline of kidney function, having a more important role than proteinuria or the GFR at the time of the diagnosis. [ABSTRACT FROM AUTHOR]

Rituximab is one of the first-line therapies for patients with membranous nephropathy (MN) at high risk of progression towards kidney failure. We investigated whether the response to Rituximab was affected by sex and anti-PLA2R antibody levels in 204 consecutive patients (148 males and 56 females) with biopsy-proven MN who were referred to the Nephrology Unit of the Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII from March 2001 to October 2016 and managed conservatively for at least 6 months. The primary outcome was a combined endpoint of complete (proteinuria <0.3 g/24 h) or partial (proteinuria <3.0 g/24 h and >50% reduction vs. baseline) remission. Patients gave written informed consent to Rituximab treatment. The study was internally funded. No pharmaceutical company was involved. Anti-PLA2R antibodies were detectable in 125 patients (61.3%). At multivariable analyses, female gender (p = 0.0198) and lower serum creatinine levels (p = 0.0108) emerged as independent predictors of better outcome (p = 0.0198). The predictive value of proteinuria (p = 0.054) and anti-PLA2R titer (p = 0.0766) was borderline significant. Over a median (IQR) of 24.8 (12.0-36.0) months, 40 females (71.4%) progressed to the combined endpoint compared with 73 males (49.3%). Anti-PLA2R titers at baseline [127.6 (35.7-310.8) vs. 110.1 (39.9-226.7) RU/ml] and after Rituximab treatment were similar between the sexes. However, the event rate was significantly higher in females than in males [HR (95%): 2.12 (1.44-3.12), p = 0.0001]. Forty-five of the 62 patients (72.3%) with anti-PLA2R titer below the median progressed to the combined endpoint versus 35 of the 63 (55.6%) with higher titer [HR (95%): 1.97 (1.26-3.07), p < 0.0029]. The highest probability of progressing to the combined endpoint was observed in females with anti-PLA2R antibody titer below the median (86.7%), followed by females with anti-PLA2R antibody titer above the median (83.3%), males with titer below the median (68.1%), and males with titer above the median (44.4%). This trend was statistically significant (p = 0.0023). Similar findings were observed for complete remission (proteinuria <0.3 g/24 h) and after analysis adjustments for baseline serum creatinine. Thus, despite similar immunological features, females were more resilient to renal injury following Rituximab therapy. These findings will hopefully open new avenues to identify the molecular pathways underlying sex-related nephroprotective effects. [ABSTRACT FROM AUTHOR]

In diabetes kidney disease (DKD), orthostatic hypotension and supine hypertension often coexist, which, when uncontrolled, contributes to the progression of proteinuria and renal dysfunction. Chronotherapy and elevation of the head of the bed during sleep are feasible clinical measures and could contribute to the control of supine hypertension and proteinuria in this group of patients. This study consists of a series of cases, in which nine consecutive patients with DKD, dysautonomia and supine hypertension (intervention group) were instructed to use chronotherapy and inclination of the head of the bed in six degrees during sleep. These patients were compared with a historical control group. The primary outcome was proteinuria behavior. The intervention group had a significant drop in proteinuria levels, while there was an increase in proteinuria in the control group (variation in the proteinuria/creatininuria index in an isolated sample from the intervention group: −6.60 ± 3.90 g/g; variation in the group control: +1.70 ± 7.10 g/g, p = 0.008). Chronotherapy and six-degree inclination of the head of the bed during sleep were associated with a significant decrease in proteinuria in patients in the intervention group, with conversion of nephrotic into non-nephrotic proteinuria in most of these patients. [ABSTRACT FROM AUTHOR]

Copyright of Hypertonia és Nephrologia is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Obesity‐related glomerulopathy (ORG) is a silent comorbidity which is increasing in incidence as the obesity epidemic escalates. ORG is associated with serious health consequences including chronic kidney disease, end‐stage renal disease (ESRD), and increased mortality. Although the pathogenic mechanisms involved in the development of ORG are not fully understood, glomerular hemodynamic changes, renin‐angiotensin‐aldosterone system (RAAS) overactivation, insulin‐resistance, inflammation and ectopic lipid accumulation seem to play a major role. Despite albuminuria being commonly used for the non‐invasive evaluation of ORG, promising biomarkers of early kidney injury that are emerging, as well as new approaches with proteomics and metabolomics, might permit an earlier diagnosis of this disease. In addition, the assessment of ectopic kidney fat by renal imaging could be a useful tool to detect and evaluate the progression of ORG. Weight loss interventions appear to be effective in ORG, although large‐scale trials are needed. RAAS blockade has a renoprotective effect in patients with ORG, but even so, a significant proportion of patients with ORG will eventually progress to ESRD despite therapeutic efforts. It is noteworthy that certain antidiabetic agents such as sodium‐glucose cotransporter 2 inhibitors (SGLT2i) or glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) could be useful in the treatment of ORG through different pleiotropic effects. In this article, we review current approaches and future perspectives in the care and treatment of ORG. [ABSTRACT FROM AUTHOR]

In recent decades, several important advances have taken place in the understanding of the pathogenesis underlying membranous nephropathy (MN) that have sparked renewed interest in its management. Four landmark trials in MN and a fifth clinical trial—which was a pilot study—have been published in recent years. The results from some of these trials have had a significant impact on the recommendations included in the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases, representing a significant step forward compared with the previous guideline in several aspects, including diagnosis, disease monitoring and treatment strategies. However, considering the rapidly evolving advances in the knowledge of MN and the recent publication of the STARMEN and RI-CYCLO trials, several recommendations contained in the guideline warrant updates. This article provides a perspective of the Immunonephrology Working Group of the European Renal Association regarding the management of MN in native kidneys of adult patients. [ABSTRACT FROM AUTHOR]

Background: Glomerular diseases (GDs) and other renal immunologic diseases are an important cause of morbidity and mortality. Providing a single point of service in collaboration with various specialists at a renal immunology clinic for such patients is not novel, but outcomes have not been reported. Here, we report the short-term outcome of Indian patients attending our clinic. Methods: This single-center prospective cohort study enrolled biopsy-proven immunologically-mediated adults with renal diseases between April 2018 and December 2019, and followed them for six months. The primary end point for the analysis was an incidence of end-stage renal disease (ESRD) or loss of >50% estimated glomerular filtration rate (eGFR) and patient survival at six months. Secondary endpoints were the rate of complete or partial remission, and impact of demographic factors. Results: Ninety two patients underwent renal biopsy for suspected immunological renal diseases. Fourteen (15.2%) cases were excluded for nonimmune etiologies, whereas 78 (84.7%) confirmed cases of immune etiology were included. Most common primary GD (n = 51) (93.5%) was membranous nephropathy (n = 20) (25.6%), whereas lupus nephritis was the most common (n = 8) (29.6%) secondary GD. Overall, 10 (12.8%) patients reached renal endpoint of ESRD or >50% fall in eGFR. Focal segmental glomerulosclerosis (FSGS) (27%) patients had worst renal outcome. Patient survival was 94.8%. Thirty patients (38.4%) achieved complete, whereas 24 each (30.7%) achieved partial remission and remained resistant to disease specific therapies, respectively. Univariate analysis identified hypertension, severity of hypertension, and resistance to achieve proteinuria remission as significantly associated (P < 0.001) factors with poor renal outcome. Conclusions: The present study shows that short term renal outcome of Indian patients with renal immune diseases remains poor. FSGS remains the GD with the worst renal outcome. Hypertension, its severity, failure to achieve proteinuria remission were significantly associated with poor renal outcomes. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major public health problem that affects more than 10% of the population worldwide and has a high mortality rate. Therefore, it is necessary to identify novel treatment strategies for CKD. Incidentally, renal fibrosis plays a central role in the progression of CKD to end-stage renal disease (ESRD). The activation of inflammatory pathways leads to the development of renal fibrosis. In fact, interleukin-33 (IL-33), a newly discovered member of the interleukin 1 (IL-1) cytokine family, is a crucial regulator of the inflammatory process. It exerts pro-inflammatory and pro-fibrotic effects via the suppression of tumorigenicity 2 (ST2) receptor, which, in turn, activates other inflammatory pathways. Although the role of this pathway in cardiac, pulmonary, and hepatic fibrotic diseases has been extensively studied, its precise role in renal fibrosis has not yet been completely elucidated. Recent studies have shown that a sustained activation of IL-33/ST2 pathway promotes the development of renal fibrosis. However, with prolonged research in this field, it is expected that the IL-33/ST2 pathway will be used as a diagnostic and prognostic tool for renal diseases. In addition, the IL-33/ST2 pathway seems to be a new target for the future treatment of CKD. Here, we review the mechanisms and potential applications of the IL-33/ST2 pathway in renal fibrosis; such that it can help clinicians and researchers to explore effective treatment options and develop novel medicines for CKD patients. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease-2019 (COVID-19) pandemic impacted healthcare services for kidney disease patients. Lockdown and social distancing were mandated worldwide, resulting in closure of medical services. The diagnosis of various kidney diseases may have been delayed during the COVID-19 pandemic because non-urgent tests and visits were postponed due to closure of medical services during the lockdown. Methods: We here report the impact of the COVID-19 pandemic on a total number of 209 native kidney diseases requiring renal biopsy for diagnosis in a retrospective observational study from a tertiary hospital in Germany. Results: The lockdown period in March and April 2020 primarily affected patients admitted to the normal medical ward with a compensatory increased rate of renal biopsies in the postlockdown phase. In addition, there was a shift toward more patients admitted with hemoglobinuria during the COVID-19 pandemic. This phenomenon of an increased number of patients with hemoglobinuria during the COVID-19 pandemic was specifically observed in a subgroup with hypertensive nephropathy requiring renal biopsy and associated with increased proteinuria, not attributed to the COVID-19 lockdown period itself. Conclusion: To our knowledge, this is the first report of identifying a subpopulation susceptible to closure of medical services during the COVID-19 pandemic and diagnostic delay of specific kidney diseases. Therefore, the COVID-19 pandemic should be regarded as a risk factor especially in patients with diseases other than COVID-19 primarily admitted to the normal medical ward. [ABSTRACT FROM AUTHOR]

Background: Proteinuria is a key biomarker in nephrology. It is central to diagnosis and risk assessment and the primary target of many important therapies. Etiologies resulting in pathological proteinuria include congenital and acquired disorders, as well as both glomerular (immune/non-immune mediated) and tubular defects. Summary: Untreated proteinuria is strongly linked to progressive loss of kidney function and kidney failure. Excess protein reaching the renal tubules is ordinarily resorbed by the tubular epithelium. However, when these mechanisms are overwhelmed, a variety of inflammatory and fibrotic pathways are activated, causing both interstitial fibrosis and glomerulosclerosis. Nevertheless, the specific mechanisms underlying this are complex and remain incompletely understood. Recently, a number of treatments, in addition to angiotensin system blockade, have been shown to effectively slow the progression of proteinuric chronic kidney disease. However, additional therapies are clearly needed. Key message: This review provides an update on the pathophysiology of proteinuria, the pathways leading to fibrosis, and an overview of current and emerging therapies. [ABSTRACT FROM AUTHOR]

Background: Obesity has become a major public health problem, and the prevalence of kidney diseases has increased in parallel. Among kidney diseases caused by metabolic disorders, obesity-related glomerulopathy (ORG) is secondary to obesity. Summary: ORG is mainly caused by glomerular hyperfiltration, dysregulation of hormone and cytokine secretion in adipose tissues, and ectopic lipid accumulation in renal cells. ORG is pathologically characterized by glomerular hypertrophy, with or without focal and segmental glomerulosclerosis. Patients with ORG usually present with proteinuria concomitant with metabolic disorders such as dyslipidemia and hypertension. Weight loss, RAAS inhibitors, and improved insulin resistance can reduce the progression of ORG. Conclusion: ORG is a growing renal pathological change in obese individuals, and a comprehensive understanding of the disease is pivotal to avoid its occurrence and improve quality of life for those with obesity. Key Messages:This review comprehensively describes the characteristics of ORG in pathological changes, clinical manifestations, pathogeneses and treatments. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Istanbul Faculty of Medicine / İstanbul Tıp Fakültesi Dergisi is the property of Istanbul Tip Fakultesi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Sodium tanshinone IIA sulfonate (STS) injection, the extractive of traditional Chinese medicine Danshen, is supposed to be a supplementary treatment in hypertensive nephropathy. Objectives: To evaluate the efficacy and safety of STS in treatment of hypertensive nephropathy. Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang database, Chinese Biomedicine Database (CBM), PubMed, Embase, Web of Science, and Cochrane Library from their inception to December 2018. All studies were screened by two reviewers according to the inclusion and exclusion criteria independently. The Cochrane Collaboration's risk tool was used to assess the methodological quality of the included studies. Reviewer Manager 5.3 was employed for statistical analysis. Results: Sixteen trials involving 1,696 patients were included. The meta-analysis results indicated a combination of STS and angiotensin receptor blockers (ARBs) was more effective than ARB monotherapy in modulating hypertensive nephropathy, as represented by improved estimated glomerular filtration rate (eGFR) [mean difference (MD) = 6.87, 95% CI (4.47, 9.28), P < 0.00001] and reduced 24 h urinary protein [MD = −0.23, 95% CI (−0.27, −0.19), P < 0.00001], serum creatinine (SCr) [MD = −21.74, 95% CI (−24.11, −19.38), P < 0.00001], cystatin-C [MD = −0.16, 95% CI (−0.24, −0.07), P = 0.0003], urinary immunoglobulin G (IgG) [MD = −0.85, 95% CI (−1.11, −0.59), P < 0.00001], and urinary transferrin [MD = −0.61, 95% CI (−1.04, −0.17), P = 0.007]. In addition, the combination therapy had better control in systolic blood pressure (SBP) [MD = −6.53, 95% CI (−8.19, −4.87), P < 0.00001] and diastolic blood pressure (DBP) [MD = −4.14, 95% CI (−5.69, −2.59), P < 0.00001]. Only three trials reported adverse events, and no adverse drug reactions were observed. Conclusions: STS combined with ARBs had a stronger effect on improving renal function in patients with primary hypertensive nephropathy than ARB monotherapy. The combination therapy also provided auxiliary hypotensive effects. Further large-scale, multicenter, and rigorously designed randomized controlled trials (RCTs) should be conducted to confirm our findings. [ABSTRACT FROM AUTHOR]

Background Among patients with nondialysis-dependent chronic kidney disease (NDD-CKD) and iron-deficiency anemia (IDA), ferric citrate increases hemoglobin and iron parameters and reduces serum phosphate and fibroblast growth factor 23 (FGF23), a key phosphate-regulating hormone. We conducted post hoc analyses of a phase 3 trial to explore associations between iron replacement, serum phosphate changes and FGF23 regulation. Methods We employed multivariable regression and longitudinal mixed-effects models to identify and confirm, respectively, whether baseline demographic and laboratory variables were associated with ferric citrate-induced changes in serum phosphate or FGF23 concentrations. We employed path analyses to determine whether changes in FGF23 concentrations were mediated via changes in serum phosphate and/or transferrin saturation (TSAT). Results We analyzed a total of 117 and 115 ferric citrate-treated and placebo-treated patients, respectively. At 16 weeks, ferric citrate significantly reduced serum phosphate versus placebo (P = 0.006) only among patients with elevated baseline serum phosphate (≥4.5 mg/dL) and did not reduce serum phosphate among patients with baseline serum phosphate within the population reference range. Ferric citrate reduced intact FGF23 and C-terminal FGF23 partially via changes in TSAT (for C-terminal FGF23) and serum phosphate (for intact FGF23) and partially via unknown/unmeasured mechanisms. Conclusions Ferric citrate reduced serum FGF23 concentrations (partially via effects on serum phosphate and iron balance) and did not reduce serum phosphate among patients with baseline serum phosphate concentrations within the population reference range. [ABSTRACT FROM AUTHOR]

Background/Aims: Cross-classification analyses are rarely reported. We investigated the prognostic factors for chronic kidney disease (CKD) progression using a body mass index (BMI)-based cross-classification approach. Methods: Patients' renal outcome (≥50% decline in the estimated glomerular filtration rate or end-stage renal disease) in each subcohort was examined. Results: The number of prognostic factors identified in the multivariate Cox analysis was smaller in the "BMI ≥25, female" and CKD stage 3 subcohorts than in other subcohorts. Prognostic factors identified in the "BMI ≥25, CKD stage 3" subcohort only comprised albuminuria and male sex, and those in the "BMI ≥25, female" subcohort only comprised albuminuria, hyperphosphatemia, and anemia. Albuminuria, kidney impairment, male sex, hyperphosphatemia, anemia, and increased pulse pressure × heart rate product (PP × HR; pulsatile stress) were stable renal prognostic factors in almost all subcohorts. On the other hand, the prognostic value of increased BMI, younger age, hypoalbuminemia, increased intact parathyroid hormone, and decreased estimated 24-h urinary potassium excretion (e24hUK) differed according to subcohort. BMI was positively associated with CKD progression in the "BMI ≥25, age ≥65 years" and "BMI ≥25, CKD stages 4–5" subcohorts, whereas it was negatively associated with CKD progression in the "BMI <25, diabetes mellitus" subcohort. PP × HR was independently associated with CKD progression in the "BMI <25, CKD stage 3" subcohort, which had relatively few identified renal prognostic factors. Decreased e24hUK was a renal prognostic factor for CKD progression in the "BMI <25, CKD stages 4–5" subcohort, while no significant factors were observed in the "BMI ≥25, CKD stages 4–5" subcohort. Conclusion: A BMI-based cross-classification approach, which provides more comprehensive findings than that in previous approaches, is expected to be an effective method for evaluating renal prognostic factors in patients with CKD who are affected by multiple risk factors. [ABSTRACT FROM AUTHOR]

Background: Obstructive uropathy (OU) is a common cause of end-stage renal disease (ESRD) in children. Children who escape the newborn period with mild-to-moderate chronic kidney disease (CKD) continue to be at increased risk. The predictive ability of clinically available markers throughout childhood is poorly defined.Methods: Patients with OU were identified in the Chronic Kidney Disease in Children Study. The primary outcome of interest was renal replacement therapy (RRT) (cases). Controls were age matched and defined as patients within the OU cohort who did not require RRT during study follow-up.Results: In total, 27 cases and 41 age-matched controls were identified. Median age at baseline and age at outcome measurement were 10 vs. 16 years, respectively. First available glomerular filtration rate (GFR) (36.9 vs. 53.5 mL/min per 1.73 m2), urine protein/creatinine (Cr) (0.40 vs. 0.22 mg/mg) and microalbumin/Cr (0.58 vs. 0.03 mg/mg), and serum CO2 (20 vs. 22 mmol/L) and hemoglobin (12.4 vs. 13.2 g/dL) differed significantly between cases and controls, respectively. GFR declined 3.07 mL/min per 1.73 m2/year faster in cases compared to that in controls (p < 0.0001). Urine protein/Cr and microalbumin/Cr increased by 0.16 and 0.11 per year more in cases compared to those in controls, respectively (p ≤ 0.001 for both). Serum phosphate increased by 0.11 mg/dL and serum albumin and hemoglobin decreased by 0.04 (g/dL) and 0.14 (g/dL) per year more for cases compared to those for controls, respectively (p < 0.05 for all).Conclusions: Age-specific baseline and longitudinal measures of readily available clinical measures predict progression to ESRD in children with mild-to-moderate CKD from OU. [ABSTRACT FROM AUTHOR]

Background/Aims: In patients with chronic kidney disease (CKD) strict blood pressure (BP) control is reno-protective. However, renal benefits from BP control might depend also on the etiology of CKD. We investigated if maintenance of BP at target is equally effective in subjects with hypertensive nephropathy (HN+) and in those with other nephropathies (HN-). Methods: We evaluated 148 patients with CKD (stages 3-5) in two visits at least 12 months apart. BP was measured both as office BP and 24h ambulatory blood pressure (ABP). Glomerular filtration rate (eGFR) was estimated with CKD-EPI formula. The slope of eGFR variation (ΔeGFR) was calculated as: (eGFR1-eGFR0)/months of follow up. Results: Cohort characteristics were: HN-(n=82) and HN+ (n=66), age (71±9 vs 74±9 years; p=0.09); prevalence of diabetes (57 vs 43%; p=0.19); average follow up (19±7 vs 21±9 months; p=0.3). HN- and HN+ did not differ regarding both baseline eGFR (34±18 vs 35±14 ml/min; p=0.97) and ΔeGFR (0.00±0.53 vs -0.06±0.35 ml/min/month, p=0.52). The proportion of patients with BP at target at both visits was similar in HN- and HN+ (office BP: HN- 18% and HN+ 27%; p=0.21; ABP: HN- 42% and HN+ 43; p=0.96). In patients with office BP at target at both visits HN- showed a significant improvement of ΔeGFR respect to HN+ (HN-: 0.240 ± 0.395 and HN+: -0.140±0.313 ml/min/ month; p=0.026). In patients with office BP not at target HN- and HN+ did not show any difference in ΔeGFR (HN- 0.00±0.47; HN+ -0.030±0.420 ml/min/month; p=0.66). ABP was not associated with differences in ΔeGFR either if it was at target (HN- 0.104±0.383 and HN+ 0.00±0.476 ml/min/month; p=0.42) or not (HN- -0.057±0.503 and HN+ -0.092±0.325 ml/ min/month; p=0.87). Conclusion: In patients with CKD and HN+ maintenance of BP targets recommended by current guidelines is less reno-protective than it is in HN-. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the effect of volume status on the progressions of renal disease in normovolemic and hypervolemic patients with advanced non-dialysis-dependent chronic kidney disease (CKD) who were apparently normovolemic in conventional physical exam-ination.Materials and Methods: This was a prospective interventional study performed in a group of stage 3-5 CKD patients followed up for 1 year. Three measurements were made for volume and renal status for every patient. The fluid status was assessed by a bioimpedance spectroscopy method. A blood pressure (BP) value > 130/80 mm Hg prompted the initiation or dose increment of diuretic treatment in normovolemic patients.Result: Forty-eight patients (48%) were hypervolemic. At the end of the 1-year follow-up, hypervolemic patients were found to have a significantly lower estimated glomerular filtration rate and higher systolic BP compared to baseline. Hypervolemia was associated with an increased incidence of death.Conclusion: We have shown that maintenance of normovolemia with diuretic therapy in normovolemic patients was able to slow down and even improve the progression of renal disease. Volume overload leads to an increased risk for dialysis initiation and a decrease in renal function in advanced CKD. Volume overload exhibits a stronger association with mortality in CKD patients. [ABSTRACT FROM AUTHOR]

ABSTRACT: Post‐transplant immunoglobulin A (IgA) nephropathy (IgAN) in the allograft is the major cause of allograft loss. Using a protocol biopsy, latent mesangial IgA deposition (IgAD) can be detected in the allograft. Latent IgAD is distinguished from IgAN by the absence of urinary abnormalities, although IgA is observed in the mesangium. However, the pathophysiology and most appropriate treatment strategy for latent mesangial IgAD in the allograft remain to be fully determined. Importantly, it is unknown whether all cases of post‐transplant asymptomatic IgAD progress to symptomatic IgAN; indeed, IgA deposits disappear in some cases. The differences in allograft prognosis between asymptomatic IgAD and IgAN have also not been determined. Non‐invasive methods of diagnosis of IgAD in the allograft using serological and pathological biomarkers are being developed. Possible serum biomarkers include serum galactose‐deficient IgA1 (Gd‐IgA1), Gd‐IgA1‐specific IgG and Gd‐IgA1‐specific IgA, and its immune complexes. Immunofluorescence analysis using Gd‐IgA1 monoclonal antibody may provide a pathological biomarker. These serological and pathological biomarkers may be suitable for the characterization of the stage of IgAD. However, there is insufficient information regarding whether serological and pathological biomarkers can predict the progression of asymptomatic IgAD to symptomatic IgAN. We propose that the pathogenesis of IgAN can be defined through the clinical study of IgAD in the allograft using protocol biopsies conducted by nephrologists involved in clinical kidney transplantation. [ABSTRACT FROM AUTHOR]

Background/Aims: Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The impact of aTRH and achievement of recommended blood pressure (BP) values on the rate of glomerular filtration rate (eGFR) loss in CKD patients is poorly known. To assess the role of aTRH and time-updated BP control (BPC) on the progression of CKD in patients with T2D and hypertension (HT) in real life clinical practice. Methods: Clinical records from a total of 2,778 diabetic patients with HT and stage 3 CKD (i.e. baseline eGFR values between 30 and 60 ml/min) and regular visits during a four-year follow-up were analyzed. The association between BPC (i.e. 75% of visits with BP <140/90 mmHg) and eGFR loss (i.e. a >30% reduction from baseline) or worsening of albuminuria status over time was assessed. Results: At baseline 33% of patients had aTRH. Over the 4-year follow-up, 20% had a >30% eGFR reduction. Patients with aTRH had an increased risk of eGFR loss >30% (OR 1.31; P<0.007). In patients with aTRH, BPC was associated with a 79% (P=0.029) greater risk of eGFR reduction despite a 58% (P=0.001) lower risk of albuminuria status worsening. In non-aTRH, no association was found between BPC and renal outcome. Conclusion: In patients with stage 3 CKD the presence of aTRH entails a faster loss of eGFR. More effective prevention of aTRH should be implemented as this condition is associated with a burden of risk not modifiable by tight BP reduction. [ABSTRACT FROM AUTHOR]

Abstract: Background: An imbalance between renal damaging molecules and nephroprotective factors contributes to the development and progression of kidney diseases. Molecules with renoprotective properties might serve as biomarkers, drug targets as well as therapeutic options themselves. Materials and methods: For this review, we generated a set of renoprotective factors based on GeneRIF (Gene Reference Into Function) information available at NCBI's PubMed. The final set of manually curated renoprotective factors was investigated with respect to tissue‐specific expression, subcellular location distribution and involvement in biological processes using information from gene ontology as well as information from protein‐protein interaction databases. We furthermore investigated the factors in the context of clinical trials of renal disease and diabetes. Results: One hundred and ninety‐three factors could be retrieved from the set of GeneRIFs on nephroprotection and renal repair. A large number of factors were either secretory molecules or plasma membrane receptors. Next to the elevated expression in renal tissue, also higher expression in connective tissue and pancreas was observed. The proteins could be assigned to the broad functional categories of cell proliferation and signalling, inflammatory response, apoptosis, blood pressure regulation as well as cellular response to different kinds of insults such as hypoxia, heat or mechanical stimulus. Eight factors are studied in clinical trials with additional ones being targeted by compounds. Conclusions: We have generated a set of renoprotective factors based on the literature information, which was functionally annotated and evaluated with respect to tested compounds in kidney disease and diabetes clinical trials. [ABSTRACT FROM AUTHOR]