Prognosis and risk factors of chronic kidney disease progression in patients with diabetic kidney disease and non-diabetic kidney disease: a prospective cohort CKD-ROUTE study

Diabetic kidney disease (DKD) is emerging rapidly as the leading cause of chronic kidney disease (CKD) worldwide. In this 3-year prospective, multicenter cohort study, a total of 1138 pre-dialysis CKD patients were recruited. Patients were categorized into two groups according to the etiologies of DKD and non-diabetic kidney disease (NDKD). Propensity score matching was performed to adjust for confounding factors, resulting in 197 patients being assigned to DKD and NDKD groups, respectively. The primary endpoints were 50% estimated glomerular filtration rate (eGFR) decline and initiation of kidney replacement therapy (KRT). The secondary endpoints were all-cause death and the development of cardiovascular disease (CVD) events. We found that DKD patients have a higher risk to develop 50% eGFR decline endpoint (HR:2.30, 95%CI [1.48–3.58], p < 0.001) and KRT endpoint (HR:1.64, 95%CI [1.13–2.37], p < 0.05) than NDKD patients. The 3-year cumulative incidence of 50% eGFR decline and KRT endpoint was significantly higher in DKD patients (26.90% vs.13.71% and 35.03% vs. 22.34%, respectively). The Cox regression analyses showed that the increased systolic blood pressure (SBP), DKD, decreased serum albumin (Alb), and higher CKD stages were risk factors for the 50% eGFR decline endpoint; the increased SBP, DKD, decreased serum Alb, serum creatinine (Scr), higher CKD stages, presence of proteinuria and CVD were risk factors for KRT endpoint; the increased age, decreased hemoglobin (Hb), decreased serum Alb were risk factors for all-cause death endpoint; the increased age, decreased serum Alb were risk factors for CVD events endpoint. Appropriate preventive or therapeutic interventions should be taken to control these predictive factors to delay the development of CKD complications, thereby improving the prognosis and reducing the disease burden of the high-risk populations.     

Effect of salt intake on progression of chronic kidney disease

PURPOSE OF REVIEW: The attempt of this review is to bring into focus the potential role of dietary salt intake in progression of chronic kidney disease. RECENT FINDINGS: Ongoing work has elucidated a role for dietary salt intake in modulating intrarenal production of transforming growth factor-beta1. The mechanism is independent of angiotensin II and systemic blood pressure and involves activation of vascular endothelium by dietary salt intake with release of this growth factor. In this model, transforming growth factor-beta1 serves an autacoid function by stimulating nitric oxide production by the endothelium. In turn, endothelium-derived nitric oxide modulates production of this growth factor. The model further predicts that individuals who have lost the requisite endothelial cell flexibility to adapt to this environmental stress (a high salt diet) are potentially at increased risk of developing end-organ damage from excess salt intake. Animal and human studies are presented to support this working hypothesis. SUMMARY: Overproduction of transforming growth factor-beta1 permits excess biological activity of this important fibrogenic growth factor with subsequent development or acceleration of vascular and kidney damage. In patients with diseases whose pathogenesis is related to excess production of transforming growth factor-beta1, such as chronic allograft nephropathy and diabetic nephropathy, increased salt intake may hasten loss of function, particularly if nitric oxide production does not increase. The role that endothelial cell plasticity plays in altering vascular tone and renal function, especially in response to changes in dietary salt intake, should be examined further in chronic kidney disease.     

Asymmetric dimethylarginine and progression of chronic kidney disease: the mild to moderate kidney disease study

Reduced bioavailability of nitric oxide (NO) is thought to play an important role in progression of renal damage. The hypothesis that the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) is involved in progression of kidney disease was tested. Plasma ADMA concentrations and other putative progression factors were assessed in 227 relatively young patients (45.7 +/- 12.6 yr) with nondiabetic kidney diseases and mild to moderate renal failure. Progression assessed as doubling of serum creatinine and/or renal replacement therapy was evaluated prospectively. Baseline plasma ADMA concentrations in renal patients correlated significantly with serum creatinine (r = 0.595), GFR (r = -0.591), age (r = 0.281), and proteinuria (r = 0.184; all P < 0.01). Patients who reached an end point during follow-up were significantly older (P < 0.05) and had significantly higher creatinine, ADMA, and parathyroid hormone blood concentrations and protein excretion rates at baseline, whereas GFR and hemoglobin were significantly lower (all P < 0.01). Cox regression analysis revealed baseline serum creatinine (odds ratio 2.00; 95% confidence interval [CI] 1.61 to 2.49; P < 0.001) and ADMA (odds ratio 1.47; 95% CI 1.12 to 1.93 for an increment of 0.1 mumol/L; P < 0.006) as independent predictors of disease progression. In patients with ADMA levels above median, progression was significantly faster (P < 0.0001), and their mean follow-up time to a progression end point was 52.8 mo (95% CI 46.9 to 58.8) as compared with 71.6 mo (95% CI 66.2 to 76.9) in patients with ADMA levels below the median. The endogenous NO synthase inhibitor ADMA is significantly associated with progression of nondiabetic kidney diseases. Lowering plasma ADMA concentrations may be a novel therapeutic target to prevent progressive renal impairment.     

Apolipoprotein A-IV predicts progression of chronic kidney disease: the mild to moderate kidney disease study

It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n = 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m(2); P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P = 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype epsilon2/epsilon4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression.     

队列研究在慢性肾脏病流行病学研究中的重要性

近10余年来,慢性肾脏病(CKD)的流行病学研究成为肾脏病领域的热点.在这一趋势的带动下,我国各个地区陆续开展了若干关于CKD患病率的横断面研究,为评估我国CKD患病现状提供了大量数据.来自北京、上海、广州3个大城市的研究显示成年人群中CKD患病率为11.8%～13.0%[1-3],与美国的水平接近.CKD的相关因素包括传统危险因素,如高血压、糖尿病、老年等,此外还有具中国特色的危险因素,如肾毒性药物等.时至今日,在此领域国际上已经鲜见针对患病率的横断面研究,取而代之的是各种队列研究提供的关于CKD危险因素、疾病进展、并发症发生等的诸多证据.我们介绍队列研究这一流行病学研究的经典方法,并阐述开展队列研究的注意事项.     

Transition from acute kidney injury to chronic kidney disease: a single-centre cohort study

Background

The incidence of acute kidney injury (AKI) is increasing. AKI is currently recognised as an inducer of chronic kidney disease (CKD) and this is known as the ‘AKI–CKD transition’. This study aimed to evaluate the rate of decline in estimated glomerular filtration rate (eGFR) associated with AKI events in individuals with and without pre-existing CKD.

Methods

Inpatients aged 18–80 years were retrospectively enrolled. AKI was diagnosed according to the kidney disease improving global outcomes (KDIGO) criteria using serum creatinine levels. Patients with a history of AKI events were divided into four groups according to eGFR before and after the AKI events. In each group, the eGFR levels after an AKI event were compared to those before the AKI event. Patients were further divided into eight groups according to clinical background based on underlying diseases, medications, and surgical history.

Results

We analysed data from 9651 patients with AKI. Not surprisingly, we found that eGFR levels during the first AKI event were significantly lower than levels before the event in each group. Furthermore, eGFR levels after the first AKI event were significantly lower than those before the first AKI event, and the eGFR levels after the second AKI event were significantly lower than those after the first AKI event. These trends were similar in each group irrespective of clinical background.

Conclusions

Our study revealed that AKI events can cause a decline in kidney function and, as more AKI events occur, acceleration of this decline.

     

Impact of metabolic syndrome on the incidence of chronic kidney disease: a Chinese cohort study

Aim: Metabolic syndrome (MetS) is a major culprit in cardiovascular disease and chronic kidney disease (CKD) in Western populations. We studied the longitudinal association between MetS and incident CKD in Chinese adults. Methods: A cohort study was conducted in a nationally representative sample of 4248 Chinese adults in Taiwan. The MetS was defined according to a unified criteria set by several major organizations and CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m². Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for sex, age, body mass index (BMI) and serum levels of total cholesterol. Results: The prevalence of MetS among participants at baseline recruitment was 15.0% (637/4248). During a median follow‐up period of 5.40 years, 208 subjects (4.9%) developed CKD. The multivariate‐adjusted HR of CKD in participants with MetS compared with those without was 1.42 (95% CI = 1.03, 1.73). Additionally, there was a significantly graded relationship between the number of the MetS components and risk of CKD. Further, the relation between MetS and incident CKD was more robust in subjects with BMI >27.5 kg/m² than in those with lower BMI. Conclusion: The results suggest that the presence of MetS was significantly associated with increased risk of incident CKD in a Chinese population. These findings warrant future studies to test the impact of preventing and treating MetS on the reduction of the occurrence of CKD.     

Mechanisms of progression of chronic kidney disease

Chronic kidney disease (CKD) occurs in all age groups, including children. Regardless of the underlying cause, CKD is characterized by progressive scarring that ultimately affects all structures of the kidney. The relentless progression of CKD is postulated to result from a self-perpetuating vicious cycle of fibrosis activated after initial injury. We will review possible mechanisms of progressive renal damage, including systemic and glomerular hypertension, various cytokines and growth factors, with special emphasis on the renin–angiotensin–aldosterone system (RAAS), podocyte loss, dyslipidemia and proteinuria. We will also discuss possible specific mechanisms of tubulointerstitial fibrosis that are not dependent on glomerulosclerosis, and possible underlying predispositions for CKD, such as genetic factors and low nephron number.     

The longitudinal chronic kidney disease study: a prospective cohort study of predialysis renal failure

Chronic kidney disease (CKD) is a significant public health problem: every year the number of Americans living with CKD and requiring renal replacement therapy increases. In addition, individuals with CKD have substantially increased morbidity and mortality compared to the general population. The Longitudinal Chronic Kidney Dialysis (LCKD) Study is a multicenter, prospective, observational study of patients with moderate to severe CKD that was designed to better describe the course of the disease and the determinants of patient outcomes. Patients with moderate to severe CKD (glomerular filtration rate [GFR] < 60 ml/min/m2) from four academic nephrology clinics were enrolled between 2000 and 2002. Special cardiac and vascular testing has recently commenced as phase II of this study. Areas that have been or are currently being studied include anemia management, health-related quality of life (HRQOL), medication use, and markers of cardiovascular disease. This article describes the LCKD Study in the context of current knowledge of CKD.     

Preoperative chronic kidney disease and complications after pancreatoduodenectomy: a retrospective cohort study

Background

Chronic kidney disease is a prevalent condition in surgical patients. Possible associations with increased postoperative morbidity and mortality have not been clearly demonstrated in patients undergoing pancreatoduodenectomy. The aim of this study was to assess the risk of postoperative complications in patients with reduced kidney function undergoing pancreatoduodenectomy.

Methods

All patients undergoing pancreatoduodenectomy at Karolinska University Hospital between 2008 and 2019 were retrospectively included. The variable of interest was chronic kidney disease, based on preoperative estimated glomerular filtration rate measurements. Unadjusted and adjusted logistic regression analyses were performed for standardized postoperative complications.

Results

A total of 971 patients were included in the study, of whom 92 (10%) had an estimated glomerular filtration rate < 60 mL/min/1.73m², equivalent to chronic kidney disease Stage 3a or worse. Patients with chronic kidney disease had a higher odds of longer hospital stay (adjusted odds ratio 1.58, 95% confidence interval 1.00–2.50) and postoperative weight increase (adjusted odds ratio 2.02, 1.14–3.56). A 10 unit increase of preoperative estimated glomerular filtration rate was associated to lower odds of intensive care unit admission (adjusted odds ratio 0.81, 0.69–0.95), delayed gastric emptying (adjusted odds ratio 0.90, 0.81–0.99), and post-operative pancreatic fistula (adjusted odds ratio 0.83, 0.74–0.94).

Conclusion

Patients undergoing pancreatoduodenectomy with decreased preoperative kidney function are more likely to experience major postoperative complications, and also postoperative weight increase. Preoperative kidney function assessment is important in risk stratification before pancreatoduodenectomies.     

Tubulointerstitial injury and the progression of chronic kidney disease

In chronic kidney disease (CKD), once injury from any number of disease processes reaches a threshold, there follows an apparently irreversible course toward decline in kidney function. The tubulointerstitium may play a key role in this common progression pathway. Direct injury, high metabolic demands, or stimuli from various other forms of renal dysfunction activate tubular cells. These, in turn, interact with interstitial tissue elements and inflammatory cells, causing further pathologic changes in the renal parenchyma. The tissue response to these changes thus generates a feed-forward loop of kidney injury and progressive loss of function. This article reviews the mechanisms of this negative cycle mediating CKD.     

Effects of statin therapy on the progression of chronic kidney disease

Statins are lipid-lowering agents that specifically, competitively, and reversibly inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in the formation of cholesterol. A large body of evidence from numerous, well-controlled, randomized trials demonstrates that statins significantly reduce fatal and nonfatal cardiovascular events in the general population. Cardiovascular benefits of statins have been conventionally attributed to reduction in levels of low-density lipoprotein cholesterol. More recently, subanalyses of large clinical trials suggest that statins may also prove beneficial in ameliorating the progression of kidney disease through their cholesterol-dependent and/or cholesterol-independent (pleiotropic) effects. This review focuses on the role of statin therapy in the progression of chronic kidney disease, the published trials that study the effect of antilipidemic agents on nephropathy, and the emerging pleiotropic effects of statins on the kidneys.     

Slowing chronic kidney disease progression: hopes and disappointments. Vascular repair of chronic kidney

In chronic kidney disease patients, inexorable renal function decline is reduced by renin-angiotensin system (RAS) blockers. ACE inhibitors and angiotensin receptor blockers decrease blood pressure and proteinuria. Guidelines recommend a reduction of blood pressure to less than 130/80 mmHg and urinary protein excretion below 0.5 g/d. The combined use of a diuretic increases anti-proteinuric effect and blood pressure control of RAS blockers. Drugs as mineralo-corticocoids receptor antagonist and endothelin receptor antagonists reduce further albuminuria in combination with RAS blocker, but side effects need to be precised. Both metabolic acidosis and hyperuricemia represent new therapeutic goals to slow renal function decline in CKD patients. Renal fibrosis treatment and regenerative medicine are stemming and will be important issues for kidney and other organs in the future.     

Effect of antitubercular medications on blood pressure control in chronic kidney disease patients with tuberculosis: a prospective cohort study

BACKGROUND: Previous anecdotal reports suggested a decrease in antihypertensive medication potency after starting antitubercular medications. This interaction could be unpredictable in presence of renal failure due to increased half-lives of most commonly used antihypertensive medications. METHODS: In a cohort study involving 135 patients with chronic kidney disease (CKD), 62 patients with tuberculosis star-ted on antitubercular medications (TB group) were prospectively compared with 73 CKD controls (with no TB and not on antitubercular medications) for a change in antihypertensive medications. Antihypertensive dose was converted to unit score. RESULTS: The TB group had a greater increase in antihypertensive medication dose as compared with controls (89% vs. 54%, p<0.0001). In absolute terms an overall increase in antihypertensive medications was observed in 60% of pa-tients in the TB group, with a 2-fold dose increase from the baseline (p<0.0001). Four patients from the TB group de-veloped a hypertensive emergency. In multivariate linear regression, the association between TB group and increase in antihypertensives remained significant ( beta =0.38; p<0.0001). CONCLUSIONS: In CKD patients, antihypertensive medication potency is reduced in TB patients on antitubercular the-rapy in a significant number of patients, to a clinically significant degree with a potential risk for hypertensive emergency.     

Hyperparathyroidism in chronic kidney disease: a retrospective cohort study of costs and outcomes

Hyperparathyroidism may play a role in the excess morbidity and mortality in chronic kidney disease. This study examined utilization and outcomes of patients with hyperparathyroidism and chronic kidney disease. In a US health maintenance organization (HMO), patients with chronic kidney disease were identified from the electronic medical record. Patients included in the study had at least one intact parathyroid hormone (iPTH) measurement ordered by a nephrologist and were at least 20 years of age with no history of renal replacement therapy (RRT, n = 455). Cohorts were determined by index iPTH level and were followed for 1 year. Rates of health care utilization were compared between cohorts using Poisson regression; costs comparisons were made using linear regression; mortality and RRT were evaluated using Cox regression. Increasing levels of iPTH were associated with a significantly elevated risk of mortality and RRT, even after adjustment for potential confounders such as stage of chronic kidney disease. Compared to iPTH of <110 pg/ml, we found a 66% increase combined mortality-RRT risk (HR 1.66, 95% CI 1.41–1.97) for those with iPTH 110–199 pg/ml, and a HR of 4.57 (95% CI 3.86–5.43) for iPTH ≥300 pg/ml. We did not find a convincing association between iPTH level and utilization. While this study provides no evidence that treating patients with higher levels of iPTH will ameliorate poor outcomes, it suggests that iPTH levels beyond the targets suggested by clinical guidelines are associated with increased harm in patients with chronic kidney disease. This work was presented in part at the National Kidney Foundation 2006 annual meeting and at the 2006 International Society for Pharmacoeconomics and Outcomes Research meeting.