An in-depth review of the evidence linking dietary salt intake and progression of chronic kidney disease

BACKGROUND: Dietary salt has been debated for decades as having a potentially deleterious influence on human health. OBJECTIVES: To determine the quality of research and the relationship between dietary salt and markers for progression of kidney disease. METHODS: Data sources included 7 electronic databases comprehensively searched for literature published between January 1, 1966, and August 31, 2004, and a manual search of bibliographies of relevant papers, and consultation with experts in the field. Differences between the paired reviewers were reconciled through consensus or by a content expert. RESULTS: Sixteen studies met the inclusion-exclusion criteria and were identified for review; however, the study methodologies were extremely heterogeneous. Conclusions commonly cited in the studies include: variations in salt consumption are directly correlated with albuminuria, and an increase in salt consumption is associated with an acute increase in glomerular filtration rate, while a reduction in salt consumption may slow the rate of renal function loss. CONCLUSIONS: The available published information, while highly variable in methods and quality, suggests that variations in dietary salt consumption directly influence albuminuria, with increasing salt intake associated with worsening albuminuria; however, results are inadequate and conflicting on the effects of dietary salt consumption on renal function, especially over a prolonged time. There was no evidence of a detrimental effect of reduced salt intake. On the other hand, there is consistent experimental evidence to link increased salt exposure with kidney tissue injury. On the basis of these data, we believe that dietary salt restriction should be considered in patients with chronic kidney disease.     

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.     

Bariatric surgery and progression of chronic kidney disease

BackgroundObesity is an independent predictor for the development and progression of chronic kidney disease (CKD). The effect of weight reduction on the progression of kidney disease in patients with pre-existing CKD is unclear.MethodsWe conducted a retrospective study at a U.S. university hospital of patients with stage 3 CKD (glomerular filtration rate [GFR] 30–59 mL/min/1.73 m²) who had undergone bariatric surgery. The renal function of the included patients was recorded for a 2-year period after surgery to analyze the rate of loss or improvement in renal function. The estimated GFR was calculated using the Modification of Diet in Renal Disease 4-variable formula. Patients who developed acute renal failure in the postoperative period were excluded.ResultsA total of 25 patients with stage 3 CKD were included. Their average body mass index at surgery was 49.8 kg/m², the mean GFR was 47.9 mL/min/1.73 m², and the mean serum creatinine was 1.4 mg/dL. The body mass index had decreased to 38.4 kg/m² (paired t test, P < .001) at the end of 6 months and to 34.5 kg/m² (P < .001) at the end of 12 months. The mean systolic blood pressure had decreased from 133 ± 13 to 128 ± 17 mm Hg at the end of 12 months. The mean GFR at 6 months of follow-up had improved to 56.6 mL/min/1.73 m² (P < .001) and to 61.6 mL/min/1.73 m² (P < .001) at 12 months.ConclusionThe renal function of patients with CKD might improve after bariatric surgery. Larger and long-term studies are warranted to further analyze the effect of bariatric surgery on proteinuria and hard end-points such as the development of end-stage renal disease.     

Therapeutic strategies to slow chronic kidney disease progression

Childhood chronic kidney disease commonly progresses toward end-stage renal failure, largely independent of the underlying disorder, once a critical impairment of renal function has occurred. Hypertension and proteinuria are the most important independent risk factors for renal disease progression. Therefore, current therapeutic strategies to prevent progression aim at controlling blood pressure and reducing urinary protein excretion. Renin-angiotensin-system (RAS) antagonists preserve kidney function not only by lowering blood pressure but also by their antiproteinuric, antifibrotic, and anti-inflammatory properties. Intensified blood pressure control, probably aiming for a target blood pressure below the 75th percentile, may exert additional renoprotective effects. Other factors contributing in a multifactorial manner to renal disease progression include dyslipidemia, anemia, and disorders of mineral metabolism. Measures to preserve renal function should therefore also comprise the maintenance of hemoglobin, serum lipid, and calcium-phosphorus ion product levels in the normal range.     

Role of anemia in progression of chronic kidney disease

Anemia is a well-known consequence of chronic kidney disease (CKD), and its prevalence progressively increases when the estimated glomerular filtration rate decreases to less than 60 mL/min/1.73 m2. However, analyses of the consequences of anemia and of the mechanisms of progression of CKD suggest that anemia also could contribute to the deterioration of kidney function. This hypothesis is based mostly on experimental data that imply that hypoxia of tubular cells plays an important role in tubulointerstitial damage associated with CKD and, thus, in the progression of renal failure. It also is supported by the fact that red blood cells represent a major antioxidant component of blood and that oxidative stress appears to contribute to glomerulosclerosis and tubulointerstitial damage. In humans, post hoc analysis of the Reduction of End points in non insulin-dependent diabetes mellitus (NIDDM) with the Angiotensin II Antagonist Losartan study and analyses of smaller prospective cohorts of CKD patients have shown that anemia is an independent risk factor for progression of CKD. In addition, 3 small randomized studies have suggested that anemia correction could slow the progression of CKD. Thus, the existence of a relationship between anemia and progression of CKD is not only plausible biologically, but also is supported by observational studies and by small intervention studies. However, only a large, randomized, prospective trial will be able to establish if anemia correction can slow the progression of CKD effectively.     

Biomarkers of inflammation and progression of chronic kidney disease

BACKGROUND: Chronic kidney disease is associated with higher levels of inflammatory biomarkers. Statins have anti-inflammatory properties and may attenuate loss of kidney function. Although inflammation may mediate progressive renal injury, the relation between statin use, markers of inflammation, and the rate of kidney function loss has not been elucidated. We examined the association between pravastatin use, levels of C-reactive protein (CRP), soluble tumor necrosis factor receptor II (sTNFrii), and the rate of kidney function loss. METHODS: We performed a post hoc analysis of data from a randomized placebo controlled trial of pravastatin 40 mg daily in people with previous myocardial infarction. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease Study (MDRD) GFR equation. We studied 687 subjects with chronic kidney disease (GFR < 60 mL/min/1.73 m(2)) who did not experience a cardiovascular event during follow-up. Multivariate linear regression was used to study the relation between baseline CRP and sTNFrii and the rate of kidney function loss in mL/min/1.73 m(2)/year. Cross-product interaction terms were used to determine if these relations varied with pravastatin use. RESULTS: Median baseline GFR was 54.5 mL/min/1.73 m(2) (interquartile range 49.7, 57.8) and median duration of follow-up was 58 months. Higher baseline CRP level was independently associated with more rapid kidney function loss (highest tertile 0.6 mL/min/1.73 m(2) per year faster than lowest tertile) (P= 0.001). A similar independent relation was observed between tertile of sTNFrii and rate of kidney function loss (highest tertile 0.5 mL/min/1.73 m(2) per year faster than lowest tertile) (P= 0.006). Subjects with both CRP and sTNFrii in the highest tertile ("inflamed" status) appeared to derive more renal benefit from pravastatin than those without (P for interaction 0.047). In these 108 subjects, renal function loss in pravastatin recipients was 0.8 mL/min/1.73 m(2)/year slower than placebo (95% CI 0 to 1.5 mL/min/1.73 m(2)/year slower) (P= 0.039). CONCLUSION: Higher CRP and sTNFrii are independently associated with faster rates of kidney function loss in chronic kidney disease. Pravastatin appears to prevent loss of kidney function to a greater extent in individuals with greater evidence of inflammation, although this was of borderline significance. These data suggest that inflammation may mediate the loss of kidney function among subjects with chronic kidney disease and concomitant coronary disease.     

Effect of organic solvent exposure on chronic kidney disease progression: the GN-PROGRESS cohort study

It has been suggested that solvent exposure may have a role in the progression of glomerulonephritis (GN) to ESRD, but this has never been tested with an appropriate cohort study design. A total of 338 non-ESRD patients with a first biopsy for primary GN between 1994 and 2001 were included: 194 IgA nephropathies (IgAN), 75 membranous nephropathies (MN), and 69 FSGS. ESRD, defined as an estimated GFR <15 ml/min per 1.73 m2 or dialysis, was registered during a mean follow-up period of 5 yr. Patients' lifelong solvent exposures before and after diagnosis were recorded by interview and assessed by industrial hygienist experts. Cox models were used to estimate adjusted hazard ratios (HR) of ESRD related to exposures. Overall, 15 and 14% of the patients had been exposed at a low and a high level before diagnosis, respectively. Forty-two with IgAN, 12 with MN, and 22 with FSGS reached ESRD. A graded relationship was observed for MN (age- and gender-adjusted HR [95% confidence interval] for low exposure versus none was 3.1 [0.5 to 18.2] and for high exposure versus none was 8.2 [1.9 to 34.7]) and for IgAN (1.6 [0.7 to 3.9] and 2.2 [1.0 to 4.8]) but not for FSGS. Solvent risk was mediated only partly by baseline proteinuria: Adjusted HR for high exposure versus none was 5.5 (1.3 to 23.9) for MN and 1.8 (0.8 to 3.9) for IgAN. In patients with IgAN, there was a trend in increasing HR with exposure duration before and its persistence after diagnosis. These findings support the hypothesized association of solvent exposure with the progression of GN to ESRD. They should prompt clinicians to give greater attention to patients' occupational exposures and possibly to consider professional reclassification.     

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.     

慢性肾脏病中的肝脏疾病及治疗进展

慢性肾脏病(CKD)患者可出现各种急性或慢性肝脏疾病.血液透析(HD)和肾移植患者中最常见的肝脏病变是乙型肝炎病毒(HBV)及丙型肝炎病毒(HCV)感染.腹膜透析患者由于不涉及体外血液操作,不需要建立血管通路,较少输血,且居家进行,出现血源性感染的风险要比HD患者小得多.本文就CKD患者,尤其是维持性透析及肾移植患者中肝脏病变的临床特点及治疗进行综述.     

The severity of acute kidney injury predicts progression to chronic kidney disease

Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with 'c' statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy ('c' 0.81-0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD.     

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.     

Fluid and nutrient intake and risk of chronic kidney disease

Aim: We evaluated the association between fluid and nutrient intake and chronic kidney disease (CKD). Methods: Two cross‐sectional population‐based studies. Validated nutrition food frequency questionnaires (FFQ) administered to people >50 years, identified in a door‐to‐door census of a well‐defined suburban area. Based upon nutrition tables we calculated intakes of over 40 nutrients (factors) and total daily energy intake. Primary outcome was CKD. Fluid (total content of fluid and drinks assessed in the FFQ) and nutrient intake was stratified in quintiles and association with CKD analysed by logistic regression, expressed as unadjusted and adjusted odds ratios, with testing for linear trend. Results: The proportion of participants who completed the FFQ and had glomerular filtration rate (GFR) measures was 2744/3654 (75.0%) for the first and 2476/3508 (70.6%) for the second survey. CKD was present in 12.4–23.5% men and 14.9–28.7% women (mean ages 66.4–65.4 years), respectively. Participants who had the highest quintile of fluid intake (3.2 L/day) had a significantly lower risk of CKD (odds ratio 0.5, 95%CI 0.32 to 0.77, P for trend = 0.003). These findings were consistent across both study periods, both equations to calculate GFR and both GFR thresholds. Conclusion: Higher intakes of fluid appear to protect against CKD. CKD may be preventable at a population level with low‐cost increased fluid intake.     

Remnant nephron physiology and the progression of chronic kidney disease

In chronic kidney disease, ongoing failure of individual nephrons leads to the progressive loss of renal function. This process results in part from a cellular and molecular response to injury that represents an attempt to maintain homeostasis but instead initiates a program that damages the nephron. As nephrons are lost, compensation by the remaining nephrons exacerbates glomerular pathophysiology. The delivery of excessive amounts of biologically active molecules to the distal nephron and tubulointerstitium generates inflammation and cellular dedifferentiation. Energy requirements of hyperfunctioning nephrons exceed the metabolic substrate available to the renal tubule, and inadequacy of the local vascular supply promotes hypoxia/ischemia and consequent acidosis and reactive oxygen species generation. In this way, mechanisms activated to maintain biological balance ultimately lead to demise of the nephron.     

慢性肾脏病生物标志物及其检测研究进展

一、生物标志物的定义 生物标志物首先是在1989年作为医学主题词被提出来的,当时定义为"可测量和定量的生物学参数".     

慢性肾脏病生物标志物及其检测研究进展

一、生物标志物的定义 生物标志物首先是在1989年作为医学主题词被提出来的,当时定义为"可测量和定量的生物学参数".