Abstract
More than 10% of the global population suffers from chronic kidney disease (CKD), a progressive condition that is extremely harmful to health. In this review of the literature, we looked at how dietary and lifestyle changes, as well as the management of hypertension (HTN) and diabetes mellitus (DM), can slow the development of CKD. The progression of CKD can be slowed by things like walking, weight loss, a low-protein diet (LPD), following the alternate Mediterranean (aMed) diet, and using the Alternative Healthy Eating Index (AHEI)-2010. However, the risk of CKD progression is raised by smoking and binge drinking. Overhydration (OH), high blood sugar (HG), abnormal lipid metabolism, chronic low-grade inflammation, hyperactivation of the renin-angiotensin-aldosterone system (RAAS), and RAAS all contribute to the development of diabetic CKD. Blood pressure (BP) should be controlled to less than 140/90 mmHg in patients without albuminuria and less than 130/80 mmHg in patients with albuminuria, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for preventing CKD progression. Epigenetic modifications, fibrosis, and inflammation are the primary targets of current medical treatments. Pentoxifylline, finerenone, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and RAAS blockers are all currently approved for the management of CKD. In addition, atrasentan, an endothelin receptor antagonist (ERA), was found to reduce the risk of renal events in patients with diabetic chronic kidney disease (CKD) in the recently concluded Study of Diabetic Nephropathy with Atrasentan (SONAR). However, other agents’ potential to slow CKD progression is being investigated in ongoing trials.
Preface and Context
Progressive kidney failure caused by chronic kidney disease (CKD) is a leading cause of death worldwide [1,2]. More than 10% of the global population now has CKD [2], and this number is rising. Major risk factors for CKD include diabetes mellitus (DM) and high blood pressure (HTN). Environmental factors, systemic infections, kidney stones, and nephrotoxins are additional risk factors [3]. Immunologic and genetic abnormalities, hypoxia and decreased perfusion of tissue, drugs, high glucose, and other substances all play a role in the pathophysiology of kidney injury [4].
Generalized weakness, pain, sleep disorders, anxiety, depression, and itching are just some of the symptoms that CKD patients may experience [5]. For a diagnosis of CKD, one or more of the following must be present for at least three months. A glomerular filtration rate (GFR) of less than 60 mL/minute/1.73 m2; albuminuria of 30 mg/day; renal structural or functional abnormalities [6]. Congruent with the GFR (Figure 1) [6, there are five stages of CKD.
Complications from CKD can be avoided or alleviated if they are caught and treated early. Screening for albuminuria, glomerular filtration rate (GFR), urine sediment, and serum creatinine (Cr) in high-risk groups (diabetes, hypertension, kidney transplant, and family history of kidney disease); treating specific renal diseases; controlling progression; preventing and treating complications; and educating and preparing patients for renal replacement therapy (RRT) are all part of the management of chronic kidney disease [7]. In this review of the literature, we explored how nutritional interventions, lifestyle changes, the management of hypertension and diabetes, and the use of medication can slow the development of chronic kidney disease (CKD).
Review
Adopting a New Way of Life
Dropping Pounds
High body mass index (BMI) beginning at 25.0 kg/m2 is associated with an increased risk of end-stage renal disease (ESRD) [8-10], and there is a graded causal relationship between central (waist circumference) and general obesity and CKD incidence. Albuminuria (albumin-creatinine ratio of 30 mg/g (3 mg/mmol)) and proteinuria were found to be significantly reduced in patients with DM who lost weight, with the effect being most pronounced in those who lost weight after bariatric surgery. [11]. Patients with ESRD who lose weight unintentionally, especially due to malnutrition and muscle wasting, have a higher risk of dying after receiving a kidney transplant [12,13].
Diet
Adherence to a low-protein diet (LPD) has been shown to reduce the risk of developing ESRD and to enhance quality of life in CKD patients [14], thanks to the efforts of the Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation. Patients on a very low protein diet (VLPD; 0.28–0.43 g/kg/body weight/day) supplemented with keto-acid analogues (KA) showed a significant reduction in serum urea and serum uric acid at the end of 15 months compared to the conventional LPD [15]. In contrast to a high-protein diet, the impact of LPD on serum creatinine is less clear [16]. The Alternative Healthy Eating Index (AHEI)-2010 and the Alternate Mediterranean (aMed) diet are two other dietary interventions for CKD [16]. According to the Chronic Renal Insufficiency Cohort Study [17], those who adhered most closely to the aMed diet and the AHEI-2010 had a lower risk of CKD progression and a lower risk of all-cause mortality. If you’re trying to prevent your serum Cr from doubling between now and end-stage renal disease (ESRD), eating less salt (less than 2.3 g/day) may help. Further research is necessary to determine the impact of a low-salt diet on the reduction of eGFR, proteinuria, and all-cause mortality [18].
Movement and Exercise
Adults should aim for at least 150 minutes of moderate-intensity physical activity per week, or 75 minutes of vigorous exercise per week, according to the Physical Activity Guidelines for Americans. In CKD, there was some debate about whether or not exercise should be discouraged due to the risk of proteinuria and renal function impairment. Rather, a meta-analysis by Villanego et al. [19] found that low-intensity physical activity enhances quality of life without compromising renal function. However, no significant difference was found between the exercise group and the control group in terms of eGFR, proteinuria, or the progression of CKD [19,20], as shown by this study and another meta-analysis by Nakamura et al. Patients with CKD who were not on dialysis made up both the exercise and control groups. Another prospective cohort study found that for every additional 60 minutes of weekly physical activity, the rate of decline in eGFR slowed by an estimated 0.5% per year in stage 3-4 CKD patients (Robinson-Cohen et al. After controlling for demographic and disease factors, the same study found that patients who did not engage in any recreational activity had a greater annual decline in GFR compared to those who followed the guidelines for physical activity. This difference in annual eGFR decline was 2.8% between the two groups.
An observational study by Chen et al. found that among patients in stages 3–5 of chronic kidney disease (mean age 70) who reported exercising, walking was the most popular choice. Independent of patient age, renal function, or comorbidities, the study found that walking reduced overall mortality and RRT rates [22]. There is a dose-dependent association between walking and overall mortality (subdistribution hazard ratio (SHR): 0.83, p=0.04 in patients who walked 1-2 times/week; 0.72, p=0.002 to patients who walked 3-4 times/week; and 0.41, p0.001 for those walking 7 times/week). This suggests that physical activity may slow the rate of decline of kidney function and may be beneficial in lowering the risk of ESRD in Patients who walked 1-2 times per week had a SHR of 0.81, while those who walked 5-6 times per week had a SHR of 0.56, indicating that the benefits of walking decrease with frequency. More research is needed, however, to determine how much exercise is needed to merely slow the progression of CKD [23].
Smoking
Assessing smoking’s cause and effect is challenging. Patients who already have chronic kidney disease (CKD) are more likely to experience a worsening of their condition if they continue to smoke. Korean researchers found that smokers had a higher risk of developing more severe CKD over the course of a three-year follow-up period. Patients with an eGFR of 45 mL/minute/1.73 m2 saw the greatest improvement [24]. In the same study, researchers found that the risk of developing CKD increased in proportion to the number of cigarettes smoked per day, demonstrating a dose-response relationship between tobacco use and the disease. In a similar vein, people who have never smoked or who have quit smoking are less likely to develop CKD than those who continue to smoke [25,26]. Moreover, a number of studies show that quitting smoking slows the development of CKD in comparison to people who continue to smoke [25].
Reducing one’s alcohol consumption
Moderate alcohol consumption, as reported by numerous studies, has no effect on the development of CKD when compared to abstinence. Unfortunately, heavy drinking is associated with a higher risk of advancing CKD [27,28].
Workload, Late Nights, and Stress
By activating the sympathetic nervous system and increasing inflammatory cytokines, stress raises the risk of diabetes, hypertension, and vascular diseases, all of which are major risk factors for chronic kidney disease [29]. The prevalence of CKD was found to be significantly correlated with working long hours (>52 hours), as determined by a cohort study. Yet more work is required to investigate the mechanism underlying this association [30]. Nearly half of people with CKD also suffer from insomnia or poor quality sleep [31].
Interventions in nutrition
In the context of CKD dietary therapy, protein intake is a common topic of discussion. Studies have shown that eating a high-protein diet (defined as >1.2 g/kg/day) significantly reduces kidney function [32]. Reducing nitrogen waste products and decreasing renal strain by lowering intraglomerular pressure have protective effects on the kidneys, especially in people with a diminished reserve of working nephrons [33], making LPD useful in the treatment of CKD patients. LPD has physiological effects on the kidneys that are analogous to those of RAAS blockers. In a study involving RAAS blockers, it was found that LPD had an additive anti-proteinuric effect [34].
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The increased resting energy expenditure due to inflammation and comorbidities necessitates a caloric intake of 25-35 kcal/kg/day to keep the nitrogen balance neutral or positive [35]. Dietary protein restriction in combination with KA supplementation likely has an overall positive effect on RRT/recovery in patients with stage 3-5 chronic kidney disease, as suggested by the 2020 Kidney Disease Outcomes Quality Initiative (KDOQI) recommendations. The advised protein intake for stable patients with non-dialysis stage 3-5 CKD is 0.55-0.60 g/kg/day. Moreover, in addition to the standard pharmaceutical approaches for CKD patients, moderate sodium restriction (2.3 g/day) is recommended for better volume control, blood pressure (BP) reduction, and proteinuria reduction [13].
Acidosis is a major risk factor for the development of chronic kidney disease. Fruits and vegetables were found in a study to be an option for oral alkali, which may reduce the danger of fluid retention and hypertension from taking bicarbonate supplements. Dietitians in this study suggested eating between 2 and 4 cups of produce daily [36]. According to another case-control study, a VLPD high in vegetables and fruits and low in protein supplemented with essential amino acids and keto-acid analogues of nonessential amino acids significantly reduced net endogenous acid production (NEAP) by 53% at six months and 67% at 12 months, and potential renal acid load (PRAL) by 120% at six months and 138% at 12 months [37].
Management of Blood Glucose
Glucose glomerular filtration, glucose reabsorption via sodium-glucose cotransporters (SGLT), and glucose production all have major effects on glucose homeostasis [38]. Even though it is the gold standard for glycemic assessment in CKD patients, haemoglobin A1C can be influenced by hematologic factors. It has been suggested that glycated albumin can be used as a marker of glycemic control in people with CKD. Proteinuria, however, can have an effect on it, so more research is needed to determine its significance in diabetic chronic kidney disease. [38]. Monitor glycemic control in CKD patients with a continuous glucose monitoring (CGM) device, a non-invasive approach. The following are possible meanings: Time in range refers to when blood sugar levels are within the recommended range (70-180 mg/dL); time above range refers to when blood sugar levels are higher than the recommended range (level 1: 181-250 mg/dL; level 2: >250 mg/dL); and time below target refers to when blood sugar levels are lower than the recommended range (level 1: 54-69 mg/dL; level 2: 54 mg/dL). [38]. Researchers in two separate retrospective cohort studies found that A1C levels of 6%-7% or >9% were associated with an increased risk of death. Strict A1C control (6.7% vs. 7.5%) was associated with a higher risk of death in CKD patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial [38].
Since the first clinical trial demonstrating the benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors was published in 2015, there has been a shift in the treatment of CKD associated with type 2 diabetes mellitus (T2DM). Prior to this finding, controlling glycemia and blood pressure (BP) were the mainstays for preventing or delaying the progression of CKD and cardiovascular diseases linked to T2DM. The major risk of cardiovascular events and the progression of chronic kidney disease in T2DM patients was found to be reduced by SGLT2 inhibitors [39]. The cardiovascular and kidney protective effects of SGLT2 inhibitors have been linked to their pleiotropic effects, which include modulating neurohormones like the RAAS, increasing hematocrit, altering energy substrate use, and attenuating systemic inflammation and oxidative stress [39]. Risk factors for kidney disease in newly diagnosed T2DM patients are poorly understood. Hypoalbuminemia and elevated albuminuria are associated with kidney failure progression in newly diagnosed T2DM patients, and the overall rate of CKD progression is relatively high [40].
Overhydration (OH), as measured by bioimpedance assay (BIA), was found to be associated with the development of CKD in patients with type 2 diabetes, as determined by a prospective cohort study. Patients with type 2 diabetes were found to have an increased risk of CKD progression when OH was present. According to the authors’ hypotheses [41], OH served as a predictor and pigment epithelium-derived factor (PEDF) was a risk factor that could be altered to slow CKD’s development. High levels of OH and relative OH (OH/extracellular water of >7%) in patients with type 2 diabetes were positively associated with the development of CKD (hazard ratio [HR] 1.45 (95% CI 1.14-1.85), p=0.003; HR 1.29 (95% CI 1.05-1.59), p=0.017). Both PEDF and OH had positive correlations with advancing CKD (=1.10; p0.001) and OH with advancing CKD (=0.21; p0.036). OH continued to be positively linked to CKD progression through PEDF [41].
Regulation of Blood Pressure
Since the prognosis of CKD patients is worsened by uncontrolled HTN, controlling blood pressure (BP) rigorously is essential [42]. One of the most typical complications of chronic kidney disease is high blood pressure. In stages 4-5 of CKD, its prevalence is nearly 100% [43]. Patients with CKD who have their blood pressure lowered are aiming to do one of two things: 1) delay the onset of further kidney damage and the subsequent need for dialysis or a kidney transplant, or 2) improve their quality of life by reducing their risk of fatal cardiovascular events.
Sleep disorders are common among people with CKD.
blood pressure that’s too high [45]. Elevated blood pressure levels during sleep are harmful and have been linked to an increased risk of cardiovascular outcomes. Nighttime blood pressure (BP) typically drops naturally from daytime levels. Dippers are those whose blood pressure drops during sleep, while non-dippers do not. Non-dippers have an increased risk of cardiovascular disease compared to dippers [46]. Patients with CKD tend to be non-dippers [47]. Increased sympathetic nervous system activity at night and the circadian rhythm of urinary sodium exertion have both been proposed as mechanisms for nighttime hypertension [45]. More research is needed to determine the relationship between dipping status and nocturnal electrolyte excretion, sympathetic nervous system activity, and the division of a 24-hour urinary collection [45].
Extensive blood pressure control (systolic BP less than 120) in people with an elevated cardiovascular risk and mild to moderate CKD significantly reduces the risk of cardiovascular events and all-cause mortality, as shown by the Systolic Blood Pressure Intervention Trial (SPRINT). However, more research is needed to determine the impact of intensive BP management on the development of CKD, the occurrence of CKD, and the rate of AKI [48]. While the American College of Cardiology/American Heart Association (ACC/AHA) 2017 guidelines recommend a systolic BP of less than 130 in non-dialysis CKD patients, the Kidney Disease: Improving Global Outcomes (KDIGO) 2021 guidelines recommend a systolic BP of less than 120 [49].
