structure and loss of nephrons with worsening interstitial fibrosis as occurs with sustained hypertension. The cornerstone of pharmacotherapy in secondary prevention is the use of angiotensin pathway modulators, also known as renin-angiotensin-aldosterone system Figure 1. Overview of the preventive measures in chronic kidney disease (CKD) to highlight the similarities and distinctions pertaining to primary, secondary, and tertiary preventive measures and their intended goals. AKI: acute kidney injury; GFR: glomerular filtration rate; BP: blood pressure; RAASi: renin-angiotensin-aldosterone system inhibitors; SGLT2i: sodium-glucose cotransporter-2 inhibitors. Braz J Med Biol Res | doi: 10.1590/1414-431X20209614 Prevention of kidney diseases 3/10 Table 1. Risk factors for de novo chronic kidney disease (CKD) and pre-existing CKD progression. Risk Factor* Contribution to de novo CKD Contribution to CKD progression Diabetes mellitus B50% of all CKDs Hypertension B25% of all CKDs Obesity 10–20% Age Seen with advancing age, especially in the setting of comorbid conditions Some suggest that older CKD patients may have slower progression Race, genetics, and other hereditary factors APOL1 gene Hereditary nephritis (Alport’s) Common among those with African American ancestors Acute glomerulonephritis (GN) Post-infectious GN Rapidly progressive GN o10% Recurrent GN or exacerbation of proteinuria Polycystic kidney disorders o10%, family history of cystic kidney disorders Acute kidney injury (AKI) Acute tubular necrosis (ATN) Acute interstitial nephritis (AIN) Repeated AKI bouts can cause CKD Repeated AKI bouts can accelerate CKD progression Autoimmune disorders Lupus erythematosus Other connective tissue disorders Pharmacologic Medications causing interstitial nephritides (NSAIDs, CNI, chemotherapy, PPI, etc) or ATN (aminoglycosides) Herbs and herbal medication Variable, e.g., in Taiwan, Chinese herb nephropathy may be an important contributor Environmental Heavy metal exposure Rare Acquired or congenital solitary kidney Cancer, donor or traumatic nephrectomy Congenital solitary kidney, unilateral atrophic kidney Acquired urinary tract disorders & obstructive nephropathy Benign prostate hyperplasia in men Gynecological cancers in women Congenital anomalies of the kidney and urinary tract Mostly in children and young adults Inadequate fluid intake Mesoamerican nephropathy Others Unknown risk, but high prevalence is suspected in Central America Whereas in earlier CKD stages adequate hydration is important to avoid pre-renal AKI bouts, higher fluid intake in more advanced CKD may increase the risk of hyponatremia High protein intake Unknown risk, recent data suggest higher CKD risk or faster CKD progression with high protein diet, in particular from animal sources Higher protein intake can accelerate the rate of CKD progression Cardiovascular diseases (cardiorenal) Ischemic nephropathy Liver disease (hepatorenal) Non-alcoholic steatohepatitis, viral hepatitis *Many of these risk factors contribute to both de novo CKD and its faster progression and, hence, are relevant to both primary and secondary prevention. Braz J Med Biol Res | doi: 10.1590/1414-431X20209614 Prevention of kidney diseases 4/10 inhibitors (RAASi). These drugs reduce both systemic blood pressure and intraglomerular pressure by opening efferent arterioles of the glomeruli, hence, leading to longevity of the remaining nephrons. Low protein diet appears to have a synergistic effect on RAASi therapy (17). In terms of the potential effect of controlling glycemic status and correcting obesity on the rate of CKD progression, there are mixed data. However, recent data suggest that a new class of anti-diabetic medications known as sodium-glucose cotransporter-2 inhibitors (SGLT2i) can slow CKD progression, but this effect may not be related to the glycemic modulation of the medication. Whereas acute kidney injury (AKI) may or may not cause de novo CKD, AKI events that are superimposed on preexisting CKD may accelerate disease progression (18). A relatively recent case of successful secondary prevention that highlights the significance of implementing preventive strategies in CKD is the use of a vasopressin type-2-receptor antagonists in adult polycystic kidney disease (19). Tertiary prevention in CKD In patients with advanced CKD, management of uremia and related comorbid conditions such as anemia, mineral and bone disorders, and cardiovascular disease is of high priority, so that these patients can achieve the highest longevity. These measures can be collectively referred to as ‘‘tertiary prevention’’ of CKD. In these individuals, cardiovascular disease burden is exceptionally high, especially if they have underlying diabetes or hypertension, while they often do not follow other traditional profiles of cardiovascular risk such as obesity or hyperlipidemia. Indeed, in these patients, a so-called ‘‘reverse epidemiology’’ exists, in that hyperlipidemia and obesity appear to be protective at this advanced stage of CKD. This could be due to the overshadowing impact of the ‘‘protein-energy wasting’’ (PEW) that happens more frequently with worsening uremia and which is associated with weight loss and poor outcomes including cardiovascular disease and death. Whereas many of these patients, if they