Chronic Kidney Disease. Nervik Roy, D.O. Internal Medicine, PGY-3 Valley Hospital Medical Center

Transcription

1 Chronic Kidney Disease Nervik Roy, D.O. Internal Medicine, PGY-3 Valley Hospital Medical Center 1

2 Disclosures No financial disclosures unfortunately 2

3 Introduction It is estimated that over 1 in 7 Americans (~15% of the population amassing ~37 million people) have CKD But, 9 in 10 American Adults who have CKD are not aware of their diagnosis. CKD is the most common cause of patients requiring Dialysis and Kidney Transplants. Patient s with CKD are at higher risk for early death than patient s with normal Kidney function. 3

4 Largest risk factors most adults are with Diabetes Mellitus and Hypertension children and adolescents younger than 18 years, polycystic kidney disease and glomerulonephritis (inflammation of the kidneys) are the main causes of CKD/ESRD. Certain agents (Over-the-counter pain medicines like ibuprofen and naproxen, Some antibiotics, and PPIs such as omeprazole and lansoprazole) can be considered nephrotoxic and large amounts over a long time can cause CKD or quicker progression to ESRD. Some other agents that can harm the kidney are contrast dyes. Kidney stones or Urinary outlet obstructions (BPH) can also lead to CKD. 4

5 The most definitive treatment to ESRD is Kidney transplant However, Transplant list is between 3-5 years and can last up to 8-10 years, depending on variety of factors. Any patient that has CKD should be followed by a Nephrologist 5

6 What is CKD? Chronic kidney disease (CKD) is defined as abnormal kidney structure or function present for >3 months. Structure Horseshoe kidney? Kidney Transplant? One singular kidney? PCKD? Function: CKD is stratified into stages 1 to 5 based on estimated glomerular filtration rate (egfr). 6

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8 Stages G1 and G2 do not have reductions in egfr and therefore are defined by the presence of anatomical defects or markers of kidney damage such as albuminuria, hematuria, or electrolyte abnormalities. Because albuminuria is associated with increased renal and cardiovascular morbidity and mortality, the Kidney Disease: Improving Global Outcomes (KDIGO) group further subdivides the egfr-based kidney stages by degree of albuminuria. This dual egfr and albuminuria staging algorithm provides a means for predicting which patients are at highest risk for developing progressive CKD into end-stage renal disease (ESRD), defined as CKD stage G5 treated with chronic dialysis or kidney transplantation. 8

9 CKD, defined by either albuminuria or egfr <60 ml/min/1.73 m 2 The prevalence of CKD is heavily influenced by age and has increased severalfold in elderly persons over the past 20 years. In the United States, the prevalence of CKD stage G3 or worse is 0.3% in those aged 20 to 39 years 3.3% in those aged 40 to 59 years 22.6% in those aged 60 years. In contrast, the prevalence of albuminuria is less age dependent. 9

10 Approximately 6% of people aged 40 to 59 years have a urine albumin-creatinine ratio 30 mg/g, compared with 8.5% of those aged 60 years. Advanced CKD, defined by stages G4 or G5, is present in <1% of the population. 10

11 CKD results from various etiologies that cause chronic damage to the glomeruli, tubulointerstitium, or both. Glomerular damage is reflected by proteinuria or albuminuria. Although a large degree of tubulointerstitial damage (both chronic inflammation and fibrosis) can exist subclinically and thus go unnoticed, eventually the underlying structural abnormalities affect kidney function, and GFR falls below normal levels. Not all patients with CKD progress to ESKD. The most important predictors of progression are the baseline level of egfr and the degree of albuminuria/proteinuria. 11

12 egfr trajectory over time also adds prognostic value for ESKD and cardiovascular outcomes. Patients with diabetic CKD usually progress faster than those without diabetes. The rate of egfr decline ranges between -3 and -6 ml per year in patients who have type 2 diabetes with high albuminuria. Renal risk variants in the apolipoprotein L1 (APOL1) gene are prevalent in black persons and are associated with higher rates of ESKD and progression of CKD, regardless of diabetes status. 12

13 Risk Factors Largest risk factor populations are those with Diabetes Mellitus, Hypertension, any history of Glomerulonephritis These account for >75% of causes of CKD Having any combination of the three above dramatically increases the chances of CKD Other risk factors: CHF Smoking NSAIDs Urinary output obstruction High protein diets 13

14 Screening CKD is typically asymptomatic except in advanced stages (G4, G5). Controversy exists regarding screening patients for CKD. USPSTF and the American College of Physicians recommend against screening for CKD in asymptomatic adults with or without risk factors for CKD. In contrast, the American Society of Nephrology advises screening all adults for CKD, including, but not limited to, those with a family history of kidney disease or adults with risk factors for CKD (diabetes, hypertension, or cardiovascular disease) 14

15 CKD is typically asymptomatic except in advanced stages (G4, G5). When egfr falls below 30 ml/min/1.73 m 2, numerous alterations in metabolic pathways, including 1,25-dihydroxyvitamin D production and erythrocyte production, become altered due to the lack of nephron mass and loss of 1α-hydroxylase and erythropoietin synthesis. Moderate to severe CKD can also result in impaired ability to excrete salt and water, and may manifest as edema. CKD in a patient with nephrotic-range proteinuria may also result in edema or anasarca. 15

16 When CKD progresses to ESKD, several nonspecific ( uremic ) symptoms can occur. Uremia: Fatigue Nausea Loss of appetite Insomnia Irritability difficulty concentrating Confusion pruritus serositis, including pleuritis and pericarditis. uremic frost 16

17 Diagnosis CKD may be clinically suspected, or it may be incidentally detected on serum creatinine. Initial assessment of GFR includes establishing egfr based on serum creatinine using the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration creatinine equation. If confirmation of GFR is required because of conditions that affect serum creatinine independent of GFR (such as extremes of muscle mass or diet), cystatin C should be measured to employ the CKD-EPI creatinine-cystatin equation, or GFR should be measured directly using a clearance procedure. 17

18 Initial assessment of albuminuria includes a random urine albumincreatinine ratio. If confirmation of albuminuria is required because of diurnal variation or conditions affecting creatinine excretion, the albumin excretion rate should be measured from a timed urine collection. Diagnosis of CKD requires a low egfr confirmed at least 3 months after initial assessment, or persistent proteinuria or albuminuria. Kidney biopsy is used to determine the etiology of CKD when a glomerulonephritis, unexplained tubulointerstitial disease, or severe proteinuria is likely based upon clinical history, urine sediment, and laboratory results and/or antibody tests 18

19 Occasionally, patients are noted to have medical Renal disease on imaging (such as US revealing hyperechoic kidneys). Urinalysis done for other nonspecific reasons may detect previously undiagnosed hematuria or proteinuria, which may suggest the presence of CKD and should prompt close observation or additional evaluation depending on the clinical scenario. Patients who experience acute kidney injury (AKI) can have slow recovery** sometimes mistaken for CKD*** 19

20 Diagnosis Quick Summary CMP/BMP/ Renal Function Panel Creatinine, BUN or electrolyte abnormalities UA Proteinuria Specific management Urine microalbumin, albumin, UPC Ultrasound 20

21 Predict Chronic Kidney Disease A kidney failure risk equation (KFRE) has been developed and validated. The KFRE uses four variables to predict 2-year and 5-year risk for ESKD in patients with CKD stages G3 to G5. age sex egfr Albuminuria*** The KFRE performs well across age, sex, race, and presence/absence of diabetes. The use of this equation is consistent with KDIGO guidelines, which recommend integration of risk prediction in the evaluation and management of CKD. eight-variable KFRE (previous four variables, plus serum calcium, phosphate, bicarbonate, and albumin); not as paramount as the 4 variable 21

22 Complications and Management According to KDIGO guidelines, referral to a nephrologist is indicated for evaluation and management of CKD in the presence of the following: AKI or an abrupt, sustained fall in GFR GFR <30 persistent albuminuria (>300 mg/g)**** progression of CKD erythrocyte casts >20 erythrocytes/hpf that is sustained and not readily explained hypertension refractory to treatment with four or more antihypertensive agents persistent abnormalities of serum potassium recurrent or extensive nephrolithiasis hereditary kidney disease 22

23 Reduction of all cause-mortality from CKD Lifestyle Modifications Diet Lower overall caloric intake decreased Potassium, Phosphorous Monitor Fluid intake as well as Sodium KidneyFund.org Exercise 30 min x day x 5 days/week Focus on large muscles and aerobic/cardio types of exercises Kidney.org 23

24 Cardiovascular Disease Cardiovascular disease is the leading cause of death among patients with CKD. **** The risk for cardiovascular-related death in patients with CKD stages G3 and G4 is 4 to 5 times higher than the risk for progression to ESKD. Mortality risk increases with decreasing egfr and increasing albuminuria. 24

25 HTN****** KDIGO and (ACC), (AHA), and nine other organizations recommend a blood pressure target of: <130/80 mm Hg in patients with CKD. An ACEi/ARB is preferred treatment of hypertension for patients with stage G3 CKD or higher or for those with stage G1 or G2 CKD with albuminuria These medications may also slow the progression of CKD in some patients. Thiazide diuretics are a cornerstone of hypertension treatment but may lose efficacy with severe CKD. 25

26 Loop diuretics therefore serve an important role in managing salt and water retention associated with proteinuria and CKD.***** Mechanism is inhibiting Loop of Henle and thus causing Salt and other electrolyte wasting, which thus causes overall water to decrease cornerstone of blood pressure management in patients with advanced chronic kidney disease. Torsemide, Furosemide, Bumetadine Dietary sodium chloride restriction is essential for blood pressure control in most forms of CKD, and KDIGO recommends restricting sodium intake to <2000 mg/d. 26

27 Dyslipidemia***** Elevated LDL cholesterol and triglyceride levels with low HDL cholesterol levels are common among patients with CKD. Statins have been shown to reduce cardiovascular and all-cause mortality in patients with CKD KDIGO recommends: statin in all patients aged 50 years with non-dialysis dependent CKD OR adults aged 18 to 49 years with non-dialysis dependent CKD and Ischemic risk factors Statins are also recommended for adult kidney transplant recipients. Dyslipidemia associated with the nephrotic syndrome helps maintain plasma oncotic pressure but, over time, may hasten the progression of glomerular injury. Dyslipidemia in the nephrotic syndrome requires aggressive treatment to prevent atherosclerotic disease, especially in patients with existing cardiovascular risk factors and in younger patients to prevent premature cardiovascular disease. 27

28 CAD There is a significantly increased prevalence of coronary artery disease (CAD) among patients with CKD compared with the general population. This is partly explained by the high prevalence of shared risk factors/comorbidities such as diabetes or hypertension. However, CKD is independently associated with CAD, and this association strengthens with declining egfr and rising albuminuria. Despite high cardiovascular mortality among patients with CKD, these patients may be less likely to undergo coronary revascularization procedures, possibly because of the increased risk for contrast-induced nephropathy. In patients with CKD, serum biomarkers for myocardial ischemia such as cardiac troponins may be chronically elevated due to decreased renal clearance. Serial troponin measurements and other markers such as creatine kinase-mb can help distinguish acute ischemia from stable elevations. 28

29 Ca and Phos homeostasis Three hormones are largely responsible for regulating calcium and phosphorus homeostasis: parathyroid hormone (PTH), vitamin D, and fibroblast growth factor 23 (FGF-23). PTH is the most important regulator of calcium and phosphorus concentrations. PTH has three separate mechanisms to increase serum calcium: It stimulates osteoclasts to resorb bone, stimulates hydroxylation of 25-hydroxyvitamin D in the kidneys, and stimulates tubular reabsorption of calcium Concurrently, PTH induces renal phosphorus excretion. FGF-23 is a peptide secreted by various types of bone cells. It acts on the kidney to induce phosphaturia and downregulates 1αhydroxylase to inhibit synthesis of 1,25 dihydroxyvitamin D. 29

30 As CKD progresses, increased FGF-23 and decreased nephron mass reduce the conversion of 25-hydroxyvitamin D to 1,25- dihydroxyvitamin D by renal tubular cells. 30

31 Secondary HyperPTH Increased plasma PTH as a result of CKD = secondary hyperparathyroidism. However, as CKD progresses, the kidney is unable to compensate for the increased release of phosphorus from bone, and phosphorus levels rise. This results in a vicious cycle as hyperphosphatemia stimulates PTH production. 31

32 Teritiary HyperPTH If secondary hyperparathyroidism cannot be adequately controlled, tertiary hyperparathyroidism can occur. Tertiary hyperparathyroidism is the result of the prolonged PTH stimulation needed to maintain eucalcemia. This prolonged stimulation results in increased calcium levels and severe hyperparathyroid hyperplasia with elevated PTH levels that are no longer responsive to the plasma calcium concentration. 32

33 Serum calcium and phosphorus levels typically remain in the normal range until the GFR drops below 20 to 30 (stages G4-G5) Ability of elevated FGF-23 and PTH levels to promote phosphorus excretion becomes overwhelmed, and hyperphosphatemia develops. Progressive decline in 1,25-d-vit D levels results in reduced intestinal calcium absorption, and hyperphosphatemia promotes precipitation of calcium and phosphorus in extra-skeletal tissues, leading to hypocalcemia. KDIGO recommends: egfr <60 (stage G3-G5) be evaluated for 25- hydroxyvitamin D deficiency and supplemented KDIGO guidelines: measure intact PTH levels in these patients to aid in the detection and management of secondary hyperparathyroidism and its complications. 33

34 Renal Osteodystrophy Renal osteodystrophy refers to alteration of bone morphology in patients with CKD KDIGO: recommends a bone biopsy if knowledge of the type of renal osteodystrophy will affect treatment decisions in patients with CKD stages G3a to G5. This recommendation is based on the growing experience with osteoporosis medications in patients with CKD, low bone mineral density, and a high risk of fracture. The lack of ability to perform a bone biopsy may not justify withholding antiresorptive therapy from patients at high risk of fracture. 34

35 Osteitis fibrosa cystica Osteitis fibrosa cystica is due to abnormally high bone turnover that can occur after prolonged exposure of bone to sustained high levels of PTH in secondary hyperparathyroidism. It is associated with an increased number and activity of osteoblasts and osteoclasts and expansion of osteoid surfaces, resulting in an increased risk for fracture. Patients can be asymptomatic or have bone pain. Classic skeletal changes on radiograph include subperiosteal resorption of bone, most prominently at the phalanges of the hands, and radiolucent bone cysts of the long bones. 35

36 Adynamic Bone Disease Adynamic bone disease occurs when there is a lack of bone cell activity and a markedly reduced rate of bone turnover. Histopathologic abnormalities include decreased osteoclast activity without an increase in osteoid due to decreased osteoblast activity, resulting in an increased risk for fracture. Patients have suppressed PTH levels (due to chronic illness or aggressive treatment with vitamin D analogues) or skeletal resistance to PTH from down-regulation of the bone PTH receptor due to high circulating PTH levels. PTH and Alk Phos levels are typically normal**** Patients may be asymptomatic or have bone pain. Adynamic bone disease should be excluded prior to bisphosphonate therapy because these drugs can cause and/or worsen the disease by inhibiting osteoclast activity. 36

37 Osteomalacia Osteomalacia is characterized by decreased mineralization of osteoid at sites of bone turnover, with increased risk of fracture. The most common symptoms include bone pain and tenderness. Although patients with CKD are at increased risk for osteomalacia, CKD does not cause osteomalacia per se; vitamin D deficiency caused by coexisting factors such as intestinal malabsorption due to gastrointestinal disorders or restricted access to sunlight is often present. 37

38 Osteoporosis Patients with CKD have many causes of reduced bone density. Current KDIGO guidelines indicate that in patients with CKD stages G3a to G5 with evidence of CKD-MBD and/or risk factors for osteoporosis, bone mineral density testing is suggested to assess fracture risk if results will affect treatment decisions. 38

39 Anemia Anemia in the setting of CKD is common, and its prevalence increases as CKD progresses into stages G4 and G5. Most often normocytic, anemia in CKD largely results from lack of erythropoietin production due to the decline in functional renal mass. Other contributors include erythropoietin resistance, neocytolysis (decreased survival time of erythrocytes), and iron deficiency. Although modest declines in hemoglobin are well tolerated, concern for inducing or contributing to the development of left ventricular hypertrophy has been the key driver in the belief that higher hemoglobin values are beneficial. 39

40 KDIGO recommendation: are to consider ESAs for patients with CKD who have hemoglobin concentrations <10. Goal Hgb concentration is between 9-12g/dL 40

41 All patients with CKD and anemia should have iron profiles assessed, including total iron-binding capacity and ferritin levels. KDIGO recommendation: 1. maintain t-saturation levels of >30% ****** 2. serum ferritin levels of >500 ng/ml using either oral or intravenous iron supplementation****** Inadequate iron stores will contribute to ESA hyporesponsiveness. Minimize the number of erythrocyte transfusions in patients with CKD and ESKD due to concerns for iron overload and sensitization to HLA antigens. 41

42 Management In patients with CKD stages G3a to G5 = serial assessments of phosphorus, calcium, and PTH levels. KDIGO recommend: that in patients with CKD stages G3a to G5, elevated phosphorus levels should be lowered toward the normal range, not into the normal range Thus, treatment should be aimed at overt hyperphosphatemia, and decisions to start phosphate-lowering treatment should be based solely on progressively or persistently elevated serum phosphorus levels.*** KDIGO recommend: avoid hypercalcemia. Mild and asymptomatic hypocalcemia can be tolerated to avoid inappropriate calcium loading. KDIGO recommends: restricting the dose of calcium-based phosphate binders (calcium carbonate and calcium acetate) in CKD stages G3a to G5, rather than restriction only in those with hypercalcemia. 42

43 For patients with CKD stages G3a to G5 who are not on dialysis, optimal PTH levels are not known. Previously, patients with PTH levels above the upper normal limit were targeted for management. KDIGO guidelines recommend against routine use of calcitriol and vitamin D analogues to lower PTH levels in patients with CKD stages G3a to G5 not on dialysis, because trials of these agents failed to demonstrate improvements in clinically relevant outcomes. Instead, these agents should be reserved for patients with CKD stages G4 to G5 with severe and progressive hyperparathyroidism. PTH goal for stage 4/5 In patients on dialysis, KDIGO guidelines recommend use of calcimimetics, calcitriol, or vitamin D analogues, or a combination of calcimimetics and calcitriol or vitamin D analogues, to lower PTH levels. Tertiary hyperparathyroidism does not respond to phosphate binders or calcitriol therapy, and patients often require parathyroidectomy for definitive treatment. 43

44 *** Metabolic acidosis frequently occurs in patients with CKD due to defective acid excretion, most commonly due to impaired ammoniagenesis. Untreated metabolic acidosis can lead to muscle loss (due to increased muscle proteolysis) and bone loss (due to increased bone resorption and impaired bone formation). In early CKD, metabolic acidosis is typically a normal anion gap hyperchloremic metabolic acidosis. As egfr declines, organic and inorganic anions are retained, and an increased anion gap metabolic acidosis develops. Alkali therapy, most commonly sodium bicarbonate or sodium citrate, can delay the progression of CKD. KDIGO: recommend alkali therapy when the serum bicarbonate is chronically <22 44

45 Nephrotoxins Two major issues exist regarding drug administration in patients with CKD: 1) Renally excreted drugs require dose adjustment to avoid accumulation and potential side effects 2) Reduced functional nephron mass increases the probability that a potentially nephrotoxic drug will cause nephrotoxicity. NSAIDS!!! STOP EM!!!! 45

46 Conceptually, compartmentalize nephrotoxic medications by their main site of action. including NSAIDs, calcineurin inhibitors, and ACE inhibitors/angiotensin receptor blockers, can have effects on glomerular blood flow. Patients with AKI who are on NSAIDs should have the medications immediately discontinued. For patients with CKD, the American Society of Nephrology recommends the avoidance of NSAIDs, including cyclooxygenase-2 inhibitors, due to the risk of worsening kidney function. ACE inhibitors or angiotensin receptor blockers are the cornerstone of treatment for patients with CKD; however, during episodes of acute illness and/or volume depletion, these drugs increase the risk for AKI due to their effects on intraglomerular pressure. Emerging literature suggests that proton pump inhibitors, in addition to their classic association with acute interstitial nephritis/aki, may contribute to the development and progression of CKD. These studies used careful comparators, including the use of H 2 blockers, and adjusted for numerous potential confounding variables, including chronic NSAID use. 46

47 Proteinuria***** The severity of proteinuria is strongly associated with adverse clinical outcomes, including progression of CKD to ESKD, cardiovascular morbidity, and mortality. It is unclear whether proteinuria is simply a marker of the underlying severity of kidney damage and disease, or if proteinuria itself activates inflammatory pathways and contributes to tubulointerstitial fibrosis. Although dual renin-angiotensin system blockade via combinations of ACE inhibitors, angiotensin receptor blockers, or direct renin inhibitors have been shown to decrease proteinuria, several clinical trials have revealed that use of combination renin-angiotensin system antagonism results in more adverse events (hyperkalemia, hypotension, AKI) without additional cardiovascular or renal benefits. insufficient evidence to recommend routine use of low protein diets to slow progression of CKD, high protein diets may precipitate or exacerbate symptoms of uremia in patients with stage G5 CKD 47

48 Considerations Imagining Intravenous iodinated contrast can cause contrast-induced nephropathy (CIN), and risk for CIN increases with increasing severity of CKD. Patients with CKD should receive IV hydration with isotonic saline or bicarbonate-containing solutions before and after receiving contrast unless there is evidence of frank pulmonary edema******** Gadolinium contrast used in MRI is associated with risk for nephrogenic systemic fibrosis (NSF) and must be avoided in patients with an egfr <30 In life-threatening situations in which benefit outweighs the risk for NSF, MRI is performed with low doses of stable gadolinium agents. Prior nephrology consult should be obtained to assess risks of gadolinium administration and guide the use of dialysis in advanced CKD and ESKD. In those with severe CKD who require gadolinium, daily dialysis for 3 days appears to be effective at clearing the gadolinium and reducing the risk for NSF. 48

49 Vaccinations Patients with CKD are at increased risk for infections that can be prevented by vaccination; however, these patients also have impaired immune responses to vaccines. The Centers for Disease Control and Prevention guidelines state that vaccinations in patients with CKD may be more effective when performed before the need for chronic dialysis or kidney transplantation. Patients with advanced CKD near dialysis dependence or those with ESKD on hemodialysis should be vaccinated against hepatitis B virus. Patients with CKD (stage not specified) or the nephrotic syndrome should receive the 23- and 13-valent pneumococcal vaccines, with revaccination with the 23- valent vaccine after a minimum of 5 years. Influenza vaccine should be administered annually to patients with CKD, but patients with ESRD should only receive the inactivated influenza vaccine due to risks associated with the live vaccines in immunocompromised patients. 49

50 Vascular access Patients with advanced CKD may ultimately require renal replacement therapy; for those who choose hemodialysis, timely vascular access creation is essential. Referral to an experienced surgeon many months before dialysis is critical because arteriovenous fistula placement can be technically challenging and may require several months for full maturation. Arteriovenous fistulas have superior clinical outcomes compared with arteriovenous grafts and tunneled catheters. Protecting the nondominant arm veins is paramount and involves limiting phlebotomy and intravenous catheters in that arm. Peripherally inserted central venous catheters should be avoided in patients with an egfr <60. Avoidance of subclavian venous catheters helps to limit subclavian stenosis, which could impair the proper functioning of an arteriovenous fistula or arteriovenous graft used for dialysis. 50

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52 Elderly CKD stages G1 through G3a in elderly patients without albuminuria is of minimal clinical importance; some may refer to this mild decrement in egfr as normal aging. For elderly persons with progressing or severe CKD necessitating discussions about renal replacement therapy and/or referral for evaluation for kidney transplantation, a patient-centered approach is preferred. Comorbid medical conditions, functional status, expected outcomes, and patient preferences regarding goals of care should be considered. For patients aged 80 years at the start of hemodialysis treatment, data demonstrate better survival among those who received pre-hemodialysis nephrology care that followed a planned management pathway, those who had a good nutritional status, and those with an arteriovenous fistula as vascular access for hemodialysis at the time of hemodialysis initiation. 52

53 Acquired cystic kidney disease Common among patients with severe CKD and ESRD. Cysts are usually detected during routine kidney ultrasonography or incidentally found on abdominal CT or MRI. These cysts are at increased risk for transformation into renal cell carcinoma, but routine screening is not recommended for most patients. A high index of suspicion is warranted for patients with new gross hematuria or unexplained flank pain. For cysts that are highly suspicious for malignancy, partial nephrectomy and nephron-sparing approaches are indicated for less severe stages of CKD. For patients with advanced CKD or ESRD, radical nephrectomy is the most prudent option. 53

54 Most important things to consider in Treatment Lifestyle, lifestyle, LIFESTYLE! BP control, consider ACEi/ARB DM control (SGLT-2i, metformin, insulin) Smoking cessation Use medications that do not target the kidney (Acetaminophen vs ibuprofen) Relieve UOP obstruction (stones, BPH) 54

55 References KDIGO Guidelines SPRINT trial NHANES survey MKSAPP 18 UpToDate Kidney.org KidneyFund.org 55

56 Center for Disease Control and Prevention. kidneyfailurerisk.com 56

57 Fin 57