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chronic renal failure (CRF)

Impaired renal function (GFR < 25-33 mL/min) > 3 months duration, generally irreversible & progressive. Classification: 1) GFR or G classification a) stage 1: GFR > 90 mL/min/1.73 m2 b) stage 2: GFR = 60-89 mL/min/1.73 m2 c) stage 3: GFR = 30-59 mL/min/1.73 m2 - stage 3a: GFR = 45-59 mL/min/1.73 m2 - stage 3b: GFR = 30-44 mL/min/1.73 m2 d) stage 4: GFR = 15-29 mL/min/1.73 m2 e) stage 5: GFR < 15 mL/min/1.73 m2 [19] 2) albuminuria or A classification - stage 1: urine albumin/creatinine ratio < 30 mg/g - stage 2: urine albumin/creatinine ratio 30-300 mg/g - stage 3: urine albumin/creatinine ratio > 300 mg/g * Thus stage G4/A3 indicates GFR 15-29 mL/min/1.73 m2 & urine urine albumin/creatinine ratio > 300 mg/g Etiology: 1) glomerulonephropathy a) primary: chronic glomerulonephritis b) secondary: diabetes mellitus (most common) 2) hypertensive nephrosclerosis (primarily vascular pathology) 3) chronic tubulointerstitial disease 4) cystic kidney disease (polycystic kidney disease) 5) obstructive uropathy 6) heart failure 7) infection a) viral hepatitis b) HIV 8) hypothyroidism 9) hypoadrenalism 10) hypercalcemia 11) medications - prolonged use of NSAIDs 12) injection drug use 13) cirrhosis 14) risk factors [4] a) diabetes mellitus b) hypertension c) dyslipidemia - seafood-based omega-3 fatty acids (EPA, DHA) reduce risk by 13% - plant-based omega-3 fatty acids (ALA) do not [66] d) cardiovascular disease e) obesity is associated with excess risk for GFR decline & end-stage renal disease [56] f) metabolic syndrome g) age > 60 years h) malignancy 1] multiple myeloma 2] kidney cancer, resection 3] chemotherapy i) family history of chronic kidney disease j) smoking k) HIV infection l) hepatitis C m) kidney stones n) autoimmune disease o) recurrent urinary tract infection - childhood recurrent urinary tract infection unlikely cause [18] p) recovery from acute renal failure q) exposure to nephrotoxic drugs 1] NSAIDs 2] COX2 inhibitors 3] alcoholic beverage consumption may decrease risk [43] r) renal transplantation 1] immunosuppression 2] transplantation rejection [4] s) premenopausal bilateral oophorectomy [54] Epidemiology: - current definition based on eGFR < 60 ml/min/1.73 m2 or albuminuria estimates ~14% of population - estimates out of proportion to prevalence of ESRD - previous estimates of ~ 1.7% of population [29] Pathology: 1) glomerular hyperfiltration in response to diminished glomerular filtration rate (GFR) 2) compensatory hypertrophy or increase in glomerular size 3) glomerular hypertension 4) glomerular sclerosis & interstitial fibrosis 5) mesangial trapping of macrophages 6) platelet aggregation in glomerular capillaries 7) damage from hyperlipidemia 8) ammonium or calcium phosphate deposition in the renal interstitium 9) pro-inflammatory & pro-coagulant millieu [5] (see Laboratory) 10) excessive sympathetic nervous system activity [7] 11) alteration in bone & mineral metabolism [4] Genetics: - high-risk ApoL1 genotype confers risk for chronic renal failure in blacks [4] Clinical manifestations: 1) persistence of renal failure > 3 months [4] 2) polyuria & nocturia a) may be earliest symptoms b) secondary to loss of concentrating ability 3) sign/symptoms do become apparent until GFR < 30 mL/min 4) sign/symptoms of uremia - dysgeusia, pruritus, anorexia, delirium 5) sign/symptoms of anemia - easily fatigued, lightheadedness (dizziness), difficulty concentrating 6) sign/symptoms of volume overload a) peripheral edema b) new or worsening hypertension c) ascites d) congestive heart failure e) dyspnea f) pericardial effusion 7) gastrointestinal disorders are more common in CRF patients 8) symptoms of secondary hyperparathyroidism a) hypocalcemia b) hyperphosphatemia c) renal osteodystrophy 9) small kidneys 10) amenorrhea & impotence is common 11) pregnancy is rare if serum creatinine > 2.0 mg/dL 12) increased insulin resistance & decreased insulin clearance 13) accelerated atherosclerosis is common 14) constipation is common & aggravated by phosphate binders 15) gout & pseudogout are common 16) peripheral neuropathy a) sensory fibers are affected more than motor fibers b) lower extremities are involved more than the upper extremities c) often associated with asterixis & seizures Laboratory: 1) serum chemistries a) serum urea nitrogen b) serum creatinine (> 1.5 mg/dL in men; 1.3 mg/dL in women) 1] may overestimate renal function 2] referral to nephrologist when > 2.0 mg/dL c) serum potassium d) serum bicarbonate - low serum bicarbonate predicts progression [53] e) serum calcium f) serum phosphorus - increased serum phosphorus is associated with increased mortality [27] g) serum albumin h) serum glucose (impaired carbohydrate tolerance) i) lipid panel - hyperlipidemia is common - target LDL cholesterol < 100 mg/dL [4] j) metabolic acidosis 1] at 1st normal anion gap - decreased secretion of NH4+ 2] then high anion gap (rarely > 25) - retention of phosphates & sulfates k) serum iron, TIBC & serum ferritin l) increased serum levels of inflammatory markers [5] -> serum IL-6, serum C-reactive protein m) increased plasma levels of pro-coagulants - fibrinogen in plasma - factor VII activity in plasma - factor VIII activity in plasma - D-dimer in plasma 2) urinalysis, including evaluation of urine sediment a) urine microscopy for hematuria b) urine microscopy for urinary casts 3) 24 hour urine a) 24 hour urine protein b) urine albumin/creatinine ratio c) creatinine clearance (eGFR) d) higher urine albumin/creatinine ratio & lower eGFR associated with excess risks for all-cause death, CV-related death & ESRD [21] 4) complete blood count (CBC) a) hemoglobin/hematocrit b) anemia workup as needed - anemia of chronic renal failure has a blood hemoglobin of ~10 g/dL - may occur with stage G3a renal failure - see anemia of chronic renal failure c) serum erythropoietin not diagnostic & not indicated [4] 5) serum & urine protein electrophoresis 6) endocrine abnormalities a) total thyroxine levels are generally low b) growth hormone levels are generally high c) increased serum gastrin d) increased serum prolactin e) increased serum PTH: maintain < 3X upper limit of normal 1] overcome bone-resistance to PTH 2] avoid excessive hyperparathyroidism f) decreased serum 1,25-dihydroxyvitamin D3 - serum 25-hydroxyvitamin D may be low g) insulin levels increase (decreased renal clearance of insulin) 7) renal biopsy (glomerular disease) * hemoglobin A1c values may not be reliable with more severe renal failure (see end-stage renal disease) Radiology: 1) renal ultrasound a) estimation of kidney size b) rule out obstructive uropathy c) renal papillary necrosis 2) if radiocontrast agent must be used a) give IV normal saline before & after procedure b) N-acetylcysteine (Mucomyst) prophylaxis 3) MRI with gadolinium contrast should be avoided in patients with GFR < 30 mL/min/1.73 m2 [4] Differential diagnosis: 1) acute renal failure (ARF) 2) chronic renal failure (CRF) a) diabetic nephropathy - early albuminuria, proteinuria, hypertension, declining GFR, coexisting retinopathy b) gomerular disease (glomerulonephritis) 1] hematuria, dysmorphic erythrocytes, erythrocyte casts, proteinuria, hypertension 2] often other systemic manifastations - lupus nephritis, post-infectious glomerulonephritis 3] nephrotic syndrome: a] membranous nephropathy b] minimal change disease 4] renal biopsy may be necessary c) tubulointerstitial disease 1] proteinuria, glucosuria, ososthenuria, sterile pyuria, leukocyte casts, renal papillary necrosis on ultrasound 2] analagesic nephropathy (NSAIDs), lead nephropathy 3] tuberculosis, legionnaires disease, leptospirosis 4] allergic drug reaction: eosinophilia, eosinophiluria 5] autoimmune disorder: sarcoidosis, systemic lupus, Sjogren's syndrome d) renal vascular disease 1] hematuria, poteinuria, associated systemic illness 2] vasculitis often presents with glomerulonephritis & palpable purpura e) polycystic kidney disease 1] imaging & family history 2] autosomal dominant types 1 & 2 most common 3] hypertension, hematuria f) post-transplantation nephropathy - chronic allograft nephropathy, drug toxicity, recurrence of renal disease Complications: 1) normocytic anemia a) anemia of chronic renal disease b) iron-deficiency anemia - GI hemorrhage from peptic ulcer disease & angiodysplasia common in patients with chronic renal failure [4] 2) renal osteodystrophy a) vitamin D deficiency is common b) hypocalcemia c) hyperphosphatemia 3) increased risk of a) cardiovascular disease - increased risk of cardiovascular events [4] - leading cause of death in patients with chronic kidney disease [4] - cardiovascular mortality [26] - if well controlled diabetes mellitus & well-controlled hypertension, coronary artery disease & MI are the major risks - patients less likely to present with chest pain [4] - uncontrolled hypertension is a risk factor for stroke b) acquired polycystic kidney disease c) renal cell carcinoma d) cognitive impairment e) depression [19] f) end-stage renal disease [20] g) mortality [20,26] 4) metabolic acidosis [4] 5) impaired clearance of medications, especially a) analgesics, including NSAIDs b) barbiturates c) antihistamines, including diphenhydramine d) decongestants containing ephedrine or ephedrine-related compounds e) muscle relaxants f) antiarrhythmic agents, including amiodarone, digoxin, short-acting calcium channel blockers [19] 6) complications of uremia (GFR < 10-15 mL/min/1.73 m2) - pericarditis, GI bleed, uremic encephalopathy, uremic neuropathy, pruritus, calciphylaxis [4] 7) patients on warfarin have higher risk of major hemorrhage; NNH = 7 patients for 1 year [44] - patients require lower warfarin doses - patient are more likely to have INRs outside the therapeutic range - increased risk for major hemorrhage when INR >= 4 & GFR is < 45 mL/minute/1.73 m2 [44] 8) disease progression - end-stage renal disease - albuminuria is a risk factor for disease progression at all levels of albuminuria & microalbuminuria with higher levels of albuminuria associated with higher risks [68] Management: 1) no definitive treatment - adjust doses of renally cleared pharmaceuticals - sodium restriction, potassium restriction, phosphate restriction - avoid protein restriction (see diet below) 2) goals of therapy a) treat reversible causes, especially 1] hypertension a] goal < 130/80 mm Hg, < 125/75 mm Hg if proteinuria > 1 g/24 hours [4] b] target systolic blood pressure < 120 mm Hg (KDIGO, grade 2B) [60] c] no benefit target blood pressure < 140/90 mm Hg [16,28] in terms of mortality, ESRD, cardiovascular events d] systolic blood pressure < 130 mm Hg associated with increased mortality [13] if diastolic BP < 70 mm Hg [31] e] BP of 130-159 mm Hg systolic & 70-89 diastolic with lowest mortality [31] f] systolic BP 132 mm Hg associated with 14% lower all-cause mortality than systolic BP of 140 mm Hg [52] g] inhibition of renin-angiotensin axis more important than blood pressure reduction (see REIN-2 trial) h] most patients require at least 2 antihypertensives - ACE inihibitor or ARB + diuretic i] low salt diet < 2 grams sodium per day; - high Na+ intake in patients with CRF associated with increased risk for cardiovascular events [48] j] ambulatory blood pressure monitoring better than BP measured in clinic [17]; - BP goals for ambulatory blood pressure may differ from those of office blood pressure [1,17] k] bedtime dosing of antihypertensives may diminish cardiovascular risk [45] 2] diabetes: maintain Hgb A1c between 7.0-7.9% [4] 3] control cardiovascular risk factors b) limit progression of renal failure c) minimize sequelae d) target hemoglobin 11.0 g/dL (see anemia of renal failure) e) control risk factors - target LDL cholesterol 100 mg/dL f) see medications to avoid in patients with CRF 3) pharmaceutical agents a) erythropoietin (EPO) 1] symptomatic anemia of chronic renal failure with blood Hgb < 10 g/dL [4] 2] except polycystic kidney disease (EPO generally normal) 3] target: blood hemoglobin of 11-12 g/dL 4] check iron, TIBC, ferritin before initiating erythropoietin (EPO) 5] maintain transferrin saturation > 30% & serum ferritin > 500 ng/mL 5] do not check serum erythropoietin [4] b) ACE inhibitors, angiotensin receptor blocker ARB 1] may preserve renal function by limiting hyperfiltration - may reduce the need for dialysis [37] 2] reduces mortality versus placebo (RR=0.79 vs placebo) in patients with microalbuminuria & cardiovascular disease or high-risk diabetes [41] 3] may cause decline in GFR 4] indicated for treatment of hypertension in patients with stage 1 to stage 3 chronic renal failure [32] 5] there is no maximum serum creatinine or mininum eGFR beyond which ACE inhibitors cannot be used [38] 6] hyperkalemia is adverse effect 7] NOT useful for polycystic kidney disease 8] addition Ca+ channel blocker not helpful (REIN-2) 9] combined ACE inhibitor/ARB dual therapy less effective than monotherapy [12] 10] cut the dose of ACE inhibitor or ARB in 1/2 or hold if serum creatinine rises by > 30% 11] hold (dose of ACE inhibitor or ARB if serum potassium >= 5.5 meq/L [38] c) flozins SGLT-2 inhibitors) may slow progression of chronic renal failure in patients with or without diabetes mellitus [64] d) investigational aldosterone receptor antagonist finerenone may slow decline in renal function in patients with diabetes mellitus [65] e) phosphate binders to prevent hyperphosphatemia 1] maintain serum phosphate 3.5-5.5 mg/dL 2] calcium acetate (PhosLo) or calcium carbonate - can bind phosphate in the gut 3] use of non-calcium-based-phosphate-binders sevelamer (Renagel, Renvela) & lanthanum (Fosrenol) associated with lower mortality than use of calcium-based- phosphate-binders (RR=0.78) & less progression of coronary artery calcification [30] 4] use of phosphate binders may allow continued use of RAAS inhibitor [4] f) vitamin D for vitamin D deficiency - 1,25-dihydroxyvitamin D (calcitriol) for elevated serum PTH & serum 25-hydroxvitamin D > 30 ng/mL in dialysis patients [4] - avoid calcitriol for CKD3-CKD5 - avoid hypercalcemia, mild asymptomatic hypocalcemia tolerable - vitamin D therapy does not reduce the risk of all-cause death in CKD [67] g) loop diuretic: 1] hypertension, edema, hyperkalemia 2] may enhance effect of ACE inhibitors 3] useful in patients with GFR < 30 mL/min/1.73 m2 h) bicarbonate replacement 1] metabolic acidosis - sodium bicarbonate [39] or sodium citrate [40] preserves renal function in patients with low GFR & metabolic acidosis 2] keep [HCO3-] 20-26 meq/L (> 22 meq/L) [4] i) EDTA chelation therapy may be of benefit [6] j) cinacalcet for secondary hyperparathyroidism k) avoid nephrotoxic agents 1] Mg+2 & phosphate containing cathartics 2] NSAIDs, COX2 inhibitors 3] iodinated contrast 4] avoid gadolinium contrast for CKD4, CKD5 4] avoid proton pump inhibitors [4] l) avoid metformin if eGFR < 30 mL/min/1.73 m2 - do not start metformin if eGFR < 45 mL/min/1.73 m2 m) use bisphosphonates with caution n) statin or ezetimibe for adults >= 50 years with eGFR < 60 mL/min/1.73 m2 [4,35] - as needed to maintain LDL cholesterol < 100 mg/dL [24,32] - may preserve renal function in patients with cardiovascular disease [9] - no benefit for dialysis patients [4,35,51] - not for renal transplantation patients [35] - reduces mortality & cardiovascular events versus placebo in patients with hyperlipidemia [41,50] - AHA/ACC says it is reasonable to initiate a moderate intensity statin with or without ezetimibe for adults 40-75 years with LDL cholesterol of 70-189 mg/dL & 10 year risk of cardiovascular disease of >7.5% [4] o) benefits of antiplatelet agents are uncertain in patients with chronic kidney disease & potentially outweighed by bleeding risks [42] 4) dialysis a) dialysis access when creatinine clearance <10-15 mL/min b) hemodialysis vs peritoneal dialysis - clinical outcomes equivalent [4] c) begin discussion of renal replacement therapy at least 1 year prior to the anticipated start of dialysis or when the GFR drops below 30 mL/min/1.73 m2 (stage 4) d) refer to surgeon for arteriovenous fistula placement prior to anticipated need for dialysis [4] e) begin dialysis in patients with uremic symptoms, electrolyte imbalances, volume overload or malnureition that cannot be controlled with medical therapy [4] f) early initiation of dialysis associated with increased mortality [15] g) maintain central venous patency in patients who may need hemodialysis [4,22] - avoid central venous catheters, including PICC lines in non-dominant arm if possible [47] - central venous stenosis most commonly occurs from endothelial damage from central venous catheters - use peripheral venous access if possible [4,22] - use hands for venipuncture & peripheral venous access if possible - use internal jugular vein for antibiotic therapy of weeks duration [2] h) avoid gadolinium contrast for MRI 5) renal transplantation a) treatment of choice for most patients with end-stage renal disease b) children must be > 10-15 kg to be eligible c) patients who are candidates for renal transplantation should be refered CKD is stage 4 when eGFR is 15-29 mL/min/1.73 m2 [4] - MKSAP19 says refer patient for renal replacement therapy education prior to referral for kidney transplant evaluation [4] d) avoid transfusions in patients who are candidates for renal transplantation e) preemptive renal transplantation prior to dialysis has a better prognosis than transplantation after dialysis [4] 6) diet a) sodium restriction to < 2 g/day b) potassium restriction to < 2 g/day c) fluid restriction to < 1.5 L/day if signs of volume overload d) protein restriction to 40 g of high-quality protein/day (0.6-1.0 g/kg/day if not on dialysis [4]) - dietary protein intake is not associated with all-cause mortality [70] - higher dietary protein intake is associated with lower mortality [71] e) phosphate restriction f) heart healthy diet - seafood-based omega-3 fatty acids (EPA, DHA) reduce risk by 13% - plant-based omega-3 fatty acids (ALA) do not [66] 7) exercise: - moderate-intensity physical activity for 150 minutes weekly [60] - attenuates decline in renal function in older adults [63] 8) pharmaceuticals to avoid - NSAIDs, COX-2 inhibitors - vasoconstrictor agents: - ephedrine, pseudoephedrine, phenylephrine, oxymetazoline - laxatives: magnesium hydroxide, sodium phosphate - antacids: aluminum hydroxide, magnesium hydroxide, sucralfate - dietary supplements - creatine - germanium - salt substitutes (KCl) - pharmaceutical herbs - aristolochic acid, ephedra [4] - hydromorphone, fentanyl, methadone, buprenorphine, hydrocodone show minimal pharmacokinetic changes in patients with renal failure [62] 9) vaccination as needed - response to vaccines is superior prior to dialysis or renal transplantation - in adults age 19-64 years, vaccination with both PCV13 & PPSV23 is indicated - with advanced kidney disease a 2nd dose of PPSV23 is recommended 5 years after the 1st [4] - annual influenza virus vaccine 10) referral to nephrologist when serum creatinine > 2.0 mg/dL or GFR < 20 mL/min/1.73 m2 (G4 or G5) [4,46] - obtain basic metabolic panel, urinalysis, 24 hour urine protein, renal ultrasound with bladder 11) referral to ophthalmologist for funduscopy if diabetic - diabetic retinopathy Prognosis: - adults with moderate chronic renal failur are unlikely to progress to end-stage renal disease (ESRD) over a 5-year period [49] - eGFR remains stable in 34%, improves in > 19% & worsens in < 18% [49] - Kidney Failure Risk Equation (KFRE) estimates 2 year risk of ESRD - 6-variable ESRD risk score (Z6) estimates risk of ESRD

Interactions

disease interactions

Related

anemia of chronic renal failure Cooperate clinical trial medications to avoid in patients with chronic renal failure Modification of diet in Renal Disease (MDRD) Study nephrotoxic substances REIN-2 clinical trial renal osteodystrophy uremia

Specific

cardiovascular-kidney-metabolic (CKM) syndrome chronic kidney disease-mineral & bone disorder (CKD-MBD) chronic renal failure in pregnancy chronic renal failure stage 2 chronic renal failure stage 3 chronic renal failure stage 4 chronic renal failure stage 5 diabetic nephropathy; diabetic glomerulosclerosis; Kimmelstiel-Wilson disease (DMN) end-stage renal disease (ESRD) hypertensive nephropathy; hypertensive nephrosclerosis; hypertensive kidney disease renal insufficiency

General

chronic kidney disease (CKD) renal failure; kidney failure

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 263-268
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 538-539
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 616-17, 626
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006. 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. Journal Watch 23(5):38-39, 2003 Shlipak MG et al Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation 107:87, 2003 PMID: 12515748
  6. Journal Watch 23(5):38, 2003 Lin JL et al Environmental lead exposure and progression of chronic renal diseases in patients without diabetes. N Engl J Med 348:277, 2003 PMID: 12540640 - Marsden PA Increased body lead burden--cause or consequence of chronic renal insufficiency? N Engl J Med 348:345, 2003 PMID: 12540649
  7. Journal Watch 25(3):23, 2005 Abbott KC, Trespalacios FC, Agodoa LY, Taylor AJ, Bakris GL. beta-Blocker use in long-term dialysis patients: association with hospitalized heart failure and mortality. Arch Intern Med. 2004 Dec 13-27;164(22):2465-71. PMID: 15596637
  8. Journal Watch 25(8):63, 2005 Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, Levey AS. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study. Ann Intern Med. 2005 Mar 1;142(5):342-51. PMID: 15738453
  9. Tonelli M, Isles C, Craven T, Tonkin A, Pfeffer MA, Shepherd J, Sacks FM, Furberg C, Cobbe SM, Simes J, West M, Packard C, Curhan GC. Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease. Circulation. 2005 Jul 12;112(2):171-8. Epub 2005 Jul 5. PMID: 15998677
  10. Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, Geng RW. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006 Jan 12;354(2):131-40. PMID: 16407508 - Hebert LA. Optimizing ACE-inhibitor therapy for chronic kidney disease. N Engl J Med. 2006 Jan 12;354(2):189-91. No abstract available. PMID: 16407515
  11. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006 Jan 3;144(1):21-8. Summary for patients in: Ann Intern Med. 2006 Jan 3;144(1):I28. PMID: 16389251
  12. Mann JFE et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): A multicentre, randomised, double-blind, controlled trial. Lancet 2008 Aug 16; 372:547. PMID: 18707986
  13. Weiss JW et al. Systolic blood pressure and mortality among older community-dwelling adults with CKD. Am J Kidney Dis 2010 Dec; 56:1062 PMID: 20961677
  14. Yaffe K, Ackerson L, Kurella Tamura M, et al. Chronic kidney disease and cognitive function in older adults: findings from the chronic renal insufficiency cohort cognitive study. J Am Geriatr Soc 2010 Feb; 58(2):338-345. Epub 2010 Jan 26. PMID: 20374407
  15. Clark WF et al. Association between estimated glomerular filtration rate at initiation of dialysis and mortality. CMAJ 2011 Jan 11; 183:47 PMID: 21135082
  16. Upadhyay A et al Systematic Review: Blood Pressure Target in Chronic Kidney Disease and Proteinuria as an Effect Modifier Annals of Internal Medicine, March 14, 2011 PMID: 21403055 http://www.annals.org/content/early/2011/03/11/0003-4819-154-8-201104190-00335
  17. Minutolo R et al Prognostic Role of Ambulatory Blood Pressure Measurement in Patients With Nondialysis Chronic Kidney Disease Arch Intern Med. 2011;171(12):1090-1098. PMID: 21709109 http://archinte.ama-assn.org/cgi/content/short/171/12/1090
  18. Salo J et al Childhood Urinary Tract Infections as a Cause of Chronic Kidney Disease Pediatrics, October 10, 2011 PMID: 21987701 http://pediatrics.aappublications.org/content/early/2011/10/06/peds.2010-3520.abstract
  19. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
  20. Mahmoodi BK et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: A meta-analysis. Lancet 2012 Sep 24 PMID: 23013600 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61272-0/fulltext - Fox CS et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: A meta-analysis. Lancet 2012 Sep 24 PMID: 23013602 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61350-6/fulltext
  21. Nitsch D et al. Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: A meta-analysis. BMJ 2013 Jan 29; 346:f32 PMID: 23360717
  22. Hoggard J, Saad T, Schon D et al Guidelines for venous access in patients with chronic kidney disease. A Position Statement from the American Society of Diagnostic and Interventional Nephrology, Clinical Practice Committee and the Association for Vascular Access. Semin Dial. 2008 Mar-Apr;21(2):186-91 PMID: 18364015
  23. Ernst ME, Gordon JA. Diuretic therapy: key aspects in hypertension and renal disease. J Nephrol. 2010 Sep-Oct;23(5):487-93. PMID: 20677164
  24. Navaneethan SD, Pansini F, Perkovic V et al HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2009 Apr 15;(2) PMID: 19370693
  25. Sprague SM, Coyne D. Control of secondary hyperparathyroidism by vitamin D receptor agonists in chronic kidney disease. Clin J Am Soc Nephrol. 2010 Mar;5(3):512-8. PMID: 20133492
  26. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23;351(13):1296-305. PMID: 15385656
  27. Palmer SC, Hayen A, Macaskill P et al Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. JAMA. 2011 Mar 16;305(11):1119-27 PMID: 21406649
  28. Wright JT Jr, Bakris G, Greene T et al Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002 Nov 20;288(19):2421-31. PMID: 12435255
  29. Moynihan R et al Chronic kidney disease controversy: how expanding definitions are unnecessarily labelling many people as diseased. BMJ 2013;347:f4298 PMID: 23900313 http://www.bmj.com/content/347/bmj.f4298
  30. Jamal SA et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: An updated systematic review and meta-analysis. Lancet. 2013 Oct 12;382(9900):1268-77 PMID: 23870817
  31. Kovesdy CP et al Blood Pressure and Mortality in U.S. Veterans With Chronic Kidney Disease: A Cohort Study. Ann Intern Med. 2013;159(4):233-242 PMID: 24026256 http://annals.org/article.aspx?articleid=1726794 - Rifkin DE and Sarnak MJ How Low Can You Go? Blood Pressure and Mortality in Chronic Kidney Disease Ann Intern Med. 2013;159(4):302-303. PMID: 24026262 http://annals.org/article.aspx?articleid=1726833
  32. Qaseem A et al Screening, Monitoring, and Treatment of Stage 1 to 3 Chronic Kidney Disease: A Clinical Practice Guideline From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. Published online 22 October 2013 PMID: 24145991 http://annals.org/article.aspx?articleid=1757302
  33. National Kidney Foundation KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012 Nov;60(5):850-86 PMID: 43788 (corresponding NGC guideline withdrawn Jan 2018)
  34. Blood Pressure Lowering Treatment Trialists' Collaboration. Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: Meta-analysis of randomised controlled trials. BMJ 2013;347:f5680 PMID: 24092942 http://www.bmj.com/content/347/bmj.f5680
  35. Tonelli M et al Lipid Management in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2013 Clinical Practice Guideline. Ann Intern Med. Published online 10 December 2013 PMID: 24323134 http://annals.org/article.aspx?articleid=1788220
  36. Eilers H, Liu KD, Gruber A, Niemann CU. Chronic kidney disease: implications for the perioperative period. Minerva Anestesiol. 2010 Sep;76(9):725-36. Epub 2010 Jun 28. PMID: 20820151
  37. Hsu TW, Liu JS, Hung SC et al Renoprotective Effect of Renin-Angiotensin-Aldosterone System Blockade in Patients With Predialysis Advanced Chronic Kidney Disease, Hypertension, and Anemia. JAMA Intern Med. Published online December 16, 2013 PMID: 24343093 http://archinte.jamanetwork.com/article.aspx?articleid=1787693 - Park M and Hsu CY An ACE in the Hole for Patients With Advanced Chronic Kidney Disease? JAMA Intern Med. Published online December 16, 2013 PMID: 24342932 http://archinte.jamanetwork.com/article.aspx?articleid=1787689
  38. Prescriber's Letter 21(6): 2014 Safe Use of ACE Inhibitors or ARBs Detail-Document#: 300618 (subscription needed) http://www.prescribersletter.com - Bhandari S, Mehta S, Khwaja A Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. N Engl J Med. 2022. Nov 3. PMID: 36326117 https://www.nejm.org/doi/full/10.1056/NEJMoa2210639
  39. de Brito-Ashurst I et al. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol 2009 Jul 18; 20:2075. PMID: 19608703
  40. Phisitkul S et al. Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR. Kidney Int 2010 Jan 15; 77:617. PMID: 20072112
  41. Fink HA, Ishani A, Taylor BC et al Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: a systematic review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2012 Apr 17;156(8):570-81 PMID: 22508734
  42. Palmer SC, Di Micco L, Razavian M et al Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012 Mar 20;156(6):445-59. PMID: 22431677
  43. Koning SH et al. Alcohol consumption is inversely associated with the risk of developing chronic kidney disease. Kidney Int 2015 May; 87:1009. PMID: 25587707
  44. Limdi NA et al. Influence of kidney function on risk of supratherapeutic international normalized ratio-related hemorrhage in warfarin users: A prospective cohort study. Am J Kidney Dis 2015 May; 65:701 PMID: 25468385 - Jun M, James MT, Manns BJ et al The association between kidney function and major bleeding in older adults with atrial fibrillation starting warfarin treatment: population based observational study. BMJ. 2015 Feb 3;350:h246 PMID: 25647223 - Limdi NA, Beasley TM, Baird MF et al Kidney function influences warfarin responsiveness and hemorrhagic complications. J Am Soc Nephrol. 2009 Apr;20(4):912-21 PMID: 19225037
  45. Hermida RC, Ayala DE, Mojon A, Fernandez JR. Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol. 2011 Dec;22(12):2313-21. Epub 2011 Oct 24. PMID: 22025630 Free PMC Article
  46. Smart NA, Titus TT. Outcomes of early versus late nephrology referral in chronic kidney disease: a systematic review. Am J Med. 2011 Nov;124(11):1073-80.e2. Review. PMID: 22017785
  47. El Ters M, Schears GJ, Taler SJ et al Association between prior peripherally inserted central catheters and lack of functioning arteriovenous fistulas: a case-control study in hemodialysis patients. Am J Kidney Dis. 2012 Oct;60(4):601-8. PMID: 22704142 Free PMC Article
  48. Mills KT Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease. JAMA. 2016;315(20):2200-2210. PMID: 27218629 http://jama.jamanetwork.com/article.aspx?articleid=2524189 - Powe NR, Bibbins-Domingo K Dietary Salt, Kidney Disease, and Cardiovascular Health. JAMA. 2016;315(20):2173-2174 PMID: 27218627 http://jama.jamanetwork.com/article.aspx?articleid=2524166
  49. Shardlow A, McIntyre NJ, Fluck RJ, McIntyre CW, Taal NW Chronic Kidney Disease in Primary Care: Outcomes after Five Years in a Prospective Cohort Study. PLOS Medicine. September 20, 2016 PMID: 27648564 Free Article http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002128
  50. Palmer SC, Navaneethan SD, Craig JC et al HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2014 May 31;(5):CD007784. Review. PMID: 24880031
  51. Palmer SC, Navaneethan SD, Craig JC et al HMG CoA reductase inhibitors (statins) for dialysis patients. Cochrane Database Syst Rev. 2013 Sep 11;(9):CD004289. Review. PMID: 24022428
  52. Malhotra R, Nguyen HA, Benavente O et al Association Between More Intensive vs Less Intensive Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease Stages 3 to 5A Systematic Review and Meta-analysis. JAMA Intern Med. Published online September 5, 2017 PMID: 28873137 http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2652833 - Kovesdy CP The Ideal Blood Pressure Target for Patients With Chronic Kidney Disease-Searching for the Sweet Spot. JAMA Intern Med. Published online September 5, 2017 PMID: 28873120 http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2652830
  53. Monaco K. Serum Bicarbonate Tied to CKD Progression. Another use for multivariate risk equations MedPage Today. April 13, 2018 https://www.medpagetoday.com/meetingcoverage/nkf/72342 - Tangri N, et al Use of the kidney failure risk equations to model clinical trial outcomes. National Kidney Foundation (NKF) 2018; Abstract #365.
  54. Kattah AG, Smith CY, Rocca LG et al CKD in Patients with Bilateral Oophorectomy. CJASN September 2018, CJN.03990318 PMID: 30232136 https://cjasn.asnjournals.org/content/early/2018/09/19/CJN.03990318
  55. Anonymous Chapter 1: Diagnosis and evaluation of anemia in CKD. Kidney Int Suppl (2011). 2012 Aug;2(4):288-291. PMID: 25018948 Free PMC Article
  56. Chang AR, Grams ME, Ballew SH, et al. Adiposity and risk of decline in glomerular filtration rate: Meta-analysis of individual participant data in a global consortium. BMJ 2019 Jan 10; 364:k5301. PMID: 30630856 Free Article https://www.bmj.com/content/364/bmj.k5301
  57. Panwar B, Gutierrez OM. Disorders of Iron Metabolism and Anemia in Chronic Kidney Disease. Semin Nephrol. 2016 Jul;36(4):252-61. Review. PMID: 27475656
  58. Valika A, Peixoto AJ. Hypertension Management in Transition: From CKD to ESRD. Adv Chronic Kidney Dis. 2016 Jul;23(4):255-61. Review. PMID: 27324679
  59. Tangri N, Grams ME, Levey AS et al Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure: A Meta-analysis. JAMA. 2016 Jan 12;315(2):164-74. PMID: 26757465 Free PMC Article
  60. Tomson CRV, Cheung AK, Mann JFE et al. Management of blood pressure in patients with chronic kidney disease not receiving dialysis: Synopsis of the 2021 KDIGO clinical practice guideline. Ann Intern Med 2021 Jun 22; PMID: 34152826 Free article https://www.acpjournals.org/doi/10.7326/M21-0834
  61. Zacharias HU et al. A predictive model for progression of CKD to kidney failure based on routine laboratory tests. Am J Kidney Dis 2022 Feb; 79:217. https://www.ajkd.org/article/S0272-6386(21)00729-0/fulltext
  62. Davison NS Clinical pharmacology considerations in pain management in patients with advanced kidney failure. Clin J Am Soc Nephrol 2019 14(6):917-931 PMID: 30833302 PMCID: PMC6556722 Free PMC article
  63. Shlipak MG et al. Effect of structured, moderate exercise on kidney function decline in sedentary older adults: An ancillary analysis of the LIFE Study randomized clinical trial. JAMA Intern Med 2022 May 2; [e-pub] PMID: 35499834 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2791340
  64. The EMPA-KIDNEY Collaborative Group Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2022. Nov 4 PMID: 36331190 https://www.nejm.org/doi/full/10.1056/NEJMoa2204233 - Heerspink HJL, Stefansson BV, Correa-Rotter R et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020 Sep 24; [e-pub]. PMID: 32970396 Free article. https://www.nejm.org/doi/10.1056/NEJMoa2024816
  65. Bakris GL, Agarwal B, Anker SD et al Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020. Oct 3. PMID: 33264825 https://www.nejm.org/doi/full/10.1056/NEJMoa2025845 - Ingelfinger JR, Rosen CJ Finerenone - Halting Relative Hyperaldosteronism in Chronic Kidney Disease. N Engl J Med. 2020. Oct 3. PMID: 33095527 https://www.nejm.org/doi/full/10.1056/NEJMe2031382
  66. Ong KL et al. Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: Pooled analysis of 19 cohorts. BMJ 2023 Jan 18; 380:e072909 PMID: 36653033 PMCID: PMC9846698 Free PMC article https://www.bmj.com/content/380/bmj-2022-072909
  67. Yeung WG, Palmer SC, Strippoli GFM et al Vitamin D Therapy in Adults With CKD: A Systematic Review and Meta-analysis. Am J Kidney Dis. 2023 Jun 24:S0272-6386(23)00693-5. PMID: 37356648
  68. Verma A, Schmidt IM, Claudel S et al Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study Ann Intern Med. 2024 Apr;177(4):467-475. PMID: 38560911 https://www.acpjournals.org/doi/10.7326/M23-2814
  69. Owsiany MT, Hawley CE, Triantafylidis LK, Paik JM. Opioid Management in Older Adults with Chronic Kidney Disease: A Review. Am J Med. 2019 Dec;132(12):1386-1393. PMID: 31295441 PMCID: PMC6917891 Free PMC article. Review.
  70. Kwon YJ, et al. The Association Between Total Protein Intake and All-Cause Mortality in Middle Aged and Older Korean Adults With Chronic Kidney Disease. Front Nutr. 2022. PMID: 35445069 PMCID: PMC9014017 Free PMC article.
  71. Carballo-Casla A, et al. Protein Intake and Mortality in Older Adults With Chronic Kidney Disease. JAMA Netw Open. 2024. PMID: 39110456 PMCID: PMC11307132 Free PMC article.