Chronic Renal Failure

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Contents 1 More Specific Terms 2 Introduction 3 Classification 4 Etiology 5 Pathology 6 Clinical-manifestations 7 Laboratory 8 Radiology 9 Complications 10 Differential-diagnosis 11 Management 12 More General Terms 13 Additional Terms 14 References

More Specific Terms

• end-stage renal disease (ESRD)
• renal insufficiency

Introduction

• Impaired renal function ( GFR < 25-33 mL/min) > 3 months duration, generally irreversible & progressive.

Classification

• stage 1: GFR > 90 mL/min/1.73 m2
• stage 2: GFR = 60-89 mL/min/1.73 m2
• stage 3: GFR = 30-59 mL/min/1.73 m2
• stage 4: GFR = 15-29 mL/min/1.73 m2
• stage 5: GFR < 15 mL/min/1.73 m2 [19]

Etiology

• glomerulonephropathy

• primary: chronic glomerulonephritis
• secondary: diabetes mellitus (most common)

• hypertensive nephrosclerosis (primarily vascular pathology)
• chronic tubulointerstitial disease
• cystic kidney disease ( polycystic kidney disease)
• obstructive uropathy
• heart failure
• infection

• viral hepatitis
• HIV

• hypothyroidism
• hypoadrenalism
• hypercalcemia
• medications - prolonged use of NSAIDs
• injection drug use
• cirrhosis
• risk factors [4]

• diabetes mellitus
• hypertension
• dyslipidemia
• cardiovascular disease
• obesity
• metabolic syndrome
• age > 60 years
• malignancy
• family history of chronic kidney disease
• smoking
• HIV infection
• hepatitis C
• kidney stones
• autoimmune disease
• recurrent urinary tract infection

• childhood recurrent urinary tract infection unlikely cause [18]

• recovery from acute renal failure
• exposure to nephrotoxic drugs

• NSAIDs
• COX2 inhibitors

Pathology

• glomerular hyperfiltration in response to diminished glomerular filtration rate ( GFR)
• compensatory hypertrophy or increase in glomerular size
• glomerular hypertension
• glomerular sclerosis & interstitial fibrosis
• mesangial trapping of macrophages
• platelet aggregation in glomerular capillaries
• damage from hyperlipidemia
• ammonium or calcium phosphate deposition in the renal interstitium
• pro- inflammatory & pro- coagulant millieu [5] (see Laboratory)
• excessive sympathetic nervous system activity [7]

Clinical-manifestations

• polyuria & nocturia

• may be earliest symptoms
• secondary to loss of concentrating ability

• sign/symptoms do become apparent until GFR < 30 mL/min
• sign/symptoms of uremia
• sign/symptoms of anemia
• sign/symptoms of volume overload

• peripheral edema
• new or worsening hypertension
• ascites
• congestive heart failure
• dyspnea
• pericardial effusion

• gastrointestinal disorders are more common in CRF patients
• symptoms of secondary hyperparathyroidism

• hypocalcemia
• hyperphosphatemia
• renal osteodystrophy

• small kidneys
• amenorrhea & impotence is common
• pregnancy is rare if serum creatinine > 2.0 mg/dL
• increased insulin resistance & decreased insulin clearance
• accelerated atherosclerosis is common
• constipation is common & aggravated by phosphate binders
• gout & pseudogout are common
• peripheral neuropathy

• sensory fibers are affected more than motor fibers
• lower extremities are involved more than the upper extremities
• often associated with asterixis & seizures

Laboratory

• serum chemistries

• serum urea nitrogen
• serum creatinine (> 1.5 mg/dL in men; 1.3 mg/dL in women)

• referral to nephrologist when > 2.0 mg/dL
• may overestimate renal function

• serum potassium
• serum bicarbonate
• serum calcium
• serum phosphorous
• serum albumin
• serum glucose (impaired carbohydrate tolerance)
• serum cholesterol ( hyperlipidemia is common)
• metabolic acidosis

• at 1st normal anion gap

• decreased secretion of NH4+

• then high anion gap (rarely > 25)

• retention of phosphates & sulfates

• serum iron, TIBC & serum ferritin
• increased serum levels of inflammatory markers [5]

• IL-6, C-reactive protein

• increased serum levels of pro- coagulants

• fibrinogen, factor VII, factor VIII, D-dimer

• urinalysis, including evaluation of urine sediment
• 24 hour urine

• 24 hour urine protein
• urine albumin/creatinine ratio
• creatinine clearance

• complete blood count ( CBC)

• hemoglobin/hematocrit

• serum & urine protein electrophoresis
• endocrine abnormalities

• total thyroxine levels are generally low
• growth hormone levels are generally high
• increased serum gastrin
• increased serum prolactin
• increased serum PTH: maintain < 3X upper limit of normal

• overcome bone- resistance to PTH
• avoid excessive hyperparathyroidism

• decreased serum 1,25-dihydroxyvitamin D3
• insulin levels increase (decreased renal clearance of insulin)

• renal biopsy ( glomerular disease)

Radiology

• renal ultrasound

• estimation of kidney size
• rule out obstructive uropathy
• renal papillary necrosis

• if radiocontrast agent must be used

• give IV normal saline before & after procedure
• N-acetylcysteine ( Mucomyst) prophylaxis

Complications

• anemia
• renal osteodystrophy
• increased risk of

• cardiovascular disease
• acquired polycystic kidney disease
• renal cell carcinoma
• cognitive impairment
• depression [19]

• impaired clearance of medications, especially

• analgesics, including NSAIDs
• barbiturates
• antihistamines, including diphenhydramine
• decongestants containing ephedrine or ephedrine-related compounds
• muscle relaxants
• antiarrhythmic agents, including amiodarone, digoxin, short-acting calcium channel blockers [19]

Differential-diagnosis

• acute renal failure ( ARF)
• chronic renal failure ( CRF)

• diabetic nephropathy

• early albuminuria, proteinuria, hypertension, declining GFR, coexisting retinopathy

• gomerular disease ( glomerulonephritis)

• hematuria, dysmorphic erythrocytes, erythrocyte casts, proteinuria, hypertension
• often other systemic manifastations

• lupus nephritis, post- infectious glomerulonephritis

• nephrotic syndrome:

• membranous nephropathy
• minimal change disease

• renal biopsy may be necessary

• tubulointerstitial disease

• proteinuria, glucosuria, ososthenuria, pyuria, leukocyte casts, renal papillary necrosis on ultrasound
• analagesic nephropathy ( NSAIDs), lead nephropathy

• renal vascular disease

• hematuria, poteinuria, associated systemic illness
• vasculitis often presents with glomerulonephritis & palpable purpura

• polycystic kidney disease

• imaging & family history
• autosomal dominant types 1 & 2 most common

• post- transplantation nephropathy

• chronic allograft nephropathy, drug toxicity, recurrence of renal disease

Management

• no definitive treatment

• adjust doses of renally cleared pharmaceuticals

• goals of therapy

• treat reversible causes, especially

• hypertension

• goal < 130/80 mm Hg, < 125/75 mm Hg if proteinuria > 1 g/24 hours [4]
• no benefit target blood pressure < 140/90 mm Hg [16] in terms of mortality, ESRD, cardiovascular events
• systolic blood pressure < 130 mm Hg associated with increased mortality [13]
• inhibition of renin-angiotensin axis more important than blood pressure reduction (see REIN-2 trial)
• most patients require at least 2 antihypertensives
• low salt diet < 2 grams sodium per day
• ambulatory blood pressure monitoring better than BP measured in clinic [17] - goals: daytime systolic BP < 136 mm Hg; nighttime systolic BP < 125 mm Hg [17]

• diabetes: maintain Hgb A1c between 7.0-7.9% [4]

• limit progression of renal failure
• minimize sequelae
• target hemoglobin 11.0 g/dL (see anemia of renal failure)

• pharmaceutical agents

• erythropoietin ( EPO)
• except polycystic kidney disease ( EPO generally normal)
• target: blood hemoglobin of 11-12 g/dL
• ACE inhibitors, angiotensin receptor blocker ARB

• may preserve renal function by limiting hyperfiltration
• may cause decline in GFR
• hyperkalemia is adverse effect
• NOT useful for polycystic kidney disease
• addition Ca+ channel blocker not helpful (REIN-2)
• combined ACE inhibitor/ ARB dual therapy less effective than monotherapy [12]

• calcium acetate ( PhosLo)

• maintain serum phosphate 3.5-5.5 mg/dL

• 1,25-dihydroxyvitamin D
• loop diuretic:

• hypertension, edema, hyperkalemia
• may enhance effect of ACE inhibitors

• bicarbonate replacement

• metabolic acidosis
• keep [[[Hco3- | HCO3-]]] 20-26 meq/L

• EDTA chelation therapy may be of benefit [6]
• cinacalcet for secondary hyperarathyroidism
• statin may preserve renal function in patients with cardiovascular diseaase [9]
• avoid nephrotoxic agents

• Mg+2 & phosphate containing cathartics
• NSAIDs, COX2 inhibitors
• iodinated contrast

• avoid metformin
• use bisphosphonates with caution

• dialysis

• dialysis access when creatinine clearance <10-15 mL/min
• hemodialysis
• peritoneal dialysis
• 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)
• early intiation of dialysis associated with increased mortality [15]

• renal transplantation

• treament of choice for most patients with end-stage renal disease
• children must be > 10-15 kg to be eligible
• avoid transfusions in patients who are candidates for renal transplantation

• diet

• sodium restriction to < 2 g/day
• potassium restriction to < 2 g/day
• fluid restriction to < 1.5 L/day if signs of volume overload
• protein restriction to 40 g of high-quality protein/day (0.6-1.0 g/kg/day if not on dialysis [4])
• phosphate restriction

• referral to nephrologist when serum creatinine > 2.0 mg/dL

• obtain basic metabolic panel, urinalysis, 24 hour urine protein, renal ultrasound with bladder

• referral to ophthalmologist for fundoscopy if diabetic

• diabetic retinopathy

More General Terms

• renal failure; kidney failure
• chronic kidney disease (CKD)

Additional Terms

• Cooperate clinical trial
• Modification of diet in Renal Disease Study
• nephrotoxic substances
• REIN-2 clinical trial
• renal insufficiency
• renal osteodystrophy
• uremia

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, American College of Physicians, Philadelphia 1998, 2006. 2009
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: [1]
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: [2]
   - Marsden PA Increased body lead burden--cause or consequence of chronic renal insufficiency? N Engl J Med 348:345, 2003 PMID: [3]
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: [4]
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: [5]
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: [6]
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: [7]
    - 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: [8]
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: [9]
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: [10]
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: [11]
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: [12]
15. Clark WF et al. Association between estimated glomerular filtration rate at initiation of dialysis and mortality. CMAJ 2011 Jan 11; 183:47 PMID: [13]
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 <PubMed> PMID: [14] <Internet> [15]
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. <PubMed> PMID: [16] <Internet> [17]
18. Salo J et al Childhood Urinary Tract Infections as a Cause of Chronic Kidney Disease Pediatrics, October 10, 2011 <PubMed> PMID: [18] <Internet> [19]
19. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
20. National Kidney Foundation KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease [20]
    - KDOQI Clinical Practice Guidelines and Clinical Practice recommendations for anemia in chronic kidney disease 2007 UPDATE OF HEMOGLOBIN TARGET [21]
21. National Guideline Clearinghouse
    - K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. National Kidney Foundation ngc-guideline: [22]
    - (1) KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. (2) 2007 update of hemoglobin target. National Kidney Foundation ngc-guideline: [23] National Collaborating Centre for Chronic Conditions ngc-guideline: [24]
    - Diagnosis and management of adults with chronic kidney disease. Michigan Quality Improvement Consortium ngc-guideline: [25]
    - KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. National Kidney Foundation ngc-guideline: [26]
    - ACR Appropriateness Criteria renal failure. ngc-guideline: [27]
    - VA/DoD clinical practice guideline for management of chronic kidney disease in primary care. Department of Veteran Affairs, Department of Defense (VA/DoD) ngc-guideline: [28]
    - Anaemia management in people with chronic kidney disease. National Clinical Guideline Centre for Acute and Chronic Conditions ngc-guideline: [29]
    - Calcium x phosphate product. Caring for Australasians with Renal Impairment ngc-guideline: [30]
    - Calcium. Caring for Australasians with Renal Impairment ngc-guideline: [31]
    - Parathyroid hormone Caring for Australasians with Renal Impairment ngc-guideline: [32]
    - Serum phosphate. Caring for Australasians with Renal Impairment ngc-guideline: [33]
    - Diagnosis and management of chronic kidney disease Scottish Intercollegiate Guidelines Network ngc-guideline: [34]
    - Preservation of peripheral veins in patients with chronic kidney disease. (Association for Vascular Access) ngc-guideline: [35]
    - Chronic kidney disease. Early identification and management of chronic kidney disease in adults in primary and secondary care. National Collaborating Centre for Chronic Conditions ngc-guideline: [36]
    - Chronic kidney disease evidence-based nutrition practice guideline. (American Dietetic Association) ngc-guideline: [37]
    - Protein intake in children. Caring for Australasians with Renal Impairment ngc-guideline: [38]
    - Sodium chloride and water intake in children. Caring for Australasians with Renal Impairment ngc-guideline: [39]
    - Sodium in pre-dialysis patients. Caring for Australasians with Renal Impairment ngc-guideline: [40]
    - Vitamins in pre-dialysis patients. Caring for Australasians with Renal Impairment ngc-guideline: [41]
    - Water/fluid in pre-dialysis patients. Caring for Australasians with Renal Impairment ngc-guideline: [42]
    - Lipid lowering therapy in patients with chronic kidney disease Caring for Australasians with Renal Impairment ngc-guideline: [43]
    - Energy intake in children. Caring for Australasians with Renal Impairment ngc-guideline: [44]
    - Energy intake in pre-dialysis patients. Caring for Australasians with Renal Impairment ngc-guideline: [45]
    - Evaluation and management of nutrition in children. Caring for Australasians with Renal Impairment ngc-guideline: [46]
    - Lipids/fats in pre-dialysis patients. Caring for Australasians with Renal Impairment ngc-guideline: [47]
    - Acidosis in pre-dialysis patients. Caring for Australasians with Renal Impairment ngc-guideline: [48]
    - Anaemia and growth in children. Caring for Australasians with Renal Impairment ngc-guideline: [49]
    - Bone disease and growth in children. Caring for Australasians with Renal Impairment ngc-guideline: [50]
    - Carbohydrates in predialysis patients. Caring for Australasians with Renal Impairment ngc-guideline: [51]
    - Complementary medicines in pre-dialysis patients. Caring for Australasians with Renal Impairment ngc-guideline: [52]
    - Other agents. Caring for Australasians with Renal Impairment ngc-guideline: [53]
    - Other forms of dietary interventions. Caring for Australasians with Renal Impairment ngc-guideline: [54]
    - Pregnancy. Caring for Australasians with Renal Impairment ngc-guideline: [55]
    - Smoking. Caring for Australasians with Renal Impairment ngc-guideline: [56]
    - Blood pressure control: role of specific anti-hypertensives. Caring for Australasians with Renal Impairment ngc-guideline: [57]
    - Blood pressure control: targets. Caring for Australasians with Renal Impairment ngc-guideline: [58]
    - Reducing proteinuria. Caring for Australasians with Renal Impairment ngc-guideline: [59]
    - Use of calcimimetic drugs. Caring for Australasians with Renal Impairment ngc-guideline: [60]
    - Use of phosphate binders in kidney disease. Caring for Australasians with Renal Impairment ngc-guideline: [61]
    - Chronic kidney disease - identification, evaluation and management of patients. Medical Services Commission, British Columbia ngc-guideline: [62]
    - Decision support for adults living with chronic kidney disease. Registered Nurses' Association of Ontario (RNAO). ngc-guideline: [63]

chronic renal failure (CRF)