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A. Definitions navigator

  1. Acute Renal Failure (ARF) - azotemia with <3 month duration
  2. Azotemia - elevated blood urea nitrogen (BUN >28mg/dL) and creatinine (Cr>1.5mg/dL)
  3. Uremia - azotemia with symptoms or signs of renal failure [17]
  4. End Stage Renal Disease (ESRD) - uremia requiring transplantation or dialysis
  5. Chronic Renal Failure (CRF) - irreversible kidney dysfunction with azotemia >3 months
  6. Creatinine Clearance (CCr) - the rate of filtration of creatinine by the kidney (GFR marker)
  7. Glomerular Filtration Rate (GFR) - the total rate of filtration of blood by the kidney

B. ARF and CRFnavigator

  1. There are about 50,000 cases of ESRD per year in USA
  2. Episodes of ARF (usually acute tubular necrosis) often lead, eventually, to CRF
  3. Over time, combinations of acute renal damage are additive and lead to CRF
  4. Most pathology in CRF involves glomerular destruction
  5. General Causes of Acute Renal Failure (ARF)
    1. Prerenal azotemia - renal hypoperfusion, usually with acute tubular necrosis
    2. Intrinsic Renal Disease, usually glomerular disease
    3. Postrenal azotemia - obstruction of some type
  6. Black men have a 3.5-4 fold increased risk of CRF compared with white men
    1. Blood pressure (BP) and socioecomonic status correlate with CRF in whites and blacks
    2. Unclear if blacks have increased risks when BP and income are similar
  7. Nephrologists should participate in care of any patient with GFR <30mL/min/1.73 m2 [1]

C. Etiology of CRF
[Figure] "Progression of Renal Failure Over Time" navigator

  1. Diabetes Mellitus (DM)
    1. DN is the most common contributor to ESRD (relative risk >10 fold)
    2. Over 30% of cases of ESRD are ascribed primarily to DM
    3. DM usually causes albuminuria initially but can cause CRF early without albuminuria [8]
    4. Insulin resistance / metabolic syndrome increases risk for CRF by 2-5X [5]
    5. Smoking is synergistic with DM for contribution to CRF
  2. Cardiovascular (CV) Risks
    1. CV disease strongly associated with development of new onset renal disease [4]
    2. Hypertension (HTN) causes about 23% of ESRD cases
    3. HTN usually causes glomerulosclerosis
    4. Reduced nephron numbers associated with increased risk for HTN in white persons [7]
    5. Smoking >1 pack per day increases CRF risk >1.8X in non-DM [26]
  3. Congestive Heart Failure (CHF) [43]
    1. CRF typically associated with advanced CHF
    2. Cardiorenal syndrome includes renal hypoperfusion and neurohormonal effects
  4. Hypertension Therapy [48]
    1. BP reduction can lead to reduced renal perfusion which leads to reduciton in GFR
    2. Treatment to reduce mean BP <100 mmHg was not beneficial in HTN related CRF [49]
    3. Reduction in GFR leads to worsening of renal function tests (BUN and creatinine)
    4. Stable reduction in renal function is acceptable with improved BP control
    5. Long term control of BP will lead to improved preservation of renal function
  5. Renal Vascular Disease
    1. Renal artery stenosis
    2. Atherosclerotic versus fibromuscular
    3. BP reduction in setting of renal vascular disease can reduce renal function [48]
  6. Other Renal Diseases
    1. Renal (glomerular) Deposition Diseases
    2. Polycystic Kidney Disease - about 5% of cases
    3. Glomerulonephritis - inflammatory lesions of kidney
    4. Glomerulonephritis causes ~10% of current CRF
    5. Vasculitis causing rapidly progressive glomerulonephritis - 2% of cases
  7. Medications
    1. Especially causing tubulointerstitial diseases (common ARF, rare CRF)
    2. Platinum based chemotherapy
    3. Analgesic Nephropathy - little risk with moderate analgesic use [37]
    4. Nonsteroidal Antiinflammatory Drugs (NSAIDs) - mainly intermediate and long acting [39]
    5. Amphotericin B - exacerbated by coexisting nephrotoxins or baseline CRF [40]
    6. Aminoglycosides can cause ARF and CRF
    7. Cyclosporine (CsA, Sandimmune®) and other calcineurin inhibitors [11]
  8. Analgesic Nephropathy [39]
    1. Drugs associated with this entity usually contain two antipyretic agents and either caffeine or codeine
    2. Polyuria is most common symptom early in disease
    3. Macroscopic hematuria can occur, particularly in setting of papillary necrosis
    4. Chronic interstitial nephritis, renal papillary necrosis, renal calcifications are seen
    5. Associated with long-term use of NSAIDs
    6. Long term acetaminophen use is also associated with CRF
    7. No evidence that NSAIDs added to ACE inhibitors or diuretics had increased risk of CRF [39]
  9. Vesicoureteric Reflux (VUR)
    1. 1-2% of apparently healthy children have this disorder
    2. Present in ~35% of children with urinary tract infections (UTI)
    3. Radiologic evidence of renal scarring in ~30% of children with chronic UTIs
    4. Can cause progressive nephropathy, HTN, and renal failure
    5. Surgical treatment of bilateral VUR in children <12 years does not appear to lead to improved renal functional outcomes [32]
  10. Risk of CRF ~15% over 5 years after transplantation of nonrenal organ [12]

D. Pathophysiology of Progressive Renal Failurenavigator

  1. Renal injury leads to reduced nephron mass
    1. Acute increase in angiotensin II (AT2) generation
    2. Volume overload on remaining nephrons leads to glomerular-capillary HTN
    3. Generally increased sympathetic activity (sympathetic "overactivity")
  2. AT2 Effects
    1. Increase resistance on efferent arterioles
    2. Increase in glomerular filtration pressure
    3. Up-regulation of transforming growth factor ß1 (TGF-ß1) gene
    4. Tubule cell hypertrophy
    5. Increased synthesis of type IV collagen
    6. This forms a thickened tubular membrane and fibrosis
  3. Glomerular Capillary HTN
    1. Increased permeability to macromolecules
    2. Increased filtration of plasma proteins leading to proteinuria
    3. Tubular reabsorption of protein then occurs
    4. Tubular cells overload with proteins in intracellular processing organelles
    5. Tubular cells become stressed, increased NF-kB dependent and independent genes
    6. Increased expression of vasoactive and inflammatory genes
  4. Vasoactive and Inflammatory proteins
    1. Released into interstitium by stressed renal tubular cells
    2. Inflammatory reaction with scarring
    3. Increased generation of fibroblasts (? from tubular cells)
    4. Proliferation of fibroblasts
    5. Deposition of fibrotic tissue (collagens, extracellular matrix)
    6. Elevated fibrinogen, prothrombin fragments, and D-dimer [27]
  5. HTN
    1. Systemic HTN accelerates decline of renal function
    2. Patients with severe (grade 4) HTN have 22X increased risk versus normal for CRF
    3. Nitric oxide production and vasodilation is impaired in CRF
    4. Endogenous inhibitor of nitric oxide synthetase is asymmetrical dimethylarginine (aDMA)
    5. aDMA accumulates in late stage CRF and likely exacerbates HTN
    6. aDMA levels in hemodialysis patients is an independent predictor of mortality [42]
  6. Apolipoprotein e4 (ApoE4) associated with reduced and ApoE2 associated with increased progression of CRF independent of other known contributors [9]
  7. Specific blockade of angiotensin II effects clearly reduces renal decline
  8. Reduction of proteinuria (reduced protein intake, reduced GFR) also reduces decline

E. Electrolyte Abnormalities
[Figure] "Sodium Excretion and GFR" navigator

  1. Excretion of Na+ is initially increased, probably due to natriuretic factors
  2. As glomerular filtration rate (GFR) falls, fractional sodium excretion rises
    1. Maintain volume until GFR <10-20mL/min, then edema will occur
    2. In renal failure with nephrotic syndrome, edema occurs early
    3. Cannot conserve Na+ when GFR <25mL/min, and FeNa rises with falling GFR
  3. Tubular K+ secretion is decreased
    1. Aldosterone mediated. Also increased fecal loss of K+ (up to 50% of K ingested)
    2. Cannot handle bolus K+, so must avoid drugs high in K+
    3. Do not use K+ sparing diuretics
  4. Control of Acids
    1. Normally, produce ~1mEq/kg/day H+
    2. When GFR <40mL/min then decrease NH4+ excretion adds to metabolic acidosis
    3. When GFR <30mL/min then urinary phosphate buffers decline and acidosis worsens
    4. Bone CaCO3 begins to act as the buffer and bone lesions result (renal osteodystrophy)
    5. Usually will not have wide anion gap even with acidosis if can make urine
    6. Acidosis caused by combination hyperchloremia and hypersulfatemia (SID reduction)
    7. Defect in renal generation of HCO3-, as well as retention of nonvolatile acids
  5. Loss of urine diluting and concentrating abilities
    1. Osmotic diuresis due to high solute concentration for each functioning nephron
    2. Reduce urinary output only by reducing solute excretion
    3. Major solutes are salt and protein, so these should be decreased
  6. Bone Metabolism
    1. GFR reduction leads to elevated blood phosphate, low calcium and acidosis
    2. In addition, reduced tubular resorption of calcium augments hypocalcemia
    3. Other defects include acidosis and decreased dihydroxy-vitamin D production
    4. Bone acts as a buffer for acidosis, leading to chronic bone loss in renal failure
    5. Low vitamin D causes poor calcium absorbtion and hyperparathyroidism (high PTH)
    6. Elevated PTH maintains normal serum Ca2+ and PO42- until GFR <30mL/min
    7. Chronic hyperPTH and bone buffering of acids leads to severe osteoporosis
    8. Secondary hyperPTH can now be treated with calcium sensor agonist cinacalcet [56,57]
  7. Other abnormalities
    1. Slight hypermagnesemia with inability to excrete high magnesium loads
    2. Uric acid retention occurs with GFR <40mL/min
    3. Vitamin D conversion to dihydroxy-Vitamin D is severely decreased
    4. Erythropoietin (EPO) levels fall and anemia develops
  8. Accumulation of normally excreted substances, "uremic toxins", MW 300-5000 daltons
  9. Uremia [17]
    1. Fatigue, malaise, reduced mental function
    2. Anorexia and nausea
    3. Sleep disturbances
    4. Peripheral neuropathy, restless legs
    5. Uremic pruritus
    6. Serositis (especially pericarditis)
    7. Ammenorhea and sexual dysfunction
    8. Progression to coma and death if untreated

F. Associated Problems and Treatmentnavigator

  1. Immunosuppression
    1. Pre-dialysis CRF patients are at increased risk for infection
    2. Cell mediated immunity is particularly impaired
    3. Hemodialysis may increase immunocompromise
    4. Patients with CRF should be vaccinated aggressively
  2. Anemia [23]
    1. Reduced renal EPO production and shortened red cell survival
    2. Occurs when creatinine rises to >2.5-3mg/dL
    3. At this level, kidney no longer regulates EPO based on hematocrit (HCT)
    4. Rarely clinically significant until 6-12 months prior to dialysis
    5. EPO therapy recommended for HCT <33% (hemoglobin, Hb <11gm/dL) [34]
    6. Goal HCT is ~34% (Hb 11.3gm/dL); higher levels HCT associated worse outcomes [68,69]
    7. EPO may also have renal protective effects [63]
    8. Assess for iron deficiency prior to initiating EPO therapy
  3. Hyperuricemia
    1. May contribute to renal dysfunction
    2. Severe, multiarticular gout is a common problem
  4. Hyperphosphatemia [28,64]
    1. Decreased renal phosphate (PO4) excretion
    2. Increased PO4 load from bone catabolism (related to acid load)
    3. Elevated PO4 levels greatly stimulate parathyroid hormone (PTH) secretion
    4. High PTH in renal failure is secondary hyperparathyroidism
    5. Secondary hyper-PTH leads to renal bone disease
    6. Eventually, parathyroid gland hyperplasia occurs
    7. Phosphate binders such as lanthanum carbonate (Fosrenol®), calcium acetate (Phoslo®), sevelamer (Renagel®; now replaced by sevelamer carbonate, Renvela®) [65] may be used
  5. Secondary Hyperparathyroidism
    1. Cinacalcet (Sensipar®) is approved for secondary hyperPTH in patients on dialysis [57]
    2. Cinacalcet is a calcium sensor agonist which fools the body into believing Ca2+ levels are higher than they actually are; this leads to a ~35% reduction in PTH [56]
    3. PTH reduction with cinacalcet is accompanied by reduced Ca-P product of 8-15%
    4. Initial dose is 30mg once daily for 2-4 weeks, then titrate up to 90mg qd [57]
  6. HTN [19]
    1. BP control is very important to slowing progression of CRF [39]
    2. Overall risk of CRF with creatinine >2.0mg/dL is ~2X in five years with HTN
    3. Higher ESRD risk with HTN and albuminuria >1gm/day, blacks, diabetics
    4. Reduction of BP to <130/85 (120/75 in African Americans) will reduce progression
    5. Mean BP goal 100-107mmHg in patients with HTN-related CRF with ACE-I first line [49]
    6. No benefit to HTN reduction to mean BP 92 mmHg in HTN-related CRF [49]
    7. Targetted mean pressure 92-98mm Hg in patients with CRF and proteinuria
    8. ACE inhibitors (ACE-I) shown be most effective at preserving renal function [45]
    9. ACE-I (enalapril) also reduce sympathetic overactivity [21]
    10. ACE-I only with caution when serum creatinine >3mg/dL
    11. EPO therapy causes HTN in ~25% of patients with CRF [34]
  7. Premature Atherosclerosis [6,13,24,30]
    1. Glomerular filtration rate <60mL/min per 1.73m2 is a ~2X risk for cardiac events [13]
    2. Multifactoral but significantly due to HTN, particularly in patients with ESRD
    3. Left ventricular hypertrophy (LVH) - 75% of ESRD
    4. Dyslipidemia - increased LDL, VLDL, lipoprotein (a); reduced HDL and ApoA1
    5. Elevated C-reactive protein, interleukin 6 [13], fibrinogen, homocysteine
    6. Increased coronary artery calcification and reduced vasodiliatory function
    7. CRF increases intimal-medial thickness and reduces brachial artery dilation [30]
    8. Mild to moderate (creatinine 1.4-2.3mg/dL) CRF associated with ~2X risk CV events/death [31]
    9. CRF is an independent risk for death in elderly patients with MI [46,47]
    10. Treatment of patients with CRF with ramipril, an ACE-I, reduces CV disease and death [31]
    11. Treatment of mild CRF with pravastatin reduced CV events >25% [51]
    12. Folate/Vitamins B6 and B12 supplements reduce homocysteine in CRF but not clinical events [18]
  8. Poor Coagulation
    1. Platelet dysfunction - usually with prolonged bleeding times
    2. May be partially reversed with DDAVP administration
    3. Early renal failure associated elevated fibrinogen, prothrombin fragments, and D-dimer [27]
  9. Proteinuria >0.25gm per day is an independent risk factor for renal decline [2]
  10. Skin Disease [58]
    1. Uremic pruritus (see below) - very common
    2. Dialysis usually improves itching; opiate antagonists (naltrexone 50mg/d) also effective
    3. ß2-microglobulin amyloidosis can occur with CRF due to poor secretion of ß2-microglobulin
  11. Nephrogenic Fibrosing Dermopathy / Nephrogenic Systemic Fibrosis (NSF)
    1. Indurated plaques, hyperpigmentation, sclerodactyly
    2. Skipped areas of induration with smooth transition to indurated plaques
    3. Must rule out scleromyxedema, morphea, systemic sclerosis, scleromyxedema
    4. Gadolinium contrast agents (Magnavist®, MultiHance®, Omniscan®, OptiMARK®, ProHance®) for MRI rarely can cause NSF in CRF patients [15]
    5. NSF is poorly treated; physical therapy and thalidomide may be helpful
  12. Calciphylaxis [16]
    1. Calcific uremic arteriopathy
    2. Initial plaque-like lesions usually very tender with dusky/purple discoloration
    3. Usually progress to ulcers with formation of eschars
    4. Calcification of media in blood vessels of skin
    5. Treated with agents that reduce calcium, PO4, Calcium-Phosphate product
    6. Reduction of phosphate levels as for hyperphosphatemia (see above)
  13. Sleep Disorders
    1. Common in patients with CRF
    2. Sleep apnea occurs in >50% of patients
    3. Nocturnal (7 nights per week) but not standard hemodialysis improves sleep apnea in CRF patients [29]
    4. Renal transplantation does improve sleep apnea
  14. Short Stature [25]
    1. Long term treatment in children with CRF induces catch-up growth
    2. Most patients achieve normal adult height
  15. Uremia - symptomatic azotemia (see above)
  16. Avoid use of gadolinium contrast agents: increased risk of nephrogenic systemic fibrosis [74,75]

G. Evaluationnavigator

  1. Determine if renal insufficiency is acute or chronic
  2. Search for underlying causes (see above)
    1. Glomerular Disease
    2. Interstitial Disease
    3. Vascular Disease
  3. Basic Laboratory Tests
    1. Full electrolyte panel and levels of calcium, phosphate, uric acid, magnesium and albumin
    2. Urinalysis: microscopic exam, protein, osmolality, creatinine, pH, glucose
    3. Calculation of creatinine clearance - based on creatine to estimate GFR
    4. Random albumin-creatinine ratio in random urine - to determine level of proteinuria
    5. Ratio or urinary protein to urinary creatinine of >1.0 in single morning specimen is a better predictor of renal decline than is 24 hour protein excretion
    6. Complete blood count - anemia can occur, low erthropoietin levels
    7. Consider complement levels, protein electrophoresis, antinuclear antibodies, ANCA
    8. Renal biopsy - particularly in mixed or idiopathic disease
    9. Erythropoietin levels may be useful in planning therapy
  4. Estimate GFR using Creatinine Clearance Equation [66]
    1. Creatinine clearance (men) ={140-age in year)x(weight kg)}÷ (72 x serum creatinine mg/dL)
    2. Creatinine clearance for women = above result x 0.85
    3. This provides a reasonable estimate of renal function (normal >90 mL/min)
    4. Other formulas, more complicated, possibly more accurate, are available [1]
  5. Cystatin C [61,62,66,67]
    1. Levels may provide a better estimate of GFR than serum creatinine
    2. Levels are independent of age, sex and lean muscle mass (unlike creatinine)
    3. Cysteine protease inhibitor (molecular weight 13K) freely filtered by glomerulus
    4. Increased cystatin levels are associated with death and cardiac disease in elderly with or without CRF and in any patient with CRF (better predictor than creatinine, GFR) [67,73]
  6. Radiographic Evaluation
    1. Renal ultrasound - evaluate for obstruction, stones, tumor, kideny size, chronic change
    2. Duplex ultrasound or angiography or spiral CT scan to evaluate renal artery stenosis
    3. Magnetic resonance angiography generally preferred over X-ray contrast agents
  7. Bone Evaluation
    1. Severe secondary hyperPTH can lead to osteoporosis
    2. Treatment with cinicalcet, a calcium sensor agonist, reduces hyperPTH levels [56]
    3. Some patients will require parathyroidectomy to help prevent this
    4. Unclear when bone densitometry should be done on patients with CRF
  8. Serology
    1. ANA and double stranded DNA Abs for lupus
    2. ANCA and Anti-GBM Abs for vasculitis
    3. Cryoglobulins for cryglobulinemia
    4. Viral infections: HCV Antibody, HBV Antibody
  9. Referral to vascular surgeon for native AV fistula construction when creatinine >2.0mg/dL or so when patients have progressive renal failure

H. Chronic Renal Failure Stages and Action Plan [1,2,44,66]navigatorTable: CRF Action Plan

StageDescriptionGFR*Actions
Stage 1Kidney Damage>89Slow progression, CAD risk reduction
Stage 2Mild GFR Reduced60-89Estimating Progression
Stage 3Moderate GFR Red30-59Evaluate and treat complications
Stage 4Severe GRF Reduc15-29Preparation for kidney replacement therapy
Stage 5Kidney Failure<15Kidney Replacement therapy
*GFR in mL/min/1.73 square meters

I. Pre-Dialysis Treatment [33,41] navigator
  1. Overview
    1. Goal is to maximize time to dialysis
    2. Aggressively treat underlying diseases: HTN, lipid disorders, diabetes
    3. ACE inhibitors and ARBs slow progression in diabetic and non-diabetic CRF [55]
    4. Aggressively treat contributing conditions: heart failure (cardiorenal syndrome) [43]
    5. Optimize medical regimens, remove or reduce nephrotoxic agents
    6. Statins appear to reduce albminuria and cardiovascular risks [35,51]
  2. Therapeutic Goals [2,33,41]
    1. Reduce proteinuria to <0.3gm/d with ACE-I or other agent (see below)
    2. Slow progression with ACE inhibitors in both diabetic and non-diabetic CRF [55]
    3. Second line angiotensin II receptor blocker (ARB), then calcium channel blockers
    4. Strongly consider combination ACE-I with ARB
    5. Blood pressure reduction to 110-130/75 mm [52] or mean arterial pressure <92 mm [14]
    6. LDL cholesterol reduction to <100mg/dL (<2.6 mMol)
    7. Reduce HbA1c to <7.5-8.0% in diabetics
  3. Maintain Normal Electrolytes
    1. Potassium, calcium, phosphate are major electrolytes affected in CRF
    2. Assessment of parathyroid hormone status is critical
    3. Reduce or discontinue other renal toxins (including long-acting NSAIDS)
    4. Diuretics (such as furosemide) may help maintain potassium in normal range
    5. However, volume depletion with diuretics can exacerbate renal dysfunction
    6. Renal diet including low protein, high calcium and low phosphate
    7. Secondary hyperparathyroidism can be mitigated with calcium sensor agonist (see above) [56]
  4. Slow Disease Progression [45,52,55]
    1. Blockade of the renin-angiotensin system is cornerstone of slowing progression
    2. ACE inhibitors (ACE-I) slow progression all types of CRF [36,38]
    3. ACE-I often acceptable in patients with creatinines normal to up to 5.0mg/dL [55]
    4. ACE-I reduce renal protein loss and slow reduction in GFR in diabetic and non-diabetic CRF
    5. Benefits of ACE-I extend beyond antihypertensive effects
    6. ACE-I combined with ARB more effective than ACE-I alone in slowing progression of non- diabetic CRF [50]
    7. Niceritrol (nicotonic acid derivative) reduced levels of LDL cholesterol, Lp(a) and urinary protein loss over 12 months in patients with CRF [53]
    8. Aggressive treatment of hypercholesterolemia with atorvastatin (Lipitor®) reduces renal decline (proteinuria) and should be added to ACE-I or ARB [59]
    9. Aggressive blood pressure reduction to mean arterial pressure <92 mm recommended [14]
    10. In non-diabetic patients, benazepril 10mg po bid reduced renal decline even in patients with Stage 4 CRF and prevented need for dialysis [55]
    11. Statins (cholesterol lowering agents) associated with reduced albuminuria [35] and reduced risk of sepsis [71]
  5. ACE-I with caution when glomerular filtration rate (GFR) < 20mL/min [54,55]
    1. Monitoring renal function is critical (as above)
    2. Biggest concern on initiating therapy is hyperkalemia
    3. Minimize potassium intake (urinary 24 hour potassium <40mEq)
    4. However, clear benefits in non-diabetic patients with Stage 4 CRF warrant use [55]
    5. K+ levels and renal function should be evaluated within 1 week of ACE-I initiation
  6. Treatment of HTN [52]
    1. Goal mean BP is ~105mmHg for HTN-related CRF, ~95mmHg with proteinuria [2,49]
    2. Maintain systolic BP 110-130mmHg with proteinuria >1gm/d [52]
    3. ACE-I are first line anti-HTN agents in diabetic and non-diabetic CRF [33,38,52]
    4. Possible that nondihydropyridine calcium channel blockers have added benefits also
    5. Combine ACE-I (or ARB) with nondihydropyridine calcium blocker for anti-HTN effects
    6. ACE-I more effective than ß-blockers or dihydropyridine calcium blockers in HTN-related CRF [49]
    7. Addition of felodipine (Plendil®) to ramipril (an ACE-I) did not slow renal decline in non- diabetic renal disease despite reduction in blood pressure [60]
  7. Ramipril Efficacy in Non-Diabetic Proteinuric Nephropathy (REIN) Study [22]
    1. Ramipril is a second generation ACE-I with efficacy in HTN and heart Failure
    2. In patients with non-diabetic proteinuria >3gm/day, ramipril reduced ESRD progression
    3. In patients with non-diabetic proteinuria 1-3gm/day, ramipril reduced ESRD progression and reduced proteinuria 13% (versus 15% increased proteinuria in controls)
    4. Drug was titrated to a diastolic BP under 90mmHg
    5. Patients with baseline GFR <45mL/min/1.73m2 and proteinuria >1.49g/24 hour had the greatest benefit of ramipril treatment
    6. Ramipril reduced rate of GFR decline by >20%, more than anti-hypertensive drugs alone
    7. Over 4.5 years, ramipril reduced rate of progression to ESRD from ~70% to 40%
    8. Ramipril reduced cardiovascular events and death in patients with mild CRF [31]
    9. Ramipril may be preferred agent for treatment of non-diabetic proteinuric nerphropathy
  8. Protein Intake
    1. Reduce protein intake to <0.6gm/kg body weight
    2. Appears to slow progression of diabetic and non-diabetic kideny disease
    3. In type 1 diabetes mellitus, protein restriction reduced levels of albuminuria
    4. Low protein diet did not slow progression in children with CRF
  9. Erthropoietin (Epogen®, Procrit®) and Darbepoetin (Aranesp®) [34]
    1. Reduces cardiovascular morbidity and mortality, improve quality of life
    2. EPO is given 3X weekly; darbepoetin is a long acting EPO given once weekly
    3. Indicated for HCT <33-36% or hemoglobin (Hb) <11gm/dL
    4. Use to maintain Hb 11-12gm/dL
    5. Hb >12gm/dL associated with increased mortality [70,72]
    6. Discontinue when Hb >12gm/dL or >4% HCT increase in 2 week
  10. Prophylactic hemodialysis after coronary angiography improves renal outcomes in patients with advanced renal failure (CRF or ARF) [77]

J. Hemodialysis [10] navigator

  1. Indications
    1. Uremia - azotemia with symptoms and/or signs
    2. Severe Hyperkalemia
    3. Volume Overload - usually with congestive heart failure (pulmonary edema)
    4. Toxin Removal - ethylene glycol poisoning, theophylline overdose, angiography dyes [77]
  2. Overview of Chronic Hemodialysis
    1. Blood is run through a semi-permeable filter membrane bathed in dialysate
    2. Composition of the dialysate is altered to adjust electrolyte parameters
    3. Electrolytes and some toxins pass through filter
    4. By controlling flow rates (pressures), patient's intravascular volume can be reduced
    5. Most chronic hemodialysis patients receive 3.5 hours dialysis 3 days per week
    6. Femoral or jugular venous access have similar levels of nosocomial events in patients requiring acute renal replacement therapy [78]
  3. Efficacy
    1. Some acids, BUN and creatinine are reduced
    2. Very effective at reducing intravascular volume and potassium levels
    3. Not all uremic toxins are removed and patients generally do not feel "normal"
  4. Chronic Hemodialysis Medications
    1. Anti-hypertensives - often labetolol, calcium blockers, ACE inhibitors
    2. Eythropoietin for anemia, used in ~80% of dialysis patients [34]
    3. Vitamin D Analogs - calcitriol given intravenously to most patients
    4. Drugs to reduce phosphate levels - phosphate binders, calcimimetics (see above)
    5. DDAVP may be effective for patients with symptomatic platelet problems
    6. Nandrolone decanoate is an anabolic steroid which led to weight gain and improvement in functional status in patients undergoing hemodialysis [20]

References navigator

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