Kidney DiseaseKidney Disease

TerminologyTerminology

CRF: Chronic Renal FailureCRF: Chronic Renal Failure ARF: Acute Renal FailureARF: Acute Renal Failure ESRD: End stage renal diseaseESRD: End stage renal disease ESRF: End stage renal failureESRF: End stage renal failure GFR: Glomular filtration rateGFR: Glomular filtration rate Azotemia: Retention of nitrogenous waste Azotemia: Retention of nitrogenous waste

products as renal insufficiency developsproducts as renal insufficiency develops

The KidneyThe Kidney

Three of the biggest jobs that the kidneys have are: Three of the biggest jobs that the kidneys have are: (1) to cleanse the blood,(1) to cleanse the blood, (2) to regulate and maintain an appropriate fluid and chemical (2) to regulate and maintain an appropriate fluid and chemical

balance in the body, and balance in the body, and (3) to produce the urine. (3) to produce the urine. Each of these functions is closely related to the other two, not Each of these functions is closely related to the other two, not

only because each involves the removal or addition of fluid and only because each involves the removal or addition of fluid and chemicals from the blood, but also because each of these chemicals from the blood, but also because each of these functions takes place in the kidney's functions takes place in the kidney's nephronsnephrons. The starting . The starting point in the nephron for each of these functions is the point in the nephron for each of these functions is the glomerulusglomerulus. It is the "gateway" that the blood must pass . It is the "gateway" that the blood must pass through in order to be cleansed by the kidneys. through in order to be cleansed by the kidneys.

The KidneyThe Kidney

There are 1 million nephrons in each kindeyThere are 1 million nephrons in each kindey The kidney has an innate ability to maintain The kidney has an innate ability to maintain

GFR by hyperinfiltration and compensatory GFR by hyperinfiltration and compensatory hypertophy of the remaining healthy hypertophy of the remaining healthy nephronsnephrons

Acute Renal FailureAcute Renal Failure

is a rapidly progressive loss of renal function, generally is a rapidly progressive loss of renal function, generally characterized by oliguria (decreased urine production, characterized by oliguria (decreased urine production, quantified as less than 400 mL per day in adults,quantified as less than 400 mL per day in adults, less than less than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); and fluid and electrolyte imbalance. AKI can result from a and fluid and electrolyte imbalance. AKI can result from a variety of causes, generally classified as variety of causes, generally classified as prerenalprerenal, , intrinsicintrinsic, , and and postrenalpostrenal. An underlying cause must be identified and . An underlying cause must be identified and treated to arrest the progress, and dialysis may be treated to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these necessary to bridge the time gap required for treating these fundamental causesfundamental causes

Causes of ARFCauses of ARF

PrerenalPrerenal causes of AKI are those that decrease effective blood flow to causes of AKI are those that decrease effective blood flow to the kidney. These include systemic causes, such as low blood volume, the kidney. These include systemic causes, such as low blood volume, low blood pressure, and heart failure, as well as local changes to the low blood pressure, and heart failure, as well as local changes to the blood vessels supplying the kidney (clots, stenosis…)blood vessels supplying the kidney (clots, stenosis…)

Sources of damage to the kidney itself are dubbed Sources of damage to the kidney itself are dubbed intrinsicintrinsic. Intrinsic . Intrinsic can be due to damage to the glomeruli, renal tubules, or interstitium. can be due to damage to the glomeruli, renal tubules, or interstitium. Common causes of each are glomerulonephritis, acute tubular Common causes of each are glomerulonephritis, acute tubular necrosis (ATN), and acute interstitial nephritis (AIN), respectivelynecrosis (ATN), and acute interstitial nephritis (AIN), respectively

PostrenalPostrenal is a consequence of urinary tract obstruction. This may be is a consequence of urinary tract obstruction. This may be related to benign prostatic hyperplasia, kidney stones, obstructed related to benign prostatic hyperplasia, kidney stones, obstructed urinary catheter, bladder stone, bladder, ureteral or renal malignancyurinary catheter, bladder stone, bladder, ureteral or renal malignancy

Chronic Renal FailureChronic Renal Failure

The most common causes of CKD are The most common causes of CKD are diabetes mellitus, hypertension, and diabetes mellitus, hypertension, and glomerulonephritis.Together, these cause glomerulonephritis.Together, these cause approximately 75% of all adult casesapproximately 75% of all adult cases

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Am J Kidney Dis 2002; 39:S1

Chronic Renal FailureChronic Renal Failure

Presence of markers of kidney damage for three Presence of markers of kidney damage for three months, as defined by structural or functional months, as defined by structural or functional abnormalities of the kidney with or without abnormalities of the kidney with or without decreased GFR, manifest by either pathological decreased GFR, manifest by either pathological abnormalities or other markers of kidney damage, abnormalities or other markers of kidney damage, including abnormalities in the composition of blood including abnormalities in the composition of blood or urine, or abnormalities in imaging tests. or urine, or abnormalities in imaging tests.

The presence of GFR <60 mL/min/1.73 mThe presence of GFR <60 mL/min/1.73 m22 for for three months, with or without other signs of kidney three months, with or without other signs of kidney damage as described above.damage as described above.

DiabetesDiabetes

A group of metabolic diseases in which a person has high blood sugar, A group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria (frequent urination), sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).polydipsia (increased thirst) and polyphagia (increased hunger).

There are three main types of diabetes:There are three main types of diabetes: Type 1 diabetes: results from the body's failure to produce insulin, and : results from the body's failure to produce insulin, and

presently requires the person to inject insulin.presently requires the person to inject insulin. Type 2 diabetes: results from insulin resistance, a condition in which : results from insulin resistance, a condition in which

cells fail to use insulin properly, sometimes combined with an absolute cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. insulin deficiency.

Gestational diabetesGestational diabetes: is when pregnant women, who have never had : is when pregnant women, who have never had diabetes before, have a high blood glucose level during pregnancy. It diabetes before, have a high blood glucose level during pregnancy. It may precede development of type 2 DM.may precede development of type 2 DM.

GFRGFR

Volume of fluid filtered from the renal glomerular capillaries into the Volume of fluid filtered from the renal glomerular capillaries into the Bowman's capsule per unit time.Bowman's capsule per unit time.

Glomerular filtration rate (GFR) can be calculated by measuring any Glomerular filtration rate (GFR) can be calculated by measuring any chemical that has a steady level in the blood, and is freely filtered but chemical that has a steady level in the blood, and is freely filtered but neither reabsorbed nor secreted by the kidneys. The rate therefore neither reabsorbed nor secreted by the kidneys. The rate therefore measured is the quantity of the substance in the urine that originated measured is the quantity of the substance in the urine that originated from a calculable volume of bloodfrom a calculable volume of blood

The GFR test measures how well your kidneys are filtering a waste The GFR test measures how well your kidneys are filtering a waste called creatinine, which is produced by the muscles. When the kidneys called creatinine, which is produced by the muscles. When the kidneys aren't working as well as they should, creatinine builds up in the blood.aren't working as well as they should, creatinine builds up in the blood.

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Stages of CKDStages of CKD

Stage 1*: GFR >= 90 mL/min/1.73 mStage 1*: GFR >= 90 mL/min/1.73 m22 Normal or elevated GFRNormal or elevated GFR

Stage 2*: GFR 60-89 (mild)Stage 2*: GFR 60-89 (mild)

Stage 3: GFR 30-59 (moderate)Stage 3: GFR 30-59 (moderate)

Stage 4: GFR 15-29 (severe; pre-HD)Stage 4: GFR 15-29 (severe; pre-HD)

Stage 5: GFR < 15 (kidney failure)Stage 5: GFR < 15 (kidney failure)

Am J Kidney Dis 2002; 39(S2): S1-246

EpidemiologyEpidemiology

19 million Americans have CKD19 million Americans have CKD Approx 435,000 have ESRD/HDApprox 435,000 have ESRD/HD

Annual mortality rate for ESRD: 24%Annual mortality rate for ESRD: 24%

Signs & SymptomsSigns & Symptoms

GeneralGeneral Fatigue & malaiseFatigue & malaise EdemaEdema

OphthalmologicOphthalmologic AV nickingAV nicking

CardiacCardiac HTNHTN Heart failureHeart failure HyperkalemiaHyperkalemia PericarditisPericarditis CADCAD

GIGI AnorexiaAnorexia Nausea/vomitingNausea/vomiting DysgeusiaDysgeusia

SkinSkin PruritisPruritis PallorPallor

NeurologicalNeurological MS changesMS changes SeizuresSeizures

UremiaUremia

Is the clinical and laboratory syndrome, Is the clinical and laboratory syndrome, reflecting dysfunction of all organ systems reflecting dysfunction of all organ systems as a result of untreated or undertreated as a result of untreated or undertreated acute or chronic renal failureacute or chronic renal failure

Changes in the bloodChanges in the blood

The kidneys work to filter toxins and waste The kidneys work to filter toxins and waste products out of the blood. When kidney products out of the blood. When kidney function declines, waste products begin to function declines, waste products begin to build up within the blood. Creatine and urea build up within the blood. Creatine and urea build up. Phosphate also accumulates in the build up. Phosphate also accumulates in the blood. A build up of hydrogen ions may also blood. A build up of hydrogen ions may also occur, leading to acidosis.occur, leading to acidosis.

Changes in electrolytesChanges in electrolytes

Because of the resulting changes to the blood Because of the resulting changes to the blood chemistry, the electrolyte balance of the blood and chemistry, the electrolyte balance of the blood and cells is disrupted. Fluid retention also results. Often cells is disrupted. Fluid retention also results. Often fluid retention is the first noticeable sign that the fluid retention is the first noticeable sign that the kidneys are beginning to shut down. The resulting kidneys are beginning to shut down. The resulting water water weight gainweight gain and edema in the hands and feet and edema in the hands and feet signal that the kidneys are not removing waste signal that the kidneys are not removing waste products and fluids as they should.products and fluids as they should.

Pulmonary EdemaPulmonary Edema

as acute renal failure worsens, fluids continue to build as acute renal failure worsens, fluids continue to build within the body and may begin to collect in the air within the body and may begin to collect in the air sacs of the sacs of the lungslungs. This condition, known as pulmonary . This condition, known as pulmonary edema, can result in difficulty breathing, restlessness, edema, can result in difficulty breathing, restlessness, anxiety and wheezing. Untreated pulmonary edema anxiety and wheezing. Untreated pulmonary edema can ultimately lead to respiratory failure. Most deaths can ultimately lead to respiratory failure. Most deaths that occur in cases of renal failure are due to either a that occur in cases of renal failure are due to either a systemic infection or respiratory failure that results systemic infection or respiratory failure that results from the initial failure of the kidneys.from the initial failure of the kidneys.

Why does edema occur in Why does edema occur in patients with kidney disease?patients with kidney disease?

Edema forms in patients with kidney disease Edema forms in patients with kidney disease for two reasons: for two reasons:

1.1. a heavy loss of protein in the urine, ora heavy loss of protein in the urine, or

2.2. impaired kidney (renal) function. impaired kidney (renal) function.

Heavy loss of protein in the Heavy loss of protein in the urineurine

The heavy loss of protein in the urine (over 3.0 The heavy loss of protein in the urine (over 3.0 grams per day) with its accompanying edema is grams per day) with its accompanying edema is termed the termed the nephrotic syndromenephrotic syndrome. Nephrotic . Nephrotic syndrome results in a reduction in the concentration syndrome results in a reduction in the concentration of albumin in the blood (hypoalbuminemia). Since of albumin in the blood (hypoalbuminemia). Since albumin helps to maintain blood volume in the blood albumin helps to maintain blood volume in the blood vessels, a reduction of fluid in the blood vessels vessels, a reduction of fluid in the blood vessels occurs. The kidneys then register that there is occurs. The kidneys then register that there is depletion of blood volume and, therefore, attempt to depletion of blood volume and, therefore, attempt to retain salt. Consequently, fluid moves into the retain salt. Consequently, fluid moves into the interstitial spaces, thereby causing pitting edema.interstitial spaces, thereby causing pitting edema.

Heavy loss of protein in the Heavy loss of protein in the urineurine

The treatment of fluid retention in these The treatment of fluid retention in these patients is to reduce the loss of protein into patients is to reduce the loss of protein into the urine and to restrict salt in the diet. The the urine and to restrict salt in the diet. The loss of protein in the urine may be reduced loss of protein in the urine may be reduced by the use of ACE inhibitors and angiotensin by the use of ACE inhibitors and angiotensin receptor blockers (ARB's). Both categories receptor blockers (ARB's). Both categories of drugs, which ordinarily are used to lower of drugs, which ordinarily are used to lower blood pressure, prompt the kidneys to blood pressure, prompt the kidneys to reduce the loss of protein into the urine. reduce the loss of protein into the urine.

Impaired kidney (renal) Impaired kidney (renal) functionfunction

Patients who have kidney diseases that impair renal Patients who have kidney diseases that impair renal function develop edema because of a limitation in function develop edema because of a limitation in the kidneys' ability to excrete sodium into the urine. the kidneys' ability to excrete sodium into the urine. Thus, patients with kidney failure from whatever Thus, patients with kidney failure from whatever cause will develop edema if their intake of sodium cause will develop edema if their intake of sodium exceeds the ability of their kidneys to excrete the exceeds the ability of their kidneys to excrete the sodium. The more advanced the kidney failure, the sodium. The more advanced the kidney failure, the greater the problem of salt retention is likely to greater the problem of salt retention is likely to become. The most severe situation is the patient become. The most severe situation is the patient with end-stage kidney failure who requires dialysis with end-stage kidney failure who requires dialysis therapy. therapy.

ManagementManagement

Identify and treat factors associated with Identify and treat factors associated with progressionprogression HTNHTN ProteinuriaProteinuria Glucose controlGlucose control Treat pulmonary edema (Bipap)Treat pulmonary edema (Bipap)

HypertensionHypertension

Target BPTarget BP <130/80 mm Hg<130/80 mm Hg

Consider several anti-HTN medications with Consider several anti-HTN medications with different mechanisms of activitydifferent mechanisms of activity ACEs/ARBsACEs/ARBs DiureticsDiuretics CCBsCCBs HCTZ (less effective when GFR < 20)HCTZ (less effective when GFR < 20)

Metabolic changes with CKDMetabolic changes with CKD

Hemoglobin/hematocrit Hemoglobin/hematocrit Bicarbonate Bicarbonate CalciumCalcium Phosphate Phosphate PTH PTH Triglycerides Triglycerides

Metabolic changes…Metabolic changes…

Monitor and treat biochemical abnormalitiesMonitor and treat biochemical abnormalities AnemiaAnemia Metabolic acidosisMetabolic acidosis Mineral metabolismMineral metabolism DyslipidemiaDyslipidemia NutritionNutrition

AnemiaAnemia

Common in CRFCommon in CRF HD pts have increased rates of:HD pts have increased rates of:

Hospital admissionHospital admission CAD/LVHCAD/LVH Reduced quality of lifeReduced quality of life

Can improve energy levels, sleep, cognitive Can improve energy levels, sleep, cognitive function, and quality of life in HD ptsfunction, and quality of life in HD pts

Treating AnemiaTreating Anemia

Epoetin alfa (rHuEPO; Epogen/Procrit)Epoetin alfa (rHuEPO; Epogen/Procrit) HD: 50-100 U/kg IV/SC 3x/wkHD: 50-100 U/kg IV/SC 3x/wk Non-HD: 10,000 U qwkNon-HD: 10,000 U qwk

Darbepoetin alfa (Aranesp)Darbepoetin alfa (Aranesp) HD: 0.45 HD: 0.45 g/kg IV/SC qwkg/kg IV/SC qwk Non-HD: 60 Non-HD: 60 g SC q2wksg SC q2wks

Metabolic acidosisMetabolic acidosis

Muscle catabolismMuscle catabolism

Metabolic bone diseaseMetabolic bone disease

Sodium bicarbonateSodium bicarbonate Maintain serum bicarbonate > 22 meq/LMaintain serum bicarbonate > 22 meq/L 0.5-1.0 meq/kg per day0.5-1.0 meq/kg per day Watch for sodium loadingWatch for sodium loading

Volume expansionVolume expansion HTNHTN

NEJM 2000; 342(20): 1478-83

Mineral metabolismMineral metabolism

Calcium and phosphate metabolism Calcium and phosphate metabolism abnormalities associated with:abnormalities associated with: Renal osteodystrophyRenal osteodystrophy Calciphylaxis and vascular calcificationCalciphylaxis and vascular calcification

14 of 16 ESRD/HD pts (20-30 yrs) had 14 of 16 ESRD/HD pts (20-30 yrs) had calcification on CT scancalcification on CT scan

3 of 60 in the control group3 of 60 in the control group

NutritionNutrition

Think about uremiaThink about uremia Catabolic stateCatabolic state AnorexiaAnorexia Decreased protein intakeDecreased protein intake

Consider assistance with a renal dieticianConsider assistance with a renal dietician

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CV diseaseCV disease

70% of HD patients have concomitant CV 70% of HD patients have concomitant CV diseasedisease

Heart disease leading cause of death in HD Heart disease leading cause of death in HD patientspatients

LVH can be a risk factorLVH can be a risk factor

Acid Base Balance Acid Base Balance

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