Introduction to NephrologyJENNIFER SMITH, FNP-S

ObjectivesProvide an overview of basic renal anatomy and physiology

Discuss the growing epidemic of chronic kidney disease due to increased incidence of obesity, hypertension, and diabetes

Define the stages of chronic kidney diseases and discuss associated complications such as: anemia of chronic kidney disease, secondary hyperparathyroidism, hypertension, cardiovascular disease, hyperkalemia, hyperphostphatemia, and bone disease

Discuss management of chronic kidney disease

Discuss other common kidney disorders that may lead to end-stage renal disease

The KidneyLocation- relatively high under lower ribs in the retroperitoneal space

Anatomy and PhysiologyAverage size of adult kidney is 12x6x3 cm

Size variations can occur with age, gender, BMI, pregnancy, kidney disease, and co-morbid conditions

Right kidney smaller

Right kidney lower than left kidney

Renal Anatomy

Structure of KidneyCortex-the outer layer of the kidney comprising the glomeruli, most of the proximal tubules, and some of the distal tubulesMedulla-formed by 7-9 cone shape pyramids which extend into the renal pelvisRenal Pelvis-flat funnel-like tube continuous with ureter as it leaves the hilusCalyces- subdivided into major and minor calycesMajor calyces- 2 or 3 branches off of renal pelvisMinor calyces- cup-shaped areas that enclose the papillae of the pyramids. Continuously collect urine draining from papillae, emptying it into the renal pelvis (Greenburg et al, 2009)

The Nephron Functional unit of kidney Consisting of glomerulus and long tubuleApproximately 1 million nephrons in each kidneyFilters plasma->reabsorption and secretion->forms filtrate free of protein->regulates the filtrate to maintain fluid volume, electrolytes, and pH

(Greenburg et al, 2009)

The NephronGlomerulus- tuft of capillaries surrounded by Bowman’s capsule. Together form the renal corpuscle.

Tubules- segmented into proximal tubule, loop of Henle, distal tubule, and collecting tubules

•Tubular Transport:

Proximal Tubule- active reabsorption of sodium

Loop of Henle and distal tubule- concentration or dilution of urine

Collecting Tubules- run through medullary pyramids (give them their striped appearance)

(Greenburg et al, 2009)

The Nephron

Blood and Nerve SupplyRenal arteries: branch off of the aorta then further divide to form: segmental arteries:

1. Lobular arteries

2. Interlobar arteries

3. Arcuate arteries

4. Interlobular arteriesMore than ¼ of the cardiac output is delivered to the kidneys each minute (1200ml/min)More than 90% of blood entering kidney perfuses the cortex

(Greenburg et al, 2009)

Blood and Nerve SupplyRenal Veins- trace pathway of arterial blood supply in reverseEmpty into the inferior vena cavaLeft renal vein is about 2x longer in order to extend to IVC in its position to right of vertebral columnRenal Plexus-network of autonomic nerve fibers and ganglia. Supplied by sympathetic fibers from thoracic and lumbar splanchnic nervesSympathetic fibers- vasomotor fibers that control renal blood flow by adjusting arteriolar diameters

(Greenburg et al, 2009)

Functions of KidneyMaintenance of body fluids composition (fluid volume, osmolarity, electrolyte, and acid/base balance.Excretion of metabolic end products and foreign substances (i.e. urea, toxins, drugs).Production/secretion of enzymes and hormones

(Greenburg et al, 2009)

Functions of KidneyRenal Hormones and Enzymes

Renin- produced in juxtaglomerular apparatus. Catalyzes production of angiotensin which is important for sodium balance and blood pressure regulationErythropoietin- stimulates maturation of RBC’s in bone marrow1,25-Dihydroxyvitamin D3- most active form of Vitamin D3, steroid hormone that helps the body regulate calcium/phosphorus balance

(Greenburg et al, 2009)

Functions of Kidney Alterations in body fluid composition and fluid volume can impact:Cardiac Output and Blood Pressure- dependent on optimal plasma volumeEnzyme Function- most function best in narrow range of pH and ion concentrationsCell Membrane Potential- depends on potassium concentrationsMembrane excitability- depends on calcium ion concentrations

Evaluation of Renal FunctionGlomerular Filtration Rate (GFR)

Serum Creatinine, Blood Urea Nitrogen

MAU/CR ratio

30-300 mg/dl microalbuminemia

>/= 300mg/dl- macroalbuminemia

24 hour urine collection

Glomerular Filtration Rate (GFR)GFR- amount of fluid filtered from blood into glomerular capsule each minuteGFR- 180 L/dayGFR controlled by:Auto-regulation (tubuloglomerular feedback)Neural regulationHormonal regulation- renal aldosterone angiotensin system

ScreeningDM- largest single cause of CKD in the U.S.

Initial screening 5 years after diagnosis of Type I DM

AT DIAGNOSIS of type II DM

Annually thereafter

HTN

Family history of CKD

Autoimmune disorders

Screening MethodsChemistries-renal panel, include albumin and MGUrinalysisMicroalbumin/Cr ratioImaging studies 24 hour urine

Abnormalities on Imaging Studies

Renal cysts-often incidental findings and usually benign. Ultrasound is preferred method to differentiate between cystic and solid lesions. (If complex cyst or indeterminate lesions follow up with MRI)

Nephrolithiasis- non-contrast CT is gold-standard

Hydronephrosis

Chronic Kidney DiseaseCKD is defined as:Kidney damage for 3 months or longer to include either structural or functional abnormalities

With or without a decrease in GFR (as seen by pathology abnormalities, markers of kidney damage in blood or urine, or abnormalities on imaging studies).GFR of less than 60 ml/min for at least 3 months

Prevalence31 million in U.S. (16% of population) and rising

1 in 10 adults have some level of CKD

Majority of people with CKD are in Stage 1-3

Incidence is increasing rapidly in those >65

ESRD expected to reach 2.2 million by 2030

ESRD males > females

Most people with CKD die before they are diagnoses, primarily of cardiovascular complications

African Americans are 4 times more likely to develop CKD than Caucasians.

(Domino, 2013)

Risk FactorsHypertension

DM

Autoimmune diseases (vasculitis, connective tissue disorder)

Congenital anomalies

Family history of CKD or transplant

Kidney stones

Frequent urinary tract infections

Exposure to certain drugs (i.e. NSAID)

Cardiovascular disease

Acute Kidney Injury

Systemic infections

Low income/education

Minority populations

Obesity

Smoking

Age > 60 years

Race

Neoplasm

Urinary Tract Obstruction

Hyperlipidemia

(Domino, 2013)

CKD Staging

(Domino, 2013)

Clinical Findings of CKD by StageStage I and

II

• Asymptomatic, BUN/CR slightly elevated or normal, acid-base, fluid, and electrolyte balance is maintained through compensation of remaining nephrons

Stage III

• Usually asymptomatic, BUN/CR increased. Erythropoietin decreased and PTH levels are increased

Stage IV

• Patient may have anemia, acidosis, hypocalcemia, hyperphosphatemia, and hyperkalemia

Stage V

• Fatigue, dysgeusia, anorexia, nausea, pruritus, asterixis, uremic breath

Associated ComplicationsHTN

Anemia

Secondary Hyperparathyroidism (SHPT)

Hyperkalemia

Cardiovascular complications

Bone disease

(Greenburg et al, 2009)

HypertensionCan be cause or effect

Inappropriate sodium reabsorption leading to increased fluid volume is primary cause of HTN in CKD

RAAS stimulation

Renal Artery Stenosis

Vascular Calcifications

Managing HTN in CKDGoal is BP < 130/80 mm/HgMany patients will require multiple drug classifications to control BP due to increased vascular resistance and increased fluid volumeUncontrolled HTN is key risk for progression of CKDAn increase in BP of 20/10mmHg doubles risk for cardiovascular disease

(Greenburg et al, 2009)

Pharmacologic Management HTN in CKDACE/ARB

“Reno protective”

Lowers intra-glomerular pressure and reduces proteinuria, slowing the progression of CKD

May see initial increase in sCr (less than 30% that returns to baseline within 2 months if acceptable)

Monitor K level

Contraindicated in renal artery stenosis, uncontrolled hyperkalemia, pregnancy, history of angioedema

Not unusual to see patients with CKD on several different classifications of medications

(Collins, 2012)

Pharmacologic Management HTNCalcium Channel Blocker:

Dihydropyrodines-Amlodipine, Valsaartan

Increase intraglomerular pressure causing worsening of proteinuria if not used in combination with a ACE/ARB

Non-Dihydropyrodines (Diltiazem, Verapamil)

If failing on ACE/ARB therapy, have been shown to reduce proteinuria

Vasodilators (Hydralazine, Isosorbide)

May be useful in patients with known renal artery stenosis

(Collins, 2012)

Pharmacology ContinuedDiuretics

Diuretic resistance may be due to high sodium diet

Loop Diuretics

Best dosed BID for CKD III or higher

May take second dose 6 hours after 1st dose

Monitor serum K+ levels, may need replacement

Thiazide Diuretics

Effective in patients with GFR>30

Monitor uric acid level as may cause gout

Monitor serum K+ levels

(Collins, 2009)

DiureticsMost CKD patients require diureticsEnhances antihypertensive therapyReduces tubular sodium reabsorption which in turn increases sodium excretion and lowers ECF volume, lowering BPChoice of diuretic depends on CKD stage, volume of fluid overload, and other individual patient factorsUse potassium sparing diuretics with caution if GFR is less than 30, or if concomitant use of ACEI/ARBDon’t decrease diuretics due to increase BUN/Cr. BUN/Cr will fluctuate with fluid volumeDon’t treat the lab, treat the patient!

(Collins, 2009)

CKD in PregnancyRenal function in CKD may deteriorate during pregnancy

CR >1.5 and hypertension are major risk factors of worsening renal function

Increased risk of premature labor, preeclampsia, and/or fetal loss

ACE inhibitors and ARBs are contraindicated

Use diuretics with caution

(Domino, 2009)

Parathyroid Gland

Secondary Hyperparathyroidism (SHPT)The parathyroid glands main function is to control calcium within the blood and bonesParathyroid glands atrophy due to constant stimuli in CKD (either hypocalcemia or hyperphosphatemia).Atrophied glands secrete PTH, causing serum levels to risePTH stimulates conversion of active Vitamin D to increase calcium absorption from the GI tractOver time, elevated PTH leads to bone disease, vascular and soft tissue calcifications, decreased quality of life, amputations, and increased mortality

(Greenberg et al, 2009)

PTH goal based on Stage of CKD

(National Kidney Foundation, 2010)

SHPTMonitoring

Intact PTH levels

Ca and Phosphorus levels

Vitamin D 1,25 level

Treatment

Oral Calcitriol, Zemplar, Hectoral, Sensipar

May need Vitamin D replacement

Treat hyperphosphatemia- if you control phosphorus you will control the parathyroid

May need parathyroidextomy

HyperphosphatemiaIncreases cardiovascular risk factors

Calcifications develop may result in bone deformities and amputations

High levels of phosphorous cause Calcium to be pulled from bone

Osteoporosis

Bone pain

Fractures

Hyperphosphatemia

Treatment for Hyperphosphatemia

Cardiovascular Complications in CKDPatients with CKD more likely to die from CVD

Survival rate of MI patients with CKD are 53% compared to 36%

Vascular calcifications common in patients with hyperphosphatemia and SHPT

Cardio-renal syndrome

Patients with CKD should have annual EKG,

stress test on file

HyperkalemiaDecreased Renal Excretion

Acute or chronic renal failure

Aldosterone deficiency (frequently associated with diabetic nephropathy, chronic interstitial nephritis, or obstructive uropathy)

Adrenal Insufficiency (Addison’s disease)

Kidney diseased that impair distal tubule function (Sickle cell, Systemic Lupus Erythematosus)

Abnormal Potassium Distribution

Insulin deficiency

B-Blockers

Metabolic and Respiratory Acidosis

Abnormal Potassium Release from Cells

Rhabdomyolysis

Tumor lysis syndrome

(Greenburg et al, 2009)

Treatment Goals to Slow Progression of CKDControl blood pressure <130/80 or <140/80 in renal artery stenosis

Low NA diet

ACE/ARB therapy

Diuretics

Nondihydropyridine Calcium Channel Blockers

Optimize control of DM (HGA1C <7.5)

Control dyslipidemia LDL goal <100

Restrict dietary protein

Low phosphorous diet

Prescribing Considerations in CKDDose adjust medications based on GFR (Metformin, Allopurinol, many antibiotics, etc)

Avoid use of nephrotoxic drugs (NSAIDS, contrast dye, Bactrim)

When treating DM with CKD less insulin may be required due to decreased gluconeogenesis

Best to avoid 1st generation sulfonylureas as they have increased risk for hypoglycemia due to decreased renal clearance

Second generation sulfonylureas are preferred (Glipizide)

As always start low and go slow!

(Greenburg et al, 2009)

Drug-Induced HyperkalemiaBlock Sodium Channel in the Distal Nephron

Potassium-sparing diuretics: amiloride, triamterene

Antibiotics: trimethoprim, pentamidine

Block Aldosterone Production

ACE inhibitors

ARBs

NSAIDS and COX-2 inhibitors

Heparin

Tacrolimus

Block Na+, K+-ATPase Activity in the Distal Nephron

Cyclosporine

Potassium Release from Injured Cells

Drug-induced rhabdomyolysis (lovastatin, cocaine)

Drug induced tumor lysis syndrome(chemotherapy agents in leukemia's, high-grade lymphomas)

Depolarizing paralytic agents (succinylcholine)

Block Aldosterone Receptor

Spironolactone

Eplerenone

NSAID’sMajor cause of CKD

Block Aldosterone Production

Widespread use of these drugs are leading to increased cases of NSAID-induced nephropathy

Not a problem if no renal impairment

Avoid in CKD and transplant patients

Diabetic NephropathyAbout 35% of patients with DM (Type I and Type II) will develop nephropathy after about 25 to 30 years

Approximately 45% of dialysis patients have diabetic nephropathy as cause of ESRD

However many type II patients die from CV disease before they reach ESRD

May not be able to tell patient has kidney disease based on GFR

Need to have a micro albumin urine test to determine level of proteinuria

Need to be on ACE/ARB for renal protection

Renal Artery StenosisClassic findings:

•Uncontrolled HTN despite multiple medications

Causes:

Usually atherosclerosis

Fibro muscular dysplasia

Diagnosis:

Nuclear renal scan, renal arteriogram, MRA, or Doppler ultrasound

Treatment:

Angioplasty or surgery

Obstructive UropathyObstruction can occur anywhere along urinary tract causing hydonephrosis

Renal calculi

BPH

Colon, cervical, or uterine cancer

Neurogenic bladder

Can be unilateral or bilateral

Treatment

Resolve obstruction- may need stents

Treat BPH

Foley catheter or nephrostomy tubes

Autosomal Dominant Polycystic Kidney DiseaseMost common inherited kidney disease

Affects 1 in 1000 people

Systemic disease causing kidney, liver, pancreas, thyroid, and subarachnoid cysts and intracranial aneurysm

Clinical hallmark sign is gradual and massive cystic enlargement of kidneys resulting in kidney failure

May be present in childhood with symptoms usually beginning in middle age

Symptoms can include abdominal pain, hematuria, nocturia, flank pain, and fatigue

Diagnosis usually made by ultrasound

Presence of enlarged kidneys with multiple cysts required for diagnosis

ADPKD

ADPKD

Hepatorenal Type I

Usually rapid decline in kidney function

sCr may double in 2 weeks

Occurs with acute hepatitis, bacterial infections, major surgery, or massive GI bleed

Type II

Moderate steady decline in GFR

Cirrhosis causes decrease in NA and water excretion, decreased renal perfusion and GFR

Decreased ability to excrete NA leads to ascites

Presence of ascites represents marked impairment or renal sodium handling

Cardio-Renal1. Abrupt worsening of cardiac function leads to AKI

2. Chronic abnormalities in cardiac function causes progression of CKD

3. Abrupt worsening of renal function causes acute cardiac dysfunction (heart failure, arrhythmia, or ischemia)

4. CKD contributes to decreased cardiac function resulting in hypertrophy and increased risk of CVD

5. A systemic condition results in both cardiac and renal dysfuction

Aging and Renal FunctionNatural decline in GFR is 8ml/min for every decade after 40 despite normal creatinine

Renal blood flow declines by 10% per decade

Renal mass decreased from 400g to 300g by age 90

All the above accelerated by: HTN, DM, lead exposure, smoking, atherosclerotic vascular disease, and male gender

Acute Kidney InjuryIncidence increasing with the number of hospitalizations with AKI diagnosis rose from 3,942 in 1996 to 23,052 in 2008

5% to 30% of hospital ICU admissions

25% of people develop while in the hospital

50% of cases are iatrogenic

Pre-renal- response to hypoperfusion->volume depetion, sepsis, heart failure, cirrhosis

Intra-renal- conditions that affect parenchyma->acute tubular necrosis, acute interstitial nephritis, nephrotoxic medications

Post-renal-obstruction of urinary outflow->BPH, renal calculi

(Domino, 2013)

Nephrotic SyndromeClinical syndrome characterized by massive proteinuria (>3g/24hrs)

Associated with many types of kidney diseases such as minimal change disease, membranous glomerulopathy, diabetes, and amyloidosis

Hypoalbuminemia

Edema

Hyperlipidemia

Lipiduria

May have fatigue, weight gain, anorexia, foamy urine

Treatment involves addressing underlying cause and complications

May need a kidney biopsy

May require long-term immunosuppressant therapy

(Domino, 2013)

End-Stage Renal Disease (ESRD)Cardiovascular disorders are leading cause of death for ESRD patients

More than 50% of dialysis patients die from cardiovascular complications

Risk of CV death is 50% higher in this population if patient also has DM

Screen patients annually for CV disease with electrocardiogram, stress test

Refer to cardiologist

Signs and Symptoms of ESRDHead-headaches, fatigue, and difficulty thinking

Mouth- food may taste bad or like metal, foul smelling breath (like urine)

Lungs-dyspnea caused by fluid or anemia

Stomach- loss of appetite, nausea and vomiting

Bladder- less or no urine. Some people still make urine but it is just fluid no waste products are removed

Hands and feet- swelling

Skin-build up of uremic wastes causes itching

Blood vessels- high blood pressure failing kidneys can no longer keep pressure under control

(Greenburg, 2009)

HemodialysisDone through a vascular access (fistula, graft, or permacath)

Usually requires four hour sessions three days a week

Special considerations

•Some antibiotics require dose adjustment/timing adjustment to avoid removal of medication

through dialysis

Peritoneal DialysisAdvantages

Convenient done at home

Daily treatments more closely match natural renal functions

Patients have less fluid/dietary restrictions

Disadvantages

High Risk for peritonitis

Requires compliance with aseptic technique

Patients with history of multiple abdominal surgeries or hernia may not be candidates

Renal TransplantEvaluation process can start when GFR is <20

Many options are available such living relative, non-related living, and cadaver

Requires extensive workup to be placed on list

Compliance

Requires immunosuppressant therapy

Caution when prescribing/adjusting transplant patient’s medication

Burden of ESRDEconomic costs

Total Medicare costs for ESRD care in 2005 were $19.3 billion

Decreased quality of life

Increased morbidity and mortality

Complications associated with dialysis

ReferralElectrolyte abnormalities

Persistent proteinuria

Uncontrolled HTN

Elevated serum CR/decreased GFR –guidelines CR 1.5 female, 2.0 male

Patient with known CKD that are likely to progress

Don’t wait to refer to nephrologist when the patient needs dialysis

Patients need to have dialysis access, education, and preparation

CollaborationCKD requires collaboration and coordination among many health care providers

CKD stages I-III usually managed by PCP

Nephrologist usually consulted when CKD III or other kidney disorder

Dietician

Cardiologist

Vascular Surgeons

Endocrinologist

Social workers

Educational ResourcesNational Kidney Foundation www.kidney.org

American Nephrology Nurse’s Association http://ww.annanurse.org

Internet School of Nephrology http://www.Ukidney.com

International Society of Nephrology http://www.theisn.org

American Society of Nephrology http://www.asn-online.org/

Questions The number one cause of death in patients with ESRD: A. Complications from DM B. Septicemia D. Cardiovascular Disease E. Cancer The functions of the kidney are: A. Production and secretion of enzymes and hormones B. Excretion of metabolic end products and foreign substances C. Maintenance of body fluid composition D. Both A & B E. All of the above The best antibiotic choice for a 69 y/o female with a urinary tract infection A. Cipro 250mg BID B. Bactrim DS 1 tablet BID C. Do not provide antibiotics wait for urine culture

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syndrome. Journal of American College of Cardiology, 52(19), 1527-1539.

Collins, T. (2012). Twelve things hospitalists need to know about nephrology. The Hospitalist.

Retrieved February 7, 2014 from http://the-hospitalist.org/details/article/3782901/12

Things Hospitalists Need to Know About Nephrology.html

Deja Review Internal Medicine (2011). Mobasser, S., McGraw Hill Medical, New York

Dunphy, L., Winland Brown, J., Porter, B., & Thomas, D. (2011). Primary Care: The art and science of advanced practice nursing. 3rd Edition.

Philadelphia: F.A. Davis. ISBN 978-0-8036-2255-5.

Domino, F. (2013). Griffith’s 5 Minute Clinical Consult. 19th Ed. Lippincott Williams & Wilkins.

Fibromuscular Dysplasia (n.d.). Retrieved February 7, 2014 from http://www.mayoclinic.com/

health/fibromuscular-dysplasia/DSO1101.

Greenburg, A., Cheung, A.K., Coffman, T.M., Falk, R. J., Jennette, J.C. (2009). Primer on kidney diseases. (5th ed.), Philadelphia, Saunders Elsevier

National Kidney Foundation (2010). Nephrology essentials: chronic kidney disease. Retrieved

February 8,2014 from http://www.kidney.org/professionals/CAP/nephEssentials.cfm

References National Kidney Foundation (2012). Clinical Practice Guidelines for Chronic Kidney Disease

Evaluation, Classification, and Stratification.

National Kidney and Urologic Diseases Information Clearinghouse (2012). Retrieved February

10, 2014 from http://www.nih.gov/kudiseases/pubs/kustats/#top

Niels-Peter, B., Farhat, A., Syed, R., Biyabani, Q., Masood, A., Imtiaz, R.(2012) Ultrasonographic

renal size in individuals without known renal disease. Journal of Pakistan Medical Association.