Chronic Kidney Disease

Internal Medicine

August 2011

Definition Structural or functional abnormalities of the

kidneys for ≥3months, as manifested by either:1. Kidney damage, with or without decreased

GFR, as defined by pathologic abnormalities markers of kidney damage, including

abnormalities in the composition of the blood or urine or abnormalities in imaging tests

Kidney transplantation2. GFR <60 ml/min/1.73 m2, with or without

kidney damage

Definition Kidney Failure is defined as either

(1) a level of GFR to <15 mL/min/1.73 m2, which is accompanied in most cases by uremia, or

(2) a need for initiation of kidney replacement therapy (dialysis or transplantation) for complications of decreased GFR.

End-Stage Renal Disease (ESRD) administrative term for disbursement by

Medicare, specifically the level of GFR (creatinine of 8mg/dl) and occurrence of kidney failure symptoms necessitating replacement therapy. ESRD includes patients treated by dialysis or transplantation.

Causes and Incidence Chronic renal failure occurs in

approximately 1 out of 1,000 people. Causative diseases include any type:

1. Diabetes mellitus - most common cause2. Hypertension3. Glomerulonephritis4. Others

chronic pyelonephritis, PKD /polycystic kidney disease, obstructive uropathy (stones, BPH, cancer, etc), Alport syndrome, and drug-induced nephropathy

Estimation of GFR Cockcroft- Gault Formula

MDRD Study Equation

CrCl (ml/min)=( 140 – age ) x Weight in Kg

72 x Serum Creat (mg/dl)x ( 0.85 if female )

GFR (mil/min/1.73 m2) = 186 x (SCr) -1.154 x (age) -.203

x (0.724 if female) x (1.210 if African American)

Stages of Chronic Kidney Disease

Symptoms INITIAL (non-specific)

unintentional weight loss

nausea, vomiting general ill feeling fatigue headache frequent hiccups generalized itching

(pruritus)

LATER increase or decrease

urine output need to urinate at night anasarca easy bruising or bleeding blood in the vomit or

stools breath odor (uremic

fetor) muscle twitching or

cramps restless legs syndrome increased skin

pigmentation uremic frost decreased sensation decreased alertness/

lethargy

Uremic Syndrome attributed to a variety of toxic substances, mainly

nitrogenous (protein and amino acid byproducts urea (when >50 mmol/l) and cyanate (CNO‑) guanidino compounds (eg guanidinosuccinic

acid) middle molecules (mw 300‑3,500) ‑ mainly

polypeptides urates and other metabolites of nucleic acids aliphatic amines and metabolites of aromatic

amino acids hormones (eg PTH) advanced glycation end-products

other factors already considered – bone disease, acidosis, and fluid and electrolyte disturbances – also contribute to the picture of full‑blown uremia.

Signs and Tests Blood pressure may be high Urinalysis may show protein, blood, pus or other

abnormalities Creatinine and BUN levels progressively increase Creatinine clearance progressively decreases Potassium elevated Calcium low and Phosphorus high Arterial blood gas show metabolic acidosis Xray of bones may show osteodystrophy

Signs and Tests Changes that indicate chronic renal failure,

including both kidneys being smaller than normal, may be seen on: abdominal ultrasound plain KUB X-ray abdominal CT scan or MRI

However, CKD with normal sized or enlarged kidneys: amyloidosis, diabetes multiple myeloma polycystic kidneys accelerated hypertension

Determinants of Rate of Progression Type of Renal Disease

rate of decline in PCKD and interstitial nephritis slower than in CGN

membranous Nephropathy may spontaneously remit with or without treatment

Hypertension Proteinuria Race – blacks fare worse Sex – women with PCKD fare better Pregnancy – GFR falls faster Diabetics – high sugar accelerates Smokers

Importance of Proteinuria

Interpretation Explanation

Marker of kidney damage

Spot urine albumin-to-creatinine ratio >30 mg/g or spot urine total protein-to-creatinine ratio >200 mg/g for >3 months defines CKD

Clue to the type (diagnosis) of CKD

Spot urine total protein-to-creatinine ratio >500-1000 mg/g suggests diabetic kidney disease, glomerular diseases, or transplant glomerulopathy.

Risk factor for adverse outcomes

Higher proteinuria predicts faster progression of kidney disease and increased risk of CVD.

Effect modifier for interventions

Strict blood pressure control and ACE inhibitors are more effective in slowing kidney disease progression in patients with higher baseline proteinuria.

Hypothesized surrogate outcomes and target for interventions

If validated, then lowering proteinuria would be a goal of therapy.

Dietary Requirements1. Protein

0.6-0.8 gm/k/day supplements of essential amino acids at 0.3

gm/k/day may allow lower protein intake to 0.4 gm/k/day intake for uremic patient not yet dialysed: 0.4 -

0.6gm/k/day for dialysed patients: increase to 1.0 - 1.2

gm/k/day2. Energy

35 kcal/k/day for sedentary, stable, non-obese HD patients

higher with strenuous labor, underweight or hypercatabolic

Dietary Requirements3. Fat

limit cholesterol <300 mg/day more proportion of mono- or polyunsaturated

than saturated4. Na+

7-10 gm/day (table salt) if with adequate urine <6 gm/day or <100 mmol/day if with fluid

retention/edema5. K+

HD: restrict to 2-3 gm/day (50-75 meq/day) PD: 3-4 gm/day or 75-100 meq/day

Dietary Requirements6. Ca++

restrict milk products so supplemental Ca++ is needed (1-1.5 gm/day) + Vitamin D to keep serum Ca++ >2.5 mg/dl

7. Phosphorus restrict to 0.6 - 1.2 gm/day to maintain s.Phos <4.5 to

5.5 mg/dl phosphate binders as needed such as calcium carbonate

and calcium acetate

8. Vitamins/ Minerals ascorbic acid < 150-200 mg maximum to avoid oxalosis folic acid 1000 mcg; vit.B1 30 or > mg/day; B6 20 or

more mg/day; Other water soluble vitamins based on RDA

provide selenium and zinc vitamin A preparations must be avoided

Management with Progressive Renal Disease1. early recognition 2. monitoring the progression 3. detection and correction of reversible causes 4. institution of interventions to delay progression,

eg diet, ACEinhibitors, BP, and sugar control 5. avoidance of additional renal injury,

eg smoking, NSAIDs, radiocontrast, aminoglycosides

6. treatment of complications, eg acid-base, mineral, and fluid-electrolyte abnormalities

7. planning ahead for renal replacement therapy (dialysis or transplantation)

Prevention to ESRD ACEI/ ARBs

established renoprotection with proteinuria reduction

higher doses recommended Blood Pressure

BP target of <130/85mmHg and when proteinuria >1gm/day or GFR <55ml/min; aim for ≤125/75

Cholesterol ideal LDL-C <100mg/dl and HDL-C >50mg/dl statins have the most benefit

Fasting Sugar intensive sugar control with target HbA1c of <7%

Prevention to ESRD Diet

Modified protein intake with 1.0gm/k/day for normal GFR 0.8gm/k/day for CRI; and 0.4-0.6gm/k/day for severe CRF Very low protein diet 0.3-0.4gm/k/day with ketoAA

supplements Educate

Exercise/ weight reduction, smoking cessation, alcohol avoidance, early nephro referral

Gases Acid-base control with giving of alkali such as NaHCO3

tablets to achieve HCO3 level ≥20mmol/L

Hemoglobin Hgb target 11-12g/L beneficial in CKD Erythropoietin replacement – best treatment

Clinical Practice Guideline for Detection, Evaluation, and Management of CKD

STAGE DESCRIPTION GFR EVALUATION MANAGEMENT

At increased risk

Test for CKD Risk factor management

1Kidney damage with normal or GFR

>90

DiagnosisComorbid conditionsCVD and CVD risk factors

Specific therapy, based on diagnosisManagement of comorbid conditionsTreatment of CVD and CVD risk factors

2Kidney damage with mild GFR

60-89Rate of progression

Slowing rate of loss of kidney function 1

3 Moderate GFR 30-59 ComplicationsPrevention and treatment of complications

4 Severe GFR 15-29Preparation for kidney replacement therapyReferral to Nephrologist

5 Kidney Failure <15 Kidney replacement therapy

1Target blood pressure less than 130/80 mm Hg. Angiotension converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mg/g.

Prognosis There is no cure for chronic renal failure.

Untreated, usually progresses to end-stage renal disease. Lifelong treatment may control the symptoms of chronic renal failure. Dialysis or kidney transplant required eventually. Otherwise, condition is terminal.

Support Groups The stress of illness can often be helped by joining

a support group where members share common experiences and problems.

Thank You!