Chronic Kidney Disease (CKD)

Shiva SeyrafianIKRC- IUMS

1392/2/19____9/5/2013

The Story of Mr. G. L.

• 45 yr with Diabetes for 10 yrs, “reasonably well controlled”

• PMH: – Hypertension for 7 yrs..well

controlled– BMI of 30– Dyslipidemia

• Fam Hx: Diabetes; • Soc Hx: Sedentary; non smoker;

Comedian• Exam

– 139/85 – Mild Obesity, rest fairly normal

• Labs– BUN 28, Creatinine 1.8, Urine

protein (dipstick) 2+

Chronic Kidney Disease

• Definition:– Chronic, irreversible loss of kidney function

attributable to loss of functional nephron mass – pathophysiologic processes for more than 3 months.

Epidemiology

• CKD affects about 26 million people in the US

• Approximately 19 million adults are in the early stages of the disease – On the rise due to increasing prevalence of

diabetes and hypertension

• Total cost of ESRD in US was approximately $40 billion in 2008

Diabetes Hypertension Chronic GN Cystic Disease Tubulointerstitial disease

Pathophysiology of CKD

• Final Common Pathway is loss of nephron mass

Mediated by vasoactive molecules, cytokines and growth factors, renin angiotensin axis

Pathophysiology• Repeated injury to kidney

Staging of Chronic Kidney Disease

Stage Description GFR (ml/min/1.73 m2)

At increased risk 90 (with CKD risk factors)

1 Kidney damage with normal or increased GFR

90

2 Kidney damage with Mildly decreased GFR

60-89

3 Moderately decreased GFR 30-59

4 Severely decreased GFR 15-29

5 Renal Failure <15 (or dialysis)

Who is at Risk for CKD?

• Family history of heritable renal disease• Diabetes• Hypertension• Auto-immune disease• Old age• Prior episode of ARF• Current evidence of renal damage, even

with normal or increased GFR

Estimation of GFR

Modification of Diet in Renal Disease (MDRD) FormulaEstimated GFR = 1.86 (Serum Creat) -1.154 X

(age) -0.203

Multiply by 0.742 for womenMultiply by 1.21 for African Americans

Cockroft Gault Formula(140 – age) X Body Weight (Kg) 72 X Serum Creatinine (mg/dL)

Multiply by 0.85 for women

MDRD GFR for Mr Lopez

• Diabetic, Hypertension, Metabolic Syndrome X

• Stage 3 CKD• GFR = 44 ml/min/1.73 m2

Stages in Progression of CKD and Therapeutic Strategies

AJKD 2002: 39(2)

Monitoring of CKD• Serial measurements of

– Creatinine– GFR

• Albumin • Albumin-creatinine ratio in the 1st morning

sample• Electrolytes including HCO3, Ca, Phos;

alkaline phosphatase, iron studies, intact PTH

• Renal sonogram• Renal biopsy

Symptoms of CKD• Stage 1 and 2

– Asymptomatic, hypertension

• Stage 3 and 4– Anemia – loss of energy– Decreasing appetite; poor nutrition– Abnormalities in Calcium, Phosphorus metabolism– Sodium, water, potassium and acid base abnormalities

• Stage 5– All of the above – accentuated; eventually overt uremia

Symptoms

• Hematuria• Flank pain• Edema• Hypertension• Signs of uremia• Lethargy and fatigue• Loss of appetite• If asymptomatic may have elevated serum

creatinine concentration or an abnormal urinalysis

Common Causes and Presentation

Cause Clinical Presentation

Diabetic kidney disease

History of diabetes, proteinuria and retinopathy

Hypertension Elevated BP, normal UA, family history

Non diabetic glomerular disease

Nephritic or nephrotic presentations

Cystic kidney disease

Urinary symptoms, abnormal sediment, radiologic findings

Tubulointerstitial disease

UTI, reflux, chronic med use, drugs, imaging abnormalities, urine concentrating defects

Convergence of Genetic Factors• Genes for heart and vascular disease• Genes that maintain ionic balance• Genes for glomerulonephritis• Genes for diabetes• Genes that may be involved in inherited renal diseases

Genetic Considerations

• Autosomal dominant PKD• Alport’s hereditary nephritis• Familial FSGS• Nephronopthisis• Medullary cystic kidney disease• Fabry’s disease

Natural History of CKD

• Most CKD has a logarithmic progression and is predictable

Mr. G. L. – Progressive Decline

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Organ System Symptoms Signs

General Fatigue, weakness Sallow-appearing, chronically ill

Skin Pruritus, easy bruisability Pallor, ecchymoses,excoriations, edema, xerosis

ENT Metallic taste in mouth, epistaxis Urinous breath / fetor

Eye   Pale conjunctiva

Pulmonary Shortness of breath Rales, pleural effusion

Cardiovascular Dyspnea on exertion, retrosternal pain on inspiration (pericarditis)

Hypertension, cardiomegaly,friction rub

Gastrointestinal Anorexia, nausea, vomiting, hiccups  

Genitourinary Nocturia, impotence Isosthenuria

Neuromuscular Restless legs, numbness and cramps in legs

 

Neurologic Generalized irritability and inability to concentrate, decreased libido

Stupor, asterixis, myoclonus, peripheral neuropathy

Symptoms of Uremia

Sodium and water Imbalance

• Sodium retention, contributes to hypertension.

• Higher than usual doses for

diuretics. In situations with volume depletion – can be severe, because of inadequate sodium retention.

Potassium Imbalance

• Potassium– GI excretion is augmented– Constipation, dietary intake, protein catabolism,

hemolysis, hemorrhage, transfusion of stored blood, metabolic acidosis,

– Drugs: ACE inhibitors, ARBs, B blockers, K sparing diuretics and NSAIDs

– Hyporeninemic hypoaldosteronism: Diabetes, sickle cell disease

Acid Base Imbalance• Damaged kidneys are unable to excrete the 1

mEq/kg/d of acid generated by metabolism of dietary proteins. – NH3 production is limited because of loss of nephron

mass– Decreased filtration of titrable acids – sulfates,

phosphates– Decreased proximal tubular bicarb reabsorption,

decreased H ion secretion• Arterial pH: 7.33 - 7.37; serum HCO3 rarely

below 15 – buffering offered by bone calcium carbonate and phosphate

• Should be maintained over 21

Bone Disease

Mineral Metabolism• Calciphylaxis

– PTH, P, Ca x P, Active Vitamin D, Fetuin A, Matrix Gla protein ( warfarin)

– Calcemic uremic arteriopathy– Extraosseous/metastatic

calcification of soft tissues and blood vessels

– Devastating complication

Cardiovascular Abnormalities

• Leading cause of morbidity and mortality in patients with CKD at all stages

• Ischemic CAD• Hypertension and LVH• Congestive heart failure• Uremic pericarditis

Cardiovascular risks in CKD• Reduced glomerular filtration rate (GFR)

and proteinuria are both independently associated with an increased risk of cardiovascular events.

•  The increase in cardiovascular risk associated with CKD.

• The risk of death, particularly due to cardiovascular disease, is typically higher than the risk of eventually requiring renal replacement therapy.

Pericarditis

• Uremic pericarditis:There is a correlation with the degree of azotemia (the BUN is usually >60 mg/dL), Except in the case of systemic immune disorders (such as lupus erythematosus or scleroderma), there is no relationship with the underlying cause of renal failure.

• Dialysis-associated pericarditis: two causses: inadequate dialysis (ie, the patient has uremic pericarditis) and/or fluid overload.

Pericarditis

• Unusual feature of uremic pericarditis:  the electrocardiogram does not show the typical diffuse ST and T wave elevations observed with other causes of acute pericarditis. 

• With the development of cardiac tamponade, typical ECG changes (eg, electrical alternans) may occur

Cardiac Complications

Lipid abnormalities

• The most common dyslipidemia in CKD patients is hypertriglyceridemia, whereas the total cholesterol concentration can be normal or low, perhaps due in part to malnutrition.

•  Some have found that low (not high) serum cholesterol values are associated with increased mortality.

Lipid abnormalities

• Some have found no association between lipid levels and mortality among patients with CKD.

•  Reflect the adverse effect of malnutrition and chronic inflammation upon mortality.

Hematological Abnormalities• Anemia: Chronic blood loss, hemolysis, marrow suppression by

uremic factors, and reduced renal production of EPO– Normocytic, normochromic

• Coagulopathy:Clinical bleeding in uremia is typically cutaneous, including easy

bruising and mucosal bleeding, or may occur in response to injury or invasive procedures.

Less frequent is epistaxis, gingival bleeding, or hematuria. – Mainly platelet dysfunction – decreased activity of platelet

factor III, abnormal platelet aggregation and adhesiveness and impaired thrombin consumption

– Increased propensity to bleed – post surgical, GI Tract, pericardial sac, intracranial

– Increased thrombotic tendency – nephrotic syndrome

Other Abnormalities• Neuromuscular

– Central, peripheral and autonomic neuropathy– Motor Neuropathy: muscle atrophy, myoclonus, and

eventual paralysis. – Mononeurpathy:

• Carpal tunnel syndrome• Dysfunction of both the vestibular and cochlear divisions of

the eighth cranial nerve  – Polyneuropathy: paresthesias, burning sensations, and

pain — tend to precede the motor symptoms. The initial finding in uremic polyneuropathy is loss of position and vibration sense in the toes and decreased deep tendon reflexes, beginning with the Achilles reflex.

The hands may become involved. – Sensory syndromes: restless leg syndrome, the

burning foot syndrome, Paradoxical heat sensation 

Other Abnormalities

• Gastrointestinal– Uremic fetor– Gastritis, peptic disease, mucosal ulcerations,

• Endocrine– Glucose metabolism

Some patients have hyperglycemia in response to oral and intravenous glucose loads, while others are able to maintain normoglycemia by raising plasma insulin levels.  Accumulation of a uremic toxin or toxins and excess parathyroid hormone (PTH), resulting from abnormalities in phosphate and vitamin D metabolism, are thought to be responsible for the insulin resistance

Other Abnormalities– HYPOGLYCEMIA   spontaneous hypoglycemia. This

complication can be seen in both diabetic and nondiabetic subjects.

– Estrogen levels – amenorrhea, frequent abortions– Male: oligospermia, germinal cell dysplasia, delayed

sexual maturation

• Dermatologic– Pallor, ecchymoses, hematomas, calciphylaxis, pruritus, uremic

frost

Dermatologic changes of Uremic

Uremic Complications

What Should Patients and Doctors Know

• In general CKD is characterized by a gradual loss of the kidney’s filtration capacity.

• Markers Don’t tell everything

What Should Patients and Doctors Know

• Prevention– Keep diabetes and blood pressure controlled– If at risk perform screening tests– Reduce exposure to nephrotoxic drugs– Eat right and exercise– Know your family history

• If you have a positive family history ask doctor to perform common screening tests for kidney function.

Thanksمتشکرم