Chronic Kidney Disease

Chronic Kidney Disease

encompasses a spectrum of different pathophysiologic processes associated with:
abnormal kidney function progressive decline in glomerular filtration rate (GFR)

National Kidney Foundation [Kidney Dialysis Outcomes Quality Initiative (KDOQI)] Guideline on CKD Classification
STAGE 0 1 GFR (ml/min per 1.73 m2) 90 90

2
3 4 5

60 89
30 59 15 29 < 15

Chronic Renal Failure

applies to the process of continuing significant irreversible reduction in nephron number typically corresponds to CKD stages 35

End-Stage Renal Disease

stage of CKD where the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys results in the uremic syndrome
This syndrome leads to death unless the toxins are removed by renal replacement therapy, using:
dialysis or kidney transplantation

Pathophysiology of CKD
involves two broad sets of mechanisms of damage:
(1) initiating mechanisms specific to the underlying etiology
immune complexes and mediators of inflammation in certain types of glomerulonephritis toxin exposure in certain diseases of the renal tubules and interstitium

(2) a set of progressive mechanisms, involving

hyperfiltration and hypertrophy of the remaining viable nephrons

 In order to stage CKD, it is necessary to estimate the GFR.

 The normal annual mean decline in GFR with age from the peak GFR (~120 mL/min per 1.73 m2) attained during the third decade of life is:
~1 mL/min per year per 1.73 m2 reaching a mean value of 70 mL/min per 1.73 m2 at age 70

The mean GFR is lower in women than in men.

For example, a woman in her 80s with a normal serum creatinine may have a GFR of just 50 mL/min per 1.73 m2.

Thus, even a mild elevation in serum creatinine concentration [e.g., 130 mol/L (1.5 mg/dL)], often signifies a substantial reduction in GFR in most individuals.

Etiology & Epidemiology

The most frequent cause of CKD is diabetic nephropathy, most often secondary to type 2 diabetes mellitus. Hypertensive nephropathy is a common cause of CKD in the elderly, in whom chronic renal ischemia as a result of small and large vessel renovascular disease may be underrecognized. Progressive nephrosclerosis from vascular disease is the renal correlate of the same processes that lead to coronary heart disease and cerebrovascular disease.

Clinical & Laboratory Manifestations

Uremia leads to disturbances in the function of virtually every organ system.
Chronic dialysis can reduce the incidence and severity of many of these disturbances However, even optimal dialysis therapy is not completely effective as renal replacement therapy, because some disturbances resulting from impaired renal function fail to respond to dialysis.

Clinical Abnormalities of CKD & Uremia

FLUID & ELECTROLYTE DISTURBANCES Volume expansion Hyponatremia Hyperkalemia Hyperphosphatemia ENDOCRINE-METABOLIC DISTURBANCES Secondary hyperarathyroidism Adynamic bone Vit D-deficient osteomalacia Carbohydrate reistance Hyperuricemia Hypertriglyceridemia Inc LDL level Dec HDL level Protein-energy malnutirition Impaired growth devt Infertility & sexual dysfunction Amenorrhea B2-microglobulin associated amyloidosis

NEUROMUSCULAR DISTURBANCES Fatigue Sleep d/o Headache Impaired mentation Lethargy Asterixis Muscular irritability Peripheral neuropathy Restless legs syndrome Myoclonus Seizures Coma Muscle cramps Dialysis disequilibrium syndrome Myopathy

CARDIO-PULMONARY DISTURBANCES Arterial hypertension CHF or pulmonary edema Pericarditis Hypertrophic or dialted cardiomyopahy Uremic lung Accelerated atherosclerosis Hypotension and arryhtmias Vascular calcification

DERMATOLOGIC DISTURBANCES Pallor Hyperpigmentation Pruritus Ecchymoses Nephrogenic fibrosing dermopathy Uremic frost

GASTROINTESTINAL DISTURBANCES Anorexia Nausea and vomiting Gastroenteritis Peptic ulcer Gastrointestinal bleeding Idiopathic ascites Peritonitis

HEMATOLOGIC & IMMUNOLOGIC DISTURBANCES Anemia Lymphocytopenia Bleeding diathesis Increased susceptibility to infection Leukopenia Thrombocytopenia