Chronic kidney disease

Acute renal failure (ARF) refers to the rapid loss of renal function over days to weeks. Chronic kidney disease (CKD)a , also called  chronic renal insufficiency (CRI) by some, is defined as a progressive loss of function occurring over several months to years, and is characterized by the gradual replacement of normal kidney architecture with interstitial fibrosis. Progressive kidney disease or nephropathy is generally synonymous with CKD, and the two phrases are often used interchangeably.

ETIOLOGY:-

Susceptibility

_ Advanced age

_ Reduced kidney mass and low

birth weight

_ Racial/ethnic minority

_ Family history

_ Low income or education

_ Systemic inflammation

_ Dyslipidemia

Initiation

_ Diabetes mellitus

_ Hypertension

_ Autoimmune disease

_ Polycystic kidney disease

_ Drug toxicity

Progression

_ Glycemia (among diabetic

patients)

_ Elevated blood pressure

_ Proteinuria

_ Smoking

C L I N I C A L PRESENTATION OF CHRONIC KIDNEY D I S E A S E

GENERAL

CKD development and progression is typically insidious in onset, often with the absence of any noticeable symptoms.

At a minimum, the diagnosis of CKD requires measurement of serum creatinine, calculation of GFR and assessment of a urinalysis for urinary microalbumin or total protein. The diagnosis of Stages 3, 4, and 5 CKD requires the work-up for other common complications including anemia, cardiovascular risks, metabolic bone disease, malnutrition, and disorders of fluids and electrolytes.

SYMPTOMS

Symptoms are generally absent in CKD Stages 1 and 2, and may be minimal during Stages 3 and 4. Classic symptoms associated with Stage 5 CKD include pruritus, dysgeusia, nausea, vomiting, and bleeding abnormalities. Symptoms associated with anemia include cold intolerance, shortness of breath, and fatigue. The severity of symptoms is related to the rate of anemia development and the degree of hemoglobin reduction.

SIGNS

Cardiovascular: Left ventricular hypertrophy, congestive heart failure, hyperhomocysteinemia, dyslipidemia, palpitations, arrhythmias, electrocardiographic changes, elevated creatine kinase-myocardial bound (CK-MB) and creatine kinase (CK), worsening hypertension, and edema.

Musculoskeletal: Cramping and muscle pain.

Neuropsychiatric: Depression, anxiety, impaired mental cognition, fatigue, and sexual dysfunction.

Gastrointestinal: Gastroesophageal reflux disease, constipation, GI bleeding, nausea, and vomiting.

LABORATORY TESTS 

Normal or abnormal GFR with or without documented renal structural abnormalities; presence of urinary albumin or

protein; and pathologic assessment of kidney tissue.

Endocrine: Increased sensitivity to insulin, secondary hyperparathyroidism, decreased vitamin D activation, β2-

microglobulin deposition, and gout.

Hematologic: Anemia, iron deficiency, and bleeding.

STAGES OF CKD

STAGES	GFR in ml/min/1.73m2 body surface area
1	>90
2	60-89
3	30-59
4	15-29
5	<15(including patient on dialysis)

PATHOPHYSIOLOGY

5 The various etiologic factors actually damage the kidney in a heterogenous manner. For example, the key structural lesion in diabetic nephropathy is glomerular mesangial expansion. In hypertensive nephrosclerosis, it is hyalinosis of the kidney’s arterioles, and in polycystic kidney disease it is the development and growth of renal cysts. A variety of morphologic glomerular changes have been noted to occur, depending on the primary diagnosis of the glomerulonephritis. The majority of progressive nephropathies share a final common pathway to irreversible renal parenchymal damage and ESKD.

 The key elements of this pathway are:

 (1) loss of nephron mass;

 (2) glomerular capillary hypertension; and

 (3) proteinuria. The presence of or exposure to the initiation risk factors results in loss of nephron mass. The remaining nephrons hypertrophy to compensate

for the loss of renal function and nephron mass. Initially this compensatory hypertrophy may be adaptive. Yet over time the hypertrophy often becomes maladaptive and leads to the development of glomerular hypertension, possibly mediated by angiotensin II. Angiotensin II, a potent vasoconstrictor of both the afferent and efferent arterioles, preferentially affects the efferent arterioles, leading to increased pressure within the glomerular capillaries. The development of intraglomerular hypertension generally correlates with the development of systemic arterial hypertension. Animal studies have demonstrated

that high intraglomerular capillary pressure impairs the sizeselective function of the glomerular permeability barrier, and results in albuminuria and proteinuria. The resultant proteinuria is thought to accelerate the progressive loss of nephrons due to direct cellular damage. The filtered proteins consist of albumin, transferrin, complement factors, immunoglobulins, cytokines, and angiotensin II, which have varying molecular weights. Numerous studies have demonstrated that the presence of these proteins in the renal tubule activate tubular cells which leads to the upregulated production of inflammatory and vasoactive

cytokines, such as endothelin, monocyte chemoattractant protein (MCP-1), and RANTES (regulated upon activation, normal T-cell expressed and secreted). Accumulating evidence now suggests that intratubular complement activation may be the key mechanism of damage in the progressive proteinuric nephropathies. Proteinuria is associated with the activation of complement components on the apical membrane of proximal tubules. These events eventually lead to scarring of the interstitium, and the progressive loss of structural nephron units, and ultimately function (reduced GFR).

Treatment:

Antihypertensive agent	MOA	Effect on renal hemodynamics
Diuretics β-Adrenergic blockers Calcium channel blockers ACEI/ARB Peripherally acting antiadrenergic drugs	Sodium and volume depletion ↑Vasodilatory prostaglandin levels (IV loop diuretics) Renal vasoconstriction (IV thiazide diuretics) ↓ Cardiac output ↑ Renal vascular resistance (nonselective agents) ↓ Renal vascular resistance ( β1-selective agents) ↓ Renal vascular resistance by vasodilation of afferent arterioles (hypertensive patients) Dilation of the efferent arteriole Direct vasodilation (postsynaptic α1-adrenoreceptor blocking agents)	Decrease in GFR and RBF Increase in RBF Decrease in GFR and RBF Decrease in GFR and RBF  Decrease in GFR and RBF No change in GFR and RBF Increase in RBF and no change in GFR Decrease in GFR and no change in RBF No change in GFR and RBF