Pharmacotherapy of Chronic Renal Failure

1. Sreenu Thalla
Associate Professor
Department of Pharmacology

2. Introduction
• Chronic kidney disease (CKD) is defined as the presence of kidney
damage or an estimated glomerular filtration rate (eGFR) less than
60 ml/min/1.73m2, persisting for 3 months or more, irrespective of
the cause.
• It is a state of progressive loss of kidney function ultimately
resulting in the need for renal replacement therapy (dialysis or
transplantation).
• Kidney damage refers to pathologic abnormalities either suggested
by imaging studies or renal biopsy, abnormalities in urinary
sediment, or increased urinary albumin excretion rates.

4. KDIGO
(Kidney Disease Improving Global Outcomes)

5. • The improved classification of CKD has been beneficial in identifying
prognostic indications related to decreased kidney function and
increased albuminuria.
• However, a downside of the use of classification systems is the possible
over diagnosis of CKD, especially in the elderly.

7. Etiology
• Diabetes mellitus type 2 (30% to 50%)
• Diabetes mellitus type 1 (3.9%)
• Hypertension (27.2%)
• Primary glomerulonephritis (8.2%)
• Chronic Tubulointerstitial nephritis (3.6%)
• Hereditary or cystic diseases (3.1%)
• Secondary glomerulonephritis or vasculitis (2.1%)
• Plasma cell dyscrasias or neoplasm (2.1)
• Sickle Cell Nephropathy (SCN) which accounts for less than 1% of
ESRD patients in the United States

9. Epidemiology
• The true incidence and prevalence of CKD are difficult to determine
because of the asymptomatic nature of early to moderate CKD.
• The prevalence of CKD is around 10% to 14% in the general
population.
• Similarly, albuminuria (microalbuminuria or A2) and GFR less than 60
ml/min/1.73 m2 have a prevalence of 7% and 3% to 5%, respectively.
• Worldwide, CKD accounted for 2,968,600 (1%) of disability-adjusted
life-years and 2,546,700 (1% to 3%) of life-years lost in 2012.
• Kidney Disease Outcomes Quality Initiative (KDOQI) mandates that
for labeling of chronicity and CKD, patients should be tested on three
occasions over a 3-month period with 2 of the 3 results being
consistently positive.

32. CKD may result from disease processes in any of the three categories:
• Prerenal (decreased renal perfusion pressure)
• Intrinsic renal (pathology of the vessels, glomeruli, or tubules-
interstitium)
• Postrenal (obstructive).

33. Mechanisms of Accelerated Progression of CKD
• Systemic and intraglomerular hypertension
• Glomerular hypertrophy
• Intrarenal precipitation of calcium phosphate
• Altered prostanoid metabolism
• All these mechanisms lead to a histological entity called focal
segmental glomerulosclerosis.
• Clinical risk factors for accelerated progression of CKD are
proteinuria, hypertension, black race, and hyperglycemia.
• Also, environmental exposures such as lead, smoking, metabolic
syndrome, possibly some analgesic agents, and obesity have also
been linked to accelerated progression of CKD.

34. History and Physical
• Nausea, Vomiting, Loss of appetite, Fatigue and weakness
• Sleep disturbance, Oliguria, Decreased mental sharpness
• Muscle twitches and cramps, Swelling of feet and ankles
• Persistent pruritus, Chest pain due to uremic pericarditis
• Shortness of breath due to pulmonary edema from fluid overload
• Hypertension that's difficult to control
Physical examination is often not helpful, but patients may have
• Skin pigmentation
• Scratch marks from pruritus
• Pericardial friction rub due to uremic pericarditis
• Uremic frost, where high levels of BUN result in urea in sweat
• Hypertensive fundal changes suggesting chronicity

35. Differential Diagnosis
• Acute kidney injury
• Alport syndrome
• Antigiomerular basement membrane disease
• Chronic glomerulonephritis
• Diabetic nephropathy
• Multiple myeloma
• Nephrolithiasis
• Nephrosclerosis
• Rapidly progressive glomerulonephritis
• Renal artery stenosis