Overview of chronic kidney disease in adults

2. Overview of chronic kidney disease in adults

3. Chronic kidney disease • Chronic kidney disease is a worldwide public health problem. • there is a rising incidence and prevalence of kidney failure • The number of patients enrolled in the ESRD program has increased from approximately 10,000 beneficiaries in 1973 to 86,354 in 1983, and to 506,256 as of December 31, 2006

4. Patients with ESRD consume a disproportionate share of health care resources. • The total cost of the ESRD program in the US was approximately $22.7 billion in 2006. • The projected number of ESRD patients by the year 2010 has been estimated to be 651,330 and the total Medicare ESRD program cost in excess of $28 billion dollars

5. Despite the magnitude of the resources committed to the treatment of ESRD and the substantial improvements in the quality of dialysis therapy, these patients experience significant mortality and morbidity, and a reduced quality of life.

6. Unfortunately, CKD, which is highly prevalent, is commonly "under-diagnosed" and/or "under-treated", resulting in lost opportunities for prevention

7. The National Kidney Foundation - Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) workgroup has defined CKD; • The presence of markers of kidney damage for ≥3 months, as defined by structural or functional abnormalities of the kidney with or without decreased glomerular filtration rate (GFR), that can lead to decreased GFR, manifest by abnormalities in the composition of blood or urine, or abnormalities in imaging tests    OR • The presence of GFR <60 mL/min/1.73 m2 for ≥3 months, with or without other signs of kidney damage

8. Stage 1 disease is defined by a normal GFR (greater than 90 mL/min per 1.73 m2) and persistent albuminuria (1.8 percent). • Stage 2 disease is a GFR between 60 to 89 mL/min and persistent albuminuria (3.2 percent). • Stage 3 disease is a GFR between 30 and 59 mL/min (7.7 percent). • Stage 4 disease is a GFR between 15 and 29 mL/min (0.35 percent). • Stage 5 disease is a GFR of less than 15 mL/min or end-stage renal disease (2.4 percent).

9. The rate of progression of chronic renal disease from one major stage to another varies based upon the underlying disease, presence or absence of comorbid conditions, treatments, socioeconomic status, individual genetics, ethnicity, and other factors.

10. The albumin/creatinine ratio combined with estimated GFR may provide a better predictor of patients at risk for progression to ESRD than estimated GFR alone

11. For small changes in serum creatinine, which may be clinically significant, the measurements are most reliable if performed in the same laboratory. • By comparison, changes in serum creatinine of ±0.3 mg/dL measured in different laboratories may represent variations in the assay rather than the GFR

12. Normal individuals demonstrate a decline in renal function over time. • Above the age of 30, this amounts to an average decrease of 0.7 to 0.9 mL/min in the glomerular filtration rate per year

13. SCREENING FOR CKD   Screening for CKD is justified because: • Various therapeutic interventions are effective in slowing or preventing the progression toward kidney failure. • CKD can be detected in its earlier stages via laboratory testing. • However, because of the relatively low prevalence of CKD, massive screening in the general population is not recommended

14. In general, the presence of the following risk factors for CKD should provoke formal testing for CKD: • History of diabetes, cardiovascular disease, hypertension, hyperlipidemia, obesity, metabolic syndrome, smoking, HIV or hepatitis C virus infection, and malignancy • Family history of CKD • Age >60 years • Treatment with potentially nephrotoxic drugs

15. he kidney is able to adapt to damage by increasing the filtration rate in the remaining normal nephrons, a process called adaptive hyperfiltration. • As a result, the patient with mild renal insufficiency often has a normal or near-normal serum creatinine • Adaptive hyperfiltration, although initially beneficial, appears to result in long-term damage to the glomeruli of the remaining nephrons, which is manifest by proteinuria and progressive renal insufficiency

16. The gradual decline in function in patients with (CKD) is initially asymptomatic. However, different signs and symptoms may be observed with advanced renal dysfunction, including volume overload, …. • Manifestations of the uremic state include anorexia, nausea, vomiting, pericarditis, peripheral neuropathy, and central nervous system abnormalities • No direct correlation exists between the absolute serum levels of blood urea nitrogen (BUN) or creatinine, and the development of these symptoms.

17. ASSOCIATION WITH CARDIOVASCULAR DISEASE • Patients with CKD are at increased risk for a variety of non-cardiovascular diseases, including infection and malignancy • Careful attention should be paid to preventive measures such as influenza and pneumococcal immunization, and age-appropriate screening for malignancy

19. GENERAL MANAGEMENT OF CHRONIC KIDNEY DISEASE • Treatment of reversible causes of renal dysfunction • Preventing or slowing the progression of renal disease • Treatment of the complications of renal dysfunction • Identification and adequate preparation of the patient in whom renal replacement therapy will be required

20. Reversible causes of renal dysfunction

21. Slowing the rate of progression • Once renal injury has occurred, independent of etiology, the decline in GFR can be accelerated by hypertension, proteinuria, and possibly by dyslipidemia ,metabolic acidosis • The rate of decline in GFR can be decelerated with early intervention. Perhaps the most successful intervention is the reduction of blood pressure • intraglomerular hypertension and glomerular hypertrophy leading to glomerular scarring

22. glomerular damage and proteinuria typically occur with progressive renal failure, even in primary TID • In diabetic nephropathy and nondiabetic chronic kidney diseases administration of ACE inhibitors or ARBs slows the progression of chronic kidney disease, with the greatest benefit in patients with higher degrees of proteinuria

23. the benefit is likely to be greatest if begun before a great deal of irreversible scar has occurred. • Thus, protective therapy has the greatest impact if it is initiated relatively early in the course, before the serum creatinine concentration exceeds 1.2 and 1.5 mg/dL in women and men, respectively, or the GFR is less than 60 mL/min per 1.73 m2.

24. ARBs are as effective as ACE inhibitors in reducing protein excretion in patients with chronic kidney disease • The reduction in proteinuria appears to be greater when ACE inhibitors are used in combination with ARBs than with either drug alone • However, it has not been proven that combination therapy improves renal outcomes and adverse effects are more common.

25. It is not known whether the benefits from ACE inhibitors/ARBs in proteinuric chronic kidney disease extend to patients older than 70 years older patients are more likely to have adverse effects from therapy (acute kidney injury and hyperkalemia)

26. ACE inhibitors and ARBs can cause a decline in renal function and a rise in plasma potassium that typically occur soon after the onset of therapy. • An elevation in serum creatinine of as much as 30 to 35 percent above baseline that stabilizes within the first two to four months of therapy is considered acceptable and not a reason to discontinue therapy with these drugs • However, a repeat plasma creatinine and potassium should be measured within three to five days.

27. A high salt intake blunts the antiproteinuric effects of angiotensin inhibitors and calcium channel blockers, even when blood pressure reduction seems appropriate • Thus, patients on ACE inhibitors or ARBs who do not have sufficient reduction in proteinuria despite appropriate blood pressure goals should be instructed to take a low sodium diet.

28. reduction in protein excretion to less than 500 to 1000 mg/day; or a minimum reduction of at least 60 percent of baseline values. • reduction in blood pressure to less than 130/80 mmHg. • Caution is advised about lowering the systolic blood pressure below 110 mmHg.

29. Protein restriction and progression of chronic kidney disease

30. The optimal level of protein intake has not been determined but it may be reasonable to restrict intake to 0.8 to 1.0 g/kg per day of high biologic value protein • Some recommend even lower levels, such as 0.6 to 0.75 g/kg per day of high value protein, with close supervision and dietary counseling

31. an increase in the GFR can be induced by animal protein and by amino acid mixtures • vegetable protein and egg whites alone produce little or no effect ( little hemodynamic activity) • lower concentrations of the amino acids that cause renal vasodilatation (such as glycine and alanine) and lesser stimulation of vasodilator prostaglandins may be involved

32. MECHANISM OF PROTEIN-INDUCED HYPERFILTRATION • Enhanced secretion of glucagons ,insulin-like growth factor I (IGF-I) and kinins direct renal vasodilator that can increase both RBF and the GFR • alterations in renin-angiotensin system • Intrarenal effects —TGF may contribute to protein-induced hyperfiltration

33.  Nutritional studies in patients with CKD suggest that protein intake can be safely lowered to 0.6 g/kg per day. • However, a very low protein diet has been associated with increased mortality over the long term

34. Protein-energy wasting can be diagnosed if three characteristics are present; • Low serum albumin, pre-albumin or cholesterol • Reduced body mass (low or reduced body or fat mass or weight loss) • Reduced muscle mass (muscle wasting, reduced mid-arm muscle circumference) • Serum transferrin, which is used as a marker of protein adequacy in general population, is not useful in CKD patients

35. Patients with CKD who are on a protein restricted diet should be carefully monitored with close follow-up every three to six months for adequate caloric intake and evidence of protein malnutrition. (body weight , serum albumin, pre-albumin, and cholesterol ). • More frequent monitoring (ie, monthly) may be necessary in patients with advanced CKD (ie, stages 4 and 5).

36. Both hyperlipidemia and metabolic acidosis should be treated • Smoking cessation should be encouraged, • Smoking enhanced risk of developing kidney disease (primarily nephrosclerosis)

37. Obesity — There is an association between morbid obesity and proteinuria. • an association between a body mass index over 35 kg/m2 and proteinuria • The relationship between body weight and glomerular filtration rate is less clear.

39. Treatment of the complications of renal dysfunction • A wide range of disorders may develop as a consequence of the loss of renal function. These include disorders of fluid and electrolyte balance, such as volume overload, hyperkalemia, metabolic acidosis, and….

40. Volume overload • Sodium and intravascular volume balance are usually maintained via homeostatic mechanisms until the GFR falls below 10 to 15 mL/min. • However, the patient with mild to moderate chronic kidney disease, despite being in relative volume balance, is less able to respond to rapid infusions of sodium and is therefore prone to fluid overload.

41. Patients with CKD and volume overload generally respond to the combination of dietary sodium restriction and diuretic therapy. • sodium intake may also help decrease progression of chronic kidney disease by lowering intraglomerular pressure

42. Hyperkalemia • The ability to maintain potassium excretion at near normal levels is generally maintained in patients with renal disease as long as both aldosterone secretion and distal flow are maintained • Thus, hyperkalemia generally develops in the patient who is oliguric or who has an additional problem such as a high potassium diet, increased tissue breakdown, or hypoaldosteronism (due in some cases to the administration of an ACE inhibitor or ARB)

43. In this setting, institution of a low-potassium diet or concurrent use of a loop diuretic often ameliorates the degree of hyperkalemia. • In selected patients, low dose Kayexalate (5 grams with each meal) can be used to lower the serum potassium concentration without the side effects

44. Metabolic acidosis • There is an increasing tendency to retain hydrogen ions among patients with chronic renal disease • This can lead to a progressive metabolic acidosis with the serum bicarbonate concentration tending to stabilize between 12 and 20 meq/L, and rarely falling below 10 meq/L

45. There are three major reasons why treatment of the acidemia may be desirable in patients with chronic kidney disease. • Bicarbonate supplementation may slow the progression of chronic kidney disease • Bone buffering of some of the excess hydrogen ions is associated with the release of calcium and phosphate from bone • Uremic acidosis can increase skeletal muscle breakdown and diminish albumin synthesis, leading to loss of lean body mass and muscle weakness.

46. alkali therapy to maintain the serum bicarbonate concentration above 23 meq/L is recommended. • If alkali is given, sodium bicarbonate (in a daily dose of 0.5 to 1 meq/kg per day) is the agent of choice

47. Hyperphosphatemia • A tendency toward phosphate retention begins early in renal disease, due to the reduction in the filtered phosphate load. • the hypersecretion of PTH is initially appropriate, since PTH can correct both hyperphosphatemia and hypocalcemia. • The price paid is secondary HPT and development of renal osteodystrophy

48. Once the GFR falls below 25 to 30 mL/min, the addition of oral phosphate binders are usually required to prevent hyperphosphatemia • The K/DOQI recommend that phosphorus levels should be between 2.7 and 4.6 mg/dL among patients with stage3 and 4, and between 3.5 and 5.5 mg/dL among those with stage 5 disease • The serum calcium-phosphorus product should also be maintained at <55 mg2/dL2

49. hormone levels begin to rise when the creatinine clearance is less than 40 to 70 mL/min • Dietary phosphate restriction may limit the development of secondary HPT in patients with chronic kidney disease.( about 800 mg/day )

50. The K/DOQI work group suggests the following target serum levels for intact PTH ; • 35 to 70 pg/mL for those with stage 3 disease • 70 to 110 pg/mL for those with stage 4 disease • 150 to 300 pg/mL for stage 5 disease