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. Treatment with potentially nephrotoxic drugs
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 stage 3 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

51. In patients with stage 3 to 5 CKD, the K/DOQI guidelines suggest that total elemental calcium intake (including both dietary calcium intake and calcium-based phosphate binders) should not exceed 2,000 mg/day.

52. Lanthanum, a rare earth element, also has significant phosphate binding properties. Although no significant clinical adverse effects have yet been reported, the long-term safety of lanthanum, particularly its possible effect on bone and other organs, remains unclear.

53. Most other phosphate binders should be avoided:
Aluminum hydroxide, the previous standard, because of the gradual induction of aluminum toxicity
Magnesium-containing antacids, because of the risk of hypermagnesemia and the frequent development of diarrhea
Calcium citrate, since it markedly increases intestinal aluminum absorption

54. Hypertension 
Hypertension is present in approximately 80 to 85 percent of patients with CKD
Treating hypertension can both slow the progression of proteinuric CKD and reduce the rate of cardiovascular complications.
The desired degree of blood pressure control can usually be safely achieved with combined therapy which usually begins with an ACE inhibitor or ARB and a diuretic.

55. A loop diuretic is recommended for the treatment of hypertension and edema in patients with chronic kidney disease.
The thiazide diuretic  in conventional dosage become less effective as monotherapy when the GFR falls below 20 mL/min. however, produce an additive effect when administered with a loop diuretic for refractory edema.
The optimal blood pressure in hypertensive patients with chronic kidney disease is uncertain

56. Anemia 
 The anemia of CKD is normocytic and normochromic, and is due to reduced production of EPO by the kidney and to shortened red cell survival
anemia becoming increasingly common as glomerular filtration rates (GFRs) decline below 60 mL/min per 1.73 m2

57. the evaluation of anemia in CKD should begin when the Hgb level is less than 12 g/dL in females, and Hgb levels of less than 13.5 g/dL in adult males
If untreated, the hematocrit of patients with advanced chronic kidney disease normally stabilizes at approximately 25 percent in the absence of bleeding or hemolysis

58. The anemia observed with chronic kidney disease is largely diagnosed by excluding non-renal causes of anemia in the patient with a suitably decreased GFR.
Targeting Hgb levels in the range of 11 to 12 g/dL
The EPO dose should be approximately 50 to 100 U/kg per week.

59. An adequate response to EPO requires the maintenance of sufficient iron
K/DOQI guidelines defined low levels of iron tests among patients with predialysis CKD as either serum ferritin <100 ng/mL or TSAT <20 percent
If oral iron is given, adults should receive a daily dose of approximately 200 mg of elemental iron, usually as ferrous sulfate  325 mg three times daily (65 mg elemental iron per tablet).

60. Dyslipidemia 
Abnormal lipid metabolism is common in patients with renal disease
The primary finding in chronic kidney disease is hypertriglyceridemia with the total cholesterol concentration usually being normal (perhaps due in part to malnutrition in some patients).
Patients with chronic kidney disease should be assessed for dyslipidemia, including a total cholesterol, LDL, HDL, and TG.

61. Beneficial effects of statins on vessel stiffening and endothelial function in renal failure have been described
anti-inflammatory role for statins in patients without renal failure have been described
Effect on proteinuria 
statins may slow the rate of progression
may improve cardiovascular outcomes

62. the goal LDL-cholesterol is similar to that in patients with CHD, which has been less than 100 mg/dL or a lower goal of less than 70 mg/dL
Limited data suggest that lipid lowering may have an additional benefit which is slowing the rate of progression of the underlying renal disease.

64. Treatment of complications of ESRD
 Once the patient has reached the stage of near end-stage renal disease (GFR less than 15 mL/min), signs and symptoms related to uremia begin to occur, such as malnutrition, anorexia, nausea, vomiting, fatigue, sexual dysfunction, platelet dysfunction, pericarditis, and neuropathy.

65. Malnutrition 
 Malnutrition is common in patients with advanced chronic renal disease because of a lower food intake (principally due to anorexia), decreased intestinal absorption and digestion, and metabolic acidosis
It is therefore desirable to monitor the nutritional status of patients with chronic kidney disease.

66. To best assess nutritional status, the serum albumin concentration and body weight should be measured serially
these should be measured approximately every one to three months for those with estimated GFRs <20 mL/min, and more frequently if necessary for those with GFRs ≤15 mL/min

67. Uremic bleeding
 An increased tendency to bleeding is present in both acute and chronic kidney disease. This appears to correlate most closely with prolongation of the bleeding time, due primarily to impaired platelet function.
No specific therapy is required in asymptomatic patients. However, correction of the platelet dysfunction is desirable in patients who are actively bleeding or who are about to undergo a surgical or invasive procedure (such as a renal biopsy).
A number of different modalities can be used in this setting….

68. Pericarditis 
Fever, pleuritic chest pain, and a pericardial friction rub are the major presentations
One relatively characteristic feature of uremic pericarditis is that the ECG does not usually show the typical diffuse ST and T wave elevation, presumably because this is a metabolic pericarditis and epicardial injury is uncommon.
The occurrence of pericarditis in a patient with mild to moderate chronic kidney disease is another clue that the renal disease is probably not responsible.

69. Uremic neuropathy 
Dysfunction of the central and peripheral nervous system, including encephalopathy, polyneuropathy, and mononeuropathy are important complications of end-stage renal disease.
Sensory dysfunction, characterized by the restless leg, are frequent presentations of uremic neuropathy.
These complications are usually absolute indications for the initiation of dialysis.

70. PREPARATION FOR AND INITIATION OF RENAL REPLACEMENT THERAPY

71. Referral to nephrologists
 Patients with CKD should be referred to a nephrologist early in the course of their disease, preferably before the plasma creatinine concentration exceeds 1.2 and 1.5 mg/dL in women and men, respectively, or the eGFR is less than 60 mL/min per 1.73 m2.

72.  It is important to identify patients who may eventually require RRT since adequate preparation can decrease morbidity and perhaps mortality.
Early identification enables dialysis to be initiated at the optimal time with a functioning chronic access and may also permit the recruitment and evaluation of family members for the placement of a renal allograft prior to the need for dialysis.

73. Protective therapy has the greatest impact if it is initiated before the plasma creatinine concentration exceeds 1.2 and 1.5 mg/dL in women and men, respectively, or the eGFR is less than 60 mL/min per 1.73m2. At this point, most patients have already lost more than one-half of their GFR.

74. Choice of renal replacement therapy
 Once it is determined that RRT will eventually be required, the patient should be counseled to consider the advantages and disadvantages of hemodialysis (in-center or at home), peritoneal dialysis (continuous or intermittent modalities), and renal transplantation (living or deceased donor)
The 2006 K/DOQI guidelines recommend that patients with a GFR less than 30 mL/min per 1.73 m2 should be educated concerning these issues

75. Kidney transplantation is the treatment of choice for end-stage renal disease. A successful kidney transplant improves the quality of life and reduces the mortality risk
Referral to a transplant program should occur once renal replacement therapy is thought to be required within the next year

76. patients should be referred for surgery to attempt access construction when it is estimated that the patient is within one year of the anticipated need for dialysis as manifested by a GFR less than 25 mL/min, a plasma creatinine concentration greater than 4 mg/mL, or a rapid rate of progression.

77. The 2006 K/DOQI guidelines recommend that a synthetic graft be placed at least three to six weeks prior to the anticipated start of hemodialysis

78. Preparation for peritoneal dialysis ;
 Peritoneal dialysis catheters, which are placed into the abdominal cavity, can be used immediately after placement. However, to minimize the risk of fluid leak, it is preferable to wait at least 10 to 14 days before beginning dialysis.
If dialysis is required less than 10 days following catheter placement, small volume exchanges performed in the recumbent position can be performed with little risk of leak

79. Indications for renal replacement therapy
 The decision to initiate dialysis in a patient with chronic kidney disease involves the consideration of subjective and objective parameters by the physician and the patient.

80. Pericarditis or pleuritis (urgent indication)
Progressive uremic encephalopathy or neuropathy, with signs such as confusion, asterixis, myoclonus, wrist or foot drop, or, in severe, cases, seizures (urgent indication)
A clinically significant bleeding diathesis attributable to uremia (urgent indication)
Fluid overload refractory to diuretics
Hypertension poorly responsive to antihypertensive medications
Persistent metabolic disturbances that are refractory to medical therapy. These include hyperkalemia, metabolic acidosis, hypercalcemia, hypocalcemia, and hyperphosphatemia.
Persistent nausea and vomiting
Weight loss or signs of malnutrition

81. Thanks for your attention